Fluorine-18-fluoro-L-DOPA dosimetry with carbidopa pretreatment

This article presents dosimetry based on the measurement of fluoro-DOPA activity in major tissues and in the bladder contents in humans after oral pretreatment with 100 mg carbidopa. METHODS: Bladder activity was measured continuously by external probe and calibrated using complete urine collections. Quantitative dynamic PET scans provided time-activity curves for the major organs. Bladder wall dosimetry was calculated using the methods of MIRD Pamphlet No. 14. Effective dose was calculated as described in ICRP Publication 60. RESULTS: Mean absorbed dose to the bladder wall surface per unit administered activity was 0.150 mGy/MBq (0.556 rad/mCi) with the realistic void schedule used in our studies. The dose was 0.027 mGy/MBq (0.101 rad/mCi) to the kidneys, 0.0197 mGy/MBq (0.0728 rad/mCi) to the pancreas, and 0.0186 mGy/MBq (0.0688 rad/mCi) to the uterus. Absorbed doses to other organs were an order of magnitude or more lower than the bladder, 0.009-0.015 mGy/MBq. The effective dose per unit administered activity was 0.0199 mSv/MBq (0.0735 rem/mCi.) CONCLUSION: Urinary excretion of fluoro-DOPA was altered significantly by pretreatment with carbidopa. In general, any manipulation of tracer metabolism in the body should be expected to produce changes in biodistribution and dosimetry. The largest radiation dose was to the bladder wall, for which our estimate was one-fifth of that from the original report. The methods used reflect realistic urinary physiology and typical use of this tracer. The principles of MIRD Pamphlet No. 14 should be used in planning studies using tracers excreted in the urine to minimize the absorbed dose.     

Computed tomographic evaluation of radiation pneumonitis in a canine model

Antiradical and antioxidative activities of dieton, phoridon, niphedipin, phlamicar, mildronat in vitro were studied by spectrophotometer's method with the use of dyfenilpycrilgydrasil and method of pulse voltametry. Also influence of drugs was studied under antioxidative insufficiency (AOI), which had modelled by exclusion of alpha-tocopherol from the animal's ration.     

Caenorhabditis elegans as a model for parasitic nematodes

Spontaneous multiquantal events are recorded at many different boutons and varicosities for which there is evidence that the receptor patch at these individual synapses is saturated by the transmitter unit. In order to reconcile these observations, a model is considered in which calcium release from a ryanodine channel within a nerve terminal can reach adjacent active zones in single synapses in sufficient concentration to occasionally trigger exocytosis from adjacent zones synchronously, giving rise to multiquantal spontaneous events. It is shown that the spatial and temporal distribution of calcium concentration at the active zone after a spontaneous opening of a ryanodine channel can predict the amplitude and time course of observed calcium-activated potassium channel currents. Similar calcium transients are sufficient to give rise to multiquantal events. Such events suggest a multi hypothesis for secretion.     

Passive Ca2+ binding in ventricular myocardium of neonatal and adult rats

In this study, passive Ca2+ binding was determined in ventricular homogenates (VH) from neonatal (4-6 days) and adult rats, as well as in digitonin-permeabilized adult ventricular myocytes. Ca2+ binding sites, both endogenous and exogenous (Indo-1 and BAPTA) were titrated. Sarcoplasmic reticulum and mitochondrial Ca2+ uptake were blocked by thapsigargin and Ru360, respectively. Free [Ca2+] ([Ca2+]F) was measured with Indo-1 and bound Ca2+ ([Ca2+]B) was the difference between [Ca2+]F and total Ca2+. Apparent Ca2+ dissociation constants (Kd) for BAPTA and Indo-1 were increased by 10-20 mg VH protein/ml (from 0.35 to 0.92 microM for Indo-1 and from 0.20 to 0.76 microM for BAPTA) and also by ruthenium red in the case of Indo-1. Titration with successive CaCl2 additions (2.5-10 nmoles) yielded delta[Ca2+]B/delta[Ca2+]F for the sum of [Ca2+]B at all three classes of binding sites. From this function, the apparent number of endogenous sites (Ben) and their Kd (Ken) were determined. Similar Ken values were obtained in neonatal and adult VH, as well as in adult myocytes (0.68 +/- 0.14 microM, 0.69 +/- 0.13 microM and 0.53 +/- 0.10 microM, respectively). However, Ben was significantly higher in adult myocytes than in adult VH (1.73 +/- 0.35 versus 0.70 +/- 0.12 nmol/mg protein, P < 0.01), which correspond to approximately 300 and 213 mumol/l cytosol. This indicates that binding sites are more concentrated in myocytes than in other ventricular components and that Ben determined in VH underestimates cellular Ben by 29%. Although Ben values in nmol/mg protein were similar in adult and neonatal VH (0.69 +/- 0.12), protein content was much higher in adult ventricle (125 +/- 7 versus 80 +/- 1 mg protein/g wet weight, P < 0.01). Expressing Ben per unit cell volume (accounting for fractional mitochondrial volume, and 29% dilution in homogenate), the passive Ca2+ binding capacity at high-affinity sites is approximately 300 and 176 mmol/l cytosol in adult and neonatal rat ventricular myocytes, respectively. Additional estimates suggest that passive Ca2+ buffering capacity in rat ventricle increases markedly during the first two weeks of life and that adult levels are attained by the end of the first month.     

Acute respiratory distress syndrome. Patient position and motion strategies

A review of the literature since 1974 indicates that, although there is no consensus as to the mechanism, positioning strategies in patients with ARDS improve PaO2 and may diminish lung parenchymal damage. The effect of these maneuvers on patient outcomes is uncertain. There is no uniform algorithm for the application of these techniques; however, there is sufficient evidence cited in the referenced articles to support the use and early application of the techniques to improve oxygenation.     

Clathrin-dependent localization of alpha 1,3 mannosyltransferase to the Golgi complex of Saccharomyces cerevisiae

Posttranslational modification of yeast glycoproteins with alpha 1,3-linked mannose is initiated within a Golgi compartment analogous to the medial Golgi cisternae of higher eukaryotes. We have characterized the synthesis, posttranslational modification, and localization of the yeast alpha 1,3 mannosyltransferase (Mnn1p) using antibodies prepared against a segment of this protein expressed in bacteria. Mnn1p is initially synthesized as a 98.5-kD, type II integral membrane glycoprotein that is modified with both N- and O-linked oligosaccharides. It is subject to a slow, incremental increase in molecular mass that is dependent upon protein transport to the Golgi complex. Self-modification of Mnn1p with alpha 1,3 mannose epitopes, primarily on O-linked oligosaccharides, is at least partly responsible for the incremental increase in molecular mass. Mnn1p is a resident protein of the Golgi complex and colocalizes with guanosine diphosphatase to at least two physically distinct Golgi compartments by sucrose gradient fractionation, one of which may be a late Golgi compartment that also contains the Kex2 endopeptidase. Surprisingly, we found that a significant fraction of Mnn1p is mislocalized to the plasma membrane in a clathrin heavy chain temperature sensitive mutant while guanosine diphosphatase remains intracellular. A mutant Mnn1p that lacks the NH2-terminal cytoplasmic tail is properly localized to the Golgi complex, indicating that clathrin does not mediate Mnnlp Golgi retention by a direct interaction with the Mnn1p cytoplasmic tail. These results indicate that clathrin plays a broader role in the localization of Golgi proteins than anticipated.     

Isolation and characterization of cDNAs encoding PDE5A, a human cGMP-binding, cGMP-specific 3'',5''-cyclic nucleotide phosphodiesterase

An attempt has been made to suppress the ethanol-induced formation of megamitochondria (MG) in the rat liver by 4-hydroxy-2,2,6,6-tetramethyl-piperidine-1-oxyl (4-OH-TEMPO), a free radical scavenger, and by allopurinol (AP), a xanthine oxidase inhibitor. Changes observed in the liver of animals given ethanol (EtOH) for 1 month were remarkable decreases both in the body weight gains during the course of the experiment and in the liver weight at the time of sacrifice compared to those of the control; remarkable increases in the level of thiobarbituric acid reactive substances and lipid soluble fluorophores both in microsomes and mitochondria; decreases in the content of cytochrome a+a3 and b and lowered phosphorylating ability of mitochondria; and formation of MG in the liver. A combined treatment of animals with EtOH plus 4-OH-TEMPO completely suppressed the formation of MG in the liver induced by EtOH and distinctly improved the changes caused by EtOH, as specified above, while AP partly suppressed the MG formation. Results described herein provide additional insight into chronic hepatotoxicity of EtOH besides that previously reported. A novelty of the present work is that we were able for the first time to demonstrate reversibility of EtOH-mediated ultrastructural changes of the liver by a simple administration of aminoxyl-type free radical scavenger, 4-OH-TEMPO. Our results suggest that free radicals may be involved in the mechanism of the formation of MG induced by EtOH.