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1
Huang, Yong, Junjie Cen, Zhuowei Liu, Jinhuan Wei, Zhenhua Chen, Zihao Feng, Jun Lu, et al. "A Comparison of Different Prophylactic Intravesical Chemotherapy Regimens for Bladder Cancer Recurrence After Nephroureterectomy for Primary Upper Tract Urothelial Carcinomas: A Retrospective 2-center Study." Technology in Cancer Research & Treatment 18 (January 1, 2019): 153303381984448. http://dx.doi.org/10.1177/1533033819844483.
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Prophylactic intravesical chemotherapy can decrease bladder cancer recurrence rate after nephroureterectomy for upper tract urothelial carcinoma. We aimed to compare the effect of different prophylactic intravesical chemotherapy regimens in bladder recurrence-free survival. From 2000 to 2016, a total of 270 patients treated with radical nephroureterectomy at both institutions were enrolled. Patients were divided into 3 groups: multiple-instillation group, single-instillation group, and no-instillation group. Univariable and multivariable analyses with Cox regression methods were performed to calculate hazard ratios for bladder recurrence using clinicopathologic data, including our different instillation strategies. Sixty-three (23.3%) of 270 patients had subsequent intravesical recurrence. Significantly fewer patients in both the instillation groups had a recurrence compared to in the no-instillation group (13.1% vs 25.4% vs 41.5%, P = .001). Furthermore, there was a significant difference between both the instillation groups ( P = .016). In different subsets of patients with upper tract urothelial carcinoma, intravesical chemotherapy, either multiple or single instillation, was a protective factor of bladder recurrence in pT2-4 ( P = .002) and high grade ( P < .0001). Importantly, Kaplan-Meier curves of bladder recurrence-free survival rate were increased observably in multiple-instillation group compared to that in single-instillation group ( P = .053 in pT2-4 subgroup; P = .048 in high-grade subgroup, respectively). On multivariable analysis, intravesical chemotherapy ( P < .001), especially multiple instillations (hazard ratio 0.230; 95% confidence interval 0.110-0.479), was identified an independent predictor of bladder recurrence-free survival. In conclusion, prophylactic intravesical chemotherapy effectively prevents bladder recurrence after nephroureterectomy, especially with multiple instillations, in patients with invasive upper tract urothelial carcinoma or at high-grade status.
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Nishizawa, Hideo, Hiroshi Yamada, Hiroshi Miyazaki, Maria Ohara, Kazuhiro Kaneko, Tadashi Yamakawa, and Jeanine Wiener-Kronish. "Soluble Complement Receptor Type 1 Inhibited the Systemic Organ Injury Caused by Acid Instillation into a Lung." Anesthesiology 85, no. 5 (November 1, 1996): 1120–28. http://dx.doi.org/10.1097/00000542-199611000-00021.
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Background Acid aspiration into one lung causes contralateral lung injury and systemic organ injury; this injury is thought to be mediated by the sequestration of activated neutrophils. Recombinant human soluble complement receptor 1 (sCR1) inhibits both the classical and alternative complement pathways; this study investigated the role of the complement system in unilateral acid lung injury by measuring the effects of administering sCR1 before or immediately after acid instillation. Methods Anesthetized rats (n = 18 in each group) underwent tracheostomy and insertion of a cannula into the anterior segment of the left lung. Then either 0.1 ml 0.1 N hydrochloric acid (HCl group) or 0.1 ml pH 7.4 phosphate buffered-saline (PBS group) was instilled. Fifteen minutes before (pre-sCR1 group) or 15 min after (post-sCR1 group) the acid was instilled, 10 mg/kg sCR1 was administered intravenously. Four hours after the acid instillation, rats were killed. In an additional 4 rats in each group, blood and bronchoalveolar lavage fluids obtained 1 h after the instillation of either acid or PBS were analyzed for tumor necrosis factor-alpha activity. Results The instillation of acid led to an increased wet-to-dry ratio of 5.2 +/- 0.1 in the acid-instilled lungs compared with their contralateral lungs (4.7 +/- 0.06). These values were greater than the values of 4.6 +/- 0.2 and 4.5 +/- 0.03 in the PBS-instilled lungs and their contralateral lungs, respectively (P < 0.05). The administration of sCR1 before or immediately after the instillation of acid did not attenuate the increase in the wet-to-dry ratio of the acid-instilled lungs. However, the small but consistent increase in the wet-to-dry ratio of the contralateral lungs was attenuated by the sCR1 infusions (P < 0.05). The instillation of acid increased the protein concentration in the bronchoalveolar lavage fluids from the injured lungs (1,000 +/- 206 micrograms/ml) compared with the protein concentration measured in the bronchoalveolar lavage fluids from their contralateral lungs (254 +/- 55 micrograms/ml). The administration of sCR1 before or immediately after the instillation of acid did not decrease the protein concentration in the bronchoalveolar lavage fluids from the acid-instilled lungs. The myeloperoxidase activity was increased in the acid-instilled lung, in their contralateral lung, and in the small intestines of the animals. The infusions of sCR1 before or immediately after the administration of acid led to significant decreases in the myeloperoxidase activities measured in the lungs and the intestines of the treated animals. Plasma tumor necrosis factor-alpha activity was only increased (2.7 +/- 1.1 U/ml) in the animals that had received acid instillations. The infusions of sCR1, administered either before or immediately after the acid instillations, significantly decreased the measured tumor necrosis factor-alpha activity in the plasma (0.5 +/- 0.6 and 1.0 +/- 0.7 U/ml, respectively). Conclusions The results suggest that the complement system plays an important role in the pathogenesis of the injury of the contralateral lung and of the small intestine after unilateral instillation of acid to the lung. Further investigation is warranted to determine the clinical utility of antiinflammatory agents in acid-induced lung injury.
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Sindelar, Richard, Anders Jonzon, Andreas Schulze, and Gunnar Sedin. "Surfactant replacement partially restores the activity of pulmonary stretch receptors in surfactant-depleted cats." Journal of Applied Physiology 100, no. 2 (February 2006): 594–601. http://dx.doi.org/10.1152/japplphysiol.00389.2005.
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Single units of slowly adapting pulmonary stretch receptors (PSRs) were investigated in anesthetized cats during spontaneous breathing on continuous positive airway pressure (2–5 cmH2O), before and after lung lavage and then after instillation of surfactant to determine the PSR response to surfactant replacement. PSRs were classified as high threshold (HT) and low threshold (LT), and their instantaneous impulse frequency ( fimp) was related to transpulmonary pressure (Ptp) and tidal volume (Vt). Both the total number of impulses and maximal fimp of HT and LT PSRs decreased after lung lavage (55 and 45%, respectively) in the presence of increased Ptp and decreased Vt. While Ptp decreased markedly and Vt remained unchanged after surfactant instillation, all except one PSR responded with increased total number of impulses and maximal fimp (42 and 26%, respectively). Some HT PSRs ceased to discharge after lung lavage but recovered after surfactant instillation. The end-expiratory activity of LT PSRs increased or was regained after surfactant instillation. After instillation of surfactant, respiratory rate increased further with a shorter inspiratory time, resulting in a lower inspiratory-to-expiratory time ratio. Arterial pH decreased (7.31 ± 0.04 vs. 7.22 ± 0.06) and Pco2 increased (5.5 ± 0.7 vs. 7.2 ± 1.3 kPa) after lung lavage, but they were the same after as before instillation of surfactant (pH = 7.21 ± 0.08 and Pco2 = 7.6 ± 1.4 kPa) during spontaneous breathing. In conclusion, surfactant instillation increased lung compliance, which, in turn, increased the activity of both HT and LT PSRs. A further increase in respiratory rate due to a shorter inspiratory time after surfactant instillation suggests that the partially restored PSR activity after surfactant instillation affected the breathing pattern.
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Kayikcioglu, Ozcan, Sinan Bilgin, and Murat Uyar. "Review on the Eyedrop Self-Instillation Techniques and Factors Affecting These Techniques in Glaucoma Patients." Scientifica 2016 (2016): 1–5. http://dx.doi.org/10.1155/2016/9183272.
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Objective. This study aims to evaluate eyedrop self-installation techniques and factors affecting these techniques in glaucoma patients.Methods. Researchers directly observed eyedrop instillation procedures of 66 glaucoma patients. Contact with periocular tissues and instillation onto ocular surface or conjunctival fornices were considered. Correlations of instillation patterns with patient characteristics including age, gender, intraocular pressure, cup-to-disc ratio, visual field loss, and total intake of glaucoma medication and handgrip strength score were searched.Results. The average handgrip strength in the instillation without periocular contact group was66.4 ± 19.7 kg, while the average handgrip strength score was55.9 ± 20.9 kg in the instillation with contact group. The difference between the two groups was statistically significant (p=0.039). No statistically significant correlation was found between handgrip strength and the mean number of glaucoma medications, c/d, intraocular pressure (p>0.05). Also there was no significant relation between mean handgrip strength score and the severity of the visual field defect (p=0.191).Conclusion. Patients especially with severe glaucomatous damage should be adequately instructed about the proper techniques for self-instillation of eyedrops and motivated to use a proper technique. Also, it is possible to suggest that patients with a higher handgrip strength, indicating the well-being of general health, may be doing better in properly instilling glaucoma eyedrops.
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Espinosa, F. F., and R. D. Kamm. "Meniscus formation during tracheal instillation of surfactant." Journal of Applied Physiology 85, no. 1 (July 1, 1998): 266–72. http://dx.doi.org/10.1152/jappl.1998.85.1.266.
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The method of surfactant instillation into the lungs for treatment of neonatal respiratory distress syndrome is an important attribute of delivery, and it may determine the overall efficacy of treatment. Previous studies primarily focused on the rate at which the bolus is instilled. These findings show that rapid injections lead to a more homogenous distribution, whereas slow infusions drain into the dependent lung with respect to gravity, resulting in a heterogeneous deposition. These results suggest that it is beneficial to form a meniscus, from which a more homogenous dispersal can proceed. The objective of the present study was to develop a functional criterion for meniscus formation during bolus injection. An in vitro experiment was used to examine the clinical setting of surfactant instillation. The physical variables examined were the bolus viscosity (μ) and density (ρ), gravity ( g), injection rate (Q), orientation of the trachea with respect to gravity (θ), tracheal size ( D), surface tension (γ), and catheter size ( d). All quantities were varied, except gravity and catheter size. Experimental results show that a meniscus will form when N St > 0.004Re2/3, where N St is Stokes number and Re is Reynolds number, N St = μQ/ D 4ρ gsinθ, a ratio of viscous effects to gravitational effects, and Re = ρQ D/ d 2μ, a ratio of inertial effects to viscous effects. Rapid injections, high viscosity, and small inclination with respect to gravity promote meniscus formation. These results can be used to refine the guidelines for administration of surfactant replacement therapy.
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Besselink, Rob A. M., Cornelis H. Schroder, and Anton M. Van Oort. "Influence of Dialysate Exchange on Cardiac Left Ventricular Function in Children Treated with CAPD." Peritoneal Dialysis International: Journal of the International Society for Peritoneal Dialysis 11, no. 2 (April 1991): 141–43. http://dx.doi.org/10.1177/089686089101100208.
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The influence of peritoneal dialysate exchange on the ventricular function in 11 children on continuous ambulatory peritoneal dialysis (CAPD) therapy was studied before and after instillation dialysate. Systolic blood pressure, pulse rate, and echocardiographical data (shortening fraction and pre-ejection period/left ventricle ejection time-ratio) were obtained before and after instillation. There were no differences present with respect to the measured parameters after the abdomen was filled. It is concluded that in children treated with CAPD the exchange of normal volumes of dialysate has no influence on the function of the left ventricle.
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Colombo, Renzo, Federico Pellucchi, Lorenzo Rocchini, Carmen Maccagnano, Pablo Katz, and Valeria Pegoraro. "A pharmacoeconomic analysis of the use of single MMC instillation in low risk NMIBC in Italy." Farmeconomia. Health economics and therapeutic pathways 14, no. 1 (January 30, 2013): 27–32. http://dx.doi.org/10.7175/fe.v14i1.635.
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BACKGROUND: Bladder cancer accounts for 5-10% of all cancers in Europe and up to 85% patients presents a noninvasive tumor, whose treatment of choice is the transurethral bladder resection (TURB) paired with adjuvant intravesical chemotherapy or immunotherapy. Despite several clinical trials showed that this treatment is safe and decreases recurrences by 17% to 44% this practice is limited for many reasons. The study objective is to analyze the economical advantages of the single immediate post operative Mitomycin C instillation in Non Muscle-invasive Bladder Cancer (NMIBC) low-risk patients.METHODS: A cost-benefit analysis was performed evaluating the economical gain that would raised from a scenario with a single immediate post operative mitomycin C instillation in each low-risk NMIBC patient who underwent to TURB. Net present value and cost-benefit ratio were calculated and sensitivity analyses were performed. Base case analysis was performed considering tumor recurrence rate reduction of 11.7% and a TURB costs of 2,167.0 €, while sensitivity analyses were performed using a recurrence rate reduction of 19.2% and 15.0% and a TURB cost of 2,472.93 €. The discount rate was 2%.RESULTS: The single immediate post operative instillation of mitomycin C resulted to be cost-beneficial with a cost-benefit ratio that goes from 0.48 to 0.79 when compared to TURB alone raising a Net Present Value that goes from 660,284.39 € to 2,650,530.79 €.CONCLUSION: This study demonstrates that even assuming conservative parameters for recurrence rates reduction, a single immediate post operative mitomycin C instillation in low risk NMIBC patients would lower not only the recurrence rate but also the caring cost for bladder cancer.
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Nishina, Kahoru, Katsuya Mikawa, Yumiko Takao, Makoto Shiga, Nobuhiro Maekawa, and Hidefumi Obara. "Intravenous Lidocaine Attenuates Acute Lung Injury Induced by Hydrochloric Acid Aspiration in Rabbits." Anesthesiology 88, no. 5 (May 1, 1998): 1300–1309. http://dx.doi.org/10.1097/00000542-199805000-00022.
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Background Neutrophils play a crucial role in the pathogenesis of acid-induced acute lung injury. Lidocaine inhibits the function of neutrophils. This study aimed to determine whether lidocaine attenuates acute lung injury induced by hydrochloric acid (HCl) instillation. Methods In study 1, rabbits were divided into four groups (n = 7 each). Lung injury was induced by intratracheal HCl (0.1 N, 3 ml/kg) in two groups. The other two groups received saline intratracheally. Lidocaine given intravenously (2 mg/ g bolus + 2 mg x kg(-1) x h(-1) infusion) was started 10 min before intratracheal instillation in one HCl and one saline group, and saline was given intravenously in the other two groups. In study 2, rabbits (four groups of seven animals each) received HCl (0.1 N, 3 ml/kg) intratracheally. Treatment with intravenous lidocaine was started 10 min before, 10 min after, or 30 min after acid instillation, or saline was given intravenously 10 min before instillation. Results In study 1, HCl caused deterioration of the partial pressure of oxygen (PaO2), lung leukosequestration, decreased lung compliance, and increased the lung wet-to-dry weight ratio and albumin, interleukin-6 (IL-6), and IL-8 levels in bronchoalveolar lavage fluid. Lidocaine pretreatment attenuated these changes. Hydrochloric acid increased superoxide anion production by neutrophils and caused morphologic lung damage, both of which were lessened by lidocaine. In study 2, lidocaine given 10 min after acid instillation was as effective as pretreatment in PaO2, lung mechanics, and histologic examination. However, PaO2 changes in lidocaine 30 min after injury were similar to those in saline given intravenously. Conclusions Intravenous lidocaine started before and immediately after acid instillation attenuated the acute lung injury, in part by inhibiting the sequestration and activation of neutrophils.
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Velazquez, M., and D. P. Schuster. "Perfusion redistribution after alveolar flooding: vasoconstriction vs. vascular compression." Journal of Applied Physiology 70, no. 2 (February 1, 1991): 600–607. http://dx.doi.org/10.1152/jappl.1991.70.2.600.
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We compared the effects of left caudal lobe (LCL) alveolar hypoxia on regional pulmonary blood flow (PBF) with the effects due to alveolar edema induced by plasma instilled directly into the LCL airways of 16 dogs. Regional measurements were made with positron emission tomography. After hypoxic ventilation of the LCL (n = 11), the LCL-to-right caudal lobe (L/R) PBF ratio fell from 0.94 +/- 0.21 during 100% oxygen ventilation of the LCL to 0.46 +/- 0.21 (P less than 0.05). After instillation of either isooncotic (n = 5) or hypooncotic plasma (n = 3) into the LCL, the L/R PBF ratio was similar to that during LCL hypoxia (0.50 +/- 0.27 and 0.64 +/- 0.10, respectively, P less than 0.05 compared with 100% oxygen ventilation of the LCL before plasma instillation). The changes in regional PBF due to LCL hypoxia and plasma instillation could be completely prevented (n = 8) by the prior administration of a single dose of endotoxin (15 micrograms/kg iv). In contrast to previous work, these results indicate that perfusion redistribution occurs regardless of the oncotic state of alveolar edema. More importantly, any change that does occur in regional PBF can be completely prevented by blocking regional vasoconstriction, indicating that mechanical compression cannot be the major factor determining the regional response of PBF to alveolar flooding.
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Harris, J. D., F. Jackson, M. A. Moxley, and W. J. Longmore. "Effect of exogenous surfactant instillation on experimental acute lung injury." Journal of Applied Physiology 66, no. 4 (April 1, 1989): 1846–51. http://dx.doi.org/10.1152/jappl.1989.66.4.1846.
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Pulmonary surfactant replacement has previously been shown to be effective in the human neonatal respiratory distress syndrome. The value of surfactant replacement in models of acute lung injury other than quantitative surfactant deficiency states is, however, uncertain. In this study an acute lung injury model using rats with chronic indwelling arterial catheters, injured with N-nitroso-N-methylurethane (NNNMU), has been developed. The NNNMU injury was found to produce hypoxia, increased mortality, an alveolitis, and alterations in the pulmonary surfactant system. Alterations of surfactant obtained by bronchoalveolar lavage included a reduction in the phospholipid-to-protein ratio, reduced surface activity, and alterations in the relative percentages of the individual phospholipids compared with controls. Treatment of the NNNMU-injured rats with instilled exogenous surfactant (Survanta) improved oxygenation; reduced mortality to control values; and returned the surfactant phospholipid-to-protein ratio, surface activity, and, with the exception of phosphatidylglycerol, the relative percentages of individual surfactant phospholipids to control values.
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FACOG, Ricardo. "Prenatal Intraamniotic Surfactant Administration Improves Lung Function at Birth and the Effects of Conventional Postdelivery Treatment in Animal Model. A Randomized Controled Trial." Obstetrics Gynecology and Reproductive Sciences 3, no. 3 (December 30, 2019): 01–05. http://dx.doi.org/10.31579/2578-8965/027.
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Introduction: Surfactant diluted in the pulmonary fluid at birth promove airway formation and prevents lung injury, for this reason some investigators have proposed that actual surfactant prophylaxis in high risk preterm deliveries, should be done before the first breath, perhaps in-uteri. Objetive: to evaluate if intraamniotic surfactant plus conventional neonatal instillation improves respiratory outcome outcome compared with only conventional neonatal instillation. Materials and Methods: randomized, controlled and double blinded protocol in a model of very immature born lambs. 125 days pregnant ewes received, with ultrasound guide, an intraamniotic injection of 240 mg of natural bovine surfactant or normal saline solution. After one hour of fetal breathing movement's stimulation with aminophylline the premature lamb’s fetuses were delivered by C-section, and a 3-mm endotracheal tube was placed by tracheotomy. Heart rate, aortic blood pressure, central temperature, respiratory rate and hemoglobin saturation, as well as mechanical ventilator settings, were continuously monitored. Variables under study were: Peak Inspiratory Pressure (PIP), Mean Airway Pressure (MAP), Oxygenation Index (OI) and Arterio-Alveolar Ratio (a/A). Conclusion: Prenatal intraamniotic surfactant instillation improves short-term respiratory outcome compared with conventional postpartum treatment in this animal model.
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Pitt, B. R., J. S. Cole, P. Davies, and C. N. Gillis. "Rapid increases in respiratory epithelial permeability occur after intratracheal instillation of PMA." Journal of Applied Physiology 63, no. 1 (July 1, 1987): 292–301. http://dx.doi.org/10.1152/jappl.1987.63.1.292.
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We measured pulmonary epithelial permeability by quantifying the disappearance of two water-soluble compounds, [14C]mannitol and [3H]inulin, after their instillation, with and without phorbol myristate acetate (PMA), into gas-filled perfused (50 ml/min) rabbit lungs in situ. Both tracers disappeared in a monoexponential fashion over 30 min with calculated first-order rate constants (control; n = 11) of 0.0008 +/- 0.0002 and 0.0027 +/- 0.0008 min-1 for inulin and mannitol, respectively. The ratio of the rate constants (3.1 +/- 0.5) was not significantly different from the ratio of diffusivities of mannitol:inulin (3.7). Addition of PMA (250 micrograms) significantly (n = 9, P less than 0.05) increased the rate constants for both inulin and mannitol to 0.0024 +/- 0.0007 and 0.0087 +/- 0.0025 min-1, respectively, while not affecting their ratio (4.3 +/- 0.5). Addition of human leukocytes (4–8 X 10(8)/l) to the perfusate did not exacerbate the effect of 250 micrograms PMA (n = 3). The addition of catalase (n = 7) completely inhibited the effect of 250 micrograms PMA. PMA (250 micrograms) did not significantly affect perfusion pressure but increased wet-to-dry weight ratios. Light microscopic histology showed damage to epithelial and endothelial cells after 250 micrograms PMA which was not seen after coinstillation of catalase. Catalase sensitivity of functional and structural effects of PMA suggests that the effect was secondary to production of hydrogen peroxide. Since this effect was noted in lungs not perfused with neutrophils and addition of leukocytes did not exacerbate the increase in permeability, we hypothesize that an undetermined pulmonary cell type was the source of hydrogen peroxide. Finally, we found no evidence for restrictive pores with radii of 0.4–1.4 nm.
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Atey, Tesfay Mehari, Workineh Shibeshi, Abeba T. Giorgis, and Solomon Weldegebreal Asgedom. "The Impact of Adherence and Instillation Proficiency of Topical Glaucoma Medications on Intraocular Pressure." Journal of Ophthalmology 2017 (2017): 1–8. http://dx.doi.org/10.1155/2017/1683430.
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Background. The possible sequel of poorly controlled intraocular pressure (IOP) includes treatment failure, unnecessary medication use, and economic burden on patients with glaucoma. Objective. To assess the impact of adherence and instillation technique on IOP control. Methods. A cross-sectional study was conducted on 359 glaucoma patients in Menelik II Hospital from June 1 to July 31, 2015. After conducting a Q-Q analysis, multiple binary logistic analyses, linear regression analyses, and two-tailed paired t-test were conducted to compare IOP in the baseline versus current measurements. Results. Intraocular pressure was controlled in 59.6% of the patients and was relatively well controlled during the study period (mean (M) = 17.911 mmHg, standard deviation (S) = 0.323) compared to the baseline (M=20.866 mmHg, S=0.383, t (358) = −6.70, p<0.0001). A unit increase in the administration technique score resulted in a 0.272 mmHg decrease in IOP (p=0.03). Moreover, primary angle-closure glaucoma (adjusted odds ratio (AOR) = 0.347, 95% confidence interval (CI): 0.144–0.836) and two medications (AOR = 1.869, 95% CI: 1.259–9.379) were factors affecting IOP. Conclusion. Good instillation technique of the medications was correlated with a reduction in IOP. Consequently, regular assessment of the instillation technique and IOP should be done for better management of the disease.
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Sapijaszko, M., J. Mackenzie, M. P. Walsh, and Y. Berthiaume. "Protein kinase C activity during the process of lung liquid clearance." American Journal of Physiology-Lung Cellular and Molecular Physiology 265, no. 1 (July 1, 1993): L57—L66. http://dx.doi.org/10.1152/ajplung.1993.265.1.l57.
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Although active transport of sodium plays an important role in the resolution of pulmonary edema, the biochemical regulation of this process is still under investigation. The purpose of this study was to evaluate the activity of protein kinase C during the process of lung liquid clearance. Alveolar flooding was induced by instilling 5% bovine serum albumin solution, saline, or heterologous serum in the air spaces of rats. The activity of protein kinase C was measured in both the instilled and control lungs at 10 min and 1 and 4 h after fluid instillation. Four hours after instillation of 5% bovine serum albumin, the ratio of protein kinase C activity in the instilled lung compared with the control lung was 2.2 +/- 0.3. Similar results were obtained following instillation with heterologous serum or saline. Since we measured a clearance rate of 0.8 ml/h in anesthetized rats, we can postulate that the activation of protein kinase C occurred when > 40% of the liquid had been cleared from the lung. This increased activity of protein kinase C was not due to an increase in kinase activity in the inflammatory cells or an increase in enzyme quantity but due to a decrease of protein kinase C inhibitory activity in the lung. These results suggest that protein kinase C second messenger system may play a regulatory role in lung liquid clearance.
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Máté, Zsuzsanna, Andrea Szabó, Edit Paulik, Zsanett Jancsó, Edit Hermesz, and András Papp. "Electrophysiological and biochemical response in rats on intratracheal instillation of manganese." Open Life Sciences 6, no. 6 (December 1, 2011): 925–32. http://dx.doi.org/10.2478/s11535-011-0080-2.
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AbstractChronic exposure to excess manganese via inhalation of metal fumes causes central nervous system damage. For modelling Mn aerosol inhalation, male Wistar rats were intratracheally instilled with MnCl2 solution (0.5 mg/kg b.w. MnCl2; n=12) 5 days a week for 5 weeks. At the end of the treatment, somatosensory cortical evoked potentials, elicited by double-pulse stimulation, were recorded from the animals in urethane anaesthesia. Body weight gain, organ weights, and Mn level in brain, lung and blood samples were also measured. In brain samples, gene expression level of MnSOD (Mn superoxide dismutase) was determined. The effect of Mn was mainly seen on the evoked potential amplitudes, and on the second:first ratio of these. Tissue Mn concentration was elevated in brain and lungs, but changed hardly in the blood. Relative weight of heart, thymus, lungs and brain was significantly altered. The level of MnSOD transcript in brain tissue decreased. The observed effects showed that Mn had access to the brain and that somatosensory cortical responses evoked by double-pulse stimulation might be suitable biomarkers of Mn intoxication.
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Matsumoto, Kazuhiro, Tatsuo Gondo, Nozomi Hayakawa, Takahiro Maeda, Akiharu Ninomiya, and So Nakamura. "The role of single instillation chemotherapy in patients who receive subsequent bacillus Calmette-Guérin: A retrospective single centre study, and systematic review of the literature." Canadian Urological Association Journal 9, no. 7-8 (July 17, 2015): 411. http://dx.doi.org/10.5489/cuaj.2818.
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Introduction: This retrospective study was undertaken to evaluate the combined effect of immediate intravesical chemotherapy and subsequent bacillus Calmette-Guérin (BCG) therapy.Methods: The study population consisted of 207 intermediate- or high-risk patients with non-muscle invasive bladder cancer who underwent an induction course of BCG between 1993 and 2007. We introduced single immediate instillation of 50 mg epirubicin for all cases in 2004, and thus earlier cases could be considered as historical controls. The primary endpoint was recurrence-free survival (RFS). For cumulative analysis, we systematically reviewed studies indexed in databases. Including ours, the records of 856 patients from a total of 7 studies, including ours, were finally analyzed.Results: In our cohort, the 5-year RFS in patients who received the combination therapy was 66.2%, compared to 55.2% in the BCG alone group (p = 0.149). Multivariate analysis on tumour recurrence showed that patients with the combination therapy had a hazard ratio (HR) of 0.74 (p = 0.189). A subsequent literature review revealed that RFS rates in the combination groups were higher than those in the corresponding BCG alone groups in 4/7 studies (p = 0.02–0.15), and lower in 1 study (p = 0.51). We identified 5 studies which examined a HR for combination therapy, and performed a cumulative analysis. Adding a single chemo-instillation prior to BCG resulted in a significant reduction in tumour recurrence (summary HR 0.69, p = 0.010).Conclusions: Our analysis suggested that the combination of single chemo-instillation with subsequent BCG therapy exhibited an additive effect against potential tumour recurrence.
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Itoh, Takefumi, Hiroaki Obata, Shinsuke Murakami, Kaoru Hamada, Kenji Kangawa, Hiroshi Kimura, and Noritoshi Nagaya. "Adrenomedullin ameliorates lipopolysaccharide-induced acute lung injury in rats." American Journal of Physiology-Lung Cellular and Molecular Physiology 293, no. 2 (August 2007): L446—L452. http://dx.doi.org/10.1152/ajplung.00412.2005.
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Adrenomedullin (AM), an endogenous peptide, has been shown to have a variety of protective effects on the cardiovascular system. However, the effect of AM on acute lung injury remains unknown. Accordingly, we investigated whether AM infusion ameliorates lipopolysaccharide (LPS)-induced acute lung injury in rats. Rats were randomized to receive continuous intravenous infusion of AM (0.1 μg·kg−1·min−1) or vehicle through a microosmotic pump. The animals were intratracheally injected with either LPS (1 mg/kg) or saline. At 6 and 18 h after intratracheal instillation, we performed histological examination and bronchoalveolar lavage and assessed the lung wet/dry weight ratio as an index of acute lung injury. Then we measured the numbers of total cells and neutrophils and the levels of tumor necrosis factor (TNF)-α and cytokine-induced neutrophil chemoattractant (CINC) in bronchoalveolar lavage fluid (BALF). In addition, we evaluated BALF total protein and albumin levels as indexes of lung permeability. LPS instillation caused severe acute lung injury, as indicated by the histological findings and the lung wet/dry weight ratio. However, AM infusion attenuated these LPS-induced abnormalities. AM decreased the numbers of total cells and neutrophils and the levels of TNF-α and CINC in BALF. AM also reduced BALF total protein and albumin levels. In addition, AM significantly suppressed apoptosis of alveolar wall cells as indicated by cleaved caspase-3 staining. In conclusion, continuous infusion of AM ameliorated LPS-induced acute lung injury in rats. This beneficial effect of AM on acute lung injury may be mediated by inhibition of inflammation, hyperpermeability, and alveolar wall cell apoptosis.
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Enkhbaatar, Perenlei, Kazunori Murakami, Katsumi Shimoda, Akio Mizutani, Roy McGuire, Frank Schmalstieg, Robert Cox, et al. "Inhibition of neuronal nitric oxide synthase by 7-nitroindazole attenuates acute lung injury in an ovine model." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 285, no. 2 (August 2003): R366—R372. http://dx.doi.org/10.1152/ajpregu.00148.2003.
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Nitric oxide (NO) has been shown to play a major role in acute lung injury (ALI) after smoke inhalation. In the present study, we developed an ovine sepsis model, created by exposing sheep to smoke inhalation followed by instillation of bacteria into the airway, that mimics human sepsis and pneumonia. We hypothesized that the inhibition of neuronal NO synthase (nNOS) might be beneficial in treating ALI associated with this model. Female sheep ( n = 26) were surgically prepared for the study and given a tracheostomy. This was followed by insufflation of 48 breaths of cotton smoke (40°C) into the airway of each animal and subsequent instillation of live Pseudomonas aeruginosa [5 × 1011 colony forming units (CFU)] into each sheep's lung. All sheep were mechanically ventilated using 100% O2. Continuous infusion of 7-nitroindazole (7-NI), an nNOS inhibitor, NG-monomethyl-l-arginine (l-NMMA), a nonspecific NOS inhibitor, or aminoguanidine (AG), an inducible NOS inhibitor, was started 1 h after insult. The administration of 7-NI improved pulmonary gas exchange (PaO2/FiO2; where PaO2 is arterial PO2 and FiO2 is fractional inspired oxygen concentration) and pulmonary shunt fraction and attenuated the increase in lung wet-to-dry weight ratio seen in the nontreated sheep. Histologically, 7-NI prevented airway obstruction. The increase in airway blood flow after injury in the nontreated group was significantly inhibited by 7-NI. The increase in plasma concentration of nitrate and nitrite (NOx) was inhibited by 7-NI as well. Posttreatment with l-NMMA improved the pulmonary gas exchange, but AG did not. The results of the present study show that nNOS may be involved in the pathogenesis of ALI after smoke inhalation injury followed by bacterial instillation in the airway.
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Yoo, Sang Hyun, Chang Wook Jeong, Cheol Kwak, Hyeon Hoe Kim, Min Soo Choo, and Ja Hyeon Ku. "Intravesical Chemotherapy after Radical Nephroureterectomy for Primary Upper Tract Urothelial Carcinoma: A Systematic Review and Network Meta-Analysis." Journal of Clinical Medicine 8, no. 7 (July 19, 2019): 1059. http://dx.doi.org/10.3390/jcm8071059.
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The aim of this study was to determine the prophylactic effect of intravesical chemotherapy. Furthermore, it aimed to compare the efficacy of regimens on the prevention of bladder recurrence, after nephroureterectomy, for upper tract urothelial carcinoma by systematic review and network meta-analysis. A comprehensive literature search was conducted to search for studies published before 22 December 2016 using PubMed, Embase, and Scopus. All studies comparing nephroureterectomy alone with prophylactic intravesical chemotherapy after nephroureterectomy were included. The primary outcome was intravesical recurrence-free survival rate. In addition, we conducted indirect comparisons among regimens using network meta-analysis, as well as three randomized controlled trials (RCTs) on multicenter setting, and one large retrospective study with a total of 532 patients were analyzed. The pooled hazard ratio (HR) of bladder recurrence was 0.54 (95% CI: 0.38–0.76) in intravesical instillation patients. On network meta-analysis, pirarubicin was ranked the most effective regimen, while maintenance therapy of mitomycin C (MMC) with Ara-C and induction therapy of MMC were ranked as the second and third most effective regimens, respectively. Our study demonstrates that intravesical chemotherapy can prevent bladder recurrence in patients with upper tract urothelial carcinoma after nephroureterectomy. It also suggests that a single instillation of pirarubicin is the most efficacious intravesical regimen.
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Kambara, K., E. H. Jerome, V. B. Serikov, M. Arakawa, and N. C. Staub. "Reliability of extravascular lung thermal volume measurements by thermal conductivity technique in sheep." Journal of Applied Physiology 73, no. 4 (October 1, 1992): 1449–56. http://dx.doi.org/10.1152/jappl.1992.73.4.1449.
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We tested the accuracy, sensitivity, and reproducibility of a new lung water computer, based on the thermal conductivity technique, in 22 anesthetized closed-chest ventilated sheep with different treatments: 1) controls (n = 8), 2) 0.05 ml/kg of oleic acid + 100 ml/kg of lactated Ringer solution (n = 6), and 3) airway instillation of saline [3.1 +/- 1.3 (SD) g/kg, n = 8]. After 4 h, we determined the extravascular lung water gravimetrically. We found a significant overall correlation between the final extravascular lung thermal volume and the gravimetric extravascular lung mass (P < 0.001). Although the average ratio of extravascular lung thermal volume to extravascular lung mass was 0.97 +/- 0.25 ml/g for all groups, the computer overestimated extravascular lung mass in controls by 10% (17 g) and underestimated it in sheep with oleic acid by 15% (95 g) and in sheep with airway instillation by 8% (37 g). The computer also underestimated the small quantities of saline placed via the airway in the alveolar space by 75% (61 g). Reproducibility of three consecutive measurements was 4.3% (SE). We conclude that the thermal conductivity technique has an ability to detect the baseline extravascular lung mass but has a poor ability to detect an accurate increment of the extravascular lung water under poor tissue perfusion in anesthetized ventilated sheep.
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S., Sandeepa H., Narendra U., Gajanan S. Gaude, and Supriya Sandeepa. "Efficacy of intrapleural instillation of streptokinase with pigtail catheter drainage in the treatment of tuberculous pleural effusion." International Journal of Advances in Medicine 6, no. 6 (November 25, 2019): 1695. http://dx.doi.org/10.18203/2349-3933.ijam20194579.
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Background: Tuberculosis is the most common cause of exudative lymphocytic pleural effusion in India. The present study was undertaken to evaluate the efficacy of intrapleural instillation of streptokinase with pigtail catheter drainage in the treatment of tuberculous pleural effusion.Methods: Clinical profile, hospital course and outcome of tuberculous pleural effusion patients at the end of six months of anti-tubercular treatment of 50 patients from January 2009 to June 2010 were analyzed. These patients were randomly divided into two groups. One group (n=25) received intrapleural streptokinase via pigtail catheter and the other group (n=25) received intercostal drainage without intrapleural streptokinase instillation. All the patients received standard daily anti TB regimen of 2HERZ/4HR for a total duration of six months.Results: Majority of the patients were above 40 years of age (60%). The male to female ratio was 2.3:1. The major symptoms of the patients were, fever in 44 patients (88%), cough in 42 patients (84%), breathlessness in 33 patients (66%), loss of appetite in 25 patients (50%) and chest pain in 25 patients (50%). Most of the patients had ADA levels between 40-70 IU/L (48%) and only 6% had ADA levels below 40 IU/L. The mean pleural drainage was 2615±126.1 ml in the study group (intrapleural streptokinase) and 1858 ± 93.3 ml in the control group (p <0.0001). Mean duration of intercostal drainage in the study group was 3.76 ± 0.144 days and it was 5.08±0.199 days in the control group (p <0.0001). The mean duration of hospitalization in the study group was 6.60±0.91 days and it was 8.60 ± 0.57 days in the control group (p=0.06). Conclusion: Intrapleural streptokinase instillation is successful in increasing the total drainage of pleural fluid and results in effective drainage of tuberculous pleural effusion. It is also associated with increased amount of pleural fluid drainage, decreased duration of intercostal drainage, decreased length of hospital stay.
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Nishina, Kahoru, Katsuya Mikawa, Yumiko Takao, Nobuhiro Maekawa, and Hidefumi Obara. "Effects of Exogenous Surfactant on Acute Lung Injury Induced by Intratracheal Instillation of Infant Formula or Human Breast Milk in Rabbits." Anesthesiology 91, no. 1 (July 1, 1999): 240–52. http://dx.doi.org/10.1097/00000542-199907000-00033.
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Background An animal experimental model of acute lung injury after intratracheal instillation of acidified milk products has been recently demonstrated. Exogenous administration of surfactant has proved to be successful treatment for acute lung injury induced by many causes including acid aspiration. The authors conducted this study to investigate whether exogenous surfactant can reduce the magnitude of lung damage induced in rabbits by acidified milk products. Methods The lung injury was induced by intratracheal instillation of acidified human breast milk or acidified infant formula (0.8 ml/kg, pH 1.8). Thirty minutes after the insult, some animals were treated with intratracheal surfactant 100 or 200 mg/kg. Lung compliance and alveolar-to-arterial oxygen gradient were recorded during ventilation. After 4 or 12 h, the lungs were excised to determine physiologic and histologic lung damage. Albumin, interleukin-8, and eicosanoids in bronchoalveolar lavage fluid and superoxide production by neutrophils were measured. Results The acidified milk products increased A-aD(O2)(550+/-52 and 156+/-28 mmHg; mean+/-SD at 4 h in saline solution and infant formula groups, respectively), lung wet-to-dry weight ratio (6.6+/-0.5 and 5.6 +/- 0.2), %neutrophils in bronchoalveolar lavage fluid (84+/-4% and 8+/-20%), and decreased compliance (0.76+/-0.09 and 1.90+/-0.11 ml/cm H2O). Surfactant improved these variables in a dose-dependent manner (A-aDO2 = 363+/-50 and 237+/-55 mmHg in 100-mg/kg and 200-mg/kg surfactant groups). Surfactant attenuated extensive histologic changes caused by the milk products. Superoxide production was less in rabbits receiving surfactant than in those not receiving it. Conclusion Exogenous surfactant improved physiologic, histologic, and biochemical lung injury induced by acidified milk products in a dose-dependent manner. The effectiveness of surfactant may be caused, in part, by inhibition of neutrophils' sequestration and activation. These data indicate that intratracheal instillation of surfactant may be a promising therapeutic modality in acute lung injury resulting from aspiration of acidified milk products.
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Miyazaki, Jun, Naoki Ishizuka, Shiro Hinotsu, Hideyuki Akaza, and Hiroyuki Nishiyama. "Analysis of tolerability of intravesical bacillus Calmette-Guérin (BCG) therapy in non-muscle-invasive bladder cancer." Journal of Clinical Oncology 30, no. 15_suppl (May 20, 2012): e15004-e15004. http://dx.doi.org/10.1200/jco.2012.30.15_suppl.e15004.
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e15004 Background: Although the effectiveness of BCG intravesical instillation with maintenance therapy (MT) has been shown (Hinotsu S. BJUI 2010), the treatment was not well tolerated. We aimed to characterize adverse events (AEs) affecting tolerability and to study the possible prediction of MT tolerability during the induction therapy (IT) by using data from the previous phase III trial. Methods: Forty-two patients received 81 mg intravesical BCG once weekly for 6 weeks as IT followed by thrice weekly instillations at 3, 6, 12 and 18 months as MT. AEs after each instillation were analyzed. The hazard ratio (HR) and 95% confidence intervals (CI) between the risk of each AE during IT and MT were analyzed by Cox regression. To assess the time between the randomization and the onset of each AE, HR and CI for patients without an AE were measured against those who developed the AE once, using the Wei-Lin-Weissfeld (WLW) Model. The WLW Model allows the analysis of recurrent AEs by controlling within-patient correlations in a marginal Cox model. Results: Fourteen of the 42 patients completed MT, of whom 11 completed as scheduled, and 3 completed with some modifications. For 28 who did not complete, 6 were withdrawn during IT and 22 during MT (of whom 15 had some MT modifications). Among 17 patients who experienced Grade (Gr) 3 AEs, 4 completed the treatment. In total there were 65 Gr3 events. Urinary frequency was most frequent event causing treatment cessation (7/38 events) and hematuria was the most common cause of treatment modification (7/13). The risk of an AE that occurred during IT recurring during MT was high for malaise (HR:3.49), pyrexia (3.33), and difficulty in urination (2.90). The WLW analysis revealed that malaise was relapsed in 18/21 patients (HR:5.81, CI:2.94-11.50, p<0.0001), difficulty in urination in 13/21 (4.56, 1.92-10.84, 0.0006), pyrexia in 14/18 (4.27, 2.18-8.37, <0.0001), hematuria in 36/39 (2.69, 1.79-4.04, <0.0001) and urinary frequency in 35/39 (2.30, 1.38-3.84, 0.0014). Conclusions: Gr3 urinary frequency was the most common cause of treatment cessation. The risk of the recurrent AE during MT will increase in those who develop AEs such as malaise, pyrexia, and difficulty in urination at IT.
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Gao, M., L. S. Levy, R. A. Braithwaite, and S. S. Brown. "Monitoring of Total Chromium in Rat Fluids and Lymphocytes Following Intratracheal Administration of Soluble Trivalent or Hexavalent Chromium Compounds." Human & Experimental Toxicology 12, no. 5 (September 1993): 377–82. http://dx.doi.org/10.1177/096032719301200506.
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1 Intratracheal instillation of sodium dichromate (CrVI) and chromium acetate hydroxide (CrIII) to male Wistar rats gave rise to increased chromium concentrations in whole blood, plasma and urine up to 72 h post exposure; peak concentrations were reached at 6 h after exposure. 2 The ratio of whole blood chromium to plasma chromium concentrations was significantly different for Cr(VI) and CR(III) treatments. Both blood chromium and plasma chromium assays should therefore be used for the assessment of chromium exposure. 3 Chromium was also detected in peripheral lymphocytes. Cr(VI), but not Cr(lll) accumulated significantly in the lymphocytes after treatment. These cells have potential to be used for biomarkers of the assessment of exposure to chromium compounds.
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Min, Rui, Ting Li, Ju Du, Yan Zhang, Jia Guo, and Wan-Liang Lu. "Pulmonary gemcitabine delivery for treating lung cancer: pharmacokinetics and acute lung injury aspects in animals." Canadian Journal of Physiology and Pharmacology 86, no. 5 (May 2008): 288–98. http://dx.doi.org/10.1139/y08-039.
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Gemcitabine, a nucleoside analogue for treating lung cancer, is clinically administered as an intravenous infusion. To achieve better patient compliance and more direct effect on the lung, we explored a new gemcitabine pulmonary delivery route and evaluated the pharmacokinetics and acute lung injury aspects in animals. Pharmacokinetics of gemcitabine were measured in Sprague–Dawley rats after intravenous (i.v.), intratracheal instillation by tracheotomy (i.t.t.), intratracheal instillation via orotrachea (i.t.o.), and intragastric (i.g.) administration of gemcitabine. Acute lung injury effects of the pulmonary delivery of gemcitabine were performed in Sprague–Dawley rats after i.t.o. and i.v. administration of gemcitabine and i.t.o. administration of lipopolysaccharide (LPS) as a positive control and physiological saline as a blank control. Indicators for acute lung injury that were evaluated included lung morphology, lung histopathology, lung coefficient, lung wet/dry weight ratio, total cell and classification counts in bronchoalveolar lavage cells (BALC), and total protein and TNF-α levels in bronchoalveolar lavage fluids (BALF). After i.t.t. or i.t.o. administration, gemcitabine was quickly absorbed, but i.g. administration led to an undetectable plasma gemcitabine concentration. Absolute bioavailability of gemcitabine after i.t.t. and i.t.o. administration was 91% and 65%, respectively. Gemcitabine given as i.t.o. administration did not cause any overt acute lung injury. All indicators for acute lung injury in the i.t.o. group were similar to those in the i.v. group or in the blank control, but significantly different from those in the positive control. In conclusion, the pharmacokinetics and acute lung injury studies suggest that pulmonary gemcitabine delivery would be a new and promising administration route.
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Kostrycki, Iberê Machado, Guilherme Wildner, Yohanna Hannah Donato, Analú Bender dos Santos, Lílian Corrêa Costa Beber, Matias Nunes Frizzo, Mirna Stela Ludwig, et al. "Effects of High-Fat Diet on eHSP72 and Extra-to-Intracellular HSP70 Levels in Mice Submitted to Exercise under Exposure to Fine Particulate Matter." Journal of Diabetes Research 2019 (January 6, 2019): 1–13. http://dx.doi.org/10.1155/2019/4858740.
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Obesity, air pollution, and exercise induce alterations in the heat shock response (HSR), in both intracellular 70 kDa heat shock proteins (iHSP70) and the plasmatic extracellular form (eHSP72). Extra-to-intracellular HSP70 ratio (H-index = eHSP70/iHSP70 ratio) represents a candidate biomarker of subclinical health status. This study investigated the effects of moderate- and high-intensity exercise in the HSR and oxidative stress parameters, in obese mice exposed to fine particulate matter (PM2.5). Thirty-day-old male isogenic B6129F2/J mice were maintained for 16 weeks on standard chow or high-fat diet (HFD). Then, mice were exposed to either saline or 50 μg of PM2.5 by intranasal instillation and subsequently maintained at rest or subjected to moderate- or high-intensity swimming exercise. HFD mice exhibited high adiposity and glucose intolerance at week 16th. HFD mice submitted to moderate- or high-intensity exercise were not able to complete the exercise session and showed lower levels of eHSP70 and H-index, when compared to controls. PM2.5 exposure modified the glycaemic response to exercise and modified hematological responses in HFD mice. Our study suggests that obesity is a critical health condition for exercise prescription under PM2.5 exposure.
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Abdullah, Syahril, Wai Yeng Wendy-Yeo, Hossein Hosseinkhani, Mohsen Hosseinkhani, Ehab Masrawa, Rajesh Ramasamy, Rozita Rosli, Sabariah A. Rahman, and Abraham J. Domb. "Gene Transfer into the Lung by Nanoparticle Dextran-Spermine/Plasmid DNA Complexes." Journal of Biomedicine and Biotechnology 2010 (2010): 1–10. http://dx.doi.org/10.1155/2010/284840.
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A novel cationic polymer, dextran-spermine (D-SPM), has been found to mediate gene expression in a wide variety of cell lines andin vivothrough systemic delivery. Here, we extended the observations by determining the optimal conditions for gene expression of D-SPM/plasmid DNA (D-SPM/pDNA) in cell lines and in the lungs of BALB/c mice via instillation delivery.In vitrostudies showed that D-SPM could partially protect pDNA from degradation by nuclease and exhibited optimal gene transfer efficiency at D-SPM to pDNA weight-mixing ratio of 12. In the lungs of mice, the levels of gene expression generated by D-SPM/pDNA are highly dependent on the weight-mixing ratio of D-SPM to pDNA, amount of pDNA in the complex, and the assay time postdelivery. Readministration of the complex at day 1 following the first dosing showed no significant effect on the retention and duration of gene expression. The study also showed that there was a clear trend of increasing size of the complexes as the amount of pDNA was increased, where the sizes of the D-SPM/pDNA complexes were within the nanometer range.
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Hachiya, A., and M. Bessho. "Relationship of blood flow to antral lesion incidence in rat gastric mucosa after hemorrhage and retransfusion." American Journal of Physiology-Gastrointestinal and Liver Physiology 266, no. 6 (June 1, 1994): G1011—G1016. http://dx.doi.org/10.1152/ajpgi.1994.266.6.g1011.
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The relationship of gastric mucosal hemodynamics, energy metabolism, and acid to antral histological lesion incidence following hemorrhage and retransfusion was investigated in rats. Decrease of mucosal blood flow and of the index of mucosal oxygen saturation (ISO2) during hemorrhage were slightly greater in the corpus than in the antrum. ATP content and redox ratio in the corpus were decreased by shock; however, these hardly changed in the antrum. The index of tissue hemoglobin concentration (IHb) recovered to above the prehemorrhage value only in the antrum after retransfusion. Histological lesion incidence in the antral mucosa was more markedly increased by acid instillation and/or retransfusion than in the corpus. From these results, it was concluded that the decrease of blood flow is related as an underlying factor to induction of ischemic damage in the antral mucosa and that intraluminal acid and/or postischemic hyperemia play a causative role in the development of histologic lesions in the antral mucosa during shock and retransfusion in the rat stomach.
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Huang, Xiaoying, Jiangfeng Tang, Hui Cai, Yi Pan, Yicheng He, Caijun Dai, Ali Chen, et al. "Anti-Inflammatory Effects of Monoammonium Glycyrrhizinate on Lipopolysaccharide-Induced Acute Lung Injury in Mice through Regulating Nuclear Factor-Kappa B Signaling Pathway." Evidence-Based Complementary and Alternative Medicine 2015 (2015): 1–8. http://dx.doi.org/10.1155/2015/272474.
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The present study aimed to investigate the therapeutic effect of monoammonium glycyrrhizinate (MAG) on lipopolysaccharide- (LPS-) induced acute lung injury (ALI) in mice and possible mechanism. Acute lung injury was induced in BALB/c mice by intratracheal instillation of LPS, and MAG was injected intraperitoneally 1 h prior to LPS administration. After ALI, the histopathology of lungs, lung wet/dry weight ratio, protein concentration, and inflammatory cells in the bronchoalveolar lavage fluid (BALF) were determined. The levels of tumor necrosis factor-α(TNF-α) and interleukin-1β(IL-1β) in the BALF were measured by ELISA. The activation of NF-κB p65 and IκB-αof lung homogenate was detected by Western blot. Pretreatment with MAG attenuated lung histopathological damage induced by LPS and decreased lung wet/dry weight ratio and the concentrations of protein in BALF. At the same time, MAG reduced the number of inflammatory cells in lung and inhibited the production of TNF-αand IL-1βin BALF. Furthermore, we demonstrated that MAG suppressed activation of NF-κB signaling pathway induced by LPS in lung. The results suggested that the therapeutic mechanism of MAG on ALI may be attributed to the inhibition of NF-κB signaling pathway. Monoammonium glycyrrhizinate may be a potential therapeutic reagent for ALI.
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Heunks, Leo M. A., Aalt Bast, Cees L. A. van Herwaarden, Guido R. M. M. Haenen, and P. N. Richard Dekhuijzen. "Effects of emphysema and training on glutathione oxidation in the hamster diaphragm." Journal of Applied Physiology 88, no. 6 (June 1, 2000): 2054–61. http://dx.doi.org/10.1152/jappl.2000.88.6.2054.
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Loading of skeletal muscles is associated with increased generation of oxidants, which in turn may impair muscle contractility. We investigated whether the load on the hamster diaphragm imposed by pulmonary emphysema induces oxidative stress, as indicated by glutathione oxidation, and whether the degree of glutathione oxidation is correlated with contractility of the diaphragm. In addition, the effect of 12 wk of treadmill exercise training on contractility and glutathione content in the normal (NH) and emphysematous hamster (EH) diaphragm was investigated. Training started 6 mo after elastase instillation. After the training period, glutathione content and in vitro contractility of the diaphragm were determined. Twitch force and maximal tetanic force were significantly reduced (by ∼30 and ∼15%, respectively) in EH compared with NH. In sedentary hamsters, the GSSG-to-GSH ratio was significantly elevated in the EH compared with the NH diaphragm. A significant inverse correlation was found between GSSG-to-GSH ratio and twitch force in the diaphragm ( P < 0.01). Training improved maximal tetanic force and reduced fatigability of the EH diaphragm but did not alter its glutathione content. In conclusion, 1) emphysema induces oxidative stress in the diaphragm, 2) training improves the contractile properties of the EH diaphragm, and 3) this improvement is not accompanied by changes in glutathione redox status.
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Hu, Yi Xin, Hua Cui, Li Fan, Xiu Jie Pan, Ji Hua Wu, Suo Zhu Shi, Shao Yuan Cui, Zhi Min Wei, and Lin Liu. "Resveratrol attenuates left ventricular remodeling in old rats with COPD induced by cigarette smoke exposure and LPS instillation." Canadian Journal of Physiology and Pharmacology 91, no. 12 (December 2013): 1044–54. http://dx.doi.org/10.1139/cjpp-2012-0464.
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The objective of this study was to investigate left cardiac damage and the cardioprotective effects of resveratrol in old rats with COPD. Rats 22 months old were divided into three groups: control (CTL), smoking and lipopolysaccharides (SM/LPS), and SM/LPS plus resveratrol (SM/LPS-Res). Cardiac function, pathology, oxidative stress, and apoptosis index were measured. Expression of myocardial SIRT1 was studied by real-time quantitative polymerase chain reaction (PCR) and Western blot detection. The heart weight – body weight ratio (LVW/BW) increased in the SM/LPS group compared with the CTL group. Both the LVW/BW and the area of fibrosis in the SM/LPS-Res group decreased compared with those in the SM/LPS group. 8-OHdG expression increased in cardiac tissue of rats in the SM/LPS group, which could be inhibited by resveratrol. Resveratrol significantly increased the activity of superoxide dismutase (SOD) and reduced the cardiac malonyldialdehyde (MDA) level in the SM/LPS-Res group. There was a significant decrease in the extent of cardiomyocyte apoptosis in the SM/LPS-Res group compared with the SM/LPS group. SIRT1 mRNA increased in the SM/LPS-Res group compared with the SM/LPS group. In conclusion, resveratrol attenuated cardiac oxidative damage and left ventricular remodeling and enhanced the decreased expression of SIRT1 in hearts of old rats with emphysema and thus might be a therapeutic modality for cardiac injury complicated in chronic obstructive pulmonary disease (COPD).
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S., Sandeepa H., Narendra U., Gajanan S. Gaude, and Supriya Sandeepa. "Complications and residual pleural thickening after intrapleural instillation of streptokinase with pigtail catheter drainage of tuberculous pleural effusion." International Journal of Advances in Medicine 7, no. 1 (December 23, 2019): 1. http://dx.doi.org/10.18203/2349-3933.ijam20195567.
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Background: Tuberculosis is the most common cause of exudative lymphocytic pleural effusion in India. Residual pleural thickening (RPT) is observed in about 50 percent of patients even after proper treatment with ATT. Pleural fluid drainage either with simple aspiration or with intercostal drainage and addition of corticosteroids along with antitubercular drugs have not shown to influence the incidence of RPT. The present study was undertaken to study the complications and residual effects of tubercular pleural effusion on the patients during the follow up period following intrapleural streptokinase instillation.Methods: Clinical profile, hospital course and outcome of tuberculous pleural effusion patients at the end of six months of anti-tubercular treatment of 50 patients from January 2009 to June 2010 were analyzed. These patients were randomly divided into two groups. One group (n=25) received intrapleural streptokinase via pigtail catheter and the other group (n=25) received intercostal drainage without intrapleural streptokinase instillation. All the patients received standard daily anti TB regimen of 2HERZ/4HR for a total duration of six months. All the patients were followed up for a total duration of 1 year for evidence of any residual pleural thickening.Results: Majority of the patients were above 40 years of age (60%). The male to female ratio was 2.3:1. The major symptoms of the patients were, fever in 44 patients (88%), cough in 42 patients (84%), breathlessness in 33 patients (66%), loss of appetite in 25 patients (50%) and chest pain in 25 patients (50%). Most of the patients had ADA levels between 40-70IU/L (48%) and only 6% had ADA levels below 40IU/L. The incidence of residual pleural thickening in the study group was less as compared to the control group (2.36±0.49mm vs 9.28±1.50mm) (p <0.0001).Conclusion: Intrapleural streptokinase instillation with pigtail catheter drainage less number of complications associated with study group and is successful with the decreased incidence of residual pleural thickening during the follow up period.
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Fu, Meijiao, Tong Shen, Ying Yang, Yaling Zheng, and Lilin Zhong. "Echinacoside attenuates lipopolysaccharide-induced acute lung injury in newborn mice via inactivation of NF- κB/NLRP3 signaling pathway." Tropical Journal of Pharmaceutical Research 19, no. 9 (November 23, 2020): 1815–19. http://dx.doi.org/10.4314/tjpr.v19i9.3.
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Purpose: To investigate the effect of echinacoside (ECH) on acute lung injury (ALI) and the underlying mechanism of action.Methods: The ALI model was established through intranasal instillation of lipopolysaccharide (LPS). Lung tissue damage was determined using hematoxylin and eosin (H&E) staining and lung wet-to-dry–weight ratio. Bronchoalveolar lavage fluid (BALF) protein concentration, cell count, and cytokine level were evaluated. Western blotting was used to determine protein expression level.Results: ECH attenuated lung tissue injury and lung wet-to-dry–weight ratio in the ALI model (p < 0.01). The total protein content and number of total cells, neutrophils, and macrophages increased in BALF of mice treated with LPS, but these increases were reversed by ECH treatment (p < 0.01). The levels of TNF-α and IL-1β increased in BALF and lung tissue of LPS-treated mice; however, ECH treatment decreased these changes (p < 0.01). In addition, ECH inhibited the activation of the nuclear factor-κB (NF-κB)/NLR family pyrin domain containing 3 (NLRP3) pathway in LPS-treated mice (p < 0.01).Conclusion: Echinacoside attenuates LPS-induced ALI via inactivation of the NF-κB/NLRP3 pathway, making echinacoside a potential drug for the treatment of ALI.
Keywords: Echinacoside, Acute lung injury, Lipopolysaccharide, Nuclear factor-κB, NLR family pyrin domain containing 3
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Tang, Bao Lin, Guang Xue Chen, Qi Feng Chen, and Jing Lei Tai. "Research on Preparation of Nano-Silver by Orthogonal Test." Materials Science Forum 694 (July 2011): 142–45. http://dx.doi.org/10.4028/www.scientific.net/msf.694.142.
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Nano-silver has received a great deal of attention in recent years for its various potential applications on medical, electronic, optical, etc. In this paper, we developed a simple way to synthesize nano-sized silver by liquid chemical reduction method with hydrazine hydrate as reductant and PVP as surface-protection reagent. In the experimental design, orthogonal test with three factors and three levels is adopted, which investigated the effect of instillation method, the PVP amount and the reaction temperature on the size and morphology of silver nano-particle. Through analyzing the orthogonal experimental results, the optimum conditions for nano-silver preparation is obtained, in which hydrazine hydrate solution is instilled into the mixture solution of silver nitrate and PVP, the molar ratio of PVP/AgNO3 is 1.5, and the temperature is 50°C. Scanning electron microscopy was used to characterize the morphology of silver nano-particles, and the results show that the dispersed spherical nano-particles with the average size of about 60 nm can be prepared in this work.
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Nicholas, T. E., H. A. Barr, J. H. Power, and M. E. Jones. "Uptake of instilled radiolabeled lamellar bodies from alveolar compartment of the rat." American Journal of Physiology-Lung Cellular and Molecular Physiology 259, no. 4 (October 1, 1990): L238—L246. http://dx.doi.org/10.1152/ajplung.1990.259.4.l238.
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Following the instillation of lamellar bodies containing dipalmitoyl phosphatidyl-[3H]choline (DPPC) down the trachea of adult rats, we found that the half-life of alveolar [3H]-DPPC was 85 min and the time constant was 120 min. As much as 85% was recycled. When we labeled the DPPC with both [3H]choline and [14C]acetate, the ratio 3H/14C increased in the alveolar compartment and then increased further in the lamellar body fraction of the recipient lungs, suggesting that some deacylation-reacylation was occurring. Further evidence of degradation was an increase in free [3H]choline in the microsomal fraction. Whereas hyperpnea induced by breathing 5% CO2-13% O2–82% N2 increased the reuptake of DPPC, reuptake did not appear to be enhanced in the rest period immediately after hyperpnea induced by swimming, when alveolar DPPC was still markedly elevated. Propranolol did not affect reuptake, suggesting that beta-adrenoreceptors were not essential. We suggest that reuptake is coupled more to release than to the amount of surfactant in the alveolar compartment.
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Keymel, Stefanie. "Talkumpleurodese über dauerhaft implantierten Katheter bei malignem Pleuraerguss." Kompass Pneumologie 7, no. 3 (2019): 149–50. http://dx.doi.org/10.1159/000500058.
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Ein maligner Pleuraerguss (MPE) wird häufig nicht operativ durch eine Talkumpleurodese behandelt, die typischerweise unter stationären Bedingungen vorgenommen wird. Als Behandlungsalternative kann ein Pleurakatheter (indwelling pleural catheter, IPC) zur intermittierenden Drainage implantiert werden. Dies kann als ambulante Prozedur vorgenommen werden. In einer klinischen multizentrischen Studie im Vereinigten Königreich wurde geprüft, ob die Instillation von Talkum über einen IPC häufiger zu einer Pleurodese führt als Plazebo. Hierfür wurden Patienten mit MPE eingeschlossen, bei denen nach Anlage eines IPC und Drainagetherapie die Lunge nach 10 Tagen entfaltet war. 69 Patienten wurde über den IPC 4g einer Talkumsuspension instilliert, 70 Patienten wurde als Plazebo über den IPC Kochsalzlösung appliziert. Der primäre Endpunkt, die erfolgreiche Pleurodese nach der Randomisierung, wurde bei 30 von 69 (43%) Patienten in der Talkumgruppe und 16 von 70 (23%) Patienten in der Plazebogruppe erreicht, dies war signifikant häufiger in der Talkumgruppe (Hazard ratio 2,20; 95% Konfidenzintervall 1,23-3,92; p = 0,008). Die Lebensqualität und die Symptomatik waren besser in der Talkumgruppe, während die Ergussmenge, die Anzahl der stationären Behandlungstage, die Mortalität oder der Anzahl von unerwünschten Ereignissen zwischen den Gruppen vergleichbar waren.
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Wu, Xiao-Li, Xue-Xuan Feng, Chu-Wen Li, Xiao-Jun Zhang, Zhi-Wei Chen, Jian-Nan Chen, Xiao-Ping Lai, Sai-Xia Zhang, Yu-Cui Li, and Zi-Ren Su. "The Protective Effects of the Supercritical-Carbon Dioxide Fluid Extract ofChrysanthemum indicumagainst Lipopolysaccharide-Induced Acute Lung Injury in Mice via Modulating Toll-Like Receptor 4 Signaling Pathway." Mediators of Inflammation 2014 (2014): 1–13. http://dx.doi.org/10.1155/2014/246407.
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The supercritical-carbon dioxide fluid extract ofChrysanthemum indicumLinné. (CFE) has been demonstrated to be effective in suppressing inflammation. The aim of this study is to investigate the preventive action and underlying mechanisms of CFE on acute lung injury (ALI) induced by lipopolysaccharide (LPS) in mice. ALI was induced by intratracheal instillation of LPS into lung, and dexamethasone was used as a positive control. Results revealed that pretreatment with CFE abated LPS-induced lung histopathologic changes, reduced the wet/dry ratio and proinflammatory cytokines productions (TNF-α, IL-1β, and IL-6), inhibited inflammatory cells migrations and protein leakages, suppressed the levels of MPO and MDA, and upregulated the abilities of antioxidative enzymes (SOD, CAT, and GPx). Furthermore, the pretreatment with CFE downregulated the activations of NF-κB and the expressions of TLR4/MyD88. These results suggested that CFE exerted potential protective effects against LPS-induced ALI in mice and was a potential therapeutic drug for ALI. Its mechanisms were at least partially associated with the modulations of TLR4 signaling pathways.
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Rehman, Faiza Ur, Bilal Khattak, Irfan Ul Islam Nasir, and Muhammad Naeem. "The Effectiveness of Single Shot Intravesical Chemotherapy with Mitomycin-C in Preventing Recurrence of Non-Muscle Invasive Bladder Cancer." Journal of Gandhara Medical and Dental Science 2, no. 2 (March 1, 2016): 21–26. http://dx.doi.org/10.37762/jgmds.2-2.52.
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OBJECTIVES:To determine the efficacy of single dose intravesical chemotherapy with Mitomycin-C following transurethral resection of non-muscle invasive bladder cancerMETHODS:It was a Descriptive case series study conducted in the admitted patients of bladder cancer in the institute of kidney disease, Peshawar within one year duration. Total of 128 patients were enrolled in the study. After TURBT patient were catheterized with 22 FR 3 ways foley’s catheter and urinary bladder irrigation was started with normal saline. Mitomycin 40 mg dissolved in 20 ml of normal saline was instilled once hematuria settles within 24 hours. All the patients were called back after 3 months for check cystoscopy and the findings were recorded so as to detect recurrence of bladder tumorRESULTS:In this study, 128 patients with transurethral resection of non-muscle invasive bladder cancer have been observed; male to female ratio was 5:1. The age ranges of patients were from 18 to 75 years. Average age was 51.13 years + 14.33SD. Recurrence was found in 20(15.62%) of cases while the remaining 108(84.38%) were free of recurrence.CONCLUSION:Our study confirmed the effectiveness of a single shot immediate Mitomycin-C instillation in patients with non-muscle-invasive bladder tumors.
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Takeda, K., M. J. Knapp, W. G. Wolfe, and J. D. Crapo. "Hypoxia enhances unilateral lung injury by increasing blood flow to the injured lung." Journal of Applied Physiology 63, no. 6 (December 1, 1987): 2516–23. http://dx.doi.org/10.1152/jappl.1987.63.6.2516.
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We hypothesized that in unilateral lung injury, bilateral hypoxic ventilation would induce vasoconstriction in the normal lung, redirect blood flow to the injured lung, and cause enhanced edema formation. Unilateral left lung injury was induced by intrabronchial instillation of 1.5 ml/kg of 0.1 N HCl. After HCl injury, blood flow to the injured left lung decreased progressively from 0.70 +/- 0.04 to 0.37 +/- 0.05 l/min and percent of flow to the injured left lung (QL/QT) decreased from 37.7 +/- 2.2 to 23.6 +/- 2.2% at 240 min. Exposure to hypoxia (12% O2) for three 10-min episodes did not affect QL/QT in normal animals, but after unilateral HCl injury, it caused blood flow to the injured left lung to increase significantly. A concomitant decrease in blood flow occurred to the noninjured right lung, resulting in a significant increase in QL/QT. The enhanced blood flow to the injured lung was associated with a significant increase in the wet-to-dry lung weight ratio in the dependent regions of the injured lung. These findings demonstrate that in unilateral HCl-induced lung injury, transient hypoxia can enhance blood flow to the areas of injury and increase lung edema formation.
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St John, R. C., L. A. Mizer, G. C. Kindt, S. E. Weisbrode, S. A. Moore, and P. M. Dorinsky. "Acid aspiration-induced acute lung injury causes leukocyte-dependent systemic organ injury." Journal of Applied Physiology 74, no. 4 (April 1, 1993): 1994–2003. http://dx.doi.org/10.1152/jappl.1993.74.4.1994.
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The adult respiratory distress syndrome is a form of acute lung injury (ALI) that is frequently associated with systemic organ injury and often occurs in the setting of wide-spread inflammatory cell activation. However, whether conditions that lead to ALI result in systemic organ injury is unclear. This study was designed to test the hypothesis that ALI induced by acid aspiration will not result in systemic organ injury. Morphological alterations and lymph-to-plasma protein ratios were measured in autoperfused cat ileum preparations of four control animals and five animals with ALI produced by the endobronchial instillation of 0.1 N HCl (0.5 ml.kg-1.lung-1). After 2 h, the lymph-to-plasma protein ratio (a measure of microvascular permeability) was increased in the ilea of HCl-injured animals compared with control animals (0.234 +/- 0.03 vs. 0.121 +/- 0.005; P = 0.012) and was accompanied by extensive morphological alterations. Four additional HCl-injured animals were pretreated with an antileukocyte adherence antibody (anti-CD18, 2 mg/kg) that blocked the HCl-induced alterations in the ileum. This study provides evidence for significant systemic organ injury after acid aspiration-induced ALI and suggests that the neutrophil may be a key mediator.
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Lewis, J. F., J. Goffin, P. Yue, L. A. McCaig, D. Bjarneson, and R. A. Veldhuizen. "Evaluation of exogenous surfactant treatment strategies in an adult model of acute lung injury." Journal of Applied Physiology 80, no. 4 (April 1, 1996): 1156–64. http://dx.doi.org/10.1152/jappl.1996.80.4.1156.
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Two exogenous surfactant preparations [Survanta and bovine lipid extract surfactant (BLES)] were evaluated in saline lavage-injured adult sheep with two different delivery methods (instillation vs. aerosolization). Instilled BLES resulted in the greatest improvement in lung function, followed by aerosolized Survanta and then instilled Survanta. Aerosolized BLES was ineffective. Total surfactant recovery and distribution patterns were similar for Survanta and BLES for each delivery method tested. There were significant differences, however, in the proportion of surfactant recovered in the alveolar wash relative to the lung tissue between the groups at killing. Moreover, the ratio of poorly functioning small surfactant aggregates to superior functioning large aggregates isolated from alveolar wash samples correlated with the physiological responses. The calculated contribution of secreted endogenous surfactant to the total alveolar phospholipid pool at killing was significantly greater for the aerosolized Survanta group compared with the aerosolized BLES group. This finding suggested that there were differences in the interaction of the exogenous surfactants and their alveolar environments. We conclude that the response to exogenous surfactant in acute lung injury depends not only on the preparation used but also on how the surfactants are delivered to the injured lung.
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Gajjar, Amar, Patricia L. Harrison, John T. Sandlund, Gaston K. Rivera, Raul C. Ribeiro, Jeffrey E. Rubnitz, Bassem Razzouk, et al. "Traumatic lumbar puncture at diagnosis adversely affects outcome in childhood acute lymphoblastic leukemia." Blood 96, no. 10 (November 15, 2000): 3381–84. http://dx.doi.org/10.1182/blood.v96.10.3381.
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Abstract The effect of traumatic lumbar puncture at the time of initial diagnostic workup on treatment outcome in children with newly diagnosed acute lymphoblastic leukemia (ALL) was investigated. The findings of the first 2 lumbar punctures performed on 546 patients with newly diagnosed ALL treated on 2 consecutive front-line studies (1984-1991) at St Jude Children's Research Hospital were retrospectively reviewed. Lumbar punctures were performed at the time of diagnosis and again for the instillation of first intrathecal chemotherapy. The event-free survival (EFS) experience for patients with 1 cerebrospinal fluid (CSF) sample contaminated with blast cells was worse than that for patients with no contaminated CSF samples (P = .026); that of patients with 2 consecutive contaminated CSF samples was particularly poor (5-year EFS = 46 ± 9%). In a Cox multiple regression analysis, the strongest prognostic indicator was 2 consecutive contaminated CSF samples, with a hazard ratio of 2.39 (95% confidence interval, 1.36-4.20). These data indicate that contamination of CSF with circulating leukemic blast cells during diagnostic lumbar puncture can adversely affect the treatment outcome of children with ALL and is an indication to intensify intrathecal therapy.
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Gajjar, Amar, Patricia L. Harrison, John T. Sandlund, Gaston K. Rivera, Raul C. Ribeiro, Jeffrey E. Rubnitz, Bassem Razzouk, et al. "Traumatic lumbar puncture at diagnosis adversely affects outcome in childhood acute lymphoblastic leukemia." Blood 96, no. 10 (November 15, 2000): 3381–84. http://dx.doi.org/10.1182/blood.v96.10.3381.h8003381_3381_3384.
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The effect of traumatic lumbar puncture at the time of initial diagnostic workup on treatment outcome in children with newly diagnosed acute lymphoblastic leukemia (ALL) was investigated. The findings of the first 2 lumbar punctures performed on 546 patients with newly diagnosed ALL treated on 2 consecutive front-line studies (1984-1991) at St Jude Children's Research Hospital were retrospectively reviewed. Lumbar punctures were performed at the time of diagnosis and again for the instillation of first intrathecal chemotherapy. The event-free survival (EFS) experience for patients with 1 cerebrospinal fluid (CSF) sample contaminated with blast cells was worse than that for patients with no contaminated CSF samples (P = .026); that of patients with 2 consecutive contaminated CSF samples was particularly poor (5-year EFS = 46 ± 9%). In a Cox multiple regression analysis, the strongest prognostic indicator was 2 consecutive contaminated CSF samples, with a hazard ratio of 2.39 (95% confidence interval, 1.36-4.20). These data indicate that contamination of CSF with circulating leukemic blast cells during diagnostic lumbar puncture can adversely affect the treatment outcome of children with ALL and is an indication to intensify intrathecal therapy.
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Lee, Jeong Ho, Dheerendra K. Reddy, Rajiv Saran, Harold L. Moore, Zbylut J. Twardowski, Karl D. Nolph, and Ramesh Khanna. "Peritoneal Accumulation of Advanced Glycosylation End-Products in Diabetic Rats on Dialysis with Icodextrin." Peritoneal Dialysis International: Journal of the International Society for Peritoneal Dialysis 20, no. 5_suppl (December 2000): 39–47. http://dx.doi.org/10.1177/089686080002005s08.
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Objective To evaluate and compare the effects of glucose-based solutions to those of icodextrin with respect to peritoneal transport characteristics and formation of advanced glycosylation end-products (AGEs) in the peritoneal membrane in the diabetic rat model of peritoneal dialysis (PD). Study Design Thirty-three male Sprague–Dawley rats weighing between 275 – 300 g were divided into 5 groups: group C ( n = 6), control rats with catheter but not dialyzed; group D ( n = 5), diabetic rats with catheter but not dialyzed; group G ( n = 7), diabetic rats dialyzed with standard 2.5% glucose solution for daytime exchanges and 4.25% glucose solution for the overnight exchange; group H ( n = 8), diabetic rats dialyzed with standard 2.5% glucose solution for daytime exchanges and 7.5% icodextrin solution for overnight exchanges; group I ( n = 7), diabetic rats dialyzed with 7.5% icodextrin solution for all exchanges. Dialysis exchanges were performed three times daily with an instillation volume of 25 mL per exchange for a period of 12 weeks. Tissue sections were stained using a monoclonal anti-AGE antibody. One-hour peritoneal equilibration tests (PET) were performed every 4 weeks for comparison of transport characteristics. Results The level of immunostaining was lowest in group C and highest in group G. Significant differences were seen between group C and groups G, H, and I ( p < 0.001, p = 0.001, and p < 0.05 respectively). Significant differences were also found between group G and groups D and I ( p < 0.05 and p < 0.05 respectively). Over time, glucose concentration at the end of an exchange versus concentration at instillation (D/D0 glucose) decreased and dialysate-to-plasma ratio (D/P) of urea increased. Significant differences were found between groups C and H for D/D0 glucose (0.40 ± 0.01 vs 0.35 ± 0.01, p < 0.05); and between groups C and H for D/P urea (0.87 ± 0.03 vs 0.97 ± 0.02, p < 0.05). Conclusions These results suggest that AGE formation is lower with the use of peritoneal dialysis solution containing icodextrin than with glucose-based solutions. We conclude that the use of icodextrin may be helpful in slowing the deterioration of the peritoneal membrane, prolonging its use for dialysis.
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Berry, Valerie, Jennifer Hoover, Christine Singley, and Gary Woodnutt. "Comparative Bacteriological Efficacy of Pharmacokinetically Enhanced Amoxicillin-Clavulanate against Streptococcus pneumoniae with Elevated Amoxicillin MICs and Haemophilus influenzae." Antimicrobial Agents and Chemotherapy 49, no. 3 (March 2005): 908–15. http://dx.doi.org/10.1128/aac.49.3.908-915.2005.
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ABSTRACT A new pharmacokinetically enhanced formulation of amoxicillin-clavulanate (2,000 mg of amoxicillin/125 mg of clavulanate twice a day; ratio 16:1) has been designed, with sustained-release technology, to allow coverage of bacterial strains with amoxicillin-clavulanic acid MICs of at least 4/2 μg/ml. The bacteriological efficacy of amoxicillin-clavulanate, 2,000/125 mg twice a day, ratio 16:1, was compared in a rat model of respiratory tract infection versus four other amoxicillin-clavulanate formulations: 8:1 three times a day (1,000/125 mg), 7:1 three times a day (875/125 mg), 7:1 twice a day (875/125 mg), and 4:1 three times a day (500/125 mg); levofloxacin (500 mg once a day); and azithromycin (1,000 mg on day 1 followed thereafter by 500 mg once a day). Bacterial strains included Streptococcus pneumoniae, with amoxicillin-clavulanic acid MICs of 2/1 (one strain), 4/2, or 8/4 μg/ml (three strains each), and Haemophilus influenzae, one β-lactamase-positive strain and one β-lactamase-negative, ampicillin-resistant strain. Animals were infected by intrabronchial instillation. Antibacterial treatment commenced 24 h postinfection, with doses delivered by computer-controlled intravenous infusion to approximate the concentrations achieved in human plasma following oral administration. Plasma concentrations in the rat corresponded closely with target human concentrations for all antimicrobials tested. Amoxicillin-clavulanate, 2,000/125 mg twice a day, ratio 16:1, was effective against all S. pneumoniae strains tested, including those with amoxicillin-clavulanic acid MICs of up to 8/4 μg/ml and against β-lactamase-producing and β-lactamase-negative ampicillin-resistant H. influenzae. These results demonstrate the bacteriological efficacy of pharmacokinetically enhanced amoxicillin-clavulanate 2,000/125 mg twice a day (ratio 16:1) against S. pneumoniae with amoxicillin-clavulanic acid MICs of at least 4/2 μg/ml and support clavulanate 125 mg twice a day as sufficient to protect against β-lactamase in this rat model.
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Sai, Na, Xiaoxv Dong, Pingqing Huang, Longtai You, Chunjing Yang, Yi Liu, Wenping Wang, et al. "A Novel Gel-Forming Solution Based on PEG-DSPE/Solutol HS 15 Mixed Micelles and Gellan Gum for Ophthalmic Delivery of Curcumin." Molecules 25, no. 1 (December 24, 2019): 81. http://dx.doi.org/10.3390/molecules25010081.
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Curcumin (Cur) is a naturally hydrophobic polyphenol with potential pharmacological properties. However, the poor aqueous solubility and low bioavailability of curcumin limits its ocular administration. Thus, the aim of this study was to prepare a mixed micelle in situ gelling system of curcumin (Cur-MM-ISG) for ophthalmic drug delivery. The curcumin mixed micelles (Cur-MMs) were prepared via the solvent evaporation method, after which they were incorporated into gellan gum gels. Characterization tests showed that Cur-MMs were small in size and spherical in shape, with a low critical micelle concentration. Compared with free curcumin, Cur-MMs improved the solubility and stability of curcumin significantly. The ex vivo penetration study revealed that Cur-MMs could penetrate the rabbit cornea more efficiently than the free curcumin. After dispersing the micelles in the gellan gum solution at a ratio of 1:1 (v/v), a transparent Cur-MM-ISG with the characteristics of a pseudoplastic fluid was formed. No obvious irritations were observed in the rabbit eyes after ocular instillation of Cur-MM-ISG. Moreover, Cur-MM-ISG showed a longer retention time on the corneal surface when compared to Cur-MMs using the fluorescein sodium labeling method. These findings indicate that biocompatible Cur-MM-ISG has great potential in ophthalmic drug therapy.
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Young, S. L., J. R. Wright, and J. A. Clements. "Cellular uptake and processing of surfactant lipids and apoprotein SP-A by rat lung." Journal of Applied Physiology 66, no. 3 (March 1, 1989): 1336–42. http://dx.doi.org/10.1152/jappl.1989.66.3.1336.
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The intracellular pathways and the kinetics of metabolism of surfactant apoprotein and lipid, which may be recycled from the alveolar space, are largely unknown. We used a lipid-apoprotein complex made from liposomes of pure lipids in a ratio found in mammalian pulmonary surfactant plus surfactant apoprotein (SP-A, Mr = 26,000–36,000) to test some possible relationships in the recycling of these major surfactant components between intrapulmonary compartments. After intratracheal instillation of 80 microliters of an apoprotein-liposome mixture with separate radiolabels in the lipid and the apoprotein, rats were killed at times from 8 min to 4 h later. The lungs were lavaged with saline, and subcellular fractions were isolated on discontinuous sucrose density gradients. Both the [14C]lipid radiolabel and the 125I-apoprotein radiolabel demonstrated a time-dependent increase in radioactivity recovered in a lamellar body-enriched fraction. Uptake of the radiolabels into other subcellular fractions did not exhibit a clear-cut time dependence; more of the protein than the lipid radiolabel was found in the Golgi-rich and microsomal fractions. We conclude that both the lipid and apoprotein portions of lung surfactant are taken up by lung cells and are incorporated into secretory granules of the cells.
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Delclaux, C., S. Rezaiguia-Delclaux, C. Delacourt, C. Brun-Buisson, C. Lafuma, and A. Harf. "Alveolar neutrophils in endotoxin-induced and bacteria-induced acute lung injury in rats." American Journal of Physiology-Lung Cellular and Molecular Physiology 273, no. 1 (July 1, 1997): L104—L112. http://dx.doi.org/10.1152/ajplung.1997.273.1.l104.
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Polymorphonuclear neutrophils (PMNs) are thought to play a major role in the pathogenesis of adult respiratory distress syndrome. Because the alveolar epithelium is a decisive factor in alveolo-capillary wall permeability, a toxic effect of emigrated PMNs in alveolar spaces is conceivable. We evaluated alveolar PMN function in two rat models of acute lung injury induced by alveolar instillation of endotoxin [lipopolysaccharide (LPS)] or live Pseudomonas aeruginosa (PYO). Alveolar PMNs were isolated from bronchoalveolar lavage fluid 4 and 24 h after the challenge. Hypoxemia was assessed based on the ratio arterial partial pressure of O2 (PaO2)/fraction of inspired O2 (FIO2) during mechanical ventilation. The severity of lung injury in the two models was clearly different, since PaO2/FIO2 were approximately 400 mmHg in PYO- and LPS-induced injuries, respectively. Both contrast, alveolar neutrophil influx, unstimulated oxygen metabolite production, and proteinase (elastase, gelatinase B) secretions of ex vivo alveolar PMNs were not larger in the PYO model. Thus the difference in severity was not associated with variations in alveolar neutrophil recruitment or activation. Moreover, gelatinase and leukocyte elastase activities were absent in bronchoalveolar fluid, indicating effective antiproteinase defense in alveolar spaces. We conclude that alveolar neutrophils are not sufficient to create severe respiratory failure.
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Hierholzer, Christian, Jörg C. Kalff, Laurel Omert, Katsuhiko Tsukada, J. Eric Loeffert, Simon C. Watkins, Timothy R. Billiar, and David J. Tweardy. "Interleukin-6 production in hemorrhagic shock is accompanied by neutrophil recruitment and lung injury." American Journal of Physiology-Lung Cellular and Molecular Physiology 275, no. 3 (September 1, 1998): L611—L621. http://dx.doi.org/10.1152/ajplung.1998.275.3.l611.
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Hemorrhagic shock (HS) initiates an inflammatory cascade that includes the production of cytokines and recruitment of neutrophils (PMN) and may progress to organ failure, inducing acute respiratory distress syndrome (ARDS). To examine the hypothesis that interleukin-6 (IL-6) contributes to PMN infiltration and lung damage in HS, we examined the lungs of rats subjected to unresuscitated and resuscitated HS for the production of IL-6 and activation of Stat3. Using semiquantitative RT-PCR, we found a striking increase in IL-6 mRNA levels only in resuscitated HS, with peak levels observed 1 h after initiation of resuscitation. Increased IL-6 protein expression was localized to bronchial and alveolar cells. Electrophoretic mobility shift assay of protein extracts from shock lungs exhibited an increase in Stat3 activation with kinetics similar to IL-6 mRNA. In situ DNA binding assay determined Stat3 activation predominantly within alveoli. Intratracheal instillation of IL-6 alone into normal rats resulted in PMN infiltration into lung interstitium and alveoli, marked elevation of bronchoalveolar lavage cellularity, and increased wet-to-dry ratio. These findings indicate that IL-6 production and Stat3 activation occur early in HS and may contribute to PMN-mediated lung injury, including ARDS after HS.
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Jahed, M., and S. J. Lai-Fook. "Stress wave velocity measured in intact pig lungs with cross-spectral analysis." Journal of Applied Physiology 76, no. 2 (February 1, 1994): 565–71. http://dx.doi.org/10.1152/jappl.1994.76.2.565.
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In anesthetized pigs (25–40 kg), we generated stress waves in the lung by rapid deflation of an esophageal balloon. The source distortion was measured by an accelerometer (1 g wt) bonded to the balloon. Stress waves were detected by three accelerometers bonded to intercostal muscle and to the skin near midchest. The distance between the source and chest receivers were measured radiographically. Cross-spectral analysis was used to calculate transit times. We measured stress wave velocities at airway pressures of 0 (functional residual capacity) and 25 cmH2O. Transpulmonary pressure (Ptp) was measured by an esophageal balloon. In vivo, stress wave velocities increased from 291 +/- 117 (SD) cm/s at 3.0 +/- 0.9 cmH2O Ptp to 573 +/- 73 cm/s at 13.8 +/- 3.5 cmH2O Ptp (n = 6). These velocities agreed with longitudinal wave velocities measured in isolated sheep lungs and predictions based on the elastic moduli of lung parenchyma. Post-mortem edema was induced by intratracheal instillation of 200 ml of saline, resulting in a wet-to-dry weight ratio of 7.7 +/- 1.4 (n = 5). At 15 cmH2O Ptp, stress wave velocities decreased from 565 +/- 155 cm/s before edema to 445 +/- 130 cm/s after edema. This decrease correlated well with predictions based on the increased lung density, as dictated by elasticity theory.