Human Papillomavirus Infections in Pregnant Women and Its Impact on Pregnancy Outcomes: Possible Mechanism of Self-Clearance

Young women are at the maximum risk of Human papillomavirus (HPV) infection which are asymptomatic in a majority of cases and spontaneously get cleared. Women in the age between 20 and 35 years are more active sexually and especially in the developing nations, this age group forms a major cohort among the population of pregnant women. The changed hormonal milieu and immune response during pregnancy might favor presence or persistence of HPV infection, while at the same time natural clearance also takes place during pregnancy with an unknown mechanism. Various HPVs have been reported to be associated with preterm rupture of membranes (PROM), fetal growth restriction (FGR), preeclampsia, placental abnormalities and preterm delivery in several populations. The risk factors involved in the intrauterine environment affects fetal development and thus increase the development risk of specific diseases in adult life as per the hypothesis of the fetal origins of adult disease (FOAD). The structural and molecular changes in the feto-maternal interface support and protect the semiallogeneic fetus from immune-mediated or inflammatory injury. On the other hand, the trophoblast cells of placenta facilitate the replication of HPV and the affliction of placenta and the vaginal infection can directly be associated with pregnancy outcomes. So, to optimize better child health care and reproductive outcomes, HPV screening might help during pregnancy. It is therefore important to understand how the HPV is affecting the early pregnancy and immune cells within the feto-maternal interface are educated for self-clearance to fulfill their biological functions or prevalence to affect the pregnancy outcomes and how the persistence of HR-HPV infection overtime increases the development of cervical cancer risk

ASSESSMENT OF CYP2D6*10 POLYMORPHISM WITH POST HERPETIC NEURALGIA PATIENTS UNDERGOING TRAMADOL TREATMENT

objective: To evaluate association of CYP2D6*10 polymorphism with respect to demographic characteristics (age at onset, genders and weight), numerical rating scale (NRS) for measuring pain intensity in relation with resting and movement associated pain and adverse drug effects of PHN patients receiving tramadol therapy. Methods: Total 246 patients of PHN (148 males and 98 females) were selected who fulfilled the inclusion/exclusion criteria. Clinicians were recorded numerical rating scores (at rest and with movement), and note down adverse drug side effects during the time of study. All samples were analyzed for CYP2D6*10 polymorphism using PCR-RFLP method. results: We observed genotype distribution of CYP2D6* 10 did not vary significantly with age at onset [non-responders (p=0.317) and responders (p=0.260)], genders[ non-responders (p=0.317) and responders (p=0.949)], and weight [non-responders (p=0.298) and responders (p=0.279)] and also did not find significant role with respect to resting (p=0.428) and movement associated type of pain (p=0.178). In addition, CYP2D6*10 was not associated with adverse effects such as somnolence (p=0.135), dizziness (p=0.178), local site reactions (p=0.535), headache (p=0.502), hypotension (p=0.567) and nausea and vomiting (p=0.268) of analgesic therapy. Therefore we conclude that, CYP2D6*10 may not be a predictor of treatment outcomes of patients with PHN receiving tramadol

HPV & HPV vaccination: issues in developing countries

Cervical cancer is the second-most common cancer in women worldwide causing most cancer related deaths in women in developing countries including India. The most predominant etiological factor for cervical cancer is persistent infection of certain high-risk types of human papillomaviruses (HR-HPVs), while low-risk types are associated with benign cervical lesions and genital warts. In India, the most common (98%) oncogenic types are HPV types 16 and 18 with HPV 16 exclusively (80-90%) prevalent. Two recently developed virus-like particle (VLP) based prophylactic HPV vaccines, quadrivalent Gardasil (HPV 16/18/6/11) and Cervarix (HPV 16/18) offer great promise. Several other therapeutic vaccines are also in clinical trials and are yet to establish their efficacy. The use of already developed VLP vaccines in resource-poor regions is limited by several factors, most importantly the high cost of the vaccine. Therefore efforts are being made in India to develop cost-effective second-generation vaccines. Besides cost, there are several socio-cultural and ethical issues involved with the implementation of already developed vaccines including the acceptability of HPV vaccination by preadolescent girls and their parents in India

Prospects and prejudices of human papillomavirus vaccines in India

Cervical cancer is the most common cancer and a leading cause of cancer deaths among women in developing countries. The disease is caused due to persistent infection of one or more of about 15 high-risk human papillomaviruses (HR-HPVs), most commonly by HPV types 16/18. In India, over 98% of cervical cancer cases harbor HPV infection and HPV 16 is the type exclusively (80-90%) prevalent. Unlike the West, HPV infection is most common in women in their third decade (26-35 years) of sexual activity and invasive cancer also arises much later with a peak at about 45-55 years of age. Recently, two successful prophylactic HPV vaccines, a quadrivalent (HPV16/18/6/11) 'Gardasil' by Merck and a bivalent (HPV16/18) 'Cervarix' by GSK have been developed. Several other approaches including plant-based edible, pentameric capsomere-based intranasal and DNA-based vaccines have also been employed to develop prophylactic vaccines. Also, several therapeutic vaccines either protein/peptide based or DNA based are in clinical trials but are yet to establish their efficacy. Though there are several issues regarding implementation of the already developed vaccines in resource limited countries, efforts are being made to develop cost-effective second-generation vaccines. If cost minimized, HPV related new technologies involved in screening tests and vaccines are expected to reduce incidence of cervical cancer and deaths it causes in women from developing countries

THE IMPACT OF PHARMACOGENETICS ON ADVERSE DRUG REACTIONS TO PREDICT THE EFFICACY OF TRAMADOL MONOTHERAPY FOR THE TREATMENT OF POST HERPETIC NEURALGIA PATIENTS

Objective: To evaluate the potential role of tramadol treatment with respect to CYP2D6 polymorphism in reducing the incidence of adverse drug reactions.Methods: The study comprised 246 patients of PHN receiving tramadol treatment. Adverse drug events during the time of the study were recorded by the physician. All samples were analyzed for CYP2D6 (*2, *4 and *10) polymorphism using PCR-RFLP method.Results: The CYP2D6 polymorphism did not find significantly among onset at age, genders and weight in non-responders and responders. The CYP2D6*4 polymorphism was significantly associated with somnolence (p=0.009), dizziness (p=0.007), local site reactions (p=0.015), headache (p=0. 039), and nausea and vomiting (p=0. 017). The dizziness (p=0. 029) and headache (p=0. 004) were found associated with CYP2D6*2 both the groups. No associations were observed between adverse events compared with CYP2D6*2 and CYP2D6*10 polymorphisms (p>0.05).Conclusion: CYP2D6*4 polymorphism may be as important drug toxicity marker predictors of experiencing adverse drug reactions as PHN patients undergoing tramadol treatment. Â

Association analysis of p16 (CDKN2A) and RB1 polymorphisms with susceptibility to cervical cancer in Indian population

The potent tumor suppressors P16 and RB1 are the key regulators of cell cycle machinery in eukaryotes. Polymorphisms in these genes play an important role in the outcome of various diseases including cancer. In the present study, we evaluated the association of p16 and RB1 polymorphisms with cervical cancer susceptibility in Indian population. We screened 150 histologically confirmed cervical cancer cases along with equal number of healthy controls with normal cervical cytology. PCR-RFLP method was employed for genotyping of SNPs in p16 C540G (rs11515), C580T (rs3088440) in the 3'-UTR of exon 3 and RB1 A153104G (rs4151580) located in the intron 18 and confirmed by direct sequencing. Both patients and controls were screened for HPV infection. In this case-control study 84.67% (127/150) of cases were found to be positive for HPV DNA sequence. Women carrying p16 C540G carrier genotypes 540 (CG/GG) may have protective effect for the development of cervical cancer (P = 0.0001, OR = 0.31, 95% CI = 0.17-0.56). And SNP at C580T of p16 gene was found to be negatively associated with the risk of cervical cancer (P = 0.0004, OR = 0.04, 95% CI = 0.002-0.63). p16 (540C/580T) has emerged as a major risk haplotype (P = 0.033, OR = 1.47, 95% CI = 1.05-2.07) whereas p16 (540G/580T) as a chief protective haplotype (P = 0.014, OR = 0.39, 95% CI = 0.18-0.83) for the development of cervical cancer among Indian women. Contrary to this, SNP at A153104G of RB1 gene showed statistically significant association (P = 0.035, OR = 1.69, 95% CI = 1.06-2.68) with increased susceptibility for the development of cervical cancer. Our results suggest that single nucleotide polymorphisms in p16, RB1 genes may affect the susceptibility to cervical cancer collectively

Perception of human papillomavirus infection, cervical cancer and HPV vaccination in North Indian population.

Human Papillomavirus (HPV) -associated cervical cancer is the second-most common cancer in women worldwide but it is the most frequent gynaecological cancer and cancer associated death in India women. The objective of this study was to assess knowledge about cervical cancer, HPV, HPV vaccine, HPV vaccine acceptance among school and undergraduates students and their parent's perception about acceptance of HPV vaccine in Northern part of India (Delhi and NCR regions).A qualitative questionnaire based survey among 2500 urban/rural students aged 12-22 years was conducted.Overall, a low frequency (15%) of HPV and cervical cancer awareness was observed in students and their parents. However, the awareness was much higher in females belonging to urban setup compared to boys with a perception that HPV causes cervical cancer in women only. Additionally, only (13%) participants who were aware of cervical cancer and HPV) were willing to accept HPV vaccination. Apparently, parents of female students were two times more willing to accept HPV vaccination for their ward than male students (p<0.001; OR 95%CI = 2.09 (1.58-2.76).Cervical cancer and HPV awareness among school, undergraduate students and also to their parents was found to be very low in this part of India. The level of awareness and education appears to be insignificant determinants in rural compared to urban setup. Better health education will be needed to maximize public awareness for cervical cancer prevention

Association of single nucleotide polymorphisms (SNPs) in TNF-LTA locus with breast cancer risk in Indian population

Purpose Cytokine milieu of tumor microenvironment affects tumorigenesis in breast cancer. The aim of the present study was to investigate the potential association of functional single nucleotide polymorphisms (SNPs) in TNF-LTA locus with breast cancer. Methods The study included 127 individuals comprising 40 breast cancer cases (35 sporadic &amp; 5 familial) and 87 individuals of high risk group (with family history of breast cancer) along with 150 healthy controls. PCR-RFLP was employed to analyze TNFA promoter polymorphisms at -238 G/A, -308 G/A, -857 C/T, -863 C/A and -1031 T/C along with +252 A/G SNP in LTA. The results were further confirmed by direct sequencing. Results Significant association was established for TNFA -308 G/A and LTA +252 A/G polymorphisms with breast cancer versus controls (P &lt; 0.0001; OR, 9.53; 95% CI, 4.11-22.13; P c &lt; 0.001) and high risk group versus controls (P &lt; 0.0001; OR, 8.27; 95% CI, 4.28-16.0; P c &lt; 0.001) respectively. GGACCT haplotype was found to be positively associated with breast cancer (P &lt; 0.0001; OR, 12.17; 95% CI = 5.12-28.92; P c &lt; 0.001) and high risk group (P, 0.03; OR, 2.95; 95% CI, 1.20-7.26; P c, 0.005) in relation to controls. While GGGCCT haplotype was significantly related with high risk group in comparison to cancer (P, 0.0002; OR, 5.71; 95% CI, 2.18-14.99; P c, 0.003) and controls (P, 0.0002; OR, 2.48; 95% CI, 1.55-3.96; P c, 0.003). Conclusion TNF-LTA locus could serve as an important biomarker for breast cancer predisposition in Indian population

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Not AvailableThe functional activity among STAT3 and PIM1, are key signaling events for cancer cell function. Curcumin, a diarylheptanoid isolated from turmeric, effectively inhibits STAT3 signaling. Selectively, we attempted to address interactions of STAT3, PIM1 and Curcumin for therapeutic intervention using in silico and in vitro experimental approaches. Firstly, protein-protein interactions (PPI) between STAT3-PIM1 by molecular docking studies reflected salt bridges among Arg279 (STAT3)-Glu140 (PIM1) and Arg282 (STAT3)-Asp100 (PIM1), with a binding affinity of − 38.6 kcal/mol. Secondly, molecular dynamics simulations of heterodimeric STAT3-PIM1 complex with curcumin revealed binding of curcumin on PIM-1 interface of the complex through hydrogen bonds (Asp155) and hydrophobic interactions (Leu13, Phe18, Val21, etc.) with a binding energy of − 7.3 kcal/ mol. These PPIs were confirmed in vitro by immunoprecipitation assays in MDA-MB-231 cells. Corroborating our results, expression levels of STAT3 and PIM1 decreased after curcumin treatment. We observed that PIM1 in teracts with STAT3 and these functional interactions are disrupted by curcumin. The calculated band energy gap of heterodimeric STAT3-PIM1-Curcumin complex was of 9.621 kcal/mol. The present study revealed the role of curcumin in STAT3/PIM1 signaling and its binding affinity to the complex for design of advanced cancer therapeutics.Not Availabl