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BACKGROUND: The presence of low back pain in nurses is becoming increasingly prominent and it has significant impact both on the individual as well as on the community. OBJECTIVE: The aim of this study was to determine the prevalence of low back pain among practicing nurses. METHODS: The research has been conducted in five health care institutions in the area of Vojvodina. Data were collected using the Nordic Musculoskeletal Questionnaire (NMQ). RESULTS: Five hundred and twelve nurses participated in this study. Most of the participants (93.95%) indicated that they experienced discomfort or pain in the lower back in the last 12 months. Due to low back pain, 61.95% of participants had reduced working abilities and 76.09% of participants have never taken time off from work. CONCLUSIONS: Due to low back pain nurses have a reduced working capacity, but they nevertheless rarely seek medical help or the change of the work place. The implementation of better ergonomic approach and adequate organization of work could reduce the occurrence of low back pain.

Emergency Medicine does not represent a simple collection of various medical conditions, but rather an urgent approach to life threatening conditions. This urgent approach progresses as fast as the science in medicine does. Modern protocols for treatment of injured and ill patients are introduced, demanding more and more knowledge and skills as well as more modern equipment and wider spectrum of drugs. However, innovations are not followed by changes within the lists of medications set by National Health Insurance Fund of Serbia (NHIFS). Paper describes drugs necessary for adequate pre-hospital treatment that are not available to the physicians due to administrative barriers. On one hand, there are drugs from B list that are necessary for treatment, and are approved for use by NHIFS at hospital level only. The use of any of these drugs at pre-hospital level may lead to severe penalties to the physician in case of complications or adverse reactions in a patient following the treatment. On the other hand, there are drugs from D list which are also necessary for the urgent treatment of patients with life threatening conditions, according to latest recommendations. These drugs may be applied at pre-hospital level, but their procurement is complicated due to NHIFS regulations and that's why some of them may rarely be used (Propafenone and Magnesium sulfate). We particularly emphasize that one of the most effective drugs for the conversion of heart rhythm, Adenosine (6 mg/ml and 10mg/ml ampoule), is not registered in the Republic of Serbia and therefore cannot be used at pre-hospital level. Through these exclusive administrative barriers adequate treatment is rendered impossible while the system of urgent treatment of patients with life threatening conditions at pre-hospital level is degraded.

Introduction/Aim Carbon monoxide (CO) is a gas produced by incomplete combustion of carbon compounds and is a leading cause of poising throughout the world. The objective of this paper is to analyze 5 cases of acute carbon monoxide poisoning in petroleum industry workers, occupying a shared accommodation and to present diagnostic, therapeutic and preventive measures. Case report the workers had to be treated by the emergency medical service during the night for health problems arising from carbon monoxide inhalation from a faulty installation. Venous blood samples were collected to measure the concentration of carboxyhemoglobin (COHb) and gas analyses were done upon admission and 120 minutes later. They were treated with parenteral therapy and oxygen by mask, and they made a complete recovery. Conclusion Faulty installation of a gas-powered heating system caused acute carbon monoxide poisoning in 5 people occupying the space. After 120 minutes in a closed environment, the carbon monoxide concentration was high enough to cause a significant increase of COHb in the venous blood. Prompt diagnosis and adequate therapy are crucial to ensure a favorable treatment outcome. Preventive measures, such as educating workers and introducing health and safety measures into the work environment are extremely important in preventing accidents such as these.

Background Professional drivers are part of the active working population, so there is a need for continuous improvement of operating efficiency and safety in driving. Reaction time is a very important driver's trait. Objective The aim of this study was to examine the effects of age and driving experience on reaction times of professional drivers. Methods This study assesses part of driving efficiency of professional drivers by measuring simple reaction time and complex reaction time which are important to driving safety. Reaction times of 278 male professional drivers were tested using a hardware-software system for determining the speed of response to psychomotor simple and complex audio-visual stimuli. Results Our results showed a positive correlation between ageing and slowing of reaction times. This suggests that the natural ageing process clearly slows down reaction times. Conclusions The response times of professional drivers are more dependent on age than on driving experience.

Introduction. Even though lumbar pain is one of the most common medical problems of today, it is difficult to determine its precise origin. When identifying the risk factors for developing lumbar pain, one should also take into account the personal characteristics such as gender, age, body mass index, smoking habits, physical activities etc. The basic goal of this study was to assess the relationship between the socio-demographic characteristics (age, gender, level of education), the body mass index, smoking habits, and lumbar pain in nurses. Material and Methods. This cross-sectional study was conducted in five healthcare institutions in the area of Vojvodina by interviewing nurses by means of the modified Nordic questionnaire. Results. The participants were predominantly female, the majority of them having secondary school degree. The study revealed a statistically significant relationship between lumbar pain and the increase of age and body mass index, while smoking habits did not influence the occurrence of lumbar pain. Conclusion. A better organization of work in relation to the age and gender as well body mass control would reduce the risk of lumbar pain.

Introduction. Anthropozoonoses are diseases that affect humans and animals and they can be transmitted naturally from animals to humans. The aim of this study was to identify characteristics and types of occupational hazards that lead to occupational anthropozoonoses, determine their incidence in economic activities of the Autonomous Province of Vojvodina. Material and Methods. Using a descriptive, epidemiological study we analysed the occupational anthropozoonoses occurring in the Vojvodina which were registered at the Institute of Occupational Health Novi Sad, Serbia, from 1992 to 2016. Results. In the observed period, a total of 481 occupational diseases were identified, out of which 62 (12.9%) cases were the occupational infectious diseases. A total of 19 cases of occupational anthropozoonoses were registered. The average annual incidence of occupational anthropozoonoses was 0.96 per 100,000 employees. The linear trend of annual incidence was neg?ative. The average age was 44.05?8.34 years. Male patients accounted for 73.7% of cases. The average length of service among patients was 19.63?8.2 years. Conclusion. In addition to the implementation of available specific immunization measures and personal protection measures that prevent contact with pathogens, it is important to continuously educate workers concerning the work?place risks and perform preventive medical examinations in order to enable early recognition and treatment of the disease. In addition, continuous education of medical practitioners of different specialities would help to better identify occupational anthropozoonoses.

Job burnout syndrome is a form of professional stress which occurs most frequently in human occupations. Three key aspects of job burnout that occur in response to chronic stress are: emotional exhaustion, depersonalization and personal achievement. The studies that have been conducted both in the highly industrialized and middle­income and developing countries have shown a high prevalence of occupational stress and job burnout syndrome in almost all branches of medicine. The direct consequences of job related stress on physicians physical and mental health indirectly lead to a decrease in the level of health services with all its consequences on the patients care. There is a need to detect stress factors and find the ways to prevent or at least mitigate them. The development of modalities in terms of training how to recognize and overcome the stressful factors of professional burnout and determining organizational reforms in health care system in order to reduce the presence of contributing factors for burnout are the priorities for the each country's society.

Sclerosing mesenteritis (SM) is a rare and poorly understood chronic benign inflammatory condition of the mesentery that sometimes can be manifested as acute abdominal emergency. In this paper sclerosing mesenteritis was discussed on the occasion of experience in the diagnosis and the treatment of patients in clinical practice, a 62-year-old man who was diagnosed SM on computed tomography (CT) which was confirmed histopathologically. SM manifests grossly as a diffuse, localized, or multinodular thickening of the mesentery. Microscopically, according to the pattern of the disease, SM can be divided into sclerosing panniculitis where necrosis and inflammation predominate and retractile mesenteritis in which fibrosis and retraction are hallmarks of the disease. Clinical presentation of patients suffering from SM is quite diverse - from asymptomatic, which is the most common, to abdominal pain, bloating, nausea, vomiting and febrile episodes. The 'fat ring sign' and peripheral pseudocapsule are virtually pathognomonic CT findings of SM. Management of SM is empirical with no guidelines yet established. SM should be listed in the differential diagnosis in every older patient with diverse abdominal complaints.

Background/Aim. It is known that bile acids improve the absorption, bioavailability and pharmacodynamic characteristics of some drugs. Morphine analgesia is produced by activation of opioid receptors within the central nervous system (CNS) at both spinal and supraspinal levels. Since a morphine molecule contains 3 polar groups and therefore hard to transfer through the blood-brain barrier, the aim of the study was to examine the potential influence of bile acids derivates, namely sodium salt of monoketocholic acid (MKH-Na) and methyl ester of monoketocholic acid (MKH-Me), on analgesic effect of morphine. Methods. White male mice of NMRI-Haan strain, with body weight of 20-24 g, were used in this study. The analgesic effect of morphine (administered by subcutaneous and intramuscular route in a dose of 2 mg/kg), with and without pretreatment with MKH-Na (4 mg/kg) and MKH-Me (4 mg/kg) was estimated by the hot plate method. Results. Administration of MKH-Me prior to subcutaneous administration of morphine increased the morphine analgesic effect but the increase was not statistically significant. At the same time administration of MKH-Na did not affect morphine analgesic effect. The analgesic effect of morphine increased when administered intramuscularly 20 min after MKH-Me administration. When compared with the group of animals treated only with morphine, a statistically significant increase in analgesic effect was detected 10, 30, 40 and 50 min after morphine administration (p < 0.05). Pretreatment with MKH-Na did not affect morphine analgesic effect. Conclusion. According to the results of this study it can be presumed that after intramuscular morphine administration methyl ester of monoketocholic acid increases morphine transport into the central nervous system and consequently the analgesic effect, as well. Further research on bile acids-morphine interaction both in vitro and in vivo is necessary to completely elucidate the mechanism of this interaction and increase in the morphine analgesic effect. [Projekat Ministarstva nauke Republike Srbije, br. 41012: Interactions of xenobiotics and the impact on biomedical system i br. 172050: Development and application of advanced chromatographic and spectroscopic techniques in analysing xenobiotics and the mechanisms of their decomposition in biotic and abiotic samples]

Various pesticides are applied in agriculture for crop protection. They could have toxic effects on nervous system, liver, kidneys and the other organs. The aim of the study was to investigate effects of occupational exposure to pesticides and consumption of alcoholic beverages on liver functions in agricultural workers. The study included sample of 117 male agricultural workers involved as tractor drivers in pesticide application at the workplace and the control group of 60 tractor drivers who do not applied pesticides. We collected data concerning age, use of alcohol and duration of exposure to pesticides. Parameters of liver functions in serum were determined in both groups of workers. In agricultural workers exposed to pesticides, activities of enzymes gamma-glutamyl transpeptidase, alanine and aspartate aminotransferases were higher comparing to the control group, but these differences were not statistically significant. Consumption of alcohol statistically significantly increased activity of gamma-glutamyl transpeptidase in both groups of workers. The most important measures concerning health protection of agricultural workers exposed to pesticides are continuous implementation of the safety measures at work, health promotion at workplace and regular health surveillance in occupational health services for the purpose of early detection of worker's health disorders.

Background/Aim. Intervertebral disc degeneration (IDD) occurs as consequence of combined effects of genetic, age-related, environmental and occupational factors. Lumbar disc herniation (LDH) develops mostly due to IDD. The aim of this study was to investigate whether the frequency of LDH is higher at the level of the most pronounced IDD, and whether a category of physical workload influences higher IDD on level L3-L4, L4-L5 and L5-S1 separately. Methods. The research included 60 patients with permanent employment, hospitalized due to LDH. A grade of IDD was assessed by lumbosacral preoperative magnetic resonance imaging (MRI), according to Pfirmann's MRI classification system. Occupational factors were determined by a specific questionnaire. Results. Out of the 60 patients participating in the study, 33.3% had jobs with easy workload, 23% had moderate workload, while 43% had heavy workload. Herniated discs were found at level L3-L4 in 8.3%, at level L4-L5 in 46.7% and at level L5-S1 in 45% patients. The symptomatic discs at level L5-S1 showed statistically significant frequency of degenerative changes of grades IV and V. Binary logistic regression results showed that the strongest predictor of IDD grade for examined levels was physical workload. Positive association of physical workload and IDD grade was observed in all cases. Higher grades of IDD are more likely for patients with both higher TE and heavier physical workload (OR 2.011) at level L3-L4. At levels L4-L5 and L5-S1 higher degree of IDD was more likely for females with heavier physical workload (OR 1.978 and 2.433 respectively). Conclusion. Symptomatic discs show higher frequency of higher grades of IDD but herniation does not occur solely at the disc of the most prominent degenerative changes. The results suggest importance of inter-influence of physical workload and the years of employment and the inter-influence of physical workload and gender, on degeneration of lumbar discs.

The toxicity of benzene is not an issue of the past, especially in developing countries. Bone marrow toxicity is demonstrated among workers. In this study, the effect of simultaneous exposure to benzene and ethanol on benzene metabolism in mice was investigated by measuring the excretion of thioethers in urine. Urinary thioether excretion significantly decreased in the mice receiving both benzene and ethanol compared with the animals receiving benzene only. The assay of determining thioethers in urine samples in this study is a simple and low-cost method, thus suitable for routine use, especially in developing countries, not only for benzene, but also for other alkilating agents, which can be found during occupational exposure. Our results suggest that further research is needed to elucidate the mechanisms of decreased urinary excretion of thioether after simultaneous exposure to benzene and ethanol.

Osteoporotic bone is a bone with decreased bone density and due to that predispose for fractures. Aim. To determine frequency of risk factors, type and localization of fractures in patients with decreased bone density. Material and method. Analysis included 763 patients of both sex. Osteodensitometry was performed and data on clinical risk factors for osteoporosis and osteoporotic fractures were collected. Results. Most of patient were female (96%) and average age was 63 years. The most frequent risk factors were early menopauses, previous fractures and fractures in relatives. Most of patients with osteoporotic fractures had T score of hip on osteopenia level and type was predominantly nonvertebral. Vertebral fractures were more frequent in patients with T score -2,5 SD. Conclusion. Besides osteodensitometry finding of decreased bone density, identifying of clinical risk factors for osteoporosis is essential for early making of diagnosis of osteoporosis and prevention of osteoporotic fractures.

Herbicide 2,4-dichlorophenoxyacetic acid (2,4-D), a synthetic auxin which promotes uncontrolled plant growth is widely used. The aim of our study was to investigate, using an experimental model, the effect of herbicide 2,4-D on liver function tests, enzyme a amylase and glucose blood level. BALB/C mice were treated i.p. with the herbicide (30 mg/ kg 2,4-D) for four consecutive days. Twenty-four hours after the last injection, the treated and the control animals were weighed and sacrificed for biochemical analysis: haematocrit, glucose blood level, serum activities of enzymes alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transferase, and a amylase, as well as liver reduced glutathione. Herbicide 2,4-D significantly decreased glucose blood level in mice. There were no changes in liver function tests or activity of enzyme a amylase. In this study on mice we confirmed the results obtained in the previous study, which showed a hypoglycemic effect of herbicide 2,4-D on agricultural workers. To elucidate the mechanism of this effect, a further research is needed.

Medicinske sestre svih nivoa obrazovanja, bez obzira na vrstu ustanove u kojoj rade, mogu da obavljaju istraživacku delatnost ukoliko ovladaju istraživackom metodologijom. Sestrinstvo se kao naucna disciplina razvija putem istraživanja. Istraživacka delatnost je od kljucne važnosti za uspostavljanje najbolje moguce prakse i protokola, kao i vodica zasnovanih na dokazima.

Indisputable is the value of pesticides for increased yield in agriculture. However, hazardous effects on man and environment are also evident. Pesticide skin absorption is probably of particular importance when pesticides are used in developing countries, because adequate protective measures are rarely applied. Aim. The aim of the study was to investigate frequency of the use of personal and hygienic work health measures in agricultural workers during pesticide application. Material and method. The study included 117 male agricultural workers involved as tractor drivers in pesticide application at the workplace. We collected data concerning age, working conditions, duration of exposure and the use of personal and hygienic work health measures. Results. Average exposure to various pesticides was 4-6 month per year and 4-7 hours per day. Concerning personal protective measures frequent use of gloves was found in 65%, and frequent use of working suit, mask and shoes in 46% interviewed workers. Gloves had never been used by 13% of workers, because they considered them uncomfortable. Hygienic measures of washing hands and taking shower after the work with pesticides were done by 65% workers. Conclusion. For the effective health protection of the exposed agricultural workers to pesticides, the essential is a comprehensive and continuous implementation of the safety measures at work (technical, personal, hygienic, legislative, medical etc.) for the purpose of reducing amount of pesticides which enter in the organism of workers and early detection of worker's health damage. .

Background/Aim. Stevioside is a glycoside that supposedly possesses a number of pharmacodynamic effects such as anti-infective, hypoglycemic, along with the beneficial influence on the cardiovascular system. The aim of this study was to determine the effect of rats pretreatment with aqueous solution of stevioside on pharmacological actions of adrenaline, metoprolol and verapamil. Methods. Rats were administered (intraperitoneally 200 mg/kg/day) stevioside as aqueous solution or physiological saline in the course of 5 days, then anaesthetized with urethane and the first ECG recording was made. The prepared jugular vein was connected to an infusion pump with adrenaline (0.1 mg/mL), verapamil (2.5 mg/mL) or metoprolol (1 mg/mL). Control animals, pretreated with saline, in addition to the mentioned drugs, were also infused with the solution of stevioside (200 mg/mL) in the course of recording ECG. Results. The infusion of stevioside produced no significant changes in ECG, even at a dose exceeding 1,600 mg/kg. In the control group, a dose of adrenaline of 0.07 ± 0.02 mg/kg decreased the heart rate, whereas in the steviosidepretreated rats this occurred at a significantly higher dose (0.13 ± 0.03 mg/kg). In stevioside-pretreated rats, the amount of verapamil needed to produce the decrease in heart rate was significantly lower compared to the control. The pretreatment with stevioside caused no significant changes in the parameters registered on ECG during infusion of metoprolol. Conclusion. The results suggest that pretreatment with stevioside may change the effect of adrenaline and verapamile on the heart rate. [Projekat Ministarstva nauke Republike Srbije, br. 41012]

A 45-year-old woman was referred for CT of the abdomen due to endoscopically detected esophageal varices. The patient complained of dizziness and long-term epigastric pain. The CT scan showed five aberrant splenic nodules (Picture a), a short pancreas (Picture b, arrowhead), a preduodenal portal vein (Picture b, arrow), intestinal malrotation (Picture c) and a symmetric midline position of the liver (Picture c), all of which were consistent with a diagnosis of polysplenia syndrome. Polysplenia syndrome (PSS) is a rare congenital disease that occurs in patients with two or more spleens and various organ anomalies. Unlike that occurring in children, PSS in adults is usually asymptomatic and discovered incidentally since cardiovascular anomalies are minor or nonexistent (1). However, anomalies of the abdominal viscera sometimes lead to clinical manifestations or represent a surgery danger (2). Fortunately, conducting a careful analysis of systemic anomalies, which is required in medical evaluations, is therefore facilitated using modern imaging techniques.

Traumatic brain injury sometimes can lead to psychotic disorder which resembles schizophrenia. We report a 17-year-old boy, admitted to psychiatric department for psychotic symptomatology. He had suffered penetrating craniocerebral injury after stabbing by a billiard stick, three years earlier. On admission, he expressed delusions with paranoid and religious content. The magnetic resonance imaging of the brain showed a 10 cm large tubular area of posttraumatic encephalomalacia of the left hemisphere, whereas the electroencephalography revealed slow left temporal activity. The patient's recovery was uneventful with clozapine at a dosage of 100 mg daily. This case shows the diagnostic challenge in differentiation between schizophrenia and psychotic disorder due to traumatic brain injury. The authors emphasise the importance of imaging of the brain, especially magnetic resonance, in establishing the diagnosis of psychotic disorder due to traumatic brain injury.

Introduction. Dental professionals may be at increased risk of developing occupational allergic diseases specially to methacrylates that can permeate protective disposable gloves. Case report. We presented a case of occupational allergic contact dermatitis in a 28-year-old dental technician. The patient had complained of itching and cracking of fingers for 6 months. The dermatitis improved over weekends. Skin erythema and scaling were present with primarily involvement of the fingertips. Patch testing with dental series gave positive vesicular reaction to methyl methacrylate. Follow-up after 6 months of allergen avoidance showed a complete regression of dermatitis. Conclusion. Methacrylates serve as bases for acrylic resins which are used in prosthetics. Methyl methacrylate as a small molecular acrylate can permeate thin protective disposable gloves. Using adequate personal protective equipment, like nitrile rubber gloves, is the most important preventive measure in this occupation. Health practitioners should recognize possible occupational hazards in dentistry and implement appropriate preventive measures to protect health of workers.

Influence of two newly synthesized bile acids derivates, namely sodium salt of monoketocholic acid MKH-Na and methyl ester of monoketocholic acid MKH-Me on tramadol (12.5 mg/kg oral and intramuscular) analgesic effect was examined in this research. Analgesic effect was measured by antinociceptive hot plate method. Interaction was estimated by detection of changes in analgesic effect of tramadol combined with bile acids (subcutaneous administration of 4 mg/kg 20 min before tramadol) compared to analgesic effect of the same dose of tramadol given alone. Hydrosoluble sodium salt of monoketocholic acid did not show interaction with tramadol, regardless of the route of administration of tramadol. However, methyl ester of monoketocholic acid increased the analgesic effect of tramadol when it was given intramuscularly. After oral administration of tramadol, methyl ester of monoketocholic acid decreased the analgesic effect of tramadol. According to the time point when interaction reached statistically significant difference, it can be presumed that after intramuscular administration of tramadol, methyl ester of monoketocholic acid increases tramadol absorption and transport to brain and in that way increases its analgesic effect. The analgesic effect of tramadol after oral administration was decreased, which could be explained by the induction of tramadol metabolism in the liver, but should be examined in more details.

The aim of ths study was to investigate the pharmacokinetics of cefotaxime sodium (CEF) pharmacokinetics after oral application in the form of sodium 3alpha,7alpha-dihydroxy-12-keto-5beta-cholanate (MKC) microvesicles (MV) in rat. Thirty Male Wister rats were divided into six groups (n=5 per group). Groups were treated orally with: (i) CEF (15 mg/kg) saline solution (15 mg/kg); (ii) CEF (15 mg/kg) saline solution with MKC (2 mg/kg); (iii) CEF saline solution mixed with blank microvesicles; (iv) CEF (15 mg/kg) encapsulated in microvesicles with saline solution; (v) CEF saline solution (15 mg/kg) mixed with blank MKC microvesicules; (vi) CEF (15 mg/kg) encapsulated in MKC microvesicules with saline solution. Data were analyzed using noncompartmental model. CEF oral bioavailability was increased twofold when coadministered with MKC and when encapsulated in microvesicles and ninefold when encapsulated in MKC microvesicles compared to the same CEF dose administered orally as saline solution. The increased bioavailability of CEF resulting from CEF encapsulation in microvesicules with MKC suggests that this formulation can extend the application of CEF from parenteral only to oral application.

Rates of fatal accidents per 100,000 workers in industry are indicators of achievement in occupational safety and health. The pattern of fatal occupational accidents varies in different regions of the world particularly in developing countries. In global estimates of fatal occupational accidents by Takala J (1999) from the International Labour Organization there are no data related to fatal occupational accidents in the Federal Republic of Yugoslavia. There are no known published studies of occupational fatalities in Yugoslavia to date. The Autonomous Province of Vojvodina is the most developed economic region in Yugoslavia. Vojvodina has an area of 21,506 km with a population of roughly 2 million. The purpose of this study was to examine the characteristics of fatal occupational injuries in the Vojvodina, the most developed region in Yugoslavia, by industry and cause of death, and the influence of the economic situation on fatal occupational injury rates in the 1990s.

Synopsis The increased incidence of congenital postural deformities among newborns with breech presentation may be associated with causes of breech presentation rather than the presentation itself.

The most important safety measure for prevention of CO poisoning is the installation of automatic systems that signal high CO concentrations in the work environment. Public health measures that include stringent pollution control, introduction of low-cost CO monitors, and public education aimed at the high-risk population (e.g., new workers, drivers) should decrease the number of deaths from CO poisoning and should save productive years of life. Toxicity of CO is a consequence of tissue hypoxia created by the displacement of oxygen from hemoglobin and the subsequent impairment of oxygen release to the tissues. Early symptoms of CO intoxication are insidious and can resemble other diseases; physical examination may be unremarkable. For these reasons, many cases of CO poisoning are not readily recognized.

Benzene has been widely used as a solvent, but its use is declining in most developed countries because it is a well established human carcinogen. An association between occupational exposure to benzene and health effects such as aplastic anaemia and leukaemia has been reported in studies of workers in various industries. For many solvent uses benzene has been replaced by other less toxic organic solvents and is considered a toxic impurity in other industrial solvents, but it is still used as a starting material in numerous chemical syntheses. In addition to industrial sources, benzene is present in the environment as a component of cigarette smoke and automobile emissions. Benzene induces hematotoxicity as a result of chronic exposure. Acute exposure to benzene causes neurotoxic and hepatotoxic effects. Toxic effects of benzene, chronic as well as acute, are the consequence of the unknown reactive metabolite produced by cytochrome P-450. Benzene is metabolized mainly by ethanol inducible cytochrome P-4502E1 (CYP2E1) in animal and human liver microsomes. Ethanol is consumed worldwide in tremendous amounts and is an effective inducer of hepatic xenobiotic metabolism, especially involving pathways accomplished by the isoform CYP2E1 of cytochrome P-450. Therefore, whenever xenobiotics that are substrates of CYP2E1, such as many organic solvents, are taken in by an individual who is also chronically consuming ethanol, the accelerated metabolism of these agents has to be considered. In contrast to the long-term consumption of ethanol, which induces the hepatic metabolism of xenobiotics, short-term consumption inhibits their metabolism because of direct competition for CYP2E1. Ethanol, when given to a living body, exerts dual effects on the xenobiotic metabolizing enzymes, i.e., inhibition and stimulation. Which one is more predominant over the other depends on the time that has elapsed after ethanol ingestion. In an early period when ethanol exists in the body in high concentrations, it may preferentially act as an inhibitor . In this study, effect of simultaneous exposure to benzene and ethanol on benzene metabolism in mice were investigated by measuring the concentration of phenol, the main metabolite of benzene.

The aim is to investigate the influence of the antidiabetic drug gliclazide on the ileal permeation of the semisynthetic bile acid, MKC, in tissues from healthy and diabetic rats. Sixteen Wistar rats (350 +/- 50 g) were randomly allocated into four groups (4 rats per group, 8 chambers per rat, i.e., n=32) two of which were made diabetic (given alloxan i.v. 30 mg/kg). Group 1 was used to measure the permeation of MKC (50 microg/ml) alone (control) while group 2 to measure MKC permeation in the presence of gliclazide (200 microg/ml). The diabetic groups 3 (gliclazide) and 4 (MKC+gliclazide) were treated in the same way. Rats were sacrificed and tissues were mounted into the Ussing chamber for the measurement of MKC mucosal to serosal (absorptive) and serosal to mucosal (secretory) fluxes. In healthy tissues, gliclazide reduced MKC absorptive flux (p0.01) and increased its secretory flux (p0.01). In diabetic tissues, gliclazide had no effect on either the absorptive or the secretory fluxes of MKC. The lack of effect of gliclazide on MKC permeation in diabetic tissues suggests the absence or suppressed drug transporters. Furthermore, gliclazide inhibition of MKC absorptive flux and induction of MKC secretory flux in healthy tissues may result from the selective inhibition of an efflux drug transporter.