Insulin resistance and idiopathic infertility: A potential possible link

Among various health issues, infertility has been always considered as one of the major health problems. Idiopathic infertility is still a matter of debate since the underlying mechanisms stay obscure. Idiopathic infertility is related to expanded chance of metabolic syndrome components, obesity and increased risk of cardiovascular diseases. This study aimed to assess insulin resistance and serum levels of irisin as one of the adipokines in patients with idiopathic infertility. This study included 50 male patients aged 25–50 years old suffering from idiopathic infertility, together with 50 healthy individuals of matched age as controls. Patients showed significantly increased homeostasis model assessment for insulin resistance values than controls. For irisin results, idiopathic infertility patients had significantly decreased values than controls indicating the potential effect of irisin in development of insulin resistance in idiopathic infertility patients.     

Is Use of BMP-2 Associated with Tumor Growth and Osteoblastic Differentiation in Murine Models of Osteosarcoma?

BackgroundThe putative benefit of rhBMP-2 is in the setting of limb reconstruction using structural allografts, whether it be allograft-prosthetic composites, osteoarticular allografts, or intercalary segmental grafts. There are also potential advantages in augmenting osseointegration of uncemented endoprosthetics and in reducing infection. Recombinant human BMP-2 might mitigate nonunion in structural allograft augmented osteosarcoma limb salvage surgery; however, its use is limited because of concerns about the prooncogenic effects of the agent.Questions/purposes(1) To assess if BMP-2 signaling influences osteosarcoma cell line growth. (2) To characterize degree of osteosarcoma cell line osteoblastic differentiation in response to BMP-2. (3) To assess if BMP-2 signaling has a consistent effect on local or systemic tumor burden in various orthotopic murine models of osteosarcoma.MethodsIn this study, 143b, SaOS-2 and DLM8-M1 osteosarcoma cell lines were transfected with BMP-2 cDNA controlled by a constitutive promoter (experimental) or an empty vector (control) using a PiggyBac transposon system. Cellular proliferation was assessed using a quantitative MTT colorimetric assay. Osteoblastic differentiation was compared between control and experimental cell lines using quantitative real-time polymerase chain reaction of the osteoblastic markers connective tissue growth factor, Runx-2, Osterix, alkaline phosphatase and osteocalcin. Experimental and control cell lines were injected into the proximal tibia of either NOD-SCID (143b and SaOS-2 xenograft model), or C3H (DLM8-M1 syngeneic model) mice. Local tumor burden was quantitatively assessed using tumor volume caliper measurements and bioluminescence, and qualitatively assessed using post-mortem ex vivo microCT. Lung metastasis was qualitatively assessed by the presence of bioluminescence, and incidence was confirmed using histology. rhBMP-2 soaked absorbable collagen sponges (experimental) and sterile-H₂O soaked absorbable collagen sponges (control) were implanted adjacent to 143b proximal tibial cell line injections to compare the effects of exogenous BMP-2 application with endogenous upregulation.ResultsConstitutive expression of BMP-2 increased the in vitro proliferation of 143b cells (absorbance values 1.2 ± 0.1 versus 0.89 ± 0.1, mean difference 0.36 [95% CI 0.12 to 0.6]; p = 0.01), but had no effect on SaOS-2 and DLM8-M1 cell proliferation. In response to constitutive BMP-2 expression, 143b cells had no differences in osteoblastic differentiation, while DLM8-M1 cells downregulated the early marker connective tissue growth factor (mean ΔCt 0.2 ± 0.1 versus 0.6 ± 0.1; p = 0.002) and upregulated the early-mid range marker Runx-2 (mean ΔCt -0.8 ± 0.1 versus -1.1 ± 0.1; p = 0.002), and SaOS-2 cells upregulated the mid-range marker Osterix (mean ΔCt -2.1 ± 0.6 versus -3.9 ± 0.6; p = 0.002). Constitutive expression of BMP-2 resulted in greater 143b and DLM8-M1 local tumor volume (143b: 307.2 ± 106.8 mm³ versus 1316 ± 387.4 mm³, mean difference 1009 mm³ [95% CI 674.5 to 1343]; p < 0.001, DLM8-M1 week four: 0 mm³ versus 326.1 ± 72.8 mm³, mean difference 326.1 mm³ [95% CI 121.2 to 531]; p = 0.009), but modestly reduced local tumor growth in SaOS-2 (9.5 x 10⁸ ± 8.3x10⁸ photons/s versus 9.3 x 10⁷ ± 1.5 x 10⁸ photons/s, mean difference 8.6 x 10⁸ photons/s [95% CI 5.1 x 10⁸ to 1.2 x 10⁹]; p < 0.001). Application of exogenous rhBMP-2 also increased 143b local tumor volume (495 ± 91.9 mm³ versus 1335 ± 102.7 mm³, mean difference 840.3 mm³ [95% CI 671.7 to 1009]; p < 0.001). Incidence of lung metastases was not different between experimental or control groups for all experimental conditions.ConclusionsAs demonstrated by others, ectopic BMP-2 signaling has unpredictable effects on local tumor proliferation in murine models of osteosarcoma and does not consistently result in osteosarcoma cell line differentiation. Further investigations into other methods of safe bone and soft tissue healing augmentation and the use of differentiation therapies is warranted.Clinical RelevanceOur results indicate that BMP-2 has the potential to stimulate the growth of osteosarcoma cells that are poorly responsive to BMP-2 mediated osteoblastic differentiation. As this differentiation potential is unpredictable in the clinical setting, BMP-2 may promote the growth of microscopic residual tumor burden after resection. Our study provides further support for the recommendation to avoid the use of BMP-2 after limb-salvage surgery in patients with osteosarcoma.     

Recurrence of primary sclerosing cholangitis after liver transplantation is associated with specific changes in the gut microbiome pretransplant – a pilot study

Primary sclerosing cholangitis (PSC) is a common indication for liver transplantation (LT). Up to 25% of patients experience recurrence of PSC (rPSC) after LT, which is associated with significant morbidity and mortality. To date, it is not possible to predict which patients are at risk for rPSC. The aetiology of PSC is complex and is speculated to involve translocation of intestinal bacteria to the liver, because of its frequent co-occurrence with inflammatory bowel diseases (IBD). Here, we investigate whether the mucosal intestinal microbiome of PSC patients (n = 97) at time of first LT can identify those patients who will develop rPSC. 16S gene sequencing of bacterial DNA isolated from formalin-fixed paraffin-embedded biopsies showed that PSC patients with Crohn’s disease (n = 15) have a reduced microbial diversity and that inflammation of the mucosa is associated with beta-diversity changes and feature differences. No differences in alpha- or beta diversity were observed between patients with rPSC (n = 14) and without rPSC (n = 83). However, many over-represented bacterial features were detected in patients with rPSC, while surprisingly, those without recurrence of disease were characterized by an increased presence of the Gammaproteobacteria Shigella. This pilot study warrants further investigation into bacterial differences between rPSC and non-rPSC patients.     

Recent Advances in Polymer Nanocomposites Based on Polyethylene and Polyvinylchloride for Power Cables

Polymer nanocomposites used in underground cables have been of great interest to researchers over the past 10 years. Their preparation and the dispersion of the nanoparticles through the polymer host matrix are the key factors leading to their enhanced dielectric properties. Their important dielectric properties are breakdown strength, permittivity, conductivity, dielectric loss, space charge accumulation, tracking, and erosion, and partial discharge. An overview of recent advances in polymer nanocomposites based on LDPE, HDPE, XLPE, and PVC is presented, focusing on their preparation and electrical properties.     

Vitamin D Receptor (VDR) Gene Polymorphisms (<Emphasis Type="Italic">Fok</Emphasis>I, <Emphasis Type="Italic">Bsm</Emphasis>I) and their Relation to Vitamin D Status in Pediatrics βeta Thalassemia Major

Vitamin D is critical for calcium, phosphate homeostasis and for mineralization of the skeleton, especially during periods of rapid growth. Vitamin D Deficiency leads to rickets (in children) and osteomalacia (in adults). Expression and activation of the vitamin D receptor (VDR) are necessary for the effects of vitamin D, in which several single nucleotide polymorphisms have been identified especially (FokI, BsmI). In this study serum 25 (OH) vitamin D3 levels were estimated by Enzyme Linked Immunosorbent Assay [ELISA], VDR (FokI, BsmI) gene polymorphisms were analyzed by polymerase chain reaction-restriction fragment length polymorphism assay [PCR–RFLP].Serum levels of calcium, phosphorus, alkaline phosphatase and ferritin were determined in 50 Pediatrics beta thalassemia major patients and 60 controls. Patients had significantly lower serum calcium (p < 0.001) lower serum vitamin D3 (p < 0.001) with elevated levels of phosphorus (p < 0.001) and alkaline phosphatase than controls (p = 0.04). Of the patients studied, 60 % had vitamin D deficiency (<20 ng/ml), 20 % had vitamin D insufficiency (21–30 ng/ml) and 20 % had sufficient vitamin D status (>30 ng/ml). Patients harboring mutant (Ff,ff) and wild (BB) genotypes were associated with lower serum calcium (p = 0.08, 0.02) respectively, lower vitamin D3 levels (p < 0.001, 0.01) respectively. They were also suffering from more bony complications although the difference was not statistically significant (p > 0.05). In conclusion, these results suggest that the VDR (FokI, BsmI) gene polymorphisms influence vitamin D status, (Ff,ff), BB genotypes had lower vitamin D levels, so they might influence risk of development of bone diseases in beta thalassemia major.     

Bacterial L-form isolation from inflammatory bowel disease patients

This study was designed to investigate a possible relationship between bacterial L forms and inflammatory bowel disease. Homogenates of intestinal mucosal biopsies from Crohn's disease, ulcerative colitis, and control patients underwent bacterial culture on hypertonic media designed for the recovery of L-form bacteria and parental organisms. L forms were recovered from 24 of 71 Crohn's disease, 51 of 121 ulcerative colitis, and 2 of 140 control biopsy specimens. These isolation rates are significantly different when Crohn's disease biopsy specimens (p less than 0.001) and ulcerative colitis biopsy specimens (p less than 0.001) are compared with controls. Six different L-form types were recovered, of which the most common were Escherichia coli and Streptococcus fecalis. No marked differences were observed in L-form recovery rates or L-form types recovered between Crohn's disease and ulcerative colitis patients. Drug treatment of inflammatory bowel disease patients did not affect L-form recovery rates or the type of L forms recovered. The results suggest either that L forms are involved in the causation of inflammatory bowel disease or that their presence in mucosal biopsy tissues is a result of the disease process.     

HCV Infection in Egyptian Patients with Acute Hepatitis

The diagnostics of community-acquired acute HCVhepatitis in an endemic area was studied in 110 Egyptianpatients with acute jaundice. In the first week of thejaundiced period 30 of 110 patients (27.3%) had anti-HCVantibodies. The majority already showed high levels ofanti-HCV IgG (25/30), associated with anti-HCV IgM innine of them. Five patients showed only an HCV IgMreactivity. Seven had also anti-HEV and/or anti-HBV: their jaundice couldthen be related to an acute infection caused by thoseviruses. All patients were infected with genotype 4a, inthree associated with the 3a. During the follow-up five patients seroconverted for IgG, whiletheir anti-HCV IgM did not show a uniform pattern ofreactivity. Patients with positive serology suspected ofan acute HCV infection were older than the patients with other acute hepatitis and showed a lowerpeak of ALT level. Seroconversion during acute hepatitisstrongly indicated HCV as the etiologic agent. However,the detection of anti-HCV IgG antibodies in the jaundiced period showed that the majorityof patients had already seroconverted to anti-HCVantibodies; in most of them it is possible tohypothesize a reactivation of a chronic HCVinfection.     

In palindromic rheumatism,hand joint involvement and positive anti-CCP antibodies predict RA development after 1 year of follow-up

This study aimed to determine the frequency of rheumatoid factor (RF) and cyclic citrullinated peptide (CCP) antibodies in a cohort of patients with palindromic rheumatism (PR) and to find determinants for progression to rheumatoid arthritis (RA). All new cases of PR (n?=?90) were included prospectively and followed up for 1 year, and a comparison group of RA cases (n?=?70) was also included. At study entry in all patients in both groups, RF and anti-CCP antibodies were tested, and the findings were compared and correlated. In the PR group at presentation, RF was positive in 30 patients (33.3 %) and, in the RA group, in 45 patients (64.3 %). Anti-CCP antibodies were positive in 35 patients (38.9 %) with PR and in 58 patients (82.9 %) with RA. In the PR group, positive correlations were observed between RF and C-reactive protein (CRP) (p?=?0.036), while anti-CCP positively correlated with disease duration (p?=?0.015) and CRP (p?<?0.001). At 1-year follow-up, 25 cases (27.5 %) had progressed to RA, 3 (3.3 %) cases had developed systemic lupus, 43 cases had responded to hydroxychloroquine with complete remission, five cases had developed other rheumatic diseases, and 14 cases had progressed to undifferentiated arthritis. After regression analysis, the involvement of hand joints and positive anti-CCP were the only predictors that determined progression into RA within a year (p?<?0.001 and p?=?0.02, respectively). Early hand joint involvement and positive anti-CCP at disease onset are good predictors for progression to RA in this domain.     

Anti-IL-6 receptor monoclonal antibody as a new treatment of endometriosis

Immunologic Research - Many pro-inflammatory cytokines especially tumor necrotic factor alpha (TNFα), interleukin (IL)-1β, and IL-6 have crucial role in the pathogenesis of endometriosis....