Digoxin-like factor in infants of diabetic mothers not receiving digoxin therapy

Serum digoxin-like factor was detected in infants of diabetic mothers who were insulin-dependent or diet controlled. No statistical difference was found between the serum digoxin-like factor levels of the infants of diabetic mothers and the controls.     

Stupor and affective state: alleviation of psychomotor disturbances by lorazepam and recurrence of symptoms after Ro 15-1788

In a single patient suffering from a major depressive episode with melancholia (DSM-III), both severe psychomotor symptoms, such as stupor and mutism, and mood disturbances could be abolished completely and promptly by administration of the benzodiazepine lorazepam. Remission of symptoms was entirely and immediately reversed by the benzodiazepine antagonist Ro 15-1788. These drug effects were constantly reproducible. Possible mechanisms of action and the influence of GABAergic neurotransmission on affective and psychomotor state are discussed.     

Comparison between a swim-up and a Percoll gradient technique for the separation of human spermatozoa

Two methods of separating human sperm were compared using twenty-two semen samples. The sperm were separated by a swim-up technique or by self-migration on a Percoll gradient followed by medium change. After separation, the sperm obtained were assessed for progressive motility, ATP content, energy charge index ([ATP + 0.5 ADP]/[ATP + ADP + AMP]) and morphology. In general, and especially for semen samples containing less than 20 X 10(6) sperm/ml, separation by Percoll gradient selected sperm that were superior to those separated by the swim-up technique. The relatively high energy charge index (greater than 0.8) showed that the sperm tolerated the separation conditions well. It is suggested that self-migration on a Percoll gradient should prove useful for obtaining sperm of high quality.     

Heterogeneous epithelial expression of class II (HLA-DR) determinants and secretory component related to dysplasia in ulcerative colitis

The intensity and degree of heterogeneous epithelial marker expression were evaluated immunohistochemically in 29 mucosal biopsy specimens from 7 ulcerative colitis (UC) patients with dysplasia. Biopsy specimens from UC patients with mild (n = 7) or severe (n = 6) inflammation and from histologically normal samples (n = 7) served as controls. HLA-DR showed heterogeneous epithelial expression in all lesions with high grade dysplasia and in 6 of 8 with low grade dysplasia. SC was heterogeneous stained in 17 of 21 lesions with high grade dysplasia and in all but two lesions with low grade dysplasia. In histologically normal mucosa, SC was homogeneously expressed and epithelial DR was virtually absent. In mildly inflamed UC lesions, SC exhibited patchy distribution in only one sample and DR in two, whereas both SC and DR showed a slight degree of heterogeneous expression in all lesions with severe inflammation. Moreover, the overall intensity of SC staining tended to decrease with increasing degree of inflammation, whereas the opposite was seen for DR. Decreased SC and increased DR expression thus seemed to be related to intensified inflammatory activity, whereas heterogeneous expression of these markers was significantly more related to dysplasia.     

Drug abuse in Africa

Apart from cannabis abuse in northern and southern Africa and khat chewing in north-eastern Africa, the history of drug abuse in Africa is relatively short. The abuse of drugs in Africa is nevertheless escalating rapidly from cannabis abuse to the more dangerous drugs and from limited groups of drug users to a wider range of people abusing drugs. The most common and available drug of abuse is still cannabis, which is known to be a contributing factor to the occurrence of a schizophrenic-like psychosis. The trafficking in and abuse of cocaine and heroin are the most recent developments in some African countries that had had no previous experience with these drugs. Efforts should be made to design and implement drug abuse assessment programmes to determine the real magnitude and characteristics of the problem and to monitor its trends. A lack of funds and a shortage of adequately trained personnel have made it difficult to implement drug abuse control programmes. In addition to formal drug control involving the implementation of legislation, there is an informal system of drug abuse control operating through the family, church, school, neighbourhood and work environment, as well as healthy recreational activities. It is suggested that efforts in African countries should be directed towards strengthening not only the formal drug control system but also informal control in order to compensate for the insufficient funds and the shortage of personnel trained in implementing formal drug control measures. It is very likely that the drug problems in African countries will worsen in future unless more effective measures are implemented to arrest the current situation.     

Quantitative ESI-MS analysis of antiarrhythmic drugs in blood plasma without chromatographic separation

A highly sensitive method for the quantitative determination of a potential antiarrhythmic drug (OF-7976) in the blood plasma has been developed. The method is based on the electron spray ionization/mass spectrometry (ESI-MS) technique without preliminary chromatographic separation and makes use of nibentan as the internal standard. A linear relationship between drug concentration and the peak intensity of ions of the analyzed substance (m/z = 398) and the internal standard (m/z = 382) is established. The detection limit is 3 ng/(0.5 ml plasma). The method is linear from 3 to 25 ng/(0.5 ml plasma) with a correlation coefficient of 0.98. The coefficient of variation was less than 7 %. __________ Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 41, No. 3, pp. 45–48, March, 2007.     

Cross-calibration of dual-energy X-ray densitometers for a large, multi-center genetic study of osteoporosis

Osteoporosis is a common disease with a strong genetic component characterized by reduced bone mass and an increased risk of fragility fractures. Bone mineral density (BMD) is the most important determinant of osteoporotic fracture risk, but the genes responsible for BMD regulation and fracture are incompletely defined. To enable multi-center studies to examine the genetic influences on BMD there is a requirement to standardize measurements across different manufacturers of bone densitometers, different versions of machines and different normative ranges. This paper describes a method developed to allow near-identical subjects with low age-adjusted BMD (based on Z-scores) to be recruited in 17 centers using 27 different densitometers. Cross-calibration was based on measurements using a European spine phantom circulated to all centers and measured ten times on each individual machine. From theses values an individual exponential curve, based on nominal versus observed BMD, was derived for each machine. As expected, there were large and significant variations in nominal BMD values, not only between scanners from different manufacturers but also between different versions of scanners from the same manufacturer. Hologic scanners tended to underestimate the nominal BMD, while Lunar scanners overestimated the value. Norland scanners gave mixed values over estimating BMD at the lower nominal value (0.5 g/cm²) while underestimating the value at the higher value (1.5 g/cm²). The validity of the exponential equations was tested using hip and spine measurements on 991 non-proband women from a familial osteoporosis study (FAMOS). After cross-calibration there was a considerable reduction in variation between machines. This observation, coupled with the absence of a similar reduction in variation attributable to a linear regression on age, demonstrated the validity of the cross-calibration approach. Use of the cross-calibration curves along with a standard normative range (in the case of this study, the Hologic normative range) allowed age-specific Z-scores to be used as an inclusion criterion in this genetic study, a method that will be useful for other trials where age-specific BMD inclusion criteria are required.     

Rational design of hypoallergens applied to the major cat allergen Fel d 1

BACKGROUND: Allergen-specific immunotherapy is the only treatment for allergic disease providing long-lasting symptom relief. Currently, it is mainly based on the use of crude allergen extracts. The treatment may be improved by the use of genetically engineered allergens, hypoallergens, aiming at a more effective and safer therapy. OBJECTIVE: The aim of this study was to provide a rational design of hypoallergen candidates for immunotherapy by using structural information and knowledge of B and T cell epitopes of an allergen. METHODS: The three-dimensional structure of the major cat allergen Fel d 1 was systematically altered by duplication of selected T cell epitopes and disruption of disulphide bonds. Seven Fel d 1 derivatives were generated and screened for allergenic reactivity in comparison with recombinant Fel d 1 in competition-ELISA. The allergenicity was further evaluated in basophil activation experiments and T cell reactivity was assessed in a lymphoproliferation assay. RESULTS: Three out of seven Fel d 1 derivatives, with two duplicated T cell epitopes and one or two disulphide bonds disrupted, were carefully evaluated. The three derivatives displayed a strong reduction in allergenicity with 400-900 times lower IgE-binding capacity than recombinant Fel d 1. In addition, they induced a lower degree of basophil activation and similar or stronger T cell proliferation than recombinant Fel d 1. CONCLUSION: By a rational approach, we have constructed three Fel d 1 hypoallergens with reduced IgE-binding capacities and retained T cell reactivities. This strategy may be applied to any well-characterized allergen to improve immunotherapy for allergic patients.     

Intersexualität

Zusammenfassung Intersexualität bezeichnet eine seltene Störung der somatosexuellen Differenzierung mit einer Inzidenz von etwa 2 pro 10.000 Geburten pro Jahr in Deutschland. Dahinter verbergen sich verschiedene Diagnosen einer vermehrten Virilisierung bei 46,XX-Karyotyp oder deutlich verminderter Virilisierung bei 46,XY-Karyotyp. Manchmal werden diese Störungen erst während der Pubertätsentwicklung entdeckt. Dann ist eine rasche Diagnostik zur Prognosestellung notwendig. Bei allen Jugendlichen mit Intersexualität muss das Management während der Pubertät viele Aspekte von der psychosexuellen Begleitung bis hin zur medizinischen Behandlung mit Hormonsubstitution oder Therapie und der Beratung hinsichtlich chirurgischer Maßnahmen enthalten.