Evaluation of the Effect of Favipiravir on QT Intervals in COVID-19 Patients with and without Diabetes Mellitus.

OBJECTIVE: To evaluate the effect of favipiravir administered to diabetic and non-diabetic COVID-19 patients on the QT/QTc interval. STUDY DESIGN: Analytical study. Place and Duration of the Study: Republic of Turkey, Ministry of Health, State Hospital, Corlu, Tekirdag, Turkiye, from March to September 2021. METHODOLOGY: Electrocardiogram (ECG) analysis was performed on all participants (n=180) divided into four groups. Group 1 included only healthy volunteers. Group 2 included only cases diagnosed with T2DM. Group 3 included only severe acute respiratory syndrome coronavirus-2 (SARS-Cov-2) cases. Group 4 included cases diagnosed with both SARS and T2DM. Favipiravir was administered only to the cases in Group 3 and Group 4. In the cases that were administered favipiravir, the QT/QTc interval was calculated and recorded at different time intervals on the first and fifth days of the therapy. The difference between groups was determined by Tukeye's test after ANOVA. Pearson's correlation test was used to determine whether there was a linear relationship between two numericals. The alpha significance value was determined to be <0.05 in all statistical analyses. RESULTS: When all groups were compared, it was seen that both QT and QTc values ​​increased in Groups 3 and 4, which were administered favipiravir (p <0.05). Favipiravir may cause an increased risk of ventricular and atrial arrhythmias. CONCLUSION: Favipiravir may cause QT interval prolongation, particularly in SARS-Cov-2 patients diagnosed with T2DM. KEY WORDS: COVID-19, Drug-induced long QT syndrome, Intra-infarct haemorrhage; Favipiravir, Type 2 diabetes mellitus.

Evaluation of Calciferol, Cobalamin, and Stromelysin-1 in Patients with Diabetic Peripheral Neuropathy due to Type-2 Diabetes Mellitus.

OBJECTIVE: To evaluate the relationship between calciferol (vitamin D), cobalamin (vitamin-B12), and Stromelysin-1 (MMP-3) circulating levels in patients with diabetic peripheral neuropathy (DPN), patients with DM type 2 (T2DM) without neuropathy, and healthy control groups. STUDY DESIGN: Cross-sectional descriptive study. PLACE AND DURATION OF STUDY: Department of Internal Medicine, Namik Kemal University of Medicine, Tekirdag, Turkey, between November 2020 and February 2022. METHODOLOGY: Healthy, age, and gender matched volunteers who were admitted to the hospital for a check-up with no health problem constituted the control group (n=30). Cases diagnosed with T2DM (n=30) and those with DPN (n=30) comprised the experimental group. Stromelysin-1, calciferol, and cobalamin levels were analysed from blood samples from all groups using enzyme-linked immunosorbent assay (ELISA) with a commercial kit. Tukey's Honest Significant Difference (HSD) test was performed after one-way analysis of variance (ANOVA) for intergroup comparisons. Alpha significance level was accepted as.

Evaluation of endocan and endoglin levels in chronic kidney disease due to diabetes mellitus.

INTRODUCTION: Endocan and endoglin have been shown to play a role in angiogenesis. Aberrant excessive angiogenesis is a main factor in the development of diabetic nephropathy. In this study we evaluated endocan and endoglin levels in diabetes patients with and without albuminuria and compared them with healthy subjects. Therefore we aimed at gaining a better understanding of the role of angiogenesis in diabetic nephropathy and to assess the predictive role of endocan and endoglin as markers of diabetic nephropathy progression. MATERIAL AND METHODS: Ninety-six type 2 diabetes patients were classified according to their 24-hour urinary albumin excretion rate. Forty type 2 diabetes patients with normoalbuminuria (urinary albumin excretion < 30 mg/day), 56 type 2 diabetes patients with diabetic nephropathy (with a urinary albumin excretion ≥ 30 mg/day) and 35 healthy non-diabetic control subjects were included. Their anthropometric features, arterial blood pressures, fasting glucose, glycated hemoglobin, urea, creatinine, lipids, endocan and endoglin levels were measured and compared to each other. RESULTS: Endocan and endoglin levels of diabetics patients were higher than those of the controls. In comparison of endocan and endoglin levels of diabetic nephropathy patients with controls, p-values were < 0.001 and 0.002 respectively. In comparison of normoalbuminuric diabetic patients with controls, p-values were 0.001 and 0.017 respectively. Endocan levels of diabetic nephropathy cases were higher than those of normoalbuminuric patients (p = 0.011) but there was no statistically significant difference in endoglin levels between them (p = 0.822). CONCLUSIONS: Endocan might be a more reliable marker of diabetic nephropathy development than endoglin.

Asymmetric dimethylarginine contributes to airway nitric oxide deficiency in patients with COPD.

INTRODUCTION: Asymmetric dimethylarginine (ADMA) and nitric oxide (NO) show their mechanism of action reciprocally, the balance between these molecules contributes to the tight regulation of airways tone and function. OBJECTIVES: The aim of this study to determine the serum levels of ADMA and NO in patients with chronic obstructive pulmonary disease (COPD) and establish whether their level vary in relation to forced expiratory volume in 1s (FEV1 ), to assess their role in pathophysiology of COPD. MATERIALS AND METHODS: This study consisted of 58 patients with COPD and 30 healthy subjects. Serum ADMA and NO levels were measured using enzyme-linked immunosorbent assay and the colorimetric method, respectively. RESULTS: Serum ADMA levels were significantly higher, however, NO levels were lower in patients with COPD compared with controls. ADMA levels were inversely correlated with NO levels. Serum ADMA and NO were significantly correlated with FEV1 . Multivariable logistic regression analysis revealed that serum ADMA and NO were independently and significantly associated with the presence of COPD. Multiple linear regression analysis showed that COPD was positively associated with ADMA, additionally COPD and ADMA were independently and inversely associated with NO. NO levels were decreased, ADMA levels were increased compliant with progression of COPD stages. CONCLUSION: While circulating ADMA is higher, NO is lower in COPD and both show a strong correlation to the degree of airflow limitation. ADMA seems to be a possible new marker of prognosis of COPD and can be a novel therapeutic target for the treatment of COPD.

The effect of ezetimibe monotheraphy on mean platelet volume in patients with hyperlipidaemia: a retrospective study of 45 patients.

OBJECTIVE: To investigate the effect of ezetimibe on platelet functions as a drug which increases mevalonate levels. METHODS: This retrospective study was conducted in Istanbul, Turkey, and comprised record of normolipidaemic and hyperlipidaemic patients taken from the outpatient clinic from October 2004 to February 2015,. The results were taken from the baseline and third-month data of ezetimibe treatment. SPSS 22 was used for statistical analysis. RESULTS: Of the total, there were 50(53%) normolipidaemic patients and 45(47%) hyperlipidaemic ones. Pre- and post-treatment values of mean platelet volume were significantly higher in the hyperlipidaemic group than controls (p<0.001). In the hyperlipidaemic group there was no significant difference between pre- and post-treatment values of mean platelet volume (8.96±0.93 vs. 8.92±0.84; p>0.05). CONCLUSIONS: The use of ezetimibe alone should not be the first choice in hyperlipidaemia treatment.

The association of vitamin D with inflammatory cytokines in diabetic peripheral neuropathy.

[Purpose] The effects of vitamin D on the circulating levels of IL-17 and IL-13 were investigated in patients with diabetic peripheral neuropathy, patients with diabetes mellitus type 2 without neuropathy, and healthy controls. [Subjects and Methods] A single-blind controlled clinical study was performed, including70 type 2 diabetic patients with or without diabetic peripheral neuropathy and 33 healthy volunteer controls. The 25(OH)D levels were evaluated using ultra-performance liquid chromatography, and IL-17 and IL-13 levels were assessed using enzyme-linked immunosorbent assays. [Results] The 25(OH) vitamin D concentration was lower in diabetic peripheral neuropathy patients than in diabetes mellitus patients without neuropathy and healthy controls. Similarly, 25(OH)D levels were lower in diabetes mellitus patients than healthy controls. IL-17 and IL-13 levels were higher in diabetes mellitus patients than in controls. Additionally, IL-13 levels were higher in diabetic peripheral neuropathy patients than in diabetes mellitus patients without neuropathy. These differences were statistically significant. There was a significant positive correlation between 25(OH)D and IL-13,and a negative correlation between 25(OH)D andIL-17 in the diabetic and diabetic neuropathy groups. [Conclusion] Vitamin D is a potential modifiable risk factor for diabetic peripheral neuropathy and may regulate inflammatory mediators, e.g., IL-17 and IL-13.

The effects of fat distribution and some adipokines on insulin resistance.

INTRODUCTION: The risk of developing insulin resistance and metabolic syndrome is particularly high in central obesity. In this study we evaluated the effects of fat distribution and some adipokines on insulin resistance in prediabetic patients. MATERIAL AND METHODS: Eighty-seven age- and sex-matched patients were divided into three groups according to their 75-gram oral glucose tolerance test results as follows: impaired fasting glucose group, impaired glucose tolerance group, and normal glucose tolerance group. Fasting insulin levels were measured. Homeostatic model assessment of insulin resistance was calculated. Body fat mass measurements were assessed by bioelectric impedance analyser and abdominal fat thicknesses (subcutaneous, visceral, and preperitoneal) by ultrasonography. The fasting serum levels of several adipokines [adiponectin, leptin, resistin, vaspin, visfatin, retinol-binding protein-4 (RBP-4), tumour necrosis factor-alpha (TNF-alpha)] were measured by ELISA method. RESULTS: The mean body mass index, fat mass measurements, and abdominal fat thicknesses of the groups were similar. There were no differences between groups in terms of the mean fasting insulin, vaspin, RBP-4, leptin, resistin, and TNF-alpha. In comparison of the prediabetic and normal groups, the levels of adiponectin (p < 0.001) and visfatin (p < 0.001) were lower in the prediabetic group. Furthermore, we found that high body mass index (p < 0.01) and fat mass (p < 0.01) and low adiponectin (p < 0.05) levels have roles in the development of insulin resistance in the prediabetic group. CONCLUSIONS: We suggested that in the prediabetic period not only obesity but also decreased adiponectin levels play some role in the pathogenesis of insulin resistance. (Endokrynol Pol 2016; 67 (3): 277-282).

The effects of melatonin on liver functions in arsenic-induced liver damage.

OBJECTIVE: Arsenic exposure is increasing in communities due to environmental pollution and industrial development. Arsenic is toxic to organ systems because it causes oxidative stress, enzymatic inhibition, and damage to protein structures. The liver, for example, is an organ that may be damaged by arsenic, and this damage may cause various clinical conditions like hepatic failure or cancer. Melatonin is a hormone that acts like an antioxidant, an anti-inflammatory agent, and a cytoprotective agent. In this study, we aimed to evaluate melatonin's protective effects on livers damaged by arsenic toxicity. MATERIALS AND METHODS: Twenty-four Sprague-Dawley male rats were classified into three groups: a control group, an arsenic applied group, and an arsenic plus 10 mg/kg melatonin applied group. At the end of the fifteen-day experiment, the rats were sacrificed. Albumin, interleukin-6 (IL-6), total protein, alanine transaminase, aspartate transaminase, macrophage migration inhibitory factor, and monocyte chemotactic protein-1 measurements were obtained. RESULTS: In rats with liver damage due to arsenic exposure, melatonin administration significantly decreased the levels of IL-6, macrophage migration inhibitory factor, and monocyte chemotactic protein-1 (p<0.001, p=0.02 and p=0.04, respectively). CONCLUSION: After evaluating liver enzymes and inflammatory markers, this study determined that melatonin exposure improves liver tissue damage caused by arsenic exposure, with the degree of improvement varying based on the levels of arsenic exposure.

Are treatment guides and rational drug use policies adequately exploited in combating respiratory system diseases?

The aim of the present study was to increase awareness regarding the rational use of medicines. The data were obtained via the Material Resources Management System Module of the Ministry of Health. For the appropriateness of treatments, the Global Initiative for Asthma, the Global Initiative for Chronic Obstructive Lung Disease, and the guidelines for the rational use of medicines were used. We also investigated whether any de-escalation method or physical exercise was performed. Statistical analyses were performed using descriptive statistics to determine the mean, standard deviation, and frequency. The results showed that healthcare providers ignored potential drug reactions or adverse interactions, and reflecting the lack of adherence to the current treatment guides, 35.8% irrational use of medicines was recorded. Thus, de-escalation methods should be used to decrease costs or narrow the antibiotic spectrum, antibiotic selection should consider the resistance patterns, culturing methods should be analyzed, and monotherapy should be preferred over combination treatments.

Protective Effect of Infliximab, a Tumor Necrosis Factor-Alfa Inhibitor, on Bleomycin-Induced Lung Fibrosis in Rats.

We aimed to investigate the preventive effect of Infliximab (IFX), a tumor necrosis factor (TNF)-α inhibitor, on bleomycin (BLC)-induced lung fibrosis in rats. Rats were assigned into four groups as follows: I-BLC group, a single intra-tracheal BLC (2.5 mg/kg) was installed; II-control group, a single intra-tracheal saline was installed; III-IFX + BLC group, a single-dose IFX (7 mg/kg) was administered intraperitoneally (i.p.), 72 h before the intra-tracheal BLC installation; IV-IFX group, IFX (7 mg/kg) was administered alone i.p. on the same day with IFX + BLC group. All animals were sacrificed on the 14th day of BLC installation. Levels of tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-ß, interleukin (IL)-6, periostin, YKL-40, nitric oxide (NO) in rat serum were measured, as well as, myeloperoxidase (MPO), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) activity, and reduced glutathione (GSH), hydroxyproline, malondialdehyde (MDA) content in lung homogenates. Lung tissues were stained with hematoxylin and eosin (H&E) for quantitative histological evaluation. The inducible nitric oxide synthase (iNOS) expression and cell apoptosis in the lung tissues were determined quantitatively by immunohistochemical staining (INOS) and by TUNNEL staining, respectively. BLC installation worsened antioxidant status (such as SOD, CAT, GPx, GSH, MPO), while it increased the serum TNF-α, TGF-ß, IL-6, periostin, YKL-40, and lipid peroxidation, and collagen deposition, measured by MDA and hydroxyproline, respectively. IFX pretreatment improved antioxidant status as well as BLC-induced lung pathological changes, while it decreased the TNF-α, TGF-ß, IL-6, periostin, YKL-40, lipid peroxidation and collagen deposition. Finally, histological, immunohistochemical, and TUNNEL evidence also supported the ability of IFX to prevent BLC-induced lung fibrosis. The results of the present study indicate that IFX pretreatment can attenuate BLC-induced pulmonary fibrosis.

Are the leading drugs against Staphylococcus aureus really toxic to cartilage?

Many studies have shown that the toxic effects of local antibiotics on bone and cartilage limit orthopedic surgeons. In this study, we evaluated three antibacterial agents used locally to treat highly mortal and morbid diseases in the field of orthopedics, such as septic arthritis. Are vancomycin, teicoplanin, and linezolid, which are archenemies of Staphylococcus aureus, really toxic to chondrocytes? The purpose of the study was to investigate the effects of antibiotics, which are used against S. aureus, on human chondrocytes in vitro. Primary cell cultures obtained from gonarthrosis patients were divided into two main groups. One of these groups was designated as the control chondrocyte culture. The other group was divided into three subgroups, and each group was exposed to vancomycin, teicoplanin, or linezolid. Cell culture samples were characterized by immunophenotyping following incubation with the three different antibiotics. Before and after the agents were administered, the cultures were subjected to inverted and environmental scanning electron microscopy. The number of live cells and the proliferation rate were monitored with the MTT-assay. We found that vancomycin, teicoplanin, and linezolid do not have chondrotoxic effects. Vancomycin, teicoplanin, and linezolid had no chondrotoxic activity during in vitro culture, which supports the argument that these agents can safely be used in orthopedic surgery, especially against methicillin-resistant S. aureus agents.

Effect of CPAP on New Endothelial Dysfunction Marker, Endocan, in People With Obstructive Sleep Apnea.

Obstructive sleep apnea (OSA) is associated with increased cardiovascular (CV) morbidity and mortality. Endocan is a surrogate endothelial dysfunction marker that may be associated with CV risk factors. In this study, we tested whether serum endocan is a biomarker for OSA. Serum endocan levels were measured at baseline in 40 patients with OSA and 40 healthy controls and after 3 months of continuous positive airway pressure (CPAP) treatment in the patients with OSA. All participants were evaluated by full polysomnography. Flow-mediated dilatation (FMD) and carotid intima media thickness (cIMT) were measured in all participants. Endocan levels were significantly higher in patients with OSA than in healthy controls. After adjusting confounders, endocan was a good predictor of OSA. Endocan levels correlated with OSA severity (measured by the apnea-hypopnea index [AHI]). After 3 months of CPAP treatment, endocan levels significantly decreased. Endocan levels were significantly and independently correlated with cIMT and FMD after multiple adjustments. The cIMT and FMD also had significant and independent correlation with AHI. Endocan might be a useful marker for the predisposition of patients with OSA to premature vascular disease.

Relationship between red cell distribution width and contrast-induced nephropathy in patients who underwent primary percutaneous coronary intervention.

OBJECTIVE: This study evaluated the relationship between contrast-induced nephropathy (CIN) and red cell distribution width (RDW) in patients who underwent primary percutaneous coronary intervention (PCI). METHODS: A total of 359 patients with ST elevation myocardial infarction (STEMI) who had undergone primary PCI were included in the study. An increase of 25% in serum creatinine value after 48 h, or an increase of >0.5 mg/dL in the basal value was defined as CIN. RESULTS: Of the patients included in the study, 49 (13.8%) developed CIN. Compared to the CIN-negative group, CIN-positive patients had increased RDW values (16.9 ± 2.00 and 14.8 ± 2.14 respectively, p<0.001). The latter were also older patients, and had increased age rates of diabetes mellitus, baseline creatinine, ∆-creatinine and amount of contrast media were higher and left ventricular ejection fraction and baseline glomerular filtration rate (GFR) were lower in the CIN-positive group than in the CIN-negative group. A statistically weak correlation was found between RDW and change in creatinine levels (∆-creatinine) (r=0.250, p=0.002). Diabetes mellitus (odds ratio [OR]: 3.252, 95% CI=1.184-8.951, p=0.022), high RDW (OR: 1.716, 95% CI=1.363-2.157, p<0.001), baseline low GFR (OR: 0.941, 95% CI=0.925-0.971, p<0.001), ∆-creatinine (OR: 1.197, 95% CI=1.061-2.986, p=0.006) and increased amount of contrast media (OR: 1.187, 95% CI=1.048-3.02, p=0.001) used were observed as independent predictors of CIN. CONCLUSION: The study found diabetes mellitus, high RDW, basal low GFR, ∆-creatinine and increased contrast amount used to be the independent predictors of CIN in STEMI patients who underwent PCI.

Are biological agents toxic to human chondrocytes and osteocytes?

PURPOSE: The aim of the present study is to investigate the effects of biological agents (BAs) on human chondrocytes and osteocytes in vitro. METHODS: Primary cell cultures obtained from gonarthrosis patients were divided into four groups, two of which were designated as control cultures of chondrocyte and osteocyte, and the other two groups were exposed to BAs administered via the culture medium. Cultured cells were characterized by immunophenotyping. Before and after administration of the agents, the cultures were observed by inverted and environmental scanning electron microscopy (ESEM). The number of live cells and the proliferation rate were monitored by MTT assay. RESULTS: Rituximab and adalimumab were the least toxic agents to chondrocytes, whereas adalimumab and etanercept were to osteocytes. CONCLUSION: During periods of intense active inflammation, the concentration of the preferred BAs after inhibition of inflammation needs to be emphasized when their effects on cartilage and bone tissue are considered at the cellular level if the clinical practice is to continue.

A metabolic syndrome case presenting with lymphocytic mastitis.

BACKGROUND: Lymphocytic mastitis is a disease of premenopausal women, and its association with type 1 diabetes mellitus is the basis for its alternative name 'diabetic mastopathy'. It is a benign condition but must be considered in the differential diagnosis of breast cancer, especially in diabetic patients. CASE REPORT: We present the case of an overweight 50-year-old dyslipidemic woman with metabolic syndrome presenting with lymphocytic mastitis. CONCLUSION: Although lymphocytic mastitis is usually regarded as an autoimmune disease seen mostly in diabetic patients, it may also be seen in nondiabetic patients with metabolic syndrome who do not have an autoimmune disease.

A remarkable intestinal lipoma case.

A 37-year-old female patient with a history of iron deficiency anemia for three years had been hospitalized and followed up with subileus. An obstruction at the proximal part of the jejunum was found by enteroclysis method and a filling defect due to a polypoid mass was determined. The small intestine was resected. It was reported as a submucosal lipoma based on results of the histopathological examination. In conclusion, benign tumors of the small intestine, including intestinal lipomas, should be considered during the diagnostic process of clinical ileus and anemia.