Formulation, optimization and evaluation of amisulpride-loaded niosomal intranasal gel for brain targeting.

Aim: To develop stable non-ionic surfactant vesicles containing amisulpride (AMS) to improve brain uptake via nose to brain mechanism. Methods: Niosomes were developed using a modified ethanol injection technique, optimized using 32 factorial design and evaluated for the vesicle size (VS), percent encapsulation efficiency (EE), zeta potential (ZP) and % cumulative drug release (%CDR). Results: Optimized niosomes (Span-60: cholesterol ratio 0:1) showed 191.4 nm VS, 84.25% EE, -38.2 ZP and 81.31% CDR. In situ gel with these niosomes displayed 78% CDR. TEM analysis revealed spherical niosomes. Pharmacokinetic and brain tissue distribution studies in rats showed enhanced plasma and brain concentrations, indicating successful brain targeting. Conclusion: This strategy demonstrates improved AMS permeation via the nasal cavity, enhancing bioavailability for treating schizophrenia.

Schizophrenia is a serious mental illness causing intense symptoms like hallucinations and delusions. Medicines like amisulpride can help, but they have problems like not dissolving well. The brain's defenses also make it hard for medicines to work. People are trying to send medicine through the nose to avoid these problems. These researchers developed tiny carriers called niosomes to carry amisulpride to the brain via the nose. To further help with delivery of amisulpride to the brain, they added the niosomes to a gel that becomes solid inside the body. They found that the nisome-containing gel can keep medicine in the nose for a long time and is effective at delivering amisulpride to the brain.

Nervous system (NS) Tumors in Cancer Predisposition Syndromes.

Genetic syndromes which develop one or more nervous system (NS) tumors as one of the manifestations can be grouped under the umbrella term of NS tumor predisposition syndromes. Understanding the underlying pathological pathways at the molecular level has led us to many radical discoveries, in understanding the mechanisms of tumorigenesis, tumor progression, interactions with the tumor microenvironment, and development of targeted therapies. Currently, at least 7-10% of all pediatric cancers are now recognized to occur in the setting of genetic predisposition to cancer or cancer predisposition syndromes. Specifically, the cancer predisposition rate in pediatric patients with NS tumors has been reported to be as high as 15%, though it can approach 50% in certain tumor types (i.e., choroid plexus carcinoma associated with Li Fraumeni Syndrome). Cancer predisposition syndromes are caused by pathogenic variation in genes that primarily function as tumor suppressors and proto-oncogenes. These variants are found in the germline or constitutional DNA. Mosaicism, however, can affect only certain tissues, resulting in varied manifestations. Increased understanding of the genetic underpinnings of cancer predisposition syndromes and the ability of clinical laboratories to offer molecular genetic testing allows for improvement in the identification of these patients. The identification of a cancer predisposition syndrome in a CNS tumor patient allows for changes to medical management to be made, including the initiation of cancer surveillance protocols. Finally, the identification of at-risk biologic relatives becomes feasible through cascade (genetic) testing. These fundamental discoveries have also broadened the horizon of novel therapeutic possibilities and have helped to be better predictors of prognosis and survival. The treatment paradigm of specific NS tumors may also vary based on the patient's cancer predisposition syndrome and may be used to guide therapy (i.e., immune checkpoint inhibitors in constitutional mismatch repair deficiency [CMMRD] predisposition syndrome) [8]. Early diagnosis of these cancer predisposition syndromes is therefore critical, in both unaffected and affected patients. Genetic counselors are uniquely trained master's level healthcare providers with a focus on the identification of hereditary disorders, including hereditary cancer, or cancer predisposition syndromes. Genetic counseling, defined as "the process of helping people understand and adapt to the medical, psychological and familial implications of genetic contributions to disease" plays a vital role in the adaptation to a genetic diagnosis and the overall management of these diseases. Cancer predisposition syndromes that increase risks for NS tumor development in childhood include classic neurocutaneous disorders like neurofibromatosis type 1 and type 2 (NF1, NF2) and tuberous sclerosis complex (TSC) type 1 and 2 (TSC1, TSC2). Li Fraumeni Syndrome, Constitutional Mismatch Repair Deficiency, Gorlin syndrome (Nevoid Basal Cell Carcinoma), Rhabdoid Tumor Predisposition syndrome, and Von Hippel-Lindau disease. Ataxia Telangiectasia will also be discussed given the profound neurological manifestations of this syndrome. In addition, there are other cancer predisposition syndromes like Cowden/PTEN Hamartoma Tumor Syndrome, DICER1 syndrome, among many others which also increase the risk of NS neoplasia and are briefly described. Herein, we discuss the NS tumor spectrum seen in the abovementioned cancer predisposition syndromes as with their respective germline genetic abnormalities and recommended surveillance guidelines when applicable. We conclude with a discussion of the importance and rationale for genetic counseling in these patients and their families.

Relationship between cortisol, Interleukin-6 and homocysteine in Alzheimer's disease.

OBJECTIVE: Alzheimer's disease (AD) is characterised by progressive cognitive decline due to neurodegeneration. Over activation of the hypothalamic-pituitary-adrenal axis, oxidative stress and inflammation potentially damage the neuronal system, affecting cognition. AIM: This study aimed to assess the relationship between serum cortisol, Interleukin-6 (IL-6) and homocysteine (Hcy) levels in AD. METHODS: Case-Control observational study consisting of 71 patients with AD and 70 healthy controls above 60 years of age. Serum samples were analysed for cortisol, IL-6 and Hcy levels using chemiluminescence immunoassay (Immulite 1000) technique. Cognitive functions were measured using the Mini-Mental State Examination (MMSE) Score. AD subjects were categorised based on the modified Kuppuswamy socioeconomic status scale. Statistical evaluation was conducted using SPSS Statistics software. Group data were analysed using a two-tailed Student's t-test, analysis of variance (ANOVA), the Mann-Whitney U test and Pearson's correlation test. RESULTS: Serum cortisol, IL-6 and Hcy levels were significantly increased (p < 0.01) in AD (cortisol: 19.69 ± 8.96 ug/dl; IL-6: 10.27 ± 2.76 pg/ml; Hcy: 23.29 ± 3.81 µmol/l), as compared with the controls (cortisol: 13.37 ± 5.59 ug/dl; IL-6: 3.37 ± 0.79 pg/ml; Hcy: 8.25 ± 2.36 µmol/l). MMSE scores in AD were negatively correlated with cortisol, IL-6 and Hcy levels. CONCLUSIONS: Serum cortisol, IL-6 and Hcy levels are independent biomarkers for AD progression. Hypercortisolaemia, hyperhomocysteinemia and inflammation play important roles in AD-related cognitive dysfunction and are interlinked.

Study of IL-6 and vitamin D3 in patients of pulmonary tuberculosis.

BACKGROUND: Mycobacterium tuberculosis can grow in hostile intracellular environment of macrophages by actively evading macrophage-associated antibacterial activities. The stress response factor contributes this process by releasing inflammatory cytokine Interleukin 6 (IL-6). IL-6 screening of patients with TB may be useful to monitor the progress of infection and to infer the risk of progression to active disease. Vitamin D has a critical role in the innate immune system, in the circulating metabolite and supports induction of pleiotropic antimicrobial responses, through the production of antimicrobial peptides, particularly cathelicidin and its active metabolite. 1,25-dihydoxyvitamin D, has long been known to enhance immune response to mycobacteria. In this study, we have studied the role of IL-6 and Vitamin D3 in M. tuberculosis. MATERIALS AND METHODS: Three groups involved in this study are Control, Category I (newly diagnosed TB) and MDR TB patients. The serum levels of IL-6 and vitamin D3 were measured using chemiluminescence and fully-automated enzyme-linked immunosorbent assay respectively. RESULTS: The serum levels of IL-6 were significantly increased, whereas vitamin D3 decreased in TB multidrug-resistant group of patients compared to the newly diagnosed TB patients. CONCLUSION: IL-6 appears to be the major cytokine elaborated by mycobacteria infection as well as play a role in the clinical manifestations and pathological events and hence may function as a potent biomarker of tuberculosis. Since, Vitamin D increases activity of cell-mediated immunity; it can be used as a supplementation during tuberculosis therapy.

Association of serum total bilirubin and plasma 8-OHdG in HIV/AIDS patients.

Oxidative stress is a major contributor in the pathogenesis of insulin resistance (IR) and DNA damage in HIV/AIDS patients. Bilirubin has been shown to have antioxidant effects. In this case-control study, 600 subjects were included. We determined serum total bilirubin and IR in all subjects. We measured 8-hydroxy-2-deoxyguanosine with 8-hydroxy-2-deoxyguanosine enzyme-linked immunosorbent assay kit. IR and oxidative DNA damage were significantly higher in HIV-positive patients with second-line antiretroviral therapy (ART) and first-line ART than ART-naive patients. However, average serum total bilirubin was higher in ART-naive patients than the HIV-positive patients with second-line ART and first-line ART. In a logistic regression analysis, serum total bilirubin was negatively associated with the IR [odds ratio (OR): 0.0127, 95% confidence interval (CI): 0.023-0.070, p = 0.0000] and DNA damage (OR: 0.525, 95% CI: 0.351-0.783, p = 0.0016). We found that prevalence of IR and DNA damage was less in ART-naive patients compared with ART first-line and ART second-line HIV-positive patients. Larger studies are warranted to determine the molecular mechanisms involved in the negative association of serum bilirubin and DNA damage in ART naive patients.

Association of Metabolic Syndrome and Oxidative DNA Damage in HIV/AIDS Patients.

HIV-infected adults may be likely to have metabolic syndrome (MS) at younger ages and in the absence of obesity compared with general population. In the present study, we determined prevalence of MS and its association with oxidative deoxy nucleic acid (DNA) damage in HIV-1 infected patients with different ART status. We used plasma level of the oxidized base, 8-hydroxy-2-deoxyguanosine (8-OHdG), as a biomarker of oxidative DNA damage. To measure plasma 8-OHdG we used 8-OHdG enzyme-linked, immunosorbent assay. The biomarkers of MS were insulin resistance, Cholesterol/HDL ratio, Waist circumference and Hypertension. MS and oxidative DNA damage were significantly higher in HIV-positive patients with second line ART and first line ART than ART-naive patients. In a logistic regression analysis, increased MS was positively associated with the increased DNA damage (OR: 29.68, 95%:13.47, CI: 65.40) P = 0.0001. ART plays a significant role in the development of MS and oxidative DNA damage in HIV-positive patients taking antiretroviral therapy. Awareness and knowledge of MS and DNA damage in HIV/AIDS patients may prove helpful to clinicians to manage non-AIDS diseases such as cardiovascular disease and cancer. To determine exact role of ART in induction of MS and DNA damage larger studies are warranted.

Report of Platythomisus octomaculatus (C. L. Koch, 1845) and Platythomisus sudeepi Biswas, 1977 from India (Araneae, Thomisidae).

BACKGROUND: The genus Platythomisus Doleschall, 1859 presently comprises 13 valid species, nine known from Africa and four from Asia. All Platythomisus species are known from females only, except P. jucundus Thorell, 1894 and P. sudeepi Biswas, 1977 from both sexes and P. quadrimaculatus from juvenile. Only, P. sudeepi was reported from India. NEW INFORMATION: Platythomisus octomaculatus (C. L. Koch, 1845) is recorded after 120 years of its last report; newly recorded from Assam, India which extends its distribution from the previously known localities, Java and Sumatra. Platythomisus sudeepi is newly recorded from the Maharashtra State. The variation in the number of abdominal spots on juvenile, sub-adult and adult of P. octomaculatus observed during rearing is reported. Although, the species name 'octomaculatus' suggests eight spots, we observed that the anterior pair of abdominal spots is fused in adults.

Protein carbonyl content: a novel biomarker for aging in HIV/AIDS patients

Abstract Background: The major complications of “treated” Human Immunodeficiency Virus (HIV) infection are cardiovascular disease, malignancy, renal disease, liver disease, bone disease, and perhaps neurological complications, which are phenomena of the normal aging process occurring at an earlier age in the HIV-infected population. The present study is aimed to explore protein carbonyl content as a biomarker for detecting oxidative DNA damage induced ART toxicity and/or accelerated aging in HIV/AIDS patients. Objective: To investigate the potential of carbonyl content as a biomarker for detecting oxidative Deoxyribonucleic acid (DNA) damage induced Antiretroviral Theraphy (ART) toxicity and/or accelerated aging in HIV/AIDS patients. Methods: In this case–control study a total 600 subjects were included. All subjects were randomly selected and grouped as HIV-negative (control group) (n = 300), HIV-infected ART naive (n = 100), HIV-infected on first line ART (n = 100), and HIV-infected on second line ART (n = 100). Seronegative control subjects were age- and sex-matched with the ART naive patients and the two other groups. Carbonyl protein was determined by the method described in Levine et al. DNA damage marker 8-OH-dG was determined using 8-hydroxy-2-deoxy Guanosine StressXpress ELA Kit by StressMarq Biosciences. Results: Protein carbonyl content levels and oxidative DNA damage were significantly higher (p < 0.05) in HIV-infected patients on second line ART and HIV-infected patients on first line ART than ART naive patients and controls. In a linear regression analysis, increased protein carbonyl content was positively associated with increased DNA damage (OR: 0.356; 95% CI: 0.287–0.426) p < 0.05. Conclusions: Carbonyl content may has a role as a biomarker for detecting oxidative DNA damage induced ART toxicity and/or accelerated aging in HIV/AIDS patients. Larger studies are warranted to elucidate the role of carbonyl content as a biomarker for premature aging in HIV/AIDS patients.

Protein carbonyl content: a novel biomarker for aging in HIV/AIDS patients.

BACKGROUND: The major complications of "treated" Human Immunodeficiency Virus (HIV) infection are cardiovascular disease, malignancy, renal disease, liver disease, bone disease, and perhaps neurological complications, which are phenomena of the normal aging process occurring at an earlier age in the HIV-infected population. The present study is aimed to explore protein carbonyl content as a biomarker for detecting oxidative DNA damage induced ART toxicity and/or accelerated aging in HIV/AIDS patients. OBJECTIVE: To investigate the potential of carbonyl content as a biomarker for detecting oxidative Deoxyribonucleic acid (DNA) damage induced Antiretroviral Theraphy (ART) toxicity and/or accelerated aging in HIV/AIDS patients. METHODS: In this case-control study a total 600 subjects were included. All subjects were randomly selected and grouped as HIV-negative (control group) (n=300), HIV-infected ART naive (n=100), HIV-infected on first line ART (n=100), and HIV-infected on second line ART (n=100). Seronegative control subjects were age- and sex-matched with the ART naive patients and the two other groups. Carbonyl protein was determined by the method described in Levine et al. DNA damage marker 8-OH-dG was determined using 8-hydroxy-2-deoxy Guanosine StressXpress ELA Kit by StressMarq Biosciences. RESULTS: Protein carbonyl content levels and oxidative DNA damage were significantly higher (p<0.05) in HIV-infected patients on second line ART and HIV-infected patients on first line ART than ART naive patients and controls. In a linear regression analysis, increased protein carbonyl content was positively associated with increased DNA damage (OR: 0.356; 95% CI: 0.287-0.426) p<0.05. CONCLUSIONS: Carbonyl content may has a role as a biomarker for detecting oxidative DNA damage induced ART toxicity and/or accelerated aging in HIV/AIDS patients. Larger studies are warranted to elucidate the role of carbonyl content as a biomarker for premature aging in HIV/AIDS patients.

Helicobacter pylori gastritis, a presequeale to coronary plaque.

Helicobacter pylori are considered the most common human pathogen colonizing gastric mucosa. Gastritis with or without H. pylori infection is associated with increase in levels of homocysteine and high-sensitivity C-reactive protein (hs-CRP) but a more pronounced increase is noted in gastritis with H. pylori infection. Increasing level of homocysteine, due to decreased absorption of vitamin B12 and folic acid, together with increased CRP levels in gastritis with H. pylori infection may be the earliest event in the process of atherosclerosis and plaque formation. Retrospective study conducted at tertiary care hospital in Mumbai by Department of Biochemistry in association with Department of Surgery. Eighty patients who underwent gastroscopy in view of gastritis were subjected to rapid urease test for diagnosis of H. pylori infection. Vitamin B12, folic acid, homocysteine and hs-CRP were analyzed using chemiluminescence immuno assay. Student's t-test, Pearson's correlation and linear regression used for statistical analysis. Patients with H. pylori gastritis had significantly lower levels of vitamin B12 (271.6±101.3 vs 390.6±176.7 pg/mL; P=0.0005), as well as higher levels of homocysteine (17.4±7.4 vs 13.8±7.8 µmol/L; P=0.037) and hs-CRP (2.5±2.9 vs 1.2±1.1 mg/L; P=0.017), than in patients without H. pylori gastritis. However, folic acid showed (8.9±3.2 vs 10.0±3.6 ng/mL; P=0.171) no significant difference. Elevated homocysteine and hs-CRP in H. pylori gastritis may independently induce endothelial dysfunction, leading to cardiovascular pathology.

Nitric oxide, carbonyl protein, lipid peroxidation and correlation between antioxidant vitamins in different categories of pulmonary and extra pulmonary tuberculosis.

BACKGROUND: Lipid peroxidation, nitric oxide, carbonyl protein, causing production of reactive oxygen and reactive nitrogen intermediates that lead to oxidative, nitrosative stress. The stress is found to cause deterioration in the cellular function, mutagenesis, and DNA damage. The oxidative stress is correlated with the antioxidant vitamins status. METHODS: Newly diagnosed cultured positive sputum pulmonary category I, II, III (n = 100 each), extra pulmonary category I (n = 35) before and after directly observed short course treatment of six months vitamins, by HPLC. RESULTS: Oxidative parameter levels were significantly increased, and activities of vitamins were found to be significantly decreased in subjects of all categories of pulmonary and extra pulmonary tuberculosis. Positive correlations between nitric oxide, carbonyl protein, and lipid peroxidation were seen among them. Negative correlations between nitric oxide, carbonyl protein, lipid peroxidation with vitamin E, C, A were seen in tuberculosis (two sided P < 0.01). CONCLUSION: Increase oxidative stress and nitrosative stress, leading to protein carbonyl formation in tuberculosis. The increased protein carbonyl, hampers many important functions of proteins. The changes were reversed after six months of antitubercular treatment in patients with good recovery but increase stress was not completely reversed.

Association between single nucleotide polymorphism in collagen IX and intervertebral disc disease in the Indian population.

BACKGROUND: Symptomatic intervertebral disc degeneration is being recently reported in younger population, questions the basis of its degenerative etiology. Latest evidences show that genetics play a significant role. Collagen IX, an important constituent of disc, is found to be altered in genetically predisposed individuals. Mutations have been reported in COL9A2 and COL9A3 genes, which encode Collagen IX, in Finnish and various other populations. The purpose of the present study is to test the significance of these genes in the Indian population. MATERIALS AND METHODS: One hundred proven cases of intervertebral disc disease (IDD) of various regions of spine were selected for the study, along with matched controls. They were tested for the above mentioned alleles by allelic discrimination method with real-time polymerase chain reaction (PCR) study after isolation of DNA from blood sample. Each blood sample was classified into one of the three types - homozygous, heterozygous, and wild (normal) type allele - separately for COL9A2 and COL9A3 genes. RESULTS: Homozygosity for COL9A2 allelic variation was associated with 100% occurrence of the disease. Heterozygous allele of COL9A2 was significantly higher in the study group (42%) as compared to the control group (17%). In contrast, allelic variation in COL9A3 gene was found to have no significant correlation with disc disease. There was no single patient with homozygous allelic variation for COL9A3, suggesting predominance of COL9A2 variation in the Indian population. CONCLUSION: This candidate gene strategy approach adds considerably to our knowledge of genetic makeup of Indian populations in relation with disc disease. This study highlights importance of COL9A2 gene variation especially of homozygous variety in contrast to COL9A3 variation in causing disc disease in Indian population.

Opportunities of habitat connectivity for tiger (Panthera tigris) between Kanha and Pench National Parks in Madhya Pradesh, India.

The Tiger (Panthera tigris) population in India has undergone a sharp decline during the last few years. Of the number of factors attributed to this decline, habitat fragmentation has been the most worrisome. Wildlife corridors have long been a subject of discussion amongst wildlife biologists and conservationists with contrasting schools of thought arguing their merits and demerits. However, it is largely believed that wildlife corridors can help minimize genetic isolation, offset fragmentation problems, improve animal dispersal, restore ecological processes and reduce man animal conflict. This study attempted to evaluate the possibilities of identifying a suitable wildlife corridor between two very important wildlife areas of central India--the Kanha National Park and the Pench National Park--with tiger as the focal species. Geographic Information System (GIS) centric Least Cost Path modeling was used to identify likely routes for movement of tigers. Habitat suitability, perennial water bodies, road density, railway tracks, human settlement density and total forest edge were considered as key variables influencing tiger movement across the Kanha-Pench landscape. Each of these variables was weighted in terms of relative importance through an expert consultation process. Using different importance scenarios, three alternate corridor routes were generated of which one was identified as the most promising for tiger dispersal. Weak links--where cover and habitat conditions are currently sub-optimal--were flagged on the corridor route. Interventions aimed at augmenting the identified corridor route have been suggested using accepted wildlife corridor design principles. The involvement of local communities through initiatives such as ecotourism has been stressed as a crucial long term strategy for conservation of the Kanha-Pench wildlife corridor. The results of the study indicate that restoration of the identified wildlife corridors between the two protected areas is technically feasible.

The roles of glutathione, glutathione peroxidase, glutathione reductase and the carbonyl protein in pulmonary and extra pulmonary tuberculosis.

BACKGROUND: This study determines the protein carbonyls which cause cellular damage and glutathione, glutathione peroxidase, glutathione reductase act as antioxidants. MATERIALS AND METHODS: This study was carried out in different categories of pulmonary and extra pulmonary tuberculosis cases of newly sputum culture positive diagnosed pulmonary categorie I (n=100), extra pulmonary patients categorie (n=35) before and after the DOTS treatment of 6 months, categorie II (n=100), categorie III (n=100) and in normal control subjects (n=100). RESULTS: The serum protein carbonyl levels were significantly increased in the pulmonary and extra pulmonary tuberculosis patients. The activities of blood glutathione, glutathione peroxidase, and glutathione reductase were found to be significantly decreased in subjects of all the categories of pulmonary and extra pulmonary tuberculosis. A negative correlation between the carbonyl protein content and glutathione, glutathione peroxidase, and glutathione reductase was seen in pulmonary tuberculosis, p<0.001. CONCLUSION: Increased antioxidant defense mechanism due to increase oxidative stress in tuberculosis. The changes were reversed after 6 months of antitubercular treatment in patients with a good recovery, but the increase in the oxidative stress was not completely reversed.

Effect of methylxanthines (coffee/tea consumers) on oral precancer and oral cancer patients with smoking and smokeless tobacco habits.

AIM: To study, whether the consumption of regular tea/coffee (methylxanthines) increases the risk of oral cancer in patients with smoking and smokeless tobacco habits. MATERIALS AND METHODS: This study was conducted on a total of 90 oral cancer and precancerous patients, from western Maharashtra (India) males in the age group of 20 to 45 years who were with smoking and smokeless tobacco habits; also regular tea/coffee consumers were subjected to biochemical parameters such as aspartate transaminase (AST) and alanine transaminase (ALT) from saliva and serum of patients with oral precancer (submucous fibrosis, leukoplakia) and oral cancer patients and compared with 90-age and sex-matched controls. Individuals consent was taken to measure their biochemical parameters, by using Hafkenscheid method in whole saliva and serum. Statistical analysis of variance (ANOVA) with Tukey's correction for multiple group comparisons was performed using Student t-test. RESULTS: Results show, that a statistically significant increase in value (p < 0.05) in ALT, AST in both saliva and serum was observed in precancerous and oral cancer patients among the study group as compared to the control group. CONCLUSION: In the present study, there was increase in the levels of ALT, AST enzymes in both saliva and serum levels in the study group as compared to the control group which was statistically significant (p < 0.05) suggesting that long-term exposure of methylxanthines results in impairment of salivary gland antioxidant system which may affect the anticarcinogenic action of saliva. CLINICAL SIGNIFICANCE: Oral fluids may be utilized effectively to study the variations in the biochemical constituents of saliva of leukoplakia, submucous fibrosis and oral cancer patients.

E-Cadherin as a diagnostic biomarker in breast cancer.

BACKGROUND: E-cadherin is expressed in most normal epithelial tissues. Selective loss of E-cadherin can cause dedifferentiation and invasiveness in human carcinomas, leading E-cadherin to be classified as a tumor suppressor. Loss of E-cadherin has been demonstrated in invasive lobular carcinoma of the breast, but the relationship between E-cadherin expression and breast cancer histopathology and prognosis is less clear. AIM: Our objective was to assess loss of E-cadherin as a diagnostic breast cancer biomarker and as an aid to the sub-classification of invasive breast cancer. We also correlated the loss of expression of E-cadherin with various clinical and pathologic prognostic factors. MATERIAL AND METHODS: Breast cancer specimens after modified radical mastectomy were obtained from women who underwent surgery at Grant Medical College and Sir J.J Group of Hospitals, Mumbai, India between May 2007 and October 2010. We stained 276 breast cancers specimens with monoclonal antibodies to E-cadherin. The breast cancers were classified by histopathological type. RESULTS: A statistical correlation of E-cadherin loss with a positive diagnosis of invasive lobular carcinoma was found, but there was no correlation with any prognostic tumor variables. A negative E-cadherin stain was a sensitive and specific biomarker to confirm the diagnosis of invasive lobular carcinoma (specificity 97.7%; negative predictive value 96.8%; sensitivity 88.1%; and positive predictive value 91.2%). Positive E-cadherin expression was also associated with tubulolobular carcinomas. CONCLUSIONS: E-cadherin immunohistochemistry is helpful in classifying breast cancer cases with indeterminate histopathologic features. E-cadherin loss is uncommon in non-lobular carcinomas but shows no correlation to currently established prognostic variables.

Study of serum homocysteine, folic Acid and vitamin b(12) in patients with preeclampsia.

The present study was carried out to evaluate the occurrence of association between homocysteine, folic acid and vitamin B(12) in patients with preeclampsia. Fifty preeclamptic patients from gynecology ward were studied for estimation of serum homocysteine, folic acid and vitamin B(12) over a period of October 2007 to June 2010. Serum homocysteine and folic acid, and vitamin B(12) were determined by means of Immulite 1000 analyzer. The statistical analysis of study group of preeclampsia compared with normotensive control group, showed significant alterations in serum homocysteine, folic acid and vitamin B(12) concentrations in preeclampsia. Inverse association between serum homocysteine and folic acid, and vitamin B(12) levels were observed in preeclampsia. The present study found hyperhomocysteinemia and deficiency of folic acid and vitamin B(12) along with increased blood pressure as a risk factor for cardiovascular disease (CVD) in preeclampsia.

Ki-67 biomarker in breast cancer of Indian women.

BACKGROUND: Biological markers that reliably predict clinical or pathological response to primary systemic therapy early during a course of chemotherapy may have considerable clinical potential. AIMS: Aims of study to evaluated changes in Ki-67 (MIB-1) labeling index and apoptotic index (AI) before, during, and after neoadjuvant anthracycline chemotherapy in breast cancer in Indian women. MATERIALS AND METHODS: Breast cancer tissues were collected from Grant Medical College and Sir J.J. Group of Hospitals, Mumbai, India. Twenty-seven patients receiving neoadjuvant FEC (5-fluorouracil, epirubicin, and cyclophosphamide) chemotherapy for operable breast cancer underwent repeat core biopsy after 21 days of treatment. RESULTS: The objective clinical response rate was 56%. Eight patients (31%) achieved a pathological response by histopathological criteria; two patients had a near-complete pathological response. Increased day-21 AI was a statistically significant predictor of pathological response (p = 0.049). A strong trend for predicting pathological response was seen with higher Ki-67 indices at day 21 and AI at surgery (p = 0.06 and 0.06, respectively). CONCLUSION: The clinical utility of early changes in biological marker expression during chemotherapy remains unclear. Until further prospectively validated evidence confirming the reliability of predictive biomarkers is available, clinical decision-making should not be based upon individual biological tumor biomarker profiles.

Triple-negative (ER, PgR, HER-2/neu) breast cancer in Indian women.

The aim of our study was to analyze triple-negative (TN) breast cancer, which is defined as being negative for the estrogen receptor (ER), the progesterone receptor (PgR), and the human epidermal growth factor receptor 2 (HER-2/neu) and which represents a subset of breast cancer with different biologic behavior. We investigated the clinicopathological characteristics and prognostic indicators of lymph node-negative TN breast cancer. Medical records were reviewed from patients with node-negative breast cancer who underwent curative surgery at Grant Medical College and Sir JJ Group of Hospitals, Mumbai, India, from May 2007 to October 2010. Clinicopathological variables and clinical outcomes were evaluated. Among 683 patients included, 136 had TN breast cancer and 529 had non-TN breast cancer. TN breast cancer correlated with younger age (<35 years, P = 0.003) and a higher histopathologic and nuclear grade (P < 0.001). It also correlated with a molecular profile associated with biological aggressiveness: negative for Bcl-2 expression (P < 0.001), positive for the epidermal growth factor receptor (P = 0.003), and a high level of p53 (P < 0.001) and Ki-67 expression (P < 0.00). The relapse rates during the follow-up period (median 56.8 months) were 14.7% for TN breast cancer and 6.6% for non-TN breast cancer (P = 0.004). Relapse-free survival (RFS) was significantly shorter among patients with TN breast cancer compared with those with non-TN breast cancer: 3.5-year RFS rate 85.5% versus 94.2%, respectively; P = 0.001. On multivariate analysis, young age, close resection margin, and triple negativity were independent predictors of shorter RFS. TN breast cancer had a higher relapse rate and more aggressive clinicopathological characteristics than non-TN in node-negative breast cancer. Thus, TN breast cancer should be integrated into risk factor analysis for node-negative breast cancer.

Cancer biomarker HER-2/neu in breast cancer in Indian women.

AIM AND OBJECTIVES: In Indian women with breast cancer, the HER-2/neu gene is amplified in 30% of cases. Elevated serum HER-2/neu levels have been shown to be associated with a poor clinical prognosis and decreased survival in early stage breast cancer patients, and testing for this may help to manage the disease. The present study was therefore to estimate serum HER-2/neu levels in breast cancer patients and associate these with other prognostic factors. MATERIALS AND METHODS: Serum HER-2/neu levels were studied in 207 patients with breast cancer, 15 with benign breast diseases, (BBD) and 175 age-matched healthy controls. Patients' age, menopausal status, node, and estrogen receptor (ER) and progesterone receptor (PgR) status were compared with serum HER-2/neu levels. RESULTS: Serum HER-2/neu overexpression was associated with age, disease stage and positive nodal status but not with menopausal status. Serum HER-2/neu levels were negatively correlated with hormone receptor positivity. CONCLUSION: HER-2/neu serum tests should be done more frequently in Indian women with breast cancer, irrespective of their ER and PgR hormone receptor status. ELISA is a reliable and economical tool to assess the HER-2/neu status in tumors, when breast tissue samples are not available.