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Background: Awareness about antibiotic resistance depends on the attitudes and information about antibiotic resistance of both patients and physicians. Persons who practice self-medication are at high risk of also self-medicating with antibiotics. The purpose of the present study was to evaluate the awareness about antibiotic resistance by investigating the practice in a group of self-medication users in a sample of adults in Romania and the variables associated with such practice., Material and Methods: A cross-sectional self-filled questionnaire based study was conducted from December 2016 through January 2017 amongst 218 self-medication users (SMUG). The attitudes, the level of knowledge, the perceptions, about antibiotic use (ABU) and about antibiotic resistance (ABR) were compared to a reference group represented by medical residents group in their specialty training (MRG) considered to have a higher level of knowledge and awareness about ABU and ABR., Results: The response rate was 87.2% in the SMUG group and 100% in the MRG group. The SMUG group reported self-medication practices for antibiotics with a high frequency at any time in life (72%), but with a very low frequency from the month previous to the date of the study (12%), comparative with the MRG group (75% and 7%, respectively). The multivariate logistic regression analysis showed that self-medication with antibiotics at any time in life in the SMUG group could be predicted by the answers to two questions regarding the practices and knowledge about ABU (Q13 and Q20). On the other hand, in the MRG group, a question about ABR perception (Q23), could be predictor for self-medication with antibiotics. Self-medication with antibiotics in the month previous to the date of the study in the SMUG group could be predicted with three questions: one about ABU practice (Q14), one about ABR perception (Q26) and one referring to ABR knowledge (Q28). On the other hand, in the MRG group, a question about ABR knowledge (Q32) could be predictor for self-medication with antibiotics. The reduced awareness about ABR in the SMUG group, is revealed by the reduced number of subjects (38%), who did not know that missing an antibiotic dose during a medical treatment contributes to ABR, comparative with the MRG group (84%). Indirectly, low ABR awareness in the SMUG group is revealed by the confusion about the appropriate use of antibiotics in bacterial or viral infections (that antibiotics are not used against viruses)., Conclusions: The findings from our study on the awareness about antibiotic resistance in the SMUG group might help the policy makers and regulatory authorities to develop educational programs directed to change the perceptions and attitudes about the appropriate use of antibiotics in order to diminish self-medication practices with antibiotics., Competing Interests: The authors declare there are no competing interests.

Nitric oxide (NO), formerly known as the endothelium-derived relaxing factor, is a mediator with a key role in the body, both in the central nervous system and in periphery. NO is synthesized by several cell types, where it acts as an autocrine and paracrine signaling molecule. Harnessing the impressive therapeutic potential of nitric oxide (NO) remains an ongoing challenge. In order to overcome the limitations linked with the use of nitric oxide and specially to increase the release of the radical in the targeted area, promising therapeutic strategies have been implemented, based on specific technologies which create releasing agents and vehicles for nitric oxide. Organic nitrites are the most known NO donor drugs, used especially in the treatment of cardiovascular diseases. In recent years, technological advances have allowed obtaining variations synthetic derivatives (such as diazeniumdiolates, S-nitrosothiols), which can generate NO in a controlled mode in the body and to chemically stabilize it; these compounds were studied with promising results in various animal models of vasospasm and pulmonary hypertension. Another high value therapeutic path is represented by the development of hybrid drugs (new nonsteroidal anti-inflammatory NO donor agents), with practical applications in inflammatory disorders accompanied by pain. Also, there is increasing evidence of the existence of NO donors with important antioxidant and hepatoprotective effects.

Hyperlipidemia is a well-known risk factor for coronary heart disease, the leading cause of death for both men and women. Current lipid-lowering treatment is not always efficient, therefore new pharmacological interventions that reduce LDL cholesterol (LDL-C) have been developed. This paper presents new class of specific LDL lipid-lowering drugs under investigation in phase II or III clinical trials. The inhibition of proprotein convertase subtilisin/kexin type 9 (PCSK9), a key enzyme in cholesterol homeostasis, improve the liver's ability to clear LDL from the plasma, reducing LDL-C levels. Currently, three monoclonal antibodies PCSK9 inhibitors (alirocumab, evolocumab and bococizumab) are evaluated in clinical outcome trials. ALN-PCSsc, the new first-in- class therapeutic RNA interference (RNAi) inhibitor of proprotein convertase subtilisin/kexin type 9 (PCSK9) is also the first-in-class investigational medicine that acts by turning off PCSK9 synthesis in the liver. The development leadership of ALN-PCSsc has now transferred from Alnylam Pharmaceuticals to The Medicines Company, who has initiated the ORION-1 Phase II study at the beginning of 2016. ALN-PCSsc has significant potential given its highly competitive profile as compared with monoclonal antibodies anti-PCSK9 MAbs, a recently approved class of LDL-C lowering drugs.

Aim: The study investigates the effects of magnesium nanovesicles on the memory processes performance in mice., Materials and Methods: L-a-phosphatidylcholine was used to obtain nano formulations as lipid vesicles systems stabilized thereafter with chitosan. The experiment was carried out on white Swiss mice, divided into 3 groups of 7 animals each, treated orally 7 consecutive days: Group I (Control): 0.1 mL/10g distilled water; Group II (Mg): 1 mmol/kbw magnesium chloride; Group III (Mg-vesicles): 1 mmol/kbw magnesium nanovesicles. The spatial memory performance was assessed by recording spontaneous alternation behavior in Y-maze test. Each animal was placed at the end of one arm and allowed to move freely through the maze during a single 8 min session. Alternation was defined as a consecutive entry in three different arms. The alternation percentage was computed according to the formula: (number of alternations/total number of arm visits--2) x 100. Data were analyzed using SPSS 17.0 software. Experimental protocols were implemented according to the recommendations of the University Committee for Research and Ethical Issues., Results: New carrier formulations entrapping magnesium chloride were designed: their mean size was 129.56 nm and the mean Zeta potential was +36.1 mV, indicating a moderate stability of the solution. Oral administration of magnesium vesicles resulted in a significant increase of spontaneous alternation percent in Y-maze test (p < 0.01), which suggests an improvement of short-term memory., Conclusions: Using magnesium chloride entrapped in lipid vesicles induced an enhancement of cognitive functions in mice especially by facilitation of learning extinction.

Aim: To investigate the effects of two serotonin receptor antagonists on spontaneous behavior in rats., Material and Method: The experiment was carried out on white male Wistar rats (150-200g) divided into 3 groups of 6 animals each, treated intraperitoneally with the same volume of solution as follows: Group I (Control): saline solution 0.1 ml/10 g weight; Group II (SB-269970): SB-269970 1 mg/kbw; Group III (NAN-190): NAN-190 1 mg/kbw. The effects of serotonin receptor antagonists on the spontaneous psychomotor skills of rats were tested in Actimeter LE-8811 (PanLab). The data were presented as mean +/- standard deviation and significance was tested by SPSS Statistics for Windows version 17.0 and ANOVA method. The experimental protocol was implemented according to the guidelines for handling and use of experimental animals of the Research Ethics Committee of the Iasi "Grigore T. Popa" University and ethical standards of the European Community., Results: The 5HT1 serotonin receptor antagonist NAN-190 determined a statistically significant reduction (p < 0.01) in both horizontal and vertical movements as compared with the control group, whereas the 5HT7 serotonin receptor antagonist SB269970 had no influence on rat behavioral manifestations., Conclusions: In our experimental conditions 1 mg/kbw NAN-190 decreased the total escape attempts, corresponding to a significant diminution of exploratory and self-maintenance spontaneous behavior in this experimental animal model. These manifestations may be correlated with the anxiolytic effect of 5HT1 serotonin receptor antagonist NAN-190 in rats. The administration of 5HT7 serotonin receptor antagonist SB-269970 did not alter the spontaneous activity in this behavioral experimental model in rats.

Aim: This paper is focused on the investigation the effects of two polymeric matrices for indomethacin in cutaneous pain models in mice. There were used two different co-polymers polyhydroxyethyl methacrylate and undecan, polymerization reactions being conducted under nitrogen, at 80 degrees C., Material and Methods: The experiments were carried out on white Swiss mice (20-25 g), divided into 6 groups of 7 animals each, treated orally. Biocompatibility properties of indomethacin-loaded copolymeric matrices ware evaluated by assessing the effects on the blood parameters, the serum biochemical tests of animals treated. The nociceptive somatic testing was performed using hot plate assay and tail immersion test. The latency (second) response to paw, respectively tail thermal noxious stimulation, was measured before the experiment and 15, 30, 60, 90, 120 minutes, 4, 6, 8, 10, 12 hours after the substances administration., Results: Laboratory analysis did not show significant differences of blood parameters, serum biochemical tests between control mice group (IND) and groups treated with 1 M, 1 IND, 3 M, 3 IND. In our experimental conditions IND determined a significant increasing of the latency period response, in hot plate and also in tail immersion tests. Using two different co-polymers for indomethacin incorporation we obtained an increasing of the latency time pain reaction in hot plate assay, respectively in tail immersion test, statistically significant (*p < 0.05) compared with the simple copolymers administration., Conclusions: We demonstrated that indomethacin co-polymeric matrices 1 IND and 3 IND determined similar immune responses with indomethacin and simple co-polymers after oral administration in mice, indicative of good in vivo biocompatibility. Oral administration of both 1 IND and 3 IND resulted in prolonged antinociceptive effects in hot plate assay and also in tail immersion test in mice.

Unlabelled: Self-medication with antimicrobial drugs is an important problem in the world and may lead to serious consequences for healthcare systems., Objective: To evaluate the prevalence and patterns of self-medication with antimicrobial drugs among university students in a Northeast region of Romania., Material and Methods: A cross-sectional questionnaire-based study was conducted to collect data from medical and non-medical students who lived in residence halls. Data were analyzed using descriptive statistics and the chi-square test, when applicable., Results: Out of the 320 questionnaires distributed, a total of 281 students completed and returned the questionnaires. Among these, 115 (41%) respondents admitted to have used at least one antibiotic in the six months prior to the survey, 44% of whom did not seek medical advice (irrational self-medication). The most common antimicrobial drugs used for self-medication were amoxicillin (37%), amoxicillin-clavulanate (33%), ciprofloxacin and penicillin (14%) and the most frequently reported reasons for self-medication were respiratory and oral infections (31%), common cold (25%), and genitourinary infections (20%). Some students mentioned the use of more than one antimicrobial drug, for more than one disease., Conclusions: self-medication with antimicrobial drugs is a relatively common practice among students in Romania. This suggests the need for interventions to prevent the irrational use of antimicrobial drugs, such as the implementation of national programs for public education regarding the risks and consequences for the health of irrational use of antimicrobials.

The light-dark cycle represents a significant component of the circadian system in most mammals. Any disturbance of this cycle is reflected in a large number of changes in the physiological and also behavioral status of the organism, together with considerable alterations of the redox balance. Increasing evidence suggests that reactive oxygen species (ROS) have their own function in the circadian system. Superoxide dismutases (SOD) family represents the first prompt antioxidant enzymatic system, identified in all aerobic organisms and able to counteract ROS toxicity; there are three distinct isoenzymes: CuZn-SOD (SOD1), Mn-SOD (SOD2), and extracellular EC-SOD (SOD3). In the case of circadian disruption, when ROS production is enhanced, the impact of the oxidative aggression on superoxide dismutases (SOD) rhythmicity and distribution is still unclear. To estimate the influence of circadian rhythms disruption on pulmonary SOD, we exposed male Wistar rats to continuous light stimuli for four weeks and then investigated the SOD immunohistochemical expression in lungs, which are among the most sensitive organs to oxygen. CuZn-SOD, Mn-SOD and EC-SOD presented a particular immunoreactivity in the investigated pulmonary tissues. These findings support our viewpoint that there is a direct correlation between the rhythmicity of circadian cycles and pulmonary SOD expression.

Aim: To evaluate drugs interactions with oral anticoagulants and their clinical relevance, in patients from two emergency departments in hospital., Material and Methods: Retrospective study, during one year, on patients (between 18 and 85 year old) with haemostatic disturbances admitted at two emergency departments in ,,Sf. Spiridon" Hospital, Iaşi and in Piatra Neamţ Public Hospital, consisted in medical records analysis: the diagnostic, therapy recommended. Data were scored and statistically analyzed by t test (Windows Excel). The experimental protocol was in agreement with recommendations of the "Gr. T. Popa" University Committee for Research and Ethical Issues., Results and Conclusions: Analysis and statistical processing of data shows that during the period of the study, 69 patients, which received oral anticoagulant therapy associated with different other medication belonged to the 60 and 80 years age group. The findings suggests the pathology is represented especially by atrial fibrillation and cerebral ischemic diseases. The correlation between the therapy consisting in OAC and amiodaronum or statines drugs association and International Normalized Ratio (INR), revealed a high level of anticoagulation and an increase of hemorragic complications.

Unlabelled: The depressing effects on the nervous central system (NCS) induced by benzodiazepines and ethanol are similar. The complications are rare in the benzodiazepine poisoning, but are a lot more frequent in association with other depressing drugs for the NCS (especially alcohol)., Material and Methods: We analyzed retrospectively patients with benzodiazepine poisoning admitted in the Internal Medicine Clinic - Toxicology during 2003 - 2009.The study attempted a complex evaluation of the consequences of acute and chronic alcoholism on the evolution of acute benzodiazepinepoisoning and the description of the clinic evolution and paraclinical particularities of the patients under investigation., Results: 343 patients with benzodiazepine poisoning were admitted, 150 were tested through measurement of alcohol level, leading to values between 1 - 415 mg/dl. Chronic alcoholism in personal pathological antecedents of the patients determined a relative risk of intoxication 1.46 times higher. The hospitalization period varied from 1 to 8 days for patients with chronic alcoholism and from 1 to 14 days for patients with acute alcoholism, a statistically important difference., Conclusions: During the period under investigation, from the total of patients admitted for acute benzodiazepine poisoning, 2 deaths were registered. Of the two deaths, one patient showed ethanol coingestion.

Aim: To investigate the effects of a Cetraria islandica extract in an animal model of hepatopathy., Material and Methods: The experiments were carried out on Wistar rats, treated intraperitoneally (excepting carbon tetrachloride which was administered orally by esogastric tube), at single daily dose, for 28 days and divided in eight groups of 6 rats each: Group 1: Saline solution (0.5ml/100g bw/day); Group 2: MgSO4 (5mg/kbw/day); Group 3: C. islandica (Ci) extract (21.56mg/kbw/day); Group 4: Ci+MgSO4; Group 5: carbon tetrachloride (CT).(0.1 ml/100g bw/day); Group 6: CT+MgSO4; Group 7: CT+Ci; Group 8: CT+Ci+MgSO4. At the end of the experiment blood samples were taken to assess the effects on the blood parameters,TGO, TGP, GGT, LDH, serum total billirubin, neutrophil phagocytic function (Nitroblue tetrazolium test) and serum complement activity. This parameters were determined with VITROS 750 XRC device, using Johnson&Johnson kits. The results were statistically processed with the help of "t-Student" test. p<0.05 was considered statistically significant., Results: In this carbon tetrachloride-induced hepatopathy animal model, C. islandica extract demonstrated hepatoprotective and immuno-stimulating effects (proved by normalization of glutamic-pyruvic transminase, glutamic-oxalocetic transminase, serum total billirubin, stimulation of neutrophils percentage and phagocytic functions, decreasing the carbon tetrachloride-induced basophilia and monocytosis, especially in association with magnesium)., Conclusions: Further studies are required to confirm the benefits of this association in hepatoprotective and immunomodulating therapies.

Aim: to investigate the influence of some stress factors on hepatic function and lipid metabolism in an experimental-induced hypertension., Material and Methods: The experiment was carried out on Wistar rats, treated intraperitoneally, for 4 weeks, as follows: Group 1: saline solution (0.5ml/100g weight); Group 2: saline solution + stress; Group 3: Endotelin-1; Group 4: Endotelin-1 + stress; Group 5: Endotelin-1 + cholesterol diet (0.2g/kbw/day); Group 6: Endotelin-1 + cholesterol diet + stress. Endotelin-1 0.25nmol/kbw was initially administered, followed by 0.5nmol/kbw 15 min later, 2 times/week. Stress-inducing factors were immobilization and water immersion. In the 28th day of the experiment blood pressure was measured and blood samples were taken from retro-orbitary plexus to assess glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT) and lactic dehydrogenase (LDH) activity, total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides levels., Results: Using immobilization and water immersion as chronic stress, our study proved an increase of GOT, GTP and total and LDL cholesterol in rats with endotelin-1-induced hypertension., Conclusions: In this animal model of endothelin-1-induced hypertension the blood pressure increased significantly under chronic exposure to stress, reaching the highest values when associating stress and experimentally induced dyslipidemia.

Aim: to study the effects of licht/dark induced-stress in an animal model of HELLP syndrome., Material and Methods: The experiment was carried out on white female Wistar rats treated intraperitoneally, for 4 weeks, as follows: Group 1: saline solution 0.5ml/100g weight; Group 2: saline solution + dark induced-stress, continuously, 28 days; Group 3: saline solution + light induced-stress, continuously, 28 days; Group 4: endotelin-l; Group 5: endotelin-1 + dark induced-stress, continuously, 28 days; Group 6: endotelin-1 + light induced-stress, continuously, 28 days. Endotelin-1 0.125nmol/kbw was initially administered, followed by 0.25nmol/kbw 30 min later, 2 times/week., Results: At the end of the experiment blood pressure was measured and blood samples were taken to assess: leukocyte formula, phagocytic capacity of peripheral neutrophils and serum complement activity, aspartate aminotransferase (ASAT), alanine aminotransferase (ALAT) and lactic dehydrogenase (LDH) activity, total bilirubin and lipid profile., Conclusions: In these experimental conditions we obtained an animal model of partial HELLP syndrome (elevated liver enzyme levels and a low platelet count, values emphasized by light induced-stress, without hemolysis). In chronically stressed animals we found the highest levels of blood pressure, a decrease of plasmatic cortisol level and of phagocytic capacity of peripheral neutrophils and an increase of total cholesterol.

Unlabelled: Oral anticoagulants (OAC) are commonly used as a life-long therapy in the prevention of systemic embolism in patients with atrial fibrillation, valvular heart disease, prosthetic heart valves, and in the primary and secondary prevention of venous thromboembolism, in patients with acute myocardial infarction and angina pectoris. Drugs, herbs, and multivitamin supplements can alter the absorption, pharmacokinetics or pharmacodynamics of OAC., Aim: To investigate the possible interactions between oral anticoagulants and different drugs administered in patients in emergency department., Methods: This 1-year exploratory investigation on 93 patients on OAC (aged 30 - 85 years), admitted at two emergency departments of the Iasi "Sf. Spiridon" Hospital and Piatra Neamţ Hospital, consisted in their medical records analysis: diagnosis, recommended treatement. Data were scored and statistically analyzed by t-test (Windows Excel). The experimental protocol was in agreement with the recommendations of the Gr.T. Popa University Committee for Research and Ethical Issues., Results and Conclusions: Analysis and statistical processing of data shows that during the study period 56 patients which received oral anticoagulant therapy associated with different other medication belonged to the 60 and 80 years age group. This finding suggests that the pathology is represented especially by atrial fibrillation and myocardial infarction. The correlation between the therapy consisting in OAC and sartan or nonsteroidal anti-inflammatory drugs and International Normalized Ratio (INR), revealed a high level of anticoagulation and an increase in hemorragic complications.

Aim: Experimental researches on the effects of a Cetraria islandica extract, with or without magnesium association, on oxidative stress in rats., Material and Methods: The experiments were carried out on Wistar rats, treated intraperitoneally for 14 days at single daily dose as follows: Group 1: Saline solution (SS) (0.5 ml/100g bw/day); Group 2: Subcutaneous pellets, SS; Group 3: Levamisole (LEV) (10mg/kbw/day); Group 4: Subcutaneous pellets, LEV; Group 5: Prednison (PDN) (5mg/kbw/day); Group 6: Subcutaneous pellets, PDN; Group 7: MgSO4 (5mg/kbw/day); Group 8: Subcutaneous pellets, MgSO4; Group 9: C. islandica (Ci) extract (21.56mg/kbw/day); Group 10: Subcutaneous pellets, Ci; Group 11: Ci+MgSO4; Group 12: Subcutaneous pellets, Ci+MgSO4. At the end of the experiment blood samples were collected for assessing the following oxidative stress parameters: malonaldehyde, catalase, glutathione peroxidase, glutathione levels., Results: In the rats with or without experimentally-induced granuloma, repeated administration of Ci for 14 days resulted in a decrease of malonaldehyde, catalase, glutathione peroxidase activity, and an increase in glutathione levels. The association of magnesium augmented the antioxidant effect of Ci in this experimental model., Conclusions: In our study experimental conditions C. islandica extract determined adaptogenic-antistress effects, confirmed by its actions on oxidative stress parameters.

Aim: To determine the pharmacokinetics of glimepiride, a sulfonylurea antidiabetic agent, after single dose administration in healthy subjects., Material and Methods: Pharmacokinetic data for modeling were extracted from a single-center, randomized, single-dose, fasting state, two-way crossover bioequivalence study on 4 mg glimepiride in 24 healthy subjects., Results: Plasma concentrations of glimepiride were measured using a validated LC/MS/MS method. The pharmacokinetic parameters were calculated using non-compartmental analysis. Different pharmacokinetic models were tested to evaluate pharmacokinetics of glimepiride. The optimal model was chosen based on Akaike's Information Criteria., Conclusion: Compartmental analysis demonstrated that oral glimepiride tablets obey one compartment open model with rapid absorption following a first order kinetics and a short half-life.

Aim: to investigate the influence of some stress factors in endothelin-1-induced hypertension., Material and Methods: The experiment was carried out on Wistar rats, treated intraperitoneally, for 4 weeks, as follows: Group 1: saline solution (0.5 ml/100 g weight); Group 2: saline solution + stress; Group 3: Endotelin-1; Group 4: Endotelin-l + stress; Group 5: Endotelin-1 + cholesterol diet (0.2 g/kbw/day); Group 6: Endotelin-1 + cholesterol diet + stress. Endotelin-1 0.25 nmol/kbw was initially administered, followed by 0.5 nmol/kbw 15 min later, 2 times/week. Stress-inducing factors were immobilization and water immersion. In the 28th day of the experiment blood pressure was measured and blood samples were taken from the retro-orbitary plexus to assess plasma cortisol, blood count, phagocytic capacity of peripheral neutrophils, and serum complement activity., Results and Discussions: Repeated administration of endotelin-1 determined an increase in blood pressure, statistically significant in stress conditions comparing to non-stressed animals. Our study proved a decrease of plasma cortisol, total leukocyte count, phagocytic capacity of peripheral neutrophils, without significant alterations in serum complement activity., Conclusions: Chronic exposure to complex stress conditions in rats with endothelin-1-induced hypertension determined a decrease of plasma cortisol levels, effect correlated with elevated blood pressure and decrease in the number and phagocytic function of peripheral neutrophils.

Unlabelled: Pregnancy induced hypertension is a condition of high blood pressure during early and mid-pregnancy. This type of hypertension is much like the chronic type, but it occurs only when the woman is pregnant and resolves completely after delivery., Aim: to evaluate some stress hormones in both normotensive and hypertensive pregnant women., Material and Methods: The study investigated the correlation between pregnancy induced hypertension and different immune/inflammatory and other markers. This exploratory investigation was performed on pregnant women diagnosed with pregnancy-induced hypertension, admitted to the lasi Cuza Voda Hospital. The psychometric assessment was performed by using the daily stress test, daily hassle scale, blood pressure measurements, and determination of anthropometrical parameters. Some parameters, such as the neuroendocrine and immune/inflammatory ones, and specific parameters for pregnancy hypertension were determined., Results and Discussions: Our study revealed that blood pressure values presented significant differences between systolic, but not diastolic blood pressure values (p < 0.05). In 75% of subjects blood cortisol levels were not changed. Daily stress level assessment proved that low potential factors and an annoying environment had a high influence on both normotensive and hypertensive pregnant women. Hypertensive women also presented leukocytosis and thrombocytopenia., Conclusions: The research results showed that plasma cortisol level was higher in hypertensive pregnant women, compared with normotensives.

Unlabelled: Hypercholesterolemia plays an important role in atherosclerosis. The dietary supplementation of proteins or specific aminoacids seems to enhance the immune status in animals and humans with a complex pathological status, decreasing morbidity and mortality., Aim: In the present study we intended to analyse the effects of some nonpolar aminoacids--valine and leucine on cholesterol blood levels in a high-fat-diet in rats. In the same time we evaluated the vascular walls impact produced by the hypercholesterolemic diet., Material and Methods: Our experiment was realised on 32 male Wistar rats, which were fed with cholesterol, valine and leucine for 8 weeks. At the end of experiment we analysed serum levels of cholesterol and also histopathological features of hypercholesterolemia on the arterial wall., Conclusion: The results of our study indicate that valine and leucine decrease the serum cholesterol and therefore the hypercholesterolemic-induced prooxidant status of the body being useful in reducing atherosclerosis.

Aim: To evaluate immune system response, skin and hepatic reactivity in Swiss mice after retro auricular local administration of two textile dyes., Material and Methods: On 3 groups of white Swiss mice: group I (Cibacron Yellow F-4G), group II (Cibacron Orange P-2R) and control group (DMSO dimethylsulfoxide), substances were applied on left retro auricular ear, in dose of 25 microL solution 10% in DMSO (the dyes were not soluble in water), once a day, for 7 days. After euthanasia, blood samples were taken to assay differential cell count, peripheral neutrophils activity (NBT test), serum opsonic capacity, peritoneal macrophages activity (phagocytic and bactericidal capacity), and activity of spleenic T-lymphocytes with rossetting capacity, and spleen cells forming Jerne plaques. There were taken skin from local application of dyes, retro auricular and later cervical nodes from left side and hepatic samples., Results: Retro auricular and later cervical nodes mass increases after administration of textile dyes, compared to control group. Basophiles percentages were increased after administration of two dyes (stronger after yellow dye). Peripheral neutrophils activity was increased after administration of two dyes, especially after orange dye. Administration of the two dyes decreased serum opsonic capacity and peritoneal macrophages activity, but did not influenced the activity of spleenic T-lymphocytes with rossetting capacity and spleen cells forming Jerne plaques. There were significant skin and hepatic changes in microscopy., Conclusion: The studied dyes influenced the activity of immune system, increased skin and hepatic reactivity.

Unlabelled: Reactive Red 183, Reactive Red 2 and Reactive Blue 204 (red dye, green dye and blue dye) are three reactive dyes frequently used in textile industry. In some atmospheric conditions ( high temperature, perspiration, pH values, UV/IR radiations), some quantities of these hydrolyzed dyes, could pass from textile clothes directly into the human skin., Material and Method: There were used 4 groups of white Swiss mice (with similar weight and number of both sexes), control group and 3 groups, treated once daily with a retro-auricular application of different reactive dyes. After 14 days of treatment, blood samples were taken from retro-orbitary plexus to assess leukocyte count, phagocytic capacity of peripheral neutrophils, serum opsonic capacity, phagocyte capacity and bactericidal capacity of peritoneal macrophages, splenic T lymphocytes with rossetting capacity and spleen cells forming Jerne plaques. The retro-acuricular and latero-cervical nodes were weighted., Results: Red dye did not influence the weight of the studied nodes, but determined statistically significant modifications on non-specific immune system parameters. Blue and grena dyes determined modifications of weight especially of retroauricular nodes. Grena dye determined important effects of non-specific immune system parameters (serum opsonic capacity, phagocyte capacity and bactericidal capacity of peritoneal macrophages). The blue dye did not determine a biological response., Conclusion: Red and green dye determined important effects on non-specific immune system parameters.

Unlabelled: The effects of the saponinic summ extracted from roots of Aralia mandshurica have been studied in experimentally animals exposed to stress., Material and Methods: The experiment was carried out on 4 groups of animals divided into 24 lots of 12 white rats each with experimentally induced chronic inflammation or/and exposed to stress induced by exposure to continuous dark or light. The drugs (Levamisole (LVM) (10mg/kg bw/day), Indometacin (IND) (1.42 mg/kg bw/day), Extract of the roots of Aralia mandshurica (SAR) (26.25 mg/kg bw/day) and saline solution (0.5 mL/100 g bw/day) were administered orally for 14 days, in unique daily dose. Blood samples were taken from rats' retroorbital plexus before the beginning of the treatment protocol (M0) and at the finish of the treatment (M1) in order to assay differential cell count, peripheral neutrophils activity (NBT test) and serum complement activity., Results: The SAR extracts exert influence on immunity defence cellular's components without influence on humoral efects, no matter of experimentally conditions. They determined decreasing of the percentage of the neutrophils in peripheral blood (at the lower levels than Indometacin (IND)., Conclusion: The experimental results demonstrated immunomodulatory effect of this saponine extract.

Three topical formulae with Allium cepa L. extract 30% (w/w) were studied for the evaluation of their release profiles of flavonoids and for their potency on experimental wounds on mice. The rates of release were performed under occluded conditions using cellulose acetate membrane. Data obtained from the in vitro release show that the gel formula F1 is the most efficient in the membrane diffusion process. The rate of wound healing was assessed by the contracting ability and the period of epithelization. The most important effect in the contracting ability was noticed in the case of F2 formula.

In order to continue the research of the rutin semisynthetic derivatives we obtained some new morpholine and piperidine derivatives. Melting points, solubility, yield, C, H, N elemental analysis and UV spectra characterised all of these compounds. The toxicity was established by intraperitoneal administration at mice; the values of LD50 are between 743.75 and 856.25 mg/kg (medium toxicity). Pharmacological assays included the following parameters: leukocytes formula, NBT test, and serum complement activity. The new derivatives of rutin have a very good solubility in water, a pH closed to physiological value and immunosuppressive activity: peripheric blood PMN and lymphocytes are decreased; fagocytic capacity of peripheric blood PMN is also decreased; serum complement activity is not changed.