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Biochar derived from pomegranate peel at different pyrolysis temperatures (450, 600, and 850 °C) was synthesized and characterized by BET, XRD, FTIR, and SEM-EDX. Its catalytic efficiency in the degradation of the antihypertensive losartan (LOS) in the presence of sodium persulfate was examined. The biochar pyrolyzed at 850 °C exhibited higher catalytic activity, which was correlated with the greater surface area and higher concentration of minerals on its surface. Interestingly, despite adsorption being favored at alkaline pH, pH 3 showed the highest LOS degradation. LOS decomposition followed pseudo-first-order kinetics. The addition of persulfate significantly increased LOS reduction, while the presence of inorganic and organic water matrix constituents such as sodium chloride, bicarbonate, and humic acid inhibited the oxidation. Experiments conducted with radical scavengers revealed that both hydroxyl and sulfate radicals, as well as singlet oxygen, participated in LOS decomposition, with the former being the dominant species. Using a continuous flow reactor, the system exhibited a satisfactory steady-state performance of 90% LOS removal for 114 h. Afterward, a moderate decrease in performance was observed, which can be attributed to the alteration of the catalyst's surface and mineral dissolution due to acidity. [ABSTRACT FROM AUTHOR]

This paper outlines a precise, swift, and convenient spectrophotometric method based on the continuous wavelet transform methodology for the estimation of losartan potassium and hydrochlorothiazide in tablets. The continuous wavelet transform method is based on the use of DMeyer (DMEY-CWT). When the original UV spectra of losartan potassium and hydrochlorothiazide are studied, it is clear that their spectra closely overlap. The analysis was completed successfully without any pre-separation using the created DMEY-CWT approach. The calibration equations for losartan potassium measurement and hydrochlorothiazide determination were obtained at 257.6 nm and 268.4 nm for losartan potassium, 250.1 nm and 263.8 nm for hydrochlorothiazide. The developed approaches were evaluated for their validity and practicality. [ABSTRACT FROM AUTHOR]

In the current study, matrices of losartan potassium were formulated with two different polymers (Ethocel 10 premium and Ethocel 10FP premium), along with a filler and a lubricant, at different drug-to-polymer w/w ratios (10:3, 10:4, and 10:5). The matrices were tested by the direct compression method, and their hardness, diameter, thickness, friability, weight variation, content uniformity, and in vitro dissolution tests were assessed to determine 24-h drug release rates. The matrices with Ethocel 10 FP at a 10:4 ratio exhibited pseudo-zero-order kinetics (n-value of 0.986), while the dissolution data of the test matrices and reference tablets did not match. The new test-optimized matrices were also tested in rabbits, and their pharmacokinetic parameters were investigated: half-life (11.78 ± 0.018 h), Tmax (2.105 ± 1.131 h), Cmax (205.98 ± 0.321 μg/mL), AUCo (5931.10 ± 1.232 μg·h/mL), AUCo-inf (7348.46 ± 0.234 μg·h/mL), MRTo-48h (17.34 ± 0.184 h), and Cl (0.002 ± 0.134 mL/min). A correlation value of 0.985 between the in vitro and in vivo results observed for the test-optimized matrices was observed, indicating a level-A correlation between the percentage of the drug released in vitro and the percentage of the drug absorbed in vivo. The matrices might improve patient compliance with once-a-day dosing and therapeutic outcomes. [ABSTRACT FROM AUTHOR]

A sensitive and robust method for determination and quantification of potential genotoxic impurities in sartans has been developed. These impurities need to be controlled at trace levels during quantification in drug substances and drug products for safe consumption. Recent regulatory requirements also suggested the need to have highly sensitive analytical method for trace level quantification of nitrosamine impurities. In this paper, we have described a simple, rapid and sensitive liquid chromatography-mass spectrometry method for six potential genotoxic nitrosamine impurities: N-Nitroso dimethyl amine (NDMA), N-Nitroso diethyl amine (NDEA), N-Nitroso Ethyl Iso propylamine (NIPEA), N-Nitroso-Nmethyl-4-aminobutyric acid (NMBA) N-Nitroso diisopropylamino (NDIPA) and N-Nitroso dibutyl amine (NDBA) in Azilsartan (AZL), Valsartan (VAL), Telmisartan (TEL), Olmesartan (OLM), Losartan (LOS) and Irbesartan (IRB) with a limit of quantification of less than 0.003 ppm. Chromatographic separation is achieved using Poroshell HPH- C18, 150 × 4.6 mm, 2.7 μm column with 0.1% formic acid in water as mobile phase A and 0.1% formic acid in methanol as mobile phase B at a flow rate of 0.5 mL/min using gradient mode of elution at a total run time of 20 min. Six nitrosamine impurities are ionized and quantified in positive mode of atmospheric pressure chemical ionization using multiple reaction monitoring. As per ICH guidelines, method validation is performed and evaluated the limit of quantification and detection and found to give good S/N ratios with good linearity range of 0.003–0.045 ppm with regression coefficient > 0.999 for all the six nitrosamine impurities. Method recoveries are also established using three-step sample preparation and are found to be satisfactory within 80–120%. The single method can be used routinely applied for the detection of nitrosamines in AZL, VAL, TEL, OLM, LOS and IRB. [ABSTRACT FROM AUTHOR]

This study aims to develop and test a topical drug delivery system for antihypertensive activity using Losartan potassium-loaded niosomes. The niosomes were created using the traditional ether injection approach, with four formulations made using cholesterol as the lipid and varying quantities of surfactants such as span 80 and span 60. The different formulations underwent testing for FTIR, particle size, zeta potential, drug content, entrapment efficiency, and in vitro release. FTIR analysis revealed that the medication was incompatible with excipients. The study concludes by highlighting current obstacles and future possibilities for the development of niosomes as effective vehicles. Overall, this analysis provides insight into the potential of niosomes in medication delivery and encourages further research in this field. [ABSTRACT FROM AUTHOR]

In this research, sponge‐activated carbon was applied as an effective adsorbent for simultaneous dispersive solid ultrasound‐assisted microextraction followed by high‐performance liquid chromatography for the preconcentration and determination of losartan (LOS) and chlordiazepoxide (CDP) drugs from urine and plasma samples. The synthesized adsorbent was characterized using scanning electron microscopy and Brunauer–Emmett–Teller techniques. To investigate the effects of different parameters, such as adsorbent dosage, pH, adsorption time, and volume of extraction solvent on the extraction process of LOS and CDP, a central composite design (CCD)‐based response surface methodology was applied. Using a CCD, the optimized factors achieved an adsorption time of 13 min, an adsorbent dosage of 14 mg, an extraction solvent (methanol) of 1.3 mL, and pH = 4.7 under the desirability function. Under the optimized conditions, the presented method showed a wide linear range of 0.005–10.0 μg/mL with a limit of detections of 0.0011 and 0.0018 μg/mL for LOS and CDP, respectively. Moreover, the applied method had relative standard deviations of 4.7% and 5.3% for LOS and CDP, respectively. [ABSTRACT FROM AUTHOR]

Background: Keloid is a skin disorder that results from excessive fibrous tissue growth in the area of the initial trauma. Treating keloids can be challenging since the success of various treatments varies from one study to another. Triamcinolone acetonide injection, a standard treatment, can cause undesirable side effects. Meanwhile, the effectiveness of existing topical therapies for keloids is not always reliable. The pro-inflammatory, pro-proliferative, and pro-fibrotic effects of angiotensin II in human skin contribute to keloid formation. Losartan potassium, an angiotensin II blocker, has the potential to act as an anti-keloid agent. Due to the thicker skin structure of a keloid and ease of application, ethosome gel is chosen as a safe and comfortable carrier for losartan potassium, making it a good choice for treating keloids. Methods: In this randomised clinical trial, 46 adults with keloids were divided into two treatment groups. One group of 23 participants received 5% losartan potassium loaded in ethosomal gel, while the other group of 23 participants received intralesional injections of 10% triamcinolone acetonide. Over 12 weeks, changes in POSAS 3.0 scores, degree of erythema and pigmentation, surface area, thickness, and pliability of the keloids will be measured at four different times: baseline, 4 weeks, 8 weeks, and 12 weeks. Statistical analysis will be conducted using SPSS software version 24, with a significance level of p < 0.05. Discussion: Losartan potassium is believed to be beneficial for keloid management because it inhibits the angiotensin II receptor, which plays a role in inflammation, proliferation, and fibrosis. This study examines the efficacy of 5% losartan potassium loaded in ethosomal gel for human keloids. Trial registration: Clinicaltrial.gov identifier NCT05893108. Registered on 7 June 2023. [ABSTRACT FROM AUTHOR]

Interleukin‐2 (IL‐2) is one of the first FDA‐approved immunotherapeutics, but its use is limited by toxicity and low efficacy. In addition, all immunotherapies are limited by the immunosuppressive and desmoplastic microenvironment of "immunologically cold" tumors, such as pancreatic ductal adenocarcinoma (PDAC) or hepatocellular carcinoma (HCC) with advanced liver fibrosis. Here, a new chemoimmunotherapy nanogel (IL2‐Pt@Nanogel) for dual delivery of IL‐2 and the type II immunogenic cell death inducer Pt‐NHC that reduces the immunosuppressive phenotype of tumor‐associated macrophages and diminishes regulatory T cell infiltration by inducing the production of type I interferon (IFN) by cancer cells is reported. Combining the angiotensin II receptor blocker losartan with IL2‐Pt@Nanogel treatment reduces desmoplasia and reprogrammes the microenvironment of PDAC and HCC toward an immunostimulatory one. These effects result in potent anti‐tumor efficacy in models of primary and metastatic PDAC and HCC with underlying liver fibrosis. This study presents a strategy for IL‐2‐based chemoimmunotherapy with the potential for clinical translation to treat solid tumors. [ABSTRACT FROM AUTHOR]

Pharmaceutical pollutants are considered emerging contaminants, representing a significant concern to the ecosystem. Thus, this study reports on the degradation of antihypertensive and cardiovascular drugs (atenolol, captopril, propranolol hydrochloride, diosmin, hesperidin, losartan potassium, hydrochlorothiazide, and trimetazidine) present in simulated wastewater through applying the technology of oxidation using supercritical water (SCW). The operational parameters of the treatment process, particularly the feed flow rate, temperature, and concentration of H2O2, were assessed. A central composite design of experiments associated with differential evolution was employed in the optimization. Both liquid and gaseous phase products were submitted to physical–chemical characterization. As a result, the optimized conditions for the treatment were discovered to be a feed flow rate of 13.3 mL/min, a temperature of 600 °C, and a H2O2 oxidation coefficient of 0.65, corresponding to the oxygen stoichiometric coefficient in the carbon oxidation chemical reaction. Under optimal conditions, the total organic carbon (TOC) decreased from 332 to 25 mg/L (92.1%), and the pharmaceutical molecules underwent near-complete degradation. The physical–chemical parameters also met with the main environmental regulations for wastewater disposal. The compounds determined in the gaseous phase were CO2 (97.9%), H2 (1.3%), CH4 (0.3%), and CO (0.5%.). Additionally, a modeling thermodynamic equilibrium of the system was performed, based on the experimental data. The results revealed that SCW technology has a great potential to oxidize/degrade organic matter and can be applied to treat pharmaceutical pollutants. [ABSTRACT FROM AUTHOR]

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This study aims to develop and test a topical drug delivery system for antihypertensive activity using Losartan potassium-loaded niosomes. The niosomes were created using the traditional ether injection approach, with four formulations made using cholesterol as the lipid and varying quantities of surfactants such as span 80 and span 60. The different formulations underwent testing for FTIR, particle size, zeta potential, drug content, entrapment efficiency, and in vitro release. FTIR analysis revealed that the medication was incompatible with excipients. The study concludes by highlighting current obstacles and future possibilities for the development of niosomes as effective vehicles. Overall, this analysis provides insight into the potential of niosomes in medication delivery and encourages further research in this field. [ABSTRACT FROM AUTHOR]

Introduction: Hypertension is common in hemodialysis patients and can often be difficult to control. Considering the high cardiovascular burden in hemodialysis patients, control of blood pressure is important to improve outcomes. First-line interventions for blood pressure control should focus on sodium restriction, adequate sodium removal during hemodialysis, and attaining an adequate "dry weight." Despite these interventions, adequate blood pressure control with thrice weekly hemodialysis typically requires the addition of pharmacologic agents. Objectives of the study: The objectives of the study was to determine the efficacy of losartan in regression of left ventricular hypertrophy and improvement in cardiac function in hypertensive CKD patients on haemodialysis. Material and Methods: Hypertensive CKD patients of 18-60 years of age on maintenance haemodialysis 3 per week through AV fistula were included in the study. All patients included in the study were be subjected to a uniform evaluation. Demographic data, history, detailed clinical examination will be recorded in a pro-forma. Informed written consent was obtained from all the patients at the time of enrolment. Laboratory evaluation of all patients included: Complete blood counts, Renal function test, Serum electrolytes (Na/K/Ca/Po4), Liver function test including serum protein and albumin, iPTH and Echo-cardiography (esp LA diameter, ejection fraction, left ventricular mass index, E/A) will be done in all patients. These patients were made dry by increasing ultra-filtrate on subsequent haemodialysis. Achievement of dry weight was defined by pre-dialysis BP less than 140/90 with 2or less anti-hypertensives without any clinical oedema. After achieving dry weight losartan treatment was started at a dose of 25 mg/day and increased after one week to a 50 mg/day dose that was maintained to the end of the study (6 months). Result: LA size decreased from 3.30 ± 0.15 cm/m² to 2.88 ± 0.18 cm/m² in the losartan arm (n=27) and from 3.33 ± 0.18 cm/m² to 3.30 ± 0.14 cm/m² in the control arm (n=25). This change was statistically significant. (p <0.001) E/A decreased from 1.51 ± 0.11 to 1.35 ± 0.10 in the losartan arm (n=27) and from 1.55 ± 0.09 to 1.46 ± 0.12 in the control arm (n=25). This change was statistically significant. (p=0.003) EF% increased from 44.22 ± 4.26 to 56.91 ± 3.90 in the losartan arm (n=27) and from 44.48 ± 4.32 to 48.24 ± 3.74 in the control arm (n=25). This change was statistically significant. (p <0.001) LVMI decreased from 170.56 ± 9.19 g/m² to 146.50 ± 7.54 g/m² in the losartan arm (n=27) and from 171.16 ± 9.29 g/m² to 166.0± 8.48 g/m² in the control arm (n=25). This change was statistically significant. (p <0.001) Conclusion: In conclusion, in our study, use of losartan improved cardiac parameters (e.g, LA size, E/A ratio, Ejection fraction and left ventricular mass index) significantly in the hypertensive chronic kidney disease haemodialysis dependant patients after our study period of 6 months. [ABSTRACT FROM AUTHOR]

Introduction: Diabetes Mellitus (DM) is a common endocrine and metabolic condition. It is one of the most rapidly growing diseases worldwide, and is a prime cause of excess cardiovascular morbidity and mortality in populations. The chronic hyperglycemia of diabetes is associated with long-term damage, dysfunction, and failure of various organs especially the eyes, kidneys, nerves, heart, and blood vessels. Losartan is an angiotensin II type one (AT1) receptor antagonist authorized for arterial hypertension (HTN) treatment. Losartan is also utilized to avoid renal damage in diabetics and those with decreased ejection fraction (EF) due to heart failure Objective: This research objects to determine the potential protective impact of Losartan administration on the induced diabetic myocardium and aorta of adult male Sprague-Dawley rats. Materials and Methods: Sixty adult male Sprague-Dawley rats were utilized in the present research. They were allocated into four groups: group I (control group), group II (Losartan received group) they were received losartan 30 mg/kg/day, group III (diabetic group) induction of DM by a single intraperitoneal injection of 65 mg/kg STZ solution freshly mixed in 0.1 M citrate buffer and group IV (diabetic with Losartan group). After 8 weeks, the animals from all groups were anaesthetized and blood samples were obtained for biochemical study. The heart and aorta were dissected, and histological, immunohistochemical and electron microscopic studies were conducted on the tissues. Results: Diabetic myocardium revealed histological alterations as fragmented muscle fibers, small darkly stained pyknotic nuclei, cellular infiltration and a significant elevation in collagen fibers percentage area with marked biochemical changes as increased plasma level of MDA. Administration of Losartan to diabetic rats made ameliorating effect on the disturbed structure, decreased the elevated tissue malondialdehyde (MDA) levels and increased the reduced activities of the enzymatic antioxidants superoxide dismutase (SOD), and catalase (CAT) in cardiac tissue. Diabetic group exhibited a significant increase (P<0.001) in collagen fibers mean percentage area, number of Caspase-3 positive cells, and a significant decrease (P<0.001) in the intensity of eNOS immunoreaction in the myocardium tissue of rats than the control group. While diabetic group treated with losartan exhibited a significant decrease (P<0.001) in collagen fibers mean percentage area, the number of Caspase-3 positive cells, and a significant increase (P<0.001) in the intensity of eNOS immunoreaction than diabetic group. Conclusion: Losartan has a protective effect on the biochemical, histological, and morphometric changes of the myocardium and the aorta of diabetic rats. [ABSTRACT FROM AUTHOR]

Background Diabetes Mellitus (DM) is a prominent health care issue worldwide. One of the most prevalent comorbidities of DM is cardiovascular disease (CVD). The objective of this study was to assess the utilization patterns of cardiovascular medications in patients with DM in Iran from 2013 to 2017. Methods This retrospective cross-sectional study was undertaken using prescription claims data from 2013 to 2017 in Iran. Epidemiological data elements used in this study were obtained from the Global Burden of Disease (GBD) 2019 study. In addition, data on total medication sales were obtained from the national regulatory authority database. The data on medication utilization were analyzed according to the Anatomical Therapeutic Chemical Classification (ATC) /Defined Daily Doses (DDD) international system. Results Based on the findings, Acetylsalicylic acid was the mainstay of treatment with a utilization rate of 191.7 DDD/ patient/ year in 2017, followed by Atorvastatin with 170.0 and Losartan with 115.1. Although there was an increasing trend in the utilization rate of the medications, the rate of Atenolol and Enalapril was constantly declining during the 2013-17 period. On the other hand, Valsartan and Metoprolol were attracting attention. Almost all medication utilization rates increased from the 30--39 age group up to the 80 + age group. Females had a higher utilization rate in each age group during the whole study period. Conclusion The present study reflects that medication utilization patterns were rational, according to the standard treatment guidelines. Utilization patterns of medications that are recommended for both prevention and treatment of CVD in diabetes were observed to be the highest. Implementation of further policies is needed to minimize cardiovascular complications of diabetes. [ABSTRACT FROM AUTHOR]

Polycythemia Vera (PV) is a myeloproliferative neoplasm characterized by the overproduction of red blood cells. First-line therapies are directed at lowering hematocrit levels. After the discovery of a mutation in the Janus kinase 2 (JAK2V617F), JAK2 inhibitors have been tested as second-line therapies. Despite these approaches, there is still the need for a major comprehension of the mechanisms involved in PV erythrocytosis and of more effective therapies. Angiotensin-converting enzyme (ACE) stimulates hematopoietic precursors proliferation and erythroid differentiation. We thus hypothesized that ACE inhibition could help in controlling erythrocytosis in PV. We assessed the clonogenic potential by colony-forming unit (CFU) assay of mononuclear cells isolated from PV JAK2 positive or JAK2 negative patients with erythrocytosis treated with enalaprilat or losartan. Treatment with drugs led to a decrease of erythroid precursor frequency both in the presence and absence of JAK2 mutation, with a high extent in JAK2 positive cells and without affecting other types of precursors. No dose-dependent effect was observed. Our results demonstrate that ACE inhibition reduces erythroid precursor frequency, confirming the involvement of ACE in erythrocytosis despite the presence of JAK2 mutation and encouraging the hypothesis that ACE inhibitors and AT1R antagonists could help in directly managing erythrocytosis in PV. [ABSTRACT FROM AUTHOR]

Background Priapism induces regulation of Transforming Growth Factor-β1 (TGF-β1) expression and collagen-type-1 deposition. This will replace the normal corpora cavernosa with fibrotic tissue which eventually resulted in erectile dysfunction. It is also known that the fibrosis process of corpora cavernosa is related to Renin-Angiotensin II System (RAS). Angiotensin II receptor blockers (ARB), especially losartan, inhibit the inflammation process and fibrotic tissue formation. This study evaluated the effect of losartan in reducing fibrosis in priapism by evaluating TGF-β1 and collagen-type-1 in cavernous tissue and determined the effect of losartan in preventing fibrosis in priapism model of Wistar rats assessed by the metavir score. Methods A total of eighteen male Wistar rats mean were divided into five groups. For the priapism models, we applied negative pressure on the penis to make an artificial erection to mimic the priapism process. The control groups were observed and the treatment groups were orally given losartan 15 mg/kg/day. Corpora cavernosa was harvested for TGF-β1 and collagen-type-1 measurement using an enzyme-linked immunosorbent assay (ELISA). The fibrotic tissue of each rat was then collected and assessed histopathologically with the metavir scoring system. Results Penile TGF-β1 concentration in the losartan-treated group was not significantly different on day 10 and day 28 of observation (p10=0,30; p28=0,17). Meanwhile, collagen-type-1 concentration was significantly lower compared to control group (p10=0,002; p28=0,01). There was a significant difference in metavir scores in rats that received losartan and those who did not (p Conclusion Losartan could suppress the fibrosis process in the priapism model. It could decrease the collagen type 1 deposition during corpora cavernosa tissue regeneration. Based on the metavir score, the group receiving losartan therapy was better than the control group.

Objective(s): Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease. Despite the promising anti-fibrotic effect, the toleration of pirfenidone (PFD) by the patients in full dose is low. Combination therapy is a method for enhancing the therapeutic efficiency of PFD and decreasing its dose. Therefore, the present study evaluated the effect of a combination of losartan (LOS) and PFD on oxidative stress parameters and the epithelial-mesenchymal transition (EMT) process induced by bleomycin (BLM) in human lung adenocarcinoma A549 cells. Materials and Methods: The non-toxic concentrations of BLM, LOS, and PFD were assessed by the MTT assay. Malondialdehyde (MDA) and anti-oxidant enzyme activity including catalase (CAT) and superoxide dismutase (SOD) were assessed after co-treatment. Migration and western blot assays were used to evaluate EMT in BLM-exposed A549 after single or combined treatments. Results: The combination treatment exhibited a remarkable decrease in cellular migration compared with both single and BLM-exposed groups. Furthermore, the combination treatment significantly improved cellular anti-oxidant markers compared with the BLM-treated group. Moreover, combined therapy markedly increased epithelial markers while decreasing mesenchymal markers. Conclusion: This in vitro study revealed that the combination of PFD with LOS might be more protective in pulmonary fibrosis (PF) than single therapy because of its greater efficacy in regulating the EMT process and oxidative stress. The current results might offer a promising therapeutic strategy for the future clinical therapy of lung fibrosis.

AIM: To evaluate the efficacy and safety of complex basic therapy for chronic heart failure (CHF) of ischemic origin in combination with chronic obstructive pulmonary disease (COPD) with the inclusion of prolonged bronchodilators. MATERIALS AND METHODS: The study included 67 patients (50 men and 17 women) with CHF IIIII functional class (FC) with left ventricular ejection fraction (LVEF) of 45% in combination with moderate-to-severe COPD (GOLD). The patients were divided into three groups: group 1 (n=30) received formoterol as part of therapy, group 2 (n=19) received aclidinium, and group 3 (n=18) received a fixed combination of aclidinum and formoterol. The basic therapy for CHF included nebivolol, losartan, eplerenone, diuretics, low-dose glucocorticosteroids, nitrates, and cardiac glycosides (if necessary). The clinical condition of patients, intracardiac hemodynamics, was indicated using echocardiography, a 6-min walking test (6MWT), bifunctional 24-h monitoring of blood pressure and heart rate, and spirometry. Quality of life was assessed using the Minnesota Living with Heart Failure Questionnaire, St. Georges Respiratory Questionnaire, and Modified Medical Research Council dyspnea scale. RESULTS: After 6 months of therapy, the clinical and instrumental parameters and quality of life improved in all groups. At the end of the observation period, the average FC of CHF and dyspnea severity decreased by 17.5, 18.2, 20.1 20.5, 24.2, and 28.1%, respectively. The increase in exercise tolerance was 22.1, 22.6, and 29.2%. An improvement in intracardiac hemodynamics was noted. The LVEF increased by 17.1, 20.5, and 24.6%, and the myocardial mass index decreased by 8.7, 14.2, and 17.4%. The total peripheral vascular resistance, degree of pulmonary hypertension, and duration and frequency of painless myocardial ischemia significantly decreased. The best results were obtained in group 3 using nebivolol, reninangiotensinaldosterone system antagonists, and a combination of long-acting bronchodilators. Therapy was well tolerated by all study groups, with no serious adverse side effects. CONCLUSION: The inclusion of nebivolol and losartan in basic therapy, while taking long-acting bronchodilators, improves the clinical and functional states of patients and quality of life, and slows down disease progression. When used in a fixed combination, the use of aclidinium and formoterol improves spirometry to a greater extent.

Background Priapism induces regulation of Transforming Growth Factor-β1 (TGF-β1) expression and collagen-type-1 deposition. This will replace the normal corpora cavernosa with fibrotic tissue which eventually resulted in erectile dysfunction. It is also known that the fibrosis process of corpora cavernosa is related to Renin-Angiotensin II System (RAS). Angiotensin II receptor blockers (ARB), especially losartan, inhibit the inflammation process and fibrotic tissue formation. This study evaluated the effect of losartan in reducing fibrosis in priapism by evaluating TGF-β1 and collagen-type-1 in cavernous tissue and determined the effect of losartan in preventing fibrosis in priapism model of Wistar rats assessed by the metavir score. Methods A total of eighteen male Wistar rats mean were divided into five groups. For the priapism models, we applied negative pressure on the penis to make an artificial erection to mimic the priapism process. The control groups were observed and the treatment groups were orally given losartan 15 mg/kg/day. Corpora cavernosa was harvested for TGF-β1 and collagen-type-1 measurement using an enzyme-linked immunosorbent assay (ELISA). The fibrotic tissue of each rat was then collected and assessed histopathologically with the metavir scoring system. Results Penile TGF-β1 concentration in the losartan-treated group was not significantly different on day 10 and day 28 of observation (p10=0,30; p28=0,17). Meanwhile, collagen-type-1 concentration was significantly lower compared to control group (p10=0,002; p28=0,01). There was a significant difference in metavir scores in rats that received losartan and those who did not (p

In addition to being recognised for involvement in cardiovascular control and hydromineral balance, the renin‐angiotensin system (RAS) has also been associated with the neuroendocrine control of energy balance. One of the main brain sites for angiotensin II (ANG II)/type 1 receptor (AT1R) signalling is the subfornical organ (SFO), a circumventricular organ related to the control of autonomic functions, motivated behaviours and energy metabolism. Thus, we hypothesised that circulating ANG II may act on the SFO AT1R receptors to integrate metabolic and hydromineral balance. We evaluated whether food deprivation can modulate systemic RAS activity and Agrt1a brain expression, and if ANG II/AT1R signalling influences the hypothalamic expression of mRNAs encoding neuropeptides and food and water ingestion in fed and fasted Wistar rats. We found a significant increase in both ANG I and ANG II plasma levels after 24 and 48 h of fasting. Expression of Agrt1a mRNA in the SFO and paraventricular nucleus (PVN) also increased after food deprivation for 48 h. Treatment of fasted rats with low doses of losartan in drinking water attenuated the decrease in glycemia and meal‐associated water intake without changing the expression in PVN or arcuate nucleus of mRNAs encoding selected neuropeptides related to energy homeostasis control. These findings point to a possible role of peripheral ANG II/SFO‐AT1R signalling in the control of refeeding‐induced thirst. On the other hand, intracerebroventricular losartan treatment decreased food and water intake over dark time in fed but not in fasted rats. [ABSTRACT FROM AUTHOR]

Aims Acute myocardial infarction (MI) causes inflammation, collagen deposition, and reparative fibrosis in response to myocyte death and, subsequently, a pathological myocardial remodelling process characterized by excessive interstitial fibrosis, driving heart failure (HF). Nonetheless, how or when to limit excessive fibrosis for therapeutic purposes remains uncertain. Galectin-3, a major mediator of organ fibrosis, promotes cardiac fibrosis and remodelling. We performed a preclinical assessment of a protein inhibitor of galectin-3 (its C-terminal domain, Gal-3C) to limit excessive fibrosis resulting from MI and prevent ventricular enlargement and HF. Methods and results Gal-3C was produced by enzymatic cleavage of full-length galectin-3 or by direct expression of the truncated form in Escherichia coli. Gal-3C was intravenously administered for 7 days in acute MI models of young and aged rats, starting either pre-MI or 4 days post-MI. Echocardiography, haemodynamics, histology, and molecular and cellular analyses were performed to assess post-MI cardiac functionality and pathological fibrotic progression. Gal-3C profoundly benefitted left ventricular ejection fraction, end-systolic and end-diastolic volumes, haemodynamic parameters, infarct scar size, and interstitial fibrosis, with better therapeutic efficacy than losartan and spironolactone monotherapies over the 56-day study. Gal-3C therapy in post-MI aged rats substantially improved pump function and attenuated ventricular dilation, preventing progressive HF. Gal-3C in vitro treatment of M2-polarized macrophage-like cells reduced their M2-phenotypic expression of arginase-1 and interleukin-10. Gal-3C inhibited M2 polarization of cardiac macrophages during reparative response post-MI. Gal-3C impeded progressive fibrosis post-MI by down-regulating galectin-3-mediated profibrotic signalling cascades including a reduction in endogenous arginase-1 and inducible nitric oxide synthase (iNOS). Conclusion Gal-3C treatment improved long-term cardiac function post-MI by reduction in the wound-healing response, and inhibition of inflammatory fibrogenic signalling to avert an augmentation of fibrosis in the periinfarct region. Thus, Gal-3C treatment prevented the infarcted heart from extensive fibrosis that accelerates the development of HF, providing a potential targeted therapy. [ABSTRACT FROM AUTHOR]

Doxorubicin (DOX) is an anthracycline derivative used for treatment of malignancies; however, its clinical use is limited by its cardiotoxicity. We investigated the effects of angiotensin II type 2 receptor agonist compound 21 (C21) on DOX induced heart failure in rat heart. We compared C21 with losartan (LOS), an AT 1 receptor antagonist used for treating heart failure. We allocated 40 rats into five groups of eight: saline treated control group, DOX group administered a single 20 mg/kg dose of DOX, DOX + C21 group administered 0.3 mg/kg C21 for 21 days following the 20 mg/kg dose of DOX, DOX + losartan (LOS) group administered a 21 day regimen of 20 mg/kg LOS following the single dose of DOX, and a DOX + LOS + C21 group administered 0.3 mg/kg C21 and 20 mg/kg LOS for 21 days following the single dose of DOX. We assessed histopathology and conducted echocardiograpic and hemodynamic measurements. Left ventricular ejection fraction (EF) was reduced only in the DOX treated group. C21, LOS and C21 + LOS therapy prevented decreased EF due to DOX. Less histopathology was observed in the DOX + LOS + C21 group than for the other treatment groups. Application of C21 decreased DOX induced cardiac injury similar to LOS. Combined use of C21 and LOS was most beneficial for DOX induced heart failure. [ABSTRACT FROM AUTHOR]

[Display omitted] Mini-tablets (MTs) with losartan potassium were developed to treat the rare disease Epidermolysis Bullosa. The focus was placed on transfer and scale-up of a direct compressible formulation from the compaction simulator STYL'One Evo (CS) to the rotary tablet press Korsch XM 12 (RP). Transfer of tabletability and compactibility profiles from CS to RP did not show good agreement, e.g. at a tableting pressure of 125 MPa mean tensile strengths (TS) of 4 MPa on CS and 1–1.5 MPa on RP were reached. These results highlight the impact of the feed frame on final product qualities depending on process and material factors. In the scale-up studies the critical quality attributes (CQAs) mass variation, content uniformity, TS and disintegration time were investigated. After an appropriate run-up time, most CQAs reached a plateau, after reaching a balance between influx, efflux and distribution of lubricant in the feed frame. TS values of 1–2 MPa, disintegration times of max. 50 s, mass variation of 0.9–2.2 % (CV) and acceptance values below 15.0 were reached depending on chosen process parameters. [ABSTRACT FROM AUTHOR]

Introduction: Differences in class or molecule-specific effects between renin–angiotensin–aldosterone system (RAAS) inhibitors have not been conclusively demonstrated. This study used South African data to assess clinical and cost outcomes of antihypertensive therapy with the three most common RAAS inhibitors: perindopril, losartan and enalapril. Methods: Using a large, South African private health insurance claims database, we identified patients with a hypertension diagnosis in January 2015 receiving standard doses of perindopril, enalapril or losartan, alone or in combination with other agents. From claims over the subsequent 5 years, we calculated the risk-adjusted rate of the composite primary outcome of myocardial infarction, ischaemic heart disease, heart failure or stroke; rate of all-cause mortality; and costs per life per month (PLPM), with adjustments based on demographic characteristics, healthcare plan and comorbidity. Results: Overall, 32,857 individuals received perindopril, 16,693 losartan and 13,939 enalapril. Perindopril-based regimens were associated with a significantly lower primary outcome rate (205 per 1000 patients over 5 years) versus losartan (221; P < 0.0001) or enalapril (223; P < 0.0001). The risk-adjusted all-cause mortality rate was lower with perindopril than enalapril (100 vs. 139 deaths per 1000 patients over 5 years; P = 0.007), but not losartan (100 vs. 94; P = 0.650). Mean (95% confidence interval) overall risk-adjusted cost PLPM was Rands (ZAR) 1342 (87–8973) for perindopril, ZAR 1466 (104–9365) for losartan (P = 0.0044) and ZAR 1540 (77–10,546) for enalapril (P = 0.0003). Conclusion: In South African individuals with private health insurance, a perindopril-based antihypertensive regimen provided better clinical and cost outcomes compared with other regimens. [ABSTRACT FROM AUTHOR]

Purpose: Current therapies for osteoarthritis (OA) are limited to analgesics and anti-inflammatory drugs. Considering the importance of oxidative stress and inflammatory mediators in OA etiology, we tested the hypothesis that targeting the renin–angiotensin–aldosterone system (RAAS) can improve OA anomalies. Diminazene (DIZE), an activator of angiotensin-converting enzyme 2 and the angiotensin 2 type-1 receptor blocker losartan (LOS) were used for this purpose. Methods: OA was induced by a single intra-articular injection of monosodium iodoacetate. The effects of exposure to DIZE or LOS for 21 days on OA anomalies in rats' knees were investigated. Evaluation of motor function, nociception, and inflammatory response was done using rotarod, knee bend and knee swelling tests. Markers of knee joint inflammation, and cellular oxidation in addition to the RAAS biomarkers, were assessed in knee tissues, along with radiological and histopathological investigations. Results: Elevations in inflammatory and oxidative markers in knee tissues of OA rats were mostly improved by the two therapeutic drugs. Such effect was also reflected in the rotarod, knee bend and knee swelling tests. Treatment with DIZE has shown a more prominent effect than LOS in controlling OA-associated inflammation and cellular oxidation. Markers of RAAS have also shown better responsiveness to DIZE over LOS. Conclusions: DIZE has shown a prominent increase in the angiotensin 1–7 amount, highlighting the involvement of the signaling pathway in the immunomodulatory effect. The radiological and histopathology examination came to confirm the outcome of biochemical markers, nominating diminazene aceturate as a possible therapeutic option for OA. [ABSTRACT FROM AUTHOR]

Serum urate is a risk factor for hypertension and gout. The DASH diet and losartan independently lower blood pressure (BP); however, their effects on serum urate are understudied. We performed a post‐hoc analysis of the DASH‐losartan trial, which randomized participants with hypertension in parallel fashion to the DASH diet or a standard American diet (control) and in crossover fashion to 4‐week losartan or placebo. Serum urate was measured at baseline and after each 4‐week period. Diets were designed to maintain weight constant. We examined the effects of DASH (vs control) and/or losartan (vs placebo) on serum urate, overall and among those with baseline serum urate ≥6 mg/dL, using generalized estimating equations. Of 55 participants (mean age 52 years, 58% women, 64% Black), mean (±SD) baseline ambulatory SBP/DBP was 146±12/91±9 and mean (±SD) serum urate was 5.2±1.2 mg/dL. The DASH diet did not significantly reduce urate levels overall (mean difference −0.05 mg/dL; 95%CI: −0.39, 0.28), but did decrease levels among participants with baseline hyperuricemia (−0.33 mg/dL; 95%CI: −0.87, 0.21; P‐interaction=0.007 across hyperuricemia groups). Losartan significantly decreased serum urate (−0.23 mg/dL; 95%CI: −0.40, −0.05) with greater effects on serum urate among adults <60 years old versus adults ≥60 years old (−0.33 mg/dL vs 0.16 mg/dL, P interaction = 0.003). In summary, the DASH diet significantly decreased serum urate among participants with higher urate at baseline, while losartan significantly reduced serum urate, especially among younger adults. Future research should examine the effects of these interventions in patients with hyperuricemia or gout. [ABSTRACT FROM AUTHOR]

Introduction: The paraventricular nucleus of the hypothalamus (PVN) contains premotor neurons involved in the control of sympathetic vasomotor activity. It is known that the stimulation of specific areas of the PVN can lead to distinct response patterns at different target territories. The underlying mechanisms, however, are still unclear. Recent evidence from sympathetic nerve recording suggests that relevant information is coded in the power distribution of the signal along the frequency range. In the present study, we addressed the hypothesis that the PVN is capable of organizing specific spectral patterns of sympathetic vasomotor activation to distinct territories in both normal and hypertensive animals. Methods: To test it, we investigated the territorially differential changes in the frequency parameters of the renal and splanchnic sympathetic nerve activity (rSNA and sSNA, respectively), before and after disinhibition of the PVN by bicuculline microinjection. Subjects were control and Goldblatt rats, a sympathetic overactivity-characterized model of neurogenic hypertension (2K1C). Additionally, considering the importance of angiotensin II type 1 receptors (AT1) in the sympathetic responses triggered by bicuculline in the PVN, we also investigated the impact of angiotensin AT1 receptors blockade in the spectral features of the rSNA and sSNA activity. Results: The results revealed that each nerve activity (renal and splanchnic) presents its own electrophysiological pattern of frequency-coded rhythm in each group (control, 2K1C, and 2K1C treated with AT1 antagonist losartan) in basal condition and after bicuculline microinjection, but with no significant differences regarding total power comparison among groups. Additionally, the losartan 2K1C treated group showed no decrease in the hypertensive response triggered by bicuculline when compared to the non-treated 2K1C group. However, their spectral patterns of sympathetic nerve activity were different from the other two groups (control and 2K1C), suggesting that the blockade of AT1 receptors does not totally recover the basal levels of neither the autonomic responses nor the electrophysiological patterns in Goldblatt rats, but act on their spectral frequency distribution. Discussion: The results suggest that the differential responses evoked by the PVN were preferentially coded in frequency, but not in the global power of the vasomotor sympathetic responses, indicating that the PVN is able to independently control the frequency and the power of sympathetic discharges to different territories. [ABSTRACT FROM AUTHOR]

This work examines the use of pristine Mo2C as an intriguing sodium persulfate (SPS) activator for the degradation of the drug losartan (LOS). Using 500 mg/L Mo2C and 250 mg/L SPS, 500 μg/L LOS was degraded in less than 45 min. LOS decomposition was enhanced in acidic pH, while the apparent kinetic constant decreased with higher LOS concentrations. According to experiments conducted in the presence of scavengers of reactive species, sulfate radicals, hydroxyl radicals, and singlet oxygen participated in LOS oxidation, with the latter being the predominant reactive species. The presence of competitors such as bicarbonate and organic matter reduced the observed efficiency in actual matrices, while, interestingly, the addition of chloride accelerated the degradation rate. The catalyst showed remarkable stability, with complete LOS removal being retained after five sequential experiments. The system was examined for simultaneous LOS decomposition and elimination of Escherichia coli. The presence of E. coli retarded LOS destruction, resulting in only 30% removal after 3 h, while the system was capable of reducing E. coli concentration by 1.23 log. However, in the presence of simulated solar irradiation, E. coli was reduced by almost 4 log and LOS was completely degraded in 45 min, revealing a significant synergistic effect of the solar/Mo2C/SPS system. [ABSTRACT FROM AUTHOR]