2, 4-Diamino-6- hydroxy pyrimidine inhibits NSAIDs induced nitrosyl-complex EPR signals and ulcer in rat jejunum

BACKGROUND: It has been suggested that one aspect of non-steroidal anti-inflammatory drugs induced intestinal damage is due to either uncoupling of mitochondrial oxidative phosphorylation or inhibition of electron transport. We investigated the latter possibility using electron paramagnetic resonance spectroscopy. RESULTS: Electron paramagnetic studies of NSAIDS on sub-mitochondrial particles revealed that indomethacin, but not with nabumetone, bound to a site near to Complex I and ubiquinone to generate a radical species. Normal rats exhibited prominent [3Fe-4S]ox signals (g ~ 2.01) at 20 K. One hour after indomethacin there was a prominent, intense and broad absorption pattern at (g ~2.07) suggesting, appearance of radical species overlapping [3Fe-4S]ox and was unaffected by pretreatment with 2,4 diamino -6-hydroxy pyrimidine. At 24 hrs, when macroscopic ulcers were seen, there was a new signal due to a nitric oxide radical (NO•). In contrast, nabumetone and 2,4 diamino-6-hydroxy pyrimidine pre-treated animals receiving indomethacin exhibited electron paramagnetic resonance spectra identical to those of controls at 24 hrs and neither was associated with small intestinal ulcers. Indomethacin and 2,4 diamino hydroxy pyrimidine pre-treated rats, but not nabumetone, had increased intestinal permeability. CONCLUSION: The results suggest that the in vivo effects of indomethacin modulate the mitochondrial respiratory chain directly at 1 h and 24 h through formation of nitric oxide. NO• appears to play an important role in the late pathogenic stages of NSAID enteropathy and may be the site for targeted treatment to reduce their toxicity

Short-course chemotherapy for tuberculosis of the spine : A comparison between ambulant treatment and radical surgery - a ten year report.

We perfomed a randomised, controlled clinical trial to compare ambulant short-course chemotherapy with anterior spinal fusion plus short-course chemotherapy for spinal tuberculosis without paraplegia. Patients with active disease of vertebral bodies were randomly allocated to one of three regimens: a) radical anterior resection with bone grafting plus six months of daily isoniazid plus rifampicin (Rad6); b) ambulant chemotherapy for six months with daily isoniazid plus rifampicin (Amb6); or c) similar to b) but with chemotherapy for nine months (Amb9). Ten years from the onset of treatment, 90% of 78 Rad6, 94% of 78 Amb6 and 99% of 79 Amb9 patients had a favourable status. Ambulant chemotherapy for a period of six months with daily isoniazid plus rifampicin (Amb6) was an effective treatment for spinal tuberculosis except in patients aged less than 15 years with an initial angle of kyphosis of more than 30° whose kyphosis increased substantially

Alterations in tumour suppressor gene p53 in human gliomas from Indian patients

Alterations in the tumour suppressor p53 gene are among the most common defects seen in a variety of human cancers. In order to study the significance of the p53 gene in the genesis and development of human glioma from Indian patients, we checked 44 untreated primary gliomas for mutations in exons 5-9 of the p53 gene by PCR-SSCP and DNA sequencing. Sequencing analysis revealed six missense mutations. The incidence of p53 mutations was 13.6% (6 of 44). All the six mutations were found to be located in the central core domain of p53, which carries the sequence-specific DNA-binding domain. These results suggest a rather low incidence but a definite involvement of p53 mutations in the gliomas of Indian patients

Prevalence, incidence and resolution of abscesses and sinuses in patients with tuberculosis of spine: A 5-year results of patients treated with short course chemotherapy with or without surgery in Madras

A controlled clinical study comparing 6 or 9 months of ambulatory chemotherapy alone with radical surgery plus 6 months of chemotherapy was undertaken in patients with spinal tuberculosis in Madras. The prevalence of sinuses and/or clinically evident abscesses was 49(19%) of 253 patients, with significantly higher proportion in patients with lumbar or lumbo-sacral lesions. The incidence of lesions appearing after the start of chemotherapy was 32 (16%) of 204 patients. By five years, all had resolved. The resolution of the lesions was significantly faster and the incidences significantly lower in the radical surgery group than in the two ambulatory series. Mediastinal abscesses were observed on radiographs in 66 (66%) of 100 patients with thoracic or thoraco-lumbar lesions. By five years, the lesions had disappeared in all except two patients and the disappearance was significantly faster in the radical surgery group than in the two ambulatory series. There was no recurrence of these lesions during a period of five years

Feasibility of utilising address card system for obtaining accurate address of patients under programme conditions

An addresscard, one on which patient's home address is asked to be recorded by a person knowing for sure the patient's address, was investigated for acceptability and efficiency, in two Government hospitals located in semiurban areas and six Primary Health Centres located in rural areas in North Arcot district. In all 394 address-cards were given to the patients from the eight centres, of which 374 were returned with the address filled in, showing an acceptability rate of 95%. In all, 373 Type A letters were then posted to these addresscard addresses in respect of which acknowledgment cards were received back from 306 (82%) patients. For 140 patients, the recorded addresses were found to be the same as on the addresscard and the treatment card: In the remaining 233, there was some difference between the two addresses. Type B letters were then posted to the 233 patients at their treatment card address. No definite information was available regarding the receipt of one or both types of letters in respect of 80 patients; so, an attempt was made to visit these patients in their homes to find out the fate of these letters. Of these, no information could be collected in 9 patients. Out of 224 patients for whom information regarding the receipt of letter was available, 143 (64%) patients received both letters and 16 (7%) received neither Type A nor Type B letter. Twenty one (9%) had probably or definitely not received the Type A letter, but had received the Type B letter. Forty four (20%) had definitely or probably not received the Type B letter, but had received the Type A letter

FV peptide induces apoptosis in HEp 2 and HeLa cells: an insight into the mechanism of induction

The present study is an attempt to evaluate the antiproliferative potential of peptide (7.6 kDa) from lionfish (Pterios volitans) venom on cultured HEp2 and HeLa cells. Different dose of purified peptide (1, 2 and 4 μg/ml) at different time points (12, 24 and 36 hrs) were tested for antiproliferative index of the peptide. Among them, 2 μg/ml at 24 hrs was found to effectively inhibit cancer cell growth in vitro and did not cause any adverse effect on normal human lymphocytes. Apoptosis was examined by propidium iodide staining, confirmed by the expression of caspase-8 and caspase-3, down regulation of Bcl-2 expression and DNA fragmentation in treated cells, when compared to untreated HEp2 and HeLa cells. Thus fish venom peptide was found to selectively induce apoptosis in cancer cell

High coverage of long-term follow-up of patients with spinal tuberculosis

A total of303 patients treated for spinal tuberculosis were systematically followed up for a period of 8 years. There were a total of 2243 attendances due during the period; the patients attended on the due date on 70.9% of these occasions, and after defaulter actions on 27.7% occasions. The coverage of 98.6% for an 5-year follow-up was obtained even though on 50% of these occasions, patients attended from a suburban area or from outside the city. An average of 13 visits per default were made and 0.9 letters were posted to retrieve those who did not attend on the due date. Thus, the high coverage obtained can be attributed to effective motivation of the patients by theclinic staff and intensive defaulter actions

Binding site conformation dictates the color of the dye stains-all. A study of the binding of this dye to the eye lens proteins crystallins

The interaction of the cationic carbocyanine dye Stains-all (1-ethyl-2-[3-(1-ethyl-naphthol[1,2-d]thiazolin-2-ylidene)-2- methylpropenyl]naphthol[1,2-d]thiazolium bromide) with the eye lens proteins crystallins has been studied. α- and γ-crystallins do not bind the dye, while β- and δ-crystallins do, consistent with the fact that the latter two proteins bind the calcium ion. β-Crystallin resembles parvalbumin in that it induces only the J-band of the bound dye. δ-crystallin, on the other hand, induces only the γ-band. Analysis of the metachromasia induced in the dye by these and other proteins suggests that Stains-all is responsive to the conformational status of the region to which it binds in a protein. The J-band of the dye is activated when it binds to a globular domain, and the γ-band is activated when it binds to a helical stretch of the protein

Efficacy of once-weekly Isoniazid-Streptomycin in preventing relapse of pulmonary tuberculosis

Two controlled studies were undertaken to assess the efficacy of streptomycin 1 g. or 0.75 g. (by random allocation) plus isoniazid 15 mg./kg. body-weight once-weekly (the SHOW regimen) in the prevention of bacteriological relapse over a 4 year period, in patients with quiescent pulmonary tuberculosis at the end of one year of chemotherapy. In the first study which involved patients with residual cavitation at one year, bacteriological relapse requiring treatment occurred in 3 per cent of 87 patients given the SHOW regimen for 12 months as compared with 21 per cent of 94 patients on a placebo, a high proportion of the relapses in the latter occurred in the 2nd year and with sensitive organisms. In the second study on patients with no residual cavitation at one year, relapse requiring treatment occurred in 2 per cent of 98 patients given the SHOW regimen for 6 months as compared with 1 per cent of 90 patients given isoniazid approximately 4.5 mg./kg. daily for 12 months

Calcium ion binding to δ- and to β-crystallins. The presence of the "EF-hand" motif in δ-crystallin that aids in calcium ion binding

Abnormal levels of endogenous calcium ions are known to induce eye lens opacity, and a variety of causative factors has been proposed, including calcium-mediated aggregation and precipitation of the lens proteins crystallins. We have specifically looked in some detail at the interaction of Ca2+ with various crystallins and its consequences. Lenses incubated in solutions containing 10 mM Ca2+ or 5 mM Tb3+ opacified. Fluorescence titration of crystallins with TbCl3 revealed that this ion binds to δ- and β-crystallins in solution. Equilibrium dialysis showed that four Ca2+ ions bind to one δ-crystallin tetramer with an affinity of 4.3 × 103 M-1. Analysis of the amino acid sequence of δ-crystallin reveals the presence of a calmodulin-type "helix-loop-helix" or "EF-hand" calcium ion binding conformational motif in the region comprising residues 300-350. This is a novel feature of the molecule not reported so far. No other crystallins appear to have this motif. β-Crystallin also binds four Ca2+ ions/aggregate unit of mass 160 kDa, with an affinity of 2.6 × 103 M-1, presumably in the midregion of the molecule that is rich in anionic and polar residues. Circular dichroism spectroscopy shows that the binding of calcium ion leads to subtle conformational changes in the molecules, notably in the tertiary structure