Preparation and bioevaluation of 99mTc-carbonyl complex of 5-hydroxy tryptamine derivative.

Studies on the development of imaging agents for targeting neuroreceptors is an area of considerable interest owing to the limited availability of specific as well as selective radiolabeled agents. Therefore, with an aim of developing a receptor-specific agent, iminodiacetic acid (IDA) derivative of 5-hydroxy tryptamine viz., HTIDA has been synthesized. HTIDA could be radiolabeled with the synthon [(99m)Tc(CO)(3)(H(2)O)(3)](+) in >98% yield. The biodistribution studies in normal Swiss mice showed that the (99m)Tc(CO)(3)-HTIDA crosses the blood-brain barrier successfully with a brain uptake of 0.5%ID/g at 5min post injection. The other relevant observations from biodistribution studies included no significant uptake in any other organ and fast clearance from blood, lungs and liver.     

Interaction of 2-halogenated dATP analogs (F, Cl, and Br) with human DNA polymerases, DNA primase, and ribonucleotide reductase

Recently, 2-halogenated deoxyadenosine analogs (F, Cl, and Br) have been shown to have antitumor activity. These analogs are phosphorylated by cells and are believed to exert their cytotoxic action at the nucleoside triphosphate level. In this work the interaction of these nucleoside triphosphate analogs with potential targets, such as DNA polymerase alpha, beta, and gamma, DNA primase, and ribonucleotide reductase was examined in detail. All of these compounds competitively inhibited the incorporation of dAMP into DNA by DNA polymerase alpha, beta, or gamma. F-dATP was able to completely substitute for dATP using DNA polymerase alpha and gamma, but not with DNA polymerase beta. Cl-dATP and Br-dATP substituted poorly for dATP using DNA polymerase alpha and beta. Extension of a 32P-labeled primer by DNA polymerase alpha, beta, or gamma on a single-stranded M13 template showed that these compounds were incorporated into the 3' end of the growing DNA chain and that elongation beyond the incorporated analogs was significantly retarded for Cl-dATP and Br-dATP using either DNA polymerase alpha or beta. DNA primase using poly(dC) as template was inhibited by these compounds at a concentration 4 to 5 times greater than that required for 2-F-araATP. The 2-halogenated dATP analogs were potent inhibitors of ADP reduction by ribonucleotide reductase. In conclusion, the cytotoxic action of 2-Cl-deoxyadenosine and 2-Br-deoxyadenosine may partially be mediated through the mechanism of "self-potentiation," by depression of the deoxynucleoside triphosphate pools due to inhibition of ribonucleotide reductase, which would facilitate their incorporation into DNA and result in the inhibition of DNA synthesis.     

Detection of medullary carcinoma of thyroid, with liver metastasis, using 99mTc DMSA(V) scintigraphy

A sixty year old female referred for thyroid and liver scintigraphy had a clinical history of progressive swelling in the neck with hepatomegaly. A large cold area was detected in the right thyroid lobe using 99mTc pertechnetate and in the right lobe of liver using 99mTc phytate. Subsequent whole body scan with 99mTC DMSA(V) showed avid tracer uptake in right lobe of thyroid and liver. Aspiration cytology of thyroid and liver showed medullary carcinoma of thyroid with its metastasis in liver. Histopathology following thyroidectomy confirmed the diagnosis. Thus 99mTc pentavalent DMSA contributes specificity to diagnose medullary carcinoma of thyroid and metastatic lesions.     

Vitamin A status of socio-economically backward children

A comprehensive survey was carried out to asses the Vitamin A status of pre-school (0–6 yrs.) and school age (6–12 yrs.) children of socio-economically backward families from slums of Bombay and its suburbs. The Vitamin A, protein, calories and iron from the rice and dal based diet was found to be below recommended dietary allowances (RDA). Among the 1956 children surveyed 20% of the children showed low (<20 μg/dl) serum vitamin A levels. 4.8% of the children were suffering from one or the other signs of Vitamin A deficiency. Rose Bengal stain test (RBST) and conjuctival impression cytology (CIC) indicted the signs of mild conjuctival xerosis and of early epithelial changes which were correlated with serum vitamin A levels. Serum iron, PCV, Hb and RBC levels were below normal. The anthropometric measurements of these children were below 50th percentile of Indian Council of Medical Research (ICMR) standards. Due to lack of proper nutrition, the overall growth of children is either retarded or not upto the standard levels as was noted in majority of the children.     

Insulin resistance syndrome in 8-year-old Indian children: small at birth, big at 8 years, or both?

We have studied 477 8-year-old Indian children to define the relationship between birth weight and cardiovascular risk factors, including insulin resistance syndrome (IRS) variables and plasma total and LDL cholesterol concentrations. All risk factors were strongly related to current weight. After adjustment for current weight, age, and sex, lower birth weight was associated with higher systolic blood pressure (P = 0.008), fasting plasma insulin and 32-33 split proinsulin concentrations (P = 0.08 and 0.02), glucose and insulin concentrations 30 min postglucose (P = 0.06 and 0.04), subscapular/triceps skinfold ratio (P = 0.003), and plasma total and LDL cholesterol concentrations (P = 0.002 and 0.001). Lower birth weight was associated with increased calculated insulin resistance (homeostasis model assessment [HOMA], P = 0.03), but was not related to the HOMA index of beta-cell function. The highest levels of IRS variables and total and LDL cholesterol were in children of low birth weight but high fat mass at 8 years. Taller height at 8 years predicted higher fasting plasma insulin concentrations, insulin resistance, and plasma total and LDL cholesterol concentrations. The most insulin-resistant children were those who had short parents but had themselves grown tall. Although the implications of our findings in relation to height are unclear, interventions to improve fetal growth and to control obesity in childhood are likely to be important factors in the prevention of cardiovascular disease and IRS in India.