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Biomedical subjects

R Shukla

Publications and source records attributed to R Shukla.

At least 91 records · Page 5Linked to original sources

Surface morphology of hamster (Mesocricetus auratus) decidual cells in vitro.

Cell surface morphology of hamster decidual cells isolated from day 8 implantation swellings was studied, using both phase-contrast and scanning electron microscopy. Two kinds of cells, fibroblastic and epithelioid, were identified in cultures examined by phase-contrast microscopy. Fibroblastic cells were spindle-shaped, having pointed or blunt terminals on one end and bifid or webbed projections at the other end. Epithelioid cells, on the other hand, were flat and discoid, having a distinctively ruffled plasma membrane. Further, the plasma membrane of epithelioid cells formed rope-like or flange-like processes. The significance of such adaptations is discussed.

Animals↗

Attenuation of alcohol-induced hypothermia by cyclo (His-Pro) and its analogs.

Acute administration of cyclo (His-Pro) to rats cause a dose-dependent decrease in ethanol-induced hypothermia. Bromination of the imidazole moiety of histidine in cyclo (His-Pro) resulted in a significant increase in its potency to attenuate ethanol hypothermia. In contrast, benzylation of the imidazole moiety of histidine or the substitution of one or both of the amino acids in cyclo(His-Pro) led to a total loss of its thermomodulatory activity. In conclusion, it appears from these preliminary data that it may be possible to design analogs of CHP that may be effective antagonists for ethanol hypothermia.

Animals↗

In vitro mutational spectrum of cyclopenta[cd]pyrene in the human HPRT gene.

Cyclopenta[cd]pyrene (CPP) is a widely distributed polycyclic aromatic hydrocarbon with potent mutagenic and carcinogenic activity. In order to acquire an understanding of the mutagenic pathways of CPP, we studied mutations induced by this chemical in human cells. Four independent cultures of a human cell line expressing cytochrome P450 CYP1A1 (cell line MCL-5) were treated with CPP, and mutants at the hypoxanthine phosphoribosyltransferase (HPRT) locus were selected en masse by 6-thioguanine (6TG) resistance. The kinds and positions of the mutations were analyzed using the combination of high-fidelity polymerase chain reaction (hifi-PCR) and denaturing gradient gel electrophoresis (DGGE). The third exon of the HPRT gene was amplified from the 6TG-resistant cells using the hifi-PCR and the amplified fragment was subsequently analyzed by DGGE to separate mutant sequences from the wild-type sequence. Mutant bands were excised from the gel, amplified using PCR and sequenced. Sixteen different mutations were identified and consisted mostly of the G to T and A to T transversions. Other mutations identified included G to A and A to G transitions, a G to C transversion, and a single G deletion. Of these mutations, six occurred within a run of six guanines. The predominance of transversions involving a guanine or an adenine observed with CPP is similar to the data previously reported for the racemic mixtures of benzo[a]pyrene (B[a]P), suggesting that the mechanisms of mutation induced by CPP may be similar to those induced by B[a]P.

Base Sequence↗

Effect of early lead exposure on children's postural balance.

This study investigated the effect of chronic exposure to lead on children's ability to maintain upright postural balance as a biological marker of lead-induced modifications of the neuromotor system. For this study, 162 six-year-old children, with a five-year geometric mean lead concentration in blood of 11.9 micrograms/dL (range 4.0-28.0 micrograms/dL), were tested for postural balance with a microprocessor-based force platform system. An increase in blood lead was significantly associated with an increase in the variable postural sway--implying poorer postural balance. This association was not influenced by socio-economic, racial or environmental factors. This simple, objective and quick technique may be useful for assessing gross motor functions in children who are at or below the United States Centers for Disease Control's class III category and/or for monitoring the effectiveness of medical interventions aimed at reversing lead-associated impairment of upright postural balance.

Child↗

Prevention of ischaemia-induced biochemical changes by curcumin & quinidine in the cat heart.

Effect of myocardial ischaemia on the bioantioxidants levels in the cat heart was evaluated. In addition, effect of curcumin, an anti-inflammatory and anti-thrombotic drug, and quinidine, a standard antiarrhythmic drug, was also studied in the cat. Myocardial ischaemia was induced by the ligation of left descending coronary artery. Quinidine (1 mg/kg, iv) was administered 15 min prior to while curcumin (100 mg/kg, ip) was given 30 min before ligation. Hearts were removed 4 h post coronary artery ligation. Levels of glutathione (GSH), malonaldelhyde (MDA), myeloperoxidase (MPO), superoxide dismutase (SOD), catalase (CAT) and lactate dehydrogenase (LDH) were estimated in the ischaemic and non-ischaemic zones. Both the drugs protected the animals against decrease in the heart rate and blood pressure following ischaemia. In the ischaemic zone, after 4 h of ligation, an increase in the level of MDA and activities of MPO and SOD (cytosolic fraction) were observed. Quinidine and curcumin pretreatment prevented the ischaemia-induced elevation in MDA contents and LDH release. Curcumin pretreatment did not prevent the increase in MPO activity while quinidine did. Results obtained indicate alterations in the bioantioxidants following ischaemia and both curcumin and quinidine prevented ischaemia induced changes in the cat heart.

Animals↗

Nifedipine in migraine and tension headache: a randomised double blind crossover study.

Nifedipine was evaluated in the prophylaxis of 28 patients each of migraine and tension headache using a double blind cross over design with random allocation to drug or placebo group. The duration of the trial was 3 months with a 2 week run-in period and 2 week wash-oat period separating two treatment periods of 4 weeks each. A satisfactory response was obtained in 71.4% of migraineurs (p < 0.001) and 28.6% of patients with tension headache (p = N.S). Minor side effects were observed in 5 patients. Nifedipine is a useful agent for the management of migraine as it reduces frequency and severity of pain but the drug cannot be recommended for tension headache.

Adult↗

Effect of age on P300 wave.

30 healthy elderly males (mean age 77.4 +/- 4.3 yrs) were subjects in this study. Equal number of young males (mean age 22 +/- 3.5 years) and middle aged subjects (mean age 46 +/- 3.2 years) served as control. P300 wave was estimated using a Neuropack 4 model of Nihon Kohden EMG machine. We observed a significantly increased latency, poorly defined and non reproducible P300 wave in 90% old subjects while in young the latency was in normal limits and the wave was well defined and reproducible. We presume P300 could serve as a future potential marker of the neurophysiological basis of aging.

Acoustic Stimulation↗

On prediction of future observation in growth curve model.

Rao proposed and compared several approaches for predicting future observations in a growth curve model. The assessment of associated prediction efficiency for different prediction methods were evaluated by Cross-Validation Assessment Error (CVAE). He used three data sets, each with a limited number of subjects (13-27) and also with a limited number of repeated measurements (4-7) per subject, to illustrate the prediction methods. In the present paper, we applied four of the prediction methods discussed by Rao, on a data set with a relatively large number of subjects (174) and also with a larger number of measurements (21) per subject, using the polynomial function and log-linear function. We propose to use the restricted cubic spline function as an alternative growth curve model and compare its performance with the polynomial function and log-linear function. It turns out that, at least for larger data sets such as that used in this paper, the prediction methods perform somewhat better when the growth is described by restricted cubic spline function than when the growth is described by polynomial function and log-linear function.

Calibration↗

Structural equation modeling and nested ANOVA: effects of lead exposure on maternal and fetal growth in rats.

This study provided an assessment of the effects of lead on early growth in rats based on structural equation modeling and nested analysis of variance (ANOVA). Structural equation modeling showed that lead in drinking water (250, 500, or 1000 ppm) had a direct negative effect on body weight and tail length (i.e., growth) in female rats during the first week of exposure. During the following 2 weeks of exposure, high correlation between growth measurements taken over time resulted in reduced early postnatal growth. By the fourth week of exposure, reduced growth was not evident. Mating began after 8 weeks of exposure, and exposure continued during gestation. Decreased fetal body weight was detected when the effects of litter size, intrauterine position, and sex were controlled in a nested ANOVA. Lead exposure did not appear to affect fetal skeletal development, possibly because lead did not alter maternal serum calcium and phosphorus levels. The effect of lead on individual fetal body weight suggests that additional studies are needed to examine the effect of maternal lead exposure on fetal development and early postnatal growth.

Analysis of Variance↗

Life span and cancer mortality in the beagle dog and humans.

This study compares the age-dependence and rate of cancer mortality in untreated Beagles over a lifetime with that of Japanese and US white men and women. The purpose of the study was to determine the extent to which there is a linkage between life span and cancer mortality in Beagle dogs and humans. The two human populations were chosen to represent contrasting races and environments. Using the age at 10% survival as the measure of life span, about 5.5 years in humans was equivalent to 1 year of life in Beagles. The age dependence and total cancer mortality was the same in men and male Beagles. The age dependence was the same in female Beagles and women, but the total cancer mortality was somewhat greater in female Beagles due to more breast cancer. Cancer in Beagles, other than breast cancer in females, consisted mostly of sarcomas and lymphomas. There was very little cancer in environmentally exposed tissues (lung and intestine). There was also some contrast between Japanese and Americans in the relative rates of cancer at certain sites. The study provides support for the life span linkage of adult cancer mortality in the two species, in spite of the different patterns of cancer types and environments.

Aging↗

Role of endogenous cyclo(His-Pro) in cold-induced hypothermia in the desert rat (Mastomys natalensis).

Central administration of exogenous cyclo(His-Pro) (CHP) is known to produce hypothermia in rodents. In the present study, we examined the role of endogenous CHP in cold-induced hypothermia in the desert rat, Mastomys natalensis. The results of these studies show that a rise in hypothalamic CHP content accompanied a decrease in rectal temperature during cold exposure. Immunoneutralization of endogenous CHP resulted in a significant decline in cold-induced hypothermia. In addition, central administration of cyclo(Ala-Gly), a structural analogue of CHP, also led to a decrease in cold-induced hypothermia. The results of these studies show that changes in endogenous CHP levels may affect body temperature regulation.

Analysis of Variance↗

Variation in quantitative respirator fit factors due to fluctuations in leak size during fit testing.

Variation in fit factors during quantitative respirator fit testing was studied for a high degree of fit (aerosol fit factors > 1000) and a low degree of fit (aerosol fit factors < 1000). In a controlled human study, fit factors were determined sequentially for three different exercises by (1) an aerosol fit test (using a portable condensation nuclei counter and room aerosol as the test agent) and (2) the newly developed dichotomous-flow fit test (Dichot). For the higher level of respirator fit, the aerosol fit factors were 30 to 60 times the corresponding flow fit factors, and for the lower level of respirator fit they were 2 to 4 times the flow fit factors. A coefficient of variation (CV) of 84% (GSD 1.6) for the higher respirator fit and 178% (GSD 2.2) for the lower respirator fit data was observed in the human study when aerosol fit factors for the three exercises were pooled. In a similar mannequin study, the center sampling probe gave aerosol fit factors with a CV of 5.4% (GSD 1.05). The flow fit factors for all three exercises pooled had a CV of 36% (GSD 1.3) for the higher respirator fit and 40% (GSD 1.5) for the lower respirator fit data, while the mannequin study gave flow fit factors with a CV of 2.2% (GSD 1.02). Thus, the variation in fit factors obtained in the human study was much higher than that obtained in a mannequin study. However, the variation in the aerosol method relative to the flow method, in the human study, os of the same order of magnitude as in the mannequin study.(ABSTRACT TRUNCATED AT 250 WORDS)

Air↗

Side effects with amiodarone therapy.

Amiodarone hydrochloride is increasingly being used in the treatment of ventricular and supraventricular arrhythmias. Although a highly effective anti-arrhythmic agent, its use is restricted by the high incidence of side effects. To elucidate the value of monitoring serum level of both the parent drug and its active metabolite in predicting the occurrence of side effects, the investigators examined 109 patients from a register of patients treated with amiodarone for the prevalence of known side effects of the drug. The register contained over 90% of patients treated with amiodarone at the Leicester General Hospital during the period of the study. The findings suggest cutaneous side effects and abnormal thyroid function tests (without overt gland dysfunction) are more likely to occur with increasing duration of treatment and cumulative dosage. However, neither the serum amiodarone level nor the serum metabolite level had any predictive power for the occurrence of side effects. In view of this finding, it is recommended that close attention be paid to the continued clinical monitoring of side effects and that there is utility in measuring the serum amiodarone level in each patient to avoid the prescription of unnecessarily high doses. This is necessary not only to lessen the occurrence of cumulative dose-related side effects, but also because the variable but very long half-life of the drug leads to difficulties in relating spot drug levels to long-term effects.

Aged↗

Adrenal tumor complicating untreated 21-hydroxylase deficiency in a 5 1/2-year-old boy.

OBJECTIVE: A 5 1/2-year-old boy presenting with virilization was diagnosed as having classic 21-hydroxylase deficiency complicated by an adrenal tumor. We attempted to document a reduction in the size of the tumor with glucocorticoid therapy. DESIGN: Case study. SETTING: Referral center. INTERVENTION: Glucocorticoid therapy was instituted for congenital adrenal hyperplasia. Surgery for the adrenal mass was deferred, and the size of the mass was monitored by serial ultrasonography. RESULTS: Baseline values of serum 17 alpha-hydroxyprogesterone (186.6 nmol/L) and testosterone (24.7 nmol/L [7.1 ng/mL]) were elevated. After instituting steroid treatment, 17 alpha-hydroxyprogesterone was suppressed (13.0 nmol/L), and testosterone remained undetectable on follow-up. However, the size of the mass increased during 6 months. Unilateral adrenalectomy performed at that time revealed a well-encapsulated adenoma in a hyperplastic gland. CONCLUSIONS: Untreated classic congenital adrenal hyperplasia may be complicated by an adrenal tumor even at a young age. Suppression of adrenal androgens by glucocorticoid therapy was not accompanied by regression of the tumor in our patient.

Adenoma↗

Multiple pituitary hormone deficiencies in a patient with spinocerebellar ataxia: magnetic resonance imaging and hormonal studies.

Degenerative spinocerebellar ataxia has a rare association with hypogonadotropic hypogonadism. In this report we present the results of the detailed endocrine evaluation and magnetic resonance imaging in one such patient. A 20-year-old male with progressive cerebellar ataxia, hypogonadism, and short stature was investigated. Basal testing revealed hypogonadotropic hypogonadism (LH < 5 mU/L, FSH < 5 mU/L, testosterone 2.5 nM/L). There was no rise in LH after stimulation with LHRH, peak LH level being < 5 mU/L. Insulin hypoglycemia testing was consistent with GH deficiency, with peak GH being 3.2 mU/L. On TRH stimulation, there was no significant rise in prolactin, though the TSH response was normal. Magnetic resonance imaging revealed cerebellar atrophy. The anterior pituitary was atrophic, with a height of 1.4 mm. The posterior pituitary and the pituitary stalk were normal in size and position. This patient with degenerative spinocerebellar ataxia had multiple pituitary hormone deficiencies. The results of our endocrine evaluation and MR imaging lead us to believe that these deficits may result from a lesion at the level of the pituitary gland.

Adult↗