Protease nexin 1 in the murine kidney: glomerular localization and up-regulation in glomerulopathies

Protease nexin 1 (PN-1), a potent serpin-class antiprotease, is thought to be synthesized in the murine kidney. However, neither the cellular localization of PN-1 synthesis nor its role has yet been defined. To address these questions, we determined by in situ hybridizations RNase protection assay and immunoblotting, the sites of PN-1 mRNA accumulation in normal mouse kidneys and the modulation of PN-1 expression in several pathological conditions. In normal kidneys, PN-1 mRNA was detected primarily in glomeruli, most likely in mesangial cells. The glomerular expression of PN-1 was substantially enhanced not only in lupus-like glomerulonephritis (induced by IgG3 monoclonal rheumatoid factors or occurring spontaneously in lupus-prone mice), but also in mild glomerular lesions associated with intracapillary thrombi induced by IgG3 anti-trinitrophenyl monoclonal antibodies. In contrast, no modulation of PN-1 mRNA levels was observed during the course of lipopolysaccharide-induced acute tubular necrosis. A constitutive PN-1 gene expression and its up-regulation during glomerular injury suggest a possible role for PN-1 in glomerular biology. In view of its high inhibitory activity towards thrombin, mesangial PN-1 may be involved in the control of glomerular coagulation following initial glomerular injuries.     

Temporal correlation between neuronal tail ganglion activity and locomotion in the leech, Hirudo medicinalis

A field study of work and sleep patterns among commercial merchant marine personnel is reported. Data collected over a 10-30-d period from 141 subjects aboard eight ships included information concerning work-rest schedules, sleep timing, alertness on the job and critical fatigue. The data indicate that watchstanders on the 4-on, 8-off schedule show considerable disruption in their sleep. The average sleep duration for all mariners is 6.6 h; watchstanders obtain their sleep in fragmented periods that are frequently less than 5 h in duration. Analysis of critical fatigue shows an incidence of 1-24% across personnel and measures. Of particular concern are the watchstanders on the 04.00-08.00 schedule, who sleep less than 4 h per 24-h period 22% of the time. Potential countermeasures, including changes in scheduling and staffing are proposed.     

High-performance liquid chromatography separation and quantitation of methylprednisolone from rat brain

A sensitive, reliable method for the extraction, separation, and quantitation of methylprednisolone from rat brain is reported. The method can accurately quantitate methylprednisolone levels between 9.8 and 2500 ng/injection using a two-step HPLC separation and monitoring absorbance at 254 nm. A 90% extraction recovery of methylprednisolone (interday variation of 9.0% and an intraday variation of 0.0 to 7.7%) from rat cortex was obtained with a double extraction method using low toxicity solvents. These solvents are known to quantitatively extract the neutral lipids and phospholipids from brain. Combined with the ability to separate the neutral lipid and methylprednisolone fractions for further separation, and the ability to separate all phospholipid classes in the first run, this method offers great utility combined with the reliable, high extraction recovery and sensitive quantitation of methylprednisolone.     

Putrescine administration reverses cadmium-associated inhibition of liver regeneration

The liver is of central importance in the metabolism of essential and toxic metals such as cadmium. Cadmium pretreatment suppressed the liver regenerative response to partial hepatectomy, due to the inhibition of the enzymatic activity of thymidine kinase. Exogenous putrescine administration has been reported to stimulate liver regeneration in animal models of acute liver failure. The purpose of this study was to document whether the administration of this polyamine enhances the impaired regenerative capacity of hepatocytes in cadmium-pretreated partially hepatectomized rats. The intraperitoneal administration of putrescine (1 or 10 mg/kg body weight), at the time of surgery and at 4 and 8 hr postoperatively partly restored the suppressed hepatocyte deoxyribonucleic acid (DNA) biosynthesis and thymidine kinase activity in cadmium-pretreated partially hepatectomized rats. Mitotic activity and the percentage of hepatocytes positive for proliferating cell nuclear antigen nuclei were in accordance with the liver proliferative status. Our results showed that exogenous putrescine administration is able to improve diminished liver regeneration after partial hepatectomy in this animal model of acute hepatic injury.     

Frequency of schistosomiasis mansoni, of its clinicopathological forms and of the ectopic locations of the parasite in autopsies in Belo Horizonte, Brazil

The frequency of schistosomiasis mansoni, of its clinicopathological forms, and of the distribution of Schistosoma mansoni eggs in ectopic locations in each clinicopathological form were studied in 1863 complete consecutive autopsies performed in Belo Horizonte, Brazil, in the period from 1971 to 1990. Three hundred and thirteen cases of S. mansoni infection (16.8%) were found. The intestinal form was the most frequent (67.4%), followed by the hepatosplenic form without pulmonary hypertension (24.9%). The intestinal form showed a smaller number of ectopic sites and a lower percentage of involvement of these sites compared to the more severe forms, particularly the hepatosplenic form with pulmonary hypertension. The distribution of the frequency of schistosomiasis mansoni cases, of the clinicopathological forms of the disease, and of the ectopic sites of S. mansoni eggs over the decades considered showed a marked reduction in all of these parameters, particularly in the more severe forms. These findings can be explained only by earlier diagnosis of the disease and the greater efficacy of the specific chemotherapy used today, preventing progression to the more severe forms of the parasitosis.