Diffuse prolonged depression of cerebral oxidative metabolism following concussive brain injury in the rat: a cytochrome oxidase histochemistry study.

Utilizing a lateral fluid percussion injury as a model of cerebral concussion, rats were studied histochemically measuring the degree of cytochrome oxidase activity present within different structures at different times following injury. After concussion, the cerebral cortex ipsilateral to the site of injury exhibited a diffuse decrease in its level of chromotome oxidase (CO) activity beginning at as soon as one day and lasting for up to 10 days after the insult. The ipsilateral dorsal hippocampus also exhibited an injury-induced decrease in CO activity, however, it was not as severe as in the cortex. These results indicate that oxidative metabolism is depressed primarily within the cerebral cortex and hippocampus for several days following a cerebral concussion. We propose that this period of metabolic depression may delineate a period of time during which the injured brain is unable to function normally and thus would be vulnerable to a second insult.     

Clinical analysis of ureteral tumours with or without renal pelvic neoplasms

Twelve patients with ureteral tumours with or without ipsilateral renal pelvic neoplasms were retrospectively analysed. Haematuria was the most common symptom. Location of all tumours was preoperatively detected by conventional diagnostic methods, such as intravenous or retrograde pyelography, washing cytology of the upper urinary tract, computed tomography, echogram and abdominal aortography. Cumulative proportion survivals of 1, 3 and 5 years were 81.9%, 68.2% and 45.5%, respectively. Patients with high Karnovsky rating survived longer (p<0.05) than those with low rating. Patients with low-stage tumours (T₁, T₂) showed longer survival rate (p<0.001) than those with high-stage tumours (T₃, T₄). Vascular invasion of tumour cells was present in removed specimens in 4 out of 7 patients who died or are alive with cancer, but none in those who survived without disease. Good therapeutic response could not be achieved unless surgery was performed.     

Central diabetes insipidus complicated with upbeat nystagmus and cerebellar ataxia]

A 34-year-old male presented with central diabetes insipidus accompanied by upbeat nystagmus and cerebellar ataxia. The patient without family history of above began to walk at the age of 2 years. Polyposia and polyuria were noted at the age of about 4 years. Dysbasia developed at the age of about 7 years. From the age of 30, lalopathy appeared together with various clinical symptoms including cataracts, disturbed intelligence, upbeat nystagmus, abnormal ocular movements, ataxic speech, cerebellar ataxia and reduction of the muscle tone of the limbs, and hypotonic polyuria. Abnormal laboratory findings included square wave jerks, upbeat nystagmus, and "bow tie" nystagmus by EOG, atrophy of the cerebellum and the brainstem by CT, a slight prolongation of the P300 latency, and a central diabetes insipidus pattern by water deprivation test and Carter-Robbins tests. There have been occasional reports of diabetes insipidus complicated by cerebellar ataxia, but in no earlier reports has diabetes insipidus been concurrent with abnormal ocular movements such as upbeat nystagmus. A degenerative disease primarily of the posterior lobe of the hypophysis, hypothalamus, cerebellum, and brainstem was suspected.     

Intrahepatic Delivery of Glutathione by Conjugation to Dextran

Glutathione was covalently attached to dextran (T-40) by the CNBr activation method. The compound obtained was a water-soluble powder containing 10 (w/w%) glutathione, which was gradually released from the conjugate in aqueous media. Mice depleted of glutathione by treatment with buthionine sulfoximine, a potent inhibitor of -glutamylcysteine synthetase, exhibited a significant increase in hepatic glutathione level after intravenous injection of the conjugate. In mice given a lethal dose of acetaminophen, the survival rate increased progressively with coadministration of the conjugate, whereas little improvement was found when free glutathione was given. The conjugate maintained the serum transaminase activities at lower level after acetaminophen administration. These findings suggest that the dextran conjugate of glutathione is transported into hepatic cells and is intracellulary hydrolyzed to free form, which protects mice from hepatotoxicity due to acetaminophen.     

Pharmacokinetic and clinical studies on cefmenoxime in neonates and infants

Pharmacokinetic and clinical studies on cefmenoxime (CMX) in neonates and infants were conducted. 1. CMX 20 mg/kg was administered by intravenous bolus injection to 6 neonates (with ages 2 to 20 days) and 5 infants (with ages 36 to 107 days) and its serum concentration and urinary excretion rates were determined. In the neonates, serum concentrations of CMX after intravenous administration reached peak levels of 48.2 to 90.7 micrograms/ml (mean 70.4 +/- 14.3 micrograms/ml) in 1/4 hour, then declined with half-lives of 1.27 to 5.19 hours (mean 2.28 +/- 1.56 hours), and were 3.6 to 16.9 micrograms/ml (mean 8.3 +/- 6.0 micrograms/ml) at 6 hours. In the infants, serum concentrations at 1/4 hour were 67.5 to 111.0 micrograms/ml (mean 95.5 +/- 18.0 micrograms/ml); half-lives were 0.64 to 0.94 hour (mean 0.81 +/- 0.13 hour); and the serum concentrations at 6 hours were 0.2 to 1.1 micrograms/ml (mean 0.7 +/- 0.4 micrograms/ml). Mean peak serum concentrations in the neonates tended to be lower than those in the infants, but higher than those in children. Regarding the age differences of serum concentrations due to age in the neonates, their peak levels tended to be lower in younger ones. Half-lives were shorter in older subjects and, in early infancy, approached values observed in children. Urinary recovery rates in the first 6 hours after intravenous administration ranged from 43.6 to 87.5% (mean 61.6 +/- 14.6%) in the neonates and from 52.1 to 90.8% (mean 78.0 +/- 15.1%) in the infants. Thus, recovery rates were high even in younger subjects and tended to be higher in older subjects. 2. CMX was administered to 27 neonates and 4 infants to investigate its clinical effect, bacteriological effect and side effects. Clinical efficacy ratings of the drug in 19 neonate cases that could be evaluated (1 with purulent meningitis, 2 with suspected septicemia, 1 with acute bronchitis, 12 with acute pneumonia, 1 with impetigo, 1 with periumbilical abscess and 1 with acute pyelonephritis) were "excellent" in 14 cases, "good" in 4, and "poor" in 1. The efficacy rate covering "excellent" and "good" was 94.7%. In 4 infants (2 with acute pneumonia, 1 with periumbilical abscess and 1 with acute pyelonephritis), "excellent" was obtained in 2 cases and "good" in 2 cases. Thus, all the cases showed "good" or higher ratings. Bacteriologically, 1 strain of Staphylococcus aureus and 3 strains of Escherichia coli in neonates were eradicated while, in infants, 1 strain of S. aureus persisted but 1 of E. coli was eradicated.(ABSTRACT TRUNCATED AT 400 WORDS)     

Microarray analysis on Phase II drug metabolizing enzymes expression in pregnant rats after treatment with pregnenolone-16alpha-carbonitrile or phenobarbital

We previously reported the expression profiles of 9 cytochrome P450 isozymes (CYPs) proteins and those of 40 CYPs genes in pregnant rat's liver, placenta and fetal liver after treatment with pregnenolone-16alpha-carbonitrile (PCN) or phenobarbital (PB). This study was carried out focusing on the gene expression profiles of Phase II drug metabolizing enzymes, Glutathione S-transferase isozymes (GSTs) and UDP-glycosyltransferase isozymes (UDPGTs). Fischer 344 (F344) pregnant rats were daily treated intraperitoneally with 50 mg/kg of PCN or 80 mg/kg of PB from 13 to 16 days of gestation (DG). They were sacrificed on 17 DG, and microarray analysis using Affymetrix Rat Expression Array 230 A was performed. Among 16 GSTs genes examined in this study, 7 genes were significantly induced in dam's liver and 3 genes in fetal liver, respectively, in the PCN-group, while 8 genes were significantly induced in dam's liver and 1 gene in fetal liver, respectively, in the PB-group. On the other hand, among 11 UDPGTs genes examined, 5 genes were significantly induced in dam's liver and 3 genes in fetal liver, respectively, in the PCN-group, while 5 genes were significantly induced in dam's liver and 1 gene in fetal liver, respectively, in the PB-group. There were no significant changes in the placenta of all groups. This is the first report of the gene expression profiles of Phase II drug metabolizing enzymes in pregnant rat and fetal livers and placenta after treatment with typical inducers of drug metabolizing enzymes.     

Potentiation of allergic bronchoconstriction by repeated exposure to formaldehyde in guinea-pigs in vivo

BACKGROUND: Indoor formaldehyde (FA) might worsen allergies and be an underlying factor for the increasing incidence and severity of asthma; the exact mechanism, however, remains unclear. OBJECTIVE: The present study examined the effects of repeated exposure to FA on methacholine- and antigen-induced bronchoconstriction in guinea-pigs in vivo. METHODS: First, non-sensitized guinea-pigs were transnasally treated with 0.1 or 1.0% FA or saline three times a week for 6 weeks, and increasing concentrations of methacholine (50, 100, and 200 microg/mL) were inhaled at 5-min intervals. Second, guinea-pigs pre-treated with transnasal administration of FA or saline using the same protocol were passively sensitized with anti-ovalbumin (OA) serum 7 days before antigen challenge. Third, guinea-pigs were actively sensitized with OA and pre-treated with transnasal administration of FA or saline using the same protocol. The lateral pressure of the tracheal tube (Pao) was measured under anesthesia and artificial ventilation. RESULTS: The antigen-induced increase in Pao in actively sensitized guinea-pigs was significantly potentiated by FA exposure in a dose-dependent manner. The dose-response curve of the methacholine-induced increase in Pao in non-sensitized guinea-pigs or of the antigen-induced increase in Pao in passively sensitized guinea-pigs was not altered by FA exposure. Transnasal administration of FA significantly increased the serum anti-OA homocytotropic antibody titre (IgG) as measured by the passive cutaneous anaphylaxis reaction in actively sensitized guinea-pigs. CONCLUSION: The results suggest that repeated exposure to FA worsens allergic bronchoconstriction through enhancing antigen sensitization.     

WIDESPREAD ECZEMA VACCINATUM ACQUIRED BY CONTACTS A Report of an Autopsy Case

A4-moth-old male infant predisposed to allergic dermatitis acquired widespread eczema vaccinatum by contacts with a recently vaccinated sibling. He died of acute purulent peritonitis following a perforation of multiple duodenal ulcers. Fluorescence immunocytochemical and electron microscopic studies on the skin lesions revealed the presence of viral antigens and numerous virus particles compatible morphologically with those of the mature form from the same batch of smallpox vaccine given to the sibling. A large number of virus particles in the developmental form were also predominantly scattered in the cytoplasm of cells at the stratum malpighii of the epidermis as well as in neutrophils and macrophages in the skin lesions. The virus isolation from the skin lesions was done by using the HeLa cells and the human embryonic lung fibroblasts. No abnormal laboratory data were noted in immunoglobulins. On the basis of atrophy of the thymus and other lymphatic tissues and an appearance of large pyroninophilic cells in association with blastoid transformation, the authors discussed a possible participation of the disturbance of cellular immunity secondary to the virus infection in the development of the disease. ACTA PATH. JAP. 29 : 435–455, 1979.     

Functional linkage of the cardiac ATP-sensitive K+ channel to the actin cytoskeleton

The role of the cytoskeleton in the rundown and reactivation of adenosine triphosphate (ATP) sensitive K⁺ channels (KATP channels) was examined by perturbing selectively the intracellular surface of inside-out membrane patches excised from guinea-pig ventricular myocytes. Actin filament-depolymerizing agents (cytochalasins and desoxyribonuclease I) accelerated channel rundown, while actin filament stabilizer (phalloidin) or phosphatidylinositol biphosphate (PIP₂; inhibitor of F-actin-severing proteins) inhibited spontaneous and/or Ca²⁺-induced rundown. When rundown was induced by cytochalasin D or by long exposure to high Ca²⁺, channel activity could not be restored by exposure to MgATP, but application of F-actin with MgATP could reinstitute channel activity. The processes of rundown and reactivation of cardiac K_ATP channels may thus be influenced by the assembly and disassembly of the actin cytoskeletal network, which provides a novel regulatory mechanism of this channel.