Wirkungen von Cyclandelat auf das ZNS — Eine doppelblinde,placebo-kontrollierte Studie an gesunden Probanden

Summary The effect of cyclandelate (Natil^®) on the CNS was tested in a double-blind, placebocontrolled pilot study on 48 healthy males using a single oral dosage of 1200 mg. The EEG was evaluated quantitatively by spectral analysis before and one hour as well as two and a half hours after drug or placebo administration under resting conditions and while performing a test of mental arithmetics. Under resting conditions the power in the alpha₂ frequency band of the signals from the frontal and central recordings was increased in the cyclandelate group in comparison to the placebo group. This effect was still observed two and a half hours after drug intake.Under the condition of mental arithmetics no drug related effect was observed in the EEG. The cyclandelate induced increase of spectral power in the alpha₂ frequency band under resting conditions demonstrates a general effect of cyclandelate on the CNS. The results are discussed with respect to the known age related decrease of spectral power in the alpha frequency band. The established effect of cyclandelate in young healthy subjects calls for a study with chronic treatment in elderly subjects or patients with cognitive deficits.

     

Increased aneuploidy in spermatozoa from testicular tumour patients after chemotherapy with cisplatin, etoposide and bleomycin

Testicular cancer is the most common neoplasia occurring in the young male population. The PEB (cisplatin, etoposide and bleomycin) adjuvant chemotherapy usually proposed after orchidectomy in non seminomatous tumours, and in metastatic seminomas, has improved the long-term survival of these patients. Following an azoospermic period, sperm cell recovery is generally observed after treatment delivery, but little is known about the genetic consequences on these new spermatozoa. To estimate the chromosomal consequences of this chemotherapy on sperm cells during the period of recovery of spermatogenesis, sperm cell aneuploidy was studied in testicular cancer patients, at 6-18 months after PEB adjuvant chemotherapy delivery, using fluorescence in-situ hybridization (FISH) of chromosomes 7, 16, 18, X and Y with specific DNA probes. A significant increase in the frequency of diploidy and disomy for chromosomes 16, 18 and XY was observed in treated patients compared with a healthy control group. Spermatozoa aneuploidy occurring during the spermatogenesis recovery period might be a possible side effect of the PEB regimen. Thus, practitioners should be advised to provide counselling about the need for an appropriate duration of contraception. Moreover, genetic counselling should be offered in cases of pregnancy occurring soon after the end of chemotherapy.     

Magnetophosphenes: a quantitative analysis of thresholds

Low-frequency and transient magnetic fields of moderate flux densities are known to generate visual phenomena, so-called magnetophosphenes. In the present study, time-variable very low frequency (10–50 Hz) electromagnetic fields of moderate flux density (0–40 mT) were used to induce magnetophosphenes. The threshold values for these phosphenes were determined as a function of the frequency of the magnetic field both in normal subjects and colour defective ones. Maximum sensitivity occurred at a frequency of approximately 20–30 Hz, and with broad-spectrum light the threshold flux density was 10–12 mT. The threshola values were found to be dependent upon the intensity and the spectral distribution of the background light. Sensitivity decreased during dark adaptation. In certain respects deutans differed from subjects with normal colour vision. Possible mechanisms for generation of magnetophosphenes are discussed. The present magnetic threshold curves show a close resemblance to corresponding curves obtained by electric stimulation at various frequencies provided the electric thresholds are divided by the a.c. frequency. These problems are under current investigation in our laboratory. This is in full agreement with the assumption that the fluctuating magnetic field affects retinal neurons by inducing currents which polarise synaptic terminals.     

Behavioral development in mice: Effects of maternal environment and the albino locus

We examined the interaction of the albino locus with the maternal environment on the behavioral development of two coisogenic strains of mice. Subjects of the pigmented C57BL/6 strain (=B6^+/+) and of the albino C57BL/6^c2J strain (=B6^c/c) were either fostered by a mother of their own strain or cross-fostered at birth to an F₁ hybrid dam. They were compared for the amount and daily distribution of activity displayed during 48 h in a seminatural device at weaning and when 75 days old. Food hoarding in the nest and food consumption at the food-search place were also recorded in adult subjects. When animals were fostered by a mother of their own strain, albino mice were more active and less nocturnal than pigmented mice at both ages. They hoarded less food in the nest and ate more at the food-search place. Most of these differences disappeared when both strains were fostered by an F₁ dam. The amount of activity displayed during 48 h increased between 21 and 75 days of age. This increase was affected by cross-fostering to an F₁ dam in B6^c/c mice only. The developmental pattern of daily distribution of activity was changed by F₁ dams in B6^+/+ mice only. Whereas these influences of F₁ dams produced subjects resembling the mother's phenotypic score, maternal effects on hoarding behavior in B6^c/c mice produced subjects which did not resemble their foster mother. The results are discussed in terms of different possible ways of hereditary transmission of behavior and some methodological consequences are emphasized.     

Hormonal contraception without estrogens

The long-term clinical effects of ethinyl estradiol and the impact on environmental safety of the alkylated estrogen components used in combined contraceptive pills remain the subject of debate. The development of improved methods for the use of progestogen-only contraception would represent a viable and desirable option. Several progestogen compounds are not alkylated, and these can be delivered through a variety of routes. Some of the progestogen-only methods are well established in clinical use. Estimates for both perfect and typical effectiveness are less than one pregnancy per 100 woman-years with oral, injectable, implantable and intrauterine methods. In practice, with the oral progestogen-only method, perfect and typical effectiveness range from three to five pregnancies per 100 woman-years. The main side effect with all progestogen-only methods is unpredictable vaginal bleeding during the first months of use, and this may lead to discontinuation. Nevertheless, continuation of use is more frequent if patients are well informed of this side effect before treatment begins. No cardiovascular- and cancer-related side effects have been proven.     

溴氰菊酯对白纹伊蚊C6／36细胞株的杀伤作用及对其形态影响的研究

本文采用ＭＴＴ微量酶反应比色法，研究了溴氰菊酯对白纹伊蚊Ｃ６／３６细胞的杀伤作用、形态影响以及受损细胞的恢复。结果发现用溴氰菊酯处理２４ｈ后，对Ｃ６／３６细胞的半数毒性浓度（ＩＣ５０）为７４８８μｇ／ｍｌ，且毒性作用强度随着药物浓度增加而增强。溴氰菊酯浓度在２０μｇ／ｍｌ以上时可以诱发Ｃ６／３６细胞形态学改变，表现为细胞呈多形性、细胞间有间隙、胞质内充满颗粒，以后随药物浓度的升高，胞质出现空泡、染色质凝成粗大颗粒或无结构大块、大片细胞脱落、崩解、死亡。高浓度溴氰菊酯（１６０μｇ／ｍｌ）作用于Ｃ６／３６细胞，其受损细胞的恢复与作用时间有关，作用２４ｈ的细胞，在经历一段生长停滞后，可缓慢恢复，而作用４８ｈ的细胞，则不可逆转的死亡     

IL-4–BATF signaling directly modulates IL-9 producing mucosal mast cell (MMC9) function in experimental food allergy

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A double-blind, placebo-controlled study of the effects of lithium on cognition in healthy subjects: mild and selective effects on learning

Background: Several studies have shown cognitive impairment in short-term memory, long-term memory and psychomotor speed in bipolar patients taking lithium. The aim of the study was to look at the effect of lithium in normal subjects (N=30) taking lithium for 3 weeks. A comprehensive battery was used to assess attention and memory. Methods: Subjects were randomized to double-blind treatment with either lithium (N=15) or placebo (N=15) for a 3-week period. Thirteen participants in the lithium group and 15 in the placebo group completed the study. The lithium and placebo were administered twice daily in doses varying from 1050 to 1950 mg (mean=1569 mg). The initial daily dose was calculated according to the Pepin formula to achieve a blood serum lithium level of about 0.8 mmol/l. Cognitive performance (attention, memory) was assessed in each subjects during three periods, i.e. at baseline, after 3 weeks of lithium or placebo, and 2 weeks after discontinuation of study medication. Results: In short-term memory tasks, the performance of subjects in the lithium group was worst 3 weeks after lithium treatment compared to 2 weeks after discontinuation. In long-term memory, a significantly higher number of words was recalled by the placebo group but not the lithium group. Conclusions. Lithium may have an effect on learning when long-term explicit memory test are administered repeatedly. It means that the practice effect when a subject performs the same task several times is less in the lithium-treated group than in the placebo group. This practice effect is related to the learning of a task.     

Impact of anxiety,stress and depression related to COVID-19 pandemic on the course of hereditary angioedema with C1-inhibitor deficiency

Background

Hereditary angioedema (HAE) attacks can be provoked with psychological factors. The aim of this study was to assess the effects of anxiety, depression and stress related to COVID-19 pandemic on disease activity of HAE patients during the quarantine period (QP) and the return to normal period (RTNP).

Methods

This study was conducted between March 2020 and September 2020 in four allergy centres. Demographic, clinical features and mental health status were evaluated in QP (from March to the beginning of June) and RTNP (from June to the beginning of September) applied by the government. The 10-point visual analogue scale (VAS10) was used to define the severity of HAE attacks. Depression, Anxiety and Stress Scales-21 (DASS-21) and Fear of COVID-19 (FC-19) scale were performed to assess mental health status.

Results

139 HAE patients were included in the study. In QP, median attack numbers and median VAS10 scores were 5 (min-max: 0–45) and 6 (min-max: 0–10), respectively. HAE attack numbers, DASS-21 stress, anxiety, depression and total DASS-21 scores, and FC-19 scores were higher in QP than RTNP (p = 0.001, p < 0.001, p = 0.001, p < 0.001, p < 0.001, p < 0.001, respectively). However, there was no difference in attack severity scores between the two periods (p > 0.05).

Conclusions

This study revealed that the restriction measures during COVID-19 outbreak cause an increase in the number of HAE attacks in relation to anxiety, depression, stress and fear of COVID-19 pandemic. Therefore, it is important to provide psychological support to HAE patients during the pandemic.

     

Reduction of side-effects from ultrarush immunotherapy with honeybee venom by pretreatment with fexofenadine: a double-blind, placebo-controlled trial

BACKGROUND: Immunotherapy with Hymenoptera venoms is highly effective but causes allergic side-effects frequently, especially when honeybee venom is used. Therefore, our objective was to investigate the effect of pretreatment with the antihistamine fexofenadine on the incidence of allergic side-effects during ultrarush immunotherapy with bee venom. METHODS: In a double-blind, placebo-controlled trial, 57 patients with a history of systemic allergic reactions to honeybee stings and positive diagnostic tests (skin tests, serum specific IgE to honeybee venom) were investigated. Bee venom immunotherapy was started with an ultrarush protocol and patients were randomized to pretreatment with either fexofenadine 180 mg or placebo on days 1, 8, 22, and 50 of the protocol. Local and systemic allergic side-effects were registered. RESULTS: Fifty-four patients completed the study, 28 on fexofenadine and 26 on placebo pretreatment. On day 1, large local reactions were significantly reduced in both extension and duration by fexofenadine pretreatment (P<0.025). Systemic allergic side-effects on the whole were not reduced. However, the symptoms pruritus, urticaria, and angioedema occurred less frequently with fexofenadine (P<0.05). CONCLUSIONS: Pretreatment with fexofenadine during venom immunotherapy reduces local allergic reactions and generalized symptoms of the urticaria and angioedema type.