Genetic variants in IL-6 and IL-10 genes and susceptibility to hepatocellular carcinoma in HCV infected patients.

BACKGROUND: Hepatitis C virus (HCV) infection is the major cause of hepatocellular carcinoma (HCC), a common primary liver malignancy, and the third leading cause of cancer-related death. The HCC risk increases with the severity of liver inflammation, and the clinical course of HCV infection depends on a balance between pro- and anti-inflammatory cytokines. The former includes interleukin (IL)-6, while the latter includes IL-10. However, the exact pathogenic mechanisms underlying IL-6 and IL-10 effects remain unclear. METHODS: The present study evaluated 174 chronic HCV Tunisian patients. Polymorphisms of IL-6 (rs1880242, rs1474847, rs2069840, rs1800797, rs1800796, rs2069845, rs2069827, rs1474348, rs1800795), and IL-10 (rs1800896, rs1800871, rs1800872, rs1554286, rs1878672, rs1518111) were determined by real-time PCR. RESULTS: Notable differences between chronic HCV-infected patients and HCC patients were observed for the three IL-10 SNPs; rs1800871 (-819T/C), rs1800872 (-592A/C), and rs1878672. Carriage of IL-6 rs1800796 G/G genotype, IL-6 rs1474358 C-allele, and IL-6 rs1800797 A-allele was more frequent in chronic HCV-infected patients than in HCC patients. On the other hand, IL-6 rs1474358 GG genotype had a favourable factor for HCC establishment. CONCLUSION: IL-10 and IL-6 SNPs markedly influence the clinical outcomes of HCV infection. These SNPs could be used as biomarkers for early detection and molecular therapy for preventing HCC, and prognostic factors for predicting the clinical outcomes of HCC.

Evaluation of the national tuberculosis surveillance system in Afghanistan.

Afghanistan has 2 tuberculosis surveillance systems, the National Tuberculosis Control Programme (NTP) and the Health Management Information System (HMIS). An evaluation of these surveillance systems in January/ February 2010 was done to identify their strengths and weaknesses and to formulate recommendations. Attributes of the programmes were evaluated using US Centers for Disease Control and Prevention guidelines. Usefulness and flexibility of the NTP system were good; stability, representativeness and data quality were average. Simplicity, acceptability and timeliness were poor. Reporting delays regularly exceeded 3 months. Positive predictive value and sensitivity were 11% and 70% respectively. The HMIS system was simple, acceptable and stable, with timely reporting. Reporting and feedback were good, as this system has strong government support. Flexibility, data quality and representativeness were average. Positive predictive value and sensitivity were 10% and 68% respectively. No outbreaks were detected by ther system. The NTP and HMIS surveillance systems are duplicative and neither covers the private sector.

Evaluation of national tuberculosis surveillance system in Afghanistan

Aighanistan has 2 tuberculosis surveillance systems/ the Natiohal Tuberculosis Control Programme [NTP] and the Health Management Information System [HMIS]. An evaluation of these surveillance systems in January/February 2010 was done to identify their strengths and weaknesses and to formulate recommendations. Attributes of the programmes were evaluated using US Centers for Disease Control and Prevention guidelines. Usefulness and flexibility of the NTP system were good; stability, representativeness and data quality were average. Simplicity, acceptability and timeliness were poor. Reporting delays regularly exceeded 3 months. Positive predictive value and sensitivity were 11% and 70% respectively. The HMIS system was simple, acceptable and stable, with timely reporting. Reporting and feedback were good, as this system has strong government support. Flexibility, data quality and representativeness were average. Positive predictive value and sensitivity were 10% and 68% respectively. No outbreaks were detected by either system. The NTP and HMIS surveillance systems are duplicative and neither covers the private sector

Photochemical interaction of ascorbic acid with riboflavin, nicotinamide and alpha-tocopherol in cream formulations.

The present work is based on a study of the effect of some vitamins such as riboflavin (RF), nicotinamide (NA) and alpha-tocopherol (TP) on the photodegradation of ascorbic acid (vitamin C) (AH2) in oil-in-water cream formulations using a UV irradiation source. A UV spectrophotometric and the official iodimetric methods have been used for the assay of AH2 in cream formulations. These methods have been validated in the presence of RF, NA and TP before their application to the creams. The recoveries of AH2 in the creams are in the range of 90-95% and the reproducibility of the method is within ±5%. The apparent first-order rate constants (k(obs) ) for the photodegradation of AH2 in the presence of RF, NA and TP, individually, in the creams have been obtained. The second-order rate constants for the photochemical interaction of AH2 and the vitamins RF, NA and TP have been determined from the plots of k(obs) for AH2 photolysis versus the individual vitamin concentration along with the values of k0 from the intercept on the vertical axis. The values of k0 in the presence of RF and NA are lower than those of the k(obs) , indicating that these vitamins act as photosensitizers for the degradation of AH2 in creams. On the contrary, the value of k0 in the presence of TP is higher than that of the k(obs) , suggesting a stabilizing effect of this vitamin on the degradation of AH2 in creams. The mode of interaction of the individual vitamins with AH2 on photolysis has been discussed.

Effect of peripheral kisspeptin administration on adiponectin, leptin, and resistin secretion under fed and fasting conditions in the adult male rhesus monkey (Macaca mulatta).

In the last few years, kisspeptin-KISS1R signaling has appeared as a major regulator of the reproductive function in several vertebrate species. However, KISS1(encoding kisspeptin) and its putative receptor, KISS1R, are expressed in several other tissues. Adipose tissue, which secretes many peptides with diverse functions in normal physiology, expresses KISS1, which is modulated by gonadal steroids as well as by body nutritional status. Similarly, KISS1Rexpression is also found in adipose tissue, but the local role of kisspeptin in adipocyte function is currently unknown. Therefore, in the present study the effects of exogenous human kisspeptin-10 (KP10) were studied on three important adipokines, namely, adiponectin, leptin, and resistin in a set of four chair-restraint habituated intact adult male rhesus monkeys under; 1) normal fed conditions, 2) 24-h fasting conditions, and 3) 48-h fasting conditions. Plasma resistin and leptin levels decreased (p<0.01), whereas adiponectin levels increased (p<0.05) in fasted monkeys. Kisspeptin administration significantly increased (p<0.05) mean plasma adiponectin levels under fed and 24-h fasting conditions as compared to pretreatment or vehicle-treatment levels. A stimulatory effect was also observed on the 48-h fasting stimulated plasma adiponectin levels, but it lacked statistical significance. In contrast, no effect of kisspeptin was observed on mean plasma leptin and resistin levels. Thus, the present study demonstrated a stimulatory effect of peripheral kisspeptin administration on the plasma adiponectin levels under fed and 24-h fasting conditions in the adult male rhesus monkey. These findings, therefore, assign a novel role to kisspeptin, a regulator of adipocyte function in higher primate.

Monitoring powder blending in pharmaceutical processes by use of near infrared spectroscopy.

Obtaining completely uniform distribution of the active principle and excipients in a pharmaceutical preparation is essential with a view to ensuring correct dosage. Uniformity in pharmaceutical formulations has usually been controlled by collecting samples at different stages of the process in order to determine the active principle using a chromatographic or UV-Visible spectroscopic method. In this work, near infrared reflectance spectroscopy (NIRS) was used to monitor blending in order to ensure uniformity in a mixture consisting of three typical pharmaceutical excipients and one active principle. To this end, a method for calculating the Mean Square of Differences between two consecutive spectra was developed with a view to expeditiously identifying the time mixture homogeneity was attained. The performance of the proposed method was compared with that of two others routinely employed to monitor blending by use of the NIRS technique and the results were found to be quite consistent.

Human genome project: pharmacogenomics and drug development.

Now that all 30,000 or so genes that make up the human genome have been deciphered, pharmaceutical industries are emerging to capitalize the custom based drug treatment. Understanding human genetic variation promises to have a great impact on our ability to uncover the cause of individual variation in response to therapeutics. The study of association between genetics and drug response is called pharmacogenomics. The potential implication of genomics and pharmacogenomics in clinical research and clinical medicine is that disease could be treated according to the interindividual differences in drug disposition and effects, thereby enhancing the drug discovery and providing a stronger scientific basis of each patient's genetic constitution. Sequence information derived from the genomes of many individuals is leading to the rapid discovery of single nucleotide polymorphisms or SNPs. Detection of these human polymorphisms will fuel the discipline of pharmacogenomics by developing more personalized drug therapies. A greater understanding of the way in which individuals with a particular genotype respond to a drug allows manufacturers to identify population subgroups that will benefit most from a particular drug. The increasing emphasis on pharmacogenomics is likely to raise ethical and legal questions regarding, among other things, the design of research studies, the construction of clinical trials and the pricing of drugs.