Strong impact of TGF-β1 gene polymorphisms on breast cancer risk in Indian women: a case-control and population-based study

Introduction: TGF-β1 is a multi-functional cytokine that plays an important role in breast carcinogenesis. Critical role of TGF-β1 signaling in breast cancer progression is well documented. Some TGF-β1 polymorphisms influence its expression; however, their impact on breast cancer risk is not clear. Methods: We analyzed 1222 samples in a candidate gene-based genetic association study on two distantly located and ethnically divergent case-control groups of Indian women, followed by a population-based genetic epidemiology study analyzing these polymorphisms in other Indian populations. The c.29C>T (Pro10Leu, rs1982073 or rs1800470) and c.74G>C (Arg25Pro, rs1800471) polymorphisms in the TGF-β1 gene were analyzed using direct DNA sequencing, and peripheral level of TGF-β1 were measured by ELISA. Results: c.29C>T substitution increased breast cancer risk, irrespective of ethnicity and menopausal status. On the other hand, c.74G>C substitution reduced breast cancer risk significantly in the north Indian group (p  =  0.0005) and only in the pre-menopausal women. The protective effect of c.74G>C polymorphism may be ethnicity-specific, as no association was seen in south Indian group. The polymorphic status of c.29C>T was comparable among Indo-Europeans, Dravidians and Tibeto-Burmans. Interestingly, we found that Tibeto-Burmans lack polymorphism at c.74G>C locus as true for the Chinese populations. However, the Brahmins of Nepal (Indo-Europeans) showed polymorphism in 2.08% of alleles. Mean TGF-β1 was significantly elevated in patients in comparison to controls (p<0.001). Conclusion: c.29C>T and c.74G>C polymorphisms in the TGF-β1 gene significantly affect breast cancer risk, which correlates with elevated TGF-β1 level in the patients. The c.29C>T locus is polymorphic across ethnically different populations, but c.74G>C locus is monomorphic in Tibeto-Burmans and polymorphic in other Indian populations

Successful management of pleural lipoma by video-assisted thoracoscopic surgery

Pleural lipoma is an extremely rare clinical entity. Symptomatic pleural lipoma is rarer. We report a case of symptomatic pleural lipoma which was successfully managed by video-assisted thoracoscopic surgery (VATS). A brief review of relevant literature has been included in the article

Helicobacter pylori in dyspepsia: Phenotypic and genotypic methods of diagnosis

Background: Helicobacter pylori affects almost half of the world's population and therefore is one of the most frequent and persistent bacterial infections worldwide. H. pylori is associated with chronic gastritis, ulcer disease (gastric and duodenal), mucosa-associated lymphoid tissue lymphoma, and gastric cancer. Several diagnostic methods exist to detect infection and the option of one method or another depends on various genes, such as availability, advantages and disadvantages of each method, monetary value, and the age of patients. Materials and Methods: Patients with complaints of abdominal pain, discomfort, acidity, and loss of appetite were chosen for endoscopy, detailed history was contained, and a physical examination was conducted before endoscopy. Biopsies (antrum + body) were received from each patient and subjected to rapid urease test (RUT), histopathological examination (HPE), polymerase chain reaction (PCR), and culture. Results: Of the total 223 biopsy specimens obtained from dyspeptic patients, 122 (54.7%) were positive for H. pylori for HPE, 109 (48.9%) by RUT, 65 (29.1%) by culture, and 117 (52.5%) by PCR. The specificity and sensitivity were as follows: RUT (99% and 88.5%), phosphoglucosamine mutase PCR assay (100% and 95.9%), and culture (100% and 53.3%), respectively. Conclusion: In this study, we compared the various diagnostic methods used to identify H. pylori infection indicating that, in comparison with histology as gold standard for detection of H. pylori infection, culture and PCR showed 100% specificity whereas RUT and PCR showed 99% and 100% sensitivity, respectively

ANTIMICROBIAL ACTIVITY OF ANISOCHILUS CARNOSUS (L.F.) WALL AGAINST THE HUMAN GASTRIC PATHOGEN HELICOBACTER PYLORI

  Objective: The prevalence of Helicobacter pylori in India is high, and majority leads to severe gastrointestinal infections. Existing treatment regimens for H. pylori infections have increased failure rates and adverse side effects that desire the search for an effective substitute therapy. Anisochilus carnosus (L.f.) wall (Lamiaceae), a herb which grows once in a year at high elevation is used widely in traditional treatment for the complaints of gastric ulcer and skin diseases. The present study was performed to assess the antibacterial activity of A. carnosus (L.f.) wall, against clinical isolates of H. pylori in vitro.Methods: A. carnosus leaves were collected-dried and extracted with water and ethanol by cold maceration with ethanol by soxhlet method. The minimum inhibitory concentration (MIC) of extracts was made and tested against 32 clinical and 1 reference strains of H. pylori. Results: A. carnosus (L.f.) wall inhibited the growth of most of the clinical H. pylori strains. The MIC of A. carnosus (L.f.) wall extracted by cold maceration (aqueous and ethanol) and Soxhlet apparatus (ethanol) ranged from 500 to 62.5 μg/ml, and the majority of the clinical H. pylori strains were inhibited at the MIC of 500 μg/ml of aqueous, ethanol, and Soxhlet ethanol extraction were 63.63%, 43.75%, and 71.87%, respectively.Conclusion: A. carnosus (L.f.) wall is an efficient inhibitor of H. pylori growth in vitro. A. carnosus (L.f.) wall revealed enormous therapeutic potential to H. pylori infection as it was extremely active in the suppression of H. pylori. Hence, it can be taken as a potential agent against several H. pylori linked gastric pathogenic progressions

Characteristics of microbial drug resistance and its correlates in chronic diabetic foot ulcer infections

Free to read While virulence factors and the biofilm-forming capabilities of microbes are the key regulators of the wound healing process, the host immune response may also contribute in the events following wound closure or exacerbation of non-closure. We examined samples from diabetic and non-diabetic foot ulcers/wounds for microbial association and tested the microbes for their antibiotic susceptibility and ability to produce biofilms. A total of 1074 bacterial strains were obtained with staphylococci, Pseudomonas, Citrobacter and enterococci as major colonizers in diabetic samples. Though non-diabetic samples had a similar assemblage, the frequency of occurrence of different groups of bacteria was different. Gram-negative bacteria were found to be more prevalent in the diabetic wound environment while Gram-positive bacteria were predominant in non-diabetic ulcers. A higher frequency of monomicrobial infection was observed in samples from non-diabetic individuals when compared to samples from diabetic patients. The prevalence of different groups of bacteria varied when the samples were stratified according to age and sex of the individuals. Several multidrug-resistant strains were observed among the samples tested and most of these strains produced moderate to high levels of biofilms. The weakened immune response in diabetic individuals and synergism among pathogenic micro-organisms may be the critical factors that determine the delicate balance of the wound healing process

SRD5A2 gene polymorphisms affect the risk of breast cancer

Androgens in breast cancer have been studied alone and in correlation with estrogens as estrogen to testosterone ratio. 5-α-reductase is one of the important enzymes participating in androgen metabolism, which affects androgen activity by affecting conversion of testosterone to dihydrotestosterone. We hypothesized that polymorphisms in the SRD5A2 gene (encoding 5-α-reductase) may affect breast cancer risk by affecting total androgen activity. Complete coding region of the SRD5A2 gene was sequenced in a group of 628 patients and 244 control samples from three southern states (Tamil Nadu, Andhra Pradesh and Karnataka) of India. We observed three common polymorphisms in this gene; namely, A49T, V89L and (TA)n repeats. A49T locus was monomorphic in the study population, but V89L showed a strong correlation with breast cancer (P = 0.03, OR = 1.40, CI = 1.02–1.91). (TA)0/(TA)9 and (TA)9/(TA)9 genotypes were at a lower risk of breast cancer (P = 0.01, OR = 0.64, CI = 0.46–0.90). We conclude that SRD5A2 genotypes significantly affect breast cancer risk in the South Indian populations

A mitochondrial DNA variant 10398G>A in breast cancer among south Indians: an original study with meta-analysis

The m.10398G > A polymorphism in the MT-ND3 gene has been linked to the manifestation of several neurodegenerative disorders and cancers. Several research groups have analyzed the association between m.10398G > A polymorphism and breast cancer; however, the results do not follow a consensus. We have studied this polymorphism in three Dravidian populations from South India. Analysis on 716 cases and 724 controls found no association between m.10398G > A polymorphism and breast cancer [OR = 0.916 (0.743–1.128); P = 0.409]. Menopausal stratification also revealed no significant association in either pre-menopausal or post-menopausal breast cancer groups. In addition, we undertook a meta-analysis on 16 study groups, comprising a total of 7202 cases and 7490 controls. The pooled odds ratio suggested no significant association of m.10398G > A substitution with breast cancer [OR = 1.016 (0.85–1.22); P = 0.86]. In conclusion, there is no evidence of association between m.10398G > A polymorphism and breast cancer risk among South Indian women. Meta-analysis suggested no overall correlation between this polymorphism and breast cancer risk