Difference spectrophotometric assay of nitrazepam in tablet formulations

A difference spectrophotometric procedure is described for the assay of nitrazepam in tablet formulations. The method is based on the measurement of absorbance at 282 nm of a solution of the tablet extract in 0.1 M hydrochloric acid (pH 1) relative to that of an equimolar solution in 0.1 M sodium hydroxide (pH 13). The method is precise and selective for nitrazepam in the presence of the tablet excipients and 2-amino-5-nitrobenzophenone, the principal hydrolysis product of nitrazepam. The absence of a constant isosbestic point in the difference spectrum of nitrazepam during hydrolysis in alkaline solution indicates the presence of a previously unrecognized intermediate hydrolysis product.     

Mouse chromosome 9 quantitative trait loci for soft tissue regeneration: Congenic analysis and fine mapping

Development of gene therapies for wound healing will depend on the identification of the genes involved in wound healing and tissue regeneration. Previous quantitative trait loci (QTL) studies in mice using the ear punch model have shown that major QTL exist on chromosome (Chr) 9 for soft tissue regeneration. In this study, we have developed a congenic line that contains the Chr 9 QTL chromosomal region from super healer MRL/MpJ in the genomic background of poor-healing SJL/J. The phenotypic effect of this QTL was confirmed in male mice, where the congenic line has shown significant healing improvement over SJL. Fine mapping of the Chr 9 QTL region with 23 markers at an average distance of 4.2 Mb using a total of 1,564 MRL/MpJ x SJL/J F(2) mice revealed the presence of at least three QTL peaks, implying that three separate loci may contribute to the phenotypic effect of this QTL. Based on the 2-LOD intervals, the total QTL region was confined to a combined length of no more than 28.2 Mb. Application of a Bayesian shrinkage estimation indicated that a major locus was located in a region of just 1.3 Mb.     

Safety and immunogenicity of oral tetravalent human-rhesus reassortant rotavirus vaccine in neonates.

We conducted a prospective randomized double blind study to determine: (1) the safety and immunogenicity of live oral tetravalent human-rhesus rotavirus reassortant vaccine in neonates; and (2) whether a second dose at the age of 6 to 8 weeks enhances the immunogenicity. Two hundred forty healthy neonates were enrolled and received vaccine (183) or placebo (57) on the second day of life. At the age of 6 to 8 weeks 133 received placebo and 88 received a second dose of vaccine. Medical events were noted within 10 days from vaccine administration in 6 of 183 (3.3%) vaccine recipients vs. 0 of 57 placebo recipients (P = 0.34) after the first dose and in 8 of 88 (9%) vs. 4 of 133 (3%) after the second dose (P = 0.069); none was severe and all were of short duration. Seroresponse of any type (detectable IgA or 4-fold increase of titer to rhesus rotavirus was 9% for the placebo, vs. 52 and 46% for those who received one and two doses of vaccine, respectively. However, neutralizing antibodies against human serotypes 1, 2 and 3 were not raised successfully in vaccinated infants when compared with placebo recipients. The same pattern was found when geometric mean titers were compared. Vaccine take was better when cord blood titers were low. At the age of 1 year the vaccinees had more often high titers for antirhesus rotavirus antibodies (> 640) than the placebo recipients (49% vs. 0%; P < 0.001). NO difference was found between the groups in neutralizing antibodies to human serotypes 1, 2 and 3 rotavirus.(ABSTRACT TRUNCATED AT 250 WORDS)     

Naltrexone Blocks Acquisition of Voluntary Ethanol Intake in Rats

The effects of naltrexone (NTX) on the acquisition of ethanol drinking was assessed in rats. NTX (0, 2.5, 5.0, or 10.0 mg/kg) was administered to rats presented with an ascending series of ethanol concentrations (2%, 4%, 6%, and 8% v/v) and water. The 2.5 and 10 mg/kg doses of NTX attenuated the acquisition of voluntary drinking of 8% ethanol, but the 5.0 mg/kg dose of NTX had no effect on ethanol intake. The acquisition paradigm was repeated in experiment 2 with naïve animals that received 0, 5.0, or 7.5 mg/kg of NTX. Neither dose of NTX affected ethanol intake, preference for alcohol, or water intake. Total fluid intake was suppressed in the NTX groups, but only on the second presentations of the 2% and 6% concentrations of ethanol. We suggest that the 2.5 and 10 mg/kg doses of NTX may have attenuated the acquisition of ethanol drinking by at least two different behavioral mechanisms.     

Comparison of intracerebral inoculation and osmotic blood-brain barrier disruption for delivery of adenovirus, herpesvirus, and iron oxide particles to normal rat brain.

Delivery of adenovirus, herpes simplex virus (HSV), and paramagnetic monocrystalline iron oxide nanoparticles (MION) to rat brain (n = 64) was assessed after intracerebral inoculation or osmotic disruption of the blood-brain barrier (BBB). After intracerebral inoculation, the area of distribution was 7.93 +/- 0.43 mm2 (n = 9) for MION and 9.17 +/- 1.27 mm2 (n = 9) for replication-defective adenovirus. The replication-compromised HSV RH105 spread to 14.00 +/- 0.87 mm2 (n = 8), but also had a large necrotic center (3.54 +/- 0.47 mm2). No infection was detected when virus was administered intra-arterially without hyperosmotic mannitol. After osmotic BBB disruption, delivery of the viruses and MIONs was detected throughout the disrupted cerebral cortex. Positive staining was found in 4 to 845 cells/100 microns thick coronal brain section (n = 7) after adenovirus administration, and in 13 to 197 cells/section (n = 8) after HSV administration. Cells of glial morphology were more frequently stained after administration of adenovirus, whereas neuronal cells were preferentially stained after delivery of both HSV vectors and MION. In a preliminary test of vector delivery in the feline, MION was detected throughout the white matter tracts after inoculation into normal cat brain. Thus MION may be a tool for use in vivo, to monitor the delivery of virus to the central nervous system. Additionally, BBB disruption may be an effective method to globally deliver recombinant viruses to the CNS.     

The epidemiology of severe injuries to children in northern Manhattan: methods and incidence rates

The epidemiology of injury incidence in inner-city children has not previously been described. This study presents the methods used and the incidence rates found for severe injury (causing hospitalisation or death) in a population of 89,000 children under age 17 years in northern Manhattan, a largely poor area of New York City. The average annual incidence rate (measured from 1983 to 1987) for severe injuries to children under 17 was 846/100,000 a year. The vast majority (79%) were classified as unintentional. Nine per cent were due to assault, 3% were self-inflicted and in an additional 9% the intention was unclear. Classified by cause, the highest incidence (per 100,000/year) was found for falls (218), vehicle-related (141, primarily pedestrian), ingestion (119) and burns (110). Guns caused 3% of the injuries (27). The death rate from injury was 18.7/100,000, 36% of which was due to homicide. In an additional 28%, intentional injury was suspected. The suicide rate was 0.4/100,000. The leading causes of injury death included guns and burns (both 2.7/100,000). Compared with childhood injury rates in predominantly rural and suburban populations, the rates reported here for northern Manhattan are higher for overall injury incidence (fatal and non-fatal) and for homicide, but lower for injury mortality not due to homicide.     

Nocturnal growth hormone secretion in schizophrenic patients and healthy subjects.

Plasma growth hormone concentrations were measured at hourly intervals between 10 p.m. and 8 a.m. the next morning in 15 drug-free chronic schizophrenic male inpatients and 14 healthy males. Growth hormone secretion was significantly lower in the patients as compared with the controls. Growth hormone release peaked around 1 a.m. in the controls, but a growth hormone peak was absent in the patient group. Increased dopamine activity, increased serotonin activity, or both could explain the absence of a nocturnal growth hormone surge in the schizophrenic patients.