Biomedical subjects
Publications and source records attributed to P S Verma.
We study two-component growth that mixes random deposition (RD) with a correlated growth process that occurs with probability p. We find that these composite systems are in the universality class of the correlated growth process. For RD blends with either Edwards-Wilkinson or Kardar-Parisi-Zhang processes, we identify a nonuniversal exponent in the universal scaling in p.
We simulate competitive two-component growth on a one-dimensional substrate of L sites. One component is a Poisson-type deposition that generates Kardar-Parisi-Zhang (KPZ) correlations. The other is random deposition (RD). We derive the universal scaling function of the interface width for this model and show that the RD admixture acts as a dilatation mechanism to the fundamental time and height scales, but leaves the KPZ correlations intact. This observation is generalized to other growth models. It is shown that the flat-substrate initial condition is responsible for the existence of an early nonscaling phase in the interface evolution. The length of this initial phase is a nonuniversal parameter, but its presence is universal. We introduce a method to measure the length of this initial nonscaling phase. In application to parallel and distributed computations, the important consequence of the derived scaling is the existence of the upper bound for the desynchronization in a conservative update algorithm for parallel discrete-event simulations. It is shown that such algorithms are generally scalable in a ring communication topology.
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The level of cyclic adenosine monophosphate (cAMP) in human platelets is known to be an important regulator of platelet function. The polyunsaturated fatty acids (PUFA) dihomo-gamma-linolenic acid (DHLA), and eicosapentaenoic acid (EPA), precursors of the prostaglandin (PG) 1 and 3 series respectively, were studied for their ability to stimulate platelet cAMP and/or PGE1 levels, and to inhibit platelet aggregation (PAg). Incubation of washed platelets (1 x 10(8)/ml) with 125 microM DHLA increased intraplatelet levels of PGE1 from 197 +/- 7 to 1622 +/- 9.7 picograms/10(8), cAMP from 3 +/- 0.8 to 31 +/- 1.9 picomoles/10(8), and inhibited collagen-induced PAg. Addition of 1 mumole of xanthine per unit of xanthine oxidase (a superoxide radical generating system) to the incubating medium potentiated the effects of both fatty acids, whereas 240 microM Hydrogen Peroxide (H2O2) inhibited these effects. These results suggest that: (1) DHLA may be more effective in inhibiting PAg than EPA, which has been reported to reduce the incidence of coronary diseases in some human populations; (2) That superoxide radical may activate the platelet cyclooxygenase system to increase lipid peroxidation of these PUFA prostanoid precursors and may result in the inhibition of PAg, whereas H2O2 may have an opposite effect.
The effect of physostigmine on plasma angiotensin converting enzyme activity in rat was studied. Following administration of the drug (0.3 mg/kg), plasma angiotensin activity fell significantly at 45 min (P less than 0.05) and continued to decline during the course of the experiment. These data demonstrate that physostigmine inhibits plasma angiotensin converting enzyme activity in rat.
Atropine sulfate (0.02 mg/kg, i.m.) was administered to normal sheep and to sheep with experimentally induced hyperthyroidism. Serum and urine concentrations of atropine measured by radioimmunoassay were monitored over an 8-h period. The time to reach maximum serum concentration was similar in both hyperthyroid and normal sheep. A comparison between normal and hyperthyroid sheep indicated that the atropine absorption rate was not changed, but its rate of elimination was significantly greater in hyperthyroid sheep (p less than 0.01). Hyperthyroidism resulted in significant decreases in atropine (p less than 0.05), MRT (p less than 0.01), AUC (p less than 0.01) and an increase in C1/F (p less than 0.01) when compared to atropine kinetics of normal sheep.
Antibodies were produced in rabbits immunized with physostigmine conjugated to bovine serum albumin (BSA) by two different methods: a diazo immunogen coupled to BSA with carbodiimide and a Mannich coupled immunogen. Both immunogens produced antibodies that could be used to develop sensitive and specific radioimmunoassays (RIA) for physostigmine. The limit of detection of the RIA is 100 pg of physostigmine in plasma or tissue homogenates (1.0 ng ml-1), without the need for an extraction procedure. The interassay and intraassay coefficients of variation were less than 13% in the RIA. No appreciable binding was observed between the antibodies and physostigmine metabolites or other drugs commonly used with physostigmine. The specificity of the RIA was further validated by measuring physostigmine concentrations in biological samples in tandem with high-pressure liquid chromatography. The RIA was used to study the time course of plasma concentrations and tissue distribution of physostigmine in rats.
The intrarenal kallikrein-kinin system was studied during the acute phase of renovascular hypertension induced by renal artery constriction and during teprotide inhibition of kininase II in the dog. Kallikrein-like activity measured by both kininogenase and esterolytic assays, was increased during renal artery constriction (p less than 0.5) and (p less than 0.01). The administration of teprotide resulted in a further increase of renal cortical kallikrein-like activity and inhibited kininase II activity (p less than 0.01). Following the inhibition of kininase II, the plasma concentration of kininogen was also significantly decreased (p less than 0.01). These results suggest that kininase II inhibition may increase levels of intrarenal and plasma kinins and that decreased degradation of kinin peptides may contribute significantly to the acute hypertensive effect of teprotide.
The role of kinins in the hypertensive response to acute renal artery constriction (RAC) was examined in the dog. RAC resulted in an increase in systemic arterial pressure (SAP) from 144 +/- 6 to 155 +/- 4 mm HG (p less than 0.05). Simultaneously, arterial plasma bradykinin decreased from 2.3 +/- 0.2 to 1.4 +/- 0.1 ng/ml (p greater than 0.01), while renal venous bradykinin remained unchanged (2.3 +/- 0.2 to 2.0 +/- 0.4 ng/ml, p greater than 0.05). At the same time urinary kallikrein decreased from 55 +/- 6 to 33 +/- 4 milliesterase units (mEU)/min (p less than 0.05), while urinary kinin decreased from 3.2 +/- 0.4 to 1.9 +/- 0.3 ng/min (p less than 0.05). There was a significant correlation between the decrease in arterial bradykinin and the rise in SAP induced by RAC (p less than 0.01). Administration of the dipeptidyl hydrolase inhibitor SQ20881 during RAC reduced angiotensin-converting enzyme levels from 578 +/- 86 to 10 +/- 0.0 mU/ml (p less than 0.005). There was an associated increase in arterial bradykinin (1.4 +/- 0.1 to 5.8 +/- 0.8 ng/ml, p less than 0.001), renal venous bradykinin (2.0 +/- 0.4 to 5.7 +/- 0.5 ng/ml, p less than 0.005), and urinary kinin (1.9 +/- 0.3 to 5.0 +/- 0.7 ng/min, p less than 0.01) in conjunction with return of SAP to control levels. Urinary kallikrein, however, remained depressed following SQ20881 (33 +/- 4 to 30 +/- 5 mEU/min, p greater than 0.05). These results suggest that (1) decreases in circulating BK may potentiate the vasoconstrictor effect of angiotensin II and contribute to the hypertension induced by RAC, and (2) urinary kallikrein is an unreliable marker of changes in plasma bradykinin in this model of hypertension.
The pharmacokinetics of desmosine following a 5 mg intravenous dose was determined in five sheep. The biological half-life (t 1/2 beta) of desmosine varied between 81-489 min. Urinary recovery of unchanged desmosine indicated that the compound is not extensively metabolized and that the primary route of elimination is via the kidney.
Angiotensin-converting enzyme (ACE) activity was measured in the serum samples of 247 patients with varying thyroid states. In 60 hyperthyroid patients, the mean (+/- SD) ACE level of 29.5 +/- 9.7 units/mL was higher than in all other groups. The serum ACE level was 17.0 +/- 5.1 units/mL in 129 euthyroid subjects and differed from the level of 13.9 +/- 5.1 units/mL observed in 34 hypothyroid patients. Twenty-four patients receiving exogenous thyroid hormone had elevated serum thyroxine values. Their mean serum triiodothyronine level was in the normal range, and the mean ACE level did not differ from the euthyroid mean. The mean serum ACE level fell from 30.8 to 17.4 units/mL in 35 hyperthyroid patients studied before and after therapy. In 12 hypothyroid subjects, the mean serum ACE level rose from 11.6 to 15.8 units/mL after thyroid hormone replacement. In eight of ten patients with transient hyperthyroidism (subacute thyroiditis or painless thyrotoxic thyroiditis), their highest ACE levels were observed in the hyperthyroid or transition phase and fell progressively with the lowest values being recorded during the hypothyroid or early recovery phases. Thus, ACE activity may respond to thyroid hormone, and interpretation of serum ACE levels may require knowledge of the patient's thyroid status. Serum ACE may be useful as a probe for exploring peripheral thyroid hormone action.
Eight patients with sickle cell anemia (SS hemoglobin) were found to have decreased plasma levels of prekallikrein compared to normal control subjects or patients with other types of anemia. The prekallikrein levels in the patients with sickle cell anemia were found to decrease further during a sickle cell crisis. These results suggest that components of the kallikrein-kinin system are profoundly affected in patients with sickle cell anemia, and during crises may play a role in the clinical presentation of patients.
Eight patients with sickle cell anemia (SS hemoglobin) were found to have decreased plasma levels of kininogen compared to normal control subjects. The kininogen level of the patients with sickle cell anemia was decreased further during sickle cell crises. The results suggest that components of the kinin system are profoundly affected in patients with sickle cell anemia, and during crises may play a role in the clinical presentation of patients.
We have studied inhibition of purified canine angiotensin converting enzyme by substance P and its nonapeptide derivative using Hip-His-Leu as the substrate. Kinetic studies indicated that both substance P and its nonapeptide derivative inhibited the hydrolysis of Hip-His-Leu at different concentrations. The mode of inhibition was competitive with a Ki of 1.15 microM for substance P. These results indicate that substance P is a potent inhibitor of angiotensin converting enzyme in vitro.
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A greatly simplified radioimmunoassay for bradykinin in human plasma is described. Current techniques require multiple chromatographic steps or extraction procedures with analytical recoveries of bradykinin of often less than 60%. We present a method in which bradykinin is separated from components of higher relative molecular mass (including kininogens) in a single step, by use of a column of Sephadex G-25 medium (PD-10). The mean analytical recovery of tritiated bradykinin added to plasma is 85.5% (SD, 3.5%). The sensitivity of this radioimmunoassay is 25 pg per assay tube, equivalent to 125 ng per liter of plasma. Twenty to 30 blood samples may be completely processed and assayed within 6 h. As determined with this technique, concentrations of bradykinin in plasma from apparently normal subjects ranged from 2.5 to 5.2 microgram/L (mean 4.2, SD 1.1 microgram/L); these values are consistent with previously reported normal values.
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