Phenylethylamine-induced stereotypies in the rat: a behavioral test system for assessment of MAO-B inhibitors

Stereotyped sniffing behavior together with forepaw padding — defined as the -phenylethylamine (PEA) syndrome — is induced by MAO-B inhibitors in rats injected with 30 mg/kg IP PEA. The comparison of the abilities of the MAO-B inhibitors to induce the syndrome and to inhibit MAO-B in rat brain homogenates indicated that at least 75% of MAO-B activity in rat brain had to be inhibited to induce the PEA syndrome. A good correlation was found between the abilities of MAO-B inhibitors to induce the behavioral syndrome and to increase levels of PEA in rat brain. Specific MAO-A inhibitors potentiated the behavioral effect of the MAO-B inhibitor deprenyl, while they did not induce the syndrome themselves or only at very high doses. Inhibitors of the reuptake of 5-HT or noradrenaline were inactive under the described experimental conditions. This behavioral test system seems to be useful in vivo screening test in rats for detecting compounds with strong MAO-B inhibiting activity.     

Carbon dioxide analysers: accuracy,alarm limits and effects of interfering gases

Six mainstream and twelve sidestream infrared carbon dioxide (CO₂) analysers were tested for accuracy of the CO₂ display value, alarm activation and the effects of nitrous oxide (N₂O), oxygen (O₂) and water vapour according to the ISO Draft International Standard (DIS) #9918. Mainstream analysers (M-type): Novametrix Capnogard 1265; Hewlett Packard HP M1166A (CO₂module HP M1016A); Datascope Passport; Marquette Tramscope 12; Nellcor Ultra Cap N-6000; Heilige Vicom-sm SMU 611/612 ETC. Sidestream analysers: Brüel &; Kjaer Type 1304; Datex Capnomac II; Marquette MGA-AS; Datascope Multinex; Ohmeda 4700 OxiCap (all type S1: respiratory cycles not demanded); Biochem BCI 9000; Bruker BCI 9100; Dräger Capnodig and PM 8020; Criticare Poet II; Heilige Vicom-sm SMU 611/612 A-GAS (all type S2: respiratory cycles demanded). The investigations were performed with premixed test gases (2.5, 5, 10 vol%, error ?1% rel.). Humidification (37° C) of gases were generated by a Dräger Aquapor. Respiratory cycles were simulated by manually activated valves. All monitors complied with the tolerated accuracy bias in CO₂ reading (≤ 12% or 4 mmHg of actual test gas value) for wet and dry test gases at all concentrations, except that the Marquette MGA-AS exceeded this accuracy limit with wet gases at 5 and 10 vol% CO₂. Water condensed in the metal airway adapter of the HP M1166A at 37° C gas temperature but not at 3(P C. The Servomex 2500 (nonclinical reference monitor), Passport (M-type), Multinex (S1-type) and Poet II (S2-type) showed the least bias for dry and wet gases. Nitrous oxide and O₂ had practically no effect on the Capnodig and the errors in the others were max. 3.4 mmHg, still within the tolerated bias in the DIS (same as above). The difference between the display reading at alarm activation and the set point was in all monitors (except in the Capnodig: bias 1.75 mmHg at 5 vol% CO₂) below the tolerated limit of the DIS (difference ≤ 0.2 vol%). The authors conclude that the tested monitors are safe for clinical use (except those failing the DIS limits). The accuracy of the CO₂-reading (average of mean absolute bias) is better in the M-type than in the S1- or S2- type analysers although no statistical (nor clinical) significant differences could be detected. Most manufacturers work with stricter limits than those proposed by the DIS.     

Effect of retinoids on the induction of colon cancer in F344 rats by N-methyl-N-nitrosourea or by 1,2-dimethyihydrazine

The possible modifying effect of synthetic and natural retinoidson the incidence of colon cancer in rats induced by 2 intrarectaldoses of 2.5 mg of N-methyl-N-nitrosourea (MNU) given once aweek for 2 successive weeks or a single 150 mg/kg body weightdose of 1,2-dime-thylhydrazine (DMH), s.c. was investigated.Emphasis was on the effect of the development of early tumorsas visualized by endoscopy. With the retinoids N-ethyl-retinamide,N-2-hydroxyethylretinamide, N-(4-hydro- xyphenyl)-all-trans-retinamide(RAHA), and retinyl acetate (RA) administered orally after thecarcinogens, significant differences in early developing tumorswere not found. At histopathological examination of the tumorsthe RAHA + DMH group had significantly fewer adenomas per animal.The percentage of adenoma bearing rats was significantly lowerin groups receiving RAHA + DMH or RA + DMH. However, food consumptionwas lower in rats consuming either RAHA or RA. Retinyl palmitate(RP) and RAHA was administered intrarectally to MNU-inducedrats either before or after the carcinogen. When administeredbefore MNU, RP caused a significant increase in the percentageof tumor bearing animals and the average number of tumors peranimal as visualized endos copically. At histopathological examination,all retinoid groups except RAHA given after the carcinogen,produced significantly more adenomas per animal and a significantlygreater adenoma incidence than did the control groups. Thus,in two systems, the oral administration of retinoids did notclearly inhibit the early or later stages of colon tumor development.Inirarectal infusion of two retinoids had no effect on colonicmor phology but at histopathological examination of later stagetumors there was an enhanced adenoma response.     

Atropine sulfate modulates estrogen binding by female, but not male, rat hypothalamus

Studies have shown that pharmacological manipulation of the dopamine, norepinephrine and muscarinic cholinergic neurotransmitter systems modulates the number of neural estrogen binding sites. Previously, we reported that the muscarinic agonist, bethanechol, increased estrogen receptor binding by hypothalamic cytosols from female, but not male, rats. Moreover, pretreatment with atropine prevented the bethanechol-induced effect. The experiments reported here were executed with the expectation that atropine alone would either decrease or fail to alter estrogen binding. However, the present data show that atropine increases estrogen binding by female, but not male, hypothalamic cytosols. Thus, it appears that a muscarinic antagonist and agonist can similarly affect the concentration of estrogen binding sites in female rat hypothalamus.     

Molekular zielgerichtete Tumortherapie durch Eingriffe in die zelluläre Signaltransduktion

The increasing knowledge on the molecular pathogenesis of cancer has led to the development of a wide spectrum of targeted treatment approaches. Key targets are molecules belonging to signaling pathways involved in the regulation of cell survival, proliferation, invasion and spread of malignant cells. Central regulators in the context of cell survival are molecules involved in the regulation of programmed cell death, epidermal growth factor receptor pathways and regulators of the tumor microenvironment. The inhibition of the epidermal growth factor receptor has already become an accepted approach. In contrast to that, direct interference with cell death signaling, i.e. death receptor based approaches and the inhibition of Bcl proteins, is still subject to clinical testing. Regarding the therapeutic modulation of the tumor microenvironment the primary drug targets are those molecules involved in the interaction of malignant cells with the surrounding normal stromal cells and/or with the extracellular matrix. Currently, inhibition of neo-angiogenesis and the blocking of intergrin-mediated adhesion of malignant cells to the surrounding tissue have entered clinical practice or are in advanced phases of clinical testing. The common denominator of all these approaches is to try to specifically target the tumor with no or minimal interference of normal tissue function. The side-effects of molecular targeted drugs fundamentally differ from those of the conventional oncological methods, such as radiotherapy and cytotoxic chemotherapy. However, for the majority of these targeting agents, clinical testing has unfortunately found only slight efficacy when used as a monotherapy. Thus, the combination of these substances with proven oncological procedures and the integration into highly complex multimodal protocols is urgently needed to evaluate the therapeutic surplus of the multitude of newly developed agents. The aim of the current article is to give a short overview of the current status of targeted interference with cell death signaling and neighboring fields.     

Determinants of attitude to volunteering in psychiatry: results of a public opinion survey in Switzerland

BACKGROUND: The United Nations proclaimed 2001 the "International Year of Volunteers". Little is known about factors influencing the attitude to volunteering in psychiatry. However, knowledge about these factors is important as target groups to be addressed by an awareness and promotion campaign could be identified. AIMS: To determine the influence of demographic, psychological and sociological factors on the attitude to volunteering in psychiatry. METHODS: Multiple logistic regression analysis of the results of an opinion survey conducted on a representative population sample in Switzerland (n = 1737). RESULTS: Public attitude is mostly positive. It depends, however, on the form of volunteering. Two explanatory models for volunteering in psychiatry were found: first, the "antipathetic person" having social distance to and negative stereotypes towards the mentally ill. Second, the "people with social responsibility and commitment" who have former experience in volunteering, a positive attitude to community psychiatry, interest in mass media, a social profession and perceive discrimination of mentally ill persons. Age and gender are significant predictors. CONCLUSIONS: An awareness and promotion campaign to use the vast potential of people willing to volunteer in psychiatry can be primarily focused on those with a basic interest in social issues. Volunteering must be limited in time and responsibility. Contacting people with a positive attitude by mass media is a promising way.     

Public acceptance of restrictions on mentally ill people

OBJECTIVE: To assess the influence of demographic, psychological, sociological and cultural variables on the public acceptance of restrictions on mentally ill people. METHOD: Multiple logistic regression analysis of the results of an opinion survey conducted on a representative sample in the German, French and Italian-speaking part of Switzerland. RESULTS: Public acceptance of restrictions depends on age, education and gender. The influence of demographic variables is reduced when including rigidity, anomie, social distance and contact with mentally ill people in the analysis. The cultural influence of the language region is significant. All these factors predict acceptance. Stereotypes and emotional reactions have no influence. CONCLUSION: Attitudes to mentally ill people are shaped on three distinct levels, the psychological, social and cultural, respectively. Demographic variables partly play the role of placeholders covering the underlying relationships.     

High-energy shock wave treatment of femoral head necrosis in adults

Adults with Stages I to III osteonecrosis of the femoral head present an overall therapeutic challenge. The objective of the current prospective study was to show the effectiveness of high-energy shock wave therapy in treatment of patients with Association Research Circulation Osseous Stage I to Stage III necrosis of the femoral head by assessing clinical and magnetic resonance imaging results. The current study presents the results of 22 patients with femoral head necrosis 1 year after shock wave treatment. The study population consisted of 10 women and 12 men with an average age of 54.9 years (+/- 12.3). The scores achieved on the visual pain analog scale decreased from 8.5 before treatment to 1.2 after 1 year. Simultaneously, the Harris hip score increased from 43.3 to 92 points. Magnetic resonance imaging visualization of a distinct zone of sclerosis around the necrotic area remaining after treatment with extracorporeal shock wave therapy indicated therapeutic failure. The results obtained so far with high-energy shock wave therapy in these patients suggest that this method may offer an alternative to invasive treatment modalities for femoral head necrosis. A noninvasive and moderately priced method then would be available for the treatment of femoral head necrosis in the early stages of the disease process.