Modulation of mRNA Expression of IL-6 and mTORC1 and Efficacy and Feasibility of an Integrated Approach Encompassing Cognitive Behavioral Therapy Along with Pregabalin for Management of Neuropathic Pain in Postherpetic Neuralgia: A Pilot Study.

OBJECTIVE: This study was designed to explore the efficacy and feasibility of cognitive behavioral therapy (CBT) along with pregabalin and compare it with pregabalin monotherapy for the management of neuropathic pain in post-herpetic neuralgia (PHN) patients and to explore the modulation of messenger RNA (mRNA) expression of interleukin (IL)-6 and mammalian target of rapamycin-1 (mTORC1) genes in these patients. DESIGN: Randomized controlled pilot study. METHODS: The patients aged >18 years of age with an established diagnosis of PHN with evident allodynia and hyperalgesia who had pain for at least 3 months after healing of rash with pain intensity ≥4/10 on NRS-Pain Scale were enrolled. The trial was registered with the Clinical Trials Registry-India (CTRI/2019/03/018014). A detailed baseline assessment regarding type and duration of pain and disability using pain-relevant self-report questionnaires was done. Two mL venous blood samples were collected for gene expression studies at base line and at end of 12 weeks of treatment. Patients were randomized into one of the two groups. Group PR received pregabalin and Group CP received CBT along with pregabalin. The pain intensity was measured using numeric rating scale (NRS)-Pain scale, neuropathic component of the pain by using Neuropathic Pain Symptom Inventory (NPSI) and Pain Detect Questionnaire (PDQ), sleep interference by NRS-Sleep, pain-related catastrophic thoughts by using Pain Catastrophizing Scale (PCS), depression and quality of life using Beck Depression Inventory-II (BDI-II) and Short Form-12 (SF-12), respectively. The research funding was supported by the intramural grant from the institution. RESULTS: A total of 40 patients with 20 in each group were included. Following integrated approach encompassing CBT and Pregabalin, group CP had significant downregulation of mRNA expression of IL-6; however, no such correlation was observed with mTOR expression. A significant decline in the intensity of pain, NPSI scoring for burning, allodynia, and pain-related catastrophizing were observed; also a significant improvement in depressive symptoms and quality of life were observed with the use of CBT. CONCLUSIONS: A significant downregulation of mRNA expression of IL-6 was observed; however, no significant correlation was observed between NRS pain score and ΔCt values of mRNA expression of both mTORC1 gene and IL-6 gene at baseline and at the end of 12th week. In addition, we note a significant decrease in pain intensity, depressive symptoms, and pain-related catastrophizing while improving QOL was observed with the use of CBT as a clinical adjunct along with pregabalin in PHN patients.

Down Regulation of KAI1/CD82 in Lymph Node Positive and Advanced T-Stage Group in Breast Cancer Patients.

BACKGROUND: Metastasis represents a deadly aspect of any cancer including breast cancer, given its high prevalence; treatment of metastatic breast cancer remains a clinically unmet need, which necessitates the exploration of metastasis suppressor genes (MSGs). KAI-1/CD82 is an important member of MSGs; the role of KAI1 has been well explored in prostate cancer, however its role in breast cancer is not fully explored and in fact the results of breast cancer studies are contentious. Thus, the present study aimed to investigate expression of KAI1 at both transcriptional and translational levels in the tissue of breast cancer patients and benign breast disease. Further, we analysed the relationship between expression levels of KAI1 and clinicopathological parameters in breast cancer patients. MATERIALS AND METHODS: mRNA expression was studied by Real time PCR and protein expression was analyzed by both Western blot and Immunohistochemistry. RESULTS: The results of the study indicate that KAI1 expression was remarkably decreased in breast cancer both at the gene and the protein levels (P < 0.05) compared to benign breast disease. In addition, KAI1 expression levels were strongly associated with axillary lymph node status and advanced T stage (p < 0.05), however no association was found with tumor grade, age, menopausal status and receptor status like ER, PR and Her2. CONCLUSION: Low expression of KAI1 might be helpful for predicting the lymph node metastasis and T staging, thus predicts malignant prognosis of breast cancer.
.

Effect of Environmental Exposure and Pharmacogenomics on Drug Metabolism.

BACKGROUND: Pesticides are major xenobiotic compounds and environmental pollutants, which are able to alter drug-metabolizing enzyme as well as pharmacokinetics of drugs. Subsequent to the release of the human genome project, genetic variations (polymorphism) become an integral part of drug development due to their influence on disease susceptibility/ progression of the disease and their impact on drug absorption, distribution, metabolism of active metabolites and finally excretion of the drug. Genetic polymorphisms crucially regulate pharmacokinetics and pharmacodynamics of drugs under the influence of physiological condition, lifestyle, as well as pathological conditions collectively. OBJECTIVE: To review all the evidence concerning the effect of environmental exposure on drug metabolism with reference to pharmacogenomics. METHODS: Scientific data search and review of basic, epidemiological, pharmacogenomics and pharmacokinetics studies were undertaken to evaluate the influence of environmental contaminants on drug metabolism. RESULTS: Various environmental contaminants like pesticides effectively alter drug metabolism at various levels under the influence of pharmacogenomics, which interferes with pharmacokinetics of drug metabolism. Genetic polymorphism of phase I and phase II xenobiotic-metabolizing enzymes remarkably alters disease susceptibility as well as the progression of disease under the influence of various environmental contaminants at various levels. CONCLUSION: Individual specific drug response may be attributed to a large variety of factors alone or in combination ranging from genetic variations (SNP, insertion, deletion, duplication etc.) to physiological setting (gender, age, body size, and ethnicity), environmental or lifestyle factors (radiation exposure, smoking, alcohol, nutrition, exposure to toxins, etc.); and pathological conditions (obesity, diabetes, liver and renal function).