Lipopolysaccharide (LPS) is known to induce oxidative stress and inflammation, leading to significant damage in cardiac tissues. This study investigates the protective effects of melatonin (MLT) against LPS-induced oxidative damage, inflammation, and apoptosis in rat heart tissue. Rats were divided into four groups (n = 6 per group): control, melatonin-treated, LPS-treated, and LPS + melatonin-treated. Oxidative stress markers, including thiobarbituric acid-reactive substances (TBARSs) and advanced oxidation protein products (AOPPs), were measured. Additionally, inflammatory markers, such as interleukin-6 (IL-6) levels, inducible nitric oxide synthase (iNOS) and nitric oxide (NO) content, and apoptotic markers, caspase-3, caspase-9, and acidic DNase activity, were evaluated. LPS treatment significantly increased TBARS, AOPP, and IL-6 levels, as well as the activity of caspase-3, acidic DNase and iNOS and NO content compared to the control group. Co-treatment with melatonin significantly reduced the levels of TBARS and AOPP levels, and caspase-3 and acidic DNase activities nearly matched those of the control group, while caspse-9 was still slightly increased. Interestingly, IL-6, iNOS and NO levels were significantly decreased but did not fully match the values in the control group. Melatonin mitigates LPS-induced oxidative stress, inflammation, and apoptosis in rat heart tissue by affecting all studied parameters, demonstrating its potential as a therapeutic agent for conditions characterized by oxidative stress and inflammation. Further research is warranted to explore the clinical applications of melatonin in cardiovascular diseases.

Melatonin (MLT), earlier described as an effective anti-inflammatory agent, could be a beneficial adjunctive drug for sepsis treatment. This study aimed to determine the effects of MLT application in lipopolysaccharide (LPS)-induced sepsis in Wistar rats by determining the levels of liver tissue pro-inflammatory cytokines (TNF-α, IL-6) and NF-κB as well as hematological parameters indicating the state of sepsis. Additionally, an immunohistological analysis of CD14 molecule expression was conducted. Our research demonstrated that treatment with MLT prevented an LPS-induced increase in pro-inflammatory cytokines TNF-α and IL-6 and NF-κB levels, and in the neutrophil to lymphocyte ratio (NLR). On the other hand, MLT prevented a decrease in the blood lymphocyte number induced by LPS administration. Also, treatment with MLT decreased the liver tissue expression of the CD14 molecule observed after sepsis induction. In summary, in rats with LPS-induced sepsis, MLT was shown to be a significant anti-inflammatory agent with the potential to change the liver’s immunological marker expression, thus ameliorating liver function.

Application of cisplatin for the treatment of various solid tumors is known to cause liver damage, through an increase in lipid peroxidation and reactive oxygen species production. Lycopene is a powerful antioxidant agent capable of preventing the cells damage, the formation of stronger intercellular bonds and faster cellular metabolism. This study aims to estimate the potential of lycopene in preventing cisplatin induced liver tissue damage by studying the levels of several biochemical parameters (arginase, aminotransferases, alkaline phosphatase, gamma-glutamyl transpeptidase activity, total protein and albumin concentration) reflecting liver function and a panel of liver tissue biomarkers (xanthine oxidase, reduced glutathione, malondialdehyde, protein carbonylated concentration and diamino oxidase activity). These parameters would be studied in male Wistar rats treated with either cisplatin alone or with cisplatin and lycopene. Additionally, microscopic analysis of liver tissue would be conducted as well. Application of the combination of lycopene and cisplatin significantly prevented the disturbance in all here-studied biomarkers of liver tissue damage. Morphological liver tissue alterations followed the changes in hepatic biochemical status. Our results suggest that lycopene could act as a protective agent in cisplatin-induced liver damage in rats.

IntroductionLiver inflammatory response occurring after toxic chemicals injection, such as cisplatin, causes the aggravation in liver damage. Lycopene, a carotenoid, has previously been proven to possess antioxidant, antiinflammatory and antiapoptotic properties. This study objective was to evaluate for the first time the protective effects of lycopene in cisplatin-induced liver damage based on the disturbances in serum and tissue inflammatory parameters. Also, to confirm the extent of changes in inflammation of the studied tissue, a microscopic analysis will be performed.Material and methodsWistar rats were divided into four experimental groups: (I) control; (II) lycopene (2 mg/kg); (III) cisplatin (10 mg/kg) and (IV) lycopene and cisplatin-treated (2 and 10 mg/kg, respectively) animals. After the experiment, we studied changes in serum liver tissue damage associated parameters (ALT, AST, and γ-GT) and liver inflammatory parameters (NO and TNF-α concentrations, myeloperoxidase and iNOS activity, as well as CD68 expression).ResultsApplication of lycopene prevented a rise in evaluated serum parameters induced by cisplatin, while at the same time it did not cause any harmful effect by itself. Lycopene, alone or in combination with cisplatin, decreased the values of all studied liver inflammatory parameters.ConclusionsWe can conclude that lycopene does not prevent liver tissue inflammatory decalin seen after cisplatin application, however, it prevents tissue damage arising from this cytostatic application.

BACKGROUND:Intellectual disability (ID) is registered in 2%-3% of newborns. In most cases, the causes are not identifiable.OBJECTIVE:We explored the correlation between the intellectual disability and gestational age, birth weight, Apgar score, familial diseases, congenital anomalies, and acquired medical disorders, with the aim to estimate the prevalence and severity of comorbidities in the affected children.METHODS:Our study included 22 children with ID, and 24 with proper psychomotor development, aged 5-10 who were not considered to have ID.RESULTS:The presence of familial disorders and CNS congenital anomalies increased the risk of ID 4.147 and 2.59 times, respectively. The risk for other congenital and noncongenital diseases was higher (7.38 and 1.4 times, respectively) in children with intellectual disability.CONCLUSIONS:Children with intellectual disabilities have higher incidence of congenital diseases, family disorders and a higher frequency of acquired disorders during childhood. Apgar score is a sensitive predictor of morbidity regarding congenital as well as noncongenital medical conditions.

Carbonic anhydrase is a metalloprotein, an enzyme with strong inhibition in antibacterial treatment. This study presents QSAR modeling for a series of 41 chemical compounds, 40 sulfonamides and one sulfamate, including 13 clinically tested drugs as carbonic anhydrase inhibitors based on the Monte Carlo optimization with molecular descriptors based on the SMILES notation and local invariants of the molecular graph, and field 3D based methods. Conformation independent QSAR models were developed for three random splits and a 3D QSAR model for one random split into the training and test sets. The statistical quality of the developed models, including robustness and predictability, was tested using various statistical approaches and the results that were obtained were very good. An excellent correlation between the results from the conformation independent and the 3D QSAR model was obtained. A novel statistical metric known as the index of ideality of correlation was used for the final assessment of the model, and the obtained results were good. Molecular fragments responsible for the increases and decreases of a studied activity were defined and further used for the computer-aided design of new compounds as potential carbonic anhydrase inhibitors. Molecular docking was applied for the final assessment of the developed QSAR model and designed inhibitors, and an excellent correlation between the results from QSAR modeling and molecular docking studies was obtained. Communicated by Ramaswamy H. Sarma

Morbilli is a viral, highly contagious droplet infection belonging to the group of rashcausing fever.The virus enters humans via the respiratory route.The disease starts with a rise in body temperature, "facies morbillosa" cough, catarrhal changes of the mucous membrane of the upper respiratory tract followed by maculopapular rash.The aim of the paper was to analyze epidemiological parameters and the vaccination status of affected children in central Kosovo and Metohija enclaves.The study enrolled 91 children (57.1% boys and 42.9% girls), in the period October 2017-March 2018 in the enclaves where Serbs, Roma, Albanians, Gorani, and Turks live.The diagnosis was established according to epidemiological and clinical parameters, blood count, and findings of specific IgM antibodies.The children were grouped according to gender, ethnicity, age, the origin of the infection, and vaccination status.Numerical properties and attributes are shown.The Student's t-test was used for comparing sets of presented numerical values.The Chi squared (χ 2 ) test and Fisher's exact test were used to illustrate and compare the difference in the frequency of attributive characteristics.The mean age of children was 9.74 ± 4.23 years.The greatest number of patients was in December, 34.1%.The majority of children were of Roma ethnicity.The number of affected unvaccinated Roma children (49.4%) was three times higher in comparison to Serbian children (17.6%) and five times higher in comparison to children of Albanian ethnicity (9.9%), which is a statistically significant difference (χ 2 : p < 0.05).A great number of children (30.7%) got infected in healthcare facilities.The majority of children who received one dose of vaccine were among Serbian children (16.5%).The number of children with nosocomial infections (30.7%) was 6 times higher in comparison to children with unknown source of infection (5.5%) (χ 2 : p < 0.05).In the enclaves of central Kosovo and Metohija, the majority of Roma children were affected because of non-vaccination, inadequate living conditions and migrations.The incidence of nosocomial infections indicates that the morbillivirus spreads rapidly.Morbilli can be eradicated by conducting healthcare education and complete immunization, primarily of Roma children.

AIM: Carbon tetrachloride (CCl4) is an organic chemical that produces different tissue-damaging effects when ingested or inhaled. Present study aims to determine whether the application of exogenous melatonin, a neurohormone with numerous biological properties, can prevent disturbances in lung tissue antioxidative capacities and arginine metabolism, tissue inflammation and oxidative damage induced by exposure to CCl4 in rats. METHODS: The effects of melatonin on the changes occurring in rat lung tissue after an acute exposure to CCl4 were studied by monitoring alterations in antioxidant capacities, inflammatory parameters, parameters of arginine metabolism, and lipid and protein oxidative damage. RESULTS: The results indicated that melatonin prevents CCl4-induced lung damage by mitigating tissue antioxidant capacity and preventing nitric oxide production through a shift from nitric oxide synthase to arginase. Also, melatonin partially prevented tissue inflammation and molecules' oxidative modification seen after exposure to CCl4. CONCLUSIONS: The protective activity of melatonin can be attributed to its ability to scavenge both free radicals, as well as to its potential to increase tissue antioxidant capacity. The modulation of inflammatory response through both decrease in tissue inflammatory parameters and influence on arginine-nitric oxide metabolism might be an additional mechanism of action (Tab. 1, Fig. 2, Ref. 33).

Acute kidney injury is a frequent disorder that can be mimicked by the application of different nephrotoxic agents, including carbon tetrachloride (CCl4), where kidney injury marker-1 (KIM-1) has been recognized as a highly specific marker. Melatonin is one of the most powerful natural antioxidants and has numerous beneficial properties. We evaluated the nephroprotective potential of 2 melatonin treatment regimens (pre- and post-intoxication) in a CCl4-induced acute kidney injury model based on the standard serum parameters, kidney tissue antioxidative capacity, KIM-1 levels, and kidney tissue morphological changes. The two treatment regimens were found to preserve kidney function, as judged from the evaluated standard serum parameters. Only when administered after the intoxication, melatonin preserved total kidney antioxidant capacity; pre-treatment melatonin only preserved reduced glutathione levels. An increase in tissue KIM-1 level was found to be prevented by both treatment regimens, which correlated with the morphological changes seen in the kidney tissues of animals treated with melatonin and CCl4. The findings of our study are in agreement with the known actions of melatonin in relieving kidney tissue oxidative burden, but also contribute to the understanding of its action by preventing an increase in KIM-1.

: This study examined the hepatoprotective and anti-inflammatory effects of anthocyanins from Vaccinim myrtillus (bilberry) fruit extract on the acute liver failure caused by carbon tetrachloride-CCl4 (3 mL/kg, i.p.). The preventive treatment of the bilberry extract (200 mg anthocyanins/kg, orally, 7 days) prior to the exposure to the CCl4 resulted in an evident decrease in markers of liver damage (glutamate dehydrogenase, sorbitol dehydrogenase, malate dehydrogenase), and reduced pro-oxidative (conjugated dienes, lipid hydroperoxide, thiobarbituric acid reactive substances, advanced oxidation protein products, NADPH oxidase, hydrogen peroxide, oxidized glutathione), and pro-inflammatory markers (tumor necrosis factor-alpha, interleukin-6, nitrite, myeloperoxidase, inducible nitric oxide synthase, cyclooxygenase-2, CD68, lipocalin-2), and also caused a significant decrease in the dissipation of the liver antioxidative defence capacities (reduced glutathione, glutathione S-transferase, and quinone reductase) in comparison to the results detected in the animals treated with CCl4 exclusively. The administration of the anthocyanins prevented the arginine metabolism's diversion towards the citrulline, decreased the catabolism of polyamines (the activity of putrescine oxidase and spermine oxidase), and significantly reduced the excessive activation and hyperplasia of the Kupffer cells. There was also an absence of necrosis, in regard to the toxic effect of CCl4 alone. The hepatoprotective mechanisms of bilberry extract are based on the inhibition of pro-oxidative mediators, strong anti-inflammatory properties, inducing of hepatic phase II antioxidant enzymes (glutathione S-transferase, quinone reductase) and reduced glutathione, hypoplasia of Kupffer cells, and a decrease in the catabolism of polyamines.

Continuous intake of alcohol leads to liver cirrhosis because of imbalance of oxidative stress/antioxidative defense and chronic 'sterile inflammation'. Hepatorenal syndrome (HRS) is the most severe complication of liver cirrhosis. The aim of our study was to assess: (1) the oxidative stress/antioxidative defense markers such as malondialdehyde (MDA), oxidative glutathione (GSH) and glutathione S-transferase (GST), (2) inflammation [C-reactive protein (CRP)], and (3) nitrate/nitrite levels (NOx) and its substrate L-arginine level. The study enrolled three groups: a group with cirrhosis and HRS (48 patients), a group with cirrhosis without HRS (32 patients), and a control group (40 healthy blood donors). All the patients with cirrhosis and HRS had type II HRS. MDA concentration was significantly higher in the groups with cirrhosis with and without HRS. Significant positive correlation was documented between the MDA level and de Ritis coefficient (AST/ALT), a marker of liver damage severity; between MDA and inflammation (CRP); between MDA and NOx concentration in the groups with cirrhosis with and without HRS. The correlation between MDA and creatinine level was significant in the group with HRS. The levels of GSH and GST were significantly lower in the groups with cirrhosis with and without HRS. The results of the study revealed that an increase in MDA and NOx concentration, along with decreased values of antioxidative defense and L-arginine, may indicate that liver damage can have an influence on progression to renal failure.

Alcoholism is one of the most common addictions affecting health and the immune system in people worldwide.Chronic alcohol consumption over a prolonged period of time causes metabolic liver injury, along with arginine metabolism and nitric oxide (NO) synthase disorders.Ethanol intoxication under cumulative nitrooxidative and nitrosative stress conditions, as well as in inflammation, stimulates the production of NO anion (NO -) and superoxide anion (O2-), i.e. peroxynitrite formation in hepatocytes and endothelium.Mitochondrial dysfunction and disorders of adenosine triphosphate (ATP) molecules synthesis in hepatocytes cause disorders of intra -and extracellular antioxidants synthesis (glutathione and superoxide dismutase) and neutralization of toxic nitrates and nitrites.Peroxynitrites damage cell membranes lipoproteins, as well as the membrane enzyme systems and the mitochondrial matrix.They also damage the enzymes of ethanol and arginine metabolism in cytosol, and nucleic acid repair enzymes in hepatocytes.In the development of alcoholic liver disease (ALD), peroxynitrites cause reversible injuries of the structure and function of hepatocytes that proceed irreversibly, and vascular sinus endothelial damage, mediated by the mechanisms of apoptosis and necrosis.Considering the fact that 3.3 million people die of ALD and its complications annually, the measures should be taken and aimed at reducing the onset, development, and progression of ALD.The priority is timely ALD diagnosis, as well as the severity of alcoholic liver damage.The studies have shown that the values of peroxynitrite elevation correlate with the severity of liver injury.It can be concluded that timely determination of peroxynitrite values followed by suitable antioxidant therapies may slow down the processes of hepatocyte apoptosis and necrosis, as well as the course of ALD.

AIMS:The present study was designed to compare the ameliorating potential of pre- and post-treatments with melatonin, a potent natural antioxidant, in the carbon tetrachloride-induced rat liver damage model by tracking changes in enzymatic and non-enzymatic liver tissue defense parameters, as well as in the occurring pathohistological changes.MAIN METHODS:Rats from two experimental groups were treated with melatonin before and after CCl4 administration, while the controls, negative and positive, received vehicle/melatonin and CCl4, respectively. Serum levels of transaminases, alkaline phosphates, γ-GT, bilirubin, and albumin, as well as a wide panel of oxidative stress-related parameters in liver tissue, were determined in all experimental animals. Liver tissue specimens were stained with hematoxylin and eosin and further evaluated for morphological changes.KEY FINDINGS:Both pre- and post-treatment with melatonin prevented a CCl4-induced increase in serum (ALT, AST, and γ-GT) and tissue (MDA and XO) liver damage markers and a decrease in the tissue total antioxidant capacity, in both enzymatic and non-enzymatic systems. The intensity of pathological changes, hepatocyte vacuolar degeneration, necrosis and inflammatory cell infiltration, was suppressed by the treatment with melatonin.SIGNIFICANCE:In conclusion, melatonin, especially as a post-intoxication treatment, attenuated CCl4-induced liver oxidative damage, increased liver antioxidant capacities and improved liver microscopic appearance. The results are of interest due to the great protective potential of melatonin that was even demonstrated to be stronger if applied after the tissue damage.

Liver cholestasis is known to accompany several major liver disorders and is adequately mimicked in rats by ligation of the bile duct (BDL). L-arginine is a semi-essential amino acid which is involved in several important metabolic pathways that are significantly affected during cholestasis. This study was conducted in order to contribute to the understanding of the enrolment of L-arginine supplementation in cholestatic liver function. This was carried out by estimation of serum and liver tissue arginase activity, along with liver tissue citrulline, nitric oxide (NO) and polyamine concentrations. Rats subjected to BDL were treated for nine days with L-arginine (150 mg/kg) or remained without any treatment. Animals from two control groups were either subjected to medial laparotomy (sham/opened group) or were without any surgical treatment and received only L-arginine. Application of L-arginine prevented a significant increase in plasma bile acid and bilirubin concentrations, as well as enzyme biochemical markers that were increased after BDL. It is worth mentioning that L-arginine was able to cause a decrease in arginase activity and liver tissue NO concentrations that were found to be significantly altered during cholestasis. On the other hand, the changes occurring in the concentration of liver polyamines (putrescine, spermidine and spermine) and the activity of polyamine metabolizing enzymes were not notably affected by the administered L-arginine. The results of the present study revealed that exogenous L-arginine was able to ameliorate or prevent changes occurring in its metabolism in liver during cholestasis.

Introduction Morbilli is a highly contagious disease manifested by catarrhal changes of the conjunctiva, mucous membrane of the upper respiratory tract, and maculopapular rash that spreads from the face and neck towards the trunk and extremities. Even nowadays, morbilli poses a significant social and health problem in the regions that have not reached adequate levels of vaccination. The aim of the study was to investigate epidemiological and clinical characteristics, as well as vaccination status of persons affected by morbilli in Serbian enclaves in Kosovo. Methods This is a retrospective 3-month study (October–January 2017). Sixty-nine affected children were treated at the Pediatric Department of the Clinical Hospital Center Pristina. The diagnosis was established according to epidemiological and clinical characteristics, blood count, and findings of specific IgM antibodies in serum. The method of descriptive epidemiology was used in the study. Studentu0027s t -test was used to compare the numerical means and the Chi 2 test and Fisheru0027s exact test were used for comparing distribution of descriptive characteristics. Results Mean age of children was 8.25 ± 3.83 years (MIN 7 months, MAX 18 years and a half), male gender: 7.16 ± 6.29, female gender: 9.43 ± 5.87 years. Age-related distribution was: 22.7% between 10–14 years, 18.7% between 2–5 years, 13.0% between 5–9 years, 9.7% between 6 months and 1 year, 6.6% less than 2-year-old, and 9.7% children between 15–19 years of age. There were 76.7% unvaccinated children and 23.3% incompletely vaccinated children. The infection was acquired: in 48.6% in school and pre-school facilities; in 23.1% in healthcare facilities; in 14.1% the infection occurred due to family epidemic, the source of the infection was of unknown etiology in 10.1%. As for ethnicity, there were 37.6% Roma children, 27.4% Albanian, and 22.4% Serbian children. Clinical signs and symptoms were: temperature (higher than 39 °C - 57.8%, up to 38.5 °C - 44.5%; 9.4% had subfebrile conditions); facies morbillosa - present in 83.5%, dry cough present in 33.7%; Kopliku0027s spots in 6.4%; nausea and vomiting in 36.7%, diarrhea in 21.2%; initial maculopapular rash retroauriculary - 79.8%, on face - 95.2%, on the trunk - 78.2%, on the extremities - 49.9%. Tipe of rashes was: dense rashes (60.7% u003e Roma children, 19.6% u003e Albanian children, 8.9% u003e Serbian children) and sparse rashes: 39.3% Serbian children. Complication of the disease was: laryngitis - 34.6%, otitis media - 11.4%; pneumonias - 53.6% and death - 1.8%. Conclusions The majority of affected children were Roma and Albanian unvaccinated children. Due to the course and complications of the disease, morbilli should be eradicated by mandatory vaccination of unvaccinated and incompletely vaccinated individuals. Epidemiological and healthcare control of affected persons in Serbian enclaves in Kosovo should be performed regarding the disease reports, laboratory and serological testing, as well as isolation and treatment of infected individuals.

Tuberculosis (TB) is an ancient infectious disease, which re-emerged with the appearance of multidrug-resistant strains and acquired immune deficiency syndrome. Enoyl-acyl-carrier protein reductase (InhA) has emerged as a promising target for the development of anti-tuberculosis therapeutics. This study aims to develop quantitative structure-activity relationship (QSAR) models for a series of arylcarboxamides as InhA inhibitors. The QSAR models were calculated on the basis of optimal molecular descriptors based on the simplified molecular-input line-entry system (SMILES) notation with the Monte Carlo method as a model developer. The molecular docking study was used for the final assessment of the developed QSAR model and designed novel inhibitors. Methods used for the validation indicated that the predictability of the developed model was good. Structural indicators defined as molecular fragments responsible for increases and decreases of the studied activity were defined. The computer-aided design of new compounds as potential InhA inhibitors was presented. The Monte Carlo optimization was capable of being an efficient in silico tool for developing a model of good statistical quality. The predictive potential of the applied approach was tested and the robustness of the model was proven using different methods. The results obtained from molecular docking studies were in excellent correlation with the results from QSAR studies. This study can be useful in the search for novel anti-tuberculosis therapeutics based on InhA inhibition. Communicated by Ramaswamy H. Sarma.

Rat bile duct ligation (BDL) represents a useful method that mimics obstructive extrahepatic cholestasis, which is known to be a frequent disorder in humans. Polyamines (putrescine, spermidine, and spermine) are one of the key molecules regulating cell proliferation and differentiation. This work aimed to evaluate the potential beneficial properties of putrescine in rat BDL model by studying several biochemical parameters reflecting liver function and polyamine metabolism. Rats that were subjected to BDL were injected with putrescine (150 mg/kg) for 9 days, while in parallel another group with BDL remained untreated. Two control groups were included as well, sham-opened and putrescine-treated group. The following plasma parameters: ALT, AST, γ-GT, ALP, bilirubin, bile acids, as well as liver malondialdehyde and polyamine concentration and the activity of enzymes involved in polyamine metabolism were studied. After BDL, significant alterations in plasma biochemical parameters occurred, where a 9-day putrescine treatment significantly alleviated liver function deterioration. Putrescine also increased liver polyamines’ concentrations and polyamine and diamine oxidase activities in rats submitted to BDL. Our results demonstrated, for the first time, that putrescine plays an important role in preserving liver tissue function in rats with experimentally induced cholestasis.

Objective: The aim of study was determining the relation between the quality of metabolic control, anthropometric parameters and ultrasound measurement of fat accumulation and carotid atherosclerotic plaques vulnerability in patients with type 2 diabetes. Methods: The study included 51 patients with type 2 diabetes mellitus and 50 healthy individuals. The assessment of plaque vulnerability relies on quantitative and qualitative plaque ultrasound analysis. The thickness of intraabdominal adipose tissue was measured as a distance between the frontal wall of abdominal aorta and the dorsal wall of rectus abdominis muscles; the measurements are performed by placing transducer 5 cm above the umbilicus. Results: Atherosclerotic plaque was found in all of diabetic patients, comparing to 28.12% in the control group; among those, 47.06% with diabetes and 25.6% of control patients had vulnerable plaque. The vulnerability of atherosclerotic plaque was significantly related to age, duration of diabetes, glycaemia, waist circumference, waist / hip ratio, intra-abdominal adipose tissue thickness, intra-abdominal/subcutaneous fat ratio, dyslipidemia and hypertension. Conclusions: Carotid atherosclerotic plaques, particularly vulnerable ones, are far more prevalent in diabetic patients. Advanced age, poor glycemic control, obesity and the intra-abdominal fat accumulation contribute to carotid atherosclerotic plaques vulnerability. Despite the significant correlations with metabolic/anthropometric measurements, none of the predisposing factors could be identified as the independent risk factor; obviously, the increased vulnerability of has been the result of the synergistic effects of multiple pathogenic mechanisms. Moreover, ultrasound measurements of intra-abdominal fat did not show a decisive advantage over the classical anthropometric measurements in estimating atherosclerotic and metabolic risk.

Introduction: Hepatitis B virus is primarily hepatotropic, causing chronic hepatitis B in 5-10% of patients. Chronic hepatitis B (CHB) infection is a dynamic process, which may have five phases: immunotolerant, immunoactive, latency phase, reactive and HBsAg negative phase. Aim: Analyze clinical and biochemical parameters in relation to morphological condition of the liver. Material and Methods: The study enrolled 35 patients diagnosed with CHB, 24 males and 11 females, aged between 12 and 62 years, in the period 2015-2016. The diagnosis was based on serological, biochemical results, and liver biopsy. In patients in an ELISA assay demonstrated the presence of HBsAg in serum. Results: The study shows that middle-aged male patients are more prone to chronic hepatitis B infection. Most patients have one or two symptoms.Fatigue and right subcostal pain are most commonly present in the groups with fibrosis in second- and third-degree, and hepatomegaly in the group with fibrosis in first-degree. Splenomegaly is present only in groups with fibrosis in third and fourth degree. Elevated average aminotransaminase levels reflected the degree of fibrosis. Significant statistical difference in aminitransaminase levels was confirmed between the group of patients with third- and forth-degree and patients without fibrosis. Conclusion: The increase in ALT levels reflect the degree of fibrosis and cirrhosis of the occurrence. ALT levels may be a predictor of the process of the fibrogenesis, as well as to indicate the degree of fibrosis in HHB infection. Due to frequent discrepancies between clinical manifestations and results of laboratory tests, liver biopsy has been considered 'gold standard' for establishing the diagnosis, staging chronic hepatitis B, making therapeutic decisions, monitoring the course of the disease, and assessing prognosis.

Hepatitis B virus is a primarily hepatotropic virus, causing both acute and chronic hepatitis (CHB).Primary chronic hepatitis B is most commonly a self-limited disease with complete recovery within 2-3 months since the onset of the disease.It is believed that 2/3 of the world population has been infected with hepatitis B virus at some point during their lifetime.According to the WHO reports, the incidence of HBV infection is decreasing due to the introduction of mandatory hepatitis B immunization.However, about 400 million people will develop chronic hepatitis B.More than million people die every year due to chronic HBV infections, liver cirrhosis and/or hepatocellular carcinoma (HCC).It means that the hepatitis B virus infection is a major global health problem.Timely diagnosis and adequate treatment significantly slow down the course and progression of chronic hepatitis B.