Med. Sci., Volume 4, Issue 4 (December 2016) – 7 articles

Iron overload is increasingly being connected to insulin resistance in Type 2 Diabetes Mellitus (T2DM) patients. Free iron causes the assembly of reactive oxygen species that invariably steer the body’s homeostasis towards oxidative stress-mediated diabetic complications. This study aims to assess the serum iron, total iron binding capacity (TIBC), and percentage transferrin saturation (Tsat) of 150 subjects divided into three groups (I,II,III) of 50. Healthy individuals (controls) constituted Group I. Group II consisted of T2DM patients with optimal glycaemic control. T2DM patients with suboptimal glycaemic control formed group III. Mean serum free iron concentration was 105.34 ± 3.5, 107.33 ± 3.45, and 125.58 ± 3.45 μg/dL in Group I, Group II, and Group III, respectively. Mean serum TIBC concentration in Group I, Group II, and Group III was 311.39 ± 5.47, 309.63 ± 6.1, and 284.2 ± 3.18 μg/dL, respectively. Mean serum transferrin saturation (%) in Group I, Group II, and Group III was 34.17 ± 1.21, 35.02 ± 1.2, and 44.39 ± 1.07, respectively. The difference between TIBC, mean serum free iron concentration, and transferrin saturation between Group I and Group III (for all, p values <0.001), as well as between Group II and Group III (p values 0.0012, 0.0015, and <0.0001, respectively) was statistically significant. The fasting plasma glucose values of Groups II and III were significantly higher than those of Group I, (p < 0.0001). Glycated haemoglobin (HbA1c) values were also shown to increase from Group I to II and then III, and the increase was highly significant (all p values <0.0001). Thus, decreased glycaemic control and an increase in the glycation of haemoglobin was the key to elevation in serum iron values and alterations in other parameters. However, a significant correlation was absent between serum iron and HbA1c (r = 0.05) and transferrin saturation (r = 0.0496) in Group III. Full article

The water-insoluble storage proteins of cereals (prolamins) are called “gluten” in wheat, barley, and rye, and “avenins” in oat. Gluten can provoke celiac disease (CD) in genetically susceptible individuals (those with human leukocyte antigen (HLA)-DQ2 or HLA-DQ8 serotypes). Avenins are present at a lower concentration (10%–15% of total protein content) in oat as compared to gluten in wheat (80%–85%). The avenins in the genus Avena (cultivated oat as well as various wild species of which gene bank accessions were analyzed) are free of the known CD immunogenic epitopes from wheat, barley, and rye. T cells that recognize avenin-specific epitopes have been found very rarely in CD patients. CD patients that consume oats daily do not show significantly increased levels of intraepithelial lymphocyte (EIL) cells. The safety and the positive health effects of the long-term inclusion of oats in the gluten-free diet have been confirmed in long-term studies. Since 2009 (EC 41/2009) and 2013 (FDA) oat products may be sold as gluten-free in several countries provided a gluten contamination level below 20 ppm. Introduction of oats in the gluten-free diet of celiac patients is advised after the recovery of the intestine. Health effects of oat consumption are reflected in European Food Safety Authority (EFSA)- and Food and Drug Administration (FDA)-approved health claims. Oats can form a healthy, nutritious, fiber-rich, and safe complement to the gluten-free diet. Full article

Celiac disease (CD) is a chronic small intestinal enteropathy triggered by gluten in genetically predisposed individuals. The susceptibility is strongly associated with certain human leukocyte antigen (HLA)-genes, but efforts are being made in trying to find non-HLA genes that are predictive for the disease. The criteria for diagnosing CD were previously based primarily on histologic evaluation of small intestinal biopsies, but nowadays are often based only on blood tests and symptoms. In this context, we elucidated the accuracy of three diagnostic indicators for CD, alone or in combination. Genetic analyses of HLA-type and nine single nucleotide polymorphisms (SNPs) known to be associated with CD were performed in 177 children previously investigated for the suspicion of CD. CD was confirmed in 109 children, while 68 were considered non-celiacs. The antibodies and urinary nitrite/nitrate concentrations of all of them were measured. The combinations of all the variables used in the study would classify 93% of the study population in the correct diagnostic group. The single best predictors were antibodies (i.e., anti-endomysium immunoglobulin A (IgA) (EMA) and transglutaminase IgA (TGA)), followed by HLA-type and nitric oxide (NO)-metabolites. The nine SNPs used did not contribute to the right diagnoses. Although our control group consisted of children with mostly gastrointestinal symptoms, the presented methodology predicted a correct classification in more than 90% of the cases. Full article

Studies have shown that human immunodeficiency virus type 1 (HIV-1) disproportionally affects more females than males. Affected individuals are susceptible to infections due to depressed immunity, qualitative defects in phagocytic function and altered phagocytosis as well as lowered oxidative burst capacity. This study seeks to determine whether sex differences exist in serum activities of respiratory burst enzymes in HIV-1–infected female and male subjects. Serum myeloperoxidase, catalase and superoxide dismutase activities were assayed in 170 confirmed HIV-1 positive and 50 HIV-1 negative subjects using ELISA. Data were analyzed using Student’s t-test and p values of less than 0.05 were considered significant. The measured enzyme activities were significantly higher (p < 0.001) in females than males in HIV-1 negative subjects while no sex differences were observed in HIV-1 positive subjects. The absence of sex differences in the activities of respiratory burst enzymes in HIV-1 infection may be due to immune activation as a result of active phagocytic leukocytes, immune reactivity and inflammation. Full article

Recent meta-analyses and publications over the past 15 years have provided evidence showing there are considerable gender differences in the pharmacokinetics of metoprolol. Throughout this time, there have not been any research articles proposing a gender stratified dose-adjustment resulting in an equivalent total drug exposure. Metoprolol pharmacokinetic data was obtained from a previous publication. Data was modeled using nonlinear mixed effect modeling using the MONOLIX software package to quantify metoprolol concentration–time data. Gender-stratified dosing simulations were conducted to identify equivalent total drug exposure based on a 100 mg dose in adults. Based on the pharmacokinetic modeling and simulations, a 50 mg dose in adult women provides an approximately similar metoprolol drug exposure to a 100 mg dose in adult men. Full article

The present study was aimed to evaluate the levels of oxidative stress markers in breast diseases by measuring the 8-hydroxy-2-deoxyguanosine (8-OHdG), vitamin A, vitamin C, vitamin E, and total antioxidant status (TAS) alterations in relation to cell proliferation activity and disease progression. Significant increases in the level of the oxidative damage marker 8-OHdG and cell proliferation activity were observed in breast carcinoma patients in comparison to benign and normal controls, which were accompanied by a significant decrease in non-enzymatic antioxidants and TAS concentrations (p < 0.05). 8-OHdG and cell proliferation levels were negatively correlated with non-enzymatic antioxidants, namely, vitamin A, vitamin C, and vitamin E levels and total antioxidant activity. Altered levels of biomarkers of oxidative stress and cell proliferation activity among the malignant, the benign, and the controls suggest a correlation of increased oxidative stress and cell proliferation activity in the progression of disease in breast carcinoma patients. In conclusion, our results showed that the characterized biomarkers (i.e., low levels of vitamin A, C and D, and the TAS status; and high levels of 8-OHdG) could be used as a suitable method for detecting subjects with malignant and benign breast diseases. Full article

Renal cell carcinoma (RCC) is the most common neoplasm that occurs in the kidney and is marked by a unique biology, with a long history of poor response to conventional cancer treatments. In the past few years, there have been significant advancements to understand the biology of RCC. This has led to the introduction of novel targeted therapies in the management of patients with metastatic disease. Patients treated with targeted therapies for RCC had shown positive impact on overall survival, however, no cure is possible and patients need to undergo treatment for long periods of time, which raises challenges to manage the associated adverse events. Moreover, many patients may not respond to it and even response may not last long enough in the responders. Many inhibitors of the Mammalian target of Rapamycin (mTOR) signaling pathway are currently being used in treatment of advanced RCC. Studies showed that inhibitions of mTOR pathways induce Mitogen-Activated Protein Kinase (MAPK) escape cell death and cells become resistant to mTOR inhibitors. Because of this, there is a need to inhibit both pathways with their inhibitors comparatively for a better outcome and treatment of patients with RCC. Full article