Pathophysiology, Volume 27, Issue 1 (December 2020) – 7 articles

The goal of our study was to analyze the time course of the effect of N^G-nitro-L-arginine methyl ester (L-NAME) on nitric oxide synthase (NOS) isoforms and nuclear factor–κB (NF-κB) protein expression, total NOS activity, and blood pressure (BP) in rats. Adult 12-week-old male Wistar rats were subjected to treatment with L-NAME (40 mg/kg/day) for four and seven weeks. BP was increased after 4- and 7-week L-NAME treatments. NOS activity decreased after 4-week-L-NAME treatment; however, the 7-week treatment increased NOS activity in the aorta, heart, and kidney, while it markedly decreased NOS activity in the brainstem, cerebellum, and brain cortex. The 4-week-L-NAME treatment increased eNOS expression in the aorta, heart, and kidney and this increase was amplified after 7 weeks of treatment. In the brain regions, eNOS expression remained unchanged after 4-week L-NAME treatment and prolonged treatment led to a significant decrease of eNOS expression in these tissues. NF-κB expression increased in both peripheral and brain tissues after 4 weeks of treatment and prolongation of treatment decreased the expression in the aorta, heart, and kidney. In conclusion, decreased expression of eNOS in the brain regions after 7-week L-NAME treatment may be responsible for a remarkable decrease of NOS activity in these regions. Since the BP increase persisted after 7 weeks of L-NAME treatment, we hypothesize that central regulation of BP may contribute significantly to L-NAME-induced hypertension. Full article

The aim of this research was to correlate indicators of proinflammatory status and the structural/functional characteristics of the cardiovascular system comparatively in male and female patients with essential hypertension (EH) complicated by diastolic chronic heart failure (CHF) with preserved left ventricular ejection fraction (LVEF). The study included 104 middle-aged patients (55 males (M) and 49 females (F)) with first- or second-degree EH complicated by CHF with preserved LVEF. They all belonged to the low functional class of CHF, with LVEF ≥50%, first- or second-degree of LV diastolic dysfunction (LVDD), LV hypertrophy (LVH), and dilatation of the left atrium (LA) with a sinus rhythm and N-terminal brain natriuretic peptide >125 pg/mL. Serum levels of C-reactive protein (CRP), tumor necrosis factor alpha (TNF-α), and interleukin-6 (IL-6) were measured. To identify the relationship between the proinflammatory pattern and cardiovascular parameters, Spearman’s rank correlation coefficients were determined. M had markedly higher levels of CRP, TNF-α, and IL-6 compared to F. However, all the mean values corresponded to the reference range. Significant direct associations of CRP level with the LV mass index (LVMI), relative wall thickness (RWT), LA volume index (LAVI), E/e’ ratio, and systolic and diastolic blood pressure (SBP, DBP) existed in both M and F, as well as negative correlations of CRP with LVDD parameter e’ and distance covered in a 6 min walk test. M and F had a positive association between IL-6 and LVMI, LAVI, E/e’ ratio, SBP, RWT, and DBP, as well as strong negative associations between IL-6 and e’ and distance passed in 6 min in each group. Significant direct correlations existed between serum TNF-α level and LVMI, RWT, LAVI, E/e’, SBP, and DBP both in M and F. Furthermore, there were negative relationships of TNF-α level with e’ and the distance covered for the 6 min walk. This study demonstrated a close relationship between the blood levels of proinflammatory autacoids and indicators of EH, exercise tolerance, LVH, LVDD, and LA enlargement, regardless of the patient’s sex. Compared to female patients, male patients had stronger correlations of CRP, TNF-α, and IL-6 levels with indicators of LVDD degree. Full article

Diabetes mellitus is associated with impairment in cognitive functions which can complicate adherence to self-care behaviors. We evaluated the incidence of cognitive impairment in patients with diabetes mellitus to determine the strength of the association between diabetic foot (a complication that occurs in about 10% of diabetic patients), adherence to the clinician’s recommendations, glycemic control, and cognitive function. A prospective study was carried out in a probabilistic sample of older patients with diabetic foot living in three nursing homes. Cognitive functions were evaluated by the MMSE (Mini-Mental State Examination), the Trail Making test (TMT), and the Michigan neuropathy screening instrument (MNSI). There were no significant associations between cognitive function and neuropathy or foot alterations, although glycated hemoglobin (HB1Ac > 7%) significantly (p < 0.05) associated with MMSE and adherence to treatment in the 1 month follow-up visit. Receiver operating characteristic curve analysis showed that both HB1Ac and the MNSI score significantly (p < 0.05) discriminate subsequent adherence to treatment for foot complication, with a sensitivity of 80.0–73.3% and specificity 70.6–64.7%, respectively. Proper control of foot complications in diabetic patients involves appropriate glycemic control and less severe neuropathy, and seems to be unrelated to cognitive dysfunction, and warrants further studies in order to tailor appropriate treatments to central and peripheral nervous system disorders. Poor glycemic control (Hb1Ac level > 7%) and a neuropathy score of 5.5 in the MNSI are the best-cut off points to discriminate poor adherence to the clinician’s recommendations for self-care behaviors in people with diabetic foot complication. In this study, we observed that foot disorders were associated with impaired global cognitive function in elderly patients (aged ≥ 65). Podiatrists and physicians should consider cognitive dysfunction as an important chronic complication in the management of diabetic foot. Full article

Hepatitis B virus (HBV) infects the liver, causing cirrhosis and cancer. In developed countries, five international guidelines have been used to make a decision for the management of patients with chronic HBV infection. In this review, since the guidelines were established by clinical and epidemiological data of developed countries, we aimed to evaluate whether (1) HBV patient profiles of developing countries are similar to developed countries, and (2) which guideline can be applicable to resource-limited developing countries. First, as an example of the most recent data of HBV infections among developing countries, we evaluated the national HBV viral load study in Nepal, which were compared with the data from other developing countries. In Nepal, the highest number of patients had viral loads of 20–2000 IU/mL (36.7%) and belonged to the age group of 21–30 years; HBV epidemiology in Nepal, based on the viral loads, gender, and age groups was similar to those of not only other developing countries but also developed countries. Next, we reviewed five international HBV treatment guidelines of the World Health Organization (WHO), American Association for the Study of Liver Diseases (AASLD), National Institute for Health and Care Excellence (NICE), European Association for the Study of the Liver (EASL), and Asian Pacific Association for the Study of the Liver (APASL). All guidelines require the viral load and alanine aminotransferase (ALT) levels for decision making. Although four guidelines recommend elastography to assess liver cirrhosis, the WHO guideline alternatively recommends using the aspartate aminotransferase (AST)-to-platelet ratio index (APRI), which is inexpensive and conducted routinely in most hospitals. Therefore, in resource-limited developing countries like Nepal, we recommend the WHO guideline for HBV treatment based on the viral load, ALT, and APRI information. Full article