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Biomedical subjects

S K Chhabra

Publications and source records attributed to S K Chhabra.

At least 19 recordsLinked to original sources
PubMed2005

Effects of Vitamin E on airway responses and biochemical parameters in guinea pigs sensitized to ovalbumin.

The effect of dietary supplementation with Vitamin E was studied in sensitized guinea pigs. After measurement of baseline airway reactivity and sensitization with ovalbumin, the animals were randomized into two groups: Group A, on a commercial feed and Group B, on dietary supplementation with oral Vitamin E (0.7 IU/kg). These were challenged with inhaled ovalbumin after 4 weeks. The following outcomes were studied: airway responses to ovalbumin inhalation, airway reactivity, sodium and calcium ion influx in isolated tracheal cells, Na+ K+ ATPase and Ca2+ ATPase activity in tracheal homogenate and plasma malonaldehyde. Sensitization increased airway reactivity in Group A but not in Group B. The tracheal cells of animals in Group B showed significantly lower rates of 45Ca and 22Na influx and lower activities of tracheal Na+ K+ ATPase and Ca2+ ATPase as compared to Group A. Plasma malonaldehyde was similar between two groups. We concluded that Vitamin E suppresses the increase in airway reactivity following sensitization and has membrane stabilizing actions.

Adenosine Triphosphatases↗
PubMed2005

Cardiovascular autonomic neuropathy in chronic obstructive pulmonary disease.

BACKGROUND: While autonomic neuropathy has been reported in chronically hypoxaemic patients of chronic obstructive pulmonary disease (COPD), whether it also occurs in patients with milder disease and in those without chronic hypoxaemia has not been explored. METHODOLOGY: Lung function measurements including spirometry and transfer factor for carbon monoxide, mean pulmonary artery pressure estimation by color-doppler echocardiography and arterial blood gas analysis were carried out in 56 patients with COPD and 11 age-matched controls. Autonomic function was assessed by tests of cardiovascular reflexes and expressed as valsalva ratio, 30:15 ratio, IE difference and the blood pressure response to postural change. RESULTS: Among patients, majority of the test responses were in the abnormal or borderline range compared to more than 90% of test responses in the normal or borderline range among normals. Almost 50% of patients had definite neuropathy as compared to none in normals. Although, the autonomic neuropathy tended to be observed more often in patients with moderate and severe COPD, it was also found in a fair proportion of patients with mild COPD. Similarly, while it was more prevalent in patients with hypoxaemia, it was also found to occur in those without hypoxaemia. The responses to tests of autonomic function had weak relationships with FEV1% predicted and PaO2. CONCLUSIONS: Cardiovascular autonomic neuropathy is common in COPD and is found even in early stages of the disease.

Adult↗
PubMed2004

Effect of sensitization on membrane ion fluxes & intracellular calcium in guineapigs.

BACKGROUND & OBJECTIVES: The biochemical mechanisms underlying the development of sensitization-induced airway hyperresponsiveness (AHR) in asthma are poorly defined. Alterations in the regulation of intracellular calcium may play an important role in its pathogenesis. We carried out this study to see the effect of sensitization with ovalbumin on membrane ion fluxes and intracellular calcium in a guinea pig model. METHODS: Airway reactivity to inhaled histamine was measured initially and after sensitization with ovalbumin in 28 guineapigs. Intracellular calcium [Ca(2+)]i was measured in tracheal smooth muscle cells and peripheral leukocytes using fluorescent dye FURA 2AM. Calcium and sodium ion influx across the cell membrane was measured in leukocytes. Ouabain-sensitive Rubidium ((86)Rb) influx was measured in tracheal smooth muscles cells. The activities of Na(+), K(+) ATPase and Ca(2+) ATPase were measured in tracheal smooth muscle cells. Lipid peroxides were measured in plasma. RESULTS: Airway responsiveness was significantly (P<0.001) increased after sensitization along with an increase in [Ca2+]i levels in leukocytes and tracheal smooth muscle cells, higher rates of (45)Ca and (22)Na influx in leukocytes and higher (86)Rb influx rates in tracheal smooth muscle cells, and increased levels of lipid peroxides in plasma. INTERPRETATION & CONCLUSION: In guineapig model of asthma sensitization to allergen increased the membrane permeability to calcium and sodium, and intracellular calcium levels. These alterations may play a role in the pathogenesis of airway hyper-responsiveness following sensitization.

Animals↗
PubMed2002

Expression of bronchodilator response: comparison of four indices.

Several indices have been suggested to express the bronchodilator response but there is no agreement on what is the ideal expression. The forced expiratory volume in I s (FEV1) was measured in 190 patients of bronchial asthma before and after inhalation of 200 micrograms salbutamol. Four different indices of bronchodilator response were calculated. The change in FEV1 was expressed as absolute value (delta FEV1), as a percentage of initial FEV1 (delta FEV1% initial), as a percentage of the predicted normal value (delta FEV1% predicted) and as a percentage of maximum achievable reversibility, i.e. the difference between predicted and initial values (delta FEV1% [predicted-initial]). A significant negative correlation was observed between delta FEV1 initial and initial FEV1% predicted (r = -0.33, P < 0.0001) but not delta FEV1 and initial FEV1% predicted, or between delta FEV1% predicted and initial FEV1% predicted. The values of delta FEV1% [predicted-initial] tended to reach towards infinity as the initial FEV1% predicted approached 100%. delta FEV1% predicted had similar sensitivity but greater specificity than delta FEV1% initial in detecting a true bronchodilator response. It was concluded that being dependent on the initial value, delta FEV1% initial was not an appropriate method to express the bronchodilator response. Although all other methods had limitations, delta FEV1 and delta FEV1% predicted appeared to be better indices.

Adult↗
PubMed2001

Mechanisms of inhibition of chemical toxicity and carcinogenesis by diallyl sulfide (DAS) and related compounds from garlic.

Diallyl sulfide (DAS) is a flavor compound derived from garlic and is sequentially converted to diallyl sulfoxide (DASO) and diallyl sulfone (DASO(2)) by cytochrome P(450) 2E1 (CYP2E1). These compounds have been shown to reduce the incidence of a multitude of chemically induced tumors in animal models. The impediment of phase I activation of these carcinogens is hypothesized to be accountable for the reduction in tumor incidence. Indeed, DAS, DASO and DASO(2) are competitive inhibitors of CYP2E1. DASO(2), in addition, is a suicide inhibitor of CYP2E1. These compounds have been shown to reduce carbon tetrachloride-, N-nitrosodimethylamine- and acetaminophen-induced toxicity in rodents. All three chemicals are substrates for CYP2E1. The protective effect was observed when the organosulfur compounds were given before, during or soon after chemical treatment. DAS and DASO(2) inhibited the bioactivation of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and related lung tumorigenesis in A/J mice. Because CYP2E1 does not play a key role in NNK activation, the inhibition of other CYP enzymes active in NNK metabolism is likely. DAS also has been shown to induce other CYP and phase II enzymes as well as decrease hepatic catalase activity. All of these effects are observed at concentrations much higher than what is normally ingested by humans. The biological activities of garlic and its related compounds at lower concentrations that mimic human consumption remain to be studied further.

Allyl Compounds↗
PubMed2001

Relationship between intracellular calcium and airway reactivity in guinea pigs.

The present study was carried out to examine the relationship between intracellular free calcium ion concentrations and its regulatory enzymes, sodium potassium adenosine triphosphatase (Na(+),K(+)-ATPase) and calcium adenosine triphosphatase (Ca(2+)-ATPase), with airway reactivity to inhaled histamine in guinea pigs. Forty-nine guinea pigs were included in this study. Of these, 34 animals responded to histamine bronchoprovocation challenge in vivo with a greater than 35% fall in specific airways conductance and were labeled as "reactive," and the remaining 15 were "nonreactive." The dose of histamine producing a 35% fall in specific airways conductance was labeled as ED(35) SGaw. The animals were then sacrificed, and the following biochemical measurements were carried out: intracellular free calcium ion concentrations [Ca(2+)](i) in leukocytes and isolated tracheal smooth muscle cells, activities of Na(+),K(+)-ATPase and Ca(2+)-ATPase in tracheal homogenate, and plasma levels of lysophosphatidylcholine (LPC). Reactive guinea pigs showed significantly higher [Ca(2+)](i) and Na(+),K(+)-ATPase and Ca(2+)-ATPase activities. Airway reactivity (ED(35) SGaw) had significant negative correlation with [Ca(2+)](i), with activities of each of the ATPases and with plasma lysophosphatidylcholine. It is concluded that the level of [Ca(2+)](i) is an important determinant of airway reactivity. Intracellular calcium levels modulate airway response to histamine with higher levels being associated with greater reactivity.

Administration, Inhalation↗
PubMed2001

Evaluation of influenza virus detection by direct enzyme immunoassay (EIA) and conventional methods in asthmatic patients.

Throat gargle specimens of fifty-seven acute asthmatic patients (age range 18-40 years) were collected for the study. Thirty-four patients were found influenza virus positive in acute asthma cases. Influenza virus was isolated by conventional culture method on MDCK cell-line and by enzyme immunoassay test (EIA). The EIA negative specimens were retested after virus amplification on MDCK cell-line. Virus shedding and virus surface receptors assay was carried out to determine influenza virus titre. Airway functions were measured by spirometry. A good relationship was observed between the degree of airflow limitation and presence of influenza virus infection (p < 0.001; r = 0.85). A comparable difference in % FEV1 was observed in relation to the symptoms. The patients with greater viral antigen load had lower % FEV1. Two specimens, which were EIA negative, turned out to be positive after amplification on MDCK cell-line. The sensitivity was 98% and specificity was 100%. It was concluded that EIA method is a useful diagnostic tool as it detects influenza viral antigen quickly as compared to conventional methods.

Adolescent↗
PubMed2000

Coexposure to ethanol with N-nitrosodimethylamine or 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone during lactation of rats: marked increase in O(6)-methylguanine-DNA adducts in maternal mammary gland and in suckling lung and kidney.

Use of alcoholic beverages increases risk of cancer at several target sites, including the breast. Of several possible mechanisms for this effect, competitive inhibition by ethanol of hepatic clearance of nitrosamines, resulting in increased dose delivery to posthepatic tissues, gives the quantitatively most pronounced enhancement. We investigated whether this effect would pertain to the mammary gland, and to ethanol and nitrosamines delivered translactationally to sucklings. Ethanol (1.6 g/kg) was administered by gavage to nursing Sprague-Dawley rats 10 min before 5 mg/kg N-nitrosodimethylamine (NDMA) or 50 mg/kg 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK); treatment was on postnatal days 1, 7, or 14. Tissues taken 4 h later for analysis of O(6)-methylguanine in DNA were liver, blood, and mammary glands from the mothers, and liver, lung, kidney, and blood from the sucklings. Ethanol cotreatment resulted in a marked, 10-fold increase in O(6)-methylguanine adducts from NDMA in mammary gland, as well as smaller but significant increases in this tissue from NNK and in maternal blood cells from both chemicals; adducts in maternal liver decreased slightly. In the sucklings, ethanol cotreatment also lowered adducts in liver after NDMA or NNK treatment. After NDMA, adducts were also detected in suckling lung and kidney and were increased five- to 10-fold after ethanol coexposure. Adducts from either chemical, with or without ethanol, decreased markedly in all suckling tissues with development from postnatal day 1 to day 14. Thus ethanol coexposure with nitrosamines increases O(6)-methylguanine DNA adducts in mammary gland and strongly influences adduct formation in suckling tissues after translactational delivery.

Animals↗
PubMed2000

Tea and tea polyphenols in cancer prevention.

The inhibitory action of tea (Camellia sinensis) and tea components against cancer formation has been demonstrated in different animal models involving different organ sites in many laboratories. The possible preventive activity of tea against cancer in humans, however, is not clear. A critical question is whether the information obtained from animal studies is applicable to humans because of possible species differences or the difference in the quantity of tea used in animal studies and that consumed by humans. This article will discuss the results from animal studies and possible cancer inhibitory mechanisms that might be applicable to human cancer prevention. To provide a basis for more quantitative analyses of the effect of tea on carcinogenesis, the levels of tea polyphenols in blood, urine and tissue samples have been analyzed, and the pharmacokinetic properties of tea polyphenols studied. Studies with cell lines have demonstrated that tea polyphenols affect signal transduction pathways, inhibit cell proliferation and induce apoptosis, but the effective concentrations are usually much higher than those observed in blood and tissues. More mechanistic studies in these areas will help us to understand the inhibitory action of tea against carcinogenesis and provide background for evaluating the effects of tea consumption on human carcinogenesis.

Animals↗
PubMed2000

Prednisolone hastens recovery from histamine-induced bronchospasm in asthmatics.

Short-term treatment with oral steroids is very effective in control ling symptoms and improving lung function in asthma but has not been shown unequivocally to reduce bronchial hyperresponsiveness. Recently it has been shown to increase the activities of sodium-potassium and calcium adenosine triphosphatases, enzymes that regulate intracellular calcium levels. This action may be expected to promote recovery of cells from an excitatory stimulus. The present study was carried out to determine how prednisolone modulates airway response to histamine, including recovery from induced bronchospasm in asthmatics. Spirometry and measurement of bronchial responsiveness (forced expiratory volume in 1 sec [FEV1] and concentration of histamine causing a 20% reduction FEV1 [PD20 FEV1]) to inhaled histamine were carried out in 10 clinically stable asthmatics. Subsequently, all of the patients were prescribed oral prednisolone, 0.6-0.75 mg/kg body weight for 1 week. At the end of 1 week, spirometry was repeated and bronchial reactivity was measured again. Comparison of PD20 FEV1 values before and after treatment (geometric means 0.66 and 0.81 mg/mL, respectively) for the whole group did not show any significant change. The mean +/- SD time for 95% recovery from histamine-induced bronchospasm was 33.00 +/- 19.47 min before treatment and decreased significantly to 18.00 +/- 7.88 min after treatment. It was concluded that short-term benefits from oral prednisolone do not result from changes in bronchial responsiveness. These benefits may be related to effects on mechanisms that lead to recovery from an excitatory stimulus.

Administration, Oral↗
PubMed2000

Metabolism of 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone by cultured monkey lung explants.

The metabolism of the tobacco-specific lung carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) was investigated in short-term cultures of monkey lung. Explants from the lungs of two patas monkeys (Erythrocebus patas) and one cynomolgus monkey (Macaca fascicularis) were incubated with 10 microM [5-(3)H]NNK and aliquots were analyzed for NNK metabolites by HPLC at various time points from 1 to 24 h. F344 rat lung tissue metabolism of NNK was assayed under the same conditions. Substantial amounts of metabolites from the alpha-hydroxylation metabolic activation pathway were detected in all cultures. In two of the monkey lung cultures, these metabolite levels were significantly higher than those formed by other pathways. All cultures also metabolized NNK by pyridine-N-oxidation and carbonyl reduction. The metabolism of NNK by cultured monkey lung was generally similar to that observed in rat lung, indicating that there are not major species differences between rodents and nonhuman primates in pulmonary metabolism of NNK.

Animals↗
PubMed1999

Risk factors for development of bronchial asthma in children in Delhi.

BACKGROUND: Information on the magnitude of the problem of childhood asthma in India and the factors influencing its occurrence is inadequate. OBJECTIVE: To measure the prevalence of asthma in schoolchildren in Delhi and study the factors determining its occurrence. METHODS: A questionnaire-based study carried out in nine randomly selected schools in Delhi. The age range was 5 to 17 years. The questionnaires were distributed to all the children (n = 21,367) for answering by either parent. The key questions relate to complaints of recurrent wheezing in the past, during the immediate last 1-year, and also wheezing exclusively induced by exercise or colds. In all, 19,456 questionnaires were received back (response rate 91%). Out of these, 18,955 were complete and analyzed. RESULTS: The prevalence of current asthma was 11.9% while past asthma was reported by 3.4% of children. Exclusive exercise-induced asthma was reported by 2.1% while that associated with colds by 2.4% of children. Boys had a significantly higher prevalence of current asthma as compared with girls (12.8% and 10.7%, respectively). Multiple logistic regression analysis showed that male sex, a positive family history of atopic disorders, and the presence of smokers in the family were significant factors influencing the development of asthma while economic class, air pollution (total suspended particulates), and type of domestic kitchen fuel were not. CONCLUSIONS: The prevalence of current asthma in children in Delhi is 11.9%. Significant risk factors for its development are male sex, a positive family history of atopic disorders, and the presence of smokers in the family.

Adolescent↗
PubMed1999

Comparison of the polymorphic regions of the cytochrome P450 CYP2E1 gene of humans and patas and cynomolgus monkeys.

Cytochrome P450 2E1 (CYP2E1) metabolizes low molecular weight toxicants. CYP2E1 gene polymorphisms have been linked to risk of various cancers and liver disease in humans. Since the patas monkey is a promising model for study of cancer-related alcohol/nitrosamine interactions, we examined CYP2E1 in this monkey for characteristics of two regions that are polymorphic in humans, an RsaI site in the 5' promoter region and a DraI site in intron 6. Another monkey species often used in biomedical research, the cynomolgus monkey, was also examined. Human DNA primers used to amplify a 413 bp segment around the RsaI site also amplified a segment of similar size (409 bp) from DNA of 25 patas monkeys, whereas a product of approximately 800 bp was amplified from DNA of eight cynomolgus monkeys. RsaI did not cut the amplified DNA product from either monkey species. Sequencing revealed that the patas RsaI site was identical to that in humans with the c2c2 CYP2E1 genotype, GTAT. The equivalent cynomolgus sequence, CTAC, has not been observed in humans. Thus, the patas monkey appears to be a useful model for CYP2E1 c2c2 humans, and this genotype, present in 2-25% of humans, may be more primitive than c1c1. For the DraI site, the human primers amplified DNA products similar in size to those from humans, from all patas and cynomolgus monkey DNA samples; none were cut by DraI. Thus, both monkey species appeared to be generally similar to humans of CYP2E1 CC DraI genotype, which is the rarer form of the gene.

Animals↗
PubMed1999

Increased intracellular calcium and decreased activities of leucocyte Na+,K+-ATPase and Ca2+-ATPase in asthma.

The present study was carried out to determine the intracellular free calcium concentration ([Ca(2+)](i)) and the activity of its regulatory enzymes (Na(+),K(+)-ATPase and Ca(2+)-ATPase) in leucocytes. Levels of plasma lysophosphatidylcholine (LPC) were also measured. Then the relationship between these parameters and the clinical severity of asthma and bronchial reactivity was studied. Patients with asthma were divided into three groups: acute asthma (subjects in acute exacerbation), uncontrolled asthma (subjects currently symptomatic) and stable asthma (subjects currently asymptomatic). A group of normal subjects was also studied. Spirometry, specific airway conductance and bronchial reactivity measurements were carried out. The following biochemical parameters were studied in venous blood: leucocyte [Ca(2+)](i), Na(+), K(+)-ATPase and Ca(2+)-ATPase activities, and plasma LPC. Leucocyte [Ca(2+)](i) was increased and the activities of Na(+),K(+)-ATPase and Ca(2+)-ATPase were decreased in patients with asthma. Plasma levels of LPC were also increased. These changes were observed to be greatest among asthmatics in acute exacerbation of asthma, and lesser in magnitude in patients with less severe asthma. The activities of both ATPases were found to have a significant positive correlation, and [Ca(2+)](i) and the levels of plasma LPC a significant negative correlation, with predicted forced expiratory volume in 1 s (FEV(1)). No significant correlation was observed between the biochemical parameters and bronchial reactivity. It is concluded that intracellular calcium homoeostasis is abnormal in asthma; specifically, the activities of Na(+),K(+)-ATPase and Ca(2+)-ATPase are decreased. These abnormalities may modulate the clinical severity of asthma.

Acute Disease↗
PubMed1998

Late asthmatic response in exercise-induced asthma.

BACKGROUND: There is a controversy over the occurrence of a late asthmatic response during exercise-induced asthma. While some workers have documented such a response as a genuine phenomenon, others have attributed this to drug withdrawal. OBJECTIVES: We carried out the present study to investigate whether a late asthmatic response occurs during exercise-induced asthma as a genuine event and, if so, what are the factors which determine its occurrence. METHODS: Sixteen, clinically stable asthmatic patients with laboratory-proven exercise-induced asthma underwent a standardized exercise challenge on a bicycle ergometer. The airway response to exercise was studied by spirometry to measure FEV1. Spirometry was carried out before the exercise, at 4, 8, 15, 30, and 60 minutes, and then hourly for the next 7 hours. Spirometry was also done repeatedly as above on a non-exercise control day, four to seven days earlier. RESULTS: Eight (50%) subjects developed a second fall of greater than 10% in FEV1, three to eight hours after recovery from the early response. The late fall in FEV1 after exercise was significantly greater than the spontaneous decay of lung function at the corresponding clocktime on the non-exercise control day. The dual responders did not differ from those with isolated early responses with respect to age, duration and severity of asthma, treatment requirements, peripheral blood eosinophilia, and atopic status. Baseline FEV1 and maximum fall in FEV1 during the early response, and the rate of its development and recovery from it were also similar. Among the dual responders, the late response was not related to the baseline FEV1 or to the intensity of the early response. CONCLUSIONS: A late asthmatic response is a genuine phenomenon in exercise-induced asthma. Its occurrence cannot however be predicted by any clinical or physiologic factors.

Adult↗
PubMed1998

Prevalence of bronchial asthma in schoolchildren in Delhi.

There is a paucity of information on the prevalence of asthma in children in India. Some evidence suggests that asthma is less common in developing than in the developed countries. The present study was carried out to estimate its current magnitude in children in Delhi. The questionnaire-based study was carried out in two randomly selected schools in Delhi. All the children were eligible. The age range was 4-17 years. The questionnaires were distributed to all the children present (n = 2867) to be answered by either parent. The key questions were related to complaints of recurrent wheezing in the past, in the last 1 year, and also wheezing exclusively induced by exercise or colds. In all, 2609 questionnaires were completed and returned (response rate 91%). There was a slight excess of males (54%). The prevalence of current asthma was 11.6% and past asthma was reported by 4.1% of children, giving a cumulative prevalence of 15.7%. Exclusive exercise-induced asthma was 2.8% and that associated with colds, 2.3%. The current prevalence of all wheezing was thus 16.7% and cumulative prevalence was 20.8%. While there was no sex-related difference in prevalence, wheezers were the highest in the 9-13 year age group. A significant association was found between the prevalence of wheezing and a family history of asthma (odds ratio 3.65) and presence of smokers in the family (odds ratio 1.62). When both the above factors combined, the odds ratio for risk of asthma was 4.58. There was no significant association with any economic class. Only 11% of asthmatics had been labeled so by their physicians. The prevalence of bronchial asthma and wheezing in children in Delhi is quite high and comparable to that reported from several developed countries. A positive family history of asthma and presence of smokers in the family emerged as significant risk factors.

Adolescent↗
PubMed1998

Forced vital capacity, slow vital capacity, or inspiratory vital capacity: which is the best measure of vital capacity?

Vital capacity can be measured as forced vital capacity (FVC), slow vital capacity (SVC), and inspiratory vital capacity (IVC). Although it is well known that the latter two are generally greater, a systematic comparison of the three in subjects with different degrees of airways obstruction has not been made. Sixty asthmatics and 20 normal subjects performed maneuvers for measurement of FVC, SVC, and IVC on a dry, rolling-seal spirometer. The severity of airways obstruction in asthmatics was classified as mild, moderate, and severe. There was no significant difference between FVC, SVC, and IVC in normal subjects. However, the three measurements of vital capacity were significantly different in all subgroups of asthmatics. FVC was smaller than both SVC and IVC. The differences were more marked in patients with moderate and severe degrees of airways obstruction. The differences between SVC and IVC were small and clinically not important. Forced expiratory volume in 1 sec (FEV1) expressed as percent of FVC, SVC, and IVC, was not different in normals and asthmatics with mild airways obstruction. The ratios were significantly different in asthmatics with moderate and severe airways obstruction. FEV1/IVC ratio was the lowest in both the groups followed by FEV1/SVC and FEV1/FVC. IVC and SVC are greater than FVC in patients with airways obstruction. This difference increases as the degree of obstruction increases. The difference between SVC or IVC and FVC serves as an indicator of air trapping. Both FVC and IVC could be measured and the largest VC used to calculate the FEV1/VC ratio because this increases the sensitivity of spirometry in detecting airways obstruction.

Adult↗