Evaluation of statins as a new therapy to alleviate chronotropic dysfunction in cirrhotic rats.

AIMS: Liver cirrhosis defines by regenerative nodules and fibrotic septa, causing a complication called cirrhotic cardiomyopathy (CCM) with chronotropic hypo-responsiveness. In addition to lowering cholesterol levels, statins yield antioxidant and anti-inflammatory effects. In liver diseases animal models, statins have been shown to decrease hepatic inflammation, fibrogenesis, and portal pressure (PP). Therefore, we evaluated the atorvastatin effect on the heart in cirrhotic rats. MATERIALS AND METHODS: Bile duct ligation (BDL) or sham operation performed on male Wistar rats and grouped as cirrhotic; BDL/Saline, BDL/Ator-7d(days) (Atorvastatin 15 mg/kg/day), and BDL/Ator-14d groups, or control; Sham/Saline, Sham/Ator-7d, and Sham/Ator-14d groups. Corrected QT interval (QTc interval), chronotropic responses, serum brain natriuretic peptides (BNP), heart tumor necrosis factor-α (TNF-α), nuclear factor erythroid 2-related factor 2 (Nrf2), and malondialdehyde (MDA) levels were studied along with atrial Ras homolog family member A (RhoA) and endothelial nitric oxide synthase (eNOS) gene expression. KEY FINDINGS: The chronotropic responses decreased in BDL/Saline and increased in BDL/Ator-7d group. The QTc interval, BNP, TNF-α, and MDA levels increased in BDL/Saline and decreased in BDL/Ator-14d group. The Nrf2 level did not change in BDL/Saline and increased in BDL/Ator-14d group. The liver inflammation and fibrosis increased in BDL/Saline and did not affect BDL/Ator-7d and BDL/Ator-14d groups. The RhoA expression was down-regulated in BDL/Saline, BDL/Ator-7d, and BDL/Ator-14d groups. The eNOS expression did not change in BDL/Saline and down-regulated in BDL/Ator-14d group. SIGNIFICANCE: Atorvastatin alleviates the chronotropic hypo-responsiveness and down-regulates the atrial RhoA and eNOS gene expression along with anti-inflammatory, antioxidant, and anti-stress effects in CCM.

Evaluation of the effect of heat shock protein 70 targeted drugs on cirrhotic cardiomyopathy in biliary cirrhotic rats.

AIMS: Liver cirrhosis leads to cirrhotic cardiomyopathy (CCM) and chronotropic incompetence (CI). Heat shock protein 70 (Hsp70) regulates cellular apoptosis and autophagy in stress. Teprenone modulates the Hsp70 and protects against cellular injury. Thus, we aimed to evaluate the effect of teprenone on CI in biliary cirrhotic rats. MAIN METHODS: Liver cirrhosis was induced in male Wistar rats through bile duct ligation (BDL). The chronotropic responses and QT interval were studied through electrocardiography (ECG) in sham, cirrhotic, and cirrhotic/teprenone (100 mg/kg) pre-treated groups. Brain natriuretic peptide (BNP), tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), and monocyte chemo-attractant protein-1 (MCP-1), and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were investigated in serum. The Hsp70, B-cell lymphoma 2 (Bcl-2), and B-cell lymphoma 2-associated X protein (Bax) expressions were quantified through real-time polymerase chain reaction (Real-time PCR). KEY FINDINGS: The chronotropic responses were decreased significantly in cirrhotic and cirrhotic/teprenone groups. The QT interval and serum BNP, TNF-α, IL-6, ALT, AST, and MCP-1 levels were increased significantly in the cirrhotic and decreased significantly, except BNP, in the cirrhotic/teprenone group. The Hsp70 and Bax expressions increased significantly in cirrhotic and decreased significantly in the cirrhotic/teprenone group while the Bcl-2 decreased significantly in cirrhotic and increased significantly in the cirrhotic/teprenone group. SIGNIFICANCE: Teprenone does not relieve the CI and BNP changes in CCM while other indices are treated. Given that CCM is a multifactorial disease and needs to target other genes and proteins concurrent with Hsp70 to relieve CCM.

Patient experiences in managing non-communicable diseases in Namibia.

INTRODUCTION: The prevalence of non-communicable diseases (NCDs) is rising in Namibia, and with it, the need for pharmacists to empower patients. This research aims to 1) identify patient-reported barriers and facilitators to managing chronic NCDs for Namibians, and 2) characterize common patient-reported medication and health-related needs of Namibians with chronic NCDs. METHODS: This qualitative study used semi-structured interviews to elicit participant perspectives regarding NCDs. The study used the conceptual frameworks of the Health Belief Model, the Theory of Planned Behavior, and the Explanatory Models of Illness to identify and understand key factors necessary to develop relevant patient-centered interventions. Participants were recruited from pharmacies throughout Namibia. Data were analyzed using thematic analysis from the transcribed interviews. RESULTS: A total of 23 interviews were conducted, with 20 being included in the final analysis. Themes identified included: 1) participants were motivated to seek care when they were symptomatic; 2) participants felt motivated to care for their condition to improve their own lives and their families for their family's sake; 3) participants integrated information from a variety of sources into their disease knowledge; 4) participants describe wanting to be more engaged in managing their health and wanting support to help manage their condition; 5) participants describe awareness of lifestyle changes necessary to improve health, but face many barriers to achieving them. CONCLUSION: This study identified key factors that are essential for pharmacists and other health care professionals to be aware of in order to support patients who are diagnosed with an NCD. Health care providers should consider strategies to engage patients to harness their motivations, enhance health education, and create systems to reduce barriers to addressing lifestyle.

Compliance to prescribing guidelines among public health care facilities in Namibia; findings and implications.

Background The World Health Organization estimates that over 50% medicines are prescribed inappropriately and the main driver of antimicrobial resistance globally. There have only been a limited number of studies evaluating prescribing patterns against national standard treatment guidelines (STGs) in sub-Saharan African countries including Namibia. This is important given the high prevalence of both infectious and non-infectious diseases in sub-Saharan Africa alongside limited resources. Objective Our aim was to assess prescribing practices and drivers of compliance to National guidelines among public health care facilities in Namibia to provide future guidance. Setting Three levels of public healthcare in Namibia. Method A mixed method approach including patient exit and prescriber interviews at three levels of health care in Namibia, i.e. hospital, health centre and clinic. Main outcome measures Medicine prescribing indicators, compliance to and attitudes towards National guidelines. Results Of the 1243 prescriptions analysed, 73% complied with the STGs and 69% had an antibiotic. Of the 3759 medicines (i.e. mean of 3.0 ± 1.1) prescribed, 64% were prescribed generically. The vast majority of prescribers were aware of, and had access to, the Namibian STGs (94.6%), with the majority reporting that the guidelines are easy to use and they regularly refer to them. The main drivers of compliance to guidelines were programmatic, that is access to up-to date objective guidelines, support systems for continued education on their use, and ease of referencing. Lack of systems to regulate noncompliance impacted on their use. Conclusion Whilst the findings were encouraging, ongoing concerns included limited prescribing of generic medicines and high use of antibiotics. A prescribing performance management system should be introduced to improve and monitor compliance to prescribing guidelines in public healthcare.

Effect of phosphatidylserine on cirrhosis-induced hepatic encephalopathy: Response to acute endotoxemia in cirrhotic rats.

BACKGROUND/AIMS: In cirrhosis, the levels of proinflammatory cytokines are high in the liver and blood. Endotoxin decreases level of consciousness in cirrhotic rats. Phosphatidylserine exists in the cell membrane structure and is essential for the survival of neurons. Phosphatidylserine receptor is found in phagocytic cells and also activates the signaling of membrane proteins in apoptotic process. Therefore this study was aimed to explore the hypothesis that hepatic encephalopathy is prevented by phosphatidylserine treatment and if so, whether this is associated with altered level of proinflammatory cytokines in the brain. METHODS: Cirrhosis was induced by surgical ligation of the bile duct in male Wister rats. The groups were treated with phosphatidylserine and saline for 4 weeks. Brain IL6, TNFα and the expression of phosphatidylserine receptor were assessed. Intraperitoneal injections of either saline or lipopolysaccharide (0.1 mg/kg) were administered to each group. Finally, animal behavior, blood ammonia and the expression of toll like receptor 4 were examined in the brain. RESULTS: Cirrhosis in rats was associated with altered expression of toll-like receptor4 in brain cortex and phosphatidylserine treatment increases toll-like receptor4 receptor expression. Phosphatidylserine had anti-inflammatory effect in healthy rats but no effect in cirrhotic rats. Chronic phosphatidylserine treatment decreased blood ammonia in BDL cirrhotic rats treated with lipopolysaccharide. CONCLUSION: The brain of cirrhotic rat is more susceptible to acute endotoxemia and chronic phosphatidylserine treatment decreases blood ammonia and encephalopathy in cirrhotic rats by encountering endotoxin. Phosphatidylserine may boost immune system against endotoxin.