Constant increase of meat quantity along with ensuring its high quality are nowadays being the pr... more Constant increase of meat quantity along with ensuring its high quality are nowadays being the priority requirements of the market towards modern meat production. With selection and animal nutrition as the basic mechanisms regulating the quantity and quality of meat, in recent years more attention has been devoted to investigations of the effects of different chemical compounds on muscle tissue, while monitoring their potential negative effects on both animals and humans as the end consumers. A group of compounds that is being increasingly studied in the last years are phytoestrogens-substances of plant origin with chemical structure very similar to estrogen, capable of causing either estrogenic or antiestrogenic reactions in the organism. The most studied phytoestrogens are daidzein and genistein, and due to their ability to mimic estrogen in the body, they are thought to be able of influencing growth and carcass composition in farm animals. This paper gives an overview of the newer results on the effects of phytoestrogens genistein and daidzein on skeletal muscle tissue in farm animals.
Background. Hepatitis C virus (HCV) infection is the most frequent cause of chronic hepatitis, ci... more Background. Hepatitis C virus (HCV) infection is the most frequent cause of chronic hepatitis, cirrhosis, and hepatocellular carcinoma in the world. Acute hepatitis C is the most commonly asymptomatic liver disease with the development of chronic HCV infection in the majority of infected patients. Studies of the natural history of HCV infection suggest that only 15-30% of patients with acute infection recover spontaneously. Others, up to 85% of the infected patients develop chronic hepatitis C. Acute hepatitis C is so uncommon and with the unpredictable occurrence, and of the low frequency, that it is difficult to determine the optimal treatment of this disease. There have been many randomized, controlled trials of the therapy in patients with chronic hepatitis C, but none of an adequate size or rigor in patients with acute hepatitis C. Therefore, the causal treatment of patients with acute hepatitis C aimed at the prevention of chronic liver disease is necessary. Case report. We have treated a patient with anicteric form of acute hepatitis C after a three-month outpatient follow-up using a combined therapy: pegylated interferon-alpha 2a, 180 μg, subcutaneously, once a week plus ribavirin 1000 mg orally once a day. The treatment lasted 24 weeks. Stable biochemical and virological response was achieved both at the end of the treatment and 6 months after the completion of the therapy. Conclusion. We believe that the above mentioned might be one of the approaches to the treatment of acute hepatitis C. Howerer, further prospective studies with significantly larges number of patients are necessary for the definite conclusions about the tretament of HCV infections.
The effect of different frequencies of direct subtetanic electrical stimulation (14, 20, and 30 H... more The effect of different frequencies of direct subtetanic electrical stimulation (14, 20, and 30 Hz) and aminophylline (AMPh) pretreatment on the effect of N G-nitro-L-arginine methyl ester (L-NAME) (1 mM) on isolated rat diaphragm was investigated. L-NAME potentiated tension developed (Td) in the diaphragm pretreated with a single concentration of AMPh (1.08 mM) in a frequency-dependent manner. The effect was significantly different in comparison with muscle incubated 30 min with Tyrode solution only. In the muscle pretreated with cumulative concentrations of AMPh (0.36-3.60 mM), the frequency-dependent potentiation of Td induced by L-NAME and the difference between L-NAME-treated and untreated muscle were lost.
Introduction: After six decades of antibiotic use, the prevalence of antibiotic-resistant bacteri... more Introduction: After six decades of antibiotic use, the prevalence of antibiotic-resistant bacteria is increasing, and organisms resistant to almost all antibiotics have been identified. Antibiotic resistance: It is important to understand why antibiotic resistance develops, in order to design strategies for its prevention. Factors that promote antibiotic resistance in community and hospital settings are: antibiotic selective pressure, prolonged antibiotic treatment, inadequate doses, prior use of a less effective drug of the same antibiotic class, protected sites or foreign bodies, and poor infection control practice. The best available ways to decrease and control antibiotic resistance are: rational use of antibiotics (e.g. appropriate selection of drug, dose, duration of treatment), good infection control procedures (hygienic practice and isolation), as well as local, national and global surveillance networks for monitoring dissemination of antimicrobial resistance and detection of new resistance mechanisms. Conclusion: Clinical guidelines, direct education, and regular reports on antibiograms may contribute to more prudent use of antibiotics. Overall, the problem of antibiotic resistance is global. However, measures need to be taken at an individual, institutional, and ultimately at national healthcare level.
We investigated the influence of CP and PC mutations and early on-treatment responses on efficacy... more We investigated the influence of CP and PC mutations and early on-treatment responses on efficacy for HBeAg-negative patients. Methods: Key patient entry criteria were HBsAg positive, HBeAg negative, HBV DNA > 6 logl0 by COBAS PCR assay, ALT 1.3 10 • ULN, and compensated liver disease. Baseline serum samples were tested by InnoLipa assays to detect CP (A17621G1764) and PC (stop-codon 28) mutations. Results: HBV genotype prevalence was: A 5.9%; B 26.6%; C 39.4%; D 27.3%; other 1.1%. The pattern of mutations down-regulating HBeAg expression differed by HBV genotype: in genotype A CP was found alone (54%) or together with PC (27%); for genotype B 7% and 42%; genotype C 27% and 51%; genotype D 2% and 74%, respectively. Telbivudine was superior to lamivudine on all measures of direct antiviral efficacy (Table). Efficacy outcomes were not affected by the pattern of precore/core mutations. On multivariate analysis, HBV DNA level achieved by week 24 was the best predictor of antiviral response and low resistance at 1 year. Endpoint Core promoter/pre-core mutation(s) Overall a Core prom.
Background/Aim. The natural history of hepatitis C virus (HCV) infection is variable and the fact... more Background/Aim. The natural history of hepatitis C virus (HCV) infection is variable and the factors determining the course of the illness are unclear. There are geographical variations in the distribution of different HCV genotypes, and some of them are related to the specific infection routes. Regarding our country, the dominant genotype is genotype 1b. It is unclear and still remains a question whether the distinct histopathological manifestations are related to the particular genotypes of HCV. Thus, the aim of this study was to determine whether the distinct histopathological manifestations of HCV infection might be in relation to the individual virus genotype. Methods. In this study we examined 126 patients with chronic HCV infection regarding the histopathological features, demographic data, and virus genotype. The observed groups of patients were predominantly infected with HCV genotypes 1b and 3a. Results. In this study we found that the patients infected with HCV genotype 1b had more frequently moderate or severe necroinflammatory activity of the disease, significantly higher grading score as compared with other genotypes (p < 0.0001). A higher degree of fibrosis was, also, more common in the patients infected with genotype 1b of HCV as compared with other genotypes (p < 0.05). There were no significant correlations between the necroinflammatory activity of the disease and the stage of fibrosis in 1b, 4 and mixed genotypes. Conclusion. The present data support the hypothesis that distinct genotypes of HCV are associated with the particular histopathological manifestation of the disease.
Fractal and GLCM algorithms were performed on PAS-stained kidney medullar tissue. A total of 320 ... more Fractal and GLCM algorithms were performed on PAS-stained kidney medullar tissue. A total of 320 digital micrographs were analyzed. For each micrograph 7 parameters of fractal and GLCM algorithms were calculated. The methods were successfully able to discriminate the damaged from the normal tissue.
Acute pretreatment with a single i.v. bolus injection of simvastatin (1 mg / kg) significantly pr... more Acute pretreatment with a single i.v. bolus injection of simvastatin (1 mg / kg) significantly protects rat kidney injured by ischemia-reperfusion (I / R) (45 min + 6 h). We aimed to determine the optimal timing of such a pretreatment. The effects of both injections of simvastatin before ischemia and reperfusion were similar regarding total histological score. However, simvastatin injected 30 min before ischemia was 30%-75% more effective in reduction of serum creatinine levels and interstitial edema score, while its injections 5 and 30 min before reperfusion were 25%-60% more effective in reduction of tubular necrosis score and fractional excretion of Na +. However, the observed differences do not seem to offer significant advantage in clinical settings.
Fentanyl, the prototype of the 4-anilidopiperidine class of synthetic opioid analgesics, is widel... more Fentanyl, the prototype of the 4-anilidopiperidine class of synthetic opioid analgesics, is widely and successfully used to supplement general anesthesia or to treat postoperative and cancer pain. However, like other m agonists, fentanyl produces serious adverse effects including respiratory depression, muscle rigidity and on prolonged use, tolerance and addiction. In order to discover an analgesic with the improved pharmacodynamic and pharmacokinetic profile, extensive efforts during last four decades have been devoted to synthesis of a large number of fentanyl analogues and establishing the structure-activity-relationship (SAR) of the 4-anilidopiperidine class of analgesics. The objective of SAR studies is to approach the ideal analgesic profile focusing mainly on potency, safety and duration of action. As a result of such efforts, several congeners of fentanyl: alfentanil, sufentanil and remifentanil were discovered and have found clinical use as anesthesia adjuncts. Several other compounds are still under extensive evaluation in animals nowadays, while some of them are proposed as a useful tools in studying the opioid receptors. An interesting SAR obtained with some newly synthesized 3-alkyl fentanyl analogues, as well as 3-carbomethoxy fentanyl (iso-carfentanil) is presented and discussed in this paper. The analgesic potency of 3-carbomethoxy fentanyl is influenced mainly by the steric factor (voluminosity of the carbomethoxy group and the cis/trans isomerism), while the chemical nature of the group is probably irrelevant. In contrast to potency, the duration of action of 3-carbomethoxy fentanyl is most likely influenced by the nature of the carbomethoxy group. Since the potency and the duration of action of this novel analgesic compound are interesting from the aspect of SAR studies, and have potential promise for clinical use, 3-carbomethoxy fentanyl deserves to be extensively evaluated.
The effects of different concentrations of N G-nitro-L-arginine methyl ester (L-NAME) (0.3, 1, 3,... more The effects of different concentrations of N G-nitro-L-arginine methyl ester (L-NAME) (0.3, 1, 3, and 10 mM), a non-selective inhibitor of NOS, on the effect of aminophylline on the isometric contraction of the isolated rat hemidiaphragm were investigated. The muscle contractions were induced by direct subtetanic electrical stimulation. Aminophylline (0.36-3.60 mM) produced a typical concentration-dependent increase in both parameters of the isometric contraction: tension developed (Td) and the maximum rate of rise of tension (dT / dt max). The second series of additions of aminophylline produced a more pronounced effect. L-NAME (0.3, 1, 3, and 10 mM, 30 min of incubation without stimulation) itself did not change Td and dT / dt max. However, L-NAME (1, 3, and 10 mM) produced a statistically significant potentiation of the effect of aminophylline on Td and dT / dt max.
Background: Peripheral facial nerve palsy is a relatively frequent, rather idiopathic, and isolat... more Background: Peripheral facial nerve palsy is a relatively frequent, rather idiopathic, and isolated nonprogressive disorder with a tendency toward spontaneous recovery in children. It is primarily characterized by unilateral paresis or paralysis of the mimic musculature, affecting verbal communication, social interactions, and quality of life. Objective: This study aimed to evaluate the clinical aspects and efficacy of different therapeutic modalities in the population of children and adolescents with acute peripheral facial nerve palsy, the quality and recovery rate in comparison to different therapy modalities and etiological factors as well as to determine parameters of recovery according to the age of patients. Methods: The retrospective study included children and adolescents (n=129) with an acute onset of peripheral facial nerve palsy, diagnosed and treated in the Clinic of Neurology and Psychiatry for Children and Youth in Belgrade (2000-2018). The mean age of the patients wa...
Constant increase of meat quantity along with ensuring its high quality are nowadays being the pr... more Constant increase of meat quantity along with ensuring its high quality are nowadays being the priority requirements of the market towards modern meat production. With selection and animal nutrition as the basic mechanisms regulating the quantity and quality of meat, in recent years more attention has been devoted to investigations of the effects of different chemical compounds on muscle tissue, while monitoring their potential negative effects on both animals and humans as the end consumers. A group of compounds that is being increasingly studied in the last years are phytoestrogens-substances of plant origin with chemical structure very similar to estrogen, capable of causing either estrogenic or antiestrogenic reactions in the organism. The most studied phytoestrogens are daidzein and genistein, and due to their ability to mimic estrogen in the body, they are thought to be able of influencing growth and carcass composition in farm animals. This paper gives an overview of the newer results on the effects of phytoestrogens genistein and daidzein on skeletal muscle tissue in farm animals.
Background. Hepatitis C virus (HCV) infection is the most frequent cause of chronic hepatitis, ci... more Background. Hepatitis C virus (HCV) infection is the most frequent cause of chronic hepatitis, cirrhosis, and hepatocellular carcinoma in the world. Acute hepatitis C is the most commonly asymptomatic liver disease with the development of chronic HCV infection in the majority of infected patients. Studies of the natural history of HCV infection suggest that only 15-30% of patients with acute infection recover spontaneously. Others, up to 85% of the infected patients develop chronic hepatitis C. Acute hepatitis C is so uncommon and with the unpredictable occurrence, and of the low frequency, that it is difficult to determine the optimal treatment of this disease. There have been many randomized, controlled trials of the therapy in patients with chronic hepatitis C, but none of an adequate size or rigor in patients with acute hepatitis C. Therefore, the causal treatment of patients with acute hepatitis C aimed at the prevention of chronic liver disease is necessary. Case report. We have treated a patient with anicteric form of acute hepatitis C after a three-month outpatient follow-up using a combined therapy: pegylated interferon-alpha 2a, 180 μg, subcutaneously, once a week plus ribavirin 1000 mg orally once a day. The treatment lasted 24 weeks. Stable biochemical and virological response was achieved both at the end of the treatment and 6 months after the completion of the therapy. Conclusion. We believe that the above mentioned might be one of the approaches to the treatment of acute hepatitis C. Howerer, further prospective studies with significantly larges number of patients are necessary for the definite conclusions about the tretament of HCV infections.
The effect of different frequencies of direct subtetanic electrical stimulation (14, 20, and 30 H... more The effect of different frequencies of direct subtetanic electrical stimulation (14, 20, and 30 Hz) and aminophylline (AMPh) pretreatment on the effect of N G-nitro-L-arginine methyl ester (L-NAME) (1 mM) on isolated rat diaphragm was investigated. L-NAME potentiated tension developed (Td) in the diaphragm pretreated with a single concentration of AMPh (1.08 mM) in a frequency-dependent manner. The effect was significantly different in comparison with muscle incubated 30 min with Tyrode solution only. In the muscle pretreated with cumulative concentrations of AMPh (0.36-3.60 mM), the frequency-dependent potentiation of Td induced by L-NAME and the difference between L-NAME-treated and untreated muscle were lost.
Introduction: After six decades of antibiotic use, the prevalence of antibiotic-resistant bacteri... more Introduction: After six decades of antibiotic use, the prevalence of antibiotic-resistant bacteria is increasing, and organisms resistant to almost all antibiotics have been identified. Antibiotic resistance: It is important to understand why antibiotic resistance develops, in order to design strategies for its prevention. Factors that promote antibiotic resistance in community and hospital settings are: antibiotic selective pressure, prolonged antibiotic treatment, inadequate doses, prior use of a less effective drug of the same antibiotic class, protected sites or foreign bodies, and poor infection control practice. The best available ways to decrease and control antibiotic resistance are: rational use of antibiotics (e.g. appropriate selection of drug, dose, duration of treatment), good infection control procedures (hygienic practice and isolation), as well as local, national and global surveillance networks for monitoring dissemination of antimicrobial resistance and detection of new resistance mechanisms. Conclusion: Clinical guidelines, direct education, and regular reports on antibiograms may contribute to more prudent use of antibiotics. Overall, the problem of antibiotic resistance is global. However, measures need to be taken at an individual, institutional, and ultimately at national healthcare level.
We investigated the influence of CP and PC mutations and early on-treatment responses on efficacy... more We investigated the influence of CP and PC mutations and early on-treatment responses on efficacy for HBeAg-negative patients. Methods: Key patient entry criteria were HBsAg positive, HBeAg negative, HBV DNA > 6 logl0 by COBAS PCR assay, ALT 1.3 10 • ULN, and compensated liver disease. Baseline serum samples were tested by InnoLipa assays to detect CP (A17621G1764) and PC (stop-codon 28) mutations. Results: HBV genotype prevalence was: A 5.9%; B 26.6%; C 39.4%; D 27.3%; other 1.1%. The pattern of mutations down-regulating HBeAg expression differed by HBV genotype: in genotype A CP was found alone (54%) or together with PC (27%); for genotype B 7% and 42%; genotype C 27% and 51%; genotype D 2% and 74%, respectively. Telbivudine was superior to lamivudine on all measures of direct antiviral efficacy (Table). Efficacy outcomes were not affected by the pattern of precore/core mutations. On multivariate analysis, HBV DNA level achieved by week 24 was the best predictor of antiviral response and low resistance at 1 year. Endpoint Core promoter/pre-core mutation(s) Overall a Core prom.
Background/Aim. The natural history of hepatitis C virus (HCV) infection is variable and the fact... more Background/Aim. The natural history of hepatitis C virus (HCV) infection is variable and the factors determining the course of the illness are unclear. There are geographical variations in the distribution of different HCV genotypes, and some of them are related to the specific infection routes. Regarding our country, the dominant genotype is genotype 1b. It is unclear and still remains a question whether the distinct histopathological manifestations are related to the particular genotypes of HCV. Thus, the aim of this study was to determine whether the distinct histopathological manifestations of HCV infection might be in relation to the individual virus genotype. Methods. In this study we examined 126 patients with chronic HCV infection regarding the histopathological features, demographic data, and virus genotype. The observed groups of patients were predominantly infected with HCV genotypes 1b and 3a. Results. In this study we found that the patients infected with HCV genotype 1b had more frequently moderate or severe necroinflammatory activity of the disease, significantly higher grading score as compared with other genotypes (p < 0.0001). A higher degree of fibrosis was, also, more common in the patients infected with genotype 1b of HCV as compared with other genotypes (p < 0.05). There were no significant correlations between the necroinflammatory activity of the disease and the stage of fibrosis in 1b, 4 and mixed genotypes. Conclusion. The present data support the hypothesis that distinct genotypes of HCV are associated with the particular histopathological manifestation of the disease.
Fractal and GLCM algorithms were performed on PAS-stained kidney medullar tissue. A total of 320 ... more Fractal and GLCM algorithms were performed on PAS-stained kidney medullar tissue. A total of 320 digital micrographs were analyzed. For each micrograph 7 parameters of fractal and GLCM algorithms were calculated. The methods were successfully able to discriminate the damaged from the normal tissue.
Acute pretreatment with a single i.v. bolus injection of simvastatin (1 mg / kg) significantly pr... more Acute pretreatment with a single i.v. bolus injection of simvastatin (1 mg / kg) significantly protects rat kidney injured by ischemia-reperfusion (I / R) (45 min + 6 h). We aimed to determine the optimal timing of such a pretreatment. The effects of both injections of simvastatin before ischemia and reperfusion were similar regarding total histological score. However, simvastatin injected 30 min before ischemia was 30%-75% more effective in reduction of serum creatinine levels and interstitial edema score, while its injections 5 and 30 min before reperfusion were 25%-60% more effective in reduction of tubular necrosis score and fractional excretion of Na +. However, the observed differences do not seem to offer significant advantage in clinical settings.
Fentanyl, the prototype of the 4-anilidopiperidine class of synthetic opioid analgesics, is widel... more Fentanyl, the prototype of the 4-anilidopiperidine class of synthetic opioid analgesics, is widely and successfully used to supplement general anesthesia or to treat postoperative and cancer pain. However, like other m agonists, fentanyl produces serious adverse effects including respiratory depression, muscle rigidity and on prolonged use, tolerance and addiction. In order to discover an analgesic with the improved pharmacodynamic and pharmacokinetic profile, extensive efforts during last four decades have been devoted to synthesis of a large number of fentanyl analogues and establishing the structure-activity-relationship (SAR) of the 4-anilidopiperidine class of analgesics. The objective of SAR studies is to approach the ideal analgesic profile focusing mainly on potency, safety and duration of action. As a result of such efforts, several congeners of fentanyl: alfentanil, sufentanil and remifentanil were discovered and have found clinical use as anesthesia adjuncts. Several other compounds are still under extensive evaluation in animals nowadays, while some of them are proposed as a useful tools in studying the opioid receptors. An interesting SAR obtained with some newly synthesized 3-alkyl fentanyl analogues, as well as 3-carbomethoxy fentanyl (iso-carfentanil) is presented and discussed in this paper. The analgesic potency of 3-carbomethoxy fentanyl is influenced mainly by the steric factor (voluminosity of the carbomethoxy group and the cis/trans isomerism), while the chemical nature of the group is probably irrelevant. In contrast to potency, the duration of action of 3-carbomethoxy fentanyl is most likely influenced by the nature of the carbomethoxy group. Since the potency and the duration of action of this novel analgesic compound are interesting from the aspect of SAR studies, and have potential promise for clinical use, 3-carbomethoxy fentanyl deserves to be extensively evaluated.
The effects of different concentrations of N G-nitro-L-arginine methyl ester (L-NAME) (0.3, 1, 3,... more The effects of different concentrations of N G-nitro-L-arginine methyl ester (L-NAME) (0.3, 1, 3, and 10 mM), a non-selective inhibitor of NOS, on the effect of aminophylline on the isometric contraction of the isolated rat hemidiaphragm were investigated. The muscle contractions were induced by direct subtetanic electrical stimulation. Aminophylline (0.36-3.60 mM) produced a typical concentration-dependent increase in both parameters of the isometric contraction: tension developed (Td) and the maximum rate of rise of tension (dT / dt max). The second series of additions of aminophylline produced a more pronounced effect. L-NAME (0.3, 1, 3, and 10 mM, 30 min of incubation without stimulation) itself did not change Td and dT / dt max. However, L-NAME (1, 3, and 10 mM) produced a statistically significant potentiation of the effect of aminophylline on Td and dT / dt max.
Background: Peripheral facial nerve palsy is a relatively frequent, rather idiopathic, and isolat... more Background: Peripheral facial nerve palsy is a relatively frequent, rather idiopathic, and isolated nonprogressive disorder with a tendency toward spontaneous recovery in children. It is primarily characterized by unilateral paresis or paralysis of the mimic musculature, affecting verbal communication, social interactions, and quality of life. Objective: This study aimed to evaluate the clinical aspects and efficacy of different therapeutic modalities in the population of children and adolescents with acute peripheral facial nerve palsy, the quality and recovery rate in comparison to different therapy modalities and etiological factors as well as to determine parameters of recovery according to the age of patients. Methods: The retrospective study included children and adolescents (n=129) with an acute onset of peripheral facial nerve palsy, diagnosed and treated in the Clinic of Neurology and Psychiatry for Children and Youth in Belgrade (2000-2018). The mean age of the patients wa...
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