Evidence of melanogenesis in porcine retinal pigment epithelial cells in vitro

Several weeks after porcine retinal pigment epithelial (RPE) cell cultures attain confluence, macroscopically visible brown foci appear. The cuboidal cells that form the foci contain numerous phase dark granules that do not exhibit the autofluorescence characteristic of lipofuscin. The data described here indicate that the granules are melanosomes. Electron microscopy revealed three types of electron-dense granules in these cells: simple spheres 0.3-0.5 microns in diameter, large spheres 1-2 microns in diameter, and lysosomal aggregations of the smaller spheres. The matrix of both spheres is composed of 40-nm microvesicles that were also found free in the cytoplasm and aggregated within vacuolar structures. Reversed-phase high-performance liquid chromatography of RPE cells and their media detected melanogens, i.e. intermediates of melanin biosynthesis, including several indole derivatives. The porcine RPE cultures therefore may be a useful system for studying melanogenic regulation.     

Pharmacokinetics, hepatic biotransformation and biliary and urinary excretion of bromosulfophthalein (BSP) in an experimental liver disease mimicking biliary cirrhosis

We studied the hepatic handling of bromosulfophthalein in healthy rabbits with hepatic coccidiosis 28 days after an experimental infection with sporulated oocysts of Eimeria stiedai, an experimental model of liver disease histopathologically resembling primary biliary cirrhosis in man. A pharmacokinetic study of the results was performed following a multicompartmental model with 7 transfer constants to describe the physiological disposition of the dye. The study showed that the plasma disappearance, distribution volume (Vi), hepatic biotransformation and the biliary and urinary elimination of conjugated (BSPc) and unconjugated (BSPu) bromosulfophthalein were markedly altered. Whereas Vi and urinary excretion of the dye were significantly increased, the hepatic clearance, biotransformation and biliary excretion of BSPc and BSPu were drastically reduced in infected rabbits. Satisfactory agreement was obtained between the experimental and estimated data, particularly those relating to biotransformation clearance and biliary and urinary excretion of the dye. These results demonstrate that severe liver disease in rabbits with histopathological liver alterations resembling several hepatic dysfunctions in man markedly reduce hepatic uptake, metabolism and biliary excretion of a xenobiotic such as BSP.     

Multicentre hospital drug utilization study on the prophylaxis of venous thromboembolism. The Venous Thromboembolism Study Group of the Spanish Society of Clinical Pharmacology.

1. Thromboembolic disease (TED) is an important cause of in-hospital morbidity and mortality. Although different prophylactic approaches have been shown to be effective and cost-effective, surveys have suggested that they are underused. The aim of this study was to estimate the prevalence of use of TED prophylaxis in our hospitals. 2. All patients admitted on a specified day to the Internal Medicine and General Surgery wards of seven Spanish university hospitals were included in the study. They were identified cross-sectionally and followed up until discharge or for 15 days. Information about the following variables was collected: risk factors for venous thromboembolism, prophylactic measures used (if any), contraindications to the use of each specific drug or other prophylactic measure, and dosage schedule of the drug used, if any. 3. Nine hundred and thirty-nine patients (53% men) were studied. The most common risk factors for venous thromboembolism were: age > or = 40 years (802; 85%), major surgery (298; 32%), immobilization > or = 6 days (285; 30%), obesity (241; 26%), and cancer (202; 22%). 4. Prophylactic measures were used in 320 patients (34%). Of these, 297 (93%) received heparin, mainly as low molecular weight heparins (248, 78%); physical measures were rarely used. 5. Five hundred and eighty-three patients (62%) fulfilled criteria for moderate or high risk of venous thromboembolism; only 275 (47%) of them received any form of prophylaxis.(ABSTRACT TRUNCATED AT 250 WORDS)     

Diagnostic value of telescoping plugged catheters in mechanically ventilated patients with bacterial pneumonia using the Metras catheter

A new guiding technique, Metras catheter (MC), for blindly introducing a telescoping plugged catheter (TPC) was applied to 25 mechanically ventilated patients with suspected bacterial pneumonia (BPN). Results obtained with TPC-MC were compared with those obtained with TPC using a conventional fiberoptic bronchoscope (FB) in random order. The diagnosis of BPN was definitely confirmed in 18 patients. In 7 patients, all TPC samples (MC and FB) were sterile, and a diagnosis other than BPN was proved. In the former group, colony-forming units equal to or greater than 10(3)/ml of one or more microorganisms were obtained in 61% of TPC-MC and in 66% of TPC-FB samples. These percentages increased to 64 and 71%, respectively, when 4 patients with previous antibiotic treatment were excluded from the study group. Agreement was observed between microorganisms cultured from both TPC samples in 11 of 18 patients with proved BPN (61%). Complete disparity was seen only in 2 patients (11%). Two patients developed a self-limiting hemoptysis after the TPC procedure (MC and FB, respectively). We conclude that TPC-MC is both a sensitive and specific technique for the diagnosis of BPN in mechanically ventilated patients. Because the diagnostic value of TPC-MC is similar to that of TPC-FB, we propose that the MC be used in patients receiving mechanical ventilation when the FB is not available. The simplicity and lower cost of this new system are important advantages to be considered over the fiberoptic bronchoscope.     

Clinical behavior of prostatic specific antigen and prostatic acid phosphatase: a comparative study

We assayed prostatic specific antigen and prostatic acid phosphatase serum levels in 1,383 patients using a double antibody radioimmunoassay (RIA) 125I. Establishing the upper normal limit in 10 ng/ml for prostatic specific antigen and 2.5 ng/ml for prostatic acid phosphatase, the false positive results were only 1.9 and 5.1% in men with nonprostatic benign or malignant pathology and 0 and 2.2% in women, respectively. We detected false positive levels in 3.5 and 4.7% of the patients with noncomplicated benign prostatic hypertrophy, 64.8 and 19.2% in complicated benign prostatic hypertrophy, 24 and 16% in acute prostatitis and 3.3% in chronic prostatitis for both tumoral markers. The sensibility in patients with prostate cancer was 87.2 and 64.1%, respectively, and there was better correlation with prostatic specific antigen than prostatic acid phosphatase levels on tumoral spread and histologic grading. Finally, the clinical efficacy was higher with prostatic specific antigen and it did not increase with the quantification of both tumoral markers.     

Acute Effects Evaluation of HgCl2 on Epidermis of Trichomycterus brasiliensis (Siluroidei; Trichomycteridae)

The effects of HgCl₂ on the epidermis of Trichomycterus brasiliensis were studied by histological, histochemical, and ultrastructural methods. First, the normal organization of the tissue was described in order to study the HgCl₂ effects on the skin structure. The epithelial cells presented a typical structural organization found in many fishes. Basically five types of cells could be detailed: goblet cells, club cells, germinative stratum cells, intermediate layer cells, and epithelial cells in the superficial layer. The goblet cells in the superficial layer present evidence of secretory activity by positive histochemical reactions. In cells exposed to HgCl₂, different morphological alterations were observed in the epithelium structure, such as an increase in the lymphocyte number, hypertrophied epithelial cells at the surface, modified taste buds, obstruction of the goblet cells pore, and high cellular proliferation. Moreover, the chemical nature of the goblet cells was not modified by the presence of the HgCl₂ dissolved in water. All animals died within 24 hr after the contamination with inorganic mercury at concentrations of 0.2 and 0.1 mg HgCl₂/liter.     

Effect of diazepam on successive negative contrast in one-way avoidance learning.

The effect of administration of diazepam on successive negative contrast in one-way avoidance learning was examined in rats. Contrast was induced by shifting rats from a large reward, 30 s spent in the safe compartment, to a small reward, 1 s spent in the safe compartment. IP administration of 2 mg/kg diazepam eliminated this negative contrast. Moreover, this effect is dose dependent, with doses of 2 and 2.5 mg/kg, but not 0.5 mg/kg, effective in reliably reducing contrast. These results suggest the existence of similar or common underlying mechanisms in both aversive and appetitive contrast effects; they are discussed in light of the current theories of frustrative nonreward and as a mean of studying the behavioral and biological mechanisms of anxiety.