QSAR Rationale of Matrix Metalloproteinase Inhibition Activity in a Class of Carboxylic Acid Based Compounds.

The matrix metalloproteinase-13 (MMP-13) inhibitory activities of carboxylic acid based compounds, in presence and absence of bovine serum albumin (BSA), have been analyzed quantitatively in terms of chemometric descriptors. The statistically validated quantitative structure-activity relationship (QSAR) models obtained through combinatorial protocol in multiple linear regression (CP-MLR) analysis and the participated descriptors in these models provided rationales to explain the inhibitory activities of these congeners. For MMP-13 inhibition activity, the identified descriptors (BEHm1, BELm1 and BEHm8) have highlighted the role of the atomic mass in terms of the highest and lowest eigenvalues derived from Burden matrix. The positive correlation with activity suggested that their higher values are desirable in improving the activity of a compound. Additionally, the descriptor C-027 representing R-CH-X type fragment in a molecular structure advocates the absence of such type of fragment for the improved activity. On the other hand presence of RCO-N< or >N-X=X type fragment (descriptor N-072) would be beneficiary to the MMP-13 inhibitory activity. The structural features, rationalized by the descriptors MSD (Balaban’s mean square distance index), nCrHR (number of ring tertiary C (sp3), H-047 (H attached to C1(sp3)/C0(sp2)) and H-050 (H attached to heteroatom) have imparted positive impact on the MMP-13 w/BSA inhibition activity. The atomic properties such as atomic polarizability and atomic Sanderson’s electronegativity have shown their positive impact on the activity via descriptors BELp4 and GATS3e in respective eigenvalues or lag. The other descriptors, MATS1m and MATS3e, have revealed the negative influence of atomic mass and electronegativity on the of MMP-13 w/BSA inhibition activity. The results obtained from CP-MLR analysis have been supported further through partial least-squares (PLS) study.

Traditional healing practice and folk medicines used by Mishing community of North East India.

Assam and Arunachal Pradesh have very rich tradition of herbal medicines used in the treatment of various ailments. Tribal communities practice different types of traditional healing practices. Enough documentation is available on the healing practices in other tribal communities except Mishing community of Assam and foot hill of East Siang district of Arunachal Pradesh hence the attempt was made for the same. A survey on folk medicinal plants and folk healers of Mishing tribe was conducted in few places of Lakhimpur and Dhemaji district of Assam and East Siang district of Arunachal Pradesh, where this ethnic group is living since time immemorial. All information was collected based on interview and fi eld studies with local healers within the community. The identifi cation of medicinal plants collected with help of indigenous healers was done. Such medicines have been shown to have signifi cant healing power, either in their natural state or as the source of new products processed by them. This study is mainly concentrated with plants used to cure diseases and to enquire about different healing systems. Detail note on the method of preparation of precise dose, the part/parts of plants used and method of application is given.

Demographic and clinical profile of oral squamous cell carcinoma patients: A retrospective study.

Background: Oral cancers are one of the ten leading cancers in the world. However, in India, it is one of the most common cancer and constitutes a major public health problem. Aim: The purpose of this study was to evaluate, retrospectively, the epidemiologic profile of patients with oral squamous cell carcinoma (OSCC). Materials and Methods: OSCC cases were retrospectively analyzed from January 2008 to September 2010 for age, gender, occupation, duration of the symptoms, habits (tobacco and alcohol consumption), site of primary tumor, and TNM staging, and the findings were formulated to chart the trends in central India population. Results: Male to female ratio was 4.18:1. Mean age was 49.73 years. The most common site of presentation of tumor was in mandibular alveolus region. Tobacco chewing was the major cause for the development of OSCC. Maximum number of patients, i.e., 201 (68.14%) were presented within 6 months of onset of symptoms. Majority of patients were presented in Stage III (82.37%). Correlation between the two variables, i.e., site to habits, staging to site involved, staging to duration of the disease, staging to habits, and staging to age of the patient, were found to be statistically nonsignificant (P>0.05). Conclusions: The aim of the study was the demographic description of oral squamous cell carcinoma. Most of the cases report at advanced stages of the disease which often leads to delay in the management coupled with the fact that health care centers are burdened with long waiting lists. Strategies to overcome the present situation must be undertaken by oral health programs for the early diagnosis and prevention and management and follow up of oral cancer.

Antimalarial plants of northeast India: An overview.

The need for an alternative drug for malaria initiated intensive efforts for developing new antimalarials from indigenous plants. The information from different tribal communities of northeast India along with research papers, including books, journals and documents of different universities and institutes of northeast India was collected for information on botanical therapies and plant species used for malaria. Sixty-eight plant species belonging to 33 families are used by the people of northeast India for the treatment of malaria. Six plant species, namely, Alstonia scholaris, Coptis teeta, Crotolaria occulta, Ocimum sanctum, Polygala persicariaefolia, Vitex peduncularis, have been reported by more than one worker from different parts of northeast India. The species reported to be used for the treatment of malaria were either found around the vicinity of their habitation or in the forest area of northeast India. The most frequently used plant parts were leaves (33%), roots (31%), and bark and whole plant (12%). The present study has compiled and enlisted the antimalarial plants of northeast India, which would help future workers to fi nd out the suitable antimalarial plants by thorough study.

Assessment of hand pump waters in three tribal dominated districts of southern Rajasthan, India.

Udaipur, Banswara and Dungarpur districts of southern Rajasthan (India) have dominance of tribal population. In these districts besides other water resources, hand pumps are catering the need for drinking water. The present study was undertaken to assess the level of chemical and bacteriological status for comparing the water quality with the prevailing standards. 18 hand pumps were studied for selected water quality parameters such as, pH, hardness, chloride, fluoride, NO3 -N, EC, orthophosphate, TDS, TSS, BOD, total coliforms and faecal coliforms, following the standard methods. The data on chemical parameters revealed that in all 18 hand pumps the water quality was within the permissible level of WHO. However, in eight hand pumps the faecal coliforms were higher (2-6 MPN/100 mL) than the permissible limit which confirm organic contamination in these drinking water resources. On the basis of this study, suitable remedial measures for protection of water quality have been suggested.

Recharging of borewells and analysis of harvested rooftop rainwater in houses of Udaipur city.

Water is an inorganic component, which covers about 3/4th of the earth's surface, but only 3 percent of it is available to man for use. The remaining 97 percent of water found in oceans is full of soluble salts, being unfit for human use and consumption. Rainwater is free source of nearly pure water. The concept of rainwater harvesting lies in tapping the rainwater it falls. The present study was conducted in houses of Udaipur city. In order to find out the water management practices adopted by the families, a sample of 100 households was selected. Out of the total samples, 30 houses were selected purposively for commissioning the rainwater harvesting system and the rooftop rainwater harvesting potential was also calculated among these 30 households. Field experiment was conducted for quantitative analysis of harvested rooftop rainwater in houses which reveals that rooftop rainwater harvesting system is very effective measure in increasing the quantity of water in borewells as compared to those borewells without having the rainwater harvesting system attached to them. The availability of water per day was found to be higher i.e. 269 litres in those houses where the rainwater harvesting potential was also higher i.e. 98.32 m3, as the catchment area of these houses was found to be more (186 sq m.) as compared to other houses.

Distribution of prognostically unfavourable product of c-erbB-2 oncogene and EGF-R in carcinomas of the breast and uterine cervix.

A comparative study was undertaken between cancer of the uterine cervix (n = 50) and female breast cancer (n = 50) with reference to the expression of c-erbB-2 oncoprotein (HER-2/neu) and that of epidermal growth factor receptor (EGF-R), both being highly homologous structurally. Expressions of EGF-R and c-erbB-2 oncoprotein were viewed in breast and cervical cancer tissues by immunochemical staining. Cervical cancer cases showed much higher expression of EGF-R which also revealed significant association with the expression of c-erbB-2 oncoprotein and tumour grading. Among breast cancer cases, over-expression of EGF-R correlated significantly with metastasis of lymph node; and expression of c-erbB-2 oncoprotein showed a significant relationship with histological grading of the tumour. Moreover, an association was noticed between the tumour grade and the concomitant immuno positive expression of EGF-R and c-erbB-2. Our study revealed an existence of a conflicting pattern in the expression of EGF-R and c-erbB-2 oncoprotein between carcinomas of the breast and uterine cervix.

Time trends in the prevalence of hypertension and associated risk factors in Chandigarh.

To estimate the changes in the prevalence of hypertension and associated risk factors over a 30 years period a cross-sectional population survey in three randomly selected sectors of Chandigarh city was carried out. Study population consisted of 1181 individuals (570 males and 611 females) aged 35 years and above. A total of 1049 subjects were interviewed using a structured interview schedule, and 937 were examined by a physician. Blood pressure and anthropometric measurements were recorded. Physical activity was graded according to the job performed by the individual. Guidelines of the Fifth Joint National Committee (JNC-V) of USA were used for diagnosis of hypertension. Estimation of body fat from skin fold thickness was done by applying Grande's formula and the method of Pascale et al. Data were compared to that of year 1968 when a similar cross-sectional survey had been carried out in Chandigarh. Age and sex standardised prevalence of hypertension according to JNC-V criteria increased from 26.9 per cent in 1968 to 44.9 per cent in 1996-97. In 1968, 70% of the male population were engaged in sedentary and light physical activity compared to 73.7 per cent in 1996-97. Total body fat has increased in both men and women. High and high middle income groups in males were 61.2% in 1996-97 compared to 37.4% in 1968. Smoking rates, however, remained unchanged, 25.4 per cent men smoked in 1968 compared to 24.6 per cent in 1996-97. The prevalence of hypertension has almost doubled over 30 years in Chandigarh. Unfavourable change in prevalence of hypertension, physical activity and body fat makes this population highly vulnerable to cardiovascular morbidity and mortality.

Effect of cancer treatment modalities on serum lipids and lipoproteins among women with carcinoma of the breast.

Serum lipids and lipoproteins were studied in 61 breast cancer patients before initiation of therapy and subsequently during and after completion of cancer therapy. Different serum lipid fractions were estimated by enzymatic method. It was observed that mean levels of serum triglycerides, total cholesterol and low density lipoprotein (LDL)-cholesterol among untreated breast cancer patients decreased significantly after treatment. On the contrary, an increasing trend in the levels of high density lipoprotein (HDL)-cholesterol was noticed in patients during the course of treatment. This study reflects the effects of cancer therapy in the alteration of levels of different serum lipid fractions in the patients with breast cancer.

Oncoprotein c-erbB-2 in squamous cell carcinoma of the uterine cervix and evaluation of its significance in response of disease to treatment.

Tissues from 50 cases of squamous cell carcinoma of the uterine cervix were analysed for immunohistochemical expression of c-erbB-2 oncoprotein and the patients were followed-up for 2 years. Immunopositivity of c-erbB-2 was studied with reference to clinical stage, histopathological differentiation and response to the cancer therapy. Expression of c-erbB-2 protein was found to be higher (37.5%) in cases with stage II disease, whereas more expressions were noticed in poorly differentiated squamous cell carcinoma (33.3%). Among cases who showed complete response to the treatment, 20.8% were positive for c-erbB-2 oncoprotein. On the contrary, 36.8% of prognostically unfavourable cases revealed positivity for c-erbB-2 immunostaining. However, the difference between c-erbB-2 expressions of these two said groups of patients, which were divided in accordance with the response to treatment, did not attain to statistical significance. Study on c-erbB-2 among larger number of patients with cervical carcinoma may prove to be an important factor in response to cancer therapy.

Meningococcal meningitis outbreak control strategies.

Meningococcal meningitis has been occurring worldwide in both endemic and epidemic forms. Serogroup A accounts for majority of cases of epidemic as well as endemic Meningococcal meningitis in developing nations, whereas group C and group B causes epidemic and endemic meningococcal meningitis in developed countries. Person to person spread of N. meningitides generally occurs through inhalation of droplets of infected nasopharyngeal secretions by direct or indirect oral contact. Incubation period varies from 2 to 10 days. N. meningitides typically causes acute infective illness characterized by sequential development of upper respiratory tract infection, meningococcemia, meningitis and focal neurological deficit. Over 90 per cent cases of adult meningococcal infections have cerebrospinal meningitis, whereas in children prevalence of meningitis is much lower (50 per cent). Acute meningitis manifests with fever, severe headache, vomiting and neck stiffness. Presentations may be non-specific in infants, elderly and in patients with fulminant meningococcemia. Diagnosis is confirmed with cerebrospinal fluid analysis. Overall mortality due to meningitis is usually around 10 per cent. In meningococcal septicemia, the case fatality rate may exceed 50 per cent. Preventive strategies include vaccination, chemoprophylaxis and early detection and treatment. Mass vaccination campaign, if appropriately carried out, has been documented to halt an epidemic of meningococcal disease due to serogroup A or C. In the present review we have discussed the available evidence with regards to prevention at primary, secondary and tertiary level. Public health approach to an outbreak of meningococcal meningitis in a community or an organization is also outlined.

Adrenocorticotropic hormone and growth factor receptors in breast cancer.

Tissues from 100 cases of breast cancer were analysed immunohistochemically for the presence of adrenocorticotropic hormone (ACTH) or ACTH-like peptides and expression of c-erbB-2 oncoprotein, epidermal growth factor receptor (EGF-R) as well as oestrogen receptor (ER). Immunopositivity for ACTH was found in 15% cases of infiltrating duct carcinoma of the breast, whereas 38% and 36% breast tumours were positive for c-erbB-2 and EGF-R respectively. While 27% cases were positive for ER. The immunoexpressions of all parameters were higher in breast cancer cases with upper age group (45 years or above) than the patients below 45 years of age. A significant correlation was observed between the tumour grade and the expression of c-erbB-2 oncoprotein. Further, a positive association between the immunoexpression of c-erbB-2 and EGF-R was noticed. Interestingly, a statistically significant relationship was found between the immunopositivity of ACTH and ER. The study reflects a probable association of ACTH or ACTH-like peptides in pathological process of breast cancer.

Glutathione level and its relation to radiation therapy in patients with cancer of uterine cervix.

Glutathione functions as an important antioxidant in the destruction of hydrogen peroxide and lipid peroxides by providing substrate for the glutathione peroxidase and also promotes the ascorbic acid. Glutathione plays a vital role in detoxification of xenobiotics, carcinogens, free radicals and maintenance of immune functions. The study was aimed to determine plasma glutathione as well as erythrocyte glutathione and glutathione peroxidase in patients with invasive cervical carcinoma (n = 30) before initiation and after completion of radiotherapy and subsequently, at the time of first three monthly follow-up visit. The levels of plasma glutathione, erythrocyte glutathione and glutathione peroxidase activity were found to be lower in all cervical cancer patients as compared to age matched normal control women. The study indicates a change in antioxidant status in relation with the glutathione system among patients with invasive carcinoma of the uterine cervix. This study also demonstrates the effect of radiation therapy on this antioxidant system.

Immunohistochemical co-expression of c-erbb-2/Neu oncoprotein, altered tumour suppressor (p53) protein, EGF-R and EMA in histological subtypes of infiltrating duct carcinoma of the breast.

Carcinoma of the breast has an unpredictable biological behaviour. Several oncogenes have been implicated in the progression of breast cancer. Immunohistochemical staining of c-erbB-2 (Neu) oncoprotein and mutant p53 protein on 45 cases of infiltrating duct carcinoma (IDC) of the breast revealed 33% membrane positivity of c-erbB-2 oncoprotein, 46% nuclear positivity of mutated p53 protein, 33% and 84% membrane positivity of EGF-R and EMA respectively. Staining profile of c-erb-B2 oncoprotein in various histological subtypes of IDC of the breast indicated a high positivity rate in comedo followed by NOS and cibriform subtype. Similarly, high incidence of immunopositivity of mutated p53 protein was observed in comedo and cibriform subtypes while papillary carcinoma were found exclusively positive for mutated p53 protein. Interestingly, tubular subtype of IDC was not positive for c-erbB-2 oncoprotein as well as p53 mutant protein. Further, comedo and cibriform subtypes of IDC revealed 'high grade' histological features of tumour of the breast with high mitotic count, presence of marked pleomorphism and multinucleation thus, reflecting a positive relationship with overexpression of c-erbB-2 (Neu) oncoprotein as well as mutant p53 protein. The results on immunoexpression of c-erbB-2 oncoprotein and mutated p53 protein in various histological subtypes of IDC of the breast demonstrated c-erbB-2 status as an important predictor and also indicated that oncogene product may be involved in growth factor response pathway.

Hypertension and the kidneys--inter-relationship and therapeutic approach.

Over the last decade, a great body of evidence has pointed towards the role of kidneys in the genesis and maintenance of a hypertensive state. There exists a relationship between a rise in the blood pressure and a proportionate increase in the urinary excretion of sodium and water called the pressure-natriuresis curve. Chronic renal diseases are the most common causes of secondary hypertension accounting for 2-5% of all cases of secondary hypertension. The prevalence rate of renovascular hypertension based upon referral patterns range from 0.2% to 10% of hypertensive population. The data provided by the International Registries on end-stage renal disease have suggested that essential hypertension is an important cause of progressive renal damage. The pathological lesion observed in malignant hypertension is fibrinoid necrosis of the small arteries and arterioles. Amongst the armamentarium of antihypertensive drugs calcium channel antagonists and the angiotensin converting enzyme inhibitors have a role in limiting glomerular hypertension. The best modality to prevent and treat renal dysfunction in the presence of hypertension is an adequate and effective control of high blood pressure.

Prevalence of serum antibodies to LA-1 oncoprotein, herpes simplex virus type-2 glycoprotein and human papillomavirus type 16 transactivator (E2) protein among Indian women with cervical neoplasia.

Prevalence of serum antibodies to synthetic peptide to oncoprotein of LA-1 known as oncogene of herpes simplex virus type-2, herpes simplex virus type-2 glycoprotein-D as an determinant of viral pathogenicity and human papillomavirus type 16 transactivator E2 protein was studied among 46 Indian women with cervical neoplasia using immunoblot assay for HSV-2 gD glycoprotein and LA-1 antibodies as well as peptide ELISA assay to detect HPV16 E2 antibodies. The seropositivity to LA-1 oncoprotein was found to be high (61%) among patients with invasive cervical carcinoma as compared to 35% in various grades of cervical intraepithelial neoplasia (CIN) and 36% in normal control women. In contrast to this, a uniformly high frequency of antibody to HPV 16 E2 was observed among women with CIN (68%), normal healthy controls (50%) and invasive cervical carcinoma (43%). However, a low frequency of seropositivity (13%) to recombinant vaccinia virus HSV-2 gD protein was found among 15 tested sera each from group of women with various grades of CIN as well as invasive cervical carcinoma as compared to 28% among seven normal healthy control. A negative correlation of LA-1 and HPV16 E2 seropositivity on patient by patient comparison among CIN and invasive cervical carcinoma group was observed which is statistically significant (P = 0.019 for CIN; P = 0.038 for invasive cervical carcinoma). However, a positive correlation (P = 0.144) was found among normal control women. The study has shown a desirable serological marker of cervical neoplasia. This serological marker could be employed as a screening tool in conjunction with cytopathological screening to diagnose women harbouring LA-1 oncogene associated cervical lesions.

Immunoexpression of mutant p53 and human papillomavirus related E6 oncoprotein in anal malignancies.

Immunohistochemical expression of mutant p53 protein and human papillomavirus (HPV) 16 and 18 related E6 oncoprotein was studied in 36 biopsy proved anal cancers. Mutant p53 was detected in 61.1% cases. HPV 16 and 18 E6 protein was expressed in 22.2% cases, all of which were squamous cell carcinomas. Coexpression of both mutant p53 and E6 protein was found in only 5 cases (13.8%). In HPV 16/18 positive anal tumors, the degradation of p53 is accelerated by viral E6 oncoprotein. In HPV negative tumors, however, other mutagenic factors probably play a role in carcinogenesis.

Immunohistochemical co-expression of human papillomavirus type 16/18 transforming (E6) oncoprotein and p53 tumour suppressor gene proteins in oesophageal cancer.

Human papillomaviruses have been widely implicated as important etiologic agents in various squamous cell carcinomas including oesophageal carcinoma. p53 mutant oncoprotein has also been implicated in various tumours. Immunohistochemical analysis was employed to detect the co-expression of HPV and p53 mutant protein in biopsy specimens of patients of cancer oesophagus as well as controls. This analysis revealed a significantly higher immunopositivity (63%) of E6 oncoprotein of HPV 16/18 in carcinoma of the oesophagus. Immunoexpression of E6 oncoprotein of HPV did not alter significantly the degree of differentiation of the tumour. Seventy-seven percent of cases of oesophageal carcinoma showed strong immuno-staining for mutant p53 protein. A higher percentage (89%) of tissues showed immunoexpression of mutant p53 protein in conjunction with E6 oncoprotein of HPV 16/18 indicating a selective degradation of key cellular protein of p53 having regulatory properties which in turn leads to uncontrolled cellular proliferation. Therefore, coexpression of oncoprotein E6 of HPV 16/18 and mutant p53 protein may be considered as a "high risk" factor for progression to oesophageal malignancy.

Comparison of two substrates in determination of plasma cholinesterase activity & genetic variability.

Two substrates, acetyl thiocholine iodide ATCI and benzoylcholine chloride BCC were compared for the determination of plasma cholinesterase ChE levels and after incorporation of dibucaine and sodium fluoride in the assay, their usefulness in determining plasma ChE genetic variability was assessed in 64 healthy subjects. With both substrates, plasma ChE levels were found to be in the reference range. However, ATCI could detect only two variants with the usual phenotype UU in 60 of 64 [93.75%] subjects whereas with BCC 6 different groups could be determined. Though both substrates are of equal value in estimation of plasma ChE levels, BCC is definitely superior in determining its genetic variants.

Normal spirometry in healthy natives of Bhutan.

We performed spirometry on 333 healthy Bhutanese men and women at Thimpu. Prediction equations were derived using age and height as regression coefficients. Age had a significant negative correlation while both height and weight had positive linear correlation with spirometric indices. The relationship of weight with FVC was explained largely on the basis of the "muscularity" effect of weight. Bhutanese have lower ventilatory parameters than the Europeans and the North Indians. The difference is likely to be ethnic in origin.