The ultrastructure of the avian Golgi tendon organ

The ultrastructure of the avian Golgi tendon organ (GTO) is described and compared with those of mammals using transverse sections through the myo-tendinous junctions of wing muscles of adult mallard ducks. The capsule, which is continuous with the perineural epithelial sheath of the Ib afferent nerve fiber, consists of four to seven flattened cellular lamellae. Two to four muscle fibers attach to large collagen bundles which enter the GTO through a tight collar at the proximal end of the fusiform capsule. These collagen bundles divide into many smaller bundles, which run longitudinally through the lumen in compartments formed by septal cells. The septal cells contain many prominent lipid accumulations. The Ib axon divides several times, and the unmyelinated branch axons weave between the small collagen bundles. Schwann cell processes or basement membrane usually intervene between the axons and collagen bundles. The small collagen bundles regroup into larger bundles, which pass through tight capsular collars and merge with the main muscle tendon. The size of the duck GTOs was measured and found to be smaller than the GTOs of man, cat or rat.     

Down syndrome patients with normal hearts: are they really normal?

Even though congenital heart disease is a common finding in down syndrome (DS) patients, some of them have anatomically normal hearts. However, the term “normal” might not be suitable, as these patients usually suffer from functional cardiac dysfunction. Several research highlighted that despite the absence of anatomical heart defects, subtle cardiac function derangements are present in DS patients. We aim to assess cardiac functions by Two-dimensional echocardiography and tissue Doppler imaging (TDI) in pediatric DS patients who have anatomically normal hearts. One hundred seventy-two patients with karyotyping confirmed DS with anatomically normal hearts and 165 healthy normal control children were enrolled in the current study. Their cardiac functions were assessed using both 2-dimensional echocardiography and TDI. Both patients and controls had structurally and anatomically normal hearts. In DS patients, the right side of the heart showed a significant reduction in both systolic and diastolic functions. Systolic dysfunction was evident by significantly decreased levels of Tricuspid annular plane systolic excursion and systolic wave by TDI. Diastolic dysfunction of the right ventricle was evident by prolonged deceleration time by conventional echocardiography and a significant decrease in annular tissue doppler velocity during early diastole/late diastole ratio by TDI. The E/De ratio was significantly increased. Even with anatomically normal hearts, DS patients should undergo cardiac function assessment by echocardiography & TDI. TDI is superior to conventional echocardiography in detecting subtle cardiac dysfunction especially left ventricular diastolic dysfunction in DS patients. TDI showed a significant decrease in the early/atrial ratio of mitral valve annulus and prolongation of left ventricle isometric relaxation time in DS children. Also, the left ventricle E/De ratio was prolonged denoting elevated filling pressures and diastolic dysfunction. This indicates that the TDI has higher sensitivity to detect diastolic dysfunction than conventional Echocardiography. Biventricular TDI-derived myocardial performance index was found to be significantly increased in DS children.     

Dihydropyrimidinones: efficient one-pot green synthesis using Montmorillonite-KSF and evaluation of their cytotoxic activity

A simple, efficient, cost-effective, recyclable and green approach has been developed for the synthesis of new dihydropyrimidinone analogs via the Biginelli reaction. The methodology involves a multicomponent reaction catalyzed by “HPA-Montmorillonite-KSF” as a reusable and heterogeneous catalyst. This method gives an efficient and much improved modification of the original Biginelli reaction, in terms of yield and short reaction times under solvent free conditions. All the derivatives were subjected to cytotoxicity screening against a panel of four different human cancer cell lines viz. colon (Colo-205), prostate (PC-3), leukemia (THP-1) and lung (A549) to check their effect on percentage growth. MTT [3-(4,5-dimethylthiazol-yl)-diphenyl tetrazoliumbromide] cytotoxicity assay was employed to check IC₅₀ values. Of the synthesized analogs, 16a showed the best activity with IC₅₀ of 7.1 ± 0.8, 13.1 ± 1.4, 13.8 ± 0.9 and 14.7 ± 1.1 μM against lung (A549), leukemia (THP-1), prostate (PC-3) and colon (Colo-205) cancer lines, respectively. The 16a analog was further checked for its effect on cancer cell properties through clonogenic (colony formation) and scratch motility (wound healing) assays and thereby was found that it reduced both the colony formation and migratory properties of the lung cancer cell line (A549). Further, molecular docking studies were performed with 16a to show its binding mode.

The general method for the preparation of DHPM analogs; cytotoxic activity and binding mode of the most active derivative against PI3Kγ and CDK2 targets.     

Aortic function is compromised in a rat model of polycystic ovary syndrome

BACKGROUND: Arterial mechanical parameters are modified in women with polycystic ovary syndrome (PCOS), before and during pregnancy. This study tested the hypothesis that aortic mechanics and endothelial function are modified in the mifepristone-treated rat model of PCOS. METHODS: Female rats injected daily with mifepristone or vehicle for 7-9 days were assessed by ultrasound to allow estimation of aortic stiffness index and compliance. The influence of acetylcholine (ACh) and sodium nitroprusside (SNP) on dissected phenylephrine-contracted aortic rings was assessed. RESULTS: Aortic compliance was reduced by 67% in mifepristone-treated rats versus controls (P<0.05), while stiffness index was increased 2.3-fold (P<0.02). ACh-induced dilation was less in aortic rings from mifepristone-treated rats (P=0.022) and was less sensitive to the nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) (P<0.001), while SNP-induced dilation was greater (P=0.001). CONCLUSIONS: Aortic mechanics in vivo and endothelial function in vitro were consistently perturbed in mifepristone-treated rats. Aortic ring behaviour suggested that NO release was depressed or degradation elevated, with a compensatory increase in NO sensitivity and/or activation of a non-NO-mediated relaxation mechanism. The mifepristone-treated rat is a valid model for investigation of the vascular deficits seen in PCOS.     

Acute pancreatitis in patients on chronic peritoneal dialysis: an increased risk?

OBJECTIVES: The primary aim of this study is to determine if patients with end-stage renal disease (ESRD) on peritoneal dialysis (PD) have a higher risk of developing acute pancreatitis (AP) than patients on hemodialysis (HD). The secondary aim is to compare the outcomes of AP between the two groups. METHOD: This is a retrospective case-control study. The study groups consisted of all patients initiated on HD and PD between January 1, 1998 and August 1, 2003. AP was identified using ICD-9 codes. Statistical analysis was carried out using Poisson regression, Kaplan-Meier curve, log-rank test, and Cox regression. RESULTS: One thousand two hundred and thirty-three and 160 eligible patients were identified in the HD and PD groups, respectively. Twenty-eight patients had AP. Eight patients were excluded as they had identifiable etiologies for AP. Of the remaining 20 patients with AP, 14 were in the HD group and 6 were in the PD group (p= 0.009). Incidence of AP was 18.4 per 1,000 person-years in the PD group and 6.5 per 1,000 person-years in the HD group (p= 0.033). Kaplan-Meier curves showed a significant difference in AP-free survival between the two groups (log-rank p= 0.026). Using time-dependent analysis, the hazard ratio for AP in PD patients after adjustment for age and sex was 3.94 (p= 0.006). There was no observed difference in length of hospital stay and ICU stay. All cases of AP were interstitial. There were no complications or deaths related to AP. CONCLUSION: PD is a risk factor for AP. There is no statistical difference in AP-related mortality and morbidity between HD and PD.     

Efficacy of ombitasvir/paritaprevir/ritonavir/ribavirin in management of HCV genotype 4 and end-stage kidney disease

Background

Till now, pooled data about the safety and efficacy of different direct-acting antiviral (DAAs) regimens in different renal situations are still under evaluation.

Instant and quantitative epoxidation of styrene under ambient conditions over a nickel(ii)dibenzotetramethyltetraaza[14]annulene complex immobilized on amino-functionalized SBA-15

Nickel(ii)dibenzotetramethyltetraaza[14]annulene complex (Nitmtaa) was synthetized and immobilized on post amino-functionalized SBA-15 (N-SBA-15) to obtain a stable and reusable nanocatalyst named as Nitmtaa@N-SBA-15. Here (3-aminopropyl)triethoxysilane (APTES) was first grafted on the surface SBA-15, then Nitmtaa was added and coordinated on the silica surface via APTES amine groups. The structure and morphology, and thermal stability of the prepared nanocatalyst was investigated using SEM, HR-TEM, BET, FT-IR, powder XRD, and TGA. HR-TEM and XRD results revealed a high dispersion of Nitmtaa on the SBA-15 surface. The catalytic activity of this nanocatalyst was evaluated in the epoxidation of styrene, under ambient conditions, using meta-chloroperoxybenzoic acid (m-CPBA) as the oxygen donor. This nanocatalyst showed an immediate and quantitative epoxidation of styrene with high turn-over-frequency ∼31.58 s⁻¹. Moreover, the superior catalytic activity and high stability of Nitmtaa@N-SBA-15 could be maintained after four successive cycles. A possible reaction mechanism is also proposed.

Immediate and quantitative epoxidation of styrene under ambient conditions catalyzed by new nanocatalyst obtained by immobilizing nickel(ii)dibenzotetramethyltetraaza[14]annulene in amino-functionalized SBA-15.