Lorazepam-valproate interaction: studies in normal subjects and isolated perfused rat liver

Valproate (VPA) has been shown to interact with all the major antiepileptic drugs (AEDs) through two mechanisms of action: displacement from albumin binding sites and inhibition of drug metabolism. More recently, evidence showed that VPA inhibits the elimination of drugs metabolized by glucuronide conjugation. Lorazepam (LZP), which is primarily eliminated by conjugation with glucuronic acid, is administered concurrently with VPA both in treatment of epilepsy and in patients treated with VPA for psychiatric disorders. Therefore, a significant drug interaction is likely. We investigated such interaction both in in vitro isolated perfused rat liver (IPRL) and in normal subjects. LZP [2 mg, intravenous (i.v.) bolus] was administered to 8 normal volunteers before and after chronic dosing with VPA. In 6 of 8 subjects, VPA significantly decreased LZP plasma clearance by an average of 40% (p < 0.05) and increased LZP concentrations by decreasing formation clearance of the LZP glucuronide. In the IPRL studies, VPA also significantly decreased formation of LZP glucuronide (from 0.72 +/- 0.14 to 0.22 +/- 0.15 ml/h/kg, p < 0.05), indicating that IPRL is a useful tool for evaluation of the effect of VPA on drugs eliminated by glucuronide conjugation.     

The effect of aluminium coating on elemental standards in X-ray microanalysis

The standardisation of frozen hydrated bulk biological specimens using gelatin standards is described. The relationship between corrected elemental X-ray counts and ionic concentration was found to be linear, and minimum detectable limits for each element are stated. Variations in uncorrected standard curves were found to be due to changes in aluminium coating thickness. There was an inverse relationship between coating thickness and elemental X-ray counts. The factors causing this are discussed. To avoid errors arising from inconsistent aluminium thickness, experimental material should only be compared with standards of similar aluminium net counts. This can be achieved most easily by mounting and analysing specimen and standard together.     

Fetus-in-fetu with malignant recurrence

Fetus-in-fetu is an unusual condition in which a vertebrate fetus is enclosed within the abdomen of another fetus. These occurrences are usually benign. This report describes an instance of malignant recurrence after resection of a fetus-in-fetu.     

Wooden sticks as the source of a pseudoepidemic of infection with Rhizopus microsporus var. rhizopodiformis among immunocompromised patients

Wooden sticks used to suspend feces obtained for surveillance cultures were found to be the source of Rhizopus microsporus var. rhizopodiformis causing a pseudo-outbreak among 17 immunocompromised patients cared for in three different wards. Nonsterile wooden products should therefore not be used for collecting, handling, and processing specimens for microbiological examination.     

Taste receptor response to sodium chloride and natriuresis in the workers and employees of an industrial enterprise

Studied in the course of one-stage epidemiologic survey of 1191 individuals were the threshold of gustatory sensitivity to table salt and nycterine natriuresis, relation of these indices to dietary habits, some risk factors for cardiovascular disorders and clinical parameters. Differing relations were established between gustatory sensitivity to table salt and natriuresis and age and gender of the examinees, the level of blood pressure, aggravated heredity in respect of arterial hypertension, smoking and alcohol abuse, this enabling one to embark upon a differential approach to dietetic correction of salt consumption.     

Evidence for an RNA binding region in the Escherichia coli processing endoribonuclease RNase E

The processing endoribonuclease RNase E (Rne), which is encoded by the rne gene, is involved in the maturation process of messenger RNAs and a ribosomal RNA. A number of deletions were constructed in order to assess functional domains of the rne gene product. The expression of the deletion constructs using a T7 promoter/RNA polymerase overproduction system led to the synthesis of truncated Rne polypeptides. The smallest gene fragment in this collection that was able to complement a temperature sensitive rnets mutation and to restore the processing of 9 S RNA was a 2.3-kilobase pair fragment with a 1.9-kilobase pair N-terminal coding sequence that mediated synthesis of a 70.8-kDa polypeptide. Antibodies raised against a truncated 110-kDa polypeptide cross-reacted with the intact rne gene product and with all of the shorter C-terminal truncated polypeptides, indicating that the N-terminal part of the molecule contained strong antigenic determinants. Furthermore, by analyzing the Rne protein and the truncated polypeptides for their ability to bind substrate RNAs, we were able to demonstrate that the central part of the Rne molecule encodes an RNA binding region. Binding to substrate RNAs correlated with the endonucleolytic activity. RNAs that are not substrates for RNase E did not bind to the protein. The two mutated Rne polypeptides expressed from the cloned gene containing either the rne-3071 or ams1 mutation also had the ability to bind 9 S RNA, while their enzymatic function was completely abolished. The data presented here suggest that the endonucleolytic activity is encoded by the N-terminal part of the Rne protein molecule and that the central part of it possesses RNA binding activity.     

Growth and characterization of GaAs films deposited on Ge/Si composite substrates by metalorganic chemical vapor deposition

We report the results of studies which have been made on heteroepitaxial layers of GaAs and AlGaAs grown by metalorganic chemical vapor deposition on composite substrates that consist of four different types of heteroepitaxial layered structures of Ge and Ge-Si grown by molecular beam epitaxy on (100)-oriented Si substrates. It is found that of the four structures studied, the preferred composite substrate is a single layer of Ge ∼1 μm thick grown directly on a Si buffer layer. The double-crystal X-ray rocking curves of 2 μm thick GaAs films grown on such substrates have FWHM values as small as 168 arc sec. Transmission electron micrographs of these Ge/Si composite substrates has shown that the number of dislocations in the Ge heteroepitaxial layer can be greatly reduced by an anneal at about 750° C for 30 min which is simultaneously carried out during the growth of the GaAs layer. The quality of the GaAs layers grown on these composite substrates can be greatly improved by the use of a five-period GaAs-GaAsP strained-layer superlattice (SLS). Using the results of these studies, low-threshold optically pumped AlGaAs-GaAs DH laser structures have been grown by MOCVD on MBE Ge/Si composite substrates.