Evaluation of 99mTc(CO)5I as a potential lung perfusion agent

IntroductionThe use of ^99mTc-macroggregated albumin for lung perfusion imaging is well established in nuclear medicine. However, there have been safety concerns over the use of blood-derived products because of potential contamination by infective agents, for example, Variant Creutzfeldt Jakob Disease. Preliminary work has indicated that Tc(CO)₅I is primarily taken up in the lungs following intravenous administration. The aim of this study was to evaluate the biodistribution and pharmacokinetics of ^99mTc(CO)₅I and its potential as a lung perfusion agent.Methods^99mTc(CO)₅I was synthesized by carbonylation of ^99mTcO_4? at 160 atm of CO at 170°C in the presence of HI for 40 min. Radiochemical purity was determined by HPLC using ⁹⁹Tc(CO)₅I as a reference. ^99mTc(CO)₅I was administered by ear-vein injection to three chinchilla rabbits, and dynamic images were acquired using a gamma camera (Siemens E-cam) over 20 min. Imaging studies were also performed with ^99mTc-labeled macroaggregated albumin (^99mTc-MAA) and ^99mTcO_4? for comparison. ^99mTc(CO)₅I was administered intravenously to Sprague–Dawley rats, and tissue distribution studies were obtained at 15 min and 1 h postinjection. Comparative studies were performed using ^99mTc-MAA.ResultsRadiochemical purity, assessed by HPLC, was 98%. The retention time was similar to that of ⁹⁹Tc(CO)₅I. The dynamic images showed that 70% of ^99mTc(CO)₅I appeared promptly in the lungs and remained constant for at least 20 min. In contrast, ^99mTcO_4? rapidly washed out of the lungs after administration. As expected ^99mTc-MAA showed 90% lung accumulation. The percentage of injected dose per gram of organ ±S.D. at 1 h for ^99mTc(CO)₅I was as follows: blood, 0.22±0.02; lung, 12.8±2.87; liver, 0.8±0.15; heart, 0.15±0.01; kidney, 0.47±0.08. The percentage of injected dose per organ ±S.D. at 1 h was as follows: lung, 22.47±2.31; liver, 10.53±1.8; heart, 0.18±0.01; kidney, 1.2±0.17. Tissue distribution studies with ^99mTc-MAA showed 100% lung uptake.Conclusion^99mTc(CO)₅I was synthesized with a high radiochemical purity and showed a high accumulation in the lungs. Further work on the mechanism and optimization of lung uptake of ^99mTc-pentacarbonyl complexes is warranted.     

Evaluation of the effectiveness of differentiated therapy in patients with chronic erosions of the gastric mucosa

Potentialities of differentiated therapy of patients with recurrent chronic erosions using medicinal and nonmedicinal methods in 119 patients were studied. During differentiated therapy one should take into account the condition of pathological microflora and circulatory disturbances. At the first stage routine therapy with subsequent incorporation of biogastrone was employed. At the second stage in the absence of a therapeutic effect local administration of a granulocytic concentrate was performed, and in insufficient effectiveness, electrocoagulation of chronic erosions of the gastric mucosa was indicated. The use of differentiated therapy contributed to a favorable prognosis of disease in these patients.     

Improving spatial functioning in children with cerebral palsy using computerized and traditional game tasks

Purpose: To examine the effectiveness of combining virtual environment (VE) instruction with additional desk-top tasks, based on the Luria-Vygotsky methodology, for spatial remediation in children having complex motor disabilities restricting movement.

Method: In Experiment 1, from among children attending for residential rehabilitation, an experimental subgroup had additional spatial training using a VE and corresponding desk-top models. All children were tested at the start and end of training, using four spatial tests. In Experiment 2, larger groups of children (pair-matched for initial performance) were given the same training as in Experiment 1, but experimentals received both VE-based training and supporting tasks designed to improve executive functions and verbal regulation of spatial functioning. Assessment involved a wider range of tests than in Experiment 1.

Results: In Experiment 1, both groups showed improvement at retest, but experimentals showed greater improvement. Children beginning with the lowest level of cognitive performance failed to benefit from the additional training. In Experiment 2 the experimental group made significantly greater improvement than controls, irrespective of initial performance level.

Conclusions: VE-based spatial training is effective for children with complex disabilities, particularly when combined with training that remediates cognitive weaknesses.     

Beneficial effects versus toxicity of medium-chain triacylglycerols in rats with NASH

BACKGROUND/AIMS: Replacing long-chain triacylglycerols (LCT) with medium-chain triacylglycerols (MCT) reduces alcohol-induced liver injury. Because of the similarity of the pathogenesis of alcohol-induced liver damage and non-alcoholic steatohepatitis (NASH), our aim was to assess whether MCT is also beneficial in NASH. METHODS: We used a rat NASH model in which corn oil (35% of total calories) was isocalorically replaced with MCT. RESULTS: Partial replacement of LCT did not ameliorate hepatic fat accumulation, 4-hydroxynonenal, collagen type I and its mRNA but it increased TNF-alpha and its mRNA (p<0.001). However, in rats given the high-fat diet restricted to 2/3 of the amount they were consuming, these adverse effects decreased, with and without MCT including less liver steatosis and lower triacylglycerols, but without beneficial effects of MCT. When 70% of the fat calories were replaced with MCT with no LCT remaining in the diet, no steatosis developed and hepatic TNF-alpha was low. When all MCT were given with carbohydrates (instead of LCT) hepatic TNF-alpha also decreased (p<0.001). CONCLUSIONS: MCT are not hepatotoxic, provided the diet contains no significant amount of LCT. Total replacement of dietary LCT with MCT fed ad libitum is beneficial whereas partial replacement becomes hepatotoxic, unless the dietary intake is restricted.     

Recommendations for management of dyslipidemia in high cardiovascular risk patients

Overwhelming evidence supports a causal relationship between elevated levels of plasma cholesterol, particularly low-density lipoprotein cholesterol, and increased risk of coronary artery disease, which remains the leading cause of death and morbidity worldwide. Low-density lipoprotein cholesterol lowering has been the main goal of therapy, and clinical trial results from recently published studies of intensive statin therapy confirm the benefits of more aggressive lipid-lowering targets, particularly in subjects at high risk for cardiovascular events. This management update will focus on the implications of risk reduction in patients at high cardiovascular risk, and will provide practical steps to help further risk stratify these patients and help them reach their target goals.     

A significant association exists between receptor tyrosine kinase-like orphan receptor 2 gene variants and the OPG/RANKL ratio in human plasma

Summary

There is a paucity of studies investigating association between ROR2 gene variants and osteoporosis and osteoarthritis-related phenotypes. The published literature suggests that osteoprotegerin (OPG) and receptor activator of nuclear factor-kB ligand (RANKL) are essential for bone metabolism and correlate with osteoarthritis manifestation and progression. The present study provides evidence of the significant association between ROR2 variants and the OPG/RANKL ratio in human plasma. The present results also suggest significant association between ROR2 polymorphisms and severity of radiographic hand osteoarthritis.

Introduction

Despite the importance of the ROR-2 in skeletal physiology, there is a paucity of studies investigating the potential association of ROR2 gene variants with phenotypes relevant to osteoporosis and osteoarthritis. On the other hand, there is a considerable body of literature suggesting that OPG and RANKL and their ratio (OPG/RANKL) are essential for regulating bone resorption. This is also correlated with osteoarthritis manifestation and progression. The present study therefore examines whether ROR2 polymorphisms may be associated with the OPG/RANKL ratio and hand osteoarthritis (HOA).

Methods

The study was conducted in a family-based sample of 1,515 Caucasian individuals, assessed for radiographic hand osteoarthritis, using the Kellgren/Lawrence score. Of these, 865 individuals were genotyped for 19 SNPs, relatively equally covering the ROR2 locus, and their plasma levels of OPG and RANKL were assayed. The association between the selected SNPs and OPG, along with the OPG/RANKL ratio and HOA, was explored using the pedigree disequilibrium test.

Results

Of the total of 57 tests, 16 nominally significant results (p?p?p?=?0.006).

Conclusions

The present study provides evidence of the significant association between ROR2 variants and the OPG/RANKL ratio in human plasma and also suggests ROR2 association with HOA.