Possible Involvement of Endothelin Peptides and L-Arginine-Nitric Oxide Pathway on the Effect of Endotoxin in the Rabbit Isolated Perfused Kidney

Escherichia coli endotoxin (LPS) when infused through the renal artery of the rabbit isolated perfused kidney prepared as constant pressure mode, caused a decrease in flow rate and kidney weight indicating its primary vasoconstrictor effect. This effect was predominant in kidneys from rabbits pretreated with LPS. Endothelin-1 at a concentration of 10−10 M and big endothelin-1 at a concentration of 10−8 M produced equal vasoconstrictor effects in kidney. Addition of endotheHn converting enzyme inhibitor, phosphoramidon, to the perfusion medium at a concentration of 10−6 M caused a reduction in the effects of both LPS and big ET-1 without altering the vasoconstrictor effect of ETol. However, addition of methylene blue (10−5 M), a soluble guanylate cyclase inhibitor and NG-nitro-L-arginine-methyl ester (10−6 M) to the perfusion medium caused a potentiation in the vasoconstrictor effect of LPS. Indomethacin at a concentration of 10−6 M did not alter the effect of LPS. These results were taken as evidence for the participation of endothelin peptides and the L-arginine-nitric oxide pathway in the effect ofLPS in rabbit isolated perfused kidney

Higher P-Wave Dispersion in Migraine Patients with Higher Number of Attacks

Objective and Aim. An imbalance of the sympathetic system may explain many of the clinical manifestations of the migraine. We aimed to evaluate P-waves as a reveal of sympathetic system function in migraine patients and healthy controls. Materials and Methods. Thirty-five episodic type of migraine patients (complained of migraine during 5 years or more, BMI < 30 kg/m2) and 30 controls were included in our study. We measured P-wave durations (minimum, maximum, and dispersion) from 12-lead ECG recording during pain-free periods. ECGs were transferred to a personal computer via a scanner and then used for magnification of x400 by Adobe Photoshop software. Results. P-wave durations were found to be similar between migraine patients and controls. Although P WD (P-wave dispersion) was similar, the mean value was higher in migraine subjects. P WD was positively correlated with P max (P < 0.01). Attacks number per month and male gender were the factors related to the P WD (P < 0.01). Conclusions. Many previous studies suggested that increased sympathetic activity may cause an increase in P WD. We found that P WD of migraine patients was higher than controls, and P WD was related to attacks number per month and male gender. Further studies are needed to explain the chronic effects of migraine

Protective effects of green tea on blood and liver of rats fed with high fructose diet

Abstract This study was designed to investigate the effects of green tea on lipid profile, liver tissue damage, and oxidative stress in rats fed a diet including high fructose. Sprague-Dawley rats were randomly divided into four groups: Control (C), Fructose (F), Green Tea (GT), and F+GT. F and F+GT groups were given 20 fructose in the drinking water for eight weeks. Green tea (2 mg kg−1) was administrated to GT and F+GT groups by oral gavage for eight weeks. Biochemical parameters in serum and oxidative stress markers in the liver were analysed. The liver sections were stained with haematoxylin-eosin. As of the 3rd week of the experiment, the body weight of rats in the F group showed a statistically significant increase in comparison with the F+GT group. The serum glucose and triglyceride levels of the F+GT group significantly decreased when compared with the F group. The fructose-induced degenerative changes in the liver were reduced with green tea. Green tea may serve a protective role against hyperlipidaemia and liver injury in rats fed a high fructose diet

Turner syndrome and associated problems in turkish children: A multicenter study

Objective: Turner syndrome (TS) is a chromosomal disorder caused by complete or partial X chromosome monosomy that manifests various clinical features depending on the karyotype and on the genetic background of affected girls. This study aimed to systematically investigate the key clinical features of TS in relationship to karyotype in a large pediatric Turkish patient population. Methods: Our retrospective study included 842 karyotype-proven TS patients aged 0-18 years who were evaluated in 35 different centers in Turkey in the years 2013-2014. Results: The most common karyotype was 45,X (50.7%), followed by 45,X/46,XX (10.8%), 46,X,i(Xq) (10.1%) and 45,X/46,X,i(Xq) (9.5%). Mean age at diagnosis was 10.2±4.4 years. The most common presenting complaints were short stature and delayed puberty. Among patients diagnosed before age one year, the ratio of karyotype 45,X was significantly higher than that of other karyotype groups. Cardiac defects (bicuspid aortic valve, coarctation of the aorta and aortic stenosi) were the most common congenital anomalies, occurring in 25% of the TS cases. This was followed by urinary system anomalies (horseshoe kidney, double collector duct system and renal rotation) detected in 16.3%. Hashimoto’s thyroiditis was found in 11.1% of patients, gastrointestinal abnormalities in 8.9%, ear nose and throat problems in 22.6%, dermatologic problems in 21.8% and osteoporosis in 15.3%. Learning difficulties and/or psychosocial problems were encountered in 39.1%. Insulin resistance and impaired fasting glucose were detected in 3.4% and 2.2%, respectively. Dyslipidemia prevalence was 11.4%. Conclusion: This comprehensive study systematically evaluated the largest group of karyotype-proven TS girls to date. The karyotype distribution, congenital anomaly and comorbidity profile closely parallel that from other countries and support the need for close medical surveillance of these complex patients throughout their lifespan. © Journal of Clinical Research in Pediatric Endocrinology

Aurora kinase A drives the evolution of resistance to third-generation EGFR inhibitors in lung cancer.

Although targeted therapies often elicit profound initial patient responses, these effects are transient due to residual disease leading to acquired resistance. How tumors transition between drug responsiveness, tolerance and resistance, especially in the absence of preexisting subclones, remains unclear. In epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma cells, we demonstrate that residual disease and acquired resistance in response to EGFR inhibitors requires Aurora kinase A (AURKA) activity. Nongenetic resistance through the activation of AURKA by its coactivator TPX2 emerges in response to chronic EGFR inhibition where it mitigates drug-induced apoptosis. Aurora kinase inhibitors suppress this adaptive survival program, increasing the magnitude and duration of EGFR inhibitor response in preclinical models. Treatment-induced activation of AURKA is associated with resistance to EGFR inhibitors in vitro, in vivo and in most individuals with EGFR-mutant lung adenocarcinoma. These findings delineate a molecular path whereby drug resistance emerges from drug-tolerant cells and unveils a synthetic lethal strategy for enhancing responses to EGFR inhibitors by suppressing AURKA-driven residual disease and acquired resistance

De novo insertions and deletions of predominantly paternal origin are associated with autism spectrum disorder

Whole-exome sequencing (WES) studies have demonstrated the contribution of de novo loss-of-function single-nucleotide variants (SNVs) to autism spectrum disorder (ASD). However, challenges in the reliable detection of de novo insertions and deletions (indels) have limited inclusion of these variants in prior analyses. By applying a robust indel detection method to WES data from 787 ASD families (2,963 individuals), we demonstrate that de novo frameshift indels contribute to ASD risk (OR= 1.6; 95% CI= 1.0-2.7; p= 0.03), are more common in female probands (p= 0.02), are enriched among genes encoding FMRP targets (p= 6× 10-9), and arise predominantly on the paternal chromosome (p< 0.001). On the basis of mutation rates in probands versus unaffected siblings, we conclude that de novo frameshift indels contribute to risk in approximately 3% of individuals with ASD. Finally, by observing clustering of mutations in unrelated probands, we uncover two ASD-associated genes: KMT2E (MLL5), a chromatin regulator, and RIMS1, a regulator of synaptic vesicle release