Synthesis, biological evaluation and in silico studies of novel thiadiazole-hydrazone derivatives for carbonic anhydrase inhibitory and anticancer activities.

Thiadiazole and hydrazone derivatives (5a-5i) were synthesized and their chemical structures were verified and described by 1H NMR, 13C NMR, and HRMS spectra. Three cancer cell lines (MCF-7, MDA, and HT-29) and one healthy cell line (L929) were used to test the cytotoxicity activity of synthesized compounds as well as their inhibitory activity against carbonic anhydrase I, II and IX isoenzymes. Compound 5d (29.74 µM) had a high inhibitory effect on hCA I and compound 5b (23.18 µM) had a high inhibitory effect on hCA II. Furthermore, compound 5i was found to be the most potent against CA IX. Compounds 5a-5i, 5b and 5i showed the highest anticancer effect against MCF-7 cell line with an IC50 value of 9.19 and 23.50 µM, and compound 5d showed the highest anticancer effect against MDA cell line with an IC50 value of 10.43 µM. The presence of fluoro substituent in the o-position of the phenyl ring increases the effect on hCA II, while the methoxy group in the o-position of the phenyl ring increases the activity on hCA I as well as increase the anticancer activity. Cell death induction was evaluated by Annexin V assay and it was determined that these compounds cause cell death by apoptosis. Molecular docking was performed for compounds 5b and 5d to understand their biological interactions. The physical and ADME properties of compounds 5b and 5d were evaluated using SwissADME.

18F-FLUORODEOXYGLUCOSE PET/CT CAN BE AN ALTERNATIVE METHOD TO ASSESSMENT OF INSULIN RESISTANCE.

BACKGROUND: Insulin resistance is routinely measured by homeostasis model assessment of insulin resistance (HOMA-IR).Positron emission tomography of 18F-fluorodeoxyglucose combined with computed tomography (18F-FDG PET/CT) is a valuable assessment tool for patients with cancer or staging tumors. 18F-FDG PET/CT imaging can also be utilised to detect the metabolic activity of glucose in the adipose tissue, liver and muscles. The aim of this study was to determine insulin sensitivity in the liver, muscle visceral adipose and subcutaneous adipose tissue separately via18F-FDG PET/CT. MATERIALS AND METHOD: Sixty three adult patients who underwent whole body 18F-FDG PET/CT scanning for clinical purposes (diagnosis or staging of cancer) between July and August of 2016 were included in the study. Patients were divided into two groups according to their BMI (Group 1: BMI<25kg/m2, Group 2: BMI>25kg/m2). HOMA-IR,fasting glucose,insulin, triglycerides, total cholesterol, HDL levels were measured. We calculated SUV as the tissue activity of the ROI (MBq/g)/(injected dose [MBq]/ body weight [g]) on PET images and measured the maximum SUVs (SUVmax) of visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT),liver and rectus muscle ROIs (2 cm). SUV corrected by blood glucose level (SUVgluc) was calculated as SUVmax×blood glucose level/100. Student-t test, Chi-square test and Pearson correlation test were used for statistical analysis. RESULTS: Mean glucose,insulin,HOMA-IR levels of the group-2 were statistically higher than of group-1. Muscle SUVmax and liver SUVmax of group-1 were statistically higher than of group-2. Muscle SUVgluc of group-1 was statistically higher than of group-2. HOMA-IR was negatively correlated with both SUVmax(r=-0.340, p=0.01) and muscle SUVmax(r=-0.373, p=0.005). CONCLUSION: 18F-FDG PET/CT has shown that the muscle tissue maximum FDG uptake was lower in the insulin resistance group. Therefore, 18-FDG PET/CT could be a valuable tool for diagnosing insulin resistance.

Effects of exercise and poor indoor air quality on learning, memory and blood IGF-1 in adolescent mice.

It is known that regular aerobic exercise enhances cognitive functions and increases blood insulin-like growth factor 1 (IGF-1) levels. People living in urban areas spend most of their time indoors and indoor air quality can affect health. We investigated the effects of aerobic exercise in poor and good air quality environments on hippocampus and prefrontal cortex (PFC) neurons, anxiety, and spatial learning and memory in adolescent mice. Poor air quality impaired spatial learning and memory; exercise did not affect learning or memory impairment. Exercise in a good air quality environment improved spatial learning and memory. Poor air quality increased apoptosis in the hippocampus and PFC. Both exercised and sedentary groups living in a poor air quality environment had lower serum IGF-1 levels than those living in a good air quality environment. Living in a poor air quality environment has negative effects on the hippocampus, PFC and blood IGF-1 levels in adolescent mice, but exercise did not alter the negative effects of poor air quality.

Procalcitonin: a novel cardiac marker with prognostic value in acute coronary syndrome.

Procalcitonin (PCT) is implicated as an inflammatory marker in early atherosclerosis. In order to investigate the clinical consequences of increased PCT levels in acute coronary syndrome (ACS), 77 patients (29 with non-ST-elevation myocardial infarction [MI], 34 with ST-elevation MI and 14 with unstable angina pectoris) were included and followed up for 6 months. The PCT levels were determined at initial presentation and within 48 h of admission. Five patients died during hospitalization and their PCT levels within 48 h of admission were significantly higher than survivors (n = 72) (0.588 +/- 0.56 versus 0.399 +/- 1.33 ng/ml, respectively). The PCT levels within 48 h post-admission in the nine patients who died within 6 months were also significantly higher compared with the survivors (0.451 +/- 0.44 versus 0.406 +/- 1.37 ng/ml, respectively). It is concluded that higher PCT levels within 48 h post-admission may reflect an inflammatory state that is associated with increased early and 6-month mortality.

Folie à famille and separation-individuation.

The case history, treatment and follow-up of a family sharing the same delusion are presented in this article. The characteristics of separation-individuation of this pathological condition and its treatment are discussed.

Self-expandable metallic stent therapy of esophagojejunal stricture in a stapled anastomosis: a case report and review of the literature.

The introduction of the stapler apparatus has provided safe and effective gastrointestinal anastomotic surgical operations for most surgeons. However, the major disadvantage of stapler surgery is an increased risk of anastomotic stricture formation. Treatment of this kind of stricture is performed mainly by using endoscopic balloon dilators. However, this therapy may fail or the patient may become reactive or uncooperative during dilatation sessions. Herein, we present a case to show the successful and uncomplicated insertion of a self-expanding metallic stent into an esophagojejunal anastomotic stricture which developed 1 month after total gastrectomy and stapled esophagojejunal anastomosis in a patient with gastric carcinoma. This is the 3rd report in the literature.

Evaluation of sponging and antipyretic medication to reduce body temperature in febrile children.

Two hundred and twenty-four children aged 6 months to 5 years, with rectal temperatures greater than or equal to 30 degrees (104 degrees F), were randomly treated with sponging alone or with medication including a single oral dose of aspirin 15 mg/kg, or paracetamol 15 mg/kg, or ibuprofen 8 mg/kg. Twenty-three children were excluded from the final analysis because they did not complete the study. Demographic characteristics of the patients were found to be comparable in all groups. Rectal temperatures were recorded every 30 min for a 3 h period. During the first 30 min of intervention, sponging was found to be more effective than all of the three medications. After 60 min, the effects of each medication became superior to sponging with tepid water in reducing body temperature. Twenty-three children were excluded from the final analysis because they did not complete the study. Comparing the effect of the three different medications, it was seen that the antipyretic efficacy of aspirin and ibuprofen were significantly more than paracetamol 3 h after intervention (P < 0.05). For the management of fever over 39 degrees C, it is therefore recommended to give children an antipyretic drug, preferably ibuprofen, and at the same time to begin sponging to provide a rapid and sustained antipyresis