Characterization of unique ADTN-catecholamine binding sites in the iris root-ciliary body of rabbits

A binding site for tritiated 2-amino-6, 7-dihydroxy-1, 2,3,4-tetrahydronaphthalene (ADTN) has been partially characterized in the rabbit iris root-ciliary body. Binding of ADTN is proportional to protein content and requires at least 60 minutes to reach equilibrium. Binding is saturable, with a Kd of 27 +/- 1 nM and a Bmax of 2.1 +/- .3 pmol/mg protein (mean +/- SEM). Dopamine competes for this site with a Ki of 100 nM and apomorphine with a Ki of 180 nM. This site is not blocked by L-timolol, phenoxybenzamine, or by several DA1 and DA2 antagonists. It appears to be a new type of catecholamine binding site, of a type not observed outside the anterior eye. It is possible that some of the effects of dopamine on intraocular pressure are mediated through this binding site.     

Structure-activity relationship (SAR) between some natural flavonoids and ocular blood flow in the rabbit.

PURPOSE: Flavonoids with two to five hydroxy groups, with or without sugar, and/or methoxy groups were studied on their effects to affect ocular blood flow. METHODS: Colored microsphere technique was used to determine the ocular blood flow in rabbit eyes. RESULTS: Flavonoids with three free hydroxy (OH) groups seemed to produce the optimal effects in increasing ocular blood flow (naringenin and hesperitin, Pfalts and Bauer, Waterbury, CT). Whether the OH groups are below three (naringenin, hesperitin, Pfalts and Bauer, Waterbury, CT) or above four (Quercetin, Pfalts and Bauer, Waterbury, CT), they produced no effects on the ocular blood flow. When OH groups are four (rutin, Aldrich, Milwaukee, WI), it produced mixed effects on ocular blood flow. The attachment of rutinose and/or methoxy group in the structure did not affect the ocular blood flow one way or the other. CONCLUSION: The ocular blood flow is increased significantly by the number of OH group in the molecule, with three the best to increase the ocular blood flow.     

Pediatric traumatic brain injuries in Taiwan: an 8-year study.

Background. This study is intended to determine the causes of pediatric traumatic brain injuries (PTBI) in children aged 14 years or less, and to identify various types of craniocerebral damage resulting from different mechanisms of injury.Methods. From July 1, 1993 to June 30, 2001, a survey on PTBI was conducted in Taiwan. The data of patients used in this study were collected from 56 major hospitals among the age group of 0-14 years. The items in the traumatic brain injury survey included sex, age, causes of injuries, severity, and the eventual outcome.Results. A total of 5349 cases were identified. The male-to-female ratio was 1.69: 1. The incidence rate was higher in the age groups of 4-9 years and 10-14 years. The main cause of PTBI was traffic injury, which accounted for 2537 of the cases (47.3%), followed by falls, 2160 (40.3%). Of all traffic injuries, motorcycle-related injury had the highest incidence, followed by the pedestrian and bicycle-related injury. This study also showed that 83.2% of the patients had mild injury, 9.8% had moderate injury, and 7.0%, severe injury.Conclusions. The results of this study suggest that it is important to decrease all the risk factors in the environment of homes and public areas as much as possible. Helmet wearing and the development of public transportation are essential for the prevention of head injury.     

Smoking and coffee intake following alcohol withdrawal in alcoholic inpatients

The aim of this study was to assess alcoholic inpatients' smoking and coffee intake variation following withdrawal. Only moderate smokers (less than 30 cigarettes/day) showed a significant increase of cigarette consumption after alcohol withdrawal. However, their urinary cotinine level did not vary, suggesting a behavioral, and not biological, compensation through smoking following alcohol withdrawal. Heavy smokers (30 cigarettes/day or more) showed no significant clinical or biological variation of smoking behavior. Coffee consumption increased after alcohol withdrawal in all patients, irrespective of smoking habits.     

Effects of epinephrine on retinal and choroidal blood flow through different routes of drug administration

Epinephrine (1, 3 and 10 micrograms/kg) was found to increase retinal and choroidal blood flow (22, 49 and 67%) when it was administered intravenously. The increase in retinal and choroidal blood flow coincided well with the increase in systemic blood pressure (44, 65 and 96%, respectively). When epinephrine (2%) was instilled to the eyes topically the retinal and choroidal blood flow decreased (15%) while systemic blood pressure remained unchanged. It is suggested that the decrease in retinal and choroidal blood flow by topical epinephrine could be the cause of epinephrine maculopathy reported previously. L-Timolol (0.25%, topically) did not affect retinal and choroidal blood flow significantly.     

Validation in the sheep of an ultrasound velocity dilution technique for haemodialysis graft flow

BACKGROUND: A simple, rapid, inexpensive method for measuring the flow in a patient's vascular access would permit routine monitoring during haemodialysis, and hence provide information of access graft deterioration sufficiently early to increase the success of minimally invasive remedial procedures. This paper reports the validation of such a method in animals. METHODS: A PTFE graft was implanted in sheep between the carotid artery and the jugular vein. While the sheep was under general anaesthesia and on an haemodialysis circuit, ultrasound velocity in its blood was perturbed by the injection of a 5-10 ml bolus of isotonic NaCl. The pump tubing flow was measured by a transit-time blood flow meter. This flow was combined with the areas of perturbation generated by the injection before and after mixing in the access flow to estimate graft flow. The calculated graft flow was compared to flow measured directly by a transit-time probe on the same carotid artery. RESULTS: Over a 10-fold range, 120-1260 ml/min, graft flow measured by ultrasound velocity dilution agreed well with graft flow measured directly with a scatter of 76 ml/min about the regression line. CONCLUSION: Ultrasound velocity dilution provides a method for measuring flow in the graft accurate enough for clinical evaluation of patients on dialysis.      

Effects of the rate and composition of fluid replacement on the pharmacokinetics and pharmacodynamics of intravenous furosemide

Effects of differences in the rate and composition of intravenous fluid replacement for urine loss on the pharmacokinetics and pharmacodynamics of furosemide were evaluated using the dog as a model animal. Each of six dogs received 8-hr constant intravenous infusion of 20 mg (15 mg used in one dog) of furosemide with 0% replacement (treatment I), 50% replacement (treatment II), and 100% replacement (treatment III) with lactated Ringer's solution, as well as with 100% replacement with 5% dextrose in water (treatment IV). Most pharmacokinetic parameters, such as plasma clearance, steady-state volume of distribution, mean residence time, and terminal half-life, were essentially the same in all four treatments. Renal clearances and urinary excretion rates of the drug in treatments II–IVwere essentially the same, but about 20% higher than those in treatment I.In spite of the similarities in kinetic properties, diuretic and/or natriuretic effects from furosemide were markedly different among the four treatments. For example, mean 10-hr urine outputs were 646, 1046, 3156, and 1976 ml and mean 10-hr sodium excretions were 87.0, 142, 383, and 97.2 mmole for treatments I–IV,respectively. Except for treatment III,diuresis and/or natriuresis were found to be time-dependent, generally decreasing with time until reaching a low plateau during later hours of infusion. The present findings also showed that (1)no fluid replacement and 100% replacement with 5% dextrose solution both produced the same degree of severe acute tolerance in natriuresis, indicating the insignificance of water compensation in tolerance development; (2)in treatment II,where neutral sodium balance was achieved, the development of acute tolerance in diuresis and natriuresis can mainly be attributed to negative water balance under this special condition; (3)at steady state the hourly diuresis and natriuresis could differ up to about ten times between treatments. Some implications for the kinetic/dynamic relationship or modeling, in the clinical use, and in the bioequivalence evaluation of dosage forms are discussed.