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Erikssen, Gunnar, Jamil Aboulhosn, Jeannette Lin, Knut Liestøl, Mette E. Estensen, Ola Gjesdal, Helge Skulstad, Gaute Døhlen, and Harald Lauritz Lindberg. "Survival in patients with univentricular hearts: the impact of right versus left ventricular morphology." Open Heart 5, no. 2 (October 2018): e000902. http://dx.doi.org/10.1136/openhrt-2018-000902.
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ObjectivePatients with univentricular hearts (UVH) have high mortality despite modern treatment, and better methods to identify patients at highest risk are needed. We wanted to improve risk stratification in patients with UVH by focusing on the prognostic significance of single right versus single left ventricular morphology (SRV vs SLV).MethodsAll 395 patients with UVH operated at our centre were prospectively included from 1972 to 2016 (195 SRV, 166 SLV, 34 mixed or indeterminate ventricular morphology). Diagnoses, UVH morphology, types of all operations and time and causes of death or heart transplantation (HTX) were recorded. The primary endpoint was death or HTX.ResultsAmong the 111 non-Fontan patients, 88 died (SRV 62 vs SLV 20; p<0.0001), 32 due to heart failure (SRV 23 vs SLV 5; p=0.0012). Twenty-five years of cumulative SRV versus SLV survival among the 284 Fontan patients (41 deaths/HTX) was 66.9% vs 87.9% (p=0.0027), partly explained by more deaths/HTX due to heart failure among patients with SRV (p=0.0006). Survival in patients with SRV with and without hypoplastic left heart syndrome (HLHS) was similar. SRV versus SLV was a strong predictor of death/HTX in multivariable proportional hazards analyses (RR 3.3, 95% CI 1.6 to 6.6).ConclusionSRV versus SLV is a strong short-term and long-term predictor of survival among patients with UVH, mainly explained by higher rates of death/HTX due to heart failure in the SRV group. Our findings apply to patients with SRV both with and without HLHS.
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Pahrudin Arrozi, Aslina, Zulzikry Hafiz Abu Bakar, Hiroyasu Taguchi, Daijiro Yanagisawa, and Ikuo Tooyama. "A Fluorine-19 Magnetic Resonance Probe, Shiga-Y5, Downregulates Thioredoxin-Interacting Protein Expression in the Brain of a Mouse Model of Alzheimer’s Disease." Molecules 26, no. 17 (September 2, 2021): 5342. http://dx.doi.org/10.3390/molecules26175342.
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Thioredoxin-interacting protein (TXNIP) is involved in multiple disease-associated functions related to oxidative stress, especially by inhibiting the anti-oxidant- and thiol-reducing activity of thioredoxin (TXN). Shiga-Y5 (SY5), a fluorine-19 magnetic resonance probe for detecting amyloid-β deposition in the brain, previously showed therapeutic effects in a mouse model of Alzheimer’s disease; however, the mechanism of action of SY5 remains unclear. SY5 passes the blood–brain barrier and then undergoes hydrolysis to produce a derivative, Shiga-Y6 (SY6), which is a TXNIP-negative regulator. Therefore, this study investigates the therapeutic role of SY5 as the prodrug of SY6 in the thioredoxin system in the brain of a mouse model of Alzheimer’s disease. The intraperitoneal injection of SY5 significantly inhibited TXNIP mRNA (p = 0.0072) and protein expression (p = 0.0143) induced in the brain of APP/PS1 mice. In contrast, the levels of TXN mRNA (p = 0.0285) and protein (p = 0.0039) in the brain of APP/PS1 mice were increased after the injection of SY5. The ratio of TXN to TXNIP, which was decreased (p = 0.0131) in the brain of APP/PS1 mice, was significantly increased (p = 0.0072) after the injection of SY5. These results suggest that SY5 acts as a prodrug of SY6 in targeting the thioredoxin system and could be a potential therapeutic compound in oxidative stress-related diseases in the brain.
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Lerche, Nicholas W., and Kent G. Osborn. "Simian Retrovirus Infections: Potential Confounding Variables in Primate Toxicology Studies." Toxicologic Pathology 31, no. 1_suppl (January 2003): 103–10. http://dx.doi.org/10.1080/01926230390174977.
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Various species of nonhuman primates are natural hosts for 6 exogenous retroviruses, including gibbon-ape leukemia virus (GaLV), simian sarcoma virus, simian T-lymphotropic virus (STLV), simian immunodeficiency virus (SIV), simian type D retrovirus (SRV), and simian foamy virus (SFV). These viruses establish persistent infections with a broad spectrum of pathogenic potential, ranging from highly pathogenic to nonpathogenic, depending on various host, virus, and environmental factors. Latent or subclinical infections are common, and various procedures associated with experimental protocols may lead to virus reactivation and disease. Adverse effects on toxicologic research by undetected retroviral infections can occur in several ways, including loss of experimental subjects (and statistical power) due to increased morbidity and mortality. In addition, results may be confounded by virus-induced clinical abnormalities, histologic lesions, alteration of physiologic parameters and responses, and interference with in vitro assays and/or destruction of primary cell cultures. Key clinical and epidemiological features of several important retroviruses are reviewed, with emphasis on viruses infecting species of macaques most commonly used as research subjects in primate toxicology studies. Examples of actual and potential confounding of toxicologic studies by retroviruses are discussed, including altered cytokine profiles in healthy STLV carriers, and clinical and pathological abnormalities induced by SRV infection. Adequate prestudy viral screening is critical to exclude retrovirus-infected primates from toxicologic research protocols and prevent potential confounding of research results.
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Ihara, Kenichiro, Hideko Onoda, Masahiro Tanabe, Akihiko Kanki, and Katsuyoshi Ito. "Hemodynamic changes of abdominal organs after CT colonography with transrectal administration of CO2: evaluation with early-phase contrast-enhanced dynamic CT." Japanese Journal of Radiology 39, no. 9 (May 8, 2021): 900–906. http://dx.doi.org/10.1007/s11604-021-01125-5.
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Abstract Purpose To evaluate the hemodynamic changes in the liver, pancreas, gastric mucosa and abdominal vessels in early-phase dynamic contrast-enhanced (DCE) CT immediately after CT colonography (CTC) with carbon dioxide expansion. Materials and methods This study included 82 patients with DCE-CT after CTC (CTC group) and 77 patients without CTC (control group). Contrast enhancement values of the gastric mucosa, liver, pancreas, portal vein (PV), splenic vein (SpV), superior mesenteric vein (SMV), and inferior mesenteric vein (IMV) in early-phase CT were measured. The presence of hepatic pseudolesions were also recorded. Results The mean contrast enhancement values of the gastric mucosa, pancreas and SpV in the CE-CTC group were significantly lower than those in the control group (p < 0.001, p < 0.001, p = 0.014). Conversely, the mean contrast enhancement values of the liver, PV, SMV and IMV in the CE-CTC group were significantly higher than those in the control group (p = 0.003, p = 0.013, p < 0.001, p < 0.001). Hypovascular hepatic pseudolesions were seen in early-phase CT in six patients after CTC, while they were not seen in the control group. Conclusions On DCE-CT performed immediately after CTC with carbon dioxide expansion, it is important to be aware of the imaging findings induced by visceral hemodynamic changes.
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Li, Chunli, Mengqi Ban, Fei Bai, Jianzhao Chen, Xiaoquan Jin, and Yongbo Song. "Anti-Nociceptive and Anti-Inflammation Effect Mechanisms of Mutants of Syb-prII, a Recombinant Neurotoxic Polypeptide." Toxins 11, no. 12 (December 1, 2019): 699. http://dx.doi.org/10.3390/toxins11120699.
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Syb-prII, a recombinant neurotoxic polypeptide, has analgesic effects with medicinal value. Previous experiments indicated that Syb-prII displayed strong analgesic activities. Therefore, a series of in vivo and vitro experiments were designed to investigate the analgesic and anti-inflammatory properties and possible mechanisms of Syb-prII. The results showed that administered Syb-prII-1 and Syb-prII-2 (0.5, 1, 2.0 mg/kg, i.v.) to mice significantly reduced the time of licking, biting, or flicking of paws in two phases in formalin-induced inflammatory nociception. Syb-prII-1 inhibited xylene-induced auricular swelling in a dose-dependent manner. The inhibitory effect of 2.0 mg/kg Syb-prII-1 on the ear swelling model was comparable to that of 200 mg/kg aspirin. In addition, the ELISA and Western blot analysis suggested that Syb-prII-1 and Syb-prII-2 may exert an analgesic effect by inhibiting the expression of Nav1.8 and the phosphorylation of ERK, JNK, and P38. Syb-prII-1 markedly suppressed the expression of IL-1β, IL-6, and TNF-α of mice in formalin-induced inflammatory nociception. We used the patch-clamp technique and investigated the effect of Syb-prII-1 on TTX-resistant sodium channel currents in acutely isolated rat DRG neurons. The results showed that Syb-prII-1 can significantly down regulate TTX-resistant sodium channel currents. In conclusion, Syb-prII mutants may alleviate inflammatory pain by significantly inhibiting the expression of Nav1.8, mediated by the phosphorylation of MAPKs and significant inhibition of TTX-resistant sodium channel currents.
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Sahoo J.K. and Joshi A.G. "Study of effect of various treatments in clinically diagnosed patients of Carpal tunnel syndrome." International Journal of Research in Pharmaceutical Sciences 11, no. 3 (July 6, 2020): 3105–13. http://dx.doi.org/10.26452/ijrps.v11i3.2419.
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Carpal tunnel syndrome is the compression neuropathy in upper extremity. Several researches have been done to see the effect of various treatments separately. But very little research work is available for comparison of treatments. So the study was aimed to study the clinical and electrophysiological findings and their Comparision before and after various treatments. NCS was carried out in 200 CTS patients before and after 6weeks of treatment. Patients were divided into 4 groups. Group I- operative, Group II-medicinal treatment, Group III-exercise, Group IV-medicine+exercise. Clinical and electrophysiological parameters all groups were compared before and after treatment. Group (I), showed significant changes in all parameters except SNAP in operated Rt. Hand as compared to Lt. Hand. Group-II showed significant changes in DML,DML(diff.),DSL,DSL(Diff.)except CMAP,SNAP,&SCV in Rt. Hand but in Lt. hand DML,DML(diff.)DSL showed significant changes where as DSL(Diff.) CMAP,SNAP,&SCV were non-significant. Group-III showed significant changes in DML, DML(diff.),DSL,DSL(Diff.) but SCV,SNAP and CMAP were non-significant in Rt. hand but in Lt. hand only DML(diff.) was significant . Group-IV showed significant changes in all parameters except SCV in Rt. hand but in Lt. hand DML, DML (diff.),DSL, DSL(Diff.) were significant , where as SNAP, CMAP, and SCV were non-significant. It was concluded that maximum improvement was observed in clinical and electrophysiological parameters in operative group, then Medicine + exercise Group, then exercise Group and minimum in Medicinal treatment Group. So operative method is the method of choice for CTS; however the duration of treatment should be more so that further improvements can be seen in all parameters.
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Leach, Karla, Shikui Tang, Jared Sturgeon, Andrew K. Lee, Ryan Grover, Parag Sanghvi, James Urbanic, and Chang Chang. "Beam-Specific Spot Guidance and Optimization for PBS Proton Treatment of Bilateral Head and Neck Cancers." International Journal of Particle Therapy 8, no. 1 (June 1, 2021): 50–61. http://dx.doi.org/10.14338/ijpt-20-00060.1.
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Abstract Purpose A multi-field optimization (MFO) technique that uses beam-specific spot placement volumes (SPVs) and spot avoidance volumes (SAVs) is introduced for bilateral head and neck (H&N) cancers. These beam-specific volumes are used to guide the optimizer to consistently achieve optimal organ-at-risk (OAR) sparing with target coverage and plan robustness. Materials and Methods Implementation of this technique using a 4-beam, 5-beam, and variant 5-beam arrangement is discussed. The generation of beam-specific SPVs and SAVs derived from target and OARs are shown. The SPVs for select fields are further partitioned into optimization volumes for uniform dose distributions that resemble those of single-field optimization (SFO). A conventional MFO plan that does not use beam-specific spot placement guidance (MFOcon) and an MFO plan that uses only beam-specific SPV (MFOspv) are compared with current technique (MFOspv/sav), using both simulated scenarios and forward-calculated plans on weekly verification computed tomography (VFCT) scans. Results Dose distribution characteristics of the 4-beam, 5-beam, and variant 5-beam technique are demonstrated with discussion on OAR sparing. When comparing the MFOcon, MFOspv, and MFOspv/sav, the MFOspv/sav is shown to have superior OAR sparing in 9 of the 14 OARs examined. It also shows clinical plan robustness when evaluated by using both simulated uncertainty scenarios and forward-calculated weekly VFCTs throughout the 7-week treatment course. Conclusion The MFOspv/sav technique is a systematic approach using SPVs and SAVs to guide the optimizer to consistently reach desired OAR dose values and plan robustness.
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Agrawal, Shashi Bhushan, and Deepanshi Jaiswal. "Impact of Light Stress on Plant Based Medicinally Active Compounds." INTERNATIONAL JOURNAL OF PLANT AND ENVIRONMENT 4, no. 02 (July 31, 2018): 50–59. http://dx.doi.org/10.18811/ijpen.v4i02.6.
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Light has several positive and negative impacts on plant growth and physiological processes. Medicinal plants contribute significantly higher proportions of world plant flora and are natural source of rich medicinal compounds. Sufficient literature is available on plant responses to light stress but studies on medicinal plants are limited. This review discusses how different light conditions affect production of plant-based medicinal compounds which are broadly secondary products formed during adverse environmental conditions to cope up the stress. Here, some medicinal plants are reviewed which were exposed to different light conditions including blue light, red light, yellow light, green light, far red light, wavelength specific light treatments, pulsed pre light, specific light intensity, light shade treatments, and supplemental ultraviolet-B radiation. Secondary metabolites considered for the review are anthocyanin, flavonoids, alkaloids, essential oils, cannabinoids and glucosinolates. Most of the results revealed increase in content of medicinal compounds under differentially exposed light conditions with maximum effect under sUV-B exposure. Advancement in the knowledge of medicinal plants response to light stress can help in understanding the mechanism of medicinal compound formation and their regulation which can be further utilized in the production of medicinally active compounds.
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Drouet, Ludovic. "Report of the French Agency for medicines on anticoagulants: national 2014 picture." Sang thrombose vaisseaux 26, no. 5 (September 2014): 225–29. http://dx.doi.org/10.1684/stv.2014.0863.
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Špokienė, Indrė. "Nemokamos medicinos pagalbos teikimo konstitucinės garantijos." Health Policy and Management 1, no. 5 (2013): 15–29. http://dx.doi.org/10.13165/spv-13-1-5-02.
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Utaminingrum, Wahyu, Nofrianti Nofrianti, and Dwi Hartanti. "Ethnomedicinal survey of traditional antidiabetic plants in Baturraden and Sumbang." MEDISAINS 18, no. 2 (August 30, 2020): 43. http://dx.doi.org/10.30595/medisains.v18i2.7169.
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Background: The scientific-based jamu development program enables the development of medicinal plants in the traditional medicine system that eventual-ly can be used in the formal healthcare system. Baturraden and Sumbang are considered as areas with abundant plant biodiversity in Java, where the local community has used those plants for medicinal purposes.Objective: This study is conducted to qualitative and quantitatively record and conserve the knowledge of the Baturraden and Sumbang community on the utilization of plants for treating diabetes mellitus.Method: The data of the plant’s local names, plant organs, methods of prepara-tion, and routes of administration of the herbal preparations used for treating diabetes mellitus were collected through semi-structured interviews with 97 informants. The species use-value (SUV), the relative frequency of citation (RFC), and fidelity level (FL) of each species were calculated accordingly to determine their relative importance and value to the local community.Result: There were 11 plant species from 10 families mentioned. The most commonly used plant organ, preparation method, and administration route were leaves, decoction, and oral, respectively. The most important and valuable plants were including Piper ornatum (SUV = 0.19, RFC = 0.13, FL = 23.09%) and An-drographis paniculata (SUV = 0.09, RFC = 0.07, FL = 42.86%).Conclusion: As the most critical antidiabetic plant in the studied area, the decoction or infusion of Piper ornatum leaves is taken orally 1-2 times a day. However, there are no reports on its anti-diabetic-related activities available to date. In contrast, the uses of Andrographis paniculata as the antidiabetic agent has been widely proven. Baturraden and Sumbang people orally consumed the decoction of this plant’s leaves once a day for the said purpose
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Enzmann, Florian K., Peter Metzger, Julio Ellacuriaga San Martin, Werner Dabernig, Fatema Akhavan, Thomas Hölzenbein, and Patrick Nierlich. "The Upper-Arm Basilic-Cephalic Loop: A Valueable Alternative for Below-Knee Arterial Reconstruction." Vascular and Endovascular Surgery 55, no. 4 (January 22, 2021): 348–54. http://dx.doi.org/10.1177/1538574420980610.
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Introduction: Despite advances of endovascular interventions, bypass surgery remains the gold standard for treatment of long and complex arterial occlusions in the lower limb. Autologous vein is regarded superior to other options. As the graft of first choice, the great saphenous vein (GSV) is often not available due to previous bypass, stripping or poor quality. Other options like arm veins (AV) are important alternatives. As forearm portions of AVs are often unusable, a graft created from the upper arm basilic and cephalic veins provides a valuable alternative. Patients and Methods: We analyzed consecutive patients treated at an academic tertiary referral center between 01/1998 and 07/2018 using arm veins as the main peripheral bypass graft. Study endpoints were primary patency, secondary patency, limb salvage and survival. Results: In the observed time period 2702 bypass procedures were performed at our institution for below-knee arterial reconstructions. Vein grafts used included the ipsilateral GSV (iGSV; n = 1937/71.7%), contralateral GSV (cGSV; 192/7.1%), small saphenous vein (SSV; 133/4.9%), prosthetic conduits (61/2.3%) and different configurations of AV (379/14%). In the majority of patients receiving AV grafts a complete continuous cephalic or basilic vein (CAV) was used (n = 292/77%). If it was not possible to use major parts of these 2 veins, either spliced arm vein grafts (SAV) (42/11%) or an upper arm basilic-cephalic loop graft (45/12%) were used. Median follow-up was 27 (interquartile range: 8-50) months. After 3 years secondary patency (CAV: 85%; SAV: 62%; loop: 66%; p = 0.125) and limb salvage rates (CAV: 79%, SAV: 68%; loop: 79%; p = 0.346) were similar between the 3 bypass options. Conclusion: The encouraging results of alternative AV configurations highlight their value in case the basilic or cephalic veins are not useable in continuity. Especially for infragenual redo-bypass procedures, these techniques should be considered to offer patients durable revascularization options.
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Justickis, Viktoras, Rita Bandzevičienė, Laimutis Paškevičius, and Ina Božokienė. "Gydytojo asmenybė ir gynybinės medicinos priemonių naudojimas." Health Policy and Management 2, no. 7 (2014): 171–90. http://dx.doi.org/10.13165/spv-14-2-7-10.
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Čižmek, Lara, Mojca Bavcon Kralj, Rozelindra Čož-Rakovac, Dmitrii Mazur, Nikolay Ul’yanovskii, Marko Likon, and Polonca Trebše. "Supercritical Carbon Dioxide Extraction of Four Medicinal Mediterranean Plants: Investigation of Chemical Composition and Antioxidant Activity." Molecules 26, no. 18 (September 20, 2021): 5697. http://dx.doi.org/10.3390/molecules26185697.
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With everyday advances in the field of pharmaceuticals, medicinal plants have high priority regarding the introduction of novel synthetic compounds by the usage of environmentally friendly extraction technologies. Herein, a supercritical CO2 extraction method was implemented in the analysis of four plants (chamomile, St. John’s wort, yarrow, and curry plant) after which the non-targeted analysis of the chemical composition, phenolic content, and antioxidant activity was evaluated. The extraction yield was the highest for the chamomile (5%), while moderate yields were obtained for the other three plants. The chemical composition analyzed by gas chromatography-high-resolution mass spectrometry (GC-HRMS) and liquid chromatography-high-resolution mass spectrometry (LC-HRMS) demonstrated extraction of diverse compounds including terpenes and terpenoids, fatty acids, flavonoids and coumarins, functionalized phytosterols, and polyphenols. Voltammetry of microfilm immobilized on a glassy carbon electrode using square-wave voltammetry (SWV) was applied in the analysis of extracts. It was found that antioxidant activity obtained by SWV correlates well to 1,1-diphenyl-2-picrylhidrazine (DPPH) radical assay (R2 = 0.818) and ferric reducing antioxidant power (FRAP) assay (R2 = 0.640), but not to the total phenolic content (R2 = 0.092). Effective results were obtained in terms of activity showing the potential usage of supercritical CO2 extraction to acquire bioactive compounds of interest.
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Yang, Yuangui, Yanli Zhao, Zhitian Zuo, Ji Zhang, Yao Shi, and Yuanzhong Wang. "Investigation of a Medical Plant for Hepatic Diseases with Secoiridoids Using HPLC and FT-IR Spectroscopy for a Case of Gentiana rigescens." Molecules 25, no. 5 (March 9, 2020): 1219. http://dx.doi.org/10.3390/molecules25051219.
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Secoiridoids could be used as a potential new drug for the treatment of hepatic disease. The content of secoiridoids of G. rigescens varied in different geographical origins and parts. In this study, a total of 783 samples collected from different parts of G. rigescens in Yunnan, Sichuan, and Guizhou Provinces. The content of secoiridoids including gentiopicroside, swertiamarin, and sweroside were determined by using HPLC and analyzed by one-way analysis of variance. Two selected variables including direct selected and variable importance in projection combined with partial least squares regression have been used to establish a method for the determination of secoiridoids using FT-IR spectroscopy. In addition, different pretreatments including multiplicative scatter correction (MSC), standard normal variate (SNV), first derivative and second derivative (SD), and orthogonal signal correction (OSC) were compared. The results indicated that the sample (root, stem, and leaf) with total secoiridoids, gentiopicroside, swertiamarin, and sweroside from west Yunnan had higher content than samples from the other regions. The sample from Baoshan had more total secoiridoids than other samples for the whole medicinal plant. The best performance using FT-IR for the total secoiridoid was with the direct selected variable method involving pretreatment of MSC+OSC+SD in the root and stem, while in leaf, of the best method involved using original data with MSC+OSC+SD. This method could be used to determine the bioactive compounds quickly for herbal medicines.
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Park, Heanim, Ji Won Seo, Tae Kyung Lee, Jae Hwan Kim, Jong-Eun Kim, Tae-Gyu Lim, Jung Han Yoon Park, Chul Sung Huh, Hee Yang, and Ki Won Lee. "Ethanol Extract of Yak-Kong Fermented by Lactic Acid Bacteria from a Korean Infant Markedly Reduces Matrix Metallopreteinase-1 Expression Induced by Solar Ultraviolet Irradiation in Human Keratinocytes and a 3D Skin Model." Antioxidants 10, no. 2 (February 15, 2021): 291. http://dx.doi.org/10.3390/antiox10020291.
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Yak-Kong is a type of black soybean that is colloquially referred to as the “medicinal bean” and it elicits several beneficial effects that are relevant to human health, including attenuating the formation of skin wrinkles. It has previously been shown that soybean extracts elicit additional bioactivity that is fermented by lactic acid bacteria. In this study of lactic acid bacteria strains that were isolated from the stools of breast-feeding infants (<100 days old), we selected Bifidobacterium animalis subsp. Lactis LDTM 8102 (LDTM 8102) as the lead strain for the fermentation of Yak-Kong. We investigated the effects of LDTM 8102-fermented Yak-Kong on solar-ultraviolet irradiation (sUV)-induced wrinkle formation. In HaCaT cells, the ethanol extract of LDTM 8102-fermented Yak-Kong (EFY) effectively reduced sUV-induced matrix metalloproteinase-1 (MMP-1) secretion. The effect of EFY was superior to that of unfermented (UFY)- and Lactis KCTC 5854 (another Bifidobacterium animalis species)-fermented Yak-Kong. Additionally, EFY reduced sUV-induced MMP-1 mRNA expression and promoter activity, as well as the transactivation of AP-1 and phosphorylation of ERK1/2 and JNK1/2. Furthermore, EFY alleviated sUV-induced MMP-1 secretion, the destruction of the epidermis, and degradation of collagen in a three-dimensional (3D) skin culture model. EFY had a higher total polyphenol content and anti-oxidative activity than UFY. Twelve metabolites were significantly (≥2-fold) increased in Yak-Kong extract after fermentation by LDTM 8102. Among them, the metabolites of major isoflavones, such as 6,7,4′-trihydroxyisoflavone (THIF), exerted the reducing effect of MMP-1, which indicated that the isoflavone metabolites contributed to the effect of EFY on MMP-1 expression as active compounds. These findings suggest that EFY is a potent natural material that can potentially prevent sUV-induced wrinkle formation.
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Gilienė, Renata. "Klasterių politika Lietuvoje. Medicinos įmonių ir įstaigų klasterizacija." Health Policy and Management 1, no. 6 (2014): 39–54. http://dx.doi.org/10.13165/spv-14-1-6-03.
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TAŞLI, Hüseyin, and İ. Hakkı BAHAR. "Determination of SHV-2, SHV-5, SHV-12 and CTX-M-3 Extended-Spectrum Beta-Lactamases in Clinical Enterobacteriaceae Isolates: Scientific Letter." Turkiye Klinikleri Journal of Medical Sciences 30, no. 5 (2010): 1701–6. http://dx.doi.org/10.5336/medsci.2009-15118.
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Stovba, L. F., V. T. Krotkov, D. I. Paveli’ev, S. A. Mel’nikov, V. N. Lebedev, and S. V. Borisevich. "Analysis and Prospects of Using Recombinant Vaccinia Virus MVA Strain as a Vector in the Development of the Vaccines against Human and Simian Immunodeficiency Virus Diseases." Problems of Particularly Dangerous Infections, no. 2 (July 3, 2019): 37–44. http://dx.doi.org/10.21055/0370-1069-2019-2-37-44.
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The review presents the results of preclinical use of vector vaccines against human immunodeficiency virus (HIV) disease and simian immunodeficiency virus (SIV) disease. Application of antiretroviral therapy exclusively is insufficient for elimination of HIV from patient’s body. This dictates the need for an effective vaccine which will reduce the number of new cases of the disease and reduce the risk of virus transmission. Current practice of medicinal product development showed the effectiveness of heterologous prime-boost regimens for the induction of expressed immune response in laboratory animals. Various vector constructs were used as priming vaccines: DNA vaccines, Bacille Calmette-Guerin vaccine, chimpanzee adenovirus, vesicular stomatitis virus, alphavirus repli-clone. Booster vaccine was represented by recombinant MVA strain. In all vector vaccines, different genes of immunodominant antigens of HIV and SIV agents were inserted. On rhesus macaques, murine, rabbit models, it was demonstrated that deployed vaccination schemes were safe and induced immune response. Because membrane HIV protein is highly variable, strongly glycoziled and subjected to structural changes during receptor binding, it cannot be viewed as a target for induction of virus neutralized antibodies. Therefore, we mainly studied the cell immune response that was presented by poly-functional CD8+ T-cells. However, some recent researches are aimed at such modification of envelope HIV immunogene that would provide for virus neutralizing antibody induction. The study of protective efficiency of the induced immunity in rhesus macaques, immunized with recombinant vectors expressing SIV’ s immunodominant antigens, in case of subsequent inoculation with virulent SIV strain has revealed that all monkeys developed illness. Assuming that the constructions with SIV’ s immunodominant antigens under protective efficiency testing on rhesus macaques imitate AIDS in humans, it seems that vaccines, developed up-to-date, will not be effective for collective immunity formation against AIDS. Therefore, the search for novel combinations of expressed immunodominant antigens for the inclusion into the composition of priming and booster vaccines remains a priority area at present time.
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Hansen, Scott G., Emily E. Marshall, Daniel Malouli, Abigail B. Ventura, Colette M. Hughes, Emily Ainslie, Julia C. Ford, et al. "A live-attenuated RhCMV/SIV vaccine shows long-term efficacy against heterologous SIV challenge." Science Translational Medicine 11, no. 501 (July 17, 2019): eaaw2607. http://dx.doi.org/10.1126/scitranslmed.aaw2607.
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Previous studies have established that strain 68-1–derived rhesus cytomegalovirus (RhCMV) vectors expressing simian immunodeficiency virus (SIV) proteins (RhCMV/SIV) are able to elicit and maintain cellular immune responses that provide protection against mucosal challenge of highly pathogenic SIV in rhesus monkeys (RMs). However, these efficacious RhCMV/SIV vectors were replication and spread competent and therefore have the potential to cause disease in immunocompromised subjects. To develop a safer CMV-based vaccine for clinical use, we attenuated 68-1 RhCMV/SIV vectors by deletion of the Rh110 gene encoding the pp71 tegument protein (ΔRh110), allowing for suppression of lytic gene expression. ΔRh110 RhCMV/SIV vectors are highly spread deficient in vivo (~1000-fold compared to the parent vector) yet are still able to superinfect RhCMV+ RMs and generate high-frequency effector-memory–biased T cell responses. Here, we demonstrate that ΔRh110 68-1 RhCMV/SIV–expressing homologous or heterologous SIV antigens are highly efficacious against intravaginal (IVag) SIVmac239 challenge, providing control and progressive clearance of SIV infection in 59% of vaccinated RMs. Moreover, among 12 ΔRh110 RhCMV/SIV–vaccinated RMs that controlled and progressively cleared an initial SIV challenge, 9 were able to stringently control a second SIV challenge ~3 years after last vaccination, demonstrating the durability of this vaccine. Thus, ΔRh110 RhCMV/SIV vectors have a safety and efficacy profile that warrants adaptation and clinical evaluation of corresponding HCMV vectors as a prophylactic HIV/AIDS vaccine.
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LAI, Hsien Yong, Cheryl C. H. YANG, Fan-Yen HUANG, Yi LEE, Yu Ling KUO, and Terry B. J. KUO. "Respiratory-related arterial pressure variability as an indicator of graded blood loss: involvement of the autonomic nervous system." Clinical Science 105, no. 4 (October 1, 2003): 491–97. http://dx.doi.org/10.1042/cs20030080.
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During positive pressure mechanical ventilation, percentile systolic pressure variation (%SPV) or respiratory-related arterial pressure variability (RAPV) have both been used in assessment of graded haemorrhage. We aimed to investigate whether changes in %SPV and RAPV are correlated during graded haemorrhage (by 5, 10 or 20% of the estimated blood volume) in anaesthetized positive pressure ventilated rats and to investigate the involvement of autonomic regulation. Saline vehicle or atropine produced no discernible effect on baseline %SPV or RAPV but, thereafter, %SPV and RAPV increased progressively with graded haemorrhage. Propranolol significantly decreased baseline %SPV and RAPV and changes induced in %SPV and RAPV by graded haemorrhage. Phentolamine significantly enhanced baseline %SPV and RAPV, and further enhancement of %SPV and RAPV by graded haemorrhage did not occur until 20% of the estimated blood volume was removed. RAPV was significantly correlated with %SPV in all experimental groups. We conclude that RAPV is comparable with%SPV as an indicator of graded haemorrhage and that, in anaesthetized and positive pressure ventilated rats, both are dependent on autonomic function, especially β-adrenoceptors.
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Eggenberger, A. L., M. R. Hajimorad, and J. H. Hill. "Gain of Virulence on Rsv1-Genotype Soybean by an Avirulent Soybean mosaic virus Requires Concurrent Mutations in Both P3 and HC-Pro." Molecular Plant-Microbe Interactions® 21, no. 7 (July 2008): 931–36. http://dx.doi.org/10.1094/mpmi-21-7-0931.
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In soybean, Rsv1, a single dominant resistance gene, invokes extreme resistance (ER) against most Soybean mosaic virus (SMV) strains, including SMV-N, but not SMV-G7, which provokes a virulent lethal systemic hypersensitive response (LSHR). The elicitor functions of the two viruses provoking Rsv1-mediated ER and LSHR have been mapped to the N-terminal 271 amino acids of P3 from SMV-N and SMV-G7, respectively, which differ by nine residues between the two strains. To identify amino acids of P3 from SMV-N provoking Rsv1-mediated ER, the unique residues of SMV-G7 were substituted with those of SMV-N. Of the mutants tested on Rsv1-genotype soybean, only SMV-G7I788R and SMV-G7T948A lost virulence. However, substitution of amino acids of SMV-N, individually or in combination, with the reciprocal residues from SMV-G7 at these two positions failed to confer virulence to SMV-N. In the search for additional virulence determinants, a series of SMV-N chimeras was generated in which fragments within a region from near the middle of the helper-component proteinase (HC-Pro) cistron to the 5′ end of the cytoplasmic inclusion cistron, nucleotides 1,605 to 3,787, were replaced with those of SMV-G7. Only SMV-N-derived chimeras harboring the 3′ region of HC-Pro, at least from nucleotide 2,013, and the entire 5′ end of P3 (nucleotides 2,430 to 3,237) from SMV-G7 were virulent whereas reciprocal exchanges resulted in loss of SMV-G7 virulence. This region of HC-Pro differs by three amino acids between SMV-N and SMV-G7. Analyses of SMV-G7-derived HC-Pro site-directed mutants showed that only SMV-G7M683R lost virulence on Rsv1-genotype soybean; however, SMV-NR682M failed to gain virulence. Nevertheless, an SMV-N derived mutant with three concurrent substitutions, R682M+R787I+A947T, gained virulence. The data indicate that both P3 and HC-Pro are involved in virulence of SMV on Rsv1-genotype soybean.
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Hajimorad, M. R., A. L. Eggenberger, and J. H. Hill. "Adaptation of Soybean mosaic virus Avirulent Chimeras Containing P3 Sequences from Virulent Strains to Rsv1-Genotype Soybeans Is Mediated by Mutations in HC-Pro." Molecular Plant-Microbe Interactions® 21, no. 7 (July 2008): 937–46. http://dx.doi.org/10.1094/mpmi-21-7-0937.
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In Rsv1-genotype soybean, Soybean mosaic virus (SMV)-N (an avirulent isolate of strain G2) elicits extreme resistance (ER) whereas strain SMV-G7 provokes a lethal systemic hypersensitive response (LSHR). SMV-G7d, an experimentally evolved variant of SMV-G7, induces systemic mosaic. Thus, for Rsv1-genotype soybean, SMV-N is avirulent whereas SMV-G7 and SMV-G7d are both virulent. Exploiting these differential interactions, we recently mapped the elicitor functions of SMV provoking Rsv1-mediated ER and LSHR to the N-terminal 271 amino acids of P3 from SMV-N and SMV-G7, respectively. The phenotype of both SMV-G7 and SMV-G7d were rendered avirulent on Rsv1-genotype soybean when the part of the genome encoding the N-terminus or the entire P3 cistron was replaced with that from SMV-N; however, reciprocal exchanges did not confer virulence to SMV-N-derived P3 chimeras. Here, we describe virulent SMV-N-derived P3 chimeras containing the full-length or the N-terminal P3 from SMV-G7 or SMV-G7d, with or without additional mutations in P3, that were selected on Rsv1-genotype soybean by sequential transfers on rsv1 and Rsv1-genotype soybean. Sequence analyses of the P3 and helper-component proteinase (HC-Pro) cistrons of progeny recovered from Rsv1-genotype soybean consistently revealed the presence of mutations in HC-Pro. Interestingly, the precise mutations in HC-Pro required for the adaptation varied among the chimeras. No mutation was detected in the HC-Pro of progeny passaged continuously in rsv1-genotype soybean, suggesting that selection is a consequence of pressure imposed by Rsv1. Mutations in HC-Pro alone failed to confer virulence to SMV-N; however, reconstruction of mutations in HC-Pro of the SMV-N-derived P3 chimeras resulted in virulence. Taken together, the data suggest that HC-Pro complementation of P3 is essential for SMV virulence on Rsv1-genotype soybean.
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Davies, Peers, and Janet Daly. "SBV transmission." Veterinary Record 172, no. 19 (May 10, 2013): 509–10. http://dx.doi.org/10.1136/vr.f2958.
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Lazutka, Justas, Aurelija Zvirbliene, Indre Dalgediene, Rasa Petraityte-Burneikiene, Aliona Spakova, Vilimas Sereika, Raimundas Lelesius, Kerstin Wernike, Martin Beer, and Kestutis Sasnauskas. "Generation of Recombinant Schmallenberg Virus Nucleocapsid Protein in Yeast and Development of Virus-Specific Monoclonal Antibodies." Journal of Immunology Research 2014 (2014): 1–8. http://dx.doi.org/10.1155/2014/160316.
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Schmallenberg virus (SBV), discovered in continental Europe in late 2011, causes mild clinical signs in adult ruminants, including diarrhoea and reduced milk yield. However, fetal infection can lead to severe malformation in newborn offspring. To develop improved reagents for SBV serology, a high-level yeast expression system was employed to produce recombinant SBV nucleocapsid (N) protein. Recombinant SBV N protein was investigated as an antigen in SBV-specific IgG enzyme immunoassay and used for generation of monoclonal antibodies (MAbs). Yeast-expressed SBV N protein was reactive with anti-SBV IgG-positive cow serum specimens collected from different farms of Lithuania. After immunization of mice with recombinant SBV N protein, four MAbs were generated. The MAbs raised against recombinant SBV N protein reacted with native viral nucleocapsids in SBV-infected BHK cells by immunofluorescence assay. The reactivity of recombinant N protein with SBV-positive cow serum specimens and the ability of the MAbs to recognize virus-infected cells confirm the antigenic similarity between yeast-expressed SBV N protein and native viral nucleocapsids. Our study demonstrates that yeast expression system is suitable for high-level production of recombinant SBV N protein and provides the first evidence on the presence of SBV-specific antibodies in cow serum specimens collected in Lithuania.
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Southwell, Rebecca Marie, Kenneth Sherlock, and Matthew Baylis. "Cross-sectional study of British wild deer for evidence of Schmallenberg virus infection." Veterinary Record 187, no. 8 (May 23, 2020): e64-e64. http://dx.doi.org/10.1136/vr.105869.
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BackgroundSchmallenberg virus (SBV) is an orthobunyavirus, carried by Culicoides biting midges, that causes reproductive problems in adult ruminants when infected during their gestation period. SBV was first detected in ruminants in the UK in 2011/2012 and then again in 2016. The reason behind the 2016 re-emergence of SBV is unknown, but one possibility is that it can be maintained in wildlife, such as deer. SBV has been detected at high seroprevalence in deer in a number of European countries, but only once in the UK in a single region.MethodsThe purpose of this study was to survey wild deer across Great Britain for recent evidence of SBV. Deer hunters were recruited for the purpose of providing postmortem blood samples to be tested for SBV antibodies.ResultsThe seroprevalence of SBV in the British wild deer population was 13.8 per cent; found in red, roe, muntjac and fallow deer species, with more in deer further south.ConclusionThese results support the growing concern that SBV is now endemic in Great Britain and highlight the need to know the role of wildlife in SBV transmission.
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Qureshi, M. I., T. R. A. Lane, H. M. Moore, I. J. Franklin, and A. H. Davies. "Patterns of short saphenous vein incompetence." Phlebology: The Journal of Venous Disease 28, no. 1_suppl (March 2013): 47–50. http://dx.doi.org/10.1177/0268355513477064.
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The significance of short saphenous vein (SSV) reflux is an under-explored territory in chronic venous disease (CVD). We have examined the origin and significance of SSV reflux in primary and secondary CVD. While the natural history of SSV incompetence remains uncertain, its prevalence has been shown to approximate 3.5%, rising with progressing clinical venous insufficiency, and bears an association with lateral malleolar venous ulceration. The most common pattern of reflux extends throughout the SSV Patterns of incompetence in recurrent disease are highly variable, but SSV reflux may itself pose a risk for recurrence, in part due to the complex anatomy of the saphenopopliteal system. Further studies are required to delineate the impact of SSV reflux in secondary venous disease and deep venous incompetence.
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Stokes, Jessica Eleanor, Rachael Eugenie Tarlinton, Fiona Lovatt, Matthew Baylis, Amanda Carson, and Jennifer Sarah Duncan. "Survey to determine the farm-level impact of Schmallenberg virus during the 2016–2017 United Kingdom lambing season." Veterinary Record 183, no. 22 (September 26, 2018): 690. http://dx.doi.org/10.1136/vr.104866.
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Schmallenberg virus (SBV) causes abortions, stillbirths and fetal malformations in naïve ruminants. The impact of the initial outbreak (2011/2012) on British sheep farms has been previously investigated, with higher farmer perceived impacts and increased lamb and ewe mortality reported on SBV-affected farms. After several years of low, or no, circulation the UK sheep flock once again became vulnerable to SBV infection. Re-emergence was confirmed in autumn 2016. This study reports the analysis of a questionnaire designed to determine the farm-level impact of SBV on the 2016/2017 UK lambing period. Higher neonatal lamb mortality, dystocia and associated ewe deaths, and higher perceived impacts on sheep welfare, flock financial performance and farmer emotional wellness were reported on SBV confirmed (n=59) and SBV suspected (n=82), than SBV not suspected (n=74) farms. Additionally, although few farmers (20.4 per cent) reported previously vaccinating against SBV, the majority (78.3 per cent) stated they would vaccinate if purchasing at less than £1 per dose. These results are largely comparable to the findings reported for the 2011/2012 outbreak, highlighting the ongoing impact of SBV on sheep farms. If SBV continues to re-emerge cyclically, the economic and animal welfare costs to the UK sheep farming industry will continue.
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Wang, Yidong, Pengfei Lu, Liping Jiang, Bingruo Wu, and Bin Zhou. "Control of sinus venous valve and sinoatrial node development by endocardial NOTCH1." Cardiovascular Research 116, no. 8 (October 7, 2019): 1473–86. http://dx.doi.org/10.1093/cvr/cvz249.
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Abstract Aims Sinus venous valve (SVV) and sinoatrial node (SAN) develop together at the sinoatrial junction during embryogenesis. SVV ensures unidirectional cardiac input and SAN generates sinus rhythmic contraction, respectively; both functions are essential for embryonic survival. We aim to reveal the potential role of endocardial NOTCH signalling in SVV and SAN formation. Methods and results We specifically deleted Notch1 in the endocardium using an Nfatc1Cre line. This deletion resulted in underdeveloped SVV and SAN, associated with reduced expression of T-box transcription factors, Tbx5 andTbx18, which are essential for the formation of SVV and SAN. The deletion also led to decreased expression of Wnt2 in myocardium of SVV and SAN. WNT2 treatment was able to rescue the growth defect of SVV and SAN resulted from the Notch1 deletion in whole embryo cultures. Furthermore, the Notch1 deletion reduced the expression of Nrg1 in the SVV myocardium and supplement of NRG1 restored the growth of SVV in cultured Notch1 knockout embryos. Conclusion Our findings support that endocardial NOTCH1 controls the development of SVV and SAN by coordinating myocardial WNT and NRG1 signalling functions.
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Neuhardt, Diana L., Sergio X. Salles–Cunha, and Nick Morrison. "Prevalence and Patterns of Small Saphenous Vein Reflux." Journal for Vascular Ultrasound 33, no. 1 (March 2009): 19–22. http://dx.doi.org/10.1177/154431670903300104.
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Objective The small saphenous vein (SSV) often is a forgotten source of venous valvular insufficiency signs and symptoms or is a “victim” of unwillingness to treat. Either way, ultrasound (US) frequently focuses on the great saphenous vein without an equivalent thorough evaluation of the SSV. We investigated the prevalence and patterns of SSV reflux during a voluntary service to the community of Santiago de Guayaquil in Ecuador. Methods Patients were screened for SSV reflux while standing. A portable laptop scanner was used to examine the SSV at the proximal, mid, and distal calf (positions A, B, and C) in 410 legs of 205 subjects. Although all patients were C1 – C6 according to the clinical CEAP (i.e., clinical severity, etiology or cause, anatomy, and pathophysiology) classification, 14% of the legs were C0. Forward and reverse flows were noted after a variety of manual compressions. Only severe reflux lasting longer than 4 seconds is reported herein. Results The prevalence of SSV abnormalities was 17% (69/410). Reflux was noted in 54 (13%) of the extremities whereas in 15 (4%), the SSV did not have reflux but was intertwined with the pathways of varicose veins. The diameters of the refluxing veins were related to the location and extent of reflux. The most common pattern was reflux in the A, B, and C positions (n = 17) of SSV averaging 4.6 (A) to 4.4 mm (C) in diameter. Reflux was noted in the AB, A, and B positions in 10, 11, and 12 SSV, respectively; diameters of these veins averaged 4.1 (A) to 3.7 mm (B), 4.1 mm (A), and 3.4 mm (B). SSV reflux in the B and C and C only positions were least common (n = 4), noted in veins averaging 2.5 mm in diameter. Varicose veins interconnected with short SSV segments were noted in all three positions (A, B, and C) in seven legs whereas in eight legs the varicosities were segmental, most commonly in the B position (n = 6). Conclusions The prevalence of SSV abnormalities was significant. SSV reflux or connection to varicose veins was noted in close to one of five legs. The SSV should be evaluated at least at the proximal and mid calf to avoid missing significant reflux.
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Carradice, D., N. Samuel, T. Wallace, F. A. K. Mazari, J. Hatfield, and I. Chetter. "Comparing the treatment response of great saphenous and small saphenous vein incompetence following surgery and endovenous laser ablation: a retrospective cohort study." Phlebology: The Journal of Venous Disease 27, no. 3 (August 3, 2011): 128–34. http://dx.doi.org/10.1258/phleb.2011.011014.
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Objective Many venous trials mix patients with great saphenous vein (GSV) and small saphenous vein (SSV) diseases. There is no evidence that both respond similarly to treatment and our aim was to test this assumption. Method This cohort study compares patients with isolated GSV and SSV incompetence following treatment with open surgical ligation or endovenous laser ablation (EVLA). Outcomes included: quality of life (QoL; Aberdeen Varicose Vein Questionnaire [AVVQ]; Short Form 36 [SF36]; Euroqol [EQ5D]; and Venous Clinical Severity Score [VCSS]). Results A total of 370 patients with no differences in baseline QoL, underwent treatment. Despite equivalent morbidity, SSV sufferers had a lower VCSS ( P < 0.001). Following surgery, SSV patients scored higher (worse) on AVVQ ( P = 0.045) than GSV sufferers, but lower (better) following EVLA ( P = 0.042). Conclusion The morbidity associated with SSV incompetence is greater than suggested by its clinical severity and responds differently following treatment to that of the GSV. Trials should consider patients with GSV and SSV reflux separately. EVLA may offer additional benefits to SSV sufferers.
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Han, Pingping, Andrew Lai, Carlos Salomon, and Sašo Ivanovski. "Detection of Salivary Small Extracellular Vesicles Associated Inflammatory Cytokines Gene Methylation in Gingivitis." International Journal of Molecular Sciences 21, no. 15 (July 24, 2020): 5273. http://dx.doi.org/10.3390/ijms21155273.
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Salivary small extracellular vesicles (sEV) are emerging as a potential liquid biopsy for oral diseases. However, technical difficulties for salivary sEV isolation remain a challenge. Twelve participants (five periodontally healthy, seven gingivitis patients) were recruited and salivary sEV were isolated by ultracentrifuge (UC-sEV) and size exclusion chromatography (SEC-sEV). The effect of UC and SEC on sEV yield, DNA methylation of five cytokine gene promoters (interleukin (IL)−6, tumor necrosis factor (TNF)-α, IL−1β, IL−8, and IL−10), and functional uptake by human primary gingival fibroblasts (hGFs) was investigated. The results demonstrated that SEC-sEV had a higher yield of particles and particle/protein ratios compared to UC-sEV, with a minimal effect on the detection of DNA methylation of five cytokine genes and functional uptake in hGFs (n = 3). Comparing salivary sEV characteristics between gingivitis and healthy patients, gingivitis-UC-sEV were increased compared to the healthy group; while no differences were found in sEV size, oral bacterial gDNA, and DNA methylation for five cytokine gene promoters, for both UC-sEV and SEC-sEV. Overall, the data indicate that SEC results in a higher yield of salivary sEV, with no significant differences in sEV DNA epigenetics, compared to UC.
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Pluymaekers, Nikki AHA, Astrid NL Hermans, Dominik K. Linz, Elton AMP Dudink, Justin GLM Luermans, Bob Weijs, Kevin Vernooy, and Harry JGM Crijns. "Frequency and Determinants of Spontaneous Conversion to Sinus Rhythm in Patients Presenting to the Emergency Department with Recent-onset Atrial Fibrillation: A Systematic Review." Arrhythmia & Electrophysiology Review 9, no. 4 (December 24, 2020): 195–201. http://dx.doi.org/10.15420/aer.2020.34.
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The exact frequency and clinical determinants of spontaneous conversion (SCV) in patients with symptomatic recent-onset AF are unclear. The aim of this systematic review is to provide an overview of the frequency and determinants of SCV of AF in patients presenting at the emergency department. A comprehensive literature search for studies about SCV in patients presenting to the emergency department with AF resulted in 25 articles – 12 randomised controlled trials and 13 observational studies. SCV rates range between 9–83% and determinants of SCV also varied between studies. The most important determinants of SCV included short duration of AF (<24 or <48 hours), low number of episodes, normal atrial dimensions and absence of previous heart disease. The large variation in SCV rate and determinants of SCV was related to differences in duration of the observation period, inclusion and exclusion criteria and in variables used in the prediction models.
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Abdul, Khaja S. M., Neha Faiz, Aleksandar Jovanović, and Wen Tan. "Isosteviol Protects H9c2 Cells Against Hypoxia-reoxygenation by Activating ERK1/2." Cardiovascular & Hematological Disorders-Drug Targets 21, no. 1 (August 20, 2021): 73–77. http://dx.doi.org/10.2174/1871529x21666210216122022.
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Aims: In the present study, we have investigated the cardioprotective properties of Isosteviol (STV) under conditions of hypoxia-reoxygenation and elucidated the underlying mechanism. Background: In our previous studies, we have determined that STV exhibits neuro- and cardio-protective properties. However, the mechanism underlying STV-induced cardioprotection has not yet been fully understood. Methods: All experiments were performed on rat heart embryonic H9c2 cell line. To induce hypoxia- reoxygenation, cells were exposed to 1% oxygen (in no glucose and no sodium pyruvate DMEM) following by reoxygenation (using fully supplemented MEM). Cells viability was tested by MTT assay, and protein levels were compared by Western blotting. Results: Treatment of heart embryonic H9c2 cells with STV (10 μM) significantly increased the survival of cells exposed to hypoxia-reoxygenation. STV (10 μM) activated ERK1/2 and DRP1 in hypoxia-reoxygenation, but did not have any effects on ERK1/2 or DRP1 in normoxia. STV (10 μM) did not regulate CAMKII, AKT or AMPK signaling pathways. Conclusions: Taken all together, our findings demonstrate that 1) STV protects H9c2 cells against hypoxia-reoxygenation and that 2) this effect is mediated via ERK1/2. The property of STV that selectively activates ERK1/2 in cells exposed to stress, but not in cells under non-stress conditions, makes this compound a promising candidate-drug for therapy against myocardial ischemia-reperfusion in clinical practice.
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Nabzdyk, Christoph S., Hope Lancero, Khanh P. Nguyen, Sherveen Salek, and Michael S. Conte. "RNA interference-mediated survivin gene knockdown induces growth arrest and reduced migration of vascular smooth muscle cells." American Journal of Physiology-Heart and Circulatory Physiology 301, no. 5 (November 2011): H1841—H1849. http://dx.doi.org/10.1152/ajpheart.00089.2011.
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Survivin (SVV) is a multifunctional protein that has been implicated in the development of neointimal hyperplasia. Nuclear SVV is essential for mitosis, whereas in mitochondria SVV has a cytoprotective function. Here, we investigated the effects of RNA interference (RNAi)-mediated SVV knockdown on cell cycle kinetics, apoptosis, migration, and gene expression in primary cultured vascular smooth muscle cells (VSMCs) from the human saphenous vein. Primary Human VSMCs were obtained from saphenous veins and cultured under standard conditions. SVV knockdown was achieved by either small interfering RNA or lentiviral transduction of short hairpin RNA, reducing SVV gene expression by quantitative PCR (>75%, P < 0.01) without a loss of cell viability. Subcellular fractionation revealed that RNAi treatment effectively targeted the nuclear SVV pool, whereas the larger mitochondrial pool was much less sensitive to transient knockdown. Both p53 and p27 protein levels were notably increased. SVV RNAi treatment significantly blocked VSMC proliferation in response to serum and PDGF-AB, arresting VSMC growth. Cell cycle analysis revealed an increased G2/M fraction consistent with a mitotic defect; 4′,6-diamidino-2-phenylindole staining confirmed an increased frequency of polyploid and abnormal nuclei. In a transwell assay, SVV knockdown reduced migration to PDGF-AB, and actin-phalloidin staining revealed disorganized actin filaments and polygonal cell shape. However, apoptosis (DNA content and annexin V flow cytometry) was not directly induced by SVV RNAi, and sensitivity to apoptotic agonists (e.g., staurosporine and cytokines) was unchanged. In conclusion, RNAi-mediated SVV knockdown in VSMCs leads to profound cell cycle arrest at G2/M and impaired chemotaxis without cytotoxicity. The regulation of mitosis and apoptosis in VSMC involves differentially regulated subcellular pools of SVV. Thus, treatment of VSMC with RNAi targeting SVV might limit the response to vascular injury without destabilizing the vessel wall.
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Kim, S.-Y., E.-A. Park, Y.-C. Shin, S.-I. Min, W. Lee, J. Ha, S. J. Kim, and S.-K. Min. "Preoperative determination of anatomic variations of the small saphenous vein for varicose vein surgery by three-dimensional computed tomography venography." Phlebology: The Journal of Venous Disease 27, no. 5 (October 28, 2011): 235–41. http://dx.doi.org/10.1258/phleb.2011.011023.
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Objective To define the anatomical variations of small saphenous vein (SSV) for varicose vein (VV) surgery by three-dimensional computed tomography venography (3D-CTV) and to analyse the impact of this preoperative evaluation on surgical outcomes. Methods A total of 120 consecutive limbs with SSV insufficiency having undergone VV surgery from January 2005 until December 2007 were enrolled. The medical records and images were analysed retrospectively. Results The relationship between SSV and gastrocnemial vein (GNV) were categorized into two: (a) SSV and GNV drained to popliteal vein (PV) separately (100 limbs, 87%) and (b) SSV and GNV made common channel which drained to PV (15 limbs, 13%). Saphenopopliteal junction morphology was normal (75 limbs), severe tortuosity near PV (19 limbs), ampullary ectasia (4 limbs) and duplicated drainage to PV (2 limbs). No recurrence of VV was noted. Conclusions CTV can provide thorough preoperative anatomic information of the SSV variations and reduce the recurrence of VV.
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Surov, Alexey, Hans Jonas Meyer, and Andreas Wienke. "Standardized Uptake Values Derived from18F-FDG PET May Predict Lung Cancer Microvessel Density and Expression of KI 67, VEGF, and HIF-1αbut Not Expression of Cyclin D1, PCNA, EGFR, PD L1, and p53." Contrast Media & Molecular Imaging 2018 (June 6, 2018): 1–10. http://dx.doi.org/10.1155/2018/9257929.
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Background. Our purpose was to provide data regarding relationships between18F-FDG PET and histopathological parameters in lung cancer.Methods. MEDLINE library was screened for associations between PET parameters and histopathological features in lung cancer up to December 2017. Only papers containing correlation coefficients between PET parameters and histopathological findings were acquired for the analysis. Overall, 40 publications were identified.Results. Associations between SUV and KI 67 were reported in 23 studies (1362 patients). The pooled correlation coefficient was 0.44. In 2 studies (180 patients), relationships between SUV and expression of cyclin D1 were analyzed (pooled correlation coefficient = 0.05). Correlation between SUV and HIF-1αwas investigated in 3 studies (288 patients), and the pooled correlation coefficient was 0.42. In 5 studies (310 patients), associations between SUV and MVD were investigated (pooled correlation coefficient = 0.54). In 6 studies (305 patients), relationships between SUV and p53 were analyzed (pooled correlation coefficient = 0.30). In 6 studies (415 patients), associations between SUV and VEGF expression were investigated (pooled correlation coefficient = 0.44). In 5 studies (202 patients), associations between SUV and PCNA were investigated (pooled correlation coefficient = 0.32). In 3 studies (718 patients), associations between SUV and expression of PD L1 were analyzed (pooled correlation coefficient = 0.36). Finally, in 5 studies (409 patients), associations between SUV and EGFR were investigated (pooled correlation coefficient = 0.38).Conclusion. SUV may predict microvessel density and expression of VEGF, KI 67, and HIF-1αin lung cancer.
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Wen, R. H., B. Khatabi, T. Ashfield, M. A. Saghai Maroof, and M. R. Hajimorad. "The HC-Pro and P3 Cistrons of an Avirulent Soybean mosaic virus Are Recognized by Different Resistance Genes at the Complex Rsv1 Locus." Molecular Plant-Microbe Interactions® 26, no. 2 (February 2013): 203–15. http://dx.doi.org/10.1094/mpmi-06-12-0156-r.
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The complex Rsv1 locus in soybean plant introduction (PI) ‘PI96983’ confers extreme resistance (ER) against Soybean mosaic virus (SMV) strain N but not SMV-G7 and SMV-G7d. Both the SMV helper-component proteinase (HC-Pro) and P3 cistrons can serve as avirulence factors recognized by Rsv1. To understand the genetics underlying recognition of the two cistrons, we have utilized two soybean lines (L800 and L943) derived from crosses between PI96983 (Rsv1) and Lee68 (rsv1) with distinct recombination events within the Rsv1 locus. L800 contains a single PI96983-derived member (3gG2) of an Rsv1-associated subfamily of nucleotide-binding leucine-rich repeat (NB-LRR) genes. In contrast, although L943 lacks 3gG2, it contains a suite of five other NB-LRR genes belonging to the same family. L800 confers ER against SMV-N whereas L943 allows limited replication at the inoculation site. SMV-N-derived chimeras containing HC-Pro from SMV-G7 or SMV-G7d gained virulence on L943 but not on L800 whereas those with P3 replacement gained virulence on L800 but not on L943. In reciprocal experiments, SMV-G7- and SMV-G7d-derived chimeras with HC-Pro replacement from SMV-N lost virulence on L943 but retained virulence on L800 whereas those with P3 replacement lost virulence on L800 while remaining virulent on L943. These data demonstrate that distinct resistance genes at the Rsv1 locus, likely belonging to the NB-LRR class, mediate recognition of HC-Pro and P3.
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Gao, Xiao-Fei, Zhi-Mei Wang, Ai-Qun Chen, Feng Wang, Shuai Luo, Yue Gu, Xiang-Quan Kong, et al. "Plasma Small Extracellular Vesicle-Carried miRNA-501-5p Promotes Vascular Smooth Muscle Cell Phenotypic Modulation-Mediated In-Stent Restenosis." Oxidative Medicine and Cellular Longevity 2021 (April 21, 2021): 1–20. http://dx.doi.org/10.1155/2021/6644970.
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Vascular smooth muscle cell (VSMC) phenotypic modulation plays an important role in the occurrence and development of in-stent restenosis (ISR), the underlying mechanism of which remains a key issue needing to be urgently addressed. This study is designed to investigate the role of plasma small extracellular vesicles (sEV) in VSMC phenotypic modulation. sEV were isolated from the plasma of patients with ISR (ISR-sEV) or not (Ctl-sEV) 1 year after coronary stent implantation using differential ultracentrifugation. Plasma sEV in ISR patients are elevated markedly and decrease the expression of VSMC contractile markers α-SMA and calponin and increase VSMC proliferation. miRNA sequencing and qRT-PCR validation identified that miRNA-501-5p was the highest expressed miRNA in the plasma ISR-sEV compared with Ctl-sEV. Then, we found that sEV-carried miRNA-501-5p level was significantly higher in ISR patients, and the level of plasma sEV-carried miRNA-501-5p linearly correlated with the degree of restenosis ( R 2 = 0.62 ). Moreover, miRNA-501-5p inhibition significantly increased the expression of VSMC contractile markers α-SMA and calponin and suppressed VSMC proliferation and migration; in vivo inhibition of miRNA-501-5p could also blunt carotid artery balloon injury induced VSMC phenotypic modulation in rats. Mechanically, miRNA-501-5p promoted plasma sEV-induced VSMC proliferation by targeting Smad3. Notably, endothelial cells might be the major origins of miRNA-501-5p. Collectively, these findings showed that plasma sEV-carried miRNA-501-5p promotes VSMC phenotypic modulation-mediated ISR through targeting Smad3.
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Lee, Ki-Young, Young-Chul Yoo, Jin-Sun Cho, Wootaek Lee, Ji-Young Kim, and Myoung-Hwa Kim. "The Effect of Intraoperative Fluid Management According to Stroke Volume Variation on Postoperative Bowel Function Recovery in Colorectal Cancer Surgery." Journal of Clinical Medicine 10, no. 9 (April 25, 2021): 1857. http://dx.doi.org/10.3390/jcm10091857.
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Stroke volume variation (SVV) has been used to predict fluid responsiveness; however, it remains unclear whether goal-directed fluid therapy using SVV contributes to bowel function recovery in abdominal surgery. This prospective randomized controlled trial aimed to compare bowel movement recovery in patients undergoing colon resection surgery between groups using traditional or SVV-based methods for intravenous fluid management. We collected data between March 2015 and July 2017. Bowel function recovery was analyzed based on the gas-passing time, sips of water time, and soft diet (SD) time. Finally, we analyzed data from 60 patients. There was no significant between-group difference in the patients’ characteristics. Compared with the control group (n = 30), the SVV group (n = 30) had a significantly higher colloid volume and lower crystalloid volume. Moreover, the gas-passing time (77.8 vs. 85.3 h, p = 0.034) and SD time (67.6 vs. 85.1 h, p < 0.001) were significantly faster in the SVV group than in the control group. Compared with the control group, the SVV group showed significantly lower scores of pain on a numeric rating scale and morphine equivalent doses during post-anesthetic care, at 24 postoperative hours, and at 48 postoperative hours. Our findings suggested that, compared with the control group, the SVV group showed a faster postoperative SD time, reduced acute postoperative pain intensity, and lower rescue analgesics. Therefore, SVV-based optimal fluid management is expected to potentially contribute to postoperative bowel function recovery in patients undergoing colon resection surgery.
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Huang, (Henry) Sung-Cheng. "Anatomy of SUV." Nuclear Medicine and Biology 27, no. 7 (October 2000): 643–46. http://dx.doi.org/10.1016/s0969-8051(00)00155-4.
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Glover, Mike, and Neil Blake. "Control of SBV." Veterinary Record 171, no. 25 (December 21, 2012): 652.1–652. http://dx.doi.org/10.1136/vr.e8596.
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Willmington, Jackie, Gavin Watkins, Kate Hovers, Ifan Lloyd, and Les Eckford. "SBV in Wales." Veterinary Record 172, no. 10 (March 8, 2013): 273.2–274. http://dx.doi.org/10.1136/vr.f1496.
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LAI, Hsien Yong, Cheryl C. H. YANG, Ching-Feng CHENG, Fan Yen HUANG, Yi LEE, Ming-Hwang SHYR, and Terry B. J. KUO. "Effect of esmolol on positive-pressure ventilation-induced variations of arterial pressure in anaesthetized humans." Clinical Science 107, no. 3 (August 24, 2004): 303–8. http://dx.doi.org/10.1042/cs20040069.
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Positive-pressure ventilation-induced variations in arterial pressure have been related to cardiac sympathetic activity in animals. However, the effect of β-adrenoceptor blockade on these variations in anaesthetized humans under positive-pressure ventilation has not yet been investigated. In the present study, RAPV (respiratory-related arterial pressure variability) and %SPV (percentile systolic pressure variation) were determined before and after esmolol treatment in ten mechanically ventilated patients. RAPV and %SPV decreased significantly after intravenous esmolol (1 mg/kg of body weight) treatment (maximal decrease of RAPV, 50% and %SPV, 35%). Linear regression analysis of RAPV and %SPV before and after esmolol treatment both revealed high correlation (r=0.93 and 0.91 respectively). The amplitudes of RAPV and %SPV also significantly increased in a graded way with higher tidal volumes. Thus we propose that esmolol suppresses the variations in arterial pressure induced by positive-pressure mechanical ventilation, and we suggest that RAPV and %SPV may be alternative choices for monitoring cardiac sympathetic regulation in anaesthetized patients under positive-pressure ventilation.
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Dorobantu, Dan Mihai, Demetris Taliotis, Robert Michael Tulloh, Mansour Thagavi Azar Sharabiani, Eltayeb Mohamed Ahmed, Gianni Davide Angelini, and Serban Constantin Stoica. "Surgical versus balloon valvotomy in neonates and infants: results from the UK National Audit." Open Heart 6, no. 1 (February 2019): e000938. http://dx.doi.org/10.1136/openhrt-2018-000938.
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ObjectiveThere are conflicting data on choosing balloon aortic valvoplasty (BAV) or surgical aortic valvotomy (SAV) in neonates and infants requiring intervention for aortic valve stenosis. We aim to report the outcome of both techniques based on results from the UK national registry.MethodsThis is a retrospective study, including all patients under 1 year undergoing BAV/SAV between 2000 and 2012. A modulated renewal approach was used to examine the effect of reinterventions on outcomes.ResultsA total of 647 patients (488 BAV, 159 SAV, 292 neonates) undergoing 888 aortic valve procedures were included, with a median age of 40 days. Unadjusted survival at 10 years was 90.6% after initial BAV and 84.9% after initial SAV. Unadjusted aortic valve replacement (AVR) rate at 10 years was 78% after initial BAV and 80.3% after initial SAV. Initial BAV and SAV had comparable outcomes at 10 years when adjusted by covariates (p>0.4). AVR rates were higher after BAV and SAV reinterventions compared with initial valvoplasty without reinterventions (reference BAV, HR=3 and 3.8, respectively, p<0.001). Neonates accounted for 29/35 of early deaths after the initial procedure, without significant differences between BAV and SAV, with all late outcomes being worse compared with infants (p<0.005).ConclusionsIn a group of consecutive neonates and infants, BAV and SAV had comparable survival and freedom from reintervention as initial procedures and when performed as reinterventions. These findings support a treatment choice based on patient characteristics and centre expertise, and further research into the best patient profile for each choice.
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Maithel, Shelley, Areg Grigorian, Nii-Kabu Kabutey, Brian M. Sheehan, Sahil Gambhir, Ronald F. Wolf, Zeljka Jutric, and Jeffry Nahmias. "Hepatoportal Venous Trauma: Analysis of Incidence, Morbidity, and Mortality." Vascular and Endovascular Surgery 54, no. 1 (September 30, 2019): 36–41. http://dx.doi.org/10.1177/1538574419878577.
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Objectives: Although traumatic injuries to the superior mesenteric vein (SMV), portal vein (PV), and hepatic vein (HV) are rare, their impact is significant. Small single center reports estimate mortality rates ranging from 29% to 100%. Our aim is to elucidate the incidence and outcomes associated with each injury due to unique anatomic positioning and varied tolerance of ligation. We hypothesize that SMV injury is associated with a lower risk of mortality compared to HV and PV injury in adult trauma patients. Methods: The Trauma Quality Improvement Program database (2010-2016) was queried for patients with injury to either the SMV, PV, or HV. A multivariable logistic regression model was used for analysis. Results: From 1,403,466 patients, 966 (0.07%) had a single major hepatoportal venous injury with 460 (47.6%) involving the SMV, 281 (29.1%) involving the PV, and 225 (23.3%) involving the HV. There was no difference in the percentage of patients undergoing repair or ligation between SMV, PV, and HV injuries ( P > .05). Compared to those with PV and HV injuries, patients with SMV injury had a higher rate of concurrent bowel resection (38.5% vs 12.1% vs 7.6%, P < .001) and lower mortality (33.3% vs 45.9% vs 49.3%, P < .01). After controlling for covariates, traumatic SMV injury increased the risk of mortality (odds ratio [OR] 1.59, confidence interval [CI] = 1.00-2.54, P = .05) in adult trauma patients; however, this was less than PV injury (OR = 2.77, CI = 1.56-4.93, P = .001) and HV injury (OR = 2.70, CI = 1.46-4.99, P = .002). Conclusion: Traumatic SMV injury had a lower rate of mortality compared to injuries of the HV and PV. SMV injury increased the risk of mortality by 60% in adult trauma patients, whereas PV and HV injuries nearly tripled the risk of mortality.
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Badovinac, David, Katja Goričar, Hana Zavrtanik, Miha Petrič, Teja Lavrin, Nina Mavec, Vita Dolžan, Aleš Tomažič, and Metka Lenassi. "Plasma Extracellular Vesicle Characteristics Correlate with Tumor Differentiation and Predict Overall Survival in Patients with Pancreatic Ductal Adenocarcinoma Undergoing Surgery with Curative Intent." Journal of Personalized Medicine 11, no. 2 (January 28, 2021): 77. http://dx.doi.org/10.3390/jpm11020077.
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Better preoperative characterization of patients with pancreatic ductal adenocarcinoma (PDAC) would aid in treatment optimization. Extracellular vesicles (EV) are promising, largely unexplored biomarkers in PDAC. This study aimed to evaluate if plasma EV characteristics are associated with PDAC clinical characteristics and overall survival (OS). The prospective cohort included 34 PDAC patients undergoing surgery with curative intent. Patient data and plasma samples were collected preoperatively, intraoperatively and one month postoperatively. Small plasma EV (sEV) concentration and size were determined by nanoparticle-tracking analysis. A Mann–Whitney test, Spearman’s rho and Cox regression were used in statistical analysis. Preoperatively, patients with poorly differentiated tumors had significantly larger plasma sEVs when compared to patients with well/moderately differentiated tumors (mean diameter 176.9 vs. 149.2 nm, p = 0.021), the sEV size even enabling discrimination of the two groups (AUC = 0.742, 95% CI = 0.560–0.923). Plasma sEV characteristics were also a predictor of OS in multivariable analysis. Patients with a more than 33.8% increase in sEV concentration after one month had 7.2 months shorter median OS (p = 0.002), while patients with a more than 28.0% decrease in sEV size had 9.2 months shorter median OS (p = 0.045). Plasma sEV concentration and size correlate with tumor differentiation and may predict OS in PDAC patients. In the future, plasma sEV characteristics could contribute to improved patient stratification for optimized treatment.
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Liu, Hongxu, Juju Shang, Fuyong Chu, Aiyong Li, Bao Wu, Xinran Xie, Weihong Liu, Hongzhi Yang, and Tong Tong. "Protective Effects of Shen-Yuan-Dan, a Traditional Chinese Medicine, against Myocardial Ischemia/Reperfusion InjuryIn VivoandIn Vitro." Evidence-Based Complementary and Alternative Medicine 2013 (2013): 1–11. http://dx.doi.org/10.1155/2013/956397.
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Objectives.The study was to investigate the effects and mechanisms of Shen-Yuan-Dan (SYD) pharmacological postconditioning on myocardial ischemia/reperfusion (I/R) injury.Methods.In thein vivoexperiment, myocardial injury markers and histopathology staining were examined. In thein vitroexperiment, cell viability and cell apoptosis were, respectively, detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays and Hoechst 33342 fluorochrome staining. The protein expressions of Bcl-2 and Bax were determined by immunocytochemistry assay.Results.Both low and high doses of SYD protected myocardium against I/R injury in rat model by reducing lactic dehydrogenase (LDH) and creatine kinase-MB (CK-MB) activity and malondialdehyde (MDA) content, increasing superoxide dismutase (SOD) activity and attenuating histopathology injury. Meanwhile, in thein vitroexperiment, SYD promoted cell viability and inhibited the cardiomyocyte apoptosis. The level of Bcl-2 protein was restored to the normal level by SYD pharmacological postconditioning. In contrast, the Bax protein level was markedly reduced by SYD pharmacological postconditioning. These effects of SYD were inhibited by LY294002.Conclusions.The results of this study suggested that SYD pharmacological postconditioning has protective effects against myocardial I/R injury in bothin vivoandin vitromodels, which are related to activating the phosphatidylinositol 3-kinase/Akt (PI3K/Akt) pathway.
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Malouli, Daniel, Scott G. Hansen, Meaghan H. Hancock, Colette M. Hughes, Julia C. Ford, Roxanne M. Gilbride, Abigail B. Ventura, et al. "Cytomegaloviral determinants of CD8+ T cell programming and RhCMV/SIV vaccine efficacy." Science Immunology 6, no. 57 (March 25, 2021): eabg5413. http://dx.doi.org/10.1126/sciimmunol.abg5413.
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Simian immunodeficiency virus (SIV) insert–expressing, 68-1 rhesus cytomegalovirus (RhCMV/SIV) vectors elicit major histocompatibility complex E (MHC-E)– and MHC-II–restricted, SIV-specific CD8+ T cell responses, but the basis of these unconventional responses and their contribution to demonstrated vaccine efficacy against SIV challenge in the rhesus monkeys (RMs) have not been characterized. We show that these unconventional responses resulted from a chance genetic rearrangement in 68-1 RhCMV that abrogated the function of eight distinct immunomodulatory gene products encoded in two RhCMV genomic regions (Rh157.5/Rh157.4 and Rh158-161), revealing three patterns of unconventional response inhibition. Differential repair of these genes with either RhCMV-derived or orthologous human CMV (HCMV)–derived sequences (UL128/UL130; UL146/UL147) leads to either of two distinct CD8+ T cell response types—MHC-Ia–restricted only or a mix of MHC-II– and MHC-Ia–restricted CD8+ T cells. Response magnitude and functional differentiation are similar to RhCMV 68-1, but neither alternative response type mediated protection against SIV challenge. These findings implicate MHC-E–restricted CD8+ T cell responses as mediators of anti-SIV efficacy and indicate that translation of RhCMV/SIV vector efficacy to humans will likely require deletion of all genes that inhibit these responses from the HCMV/HIV vector.
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Sullivan, Michelle N., Samuel A. Brill, Lisa M. Mangus, Yea Ji Jeong, Clarisse V. Solis, Audrey C. Knight, Carlo Colantuoni, et al. "Upregulation of Superoxide Dismutase 2 by Astrocytes in the SIV/Macaque Model of HIV-Associated Neurologic Disease." Journal of Neuropathology & Experimental Neurology 79, no. 9 (August 12, 2020): 986–97. http://dx.doi.org/10.1093/jnen/nlaa084.
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Abstract HIV-associated neurocognitive disorders (HAND) remain prevalent despite implementation of antiretroviral therapy (ART). Development of HAND is linked to mitochondrial dysfunction and oxidative stress in the brain; therefore, upregulation of antioxidant defenses is critical to curtail neuronal damage. Superoxide dismutase 2 (SOD2) is a mitochondrial antioxidant enzyme essential for maintaining cellular viability. We hypothesized that SOD2 was upregulated during retroviral infection. Using a simian immunodeficiency virus (SIV)-infected macaque model of HIV, quantitative PCR showed elevated SOD2 mRNA in cortical gray ([GM], 7.6-fold for SIV vs uninfected) and white matter ([WM], 77-fold for SIV vs uninfected) during SIV infection. Further, SOD2 immunostaining was enhanced in GM and WM from SIV-infected animals. Double immunofluorescence labeling illustrated that SOD2 primarily colocalized with astrocyte marker glial fibrillary acidic protein (GFAP) in SIV-infected animals. Interestingly, in ART-treated SIV-infected animals, brain SOD2 RNA levels were similar to uninfected animals. Additionally, using principal component analysis in a transcriptomic approach, SOD2 and GFAP expression separated SIV-infected from uninfected brain tissue. Projection of these data into a HIV dataset revealed similar expression changes, thereby validating the clinical relevance. Together, our findings suggest that novel SOD2-enhancing therapies may reduce neuroinflammation in ART-treated HIV-infected patients.