Effect of levofloxacin and pefloxacin on humoral immune response elicited by bovine serum albumin docked in gelatin microparticles and nanoparticles.

The aim of the present investigation was to study the effect of levofloxacin and pefloxacin on the humoral immune response elicited by bovine serum albumin (BSA) encapsulated in gelatin particulate systems. FITC-BSA (Fluoresceine isothiocynate-bovine serum albumin) was entrapped in gelatin microparticles (GM) and gelatin nanoparticles (GN) prepared by emulsion polymerization and nanoemulsion methods, respectively. The prepared particulate carriers were evaluated for particle size, surface morphology, entrapment efficiency, zeta potential and in vitro antigen release. The optimized formulation of FITC-BSA loaded GM and GN were administered s.c. to albino rats and humoral immune response was measured in terms of systemic IgG antibody titre by ELISA method. The serum IgG response elicited was compared to that was obtained by s.c. administration of either free antigen or antigen emulsified (1:1) with Freund's in complete adjuvant (FIA). The vaccination of 2.41 +/- 1.56 microm sized GM elicited significantly (P<0.05) higher serum IgG response than that obtained with administration of 107 +/- 25 nm sized GN. Similarly, levofloxacin significantly (P<0.05) decreased the antibody titre in rats immunized with BSA docked GM whereas pefloxacin did not reduce the antibody titre significantly. The study will help in programming a new drug management and in characterization of vaccine-drug interaction.

Polymorphism of glutathione S-transferase M1 and T1 gene loci in COPD.

Chronic obstructive pulmonary disease (COPD) is a complex combination of signs and symptoms in patients with chronic bronchitis and emphysema, diseases that largely result from cigarette smoking. A little information is available for the underlying molecular mechanisms that are responsible for its occurrence. Polymorphisms in genes of xenobiotics metabolizing enzymes are expected to modulate individual responses to genotoxic carcinogens. Present study was a case-control study of COPD patients and healthy controls. Genetic polymorphisms of GSTM1 and GSTT1 genes in 50 COPD patients and 50 healthy controls were investigated using multiplex polymerase chain reaction-restriction fragment length polymorphism techniques to determine whether polymorphisms of these genes are linked to genetic susceptibility to COPD. All subjects were males and smokers. The frequency of GSTM1 homozygous null genotype was 28.0% in COPD cases when compared with controls (32.0%). The difference was not significant showing that risk of COPD was not associated with the GSTM1 null genotypes. The frequencies of homozygous null genotypes of GSTT1 were significantly higher in COPD cases as compared with controls (40% versus 14.0%) suggesting that the theta-glutathione S-transferases null genotype may be associated with the susceptibility to COPD. No significant differences were observed when comparisons were performed according to severity of disease and smoking for GSTM1 and GSTT1. It was also observed that COPD developed in the early age and with a shorter pack-year history in Indian population.

An epidemiological study to identify the risk factors with two different types of controls in high-grade cervical lesions including invasive cancer.

A multidisciplinary study on pre-cancerous and early cancerous lesions of uterine cervix was carried out at our Institute from which the subjects (cases and one group of control) for the present study were selected with the objective to identify the possible risk factors related to high-grade cervical lesions including invasive cancer through an epidemiological study by selecting two different types of controls and to assess the feasibility whether the cancers of other organs could be taken as controls at the same time studying the risk factors associated with cervical cancer. One group of control was women with negative Pap smear and second group of control was the women with breast cancer but negative Pap smear. A total of 100 biopsy-proven cases of high-grade cervical intraepithelial lesions and Invasive cancer were recruited. The results of the study show that some of the risk factors associated with the cervical cancer get exaggerated when breast cancer cases were used as controls because risk factors of both cancers are opposite to each other. So it is concluded that in order to remove any bias, normal hospital controls or controls selected from multiple cancers should be taken to study the risk factors involved in cervical carcinogenesis.

Prevalence of high-risk human papillomavirus type 16/18 infection among women with normal cytology: risk factor analysis and implications for screening and prophylaxis.

OBJECTIVE: To determine the prevalence of high-risk human papillomavirus (HR-HPV) 16/18 infection of uterine cervix among women in the reproductive age group, with cytologically normal cervical (Pap) smears; to analyse the risk factors for HR-HPV acquisition and to address their implications for cervical cancer screening and prophylaxis in a low resource setting. METHODS: Cervical samples from 769 cytologically negative women (age 18-45 years) attending a tertiary care centre in Delhi were subjected to HPV DNA testing and HR-HPV 16/18 and low-risk (LR)-HPV 6/11 sub-typing by polymerase chain reaction. Univariate risk factor analysis was carried out in HR-HPV positive (n = 86) versus HR-HPV negative women (n = 683) by chi-square test. RESULTS: The overall HPV prevalence among cytologically normal women was 16.6%. HR-HPV16 was detected in 10.1%, whereas HPV18 was detected in 1% of women. HR-HPV 16/18 comprised 67% of the total HPV positives. There was no decline in HR-HPV positivity with age, and women aged 40-44 years were at significantly increased risk for HR-HPV prevalence (P = 0.03). Statistically significant associations of HR-HPV infection were found with risk factors such as high parity (P = 0.04), cervicitis/hypertrophic cervix (P = 0.01), unhealthy cervix (P = 0.04), rural residence (P = 0.03), low socioeconomic status (P = 0.01) and illiteracy (P = 0.07). CONCLUSIONS: Although the sample size was small, based on the observation that HR-HPV 16 and 18 contributed significantly to the overall HPV prevalence in our setting, we speculate that testing/prophylaxis for these prevalent high-risk types could perhaps make cervical cancer screening and preventive programmes cost-effective. Larger community-based studies on HPV prevalence and persistence are required to validate these findings before definitive recommendations can be made to the policy makers.

Genetic polymorphism at GSTM1 and GSTT1 gene loci and susceptibility to oral cancer.

GSTs are phase II enzymes which are involved in the detoxification of active metabolites of many potential carcinogens from tobacco smoke and therefore may play an important role in modulating susceptibility to tobacco related cancers. This study evaluates the influence of genetic polymorphisms of GSTM1 and GSTT1 gene loci on susceptibility to oral cancer. The genotyping was based on multiplex PCR assay that identified the GSTM1 and GSTT1 null (-/-) genotypes but didn't distinguish homozygous wild type+/+ and heterozygous +/- individuals. Genomic DNA was isolated from cases with oral cancer (n=40) and normal controls (n=87). The prevalence of the GSTM1 null genotypes was 29/87 (33.3%) and 21/40 (52.5%) in controls and oral cancer cases, respectively but the differences were not significant (OR=2.2; 95%CI=0.96-5.1; p=0.06). The frequency of homozygous GSTT1 null genotype in cancer cases was 17/40 (42.5%) as compared to 13/87 (14.94%) in controls and the differences were highly significant (OR=4.2; 95%CI=1.64-10.9; p=0.0002). Oral cancer cases had higher proportion of both GSTM1 and GSTT1 null genotypes as compared to controls but the differences were not statistically significant (OR=2.9; 95%CI=0.71-11.9; p=0.17). When individuals were categorized into two groups, no differences were observed for GSTM1 null genotype frequencies in control and cancer cases (OR=2.9; 95%CI=0.9-9.6; p=0.08) (OR=1.6; 95%CI=0.44-6.1; p=0.58) in <=50 yrs and >50 yrs of age groups. Significant differences between control and cancer cases were observed for GSTT1 null genotypes both in <=50 yrs and >50 yrs of age groups (OR=4.0; 95%CI=1.1-15.0; p=0.03) (OR=4.5; 95%CI=0.97-22.29; p=0.05), respectively. The effect of smoking on GSTM1 null individuals was not found significant (OR=1.0; 95%CI=0.19-4.86; p=0.75) but it was significant in case of GSTT1 null individuals (OR=6.33; 95%CI=1.0-44.1; p=0.02). Our results thus suggest that GSTT1 gene polymorphisms modulate susceptibility to tobacco-related cancer of the oral cavity.

Wound healing following refractive surgery in hens.

The wound-healing response is critical to the outcome of refractive surgery and studying wound healing contributes to an understanding of the pathophysiology of other corneal injuries. Animal models allow research to be conducted with sufficient samples and under controlled parameters. We studied the hen to determine the healing process from clinical, biophysical, and biological standpoints after photorefractive keratectomy (PRK). PRK (-6.0 diopters) was performed in hen eyes. At 3, 6, 12, 24, 48, and 72 h and 5, 7, 15, 30, and 60 days postoperatively, we studied the clinical follow-up, objective measurements of light transmission (direct transmittance), apoptosis by TUNEL assay, proliferation by immunocytochemical analysis of 5-bromo-2'-deoxyuridine, and expression of alpha smooth muscle actin (SMA) in myofibroblasts in the corneas. Hen corneas reepithelialize quickly. Haze developed from 5 to 60 days after surgery and was correlated with the appearance and finalization of the expression of SMA. The direct transmittance of light was low during the first 15 days and improved at 30 and 60 days. TUNEL-positive cells were observed 3 h after surgery and the numbers decreased thereafter. Epithelial proliferation began at 12 h and was greater at 48 h, while stromal cell proliferation began at 24 h and was greater at 72 h. The hen cornea is anatomically similar to the human cornea, and the manner in which it heals is a good model for studying different surgical techniques and pharmacologic assays.

Rapid rescreening of cervical smears by cytopathologists: experience at a WHO collaborating centre for research in cytology.

The conventional 10% random full rescreening of cervical smears has been criticized as a quality assurance measure as it is not scientifically based and tends to detect only a few false negative cases. Rapid rescreening (RR) of negative cervical smears seems to be a viable alternative, especially in developing countries, as it picks up more positive lesions, reduces the false negative rate and is cost effective. We performed rapid review on 12374 cervical smears received under a hospital based cervical cancer screening programme. An additional 498 lesions were picked up on RR including a sizeable number of low and high grade lesions as well as 2 malignant cases. Thus RR led to an increase in efficiency of our laboratory.

Predicting anticonvulsant activity of benzamides/benzylamines: computational approach using topological descriptors.

The relationship of Wiener's index (a distance-based topological descriptor), Zagreb group parameter (an adjacency-based topological descriptor) and eccentric connectivity index (an adjacency-cum-distance-based topological descriptor) with the anticonvulsant activity of a series of substituted benazamides/benzylamines has been investigated. A training set comprising 41 analogues of substituted benazamides/benzylamines was selected for the present investigations. The values of the Wiener's index, Zagreb group parameter and eccentric connectivity index and of each of 41 analogues comprising the data set were computed and active ranges were identified. Subsequently, a biological activity was assigned to each analogue involved in the data set which was then compared with the reported anticonvulsant activity. An exceptionally high accuracy of predictions ranging from a minimum of approximately 88% for the Zagreb group parameter to a maximum of approximately 97% for Wiener's index were obtained.

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.

Reduction in the cumulative incidence rate of cervical cancer by one life time selective screening.

Mass scale cervical cytology which is the most accepted strategy for the control of cervical cancer cannot be undertaken in developing countries in view of paucity of resources, hence a need arises to examine alternate strategy. The present exercise attempts to study the reduction in cumulative incidence rate of cervical cancer by one life time selective screening. The results revealed that cumulative incidence rate (CIR) of cervical cancer per 100,000 in cohort of women during the age of 20 to 64 years was found to be 2555.0 in the absence of screening. One life time selective screening at the age of 40 and 45 years showed the reduction of 11.6 and 17.2% in CIR respectively where as respective estimates in case of complete screening at mentioned age groups were found to be 21.5% and 25%. In order to further conserve the resources the strategy seems to be optimum for developing countries.

Biological behaviour of moderate dysplasia--a prospective study.

The present communication reports the biological behaviour of women with moderate dysplastic lesions of uterine cervix based on a long term prospective study. Two hundred and thirty nine women with moderate dysplasia by cervical cytology who satisfied the criteria for registration were longitudinally followed up at 3 +/- 1 monthly intervals along with age and parity matched controls for a period ranging from 4 to 132 months. The cumulative rate of progression from moderate dysplasia to malignancy (CIS) was observed to be 23.0% at the end of 72 months of follow up with mean transition interval of 24.2 months. Out of 239 cases, 142 women who had more than 24 months of follow up were considered for studying the biological behaviour of the lesion. It was observed that during a follow up of 132 months, 14(9.9%) and 15(10.6%) women progressed to carcinoma in-situ and severe dysplasia respectively. The persistence of lesion was observed in 21(14.8%) women while 11(7.3%) and 81(57.0%) regressed to mild dysplasia and normalcy respectively.

Epidemiologic analysis of Trichomonas vaginalis infection in inflammatory smears.

Infections of the lower reproductive tract are common in Indian women of reproductive age. Hospital-based cytologic screening was undertaken on 63,265 women. The smears were examined for the presence of specific infections, such as Candida, herpes simplex virus, human papillomavirus, Trichomonas vaginalis (TV) and Chlamydia. This paper highlights the prevalence of TV infection in inflammatory cervical smears. Among the various infections detected, the rate of TV infection was the highest (5.1%). On further analysis the rate of TV infection showed an increasing trend up to the age of 49 years; an inverse association was observed with the educational status of the women. The prevalence was high in women with clinical signs (vaginitis, 6.9%) and low in those with a prolapsed uterus (1.2%) as compared to a normal cervix. These observations reveal the need for providing proper counseling and education on sexual behavior and genital hygiene besides treatment to control and prevent these infections.

Role of male behavior in cervical carcinogenesis among women with one lifetime sexual partner.

BACKGROUND: The role of male behavior in the genesis of cervical cancer was examined. In India, where the incidence of cervical cancer is among the highest in the world, promiscuity among women is virtually unknown. In this study, the authors investigated the role of male behavior in cervical carcinogenesis among Indian women who had one lifetime sexual partner. METHODS: A case-control study was used. RESULTS: Premarital sexual relationships (relative risk [RR], 1.9; confidence interval, 1.2-3.2) and extramarital sexual relationships (RR, 2.7; confidence interval, 1.5-4.9) of husbands were risk factors. When husbands had sexual relationships both before and during the marriage, their wives' risk of getting cervical cancer increased by 6.9 (CI, 2.3-20.7). Risk also increased with husbands having three or more extramarital sexual partners (RR, 3.05; CI, 1.25-12.6). Sexual contact with prostitutes before or after marriage, however, did not increase the risk. History of sexually transmitted disease before marriage (RR, 2.9) or after marriage (RR, 5.9) was an important risk factor, which persisted after controlling for other factors. Sexual abstinence for 40 or more days after a wife's giving birth or having an abortion provided protection. Sex with uncircumcised men or men circumcised after age 1 year increased the risk of cervical cancer (RR, 4.1). Bidi smoking (bidi is a cheap smoking stick of 4-8 cm, consisting of a rolled piece of dried temburni leaf [Diospyres melanoxylon] containing 0.15-0.25 g of coarsely ground tobacco) for more than 20 years was a significant risk factor (RR = 2.4), whereas cigarette smoking was not a risk factor. CONCLUSIONS: Male sexual partners play a role in cervical carcinogenesis.

Quantitative analysis of nuclear area variation in benign and malignant breast fine needle aspirates.

The measurement of nuclear area was carried out in 30 benign and 32 malignant breast lumps using Omnicon Alpha 500 Image Analyzer. The mean nuclear area of duct cells in malignant group was greater (157.6 +/- 58.64 sq.microns with a peak around 140 sq.microns) and more heterogenous within and amongst cases than observed in duct cells from most of the cases of fibroadenoma (85.05 ae 14.2 sq.microns with a peak around 80 sq.microns). Taking into consideration 110 sq.microns as a differentiating limit, a significant difference was observed between benign and malignant conditions (p). Similarly taking 118 sq.microns as differentiating limit duct cell carcinomas could be divided into two groups i.e. 9(28.1%) cases of small nuclear type with a range of 80-118 sq.microns and 23(71.9%) cases of large nuclear type with a range of 118-320 sq microns .6(18.8%) cases with small nuclei had an overlap with fibroadenoma. Although 13(72.2%) cases of large nuclear type carcinomas had lymph node metastasis as against 4(44.4%) in small nuclear group, the difference was not statistically significant.

Influence of the lamp windows in end-on measurements of the refractivity in a pulsed plasma.

During measurement of the refractivity of a pulsed plasma, we have detected, with the help of a Jaminlike interferometer, the optical path variation caused by lamp windows. We attribute this variation to two causes: mechanical vibration and the slow cooling that follows the sharp heating. We conclude that neither has any influence on the measurement of plasma refractivity.