Morphological and biochemical studies of a mouse mutant (fro/fro) with bone fragility.

The mutation fragilitas ossium (fro) was discovered in a random-bred stock of mice during an experiment aimed at detecting recessive lethal mutations after treatment of the postmeiotic germ cells of male mice with tris (1-aziridinyl)phosphine sulphide. The affected mice were moderately runted and had deformities in all four limbs. The radiological and histological findings indicate that the mutant is similar to human osteogenesis imperfecta. The ash content of long bones was lower in the mutant. A defect of type I collagen could not be detected. The electrophoretic patterns of alpha bands of type I and V collagen and CB derived peptides of type I collagen from bone and skin showed no abnormalities. The total collagen synthesis and secretion in cultures of dermal fibroblasts, as well as the gel electrophoresis of procollagen and collagen chains synthesized, and of their CB peptides, were the same as those found in the controls. The percentage of type I and type V collagen synthesized was similar; that of type III was lower in the mutants. Bone osteonectin was found to be decreased by 30% and bone sialoprotein by 5%. The mRNA level for osteonectin was decreased in the fibroblasts of the mutant by about 50%. Whether the defective expression of the osteonectin in fro/fro mice is due to a mutation in the gene itself or its regulatory site(s), or is secondary to other factors remains to be established. The fro/fro mouse may represent a model for some forms of human bone fragility without collagen abnormalities.     

Prevalence of hepatitis B virus (HBV) markers and human immunodeficiency virus (HIV) in employees of a blood transfusion centre

Blood bank staff, 8 out of 25 (32%) have been exposed to hepatitis B virus (HBV) and the prevalence of HBV markers in blood bank employees handling high risk subjects show hepatitis B surface antigen (n = 1), hepatitis B surface antibody (n = 7), hepatitis B core antibody (n = 6) and combined hepatitis B surface antibody and hepatitis B core antibody (n = 6) seropositivity but all are negative to human immunodeficiency virus (HIV). Serum alanine aminotransferase was raised in the employees than normal subjects and it is suggestive of sub-clinical hepatitis. The employees of blood bank should be trained for proper handling of test materials and must be periodically monitored for HBV and HIV. Immunisation for HBV is mandatory only for the employees of transfusion centre which handles high risk subjects.     

Activation of glucocorticoid receptors and the effect of naloxone during hemorrhagic hypotension.

Evidence indicates that endogenous opioid peptides and glucocorticoids participate in the control of cardiovascular regulation during hemorrhagic shock. In the present study, we investigated a possible interaction between brain opioid peptides and adrenal corticosteroids regarding the control of arterial pressure during hemorrhage. The bleeding volumes required to lower arterial pressure to 80, 60 and 40 mmHg were studied in anesthetized sham-operated (SHAM) and adrenalectomized (ADX) rats. I.c.v. administration of 10 micrograms of naloxone resulted in a significant increase in the bleeding volume required to lower arterial pressure from 60 to 40 mmHg in SHAM animals, whereas no effect of naloxone was observed in ADX animals. Replacement therapy with a 100% corticosterone pellet (100 mg, s.c.), but not with a 12.5% corticosterone pellet (12.5 mg corticosterone and 87.5 mg cholesterol, s.c.), resulted in an effect of naloxone on the bleeding volume in ADX animals. The effect of replacement therapy could be inhibited by i.c.v. pretreatment with the synthetic glucocorticoid receptor antagonist, RU38486 (100 ng). These data suggest that (1) opioid mechanisms are involved in the regulation of blood pressure during hemorrhage, and (2) occupancy of glucocorticoid receptors is required for naloxone to exert its hemodynamic effect during hemorrhagic hypotension in ADX rats.     

Endourological experience with cystine calculi and a treatment algorithm

Between May 1984 and January 1988, 18 patients (31 pyeloureteral units) with documented symptomatic cystine stones were treated. Stone size ranged from 5 to 56 mm. in largest diameter, with an average of 21 mm. All pyeloureteral units were treated initially by endourological methods, including ureteroscopy in 10, percutaneous ultrasonic lithotripsy in 9, extracorporeal shock wave lithotripsy (ESWL) in 10 and chemolysis in 2. Of the patients 10 required a combination of these technologies and 2 required an open operation. Of the 31 units 23 were free of stones when the patient was discharged from the hospital. Of 8 patients with retained stones only 3 had fragments greater than 3 mm. in diameter. Based on this experience an algorithm was developed for the urological management of cystine stones. Ureteral calculi may be removed by ureteroscopic techniques or manipulated into the renal pelvis and managed as renal stones. Cystine renal calculi of less than 1.5 cm. may be treated with ESWL monotherapy. Stones of 1.5 to 3 cm. may be treated with ESWL and dissolution, or percutaneous ultrasonic lithotripsy plus dissolution. Staghorn calculi may be treated by percutaneous ultrasonic lithotripsy plus ESWL and/or dissolution for retained fragments.     

Circulating immune complexes in pre-eclampsia.

Serum samples from 20 non-pregnant women, 30 women with normal pregnancy and 50 women with pregnancy associated with pre-eclampsia were tested for circulating immune complexes using the polyethyleneglycol precipitation method. A highly significant positive correlation was found between circulating immune complexes and severe pre-eclampsia (BP greater than 140/90 mm Hg, albuminuria greater than 0.25 g/l). In contrast to this the difference in immune complex levels between non-pregnant subject, normal pregnancy cases and patients with mild pre-eclampsia was not statistically significant. A significant positive correlation was found between the level of circulating immune complexes and the severity of albuminuria. These findings suggest that circulating immune complexes, though not seeming to play an aetiological role in pre-eclampsia may very well be involved in its pathogenesis.     

Dermal absorption of niclosamide in rats and minipigs

The dermal absorption of niclosamide, a drug shown to prevent Schistosomiasis by blocking the dermal penetration of cercariae, has been examined in Sinclair minipigs and rats. Radioactivity in the urine and feces collected daily for 7 days after application of 14C-niclosamide accounted for less than 2 per cent and 10 per cent of the labelled compound applied to pig and rat skin, respectively. Approximately 20 per cent of the radioactivity from the dose solution was recovered on the skin excised from the area of application in both minipigs and rats. No radioactivity was detected in organs removed from the pig 7 days after application of radiolabelled drug while less than 6 per cent of the dose could be accounted for in the rat organs/carcass. Radioactivity in swine blood, removed 0.5, 1, 2, 4 and at 24 h intervals after dosing, was at or below three times background in all of the samples. Total recovery of the applied radioactivity was 78 per cent in pigs and 57 per cent in rats. These studies indicate that niclosamide is very poorly absorbed after dermal application. The results are consistent with earlier comparative studies showing that dermal penetration of xenobiotics in rats is generally higher than in swine.     

Detection of optic pathway misrouting in the human albino neonate.

The diagnosis of albinism is indicated by the presence of visual pathway misrouting in which temporal retinal fibers erroneously decussate at the optic chiasm disrupting the normal topographical distribution of retinal geniculate-cortical projections. Detection of misrouted fibers is effected by non-invasive electrophysiological assessment of the topographical representation of the visual evoked potential (VEP) following full field monocular stimulation. By combining appropriate state defined neonatal recording procedures with the albino VEP test paradigm, the presence of aberrant optic pathway projections was detected in a five-day-old full-term infant. The electrophysiological signature pathognomonic to albinism was observed within a long (300 ms) latency window of an otherwise normal neonatal luminance flash response. The results of this study indicate that the VEP misrouting test can be extended to reliable albino diagnosis within the neonatal period.     

Dibutyryl-cAMP induces SNAP-25 translocation into the neurites in PC12.

SNAP-25 immunoreactivity was translocated into the endings of the processes induced in PC12 cells by dibutyryl-cAMP-treatment. Conversely, the protein was not present in the endings of the processes seen after NGF-treatment unless dibutyryl-cAMP was used simultaneously. This redistribution of SNAP-25 immunoreactivity appeared to be dependent upon new protein synthesis. Finally, dibutyryl-cAMP was capable of inducing SNAP-25 expression.