Necrotizing myopathy with paracrystalline inclusion bodies in hypervitaminosis E

Summary A necrotizing, nonprogressive myopathy with unusual paracrystalline inclusion bodies is described in a patient who underwent long-term treatment with megadoses of vitamin E. The clinical course and morphological findings suggest a close relationship to the administration of the vitamin. The theoretical pathogenesis of muscle damage and the possible origin of paracrystalline inclusion bodies are discussed.Presented at the Jahrestagung der österreichischen Gesellschaft für Neuropathologie in Bad Ischl, on April 17, 1986This study was supported by a grant from the Deutsche Forschungsgemeinschaft (Ba 916)     

Is cholic acid responsible for embryo-toxicity of the post-receptive uterine environment?

HPLC analysis of the embryo-toxic fraction of human uterinefluid, collected between the 22nd and 25th days of the menstrualcycle, revealed the presence of cholic acid at high concentrations.It is suggested that cholic acid could be responsible for theembryo-toxicity of the uterine environment, which follows thereceptive period for implantation.     

Laser induced autofluorescence studies of animal skin used in modeling of human cutaneous tissue spectroscopic measurements

BACKGROUND/PURPOSE: Laser-induced autofluorescence spectroscopy provides excellent possibilities for medical diagnostics of different tissue pathologies including cancer. However, to create the whole picture of pathological changes, investigators collect spectral information from patients in vivo or they study different tumor models to obtain objective information for fluorescent properties of every kind of healthy and diseased tissue. Therefore, it is very important to find the most appropriate, and close to the human skin, animal samples from the fluorescence point of view, which will allow the extrapolation of the animal data to human spectroscopic diagnostics. METHODS: In the present work, we examined the autofluorescence properties of different animal skin tissues, which are considered as the most common skin models. A nitrogen laser was used as an excitation source. Samples of healthy mouse, chicken and pig skin in vivo and/or ex vivo were studied and were compared with results obtained from investigations of healthy human skin in vivo. RESULTS AND CONCLUSION: Specific features of the recorded spectra are discussed and the possible origin of the obtained fluorescence signals is proposed. Quantitative evaluation of data extrapolation for each skin type is also depicted.     

雷公藤内酯对人胃癌细胞株FGC_(85)杀伤作用的光镜和电镜观察

本文应用核苷掺入技术及电镜观察首次证实雷公藤内酯对人胃癌细胞株 FGC_(85)的杀伤作用。用药早期,细胞数,分裂指数及 DNA,RNA 合成无明显变化,但出现核仁脱粒及核仁破碎等变化;晚期,电镜观察发现细胞以凋落方式死亡,药物主要作用于间期细胞,其杀伤机构的始动环节可能与核酸代谢障碍无关。     

Codeine-induced histamine release in intact human skin monitored by skin microdialysis technique: comparison ofintradermal injections with an atraumatic intraprobe drug delivery system

Background The skin microdiallysis technique makes it possible to measure histamine release in intact human skin in vivo directly. In this study we have used the microdialysis technique to characterize histamine release by codeine after intracutaneous injectioin and following skin challenge by a novel atraumatic delivery technique. Objective The purpose of the study was to compare histamine release in human skin by codeine. delivered by an intraprobe drug delivery system (IPD) and intracutaneous injections (ICT), with respect to dose-response relations, kinetics of histamine appearance and decay, corelations between histamine release and skin respones, and reproducibility. Methods Hollow dialysis fibres were inserted intradermally in 12 healthy subjects. Twelve fibres were inserted in each subjects, six fibres in each arm. Each fibre was perfused at a rate of 3 μL/min, and samples were collected in 2 min fractions. By the IPD technique, codeine was administrered to the skin by adding codeine to the perfusion medium. Sequential IPD challenges were performed in one arm. and ICTs were done on the other arm. Results Sixfold serial dilutions of codeine (0.01-3 mg/mL) caused a significant doserelated histamine release by ICT and IPD. Peak histamine release was found within the first 4 min after skin challenge by ICT and IPD, followed by a fast decline with a dialysate histamine half life of approximately 2-3 min. Peak hisamine release was linearly correlates with cumulative release of the 20 min sampling period, and histamine release correlated with weal soze. The coefficient of variation on peak histamine releae was 18.9% and 4.8% for codeine ICT and IPD, respectively. Conclusioin We have described in detail codeine-induced histamine release in intact human skin in vivo by the microdialysis technique. It was possible to administer codeine atraumaticallyl to the skin by intraprobe delivery. The skin microdialysis codeine atraumaticallly to the skin by intraprobe delivery. The skin microdialysis technique opens up possibilities for measurement of infllammatory mediators release in normal and diseases skin, and it will be possible to deliver immunopharmacologically active drugsto the skin by intraprobe delivery.     

Case Report: Gianotti-Crosti Syndrome Associated with Human Herpesvirus-6 Infection

We report a case of Gianotti-Crosti syndrome associated with human herpesvirus-6 (HHV-6) infection. An eight-month-old girl developed monomorphous papules on her cheeks, buttocks, and extremities after the subsidence of exanthema subitum. Viral antibody analysis confirmed primary HHV-6 infection. HHV-6 may be added to the list of causative agents of Gianotti-Crosti syndrome.     

HIV neuropathogenesis and therapeutic strategies

Abstract Human immunodeficiency virus (HIV)-l neuropathogenesis can be divided into three important components: (i) virus entry into the nervous system; (ii) the role of viral proteins and/or cellular products in neural tissue damage; and (iii) the mechanisms of neuronal injury/death. Both blood derived macrophages or trafficking HIV-1 infected T-lymphocytes have been implicated in viral entry to the central nervous system (CNS). The major cell type harboring productive HIV-1 infection in the nervous system is the perivascular macrophage/ microglia. The HIV-1 infection of brain astrocytes, restricted to the expression of regulatory gene products, may cause astrocyte dysfunction and contribute to neuronal injury or to disruption of the blood-brain barrier (BBB). Studies of cerebrospinal fluid and postmortem tissues reveal chronic inflammation/immune activation in the nervous system during the later stages of HIV-1 infection associated with disruption of BBB integrity. Blood-brain barrier damage may underlie the white matter pallor described in HIV-1 infection and could result in further entry into the CNS of toxic viral or cellular products, or additional HIV-1 infected cells. The HIV infected and activated macrophages/microglia produce excessive amounts of pro-inflammatory cytokines, including tumor necrosis factor alpha, and platelet activating factor. These products are directly toxic to human neurons in vitro. The HIV-1 envelope glycoprotein, gp 120 may stimulate the release of toxic factors from brain macrophages. Blocking N-methyl-D-aspartate (NMDA; or AMPA) glutamate receptors can antagonize candidate toxins of both viral and cellular origin. It has been postulated that (weak) excitotoxicity leads to oxidative stress in neurons and ultimately to apoptosis. Neuronal apoptosis occurs in the brains of both children and adults with HIV-1 infection. This understanding of HIV neuropathogenesis implies that therapeutic strategies should include: (i) anti-retroviral medications to decrease systemic and CNS virus load, and possibly to prevent perinatal transmission of HIV; (ii) anti-inflammatory compounds to decrease the chronic immune activation in microglia and allow the restoration of BBB integrity; and (iii) neuroprotective compounds to reduce neuronal injury and apoptotic death.     

Benign intracranial hypertension and recombinant growth hormone therapy in Australia and New Zealand

Benign intracranial hypertension (BIH) is reported in three children from Australia and one from New Zealand, who were being treated with recombinant human growth hormone (rhGH). Three males and one female, aged between 10.5 and 14.2 y, developed intracranial hypertension within 2 weeks to 3 months of starting treatment. A national database, OZGROW, has been prospectively collecting data on all 3332 children treated with rhGH in Australia and New Zealand from January 1986 to 1996. The incidence of BIH in children treated with growth hormone (GH) is small, 1.2 per 1000 cases overall, but appears to be greater with biochemical GHD (<10IUml ^-1), i.e. 6.5/1000 (3 in 465 cases), relative risk 18.4, 95% confidence interval 1.9-176.1, than in all other children on the database. The incidence in patients with Turner's syndrome was 2.3/1000 (1 in 428 cases). No cases in patients with partial GHD (10–20 IUml ^-1) or chronic renal failure were identified. Possible causative mechanisms are discussed. The authors'practice is now to start GH replacement at less than the usual recommended dose of 14IUm-² week^-1 in those children considered to be at high risk of developing BIH. Ophthalmological evaluation is recommended for children before and during the first few months following commencement of rhGH therapy and is mandatory in the event of peripheral or facial oedema, persistent headaches, vomiting or visual symptoms. The absence of papilledema does not exclude the diagnosis.     

Absorption of Propranolol in Humans Following Oral,Jejunal, and Heal Administration

Pharmaceutical Research -     

Dietary behaviour of an adolescent French male population

The dietary history method was used to determine the total energy and macronutrient intake, the distribution of daily energy from the different meals and the energy contribution of various food groups, in a population of 299 boys, aged between 10 and 15 years. The effects of age, the social status of the father (SPS), the ponderal index, the importance of breakfast or lunch, and the level of energy intake on dietary indicators, were studied. In our population, energy intake increased with increasing age but the energy contribution of macronutrients did not vary. The diet of boys whose fathers were in the upper SPS classes differed from the diet of those boys whose fathers were manual workers: for example they consumed less energy and pastries, but more animal protein (in percentage of energy intake), more dairy products, and more fruit. The ponderal index was negatively related to energy intake but positively related to protein intake, especially from meat and meat products. The energy intake from protein, animal protein and the energy contribution of dairy products, meat and meat products, fish and vegetables was lower among large eaters than among small eaters. The energy contribution of pastries, sugar and sweets was higher among large eaters.
Similarily, the energy intake from morning and evening snacks was also higher among large eaters. It should be noted that boys who had a substantial breakfast took in less energy from all other meals (including snacks and main meals). Such informaton is necessary in order to develop an effective health programme.