Exhaled breath condensate MMP-9 level and its relationship wıth asthma severity and interleukin-4/10 levels in children

BackgroundMatrix metalloproteases (MMPs) are key mediators in airway remodeling, and MMP- 9 is the main type investigated to discover its implication for the pathogenesis and severity of asthma.ObjectiveTo evaluate MMP-9 and its natural tissue inhibitors of metalloproteinases (TIMP-1) levels of exhaled breath condensate (EBC) in children with asthma. We also analyzed any potential relationship between these enzymes and EBC interleukin (IL)-4/10 levels as well as asthma severity.MethodsThree study groups were formed: group 1, children with persistent asthma (n = 20); group 2, children with intermittent asthma (n = 10), and group 3, healthy controls (n = 12). Pulmonary functions were measured as forced expiratory volume in 1 second (FEV₁), peak expiratory flow (PEF), and forced expiratory flow from 25% to 75% of vital capacity values by spirometry, and MMP-9, TIMP-1 and IL-4/10 levels in EBC were analyzed by enzyme-linked immunosorbent assay (ELISA).ResultsThe MMP-9 levels of EBC were found to be 57.7 ± 17.5, 35.4 ± 11.7, and 30.6 ± 3.7 ng/mL in children belonging to group 1, group 2 and group 3, respectively. Children belonging to group 1 and group 2 showed significantly higher MMP-9 levels of EBC in comparison with the controls (P < .001 and P = .047, respectively). No statistically significant difference was found between groups regarding TIMP-1 levels of EBC. EBC MMP-9 levels were inversely correlated with both FEV₁ and PEF values (r = ?0.472, P = .011, and r = ?0.571, P = .002, respectively) in children with asthma. Positive correlations were also seen between MMP-9 levels and IL-4/10 levels of EBC (r = 0.419, P = .027 and r = 0.405, P = .032, respectively) in children with asthma.ConclusionWe showed that MMP-9 levels of EBC are elevated in children with asthma and correlated with lung functions and other inflammatory markers such as IL-4/IL10 in EBC.     

Survivin expression in non-small-cell lung carcinomas: correlation with apoptosis and other apoptosis-related proteins, clinicopathologic prognostic factors and prognosis.

The role of survivin that regulates the biological behavior of non-small-cell lung carcinoma (NSCLC) is still controversial. We aimed to investigate survivin expression in NSCLC and to define any correlation with expressions of p53, bcl-2, bax, apoptotic index (AI), tumor cell proliferation, clinicopathologic variables, and overall survival. Tumors of 63 patients with NSCLC were examined for expressions of survivin, p53, bcl-2, bax, and Ki-67 by immunohistochemistry. AI was also evaluated. Results for each antibody were correlated with each other, and with clinicopathologic variables including age, sex, histologic subtype, TNM (T: primary tumor, N: regional lymph node metastasis, M: distant metastasis) stage, lymph node status, smoking history, and prognosis. Nuclear survivin expression was inversely correlated with p53 expression (P = 0.04, r = - 0.367), and tumor stage (P = 0.03, r = - 0.273), and positively correlated with tumor cell proliferation (P = 0.009, r = 0.329). Cytoplasmic survivin expression positively correlated with smoking history (P = 0.02, r = 0.282). Survivin/bax ratio was inversely correlated with AI (r: - 0.004). By Kaplan-Meier analysis, TNM stage (P < or = 0.001), lymph node metastasis (P = 0.04), and Ki-67 index (P < or = 0.001) were associated with survival, whereas survivin was not. In multivariate analysis, only TNM stage was an independent predictor. Although survivin and other apoptosis-related protein expressions fail to predict the clinical outcome, the present findings suggest that survivin is involved in tumor cell apoptosis and proliferation and may play a role in critical steps of cancer progression in NSCLC.     

Endothelial molecules decipher the mechanisms and functional pathways in antibody-mediated rejection

Microvascular endothelium is the main target of injury in antibody-mediated rejection of human organ transplants. Hence, antibody-mediated rejection histologically presents with microvascular inflammation (pulmonary or myocardial or peritubular capillaritis, glomerulitis), thrombosis, and endothelial remodeling (duplication and/or multilayering of glomerular and capillary basement membranes). We previously observed upregulation of several endothelial genes in kidney transplant biopsies from patients with donor specific antibodies, indicating active antibody-mediated rejection and poor graft survival. Furthermore, endothelial molecular signals discovered a previously unknown clinical phenotype: C4d negative antibody-mediated rejection. With the recognition of C4d negative antibody-mediated rejection, data from multiple transplant centers now show that antibody-mediated rejection is the most common cause of late kidney transplant failure. This paper reviews the current understanding of endothelial cell biology in antibody-mediated rejection, emphasizing recent advances and pending questions. Furthermore, the paper discusses functionally active pathways in human antibody-mediated rejection, which include aspects of endothelial activation with increased endothelial adhesive and pro-coagulant signals facilitating leukocyte trafficking and attachment, cell-to-basement membrane interactions, platelet activation, coagulation, and endothelial repair responses. To understand effector mechanisms of antibody-mediated rejection and quantify the degree of antibody-mediated tissue injury in clinical transplants, endothelial cells provide a useful read-out.     

Is it the time for metformin to take place in adjuvant treatment of Her-2 positive breast cancer? Teaching new tricks to old dogs

Breast cancer is the most common malignancy diagnosed among women. According to the new molecular subclassification, basal like and Her-2 positive breast cancers have the worst outcome and these are the ones in which chemotherapy is a must as a part of adjuvant treatment. New treatment options that could be used as an adjuvant maintenance treatment are still being investigated. Insulin hormone is one of the reasons of breast cancer recurrence and death in breast cancer survivors. Targeting insulin as a therapeutic modality in breast cancer could be an option in the adjuvant treatment of breast cancer. It seems that insulin may signal to activate a cascade of proliferative and anti-apoptotic events in the cancer cell. Metformin, an oral anti-diabetic known for 50 years, may also have direct effects on cancer cells. Metformin causes Her-2 suppression via the inhibition of mTOR in breast cancer cells. Thus, we believe that the time has arrived both to target insulin reduction and to alter Her-2 oncogene based molecular pathogenetic steps in breast cancer by using metformin as an adjuvant therapy in breast cancer patients.     

Pdgfra and Pdgfrb genetically interact during craniofacial development

Background: One of the most prevalent congenital birth defects is cleft palate. The palatal skeleton is derived from the cranial neural crest and platelet‐derived growth factors (Pdgf) are critical in palatogenesis. Of the two Pdgf receptors, pdgfra is required for neural crest migration and palatogenesis. However, the role pdgfrb plays in the neural crest, or whether pdgfra and pdgfrb interact during palatogenesis is unclear. Results: We find that pdgfrb is dispensable for craniofacial development in zebrafish. However, the palatal defect in pdgfra;pdgfrb double mutants is significantly more severe than in pdgfra single mutants. Data in mouse suggest this interaction is conserved and that neural crest requires both genes. In zebrafish, pdgfra and pdgfrb are both expressed by neural crest within the pharyngeal arches, and pharmacological analyses demonstrate Pdgf signaling is required at these times. While neither proliferation nor cell death appears affected, time‐lapsed confocal analysis of pdgfra;pdgfrb mutants shows a failure of proper neural crest condensation during palatogenesis. Conclusions: We provide data showing that pdgfra and pdgfrb interact during palatogenesis in both zebrafish and mouse. In zebrafish, this interaction affects proper condensation of maxillary neural crest cells, revealing a previously unknown interaction between Pdgfra and Pdgfrb during palate formation. Developmental Dynamics 245:641–652, 2016. © 2016 Wiley Periodicals, Inc.     

Human colorectal adenomas demonstrate a size-dependent increase in epithelial cyclooxygenase-2 expression

Non-steroidal anti-inflammatory drugs are chemopreventive for colorectal cancer. This effect is due in part to their ability to inhibit the inducible isoform of cyclooxygenase (COX-2). However, the cellular expression and role of COX-2 in the premalignant stages of colorectal tumourigenesis is unclear. COX-2 expression was assessed in 35 human colorectal adenomas and 38 sporadic invasive colorectal adenocarcinomas. Adenomas were classified as small (<5 mm in diameter), medium (5-10 mm), and large (>10 mm). All tissues were paraffin-embedded and formalin-fixed. COX-2 protein expression was determined using immunohistochemistry. COX-2 was detected in the epithelial cells in 35 of 38 carcinomas (92%) and in 8 of 8 (100%) lymph node metastases. All of the epithelial cells expressed COX-2 in 30 of 35 (86%) carcinomas and in 100% of the lymph node metastases. Twenty-three of 35 (66%) adenomas expressed COX-2 in the tumour epithelium. With an increase in the size of adenoma (<5 mm, 5-10 mm, >10 mm), there was an increase in (i) the proportion of adenomas with immunoreactive COX-2 in the epithelium (p = 0.036)-this was 38% in small adenomas and 82% in large adenomas; (ii) the extent of epithelial COX-2 staining within a given tumour (p = 0.003)-100% of epithelial cells were COX-2-positive in 15% of small adenomas and in 73% of large adenomas; and (iii) the intensity of epithelial COX-2 staining (p = 0.009)-strong COX-2 staining occurred in 8% of small adenomas and in 36% of large adenomas. COX-2 immunoreactivity was not detected in adjacent normal epithelium but was apparent in fibroblasts and inflammatory mononuclear cells of adjacent normal, adenoma, and carcinoma tissue. These results suggest that epithelial COX-2 activity is important for the growth and/or survival of adenomatous epithelial cells from an adenoma diameter of less than 5 mm and that there is a selective advantage for adenoma epithelial cells expressing higher levels of COX-2.     

Anihypercholesterolemic effect of Semecarpus anacardium Linn nut milk extract in high-cholesterol-fed rats

The present study was carried to bring about the hypolipidemic effect of the drug Semecarpus anacardium Linn nut milk extract (SA) in hypercholesterolemia-induced rat model. Adult male Wistar rats were divided into four groups which included control rats, hypercholesterolemia-induced rats (high-cholesterol diet (4 %) for 30 days), hypercholesterolemic rats treated with the drug SA (200 mg/kg/b. wt oil), and the control rats treated with the drug SA (200 mg/kg/b. wt). Increased level of ROS and lipid peroxides were observed in hypercholesterolemic rats, whereas the levels of activities of antioxidant enzymes were found to be decreased in animals fed with a high-fat diet. Simultaneous administration of SA to these rats reverted back the changes to near-normal levels. Similarly, an increase in the expression of iNOS and LOX-1 were observed in high-fat-fed rats when compared to normal rats. Upon treatment with the drug SA, their expressions were brought back to near-normal levels. No adverse effects were observed in SA-alone treated group of rats, indicating its protective nature. The present study suggests that SA could play a protective role against hypercholesterolemia, thereby preventing coronary heart disease.     

A twenty years’ results of the antimicrobial resistance profile and multidrug resistance trend of invasive Streptococcus pneumoniae isolates recovered from adult patients in Turkey: A literature review

PurposeThe aim of this study is to analyze antimicrobial resistance and multidrug (MDR)/extensively (XDR) resistance trend among Streptococcus pneumoniae isolates causing invasive disease in adult patients.MethodsWe analyzed antimicrobial resistance and multidrug resistance trend among invasive S.pneumoniae isolates recovered from adult patients (≥18-years) in a tertiary University Hospital, Turkey between 1996 and 2018. The antibiotic susceptibility pattern was determined by using gradient-test for penicillin and cefotaxime and disk-diffusion method for other antibiotics.ResultsA total of 272 isolates (74.3% from the bloodstream) of S. pneumoniae were collected during the study period. The highest non-susceptibility rate was obtained for tetracycline (63.5%), followed by trimethoprim/sulfamethoxazole (48%), penicillin-oral (30.4%), erythromycin (21.7%), clindamycin (15.8%), ciprofloxacin/levofloxacin (5.9%), penicillin-parenteral (5.5%), cefotaxime (2.2%), and rifampisin (1.8%), respectively. No resistance was observed against vancomycin during the years studied. Over the study period, a significant increase in the rate of antimicrobial resistance among invasive pneumococcal isolates was detected with a peak at period 2014–2018. Although there was an increase in the rates of non-susceptibility to penicillin oral, parenteral penicillin, cefotaxime, erythromycin and clindamycin in adult patients, the results were not statistically significant except erythromycin. Prevalence of MDR and XDR S. pneumoniae were 29% and 9.2% respectively. When the serotypes of MDR isolates were examined, it was noted that serotype 19F (35%) and 14 (12.5%) were the most common.ConclusionsOur study showed an overall increase in non-susceptibility rates of penicillin and erythromycin in invasive S.pneumoniae isolates recovered from Turkish adult patients. Although the prevalence of MDR showed fluctuation between years, the incidence of MDR remained stable. These data indicate the necessity for continuous monitoring and assessment of serotypes and antimicrobial resistance trends in S.pneumoniae in different age groups at both the national and the regional levels as it can be affected by the serotypes dominant in that region, rational use of antibiotics and the vaccination programs.     

Hepatitis A super infection as a cause of liver failure in a child with Wilson's disease

Infection with hepatitis A virus can cause severe or even fatal illness in patients with chronic liver disease. Here we describe a seven-year-old girl who presented as acute liver failure and was diagnosed with Wilson's disease and later with coexistent hepatitis A infection. Wilson's disease was demonstrated on the basis of low ceruloplasmin, high urinary copper excretion, histological evidence of cirrhosis, and high biochemical estimation of liver copper concentration. Hepatitis A was diagnosed serologically. Our case suggests that acute hepatitis A may play a part in the acute decompensation seen in some cases of unrecognized Wilson's disease. We also emphasize the importance of prevention measures of hepatitis A infection in patients with chronic liver disease.