Synthesis,molecular modeling studies,ADME prediction of arachidonic acid carbamate derivatives,and evaluation of their acetylcholinesterase activity

In this work, a series of novel anandamide units containing carbamate were designed and synthesized. All the derivatives were evaluated in vitro for their inhibitory potential against the electric eel acetylcholinesterase enzyme (AChE) and showed reversible inhibitions. The compounds 7a , 7d , 7e , and 7f are mixed inhibitors of AChE, while the compounds 7b , 7c , and 7g are uncompetitive (K_i in the range 0.93–8.86 μM). The kinetic studies revealed that compounds 7b , 7c , 7f , and 7g inhibit considerably AChE activity. Molecular docking analyses were made to evaluate the binding type and interactions of the synthesized compounds to the ligand-binding site of hAChE. It was observed that the docking results were in parallel with the in vitro results. The adsorption, distribution, metabolism, and excretion properties were computed for the compounds, and were found within the acceptable range. This study suggests the compounds 7b , 7c , 7f , and 7g identified as novel reversible AChE inhibitors may be useful lead compounds for the treatment of Alzheimer's disease.     

Measurement of the active toxoplasma retinochoroiditis lesion size during the disease course with swept-source optical coherence tomography angiography: A retrospective image analysis

International Ophthalmology - To measure the lesion size reduction in eyes with active toxoplasma retinochoroiditis during the disease course with swept-source optical coherence tomography...     

Chromosome heteromorphisms: an impact on infertility

INTRODUCTION: Cytogenetic heteromorphisms are described as heritable variations at specific chromosomal regions without a proven impact on phenotype. MATERIALS AND METHODS: We compared the presence of chromosome heteromorphisms in the karyotypes of two patient groups. The first group of patients consisted of 276 individuals of 138 infertile couples. The second group, consisted of 1,130 amniocentesis samples. This group was considered to be a sample of the fertile population, as the fetus being karyotyped is the result of a spontaneous pregnancy. Fetal karyotyping was made due to the standard indications for prenatal diagnosis, such as abnormal maternal serum screening results. RESULTS AND DISCUSSION: Eighteen infertile patients (6.52%) and twenty fetuses (1.77%) were found to have chromosome heteromorphisms. The difference between the two groups was statistically significant (p < 0.0001). CONCLUSION: These results are consistent with other similar studies that suggest the yet undefined relationship between chromosome heteromorphisms and infertility.     

Specific Functions of Melanocortin 3 Receptor (MC3R)

Melanocortin 3 receptor (MC3R) is a G-protein coupled receptor which has been defined mostly as a regulator of the appetite/hunger balance mechanisms to date. In addition to its function regarding the weight gain and appetite control mechanisms of MC3R, recent studies have shown that MC3R controls growth, puberty, and circadian rhythms as well. Despite the drastic effects of MC3R deficiency in humans and other mammals, its cellular mechanisms are still under investigation. In this review paper, we aimed to point out the importance of MC3R regulations in three main areas: 1) its impact on weight and appetite control, 2) its role in the control of growth, puberty, and the circadian rhythm, and, 3) its protein-protein interactions and cellular mechanisms.     

Should Core Needle Biopsy be Used in the Evaluation of Thyroid Nodules?

Fine needle aspiration (FNA) is the first choice in thyroid nodules suspected of harboring malignancy on sonography in routine practice. However, sampling with core needle biopsy (CNB) is also being used, especially in cases with repeated nondiagnostic/indeterminate diagnoses. The aim of this study was the retrospective evaluation of CNB samples. A total of 604 thyroid CNB samples registered in the Department of Pathology at Bezmialem Foundation University Medical Faculty within the 1-year period between June 2014 and June 2015 were re-evaluated by correlation with previous FNA and later resection results. CNB was divided into diagnostic groups of insufficient, malignant, suspicious for malignancy, no evidence of malignancy/benign, atypia of uncertain significance (AUS)/follicular lesions of uncertain significance (FLUS), and follicular neoplasm (FN)/suspicious for follicular neoplasm (SFN). Among the 604 cases, 15 cases (2.48 %) were classified as malignant and 9 cases (1.49 %) as suspicious for malignancy. No evidence of malignancy was seen in 512 cases (84.76 %). There were 26 (4.3 %) cases in the AUS/FLUS-FN/SFN group, and the sample was inadequate in 42 cases (6.95 %). Resection was performed for 17 of the cases classified as malignant or suspicious for malignancy, and all were found to be malignant. There were also 10 resected cases with a diagnosis of no evidence of malignancy, and all were found to be benign. We think that sampling with CNB may be useful especially in repeating inadequate biopsies or cases diagnosed with AUS/FLUS that have hesitations regarding clinical management. Larger series including comparisons with FNA and resection results are required.     

Coexistence of Hermansky-Pudlak syndrome and JAK2V617F-positive essential thrombocythemia

Hermansky-Pudlak syndrome (HPS) is an autosomal recessive disorder consisting of oculocutaneous albinism, platelet storage pool deficiency, and lysosomal accumulation of ceroid lipofuscin. The storage pool deficiency of HPS is associated with the lack of dense bodies in the platelets, resulting in impaired response in the secondary phase of aggregation. Patients with HPS have normal coagulation tests; however, their bleeding time is usually prolonged despite normal or increased platelet counts. Essential thrombocythemia (ET) is an uncommon condition, with an incidence of approximately 1.1 per 100,000/year, and it is the most common cause of primary thrombocytosis. JAK2^V617F positivity can be observed in approximately half of the patients with ET. Bleeding events in ET have usually been associated with acquired von Willebrand syndrome paradoxically occurring when the platelet counts are extremely high. We, herein, present a case with bleeding diathesis diagnosed as having both HPS and JAK2^V617F-positive ET.     

The effects of levobupivacaine infiltration on post-tonsillectomy pain relief in adults: a single-blinded, randomized, and controlled clinical study

The aim of this prospective single-blinded and controlled study is to evaluate the efficacy of levobupivacaine infiltration on post-tonsillectomy pain relief in adults. The study was conducted with 40 adult patients who underwent tonsillectomy. These patients were randomized in either study group (SG) who received levobupivacaine infiltration to peritonsillary fossae prior to surgery or control group (CG) with no medication. After surgery, all the patients were queried for pain scores by visual analog scale. In addition, the volume of intraoperative bleeding, the duration of operation, the severity of postoperative complications, and the amount of analgesic requirement were the other outcome measures of this study. There were significant differences between groups regarding pain scores for the first 24 h in favor of SG. The analgesic requirement was also significantly lower in SG (p = 0.009). Although there was a sustained decrement at pain score during first 24 h for SG, however, the change from baseline score (immediate score) for each time interval revealed no significance compared to CG. In addition, the duration of operation and the volume of intraoperative bleeding were similar (p = 0.64 and p = 0.165). In conclusion, preincisional infiltration of levobupivacaine is a safe and reliable method for post-tonsillectomy pain reduction in adults. However, more in-depth, double-blinded and placebo controlled studies are required to elucidate its long term benefits.