Facile synthesis and characterization of novel pyrazole-sulfonamides and their inhibition effects on human carbonic anhydrase isoenzymes

In the current study, a series of pyrazole-sulfonamide derivatives (2–14) were synthesized, characterized, and the inhibition effects of the derivatives on human carbonic anhydrases (hCA I and hCA II) were investigated as in vitro. Structures of these sulfonamides were confirmed by FT-IR, ¹H NMR, ¹³C NMR and LC–MS analysis. ¹H NMR and ¹³C NMR revealed the tautomeric structures. hCA I and hCA II isozymes were purified from human erythrocytes and inhibitory effects of newly synthesized sulfonamides on esterase activities of these isoenzymes have been studied. The K_i values of compounds were 0.062–1.278 μM for hCA I and 0.012–0.379 μM for hCA II. The inhibition effects of 7 for hCA I and 4 for hCA II isozymes were almost in nanomolar concentration range.     

Factors predicting treatment adherence in patients with adult attention-deficit/hyperactivity disorder: a preliminary study

This study aimed to elicit patient- and treatment-related factors that can potentially predict treatment adherence in adult ADHD. Subjects who were over 18 and received a diagnosis of ADHD were included in the study. Chart review data of 102 subjects regarding demographics, medications, comorbidities, concomitant medications and domains of functional impairment were collected, and predictors were assessed using a binominal logistical regression model. One hundred and two patients (78.4 % male) with a mean age of 28.8 (SD = 9.8, range = 18–55) years were enrolled in the study. Childhood diagnosis of ADHD, agents used for treatment (MPH or atomoxetine), individual domains of dysfunction and use of additional psychotropic drugs were not found to be related to treatment adherence. Patients with a university education and those referred for family history of ADHD were more likely to adhere to treatment (p = 0.05 and 0.03, respectively). On the other hand, reasons for referral other than ADHD were significantly more frequently related to non-adherence (p = 0.02). Treatment noncompliance remains a significant problem despite therapeutic effects of medications. Identification of predictors of non-adherence can lead to heightened awareness of special populations at risk. We have found that prior awareness on ADHD (via past history/media/friends) leading to self/clinician referral to rule out ADHD and pervasiveness of symptoms across functional domains led to better compliance in our sample. Future research with prospective design utilizing objective tools for adherence is required.     

Influence of nano‐zinc oxide on tropane alkaloid production,h6h gene transcription and antioxidant enzyme activity in Hyoscyamus reticulatus L. hairy roots

The use of nanotechnology and biotechnology to improve the production of plant bioactive compounds is growing. Hyoscyamus reticulatus L. is a major source of tropane alkaloids with a wide therapeutic use, including treatment of Parkinson's disease and to calm schizoid patients. In the present study, hairy roots were obtained from two‐week‐old cotyledon explants of H. reticulatus L. using the A7 strain of Agrobacterium rhizogenes. The effects of different concentrations of the signaling molecule nano‐zinc oxide (ZnO) (0, 50, 100 and 200 mg/L), with three exposure times (24, 48 and 72 h), on the growth rate, antioxidant enzyme activity, total phenol contents (TPC), tropane alkaloid contents and hyoscyamine‐6‐beta‐hydroxylase (h6h) gene expression levels were investigated. Growth curve analysis revealed a decrease in fresh and dry weight of ZnO‐treated hairy roots compared to the control. ANOVA results showed that the antioxidant activity of the enzymes catalase, guaiacol peroxidase and ascorbate peroxidase was significantly higher in the ZnO‐treated hairy roots than in the control, as was the TPC. The highest levels of hyoscyamine (37%) and scopolamine (37.63%) were obtained in hairy roots treated with 100 mg/L of ZnO after 48 and 72 h, respectively. Semi‐quantitative RT‐PCR analysis revealed the highest h6h gene expression was in hairy roots treated with 100 mg/L of ZnO after 24 h. It can be concluded that ZnO is as an effective elicitor of tropane alkaloids such as hyoscyamine and scopolamine due to its enhancing effect on expression levels of the biosynthetic h6h gene.     

Inactivation and injury of Escherichia coli O157:H7 and Staphylococcus aureus by pulsed electric fields

Two pathogenic microorganisms Escherichia coli O157:H7 and Staphylococcus aureus, suspended in peptone solution (0.1% w/v) were treated with 12, 14, 16 and 20 kV/cm electric field strengths with different pulse numbers up to 60 pulses. Pulsed electric field (PEF) treatment at 20 kV/cm with 60 pulses provided nearly 2 log reduction in viable cell counts of E. coli O157:H7 and S. aureus. S. aureus cells were slightly more resistant than E.coli O157:H7 cells. The results related to the effect of initial cell concentration of E. coli O157:H7 on the PEF inactivation showed that more inactivation was obtained by decreasing initial cell concentration. Any possible injury by PEF was also investigated after applying 20 kV/cm electric field to the microorganisms. As a result, it was determined that there was 35.92 to 43.36% injury in E. coli O157:H7 cells, and 17.26 to 30.86% injury in S. aureus cells depending on pulse number. The inactivation results were also described by a kinetic model.     

Angiotensin converting enzyme I/D,angiotensinogen M235T and AT1-R A/C1166 gene polymorphisms in patients with acromegaly

Acromegaly is associated with increased morbidity and mortality related to cardiovascular disease. Hypertension is one of the most common cardiovascular risk factors in acromegalic patients. The aim of this study was to investigate association between the frequencies of angiotensin converting enzyme (ACE) I/D, angiotensinogen (AGT) M235T and the angiotensin II type 1 receptor (AT1-R) A/C1166 gene polymorphisms and some clinical parameters of acromegalic patients. Total of 33 acromegalic patients and 63 controls were enrolled to study. We determined the ACE I/D, AGT M235T and AT1-R A/C1166 gene polymorphisms. Serum insulin, glucose, triglyceride, HDL-cholesterol, LDL-cholesterol, growth hormone and Insulin-like growth factor I (IGF-I) levels of subjects were analyzed. The frequencies of ACE and M235T AGT genotype were not significantly different between control and patients. The distribution of AT1R A/C1166 genotypes was significantly different between patients and control subjects (P = 0.016). None of the three ACE genotypes, DD, ID and II displayed significant difference in acromegalic patients. A significant difference in systolic blood pressure and the serum IGF-I levels among the three AGT genotype, MM, MT and TT genotypes was found in patient group. Individuals with MT genotypes had significantly higher serum IGF-I levels and systolic blood pressure than MM and TT genotype subjects, P < 0.05. In addition, serum triglyceride and HDL levels differed significantly between MM and MT genotypes, P < 0.05. However, systolic blood pressure of patients with CC genotypes was found to be significantly higher than AA genotypes individuals in acromegaly group, P < 0.05. It can be said that the angiotensinojen MT and AT1R CC1166 genotype carriers may have more risk than other genotypes in the development of hypertension in acromegaly.     

Expression of glucocorticoid receptor and glucose transporter-1 during placental development in the diabetic rat

In various tissues, glucocorticoids (GCs) are known to downregulate glucose transport systems; however, their effects on glucose transporters (GLUTs) in the placenta of a diabetic rat are unknown. Glucocorticoid hormone action within the cell is regulated by the glucocorticoid receptor (GR). Thus, this study was designed to investigate the relationship between GR and glucose transporter expression in the placenta of the diabetic rat. Our immunohistochemical results indicated that GR and glucose transporter protein 1 (GLUT 1) are expressed ubiquitously in the trophoblast and endothelial cells of the labyrinthine zone, where maternal fetal transport takes place in the rat placenta. Expression of GR in the junctional zone of the rat placenta was detected in giant cells, and in some spongiotrophoblast cells, but not in the glycogen cells. GLUT 1 was present, especially in glycogen cells during early pregnancy, and in the spongiotrophoblast cells of the junctional zone during late pregnancy. Amounts of GR and GLUT 1 protein were increased towards the end of gestation both in the control and the diabetic placenta. However, at days 17 and 19 of gestation, only the placental GR protein was significantly increased in the streptozotocin-induced diabetic rats compared to control rats. Diabetes led to a significant decrease in placental weight at gestation day 15. In contrast, at gestational days 17 and 21, the weights of the diabetic placenta were significantly increased as compared with the controls. Moreover, diabetes induced fetus intrauterine growth retardation at gestational days 13, 17 and 21. In conclusion, the localization pattern of GR and GLUT 1 proteins in the same cell types led us to believe that there might be a relationship between GR and GLUT 1 expressions at the cellular level. GLUT 1 does not play a pivotal role in diabetic pregnancies. However, placental growth abnormalities during diabetic pregnancy may be related to the amount of GR.     

Chemical Composition and Pharmacological Evaluation and of Toddalia asiatica (Rutaceae) Extracts and Essential Oil by in Vitro and in Silico Approaches.

Toddalia asiatica (L.) Lam. is extensively used in traditional medicinal systems by various cultures. Despite its frequent use in traditional medicine, there is still a paucity of scientific information on T. asiatica growing on the tropical island of Mauritius. Therefore, the present study was designed to appraise the pharmacological and phytochemical profile of extracts (methanol, ethyl acetate and water) and essential oil obtained from aerial parts of T. asiatica. Biological investigation involved the evaluation of in vitro antioxidant and enzyme inhibitory potentials. The chemical profile of the EO was determined using gas chromatography coupled to mass spectrometry (GC/MS) analysis, while for the extracts, the total phenolic (TPC) and flavonoid content were quantified as well as their individual phenolic compounds by LC/MS/MS. Quinic acid, fumaric acid, chlorogenic acid, quercitrin and isoquercitrin were the main compounds in the extracts. Highest total phenolic (82.5±0.94 mg gallic acid equivalent (GAE/g)) and flavonoid (43.8±0.31 mg rutin equivalent (RE/g)) content were observed for the methanol extract. The GC/MS analysis has shown the presence of 26 compounds with linalool (30.9 %), linalyl acetate (20.9 %) and β-phellandrene (7.9 %) being most abundant components in the EO. The extracts and EO showed notable antioxidant properties, with the methanol extract proved to be superior source of antioxidant compounds. Noteworthy anti-acetylcholinesterase (AChE) and anti-butyrylcholinesterase (BChE) effects were recorded for the tested samples, while only the methanol and ethyl acetate extracts were active against tyrosinase. With respect to antidiabetic effects, the extracts and EO were potent inhibitors of α-glucosidase, while modest activity was recorded against α-amylase. Docking results showed that linalyl acetate has the highest affinity to interact with the active site of BChE with docking score of −6.25 kcal/mol. The findings amassed herein act as a stimulus for further investigations of this plant as a potential source of bioactive compounds which can be exploited as phyto-therapeutics.