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Biomedical subjects

K M Nair

Publications and source records attributed to K M Nair.

At least 19 recordsLinked to original sources
PubMed2002

Primary malignant mucosal melanoma of the head and neck region: pooled analysis of 60 published cases from India and review of literature.

Malignant melanoma arising in the head and neck mucosa is a rare entity with incidence ranging from 2% to 10%. Because of the lack of data, the biological behaviour of these lesions still remains unpredictable and outcome dismal. We carried out a literature review for cases of mucosal melanoma of the head and neck reported from India and performed a pooled analysis on the available data. A total of 60 cases of head and neck melanomas were reported, of which 46 were in men. Palate and alveolus were the commonest sites. A total of 29 (48.3%) patients had regional node metastasis at presentation while five (12%) had distant metastasis. Three-year overall survival of 27.7% was observed. However, the disease-free survival rates at 3, 5 and 6 years were 39.4%, 39.4% and 13.1%, respectively. Metastasis at presentation and use of adjuvant radiotherapy were found to be the only significant predictors of survival. Malignant mucosal melanoma has aggressive biological behaviour and poor outcome. Radical surgery and adjuvant radiotherapy may provide a better local control and may help in improving survival.

Disease-Free Survival↗
PubMed2001

Oral repletion of iron induces free radical mediated alterations in the gastrointestinal tract of rat.

Free radical mediated effects on the gastrointestinal (GI) tract were studied by supplementing 8 mg of iron orally for 15 days to groups of both control (C+) and iron deficient (D+) rats. They were compared with their respective unsupplemented groups C and D. Incorporation of 3H-thymidine into the isolated mucosal cells, as a measure of cell turn over, was lowered significantly in both the D+ and C+ groups compared to their respective controls D and C. It was observed that a single dose of 8 mg of iron given orally to control rats could cause apoptosis of GI tract mucosal cells as shown by the ladder pattern of DNA on electrophoresis. Continuous administration of the same dose of iron for a period of 15 days resulted in necrosis of the GI tract absorptive surface in D+ and C+ rats. In addition to this, a reduction of microvillus height in C+ and complete erosion of the same in D+ were observed by the transmission electron microscopy. EPR spectroscopy identified production of hydroxyl and methoxyl radicals in both the luminal and mucosal contents in the GI tract of rats. These results suggest that when iron is orally administered, free radicals are formed at the site of absorption causing damage to the GI tract mucosa.

Administration, Oral↗
PubMed2000

Supplementation with alpha-tocopherol or a combination of alpha-tocopherol and ascorbic acid protects the gastrointestinal tract of iron-deficient rats against iron-induced oxidative damage during iron repletion.

Recently we have shown the susceptibility of Fe-deficient rat intestine to oxidative damage during Fe repletion. The role of dietary antioxidants like ascorbic acid, alpha-tocopherol and a combination of both in counteracting the oxidative stress was tested in this study. Five groups of thirteen weanling WKY female rats were fed with an Fe-deficient diet for a period of 5 weeks. Another set of thirteen rats received an Fe-sufficient diet and served as the control group (Con). Oral administration of either vehicle (D), 8 mg Fe alone (D+) or in the presence of 24 mg ascorbic acid (D+ + C), 40 mg alpha-tocopherol (D+ + E) or a combination of both (D+ + C + E) per d for 15 d was carried out in Fe-depleted rats. The impact of this treatment protocol on Fe status, oxidative stress and antioxidant status at the site of Fe absorption was assessed. It was observed that though the indicators of Fe status were normalised on Fe supplementation, the oxidative stress as reflected by the levels of both thiobarbituric-acid reactive substances (TBARS) and protein carbonyls were significantly greater in D+ and D+ + C compared to D+ + E, D+ + C + E and Con groups. The mucosal cell DNA damage was seen in D+, D+ + C and D+ + E groups on electrophoresis. Functional integrity as assessed by the activities of alkaline phosphatase and lys-ala-dipeptidyl aminopeptidase were normalized in all the groups treated with the antioxidant(s). There were significant positive alterations in some of the endogenous antiperoxidative systems and in serum caeruloplasmin activity in D+ + E and D+ + C + E groups. Paradoxically, serum ascorbate levels were significantly lower in D+ + C than in D+ + E and D+ + C + E groups. This could be due to the protection offered by alpha-tocopherol in the presence of Fe. It is concluded that supplementation of alpha-tocopherol alone or in combination with ascorbic acid protects the gastrointestinal tract of Fe-deficient rats against Fe-mediated oxidative damage during Fe repletion. However, ascorbic acid alone does not protect the gastrointestinal tract against Fe-induced oxidative stress.

Administration, Oral↗
PubMed1999

Decreased programmed cell death in the uterine cervix associated with high risk human papillomavirus infection.

The relationship between apoptosis, apoptosis regulatory proteins, cell proliferation and human papillomavirus infection during various phases of tumor progression in the uterine cervix was studied. Apoptosis was defined by morphological criteria and the TUNEL assay. Expression of p53, bcl-2, bax, cyclin D1, Ki 67 and E6 protein was evaluated by immunocytochemistry. Presence of mutant p53 was detected using a mutant specific ELISA. Type of HPV infection was determined by PCR using type specific primers. Apoptosis showed significant negative correlation with increasing histological abnormality (p=0.0005). Higher tumor cell proliferation was associated with increasing histological abnormality (p=0.001 for Ki 67 and cyclin D1). There was significant correlation between histological grade and immunoreactivity of p53 (p=0.0001 ) and bcl-2 (p=0.0002). However, mutant p53 was expressed by only 12 of the 230 samples. Expression of bax and the bax/bcl-2 ratio showed an inverse correlation to histological grade (p=0.0003 and 0.0001, respectively). There was also an inverse correlation between extent of apoptosis and immunoreactivity of p53 (p=0.0001) and bcl-2 (p=0. 0001). A significant positive correlation between expression of the bax protein and apoptosis was evident (p=0.0001). HPV infection significantly correlated to the extent of histological abnormality (p=0.0001). High risk HPV-E6 protein also showed this significant correlation (p=0.0002). There was an inverse correlation between apoptosis and HPV infection (p=0.0002). High risk HPV infection was associated with decreased apoptosis and also increased human cell proliferation. Lowest levels of bax/bcl-2 ratio was also associated with HPV 16 and 18 infection (p=0.0001). Modulation of apoptosis and apoptotic regulatory proteins by high risk HPV infection may be an important factor in the development of cervical cancer.

Apoptosis↗
PubMed1998

Prediction of radiosensitivity of oral cancers by serial cytological assay of nuclear changes.

BACKGROUND AND PURPOSE: To identify the relationship between the radiosensitivity of oral cancers and the induction of micronucleation, nuclear budding and multinucleation (polynucleation) evaluated by serial cytology during fractionated radiotherapy. MATERIALS AND METHODS: Forty-four patients with epidermoid cancer of the oral cavity receiving radiotherapy (60 Gy in 25 fractions over 5 weeks) were studied. Serial scrape smears were taken from the tumour before and during radiotherapy and stained by Giemsa and the frequency of micronucleated cells (MNC), nuclear budded cells (NBC) and multinucleated cells (PNC) was evaluated by light microscopy. After a minimum follow-up period of 30 months the patients were classified as having resistant or sensitive tumours, depending on whether the primary tumour had recurred or not within that time. Within-group and between-group analysis on the induction of the above individual parameters and two combined parameters, the micro- or multinucleated cell (MPC) count and the abnormally nucleated cell (ANC) count, was done. The counts were expressed per 1000 uni-nucleated cells. RESULTS: In both groups each parameter showed a statistically significant increase with dose, the increase being higher in the sensitive group. The ANC count showed the greatest increase, the mean counts before treatment and after 28.8 Gy being 24.3 and 157.8 (P < 0.0005), respectively, in the sensitive group and 21.0 and 65.2 (P < 0.0005), respectively, in the resistant group. After 28.8 Gy the sensitive tumours had significantly higher ANC (P = 0.01), MPC (P < 0.05) and PNC (P < 0.05) counts. CONCLUSION: The study shows that serial cytological assay of nuclear changes (SCANCing) during radiotherapy is a potentially useful test to predict radiosensitivity. The fact that multinucleation showed the greatest relation with radiosensitivity suggests that injury to the cytokinetic apparatus is important in determining tumour radiosensitivity.

Adult↗
PubMed1998

Primary malignant melanoma of the mucous membranes.

AIMS: To investigate malignant mucosal melanoma (MMM), a rare disease and one which has, till lately, remained unrecognized. Incidence of MMM ranges from 2 to 10% in various series. METHODS: We retrospectively reviewed the cases of malignant melanoma treated at the Regional Cancer Centre, Trivandrum, India, over a period of 15 years. RESULTS: A total of 163 cases of melanoma were identified, of which 21 had a lesion in mucosal sites. There were eight cases of upper aero-digestive tract (UADT) melanoma, seven cases of rectal melanoma, five cases with lesions in the vagina and one case with a lesion in the urethra. The mean age of the patients was 52.8 years; mean age of presentation in urogenital and anorectal lesions was similar to overall mean age, while this was lower (47.5 years) for UADT lesions. Almost half of the patients presented with ulcer or nodule with or without pigmentation. Pain was present in three-quarters and vaginal bleeding was present in all cases of vaginal lesions. Almost one-third of the patients failed locally while another third developed distant metastasis during the follow-up period. A 2-year disease-free survival rate of 13.2% (95% CI: 2.2-34.1) was observed, which dropped to 6.6% (95% CI: 0.4-25.7) after 3 years. Survival appeared a little better in UADT melanoma compared to urogenital and anorectal melanoma; however, the difference was not statistically significant. CONCLUSIONS: Malignant mucosal melanoma seems to have an aggressive biological behaviour with a high incidence of local failure and metastasis.

Adult↗
PubMed1998

Iron-deficient intestine is more susceptible to peroxidative damage during iron supplementation in rats.

Redox-active forms of iron are known to catalyze free radical mediated peroxidative reactions. There is scanty information on such effects at the sites of iron absorption. This was tested in iron-deficient WKY female rats supplemented for 15 days with FeSO4 equivalent to 8 mg of iron (D+) and compared with iron deficient (D) and iron adequate (C) rats. The levels of intestinal MDA and protein carbonyls and the activities of various antioxidant enzymes were estimated. As markers of functional integrity, the activities of alkaline phosphatase and Lys-Ala-dipeptidyl aminopeptidase were evaluated. In addition, we measured the concentrations of ferritin, transferrin, and ceruloplasmin levels in serum and in intestinal mucosa. It was observed that correction of iron deficiency resulted in significant increase in MDA and protein carbonyl formation. Activities of both alkaline phosphatase and Lys-Ala-dipeptidyl aminopeptidase were significantly decreased in D+ compared to C. The increase in catalase and decrease in Gpx was found to be sensitive to iron administration. Neither iron deficiency nor its correction had any effect on the activity of SOD and GSH levels. Iron supplementation has resulted in decreased mobilization of stored iron as reflected by increased mucosal ferritin level and decreased serum ceruloplasmin ferroxidase activity contributing to greater peroxidative stress in the intestine. These results suggest that iron-deficient intestine of rat is more susceptible to iron-mediated peroxidative damage and functional impairment during correction of deficiency with iron.

Administration, Oral↗
PubMed1998

Biological efficacy and plasma norethisterone levels of orally administered norethisterone enanthate in rat and hamster.

Norethisterone enanthate (NET-En) is a well known intramuscular contraceptive drug. The long acting nature of this preparation when administered orally was evaluated in female rats and hamsters using fertility inhibition test and from the plasma levels of norethisterone (NET). An oral dose of 20-60 mg NET-En was administered to random groups of six female rats and hamsters and were mated after five and ten days with males of proven fertility. The fertility inhibition rate was determined from vaginal delivery. A dose-dependent reduction in fertility was seen in rats 5 days after oral administration of NET-En. This effect was found to be less pronounced and not significant 10 days after administration of similar doses of NET-En. In hamsters, a similar but less pronounced effect was noted. The decrease in fertility was significant only at the 60 mg dose. The plasma levels of NET estimated by RIA over a period of 15 days, in a different set of treated rats, suggested rapid absorption of NET-En within a day, and drug concentration decreased slowly, the levels on the 4th day ranged from 0.9-2.3 with the 10 mg and 1.0-4.0 ng/ml with the 20 mg dose. Detection of adequate levels of NET in plasma during the estrous cycle in rats, and the fertility inhibition observed in female rats and at higher doses in hamsters, suggest that NET-En is orally active.

Animals↗
PubMed1998

Impact evaluation of iron & iodine fortified salt.

As a novel approach to tackle the problems of iron deficiency anaemia and iodine deficiency disorders (IDDs), which often coexist, the National Institute of Nutrition has developed iron and iodine fortified common salt (double fortified salt-DFS) as a public health measure. This salt has undergone a battery of laboratory and field tests to evaluate its feasibility for use in a national programme. The DFS is designed to provide 1 mg of iron and 15 micrograms of iodine per gram of common salt. This was made possible by the inclusion of a polyphosphate stabilizer, sodium hexametaphosphate (SHMP) at 1 per cent level. The stability of iron and iodine was found to be good up to 6 months. However, the stability of iodine depended upon the quality of the salt used for fortification. The biological effects of long-term consumption of DFS were evaluated in experimental rats and in field trials. Both iron and iodine from the salt were found to be biologically available in regenerating haemoglobin and in increasing excretion of iodine in urine. When this salt was tested in tribal villages endemic for goitre and iron deficiency anaemia, the bioresponse was good with regard to the iodine status but was not uniform in all segments with regard to iron, probably due to confounding variables. In a study carried out in residential school children where such variables did not exist, DFS was found to have significant impact on haemoglobin status in anaemic children and improved their urinary iodine excretion. The consumption of DFS for 2 yr did not have any adverse effects in school children as well as in the tribal population. Parameters related to calcium homeostasis were not altered in children receiving DFS. Histopathological examination of tissues and radiological examination of bone did not reveal any abnormality in DFS fed rats. Similarly serum and urinary parameters related to calcium and phosphorus were not altered in DFS fed rats. Therefore, DFS is presented as a feasible and effective strategy to control the double deficiency of iron and iodine in our community.

Animals↗
PubMed1997

Pharmacokinetics of orally administered norethisterone enanthate in rabbit, monkey, and women.

Norethisterone enanthate (NET-En), an established intramuscular long-acting contraceptive agent, has previously been shown to be effective in inhibiting fertility in two rodent species even 4 days after oral ingestion. Pharmacokinetics of NET and NET-En were studied after oral and intramuscular doses in two animal species and a few women. The results suggest that the NET-En was absorbed within a day in all the species after oral dose. The estimates of relative bioavailability ranged from 13 to 51% in rabbits, monkeys, and women. The elimination half-life was 5-10 days. The presence of the active component, NET, in the circulation over the experimental period of 15 days suggests that NET-En could be useful as a long-acting oral pill. The suppression of progesterone levels during the luteal phase of menstrual cycle in women also supports this finding.

Administration, Oral↗
PubMed1997

Systemic and mucosal immune response to polio vaccination with additional dose in newborn period.

Administration of supplementary dose of oral polio vaccine (OPV) during neonatal period is recommended by WHO in countries like India, where host response to the regular to the regular three-dose schedule is not satisfactory and poliomyelitis continues to be a problem. The efficacy of this dose +3, and +5 doses of OPV in terms of seropositivity, seroconversion, systemic, and mucosal antibody responses were measured in 51 infants in a follow-up study from birth to 30 weeks. Administration of the additional dose in the newborn period significantly improved seropositivity and seroconversion rates compared to the conventional 3 or 5 dose schedules. Systemic antibody titres improved with each dose of the vaccine and 40-60 per cent of infants had > 1:128 titres to the three types of polioviruses that could prevent re-infection of the gut and 50 per cent of them had mucosal antibodies as evidenced by specific IgA in nasopharyngeal secretions. Therefore, administration of OPV in the neonatal period should be made compulsory in countries where poliomyelitis still continues to be a problem.

Antibodies, Viral↗
PubMed1997

Changes in biochemical indicators of iron status during iron repletion and depletion in monkeys.

Different modes of iron depletion and repletion were studied in monkeys to understand the sequential changes in and the relative importance of different biochemical indicators of iron status. Six control monkeys were divided into two groups, one was fed an iron-deficient diet (group 1) and the other underwent phlebotomy in addition to receiving an iron-deficient diet (group 2). Previously iron-depleted monkeys were subdivided into 4 groups of 3 animals each. While one group was continued on the iron-deficient diet (group 3), the second group received parenteral iron (group 4), the third group (group 5) received a sufficient-iron-containing diet, and the fourth group was fed 50% of the iron requirement. All indicators of iron status like hemoglobin (Hb), erythrocyte protoporphyrin (EPP), serum transferrin saturation and serum ferritin were monitored periodically, in addition to liver and bone marrow iron. all the indicators except serum ferritin and liver iron showed a decrease in group 2. On the other hand, animals receiving parenteral iron (group 4) showed an increase in all the parameters except serum ferritin. The dietary supplementation produced an increase in Hb and a decrease in EPP only (groups 5 and 6). There was a significant positive correlation between changes in bone marrow iron and Hb concentration depending on the severity of depletion and repletion. Both serum ferritin and liver iron did not respond to changes in dietary iron. Another parameter which responded to repletion was EPP. Serum ferritin and liver iron did not respond to changes in dietary iron or was not sensitive to subclinical iron deficiency. The results indicate that change in Hb is more sensitive to detect the deficiency of iron. It was also observed that different parameters respond variably under different modes of depletion and repletion.

Animals↗
PubMed1997

Protective effects of antioxidant enzymes and GSH in vivo on iron mediated lipid peroxidation in gastrointestinal tract of rat.

The protective mechanisms operating in the gastrointestinal (GI) tract to counteract the potential oxidizing effects of excess free iron, was tested in rats fed with excess iron. The activities of some antioxidant enzymes, the levels of GSH and the extent of lipid peroxidation at the site of iron absorption were measured. Based on the amount of thiobarbituric acid reactive substances (TBARS) produced, it could be deduced that the duodenal segment of GI tract is resistant to iron mediated lipid peroxidation. The duodenal function as judged from the activities of marker enzymes, namely, alkaline phosphatase and Lys-Ala-dipeptidyl aminopeptidase was normal. There was depletion of GSH possibly due to the increased activities of Cu, Zn SOD and catalase. However, the activity of Gpx was decreased in the Fe fed group. It was also observed that the ratios of SOD/Gpx and Cat/Gpx had significantly increased in the treated group whereas SOD/Cat remained constant suggesting that antioxidative enzymes play a key role in rendering the intestinal mucosal cells resistant to iron induced oxidative damage in rats.

Animals↗
PubMed1995

A direct ELISA technique to detect antibodies against polioviruses.

A direct ELISA test was developed to detect circulating antibodies specific to poliovirus types 1, 2 and 3. Specificity of the test was established by using known polio negative and positive sera. The assay was compared with the standard microneutralization test using sera from polio and non polio cases vaccinated and unvaccinated subjects and standard positive sera obtained from WHO/EPI (Geneva). The reproducibility of the results was tested using different batches of the antigen prepared from Sabin strain of poliovirus supplied by ERC Bombay and from Sabin strain of virus obtained from WHO/EPI. ELISA was found to be as sensitive as microneutralization test in detecting seronegatives and was found to be specific to polio by giving negative results with non polio cases. ELISA is thus a rapid and simple method that may be useful for mapping seroepidemiology of poliomyelitis and as a tool for effective surveillance of the disease by offering rapid diagnosis in acute cases.

Antibodies, Viral↗
PubMed1994

Induction of dietary iron deficiency in rhesus monkeys: sequential changes in serum ferritin and other biochemical indicators of iron status.

The usefulness of serum ferritin as a measure of subclinical stages of iron deficiency has been tested in monkeys by inducing a mild iron deficiency dietarily over a period of 12 months. Various biochemical indicators of iron status were measured periodically along with analysis of liver iron and iron staining of bone marrow samples obtained by biopsy, at the end of the experiment. A mild form of iron deficiency was confirmed by bone marrow staining for iron. Of all the biochemical indicators tested, significant decreases were seen in hemoglobin and hematocrit at the 11th and 10th months, respectively. These changes were consistent with the changes later found in bone marrow grading for iron. Serum ferritin concentration and liver iron concentration did not show any significant difference between the controls and iron-deficient monkeys. Thus, these results do not support the existence of a latent stage of iron deficiency. In the mild form of iron deficiency, the functional compartment, represented by bone marrow iron and hemoglobin, is sensitive to depletion even when there were no changes in storage compartment represented by liver iron and serum ferritin.

Anemia, Iron-Deficiency↗
PubMed1987

Phase abnormalities in right heart studies. Demonstration of six different patterns.

Phase imaging abnormalities of the right side of the heart detected on multiple gated blood pool angiography (MUGA) have received less attention than similar abnormalities of the left ventricle. It has been found that certain different patterns of phase abnormalities of both right ventricle and right atrium are useful in the detection of six pathological conditions: right bundle branch block, ischemic right coronary artery disease, pericardial effusion, tricuspid regurgitation, pulmonary hypertension, and atrial septal defect. The authors emphasize the importance of these abnormal phase patterns during interpretation of gated cardiac studies, as they are helpful in directing the physicians attention towards the proper diagnosis.

Adult↗