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.

Detection of neurovascular structures using injection pressure in blockade of brachial plexus in rat.

In the last few decades there has been a great development of regional anesthesia; all the postulates are defined and all the techniques of usage are perfected. However, like any other medical procedure, the block of brachial plexus carries a risk of certain unwanted complications, like possible intraneural and intravascular injections. The reason for great discrepancy between the injury of brachial plexus and other periphery nerves while performing the nerve blockade is the frequent usage of this block, but also the specific proximity of neurovascular structures in axilla. The purpose of this work is to determine the values of pressures which appear in para-neural, intraneural and intravascular injection applications of local anesthetic, and to compare those values in order to avoid cases of intraneural and intravascular injections in clinical practice with consequential complications. In experimental study there have been used 12 Wistar rats of both genders. After anesthesia with ether and mid-humoral access to the neurovascular structures in axilla, the injection of 2% lidocaine with epinephrine was performed with the help of automatic syringe charge. The needle was at first placed para-neural, and then also intraneural and intravascular. During every application the pressure values were monitored using the manometer, and then they were analyzed by special software program. All para-neural injections resulted with the pressure between 13,96-27,92 kPa. The majority of intraneural injections were combined with the injection pressure greater than 69,8 kPa, while the intravascular injections were combined with injection pressure less than 6,98 kPa. Based on the available data it can be noticed that so far none of the methods of prevention from unwanted complications of regional anesthesia can insure the avoidance of intraneural and intravascular injection of local anesthetic. Based on our research it is obvious that the measuring of pressure during the nerve blockade is very important in order to decrease the risk of neurological and possible systematic complications. It is also clear that a small, mobile, and financially quite available apparatus for pressure measurement can help in differentiation between para-neural, intraneural and intravascular injection. Avoiding high injection pressure prevents from lodging the needle into intraneural space, while avoiding a very low injection pressure prevents from lodging the needle into intravascular space followed by consequential complications. The usage of this apparatus can find its application in other blockades of periphery nerves, and in other branches of medicine as well.

Models of treatment with antipsychotics of the schizophrenic patients.

The aim of this study were to determine which antipsychotic are currently in use, to establish which doses are administrated to patients, to find out is there a practice of proscribing simultaneously more then one antipsychotic drug, to determine whether antipsychotic are proscribed in divided doses, to establish whether there is, besides antipsychotics, treatment with other medicaments (co-administration), especially with antiparkinsonics. The research (study) is epidemiological-clinical prospective, descriptive and analytical and it was conducted at University hospitals in Sarajevo, Tuzla and Mostar. Criteria for inclusion, non-inclusion and exclusion from the study were precisely defined as a mean for formation of sample. Based on this hypothesis were established, zero and alterative. According to zero hypothesis in the treatment of schizophrenia at University hospitals in FBiH new antipsychotic drugs are in use, small doses are proscribed (up to 20 mg), not more then one antipsychotic drug is used simultaneously, antipsychotics are administrated once a day and alongside with antipsychotics other medicaments are not co-administrated, especially antiparkinsons. The results of our study are showing that majority of patients are treated with classical antipsychotics. Minority of patients is treated with atypical neuroleptics like olanzapine, which is proscribed only in Sarajevo. Use of risperidone and ziprasidone is registered also only in Sarajevo, but only small number of patients is treated with these drugs. Most frequent antipsychotics were promazine and haloperidol. The range between minimal and maximal daily dose of promazine was from 50 to 450 mg/daily, and for haloperidol from 1 to 75 mg/daily. Above-mentioned drugs were administrated in an average from two to three times a day. Alongside with antipsychotics, other drugs were used. Most frequent was the use of biperidine in oral and parenteral formulation, as well as nitrazepam and diazepam. The importance of this study is following: data are useful for the current mental health care reform in FBiH, results will point out place and position of FBiH in contemporary world trends in the treatment of schizophrenia, they will contribute to rational use of antipsychotic therapy, they will point out possible ways in reduction of side effects, often dangerous adverse effects of antipsychotics, and they will give contribution to faster rehabilitation of schizophrenics with the reduction of financial means for the treatment of patients with schizophrenia.

Clinical study on safety and efficacy of the administration of amlodipine in a combination with lisinopril in hypertensive patients.

AIM: Evaluation of efficacy and safety of long-term (24 weeks) administration of a combined therapy of ACE inhibitors (lisinopril) and calcium-channel antagonists with long-term action (amlodipine) (with or without diuretics). METHOD: A total number of 98 patients of both genders were included in the prospective, open trial. Evaluation of efficacy of the trial was carried out by careful monitoring of anamnesis and physical examination, blood-pressure values, pulse, body weight, ECG test and echocardiographic test. Evaluation of safety of the trial was based on the evaluation of a physician, standard laboratory evaluation, adverse effects. RESULT: Mean value of blood pressure in the beginning of clinical trial was significantly reduced (from 197.65 +/- 18.05/107.1+/-13.1 mm Hg, to 139.85 +/-10.45/82.6+/-5.47 mmHg) after 24 weeks, without special oscillations in last three months. The pulse remained within physiological limits. In 73.08% patients, echocardiographic test has proven an improvement of ejection fraction. Minor adverse effects have been reported, which were not a reason for interruption of the treatment, with the exception of 3 cases (lower leg oedema, dry cough). CONCLUSION: An extremely good effect in patients with moderate hypertension was reported in the trial, as well as in patients with severe hypertension with good tolerance.

[Nitric oxide--a potential modulator of left ventricular diastolic function in hemodialysis patients treated with erythropoietin]. / Dusicni oksid--potencijalni modulator dijastolne funkcije lijeve srcane komore u hemodijaliznih pacijenata tretiranih eritropoetinom.

UNLABELLED: Left ventricular hypertrophy (LVH) is commonly present in hemodialysis patients (HD pts) and is considered as an independent risk factor for high mortality. Many studies have confirmed sound connection between anemia and LVH in this patients. OBJECTIVE: To analyse dystolic function of LVH in uraemic pts during the 6 months human recombinant erythropoectin (rHu-Epo) treatment of anemia, with emphasis on the role of nitric oxide (NO), whose role in regulation of LV diastolic distensibility has been hinted in some recent studies. PATIENTS AND METHODS: The study included 20 HD pts, aged 39.6 +/- 5.3 yrs, with the same condition of HD treatment, signs of anemia and echocardiographically verified LVH. Pulse Doppler echocardiography confirmed LV diastolic function as a ratio of early to late diastolic mitral flow velocity (E/A). Nitrate concentration was determined by colorimetric method using Greiss reagent. Renal anemia was treated with rHuEpo. RESULTS: Six months rHuEpo treatment of anemia in HD pts with LVH caused significant reduction of LV mass index (p = 0.008). However, we observed unfavourable fall in LV diastolic function (E/A = 0.83, p = 0.007). In the same time, it was found that the serum NO level was higher for 11.8% in HD pts with LVH as compared with the pts with normal LV mass. Also, the significant positive correlation was found between the level of NO and LV mass index before (p = 0.004) and after rHuEpo therapy (p = 0.03), as well as a significant positive correlation between NO and E/A in the same conditions (p = 0.002) and p = 0.049). Level of NO negatively correlates with blood hemoglobin level, but without statistical significance. CONCLUSIONS: Correction of anemia with rHuEpo leads to the significant partial regression of LVH. Reduction of diastolic function of LV, observed after diminished LV mass index, could be related to the significant fall of NO level and damaged response of LV to NO. The results of the study strongy suggest that NO can present an important determinant of LV diastolic function in uraemic pts.

Endodontic-periodontal locally delivered antibiotics.

Endodontic pathology is a bacterial disease. It is well established that periapical disease is the result of bacteria, their product, and the host response to them. Periradicular disease will occur after microorganisms and their metabolic products affect the periradicular tissue. Aim of using antibiotics as part of a treatment regimen is to achieve, within the periodontal environment, a concentration of the drug that is sufficient either to kill (bactericidal) or arrest the growth (bacteriostatic) of pathogenic microorganisms. There are two possible approaches to improve the drug action: sustained and controlled drug release to reduce or eliminate side effects by improving the therapeutic index and site-specific drug delivery to minimize systemic effects. These two strategies have been explored by the association of drugs with different vehicles, either naturals or synthetics. A wide variety of specialized local delivery systems (i.e.intrapocket devices) have been designed to maintain the antibiotic in the GCF (gingival crevicular fluid) at a concentration higher than the MIC (minimum inhibitory concentration). Fibres, films, strips and microparticles made of biodegradable or non-biodegradable polymers have been reported as effective methods to administer antibacterial agents for periodontal therapy. Together with these solid devices, semisolid adhesive or non-adhesive formulations have also been proposed.

Etiological findings in endodontic-periodontal infections.

The endodontium and periodontium are closely related and disease of one may lead to secondary disease in the other. The differential diagnosis of endodontic and periodontal disease is of vital importance, so that the appropriate treatment can be done. Microorganisms play a primary role in endodontic and periodontal infections. The magnitude of the host response will be directly proportional to the virulence and the number of microbial cells present. Tissue damage caused by bacteria is mediated by either direct or indirect mechanisms. Direct harmful effects caused by bacteria involve their products, such as enzymes (collagenase, hyaluronidase, condroitinase, acid phosphatase), exotoxins and metabolites (bytrate, propionate, ammonium polyamines, sulphured compounds). In addition, bacterial components such as peptidoglycan, teichoic acid, fimbriae, outer membrane proteins, capsule, and lypopolysaccharide, stimulate the development of host immune reaction capable of causing severe tissue destruction.

Testing of analgesic effect of fluoxetine.

Fluoxetine is used in treatment of depression caused by a variety of different factors and from year to year new indications are being added, especially in conditions followed with strong bouts of pain. Additional fluoxetine based therapy that is known to help in improvement of mental state and mood stabilization can significantly increase analgesic effects. Analgesic effects of fluoxetine as well as of fluoxetine in combination with morphine were analyzed on albino mice of both genders. The sense of pain was induced by thermal stimulus by the method of hot plate. Analgesic effect was measured 30, 60, 90 and 120 minutes after a single i.p. administration of fluoxetine in following dosages: 5, 10 and 20 mg/kg. The control group was treated with 0.1 ml/10 g physiological solution. Test group injected with morphine s.c. (7 mg/kg) was used to observe the effect of fluoxetine in combination with morphine. Fluoxetine applied in 5 mg/kg dosage causes increased pain reaction 60 and 90 minutes (p=0.049 and p=0.002) (t-test) following application when compared with corresponding values of control group. When fluoxetine is applied in 10 mg/kg dosage duration of pain reaction is significantly increased after 30 (p=0.01), 60 (p=0.001) and 90 minutes (p=0.026), when compared to the control group. When fluoxetine is applied in 20 mg/kg dosage duration of pain reaction is increased 60 and 120 minutes (p<0.001) after application when compared to the control group. After application of fluoxetine (5 mg/kg) in combination with morphine, reaction time to pain is significantly extended (p<0.001) 60, 90 and 120 minutes after application when compared to the control group injected exclusively with morphine. Fluoxetine causes analgesic effect in all three applied dosages as well as it significantly increases analgesic effect when applied in 5 mg/kg dosage in combination with morphine.

Trazodone influence on rat sera beta-endorphins level.

Some 25 years ago it was found that parts of CNS could produce strong analgesic response on little morphine quantities. Later studies proved the existence for dozen of morphine-like substances, called opioids, which are normally produced in the brain. The most important are endorphins, met- and leu-encephalin and dinorphin produced both in hypothalamus and pituitary gland. The aim of our study was to found whether and how strong produce of beta-endorphins is to be expected when psychotropic drugs are used. Trazodon as antidepressant was used, and RIA technique for quantification of sera beta-endorphins. The results showed significant difference in rat sera beta-endorphins between certain days of drug application. These studies showed that beta-endorphins could be of great importance, used as markers for evaluation of patient treatment and eventual abuse of psychotropic drugs.

The effect of erythropoietin treatment on left ventricular hypertrophy in haemodialysis patients.

Anaemia appears to play an important role in left ventricular (LV) enlargement in chronic kidney disease patients. The objective of this study was to evaluate LV echocardiography changes during anaemia correction with recombinant human erythropoietin (rHu-Epo) in chronic haemodialysis patients (HD pts) with signs of anaemia and LV hypertrophy (LVH). The study included 20 HD pts aged 39,6 +/- 5,3 yrs, with the same condition of HD treatment, anaemia and echocardiographically LVH verified. At the beginning of the rHu-Epo treatment haemoglobin (Hb) level was < 90 g/L and the target Hb level was 110 g/L. Echocardiography was performed at the beginning (baseline) and after six months of rHu-Epo treatment. LVH was defined as LV mass index >100 g/m2 in women and >131 g/m2 in men. We observed significant reduction of LV mass index (LVMI) (mean 26,4%, p=0.008), as well as LV volumen. There was a significant negative correlation between Hb level and LVMI with predictive LVMI reduction of 2,317 g/m2 for each 1g/L rising of mean Hb level. The results of the study confirm the importance of early anaemia correction in haemodialysis patients aimed to improve LV parameters.

Clinical application of calcium hydroxide in dental pathology and endodontics.

Calcium hydroxide has a hard tissue inducing effect. It is a powder, that can be mixed with a physiological saline to a paste. The paste is highly alkaline with a pH 12.5 and its application to the pulp results in necrosis of the part of coronal pulp tissue shows no or only a milled inflammatory reaction. Analyzing the pH and the concentration of calcium ions in the periapical area, it is obvious that at least 2 weeks are necessary for calcium hydroxide bactericide activity. Calcium hydroxide retains its anti-bacterial properties for about two months when placed under a restoration, after which it degrades to calcium oxide and other less effective calcium salts. All calcium hydroxide preparations have a limited shelf life as they eventually turn into calcium oxide. Calcium hydroxide can be used as linings, for indirect and direct pulp cupping, root dressing, root canal sealant, apical closure. The vehicles play a supportive role, giving pastes chemical characteristics such as dissociation and diffusion as well as favoring the correct filling of the root canal which are decisive factors for antimicrobial potential and tissue healing. The mechanism of action of calcium hydroxide on tissues, inducing the deposition of mineralized tissue, is an extremely important aspect for the indication of calcium hydroxide, because it demonstrates biological compatibility of calcium hydroxide.

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.

Experimental model of the burn wound topical treatment.

BACKGROUND AND PURPOSE: Clinical research of drugs is a researching step subsequent to the preclinical studies in experimental animals. The aim of our research was to evaluate animal model of wound healing process after the burn inducement and effects of the ointment containing natural plants on the process of burn healing. MATERIAL AND METHODS: Burn wounds were experimentally induced in two species of experimental animals which were treated with topically applied herbal preparation with concomitant monitoring of the healing process. Experimental groups (1) of 15 animals each (mice and rats), while control group (2) of 10 animals each (mice and rats) that were not being treated with herbal ointment. After the hair removal, burn was induced on the back of animals by heated brass seal. Different clinical symptoms including oedema of surrounding tissue, redness, exudation, size of the burn surface, histological and microbiological findings were monitored on the days 1, 3, 7, 14 and 21. A statistically significant difference was observed throughout descriptive statistics and paired Student's t-test. CONCLUSION: Physiological healing processes of the acute burn wound following the topical application of herbal preparation can be monitored on the utilized animal model. A three-week treatment resulted in the 90% of completed epithelization in both animal species, indicating the effectiveness of topically applied herbal preparation.

Frequency and characteristics of side effects associated with antidepressant drugs.

Depression is among the most common of chronic health problems. WHO report predicts that depression will be the leading cause of disability in the industrial world by the year 2020. To be successful, treatment for the patients suffering from depression must be continued until complete recovery, but most patients do not stay on their antidepressant medication long enough. One of the most frequent reasons for break down is appearance of unpleasant side effects. In this study we followed up dynamics of the characteristic side effects of antidepressant therapy, with the major goal to assess their frequency and characteristics. The sample was all female patients taking antidepressant drugs in the Department of Psychiatry of Clinical Centre of University in Sarajevo. The treatment with antidepressants was efficient in most of the patients. A major advantage of SSRI over TCA was less pronounced side effects. The most intensive side effects of TCA (amitriptyline) were dry mouth, tremor and tachycardia while the most frequent side effects included blurred vision, tachycardia, dry mouth, tremor and sedation. Side effects of SSRI (fluoxetine/fluvoxamine) were mild, and the most frequent were nausea, tachycardia, swelling, dry mouth.

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.