Beyond GnRH, LH and FSH: The role of kisspeptin on hypothalalmic-pituitary gonadal (HPG) axis pathology and diagnostic consideration.

Kisspeptin as a neuropeptide was established initially as regulator for gonadotropin-releasing hormone for pulse frequency and intensity. In the current review, initial search on PubMed was done with key word "Kisspeptin" with further filters to include reviews and trials from the last 10 years. Of the 313 articles shortlisted, 160(51%) dealt with kisspeptin pathology and diagnostic evaluation in various physiological conditions like puberty, while 57(18.2%) dealt with pathological conditions like hypogonadism, 53(17%) infertility, and 43(13.7%) with polycystic ovarian syndrome. This review explored existing data regarding understanding of the negative and positive influences on the kisspeptin hormone-release kinetics. It highlighted the recently identified ligands and pathways which could affect the gonadal steroids, including various metabolic alterations and environmental triggers. Also, the review highlighted the kisspepetin/G-protein coupled receptor-54 interaction which were influenced by neighbouring endocannabinoid system, Gamma aminobutyric acid (GABA)-ergic neuronal outputs and other chemical agents. It was also highlighted that the release of kisspepetin was identified as a group of neurons termed kisspeptin, neurokinin B, and dynorphin, or KNDy, in the arcuate nuclei. The data indicated the use of kisspepetin as a diagnostic marker for precocious puberty, puberty confirmation, hypogonadism, infertility and polycystic ovarian syndrome.

Comparison of various steady state surrogate insulin resistance indices in diagnosing metabolic syndrome.

BACKGROUND: Insulin resistance is core cause of metabolic syndrome. Determining insulin resistance is one of the foremost requirements imperative to understanding the pathophysiology of disease. The gold standard "Euglycaemic clamp test" is cumbersome, long and non-feasible in routine clinical setups to diagnose metabolic syndrome. Various continuous and steady state insulin resistance indices are now available in literature. We plan to evaluate commonly utilized steady state insulin resistance indices directly and Homeostasis Model Assessment for Insulin Resistance (HOMAIR) with added triglyceride (HOMA-TG index). METHODS: The cross-sectional study was carried from Jan-2016 to Dec-2018 at PNS HAFEEZ and department of chemical pathology, AFIP with following objectives: (1) To evaluate steady state insulin resistance markers for diagnosing metabolic syndrome as per IDF defined criteria by ROC curve analysis, (2) to measure Kendal Concordance between various insulin resistance indices and (3) to correlate steady state insulin resistance markers with anthropometric and lipid indices. After several exclusions we selected 224 subjects based upon "non-probability convenience sampling" for inclusion in study. Clinical history, anthropometric measures were calculated and sampling was done for insulin, glucose and other biochemical parameters. Metabolic syndrome was diagnosed as per IDF criteria, while HbA1c was utilized to diagnose diabetes mellitus. Pearson correlation was used to correlate various steady state insulin resistance indices including HOMAIR, HOMA2 index, QUICKI, G/I ratio, HOMA-TG index and serum insulin. AUC was calculated by ROC analysis for all surrogate insulin measures in diagnosis of metabolic syndrome. RESULTS: "HOMA-TG index" has shown the highest AUC for diagnosing metabolic syndrome along with higher correlation with lipid markers and anthropometric indices in comparison to other steady-state insulin resistance markers. Furthermore, QUICKI and G/I ratio showed the lowest AUC for detection of metabolic syndrome. CONCLUSION: "HOMA-TG index" has shown highest AUC for metabolic syndrome diagnosis. However, QUICKI and G/I ration showed the lowest AUC for detection of metabolic syndrome. It is hoped that the potential "HOMA-TG index" may provide better diagnostic efficiency for diagnosing metabolic syndrome.

Genetic polymorphism in ERCC5 and breast cancer risk.

ERCC5 plays crucial role in excision repair DNA damage induced by UV in NER pathway. Single neuleotide polymorphism in ERCC5 were responsible for different cancers. Therefore, current study evaluated the relationship between ERCC5 (rs1047768 T>C) polymorphism and the risk of breast cancer in Pakistani population. The rs1047768 polymorphism was screened among 175 females including one hundred breast cancer cases and age matched seventy-five healthy controls. Genotyping was performed with Tetra amplification-refractory mutation system (ARMS) PCR and products were observed through electrophoresis. Multivariate logistic regression was used to calculate odds ratio (OR) and 95% confidence interval (95% CI) investigating relationship between genotypes, clinical parameters and risk of breast cancer. Statistical analysis exhibited significant relationship between the TC genotype (OR=7.2, 95% CI=1.5-34.3) and increased breast cancer risk. Moreover, family history (OR=6.25; 95% CI= 2.61-15.00) and late menopause (OR=2.41; 95% CI=1.20-4.83) were found to be breast cancer associated risk factors. In conclusion, ERCC5 (rs1047768 T>C) polymorphism may contribute towards increased risk of breast cancer in Pakistani population.