Evaluation of the rat tail model for estimating dermal absorption of lindane

Dermal absorption of the insecticide lindane was determined following topical application of ring 14C-labeled lindane to the tail of Sprague-Dawley rats. The tail was tested as a practical alternative to the rat mid-dorsal (back) region, and the data obtained were compared to those with rat back and with those of rhesus monkeys in our previous reports. There was no significant difference between total percentage urinary 14C recovery for rats dosed on the tail with occlusive tail covers (52 +/- 6.2%; t1/2 = 2.7 d) compared to those with nonocclusive covers (55 +/- 4.4%; t1/2 = 2.9 d). Neither the total percentage urinary recovery nor the t1/2 values obtained for the rat tail and rat back models differed significantly. Carbon-14 activity was still detectable in urine samples taken after 72 d post-treatment. However, an extensive tissue analysis failed to demonstrate 14C activity persisting at 72 d, with the exception of trace levels detected in blood serum and tail tissue. Advantages of the rat tail model are highlighted.     

Zinc, calcium, and magnesium metabolism: effects on plasmacytomas in Balb/c mice

The effects of different amounts of dietary zinc on the Zn absorption rate and on Zn, calcium and magnesium concentrations in tissues of MOPC 104E tumor-bearing Balb/c mice were determined. The Zn absorption rate was inversely related to the amounts of Zn in their diets and was lower than that of nontumor-bearing control mice fed a laboratory mice chow. Zn concentrations of tumor-bearing mice were also low compared with control mice but tumor Zn concentrations, regardless of the concentrations of Zn in the diets, were higher than those of normal tissues of the host other than the pancreas. Ca concentrations in tumor and tissues of tumor-bearing mice were higher than in control animals but Mg concentrations in tissues of tumor-bearing mice appeared to be similar to those of control mice. Results suggest that tumor-bearing mice have a lower intestinal Zn absorption capacity and a higher Zn uptake rate causing other tissues to become hypozincemic and hypercalcemic.     

PharmaTrend as a management tool: capturing workload data

Several methods of collecting workload data for use in PharmaTrend, a computerized pharmacy management information system, are described. Although the number of indicators produced by PharmaTrend is limited by the input of the user, the integrity of the indicators that are produced is not compromised; this allows the user to implement PharmaTrend on a limited scale, such as for workload only. Workload data that can be used in PharmaTrend are collected routinely by most pharmacies. Many activities are already recorded in logs and other noncomputerized sources. The aid of members of the pharmacy department and other departments may be enlisted in collecting these data. Self-reporting through time sheets and cards can also be used to obtain data on the distribution of work hours. Recording is simplified if employees are told to record only exceptions to their usual job responsibilities. The PharmaTrend manual contains detailed definitions of the workload categories, but simpler and more practical definitions may have to be used. A computer spreadsheet program should probably be used for compiling data if they are collected from several sources; this will facilitate entry into PharmaTrend. Simple methods are available for capturing workload data for input into the PharmaTrend program.     

Fatal and non-fatal stingray envenomation

A fatality occurred in a previously healthy 12-year-old boy after a penetrating chest injury from a stingray barb. The injury occurred under freak circumstances. Death was a result of cardiac tamponade which was secondary to venom-induced, localized myocardial necrosis and spontaneous perforation, six days after the direct penetration of the right ventricle by the barb. Three other cases of less serious stingray envenomation are described which illustrate the significant localized morbidity that may occur without immediate wound exploration and toilet after adequate anaesthesia. We also report a study of a series of 100 minor stingray envenomations which, when treated, resulted in no morbidity. It is possible that local infiltration with 1% plain lignocaine may have a direct counteraction against stingray venom that remains in the wound area. Stingray venom has insidious, but powerful, localized tissue necrosing properties in humans.     

Effect of morphine on the mechanical activity of common bile duct isolated from the guinea pig

The contractile response of isolated guinea pigs common bile ducts (CBD) to transmural electrical stimulation and the effects of morphine and naloxone was studied. Contractile responses increased as a function of stimulus frequency. In the absence of naloxone morphine inhibited the contractile response to electrical stimulation in a dose-dependent manner. Naloxone prevented the inhibitory effect of morphine on the contractile response to electrical stimulation. We conclude that smooth muscle of the CBD in guinea pig is functional and can contribute to biliary motility, and that opiate receptors exist in nerve elements in the CBD.     

Protection of photosensitized rats against long ultraviolet radiation by topical application of compounds with structures similar to that of dihydroxyacetone

Dihydroxyacetone (DHA), a browning agent, protects photosensitive rats and humans against long ultraviolet radiation (UVA, 320-400 nm) and visible (blue) light. The photoprotective efficacy of DHA and structurally similar compounds was assessed as prevention of edema in the paws of psoralen-sensitized rats, after exposure to blacklight fluorescent lamps. Methylglyoxal produced a yellow-brown color and provided nearly the same protection as DHA, whereas monohydroxyacetone did not color the skin and afforded little or no protection. Glyceraldehyde provided a moderate amount of protection, which was enhanced by prior exposure of the agent to alkaline pH. A solution of 5-hydroxymethylfurfuraldehyde was yellow and provided minimal protection by staining the skin rather than browning it. We conclude that the ability to produce a brown color in skin is a useful criterion for screening compounds for photoprotective efficacy against UVA radiation.     

Clinical phase I study of T-2588

A clinical phase I study for T-2588 was carried out in 25 healthy male volunteers. Each volunteer received T-2588 in one of the following doses: 100 mg capsule or tablet as a single oral administration in fasting or non-fasting state, 200 or 400 mg capsule as a single oral administration in non-fasting state or 300 or 600 mg daily for 14 approximately 15 days as a repeated administration in non-fasting state. The results are summarized below. No subjective or objective adverse effects were noted after a single oral administration. But repeated dose of 300 mg daily for 15 days and 600 mg daily for 14 days brought about abdominal distension in 1 case and soft stool in 1 case, respectively. As an abnormal change in clinical laboratory findings, 1 case with slight increase in transaminase after a single administration and 3 cases with slight increases in transaminase after repeated doses were observed. Time to reach a maximum concentration of T-2525 in blood (Tmax) was longer in subjects at non-fasting states than subjects in fasting states. Maximum blood concentration was lower in the latter than in the former. Urinary excretion rate in 8 hours after an oral administration was 19 approximately 28% and it was higher in non-fasting subject than in fasting subject. No accumulation of T-2588 was noted after repeated doses.     

271. Tuberkulose nach lebertransplantation

Zusammenfassung Bei einem 55jährigen Mann wurde 7 Monate nach orthotoper Lebertransplantation eine Lungentuberkulose diagnostiziert. Die tuberculostatische Therapie erfolgte mit Isoniazid (3 x 0,2 g/Wo) und Ethambutol (1,6 g/d) über 11 Monate. Nach 3 Monaten waren keine Mycobakte rien mehr nachweisbar, und der Patient ist im 3. Jahr nach Transplantation ohne Zeichen einer aktiven Tuberkulose in gutem Gesundheitszustand bei guter Transplantatfunktion. Die Tuberculostatica-Dosierung sollte je nach Metabolisierungsleistung des Transplantats reduziert werden. Bei Beachtung dieses Kardinalpunktes könnte eine Tuberkulose nach Lebertransplantation erfolgreich behandelt werden.