Visfatin Levels in Subclinical Hypothyroidism

Alterations in thyroid function are associated with changes in body weight, metabolism, and low-grade inflammation abnormal thyroid function may be associated with disturbances in the production of adipokines also. Although there have been studies showing changes in visfatin levels in thyroid dysfunction, exact relationship between them was still unclear. Our aim was to evaluate serum concentrations of visfatin in patients with subclinical thyroid dysfunction before and after normalization of thyroid function tests. The study included 43 patients (mean age 50.1 ± 10.6 years) with subclinical hypothyroidism. Serum insulin, visfatin, TSH, free T4 (FT4) and free T3 (FT3) levels of subjects were analyzed. Visfatin levels were measured in all patients before starting therapy and after normalization of thyroid function. Serum visfatin levels of subclinical hypothyroid patients were 0.99 ± 0.45 and they were similar after normalization of thyroid function (p = 0.394). Serum visfatin levels were negatively correlated with FT4 levels before treatment (r = ?0.329 p < 0.05). There was no significant correlation between serum levels of visfatin and the serum levels of TSH and FT3. Serum visfatin levels did not correlate with insulin, fasting blood glucose, total cholesterol, HDL cholesterol, LDL cholesterol and triglyceride levels. In this study, it was shown visfatin levels did not change after replacement therapy in patients with subclinical hypothyroidism. Subclinical hypothyroid state may be an earlier stage regarding the changes of adipocytokines specifically the visfatin secretion as seen in overt hypothyroidism.     

Distribution, population biology, and trophic ecology of the deepwater demersal fish Halosauropsis macrochir (Pisces: Halosauridae) on the mid-Atlantic Ridge

Halosauropsis macrochir ranked amongst the most abundant and widespread demersal fishes on the mid-Atlantic Ridge of the North Atlantic (Iceland-Azores) with greatest abundance at 1700-3500 m. All sizes, ranging from 10-76 cm total length, occurred in the area without any apparent spatial pattern or depth trend. Using otolith sections displaying growth increments assumed to represent annuli, the age range recorded was 2-36 years, but most individuals were <20 years. Length and weight at age data were used to fit growth models. No differences between sexes in length and weight at age were observed. The majority of samples had a surplus of males. Diet analysis showed that H. macrochir feeds on Crustacea, Teleostei, Polychaeta, and Cephalopoda, but few prey could be identified to lower taxonomical levels. The mid-Atlantic Ridge constitutes a major portion of the North Atlantic living space of the abyssal halosaur where it completes its full life cycle, primarily as an actively foraging euryophagous micronekton/epibenthos and infauna feeder, becoming a partial piscivore with increasing size.     

Diet of free-ranging American mink and European polecat in Denmark

Stomach and intestine contents of 211 American minkMustela vison Schreber, 1777 from two areas (Thy and Bornholm) in Denmark and stomach contents of 47 polecatsM. putorius Linnaeus, 1758 from Thy were analysed. Sympatric mink (from Thy) preyed mostly on mammals (55% occurrence), followed by amphibians (36%), birds (33%) and fish (30%), whereas polecat preyed mostly on amphibians (87%) and mammals (34%), and only occasionally on birds (9%) and fish (6%). Allopatric mink (from Bornholm) preyed mostly on birds (50%), followed by mammals (42%), fish (25%) and amphibians (4%). With the possible exception of some amphibians, no endangered species were found in their diet. No differences were found in food composition between wild and escaped farm mink. The concern that mink in general might have a detrimental effect on its prey species and other mustelids in terms of food competition in Denmark may be unjustified. It cannot be ruled out, however, that mink may locally have a seriously negative effect on some specific prey species, and clearly, more data is needed on eg prey abundance and spring and summer mink diet, to make stronger conclusions.     

Association between osteoporosis and polymorphisms of the bone Gla protein, estrogen receptor 1, collagen 1-A1 and calcitonin receptor genes in Turkish postmenopausal women

In this study, we have investigated the association between osteoporosis and osteocalcin (BGLAP) − 298 C>T, estrogen receptor 1 (ER1) 397 T>C, collagen type1 alpha 1 (Col1A1) 2046 G>T and calcitonin receptor (CALCR) 1340 T>C polymorphisms. Genomic DNA was obtained from 266 persons (158 osteoporotic and 108 healthy controls). Genomic DNA was extracted from EDTA-preserved peripheral venous blood of patients and controls by a salting-out method and analyzed by PCR-RFLP. As a result, there was no statistically significant difference in the genotype and allele frequencies of patients and controls for BGLAP − 298 C>T, Col1A1 2046 G>T, ER1 397 T>C and CALCR 1340 T>C polymorphisms. However, ER1 CC genotype compared with TT + TC genotypes was found to increase the two fold the risk of osteoporosis [p = 0.039, OR = 2.156, 95% CI (1.083–4.293)] and CALCR CC genotype compared with TT + TC genotypes was found to have protective effect against osteoporosis [p = 0.045, OR = 0.471, 95% CI (0.237–0.9372)]. In the combined genotype analysis, ER1/CALCR TCCC combined genotype was estimated to have protective effect against osteoporosis [p = 0.0125, OR = 0.323, 95% CI (0.1383–0.755)] whereas BGLAP/Col1A1 CCTT and ER1/CALCR CCTT combined genotypes were estimated as risk factors for osteoporosis in Turkish population (p = 0.027, p = 0.009 respectively).     

The Effects of Exendin-4 Treatment on Graft Failure: An Animal Study Using a Novel Re-Vascularized Minimal Human Islet Transplant Model

Islet transplantation has become a viable clinical treatment, but is still compromised by long-term graft failure. Exendin-4, a glucagon-like peptide 1 receptor agonist, has in clinical studies been shown to improve insulin secretion in islet transplanted patients. However, little is known about the effect of exendin-4 on other metabolic parameters. We therefore aimed to determine what influence exendin-4 would have on revascularized minimal human islet grafts in a state of graft failure in terms of glucose metabolism, body weight, lipid levels and graft survival. Introducing the bilateral, subcapsular islet transplantation model, we first transplanted diabetic mice with a murine graft under the left kidney capsule sufficient to restore normoglycemia. After a convalescent period, we performed a second transplantation under the right kidney capsule with a minimal human islet graft and allowed for a second recovery. We then performed a left-sided nephrectomy, and immediately started treatment with exendin-4 with a low (20μg/kg/day) or high (200μg/kg/day) dose, or saline subcutaneously twice daily for 15 days. Blood was sampled, blood glucose and body weight monitored. The transplanted human islet grafts were collected at study end point and analyzed. We found that exendin-4 exerts its effect on failing human islet grafts in a bell-shaped dose-response curve. Both doses of exendin-4 equally and significantly reduced blood glucose. Glucagon-like peptide 1 (GLP-1), C-peptide and pro-insulin were conversely increased. In the course of the treatment, body weight and cholesterol levels were not affected. However, immunohistochemistry revealed an increase in beta cell nuclei count and reduced TUNEL staining only in the group treated with a low dose of exendin-4 compared to the high dose and control. Collectively, these results suggest that exendin-4 has a potential rescue effect on failing, revascularized human islets in terms of lowering blood glucose, maintaining beta cell numbers, and improving metabolic parameters during hyperglycemic stress.     

Complexity and catalytic efficiency of hepatitis C virus (HCV) NS3 and NS4A protease quasispecies influence responsiveness to treatment with pegylated interferon plus ribavirin in HCV/HIV-coinfected patients

The role of the hepatitis C virus (HCV) NS3/4A protease in ablating the signaling pathway involved in the production of alpha/beta interferon (IFN-α/β) suggests a relationship between NS3/4A proteolytic activity and a patient's response to IFN-based therapy. To identify viral factors associated with the HCV treatment response, we analyzed the pretreatment NS3/4A protease gene quasispecies composition of 56 HCV genotype 1-HIV-1-coinfected patients treated in our clinic with pegylated IFN (pegIFN) plus ribavirin (RBV). The catalytic efficiency of the dominant (i.e., the most abundant) quasispecies was also assayed for Cardif cleavage and correlated with treatment outcome. A total of 1,745 clones were isolated and sequenced. Significantly less nucleotide quasispecies heterogeneity and lower Shannon entropy values were detected within the responder group (P < 0.05). A correlation was also found between the efficiency of NS3/4A protease Cardif cleavage and therapy outcome. Proteases from sustained responder patients were more efficient at processing Cardif (mean ± standard error of the mean [SEM], 0.8960 ± 0.05568; n = 19) than proteases from nonresponders (mean ± SEM, 0.7269 ± 0.05306; n = 37; P < 0.05). Finally, the amino acid p distance (the proportion [p] of nucleotide sites at which two sequences being compared are different) was significantly shorter in patients with an interleukin-28B (IL-28B) risk allele (P < 0.01), suggesting that IL-28B risk allele carriers exert a lower positive selection pressure on the NS3/4A protease. NS3/4A protease efficiency in cleaving Cardif may be associated with the pegIFN-RBV treatment response, as shown in our cohort of HIV-HCV-coinfected patients. Greater NS3/4A nucleotide heterogeneity and higher Shannon entropy values in nonresponders suggest that less HCV quasispecies complexity may favor a better response to pegIFN-RBV.     

The combined QF-PCR and cytogenetic approach in prenatal diagnosis

In this study, the importance of quantitative fluorescence polymerase chain reaction (QF-PCR) aneuploidy diagnosis test which provides earlier and easier results were discussed. The cell cultures and DNA isolations were performed on 100 amniotic fluids. DNA isolations were made from peripheral blood samples of mothers who had blood-stained amniotic fluid samples. The reasons of references of these pregnant women to our division were increased maternal age, positive double/triple screening test and fetal anomaly history. QF-PCR applied to 19 short tandem repeat markers in the chromosomes 13, 18, 21 and genes X and Y chromosomes. All electropherogram peaks were evaluated on ABI3130. Thirty two (32 %) samples have high maternal age, seven (7 %) have fetal anomaly and the others have double/triple screening test positivity. Ninety-nine (99 %) of the 100 amniotic fluid samples were resulted, but one (1 %) of them could not examined because of the culture failure. The maternal contamination rates were determined as 3 %. Of 100 samples, 2 had trisomy 21 (2 %), 1 had trisomy 13 (1 %), 1 had structural abnormalities (1 %) and the others (97 %) have not any aneuploidy. The results of QF-PCR were in compatible with the results of cell culture and chromosome analysis. Although QF-PCR is an easier and an earlier test, it has a limitation of not to able to scan full genome. It is also sensitive for maternal contamination, so it should be tested together with maternal blood samples. QF-PCR aneuploidy test is the fastest diagnostic test for prenatal diagnosis and so it provides less stressful period for pregnant women.     

A collection of programs for one‐dimensional Ising analysis of linear repeat proteins with point substitutions

A collection of programs is presented to analyze the thermodynamics of folding of linear repeat proteins using a 1D Ising model to determine intrinsic folding and interfacial coupling free energies. Expressions for folding transitions are generated for a series of constructs with different repeat numbers and are globally fitted to transitions for these constructs. These programs are designed to analyze Ising parameters for capped homopolymeric consensus repeat constructs as well as heteropolymeric constructs that contain point substitutions, providing a rigorous framework for analysis of the effects of mutation on intrinsic and directional (i.e., N‐ vs. C‐terminal) interfacial coupling free‐energies. A bootstrap analysis is provided to estimate parameter uncertainty as well as correlations among fitted parameters. Rigorous statistical analysis is essential for interpreting fits using the complex models required for Ising analysis of repeat proteins, especially heteropolymeric repeat proteins. Programs described here are available at https://github.com/barricklab-at-jhu/Ising_programs .     

In vitro bioactive luteinizing hormone assay shows cyclical,seasonal hormonal changes and response to luteinizing-hormone releasing hormone in the squirrel monkey (Saimiri boliviensis boliviensis)

Studies on the reproductive mechanisms of the squirrel monkey have been hampered by inadequate measurements of luteinizing hormone (LH). The mouse interstitial cell bioassay, which measures testosterone production as the endpoint, was validated for use in the squirrel monkey by parallel responses of serum to LH standards and by in vivo responses to an LH-releasing hormone (LHRH) analogue. The LH surge profile, as determined by daily blood sampling, was found to be of 1–2 days duration and comparable in amplitude to those of other primates. A 9.7-day ovulatory cycle length was also calculated and was similar to previous estimates based on other hormonal and behavioral methods. A 150-fold decrease in basal LH was found in the nonbreeding season, as was a decreased LHRH response. This assay makes possible future studies on hypothalamic-ovarian mechanisms in this species.