Long-term modulatory effect of Mycobacterium vaccae treatment on histopathologic changes in a murine model of asthma.

BACKGROUND: Mycobacteria are being investigated for modulation of inflammation in asthma and atopic disorders by eliciting particularly strong protective TH1 immune responses. OBJECTIVE: To investigate the long-term effects of intratracheally administered Mycobacterium vaccae on an experimental murine model of asthma. METHODS: BALB/c mice were placed in 4 groups: long-term M. vaccae, M. vaccae, asthma, and control groups. All groups but controls were sensitized intraperitoneally and challenged intratracheally with ovalbumin. The long-term M. vaccae and M. vaccae groups were treated with M. vaccae intratracheally simultaneously during challenges. Finally, mice in the long-term M. vaccae group were rechallenged with ovalbumin nebulization 24 days later. Evaluations of lung histopathologic findings and serum cytokine levels were performed. RESULTS: Comparison of the long-term M. vaccae group with the asthma model group revealed that the number of hyperplasic goblet cells in small and large airways (small airway: P < .05; large airways: P < .01) and thickness of basement membrane in large airways were significantly less in the long-term M. vaccae group. Furthermore, numbers of hyperplasic goblet cells in small airways (P < .05) and basement membrane in the large airway (P < .05), as well as inflammation in small airways (P < .01), were significantly less in the M. vaccae group when compared with the asthma model group. Interferon-gamma secretion from splenocytes of the M. vaccae group was significantly higher than the asthma model and long-term M. vaccae groups. CONCLUSION: Intratracheal administration of M. vaccae exerted a long-lasting ameliorating effect on airway histopathologic features of a murine asthma model.     

Novel ENAM mutation responsible for autosomal recessive amelogenesis imperfecta and localised enamel defects

The genetic basis of non-syndromic autosomal recessive forms of amelogenesis imperfecta (AI) is unknown. To evaluate five candidate genes for an aetiological role in AI. In this study 20 consanguineous families with AI were identified in whom probands suggested autosomal recessive transmission. Family members were genotyped for genetic markers spanning five candidate genes: AMBN and ENAM (4q13.3), TUFT1 (1q21), MMP20 (11q22.3-q23), and KLK4 (19q13). Genotype data were evaluated to identify homozygosity in affected individuals. Mutational analysis was by genomic sequencing. Homozygosity linkage studies were consistent for localisation of an AI locus in three families to the chromosome 4q region containing the ENAM gene. ENAM sequence analysis in families identified a 2 bp insertion mutation that introduced a premature stop codon in exon 10. All three probands were homozygous for the same g.13185_13186insAG mutation. These probands presented with a generalised hypoplastic AI phenotype and a class II openbite malocclusion. All heterozygous carriers of the g.13185_13186insAG mutation had localised hypoplastic enamel pitting defects, but none had AI or openbite. The phenotype associated with the g.13185_13186insAG ENAM mutation is dose dependent such that ARAI with openbite malocclusion segregates as a recessive trait, and enamel pitting as a dominant trait.     

Inhibition of chemokines prevents intraperitoneal adhesions in mice

BACKGROUND: The present study evaluates the efficacy of a broad-spectrumchemokine inhibitor, NR58-3.14.3, in the prevention of adhesionformation after i.p. surgery in mice. METHODS: A total of 110eight week old female Balb/c mice underwent laparotomy. Fortyanimals were randomly assigned to receive daily i.p. injectionsof either vehicle (control) or NR58-3.14.3. Time-course of adhesionformation was assessed. A titration of NR58-3.14.3 was conductedfor i.p. and s.c. administrations. The effectiveness of a singleintra-operative dose of NR58-3.14.3 was evaluated. Number, extent,location and type of adhesions were recorded. Immunohistochemistryof adhesions was done with leukocyte common antigen, CD45. RESULTS:Adhesion scores peaked on post-operative days 6–8. Onboth days 6 and 8, there were smaller adhesion size and lowercumulative adhesion scores in NR58-3.14.3-treated group. Moreover,on day 8, there were significantly fewer adhesions in NR58-3.14.3-treatedgroup compared to controls. The least effective dose for i.p.administration of NR58-3.14.3 was 0.45 mg/animal. Subcutaneousand single intra-operative i.p. administrations were also effectivein the prevention of i.p. adhesions. Although NR58-3.14.3 decreasedthe number of CD45⁺ inflammatory cells in the adhesions by 22.5%compared to control group, this was not significant. CONCLUSIONS:Our results show that this broad-spectrum chemokine inhibitorprevents post-operative adhesions in mice and may have a potentialclinical use.     

Removal of hydrosalpinges increases endometrial leukaemia inhibitory factor (LIF) expression at the time of the implantation window

BACKGROUND: The presence of hydrosalpinges is associated with lower implantation and pregnancy rates in women undergoing IVF-embryo transfer, while salpingectomy improves these parameters. Although the mechanism by which hydrosalpinges affects fertility is not entirely understood, an adverse effect on endometrial receptivity has been postulated. In this study, we hypothesized that the adverse effects of hydrosalpinges on fertility may be in part mediated by inappropriate endometrial expression of leukaemia inhibitory factor (LIF), a cytokine implicated in implantation. METHODS: In order to test our hypothesis, we prospectively examined the expression of LIF during the window of implantation in the endometrium of infertile women (n = 10) with hydrosalpinges prior to and following salpingectomy and of fertile controls (n = 10) by Western blotting and immunohistochemistry. RESULTS: LIF expression was significantly lower in infertile women with hydrosalpinges compared with fertile controls (P < 0.05). Salpingectomy resulted in an increase in LIF expression in eight out of 10 women with hydrosalpinges. LIF levels were increased by 231 +/-49% (mean +/- SEM) following salpingectomy. Immunohistochemical analysis confirmed the Western blot findings. The increased LIF immunoreactivity was predominantly localized to luminal and glandular epithelial cells. CONCLUSIONS: Our findings suggest that observed benefit from salpingectomy in infertile women with hydrosalpinges may be in part mediated by the up-regulation of endometrial LIF expression.     

Inherited vitamin K deficiency: case report and review of literature

Vitamin K is the cofactor for the hepatic carboxylation of glutamic acid residues in a number of proteins including the procoagulants factors II, VII, IX, and X. The role of vitamin K in normal bone function is not fully understood. Inherited deficiency of vitamin K dependent coagulation factors is a rare bleeding disorder reported only in a few patients. Here we present an 18-month old child who presented with osteopeni due to inherited vitamin K deficiency. While the patient had high bone specific alkaline phosphatase and parathyroid hormone levels and low osteocalcin and bone mineral density values, with the regular supplementation of vitamin K all the mentioned parameters returned to normal values.     

Is there any correlation between restriction fragment length polymorphism of the L-MYC gene and metastasis of human nonsmall cell lung cancer?

A potential molecular marker associated with cancer susceptibility as well as metastasis, prognosis and adverse survival, is the L-myc gene. The studies of lung cancer patients from different populations have yielded controversial results. We studied 64 nonsmall cell lung cancer (NSCLC) patients and 37 healthy controls of Turkish origin for L-myc gene polymorphism. Our aim was to test the hypothesis that there was association between L-myc S allele in NSCLC and predisposition to the disease and TNM stage indicating tumor size, node classification and metastasis. Polymerase chain reaction restriction fragment length polymorphism and agarose gel electrophoresis were used to determine the L-myc oncogene genotypes. We found no significant difference, both in the distribution of the LL, LS and SS genotypes and in the allelic frequencies, between the patient group and the control group; that is, the frequencies of L-myc alleles were, L and S, 0.59 and 0.41, 0.60 and 0.40, respectively. Our data between the patient group and the control group; that is, the frequencies of L-myc alleles were, L and S, 0.59 and 0.41, 0.60 and 0.40, respectively. Our data concerning age, sex, size of tumors, histological type of tumors showed no significant association with L-myc genotype. However, a higher frequency of L-myc S allele in the squamous cell carcinoma compared to other histological groups was found, although this difference was not statistically significant. No association was found between the L-myc RFLP and increased risk of metastasis either to the lymph nodes or to other organs. Our results suggested that L-myc gene polymorphism was not a suitable prognostic marker of metastatic development in Turkish NSCLC patients.     

The “vaccine” hubbub: Viral load comparisons of SARS-CoV-2 Delta and Omicron variants against different vaccine–booster vaccine combinations

There is a significant body of evidence showing that efficient vaccination schemes against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is helping control the coronavirus disease 2019 (COVID-19) pandemic. However, this goal cannot be achieved without real world data highlighting the impact of vaccines against viral spread. In this study, we have aimed at differentially investigating the impact of COVID-19 vaccines (CoronaVac, Pfizer/BioNTech, Astra/Zeneca Oxford, Janssen) used in North Cyprus in limiting the viral load of Delta and Omicron variants of SARS-COV-2. We have utilized real-time quantitative polymerase chain reaction cycle threshold values (Ct values) as a proxy of viral load of the two SARS-CoV-2 variants. Our results indicate that the administration of at least two doses of the messenger RNA-based Pfizer/BioNTech vaccine leads to the lowest viral load (highest Ct values) obtained for both Omicron and Delta variants. Interestingly, regardless of the vaccine type used, our study revealed that Delta variant produced significantly higher viral loads (lower Ct values) compared with the Omicron variant, where the latter was more commonly associated with younger patients. Viral spread is a crucial factor that can help determine the future of the pandemic. Thus, prioritizing vaccines that will play a role in not only preventing severe disease but also in limiting viral load and spread may contribute to infection control strategies.     

Polyether Synthesis through Reductive Etherification Reaction Strategy

The reductive etherification reaction (RER) of carbonyl groups (aldehydes or ketones) through silane as a reducing agent together with Bronsted or Lewis acid affords the synthesis of symmetrical and unsymmetrical ethers. This strategy is applied at the macromolecular level for the first time in 1993, and isophthalaldehyde is self-polymerized in the presence of triethylsilane (Et₃SiH)/ tritylperchlorate (TrClO₄) to yield polyethers with low to moderate molecular weights. Next, the polyethers with alternating structures are achieved by reacting isophthalaldehyde with bis(trimethylsilyl) ethers or diols as comonomers using reducing agent silane and Lewis acid. Moreover, in recent years, it is shown that polyether synthesis and post-polymerization modification (PPM) of polymers proceeds smoothly and effectively with the RER strategy in the presence of chlorodimethylsilane (CDMS), which acts as both a reducing agent and a Lewis acid.     

Epidermoid carcinoma of the male urethra. Case report

A case of voiding difficulties was investigated. Other than usual prostatic obstruction or urethral stricture, a small mass at the anterior region of the bulbous urethra was present. Detailed investigation by urethroscopy, biopsy, CT imaging and ultrasonography revealed epidermoid carcinoma of the urethra.