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1.
Front Oncol ; 14: 1410819, 2024.
Article in English | MEDLINE | ID: mdl-38817898

ABSTRACT

The risk of developing subsequent breast cancer is higher in women diagnosed with benign breast disease (BBD) but these studies were primarily performed in non-Hispanic white populations. Still, these estimates have been used to inform breast cancer risk models that are being used clinically across all racial and ethnic groups. Given the high breast cancer mortality rates among African American (AA) women, it is critical to study BBD in this population, to ensure the risk models that include this information perform adequately. This study utilized data from AA women who underwent benign breast biopsies at a hospital served by the University Pathology Group in Detroit, Michigan, from 1998 to 2010. Patients were followed for subsequent breast cancers through the population-based Metropolitan Detroit Cancer Surveillance System (MDCSS). BBD lesion scores were assigned to represent the severity or extent of benign breast lesions, with higher scores indicating a greater number of distinct lesion types. Of 3,461 eligible AA women with BBD in the cohort, 6.88% (n=238) subsequently developed breast cancer. Examined individually, six of the eleven lesions (apocrine metaplasia, ductal hyperplasia, lobular hyperplasia, intraductal papilloma, sclerosing adenosis, columnar alterations and radial scars) were significantly associated with increased risk of breast cancer after adjustment for age and year of biopsy and were further considered in multiple lesion models. For every different type of benign breast lesion, subsequent risk of breast cancer increased by 25% (RR=1.25, 95% CI: 1.10, 1.42) after adjustment for age at biopsy and proliferative versus non-proliferative disease. In summary, this study affirms the increased breast cancer risk in AA women with BBD, particularly in those with multiple lesions. These findings have implications for the management of breast cancer risk in millions of women affected by BBD, a high risk group that could benefit from personalized surveillance and risk reduction strategies.

2.
J Community Health ; 2024 Jan 29.
Article in English | MEDLINE | ID: mdl-38286964

ABSTRACT

Deaths from liver cancer are on the rise and disproportionately affect minority racial/ethnic groups. In this study, we examined associations between physicians' recommendations for hepatitis B virus (HBV) and hepatitis C virus (HCV) screening and sociodemographic and lifestyle factors among minority populations in the areas of Greater Philadelphia and New York City. Using Poisson regression with robust variance estimation, we evaluated potential associations for 576 Hispanic American (HA), African American (AA), and Asian Pacific American (APA) adults, using blood tests as an outcome measure, with adjustment for sociodemographic factors We found that APAs (34.2%) were most likely to have a physician recommend HBV and HCV screening tests (34.2% and 27.1%, respectively), while HAs were least likely to receive an HBV recommendation (15.0%) and AAs were least likely to receive an HCV recommendation (15.3%). HAs were significantly likely to have never received a blood test for either HBV or HCV (RR = 1.25, 95% CI: 1.05, 1.49). APAs were significantly more likely to receive a screening recommendation for HBV (RR = 1.10, 95%CI: 1.01, 1.20) and to have a blood test (RR = 1.57, 95% CI: 1.06, 2.33). Our findings show that, among HAs, AAs, and APAs, physician recommendations are strongly associated with patients undergoing blood tests for HBV and HCV and that minority populations should increasingly be recommended to screen for HBV and HCV, especially given their elevated risk.

3.
Indian J Anaesth ; 67(1): 39-47, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36970476

ABSTRACT

The patients presenting for surgery today often belong to the extremes of age, have multiple co-morbidities, and undergo complex surgeries. This makes them more prone to morbidity and mortality. A detailed preoperative evaluation of the patient can contribute to reducing this mortality and morbidity. There are various risk indices and validated scoring systems and many of them need to be calculated using preoperative parameters. Their key objective is to identify patients vulnerable to complications and to return them to desirable functional activity as soon as possible. Any individual undergoing surgery should be optimised preoperatively, but special considerations should be given to patients with comorbidity, on multiple drugs, and undergoing high-risk surgery. The objective of this review is to put forth the latest trends in the preoperative evaluation and optimisation of patients undergoing noncardiac surgery and emphasise the importance of risk stratification in these patients.

4.
Indian J Endocrinol Metab ; 26(3): 252-258, 2022.
Article in English | MEDLINE | ID: mdl-36248036

ABSTRACT

Background and Objectives: Polycystic ovarian syndrome (PCOS) is one of the most common endocrinopathies in women frequently presenting with anovulatory infertility. Low successful pregnancy and live birth rates even after successful ovulation induction (OI) and in vitro fertilization (IVF) in these patients indicate that endometrial dysfunction may be another important factor contributing to infertility. Vitamin D acting through nuclear receptors induces the expression of various genes required for cell growth and differentiation and plays a crucial role in reproduction. Homeobox 10 (HOXA10) may be one of the potential targets for vitamin D action. HOXA10 gene product promotes the differentiation of endometrial cells, making the endometrium receptive for implantation. The present study was undertaken to determine the effect of circulating vitamin D levels on HOXA10 gene expression in endometrial tissues and its possible influence on the reproductive outcome of PCOS patients undergoing OI procedure. Materials and Methods: A prospective cohort study was conducted on 110 infertile PCOS patients. The patients were divided into two groups: Group 1: Vitamin D ³20 ng/ml, Group 2: Vitamin D <20 ng/ml. Endometrial samples were obtained from 22 patients using pipelle biopsy, used to determine HOXA10 mRNA (messenger ribonucleic acid) expression by quantitative RT-PCR (reverse transcription-polymerase chain reaction) and protein expression by Western blotting. OI was performed using Clomiphene citrate or Letrozole from the 3rd day of the cycle, and patients were followed up for a maximum of five cycles. Attainment of successful pregnancy was considered a positive outcome. Results: Both the groups were similar in mean age and other endocrine parameters. Serum vitamin D levels were significantly low (P < 0.001), and BMI (body mass index) was significantly high (P = 0.032) in group 2 compared to group 1. Endometrial HOXA10 mRNA (by quantitative rtPCR) and protein expression (by western blotting) were significantly low in group 2 compared to group 1. The clinical pregnancy rate was low in group 2 (28.6%) compared to group 1 (42.3%), but this difference was not significant (P = 0.22). On regression analysis adjusted for age and BMI, vitamin D was an independent predictor of successful pregnancy after OI (P = 0.09). Conclusion: Circulating vitamin D levels influence the endometrial HOXA10 gene expression, and this may be reflected on the reproductive outcome of infertile PCOS patients undergoing OI.

5.
Rev Recent Clin Trials ; 17(2): 86-91, 2022.
Article in English | MEDLINE | ID: mdl-35260062

ABSTRACT

BACKGROUND: The COVID-19 pandemic has encouraged doctors to look for novel ways of treating patients with respiratory failure due to the limited availability of ventilators and highflow nasal cannula. The study aims to assess the efficacy of using the Bains circuit as an alternative to HFNC and NIV as life-saving tools in patients with respiratory failure during the second wave of the COVID-19 pandemic in India. METHODS: This is a prospective interventional study carried out in the intensive care unit of Shri B.M Patil Medical College Hospital and Research Centre, Vijayapur, India, from May 2021 to June 2021. All patients (n=90) with respiratory failure not responding to therapy with an oxygen mask were included. Patients were placed on Bain circuits, one end connected to a non-invasive ventilation mask fitted to the face of the patients, and the other end connected to a central oxygen port. Patients' vital parameters were assessed on an hourly basis. The blood gas analyses were done before and after using Bains. RESULTS: The study showed diabetes (33.4%), hypertension (22.2%), and diabetes with hypertension (11.1%) as comorbid factors among the ICU admitted patients. The results from the arterial blood gas analyses showed a statistically significant increase in Sp02 (%) and a decrease in respiratory rate (cycles/min) in the patients after being kept on Bains (p<0.05). Further, it showed that 72% of ICU patients with 70-79% Sp02 had a recovery by using Bains. The overall outcome of ICU admitted COVID-19 patients on Bains showed that 38.9% of patients improved and were shifted to 02/NRBM masks. CONCLUSION: The study highlights a novel concept of using the Bains circuit as an effective alternative to HFNC and NIV for oxygenation in critically ill COVID-19 patients during scarcity of NIV and HFNC at the peak of the pandemic.


Subject(s)
COVID-19 , Hypertension , Respiratory Insufficiency , Humans , Pandemics , Oxygen Inhalation Therapy , COVID-19/epidemiology , COVID-19/therapy , Critical Illness/therapy , Prospective Studies , Respiratory Insufficiency/etiology , Respiratory Insufficiency/therapy , Oxygen , Hypertension/therapy
6.
J Lab Physicians ; 13(3): 257-262, 2021 Sep.
Article in English | MEDLINE | ID: mdl-34602791

ABSTRACT

Objectives Prediabetes is defined as an intermediate state of hyperglycemia with glucose levels above normal but below the diagnostic cutoff of diabetes mellitus. Prediabetes is considered as an important risk factor for the development of diabetes and complications associated with diabetes. Since glomerular hyperfiltration (elevated GFR) and albuminuria represent early and reversible stages of kidney damage seen in patients with type 2 diabetes, we aim to assess the impact of hyperglycemia in prediabetic range on renal functions measured by estimated GFR and urine albumin excretion (UAE). Materials and Methods The study included 1,031 patients aged 30 to 70 years, attending regular health checkup. Patients were grouped as normal, prediabetes, and diabetes according to the American Diabetic Association (ADA) criteria based on fasting blood sugar and hemoglobin A1c (HbA1c). Further, the patients were grouped into multiple subgroups based on age and gender. UAE was measured by using immunoturbidimetric method, and GFR was estimated by chronic kidney disease epidemiology collaboration (CKD EPI) equation. Statistical Analysis Prevalence of hyperfiltration (estimated glomerular filtration rate above the age and gender specific 95th percentile), and albuminuria in prediabetes and diabetes was compared with normal controls. Odds ratio and 95% confidence interval were calculated by using logistic regression analysis to predict the occurrence of hyperfiltration in prediabetes and diabetes. Analysis of variance followed by post hoc comparison was done to assess the significance of difference, and p -value < 0.05 was considered statistically significant. Results Prevalence of hyperfiltration was more in prediabetes and diabetes compared with normal controls, and it increased with surging HbA1c level that was shown as higher odds ratio for hyperfiltration in both the groups. UAE was more in the prediabetes and diabetes group when compared with normal controls, but the difference was significant only in diabetes. Conclusion Since glomerular hyperfiltration represents an early and reversible stage of renal damage manifesting before the appearance of albuminuria, elevated GFR can be used to identify asymptomatic patients with intermediate hyperglycemia having high risk of developing nephropathy in the future. Prediabetes represents a window of opportunity to initiate preventive strategies at an early stage before the occurrence of significant renal damage.

7.
J Investig Clin Dent ; 10(4): e12469, 2019 Nov.
Article in English | MEDLINE | ID: mdl-31541512

ABSTRACT

AIM: To study the expression of tumor necrosis factor-like weak inducer of apoptosis (TWEAK) and fibroblast growth factor-inducible immediate early response protein 14 (Fn14) in oral squamous cell carcinoma (OSCC), to elucidate the possible role of TWEAK-Fn14 in OSCC development. METHODS: Immunohistochemistry for TWEAK-Fn14 was performed on 61 oral mucosal samples: healthy oral mucosa (HOM; N = 15); oral dysplastic lesions (ODL; N = 15); and OSCC (N = 31). Extent of staining (ES) and immunoreactive score (IRS) were assessed. The data was statistically analyzed. RESULTS: All OSCC expressed TWEAK, and the Fn14 expression was noted in 90% of OSCC. A significant difference in the TWEAK and Fn14 expression was noted among the groups. ES and IRS of TWEAK-Fn14 significantly increased in OSCC compared with ODL and HOM. ES of TWEAK was significantly higher than Fn14 in all 3 groups. ES of TWEAK-Fn14 was significantly higher at the invasive tumor front (ITF) than in the whole tumor. TWEAK-Fn14 showed a significant association with clinicopathological parameters of prognostic significance. CONCLUSION: Findings suggest that TWEAK and Fn14 may participate in the growth and progression of OSCC. Increased expression of TWEAK-Fn14 at the ITF may facilitate increased proliferation, altered differentiation and invasion.


Subject(s)
Carcinoma, Squamous Cell , Mouth Neoplasms , Apoptosis , Fibroblast Growth Factors , Humans , Receptors, Tumor Necrosis Factor , TWEAK Receptor
8.
Mol Med Rep ; 20(5): 4688-4694, 2019 Nov.
Article in English | MEDLINE | ID: mdl-31545477

ABSTRACT

Limbal stem cell deficiency (LSCD) is one of the leading causes of corneal damage. Injury or inflammation in the cornea causes LSCD, which may be unilateral or bilateral depending upon the cause. Limbal epithelial cell implants successfully improve vision in patients with chemical injury­induced LSCD. Transplantation of cultured epithelial stem cells has become a treatment of choice for numerous patients with LSCD. Bilateral LSCD is frequently observed in the general population, where no residual stem cells are available for ex vivo culture. Allografts are associated with a high risk of rejection, neoplasia, and disease transmission. In this respect, allogenic cell populations from other regions in the patient may substitute for allogenic material. In the present study, dental pulp stem cells were cultured in limbal stem cell media and these cells were characterized against limbal stem cells, revealing the significance of using dental pulp stem cell treatment in bilateral LSCD. The morphology and culture pattern of both limbal and dental pulp stem cells grown in limbal stem­specific media were similar. Polymerase chain reaction analysis revealed that stem cell markers were highly expressed in limbal stem cells compared to in dental pulp stem cells, regardless of the medium and scaffold in which they were grown. Although dental pulp stem cell molecular expression is quite low at the transcript level, the functional protein level according to immunocytochemistry and western blot analyses demonstrated that stem cells and corneal differentiation molecule levels were quite high, indicating their potential as limbal stem cells in the respective microenvironment.


Subject(s)
Corneal Diseases/pathology , Corneal Injuries/pathology , Dental Pulp/cytology , Stem Cell Transplantation , Stem Cells/cytology , Stem Cells/metabolism , Biomarkers , Cells, Cultured , Corneal Diseases/metabolism , Corneal Diseases/therapy , Corneal Injuries/metabolism , Corneal Injuries/therapy , Fluorescent Antibody Technique , Gene Expression , Humans , Stem Cell Transplantation/methods
9.
Indian J Community Med ; 44(2): 129-133, 2019.
Article in English | MEDLINE | ID: mdl-31333290

ABSTRACT

BACKGROUND: Infertility is an iceberg phenomenon where the majority of couples are undiagnosed. The main challenge in estimating the actual burden of infertility is the paucity of population-based studies. Various sociocultural practices such as believing infertility as curse and seeking healing from supernatural powers are still predominant in the community. Hence, the present study was undertaken to know the prevalence and sociocultural practices of infertility in field practice area. MATERIALS AND METHODS: A cross-sectional study was conducted in rural and urban field practice areas of tertiary care hospital. A complete enumeration of all the houses was done to list all the eligible couples residing in the area; among them, those at risk of pregnancy were identified so as to find out couples with either primary or secondary infertility. Data were tabulated and analyzed using the SPSS software version 16. The results were expressed in terms of percentages, and Fisher's exact test was used wherever applicable. RESULTS: The prevalence of infertility in rural area was 7.6% and in urban slum, it was 8.8%. Most of them think infertility as a result of past sins and practice unscientific methods to overcome the problem. CONCLUSION: Infertility stigma is high and there is no proper knowledge about infertility, fertile period and most of them think it as result of past sins.

10.
J Oral Maxillofac Pathol ; 23(3): 369-377, 2019.
Article in English | MEDLINE | ID: mdl-31942116

ABSTRACT

OBJECTIVE: Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) has been implicated in the pathogenesis of cancer, as it participates in the progression of internal malignancies. However, its role in the biology of squamous cell carcinoma (SCC) is uncertain. Studies regarding TWEAK in SCC have shown inconsistent results. We aimed to study the expression of TWEAK in healthy oral mucosa, oral dysplastic lesions and in oral SCC (OSCC). METHODS: Immunohistochemistry for TWEAK was performed on one hundred oral mucosal tissues, healthy control (HC) (n = 20), oral dysplasia (OD) (n = 20) and OSCC (n = 60). Staining intensity, extent of staining (ES) and immunoreactive Score (IRS) were assessed for each sample. Kruskal-Wallis ANOVA, Mann-Whitney U, Chi-square and Spearman's rank correlation coefficient were applied. RESULTS: TWEAK was expressed in 55% of HC, 90% of OD and in all cases of OSCC, with variable intensities. A significant difference in the ES and IRS of TWEAK was noted among the three groups. ES and IRS were highest in OSCC group. ES of TWEAK was significantly higher at invasive tumor front (ITF) than in the whole tumor, with a significant positive correlation. TWEAK expression showed a significant association with invasive front grading, pattern of invasion and surgical margins of OSCC. CONCLUSIONS: TWEAK may contribute to the progression of OSCC. It might also sustain altered differentiation, invasion and migration of tumor cells at ITF.

11.
Mol Biol Rep ; 46(1): 83-95, 2019 Feb.
Article in English | MEDLINE | ID: mdl-30426384

ABSTRACT

Annexin A2 has been implicated in several immune modulated diseases including Rheumatoid arthritis (RA) pannus formation. The most relied treatment option for RA pathogenesis is glucocorticoids. Glucocorticoids regulate the synthesis, phosphorylation and cellular deposition of Annexin A1. This annexin mediates the anti-inflammatory actions of glucocorticoids. These two first characterized members of annexin superfamily proteins acts reciprocally, one as an anti-inflammatory and the other proinflammatory in nature. The possibility of these molecules as soluble biomarkers and as an upstream regulator of major cytokine devastation at RA microenvironment has not been previously explored. Current study elucidates the reciprocal regulation of these two annexins in RA pathogenesis. These Annexin A2/A1 and downstream cytokines in RA serum were analysed by ELISA. Western blot, Immunocytochemistry, immunoprecipitation and Immunohistochemistry were adapted to analyse these molecules in tissue and synovial fibroblasts and also in different experimental conditions. Significant increase in the level of Annexin A2 was noticed in naïve RA patients compared to controls (14.582 ± 1.766 ng/ml vs. 7.37 ± 1.450 ng/ml; p ≤ 0.001). In remission cases significant low levels was detected. On the contrary, significant decrease in the level of Annexin A1 was noticed in naïve RA patients compared to healthy controls (12.322 ± 2.91 vs. 16.998 ± 4.298 ng/ml; p ≤ 0.001), wherein remission cases serum Annexin A1 was significantly high. The knockdown of proinflammatory Annexin A2 by siRNA/antibody treatment could mimic the glucocorticoid treatment as which induced cellular Annexin A1 and membrane translocation resulting in the terminal action. Current data elucidating the regulatory interplay between Annexin A2 and Annexin A1 in RA pathogenesis.


Subject(s)
Annexin A1/physiology , Annexin A2/physiology , Arthritis, Rheumatoid/pathology , Adult , Annexin A1/blood , Annexin A2/blood , Annexin A2/metabolism , Anti-Inflammatory Agents , Female , Fibroblasts/metabolism , Glucocorticoids/metabolism , Humans , Male , Middle Aged , Synovial Membrane/metabolism
12.
J Lab Physicians ; 10(1): 50-55, 2018.
Article in English | MEDLINE | ID: mdl-29403205

ABSTRACT

INTRODUCTION: Patients with subclinical hypothyroidism (SCH) have a few or no symptoms or signs of thyroid dysfunction and thus by its very nature, SCH is a laboratory diagnosis. Serum creatinine is elevated and glomerular filtration rate (GFR) values are reversibly reduced in overt hypothyroid patients. We hypothesize that SCH also may be associated with low GFR. AIMS AND OBJECTIVES: The objective of this study was (1) to know the effect of SCH on kidney function, (2) to find the correlation between the renal function parameter creatinine, estimated GFR (eGFR), and thyroid-stimulating hormone (TSH), and (3) to know if creatinine values can be predicted by TSH values in SCH cases. MATERIALS AND METHODS: This is a hospital-based cross-sectional study for 1 year. A total of 608 subjects of either sex were included in the study and were divided into 3 groups: (1) SCH, (2) overt hypothyroidism (OHT), and (3) euthyroidism (ET). TSH, free triiodothyronine, free thyroxine, and serum creatinine were estimated and eGFR was calculated using modification of diet in renal disease study equation and the chronic kidney disease epidemiology collaboration equations. RESULTS: Serum creatinine levels were higher and eGFR was lower significantly in the subclinical hypothyroid group when compared to the control ET group (P < 0.001). The overtly hypothyroid group had significantly higher levels of serum creatinine and lower eGFR when compared to both the groups (P < 0.001). Significant correlation between TSH, creatinine, and eGFR was found in OHT group only. Linear regression analysis showed the regression in creatinine upon TSH is attributable to 44.5% among OHT group, 48.2% in SCH group. CONCLUSION: It can be concluded that the SCH group behaves biochemically similar to OHT group and changes in serum creatinine reflect tissue hypothyroidism in SCH cases.

13.
Article in English | MEDLINE | ID: mdl-28888333

ABSTRACT

Maternal nutrition plays a crucial role in influencing fetal growth and birth outcome. Any nutritional insult starting several weeks before pregnancy and during critical periods of gestation is known to influence fetal development and increase the risk for diseases during later life. Literature suggests that chronic adult diseases may have their origin during early life - a concept referred to as Developmental Origins of Health and Disease (DOHaD) which states that adverse exposures early in life "program" risks for later chronic disorders. Long chain polyunsaturated fatty acids (LCPUFA), mainly omega-6 and omega-3 fatty acids are known to have an effect on fetal programming. The placental supply of optimal levels of LCPUFA to the fetus during early life is extremely important for the normal growth and development of both placenta and fetus. Any alteration in placental development will result in adverse pregnancy outcome such as gestational diabetes mellitus (GDM), preeclampsia, and intrauterine growth restriction (IUGR). A disturbed materno-fetal LCPUFA supply is known to be linked with each of these pathologies. Further, a disturbed LCPUFA metabolism is reported to be associated with a number of metabolic disorders. It is likely that LCPUFA supplementation during early pregnancy may be beneficial in improving the health of the mother, improving birth outcome and thereby reducing the risk of diseases in later life.


Subject(s)
Fatty Acids, Unsaturated/metabolism , Fetal Development , Placentation , Female , Humans , Maternal Nutritional Physiological Phenomena , Pregnancy , Pregnancy Outcome
14.
J Lab Physicians ; 9(1): 36-41, 2017.
Article in English | MEDLINE | ID: mdl-28042215

ABSTRACT

INTRODUCTION: Postprandial hyperglycemia is a major risk factor for the development of cardiovascular diseases (CVDs), and Most of the times it occurs in patients with normal glycemic control diagnosed by fasting blood glucose (FBG) and glycated hemoglobin levels. Urine albumin excretion (UAE) is an independent predictor of CVD risk. AIM: To estimate UAE in isolated postprandial hyperglycemia (IPPHG) patients and to assess the relationship of UAE with FBG and postprandial blood glucose (PPBG) levels. SETTINGS AND DESIGN: A cross-sectional study was carried out in 318 patients with Type II diabetes in the age group 30-60 years for 6 months. MATERIALS AND METHODS: Patients were divided into five groups based on their FBG and PPBG values. UAE and lipid profile were measured in all the groups. STATISTICAL ANALYSIS: UAE and lipid profile in different groups were compared using ANOVA. Regression analysis was used to predict the variation of UAE with FBG, PPBG, and total cholesterol (TC). RESULTS: Patients with IPPHG had significantly higher albumin excretion compared to normoglycemia (NG) group [P < 0.0001]. In impaired glucose tolerance and isolated fasting hyperglycemia groups, it did not differ significantly from NG group [P = 0.206 and P = 0.173]. Lipid profile did not show any significant difference between the groups. On regression analysis, PPBG but not FBG or TC correlated positively with UAE. CONCLUSION: UAE is easy, less expensive, and Widely available method done on spot urine samples which predicts the acute glycemic changes and increased risk of developing CVDs in patients with IPPHG.

15.
Ann Clin Biochem ; 54(4): 463-471, 2017 Jul.
Article in English | MEDLINE | ID: mdl-27496793

ABSTRACT

Background AnnexinA2 (AnxA2) membrane deposition has a critical role in HB-EGF shedding as well as IL-6 secretion in breast cancer cells. This autocrine cycle has a major role in cancer cell proliferation, migration and metastasis. The objective of the study is to demonstrate annexinA2-mediated autocrine regulation via HB-EGF and IL-6 in Her-2 negative breast cancer progression. Methods Secretory annexinA2, HB-EGF and IL-6 were analysed in the peripheral blood sample of Her-2 negative ( n = 20) and positive breast cancer patients ( n = 16). Simultaneously, tissue expression was analysed by immunohistochemistry. The membrane deposition of these secretory ligands and their autocrine regulation was demonstrated using triple-negative breast cancer cell line model. Results Annexina2 and HB-EGF expression are inversely correlated with Her-2, whereas IL-6 expression is seen in both Her-2 negative and positive breast cancer cells. RNA interference studies and upregulation of annexinA2 proved that annexinA2 is the upstream of this autocrine pathway. Abundant soluble serum annexinA2 is secreted in Her-2 negative breast cancer (359.28 ± 63.73 ng/mL) compared with normal (286.10 ± 70.04 ng/mL, P < 0.01) and Her-2 positive cases (217.75 ± 60.59 ng/mL, P < 0.0001). In Her-2 negative cases, the HB-EGF concentrations (179.16 ± 118.81 pg/mL) were highly significant compared with normal (14.92 ± 17.33 pg/mL, P < 0.001). IL-6 concentrations were increased significantly in both the breast cancer phenotypes as compared with normal ( P < 0.001). Conclusion The specific expression pattern of annexinA2 and HB-EGF in triple-negative breast cancer tissues, increased secretion compared with normal cells, and their major role in the regulation of EGFR downstream signalling makes these molecules as a potential tissue and serum biomarker and an excellent therapeutic target in Her-2 negative breast cancer.


Subject(s)
Annexin A2/genetics , Biomarkers, Tumor/genetics , Breast Neoplasms/diagnosis , Gene Expression Regulation, Neoplastic , Heparin-binding EGF-like Growth Factor/genetics , Interleukin-6/genetics , Receptor, ErbB-2/genetics , Adult , Annexin A2/blood , Autocrine Communication , Biomarkers, Tumor/blood , Breast Neoplasms/blood , Breast Neoplasms/genetics , Breast Neoplasms/pathology , Case-Control Studies , Cell Line, Tumor , Diagnosis, Differential , Female , Genotype , Heparin-binding EGF-like Growth Factor/blood , Humans , Immunohistochemistry , Interleukin-6/blood , Middle Aged , Phenotype , Receptor, ErbB-2/deficiency , Signal Transduction
16.
Braz. j. pharm. sci ; 52(3): 433-442, July-Sept. 2016. tab, graf
Article in English | LILACS | ID: biblio-828269

ABSTRACT

ABSTRACT Punarnava (Boerhaavia diffusa L.- Nyctaginaceae) is a promising drug to rejuvenate new cells in the body. It is well known in Ayurvedic medicine and locally called Tambadivasu. Superficially it is similar to other species of Boerhaavia and species of Trianthema and Sesuvium. Due to the minute morphological differences, the above plants are erroneously used in medicine as Punarnava, and at times on purpose as an adulterant. Therefore, it is necessary to highlight the anatomical features of Punarnava for proper identification of the medicinal plant species for local people and for scientific research. Due to the ambiguity in local names and similar apparent appearance, market samples of Punarnava are often adulterated with various species of Trianthema and Sesuvium. These adulterated samples contain neither the Punarnavine alkaloid, nor does it possess anisocytic stomata but possess paracytic stomata. Comparative study of stem anatomy showed two main characteristic differences. First, plenty of starch grains can be seen in both the ground parenchymatous tissues present in between successive cambia and xylem parenchyma of Punarnava which is not observed in species of Trianthema, and second, the phloem around the xylem of Punarnava root has semi-circular or eccentric patches, while that of Trianthema only has narrow strips. This study is focused on comparative SEM study of leaf morphologies and anatomy of leaf, stem, and root of Boerhaavia diffusa L., Trianthema portulacastrum L. and Sesuvium portulacastrum L.


Subject(s)
Comparative Study , Nyctaginaceae/anatomy & histology , Plants, Medicinal/anatomy & histology , Microscopy, Electron/methods , Medicine, Ayurvedic
17.
J Clin Diagn Res ; 10(3): BC17-20, 2016 Mar.
Article in English | MEDLINE | ID: mdl-27134858

ABSTRACT

INTRODUCTION: Dyslipidaemia of Nephrotic Syndrome (NS) is known to be linked to oxidative reactions and atherosclerosis. Paraoxonase (PON1) has been implicated in the prevention of Low Density Lipoprotein (LDL) lipid peroxidation and also degrades biologically active oxidised lipids in lipoprotein. AIM: The present study was taken up to assess PON1 levels in paediatric nephrotic syndrome and also to see if any correlation exists between lipid parameters and PON1. MATERIALS AND METHODS: This study consists of Group 1 with 40 cases of NS in the age group of 2-14 years and Group 2 with 40 age and sex matched healthy controls. Lipid profile and paraoxonase activity was measured in serum samples of both the groups. RESULTS: Statistical analysis by student's t-test showed that the mean levels of Total Cholesterol, Trigylycerides, LDL, and VLDL were significantly increased in Group 1 when compared to Group 2 (p <0.001). The mean levels of HDL were similar in both groups. The levels of PON1 were significantly lowered in Group 1 when compared to Group 2. Correlation studies showed no significant correlation between lipid profile and PON1. CONCLUSION: Cases have atherosclerotic dyslipidaemia and significantly decreased PON1 activity. Decreased PON1 may lead to increased oxidation of LDL accelerating the process of atherosclerosis.

18.
J Clin Diagn Res ; 10(4): BC12-6, 2016 Apr.
Article in English | MEDLINE | ID: mdl-27190790

ABSTRACT

INTRODUCTION: The prevalence of periodontitis is significantly higher among people with poorly controlled diabetes mellitus. Majority of tissue destruction in periodontitis is considered to be the result of an aberrant inflammatory/immune response to microbial plaque and involve prolonged release of reactive oxygen species (ROS). There is increased evidence for compromised antioxidant capacity in periodontal tissues and fluids which may be an added factor for tissue damage in periodontitis. AIM: To study the possible role of Reactive oxygen species (ROS) and antioxidant status in blood among chronic periodontitis patients with and without Type 2 Diabetes mellitus. MATERIALS AND METHODS: The study comprised of total 100 subjects among which 25 were normal healthy controls, 25 were gingivitis patients, 25 were chronic periodontitis patients (CP) and 25 were having chronic periodontitis with type 2 diabetes (CP with DM). ROS levels were determined as MDA (Malondialdehyde) and antioxidant status as plasma total antioxidant capacity (TAC), vitamin C and erythrocyte Superoxide dismutase (SOD) and catalase activity. RESULTS: There was significant increase in MDA levels in all the patient groups compared with healthy controls (p<0.05). The decrease in TAC, Vitamin C and SOD levels among CP with DM patients as compared to controls was highly significant (p<0.01). There was a positive correlation between the probing pocket depth and MDA levels among periodontitis patients with diabetes (r=0.566, p=0.003). CONCLUSION: There is increased oxidative stress in chronic periodontitis with and without type 2 diabetes indicating a common factor involvement in tissue damage. More severe tissue destruction in periodontitis is associated with excessive ROS generation which is positively correlated in type 2 diabetic subjects.

19.
Clin Exp Hypertens ; 38(2): 225-32, 2016.
Article in English | MEDLINE | ID: mdl-26817695

ABSTRACT

Preeclampsia (PE) is a pregnancy-specific disorder, defined as new onset of maternal hypertension and proteinuria after 20 weeks of gestation. Our earlier study has shown increased maternal oxidative stress at delivery to be associated with poor birth outcome in PE. However, these results were observed when the pathology had progressed and may have been secondary to the effects of the disorder. To understand the role of antioxidant defense mechanisms in PE right from early pregnancy, in this prospective study, we measured malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione (GSH) concentrations in maternal blood at 3 time-points of gestation [16-20 weeks (T1), 26-30 weeks (T2), at delivery (T3)] and in cord blood. Gene expression of SOD and GPx and protein levels of endothelial nitric oxide synthase (eNOS) enzyme were also analyzed in the placenta. MDA levels were higher at T1 (p < 0.01) and T2 (p < 0.01) in women with PE as compared with control. GPx levels were higher at T3 (p < 0.05) while SOD levels were lower at T2 (p < 0.05), T3 (p < 0.01) and in cord (p < 0.01) in PE. GSH levels at T1 (p < 0.05) and expression of GPx in the placenta were lower in PE as compared with control. In conclusion, this study demonstrates that women who develop PE exhibit increased oxidative stress right from 16 to 20 weeks of gestation. This may alter placental development and lead to fetal programming of adult non-communicable disease in the offspring.


Subject(s)
Glutathione Peroxidase/genetics , Nitric Oxide Synthase Type III/genetics , Oxidative Stress/genetics , Placenta/metabolism , Pre-Eclampsia/genetics , RNA, Messenger/metabolism , Superoxide Dismutase/genetics , Adult , Antioxidants , Case-Control Studies , Female , Fetal Blood/chemistry , Gene Expression , Gestational Age , Glutathione/metabolism , Glutathione Peroxidase/metabolism , Humans , Malondialdehyde/metabolism , Nitric Oxide Synthase Type III/metabolism , Pre-Eclampsia/metabolism , Pregnancy , Pregnancy Trimester, Second , Pregnancy Trimester, Third , Prospective Studies , Superoxide Dismutase/metabolism , Young Adult
20.
Mol Cell Biochem ; 411(1-2): 221-33, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26438086

ABSTRACT

Overexpression and activation of tyrosine kinase receptors like EGFR and Src regulate the progression and metastasis of Her-2 negative breast cancer. Recently we have reported the role of cell membrane interaction of phospholipid-binding protein annexin A2 (AnxA2) and EGFR in regulating cellular signaling in the activation of angiogenesis, matrix degradation, invasion, and cancer metastasis. Beta-galactoside-specific animal lectin galectin-3 is an apoptosis inhibitor, and cell surface-associated extracellular galectin-3 also has a role in cell migration, cancer progression, and metastasis. Similar expression pattern and membrane co-localization of these two proteins made us to hypothesize in the current study that galectin-3 and AnxA2 interaction is critical for Her-2 negative breast cancer progression. By various experimental analyses, we confirm that glycosylated AnxA2 at the membrane surface interacts with galectin-3. N-linked glycosylation inhibitor tunicamycin treatment convincingly blocked AnxA2 membrane translocation and its association with galectin-3. To analyze whether this interaction has any functional relevance, we tried to dissociate this interaction with purified plant lectin from chickpea (Cicer arietinum agglutinin). This highly specific 30 kDa plant lectin could dissociate AnxA2 from endogenous lectin galectin-3 interaction at the cell surface. This dissociation could down-regulate Bcl-2 family proteins, cell proliferation, and migration simultaneously triggering cell apoptosis. Targeting this interaction of membrane surface glycoprotein and its animal lectin in Her-2 negative breast cancer may be of therapeutic value.


Subject(s)
Annexin A2/metabolism , Breast Neoplasms/metabolism , Epidermal Growth Factor/metabolism , Galectin 3/metabolism , Signal Transduction , Breast Neoplasms/genetics , Breast Neoplasms/pathology , Cell Line, Tumor , Female , Genes, erbB-2 , Glycosylation , Humans , Tunicamycin/pharmacology
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