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.     

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.     

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.     

44Sacral extracorporeal magnetic stimulation is an effective treatment for pelvic floor dyssynergia; Comparative study with biofeedback therapy

Background: Recent development of extracorporeal magnetic stimulation (ECMS) which uses current‐changing magnetic fields allows the induction of electrical stimulation in the desired deep tissue. Recent study showed the sacral nerve stimulation reduces corticoanal excitability that may play a functional role in anal continence mechanisms. Preliminary study shows that ECMS of sacral nerve can modify pelvic floor function and expel rectal balloon in patients with pelvic floor dyssynergia (PFD). Aims: To evaluate the effect of ECMS compared with biofeedback therapy (BF) in patients with PFD. Methods and Materials: Thirty‐eight patients who fulfilled Rome II criteria for PFD by colon transit time and anorectal function tests, were randomly treated with 8 sessions of ECMS (2/weeks; n = 19) at prone position or BF (2/weeks; n = 19) at sitting position. Stimulation parameters were set at 50–80% of maximum intensity, 10 and 50 Hz frequency, 3 s burst length with 3 and 6 s off using arm‐typed stimulator (BioCom‐1000, Mcube Co., Korea). Symptom scores for constipation with/without anorectal function test were repeatedly measured after each treatment. Response was defined as 50% or more decreased symptom score after treatment (partial response: 30–50%, poor: <30%). Results: Fifteen patients (age 49.1 ± 13.4 years, mean ± SD; 4 men) completed 8 session of BF and 14 patients (54.5 ± 17.6 years, 3 men) completed 8 session of ECMS. Four patients of BF group discontinued treatment due to unsatisfactory therapeutic effect (n = 1) and withdrew consent (n = 3) and 5 patients of ECMS group discontinued treatment because of same reasons (n = 1, 4). Total symptom scores were significantly decreased after treatment of 8 session in both treatment groups (13.4 ± 6.6 vs. 4.3 ± 4.0 for BF, p = 0.009; 14.9 ± 5.6 vs. 3.4 ± 4.0 for ECMS, p < 0.001). Bowel movements per week were also significantly increased after treatment in both groups (median 2 vs. 7 for BF, p = 0.035; median 2 vs. 7 for ECMS, p = 0.008). Thirteen out of 15 patients showed response in BF group and 12 out of 14 showed good response in ECMS group. No adverse effects in both groups. Conclusions: ECMS is as effective as BF for the treatment of PFD. Long‐term effect of ECMS for the patients with pelvic floor dyssynergia need to be evaluated in the near future.     

Epstein-Barr virus latent and replicative gene expression in oral hairy leukoplakia

Oral hairy leukoplakia is an epithelial lesion of the tongue associated with productive infection by Epstein-Barr virus (EBV). However, no data concerning the pattern of EBV latent gene expression have been reported, and it remains unresolved whether true latent infection occurs in basal cell layers of oral hairy leukoplakia. We have studied six cases of oral hairy leukoplakia using monoclonal antibody immunohistology for EBV latent--EB nuclear antigen (EBNA) 1, EBNA 2 and latent membrane protein 1 (LMP 1); immediate-early (BZLF1); and replicative (EA, VCA, MA) proteins, and for the EBV-receptor (CD21 antigen). EBV DNA was demonstrated by nucleic acid in situ hybridization. Mid- to upper-zone keratinocytes contained EBV DNA and co-expressed EBNA 1, EBNA 2 (5 of 6 cases), LMP 1, BZLF1 protein, EA, VCA and MA. No EBV genome or gene expression could be demonstrated in basal or parabasal cells. Spinous keratinocytes were labelled by anti-CD21 antibodies HB5 and B2, but did not express the EBV-receptor as defined by reactivity with OKB7. The co-expression of latent and replicative infection-associated antigens is striking, indicating possible functional roles for latent proteins during the productive cycle. Our results suggest that oral hairy leukoplakia is caused by repeated direct infection of upper epithelial cells with virus from saliva or adjacent replicatively infected cells, rather than by a latent EBV infection of basal epithelial cells with a differentiation-dependent switch to productive infection as previously proposed.