Free radicals hasten head and neck cancer risk: A study of total oxidant, total antioxidant, DNA damage, and histological grade.

BACKGROUND: Free radicals such as reactive oxygen species (ROS), which induce oxidative stress, are the main contributors to head and neck carcinogenesis (HNC). The present study was conducted with the aim to assess the oxidant/antioxidant status and DNA damage analysis in head and neck cancer/control patients. MATERIALS AND METHODS: This prospective study was conducted on 60 patients with biopsy-proven HNC and 17 patients of head and neck disease (HND). The total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI) were determined by novel automatic colorimetric methods from tissue homogenate. DNA damage analysis was determined by single cell gel electrophoresis (SCGE). RESULTS: The mean age of the study cohort was 46.65 ± 14.84 years for HNC patients, while it was 49.41 ± 13.00 years for HND patients. There were no significant differences found between the two groups with respect to demographic presentation except tobacco addiction. The association between oxidative stress parameters and DNA damage analysis with study group revealed the following. (A) DNA damage - tissue homogenate TOS and OSI were significantly higher in HNC subjects than in HND (16.06 ± 1.78 AU vs 7.86 ± 5.97 AU, P < 0.001; 53.00 ± 40.61 vs 19.67 ± 21.90, P < 0.01; 7.221 ± 5.80 vs 2.40 ± 2.54, P < 0.01, respectively), while TAS was significantly decreased. (B) Aggressive histological features were identified, more commonly with higher TOS and lower TAS [probability (P) = 0.002, relative risk (RR) = 11.838, 95% confidence interval CI = 2.514-55.730 and P = 0.043, RR = 0.271, 95% CI = 0.077-0.960, respectively]. CONCLUSION: The increase in free radicals may be the event that led to the reduction of antioxidant status in HNC, thus explaining the oxidative damage of DNA and the severity of disease. Increased OSI represents a general mechanism in its pathogenesis.

A clinical study on cortisol and certain metabolites in some chronic psychosomatic disorders.

Present clinical study involved two groups of psychosomatic disorders, bronchial asthma and rheumatoid arthritis. In the study, the levels of plasma cortisol, blood glucose, total cholesterol and triglycerides were estimated in 125 clinical subjects, (50 normal controls, and 40 having bronchial asthma and 35 suffering from rheumatoid arthritis. The results showed a significant change in the levels of plasma cortisol and blood glucose in both the stressed clinical groups' vis-à-vis normal controls. The levels of atherogenic lipids (total cholesterol and triglycerides) were found quite elevated in both the diseased groups. However, in rheumatoid arthritis, the physiological changes were relatively more pronounced. The findings of this study indicate that rheumatoid arthritis is a relatively more chronic and late onset disorder as the functional performance of hypothalamopituitary-adrenocortical axis gradually declines with passage of time and the ability of the adrenocortical response to return to normalcy becomes impaired.

Visceral leishmaniasis (kala-azar): challenges ahead.

Indian visceral leishmaniasis (VL) is a parasitic disease caused by a haemoflagellete Leishmania donovani and transmitted by the bite of sand fly Phlebotomus argentipes. It affects various age groups. In India about 1,00,000 cases of VL are estimated to occur annually; of these, the State of Bihar accounts for over than 90 per cent of the cases. Diagnosis of VL typically relies on microscopic examination of tissue smears but serology and molecular methods are better alternatives currently. Notwithstanding the growing incidence of resistance, pentavalent antimony complex has been the mainstay for the treatment of VL during the last several decades. The second line drugs such as amphotericin B, lipid formulations of amphotericin B, paromomycin and recently developed miltefosine are the other alternatives. In spite of significant development in various areas of Leishmania research, there is a pressing need for the technological advancement in the understanding of immune response, drug resistance and the pathogenesis of leishmaniasis that could be translated into field applicable and affordable methods for diagnosis, treatment, and control of the disease.

Role of butorphanol and ondansetron premedication in reducing postoperative shivering after general and spinal anesthesia: A randomized comparative study from North India.

BACKGROUND: Postoperative shivering (PAS) is a common problem following general and spinal anesthesia and may lead to multiple complications. This placebo-controlled, randomized study was performed to evaluate the efficacy of Ondansetron and butorphanol premedication reduces shivering after general and spinal anaesthesia. AIMS: The aim of this study to highlight the efficacy of Butorphenol and ondosteron in controlling postoperative shivering. MATERIALS AND METHODS: This clinical trial included 180 patients scheduled for elective general surgery, E.N.T., Ophthamological operations, randomly divided to six groups. Three groups in which General Anaesthesia was used i.e. Group 1-ondansetron 8 mg intravenously(IV).Group 2 butorphanol 2 mg IV and Group 3 - saline 4 ml IV. And three groups where spinal Anaesthesia was used i.e. Group 4-Ondosteron 8 mg IV, Group 5 butorphanol 2 mg IV and Group 6 - saline 4 ml IV 3-5 minutes before anaesthesia. Patients were observed in terms of vital signs, side effects and shivering. SETTINGS AND DESIGN: The type of the study was double blind randomized trial. STATISTICAL ANALYSIS USED: Statistical Package for Social Sciences version 13.0 statistical analysis software. RESULTS: Postoperative shivering was observed in 15.5%, 22.2% and 60% in general anaesthesia groups I II and III respectively. The reduction of core and dermal temperature during the anaesthesia and recovery, changes in systolic and diastolic blood pressure and heart rate were similar in all three groups (i.e. Group I,II,III). In spinal anaesthesia groups, PAS occurred 10%, 13.3% and 43.3% in group IV, V, VI respectively. The reduction of core temperature is similar in all three groups of spinal anaesthesia. But heart rate and mean arterial pressure increase were significant in control saline group in post operative recovery time. No complication seen in any of the six groups. CONCLUSION: This study suggested that use of Butorphanol and Ondansteron both are effective in reducing the incidence of PAS after general and spinal anaesthesia.

CSF levels of prostaglandins, especially the level of prostaglandin D2, are correlated with increasing propensity towards sleep in rats.

The concentration of PGD2, PGE2, and of PGF2 alpha was measured in the cerebrospinal fluid (CSF) collected from the cisterna magna of conscious rats (n = 29), which, chronically implanted with a catheter for the CSF sampling, underwent deprivation of daytime sleep. Significant elevation of the CSF level of PGD2 was observed following 2.5-h sleep deprivation (SD), and the elevation became more marked following 5- and 10-h SD, apparently reaching the maximum at 5-h SD (703 +/- 140 pg/ml (mean +/- S.E.M.) for baseline vs. 1734 +/- 363 pg/ml for SD, n = 10). The levels of PGE2, and PGF2 alpha also significantly increased following 5- and 10-h SD, but not following 2.5-h SD. It is unlikely that these changes were simply caused by some responses of the animals to stress stimuli, because stress stimuli derived from restraint of the animal at the supine position to a board for 1 h did not produce any acute responses in the CSF levels of prostaglandins (n = 13). In a different group of animals (n = 11) implanted with electrodes for recording electroencephalogram (EEG) and electromyogram (EMG) in addition to the catheter, the levels of the prostaglandins in CSF were determined for slow-wave sleep (SWS) and wakefulness in the day and for SWS and wakefulness in the night. The highest PGD2 value was obtained at daytime SWS, whereas the lowest was at night wakefulness; furthermore, a significant difference was observed between SWS and wakefulness rather than between day and night. The CSF level of PGE2 also showed a similar tendency. In an additional group of animals (n = 6), not only PGD2 but also PGE2 and PGF2 alpha significantly increased the sleeping time of the animal when applied into the subarachnoid space underlying the ventral surface area of the rostral basal forebrain, the previously defined site of action for the sleep-promoting effect of PGD2. The promotion of sleep by PGE2 applied to the subarachnoid space was an effect completely opposite to the well-established awaking effect of the same prostaglandin demonstrated in the hypothalamic region in a series of previous studies. Based on these results, we conclude that increases in CSF levels of prostaglandins, especially that of PGD2, are correlated in rats with heightened propensity towards sleep and further with the depth of sleep under normal as well as SD conditions.

Influence of different combinations of antibodies and penicillinase-labeled testosterone derivatives on sensitivity and specificity of immunoassays.

Three antisera raised against bovine serum albumin (BSA) conjugates of testosterone-3-(O-carboxy-methyl)-oxime (T-3-CMO), 11 beta-hydroxytestosterone-11-carboxymethyl ether (T-11 beta-O-CME) and 19-hydroxytestosterone-19-carboxymethyl-ether (T-19-O-CME) were evaluated in enzyme immunoassays (EIAs) in combinations with penicillinase-labeled T-3-CMO, T-11 beta-O-CME, T-19-O-CME, and testosterone-17 beta-hemisuccinate (T-17 beta-HS) for their influence on the sensitivity and specificity of EIAs. Of the various combinations, anti-T-3-CMO antiserum along with T-11 beta-O-CME-penicillinase showed no cross-reaction with any of the closely related steroids, although the same antibody had 21.6% binding to 5 alpha-dihydrotestosterone (5 alpha-DHT) in radioimmunoassay. All the homologous combinations appeared to be less sensitive due to their low affinity for testosterone. It was also apparent that of all the heterologous systems tested, only two combinations, (a) anti-T-19-O-CME antiserum and T-3-CMO-penicillinase and (b) anti-T-3-CMO antiserum and T-11 beta-O-CME-penicillinase, were found to be more sensitive. The former was less specific; it showed 70% cross-reaction with 5 alpha-DHT. The ability of testosterone to displace the hapten-enzyme conjugate and the specificity of the assay appear to depend on the position of the enzyme label on the steroid molecule as well as on the availability of antigenic sites in particular combinations of antibody and hapten-enzyme conjugates.

Correlation of serotonin and monoamine oxidase levels with anxiety level in diarrhea-predominant irritable bowel syndrome.

BACKGROUND: Irritable bowel syndrome (IBS) is generally considered to have a psychogenic component in its physiopathology. AIM: To study the role of serotonin (5-hydroxytryptamine; 5-HT), monoamine oxidase (MAO) and anxiety, and to elucidate the relationship between these in patients with diarrhea-predominant IBS. METHODS: 5-HT and MAO activity and anxiety levels were studied in 20 healthy volunteers (aged 18-25 years; all men) and 57 patients with diarrhea-predominant IBS (30-60 years; all men). RESULTS: The concentrations of 5-HT (0.3 [0.04] microg/ mL) and MAO (15.5 [3.2] U/mL), and the anxiety level score (14.4 [2.9]) were significantly higher (p < 0.001) in patients than in healthy volunteers (0.1 [0.02], 6.4 [1.4] and 3.4 [1.2], respectively). These parameters correlated with each other in both patients and volunteers. CONCLUSIONS: Elevated 5-HT and MAO activity and anxiety may play a role in patients with diarrhea-predominant IBS.

A study on physiological changes in certain psychosomatic disorders with reference to cortisol, blood glucose and lipid profile.

Plasma cortisol, blood glucose, serum lipids and lipoproteins were estimated in diseased human subjects and normal control volunteers. Serum triglyceride (Tg) total cholesterol (Tc) and cholesterol content of very low density lipoprotein (VLDLc), low density lipoprotein (LDLc) and high density lipoprotein (HDLc) were assayed under lipid profile. Clinical investigations were carried out on 115 subjects which involved 30 control, 25 irritable bowel syndrome (IBS), 30 bronchial asthma and 30 rheumatoid arthritis patients. The results of this preliminary study showed a significant change in the levels of all the biochemical parameters in diseased subjects in comparison with controls. Increased levels of atherogenic lipids, Tg, VLDLc and LDLc were found in rheumatoid arthritis subjects. This suggests that arthritis subjects are relatively at higher risk of developing coronary heart disease. Furthermore hypercholesterolemia may aggravate the risk condition in arthritis patients by artereosclerosis. The significant elevation in the levels of plasma cortisol reveals the fact that rheumatoid arthritis is a stabilized and chronic psychosomatic disorder, since, homeostatic competence is disrupted following decline in the tendency of stress-response to return to normalcy.

A study on physiological changes in essential hypertension and rheumatoid arthritis with reference to the levels of cortisol, blood glucose, triglycerides and cholesterol.

The levels of plasma cortisol, blood glucose, serum triglycerides (TG) and total cholesterol (TC) were estimated in 175 human subjects (50 normal controls, 65 having essential hypertension and 60 suffering from rheumatoid arthritis. The results showed a significant elevation in the levels of plasma cortisol and blood glucose in both the stressed clinical groups with respect to controls. Increased levels of atherogenic lipids (TG and TC) were also observed in diseased group. However, in rheumatoid arthritis the biochemical changes were comparatively more pronounced than in hypertensives. The findings in vitro reveal that rheumatoid arthritis is a relatively more chronic and late onset disorder, since the functional performance of hypothalamo-pituitary-adrenocortical (HPA) axis declines with chronicity and the efficacy of adrenocortical response to return to normalcy becomes impaired.

A study on evaluation of apoptosis and expression of bcl-2-related marker in wound healing of streptozotocin-induced diabetic rats.

Uncontrolled blood sugar is a major cause of vascular complications and delayed wound healing in diabetes mellitus. During wound healing process, normally, apoptosis is responsible for events such as removal of inflammatory cells and evolution of granulation tissue into scar which occur during the late phase of wound healing. Early apoptosis can lead to abnormal wound healing by removing granulation tissue including fibroblast, endothelial cell, and small vessels. To determine the role of apoptosis in association with hyperglycemia in diabetic wound healing, apoptosis-related intracellular marker such as expression of Bcl-2 protein by immunohistochemistry and normal histology has been studied. Histological findings show higher level of apoptosis and diminished granulation tissue formation in diabetic rats wounds along with minimal expression of Bcl-2 in diabetic rats wounds when compared with nondiabetic rats wounds. It can be concluded from this study that elevated blood sugar level may be associated with increased apoptosis and the least expression of Bcl-2 protein which might cause deregulation of the wound healing processes in streptozotocin-induced diabetic rats.

Advanced stage of breast cancer hoist alkaline phosphatase activity: risk factor for females in India.

Breast cancer is the most common neoplasm affecting women in the western world with an average frequency of 1 in 11, developing the malignancy and it is second most common cancer in India. Variations in serum levels of biochemical parameters especially alkaline phosphatase (ALP) changes may be of great help in diagnosis of breast carcinoma. Serum ALP activity was assayed in 388 histopathologically proven breast cancer patients using spectrophotometric methods and monitored association with cancer stages. Breast cancer is a female-biased disease and our study was conducted in a group of female patients with mean age of 48.67 ± 8.32 years. A significant increase in levels of ALP (809.65 ± 145.97 IU/L) was observed in stage IV of the disease. The logistic regression study gave a significant result (P < 0.001) when we compared the group of ALP level (>500 IU/L) with metastatic presentation. The present study besides being cost effective suggested the usefulness of ALP in differentiating breast cancer stages and metastasis.

Identification of some unknown transcripts from SSH cDNA library of buffalo follicular oocytes.

A buffalo oocyte-specific subtracted cDNA library was constructed to identify exclusively or preferentially oocyte-expressed genes. The library represented an enriched population of transcripts obtained from oocytes of diverse ovarian follicular origin and at different stages of in vitro maturation. A total of 1173 high-quality sequences of oocyte-specific genes were clustered into 645 unique sequences, out of which 65.76% were represented as singlets and 34.26% as contig expressed sequence tags (ESTs; clusters). Analysis of sequences revealed that 498 of these sequences were identified as a known sequence in mammalian species including buffalo, 103 as uncharacterized ESTs and 44 unknown sequences including 1 novel EST, so far not reported in any species. Gene ontology annotation classified these sequences into functional categories of cellular events and biological processes associated with oocyte competence. Expression status of the isolated unknown ESTs confirmed that many of these are expressed in oocytes exclusively and in others preferentially, some in excess of 80-fold greater in comparison with a variety of somatic tissues. The isolated novel EST was detected to be expressed exclusively in oocytes and testicular cells only. To our knowledge, this is the first report giving a detailed transcriptome account of oocyte-expressed genes in buffalo. This study will provide important information on the physiological control of oocyte development, as well as many questions yet to be addressed on the reproductive process of buffalo.

Prospects of nano-material in breast cancer management.

Breast cancer evaluation and early diagnosis are core complexity worldwide and an ambiguity for scientists till date. Nano-materials are innovative tools for rapid diagnosis and therapy, which may induce an immense result in the field of oncology. Their exceptional size-dependent properties make them special and superior materials and quite indispensable in several fields of the human activities. The major obstacle in finding cure for malignant breast cancer is to increase in development of resistances for tumors to the therapeutic treatments. The widespread mammo-graph particle is being developed by nations to diagnosis disease in primitive stage to decline the mortality rates caused by breast carcinoma. The advancement of nano-particle based diagnostic tools facilitates in evaluation and provides encouraging development in breast cancer therapeutics. In this compact review, efforts have been made to compose the current advancements in the area of functional nano-particles. Furthermore, in vivo and in vitro applications of nano-materials in breast cancer management are also discussed.

Tobacco addiction augments obesity and carcinogenesis: Matter of concern for Indian patients.

PURPOSE: Life-style and tobacco addiction is the major risk factors for cancer progression in all over the world. Knowledge gaps between tobacco addiction, obesity and cancer in Indian patients brought an interdisciplinary group of investigators together to discuss the present study. PATIENTS AND METHODS: We calculated the body mass index (BMI) of all the patients (N = 927) who were diagnosed with cancer for its treatment. National Institutes of Health (NIH) criteria were used to categorize the patients. All the patients of this disease could be contacted in person to find out the history of the disease. RESULTS: The frequency of addiction in urban cancer patient was found to be about 53.3% and in a rural area it was only 33.7%. Tobacco addiction was independently associated with younger age of cancer patient (odds ratio [OR] 2.242; 95% Confidence interval (CI) 1.653-3.042), obese (OR 7.433; 95% CI 3.746-14.750), overweight (OR 4.676; 95% CI 3.381-6.468) and advanced stage of cancer (OR 11.950; 95% CI 5.283-27.030). CONCLUSION: Tobacco consumption appears to be a major contributor to cancer in younger age with elevated BMI in India. Rapid changes in diet and life-style, increase in tobacco consumption appear to be strongly associated with the carcinoma in this middle-income country.

Characterization of Vibrio cholerae O139 belonging to multiple ribotypes and isolated from diarrhoeal patients in Kerala, southern India.

Twenty-four Vibrio cholerae O139 strains isolated from Kerala, southern India were characterized by PCR, CTX typing and ribotyping; all of which, except three strains, carried the core of the CTX genetic element, colonization-toxin co-regulated pilus, the adherence outer membrane protein, haemolysin, central regulatory protein encoded toxR, SXT genetic element, and produced cholera toxin and biofilm. Results of RFLP analysis revealed twenty-one of the O139 strains possess two copies of CTXΦ and pre-CTXФ always preceded by tandemly arranged RS1 element; one had two copies of pre-CTXΦ and two a single copy of pre-CTXΦ. Nucleotide sequencing detected classical ctxB in CTX(ET)Φ and CTX(Calc)Ф with additional change at 28th amino acid position of CTX(Calc)Ф. Ribotype analysis revealed the presence of multiple ribotypes, including B-I and B-II, and new ribotypes designated B-VIIIa, B-VIIIb and B-IX, not reported earlier among V. cholerae O139 strains. These observations thus indicate that genetic recombination or mutations had occurred in conserved rrn operon and variations in CTXΦ may have implications on the evolution of the organism.

Sero-epidemiological study of kala-azar in a village of Varanasi district, India.

OBJECTIVE: To evaluate five kala-azar serological tests for field use. METHOD: Serological survey in Pandit Ka Purva village in Varanasi district, India, using Sia water test, aldehyde test, direct agglutination test (DAT), micro-enzyme-linked immunosorbent assay (ELISA) and dot-ELISA. RESULTS: The total population of the village was 518, 67 of whom showed typical clinical and parasitological features of kala-azar, including seven who died. The age distribution of kala-azar cases showed significant differences, being highest among the 45-54-year age group. The disease was more prevalent among males. Serum samples were collected from 498 persons (96% of total population) including 67 kala-azar cases and 40 disease controls (malaria, TB, leprosy, typhoid). Ten 10 serum samples from healthy controls living in endemic area were also collected. The test sensitivities were: Sia water test, 85.0%; aldehyde test, 62.7%; DAT, 94.0%; micro-ELISA, 91.0% and dot-ELISA, 97.0%. The test specificities were: Sia water test 92.5%, aldehyde test, 93.2%, DAT, 96.7; micro-ELISA, 97.6% and dot-ELISA, 98.4%. CONCLUSION: The dot-ELISA is highly sensitive and specific, cheap, and easy to interpret with the naked eye, making it a powerful screening test for the surveillance and diagnosis of Indian kala-azar at field level.

Concentration of prostaglandin D2 in cerebrospinal fluid exhibits a circadian alteration in conscious rats.

Cerebrospinal fluid (CSF) was withdrawn from the cisterna magna of unanesthetized conscious rats (n = 14) through a chronically implanted catheter, and prostaglandins (PGs) D2, E2, and F2 alpha were measured. From each rat, CSF samples were taken at different clock-hours of the day (1000, 1400, and 1800 hr) and night (2200, 0200, and 0600 hr) in succession at 76-hour intervals. The concentration of PGD2 alone exhibited a significant circadian fluctuation, with its peak value at 1400 hr (mean +/- SEM: 1197 +/- 361 pg/ml) and its lowest level at 0600 hr (438 +/- 106 pg/ml). Thus, the mean level of PGD2 during the daytime (903 +/- 162 pg/ml) was significantly higher than that during the night (503 +/- 78 pg/ml). The results obtained are consistent with the postulated role of PGD2, acting in the surface layer of the rostral basal forebrain, as an endogenous factor to promote sleep.

Evaluation of antibody responses in Indian kala-azar by immunoblot.

When infected with Leishmania species, patients develop specific antibodies that constitute the basis of serodiagnosis. using Western blot analysis we studied the specificity of anti-leishmania donovani antibodies in patients with visceral leishmaniasis, healthy subjects living in an endemic and non-endemic areas, and patients of other infectious diseases like malaria, leprosy, tuberculosis and tropical splenomegaly. Sera from patients with kala-azar recognised numerous antigens that had a molecular weight of 150 KD, 145 KD, 120 KD, 92 KD, 87 KD, 72 KD, 65 KD, 56 KD, 50 KD, 40 KD, 26 KD, 21 KD, 14 KD, AND 12 KD. The 150, 145, 120, 92, 87, 81, 65, 25, 21, 14, and 12 KD antigens had the greatest specificity for kala-azar sera while the bands of molecular weights 72, 56, 50, and 40 KD were found to be cross reactive with sera of patients of other diseases.