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Biomedical subjects

R C Gupta

Publications and source records attributed to R C Gupta.

At least 217 records · Page 12Linked to original sources
PubMed1988

Evaluation of DNA damage in the oral mucosa of tobacco users and non-users by 32P-adduct assay.

Tobacco and its combustion products contain several known or potential human carcinogens and studies are now beginning to emerge for detecting DNA and protein adducts in tobacco users. A highly sensitive 32P-adduct assay, capable of measuring a wide spectra of aromatic and/or hydrophobic DNA adducts, was used to evaluate tobacco use-related adducts in human oral mucosal cells. Two volunteer groups of people participated: one, a random group of cigarette smokers (n = 28) with non-smoker controls (n = 13) from our Institute, and the other, a fisherfolk community of tobacco chewers (n = 19) with appropriate non-chewer controls (n = 15) from Bombay. The cells were dislodged from the oral cavity with either a cotton swab or a toothbrush. One to as many as 16 adduct spots in the range of 5-200 amol/micrograms DNA were detected in tobacco users as well as non-users. No adduct spot was detected in the tobacco users' samples that was not present in the controls, suggesting that tobacco use may not be responsible for the formation of these DNA adducts detected in the oral mucosa. The chromatographic behavior of the oral mucosal DNA adducts by selective PEI--cellulose TLC and their extractability in 1-butanol suggest that they have an aromatic and/or hydrophobic moiety and two of the major adducts have been tentatively assigned as aromatic amine derivatives. We have discussed various possibilities of endogenous and/or exogenous factors being involved in the formation of these adducts.

DNA↗
PubMed1988

32P-adduct assay: comparative recoveries of structurally diverse DNA adducts in the various enhancement procedures.

A 32P-adduct assay for the measurement of low levels (1 adduct per 10(7) nucleotides) of binding of carcinogens to DNA has been reported previously. In this procedure, DNA is enzymatically hydrolyzed to 3'-monophosphates of normal nucleosides and adducts, which are 5'-32P-labeled by T4 polynucleotide kinase and [gamma-32P]ATP. Labeled adducts are resolved by TLC. Enrichment of adducts by extraction in 1-butanol [Gupta, R.C. (1985) Cancer Res., 45, 5656] or digestion with nuclease P1 [Reddy, M.V. and Randerath, K. (1986) Carcinogenesis, 7, 1543] prior to 32P-labeling, however, increased the sensitivity of detection for many adducts to a level of 1 per 10(9-10) nucleotides, although adduct recovery particularly in the latter assay depended on the chemical nature of adducts. We have now compared recoveries for greater than 70, different carcinogen-DNA adducts of known and unknown chemical nature in the two enrichment procedures as well as in a new procedure in which polynucleotide kinase is substituted for nuclease P1. When compared with the butanol extraction procedure, arylamines (such as 2-aminofluorene, 2-aminophenanthrene, 2-naphthylamine, 4-aminobiphenyl, 4-azoaminobenzene and N'-acetylbenzidine) bound to the C8 position of guanine were lost almost completely (0.2-4% recovery) in the nuclease P1-mediated assay, but the presence of a polar group in the aromatic amine moiety (such as 2-acetylaminofluorene, 2-acetylamino-phenanthrene and methyl-4-azoaminophenyl) rendered similar recovery. In contrast, aromatic amines (2-amino-phenanthrene, 2-acetylaminophenanthrene, 2-acetylaminofluorene and methyl-4-azoaminobenzene) and polycyclic aromatic hydrocarbons (benzo[a]pyrene, bromomethylbenzanthracene and benzanthracene) bound to the exocyclic positions of guanine or adenine showed extensive or as complete recovery in the nuclease P1 procedure as in the extraction procedure. Some of the unknown presumably polar adducts showed a lower recovery (30-70%) in the butanol procedure as compared to the nuclease P1 enrichment. The recovery pattern of most adducts examined in the polynucleotide kinase-enrichment assay was essentially the same as found in nuclease P1-mediated assay, except that overall lower values were obtained. Our data suggest that a given DNA sample should be analyzed by different versions of the 32P-adduct assay, particularly, DNA of specimens of humans exposed to low levels of unknown carcinogens. The observation that chemical structure of an adduct may be detrimental in its recovery in the enzyme- and extraction-mediated enrichment procedures may serve as a probe in the structural characterization of adducts of unknown carcinogens.

Butanols↗
PubMed1988

Miliary tuberculosis due to intravesical bacillus Calmette-Guerin therapy.

While receiving treatment for bladder carcinoma with intravesical BCG, a 78-year-old man developed a clinical illness and roentgenographic manifestation of miliary tuberculosis. The transbronchial lung biopsy demonstrated granulomas with giant cells. Treatment with antituberculosis therapy resulted in complete resolution of the illness. The pathogenesis of this complication was considered to be due to pulmonary infection by BCG from the bladder source and differs from previously reported cases of interstitial pulmonary infiltrates which more likely represent a hypersensitivity reaction to BCG.

Administration, Intravesical↗
PubMed1987

Biochemical and histochemical alterations following acute soman intoxication in the rat.

Rats injected with a nonlethal acute dose (100 micrograms/kg, sc) of soman (pinacolyl methylphosphonofluoridate) exhibited signs of anticholinesterase toxicity beginning at 5-15 min with increasing severity and lasting for 4-6 hr. Generalized tremors and seizure activity indicated comparatively greater involvement of the central cholinergic system than peripheral neuromuscular effects. During peak toxicity, all the brain regions tested showed more than 95% inhibition of acetylcholinesterase (AChE) activity. The cortex area was maximally affected (99% inhibition). Among skeletal muscles, soleus AChE was most severely affected (94%) and extensor digitorum longus (EDL) the least (72%). Inhibition of EDL AChE occurred at a much slower rate than in brain and other muscles. Significant recovery of AChE activity was seen by 48-72 hr after soman treatment in both brain and skeletal muscles. By Day 7, recovery was virtually complete in skeletal muscles but not in brain, although significant recovery had occurred by this time. Muscle fiber necrosis developed within 6 hr in the soleus and diaphragm, while no necrotic fibers were found in the EDL. The 16 S AChE molecular form showed the fastest recovery of the AChE isozymes in all three muscles. Full recovery was seen after 7 days in soleus and was increased to greater than control activity in diaphragm and EDL. The inhibition pattern of butyrylcholinesterase (BuChE) activity was similar to that described for AChE activity, but the recovery was comparatively faster. Carboxylesterase activity in plasma was decreased to less than 10% of control within 1 hr and recovered to 53% of control within 24 hr. No significant inhibition was seen in hepatic carboxylesterase activity. It can be concluded that soman-induced acute toxicity is directly related to the rate and degree of AChE inhibition. A significant amount of soman binds to non-AChE enzymes with serine sites such as BuChE and carboxylesterases.

Acetylcholinesterase↗
PubMed1987

iso-OMPA-induced potentiation of soman toxicity in rat.

Male Sprague-Dawley rats, injected with the irreversible acetylcholinesterase (AChE) inhibitor soman (pinacolyl methylphosphonofluoridate) 25 micrograms/kg sc, showed no signs of toxicity. Pretreatment with iso-OMPA (tetraisopropylpyrophosphoramide) 1 mg/kg sc 1 h before the soman administration, caused severe signs of hypercholinergic activity, similar to those seen with an acute signs-producing nonlethal dosage (100 micrograms soman/kg sc). Within 1 h iso-OMPA alone significantly reduced the activity of carboxylesterases (CarbE) in all tissues studied and butyrylcholinesterase (BuChE) activity was significantly reduced in plasma (22%) and liver (27%). Soman (25 micrograms/kg) alone significantly reduced the plasma activity of CarbE (15%), BuChE (53%) and AChE (18%), but had no effect on these enzymes of liver. The combined treatment of iso-OMPA and soman, however, reduced CarbE activity in liver (0%) and produced significantly greater effects than iso-OMPA or soman alone on AChE and BuChE in all the brain areas and skeletal muscles tested. The number of necrotic lesions found in skeletal muscles was many times higher with the combined treatment than seen with soman (25 micrograms/kg) alone, and was equal to those seen with an acute toxicity signs-producing dose of soman. It is concluded that the observed iso-OMPA-induced potentiation of soman toxicity is probably caused via reduced nonspecific binding sites (BuChE and CarbE) for soman leading to greater inhibition of AChE.

Acetylcholinesterase↗
PubMed1987

Differences in central and peripheral neural actions between soman and diisopropyl fluorophosphate, organophosphorus inhibitors of acetylcholinesterase.

Toxic doses of acetylcholinesterase (AChE) inhibitors produce prominent motor symptoms (fasciculations, fibrillations, and body tremors) and muscle fiber necrosis. The severity and quality of motor symptoms and fiber necrosis depend upon the specific AChE inhibitor. To examine the importance of nerve and muscle activity in producing muscle necrosis, we recorded electromyographic activity from normal and acutely denervated rat gastrocnemius muscle following administration of the organophosphorus AChE inhibitors soman and diisopropyl fluorophosphate (DFP). The motor symptoms induced on the denervated side represented activity originating at the nerve terminal while those of the contralateral nondenervated muscle represented the sum of peripheral plus central descending activity. The results indicate that soman and DFP produce different responses. At nonlethal toxic doses, the majority of motor symptoms induced by soman is due to impulses descending from the central nervous system, and a proportion of these symptoms are epileptiform activity. This activity is not generated at spinal levels. In contrast, DFP produces motor symptoms mainly by peripheral action that is dependent on a functioning nerve terminal. At lethal doses, both agents have central and peripheral effects. Different patterns of electrical activity are associated with each of the motor symptoms. We found that muscle fiber necrosis correlates best with peripherally generated high-frequency repetitive discharges.

Acetylcholinesterase↗
PubMed1987

Interaction of cycloheximide and diisopropylphosphorofluoridate (DFP) during subchronic administration in rat.

Male Sprague-Dawley rats daily treated with DFP (0.5 mg/kg/day, sc) exhibited signs of cholinergic toxicity such as tremors and muscle fasciculations between Days 3 and 5 comparable to those observed 15 min after a single acute signs-producing dose (1.5 mg/kg, sc). Further administration of DFP (0.5 mg/kg/day, sc) for 6-14 days led to tolerance development as evidenced by disappearance of the described toxicity signs. The protein synthesis inhibitor cycloheximide, when given in a nontoxic dose (0.5 mg/kg/day, sc) 1 hr before DFP (0.5 mg/kg/day, sc) administration, potentiated the DFP toxicity and rats died after the fifth injection. DFP-tolerant rats developed toxicity signs when subsequently treated with cycloheximide (0.5 mg/kg/day, sc) and DFP (0.5 mg/kg/day, sc). Each drug when given alone for 4 days caused 30-50% reduction of [14C]valine uptake in vivo into the free amino acids pool as well as its incorporation into proteins of brain and skeletal muscles. A combination of these drugs caused a significantly greater inhibitory effect on [14C]valine incorporation into proteins. Cycloheximide (0.5 mg/kg/day, sc) administered for 4 days did not significantly alter the levels of acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), or carboxylesterase (CarbE) activities but potentiated the DFP-induced inhibition of the activities of these enzymes. It is concluded that the cycloheximide pretreatment potentiates DFP toxicity by a mechanism that is related to inhibition of the synthesis of proteins such as AChE, BuChE, and CarbE.

Acetylcholinesterase↗
PubMed1987

Alterations of high-energy phosphate compounds in the skeletal muscles of rats intoxicated with diisopropylphosphorofluoridate (DFP) and Soman.

The purpose of the present investigation was to determine the changes in high-energy phosphate compounds and to establish their relationship with organophosphate-induced necrotic lesions in skeletal muscles of rats. Following an acute toxicity signs-producing dose of either diisopropylphosphorofluoridate (DFP) (1.5 mg/kg, sc) or soman (0.1 mg/kg, sc), a significant decline in phosphocreatine (PC) was seen as early as within 1 hr, coinciding with the appearance of necrotic lesions, as reported earlier. The maximum decrease in PC was measured after 6 hr. At this time, among the muscles studied, the hemidiaphragm (the muscle which is known to show the greatest number of necrotic lesions with both of the organophosphorus compounds) showed maximum decrease in PC (57%) with soman treatment. A detailed analysis of adenine nucleotides indicated a significant decrease of adenosine triphosphate (ATP) in all three skeletal muscles, with a marked increase in adenosine monophosphate (AMP) and adenosine diphosphate (except in extensor digitorum longus (EDL)). The levels of creatine in all three skeletal muscles remained unaltered throughout the time-course of study. The observed changes in PC, ATP, and AMP were reversed toward control baseline values after 72 hr. Daily administration of DFP (0.5 mg/kg, sc/day) for 14 days caused only a significant decrease of PC in EDL and soleus during the toxic phase (Day 5), with recovery toward the normal value during the tolerance phase (Day 14). It is concluded that both DFP and soman reduced the PC in skeletal muscles, and the time-course for PC reduction correlates well with the previously reported time-course for muscle fiber necrosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenine Nucleotides↗
PubMed1987

Acute tabun toxicity; biochemical and histochemical consequences in brain and skeletal muscles of rat.

Male Sprague-Dawley rats injected s.c. with an acute non-lethal dose (200 micrograms/kg) of ethyl N,N-dimethylphosphoramidocyanidate (tabun) showed onset of hypercholinergic activity within 10-15 min. The maximal severity of toxicity signs was evident within 0.5-1 h and persisted for 6 h. Except for mild tremors no overt toxicity signs were evident after 24 h. Within 1 h a dramatic decline of acetylcholinesterase (AChE) activity occurred in all the brain structures (less than 3%) and skeletal muscles (less than 10% in soleus and hemi-diaphragm; and 32% in extensor digitorum longus (EDL)). No significant recovery was seen up to 48-72 h. Within 7 days rats became free of toxicity signs and AChE activity had recovered to about 40% in brain structures (except cortex, 14%) and 65-70% in skeletal muscles. Within 1 h the 16 S molecular form of AChE located at the neuromuscular junction was most severely inhibited in soleus, followed by hemi-diaphragm and least in the EDL, and had fully recovered in all the muscles when examined after day 7. Muscle fiber necrosis developed within 1-3 h in soleus and hemi-diaphragm and after a delay of 24 h in EDL. The highest number of necrotic lesions in all muscles was seen at 72 h with the hemi-diaphragm maximally affected and EDL the least. To determine detoxification of tabun by non-specific binding, the activity of butyrylcholinesterase (BuChE) and carboxylesterase (CarbE) was measured. The inhibition and recovery pattern of BuChE activity was quite similar to that of AChE, except that the rate of recovery was more rapid. Within 1 h the remaining activity of CarbE was 10% in plasma, about 30% in brain structures, and 79% in liver; recovery was complete within 7 days. The inhibition of BuChE and CarbE can serve as a protective mechanism against tabun toxicity by reducing the amount available for AChE inhibition. The prolonged AChE inhibition in muscle and brain may indicate storage of tabun and delayed release from non-enzymic sites. Since tabun is a cyanophosphorus compound, the toxic effects from the released cyanide (CN) could be another reason for the delayed recovery after tabun.

Acetylcholinesterase↗
PubMed1987

32P-postlabeling analysis of liver DNA adducts in rats chronically fed a choline-devoid diet.

Liver DNA, obtained at various time intervals from rats chronically fed a choline-devoid diet, was analysed for the presence of aromatic or alkyl adducts by the 32P-postlabeling assay. Alkyl adducts were not detected. Aromatic DNA adduct lesions were revealed, but only at levels (1 adduct per 0.5-3 X 10(9) nucleotides) which are at the limits of the extremely high sensitivity of the method used, levels which remained constant throughout the period of feeding. Thus, contamination of the total environment of the animals with chemical carcinogens does not appear to be responsible for the genesis of the hepatocellular carcinomas that develop in rats chronically fed a choline-devoid diet. The diet, therefore, either acts as a complete carcinogen, or promotes the evolution to cancer of endogenous, 'spontaneously' initiated liver cells.

Animals↗
PubMed1987

Medical implications of organization of the home help service.

The organizational structure and of the role of home help service is described. Doctors working in both geriatric medicine and the community are aware of the home help service through shared contact mainly with frail elderly patients. They are usually well informed about the practical value of the home help service to the patients but seem to lack knowledge about the internal structure of the home help service and its value as an important source of information about the mental and physical ability of the elderly in the community. In our experience direct contact with the home help service is more effective than indirect contact--through the hospital Social Worker. Home care organizers should be part of the multi-disciplinary team when discussing the possible discharge of a frail elderly patient. All medical staff caring for the elderly, whether community or hospital based, should be aware of the administration structure of the home help service to facilitate the interchange of information.

Activities of Daily Living↗
PubMed1987

Treatment of elderly hypertensives with beta-blocker/thiazide combination.

The aim of the study was to determine the efficacy and tolerability of a low dose beta-blocker and diuretic combination in elderly hypertensives. In a prospective, double blind, placebo-controlled cross over study 30 patients with blood pressure higher than 160/90 mmHg and a mean age of 71.5 years were treated with a combination of sotalol hydrochloride 80 mg and hydrochlorothiazide 12.5 mg. With this regimen a significant drop in systolic and diastolic blood pressure (patient in sitting position) was obtained when compared with placebo (p less than 0.05). No significant side effects were noted because high-risk patients were excluded and the beta-blocker was used in low dose combination with thiazide diuretic for synergistic action. We conclude that a combination of beta-blocker and diuretic is an effective and safe therapy in carefully selected elderly patients with mild to moderate hypertension.

Age Factors↗
PubMed1987

Hypertrophic osteoarthropathy associated with a rejected liver transplant.

A patient with severe hepatic transplant rejection presented with evidence of hypertrophic osteoarthropathy. The classic triad of clubbing, periostitis, and arthritis was present along with typical radiographic and bone scan findings. A second liver transplant was not successful and the patient died secondary to massive bleeding. Although hypertrophic osteoarthropathy is known to occur rarely in association with chronic liver disease, it has not been reported accompanying liver transplant rejection. This syndrome is to be differentiated from other causes of arthritis and musculoskeletal pain in liver transplant patients and may contribute towards additional morbidity in these patients.

Adult↗