Effects of vasoactive substances on biomechanics of small resistance arteries of male and female Dahl salt-sensitive rats.

Changes in vascular biomechanics leading to increase in arterial stiffness play a pivotal role in circulatory dysfunction. Our objectives were to examine sex-specific pharmacological changes related to the biomechanics and any structural modifications in small resistance arteries of Dahl salt-sensitive male and female rats. The composite Young modulus (CYM) was determined using pressure myograph recordings, and immunohistochemistry was used for the evaluation of any structural changes in the third-order mesenteric arteries (n = 6). Animals on high-salt diet developed hypertension with significant elevation in central and peripheral blood pressures and pulse wave velocity compared to those on regular diet. There were no significant differences observed in the CYM between any of the groups (i.e., males and females) in vehicle-treated time-control studies. The presence of verapamil (0.3 µM) significantly reduced CYM in hypertensive males without changes within females compared to vehicle. This effect was abolished by phenylephrine (0.3 µM). BaCl2 (100 µM), ouabain (100 µM), and L-NAME (0.3 µM) combined significantly increased CYM in vessels from in normotensive males and females but not in hypertensive males compared to vehicle. The increase in CYM was abolished in the presence of phenylephrine. Sodium nitroprusside (0.3 µM), in the presence of phenylephrine, significantly reduced CYM in male normotensive versus hypertensive, with no differences within females. Significant differences were observed in immunohistochemical assessment of biomechanical markers of arterial stiffness between males and females. Our findings suggest sex possibly due to pressure differences to be responsible for adaptive changes in biomechanics, and varied pharmacological responses in hypertensive state.

Knowledge and awareness of mitochondrial diseases among physicians in the tertiary hospitals in Ghana.

BACKGROUND: Mitochondrial diseases/disorders (MDs), for decades, have been identified as a key underlying condition for many chronic diseases globally. However, data on the knowledge and prevalence of MDs in many countries in sub-Saharan Africa are lacking. This study assessed the knowledge, and awareness, of MDs among senior medical doctors in the five tertiary hospitals in Ghana. METHOD: Data were collected from one hundred and twenty-eight (128) medical doctors in the five Tertiary Hospitals in Ghana using both closed and open-ended questionnaires and analysed using descriptive statistics. RESULTS: Of the 128 respondents, 70.32% were senior medical officers and above, 87% of them indicated that they were aware of MDs and over 90% said physicians do not often diagnose MDs in Ghana. About 81% indicated that MDs are associated with chronic illnesses whilst 72% said the disease is diagnosed in both males and females. About 45% of the respondents alluded to the fact that MDs are difficult to diagnose, are associated with mutations in both the mitochondrial and the nuclear DNA, and are non-infectious diseases. Approximately 85% said nervous system dysfunction and muscle weakness are some of the symptoms associated with MDs whilst 77% said fatigue is also one of the symptoms. About 38% of the respondents specified that they encounter myopathies. A majority (70%) did not know about the availability of any consensus or standard diagnostic procedure and/or drugs for MDs. CONCLUSION: There is a high level of knowledge and awareness of MDs among the respondents. However, there is a low disease encounter, which could be due to a lack of diagnostic protocols or a low disease prevalence. It is, therefore recommend that a patient perspective study, which looks at clinical records and laboratory data be conducted to fully ascertain the prevalence of MDs in Ghana and that appropriate educational strategies and interventions aimed at improving the diagnosis of mitochondrial diseases in Ghana be put in place.

Differential biomechanics in resistance arteries of male compared with female Dahl hypertensive rats.

BACKGROUND: Increase in vascular stiffness is associated with a higher risk of cardiovascular morbidity and mortality and is likely sex-specific. METHOD: Our objectives were to compare structural and functional alterations in small resistance arteries as related to vascular stiffness from Dahl salt-sensitive male and female rats (n = 8, mean ±â€Šs.e.m.). RESULTS: Arterial blood pressure and pulse wave velocity were significantly (P < 0.05) elevated in males (161 ±â€Š3 mmHg; 6.4 ±â€Š0.2 m/s) and females (147 ±â€Š2 mmHg; 5.5 ±â€Š0.1 m/s) on a high (H) salt compared with regular (R) diets but were significantly higher in males (H) than in all others. Significant increases in collagen and smooth muscle cell areas were evident in ultrastructure of mesenteric arteries of hypertensive males compared to normotensive or corresponding females. There were no significant differences in composite Young's modulus (CYM) between groups. Vasoconstriction resulted in significantly higher CYM in male (H: 8.6 ±â€Š1 KPa) than R (4.5 ±â€Š0.8 KPa), and the corresponding females (H: 5.6 ±â€Š0.6 KPa and R: 5 ±â€Š0.9 KPa). In contrast, vasodilation significantly reduced CYM in the male groups (H: 2.5 ±â€Š0.4 KPa and R: 2.7 ±â€Š0.5 KPa) compared with the corresponding values in females (H: 4.2 ±â€Š0.6 KPa and R: 5 ±â€Š0.5 KPa). Moreover, the slope of pressure-volume curves revealed significantly greater distended vascular compliance in male H than R, and the corresponding females. CONCLUSION: Our findings are supportive of a link between high salt intake and elevated blood pressure as being sex specific, likely involving sex-dependent changes in ultrastructure of the vessels, which ultimately may alter the biomechanics, and thus, the haemodynamic functions of both macro-circulation and micro-circulations.

Association between Antiretroviral Treatment and Markers of Systemic Inflammation among HIV Patients in Ghana.

BACKGROUND: Studies from high-income countries have reported that even after receiving antiretroviral treatment (ART), HIV-infected adults may not achieve normal levels of certain inflammatory markers that are known to be associated with the onset and development of non-communicable diseases. OBJECTIVE: The aim of this study is to examine the relationship between ART and markers of systemic inflammation in HIV/AIDS patients at an urban antiretroviral clinic in Ghana. METHODS: We examined serum levels of high sensitivity CRP (hsCRP), interleukin-6 (IL-6), interleukin- 18(IL-18), and tumor necrosis factor-α (sTNFR1 and sTNFR2) from 40 HIV infected patients. Kruskal-Wallis Test was used to examine the differences in markers of systemic inflammation according to the types of ART medication taken. We then utilized generalized additive models (GAM) with non-linear function to examine the association between ART and markers of systemic inflammation after adjusting for potential confounders. RESULTS: Overall, 30 (75.0%) of the participants received ART and 35 (85%) were female. Kruskal- Wallis Test revealed no significant differences in the markers of systemic inflammation among the three categories of ART (none, AZT, 3TC, EFV/NVP, and TDF, 3TC/FTC, EFV/NVP). In the multivariable- adjusted GAM model, we found a significant but non-linear association between time since diagnosis and CRP levels (p=0.006). CONCLUSION: Although the relatively small sample size limits the scope of the study's findings, these results suggest that individuals on ART need to be screened periodically for the development of chronic conditions. This line of investigation has the potential to influence treatment and clinical guidelines that will improve the quality of care for HIV-infected patients.

Symptoms of Toxicity and Plasma Cytochrome c Levels in Human Immunodeficiency Virus-infected Patients Receiving Anti-retroviral Therapy in Ghana: A Cross-sectional Study.

BACKGROUND: Side effects and toxicity have posed a threat to the positive contribution of Antiretroviral Therapy (ART) in the management of human immunodeficiency virus (HIV) infection and Acquired Immune Deficiency Syndrome (AIDS). Symptoms of mitochondrial toxicity including myopathy, pancreatitis, hyperlipidaemia and lactic acidosis are found among HIVinfected patients on ART. To date, there is not a reliable biomarker for monitoring ART-related mitochondrial toxicity. Plasma level of Cytochrome c (Cyt-c) has been proposed as a potential biomarker for ART-related toxicity due to its strong association with apoptosis. OBJECTIVE: The present study assessed toxicity and level of plasma Cyt-c among HIV-infected patients receiving ART in Ghana. METHODS: A total of eighty (80) HIV patients were recruited into the study. Demographic data were obtained from personal interview and medical records. Plasma samples were screened for toxicity from sixty (60) participants due to limited resources, and plasma Cyt-c levels were determined using ELISA. Data were analyzed using Stata version 13. RESULTS: Out of the 60 participants, 11 (18.3%) were found with symptoms of myopathy, 12 (20%) with pancreatitis, 21 (35%) with hyperlipidaemia and 36 (60%) with at least one of the symptoms. The concentration of plasma Cyt-c was higher (0.122 ng/ml) in patients with toxicity than in those without toxicity (0.05 ng/ml), though the difference was not statistically significant (p = 0.148). There was a weak correlation between plasma Cyt-c level and duration of ART (Spearman rho = 0.02, p = 0.89). CONCLUSION: This study, therefore, demonstrated a high prevalence of ART-related toxicity and high levels of Cyt-c in HIV-infected patients in support of the argument that plasma Cyt-c levels are potential biomarkers for determining ART-related toxicity in HIV patients.