Pharmacokinetics of nicardipine enantiomers in healthy young volunteers

Objectives: The present study was conducted to compare pharmacokinetic behaviors of nicardipine enantiomers given in different doses with different formulations of racemic nicardipine in healthy volunteers. Methods: One or two 20-mg racemic nicardipine tablets, and a 40-mg sustained-release capsule of nicardipine were administered to eight healthy volunteers in a cross-over fashion and pharmacokinetic parameters were evaluated. Enantiomer concentrations were determined by GC-MS combined with chiral stationary phase HPLC. Results and conclusions: Serum concentration of (+)-nicardipine was approximately 2–3 times higher than that of (−)-nicardipine in 20- and 40-mg doses of conventional formulations and a non-linear increase in bioavailability with dose was demonstrated. The value for AUC of (+)-nicardipine was approximately 2.3–2.8 times greater than that of the (−)-nicardipine (P < 0.05) when 20 and 40 mg racemic nicardipine were administered in a conventional preparation. Relative bioavailability of the sustained-release preparation vs the conventional preparation was 28% and 44% for (+)- and (−)-nicardipine, respectively, for the 40-mg dose. Received: 23 September 1996 / Accepted in revised form: 23 February 1997     

The long-term growth rate of residual acoustic neurinomas

Summary The growth rate of 19 residual acoustic neurinomas was examined in a long-term follow-up study (median, 10 years; range, 5 to 17 years) following intracapsular removal. Of these, 10 (53%) had regrowth, three (16%) showed regression, and six (32%) were unchanged. The 10 acoustic neurinomas showing regrowth were divided into two categories, either solid or cystic, according to computed tomographic findings. Five acoustic neurinomas with cyst formation showed rapid regrowth, with the tumour doubling time ranging from 0.15 to 5.0 years (median, 4.5 years), and required re-operation. Five solid tumours showed slow regrowth, with the tumour doubling time ranging from 9 to 34 years (median, 15 years). Although cyst formation is a major factor in rapid regrowth, residual acoustic neurinomas without cyst formation have a slower growth potential. In this study, 74% of the residual acoustic neurinomas have never required re-operation. It is advisable to choose intracapsular removal if there is major risk of neurological deficits.     

Secretion of amyloid precursor protein and laminin by cultured astrocytes is influenced by culture conditions

Although normally quiescent, astrocytes in the adult brain respond to various types of brain injury by rapidly dividing, swelling, extending cellular processes, and expressing increased amounts of glial fibrillary acidic protein (GFAP). These phenomena are collectively referred to as “astrogliosis.” Similarly, astroglia in primary culture stop dividing when they attain confluency, yet, as seen in situ, they retain their proliferative capacity for extended periods and resume rapid division when subcultured. To examine the impact of glial division on secretion of neuritepromoting factors, conditioned medium (CM) was removed from subconfluent, newly confluent, and longterm confluent (“aged”) neonatal rat astrocyte cultures, and from aged confluent cultures that had been repassaged, “Lesioned” (scraping with a rubber policeman), or triturated 3 days before harvest. Secretion of neurite-promoting factor(s) by glial cells into these CM was then assayed by treating neuroblastoma cultures with these various CM and quantitating neurite elaboration. Extensive neurite sprouting was elicited by CM from cultures just reaching confluency and from repassaged, lesioned, or triturated cultures. CM from aged confluent cultures did not induce sprouting. These results indicate that secretion of neurite-promoting factors(s) is regulated by glial division, and suggest that gliosis in situ may contribute to neurite sprouting by similar mechanisms. Immunoblot analysis demonstrated the presence in CM of varying amounts of laminin and amyloid precursor protein (APP), including isoforms containing the Kunitz-type protease inhibitor domain. CM from subconfluent cultures contained trace amounts of these protiens, but CM from cultures just reaching confluency contained significant amounts. Although CM from aged cultures contained barely detectable levels of either protein, trituration or repassage of aged cultures dramatically increased secretion of these proteins. APP-and laminin-enriched CM fractions promoted neuritogenesis to a similar level as respective unfractionated CM; anti-APP and antilaminin antisera blocked this effect. Purified human brain APP promoted neuritogenesis when added to non-conditioned medium and aged CM. Increased secretion of APP and laminin therefore mediates at least a portion of CM-induced neuronal sprouting; these proteins may perform analogous functions during astrogliosis in situ. © 1994 Wiley-Liss, Inc.     

Soluble interleukin-6 receptor is released from receptor-bearing cell lines in vitro.

Soluble interleukin-6 receptor (sIL-6R) was found to be spontaneously released from human myeloma cell line U266 cells into culture supernatant, and was quantitatively measured with a fluorescence sandwich enzyme-linked immunosorbent assay employing antibodies specific to IL-6R. The supernatant IL-6R was generated only from IL-6R-positive cell lines; myeloma cell lines RPMI8226 and PRMI1788, and myelomonocytic cell lines U937, THP-1, and HL-60. In contrast, it was not released from the IL-6R-negative cells; T cell line Molt-4 and Burkitt lymphoma cell line Raji. SDS-PAGE analysis of the soluble IL-6R from U266 cells suggested a molecular weight of approximately 50-55 kDa, 25-30 kDa smaller than the mature cell surface receptor. These results suggest that the generation of soluble IL-6R may be a maker of myeloma cells and myelomonocytic cells.     

Detection of human immunodeficiency virus, hepatitis B virus, and hepatitis C virus in donor eyes using polymerase chain reaction.

Detection of human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV) in donor eyes was performed. DNAs were extracted from the uvea, and they were amplified using the polymerase chain reaction (PCR). Amplified viral DNAs were detected with liquid hybridisation and chemiluminescent assay in which no radioactive materials were used. This method was shown to have a sensitivity limit of fewer than 10 copies of HIV, making it much more sensitive than the current techniques employed in eye banks. The method was applied to 120 donor eyes, including four from donors seropositive for HBV. The HBV gene was detected in one case in which the donor's blood had not been tested for HBV. HIV and HCV genes were not detected in any of the samples. The assay could be an effective screening test for the detection of these viruses in eye bank eyes.     

Studies on the hepatotoxicity induced by bis (tributyltin) oxide

The toxic effects of bis (tributyltin) oxide (TBTO) on the rat liver were studied with an electron microscope and the accumulation sites of tin were determined with an X-ray microanalyzer. The activities of serum enzymes and the concentration of serum bilirubin were also analyzed. Male Wistar rats received an intramuscular injection of 0.5 ml/kg of TBTO. Marked swelling of the mitochondria appeared in the hepatocytes 4 h after injection of TBTO. Cytoplasmic vacuoles, which contained degenerated mitochondria, gradually increased in number in these hepatocytes. This in turn may have caused a decrease in the volume of hepatic cell cords and an enlargement of sinusoids in the entire hepatic lobule. However, fine structures of intrahepatic bile ducts were not altered. By X-ray microanalysis, tin peaks were preferentially obtained from swollen mitochondria of the hepatocytes. By polarographic analysis of the respiratory responses of mitochondria, it was demonstrated that rates of state 4 respiration and respiratory control ratio were significantly disturbed in TBTO-treated rats in comparison with those of controls. The activities of AST (aspartate aminotransferase) and ALT (alanine aminotransferase) were significantly increased after TBTO treatment, but those of ALP (alkaline phosphatase), LAP (leucine aminopeptidase) and total bilirubin were not changed. These results indicated that parenterally administered TBTO accumulated in the liver cell mitochondria and disturbed oxidative phosphorylation. Mitochondrial dysfunction might induce severe damage of the hepatocytes. Four days after injection of TBTO, hepatic structures and chemical indices were almost restored by the regeneration of hepatocytes.     

Topical applications of trichloroacetic acid as therapy for nasal allergy

A group of 22 patients (27 nostrils) with nasal allergies was treated with 80 w/v trichloroacetic acid applied to the inferior turbinates. Patients were then evaluated prospectively based on both subjective responses and clinical examinations. Allergic symptoms were reduced significantly, especially those involving nasal obstruction and watery rhinorrhea. Nasal airflow resistance also improved after treatment (P<0.001). Nasal provocation testing revealed a signfiicant decrease in post-treatment responses (P<0.001). No severe side effects were noted after treatment. Findings demonstrated that local application of trichloroacetic acid is a safe, effective and simple treatment for outpatinets with symptomatic nasal allergies.     

Diffusely calcified renal cell carcinoma: CT features.

Calcifications of renal masses are common. They are usually dense, partial, small, punctate, and linear opacities. Diffuse calcification is an extremely rare feature of renal masses. Generally, calcified renal cell carcinomas are hypovascular, with calcifications in the interstitium, and they also contain fibrotic capsules, necrotic areas, or hyalinization. We recently observed a renal neoplasm with diffuse calcification on CT and intermediate vascularity on angiography, which was diagnosed histologically as renal cell carcinoma, clear cell type. Interestingly, there were numerous calcific deposits within the tumor cells.     

A Novel Method to Evaluate Thromboresistance of Drip Chambers with Filter Used in Extracorporeal Blood Circuits for Hemodialysis

Abstract: We have developed a novel method to simultaneously evaluate thromboresistance of two different types of drip chambers with a filter used in extracorporeal blood circuits for hemodialysis using canine arteriovenous shunt models. Bilateral bypasses between the femoral artery and vein on both sides of the animal were formed with 2 test circuits consisting of polyvinyl chloride tubing and two types of drip chambers with filters. Blood flow was derived into the drip chambers with a filter and returned to the femoral vein without using peristaltic pumps and systemic anticoagulants. By monitoring the quantitative changes of the blood flow rate through each drip chamber with a filter and measuring the time elapsed before the blood flow through its was completely obstructed by clots, thromboresistance of the drip chambers was evaluated under the same blood conditions. The drip chamber with a filter that had a small effective filter area, a big pore size, and slitlike pores showed better thromboresistance. This novel method proved useful in evaluating the thromboresistance of differently designed drip chambers with a filter.