Generation of two human iPSC lines (HIMRi002-A and HIMRi003-A) derived from Caveolinopathy patients with rippling muscle disease.

Here we introduce the human induced pluripotent stem cell lines (hiPSCs), HIMRi002-A and HIMRi003-A, generated from cultured dermal fibroblasts of 61-year-old (HIMRi002-A) and 38-year-old (HIMRi003-A) female patients, carrying a known heterozygous pathogenic variant (p.A46T) in the Caveolin 3 (CAV3) gene, via lentiviral expression of OCT4, SOX2, KLF4 and c-MYC. HIMRi002-A and HIMRi003-A display typical embryonic stem cell-like morphology, carry the p.A46T CAV3 gene mutation, express several pluripotent stem cell markers, retain normal karyotype (46, XX) and can differentiate in all three germ layers. We postulate that the HIMRi002-A and HIMRi003-A iPSC lines can be used for the characterization of CAV3-associated pathomechanisms and for developing new therapeutic options.

Effects of vitamin D receptor gene polymorphisms on susceptibility to disease and bone mineral density in Turkish patients with type 1 diabetes mellitus.

BACKGROUND: Vitamin D receptor (VDR) gene is regarded as one of the candidate genes for type 1 diabetes mellitus (T1D) susceptibility and of some genetic factors involved in the development of osteoporosis in this group. STUDY DESIGN: We characterized the VDR gene polymorphism (BsmI, ApaI, TaqI, FokI and Cdx-2 binding site) in a group of Turkish patients with T1D (n=90) and correlated respective VDR genotypes with the bone mass and some parameters of bone turnover. RESULTS: There were no differences in the genotype frequencies of the BsmI, ApaI, TaqI and Cdx-2 polymorphisms in patients and control subjects. We found a significantly higher prevalence of the F allele/the FF genotype in the patients compared to controls (p=0,0031, odds 1.96 (1,27-3,01)). We observed no difference in markers of bone turnover (Serum levels of osteocalcin, PINP and alkaline phosphatase, urinary levels of calcium/ creatinine and N-telopeptid) among different VDR genotypes. No correlation was found between VDR polymorphisms and DEXA measurements of these patients. CONCLUSIONS: Although the FF genotype was found to be a risk factor in a Turkish population, elucidation of this result is necessary in other larger study groups drawn from the same ethnic population.

Integration of GARD Turkey national program with other non-communicable diseases plans in Turkey.

For the prevention and control of non-communicable diseases (NCD), an action plan on NCDs is intended to support coordinated, comprehensive and integrated implementation of strategies and evidence-based interventions across individual diseases and risk factors, especially at the national and regional levels by World Health Organization (WHO). The Global Alliance against Chronic Respiratory Diseases (GARD) is making every attempt to align with WHO's non-communicable diseases action plan. GARD activities have been commenced in over 40 countries and in 11 countries an integrated NCD action plan is being prepared or has already been initiated. This integrated approach of GARD has also targeted to GARD Turkey project. The Turkish Ministry of Health has decided to apply this national control program in conformity with other NCD action plans. This article is intended to summarize these integration efforts of GARD Turkey (the National Control Program on Chronic Airway Diseases) with other NCD national programs.

Green synthesis of ZnO nanoparticles with Veronica multifida and their antibiofilm activity.

In the present study, Veronica multifida leaf extract and zinc acetate dihydrate were utilized to synthesize zinc oxide (ZnO) nanoparticles (NPs) eco-friendly and cost-effectively under different physical conditions. Soxhlet extractor was used for the preparation of aqueous plant extract. UV-Vis (ultraviolet-visible) spectrophotometer, X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and transmission electron microscope (TEM) were used to characterize the ZnO NPs. UV-Vis spectrophotometer in the range of 200-800 nm was used to get information about the formation of ZnO NPs at different pH and temperatures. FTIR spectrum revealed the presence of functional groups in ZnO NPs. XRD, scanning electron microscope, and TEM analyses confirmed the crystal structure and average size of ZnO NPs. The antimicrobial activities of ZnO NPs were tested on microorganisms, that is, Escherichia coli ATCC 43895, Staphylococcus aureus ATCC 29213, Bacillus subtilis, Bacillus licheniformis, Pseudomonas aeruginosa, and Salmonella typhimurium. Moreover, antibiofilm activity of ZnO NPs was performed against P. aeruginosa and S. aureus ATCC 29213. ZnO NPs have shown effective antimicrobial and antibiofilm activities against tested microorganisms. The results elucidated that eco-friendly and cost-effectively produced ZnO NPs could be used as coating materials and in a wide range of industrial applications, such as pharmaceutical industries and cosmetics.

Comparison of spirometry criteria for the diagnosis of COPD: results from the BOLD study.

Published guidelines recommend spirometry to accurately diagnose chronic obstructive pulmonary disease (COPD). However, even spirometry-based COPD prevalence estimates can vary widely. We compared properties of several spirometry-based COPD definitions using data from the international Burden of Obstructive Lung Disease (BOLD)study. 14 sites recruited population-based samples of adults aged > or =40 yrs. Procedures included standardised questionnaires and post-bronchodilator spirometry. 10,001 individuals provided usable data. Use of the lower limit of normal (LLN) forced expiratory volume in 1 s (FEV(1)) to forced vital capacity (FVC) ratio reduced the age-related increases in COPD prevalence that are seen among healthy never-smokers when using the fixed ratio criterion (FEV(1)/FVC <0.7) recommended by the Global Initiative for Chronic Obstructive Lung Disease. The added requirement of an FEV(1) either <80% predicted or below the LLN further reduced age-related increases and also led to the least site-to-site variability in prevalence estimates after adjusting for potential confounders. Use of the FEV(1)/FEV(6) ratio in place of the FEV(1)/FVC yielded similar prevalence estimates. Use of the FEV(1)/FVC

Adoption of European Union's IPPC Directive to a textile mill: analysis of water and energy consumption.

The present study was undertaken as part of the first application and evaluation of the BREF (Best Available Techniques; BAT Reference Document) Textile Document within the context of the European Union's Integrated Pollution Prevention and Control (IPPC) Directive to a large scale textile mill in Turkey. The BAT requirements for the denim manufacturing textile mill were selected in cooperation with the factory management. Detailed mass balance calculations were conducted to evaluate the overall effect of the selected BAT options. The initial findings indicated that the adoption of the selected BAT options resulted in considerable savings in water and energy consumption in the mill. Besides the installation of flow meters and use of semi-counter current rinsing in the most water-intensive processes, minimization of wash waters in the water softening plant, reuse of the concentrate stream from the reverse osmosis plant and compressor cooling waters provided a 29.5% reduction in the total specific water consumption of the mill, reaching the lower limits suggested by the BREF Textile Document. In terms of energy consumption, use of waste heat from finishing wastewater streams in heating up the wash waters, heat insulation and maintenance applications in addition to BAT measures taken for water minimization reduced specific energy consumption by 9% achieving the limits set by the BREF Textile Document.

The WHO global alliance against chronic respiratory diseases in Turkey (GARD Turkey).

In order to prevent and control non-communicable diseases (NCDs), the 61st World Health Assembly has endorsed an NCD action plan (WHA resolution 61.14). A package for essential NCDs including chronic respiratory diseases (CRDs) has also been developed. The Global Alliance against Chronic Respiratory Diseases (GARD) is a new but rapidly developing voluntary alliance that is assisting World Health Organization (WHO) in the task of addressing NCDs at country level. The GARD approach was initiated in 2006. GARD Turkey is the first comprehensive programme developed by a government with all stakeholders of the country. This paper provides a summary of indicators of the prevalence and severity of chronic respiratory diseases in Turkey and the formation of GARD Turkey.

Does the expired-air carbon monoxide level reflect the severity of inflammation in COPD?

OBJECTIVES: The aim of this study is to evaluate the expired-air carbon monoxide level which relates to the severity of inflammation in patients with chronic obstructive pulmonary disease (COPD). DESIGN: Cross sectional study. SETTING: Cukurova University, Faculty of Medicine, Department of Chest Disease, Out-patient clinic. PATIENTS: The characteristics of patients enrolled in this study were following; 20 ex-smokers with stable COPD (mean age: 68.8 +/- 7.2 years, FEV1: 45.6 +/- 16.6% of predicted), 22 current smokers with stable COPD (mean age: 58.7 +/- 8.2 years, FEVI: 57.5 +/- 20.9% of predicted), 20 healthy smokers (mean age: 55.916.0 years, FEVI: 86.7 +/- 14.2% of predicted), and 20 healthy non-smokers (mean age: 60.8 +/- 9.2 years, FEV1: 95.3 +/- 13.5% of predicted). INTERVENTION: CO level was measured in expired-air. MEAAUREMENT AND RESULTS: The measurement of expired-air CO level was measured by DisCOver, carbon monoxide analyser. It is known that the level of expired-air carbon monoxide in healthy smokers (11.8 +/- 6.4 ppm) and in current smokers with COPD (11.1 +/- 7.4 ppm) is higher than in healthy non-smokers (1.7:0.7 ppm) and in ex-smokers with COPD (2.0 +/- 1.8 ppm) (p = 0.0001). CONCLUSION: We assumed that the level of expired-air carbon monoxide may not useful in assessing the severity of inflammation in COPD (Tab. 1, Fig. 2, Ref. 23).

Transcriptome analysis of channel catfish (Ictalurus punctatus): genes and expression profile from the brain.

Expressed sequence tag (EST) analysis was conducted using a complementary DNA (cDNA) library made from the brain mRNA of channel catfish (Ictalurus punctatus). As part of our transcriptome analysis in catfish to develop molecular reagents for comparative functional genomics, here we report analysis of 1201 brain cDNA clones. Of the 1201 clones, 595 clones (49.5%) were identified as known genes by BLAST searches and 606 clones (50.5%) as unknown genes. The 595 clones of known gene products represent transcripts of 251 genes. These known genes were categorized into 15 groups according to their biological functions. The largest group of known genes was the genes involved in translational machinery (21.4%) followed by mitochondrial genes (6.2%), structural genes (3.1%), genes homologous to sequences of unknown functions (2.3%), enzymes (2.7%), hormone and regulatory proteins (2.5%), genes involved in immune systems (2.1%), genes involved in sorting, transport, and metal metabolism (1.8%), transcriptional factors and DNA repair proteins (1.6%), proto-oncogenes (1.2%), lipid binding proteins (1.2%), stress-induced genes (0.7%), genes homologous to human genes involved in mental diseases (0.6%), and development or differentiation-related genes (0.3%). The number of genes represented by the 606 clones of unknown genes is not known at present, but the high percentage of clones showing no homology to any known genes in the GenBank databases may indicate that a great number of novel genes exist in teleost brain.

Combination of chemotherapy and recombinant interferon-alpha in advanced non-small cell lung cancer.

Some studies have shown that the combination of chemotherapy and interferon in non-small cell lung cancer (NSCLC) and other solid tumors is feasible and possesses antitumor activity. Our study was aimed at verifying whether the addition of recombinant human interferon alpha (rh-IFN alpha) to combined chemotherapy would be able to increase the response rate and survival of patients with NSCLC. Thirty-eight patients with previously untreated advanced NSCLC were evaluated in this study. Median age of patients was 57 years; performance status according to ECOG 0 and 1, 37 pts (97%); stage IIIB, 27 pts (71%); stage IV, 11 pts (29%). Histology was squamous cell carcinoma in 53%, adenocarcinoma 44% and large cell carcinoma 3%. Our schedule consisted of 80 mg/m2 cisplatin I.V., 100 mg/m2 etoposide I.V., 10 million U rh-IFN alpha IM and 10 million U rh-IFN alpha I.V. on first day of treatment, every 3 weeks. None of the patients had complete response. Partial response rate was 34%. Median response duration was 7 months (range 3-19 months), median survival time was 11 months (range 4-41 months). Twenty-nine percent of patients had grade 3 nausea and vomiting, 24% had grade 2 leucopenia, 5% had grade 2 cardiotoxicity, 2.6% had flu-like syndrome. According to these results, in advanced NSCLC, the addition of rh-IFN alpha did not increase the cisplatin-etoposide combined chemotherapy induced response rate and survival time.

A randomised trial of two cisplatin-containing chemotherapy regimens in patients with stage III-B and IV non-small cell lung cancer.

Seventy-four newly diagnosed patients with histologically proven Stage III-B and IV non-small cell lung cancer were randomized to receive either cisplatin: 20 mg/m2 x day x 5, ifosfamide: 1.8 g/m2 x day x 5, mesna: 1.2 g/m2 x day x 5, etoposide: 100 mg/m2 x day x 5 (ICE) or cisplatin: 20 g/m2 x day x 5 and etoposide: 100 mg/m2 x day x 5. Response rates were 59% in the ICE and 40% in the CE arm with a significant advantage in response duration and overall survival in the ICE receiving patients (P = 0.03, P = 0.0008). As we used granulocyte colony stimulating factor (G-CSF) very frequently, myelotoxicity remained substantial but acceptable.

Value of preoperative spirometry to predict postoperative pulmonary complications.

In order to determine the incidence of postoperative pulmonary complications (POPC) and the value of preoperative spirometry to predict pulmonary complications after upper abdominal surgery, 24 women and 36 men (total 60 patients) were studied prospectively (mean age 48 center dot 3 years). On the day before the operation and for 15 days after the operation, each patient's respiratory status was assessed by clinical examination, chest radiography, spirometry and blood gas analysis, and patients were monitored for pulmonary complications by a chest physician and a surgeon independently. In this study, postoperative pulmonary complications developed in 21 (35%) patients (pneumonia in 10 patients, bronchitis in nine patients, atelectasis in one patient, pulmonary embolism in one patient). Of 31 patients with abnormal preoperative spirometry, 14 (45 center dot 2%) patients showed complications, whereas among 29 patients with normal preoperative spirometry, 7 (24 center dot 1%) patients showed complications (P <0 center dot 05). The incidence of POPC was higher in patients with advanced age, smoking, preoperative abnormal findings obtained from physical examination of the chest, higher ASA class and longer duration of operation. The sensitivity (0 center dot 76) and specificity (0 center dot 79) of abnormal preoperative findings obtained from physical examination to predict POPC were higher than abnormal preoperative spirometry (0 center dot 67 and 0 center dot 56 retrospectively). There was no significant difference between patients with and without pulmonary complications in regard to weight, serum albumin, type of incision, incidence of abnormal preoperative blood gases and duration of postoperative hospital stay. We conclude that POPC is still a serious cause of postoperative morbidity. Multiple risk factors include preoperative abnormal spirometry responsible for development of POPC. If used alone, spirometry has limited clinical value as a screening test to predict POPC after upper abdominal surgery.

Anticipated administration of GM-CSF in the treatment of non small cell lung cancer.

The purpose of this study was to verify the kinetic response of the human marrow myeloid progenitor cells to the short term use of GM-CSF and its impact on the therapeutic activity of this three-drug cisplatinum containing regimen in non small cell lung cancer (NSCLC). Sixty patients with stage III-B and IV NSCLC were randomised to receive GM-CSF for 3 days, five days prior to the onset of chemotherapy. The chemotherapy regimen consisted of Mitomycin-C: 6 mg/m2 on day one, Ifosfamide: 2000 mg/m2 days 1 to 3, Mesna: 2000 mg/m2 days 1 to 3, Cisplatinum: 30 mg/m2 days 1 to 3, and was repeated every 4 weeks. All the patients received 30-50 Gy of radiotherapy to the primary and/or metastatic sites. There were positive correlations between stage of the disease, chemosensitivity of the tumor, number of chemotherapy cycles and overall survival (p=0.000). Administration of GM-CSF was an independent prognostic parameter in locally advanced and metastatic disease (p=0.041). In the GM-CSF receiving arm more courses could be given (117 versus 99, p=0.0415), and less courses were postponed (6 versus 22). In this arm, the mean of granulocyte nadir was higher (p=0.033) and mean time to granulocyte recovery became shorter (p=0.001) as the number of chemotherapy cycles increased. It was concluded that, dose intensification with GM-CSF prophylaxis is benefical in increasing the treatment tolerability by decreasing the intensity of granulocytopenia as well as providing rapid recovery.

Ifosfamide, cisplatin and etoposide (ICE) combined chemotherapy with recombinant human granulocyte colony-stimulating factor support in small cell lung cancer.

This study was aimed to evaluate the effect of ifosfamide, cisplatin and etoposide (ICE) combined chemotherapy in small cell lung cancer (SCLC), and to test the feasibility of adding recombinant human granulocyte colony-stimulating factor (rhG-CSF) to aggressive chemotherapy. Thirty consecutive, previously untreated, patients with SCLC (17 with limited disease and 13 with extensive disease) entered this study. The ICE regimen consisted of ifosfamide (I) 4 g/m2 i.v. with same dose mesna i.v. on first day, cisplatin (C) 25 mg/m2 i.v. on days 1 to 3 and etoposide (E) 100 mg/m2 i.v. on days 1 to 3. A total of 30 MU rhG-CSF i.v. were given from day 7 to 14 if WBC were lower than 3000 x 10(6)/L, neutrophils were lower than 1000 x 10(6)/L. Overall response (OR) rate was 93% with a complete response (CR) rate of 23%. Median survival was 12 months [95% confidence interval (CI): 11-14] and median response duration was 10 months [95% CI: 8-10]. Thirty-seven percent of patients had grade 3 neutropenia, 40% had grade 3 anemia, and 1% had grade 2 thrombocytopenia. Nonhematologic toxicity was mild with nausea and vomiting being the most common. RhG-CSF, which reduced leukopenic nadirs and shortened the neutropenic period, was also well tolerated. This chemotherapy protocol seems to be active, well tolerated and is currently being compared with various conventional chemotherapies.

Hermansky Pudlak Syndrome and Pulmonary Alveolar Proteinosis at the same patient: first case report in the world literature.

Hermansky-Pudlak Syndrome (HPS) is a rare autosomal recessive disorder presenting with oculocutaneous albinism, bleeding diathesis and lysosomal accumulation of ceroid lipofuscin which leads to interstitial fibrosis in lung. Pulmonary fibrosis which is usually associated with HPS-1 and HPS-4 subtypes usually manifests in the third/fourth decades of life representing with giant lamellar bodies of alveolar type-II-cells and their apparent degeneration causes restrictive lung disease. Pulmonary manifestation of this syndrome may lead to premature death. Pulmonary Alveolar Proteinosis(PAP) is another rare disease characterized by alveolar deposition of surfactant phospholipids and proteins secondary to defective clearance by alveolar macrophages. PAP may occur as autoimmune diseases and/or secondary to toxic inhalation, systemic infections or hematological disorders. None of the cases were reported secondary to HPS according to the best our knowledge. As well, pulmonary involvement of HPS was never reported as PAP. We report the first case of PAP in a patient with HPS.

Restricted spirometry in the Burden of Lung Disease Study.

BACKGROUND: The presence of restrictive lung disease has classically required the measure of total lung capacity to document 'true' restriction, which has limited its detection in large population-based studies. METHODS: We used spirometric data to classify people with restricted spirometry (forced expiratory volume in 1 second [FEV(1)]/forced vital capacity ≥ 0.70 and FEV(1) < 80% predicted) in the Burden of Lung Disease (BOLD) Study and determined the relation between this finding and demographic factors and the presence of chronic diseases, including diabetes mellitus, hypertension and cardiovascular disease. RESULTS: Overall, we found that 11.7% of men (546/4664) and 16.4% of women (836/5098) had restricted spirometry. Prevalence varied widely by site, from a low of 4.2% among males in Sydney, Australia, to a high of 48.7% among females in Manila, The Philippines. Compared to people with normal lung function, those with restricted spirometry had a higher prevalence of diabetes (12.2% vs. 4.6%), heart disease (15.0% vs. 7.7%) and hypertension (38.8% vs. 22.8%). CONCLUSIONS: Restricted spirometry is a common finding in population studies. Additional research is needed to better define and describe the mechanisms that lead to restricted spirometry and potential interventions.

Chemical and topographical modification of PHBV surface to promote osteoblast alignment and confinement.

Proper cell attachment and distribution, and thus stronger association in vivo between a bone implant and native tissue will improve the success of the implant. In this study, the aim was to achieve promotion of attachment and uniform distribution of rat mesenchymal stem cell-derived osteoblasts by introducing chemical and topographical cues on poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) film surfaces. As the chemical cues, either alkaline phosphatase was covalently immobilized on the film surface to induce deposition of calcium phosphate minerals or fibrinogen was adsorbed to improve cell adhesion. Microgrooves and micropits were introduced on the film surface by negative replication of micropatterned Si wafers. Both chemical cues improved cell attachment and even distribution on the PHBV films, but Fb was more effective especially when combined with the micropatterns. Cell alignment (<10 degrees deviation angle) parallel to chemically modified microgrooves (1, 3, or 8 microm groove width) and on 10 microm-thick Fb lines printed on the unpatterned films was achieved. The cells on unpatterned and 5 microm-deep micropitted films were distributed and oriented randomly. Results of this study proved that microtopographies on PHBV can improve osseointegration when combined with chemical cues, and that microgrooves and cell adhesive protein lines on PHBV can guide selective osteoblast adhesion and alignment.

Functional consequences of homo- but not hetero-oligomerization between transporters for the biogenic amine neurotransmitters.

Before this study, the human norepinephrine transporter (hNET) was the only member of the biogenic amine neurotransmitter transporter family that had not been demonstrated to be a functional homo-oligomer. Here, using two forms of the transporter, I155C and hNET-myc, with distinct antigenicity and inhibitor sensitivity, we demonstrated that hNET exists as a homo-oligomer. hNET I155C is a functional mutant and is sensitive to inactivation by the sulfhydryl reagent [2-(trimethylammonium)ethyl]methanethiosulfonate, while hNET-myc is resistant to inactivation by this reagent. Coimmunoprecipitation of these two forms demonstrated that a physical interaction exists between norepinephrine transporter monomers. Further characterization of this physical interaction has revealed that the activity of norepinephrine transporters depends on interactions between monomers. Because norepinephrine transporters and serotonin transporters are the only two members of the neurotransmitter transporter family endogenously expressed in the cell membrane of the same cells, placental syncytiotrophoblasts, we tested the ability of norepinephrine transporters and serotonin transporters to associate and function in a hetero-oligomeric form. Similarly, coexpression of hNET-myc with serotonin transporter-FLAG showed a physical interaction in coimmunoprecipitation assays. However, coexpression of serotonin and norepinephrine transporters did not sensitize norepinephrine transporter activity to inhibition by citalopram, a selective serotonin transport inhibitor. Thus, the norepinephrine transporter-serotonin transporter physical association did not produce functional consequences. Based on this, we propose that the transporters for biogenic amine neurotransmitters interact functionally in homo- but not hetero-oligomeric forms.

The oxidant-antioxidant balance in mild asthmatic patients.

We investigated the oxidant-antioxidant balance and the effect of inhaled corticosteroids on this balance in mild stable asthmatics. Included in the study were 30 mild asthmatic patients (11 male, 19 female, mean age (year) +/- SD: 35.1 +/- 9.7) and 26 healthy adults (7 male, 19 female, mean age (year) +/- SD: 40.8 +/- 13.3). In all study groups, the peripheral venous blood samples were taken for plasma malonyldialdehyde (MDA), a parameter of lipid peroxidation caused by the oxidants, and erythrocyte superoxide dismutase (SOD), an antioxidant enzyme. The mean plasma MDA level was lower in the asthmatic group (5.7 +/- 1.2 nmol/ml) than in the healthy group (6.3 +/- 1.7 nmol/ml); and the mean erythrocyte SOD level was higher in asthmatic group (1086.4 +/- 247.4 U/gHb) than in the healthy group (1028.0 +/- 230.0 U/gHb). However, there were no significant differences in measurements of both plasma MDA levels and erythrocyte SOD enzyme activities between the groups (respectively, p = 0.1 and p = 0.4). When asthmatic patients were divided into subgroups as "inhaled steroid user" and "no inhaled steroid user", no significant differences were observed in the measurements of either plasma MDA level or erythrocyte SOD enzyme activity between the mentioned subgroups. According to the results of our study, we can say that oxidant-antioxidant balance is not significantly affected in mild asthmatics or measurement of plasma level of MDA and erythrocyte SOD enzyme activity is not sensitive to the oxidant-antioxidant balance in mild asthmatics.