Dapagliflozin Pretreatment Prevents Cardiac Electrophysiological Changes in a Diet and Streptozotocin Induction of Type 2 Diabetes in Rats: A Potential New First-Line?

Purpose: Dapagliflozin exerts cardioprotective effects in Type 2 Diabetes Mellitus (T2DM). However, whether these effects prevent electrocardiographic changes associated with T2DM altogether remain unknown. Our aim was to investigate the prophylactic effect of dapagliflozin pretreatment on the rat ECG using a high-fat, high-fructose (HFHf) diet and a low dose streptozotocin (STZ) model of T2DM. Methods: Twenty-five (25) rats were randomized into five (5) groups: normal control receiving a normal diet while the other groups received an 8-week HFHf and 40mg/kg STZ on day 42, and either: saline for the diabetic control (1 mg/kg/d), low dose (1.0 mg/kg/d) and high dose dapagliflozin (1.6 mg/kg/d), or metformin (250 mg/kg/d). Oral glucose tolerance (OGT), electrocardiograms (ECGs), paracardial adipose mass, and left ventricular fibrosis were determined. Data were analyzed using GraphPad version 9.0.0.121, with the level of significance at p < 0.05. Results: Compared to the diabetic control group, a high dose of dapagliflozin preserved the OGT (p = 0.0001), QRS-duration (p = 0.0263), QT-interval (p = 0.0399), and QTc intervals (p = 0.0463). Furthermore, the high dose dapagliflozin group had the lowest paracardial adipose mass (p = 0.0104) and fibrotic area (p = 0.0001). In contrast, while metformin showed favorable effects on OGT (p = 0.0025), paracardial adiposity (p = 0.0153) and ventricular fibrosis (p = 0.0291), it did not demonstrate significant antiarrhythmic effects. Conclusion: Pretreatment with higher doses of Dapagliflozin exhibits prophylactic cardioprotective characteristics against diabetic cardiomyopathy that include antifibrotic and antiarrhythmic qualities. This suggests that higher doses of dapagliflozin could be a more effective initial therapeutic option in T2DM.

Dietary regimens appear to possess significant effects on the development of combined antiretroviral therapy (cART)-associated metabolic syndrome.

INTRODUCTION: This study investigated the interactions between a low protein high calorie (LPHC) diet and an integrase inhibitor-containing antiretroviral drug regimen (INI-CR)in light of evidence suggesting that the initiation of cART in patients with poor nutritional status is a predictor of mortality independent of immune status. METHODS: Freshly weaned Sprague Dawley rats (120) were randomized into the standard, LPHC and normal protein high calorie (NPHC) diet groups (n = 40/group) initially for 15 weeks. Thereafter, experimental animals in each diet group were further randomized into four treatment sub-groups (n = 10/group) Control (normal saline), group 1(TDF+3TC+DTG and Tesamorelin), group 2 (TDF+3TC+DTG), and Positive control (AZT+3TC+ATV/r) with treatment and diets combined for 9 weeks. Weekly body weights, fasting blood glucose (FBG), oral glucose tolerance test (OGTT); lipid profiles, liver weights, hepatic triglycerides and adiposity were assessed at week 24. RESULTS: At week 15, body weights increased between the diet group in phase 1(standard 146 ± 1.64 vs. 273.1 ± 1.56 g), (NPHC, 143.5 ± 2.40 vs. 390.2 ± 4.94 g) and (LPHC, 145.5 ± 2.28 g vs. 398.3 ± 4.89 g) (p< 0.0001). A similar increase was noted in the FBG and OGTT (p< 0.0001). In phase 2, there was an increase in FBG, OGTT, body weights, lipid profile, liver weights, hepatic triglycerides, adiposity and insulin levels in group 2 and positive control in both NPHC and LPHC diet groups (p<0.0001). Growth hormone levels were decreased in Tesamorelin-free group 2 and positive control in both NPHC and LPHC (p< 0.0001). CONCLUSIONS: The obesogenic activities of the LPHC diet exceeded that of the NPHC diet and interacted with both integrase-containing and classical cART drug regimens to reproduce cART associated metabolic dysregulation. The effects were however reversed by co-administration with tesamorelin, a synthetic growth hormone releasing hormone analogue.

Co-administration of rimonabant prevents glucose intolerance in Sprague-Dawley rats treated chronically with lopinavir/ritonavir and zidovudine: an experimental study design.

Introduction: treatment of HIV infection with Protease Inhibitors (PIs) and Nucleoside Reverse Transcriptase Inhibitors (NRTIs) can lead to insulin resistance and changes in body fat distribution. Overactivity of the endogenous cannabinoid system produces similar disturbances in metabolic syndrome within the general population. However, Cannabinoid receptor type 1 antagonism, in both human and animal studies, reverses many of these biochemical and physical derangements observed in the metabolic syndrome. Methods: using an experimental study design, fifteen adult male Sprague-Dawley rats housed under standard conditions were randomized into three groups; Control, combined Anti-Retroviral Therapy (cART) only and cART + rimonabant. Drugs were administered daily by oral gavage for four weeks. After four weeks, insulin tolerance tests were conducted, the rats were euthanised and fat depots were excised and weighed. Experimental data were analysed using STATA 16.0 with the significance level set at p<0.05. The Shapiro-Wilk test determined normalcy. In cases of significance, post hoc analysis was performed by either the Dunn test or the Tukey HSD test. Results: Sprague Dawley rats treated with cART + rimonabant demonstrated better insulin sensitivity (p = 0.0239) and lower body weight (p = 0.044) than rats treated with cART alone. They had leaner body composition with 58% less adiposity than cART-only rats. Conclusion: the study results suggest a role for the endogenous cannabinoid system in cART induced metabolic derangements and physical changes. Future studies can directly assay ECS activity in cART associated metabolic syndrome.

[Bradycardia in pregnancy : Case report and review of the literature]. / Bradykardie in der Schwangerschaft : Fallbericht und Blick auf die Literatur.

We report the case of a pregnant woman with complete heart block during her first trimester who presented with dyspnea at the East African Heart Rhythm Project in Nairobi. There was no evidence of an acute cause (e.g., myocarditis, cardiomyopathy, autoimmune or neuromuscular disease). No ECG had been previously documented; therefore, congenital complete heart block was likely. We implanted a dual-chamber pacemaker using conventional fluoroscopy. Several measures at implantation allowed us to limit fluoroscopy to 30 s and radiation to < 100 µGym2. The implantation was uneventful, dyspnea improved instantaneously and further pregnancy, labor and birth were uncomplicated. Bradycardia requiring pacemaker implantation is rare during pregnancy and usually consists of symptomatic complete heart block. Beyond undiagnosed or untreated pre-existing atrioventricular block, drug therapy for fetal tachycardia, myocarditis (including Lyme borreliosis and Chagas disease), inflammatory infiltrative diseases (e.g., sarcoidosis), cardiomyopathies and neuromuscular disease may have caused bradycardia. In the absence of treatable causes, pacemaker implantation becomes necessary if bradycardia brings about risks for the mother or the fetus. Using transesophageal or intracardiac echocardiography, radiation can be avoided completely or, by taking some simple measures, may be kept to a minimum so that there is no risk for the fetus.

Aqueous Tuber Extracts of Tylosema fassoglense (Kotschy ex Schweinf.) Torre and Hillc. (Fabaceae). Possess Significant In-Vivo Antidiarrheal Activity and Ex-Vivo Spasmolytic Effect Possibly Mediated by Modulation of Nitrous Oxide System, Voltage-Gated Calcium Channels, and Muscarinic Receptors.

Tylosema fassoglense (TFG) is used as an antidiarrheal traditional medicine in Western Kenya. This study aimed to investigate the antidiarrheal activity of its aqueous extracts in-vivo and the putative mechanism (s) of action ex-vivo using Sprague-Dawley rats and New Zealand white rabbits respectively. The in-vivo antidiarrheal effects of the extract were evaluated in castor oil-induced diarrhea, the castor oil-induced enteropooling, and phenol red gastric motility tests. On the other hand, isolated rabbit's jejunal segments were used to evaluate the spasmolytic effect of TFG on spontaneous contraction, in acetylcholine-induced contraction, in presence of 80mMK+, calcium chloride-induced contraction as well as in presence of the following antagonists: naloxone, methylene blue, L-NAME, prazosin, and propranolol in the ex-vivo studies. The data were express as Mean ± S.E.M and analyzed by one-way ANOVA and Tukey's post hoc test in cases of significance which was set at p < 0.05. The extract was phytochemically characterized using Liquid chromatography Mass spectroscopy (LC-MS).The extract possessed significant inhibitory effect in the in-vivo experiments. The extract exhibited significant spasmolytic effect on both spontaneous contraction and in jejunal segment pre-contracted acetylcholine as well as in presence of 80mMK+ solution. It also attenuated the spasmogenic effect of various concentration of calcium chloride. The extract's spasmolytic effect was, however, significantly attenuated in presence of several antagonists (methylene blue and L-NAME) but the adrenergic blockers (prazosin and propranolol) had no significant effect in the ex-vivo studies. LC-MS identified thirty compounds where Proathocyanidin (11.54%), Syringic acid (7.30%), and 4-Hydroxybenzoic acid (6.19%) had the highest percentage abundance. In conclusion, the results obtained in this study partially validate the traditional uses of the tubers of this plant species as an antidiarrheal. These antidiarrheal effects are probably mediated via modulation of nitrous oxide pathway, voltage gated calcium channels, and muscarinic receptors.

Hospital-Based Quality Improvement Interventions for Patients With Acute Coronary Syndrome: A Systematic Review.

BACKGROUND: Quality improvement initiatives have been developed to improve acute coronary syndrome care largely in high-income country settings. We sought to synthesize the effect size and quality of evidence from randomized controlled trials (RCTs) and nonrandomized studies for hospital-based acute coronary syndrome quality improvement interventions on clinical outcomes and process of care measures for their potential implementation in low- and middle-income country settings. METHODS AND RESULTS: We conducted a bibliometric search of databases and trial registers and a hand search in 2016 and performed an updated search in May 2018 and May 2019. We performed data extraction, risk of bias assessment, and quality of evidence assessments in duplicate. We assessed differences in outcomes by study design comparing RCTs to nonrandomized quasi-experimental studies and by country income status. A meta-analysis was not feasible due to substantial, unexplained heterogeneity among the included studies, and thus, we present a qualitative synthesis. We screened 5858 records and included 32 studies (14 RCTs [n=109 763] and 18 nonrandomized quasi-experimental studies [n=54-423]). In-hospital mortality ranged from 2.1% to 4.8% in the intervention groups versus 3.3% to 5.1% in the control groups in 5 RCTs (n=55 942). Five RCTs (n=64 313) reported 3.0% to 31.0% higher rates of reperfusion for patients with ST-segment-elevation myocardial infarction in the intervention groups. The effect sizes for in-hospital and discharge medical therapies in a majority of RCTs were 3.0% to 10.0% higher in the intervention groups. There was no significant difference in 30-day mortality evaluated by 4 RCTs (n=42 384), which reported 2.5% to 15.0% versus 5.9% to 22% 30-day mortality rates in the intervention versus control groups. In contrast, nonrandomized quasi-experimental studies reported larger effect sizes compared to RCTs. There were no significant consistent differences in outcomes between high-income and middle-income countries. Low-income countries were not represented in any of the included studies. CONCLUSIONS: Hospital-based acute coronary syndrome quality improvement interventions have a modest effect on process of care measures but not on clinical outcomes with expected differences by study design. Although quality improvement programs have an ongoing and important role for acute coronary syndrome quality of care in high-income country settings, further research will help to identify key components for contextualizing and implementing such interventions to new settings to achieve their desired effects. Systematic Review Registration: URL: https://www.crd.york.ac.uk/PROSPERO/. Unique identifier: CRD42016047604.

Presentation, management and outcomes of acute coronary syndrome: a registry study from Kenyatta National Hospital in Nairobi, Kenya.

BACKGROUND: Acute coronary syndrome (ACS) is understudied in sub-Saharan Africa despite its increasing disease burden. We sought to create an ACS registry at Kenyatta National Hospital to evaluate the presentation, management and outcomes of ACS patients. METHODS: From November 2016 to April 2017, we conducted a retrospective review of ACS cases managed at Kenyatta National Hospital between 2013 and 2016, with a primary discharge diagnosis of ACS, based on International Classification of Diseases (ICD) 10 coding (I20-I24). We compared the presentation, management and outcomes by ACS subtype using analysis of variance testing. We created multivariable logistic regression models using the Global Registry of Acute Coronary Events (GRACE) risk score to evaluate the association between clinical variables, including guideline-directed medical therapy and in-hospital outcomes. RESULTS: Among 196 ACS admissions, the majority (65%) was male, and the median age was 58 years. Most (57%) ACS admissions were for ST-segment-elevation myocardial infarction (STEMI). In-hospital dual antiplatelet (> 85%), beta-blockade (72%) and anticoagulant (72%) therapy was common. A minority (33%) of patients with STEMI was eligible for reperfusion therapy but only 5% received reperfusion. In-hospital mortality rate was 17%, and highest among individuals presenting with STEMI (21%). After multivariable adjustment, higher serum creatinine level was associated with higher odds of in-hospital death (OR = 1.84, 95% CI: 1.21 - 2.78), and STEMI and Killip class > 1 were associated with in-hospital composite of death, re-infarction, stroke, major bleeding or cardiac arrest (STEMI: OR = 8.70, 95% CI: 2.52 - 29.93; Killip > 1: OR = 10.7, 95% CI: 3.34-34.6). CONCLUSIONS: We describe the largest ACS registry at Kenyatta National Hospital to date and identify potential areas for improved ACS care related to diagnostics and management to optimise in-hospital outcomes.

Facilitators, context of and barriers to acute coronary syndrome care at Kenyatta National Hospital, Nairobi, Kenya: a qualitative analysis.

BACKGROUND: The prevalence of ischaemic heart disease and its acute manifestation, acute coronary syndrome (ACS), is growing throughout sub-Saharan Africa, including Kenya. To address this increasing problem, we sought to understand the facilitators, context of and barriers to ACS care at Kenyatta National Hospital, with the aim of improving the quality of care of ACS. METHODS: We conducted in-depth interviews with healthcare providers involved in the management of ACS patients from January to February 2017 at Kenyatta National Hospital in Nairobi, Kenya. We selected an initial sample of key participants for interviewing and used a snowballing technique to identify additional participants until we achieved saturation. After transcription of audio recordings of the interviews, two authors conducted data coding and analysis using a framework approach. RESULTS: We conducted 16 interviews with healthcare providers. Major themes included the need to improve the diagnostic and therapeutic capabilities of the hospital, including increasing the number of ECG machines and access to thrombolytics. Participants highlighted an overall wide availability of other guideline-directed medical therapies, including antiplatelets, beta-blockers, statins, anticoagulants and ACE inhibitors. All participants also stated the need for and openness to accepting future interventions for improvement of quality of care, including checklists and audits to improve ACS care at Kenyatta National Hospital. CONCLUSION: Major barriers to ACS care at Kenyatta National Hospital include inadequate diagnostic and therapeutic capabilities, lack of hospital-wide ACS guidelines, undertraining of healthcare providers and delayed presentation of patients seeking care. We also identified potential targets, including checklists and audits for future improvements in quality of care from the perspective of healthcare providers.

Relationship between anthropometric measures and early electrocardiographic changes in obese rats.

BACKGROUND: The degree of cardiovascular function impairment parallels the degree of obesity and obese subjects have abnormal changes on the electrocardiogram (ECG). Early ECG changes in obesity have not been previously studied. The objective of the present study was to determine the early ECG changes in obese rats and their relationship with anthropometric measurements. RESULTS: At seven weeks all rats in the experiment were obese and in sinus rhythm. In the experiment resting heart rate was increased (364±13 vs. 313±12 bpm, P<0.01). In contrast, the following parameters were shortened: QRS duration (77±3.6 vs. 65±2.6 ms, P<0.01); QT interval (102±5.2 vs. 88±3.7 ms, P<0.05); Q wave amplitude (-12.8±1.0 vs. -5.1±0.9 µv, P<0.01); and T wave amplitude (18.8±1.4 vs. 5.8±0.6, P<0.01). All other ECG parameters remained unchanged. With increased weight the resting heart rate (r=0.46, P<0.01) and R wave amplitude (r=0.60, P<0.01) increased. CONCLUSION: Early in obesity there are no rhythm disturbances, but resting heart rate is increased. The QRS duration is shortened and Q and T-wave amplitudes reduced signifying ventricular changes related to impaired myocardial depolarization and repolarization. Furthermore, weight gain is correlated with an increase in heart rate and accentuation of the R wave amplitude.

Millennium Global Village-Net: bringing together Millennium Villages throughout sub-Saharan Africa.

The Millennium Villages Project (MVP), based at The Earth Institute at Columbia University, is a bottom-up, community led approach to show how villages in developing countries can get out of the poverty trap that afflicts more than a billion people worldwide. With well-targeted, practical inputs can help the community invest in a path leading to self-sustaining development. There are 80 Millennium Villages clustered in 10 countries throughout sub-Saharan Africa. MVP is an important development process for empowering communities to invest in a package of integrated interventions aiming to increase food production, improve access to safe water, health care, education and infrastructure. The process benefits from synergies of the integrated approach and relies on community leadership as empowered by proven technological inputs. MVP is committed to a science-based approach to assess and monitor the progress of the communities towards clear objectives; the Millennium Development Goals (MDGs) and to do so with mechanisms that are scalable and sustainable. This approach offers much more than simply collecting and analyzing data since the mechanism used for recording progress would provide a bridge over the divide which separates the haves and the have-nots (by facilitating the sharing of solutions from one community to another bidirectionally). By so doing, it allows people to enhance their own futures in a sustainable manner. Solutions found in one community are transferable to similar communities in other MVP villages. To achieve this goal, the MVP requires an information and communication system which can provide both necessary infrastructure for monitoring and evaluation, and tools for communicating among the villages, cities and countries. This system is called the Millennium Global Village-Net (MGV-Net). It takes advantage of the latest in open source software (OpenMRS), databases (MySQL), interface terminology, a centralized concept dictionary, and uses appropriate technology locally for data entry.

Information needs of health care workers in developing countries: a literature review with a focus on Africa.

Health care workers in developing countries continue to lack access to basic, practical information to enable them to deliver safe, effective care. This paper provides the first phase of a broader literature review of the information and learning needs of health care providers in developing countries. A Medline search revealed 1762 papers, of which 149 were identified as potentially relevant to the review. Thirty-five of these were found to be highly relevant. Eight of the 35 studies looked at information needs as perceived by health workers, patients and family/community members; 14 studies assessed the knowledge of health workers; and 8 looked at health care practice. The studies suggest a gross lack of knowledge about the basics on how to diagnose and manage common diseases, going right across the health workforce and often associated with suboptimal, ineffective and dangerous health care practices. If this level of knowledge and practice is representative, as it appears to be, it indicates that modern medicine, even at a basic level, has largely failed the majority of the world's population. The information and learning needs of family caregivers and primary and district health workers have been ignored for too long. Improving the availability and use of relevant, reliable health care information has enormous potential to radically improve health care worldwide.

Information technology for health in developing countries.

Poverty has deepened the crisis in health-care delivery in developing countries, particularly sub-Saharan Africa, which is a region facing a disease burden that is unmatched in the world. Whether access to proven and powerful information and communication technologies (ICTs) can improve health indicators is an ongoing debate. However, this brief review shows that in the last decade there has been significant growth in Internet access in urban areas; health-care workers now use it for communication, access to relevant health-care information, and international collaboration. The central message learned during this period about the application of ICTs is that infrastructural and cultural contexts vary and require different models and approaches. Thus, to harness the full potential of ICTs to the benefit of health systems, health workers, and patients will demand an intricate mix of old and new technologies.