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Biomedical subjects

S C Srivastava

Publications and source records attributed to S C Srivastava.

At least 19 recordsLinked to original sources

The use of a new radiopharmaceutical, 97Ru-DISIDA, and of 99Tcm-sulphur colloid for the simultaneous evaluation of duodenogastric reflux and gastric emptying.

There is no consensus or a uniform technique for measuring gastric emptying and numerous modalities have been reported. We report here the results obtained using a modification of the published techniques for the simultaneous measurement of duodenogastric reflux and gastric emptying utilizing simultaneously the recently developed radiopharmaceutical 97Ru-DISIDA, intravenously, and the oral administration of 99Tcm-sulphur colloid incorporated in a 'solid' test meal.

Administration, Oral

Progress in research on ligands, nuclides and techniques for labeling monoclonal antibodies.

This paper reviews the current methods for radiolabelling monoclonal antibodies with particular emphasis on radiometals useful for radioimmunoscintigraphy. The discussion, however, is equally applicable to therapeutic radionuclides. The advantages and the pitfalls of the various techniques are critically evaluated. Both direct labeling methods, as well as indirect methods using the bifunctional chelating agent approach, are covered. Recent work on the development and synthesis of new and more specific chelating agents, including the approach of utilizing rigid polyaminocarboxylates, is described. Preliminary promising results with these newer generation chelating agents are presented.

Aged

Interpretation of treadmill stress test in patients with coronary artery disease receiving beta blocker therapy.

Graded maximal treadmill exercise responses were studied before and after beta blockade (atenolol 100 mg once daily for 2 weeks) in 20 male patients with chronic stable angina. Beta-blocking effect consisted of significant reduction of resting heart rate (HR) by 21%, systolic blood pressure (SBP) by 12% and rate pressure product (RPP) by 30%. While the maximum exercise capacity was marginally increased by mean 1.7 min +/- 1.6 SD (P less than 0.001) under the influence of therapy, peak HR, SBP and maximum RPP were significantly lower (P less than 0.001) than in preatenolol exercise tests. Similarly, while the configuration and magnitude of ST segment depression did not differ materially between the pre and post atenolol tests, onset time of ST change was delayed and offset time shortened significantly. These parameters cannot be relied upon to assess the extent and severity of coronary artery disease (CAD) if stress test is carried out while the patient is on a beta-blocking drug. The overall sensitivity of the stress test to detect coronary disease is, however, not likely to be compromised because of negligible influence of beta-blockers upon ST segment depression provided maximally tolerated (not submaximal) exercise is performed. ST/HR slope, an exercise test variable known to correlate well with the extent of CAD, was shown to be uninfluenced by beta-blockade. Its measurement is therefore recommended in interpreting stress tests performed in patients receiving beta-blocker therapy. This, however, requires a meticulously prepared protocol of recording computer averaged QRST complexes and multilead ECG tracings at very frequent intervals throughout the exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

In vivo effects of di-n-butyltin dichloride on some enzymes and lipids of rat liver plasma membrane.

The in vivo effects of di-n-butyltin dichloride (DBT) on the enzyme activity and lipid constituents of liver plasma membrane were studied in male Albino rats. The rats were intraperitoneally administered with 0.1 ml (10% v/v) ethanol either alone or containing DBT (10 or 30 mg/kg/d) for 7 consecutive days. A significant inhibition of plasma membrane marker enzymes such as 5'-nucleotidase, gamma-glutamyltranspeptidase, alkaline phosphatase, Mg2(+)-ATPase, Na+/K(+)-ATPase and Ca2(+)-ATPase occurred in DBT-treated rats when compared with respective controls. Other important bioconstituents such as sialic acid and total phospholipid/cholesterol ratio were also significantly decreased in DBT-treated rats when compared with corresponding controls. These results suggest that interaction of DBT with liver plasma membrane constituents might cause derangement of its structural and functional organization, thus leading to hepatotoxicity.

5'-Nucleotidase

Radioactive gold cluster immunoconjugates: potential agents for cancer therapy.

An 11 gold atom (undecagold) cluster was covalently attached to specific sites on Fab', F(ab')2 and whole IgG molecules such that each carried 11-33 gold atoms without significant loss of native immunospecificity. Gold cluster labeled 17-1A monoclonal F(ab')2 antibody fragments showed 80% immunoreactivity compared to native antibody fragments in binding to human colon carcinoma cells in vitro. Radioactive gold in vivo biodistributions in nude mice with human tumors are also reported. By using clusters, potentially a larger destructive payload can be carried per antibody.

Animals

Blood cell labeling with 99mTc: progress and perspectives.

Blood cell labeling with 99mTc has progressed through various developmental phases. In the case of red cell labeling, the science seems to have matured sufficiently, although minor refinements in the procedures will no doubt continue to be made. During the last 3 to 5 years, there has been a resurgence of interest in labeling leukocytes and platelets with 99mTc. As a result of these efforts, the techniques for these cell types appear to be developing slowly, having finally come out of their infancy. Progress in these directions over the last 3 1/2 years is summarized and discussed in this article. Emerging techniques that offer the promise of combining simplicity and convenience with reliable and reproducible data are highlighted. Mechanisms involved in the various labeling approaches, if studied and understood, are included. Recent efforts on cell labeling with 99mTc using the monoclonal antibody approach are summarized. Although results in this area are quite preliminary, the monoclonal antibody approach holds the greatest promise for labeling leukocytes and platelets in vivo, and thus overcoming the biggest drawback of current techniques, ie, cell separation and handling before labeling. This is a US government work. There are no restrictions on its use.

Animals

Recent developments in blood cell labeling research.

A number of recent developments in research on blood cell labeling techniques are presented. The discussion relates to three specific areas: 1) A new in vitro method for red blood cell labeling with 99mTc, 2) a method for labeling leukocytes and platelets with 99mTc, and 3) the use of monoclonal antibody technique for platelet labeling. The advantages and the pitfalls are examined in the light of available mechanistic information. Problems that remain to be resolved are reviewed. An assessment is made of the progress as well as prospects in blood cell labeling methodology including that using the monoclonal antibody approach.

Animals

Development of a new radiolabel (203Pb) and new chelating agents for labeling monoclonal antibodies for imaging.

High liver uptake and slow body clearance presently limit the usefulness of 111In labeled antibodies for tumor imaging. We have investigated 203Pb as an alternative and better antibody label. The DTPA and cyclohexyl EDTA (CDTA) conjugates of an anticolon carcinoma antibody, 17-1A, were labeled (bicyclic anhydride method) with 203Pb and 111In with 60 and 90 per cent labeling yields, respectively. The biodistribution of 203Pb-17-1A conjugates was compared with the corresponding 111In-labeled preparations and with 203Pb-DTPA, 203Pb-nitrate and nonrelevant antibody controls in normal and human tumor (SW948) xenografted nude mice at 24 and 96 h. 203Pb labeled CDTA and DTPA antibody conjugates gave similar in vivo distributions. Even though the lead bound to these chelate-antibody conjugates was more labile in serum and in vivo, compared with indium, it cleared much faster from the liver and the whole body. A new series of chelating agents based on the incorporation of a trans-1,2-diaminocyclohexane moiety into the carbon backbone of polyaminocarboxylates is being synthesized. These are expected to provide stronger complexing ability for lead and produce greater in vivo stability. These ligands are also expected to be superior to EDTA and DTPA for labeling antibodies with other radiometals, including indium.

Animals

Indium-111-labeled LDL: a potential agent for imaging atherosclerotic disease and lipoprotein biodistribution.

Radiolabeling of low-density lipoprotein (LDL) and external imaging with a gamma camera would offer a means of taking advantage of the metabolic activity of developing atherosclerotic lesions in order to noninvasively detect and determine the extent of atherosclerotic cardiovascular disease. Indium-111-(111In) labeled LDL was prepared and its purity demonstrated by agarose electrophoresis and ultracentrifugation. In vitro studies with cultured human fibroblasts demonstrated significant inhibition of iodine-125-(125I) LDL binding to LDL receptors by 111In-LDL, although this was less than the inhibition produced by unlabeled LDL. Adrenal gland uptake of 111In-LDL by hypercholesterolemic rabbits was reduced by 86% compared to the level of uptake observed in normal rabbits. These results were compatible with downregulation of adrenal LDL receptors in the hypercholesterolemic rabbits. Uptake of 111In-LDL in the atherosclerotic proximal aorta of hypercholesterolemic rabbits was 2.5 times higher than in normal rabbits. These results suggest that 111In-LDL has the potential to be a useful agent for external imaging of atherosclerotic lesions and lipoprotein biodistribution.

Animals

Role of corrosion in Harrington and Luque rods failure.

Ten in-vivo failed spinal instrumentation systems, i.e. six Harrington distraction rods with sublaminar hooks, one Harrington distraction rod with segmental wiring and three Luque rods with sublaminar wires, were fractographically analysed. In both Harrington and Luque rods corrosion fatigue was the predominant mechanism resulting in the failure. Five Harrington rods fractured at the first ratchet junction; fractures of the Luque rods were initiated by fretting of sublaminar wire with the rod surface in the presence of spinal non-union. Fretting and crevice corrosion were found to play an important role in compromising the segmental spinal instrumentation. The susceptibility of the 316 L CW austenitic stainless steel to pitting and relative resistance to crevice corrosion were measured by cyclic anodic polarization tests. The oxide inclusions have been found to play a significant role in the pitting of the alloy.

Corrosion

Synthesis and biological properties of the lipophilic technetium-99m complex 99mTc(acac)3.

In the development of technetium-99m radiopharmaceuticals for the evaluation of regional cerebral perfusion, one series of complexes that has remained unexplored is the neutral lipophilic tris complexes formed with beta-diketonato ligands. The prototype complex of this series, tris(2,4-pentanedionato) technetium(III), has been prepared via a new synthetic route and chemically characterized using 99Tc and the biodistribution of the no-carrier-added 99mTc complex has been determined. The 99mTc complex was found to be distributed throughout the body with persistent high blood levels indicative of a high degree of protein binding. The primary route of excretion was the hepatobiliary system as indicated by the appearance of 99mTc in the gut and feces at longer sample times post-injection. Although this complex was not retained by the brain, it does provide a starting point from which a more effective agent might be developed.

Animals

A new cholescintigraphic agent: ruthenium-97-DISIDA.

These are the first human experiments with 97Ru-DISIDA, a potentially new alternative to 131I-rose bengal where delayed imaging is indicated. 97Ru has a convenient half life. A DISIDA labeling kit was utilized to prepare the radiotracer for 17 patients (age 6 weeks-84 years). The cholescintigraphic data correlated well with other imaging procedures and with clinical findings. Dosimetric calculations were carried out and were compared with the radiation burden associated with the use of 99mTc-DISIDA and 131I-rose bengal.

Biliary Tract Diseases

Comparative dual-tracer studies of carbon-14 tryptophan and iodine-131 HIPDM in animal models of pancreatic diseases.

Our previous studies have shown that a significant amount of the diamine derivative 131I-N,N,N'-trimethyl-N'-(2-hydroxy-3-methyl-5-iodobenzyl)-1,3- propanediamine (HIPDM) is taken up and retained by the normal pancreas. Therefore, we studied the uptake of [131I]HIPDM in various pathophysiological models in mice (chronic alcoholism, diabetes with beta-cell atrophy and obesity with beta-cell hypertrophy) and compared to 14C-L-Tryptophan (TRY) distribution in order to determine the factors influencing their pancreatic uptake. In normal animals, the pancreas uptake of TRY was generally higher than HIPDM. In diabetes, the relative concentration of both compounds was higher over the controls; however, in obesity, TRY showed lower accumulation than in controls while HIPDM showed no significant difference. Chronic ethanol (20%) ingestion increased TRY uptake in the pancreas compared to controls (36.88 +/- 3.21 vs. 30.03 +/- 4.17% ID/g; p less than 0.01) after 5 wk study period, but it decreased by 10 wk (22.36 +/- 0.95% ID/g; p less than 0.005). There were no significant changes in [131I]HIPDM distribution in alcoholics as compared to the controls. Radioiodinated HIPDM has potential advantages over [11C]TRY for pancreatic imaging since conventional imaging techniques can be employed. Our data, however, suggest that 11C-L-TRY is a more sensitive indicator of various pancreatic disorders.

Animals

Modified in vitro method to label equine red blood cells with technetium 99m in concentrated whole blood.

An in vitro method to label equine RBC with technetium 99m was modified to achieve quantitative labeling of cells in concentrated whole blood. After a blood sample was incubated with a reducing agent (stannous citrate), an oxidizing reagent (NaOCl) and a chelating agent (EDTA) were added to inactivate residual Sn2+ in the plasma. This step prevented premature reduction of pertechnetate in plasma. Labeling of RBC from 9 healthy horses, using a standard whole blood protocol, resulted in only moderate labeling efficiency (44 to 85%) and indicated a linear relationship between labeling efficiency and PCV. Effects of increased incubation time, increased incubation temperature, prelabeling sedimentation, and double addition of NaOCl/EDTA were investigated in whole blood from 10 healthy horses. Labeling efficiency was improved by each independent factor and by combination of factors. Highest labeling efficiencies (96 to 97%) were achieved when blood samples were sedimented for 20 minutes before being labeled, regardless of incubation time or incubation temperature. Morphologic features of RBC were unaffected by labeling procedures. In vivo whole blood clearance time for labeled cells was determined in 5 healthy horses. Sedimented blood samples were labeled, using a standard 15-minute incubation time at 20 to 22 C. Mean clearance half-time for 5 horses was approximately 20 hours. More than 95% of 99mTc activity was associated with the cells during the 24 hours after reinjection.

Animals

Production of no-carrier added 67Cu.

Copper-67 has been produced at the BLIP by 68Zn(p, 2p) and 70Zn(p, alpha) reactions with 193 MeV protons and at the HFBR using the 67Zn(n, p) route. The effective cross-sections of natZn(p, 2pxn)61,64,67Cu reactions were measured at 200 MeV and compared with predicted values obtained from semi-empirical formulae given by Silberberg and Tsao. From these cross-sections, the fraction of 64Cu in the final 67Cu preparations was estimated and compared with the experimental values. A procedure has been developed consisting of electrodeposition and ion-exchange for isolation of no-carrier-added radiocopper from a Zn target. The method is adaptable for remote hot cell operation. The overall radiochemical yield of 67Cu and the separation factors from a Zn target and other radionuclides were evaluated. The saturation yield of 67Cu produced by the fast neutron 67Zn(n, p) reaction and the corresponding cross-section were remeasured. Experiments have been initiated to attach 67Cu to monoclonal antibodies for immunotherapy applications.

Antibodies, Monoclonal