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Ul Haq, Faizan, Mikko Englund, Yury Antonov, Miikka Tenhunen, Kari Stadius, Marko Kosunen, Kim B. Ostman, Kimmo Koli i Jussi Ryynanen. "A Six-Phase Two-Stage Blocker-Tolerant Harmonic-Rejection Receiver". IEEE Transactions on Microwave Theory and Techniques 68, nr 5 (maj 2020): 1964–76. http://dx.doi.org/10.1109/tmtt.2020.2966152.
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Lenka, Manas Kumar, i Gaurab Banerjee. "A Wideband Blocker-Tolerant Receiver With Frequency-Translational Resistive Feedback". IEEE Transactions on Very Large Scale Integration (VLSI) Systems 27, nr 5 (maj 2019): 993–1006. http://dx.doi.org/10.1109/tvlsi.2019.2895624.
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Murphy, David, Hooman Darabi, Asad Abidi, Amr A. Hafez, Ahmad Mirzaei, Mohyee Mikhemar i Mau-Chung Frank Chang. "A Blocker-Tolerant, Noise-Cancelling Receiver Suitable for Wideband Wireless Applications". IEEE Journal of Solid-State Circuits 47, nr 12 (grudzień 2012): 2943–63. http://dx.doi.org/10.1109/jssc.2012.2217832.
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Wu, Hao, Mohyee Mikhemar, David Murphy, Hooman Darabi i Mau-Chung Frank Chang. "A Blocker-Tolerant Inductor-Less Wideband Receiver With Phase and Thermal Noise Cancellation". IEEE Journal of Solid-State Circuits 50, nr 12 (grudzień 2015): 2948–64. http://dx.doi.org/10.1109/jssc.2015.2458956.
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Kaltiokallio, Mikko, Risto Valkonen, Kari Stadius i Jussi Ryynanen. "A 0.7–2.7-GHz Blocker-Tolerant Compact-Size Single-Antenna Receiver for Wideband Mobile Applications". IEEE Transactions on Microwave Theory and Techniques 61, nr 9 (wrzesień 2013): 3339–49. http://dx.doi.org/10.1109/tmtt.2013.2274434.
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Mincey, John S., Jose Silva-Martinez, Aydin Ilker Karsilayan i Christopher T. Rodenbeck. "Blocker-Tolerant and High-Sensitivity $\Delta \Sigma $ Correlation Digitizer for Radar and Coherent Receiver Applications". IEEE Transactions on Microwave Theory and Techniques 65, nr 9 (wrzesień 2017): 3453–63. http://dx.doi.org/10.1109/tmtt.2017.2679008.
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Lenka, Manas Kumar, i Gaurab Banerjee. "Corrections Corrections to “A Wideband Blocker-Tolerant Receiver With Frequency-Translational Resistive Feedback” [May 19 993-1006]". IEEE Transactions on Very Large Scale Integration (VLSI) Systems 27, nr 5 (maj 2019): 1238. http://dx.doi.org/10.1109/tvlsi.2019.2902297.
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Shin, Donguk, Kyudo Lee i Kuduck Kwon. "A Blocker-Tolerant Receiver Front End Employing Dual-Band N-Path Balun-LNA for 5G New Radio Cellular Applications". IEEE Transactions on Microwave Theory and Techniques 70, nr 3 (marzec 2022): 1715–24. http://dx.doi.org/10.1109/tmtt.2021.3136295.
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Wu, Hao, Ning-Yi Wang, Yuan Du i Mau-Chung Frank Chang. "A Blocker-Tolerant Current Mode 60-GHz Receiver With 7.5-GHz Bandwidth and 3.8-dB Minimum NF in 65-nm CMOS". IEEE Transactions on Microwave Theory and Techniques 63, nr 3 (marzec 2015): 1053–62. http://dx.doi.org/10.1109/tmtt.2015.2393310.
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Trotskovsky, Konstantin, Amy Whitcombe, Gregory Lacaille, Antonio Puglielli, Pengpeng Lu, Zhongkai Wang, Nathan Narevsky i in. "A 0.25–1.7-GHz, 3.9–13.7-mW Power-Scalable, −10-dBm Harmonic Blocker-Tolerant Mixer-First RF-to-Digital Receiver for Massive MIMO Applications". IEEE Solid-State Circuits Letters 1, nr 2 (luty 2018): 38–41. http://dx.doi.org/10.1109/lssc.2018.2813010.
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Poursaadati Zinjanab, Ali, Mohammad Elmi i Ali Jalali. "A standard-blocker tolerant receiver front-end using noise-canceling LNA with passive N-path filter and variable pulse-width multi-phase clock generator". Analog Integrated Circuits and Signal Processing 97, nr 3 (21.09.2018): 579–91. http://dx.doi.org/10.1007/s10470-018-1331-1.
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Poursaadati Zinjanab, Ali, Ali Jalali i Hamed Taghipour Farshi. "A standard and harmonic blocker tolerant receiver front-end using a harmonic rejection differential N-path notch filter and blocks withstand to possible variations". AEU - International Journal of Electronics and Communications 125 (październik 2020): 153356. http://dx.doi.org/10.1016/j.aeue.2020.153356.
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Frank, L. "Endotoxin-tolerant rats are still protected from oxygen toxicity by low-dose endotoxin treatment". Journal of Applied Physiology 58, nr 3 (1.03.1985): 819–22. http://dx.doi.org/10.1152/jappl.1985.58.3.819.
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To determine if we could reduce endotoxin's potential for toxicity, we produced “endotoxin-tolerant” rats by administering progressively increasing daily doses of endotoxin (10 ng, 100 ng, 1 microgram, 10 micrograms/kg). This dosage regimen produced a high degree of tolerance to the toxic actions of endotoxin: whereas only 3/17 (18%) of control rats survived a normally lethal dose of endotoxin (25 mg/kg), survival for the endotoxin-tolerant rats was 16/16. When endotoxin-tolerant rats received a standard protective dose of 500 micrograms/kg endotoxin just before transfer to 96–98% O2, 19/20 survived the 72-h exposure period vs. 20–30% survival for controls. Thus whereas the endotoxin-tolerant state blocked the tested lethal and toxic effects of endotoxin, it did not nullify the O2 protective action of endotoxin. In addition, endotoxin's stimulatory effects on the lung antioxidant enzymes in the 96–98% O2-exposed rats was also not blocked by the endotoxin-tolerant state. Thus the therapeutic ratio (TR) of endotoxin as an experimental pharmacological treatment against O2-induced lung damage has been markedly enhanced (TR = ratio of dose producing beneficial effects to dose producing toxic effects).
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Abouzied, Mohamed, Hatem Osman, Ahmed Emira i Ahmed N. Mohieldin. "A process-tolerant out-of-band blocker rejection technique for SAW-less receivers". Microelectronics Journal 45, nr 3 (marzec 2014): 297–310. http://dx.doi.org/10.1016/j.mejo.2014.01.004.
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Abdulaziz, Mohammed, Eric A. M. Klumperink, Bram Nauta i Henrik Sjoland. "Improving Receiver Close-In Blocker Tolerance by Baseband $G_m-C$ Notch Filtering". IEEE Transactions on Circuits and Systems I: Regular Papers 66, nr 3 (marzec 2019): 885–96. http://dx.doi.org/10.1109/tcsi.2018.2872469.
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Ghadiri-Sadrabadi, Mohammad, i Joseph C. Bardin. "A Discrete-Time RF Signal-Processing Technique for Blocker-Tolerant Receivers With Wide Instantaneous Bandwidth". IEEE Transactions on Circuits and Systems I: Regular Papers 65, nr 12 (grudzień 2018): 4376–89. http://dx.doi.org/10.1109/tcsi.2018.2842694.
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Podzolkov, V. I., A. E. Bragina, A. I. Tarzimanova, E. S. Ogibenina, I. I. Shvedov, E. E. Bykova i A. A. Ivannikov. "Comparative efficacy of ivabradine and beta-blockers in the treatment of tachycardia in patients after COVID-19". Cardiovascular Therapy and Prevention 21, nr 7 (20.06.2022): 3330. http://dx.doi.org/10.15829/1728-8800-2022-3330.
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Aim. To assess the changes of heart rate (HR), exercise tolerance and quality of life in patients after coronavirus disease 2019 (COVID-19) during treatment with ivabradine monotherapy or in combination with beta-blockers (BB) compared with BB monotherapy.Material and methods. This randomized comparative study included 90 patients discharged from a university hospital after an acute COVID-19. The main group (n=60) received, in addition to standard therapy, ivabradine monotherapy or in combination with BB, while the control one (n=30) — standard therapy in combination with BB. The follow-up period lasted 24 weeks. Statistical processing was performed using the STATISTICA 8.0 program. The level of statistical significance was p<0,05.Results. There was a significant decrease in heart rate, an increase in physical activity, as well as an improvement in the quality of life in both groups. In the ivabradine group, significantly lower heart rates (71,2±4,1 vs 73,9±5,1 bpm (p=0,015)), significantly higher increase in physical activity (80 (60; 135) vs 65 m (40; 100) (p=0,017)) and quality of life (35 (27; 45) vs 30 (26; 36) points (p=0,03)) was revealed.Conclusion. It has been shown that ivabradine and beta-blockers can be used in post-COVID-19 tachycardia. Ivabradine monotherapy or in combination with beta-blockers causes a more pronounced decrease in heart rate compared to beta-blocker monotherapy, accompanied by a significant improvement in exercise tolerance and quality of life in this category of patients.
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Wang, Huan, Zisong Wang i Payam Heydari. "An LO Leakage Suppression Technique for Blocker-Tolerant Wideband Receivers With High-Q Selectivity at RF Input". IEEE Journal of Solid-State Circuits 56, nr 6 (czerwiec 2021): 1682–96. http://dx.doi.org/10.1109/jssc.2020.3046248.
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Ying, Kuangyuan, Hao Gao, Dusan Milosevic i Peter Baltus. "A Nonlinear Transfer Function Based Receiver for Wideband Interference Suppression". Journal of Sensors 2017 (2017): 1–15. http://dx.doi.org/10.1155/2017/2405942.
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Wideband receivers for multistandards operation can simplify the system and lower the cost. In a wideband receiver, the tolerance of large interference signal within the operating band is important. Traditional frequency-domain filtering suffers from lacking in filtering capability for in-band interference signals. This paper describes a receiver system exploiting nonlinear transfer function. Based on the fundamental nonlinear theory, the receiver with nonlinear method can provide frequency-independent filtering for large blockers and linear amplification for weak desired signals simultaneously. The interference suppression performance depends on the amplitude discrimination between the envelope of the large and small signal. The operation of the nonlinear receiver is based on the amplitude of the interferer envelope. A feedforward path is designed to extract the envelope information of the interferer and a feedback path is added to keep track of the environment. With frequency-independent filtering, the nonlinear receiver system enhances both in-band and out-of-band linearity, thus enabling wideband multimode operation.
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Ahsan, Naveed, Christer Svensson, Rashad Ramzan, Jerzy Dabrowski, Aziz Ouacha i Carl Samuelsson. "A 1.1 V 6.2 mW, wideband RF front-end for 0 dBm blocker tolerant receivers in 90 nm CMOS". Analog Integrated Circuits and Signal Processing 70, nr 1 (19.06.2011): 79–90. http://dx.doi.org/10.1007/s10470-011-9667-9.
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Barbosa, Adriana Dias Elpo, i Gina Struffaldi Morato. "Influence of epipregnanolone on the modulation of rapid tolerance to ethanol by neurosteroids". Revista Brasileira de Psiquiatria 29, nr 4 (grudzień 2007): 337–45. http://dx.doi.org/10.1590/s1516-44462007000400008.
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OBJECTIVE: The objective of the present study was to investigate the effect of epipregnanolone on the influence of neurosteroids on the development of rapid tolerance to the motor impairing and hypothermic effects of ethanol. METHOD: Experiment 1: on Day 1 groups of mice were pretreated with saline or with epipregnanolone. After 30 min each group was further divided in subgroups that received ethanol or saline. Thirty, 60 and 90 min after the injections the animals were tested on the rota-rod or the body temperature was measured. On Day 2 all groups received ethanol and a similar procedure was followed to evaluate rapid tolerance. Experiment 2 and 3: On Day 1 groups of mice were treated with epipregnanolone and after 15 min each group was divided into three groups in order to receive pregnenolone sulfate, dehydroepiandrosterone sulfate or saline. Thirty minutes later, each group was further divided into two subgroups in order to receive ethanol or saline, respectively, and 30, 60 and 90 min later the animals were tested as in the experiment 1. On Day 2 all groups received ethanol and a similar procedure was followed to evaluate rapid tolerance. RESULTS: Pretreatment with epipregnanolone (0.10-0.30 mg/kg) significantly blocked the development of tolerance to the motor impairing and hypothermic effects induced by ethanol in mice. Considering tolerance to ethanol-induced motor impairment, epipregnanolone (0.15 mg/kg) reversed the stimulatory action of dehydroepiandrosterone sulfate (0.15 mg/kg), but did not affect the actions of pregnenolone sulfate (0.08 mg/kg). Moreover, epipregnanolone prevented the inhibitory action of allotetrahydrodeoxycorticosterone (0.10 mg/kg). In relation to ethanol-induced hypothermia, the results showed that pretreatment with epipregnanolone (0.30 mg/kg) significantly prevented the stimulatory action of dehydroepiandrosterone sulfate and pregnenolone sulfate, as well as the inhibitory action of allotetrahydrodeoxicorticosterone (0.20 mg/kg), on tolerance to this effect. CONCLUSIONS: The results suggest a differential interaction between neurosteroids that might modulate the development of rapid tolerance to ethanol.
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Tashchuk, V., O. Malinevska-Biliichuk, D. Onofreichuk, P. Ivanchuk i M. Tashchuk. "Program «Smart ECG – ranolazin» - own experience and world approach". Bukovinian Medical Herald 24, nr 4 (96) (26.11.2020): 110–16. http://dx.doi.org/10.24061/2413-0737.xxiv.4.96.2020.119.
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Purpose - comprehensive analysis of the world approach of the use of ranolazine in various clinical trials and the introduction of the program "Smart ECG" to assess the effectiveness of ranolazine.Matherial and methods. Evaluation of European guidelines, analysis of global randomized clinical trials of the ranolazine use, presentation of our own trial: we examined 40 patients with Q wave myocardial infarction (STEMI), were instituted basic therapy according to the modern recommendations which contained interventional treatment with restoration of patency of a heart attack-conditioned coronary artery, double antiplatelet therapy, statins, β-adrenergic blocker, angiotensin-converting enzyme inhibitors, aldosterone antagonists with addition of ranolazine (group I, 30 patients diagnosed STEMI), control - group II, 10 patients with STEMI, who received basic therapy without addition of ranolazine. Results. Analysis of clinical trials (CARISA, MARISA, ERICA, TERISA, MERLIN-TIMI, RIVER-PCI, RIMINI-TRIAL) proved the effectiveness of ranolazine as an antianginal and anti-ischemic drugs. The use of own program «Smart ECG» demonstrates the positive effect of ranolazine on STEMI and requires further implementation.Conclusion. In the European Society of Cardiology guidelines of the management of stable angina pectoris, ranolazine is given a class IIa (level of evidence B) recommendation as a second-line treatment to reduce angina frequency and improve exercise tolerance in subjects who cannot tolerate, have contraindications to, or whose symptoms are not adequately controlled by β- adrenergic blockers, calcium channel blockers and long-acting nitrates. In subjects with baseline low heart rate and low blood pressure, ranolazine may be considered as a first-line drug to reduce angina frequency and improve exercise tolerance - class IIa (level of evidence C) recommendation. Own study, which partially reflects the global approach according to the analyzed clinical studies, demonstrates the positive effect of ranolazine for patients with STEMI - analogue scale EQ–VAS indicates a positive effect, positive influence on the markers of electrical myocardial instability: decreasing of the probability of cases of SDNN decrease, depression of QT and maybe increase of ratio of maximum velocity for differentiated T wave.
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Matsuhisa, Seiji, Hajime Otani, Toru Okazaki, Koji Yamashita, Yuzo Akita, Daisuke Sato, Akira Moriguchi, Hiroji Imamura i Toshiji Iwasaka. "Angiotensin II type 1 receptor blocker preserves tolerance to ischemia-reperfusion injury in Dahl salt-sensitive rat heart". American Journal of Physiology-Heart and Circulatory Physiology 294, nr 6 (czerwiec 2008): H2473—H2479. http://dx.doi.org/10.1152/ajpheart.91533.2007.
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Oxidative stress is involved in the tolerance to ischemia-reperfusion (I/R) injury. Because angiotensin II type 1 receptor blockers (ARBs) inhibit oxidative stress, there is concern that ARBs abolish the tolerance to I/R injury. Dahl salt-sensitive (DS) hypertensive and salt-resistant (DR) normotensive rats received an antioxidant, 2-mercaptopropionylglycine (MPG), or an ARB, losartan, for 7 days. Losartan and MPG significantly inhibited oxidative stress as determined by tissue malondialdehyde + 4-hydroxynoneal and increased expression of inducible nitric oxide synthase (iNOS) in the DS rat heart. However, losartan but not MPG activated endothelial nitric oxide synthase (eNOS) as assessed by phosphorylation of eNOS on Ser1177. Infarct size after 30-min left coronary artery occlusion followed by 2-h reperfusion was comparable between DS and DR rat hearts. Although MPG and losartan had no effect on infarct size in the DR rat heart, MPG but not losartan significantly increased infarct size in the DS rat heart. A selective iNOS inhibitor, 1400W, increased infarct size in the DS rat heart, but it had no effect on infarct size in the losartan-treated DS rat heart. However, a nonselective NOS inhibitor, Nω-nitro-l-arginine methyl ester, increased infarct size in the losartan-treated DS rat heart. These results suggest that losartan preserves the tolerance to I/R injury by activating eNOS despite elimination of redox-sensitive upregulation of iNOS and iNOS-dependent cardioprotection in the DS rat heart.
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Cheng, Xu, Feng-Jun Chen, Liang Zhang, Hao Gao, Jiang-An Han, Jing-Yu Han, Yang Yu i Xian-Jin Deng. "A Closed-Loop Reconfigurable Analog Baseband Circuitry With Open-Loop Tunable Notch Filters to Improve Receiver Tx Leakage and Close-in Blocker Tolerance". IEEE Transactions on Circuits and Systems II: Express Briefs 69, nr 3 (marzec 2022): 839–43. http://dx.doi.org/10.1109/tcsii.2021.3125305.
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Bhattacharyya, Gouri Shankar, K. Govind Babu, Shailesh Arjun Bondarde, Ghanashyam Biswas, Anantbhushan Ranade, Purvish M. Parikh, Newell F. Bascomb i Hemant Malhotra. "Effect of coadministered beta blocker and COX-2 inhibitor to patients with pancreatic cancer prior to receiving albumin-bound (Nab) paclitaxel." Journal of Clinical Oncology 33, nr 3_suppl (20.01.2015): 302. http://dx.doi.org/10.1200/jco.2015.33.3_suppl.302.
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302 Background: Paclitaxel protein-bound particles nab-paclitaxel plus gemcitabine is rapidly becoming the standard of care for patients with metastatic adenocarcinoma of the pancreas (mPCa). Preclinical and clinical studies of beta-blockers and NSAIDs show a benefit of these drugs in pancreatic cancer. The aim of this study was to evaluate the impact of the co-administration of the beta blocker propranolol (P) and the selective COX-2 inhibitor etodolac (E) on survival of patients with mPCa receiving GemNab as standard of care. PE is presumed to target the adrenergic and prostaglandin stress systems activated in cancer that induce changes in tumor microenvironment, immune system, and HPA axis leading to tumor promotion and immune tolerance. Data on the use of nab-paclitaxel plus gemcitabine (GemNab) with a beta blocker and NSAID in the clinical setting is lacking. Methods: Patients with mPCa were eligible for this randomized investigator initiated trial. Patients received PE daily for one week prior to starting GemNab. PE was administered in a chronodosed regimen to maximize the therapeutic benefit and minimize side effects. The primary endpoint was survival. Twenty-three patients were randomized to either GemNab or GemNab after one week of propranolol and etodolac (PEGemNab). The median age was 62.8 years; 68.2% male. Pain at time of diagnosis as reported in 80% of the patients in the GemNab arm and in 76.9% of the PEGemNab arm and jaundice was observed in 40% and 23% of the GemNab and PEGemNab arms, respectively. Results: Progression free survival was 7.2 and 11.8 months in the GemNab and PEGemNab arms, respectively. Overall survival was 10.5 months for the GemNab arm and 15.9 months for the PEGemNab arm. The treatment was well-tolerated with no unexpected adverse events. Conclusions: Administration of PE one week prior to Paclitaxel protein-bound particles with gemcitabine significantly increased progression free and overall survival. No unexpected adverse reactions were seen. Additional data on cytokine and cancer markers will be presented.
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Liu, Qing, i Michael S. Gold. "Opioid-induced Loss of Local Anesthetic Potency in the Rat Sciatic Nerve". Anesthesiology 125, nr 4 (1.10.2016): 755–64. http://dx.doi.org/10.1097/aln.0000000000001239.
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Abstract Background Previous evidence suggests that opioid-tolerant patients are less responsive to local anesthetics (LAs) for postoperative pain management. Methods To determine whether this apparent loss of LA potency is due to an intrinsic change in the peripheral nerve, the effect of systemic morphine was assessed on the potency of lidocaine-induced block of the compound action potential in isolated rat sciatic nerves. Analgesic efficacy was assessed with the heat withdrawal assay. Results While acute administration of 10 mg/kg morphine had no detectable influence on lidocaine potency, seven daily subcutaneous injections of morphine produced a three-fold decrease in potency (EC50 for block A and C waves for naive rats were [mean ± SD] 186 ± 32 μM [n = 6] and 201 ± 31 μM [n = 6], respectively, vs. 608 ± 53 μM [n = 6] and 613 ± 42 μM [n = 6], respectively [P < 0.001], in nerves from rats that had received seven daily injections of morphine [10 mg/kg]). This loss in potency was both dose-dependent and injection number dependent, such that the magnitude of the loss of lidocaine potency was significantly (n = 6; P < 0.01) correlated (r2 = 0.93) with the development of morphine tolerance. Interestingly, despite the complete recovery of analgesic efficacy within days after cessation of morphine administration, the morphine-induced decrease in lidocaine potency was fully manifest even 35 days after the last morphine injection. Coadministration of naloxone (1 mg/kg, intraperitoneally), but not of naloxone methiodide (1 mg/kg, subcutaneously), with each of seven daily injections of morphine blocked the decrease in lidocaine potency. Conclusions These preclinical data suggest that the morphine-induced decrease in LA potency is due, at least in part, to the intrinsic changes in the peripheral nerve. Identification of the underlying mechanisms may suggest strategies for more effective postoperative pain management in the growing population of opioid-tolerant patients.
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Al- Shukri, Adel S., Stanislav V. Kostyukov i Albina V. Maksimova. "Comparative evaluation of the effectiveness and safety of different dosages of Glancin (tamsulosin) in the treatment of patients with lower urinary tract symptoms due to benign prostatic hyperplasia". Urology reports (St. - Petersburg) 12, nr 4 (22.01.2023): 287–95. http://dx.doi.org/10.17816/uroved109022.
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BACKGROUND: Alpha-blockers are the first-line treatment for the elimination of symptoms of impaired urination due to benign prostatic hyperplasia. At the same time, the focus is not only on efficiency, but also on the safety of their appointment.
AIM: Comparison of the efficacy and tolerability of the alpha1-blocker tamsulosin at a dosage of 0.2 mg twice a day and 0.4 mg once a day in patients with benign prostatic hyperplasia presenting with mild to moderate LUTS.
MATERIALS AND METHODS: The study is based on the results of examination and treatment of 90 patients with symptoms of impaired urination in benign prostatic hyperplasia, aged 50 to 80 years. In the 1st group (n = 45) patients received tamsulosin 0.2 mg twice a day, in the 2nd group (n = 45) 0.4 mg once a day. The duration of treatment was 4 weeks.
RESULTS: In patients of both groups, according to the IPSS questionnaire, a statistically significant decrease in the severity of obstructive and irritative symptoms, an improvement in the quality of life, an increase in the maximum urine flow rate, and a decrease in the volume of residual urine were revealed. When comparing the dynamics of clinical indicators in patients of the 1st and 2nd groups, no significant differences were found between the groups. At the same time, treatment tolerance was somewhat better in patients of the 1st group, which manifested itself in a smaller number of adverse events from the cardiovascular system and ejaculatory function disorders.
CONCLUSIONS: The results of the study demonstrate the same efficacy of tamsulosin 0.2 mg twice a day and 0.4 mg once a day. At the same time, taking tamsulosin at a dose of 0.2 mg twice a day was characterized by better tolerability of therapy.
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McNitt, Dudley H., Bryan A. Joosse, James W. Thomas i Rachel H. Bonami. "Productive Germinal Center Responses Depend on the Nature of Stimuli Received by Anti-Insulin B Cells in Type 1 Diabetes–Prone Mice". ImmunoHorizons 7, nr 6 (1.06.2023): 384–97. http://dx.doi.org/10.4049/immunohorizons.2300036.
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Abstract Islet autoantibodies, including those directed at insulin, predict type 1 diabetes (T1D) in mice and humans and signal immune tolerance breach by B lymphocytes. High-affinity insulin autoantibodies and T follicular helper cell involvement implicate germinal centers (GCs) in T1D. The VH125SD BCR transgenic model, in which 1–2% of peripheral B lymphocytes recognize insulin, enables direct study of insulin-binding B cells. Our prior studies showed that anti-insulin B cell receptor transgene site-directed to H chain locus mice fail to generate insulin Ab following T-dependent immunization, but it was unclear whether anti-insulin B cells were blocked for GC initiation, survival, or differentiation into Ab-secreting cells. Here, we show that insulin-binding B cells in T1D-prone anti-insulin B cell receptor transgene site-directed to H chain locus mice can spontaneously adopt a GC phenotype and undergo class switching to the IgG1 isotype, with little if any switching to IgG2b. T-dependent immunizations with insulin SRBC or insulin CFA drove anti-insulin B lymphocytes to adopt a GC phenotype, despite blunted insulin Ab production. Dual immunization against self (insulin) and foreign (4-hydroxy-3-nitrophenylacetyl hapten conjugated to keyhole limpet hemocyanin) Ags showed an anti-insulin (but not anti-4-hydroxy-3-nitrophenylacetyl) Ab block that tracked with increased expression of the apoptosis marker, activated caspase 3, in self-reactive GC B cells. Finally, T-independent immunization with insulin conjugated to Brucella abortus ring test Ag released immune tolerance to allow robust expansion of anti-insulin GC B cells and IgG-switched insulin Ab production. Overall, these data pinpoint GC survival and Ab-secreting cell differentiation as immune tolerance blocks that limit T-dependent, but not T-independent, stimulation of anti-insulin B cell responses.
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Pendharkar, D., S. Gupta, M. K. Pal, S. Hakim i T. Rashid. "Feasibility of combining humanized anti-epidermal growth factor receptor monoclonal antibody h-R3 (nimotuzumab) with chemotherapy-A study of toxicity profile and tolerance". Journal of Clinical Oncology 25, nr 18_suppl (20.06.2007): 14151. http://dx.doi.org/10.1200/jco.2007.25.18_suppl.14151.
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14151 Background. Anti-EGFR antibodies have been approved in combination with radiotherapy for the treatment of head and neck squamous cell carcinoma(SCCHN) and being tried in glioblastoma multiforme(GBM). The overall toxicity profile is tolerable. There is no data available on Humanized Anti EGFR antibody in combination with chemotherapeutic agents. Nimotuzumab, the humanized MAb derived from ior EGFR/R3, is a genetically engineered IgG1, with high affinity and specificity to EGFR. This study was undertaken to record the immediate and early toxicity of combining Nimotuzumab with various chemotherapeutic agents. Methods. Patients with SCCHN and GBM, scheduled to receive chemotherapy alone were additionally given 400mg of Nimotuzumab, every three weeks. Two patients with GBM received weekly Nimotuzumab 200 mg along with radiation and chemotherapy. Overall 19 events have been analyzed. The chemoschedules used in combination with Nimotuzumab included-Docetaxel, Carboplatin and Capecitabine in patients with SCCHN and Temozolamide/ Procarbazine in GBM. Antibody infusion was always preceded by antihistaminics and dexamethasone. Results.The combination of Nimotuzumab with chemotherapy was well tolerated. There were no acute infusion related events. No febrile, allergic or anaphylactic episodes were seen. Cutaneous rash classical of other EGFR blockers was not recorded. Two episodes of grade 3 diarrhea, and four events of asthenia were seen. Dryness of the mouth was a complaint in SCCHN patients. None of the patients showed neurological or cardiovascular adverse events. Hematological and biochemical derangements were not observed. Conclusion. Nimotuzumab can safely be combined with various chemotherapeutic agents .There is no unacceptable toxicity associated with combination of chemotherapy and humanized anti-EGFR monoclonal antibody. New schedules combining Nimotuzumab and chemotherapy can be safely explored. No significant financial relationships to disclose.
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Al-Dorzi, Hasan M., Reem Yaqoub, Reema Alalmaee, Ghafran Almutairi, Allulu Almousa i Leen Aldawsari. "Enteral Nutrition Safety and Outcomes of Patients with COVID-19 on Continuous Infusion of Neuromuscular Blockers: A Retrospective Study". Journal of Nutrition and Metabolism 2023 (28.06.2023): 1–10. http://dx.doi.org/10.1155/2023/8566204.
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Background. Intravenous infusions of neuromuscular blocking agents (NMBAs) and prone positioning are recommended for acute respiratory distress syndrome (ARDS) due to COVID-19. The safety of enteral nutrition (EN) during these treatments is unclear. This study assessed EN tolerance and safety during NMBA infusion in proned and nonproned patients with ARDS due to COVID-19. Methods. This retrospective study evaluated patients who were admitted to a tertiary-care ICU between March and December 2020, had ARDS due to COVID-19, and received NMBA infusion. We assessed their EN data, gastrointestinal events, and clinical outcomes. The primary outcome was gastrointestinal intolerance, defined as a gastric residual volume (GRV) ≥500 ml or 200–500 ml with vomiting. We compared proned and nonproned patients. Results. We studied 181 patients (mean age 61.2 ± 13.7 years, males 71.1%, and median body mass index 31.4 kg/m2). Most (63.5%) patients were proned, and 94.3% received EN in the first 48 hours of NMBA infusion at a median dose <10 kcal/kg/day. GRV was mostly below 100 ml. Gastrointestinal intolerance occurred in 6.1% of patients during NMBA infusion and 10.5% after NMBA discontinuation (similar rates in proned and nonproned patients). Patients who had gastrointestinal intolerance during NMBA infusion had a higher hospital mortality (90.9% versus 60.0%; p = 0.05 ) and longer mechanical ventilation duration and ICU and hospital stays compared with those who did not. Conclusion. In COVID-19 patients on NMBA infusion for ARDS, EN was provided early at low doses for most patients, and gastrointestinal intolerance was uncommon in proned and nonproned patients, occurred at a higher rate after discontinuing NMBAs and was associated with worse outcomes. Our study suggests that EN was tolerated and safe in this patient population.
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Yakovlev, A. V., S. N. Shilov, E. N. Berezikova, N. F. Yakovleva, A. T. Teplyakov, E. V. Grakova, K. V. Kopeva i I. A. Efremov. "Chronic Heart Failure in Patients with Arterial Hypertension Associated with Obstructive Sleep Apnea Syndrome: Possible Options to Pathogenetic Therapy". Rational Pharmacotherapy in Cardiology 17, nr 3 (13.07.2021): 444–49. http://dx.doi.org/10.20996/1819-6446-2021-06-07.
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Aim. To study approaches to the treatment of chronic heart failure (CHF) with reduced and mid-range left ventricular ejection fraction (LVEF) in patients with arterial hypertension (AH) against the background of obstructive sleep apnea (OSA).Material and methods. The study included 136 patients with CHF and AH. Inclusion criteria for the study: 1) moderate and severe OSA (with an apnea/hypopnea index of more than 15 per hour); 2) II-IV functional class of CHF according to NYHA; 3) the level of brain natriuretic peptide precursor (NT-proBNP) ≥125 pg/ml; 3) LVEF <50%; 4) the duration of hypertension is at least 2 years. Patients received drug therapy, including beta-blockers, mineralocorticoid receptor antagonists, diuretics, ACE inhibitors or angiotensin receptor inhibitors or valsartan/sacubitrile. After 12 months of followup, the patients were divided into 2 groups depending on the medication being administered. Group 1 included patients (n = 50) receiving therapy with valsartan/sacubitril, group 2 included patients (n = 86) receiving therapy without this drug. Effective CPAP-therapy also was registered in each group.Results. In patients with CHF who received valsartan/sacubitril, disease progression was recorded in 28% of cases, while in patients who did not receive therapy with this drug, an unfavorable course of CHF was recorded in 42.8% (p = 0.001). In group 1, the NT-proBNP level significantly (p = 0.034) decreased by 34%, while in group 2, a significant (p = 0.002) increase in biomarker levels was revealed by 35.5%. In the group of patients receiving therapy with valsartan/sacubitril an increase in LVEF (p = 0.007) was revealed by 12.5%. In group 1, an increase in exercise tolerance was achieved in the form of a significant (p = 0.012) increase in the distance of the six-minute walk test by 18.2%, while in group 2, the six-minute walk distance decreased by 19.2% (p = 0.034). In the subgroup of patients receiving CPAP therapy in combination with valsartan/sacubitril therapy (n=8), LVEF increased by 11.6% (p = 0.043), the six-minute walk test distance increased by 29.7% (p = 0.046), and NT-proBNP decreased by 22.5% (p = 0.039), while in the group of patients who received only CPAP therapy (n=19).Conclusion. The most significant slowdown in the rate of progression of CHF in patients with AH associated with OSA, an increase in exercise tolerance, as well as the most pronounced tendency to the reverse development of pathological echocardiographic changes in the myocardium when using valsartan/sacubitrile in drug therapy in combination with effective hardware CPAP therapy.
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Rickels, Michael R., Elys M. Perez, Amy J. Peleckis, Erica Alshehabi, Huong-Lan Nguyen, Darko Stefanovski, Karl Rickels i Karen L. Teff. "Contribution of parasympathetic muscarinic augmentation of insulin secretion to olanzapine-induced hyperinsulinemia". American Journal of Physiology-Endocrinology and Metabolism 315, nr 2 (1.08.2018): E250—E257. http://dx.doi.org/10.1152/ajpendo.00315.2017.
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Atypical antipsychotic drugs have been associated with the development of obesity and diabetes. In particular, olanzapine can induce peripheral insulin resistance and compensatory hyperinsulinemia independent of weight gain or psychiatric disease. To determine if this compensatory increase in insulin is mediated by parasympathetic muscarinic stimulation, we randomized 15 healthy subjects 2:1 to receive double-blind olanzapine or placebo for 9 days under diet- and activity-controlled inpatient conditions. Before and after 7 days of study drug administration, subjects underwent frequently sampled intravenous glucose tolerance tests with either saline or atropine infused on subsequent days to assess insulin secretion and hepatic insulin extraction in the absence or presence of muscarinic blockade. We found that olanzapine led to an increase in the acute insulin response to glucose, which was not seen with placebo, and was attenuated in the olanzapine group by atropine. Deconvolution of C-peptide data confirmed an increase in insulin secretion with olanzapine, which was blocked by atropine, with a modest reduction in hepatic insulin extraction with olanzapine. These results support the contribution of muscarinic augmentation of insulin secretion to olanzapine-induced hyperinsulinemia, and provide a mechanism for the compensatory hyperinsulinemia that normally serves to prevent deterioration of glucose tolerance under conditions of metabolic challenge.
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Fox, Bernard A., Brian C. Boulmay, Rui Li, Kyle T. Happel, Christopher Paustian, Tarsem Lal Moudgil, Sachin Puri i in. "T cell population expansion in response to allogeneic cancer vaccine alone (DPV-001) or with granulocyte-macrophage colony-stimulating factor (GM-CSF) or imiquimod (I) for definitively-treated stage III NSCLC patients (pts)." Journal of Clinical Oncology 35, nr 15_suppl (20.05.2017): e14639-e14639. http://dx.doi.org/10.1200/jco.2017.35.15_suppl.e14639.
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e14639 Background: The DPV-001 DRibble is a dendritic cell-targeted microvesicle (proteasome blocked autophagosome) vaccine derived from an adenocarcinoma and a mixed histology cell line. It contains multiple TLR agonists and > 130 potential NSCLC antigens, many as prospective altered-peptide ligands. In preclinical studies, DRibble immunotherapy provided significant anti-cancer effects in a dozen models. We hypothesize that DRibble’ vaccination efficacy can be attributed to their capacity to present tumor-derived short-lived proteins (SLiPs) and defective ribosomal products (DRiPs) that are typically not processed and presented by professional antigen presenting cells and against which the host may be less tolerant. Methods: Pts received induction cyclophosphamide, 7 vaccines every 3-weeks, then every 6 weeks x 4 more doses. Pts were randomized to receive DRibble alone (A), or with I (B) or GM-CSF (C). PBMCs /serum were collected at baseline and at each vaccination to assess changes in antibodies (Ab) (ProtoArray and microsphere affinity proteomics), peripheral lymphocyte populations (flow cytometry) and T cell receptor (TCR) repertoires (Adaptive immunoSEQ). Results: 13 pts were enrolled (Arm A: 5; B: 4; C: 4). We previously reported that vaccination induced or increased IgG Ab responses against targets over-expressed by NSCLC. Patients receiving DPV-001 had a significant (p < 0.04) increase in total (CD4 + CD8) TCRs that increased 10 fold over baseline compared to normal controls (independent from trial, n = 3) and the increase in CD4 clones was similar to that seen following ipilimumab (melanoma pts, independent from trial, n = 9). Analysis of a resected metastasis (progressing on treatment), identified brisk infiltration of T cells and tumor that was strongly PD-L1+. Conclusions: Vaccination with DPV-001 expanded populations of T cells over that observed in controls and the increase in CD4 T cells was similar to that observed in patients receiving ipilimumab and may represent vaccine-reactive T cells. Clinical Trial Identifier: NCT01909752, Support: R44 CA121612 Clinical trial information: NCT01909752.
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Holov, G. A., S. I. Abdijalilova, U. Sh Ganiev, Sh N. Salohidinov i B. M. Shakirov. "Nebivaolol Effect in Patients with Chronic Obstructive Disease of the Lungs". International Journal of Pharmacology, Phytochemistry and Ethnomedicine 1 (grudzień 2015): 74–80. http://dx.doi.org/10.18052/www.scipress.com/ijppe.1.74.
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Introduction: Chronic obstructive disease of the lungs (CODL) is one of the leading cases of morbidity and mortality all over the world. It is one of the causes which may form the basis of sudden death, it serves as disturbance of cardiac contractions rhythm. Aim of the research is to evaluate the effect of adrenoreceptor – nebivaolol by selective blocker β1 on pulmonary hypertension degree in patients with chronic obstructive disease of the lungs. Material and methods: 60 patients with chronic obstructive disease of the lungs of III-IV stage in exacerbation phase were enrolled in the study. The patients were subdivided into 2 groups: group A for comparison (n-25) and group B for study (n=35). The patients of both groups received standard therapy, directed to elimination of inflammatory process and improvement of bronchial permeability: antibiotics, broncholytics, mucolytics. The patients of group B were treated with nebivaolol in the dosage 10 mg 24 hours (5 mg dose 2 times 24 hours) for 14 days. Results: In absence of negative effect on hemodynamic indexes, electrophysiological parameters and sporometric data reveal changes in the rate of cardiac contractions to adequate values and significant increase of tolerance to physical exertion in 2 weeks after taking nebivaolol. Decrease of heart rate correlates with decrease of pulmonary hypertension. Conclusion: Taking into account the received findings nebivaolol can be recommended for treatment of patients with chronic obstructive disease of the lungs and pulmonary hypertension.
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Petersen, Kristian Kjær, Hjalte Holm Andersen, Masato Tsukamoto, Lincoln Tracy, Julian Koenig i Lars Arendt-Nielsen. "The effects of propranolol on heart rate variability and quantitative, mechanistic, pain profiling: a randomized placebo-controlled crossover study". Scandinavian Journal of Pain 18, nr 3 (26.07.2018): 479–89. http://dx.doi.org/10.1515/sjpain-2018-0054.
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AbstractBackground and aimsThe autonomic nervous system (ANS) is capable of modulating pain. Aberrations in heart rate variability (HRV), reflective of ANS activity, are associated with experimental pain sensitivity, chronic pain, and more recently, pain modulatory mechanisms but the underlying mechanisms are still unclear. HRV is lowered during experimental pain as well as in chronic pain conditions and HRV can be increased by propranolol, which is a non-selective β-blocker. Sensitization of central pain pathways have been observed in several chronic pain conditions and human mechanistic pain biomarkers for these central pain pathways include temporal summation of pain (TSP) and conditioned pain modulation (CPM). The current study aimed to investigate the effect of the β-blocker propranolol, and subsequently assessing the response to standardized, quantitative, mechanistic pain biomarkers.MethodsIn this placebo-controlled, double-blinded, randomized crossover study, 25 healthy male volunteers (mean age 25.6 years) were randomized to receive 40 mg propranolol and 40 mg placebo. Heart rate, blood pressure, and HRV were assessed before and during experimental pain tests. Cuff pressure pain stimulation was used for assessment of pain detection (cPDTs) and pain tolerance (cPTTs) thresholds, TSP, and CPM. Offset analgesia (OA) was assessed using heat stimulation.ResultsPropranolol significantly reduced heart rate (p<0.001), blood pressure (p<0.02) and increased HRV (p<0.01) compared with placebo. No significant differences were found comparing cPDT (p>0.70), cPTT (p>0.93), TSP (p>0.70), OA-effect (p>0.87) or CPM (p>0.65) between propranolol and placebo.ConclusionsThe current study demonstrated that propranolol increased HRV, but did not affect pressure pain sensitivity or any pain facilitatory or modulatory outcomes.ImplicationsAnalgesic effects of propranolol have been reported in clinical pain populations and the results from the current study could indicate that increased HRV from propranolol is not associated with peripheral and central pain pathways in healthy male subjects.
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Zabihi, Mohsen, Fatemeh Askarian, Seyed Hossein Hekmati Moghaddam i Majid Rajaee. "Carvedilol: A Promising Drug Combined With Lipid-lowering Medications for Patients With Hypertension and Heart Failure". Iranian Journal of Toxicology 14, nr 4 (1.10.2020): 245–52. http://dx.doi.org/10.32598/ijt.14.4.708.1.
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Background: Statins frequently cause myopathy especially in combination with fibrates, and physical activity is considered a trigger for the muscle disorder. Elevated plasma levels of creatine kinase (CK), lactate dehydrogenase (LDH) and aldolase, are the main indicators of the severity of myopathy. Carvedilol is commonly used with lipid-lowering drugs in the management of heart failure, hypertension and dyslipidemia. It is not yet clear whether carvedilol, an alpha and β blocker, and anti-oxidant, may influence the development of myopathy when combined with statins and fibrates in cardiac patients. Methods: In this animal experiment, a 10 days regimen containing oral atorvastatin and gemfibrozil at doses of 80 and 1000 mg/kg/day, respectively, was used to induce myopathy in rats. The animals were forced to swim in a pool on days 8, 9 and 10 into the study. Carvedilol (2.5 mg/kg/day) was added to atorvastatin and gemfibrozil during the 10-day study period, in addition to the exercise protocol given to the treatment groups only. The mean of swimming tolerance times and the serum levels of CK, LDH and aldolase were measured at the completion of the study. Results: Carvedilol did not significantly alter the swimming tolerance time or the plasma levels of CK, LDH and aldolase in the rats receiving ATV, GMF and carvedilol plus the exercise protocol, compared with those that did not receive carvedilol (P>0.05). Conclusion: Carvedilol may be used in combination with lipid-lowering drug in the management of patients with heart failure and hypertension, pending its safety approval by clinical studies in humans.
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Fahn, Stanley. "Systemic Therapy of Dystonia". Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques 14, S3 (sierpień 1987): 528–32. http://dx.doi.org/10.1017/s0317167100038051.
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ABSTRACT:A number of pharmacologic agents have been found to be effective for the dystonias. Anticholinergic drugs have been shown to be the most effective in terms of percentage of subjects who receive moderate to marked benefit. About 50% of children and 40% of adults obtain such improvement. Peripheral adverse effects are usually overcome by pyridostigmine. It may be necessary to utilize pilocarpine eyedrops for blurred vision. Central adverse effects, such as forgetfulness, can be reduced only by a reduction in dosage of the anticholinergic. In comparing trihexyphenidyl and ethopropazine, we found that children tend to have better tolerance of the former and adults tend to have better tolerance of the latter. The antidopaminergics are the group of drugs that were found to be the next most effective agents in terms of percentage of patients who respond. However, these drugs, particularly the dopamine receptor blockers, have the capacity to induce tardive dyskinesia and tardive dystonia. Tardive syndromes are difficult to treat and can persist indefinitely. Other agents that have shown usefulness in controlling dystonia are levodopa, baclofen, carbamazepine, and the benzodiazepines, either alone or in combination with each other and with the anticholinergics. Stereotactic thalamotomy is particularly useful in contralateral hemidystonia. The risk of adverse effects is less than with bilateral thalamotomy, which may need to be employed when generalized dystonia is severely disabling and not responsive to pharmacotherapy.
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Kushnarenko, N. N., T. A. Medvedeva, M. Yu Mishko i T. M. Karavaeva. "Heart rate-lowering therapy in gout patients with stable coronary artery disease: focus on ivabradine". Russian Journal of Cardiology 25, nr 7 (15.08.2020): 3980. http://dx.doi.org/10.15829/1560-4071-2020-3980.
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Aim. To study the effect of ivabradine and bisoprolol on cardiac hemodynamics and diastolic remodeling in gout patients with coronary artery disease and hypertension and without left ventricular systolic dysfunction.Material and methods. The open randomized parallel clinical trial of 35 men with intercritical gout at the age of 41,4±3,3 years, with class II-III stable angina, hypertension and sinus rhythm without data suggestive of heart failure was performed. All patients included in the study were randomly divided into two groups: eighteen patients took bisoprolol at a dose of 2,5 to 10 mg/day, 17 subjects received bisoprolol 2,5 mg/day with ivabradine (Coraxan, SERVIER, France) 5 mg 2 times a day. Adjustment of the therapy was carried out every 2 weeks until the target heart rate (HR) was reached at 55-60 beats/min and then remained unchanged until 12 weeks of therapy. All patients underwent echocardiography, 24-hour Holter and central aortic blood pressure monitoring, and 3-minute cycle ergometer test with a power of 25, 50, 75 and 100 watts.Results. There was a comparable decrease in the maximum and minimum 24-hour average heart rates in patients receiving only bisoprolol and those taking bisoprolol+ivabradine. Patients taking bisoprolol+ivabradine had a decrease of central systolic and diastolic blood pressure (BP). Pulse pressure in the bisoprolol group increased by 17,7% (p=0,02), and when ivabradine was added, on the contrary, it decreased by 7,0% (p=0,04). Twelve-week therapy with beta-blockers and ivabradine was accompanied by an effective decrease in the pulse wave velocity in both groups (p<0,05). All gout patients did not have a decrease of systolic function and there was an improvement in diastolic remodeling with beta-blockers and ivabradine therapy.Conclusion. The results obtained indicate that the addition of ivabradine to bisoprolol leads to an effective decrease in heart rate, an improvement in arterial stiffness and exercise tolerance. Combination therapy with ivabradine is accompanied by an improvement in clinical outcomes using lower doses of bet-blockers, which requires further study and a double-blind controlled study.
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Ishikawa, H., J. Hayakawa i T. Shiohara. "Cytotoxic T cell responses to minor H-43 alloantigens in H-43a and H-43b mice. Distinctive MHC class I restriction specificity and clonal inactivation are inherent properties of the H-43 system." Journal of Immunology 151, nr 5 (1.09.1993): 2436–43. http://dx.doi.org/10.4049/jimmunol.151.5.2436.
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Abstract Our previous studies demonstrated that CTL responses to the newly identified minor H-43a and H-43b alloantigens induced in H-43b and H-43a responder mice, respectively, utilized the same H-2Kb (Kb) MHC class I restriction element, whereas many allelic class I products were not utilized. Also, a single i.v. injection of H-43b recipient mice with spleen cells (SC) from H-43 congenic mice induced specific and lasting CTL tolerance to H-43a rather than priming. We have produced a H-43b C3H.AU mouse strain (H-2p), which we regard as H-43 congenic to the C3H.NB (H-2p, H-43a) strain. Using this strain we demonstrate that Kp and/or Dp alleles can serve as class 1 restricting elements in the CTL responses to H-43a and H-43b alloantigens. Injection of H-43a recipient mice with antigenic H-43b SC from the paired H-43 congenic abrogated the anti-H-43b CTL response, irrespective of MHC class I specificity, i.e., in the contexts of Kb and of Kp and/or Dp elements. A corresponding result was obtained upon injection of H-43b recipient mice with congenic H-43a SC. The tolerance-inducing capacity of H-43a congenic SC was so strong that injection of these cells into H-43b responders that had previously received immunogenic H-43a SC completely blocked the previously activated Kb-restricted memory CTL activity specific for the H-43a alloantigen.
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An, Qi, Yangchao Huang, Hang Hu, Yu Pan i Huizhu Han. "Energy-Spectrum Efficiency Trade-Off in UAV-Enabled Mobile Relaying System with Bisection-PSO Algorithm". Electronics 11, nr 18 (13.09.2022): 2891. http://dx.doi.org/10.3390/electronics11182891.
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Unmanned aerial vehicle (UAV)-enabled mobile relaying is regarded as an important wireless connectivity component in areas without infrastructure coverage due to its rapid response, strong mobility, and low cost. This paper studies a delay tolerant UAV-enabled mobile relaying system and adopts the load-carry-and-deliver paradigm. The UAV is employed to assist in the information transmission from a ground transmitter to a ground receiver with their direct link blocked. Two kinds of UAV flight trajectories are proposed in this system, i.e., a straight line and circular trajectory. Suppose that the UAV employs time-division duplexing (TDD)-based decode-and-forward (DF) relaying. This paper then aims to maximize the spectrum efficiency (SE) and energy efficiency (EE) in of the UAV-enabled relaying system by jointly optimizing the time allocation, flight speed, and the flying radius of the circular trajectory. Then, we develop an efficient algorithm by leveraging the bisection method and particle swarm optimization (PSO) algorithm. Simulation results show the superiority of the proposed algorithm as compared to other benchmark schemes. In addition, numerical results show that, when the communication distance is 1000 m, the SE and EE performance of the circular trajectory is better than the SLF trajectory when the obstacle height is greater than 300 m. Thus, the height of the obstacle between the communication nodes and the trade-off between the SE and EE should be taken into account when we design the optimal trajectory of the UAV-enabled mobile relaying system.
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Martsevich, S. Yu, E. D. Zharkova, N. P. Kutishenko, Yu V. Lukina, S. N. Tolpygina, V. P. Voronina i A. V. Zagrebelnyy. "An Attempt to Accord the Quality of Therapy of Stable Coronary Heart Disease Patients with Current Clinical Guidelines (ALIGN study): Design and the First Results". Rational Pharmacotherapy in Cardiology 16, nr 1 (2.03.2020): 75–81. http://dx.doi.org/10.20996/1819-6446-2020-02-08.
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Aim. To assess the quality of therapy in stable coronary heart disease (CHD) patients, who first sought consultation in the specialized cardiology department of the research center, and try to adjust the therapy in accordance with current clinical guidelines, paying special attention to achieving the target levels of blood pressure, low-density lipoprotein cholesterol (LDL), and glycosylated hemoglobin (in patients with diabetes mellitus), increasing exercise tolerance and improving the quality of life (QL).Material and methods. The ALIGN study is an integral part of the PROFILE outpatient registry. ALIGN study included all patients with verified coronary heart disease who came for consultation to the specialized institution for the first time or for the first time in more than the last 3 years. Patients have been recruited from December 01, 2017 to December 31, 2019. The study consisted of 4 visits: the first-time visit – inclusion in the study (V0), when drug therapy, QL, and adherence were evaluated, and therapy correction was made in accordance with clinical guidelines. In 3 months (V1) the target values of clinical and laboratory parameters were estimated. The third visit (V2) was planned to take place 1 year after the first visit with reevaluation of QL and patients' adherence to treatment, and effectiveness of the therapy. The fourth visit (V3)/telephone contact was planned in 2 years after the first visit to assess life status, get information about complications and therapy.Results. 389 people were included in the PROFILE registry for the specified period of time, 79 had a verified diagnosis of CHD, and 71 patients were included in the ALIGN study: 55 men (aged of 68.7±8.96 years) and 16 women (aged of 67.5±8.08 years). Arterial hypertension was registered in 90.1% of patients, stable angina class I-III – in 62%, 47.9% of patients had a history of acute myocardial infarction (AMI), 52.1% had percutaneous coronary intervention, 15.5% of patients had coronary artery bypass graft, chronic heart failure was detected in 40.8%, diabetes mellitus – in 21.1%, atrial fibrillation – in 15.5% of patients. Lipid-lowering drugs were taken by 53 (74.6%) patients, but only 21 (29.6%) achieved the target values of LDL cholesterol. Angiotensin-converting enzyme inhibitors were taken by 34 patients (47.9%), and angiotensin receptor blockers by 15 (21%) of patients, 47 (66.2%) patients took beta-blockers, antiplatelet agents were taken by 61 people, and anticoagulants by 10 patients. Patients who had a history of AMI had been prescribed BB in 88%, statins – in 90%, and renin-angiotensin-aldosterone system (RAAS) blockers – in 80% of cases.Conclusions. Initial quality of therapy for patients with stable CHD did not fully match the clinical guidelines: a quarter of patients did not receive lipidlowering therapy, and target levels of LDL cholesterol were achieved only in one third of patients. Among patients who had a history of AMI, every fifth patient did not receive RAAS blockers.
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Tran, Johnson Q., Marcus O. Muench i Rachael P. Jackman. "Pathogen-reduced PRP blocks T-cell activation, induces Treg cells, and promotes TGF-β expression by cDCs and monocytes in mice". Blood Advances 4, nr 21 (9.11.2020): 5547–61. http://dx.doi.org/10.1182/bloodadvances.2020002867.
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Abstract Alloimmunization against platelet-rich plasma (PRP) transfusions can lead to complications such as platelet refractoriness or rejection of subsequent transfusions and transplants. In mice, pathogen reduction treatment of PRP with UVB light and riboflavin (UV+R) prevents alloimmunization and appears to induce partial antigen-specific tolerance to subsequent transfusions. Herein, the in vivo responses of antigen-presenting cells and T cells to transfusion with UV+R-treated allogeneic PRP were evaluated to understand the cellular immune responses leading to antigen-specific tolerance. Mice that received UV+R-treated PRP had significantly increased transforming growth factor β (TGF-β) expression by CD11b+ CD4+ CD11cHi conventional dendritic cells (cDCs) and CD11bHi monocytes (P < .05). While robust T-cell responses to transfusions with untreated allogeneic PRP were observed (P < .05), these were blocked by UV+R treatment. Mice given UV+R-treated PRP followed by untreated PRP showed an early significant (P < .01) enrichment in regulatory T (Treg) cells and associated TGF-β production as well as diminished effector T-cell responses. Adoptive transfer of T-cell–enriched splenocytes from mice given UV+R-treated PRP into naive recipients led to a small but significant reduction of CD8+ T-cell responses to subsequent allogeneic transfusion. These data demonstrate that pathogen reduction with UV+R induces a tolerogenic profile by way of CD11b+ CD4+ cDCs, monocytes, and induction of Treg cells, blocking T-cell activation and reducing secondary T-cell responses to untreated platelets in vivo.
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Rakhimova, Idaliya, Talgat Khaibullin, Yerbol Smail, Zhanar Urazalina, Vitalii Koval`chuk i Ayan Abdrakhmanov. "Home Management of the Device Detected Atrial Fibrillation during COVID-19 Pandemic: A Case Report". Open Access Macedonian Journal of Medical Sciences 9, nr C (20.09.2021): 170–73. http://dx.doi.org/10.3889/oamjms.2021.6687.
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BACKGROUND: Patients with heart failure (HF) and implanted heart devices constitute a vulnerable category during the coronavirus disease –2019 (COVID-19) pandemic. The remote monitoring function allows the physician to detect atrial fibrillation (AF) in these patients and to prevent thromboembolic complications by prescribing anticoagulants. Under quarantine conditions, such patients can receive fully remote consultation and treatment, which will protect them from the risk of infection, and also reduce the burden on medical institutions. CASE REPORT: A 56-year-old man presented to the clinic with shortness of breath when climbing the second floor, moderate non-specific fatigue, general weakness, and a decrease in exercise tolerance. The patient received standard treatment for HF for at least 3 months (ACEI, beta blockers, MR antagonists, and loop diuretics) in individually selected adequate doses. ECG on admission showed a QRS of 150 ms, left bundle branch block (LBBB). Echo showed dilatation of all heart chambers, diffuse hypokinesis of the walls with akinesis of the apical, middle anterior LV segments, as well as hypokinesis of the basal, middle apical, and anterior septal segment of the LV. The ejection fraction was reduced to 35%. RV function is reduced. After a detailed discussion with the team, it was decided to do implantation of a cardioverter-defibrillator with resynchronization function, equipped with remote monitoring (Biotronik, and Home monitoring). Date of implantation is June 19, 2014. Due to the fact that the patient was connected to the remote monitoring system, May 5, 2020, he was diagnosed with asymptomatic AF. The episode lasted 1 min 22 s. On the following days of monitoring, episodes of AF were also recorded. The duration of the episodes ranged from a few seconds to 12 h/day. The patient received a doctor’s consultation through phone call, his risk of stroke was four when assessed using the CHA2DS2VASc scale. In treatment, it was recommended to add antiarrhythmic drugs (amiodarone 600 mg a day) and oral anticoagulants (rivaroxaban 20 mg × 1 time/day). Later, periodic IEGM showed absence of AF. CONCLUSION: In the context of the COVID-19 pandemic, health-care providers should rethink their approach to managing patients with implanted heart devices. Modern cardiovascular implantable electronic devices allow the physician to monitor the status of patients and immediately respond to situations requiring a change in treatment. Consultations can be carried out completely online.
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Rakhimova, Idaliya, Talgat Khaibullin, Yerbol Smail, Zhanar Urazalina, Vitalii Koval`chuk i Ayan Abdrakhmanov. "Home Management of the Device Detected Atrial Fibrillation during COVID-19 Pandemic: A Case Report". Open Access Macedonian Journal of Medical Sciences 9, nr C (20.09.2021): 170–73. http://dx.doi.org/10.3889/oamjms.2021.6687.
Pełny tekst źródłaStreszczenie:
BACKGROUND: Patients with heart failure (HF) and implanted heart devices constitute a vulnerable category during the coronavirus disease –2019 (COVID-19) pandemic. The remote monitoring function allows the physician to detect atrial fibrillation (AF) in these patients and to prevent thromboembolic complications by prescribing anticoagulants. Under quarantine conditions, such patients can receive fully remote consultation and treatment, which will protect them from the risk of infection, and also reduce the burden on medical institutions. CASE REPORT: A 56-year-old man presented to the clinic with shortness of breath when climbing the second floor, moderate non-specific fatigue, general weakness, and a decrease in exercise tolerance. The patient received standard treatment for HF for at least 3 months (ACEI, beta blockers, MR antagonists, and loop diuretics) in individually selected adequate doses. ECG on admission showed a QRS of 150 ms, left bundle branch block (LBBB). Echo showed dilatation of all heart chambers, diffuse hypokinesis of the walls with akinesis of the apical, middle anterior LV segments, as well as hypokinesis of the basal, middle apical, and anterior septal segment of the LV. The ejection fraction was reduced to 35%. RV function is reduced. After a detailed discussion with the team, it was decided to do implantation of a cardioverter-defibrillator with resynchronization function, equipped with remote monitoring (Biotronik, and Home monitoring). Date of implantation is June 19, 2014. Due to the fact that the patient was connected to the remote monitoring system, May 5, 2020, he was diagnosed with asymptomatic AF. The episode lasted 1 min 22 s. On the following days of monitoring, episodes of AF were also recorded. The duration of the episodes ranged from a few seconds to 12 h/day. The patient received a doctor’s consultation through phone call, his risk of stroke was four when assessed using the CHA2DS2VASc scale. In treatment, it was recommended to add antiarrhythmic drugs (amiodarone 600 mg a day) and oral anticoagulants (rivaroxaban 20 mg × 1 time/day). Later, periodic IEGM showed absence of AF. CONCLUSION: In the context of the COVID-19 pandemic, health-care providers should rethink their approach to managing patients with implanted heart devices. Modern cardiovascular implantable electronic devices allow the physician to monitor the status of patients and immediately respond to situations requiring a change in treatment. Consultations can be carried out completely online.
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Espínola, Silvio. "Type IV hypersensitivity to timolol". International Journal of Cosmetics and Dermatology 1, nr 1 (25.06.2021): 10–11. http://dx.doi.org/10.55124/ijcd.v1i1.81.
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Glaucoma is the leading cause of irreversible blindness in the world. Currently, glaucoma affects more than 60 million people and it is expected to reach 76 million by 2020 (1).
Introduction
Glaucoma is the leading cause of irreversible blindness in the world. Currently, glaucoma affects more than 60 million people and it is expected to reach 76 million by 2020.1
There are two kinds of chronic glaucoma:
Open-angle glaucoma
Closed-angle glaucoma 2
Glaucoma is characterized as an optic neuropathy determined by structural changes and functional deficiencies. Primary glaucoma (open-angle) is the most prevalent in the general population (40-80 years 3-4%), and it constitutes the leading cause of irreversible vision loss in industrialized countries.3
Current pharmacological treatments seek to obtain optimal local tolerance, using preservative-free formulations in simple presentations or combinations, both in single-dose and multi-dose.
Contact dermatitis is caused by an ample inflammation which arises from the release of pro-inflammatory cytokines from keratinocytes, usually in response to chemical stimuli. Mainly, this causes alteration of the skin barrier, cellular changes at the epidermal level, and release of cytokines.4
Allergic contact dermatitis caused by eye medication is mainly attributed to active ingredients. But other excipient ingredients should also be analyzed in addition to the products on an "as is" basis.5
There is an entity called the Ocular Pharmacological Intolerance Syndrome (SIFO, in Spanish), which is an intolerance to the drop-based treatment for glaucoma which causes: conjunctival hyperemia, itching, sensation of foreign body presence, light sensitivity, lacrimation, and blepharitis. Exceptionally, these symptoms could also be present: superficial keratitis, deposits on the cornea, palpebral swelling, and blurred vision. SIFO in some of its degrees can also be caused by other topical drugs such as dyes, anesthetics, antibiotics, anti-inflammatories, antivirals, etc.
This paper presents a case of allergic contact dermatitis in a patient sensitized to timolol present in the ophthalmic preparations the patient used as a treatment for glaucoma.
Clinical Case
The patient is a 37-year-old male who was diagnosed 2 years ago with bilateral primary open angle glaucoma (POAG), with prescription of dorzolamide and a topical ß-adrenergic blocker (timolol) in drops, twice a day. In August of 2019, the patient seeked medical help for conjunctival hyperemia, itching, and inflammation of the eyelids of both eyes followed by erythematous dermatitis, which improved once the treatment was suspended. These symptoms repeated when the drug was used.
The patient was known to be hypertensive and received treatment with enalapril 10 mg and Aspirin 125 mg. The patient was not known to be asthmatic or allergic to drugs, nor was he known to be diabetic.
Thinking of a hypersensitivity reaction, a provocation test with timolol was performed and there was no immediate reaction. Then, provocation tests were performed, first with enalapril and later with aspirin. Both were negative for an immediate hypersensitivity reaction. Given the clinical situation of the patient and the risk of being without treatment, the patient was suggested to consult his ophthalmologist to look for another alternative treatment. While waiting for a response, the patient received the patch test with all the prescribed active ingredients of the drug used, through drops; The results were negative in the reading at 48 hours. At 96 hours the patient was called, who for work reasons could not attend the clinic, clarifying however that there had been no changes. After 7 days he was screened at the clinic, and no changes were found. In some cases where different beta-blockers for ophthalmic use are tested, and which have caused dermatitis in the eyelid area, negative results can be observed in the patch test. This occurs because the skin of the eyelids has greater penetrability than the skin of the back, where skin patches are usually applied.6,7 This would explain why the epicutaneous tests were negative for this patient, and the conjunctival provocation tests were positive.
Subsequently, provocation tests were performed using the provocation technique with increasing dilutions of 1/1000, 1/100, 1/10 and concentrated. As first dose tears were used as placebo, checking every 15 minutes the pulse of the patient as well as the pressure, the presence of pruritus, irritation, erythema, chemosis and epiphora. The patient remained in the hospital from 2 pm to 8 pm and the provocation was negative. The patient returned after 24 hours, and the provocation was once again negative. At 48 hours the reactions were positive (timolol maleate 0, 5%), with irritation, tearing, chemosis, and erythema in both eyelids.
Discussion
There are numerous substances contained in ophthalmic preparations responsible for producing true allergic contact reactions. The most important group responsible for this frequency is constituted by antimicrobial agents, and preservatives such as thimerosal, benzyl alcohol, benzalkonium chloride (BAC), ethylenediamine and parabens, among others.8,9
In recent years, there have been reports of contact dermatitis due to beta-blockers used in the treatment of glaucoma such as timolol 10, levobunolol 11, carteolol 12 or betaxolol 13. In all cases, eczematous-like reactions on the eyelids, blepharoconjunctivitis, itching with inflammation and edema, conjunctival chemosis, and blurred vision manifested with different intensity.
Timolol is a non-selective beta-blocker commonly more preferred than other agents in terms of efficacy, adverse effects, and cost. Its topical application can produce a foreign body sensation, pruritus, conjunctivitis and in some instances contact dermatitis.14
Several authors have suggested the possible existence of cross reactions between the different beta-blockers 15,16, so that the replacement of the drug involved in sensitization by another one from the same family would not proceed.
Although there are many medications and ophthalmic products which can cause adverse effects at the ocular level, fortunately in most cases these adverse effects reverse once the medication is discontinued.
However, when these adverse effects are not detected early, some reactions can prolong causing irreversible eye damage.17
Bibliography
Patch test with timolol alone, timolol dorzolamide and excipients, enalapril and ASA
Negative patch test at 72 hours
Positive conjunctival provocative test at 48 hours
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Hryvusevich, Palina V., Veranika V. Samokhina i Vadim V. Demidchik. "Stress-induced electrolyte leakage from root cells of higher plants: background, mechanism and physiological role". Experimental Biology and Biotechnology, nr 2 (12.07.2022): 4–18. http://dx.doi.org/10.33581/2957-5060-2022-2-4-18.
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Electrolyte leakage from tissues is one of the central reactions of the plant organism to stress. It is observed under almost any type of stresses, both abiotic and biotic. The loss of key electrolytes can lead to significant changes in metabolism and, in some cases, to the death of cells or the whole organism. For a long time, it was believed, that electrolyte leakage is associated with disruption of cell integrity and plasma membranes degradation, and that it is an unregulated process. However, in recent years, a lot of evidence has been received that, in most cases, electrolyte leakage is inhibited by ion channel blockers and reversible. It means that it is associated with the transfer of ions through the membrane by transport proteins, such as ion channels. Recently, the experimental evidence has been obtained, that under salinity, drought, pathogen attack, excessive levels of heavy metals, hypo- and hyperthermia, as well as oxidative stress, the electrolyte leakage in plant cells is mediated by several types of cation and anion channels, including K+-selective channels (SKOR and GORK), anion channels (such as ALMT1) and a number of non-selective cation channels. It has been demonstrated that the primary reactions that induce electrolyte leakage are plasma membrane depolarisation and generation of reactive oxygen species, leading to the activation of redox-regulated outwardly rectifying K+ channels, such as SKOR and GORK. Potassium efflux is up-stream and stimulates the counterion flow (transport of anions) through the anion channels. The regulation of electrolyte leakage at the ion channel level and the corresponding selection for ion channel properties can become an important link in the directed control of stress resistance in higher plants. This can be applied in agriculture via breeding of stress-tolerant plant varieties, as well as developing modern amelioration techniques.
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Dadashova, G. M. "Gender differences of response to various options of drug therapy in patients with chronic heart failure after suffered myocardial infarction". Kazan medical journal 97, nr 1 (15.02.2016): 17–25. http://dx.doi.org/10.17750/kmj2016-17.
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Aim. To evaluate gender features of treatment in patients with chronic heart failure who suffered myocardial infarction, determine the effect of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers II, as well as antidepressants in the clinico-functional and psycho-emotional status, morphological and functional parameters of the heart in the treatment of men and women with this pathology.Methods. The study included 205 men and 185 women with chronic heart failure after suffering a myocardial infarction. Patients were randomized into three groups. Patients of the first group (80 men and 70 women) received background treatment (cardiac glycosides, diuretics, aldosterone antagonists, prolonged nitrates if necessary, acetylsalicylic acid, atorvastatin and perindopril 5-10 mg/day. The patients of the second group (80 men and 70 women) received valsartan 80-160 mg/day in addition to the above-noted background treatment. In the therapeutic regimen of the third group of patients (45 men and 45 women) sertraline in a dose of 50 mg/day was included in addition to background treatment. All the patients underwent usual methods of general clinical examination, the 6-minute walk test, clinical status evaluation, the anxiety syndrome severity assessment using a Hamilton scale, echocardiography. The patients dynamic monitoring was carried out for 6 months.Results. The study results showed that provided therapy has comparable clinical effect in both men and women in all three groups. Statistically significant improvement in clinical condition indicators was reported and as a result, exercise tolerance increased. At the same time the quality of life improvement was more pronounced (p <0.001) in patients of the third group, amid the perindopril and sertraline use. According to the results of our study in patients of all three groups provided therapy has a comparable positive effect on echocardiography indicators, including those which characterize left ventricular hypertrophy.Conclusion. Amid the provided treatment in all three groups positive dynamics of clinical status indicators and intracardiac dynamics was reported; in addition to that the dynamics of both clinical status and linear and volumetric heart parameters was more pronounced amid the treatment with perindopril in combination with sertraline.
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Rofieva, H. Sh. "Efficiency of nitrate oxide donor Tivortin in women with post-infarction cardiosclerosis in the perimenopausal period with heart failure". Infusion & Chemotherapy, nr 3.1 (11.10.2020): 93–94. http://dx.doi.org/10.32902/2663-0338-2020-3.1-78.
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Objective. To study the effectiveness of the effect of L-arginine in women in the perimenopausal period with post-infarction cardiosclerosis with manifestations of heart failure.
Materials and methods. The study included 135 women who were hospitalized at the age from 45 to 60 years. All patients were divided into two groups: group I consisted of 80 women (mean age ‒ 45.1±6.6 years) in the perimenopausal period; group II included 55 women (mean age ‒ 60.6±4.6 years) in the postmenopausal period. The functional state of the heart was investigated by the echo-Doppler method. Treatment and observation continued for 3 months. To identify the effectiveness of the therapy was assessed by monthly echo-Doppler sonography. The first group, against the background of basic therapy (nitrates, β-blockers, antiplatelet agents, statins), additionally received the drug L-arginine 4.2 % (Tivortin) solution of 100 ml intravenously drip for 7-8 days, followed by 5 ml (1 g) 3 times per day inside within 3 months. The second group received only the main therapy without the use of L-arginine.
Results. When conducting a comparative assessment of the structural and functional indicators of the heart in women of the first group, it showed that against the background of the main therapy when receiving the drug L-arginine 4.2 % solution 100 ml intravenously before and after treatment were as follows: left atrium size ‒ 5.13±0.18 up to, 4.61±0.14 after; the size of the right ventricle ‒ 3.11±0.01 up to, 2.90±0.08 after; thickness of the interventricular septum ‒ 1.42±0.05 up to, 1.34±0.04 after; posterior wall thickness of left ventricle ‒ 1.38±0.04 up to, 1.34±0.04 after; index of left ventricle myocardial mass ‒ 127.0±5.4 up to, 112.0±4.7 after; end diastolic volume ‒ 144±0.80 up to, 122.0±6.4 after; minute volume ‒ 4.36±0.20 up to, 5.30±0.20 after; ejection fraction ‒ 48 % up to, 52 % after; stroke volume ‒ 54 ml up to, 62 ml after. Clinically noted an increase in exercise tolerance, a decrease in the frequency of nitrate intake and an improvement in the quality of life.
Conclusions. In women of group 1, against the background of basic therapy with the addition of L-arginine 4.2 %, the functional class of heart failure decreases from II to I, the indicators of diastolic filling of the left ventricle are normalized, and the incidence of repeated myocardial infarction decreases.
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Kaliks-Guendelmann, R., P. Santi, A. Cardoso i A. Del Giglio. "Complete androgen blockade as second-line hormone manipulation and delay of chemotherapy in metastatic prostate cancer". Journal of Clinical Oncology 27, nr 15_suppl (20.05.2009): e16141-e16141. http://dx.doi.org/10.1200/jco.2009.27.15_suppl.e16141.
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e16141 Background: Complete androgen blockade (CAB) after failure of castration or androgen receptor blocker (ARB) has not shown to prolong survival in patients with metastatic prostate cancer, unlike docetaxel-based chemotherapy. The widely variable clinical benefit seen with CAB as second-line hormone manipulation still justifies the identification of the patients to whom it should be offered. Objective: to evaluate progression-free survival (PFS) and overall survival (OS) in patients treated with CAB after failure of castration or ARB and to identify clinical predictors of benefit. Methods: We performed a retrospective analysis of all patients with metastatic prostate cancer treated with CAB as second-line hormone manipulation in a single institution after September 2005. OS and PFS were estimated using Kaplan-Meyer plots. We identified 78 patients and evaluated correlations of prostate specific antigen (PSA), Gleason scores, age, type and length of first-line hormone manipulation with OS and PFS during CAB. Fifty-four patients had failed castration and 24 had failed ARB. Forty-four patients received chemotherapy after failing CAB. Results: With a median follow-up of 21 months, median PFS with CAB was 12 months (CI 6.8–17.2). We did not find any correlation of PFS with type of first-line hormone manipulation (castration vs ARB, p = 0.10), age group (≤70 or >70 years old, p = 0.10), level of PSA at diagnosis (≤50 or >50 ng/mL, p = 0.17) or length of first-line hormone manipulation (≤14m vs >14 m, p = 0.78). There was no significant correlation between PFS and Gleason score at diagnosis (score ≤7 or >7, p = 0.25), nor between the level of testosterone at the beginning of CAB and PFS. Median OS for patients on CAB after failing castration was 36 months (CI 24–48), and median OS of patients on chemotherapy was not reached at 9.5 months follow-up. Conclusions: Based on a PFS of 12 months, OS of 36 months and good patient tolerance, we believe CAB should still be used in CRPC, prior to initiation of chemotherapy. Predictors of clinical benefit are still to be identified. No significant financial relationships to disclose.
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Kapsargin, F. P., V. S. Saenko, V. M. Troyakov, L. F. Zueva, N. S. Tikhomirov, D. G. Golubeva i E. Yu Khlebnova. "The role of herbal preparations in lithokinetic therapy and metaphylaxis of urolithiasis". Experimental and Сlinical Urology 14, nr 2 (29.06.2021): 92–98. http://dx.doi.org/10.29188/2222-8543-2021-14-2-92-98.
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Relevance. Urolithiasis is still one of the most widespread and actively progressing diseases. The high incidence of complications from taking chemical drugs has become the main reason for the change in attitudes towards herbal medicines, and now the treatment with herbal medicines is returning again, revealing its benefits based on evidence-based medicine. Phytochemicals have a positive effect on the gut microbiome and are widely used to prevent and treat obesity, liver, intestinal and inflammatory diseases. Materials and methods. The study involved 100 patients with a verified diagnosis of urolithiasis aged 25 to 78 years. The first group included 30 patients who underwent 1-2 sessions of extracorporeal lithotripsy (EBL) or percutaneous nephrolithotripsy (PCNL) for kidney stones up to 20 mm in size. The second group included 70 patients who were diagnosed with calculus during outpatient examination based on ultrasound and X-ray examinations. Each patient group was randomly divided into 2 subgroups. Patients of the subgroup A - A1 and A2 received standard lithokinetic therapy - α-blockers, antispasmodics, adherence to daily urine output of at least 2 liters per day, if necessary, analgesic therapy with non-steroidal anti-inflammatory drugs. Patients of the subgroup B - B1 and B2 received a similar therapy with the addition of dietary supplements Nereus . During the observation period, an assessment of daily diuresis, fluctuations in the pH level of urine, clinical and laboratory studies of biochemical parameters of blood and daily urine, general clinical blood and urine tests, urine culture for flora and the degree of bacteriuria were carried out. To assess the severity of the pain symptom, a 10-point visual analogue pain scale (VAS) was used. Re-examination was performed after 1 and 3 months of treatment. Results. The use of the combined herbal preparation Nereus in lithokinetic therapy and metaphylaxis of urolithiasis reduces the need for analgesic and antispasmodic therapy, promotes an increase in urine output by 37%, maintains urine pH at physiological values, effectively reduces the level of leukocyturia and bacteriuria, accelerates the passage of stones and their fragments from various parts of the urinary tract. In all patients who took the herbal preparation Nereus , there were no undesirable or side effects affecting the quality of life of patients. Conclusions. The study of the efficacy and safety of the drug Nereus in lithokinetic therapy and metaphylaxis of urolithiasis showed a significant effect of the phytocomplex on increasing urine output, eliminating the infectious-inflammatory process and passing stones from the urinary tract, good tolerance and absence of side effects.