Management of diabetic neuropathy with memantine: A randomized clinical trial.

BACKGROUND: Diabetes patients frequently experience diabetic neuropathy (DN), a microvascular complication that significantly reduces patients' quality of life. Memantine has demonstrated potential benefits for neuropathic pains in preclinical studies. This study aimed to assess the efficacy of memantine in the management of peripheral neuropathy in patients with type 2 diabetes mellitus (T2DM). METHOD: This randomized clinical trial includes 143 diabetic patients (aged between 18 and 75 years) with a confirmed diagnosis of diabetic neuropathy. Patients were randomly assigned to receive memantine 5 mg twice daily for 1 week, followed by 10 mg twice daily plus gabapentin 300 mg daily (n = 72) or just gabapentin 300 mg daily (n = 71) for 8 weeks. The DN4 questionnaire, monofilament, tuning fork, and Tip-therm tests were used to measure neuropathy at baseline and after the 8-week intervention. RESULTS: The mean score of the DN4 questionnaire in the memantine group was significantly lower than the control group (p. value: .001). The number of patients with diabetic neuropathy remarkably decreased in the memantine group at the end of the study based on the performed tests (p. value: .001). CONCLUSION: Memantine functions as a beneficial agent in the management of diabetic neuropathy, which would significantly improve the quality of life in diabetic patients.

Anti-hyperglycemic effect of Abelmoschus culentesus (Okra) on patients with diabetes type 2: a randomized clinical trial.

Okra (Abelmoschus esculentus) has traditionally been used in diabetes treatment. This study investigated the effect of Okra whole fruit on blood glucose level of patients with diabetes mellitus type 2 with concomitant use of oral hypoglycemic agents. In this double-blind randomized clinical trial, 120 diabetic patients were assigned to okra group (n = 60) and control group (n = 60). The okra group received 1,000 mg of A.esculentus whole fruit capsules orally, every 6 hr for 8 weeks. The control group received placebo capsule in the same manner. The levels of FBS (fasting blood sugar), BS (blood sugar), and Hemoglobin A1C (HgA1c) were measured at baseline and after intervention in both groups. The levels of FBS, BS, and HgA1c were significantly decreased in okra group within the intervention compared to control group (p < .05). Moreover, the numbers to treat (NNT) for FBS, BS, and HgA1C were seven, eight, and seven, respectively. Okra whole fruit supplementation has a promising anti-hyperglycemic effect in patients with diabetes mellitus type 2 who received oral agents. Diabetic patients could benefit from adjuvant therapy of okra with other medication.

Real-state of autophagy signaling pathway in neurodegenerative disease; focus on multiple sclerosis.

The occurrence of neurodegenerative disease is increasingly raised. From physiopathological aspect, the emergence of auto-reactive antibodies against the nervous system antigens contributes to de-myelination in Multiple sclerosis (MS). These features cause the nervous system dysfunction. The follow-up of molecular alterations could give us a real-state vision about intracellular status during pathological circumstances. In this review, we focus on the autophagic response during MS progression and further understand the relationship between autophagy and MS and its modulatory effect on the MS evolution. The authors reviewed studies published on the autophagy status in neurodegenerative disease and on the autophagy modulation in MS prognosis, diagnosis, and possible therapies. The inevitable role of autophagy was shown in the early-stage progression of MS. Due to critical role of autophagy in different stage of cell activity in nervous system, the distinct role of autophagy should not be neglected in the development, pathogenesis, and treatment of MS.

Role of autophagy in atherosclerosis: foe or friend?

Athrosclerosis is conceived as a chronic inflammatory status affecting cells from vascular walls. Different mechanisms and pathological features are evident at the onset of atherosclerotic changes via the engaging different cells from the vascular wall and circulatory cells. Attempts are currently focused on the detection of cell compensatory mechanisms against atherosclerotic changes to restore cell function and/or postpone severe vasculitis. Autophagy is an intracellular self-digesting process commonly protrudes exhausted organelles and injured cytoplasmic constituents via double-lipid bilayer membrane vesicles out the target cells. Recent investigations point to the critical and defensive role of autophagy in the vascular cells behavioral function such as endothelial cells and smooth muscle cells against different insults. Autophagy response and related effectors could be modulated in the favor to restore cell function and reduce pro-inflammatory status under pathological conditions. In this review, the recent findings were collected regarding the role of autophagy during atherosclerotic changes. We aimed to answer the question of how autophagy stimulation and/or inhibition could provide a promising effect on developing a sophisticated treatment for AS.

What does the research say about androgen use and cerebrovascular events?

Many studies have investigated the benefits of androgen therapy and neurosteroids in aging men, while concerns remain about the potential associations of exogenous steroids and incidents of cerebrovascular events and ischemic stroke (IS). Testosterone is neuroprotective, neurotrophic and a potent stimulator of neuroplasticity. These benefits are mediated primarily through conversion of a small amount of testosterone to estradiol by the catalytic activity of estrogen synthetase (aromatase cytochrome P450 enzyme). New studies suggest that abnormal serum levels of the nonaromatized potent metabolite of testosterone, either high or low dihydrotestosterone (DHT), is a risk factor for stroke. Associations between pharmacologic androgen use and the incidence of IS are questionable, because a significant portion of testosterone is converted to DHT. There is also insufficient evidence to reject a causal relationship between the pro-testosterone adrenal androgens and incidence of IS. Moreover, vascular intima-media thickness, which is a predictor of stroke and myocardial symptoms, has correlations with sex hormones. Current diagnostic and treatment criteria for androgen therapy for cerebrovascular complications are unclear. Confounding variables, including genetic and metabolic alterations of the key enzymes of steroidogenesis, ought to be considered. Information extracted from pharmacogenetic testing may aid in expounding the protective-destructive properties of neurosteroids, as well as the prognosis of androgen therapy, in particular their cerebrovascular outcomes. This investigative review article addresses relevant findings of the clinical and experimental investigations of androgen therapy, emphasizes the significance of genetic testing of androgen responsiveness towards individualized therapy in post-IS injuries as well as identifying pertinent questions.

Chronic Exposure of Human Endothelial Progenitor Cells to Diabetic Condition Abolished the Regulated Kinetics Activity of Exosomes.

By virtue of lifestyle change, incidence of diabetes mellitus type 2 is increasingly being raised with different up-surging pathologies. It was showed that endothelial progenitor cells (EPCs) were disqualified in neo-angiogenesis induction. Besides, to an aborted differentiation property, malfunctioned paracrine activities worsen off vascular abnormality. Nano-scaled exosomes play essential roles in reciprocal cell-cell crosstalk via bioactive molecules. To address the effect of diabetic serum on exosome secretion capacity, EPCs were exposed to diabetic condition for seven days. In addition to in-vitro tubulogenesis, migration and LDL uptake assessment, exosome release capacity, and expression profiles of three genes participating in exosome kinetics, including CD63, Alix and Rab27a, revealed by Real-time PCR method. Data showed diabetic sera not only abolished the in-vitro tubulogenesis, migration and LDL uptake properties but also decreased exosome release and expression of related genes. This study sheds lights on the adverse effect of diabetic condition on exosome kinetics in EPCs.

Effect of probiotic supplements in women with gestational diabetes mellitus on inflammation and oxidative stress biomarkers: a randomized clinical trial.

BACKGROUND AND OBJECTIVES: Very little is known about the use of probiotics among pregnant women with gestational diabetes mellitus (GDM) especially its effect on oxidative stress and inflammatory indices. The aim of present study was to measure the effect of a probiotic supplement capsule on inflammation and oxidative stress biomarkers in women with newly-diagnosed GDM. METHODS AND STUDY DESIGN: 64 pregnant women with GDM were enrolled in a double-blind placebo controlled randomized clinical trial in the spring and summer of 2014. They were randomly assigned to receive either a probiotic containing four bacterial strains of Lactobacillus acidophilus LA-5, Bifidobacterium BB-12, Streptococcus Thermophilus STY-31 and Lactobacillus delbrueckii bulgaricus LBY-27 or placebo capsule for 8 consecutive weeks. Blood samples were taken pre- and post-treatment and serum indices of inflammation and oxidative stress were assayed. The measured mean response scales were then analyzed using mixed effects model. All statistical analysis was performed using Statistical Package for Social Sciences (SPSS) software (version 16). RESULTS: Serum high-sensitivity C-reactive protein and tumor necrosis factor-α levels improved in the probiotic group to a statistically significant level over the placebo group. Serum interleukin-6 levels decreased in both groups after intervention; however, neither within group nor between group differences interleukin-6 serum levels was statistically significant. Malondialdehyde, glutathione reductase and erythrocyte glutathione peroxidase levels improved significantly with the use of probiotics when compared with the placebo. CONCLUSIONS: The probiotic supplement containing L.acidophilus LA- 5, Bifidobacterium BB- 12, S.thermophilus STY-31 and L.delbrueckii bulgaricus LBY-2 appears to improve several inflammation and oxidative stress biomarkers in women with GDM.

The effect of pioglitazone on weight, lipid profile and liver enzymes in type 2 diabetic patients.

BACKGROUND: Pioglitazone is one of the antidiabetic agents used in the management of type 2 diabetes mellitus (DM). The effect of pioglitazone on blood glucose, lipid profile, liver enzymes and weight has been shown with conflicting results. In this study we aim to evaluate the effect of pioglitazone on the weight, lipid profile and liver enzymes in patients with DM. METHODS: In this single-arm clinical trial, 110 poorly controlled diabetic type 2 patients (63.6% female with mean age of 54.26 ± 8.96 years) who were on maximal dosage of metformin and glibenclamide were enrolled. Patients were treated with pioglitazone for 3 months and laboratory. Fasting blood sugar (FBS), haemoglobin A1C (HbA1C), cholesterol, triglyceride, low-density lipoprotein (LDL) and high-density lipoprotein (HDL), alkaline phosphatase (ALK-P), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and weight changes were measured before and at the end of the study. RESULTS: The levels of FBS (p < 0.001), HbA1c (p < 0.001), triglyceride (p = 0.001), ALT (p = 0.005) and ALK-P (p = 0.001) were significantly decreased, but weight was significantly increased (p < 0.001) after the intervention. There were no significant difference in cholesterol, LDL and HDL values before and after study. CONCLUSION: Although pioglitazone causes a significant decrease in FBS, HbA1C and triglyceride levels, it is associated with weight gain, which would limit its utility. IRCT registration code: IRCT201209276712N2.