Genome-wide analyses on loss of heterozygosity in head and neck squamous cell carcinomas

Head and neck squamous cell carcinoma (HNSCC) is a frequent malignancy with a poor survival rate. Identifying the tumor suppressor gene (TSG) loci by genomic studies is an important step to uncover the molecular mechanisms involved in HNSCC pathogenesis. We therefore performed comprehensive analyses on loss of heterozygosity (LOH) using a genome-wide panel of 191 microsatellite markers in 22 HNSCC samples. We found 53 markers with significantly high LOH (>30%) on 21 chromosomal arms; the highest values of those were observed on 3p, 9p, 13q, 15q, and 17p, corresponding to D3S2432 (67%), D9S921-D9S925 (67%) and GATA62F03 (86%), D13S1493 (60%), D15S211 (62%), and D17S1353 (88%), respectively. Fifteen hot spots of LOH were defined in 13 chromosomal arms: 2q22-23, 4p15.2, 4q24-25, 5q31, 8p23, 9p23-24, 9q31.3, 9q34.2, 10q21, 11q21-22.3, 14q11-13, 14q22.3, 17p13, 18q11, and 19q12 as loci reported previously in HNSCCs. Furthermore, we identified five novel hot spots of LOH on three chromosomal arms in HNSCC at 2q33 (D2S1384), 2q37 (D2S125), 8q12-13 (D8S1136), 8q24 (D8S1128), and 15q21 (D15S211). In conclusion, our comprehensive allelotype analyses have unveiled and confirmed a total of 20 possible TSG loci that could be involved in the development of HNSCC. These results provide useful clues for identification of putative TSGs involved in HNSCC by fine mapping of the suspected regions and subsequent analysis for functional genes.     

Melatonin attenuates renal ischemia-reperfusion injury in nitric oxide synthase inhibited rats

Recent studies show that melatonin reduces the blood pressure (BP) and ischemia/reperfusion (I/R)-induced damage. This study was designed to investigate the effects of melatonin on the renal I/R injury in rats given the nitric oxide synthase (NOS) inhibitor, N(omega)-nitro-L-arginine methyl ester (L-NAME). After right nephrectomy, I/R was induced by occlusion of the left renal vessels for 60 min, followed by 24h reperfusion. The administration of melatonin significantly attenuated BP in NOS-inhibited hypertensive rats. Malondialdehyde (MDA) levels, a stable metabolite of the free-radical-mediated lipid peroxidation cascade, were found to be significantly higher in the I/R group (3.48+/-0.2mg/l serum) than in the control group (2.69+/-0.2mg/l serum). L-NAME (40 mgkg(-1) for 15 days)+I/R significantly increased the MDA levels compared to I/R alone. Melatonin administration to L-NAME rats significantly reduced the MDA values resulting from I/R. We also demonstrated that I/R, and especially L-NAME+I/R, lead to structural changes in the kidney and that melatonin attenuates these changes. These results suggest that melatonin reduces BP and I/R injury in NOS inhibited rats by L-NAME.     

Prenatal diagnosis of 20p13 microdeletion syndrome

ObjectiveThe objective of this study was to report the first case of prenatal diagnosis of the fetal 20p13 microdeletion syndrome in the literature.Case reportThe mother was 31 years old and had a first trimester serum screening that indicated the fetus was at low risk. The prenatal ultrasound at 23 weeks of gestation showed mild ventriculomegaly (10.2 mm) and absent septum pellucidum. She underwent amniocentesis because of the abnormal imaging results. Karyotype analysis revealed normal results. Chromosome microarray analysis (CMA) was then performed to provide genetic analysis of the fetus and parents. CMA detected 317.902 kb deletion of 20p13 in fetus. Finally, pregnancy was terminated at 32 weeks of gestation.ConclusionThis study is the first to report the prenatal diagnosis of a 20p13 microdeletion syndrome. Our results further confirmed that genes in this region, including SOX12, NRSN2 are essential for normal fetal growth and TBC1D20 for normal brain development.     

Effects of lisinopril treatment on the pathophysiology of PCOS and plasminogen activator inhibitor-1 concentrations in rats

Research questionAngiotensin-converting enzyme inhibition results in a significant reduction in plasma concentrations of plasminogen activator inhibitor-1 (PAI-1). What are the effects of lisinopril treatment on PAI-1 concentrations and the morphology and function of the ovaries in the letrozole-induced polycystic ovary syndrome (PCOS) rat model?DesignThis prospective randomized controlled animal study involved female Wistar albino rats. Twelve rats were assigned as controls (group I). In the study group (n = 48), letrozole (an aromatase inhibitor) was administered for PCOS modelling for 9 weeks. After confirming disrupted oestrous cycles, the study group was randomized into two groups: group II (n = 24; letrozole only) and group III (n = 24; letrozole + lisinopril 15 mg/kg per day). After 12 weeks, each group was divided randomly into two. Biochemical, histopathological and immunohistochemical analyses was performed in subgroups designated A, and fertilization rates were studied in subgroups designated B.ResultsLisinopril treatment reduced the weight and area of the ovaries, the number and wall thickness of cystic follicles, and serum concentrations of LH and testosterone, relative to group II (P < 0.001). Circulating PAI-1 concentrations were significantly different among three groups (7.7 ± 0.9 ng/ml, 9.8 ± 0.7 ng/ml and 8.6 ± 0.7 ng/ml for groups IA, IIA and IIIA; P < 0.001). Pregnancy rates were 100%, 0% and 16.7% in groups IB, IIB and IIIB.ConclusionsIn the letrozole-induced rodent PCOS model, lisinopril modifies the action of letrozole, possibly by inhibition of systemic and ovarian production of PAI-1. The use of PAI-1 inhibitors deserves further investigation in understanding the pathogenesis of PCOS.     

Bisphosphonate treatment at spondylo-ocular syndrome due to a novel compound heterozygote variant in XYLT2 and review of the literature

Spondylo-ocular syndrome is a rare autosomal recessive disorder characterized by generalized osteoporosis, hearing loss, visual impairment due to cataract, and platyspondyly. Previous studies have revealed that the syndrome is caused by pathogenic variants in the XYLT2 gene. A patient with spondylo-ocular syndrome and two heterozygous pathogenic variant in the XYLT2 gene in compound state are described here. The patient presented with osteoporosis, platyspondyly, ocular findings, hearing loss, kyphosis, scoliosis, facial findings, intellectual disability, and undescended testicles. Previous reports of bisphosphonate treatment response were variable, whereas a long-term follow-up with bisphosphonate treatment in this case resulted in normalization of vertebral structures. Reporting such cases helps to determine the appropriate genotype–phenotype correlation in patients with XYLT2-related pathogenesis.     

Robust Polyion Complex Vesicles (PICsomes) Based on PEO-b-poly(amino acid) Copolymers Combining Electrostatic and Hydrophobic Interactions: Formation,siRNA Loading and Intracellular Delivery

Two pairs of oppositely charged PEO-b-poly(amino acid) copolymers with neutral poly(ethylene oxide) block and polypeptide block composed of the hydrophobic l -phenylalanine (Phe) amino acid mixed with either negative l -glutamic acid (Glu) or positive l -lysine (Lys) units are synthesized. N-carboxyanhydride (NCA) ring opening polymerization is performed with either PEO₄₆-NH₂ or PEO₁₁₄-NH₂ macroinitiators, leading respectively to PEO₄₆-b-P(Glu₁₀₀-co-Phe₆₅) and PEO₄₆-b-P(Lys₁₀₀-co-Phe₆₅), and PEO₁₁₄-b-P(Glu₆₀-co-Phe₄₀) and PEO₁₁₄-b-P(Lys₆₀-co-Phe₄₀). Polyion complexes (PIC) formed at near charge equilibrium led to vesicle formation (PICsomes), as shown by DLS, zetametry, and TEM. The good stability of PICsomes, even in high salinity media, is interpreted by π π stacking hydrophobic interactions between the Phe residues, playing the role of “physical cross-linking”. These PICsomes are successfully loaded with small interfering ribonucleic acid (siRNA) directed against firefly luciferase enzyme expression. They also exhibit minimal cell cytotoxicity while superior silencing efficacy is shown by cell bioluminescence assay as compared to free siRNA and a standard lipofectamine-siRNA complex. As such, self-assembly of oppositely charged PEO-b-poly(amino acids) block copolymers enables forming PICsomes of high stability thanks to π π interactions of the Phe co-monomer in the polypeptide block, with high potential as biocompatible nanocarriers for RNA interference.     

Is there a relationship between endometrial polyps and obesity,diabetes mellitus,hypertension?

Objective

The purpose of our study was to evaluate the relationship between endometrial polyps and obesity, diabetes mellitus (DM) and hypertension (HT).

Materials and methods

202 patients who applied to our gynecology clinic with complaints of infertility, recurrent pregnancy loss and abnormal uterine bleeding, diagnosed to have endometrial polyps by hysteroscopy, were compared with 79 patients without polyps, retrospectively. The relationships between risk factors and presence of a polyp and polyp size were analyzed.

Results

The mean age of cases with endometrial polyps was significantly greater than the controls. The mean body mass index (BMI) of the cases with polyps was also significantly greater than the controls. There was no significant difference between groups with respect to prevalence of DM or HT.

Conclusion

This study suggests that obesity is an independent risk factor in the development of endometrial polyps. Clinicians should be aware in terms of endometrial polyps in the assessment of patients with BMI ≥30. There was no relationship between HT or DM with presence of polyps.     

Affective temperaments in pregnancy

Aim: There are many studies on the mood disorders that occur during pregnancy, but no studies that question how affective temperaments, which are the antecedents of the mood disorders, are influenced by pregnancy. This study aims to examine the affective temperaments in women without any psychiatric diagnoses during the pregnancy period.

Method: The study included 100 pregnant women at the third trimester of their pregnancy (pregnant group) and 75 non-pregnant women (control group). Structured Clinical Interview for DSM Axis-I Disorders (SCID-I) was used for the evaluation of psychiatric disorders; Temperament Evaluation of Memphis, Pisa, Paris and San Diego Auto-questionnaire (TEMPS-A) was used for the evaluation of affective temperaments.

Results: The cyclothymic, irritable and anxious temperament scores of the pregnant women were significantly lower than that of the non-pregnant women (p?Conclusion: The third trimester of pregnancy is associated with significantly lower affective temperament. Future studies may help to understand the biological background of the present findings.     

Spectrum of abdominal pathologies detected with CT in long term dialysis patients

As a consequence of the expanded use of long term hemodialysis and continuous ambulatory peritoneal dialysis (CAPD) treatments and extended life spans, complications of end-stage renal disease and dialysis treatments are being encountered with increasing frequency in these patients. Computed tomography can accurately depict many of the potential complications of end-stage renal disease on dialysis. This article presents the abdominal CT findings of 429 end-stage renal disease patients who are on either hemodialysis or continuous ambulatory peritoneal dialysis treatment.