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.     

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.     

Potential-dependent calcium channels of neurons of mollusks of various ages]

It is shown that with the holding potentials (Eh) ranging from -50 to -30 mV the amplitudes of the inward Ca current of identified neurons are significantly higher in old (20-24 months) Lymnaea stagnalis molluscs than in adult ones.     

Comparison of primary orchiectomy with oestrogen therapy in advanced prostatic cancer. A 2-year follow-up report of a national, prospective prostatic cancer study

Two hundred and seventy-seven patients with advanced prostatic cancer were treated by either orchiectomy or oestrogen. During the 2-year follow-up period, the response to treatment was considered more favourable in the oestrogen group, and this response was particularly emphasised in patients with poorly differentiated tumour and metastases at the time of diagnosis. Further evaluations included the cardiovascular side effects of oestrogen therapy.     

The effects of severe visual challenges on steering performance in visually healthy young drivers.

PURPOSE: Two experiments explored the extent to which induced blur, reduced luminance, and reduced visual fields affect drivers' steering performance in a driving simulator. METHODS: In experiment 1, ten young participants (M = 21.2 years) drove at approximately 89 km/h (55 mph) along a curvy roadway while being exposed to blur (0 to + 10 D), luminance (0.003 to 16.7 cd/m), and visual field (1.7 and 150 degrees) manipulations. In experiment 2, a new group of ten young participants (M = 18.5 years) drove while exposed to seven visual field sizes (1.7 to 150 degrees). RESULTS: Steering was sensitive to a reduced field size but not to the blur and luminance challenges. Acuity, on the other hand, was sensitive to the blur and luminance challenges but not to reduced field size. DISCUSSION: In healthy young drivers, steering performance is remarkably robust to severe blur and to extremely low luminances. These results support a key element of the selective degradation hypothesis advanced by Leibowitz and colleagues--that steering abilities are preserved at night even when the ability to recognize objects and hazards is not. Additional research should address the other element of this hypothesis--that drivers fail to appreciate the extent to which their visual abilities are degraded at night.