Immunohistochemical analysis of survivin expression in thyroid follicular adenoma and carcinoma.

Survivin is one of the 8 members of human inhibitor of apoptosis , which is differentially expressed in cancerous/transformed cells versus normal differentiated tissues. This retrospective study of thyroid histologic samples aimed to assess the clinical usefulness of survivin immunostaining for discrimination between follicular adenoma and carcinoma of thyroid. Immunohistochemical staining for survivin was performed on 41 lesions from patients who had undergone surgery for either follicular adenoma or carcinoma of thyroid. Survivin expression was significantly (P < 0.005) higher in the cases that received a diagnosis of carcinoma in comparison with follicular adenomas cases. Odds ratio of follicular carcinoma for survivin expression was 21.375 (95% CI: 3.283 to 139.177). Our results showed potential value of survivin in discrimination between follicular thyroid adenoma and follicular thyroid carcinoma. We conclude that survivin is a potential candidate for further investigation in the proper histologic diagnosis of thyroid cancers.     

Histamine regulates pancreatic carcinoma cell growth through H3 and H4 receptors

Inflammation Research -     

Lack of association between single polymorphic variants of the mitochondrial nicotinamide adenine dinucleotide dehydrogenase 3, and 4L (MT-ND3 and MT-ND4L) and male infertility

Male infertility is a multifactorial condition associated with different genetic abnormalities in at least 15%–30% of cases. The purpose of this study was to identify suspected correlations between infertility and polymorphisms in mitochondrial NADH dehydrogenase subunits 3 and 4L (MT-ND3 and MT-ND4L) in subfertile male spermatozoa. Sanger sequencing of the mitochondrial DNA target genes was performed on 68 subfertile and 44 fertile males. Eight single nucleotide polymorphisms (SNPs) in MT-ND3 (rs2853826, rs28435660, rs193302927, rs28358278, rs41467651, rs3899188, rs28358277 and rs28673954) and seven SNPs in MT-ND4L (rs28358280, rs28358281, rs28358279, rs2853487, rs2853488, rs193302933 and rs28532881) were detected and genotyped. The genotypes and allele frequencies of the study population have shown a lack of statistically significant association between MT-ND3 and MT-ND4L SNPs and male infertility. However, no statistically significant association was found between the asthenozoospermia, oligozoospermia, teratozoospermia, asthenoteratozoospermia, oligoasthenoteratozoospermia and oligoteratozoospermia subgroups of subfertile males. However, rs28358278 genotype of the MT-ND3 gene was reported in the subfertile group but not in the fertile group, which implies a possible role of this SNP in male infertility. In conclusion, the investigated polymorphic variants in the MT-ND3 and MT-ND4L genes did not show any significant association with the occurrence of male infertility. Further studies are required to evaluate these findings. Moreover, the subfertile individuals who exhibit a polymorphism at rs28358278 require further monitoring and evaluation.     

Left atrial appendage perforation with Watchman device implantation: Strategies for surgical repair

Percutaneous occlusion of the left atrial appendage is increasingly being used as an alternative for stroke prevention in patients with non‐valvular atrial fibrillation at high risk of complications from long term anticoagulation. We describe a case of left atrial appendage perforation during Watchman device implantation requiring emergency repair of the left atrium using sternotomy and cardiopulmonary bypass. Technical considerations for surgical decision making are discussed; in hemodynamically unstable patients as well as those at high risk for embolization.     

In Vitro Impact of Pro-Senescent Endothelial Microvesicles on Isolated Pancreatic Rat Islets Function

BackgroundIschemia-driven islet isolation procedure is one of the limiting causes of pancreatic islet transplantation. Ischemia-reperfusion process is associated with endothelium dysfunction and the release of pro-senescent microvesicles. We investigated whether pro-senescent endothelial microvesicles prompt islet senescence and dysfunction in vitro.Material and methodsPancreatic islets were isolated from male young rats. Replicative endothelial senescence was induced by serial passaging of primary porcine coronary artery endothelial cells, and microvesicles were isolated either from young passage 1 (P1) or senescent passage 3 (P3) endothelial cells. Islet viability was assessed by fluorescence microscopy, apoptosis by flow cytometry, and Western blot. Function was assessed by insulin secretion and islet senescence markers p53, p21, and p16 by Western blot. Microvesicles were stained by the PKH26 lipid fluorescent probe and their islet integration assessed by microscopy and flow cytometry.ResultsRegardless of the passage, half microvesicles were integrated in target islets after 24 hours incubation. Insulin secretion significantly decreased after treatment by senescent microvesicles (P3: 1.7 ± 0.2 vs untreated islet: 2.7 ± 0.2, P < .05) without altering the islet viability (89.47% ± 1.69 vs 93.15% ± 0.97) and with no significant apoptosis. Senescent microvesicles significantly doubled the expression of p53, p21, and p16 (P < .05), whereas young microvesicles had no significant effect.ConclusionPro-senescent endothelial microvesicles specifically accelerate the senescence of islets and alter their function. These data suggest that islet isolation contributes to endothelial driven islet senescence.     

Vitreoretinal toxicity of basic fibroblast growth factor

Basic fibroblast growth factor (b-FGF) is one of the multifunctional growth factors with important therapeutic potential in the field of ophthalmology. It is also implicated in pathogenesis of vitreoretinal proliferative diseases. In the present study, we evaluated its vitreoretinal toxicity by means of clinical observation, electroretinography (ERG), and histopathology after injection of different doses of b-FGF into the vitreous of rabbit eyes. Doses of b-FGF up to 2 g per eye caused no toxicity; however, injection of 4 g or more resulted in sight-threatening vitreoretinal proliferative changes. This information is important for studies aimed at evaluating the therapeutic potential of b-FGF in retinal diseases.Despite some degree of vitreous organization and opacification, retinal folds, and small areas of traction retinal detachment, the amplitudes of ERGs were normal or even increased (hyperpolarization) in eyes which received 8 g of b-FGF.     

Soy protein isolate reduces the oxidizability of LDL and the generation of oxidized LDL autoantibodies in rabbits with diet-induced atherosclerosis

The incidence of atherosclerosis can be modified by diet, and plant-derived proteins have a beneficial effect, but the underlying mechanisms remain unclear. It has been suggested that oxidized LDL (oxLDL) and autoantibodies against oxLDL are important in the development of atherosclerosis. We analyzed these factors in rabbits fed a nonpurified diet supplemented with high cholesterol (10.0 g/kg) containing either 270.0 g/kg casein (CAS, n = 10) or 270.0 g/kg soy protein isolate (SPI, n = 10) for 2 mo. Plasma and purified serum LDL from rabbits were analyzed at d 0, 15, 30, 45 and 60 of treatment, and the size of atherosclerotic lesions was evaluated at d 60 of treatment. CAS-fed rabbits had significantly higher plasma cholesterol at d 15-45 and LDL cholesterol levels at d 15 and 30. Levels of trilinolein and phosphatidylcholine hydroperoxides were higher in the LDL fraction of rabbits fed CAS than in those fed SPI. Also, CAS-fed rabbits had higher levels of highly oxidized LDL [monoclonal antibody (mAb) 24-reactive oxLDL] in plasma at d 60, whereas SPI-fed rabbits had higher levels of minimally oxidized LDL (mAb 28-reactive oxLDL) at d 45. These results were consistent with the earlier formation of anti-oxLDL antibodies and the presence of a larger area of atherosclerotic lesion in rabbits fed the CAS diet. These data indicate the importance of both the type of dietary protein used in the induction of atherosclerosis and the relevance of immunologic mechanisms in addition to biochemical and physiologic factors in the pathogenesis of atherosclerosis.