PubMed HealthSearch

Biomedical subjects

S B Lall

Publications and source records attributed to S B Lall.

At least 19 recordsLinked to original sources

Biochemical and histopathological changes in respiratory system of rats following exposure to diesel exhaust.

Effect of exposure to diesel exhaust (DE) for different durations was evaluated using histopathological and biochemical parameters in respiratory system of the rats. Animals were exposed to 1 part DE diluted with 5 parts of clean air in a simulation chamber for 15 min/day for 1, 7, 14 and 21 days. After completion of various exposures, biochemical parameters including elastase inhibitory capacity (EIC) and protein content of the bronchial airway lavage (BAL) and histopathological changes along with lung/body weight ratio were assessed. The elastase inhibitory capacity (an index of the protection against destruction of elastin, a lung connective tissue) was maximum at 1 week indicating thereby that the body renders protection against injury by increasing EIC levels in the initial phase. However, protein content in the BALF increased after 1 week and reached maximum at 2 weeks. Histopathological changes followed similar time course of pattern with accumulation of macrophages and protein exudation. Prolonged exposure up to 3 weeks, however was accompanied by chronic inflammatory changes and thickening of alveolar septa and blood vessels. Changes in lung/body weight ratio and suspended particulate matter (SPM) deposited on filters (simulation chamber) correlated well with EIC, protein content in BALF and histopathological changes. The biochemical findings accompanied with chronic structural changes in the lungs of rats following exposure to DE could be relevant to the clinical observation of increased incidence of chronic lung diseases after continued DE exposure.

Air Pollutants

Cadmium induced nephrotoxicity in rats.

Onset of hypertension and nephropathy after 1,2, and 4 weeks of exposure to cadmium chloride (1 mg/kg, ip) was studied in rats by measuring changes in blood pressure and renal function (urinary output, electrolytes, serum creatinine, inulin clearance and Na+K+ ATPase). Significant decrease in body weight and rise in blood pressure were observed as early as one week of exposure while microalbuminuria was detected in 50% of the animals after 2 weeks. Na+K+ ATPase, a renal tubular enzyme, was depressed after 1 week with maximum lowering occurring after 4 weeks. There were no detectable changes in fluid intake, urine output, electrolytes, inulin clearance and serum creatinine even after 4 weeks. It is concluded that hypertension and tubular lesion set in earlier than glomerulopathy as indicated by microalbuminuria and the latter could be the consequence of rise in blood pressure.

Animals

Involvement of renin-angiotensin system in hypertensive effect of cadmium in rats.

Role of renin-angiotensin system in hypertension induced by cadmium chloride (CdCl2) in rats has been investigated. Intravenous administration of CdCl (1 mg/kg) produced a biphasic response i.e. a transient fall followed by a marked and consistent rise in blood pressure. The peak hypertensive effect was accompanied by raised PRA levels. Pretreatment with captopril (1 mg/kg, i.v.) losartan (1 mg/kg, i.v.) or captopril + losartan attenuated the pressor response to Cd by 62%, 42% and 100% respectively in separate groups. Central administration of Cd (10 micrograms/rat, i.c.v.) showed a biphasic response similar to that observed after i.v. route. However, it was not accompanied by raised PRA levels. Prior treatment with losartan (10 micrograms/rat, i.c.v.) completely abolished the pressor response to Cd (i.c.v.) whereas it was not affected significantly by captopril (10 micrograms/rat, i.c.v.). On the other hand, centrally administered losartan only partially reduced the pressor response to i.v. Cd. The results are discussed in light of a differential involvement of central vs peripheral renin-angiotensin system in the hypertensive effect of Cd.

Animals

An experimental study on cardiotoxicity of aluminium phosphide.

Aluminium phosphide(AlP), a grain fumigant pesticide, was studied for its cardiotoxicity in anaesthetised rats. The hemodynamic and cardiac biochemical changes were investigated following intragastric administration of different doses of AlP (10, 20 and 40 mg). With 10 and 20 mg dose of AlP an immediate fall in BP was observed which recovered partially and stabilized for 10 minutes followed by a gradual fall till the animal died. However, with a higher dose (40 mg) there was no recovery in BP, instead the initial fall continued till the death of the animal. An increase in the heart rate was observed with 10 and 20 mg dose of AlP for 15 minutes which was followed by a marked fall till cardiac arrest ensued. On the other hand, 40 mg dose produced only a transient tachycardia followed by a prolonged bradycardia. ECG changes at all dose levels included initial tachycardia and ST segment elevation progressing to QRS broadening. However, marked conduction defects as evidenced by the ventricular ectopics were noticed only with 40 mg. The mean survival time dose dependently decreased with 10 mg(55 +/- 3 min), 20 mg(35 +/- 2 min) and 40 mg(18 +/- 2 min) of AlP. The cardiac glycogen, ATP and CP levels were significantly lowered in animals treated with 10, 20 and 40 mg of AlP. Higher levels of MDA in the cardiac tissue were observed with 10, 20 and 40 mg of AlP. Thus it is suggested that the deleterious effect of AlP on heart is mediated by both declined cellular metabolism of the myocardium as well as by necrosis of the cardiac tissue resulting in the release of reactive oxygen intermediates.

Aluminum Compounds

Effect of short and long-term exposure to diesel exhaust on sensitivity of guinea pig tracheal preparation to histamine.

Single exposure, to diesel exhaust (1 part exhaust diluted by 5 parts of clean air) reduced EC50 of histamine indicating hyperresponsiveness of the receptors in trachea of exposed guinea pigs. In contrast, following repeated exposure for 7, 14 or 21 days (15 min/day), EC50 was progressively increased indicating the possibility of down-regulated histamine receptors. Further, simultaneous significant increase in histamine levels (bioassayed on guinea pig ileum) in bronchial airway lavage fluid supports the aforementioned hypothesis. The change in lung/body weight ratio and suspended particulate matter deposited on filters followed the same temporal pattern as EC50. The findings are suggestive of differential effects of diesel exhaust on airway depending upon the duration of exposure.

Air Pollutants

Angiotensin II--receptor subtypes characterization and pathophysiological implications.

In the past decade there have been considerable advances in basic knowledge of the renin-angiotensin system (RAS). The most important new development has been the appreciation of a tissue based RAS that can be independently regulated from the renal and vascular RAS. Greater insight into the mechanism by which angiotension-II (AII) exerts its action has been achieved through the study of molecular biology and pharmacological characterization of multiple receptor subtypes. This review summarises the features and distribution of several binding subtypes that may mediate the diverse functions of AII. Of these AT1 subtype is the most well known receptor which preferentially binds AII and AIII. The AT1 receptor site appears to mediate the classic angiotensin responses concerned with the body water balance and the maintenance of blood pressure. Less is known about the AT2 sites which also bind AII and AIII and may play a role in vascular growth. Recently, an AT3 has been discovered in cultured neuroblastoma cells and an AT4 site which preferentially binds AIV. It has been implicated in memory aquisition and retrieval and in the regulation of blood flow. Another important aspect covered is the primary and secondary messengers involved during the signal transduction after the binding of AII with receptors. A stress has also been given on the regulation of density and affinity of AII receptors by various physiological parametres as they affect the responses of RAS. Autoregulation by RAS, salt intake, development and aging and some of the hormones are important variables which could affect the AII receptors. Interactions of AII with various neuroeffector transmission involved in the regulation of water-electrolyte balance and BP regulation play an important role in the maintenance of the homeostasis. AII has been suggested to increase the NAergic transmission by enhancing synthesis, release, inhibiting reuptake by the presynaptic nerve terminals as well as enhancing cell responsiveness to the transmitter. The finding of existence of AII receptors in vagal afferent nerve terminals suggests that its baroreflex inhibitory effect is mediated by inhibiting neurotransmitter release at NTS in the baroreflex arc. Moreover, AII acts on the central receptors to stimulate AVP and ACTH secretion, drinking and peripherally increase synthesis and secretion of aldosterone. Interactions of RAS with kallikrein-kinin system and prostaglandins strongly support the existence of a balance between renal depressor and pressor substances. AII is now considered a growth promotor in cardiovascular tissues and the resultant vascular hypertrophy could contribute in the maintenance of hypertension. AII also plays a role in the kidney, not only as a regulator of hemodynamics but also in the structural changes occurring in a variety of renal disorders. In addition to the more well studied functions of RAS in RVH the review also highlights the potential contribution by the RAS to other clinically relevant syndromes such as aortoarterities induced RVH, hyperaldosteronism, heavy metal induced cardiovascular effects, diabetes mellitus and thyroid dysfunction. Although the receptor subtypes involved in these pathological states have not been definitely identified, research efforts in this direction are ongoing.

Animals

Plasma renin activity in normal healthy volunteers: effect of physiological variables.

Plasma renin activity was determined in hundred normal subjects of either sex (M = 65, F = 35, age range 2-70 yr) using Angiotensin-I test kits. The effect of various physiological variables viz, age, sex, posture and salt intake was determined. The basal values for PRA ranged from 1.19 +/- 0.09 ng/ml/hr for males and 1.02 +/- 0.12 ng/ml/hr for females in erect posture. In contrast high basal supine PRA was noticed in subjects on low salt diet, which showed a significant increase in erect posture. A marked decrease in PRA with advancing age in both the sexes with significantly low values at higher age range was noticed. Captopril produced an insignificant effect on PRA and BP in salt replete supine state, whereas in salt deplete state there was a significant rise in both the parameters.

Adolescent

Radioimmunoassay of angiotensin-II: methodology and standardization.

The study was planned to set up and standardize the radioimmunoassay of Ang-II and to validate the procedure in terms of precision, sensitivity, specificity and recovery. The application of the developed assay was studied in normal healthy volunteers and in patients of renovascular hypertension (RVHT) and renal hypertension (RH). Synthetic human Ang-II was coupled to BSA by carbodimide condensation to get the hapten carrier conjugate which was injected in rabbits to raise the antibodies. The titre of 1:250 showed significant binding (56.79%) and was used for the assay. The sensitivity of the assay was 2 pg/ml and cross-reactivity with analogues of Ang-II was minimum. Mean Ang-II levels in normal subjects was 16 +/- 3.6 pg/ml. In patients of RVHT and RH, the peripheral blood Ang-II levels were found to be 876 +/- 8.6 and 108 +/- 2.3 pg/ml respectively. In patients of unilateral RVHT, renal vein Ang-II levels of the affected side were significantly higher than the unaffected side (P < 0.001). The results indicate that unextracted samples can be successfully utilized to estimate Ang-II levels.

Adult

Reduced urinary kallikrein excretion in human renovascular hypertension caused by nonspecific aortoarteritis and other disorders.

In this study urinary kallikrein excretion was measured using the kininogenase bioassay technique in 12 normal volunteers and 23 patients with angiographically-proven renovascular hypertension (RVHT). In 13 of these (group I), RVHT was due to nonspecific aortoarteritis (NSAA) and in 10 (group II) due to other causes. Urinary kallikrein (UKa) excretion was significantly lower in patients, with values still lower in NSAA. PRA was high in both the groups in comparison with controls; however, the levels were significantly lower in group I compared with group II. Finding of both UKa and PRA lower in group I is suggestive of long standing hypertension becoming volume dependent with nephrosclerotic changes in the kidney. These results point to decreased renal kallikrein-kinin system activity as a feature of NSAA that probably contributes chiefly to the maintenance of the hypertensive state. Normalisation of BP with restoration of UKa and PRA towards normal in three patients of group I and five in group II further support the role of UKa not only when over activity of renin-angiotensin system is responsible for RVHT as in group II but also in group I when the hypertension becomes volume dependent.

Adolescent

Peripheral and renal vein renin activity in patients with renovascular hypertension due to nonspecific aortoarteritis.

The diagnostic utility of peripheral and renal vein renin estimations in relation to angiographic findings was evaluated in 13 patients with renovascular hypertension and non-specific aortoarteritis (NSAA, Gr I), in comparison with 10 patients with renal artery stenosis due to other causes (Gr II). Plasma renin activity (PRA) was measured by radioimmunoassay. Blood samples were collected after angiography from the femoral vein and renal vein on the affected side followed by sampling from the less affected or unaffected side. Renal vein renin ratio (RVRR) was calculated from renal vein renin values. The effect of captopril (25 mg oral) on blood pressure, PRA, and RVRR was examined in 8 patients from each group. Normotensive volunteers (8) with moderately low salt intake were also included in the study for comparison of twenty-four-hour urinary sodium output, peripheral PRA, and response to captopril. The mean peripheral PRA was high in both groups as compared with normotensive controls; however, the values were lower in patients with NSAA. The rise in PRA in response to captopril was insignificant in Gr I (p greater than 0.05) and RVRR greater than 1.5 was observed in 5 of 13 patients in contrast to 9 of 10 in Gr II (p less than 0.05). A paradoxical ratio, ie, (high renal vein renin levels on the less stenotic side) was noticed in 3 patients of Gr I, whereas none of the patients of GR II showed such a ratio. An improvement in RVRR after captopril was observed in 50% of patients of Gr I as compared with a marked response in all patients of Gr II.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

Physical and behavioral development in rats after late prenatal exposure to diazepam.

The effect of late prenatal exposure to diazepam (DZP) on physical and behavioral development of rat pups was investigated. Prenatal exposure to DZP (20 mg/kg, sc, in last week of pregnancy) did not alter litter size and no gross malformations were noted at birth. Body weight at birth and subsequent weight gain was significantly less in these animals. The development of reflexes and neuromuscular maturation was normal. Open field locomotor activity and rearing scores were significantly decreased. Test of social play in juvenile rats revealed normal pattern of sexual dimorphism with increased masculinized behavior. Acquisition and retention of passive avoidance task was not affected by DZP exposure, however, retention of brightness discrimination task was significantly decreased. The hypnotic effect of a challenge dose of DZP and convulsive effect of pentylene tetrazole remained unaltered. Open field activity test in adult animals revealed increased ambulation. Probe dose of amphetamine in these animals caused paradoxical decrease in activity. It is concluded that exposure to high dose of DZP during late prenatal period may not manifest in physical or neuromuscular impairment during early development period, except for weight loss, however, it may have long term effects on behavior becoming manifest in adolescence and at maturity.

Amphetamine

Increased brainstem angiotensin-I levels in chronic 2 KIC hypertensive rats.

A study was undertaken on the role of brainstem renin-angiotensin system in maintenance of hypertension in chronic renovascular hypertensive rats. Hypertension was induced by unilateral renal artery clamping, while the contralateral kidney was left intact (2 KIC). Blood pressure (BP), plasma renin activity (PRA) and brainstem angiotensin (ang-I) levels were measured after 24 days, in hypertensive and sham-operated animals. In separate subgroups of these animals, the effect of intracerebroventricular administration of captopril on the parameters listed was studied. The results showed high ang-I levels in 2 KIC rats as compared to controls (P less than 0.05). Captopril administration (500 micrograms/50 microliters icv) caused a fall in BP and increase in brainstem ang-I levels (P less than 0.01). In control animals, however, captopril produced a rise in BP without any significant change in brainstem ang-I levels. Peripheral plasma renin activity was normal, despite significant sodium retention in 2 KIC rats. The results are suggestive of activation of brainstem renin-angiotensin system (RAS) in chronic 2 KIC hypertension.

Angiotensin I

Comparison of histoenzymological alterations in the contralateral ovary of nulliparous and parous females of the bat Taphozous melanopogon melanopogon Temmnick (Microchiroptera, Mammalia) displaying absolute dextral dominance of the genital tract.

Taphozous melanopogon melanopogon is a unique emballonurid microchiropteran which exhibits a 100% dextral dominance of the female genital tract. Folliculogenesis occurs in the contralateral ovaries, but it is only in the right ovary that a single Graafian follicle attains maturity and ovulates. The product of fertilization is implanted in the dextral uterine cornu. Seven types of follicles were identified in the right ovary, as compared with five in the left, on the basis of shape, size and number of associated granulosa cells. In the parous bats, a single, nearly extroverted corpus luteum was discerned in the ovary which survived for 2-2 1/2 months. The left ovary was nearly a vestigial structure during pregnancy. The structural asymmetry of the internal genitalia was observed to be correlated with the histochemical site and pattern of distribution of acid phosphatase and alkaline phosphatase. Differential activities of phosphatases were discerned in the developing primary, secondary, preantral and antral follicles and the interstitial tissues of the contralateral ovary during the nulliparous state. A high enzyme reaction was displayed by follicles undergoing atretic and degenerative changes. In the parous bats, pronounced differences were noted in the histologic constituents of the contralateral ovary. This study shows a significant link between functional asymmetry of the genitalia and the structural and enzymological characteristics of the ovarian tissues.

Acid Phosphatase

Spermatogenesis in the non-scrotal bat-Rhinopoma kinneari Wroughton (microchiroptera: mammalia).

Spermatogenesis in the non-scrotal, insectivorous microchiropteran, Rhinopoma kinneari Wroughton, is a cyclic phenomenon. It comprises (i) eleven cell associations, and (ii) 16 evolutive steps in spermiogenesis. In the seminiferous epithelium, spermatogonia of the A, intermediate (In), and B type are characteristically present. Leptotene, pachytene and diakinesis stages were easily discerned in dividing spermatocytes. During the 16-step spermiogenesis, the acrosomic system develops through the Golgi, cap, acrosome and maturation phases. The relative frequency of various cell associations differs markedly and is significantly at variance with other mammalian species. Fully formed spermatozoa are dimorphic with conical or blunt heads.

Animals

Histoenzymological comparison of the prostate gland of sexually 'quiescent' and 'active' Taphozous melanopogon melanopogon Temmnick (Microchiroptera: Mammalia).

Lysosomal hydrolases (e.g., acid phosphatase, AcPase; adenosine triphosphatase, ATPase, and lipase) and the mitochondrial 'marker' enzyme succinic dehydrogenase (SDH) were evaluated histochemically in the prostate gland of sexually 'quiescent' and 'active' bats. During the former state, AcPase activity was significantly less than in sexually active animals, suggesting that prostate AcPase activity is androgen dependent. Levels of lipase activity also were highest in the prostate of sexually active bats, suggesting the importance of endogenous lipids which may be mobilized and used as a source of energy. SDH and ATPase sites and patterns of distribution in the prostate gland of bats were closely similar during the two reproductive states. Differential enzymological patterns do not seem to have any significant correlation with the morphological changes which occur in the glandular epithelium, musculature, urethra and the luminal fluid, as the animals pass from a 'quiescent' phase to one of activity and vice versa as observed in the present study.

Acid Phosphatase