Hypoxic growth of bovine pulmonary artery smooth muscle cells: dependence on synergy, heterogeneity, and injury-induced phenotypic change.
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Animals↗
Biomedical subjects
M Das
Publications and source records attributed to M Das.
The Ca2+-dependent isozymes of protein kinase C are uniquely important in the enhanced growth of immature adventitial fibroblasts isolated from the bovine pulmonary arterial wall at a time of heightened susceptibility to vascular injury.
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Animals↗
Cardiac nociception induced rectal response: relation with haemodynamic changes.
Epicardial application of nicotine (200 micrograms/ml) over the left ventricle or occlusion of the left anterior descending coronary artery (LAD) in lightly anaesthetised cats resulted a biphasic change in rectal motility-initial relaxation followed by contraction along with biphasic changes of blood pressure (B.P.) with epicardial nicotine and only hypotension with LAD occlusion. Desensitisation of ventricular receptors by epicardial application of 2% lignocaine abolished the rectal response and the biphasic blood pressure response but not the LAD occlusion induced hypotension. Sectioning of left inferior cardiac nerve (LICN) abolished such cardiorectal reflex but not the B.P. changes. Stimulation of central cut end of LICN elicited similar cardiorectal reflex keeping the B.P. unaltered. Atropinization (1 mg/kg) abolished only the contractile phase of the cardiorectal reflex and also the hypotension induced by epicardial nicotine. Intra-arterial NG-nitro-L-Arginine (LNNA) at a dose of 2 mg/kg abolished the relaxation phase of such cardiorectal reflex keeping the B.P. changes unaltered. LAD occlusion induced hypotension was neither counteracted by atropine nor by LNNA pretreatment. These indicate that though the cardio-rectal reflexes are associated with B.P. changes, they do not have any direct correlation.
Animals↗
Azo reductase activity of microbial population from gastrointestinal tract segments of various animals species.
Azo reductase activity of microbial population of stomach, small intestine, caecum and large intestine of different animals was investigated. There was low activity in stomach flora of wistar rat and 3 strains of mice. Flora of proximal portion of small intestine in different species revealed that carnivorous animals exhibited maximum activity followed by grazing animals. Maximum activity in middle portion of small intestine was noted in dog (98.2%), while minimum was observed in guinea pig (23.3%). Majority of test animals revealed maximum floral azo reductase activity (58-98%) in caecum. Activity in proximal portion of large intestine was highest in dog while pigeon and guinea pig had least activity (23.3-27.1%). Appreciable microbial activity in distal end of large intestine was noted in sheep and goat. In all the 15 animal species investigated caecum showed maximum activity followed by pre and post caecal segments while stomach possessed the least. The results suggest that inter-species differences exist in microbial reductive activity which may be due to variation in composition and distribution of GI tract microflora and thus can influence toxicological implication of various dyes.
Animals↗
Prevalence of canine demodicosis in Orissa (India).
Examination of the records of 12 hospitals from the five districts of Orissa showed that 50,987 dogs were presented for treatment during the period of 5 years covering 1987-1988 to 1991-1992. Demodicosis was detected in 1697 (3%) cases. There was no difference in the occurrence of the disease in male (51%) and female (49%) dogs. The disease was recorded in 60%, 23% and 17% of dogs up to 1 year, 1-2 years and above 2 years of age respectively, suggesting that young dogs up to 1 year of age are more susceptible. Further study revealed that Tibetan apso are more susceptible (47%) than Doberman (23%), Alsatian (18%) and mongrels (12%). A total of 912 dogs with natural dermatitis were examined during the 5-year period and 35% of the dogs were found to have demodicosis. Out of these, 208 dogs (65%) had localised lesions and 111 (35%) had generalised lesions. The study revealed that dogs up to 1 year of age are more frequently affected (60%) than dogs of 1-2 years (23%) and above 2 years of age (17%). There was no difference between the susceptibility of male (49%) and female (51%) dogs. The prevalence was high in Tibetan apso (41%) as compared to Doberman (26%), Alsatian (16%) and mongrels (17%).
Age Factors↗
Rectal response of cardiac origin in the cat: involvement of nitric oxide and acetylcholine.
Local application of nicotine over the surface of the left ventricle and also occlusion of the left anterior descending coronary artery in the lightly anaesthetised, open-chested, artificially ventilated cat resulted a biphasic rectal movement--initial relaxation followed by sustained contraction. However, distension of the atrial appendage did not evoke any change in rectal motility, indicating the non-involvement of atrial volume receptors in initiating this rectal response of cardiac origin. The relaxation phase of this response was not abolished by pretreatment with atropine or with phentolamine or propranolol but was abolished by the nitric oxide inhibitor, N(G)-nitro-L-arginine (LNNA), and this blockade of the relaxation phase by LNNA was reversed by L-arginine. The contraction phase, however, was abolished by atropine. From these observations it is clear that the relaxation phase of the rectal response to coronary occlusion or epicardial nicotine is mediated through neither cholinergic nor adrenergic pathways but through the release of nitric oxide whereas the contraction phase of such a cardio-rectal response is mediated through the release of the neurotransmitter, acetylcholine.
Acetylcholine↗
Metanil yellow: a bifunctional inducer of hepatic phase I and phase II xenobiotic-metabolizing enzymes.
Metanil yellow, a non-permitted food colour, has been found in various foodstuffs. The induction potential of metanil yellow on hepatic microsomal cytochrome P-450 (P-450)-dependent monooxygenases and cytosolic detoxification enzymes, namely, glutathione S-transferase (GST) and quinone reductase (QR), was investigated. Oral administration of metanil yellow (430 mg/kg body weight) to four animals for seven days caused significant induction of hepatic P-450 (48%) and its dependent aryl hydrocarbon hydroxylase (100%) activity and cytosolic GST (136%) and QR (92%) activities. Parenteral administration of metanil yellow (80 mg/kg body weight) to another set of four animals for 3 days resulted in higher induction of ethoxyresorufin-O-deethylase (228%) as compared to other monooxygenases (64-92%), while GST and QR were also found to be induced (59-95%). Spectra of metanil yellow-induced microsomes showed an increase in P-450 with a shift of 2.2 nm in the soret region. The results suggest that metanil yellow acts as a bifunctional inducer of specific isozymes of P-450 and cytosolic enzymes and thus may involve the cytosolic aryl hydrocarbon (Ah) receptor for this type of induction.
Administration, Oral↗
Effect of green tea (Camellia sinensis) extract on the rat diaphragm.
The effect of hot water extract of green tea on skeletal muscle and its neurotransmission was studied employing innervated and denervated rat diaphragm. Green tea extract (GTE) has a facilitatory effect at lower concentrations and a paralytic effect at higher concentrations on skeletomotor function. GTE did not have any effect on direct twitch responses or on acetylcholine (ACh) and KCl induced contractures of denervated rat diaphragm and it antagonised the submaximal paralytic effect of D-tubocurarine and decamethonium. GTE-induced facilitation and inhibition were nullified in the presence of magnesium chloride. Nifedipine, reduced GTE-induced facilitation as well as inhibition of twitch responses as a function of its concentration. It was suggested that GTE might act on Ca2+ channels at the skeletomotor junction. The effect of crude polyphenol on neuromuscular junctions was found to be similar to that of GTE. Therefore, it is suggested that the crude polyphenol content of GTE was the active constituent responsible for its effect on neuromuscular junction.
Animals↗
Differential kinship effect on reconciliation in three species of macaques (Macaca fascicularis, M. fuscata, and M. sylvanus).
Macaque societies are typically characterized by despotic dominance styles and strong bonds between related individuals. Interspecies variation in dominance style, however, has been recently documented. This study investigated whether kinship effects on social interactions vary depending on the species dominance style. Reconciliation was chosen as as a measure of relationship quality between group members. Groups of Japanese (Macaca fuscata) and long-tailed (M. fascicularis) macaques were selected for their highly despotic style, and Barbary (M. sylvanus) macaques were chosen for their lower level of despotism. The findings confirmed the hypothesis that kinship effects on reconciliation are stronger the more despotic the species is. Barbary macaque nonkin reconciled more often than nonkin of the other 2 species. In addition, the differences in reconciliation frequency between kin and nonkin were less pronounced among the less despotic Barbary macaques.
Animals↗
Effectiveness of problems used in problem-based learning.
Where problem-based learning (PBL) is the main method used in medical curricula, the literature suggests that it is crucial that the problems used are effective in facilitating students to identify relevant learning issues. These learning issues guide the students' studying. The present investigation explores the extent to which students identify relevant issues following exposure to prepared paper problems. In the preparatory year, in an Introduction to Medicine module, four groups of students were exposed to six themes (Health Care System, Environment and Health, Alternative and Islamic Medicine, Chronic Illness, Infectious Diseases, and Prevention and Health Promotion). Each group had two facilitators per theme. Having discussed the prepared problems, the students identified learning issues which were collected for the purpose of the study. Two content experts, using a Likert scale, analysed learning issues for their concordance to staff objectives per theme. Kappa coefficients were computed for the six PBL themes in order to assess inter-rater agreement. Learning issues identified as having no relationship to theme objectives were further analysed for their relevance to theme objectives. No objective was totally omitted by any student group. There was a 100% concordance of objectives to learning issues demonstrated over four themes. The relationship of learning issues to theme objectives ranged from 55-85% in the theme on health care system, and 73-94% in the theme on environment and health. Irrelevant learning issues were identified in the first two PBL themes addressed. Kappa coefficients over the six PBL themes varied from 0.49 to 0.82.
Education, Medical, Undergraduate↗
Infective endocarditis caused by HACEK microorganisms.
The HACEK group of fastidious gram-negative organisms is a recognized but unusual cause of infective endocarditis, responsible for approximately 3% of cases. We report our experience with 45 cases of endocarditis caused by HACEK organisms. In Olmsted County, Minnesota, the incidence of HACEK endocarditis was 0.14 per 100,000 person-years. In patients with native valves, 33 cases occurred, and in patients with prosthetic valves, 12 cases occurred. The most common presenting symptoms were fever, splenomegaly, new or changing murmur, and microvascular phenomena. Symptoms were present in the majority of patients anywhere from two weeks to six months prior to diagnosis. Blood cultures became positive in a mean 3.375 days, and therapy with a beta-lactam alone or as part of a combination was given for anywhere between three and six weeks. Within the first month of diagnosis, surgery was performed for 13 regurgitant valves in 11 patients (24%). Echocardiography was an insensitive predictor of subsequent major arterial embolization (odds ratio, 1.33; 95% confidence interval, 0.31-5.67). The overall survival in our cohort of patients was 87%. These results confirm previous reports that HACEK endocarditis portends a favorable prognosis.
Adult↗
Pulmonary artery smooth muscle cells from chronically hypoxic neonatal calves retain fetal-like and acquire new growth properties.
Growth properties retained and acquired by immature pulmonary artery (PA) smooth muscle cells (SMC) in vivo after chronic exposure to hypoxia and the mechanisms that regulate hypoxia-induced change in proliferative phenotype are not known. We tested the hypothesis that PA SMC from neonatal calves exposed to hypoxia after birth would both retain fetal-like and acquire new growth characteristics and that these changes would be at least partially dependent on protein kinase C (PKC), a key proproliferative signal transduction pathway. Like fetal cells, PA SMC from hypoxic calves grew faster in the presence and absence of serum and were more responsive to insulin-like growth factor I and platelet-derived growth factor-BB than control neonatal and adult cells. PA SMC from hypoxic calves also acquired other growth properties (i.e., including increased hypoxic growth after PKC activation) that were new compared with those observed for fetal cells. The proliferative response to hypoxia was first detectable in the neonatal period and was further increased in cells from hypoxic calves. SMC from fetuses and hypoxic calves were more susceptible to the growth-inhibiting effects of PKC antagonists (dihydrosphingosine and calphostin C) than control neonatal and adult cells. To test if the Ca(2+)-dependent isozymes of PKC were uniquely important in the developmental and acquired growth changes observed, the antagonistic effect of the specific, but isozyme nonselective, PKC inhibitor Ro-81-8220 was then compared with GF-109203X, a structural analog with relative specificity for the Ca(2+)-dependent isozymes of PKC (alpha and beta in PA SMC). The faster growing PA SMC from bovine fetuses and hypoxia-exposed calves again demonstrated greater growth inhibition in response to both inhibitors. GF-109203X was equipotent to Ro-31-8220, and its antiproliferative effects were shown to not be due to an increase in apoptosis. Phorbol ester-induced PKC downregulation, another inhibitor strategy that selectively depletes bovine PA SMC of PKC-alpha, but not -beta, mimicked the antiproliferative effects of GF-109203X. Whole cellular PKC catalytic activity paralleled the pattern of peptide-induced growth and susceptibility to PKC inhibition. These results suggest that PA SMC from hypoxia-exposed neonatal calves retain enhanced fetal-like proliferative capacity and acquire new growth properties that are at least partially dependent on the Ca(2+)-regulated isozymes of PKC and in particular PKC-alpha.
Aging↗
Selected isozymes of PKC contribute to augmented growth of fetal and neonatal bovine PA adventitial fibroblasts.
We sought to determine which isozymes of protein kinase C (PKC) contribute to the increased proliferation of immature bovine pulmonary artery (PA) adventitial fibroblasts. Seven were identified in lysates of neonatal PA fibroblasts by Western blot: three Ca2+ dependent (alpha, beta I, and beta II) and four Ca2+ independent (delta, epsilon, zeta, and mu). Four isozymes (gamma, eta, theta, and iota) were not detected in fibroblasts isolated at any developmental stage. Of the seven detected isozymes, only PKC-alpha and -beta II protein levels were higher in fetal and neonatal cells compared with adult fibroblasts. Their role in the enhanced growth of immature fibroblasts was then evaluated. The isozyme nonselective PKC inhibitor Ro-31-8220 was first compared with GF-109203X, a structural analog of Ro-31-8220 with relative specificity for the Ca(2+)-dependent isozymes of PKC. GF-109203X selectively inhibited the growth of immature cells and was nearly as potent as Ro-31-8220. Go-6976, a more specific inhibitor of the Ca(2+)-dependent isozymes, mimicked the antiproliferative effect of GF-109203X. PKC downregulation with 1 microM phorbol 12-myristate 13-acetate had the same selective antiproliferative effect on immature fibroblasts as GF-109203X and Go-6976. The protein levels of PKC-alpha and -beta II, but not of PKC-beta I, were completely degraded in response to phorbol 12-myristate 13-acetate pretreatment. These results suggest that PKC-alpha and -beta II are important in the augmented growth of immature bovine PA adventitial fibroblasts.
Aging↗
Clinicoepidemiological, toxicological, and safety evaluation studies on argemone oil.
Consumption of oil extracted from accidental or deliberate contamination of argemone seed to mustard seed is known to pose a clinical condition popularly referred to as Epidemic Dropsy. Several outbreaks of Epidemic Dropsy have occurred in the past in India as well as in Mauritius, Fiji Island, and South Africa. Clinico-epidemiological manifestations of argemone oil poisoning include vomiting, diarrhea, nausea, swelling of limbs, erythema, pitting edema, breathlessness, etc. In extreme cases, glaucoma and even death due to cardiac arrest have been encountered. The toxicity of argemone oil has been attributed to two of its physiologically active benzophenanthridine alkaloids, sanguinarine and dihydrosanguinarine. Histopathological studies suggest that liver, lungs, kidney, and heart are the target sites for argemone oil intoxication. Studies have shown to elucidate the cocarcinogenic potential of argemone oil that can be correlated with the binding of sanguinarine with a DNA template. Pharmacological response in intestine revealed immediate stimulation of tone and peristaltic movements of the gut in the sanguinarine-treated animals. Argemone oil/Sanguinarine caused a decrease in hepatic glycogen levels which may be due to the activation of glycogenolysis leading to an accumulation of pyruvate in the blood of Epidemic Dropsy cases. The increase in pyruvate levels causes uncoupling of oxidative phosphorylation leading to breathlessness, as observed in patients. Sanguinarine has been shown to inhibit Na+, K(+)-ATPase activity of different organs such as brain, heart, liver, intestine, and skeletal muscle, which may be due to the interaction with the glycoside receptor site on ATPase enzyme, thereby causing a decrease in the active transport of glucose. Argemone oil/alkaloid showed a Type II binding spectra with hepatic cytochrome P-450 (P-450) protein, thereby causing loss of P-450 content and an impairment of phase I and phase II enzymes. A green fluorescent metabolite of sanguinarine, benzacridine was detected in the milk of grazing animals. The delayed appearance of this metabolite in urine and feces of experimental animals suggests the slow elimination of the alkaloid. Argemone oil enhances hepatic microsomal and mitochondrial lipid peroxidation, indicating that these two organelles are the sites of membrane damage. Furthermore, studies suggest that singlet oxygen and hydroxyl radical are involved in argemone oil toxicity. Several bioantioxidants show protective effect in argemone oil-induced toxicity in experimental animals. The line of treatment in argemone-intoxicated epidemics has so far been only symptomatic, and specific therapeutic measures are still lacking, although it has been suggested that diuretics, bioantioxidants, steroids, vitamins, calcium- and protein-rich diet had some beneficial effects on Epidemic Dropsy cases.
Animals↗
A comparative study on the effect of felodipine and propranolol on serum lipid profile of rabbits.
Effect of felodipine on serum lipids of rabbits was studied and was compared with that of propranolol. Lipid parameters were estimated at basal (0 wk), end of 4th and 16th week of diet/drug administration by using standard kits for analysis. There was a significant increase in mean serum cholesterol, TG, VLDLc, LDLC and decrease in HDLc, (P<0.05) in the group of rabbits receiving Atherogenic diet (AD)/Propranolol. This effect was maximally observed in rabbits receiving both AD and propranolol. This change was satisfactorily prevented when felodipine was administered from very beginning (P<0.001). In addition, there was a significant increase in HDLc (28.89%) of rabbits receiving felodipine from beginning. Thus both AD and propranolol have dyslipidemic effect and early administration of felodipine favorably changes all lipid parameters.
Animals↗
Heterogeneity in the proliferative response of bovine pulmonary artery smooth muscle cells to mitogens and hypoxia: importance of protein kinase C.
Pulmonary artery (PA) smooth muscle cell (SMC) proliferation is an important contributor to the vascular remodeling that occurs in chronic hypoxic pulmonary hypertension. The earliest SMC proliferative changes in response to hypoxia occur in the outer media. We tested the hypothesis that the pattern of hypoxia-induced PA SMC proliferation observed in vivo is determined at least in part by intrinsic differences in proliferative response of SMC isolated from different medial layers to relevant peptide mitogens and hypoxia. Adult bovine PA SMCs were isolated at the same proximal site from the middle (layer 2) and outer (layer 3) media. In response to maximal serum stimulation, PA SMCs from the outer media grew faster than cells from the middle media. The outer medial cells also had increased responsiveness to multiple peptide mitogens (IGF-I, PDGF-BB, bFGF, and EGF). Because protein kinase C (PKC), a key pro-proliferative signal transduction pathway, has been shown to play an important role in this type of global increase in growth, responsiveness to a direct cell-permeable activator of PKC (PMA, phorbol 12-myristate 13-acetate) was then measured. PA SMCs from the outer media had greater DNA synthesis in response to selective PKC activation than middle medial cells. Since activation of this kinase is a requisite step for PA SMCs to proliferate in response to hypoxia, the hypoxic growth potential of cells from the middle and outer media was then compared. SMCs from the outer media had an augmented proliferative response to hypoxia compared with those from the middle media. These data suggested an important role for PKC in the enhanced growth of PA SMCs from the outer media. Therefore, whole cellular activity, expression, and hypoxia-induced activation of PKC were measured in both subpopulations of PA SMCs. Outer medial cells had greater total cellular activity, expression, and hypoxia-induced activation of PKC (and the alpha isozyme in particular) than cells isolated from the middle media. These findings support the concept that heterogeneity in growth capacity of PA SMCs exists within the bovine PA media, that these intrinsic differences in growth govern, at least in part, the pattern of abnormal SMC proliferation observed in vivo, and that the PKC pathway (and PKC-alpha in particular) is likely an important determinant of the subpopulation-specific differences found.
Animals↗
Glutathione status of some homeothermic vertebrate species and its relation with diabetogenesis.
The pancreatic glutathione levels of birds are higher than that of mammalian species. Refractoriness of birds towards the action of diabetogens may indeed be correlated with this fact. However, the higher pancreatic glutathione value found in owl, in comparison to that of pigeon, seems contradictory since owl is more susceptible to diabetogens.
Animals↗
Breast feeding practices in a teaching hospital of Calcutta before and after the adoption of BFHI (Baby Friendly Hospital Initiative).
A comparative study has been made on two groups of 102 mothers each who delivered children in the postnatal ward of obstetrics and gynaecology department of Calcutta National Medical College before and after the introduction of BFHI (Baby Friendly Hospital Initiative). The study revealed that only 14.3% of the babies who were delivered normally were given their first breast feed in time, the ideal time of half an hour, while not a single baby delivered by caesarean section were given their breast feed within the stipulated time period of 4-6 hours. However, there has been a significant overall reduction in the time gap between the birth and the first breast feed in all types of delivery. BFHI has also made significant reduction of prelacteal feeds and in-between feeds in the newborns especially those delivered normally. The fact that babies of first order and those delivered by caesarean section are lagging behind as far as exclusive breast feeding is concerned has been highlighted in the study.
Breast Feeding↗