The role of Helicobacter pylori in patients with hypothyroidism in whom could not be achieved normal thyrotropin levels despite treatment with high doses of thyroxine

Background: Helicobacter pylori infection is a most frequent cause of chronic gastritis. H. pylori may decrease absorption of oral thyroxine by decreasing gastric acid secretion in the stomach. In this study, we aimed to investigate the change in thyroid function tests of the cases after H. pylori eradication who were not responding to high doses of thyroxine treatment before H. pylori eradication. Methods: Hypothyroid cases who were not responding to high doses of thyroxine among the ones presented to Endocrinology and Gastroenterohepatology Clinics of Sisli Etfal Training and Research Hospital between 2009 and 2010 were included in the study. Thyroid function tests were performed two times in all cases before and after H. pylori eradication. Duodenal, antral and corporal biopsies, and jejunal aspirates and biopsies were taken during upper gastrointestinal system endoscopies performed in all patients. Cases without intestinal pathology were included in the study. Results: Serum thyrotropin (TSH), free T3, and free T4 values before H. pylori eradication were 30.5 ± 28.8 IU/mL, 2.64 ± 0.56 pg/mL, and 0.92 ± 0.32 ng/mL, respectively, and after eradication were found to be 4.2 ± 10.6 IU/mL, 3.02 ± 0.61 pg/mL, and 1.3 ± 0.34 ng/mL, respectively (p values <.001, .002, and <.001, respectively). After H. pylori eradication treatment, TSH decreased in all of the cases, factitious thyrotoxicosis developed in % 21 of these cases. Conclusion: In hypothyroid cases, H. pylori gastritis may be responsible for an inadequate response to the treatment. H. pylori eradication in the cases receiving high doses of thyroxine has a risk for thyrotoxicosis.     

Quality by Design Approach: Application of Artificial Intelligence Techniques of Tablets Manufactured by Direct Compression

The publication of the International Conference of Harmonization (ICH) Q8, Q9, and Q10 guidelines paved the way for the standardization of quality after the Food and Drug Administration issued current Good Manufacturing Practices guidelines in 2003. “Quality by Design”, mentioned in the ICH Q8 guideline, offers a better scientific understanding of critical process and product qualities using knowledge obtained during the life cycle of a product. In this scope, the “knowledge space” is a summary of all process knowledge obtained during product development, and the “design space” is the area in which a product can be manufactured within acceptable limits. To create the spaces, artificial neural networks (ANNs) can be used to emphasize the multidimensional interactions of input variables and to closely bind these variables to a design space. This helps guide the experimental design process to include interactions among the input variables, along with modeling and optimization of pharmaceutical formulations. The objective of this study was to develop an integrated multivariate approach to obtain a quality product based on an understanding of the cause–effect relationships between formulation ingredients and product properties with ANNs and genetic programming on the ramipril tablets prepared by the direct compression method. In this study, the data are generated through the systematic application of the design of experiments (DoE) principles and optimization studies using artificial neural networks and neurofuzzy logic programs.KEY WORDS: artificial neural networks (ANNs), gene expression programming (GEP), optimization, quality by design (QbD)     

Electrochemical DNA biosensor for detecting cancer biomarker related to glutathione S-transferase P1 (GSTP1) hypermethylation in real samples

An electrochemical genosensor for the detection of hypermethylation of the glutathione S-transferase P1 (GSTP1) gene, a specific marker of prostate cancer, was reported. This new sensor was used in combination with a single-use carbon graphite working electrode and differential pulse voltammetry, with the results of sample analysis based on the guanine oxidation signals obtained at +1.0 V before and after hybridization between probe and synthetic target or denatured PCR samples. The detected DNA hybridization was also characterized by electrochemical impedance spectroscopy with potassium ferri/ferrocyanide as a redox probe. The protocol consisted of 2 different modes: (i) capture probes selective for methylation-specific and unmethylated GSTP1 sequences were immobilized onto the sensor directly, and hybridization was formed on the electrode surface; (ii) probe/target or probe/noncomplementary target couples were mixed in solution phase, and the transducer was modified through simple adsorption. The limit of detection (S/N=3) was calculated as 2.92 pmol of target sequence in a 100-μl reaction volume. The optimum analytical detection parameters for the biosensor, as well as its future prospects, were also presented.     

S100A1 as a Potential Diagnostic Biomarker for Assessing Cardiotoxicity and Implications for the Chemotherapy of Certain Cancers

This study examined the value of blood marker S100A1 in detecting cardiotoxicity induced by chemotherapy agents; trastuzumab and lapatinib, in normal rat heart. The rats were divided into three groups: control (n = 8, no treatment), T (n = 8, one time ip treatment with 10 mg/kg trastuzumab) and L (n = 8, oral treatment with 100 mg/kg/day lapatinib for 7 days). The activities of oxidative stress parameters Malondialdehyde (MDA), Superoxide dismutase (SOD), Catalase (CAT) and Glutathione (GSH) were measured from the extracted cardiac tissues. The levels of troponinI and S100A1 expressions were measured from blood samples. All biomarkers responded to the treatments as they exhibited alterations from their normative values, validating the chemically induced cardiotoxicity. S100A1 expression attenuated significantly (75%), which made the sensitive detection of cardiotoxicity feasible. Assessment of cardiotoxicity with S100A1 may be a valuable alternative in clinical oncology of cancers in some organs such as breast and prostate, as they do not overexpress it to compete against.     

Antiprotozoal alkaloids from Galanthus trojanus

Two new alkaloid N-oxides, 1-O-acetyldihydromethylpseudolycorine N-oxide, and 11-hydroxyvittatine N-oxide, ten known alkaloids; arolycoricidine, haemanthamine, O-methylnorbelladine, narcidine, dihydrolycorine, 8-O-demethylmaritidine, stylopine and protopine, nicotinic acid and tyramine were isolated from Galanthus trojanus A.P. Davis & N. Özhatay (Amaryllidaceae). The chemical structures of the isolates were elucidated by UV, IR, MS, CD, 1D and 2D NMR experiments. The in vitro antiprotozoal and cytotoxic potentials of the compounds were also evaluated.     

Genetic diversity of local geese of varying productivity and feather color in Kars

The local geese in the transition region between the Caucasus Mountains and Anatolia have economically significant differences in productivity and are identified by four feather colors, white, black, piebald, and yellow. This study was undertaken to determine the genetic structure, evolutionary relationships, and genetic diversity among these birds. DNA samples were obtained from 100 animals, and 50 random primers were screened. Genetic relationships were determined by random amplified polymorphic DNA polymorphisms obtained from a total of 48 loci, showing 40 bands (83.33%) that were polymorphic among all the populations investigated. A dendrogram constructed for this study revealed a close relationship between the white and the black birds. Additionally, the piebald birds showed close similarity to white and black geese, and the yellow birds displayed a clear distance from the other three populations.     

Cisplatin resistance induced by decreased apoptotic activity in non-small-cell lung cancer cell lines

We have investigated defective steps in apoptosis that might account for the development of resistance. For this purpose, A549 and Calu1 NSCLC (non-small-cell lung cancer) cell lines were treated with cisplatin to obtain resistant sub-lines. Gene expression profiles and the phosphorylation status of the BAD (Bcl-2/Bcl-XL-antagonist, causing cell death) protein were determined for each cell line. Cell death and cytochrome c release were analysed after treating cell lines with their appropriate cisplatin doses. Gene expression of BAD, Bid, caspases 4 and 6 were clearly decreased in the resistant cell lines, and the differential phosphorylation status of BAD also seemed to play a role in the development of cisplatin resistance. Since this is a new cisplatin-resistant Calu1 cell line, it is noteworthy that DNA fragmentation, apoptotic cell ratio and cytochrome c levels were most decreased in the CR-Calu1 cell line.