Oral acute toxicity of polyenylphosphatidylcholine (PPC) in rats.

Endogen phospholipids play a major role in determining the structure and nature of cell membranes. A deficiency of phospholipids in cellular membranes makes it almost impossible for the cell membrane to perform its function as a selective barrier between what passes in and out of the cell. Polyenylphosphatidylcholine chemical structure corresponds to that of endogen phospholipids, but it possesses functional superiority because of its content of unsaturated fatty acids. Polyenylphosphatidylcholine integrates in the cell membrane and organelle systems while becoming their constitutive elements. A healthy cell membrane leads to healthy cells and then healthy tissue and then to healthy organs or body systems and finally, healthy bodies and minds. For a long time, polyenylphosphatidylcholine in combination with vitamins has been used in the treatment of numerous health problems such as liver diseases, dyslipoproteinaemias and different intoxications with consequent liver failure. The main aim of toxicology studies is evaluation of the toxic potential and risks of human exposition to the substance. According to the Organization for Economic Cooperation and Development (OECD) acute oral toxicity refers to those adverse effects occurring following oral administration of a single dose of a substance or multiple doses given within 24 hours. LD50 (median lethal dose), oral, is a statistically derived single dose of a substance that can be expected to cause death in 50 per cent of animals when administered by the oral route. Our acute toxicity study was performed on albino Wistar rats. Animals were randomised in three experimental and one control group, each of 5 males and 5 females. Study was based on the administration of a single oral dose of the test substance (polyenylphosphatidylcholine) to each experimental animal. There were three dose-levels of the test substance: 300, 500 and 1000 mg/kg. Test substance administration day was the first day of the observation period that lasted 14 days. Control animals were given milk vehicle. At the end of the study, no statistically significant differences between experimental and control animals were observed concerning the recorded parameters: body weight, respiratory rate, tremor, faeces and phonation quality, indicating the absence of the test substance acute toxicity.

Suicidal thoughts related to psychoactive substance abuse among adolescents.

The enquiry of suicide is of particular importance. According to WHO statistics suicide in people aged from 15 to 24 years has shown the greatest increase of relative mortality. In the group of suicidal adolescents, depression, behavioural disorders, abuse of different substances and personality deviations are frequent factors in presence. The aim of our investigation was to determine the correlation between psychoactive substance abuse and the occurrence of suicidal thoughts in adolescents. The specific "Q 2000" test was used to question 600 adolescents, from Tuzla and Sarajevo Cantons, with the same gender and age distribution and rural-urban ambient. The more prevailing suicidal idea occurrence was observed in cannabis abusers (50.0%) and alcohol abusers (36.6%) in comparison to non-abusers regardless gender and/or living ambient (settlement types) (19.5% and 17.6% per each, x2 = 17.184 p = 0.00001). The augmentation in number of suicidal ideas was not observed in tobacco smokers.

Simultaneous abuse of different psychoactive substances among adolescents.

Although the drug abuse has been evidenced in every age of the human life, it seems that its occurrence is crucial during adolescence period with its well-known consequences on the further personality development. Adolescents like to experiment with risky lifestyles without adequate knowledge about their possible harmful effects and consequences. International experiences have represented that early onset of the risky behaviour predisposes young persons for serious problems in social, psychological and physical future lives. It has been noticed that adolescents like to combine different psychoactive substances. Therefore the aim of this study was to present the most important and the most actual substances abused by young adolescents together with the substance characteristics. This research included 600 adolescents with the same prevalence regarding age, sex and living zone (rural-urban). Our research showed that simultaneous abuse of various harmful psychoactive substances (polydrug abuse) is the most common (tobacco smoking and cannabis consumption in 75% of cases, alcohol consumption and cannabis consumption in 80% of cases).

Oral acute toxicity of HEPALIP FORTE in rats.

The main active component of preparation HEPALIP FORTE is EPL--essential phospholipids. Their chemical structure corresponds to that of endogen phospholipids, but they have functional superiority because of the content of unsaturated fatty acids. Essential phospholipids in combination with the vitamins have been used in the treatment of liver diseases, dyslipoproteinaemias and intoxications with consequent liver failure. Acute toxicity study on HEPALIP FORTE was performed on Wistar rats. The main aim of toxicology studies for the drug registration process is evaluation of the toxic potential and risks of human exposition to the substance (Gelbke et al., 1999). Acute toxicity is an orientation point of the test substance toxicity and represents a starting test for the toxicological evaluation. Study included one oral dose of the substance, applied with oesophageal intubations. There were three dose-levels: 300, 500 and 1000 mg/kg. No lethality was recorded and statistical analysis of body weight variations failed to show any significant difference between the groups. Reversible tremor was more frequently recorded in females and was not present in control animals. After the planed sacrifice, no changes related to the test substance were recorded. We noticed a statistically significant difference in the liver weights between males of 3M and 2M groups in comparison to the control. Similar (not significant) tendency was noticed in females. Significant differences in organ weights might be suggestive of a toxic effect that experimental animal managed to recover from in partial manner. The histopathological analysis detected no changes in the structure and morphology of liver parenchyma.

Food and water consumption in assessment of acute oral toxicity of HEPALIP FORTE in rats.

Body weight variations during toxicological testing can be one of the indicators of the test substance toxic effects. Data on food and water consumption are true indicators of the rate of growth of experimental animals (Stevens & Gallo, 1989). Daily recording of the food and water consumption was done during the acute toxicity testing of HEPALIP FORTE. The study was performed on Wistar rats. The active component of HEPALIP FORTE is EPL substance--essential phospholipids, a natural substance present in every living cell. Essential phospholipids in combination with vitamins have been used in the treatment of liver diseases, dyslipoproteinaemias and intoxications accompanied with liver failure. Statistical analysis of the body weight variations was performed separately, for males and females. The analysis failed to show any significant difference between the groups. There was a significant difference in water consumption between the male group 2M and female groups 3F and 2F in comparison with control groups. Statistical analysis of the variations of food consumption showed a significant difference in all male groups in comparison with control groups, and only in the 3F female group in comparison with a control group. Considering the absence of lethality and the lack of significant influence of the test substance on animal body weights, we concluded that the test substance was not acutely toxic in rats, if applied orally, in single doses of 300 mg/kg, 500 mg/kg and 1000 mg/kg. Significant differences found in food and water consumption suggest a need of their during the future chronic toxicity testing.

Frequency of the antipsychotic therapy acute side effects in the treatment of acute psychosis.

Antipsychotic drugs produce a wide spectrum of physiological actions. Some of these effects differ among the various classes of antipsychotics. This medications have indications in the treatment of acute psychotic disorders. The main goal of this investigation was to determine the incidence and prevalence of the neuroleptic therapy acute side effects. The reason for this epidemiological investigation performing was the lack of knowledge of the exact neuroleptic therapy side effects incidence. Qualitative study on this problem has not been performed yet. Antipsychotic therapy side effects prevalence rate according to the literature data is ranging from 24% to 74%. Different prevalence rate is a consequence of different antipsychotic drug usage, different drug administration method and different side effects identification. On account of all these facts, we put the hypothesis on the correlation between the antipsychotic therapy and occurred side effects. Our experiment included all patients hospitalised from December 31st 1999 to January 31st 2000 in Intensive Care Unit of Biological Psychiatry Department of Psychiatric Clinic in Sarajevo. All patients were divided in three groups according to the applied therapy. All of them met ICD-10 criteria for schizophrenia (F20-29). During our study the following examinations were performed: psychiatric interview, BRPS, scale of side effects, psychophysiological tests, general clinical impression, scale of appetite, carbon hydrate needs scale. Psychiatric and statistical evaluations were done as well. The evaluation of our examination is showing successful results in all groups of patients. The improvement of psychopathological symptoms was insignificant. Reported side effects were minimal with low incidence rate and relatively high prevalence rate. Statistical tests were calculated from the obtained data after what the null hypothesis was rejected. Consequently, an alternative hypothesis was confirmed and it indicated that the acute side effects incidence and prevalence were within the range of expectation. Intensity of the recorded side effects was moderate to mild. On the basis of the obtained data, it has been concluded that applied antipsychotic agents did not induce more psychophysiological function impairments in the treated patients. Psychophysiological functions remained in physiological range limits and their changes were not significant. Neuroleptic therapy side effects were minimal, meaning no toxic signs or therapy discontinuations were recorded.