Antileukemic pseudoguaianolides from Hymenoxys grandiflora (T. and G.) Parker. Application of lanthanide-induced shifts to structure determination.
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Biomedical subjects
Publications and source records attributed to A Srinivasan.
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Juvenile hormone (JH) titer in virgin females of Heliothis virescens is significantly lower than that in mated females of the same age. The JH titer in virgin females follows a diel pattern in which it begins to increase towards the end of photophase, remains high around the onset of scotophase, and declines during scotophase. The titer reaches its lowest levels at the onset of photophase, and remains low during the first half of photophase. In mated females, the diel pattern of JH titers is not as pronounced. JH-esterase (JHE) activity in mated females is significantly lower than that of virgin females during photophase; JHE levels in the former are similar to levels seen in newly emerged females. JHE activity in mated females also exhibits a diel pattern, in which activity is low during photophase and high at the onset of scotophase. Evidence for the indirect involvement of JHE in the mating-stimulated egg development is provided by the effect of selected JHE inhibitors in inhibiting JHE activity and stimulating egg production in virgin females.
Various tetradentate N3S ligands which contain pyridyl, morpholino, or imidazolyl moieties were prepared and labeled with technetium and rhenium. Metal complexation of the ligands occurred efficiently over the pH range from 2 to 11. Ligands possessing the S-THP (tetrahydropyranyl)-protected mercapto group labeled efficiently even under alkaline conditions, and among the three types of heterocyclic metal complexes, a marked difference in stability was observed; rhenium complexes decomposed to ReO4 whereas technetium complexes decomposed to TcO2/TcO4. In general, imidazolyl complexes of both technetium and rhenium were very stable in saline; less than 10% decomposition after 24 h. The technetium histidyl complex and technetium pyridyl complex were quite stable even under cysteine challenge; less than 10% decomposition after 24 h. The rhenium and technetium morpholino complexes were very unstable; greater than 10% decomposition after only 1 h in saline and greater than 25% decomposition in 1 h under cysteine challenge. Profound pharmacokinetic differences among these metal complexes were also observed in rat biodistribution studies. The neutral pyridyl complexes exhibited high blood and liver uptake and slow clearance from these tissues. The replacement of a hydroxyl group by a carboxyl group, which resulted in an anionic complex at physiological pH, resulted in a dramatic decrease in blood and liver uptake. The neutral imidazolyl complex exhibited marked reduction in blood uptake and much faster clearance from blood and liver compared to the neutral pyridyl complex. Finally, the anionic histidyl complex, which contains both the imidazolyl and carboxyl groups, had the most favorable pharmacokinetic properties in that it exhibited very low blood, liver, and kidney uptakes and a rapid clearance from the body via the renal system. The combination of the high stability and favorable pharmacokinetic properties of the imidazolyl complexes should render them useful for targeted delivery of the medically important isotopes.
A simplified kiet has been developed for 99mTc protein radiolabeling using an N3S triamide mercaptide bifunctional chelating agent and the preformed chelate approach. The process combined N3S chelating agent, gluconate intermediate transfer agent, stannous reducing agent, and gentisic acid stabilizer into a lyophilized formulation. With sulfur donor atom hemithioacetal protection of the ligand, delta-2,3,5,6-tetrafluorothiophenyl alpha-S-(1-ethoxyethyl)mercaptoacetamido-L-adipoylglycylglycine , optimum 99mTc chelation was achieved in a single step. Subsequent reaction with NR-LU-10 antibody Fab fragment followed by purification via QAE Sephadex anion exchange resin filter afforded 99mTc-N3S-NR-LU-10 Fab conjugate with retained immunoreactivity and effective tumor targeting properties.
Indium-111-diethylenetriaminepentaacetic Acid-D-phenylalanine-octreotide ([111]In-DTPA-octreotide) is a cyclic eight amino acid somatostatin analogue which is approved for gamma scintigraphy of neuroendocrine tumors. To address the factors that contribute to liver and kidney retention of this radiopharmaceutical, its metabolism was evaluated in normal and tumor-bearing rats. The soluble fractions from nontarget (liver and kidney) and target (tumor, pancreas, adrenals) organ homogenates were analyzed out to 21 h postinjection, and urine was analyzed out to 12 h postinjection. The blood was analyzed at shorter time intervals due to the rapid clearance of (111)In-DTPA-octreotide. Radio-TLC and HPLC were used to analyze organ homogenates, blood, and urine. By TLC, intact (111)In-DTPA-octreotide was resolved from the soluble metabolites, and a similar apparent rate of metabolism was observed in the liver, kidney, tumor, and pancreas with approximately 30% intact (111)In-DTPA-octreotide at 4 h postinjection. In the adrenals, metabolism occurred more slowly with approximately 60% intact (111)In-DTPAoctreotide at 4 h postinjection. At 4 h postinjection, the activity excreted in the urine consisted of 85% intact (111)In-DTPA-octreotide. HPLC provided resolution of the individual extractable metabolites. In an attempt to identify these metabolites, two DTPA-amino acid sequences were synthesized: DTPA-D-Phe-Cys and DTPA-D-Phe. Under the conditions used for metabolite analysis, (111)In-DTPA-D-Phe-Cys-OH eluted at 14.6 min and (111)In-DTPA-D-Phe-OH eluted at 7.0 min. Each of these standard sequences was combined with the soluble portion of the organ homogenate and was shown by HPLC to coelute with the metabolites. These data suggest that (111)In-DTPA-octreotide was initially degraded to (111)In-DTPA-D-Phe-Cys-OH and (111)In-DTPA-D-Phe-OH. The (111)In-DTPA-D-Phe-Cys-OH was further degraded to (111)In-DTPA-D-Phe-OH, which appeared to be the final metabolite that was extracted from the organs. From these results, it can be concluded that at longer time points (> 2 h postinjection) a significant amount of (111)In was retained in nontarget organs as (111)In-DTPA-D-Phe-OH and (111)In-DTPA-D-Phe-Cys-OH and not as intact (111)In-DTPA-octreotide.
Swine serve as excellent models for many laparoscopic procedures. As more operations are being performed laparoscopically, it is essential for the surgeon to have a good understanding of laparoscopic techniques. This manuscript reviews some commonly performed laparoscopic operations with an emphasis on models in swine. Porcine anatomy is generally similar to human anatomy with some minor differences. Practice on porcine models can help refine techniques and increase efficiency and skill.
This paper investigates the relationship of features of in-vitro fertilization (IVF) embryos and the associated oocyte and follicle to the outcome of transfer. It differs from previous studies in including a range of features (n = 53) and in using class probability tree analysis. This is a non-parametric multivariate method which expresses relationships as simple rules of features characterizing the 'take home baby' and 'no take home baby' (negative pregnancy test) classes of embryo batches. Data were analysed retrospectively. Fifty-three (embryo, oocyte and follicular) features for each of the three embryos in the transferred batch were collected for 200 IVF patients. Each batch of three embryos was described by a representative value for each feature. The relationship between features and outcome of transfer was analysed. Only four of the 53 features were identified as predictive. However, an appropriate combination of these four (embryo grade, cell number, follicle size and follicular fluid volume) achieved satisfactory predictivities while offering a simplified and more quantitative basis than regularly used criteria. The key component of the composite embryo grading allotted by embryologists turned out to be cell number. The existing predictive use of follicular size was corroborated and an independent additional predictive contribution of follicular fluid volume was found. The study also suggests that the 49 remaining features have little additional predictive value.
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Congenital absence of the major salivary glands is an infrequent disorder. Clinically, patients may be asymptomatic or may present with dryness of the mouth, difficulty in chewing and swallowing, and dental caries. The absence of the submandibular gland may be associated with hypertrophy of the contralateral submandibular gland. We report a case of ipsilateral sublingual hypertrophy associated with unilateral submandibular aplasia.
UNLABELLED: Lesions containing somatostatin receptors (SSR) in rats and in man can be visualized in vivo using radiolabeled octreotide (OCT) analogs. SSR scintigraphy was initially performed with [123I-Tyr3]OCT and later with [111In-DTRA0]OCT. With the latter the residence time of radioactivity (111In) in SSR-positive targets is prolonged, most probably due to the DTPA group. Therefore, we hypothesized that its presence might also affect the metabolism of radioiodinated DTPA-OCT analogs. [D-Tyr1]OCT, [DTPA0, D-Tyr1]OCT, [Tyr3]OCT and [DTPA0,Tyr3]OCT were synthesized, and all 4 showed high and specific binding to the SSR in vitro, with IC50 values in the nanomolar range. The rate of internalization of the 4 radioiodinated OCT analogs by mouse AtT20 pituitary tumors cells was in accordance with the IC50 values. The metabolism and tissue distribution of the 4 radioiodinated analogs were investigated in rats at 4, 24 and 48 hours pi, and the tissue vs blood ratios were calculated. High uptake of all OCT analogs was found in the somatostatin receptor-positive tissues at 4 hours, but only remained high at 24 and 48 hours with [125I-D-Tyr1]OCT and [DTPA0,125I-D-Tyr1]OCT. Kidney uptake of [125I-D-Tyr1]OCT and [DTPA0,125I-D-Tyr1]OCT was also high. Blood clearance and disappearance from muscle was rapid for all 4 analogs. Urinary excretion of [125I-D-Tyr1]OCT, [DTPA0,125I-D-Tyr1]OCT,[125I-Tyr3]OCT and [DTPA0, 125I-Tyr3]OCT amounted to 63%, 67%, 31% and 80% of injected dose respectively. [DTPA0,125I-D-Tyr1]OCT showed highest tissue to blood ratio and residence time in SSR-positive tissues, such as adrenals (ratio: 31, 79, and 66 at 4, 24 and 48 hours respectively) and pancreas (ratio: 14, 48 and 44 at 4, 24 and 48 hours respectively). CONCLUSION: The position of the Tyr residues and the addition of the DTPA group greatly influence the biodistribution of radioiodinated [Tyr]OCT analogs.