PubMed Health⌕ Search

Biomedical subjects

A Shukla

Publications and source records attributed to A Shukla.

At least 19 recordsLinked to original sources
PubMed1999

Characterization of cadmium-induced apoptosis in rat lung epithelial cells: evidence for the participation of oxidant stress.

The mode of cadmium-induced cell death was investigated in a rat lung epithelial cell line. Cells, grown to near confluence, were exposed to 0-30 microM CdCl2 for 0-72 h. Phase contrast microscopy and fluorescent nuclear staining showed that Cd caused morphological alterations in lung epithelial cells that are characteristic of apoptosis. These changes included cell shrinkage, detachment of the cell from its neighbors, cytoplasmic and chromatin condensation, and fragmentation of the nucleus into multiple chromatin bodies surrounded by remnants of the nuclear envelope. Apoptotic DNA degradation was validated and quantitated using a sensitive enzyme-linked immunosorbent assay (ELISA) which measures the amount of histone-bound DNA fragments in the cytosol. Using this technique, a maximum level of apoptosis (5-fold higher than control) was observed in cultures exposed for 48 h to 20 microM CdCl2. The terminal deoxyribonucleotidyl transferase mediated dUTP nick end labeling method (TUNEL) was subsequently used to determine the percentage of cells that contained Cd-induced DNA strand breaks. After 48 h, approximately 54% of the cells exposed to 20 microM Cd were TUNEL positive compared to less than 2% for control cells. Although the mechanisms by which Cd initiates apoptosis in these cells are presently not known, reactive oxygen species are likely to play a role. This possibility is supported by the finding that the first morphological features indicative of apoptosis were preceded by the up-regulation of oxidant stress genes (glutathione S-transferase-alpha, gamma-glutamylcysteine synthetase, and metallothionein-1), activation of redox sensitive transcription factors (AP-1 and NF-kappaB), and changes in various forms of glutathione (reduced, oxidized, and protein-bound).

Animals↗
PubMed1999

Asiaticoside-induced elevation of antioxidant levels in healing wounds.

Asiaticoside derived from the plant Centella asiatica is known to possess good wound healing activity. Enhanced healing activity has been attributed to increased collagen formation and angiogenesis. Since antioxidants have been reported to play a significant role in the wound healing process we studied the effect of asiaticoside on the levels of certain antioxidants in the wound so as to explore the possible involvement of such a mechanism in the asiaticoside induced wound healing. Asiaticoside application (0.2%, topical) twice daily for 7 days to excision-type cutaneous wounds in rats led to increased enzymatic and non-enzymatic antioxidants, namely superoxide dismutase (35%), catalase (67%), glutathione peroxidase (49%), vitamin E (77%) and ascorbic acid (36%) in newly formed tissues. It also resulted in a several fold decrease in lipid peroxide levels (69%) as measured in terms of thiobarbituric acid reactive substance. However, continued application for 14 days showed no significant difference in these antioxidants compared with their values in vehicle treated wound tissue. It appears from the present study that asiaticosides enhanced induction of antioxidant levels at an initial stage of healing which may be an important contributory factor in the healing properties of this substance.

Animals↗
PubMed1999

In vitro and in vivo wound healing activity of asiaticoside isolated from Centella asiatica.

The activity of asiaticoside, isolated from Centella asiatica, has been studied in normal as well as delayed-type wound healing. In guinea pig punch wounds topical applications of 0.2% solution of asiaticoside produced 56% increase in hydroxyproline, 57% increase in tensile strength, increased collagen content and better epithelisation. In streptozotocin diabetic rats, where healing is delayed, topical application of 0.4% solution of asiaticoside over punch wounds increased hydroxyproline content, tensile strength, collagen content and epithelisation thereby facilitating the healing. Asiaticoside was active by the oral route also at 1 mg/kg dose in the guinea pig punch wound model. It promoted angiogenesis in the chick chorioallantoic membrane model at 40 microg/disk concentration. These results indicate that asiaticoside exhibits significant wound healing activity in normal as well as delayed healing models and is the main active constituent of Centella asiatica.

Administration, Oral↗
PubMed1999

Esophageal-directed pressure support ventilation in normal volunteers.

STUDY OBJECTIVES: To ascertain whether inspiratory pressure support (IPS) can be triggered reliably from and targeted at esophageal pressures (Pes), and to compare the work of breathing and time delay to initiation of inspiratory flow between conventional pressure support and esophageal-directed pressure support (EDPS). DESIGN: Prospective laboratory study. SETTING: University medical school. PATIENTS OR PARTICIPANTS: Five normal volunteers. INTERVENTIONS: IPS at a level to achieve tidal volume of 10 mL/kg, and EDPS with a target Pes of 0 cm H2O via full facemask. MEASUREMENTS AND RESULTS: Pes, airway pressure, and inspiratory flow were measured during spontaneous breathing. Peak Pes and pressure time product (PTP) of Pes were calculated during spontaneous breathing and through linear resistances. Measurements were repeated during IPS and EDPS ventilation. At rest, PTP was 7.56 (+/- 3.6) and peak Pes was -5.8 cm H2O (+/- 1.44). When subjects were breathing through the resistors, PTP increased to 12.4 (+/- 8.1) and 30.3 (+/- 8.9) and peak Pes decreased to -7.2 and -15.3 cm H2O respectively. With facemask IPS, unloaded PTP fell to 1.7 (+/- 1.3) and peak Pes fell to -3.3 cm H2O (+/- 1.3). When ventilated through the highest resistance with IPS, mean PTP increased to 21.9 and peak Pes increased to -11.9 (+/- 4.2) cm H2O relative to baseline. During EDPS with the resistor, PTP fell to 1.5+/-1.1 (p < 0.007) and peak Pes fell to -1.9+/-1.1 cm H2O (p < 0.0001). CONCLUSIONS: It was possible to initiate supported breathing from Pes values. The work performed, as measured by PTP, was lower during EDPS than during either unsupported breathing or conventional IPS.

Feasibility Studies↗
PubMed1998

Differential expression of proteins during healing of cutaneous wounds in experimental normal and chronic models.

Recent studies have demonstrated growth factors and other cellular proteins as being important in the healing process. In this study, we have investigated the differential expression of proteins in wound tissues of normal and chronic animal models. Proteins were identified by specific antibodies, partial N-terminal amino acid sequence, and molecular weight homology. In normal wound tissues de novo synthesis of a heat shock protein, platelet derived growth factor (PDGF), and fibroblast growth factor (FGF) was induced within 24 h of skin injury. Proteins resembling vascular endothelial growth factor, receptors for PGDF, FGF, and epidermal growth factor, were synthesized. The elevated synthesis declined to a basal level in 7 to 14 days after skin injury which coincided with healing of wounds. These changes occurred only in wound site tissues but not in distal tissues. In contrast, the chronic wounds presented a different picture. The expressions of these proteins were either delayed or inhibited. This suggested the role of these proteins during normal and chronic wound healing. The proteins which were down regulated in chronic wounds may be used in the management of wounds and exploited as targets for therapeutic development.

Animals↗
PubMed1997

Comparison of commonly used clinical indicators of hypovolaemia with gastrointestinal tonometry.

OBJECTIVE: The gastrointestinal tonometer, which allows measurement of gastrointestinal mucosal CO2 and subsequent derivation of gut intramucosal pH (pHi), has been demonstrated to be a sensitive predictor of outcome following major surgery. Current theory suggests that the origin of the low pH may be hypovolaemia. This study was designed to compare the temporal sequence of changes in tonometric readings with invasive blood pressure, stroke volume, heart rate, lactate and arterial blood gas measurements during progressive haemorrhage. DESIGN: Observational healthy volunteer study. SETTING: Intensive care unit at University College London Hospitals. SUBJECTS: Six healthy, medically qualified volunteers. INTERVENTIONS: After obtaining baseline measurements, the subjects were progressively bled 25% (range = 21-31%) of their blood volume over a period of 1 h in two approximately equal aliquots. Equilibration was allowed for 30 min following the bleed, after which further measurements were made and the blood was then retransfused over 30 min. MEASUREMENTS AND MAIN RESULTS: There was no consistent change in any of the haemodynamic variables other than gastric intramucosal CO2:arterial CO2 gap (PiCO2-PaCO2) after removal of the first aliquot of blood, although five of the six subjects also demonstrated a fall in pHi. After removal of the second aliquot of blood, PiCO2-PaCO2 gap and pHi continued to indicate a worsening gastric intramucosal acidosis; stroke volume, as measured by suprasternal Doppler, demonstrated a marked fall, while all other variables measured had not altered consistently or to such a degree as to elicit a clinical response or cause suspicion of a hypovolaemic state. On retransfusion, all variables returned towards baseline. CONCLUSIONS: This study demonstrates the value of tonometry as an early monitor of hypovolaemia and highlights the shortcomings of other more commonly measured clinical variables.

Adult↗
PubMed1997

Assessment of exposure to chemical agents and ergonomic stressors in tanneries in Kanpur, India.

In developing countries qualitative assessment of exposure at the workplace may be an essential tool in evaluating hazardous working conditions. This survey reports on qualitative assessment of exposure to chemicals, dust, and ergonomic stressors among 298 workers in 15 tanneries in Kanpur, India. In general, chemical exposure and dermal exposure were highest among beamhouse workers, less for workers involved in dry finishing activities, and lowest for those performing the wet finishing of hides. Dermal exposure was rated as high to very high during beamhouse activities, reflecting direct contact with wet hides and manual handling of hides in soak tanks. Relevant dust exposure was observed only during dry finishing activities. Most workers experienced severe postural load due to working in trunk flexion and rotation for more than 50% of their daily work time. In addition, manual materials handling with loads over 20 kg frequently occurred. The size of the tannery, in general a reflection of state of technology, showed no systematic influence on exposure profiles. The survey suggested that mechanization of material transfer and application of trolleys reduced the work time with trunk flexion and rotation and implied less manual lifting. The presence of local exhaust ventilation in large tanneries seemed to reduce the chemical exposure. This survey has demonstrated the importance of rapid appraisal techniques for evaluating hazardous conditions at the workplace. In developing countries this approach may facilitate occupational hygiene research and practice.

Dust↗
PubMed1997

Respiratory disorders, skin complaints, and low-back trouble among tannery workers in Kanpur, India.

In a cross-sectional survey health complaints among 418 laborers in 15 Indian tanneries were studied. Low-back pain (61%), asthma (38%), dermatitis (23%), and chronic bronchitis (14%) were the most frequently reported complaints in the 12 months prior to the survey. In general, beamhouse workers reported the highest prevalence but only chronic low-back pain was significantly elevated compared with workers in the finishing departments. When using individual exposure estimates, clear associations were presented among manual lifting over 20 kg and low-back pain (OR = 3.5) and skin exposure and dermatitis (OR = 2.6). Frequent lifting of loads was also associated with self-reported asthma. About 44% of the laborers reported at least one period of sickness absence, and 17% were involved in a serious occupational accident that required a visit to the local physician. Logistic regression analysis showed that sickness absence occurred more often in small tanneries (OR = 2.7) and also was significantly associated with low-back pain (OR = 3.3) and occupational accidents (OR = 2.2). This epidemiologic survey on health complaints in tannery workers is among the few in occupational populations in low-income countries. For many reasons these populations are easily overlooked. The results of this descriptive study indicate that there is a clear need for epidemiologic surveys in these countries to obtain information on working conditions and associated health problems.

Adult↗
PubMed1997

Depletion of reduced glutathione, ascorbic acid, vitamin E and antioxidant defence enzymes in a healing cutaneous wound.

In the present investigation the involvement of free radicals in a self-healing cutaneous wound has been demonstrated. The levels of different enzymatic and non-enzymatic antioxidants have been studied in 2,4,7 and 14 days old wounds and compared with normal skin. Except for glutathione reductase (GR), all other enzymatic and non-enzymatic antioxidants were found to decrease following wounding. The decrease was 60-70% in superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione-S-transferase (GST) at 2, 4 and 7 days, while in the case of catalase (CAT) the decrease was 40-60% during this period. Although a complete recovery in the activity of CAT was observed, SOD and GPx did not recover completely and GST was found to be slightly elevated on 14th day post wounding. Non-enzymatic antioxidants viz, ascorbic acid, vitamin E and glutathione were also found to decrease to about 60-70% and except glutathione none of them was found to recover completely at 14th day postwounding. Interestingly thiobarbituric acid reactive substance (TBARS) expressed as malondialdehyde (MDA) equivalent, a marker of lipid peroxidation, decreased following wounding which could be because of meagre availability of lipid substrate and/or of ascorbic acid. The results indicate that wounding results in loss of different free radical scavengers both enzymatic and non-enzymatic which either partially or completely recover following healing.

Animals↗
PubMed1996

Nitric oxide-dependent blood-brain barrier permeability alteration in the rat brain.

The role of nitric oxide (NO), a well known vasodilator, in the regulation of blood-brain barrier (BBB) permeability is not clear. Therefore, the present study was planned to assess the role of NO-releasing compounds like sodium nitroprusside (SNP) and the active metabolite of molsidomine, SIN-1, as well as a precursor on NO, L-arginine, on this physiological barrier. The permeability was assessed by using several tracers. All three agents increased the permeability of BBB to the tracer. The increase in permeability caused by L-arginine was not blocked by N-nitro-L-arginine methyl ester (L-NAME). L-Arginine-treated brains did not show an elevation of nitrite content, thus ruling out the possibility of NO generation and its involvement in BBB permeability alteration. It is concluded that NO itself causes an increase in the permeability of BBB. However, arginine-induced opening is not NO mediated.

Animals↗
PubMed1996

Cadmium-induced alterations in blood-brain barrier permeability and its possible correlation with decreased microvessel antioxidant potential in rat.

1. Male albino rats of 21 days age were exposed to 10 p.p.m. cadmium (CdCl2 salt) in drinking water, ad libitum, for 90 days. It increased the brain cadmium levels by 76% (P < 0.05) and 165% (P < 0.001) respectively at 30 and 90 days of exposure compared to controls. 2. Cadmium increased blood-brain barrier permeability of fluoroscein dye (24%, P < 0.02) and the levels of brain microvessel malondialdehyde (31%, P < 0.01) at 90 days of exposure. However, these parameters did not alter significantly at 30 days of exposure. 3. Increased activities of microvessel superoxide dismutase (18%, P < 0.02), glutathione peroxidase (20%, P < 0.01) and catalase (28%, P < 0.01) were observed at 30 days of exposure. 4. The continuation of the Cd treatment for 90 days decreased the levels of superoxide dismutase (30%, P < 0.001), glutathione peroxidase (23%, P < 0.005), catalase (25%, P < 0.005), glutathione reductase (18%, P < 0.02), vitamin E (20%, P < 0.01), glutathione (26%, P < 0.01), ascorbic acid (18%, P < 0.05) and ceruloplasmin (13%, P < 0.05) in the microvessal preparation compared to controls. 5. It appears that Cd-induced blood-brain barrier dysfunction may be related to the depletion of microvessel antioxidant substances along with increase in lipid peroxidation at 90 days of exposure.

Administration, Oral↗
PubMed1996

Industrial Counseling: Linking Occupational and Environmental Health in Tanneries of Kanpur, India.

This paper describes an occupational health program in tanneries in Kanpur, India. The program was instituted as part of a bilateral cooperative effort of India and The Netherlands focusing on providing engineering solutions to prevent industrial waste and community sewage from polluting the Ganges river. The occupational health program was linked to the environmental activities by adopting the concept of industrial counseling. This method aims to increase production and product quality of enterprises and at the same time improve working conditions in these enterprises. The tanneries in Kanpur were targeted for industrial counseling by the Indo-Dutch Environmental and Sanitary Engineering Project Kanpur- Mirzapur under the Ganga Action Plan. Recovery of chrome from wastewater, automation of hydraulic press machines, use of an air-pollution-prevention system in the spray-painting section, and automation of transport are examples of measures used to increase productivity and improve leather quality. Working conditions were improved by adding local exhaust ventilation, mechanizing material transfer, instituting safer procedures for storage and use of toxic materials, and introducing breathing apparatus for operations done in confined spaces to prevent hydrogen sulfide intoxication. The linkage of occupational health problems to environmental issues proved to be effective in drawing attention to working conditions. Also, the application of simple survey techniques to identify and evaluate environmental and occupational hazards substantially increased awareness of these hazards and comprehension of the need to adopt changes among employers, workers, and occupational health professionals. The article discusses the core elements of this successful program.

Journal Article↗
PubMed1996

Body mass index of tannery workers in Kanpur, India.

During two cross sectional surveys in 1988 and 1994 the body mass index among tannery workers in Kanpur, India and its association with exposure to chemicals, dust and awkward ergonomic conditions, socio-economic and health status were studied. Fifty six per cent of the workers had in 1988 a BMI of less than 18.50, the cut-off value for malnutrition. In 1994 the proportion of malnourished workers had decreased to 41 per cent, being statistically significant lower than in 1988. Workers with a high exposure to lifting weights of more than 20 kg had significantly lower BMI than workers without this exposure. No other differences in mean BMI were found between workers without exposure to chemicals, dust and other awkward ergonomic conditions and workers with high or very high exposures, nor did the mean BMI of workers with occupational related conditions such as dermatitis, work related respiratory symptoms and low back pain differ from those without these conditions. There was no association between mean BMI and industrial modifications. In the 1994 survey workers who took sick leave in the year prior to the survey, workers of small/medium sized tanneries and workers without an ESI card had significantly lower BMI than workers without sick leave, workers of large tanneries and workers with an ESI card. Mean BMI of labourers with a monthly income of less than Rs 550 was significantly lower than that of tannery staff not engaged in leather work in this income group. No association was found between mean BMI and smoking, use of alcohol, educational level and income. The nutritional status of labourers in developing countries deserves more attention within the field of occupational health and safety.

Adult↗
PubMed1996

Cytogenetic studies in ataxia telangiectasia & their use in prenatal diagnosis.

Cytogenetic studies were carried out in obligate ataxia telangiectasia (AT) heterozygotes, AT homozygotes and control subjects. Rate of chromosomal aberrations and the frequency of micronuclei were examined before and after radiation (100 rads). Significant differences in the rate of chromosomal aberrations and micronuclei were observed among heterozygotes, homozygotes and controls. The same methods were then applied for prenatal diagnosis of AT using amniotic cell culture in two families.

Ataxia Telangiectasia↗