The Influence of Finasteride on Mean and Relative Spectral Density of EEG Bands in Rat Model of Thioacetamide-Induced Hepatic Encephalopathy.

Liver failure is associated with a neuropsychiatric syndrome, known as hepatic encephalopathy (HE). Finasteride, inhibitor of neurosteroid synthesis, may improve the course of HE. The aim of our study was to investigate the influence of finasteride on mean and relative power density of EEG bands, determined by spectral analysis, in rat model of thioacetamide-induced HE. Male Wistar rats were divided into groups: (1) control; (2) thioacetamide-treated group, TAA (900 mg/kg); (3) finasteride-treated group, FIN (150 mg/kg); and (4) group treated with finasteride (150 mg/kg) and thioacetamide (900 mg/kg), FIN + TAA. Daily doses of FIN (50 mg/kg) and TAA (300 mg/kg) were administered during 3 subsequent days, and in FIN + TAA group FIN was administered 2 h before every dose of TAA. EEG was recorded 22-24 h after treatment and analyzed by fast Fourier transformation. While TAA did not induce significant changes in the beta band, mean and relative power in this band were significantly higher in FIN + TAA versus control group (p < 0.01). TAA caused a significant decline in mean power in alpha, theta, and delta band, and in FIN + TAA group the mean power in these bands was significantly higher compared with control. While in TAA group relative power was significantly decreased in theta (p < 0.01) and increased in delta band (p < 0.01) versus control, the opposite changes were found in FIN + TAA group: an increase in theta (p < 0.01) and a decrease in delta relative power (p < 0.01). In this study, finasteride pretreatment caused EEG changes that correspond to mild TAA-induced HE.

Dynamics of oxidative/nitrosative stress in mice with methionine-choline-deficient diet-induced nonalcoholic fatty liver disease.

Insulin resistance, oxidative stress, and proinflammatory cytokines play a key role in pathogenesis of nonalcoholic fatty liver disease (NAFLD). The aim of our study was to investigate the dynamics of oxidative/nitrosative stress in methionine-choline-deficient (MCD) diet -induced NAFLD in mice. Male C57BL/6 mice were divided into following groups: group 1: control group on standard diet; group 2: MCD diet for 2, 4, and 6 weeks (MCD2, MCD4, and MCD6, respectively). After treatment, liver and blood samples were taken for histopathology, alanine- and aspartate aminotransferase, acute phase reactants, and oxidative/nitrosative stress parameters. Liver malondialdehyde level was higher in all MCD-fed groups versus control group (p < 0.01), while nitrites + nitrates level showed a progressive increase. The activity of total superoxide dismutase and its isoenzymes was significantly lower in all MCD-fed groups (p < 0.01). Although catalase activity was significantly lower in MCD-fed animals at all intervals (p < 0.01), the lowest activity of this enzyme was evident in MCD4 group. Liver content of glutathione was lower in MCD4 (p < 0.05) and MCD6 group (p < 0.01) versus control. : Ferritin and C-reactive protein serum concentration were significantly higher only in MCD6 group. Our study suggests that MCD diet induces a progressive rise in nitrosative stress in the liver. Additionally, the most prominent decrease in liver antioxidative capacity is in the fourth week, which implies that application of antioxidants would be most suitable in this period, in order to prevent nonalcoholic steatohepatitis but not the initial NAFLD phase.

Influence of aging on ethanol-induced oxidative stress in digestive tract of rats.

Aging and ethanol induce oxidative stress due to increased prooxidant production and decreased antioxidative capacity. The aim was to investigate the influence of aging on oxidative stress in liver, stomach and pancreas in acute ethanol intoxication. Adult (3 months) and old (18 months) male Wistar rats were divided into the following groups: control (control group rats aged 3 months (C3) and control group rats aged 18 months (C18)) and ethanol-treated groups (ethanol-treated 3-month-old rats (E3) and ethanol-treated 18-month-old rats (E18)). Ethanol was administered in five doses of 2 g/kg at 12-h intervals by orogastric tube. Tissue samples were collected for the determination of oxidative stress parameters. Malondialdehyde (MDA) concentration was increased in all the experimental groups and investigated organs versus C3 group ( p < 0.01). The highest MDA level was observed in the stomach in E18 group when compared with C18 and E3 groups ( p < 0.01). Activity of total superoxide dismutase (SOD) and its isoenzymes (copper-/zinc-SOD and manganese-SOD) in E18 group was significantly decreased when compared with E3 and C18 groups ( p < 0.01). Nitrates and nitrites (NO x ) concentration was increased in stomach and pancreas for all the groups when compared with C3 group ( p < 0.01). Hepatic, gastric and pancreatic NO x level was significantly increased in E18 group when compared with E3 group ( p < 0.01). Moreover, level of NO x in liver and pancreas in E18 group was significantly increased when compared with C18 group ( p < 0.01). Aging potentiates ethanol-induced oxidative stress in liver, stomach and pancreas due to increased lipid peroxidation and nitrosative stress and decreased antioxidative tissue capacity.

Spectral analysis of thioacetamide-induced electroencephalographic changes in rats.

Thioacetamide (TAA) is widely used as a model of hepatic encephalopathy (HE). The aim of our study was to investigate the effects of TAA on electroencephalographic (EEG) changes in rats and to compare them with human HE. Male Wistar rats were divided into groups: (1) saline-treated group and (2) TAA-treated groups: TAA(300) (300 mg/kg), TAA(600) (600 mg/kg), and TAA(900) (900 mg/kg). Daily dose of TAA (300 mg/kg) was administered intraperitoneally once (TAA(300)), twice (TAA(600)), or thrice (TAA(900)) in subsequent days. EEG changes were recorded about 24 h after the last dose of TAA. Absolute and relative power density in alpha bands were significantly higher in TAA(300) versus control group. In TAA(300), absolute beta power density was higher and relative beta power density was lower versus control group. Absolute alpha, theta, delta, and relative theta power were significantly lower, while relative power in delta band was significantly higher in TAA(900) versus control group (p < 0.01). In conclusion, decrease in EEG voltage with an increase in delta relative power, which correspond to the EEG manifestations of severe HE in humans, was observed in TAA(900) group. Electrical activity in TAA(300) group correlates with mild HE in humans.

Results of the femur fractures treated with the new selfdynamisable internal fixator (SIF).

PURPOSE: As axial dynamisation is a recognised method, many authors using interlocking femoral nail perform an additional small operation two months after the primary operation in order to remove one screw so as to provide axial dynamisation. According to the literature, dynamisation happens in about 15-25% of cases, but it cannot be predicted which patient or fracture will need dynamisation. The aim of this study is to present a new selfdynamisable implant and a minimally invasive method for the internal fixation of different femoral fractures. MATERIALS AND METHODS: The study was conducted between 2000 and 2008 and included 849 patients with 871 fractures receiving the selfdynamisable internal fixator (SIF) for proximal, diaphyseal and distal femur fractures. RESULTS: The average operative time was 44 min (23-119 min) and the average fluoroscopy time was 12 s (6-92 s), while the average blood loss was 90 ml (60-250 ml) when a minimally invasive technique was used. None of the patients developed complications during the intra-operative period. Complete follow-up was available in 726 patients with 738 fractures. The healing time was 3.9 months (3-9 months). Healing was achieved in 99.1% of patients. Superficial infection developed in seven fixations (0.9%), while deep infection developed in four patients (0.5%). Screw-breaking occurred within 6-18 weeks in 19 fixations (2.6%). Cut-out phenomenon happened in 24 cases. Spontaneous axial dynamisation was observed in 71 (23.8%) out of 738 fractures, being 5 mm on average (2-12 mm). CONCLUSION: The SIF is an effective method for the treatment of femoral fractures. This method is particularly valuable in the treatment of comminuted fractures with regard to minimally invasive surgery. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00068-011-0157-7) contains supplementary material, which is available to authorized users.

The correlation between lipid peroxidation in different brain regions and the severity of lindane-induced seizures in rats.

The aim of this study was to investigate the dynamics of lipid peroxidation and the possible correlation between lipid peroxidation in different brain regions and behavioral manifestations in lindane-induced seizures in rats. Male Wistar rats were divided into the following groups: 1. control, saline-treated group; 2. dimethylsulfoxide (DMSO)-treated group; 3. lindane-treated group (8 mg/kg), intraperitoneally. Animals were sacrificed 0.5 or 4 h after treatment and the malondialdehyde level and superoxide dismutase (SOD) activity were determined in various brain regions spectrophotometrically. Behavioral changes were classified according to the descriptive scale (0--no response, 1--head nodding, lower jaw twitching; 2--myoclonic body jerks, bilateral forelimb clonus with full rearing; 3--progression to generalized clonic convulsions followed by tonic extension of fore- and hind limbs and tail; 4--status epilepticus). A significant rise in the malondialdehyde level was detected in the cerebral cortex, hippocampus, and thalamus of lindane-treated animals 0.5 and 4 h after administration (P < 0.05). SOD activity (total and mitochondrial) was significantly decreased in the hippocampus and the cortex of lindane-treated animals at both time points (P < 0.05). An initial fall in SOD activity was detected in the thalamus 4 h after lindane administration (P < 0.05). A positive correlation between seizure severity and the malondialdehyde level was found in the hippocampus at both time points (P < 0.01). These results suggest that lipid peroxidation may contribute to the neurotoxic effects of lindane in early acute lindane intoxication and that behavioral manifestations correlate with lipid peroxidation in the hippocampus of lindane-treated rats.

Oxidative stress in liver and red blood cells in acute lindane toxicity in rats.

The aim of our study was to determine the role and dynamics of oxidative and nitrosative stress, as well as superoxide dismutase (SOD) and catalase activity in the hepatocytes and erythrocytes in early phase of acute lindane intoxication. Male Wistar rats were divided into groups: control, dimethylsulfoxide and lindane-treated groups (L, 8 mg/kg, intraperitoneally). Animals were sacrificed 0.5 and 4 hours after treatment (L(0.5) and L(4) groups, respectively). Oxidative and nitrosative stress parameters and antioxidant enzymes were determined spectrophotometrically. Liver and plasma thiobarbituric acid reactive substances (TBARS) concentration were significantly increased 0.5 after lindane administration (p < .01), with subsequent additional rise within 4 hours (p < .01), while plasma nitrite + nitrate level was significantly higher only 4 hours after lindane treatment. Total liver SOD activity was significantly increased in L(4) group in comparison with control group (p < .01). In conclusion, oxidative and nitrosative stress play an important role in early phase of acute lindane hepatotoxicity. Antioxidant capacity of hepatocytes is partly increased, due to an adaptive increase in SOD activity.

Liver antioxidant capacity in the early phase of acute paracetamol-induced liver injury in mice.

The aim of our study was to investigate the relationship between liver antioxidant capacity and hepatic injury in the early phase of acute paracetamol intoxication in mice. Male Swiss mice were divided into groups: (1) control, that received saline, (2) paracetamol-treated group (300 mg/kg intraperitoneally). Animals were sacrificed 6, 24 and 48 h after treatment. Oxidative stress parameters were determined in blood and liver samples spectrophotometrically. Liver malondialdehyde and nitrite + nitrate level were significantly increased 6 h after paracetamol administration in comparison with control group (p < 0.05). Paracetamol induced a significant reduction in total liver superoxide dismutase (SOD) and copper/zinc SOD activity at all time intervals (p < 0.01). However, manganese SOD activity was significantly increased within 6 h (p < 0.01), while its activity progressively declined 24 and 48 h after paracetamol administration in comparison with control group (p < 0.01). Content of sulfhydryl groups in the liver was increased 24 h after paracetamol administration (p < 0.05), while its level was decreased within next 24 h when compared to control animals (p < 0.01). Our data showed that liver antioxidant capacity increases in first 24 h of paracetamol-induced liver injury were in correlation with manganese SOD activity and increase in level of sulfhydryl groups.

Effect of acute lindane and alcohol intoxication on serum concentration of enzymes and fatty acids in rats.

This study examines possible synergistic effects of lindane and ethanol on inducing liver injury and serum fatty acid derangement in adult male Wistar rats. When administered together, ethanol and lindane-induced even more pronounced increase of alanine aminotransferase (165 +/- 10 U/L) and gamma-glutamyltranspeptidase activity (10.3 +/- 0.6 U/L) than after isolated administration of either substance. In addition, separate administration of lindane and ethanol was followed by a significant decrease of linoleic acid level in the serum (301 +/- 38 mg/L, 276 +/- 35 mg/L vs. 416 +/- 48 mg/L). However, when ethanol administration was followed by lindane injection, serum linoleic acid was at the similar level found in the control group (516 +/- 62 mg/L). Ethanol-treated rats that received lindane 30 min after ethanol administration have shown a marked increase of palmitic (421 +/- 27 mg/L) and linolic acid level (43 +/- 5 mg/L) in comparison with rats that have been treated only with ethanol (316+/-26 mg/L for palmitic and 32 +/- 2 mg/L for linolic acid) or lindane (295 +/- 26 mg/L for palmitic and 301 +/- 38 mg/L for linolic acid). Linolic acid level was significantly greater in comparison with control group (29 +/- 1 mg/L). In conclusion, this study found enough evidence to support the hypothesis that acute ethanol intoxication potentiates lindane-induced liver injury and enhances lipid derangement.

[Treatment of femoral shaft fractures in polytrauma patients using Mitkovic type internal fixator].

Polytrauma remains a major social, economic and medicine affliction. Successful surgical treatment of polytrauma patient's requires an approach predicated on prioritizing injuries. An isoleted fractures rarely poses any threat but in association with multiple injuries, a fractures assumes greater significance. Proper management of femur fractures in po-lytrauma can gretly reduce the mortality and morbidity. In this work the results of the operative treatments of the femoral shaft fractures in polytrauma patients using Mitkovic type internal fixator (14 patients) and Kuntscher nail (9 patients) are compared. The average patients age was 28.43 years (range 16 to 61). Internal fixation using Mitkovic type internal fixator can be method of choose in treatment of femur fractures in polytrauma patient's. Its application is relatively simple. It doesn't damage the periosteal and meduullary bone vascularization, which favors osteosynthesis and provides considerable contribution in osteogensis.

Ethanol suppressed seizures in lindane-treated rats. Electroencephalographic and behavioral studies.

This study examines the effects of ethanol on lindane-induced seizures in rats. The animals were divided into following groups: 1. saline, 2. DMSO (dimethylsulfoxide), 3. lindane dissolved in DMSO in the dose of 4, 6 or 8 mg/kg (L(4), L(6) and L(8) groups, respectively), 4. ethanol 2 g/kg administered 30 min prior to lindane (protected groups AL(4), AL(6) and AL(8)) and 5. ethanol alone (2 g/kg). In order to determine ethanol concentration in plasma, blood samples were collected by cardiac puncture 30 and 60 min after ethanol injection. For EEG and power spectra recordings, electrodes were implanted into the skull. The lindane treatment resulted in a dose-dependent increase of seizure incidence and severity. The rats displayed severe seizure patterns characterized by high voltage spike-wave complexes, poly-spikes and sleep-like patterns in EEG, while the power spectra were intensively elevated in comparison to the corresponding controls. Ethanol alone led to increased EEG power spectra, which became dominant in the range of 0-4 Hz. For evaluation of anticonvulsant ethanol action we compared latency to seizure, incidence and seizure severity (scale from 0 to 4) in the examined groups. Ethanol diminished seizure incidence in AL(4) and AL(6) groups, decreased intensity of convulsions, and prolonged duration of latency period in AL(8) group. We observed suppression of the EEG signs of lindane-provoked epileptiform activity in AL(4) and AL(6), but not in AL(8) group. These results suggest that ethanol acted protectively on lindane-induced seizures and suppressed behavioral and epileptic EEG spiking activity.

New concept in external fixation.

A new concept in external skeletal fixation is presented. A 3D unilateral system developed by Mitkovic has widely been investigated biomechanically in AO institute in Davos (Switzerland). Consists of three components only providing extremely simple application and dynamic fixation of bones and different joints. This simple external fixator functions as an accurate reduction device at the same time, minimizing need for fluoroscopy. Clinically this system has been applied to mere then 13 thousand patients in 43 clinics. This paper presents the results of its application for treatment of open fractures, war wounds with fractures and for comminuted and intraarticular closed fractures in the series of 597 patients. Overall average time for union time was 3.2 months. Overall success of fracture healing was 96.8% including open and closed fractures. Our study suggests that the use of this 3D unilateral system is suitable for routine use.

New biological method of internal fixation of the femur.

One of the main goals in fracture treatment is reservation of both intramedular and periosteal vascularisation. The aim of this paper is to show a new method of internal fixation which accomplishes these goals. The paper presents the results of clinical application of Mitkovic Internal Fixator, new self-dynamisable device, which provides fixation of the femur using minimally invasive technique. This device has been investigated experimentally on 60 animals. It has been applied to 267 patients. Here is presented a series of 92 fixations of femoral diaphyses after fresh fractures and after unsuccessful treatment using other methods. Follow-up was 3.1 years (2 to 7 years). Bone healing was achieved in all patients within 3.5 months (2.7-9 months) with big amount of periosteal callus formation. There were no complications in all patients seen. It can be concluded that this method and device meet biological and biomechanical requirements for safe fracture treatment.

Reconstructive procedures on lower extremities using Mitkovic external fixation system.

The results of limb lengthening, correction of limb deformities and solving of bone loss, by the use of Mitkovic external fixation system and minimally invasive technique on the series of 96 operations in 89 patients are shown. Only lower extremities were included in this series. The advantages of this external fixation system in comparison to other systems are pointed out. The main advantages are the optimal biomechanical conditions including unilateral but 3-dimensional frame, which provides conditions very similar to natural biomechanical features of the human long bones, simplicity of application and low cost. The received result was excellent or very good in 98.4%. Maximal limb lengthening was 18 cm (at the same time in the femur and the tibia). Angular deformity correction is extremely simplified with minimized possibility of complications. The frame for bone transport is very simple. It can be concluded that presented methods are suitable for routine use.

[Gentamycin-polymethylmethacrylate in the treatment of osteoarticular panaritium]. / Primena gentamicin-polymethyl methacrilata u lecenju osteoartiikularnih panaricijuma.

The authors present treatment results by Gentamicin-polymethyl methacrylate in severe forms of osteoarticular panaritium in the duration of three years when 16 patients with the age ranging form 19 to 64 Years were studied. Serial pearls 7 mm and 5 x 3 mm in diameter were used. The application of pearls was done in pale stasis, upon completing surgical treatment of the fingers and filling of the created cava. The immobilization was placed and 14 days later pearls extracted. Inflammatory process was restrained in all patients with a complete reparation of the fingers' soft tissue. In five patients who had through destruction of the phalangealarticular surfaces developed functional ankylosis in the period of rehabilitation. There were no amputations of the phalanges. Our initial experience in treating destructive inflammatory changes in phalanges by Gentamicin-polymethyl methacrylate points to the shorter treatment period and lower degree of disability when compared to the conventional treatment methods.

[Effectiveness of a lactobacillus vaccine on trichomonas infections in women. Preliminary results]. / Wirkung einer Laktobazillus-Vakzine auf die Trichomonas-Infektion der Frau. Vorläufige Ergebnisse.

This is the report on a multi-centre study of the treatment of 444 women with trichomoniasis vaginalis using Solcotrichovac, a vaccine containing at least 7 x 10(9) inactivated microorganisms of various strains of lactobacillus acidophilus in each 0.5 ml dose. One year after the first vaccination 427 of the patients (96.2%) were followed up, and 92.5% of them were found to be cured of clinical symptoms; the remaining 7.5% must be considered as not cured, as either the slide or the culture was positive. We are convinced by these results that vaccination with Solcotrichovac represents an enhancement of therapeutic opportunities for the treatment of trichomoniasis vaginalis.