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Biomedical subjects

S Garg

Publications and source records attributed to S Garg.

At least 127 records · Page 7Linked to original sources
PubMed1975

Cystine deficiency during dietotherapy of homocystinemia.

Cystine deficiency was inadvertently produced in a boy receiving specific dietary therapy for homocystinuria. This was manifested as a loss in weight, the reappearance of significant amounts of homocystine in the plasma and urine, and the elevation of the plasma methionine level. In addition, there was a significant reduction in the level of cystine in the plasma. This reduction in plasma cystine level differentiates cystine deficiency from loss of biochemical control due to failure to keep the prescribed diet. The addition of cystine to the regime of this child, without any other dietary modification, resulted in a complete remission.

Body Weight↗
PubMedDate not supplied

Para-[18F]fluorobenzylguanidine kinetics in a canine coronary artery occlusion model.

BACKGROUND: The kinetics of para-[18F]fluorobenzylguanidine ([18F]PFBG) were investigated in a canine coronary artery occlusion model. METHODS AND RESULTS: Five dogs were imaged by positron emission tomography (PET) before and after complete surgical ligation of the left anterior descending coronary artery. PET studies included a 10-minute dynamic [13N]NH3 perfusion scan, followed 1 hour later by 3-hour dynamic [18F]PFBG scanning. [18F]PFBG and [13N]NH3 images demonstrated homogeneous myocardial uptake/perfusion before infarction. One hundred eighty minutes after [18F]PFBG administration, myocardial accumulation was decreased by 60% (day 2, 0.0065% +/- 0.0015% injected dose/ml) and 58% (day 16, 0.0069% +/- 0.003% injected dose/ml) compared with a similar myocardial region of interest from the preinfarction (0.016% +/- 0.005% injected dose/ml) study. Myocardial accumulation of [13N]NH3 at 9 minutes showed a 52% (day 2) and 7% (day 16) decrease compared with the preinfarction study. The accumulation of [18F]PFBG in the infarction was decreased significantly at 120 and 180 minutes on all postinfarction studies (p = 0.01). In three dogs a significant decrease in the myocardial norepinephrine concentration was documented in the area of infarction (237 +/- 94 ng/gm) versus the noninfarcted (1018 +/- 48 ng/gm) myocardium (p = 0.001). CONCLUSIONS: A decreased accumulation of [18F]PFBG was observed in the area of myocardial infarct in this canine model. The magnitude of the decrease in [18F]PFBG was larger than that seen with [13N]NH3 on day 16 after infarction, suggesting reperfusion and persistent sympathetic neuronal dysfunction.

Animals↗
PubMedDate not supplied

Fluorine-18 labeling of monoclonal antibodies and fragments with preservation of immunoreactivity.

A new method is reported for labeling proteins with the positron-emitting nuclide 18F. Initially, 4-[18F]-fluorobenzylamine was prepared in two steps from aqueous [18F]fluoride in high yield. The 18F acylation agent was formed by reaction of this product with disuccinimidyl suberate. Overall yields for the 4-[18F]fluorobenzylamine succinimidyl ester ([18F]SFBS), decay corrected to the end of cyclotron bombardment, were about 30% in a synthesis time of 60 min. After a 15-min reaction, 30-45% (decay corrected) of the [18F]SFBS could be coupled to intact antibodies and their F(ab')2 and Fab fragments. Coupling yields were dependent on protein concentration but not reaction time. HPLC purification of [18F]SFBS was necessary to obtain optimal coupling efficiency and immunoreactivity. The immunoreactivities of 18F-labeled F(ab')2 and Fab fragments of an antimyosin antibody were 89 +/- 5% and 75 +/- 9%, respectively. Biodistribution studies in normal mice demonstrated similar in vivo behavior of 18F-labeled antibody fragments and those labeled with 125I by using N-succinimidyl 3-[125I]iodobenzoate. These results indicate that this method may be useful for labeling monoclonal antibodies and other proteins and peptides with 18F.

Acetylation↗
PubMedDate not supplied

N-succinimidyl 5-(trialkylstannyl)-3-pyridinecarboxylates: a new class of reagents for protein radioiodination.

N-Succinimidyl 5-(trialkylstannyl)-3-pyridinecarboxylates (alkyl = Me, Bu) have been prepared and used as a precursor to label N-succinimidyl 5-[131I]iodo-3-pyridinecarboxylate (SIPC). SIPC was obtained in greater than 80% yield from either the methyl or butyl precursor with N-chlorosuccinimide and heating at 60-65 degrees C. Significantly lower yields were observed with tert-butyl hydroperoxide. After a 30-min incubation with [131I]SIPC at pH 8.5, goat IgG, an intact monoclonal antibody (MAb), and a MAb F(ab')2 fragment were labeled in 60-65% yield. Specific binding of the MAb and MAb fragment after SIPC labeling was identical with that observed with N-succinimidyl 3-iodobenzoate and higher than that reported previously for these MAbs after labeling by using the Iodogen method. When 5-[131I]iodonicotinic acid was injected into normal mice, thyroid uptake was less than 0.2% of the injected dose, reflecting the inertness of this compound to deiodination. Paired-label biodistribution studies indicate that for both the MAb and the F(ab')2 labeled by using SIPC, accumulation of activity in the thyroid and other tissues is comparable to that observed when these proteins were labeled by using N-succinimidyl 3-iodobenzoate. The results of this study suggest that SIPC may be a reagent for labeling MAbs with halogen nuclides.

Animals↗
PubMedDate not supplied

Mathematical programming assisted drug design for nonclassical antifolates.

A concept from optimization theory, specifically, mathematical programming, is proposed for designing drugs with desired properties. The mathematical programming formulation is solved to obtain the optimal descriptor values, which are employed in the Cerius(2) modeling environment to infer the optimal lead candidates, in the sense that they exhibit both high selectivity and activity while ensuring low toxicity. It has been observed that unique substituent groups and their molecular conformations are responsible for attaining the goal of simultaneous high selectivity and activity. Both linear and nonlinear quantitative structure activity relationships (QSARs) have been developed for use in the proposed approach. A comparative study of these models is done, and it is shown that the QSARs are well represented by nonlinear models. The proposed mathematical programming strategy has been demonstrated for a class of nonclassical antifolates for Pneumocistis carinii and Toxoplasma gondii dihydofolate reductase. Some of the potential leads found in this study have biological properties similar to those in the open literature. We believe the technique proposed is general and can be applied to other structure based drug design.

Algorithms↗
PubMedDate not supplied

Intravalvular implantation of aortic valve prosthesis.

A simplified technique is described to overcome the problem of aortic valve replacement in a severely dilated aortic root (> 30-mm diameter). Intravalvular implantation of an inverted mitral prosthesis after imbrication of aortic cusps was performed in a patient with severe aortic regurgitation with gross annular dilatation. The technique may be applicable in a select subset of patients.

Adult↗
PubMedDate not supplied

Biological activity assessment of a novel contraceptive antimicrobial agent.

Microbicides are a new category of compounds being developed as a prophylactic approach for the prevention of transmission of sexually transmitted diseases (STDs), including the human immunodeficiency virus (HIV). These are primarily being developed as women-controlled methods, with the target of designing new compounds or formulations that can be used without the knowledge of a male partner. Microbicide screening can be initially based on their hyaluronidase-inhibiting (HI) activity, as this enzyme plays a major role in the sperm and microbe penetration into the substrate. Derivatives of hesperidin, a citrus flavonoid glycoside, have been reported in the literature for their HI effects. Hesperidin was thereby sulphonated under strictly controlled conditions and the active fraction isolated and characterized, based on its HI activity. This derivative was screened for antimicrobial and enzyme-inhibitory activities, specifically for the reproductive tract. Sulphonated hesperidin (SH) was found to completely inhibit the sperm enzymes hyaluronidase, giving an indication toward its contraceptive effects. It was also been found to inhibit various sexually transmitted pathogens, including Chlamydia trachomatis, Neisseria gonorrhoea, HIV, and Herpes Simplex virus type 2 (HSV-2). Its safety assessment was based on its noninterference in sperm motility and its penetration through the cervical mucus, and no effect on the growth of lactobacilli, the normal vaginal flora. It was also found to be nontoxic to the HIV substrate cells (MT2 cells). The study concludes that sulphonated hesperidin can be developed as a potential microbicide for a dual prophylaxis of contraception and transmission of STDs and AIDS.

Anti-Bacterial Agents↗
PubMedDate not supplied

Diaphragm disease of duodenum following long-term NSAIDs use: endoscopic management.

We report our experience with endoscopic management of 3 men (aged 62, 63 and 65 years) with duodenal diaphragm disease following NSAID use for 5-15 years. In the first patient a 24 F through-the-scope balloon dilatation was attempted but failed; he subsequently underwent gastro-jejunostomy. The other two patients subsequently underwent radial incisions of the web with mixed cutting and coagulation current using a standard 5 F sphincterotome.

Aged↗
PubMedDate not supplied

Diaphragm disease of the ileum: a case report.

Non-steroidal anti-inflammatory drugs induced diaphragm like lesions are a rare cause of small intestinal obstruction. They occur most commonly in elderly patients who have been consuming these drugs for prolonged periods for pain relief. We report the first case of ileal diaphragm disease from Asia. She responded well to localised resection of the diseased ileum. Intra-operative enteroscopy may be helpful in deciding the extent of intestinal resection.

Anti-Inflammatory Agents, Non-Steroidal↗