Open Access Macedonian Journal of Medical Sciences

195-201

Authors: Alyaa Hessin, Rehab Hegazy, Azza Hassan, Nemat Yassin, Sanaa Kenawy

BACKGROUND: Liver fibrosis is the common pathologic consequence of all chronic liver diseases. AIM: Lactoferrin (Lf) was investigated for its possible hepatoprotective effect against thioacetamide (TAA)-induced liver fibrosis rat model. MATERIAL AND METHODS: Rats received TAA (200 mg/kg/biweekly, ip) for four successive weeks. Lf (200 mg/kg/day, p.o.) or vehicle (VHC) was administered for one month before and another month during TAA injection. Body weight and mortality rate were assessed during the month of TAA-intoxication. Thereafter, serum and liver tissues were analyzed for liver function, oxidative, fibrotic and apoptotic markers. RESULTS: Lf conserved rats against TAA-induced body weight-loss and mortality. Preservation of serum albumin, alkaline phosphatase and total bilirubin levels was also observed. Lf also protected rats against TAA-induced decrease in reduced glutathione and increase in malondialdehyde liver contents. Normal liver contents of hydroxyproline, nuclear factor kappa B and alpha fetoprotein; as markers of fibrosis; were increased with TAA and conserved with Lf-TAA. Lf maintained the normal architecture of the liver and immunohistochemical findings revealed increase in apoptotic bodies compared to TAA that favored necrosis. CONCLUSION: In conclusion, Lf improved liver function, reduced oxidative stress and liver fibrosis, and enhanced apoptosis in rats with liver fibrosis, suggesting it to have useful therapeutic potential in patients with liver fibrosis.

209-214

Authors: Manal A. Badawi, Dalia M. Abouelfadl, Sonia L. El-Sharkawy, Wafaa E. Abd El-Aal, Naglaa F. Abbas

AIM: This study aimed to clarify how macrophages affect prognosis in cancer colon and their association with tumor angiogenesis. MATERIAL AND METHODS: Forty four biopsies of colon carcinoma and 15 of benign adenomatous polyps were investigated for macrophages infiltration and microvessels density using immunohistochemistry and image morphometric analysis. Macrophages and blood vessels were stained immunohistochemically by CD68 and F-VIII markers respectively. The morphometric analysis was carried out on the immunohistochemically stained slides using the Leica Qwin 500 Image Analyzer. Both of macrophages infiltration and microvessels density were correlated with histological tumor grade, stage and lymph node metastases and were correlated with each others. RESULTS: Macrophage infiltration was significantly higher in malignant cases than in benign polyps. High macrophage infiltration and hypervascularity were significantly correlated with T-staging and lymph nodes metastasis. A significant correlation was found between macrophage infiltration and microvessels densitie in malignant tumors where hypervascularity was significantly correlated with high macrophages infiltration. CONCLUSION: The significant correlation between macrophage infiltration and tumor angiogenesis suggests an interaction between macrophages and cancer cells stimulating microvessels formation, tumor invasion and metastasis in colon cancer. We recommend that macrophages infiltration should be evaluated to investigate their clinical value in development of individualized therapeutic regimens for management of colon carcinoma.

224-230

Authors: Detelina Valchkova Lukanova, Nadelin Krasimirov Nikolov, Kameliya Zaharieva Genova, Mario Draganov Stankev, Elisaveta Valcheva Georgieva

BACKGROUND: The stroke is leading cause of death and severe disability worldwide. Atherosclerosis is responsible for over 30% of all ischemic strokes. It has been recently discovered that plaque morphology may help predict the clinical behavior of carotid atherosclerosis and determine the risk of stroke. The noninvasive imaging techniques have been developed to evaluate the vascular wall in an attempt to identify “vulnerable plaques”. AIM: The purpose is to investigate the diagnostic accuracy of ultrasound, multidetector computed tomography and magnetic resonance imaging in the identification of plaque components associated with plaque vulnerability. MATERIAL AND METHODS: One hundred patients were admitted for carotid endarterectomy for high grade carotid stenosis. We defined the diagnostic value of B-mode ultrasound of carotid plaque in a half, and the accuracy of multidetector computed tomography and magnetic resonance imaging, in the other group, for detection of unstable carotid plaque. The reference standard was histology. RESULTS: Sensitivity of ultrasound, multidetector computed tomography and magnetic resonance imaging is 94%, 83% and 100%, and the specificity is 93%, 73% and 89% for detection of unstable carotid plaque. CONCLUSION: The ultrasound has high accuracy for diagnostics of carotid plaque morphology, magnetic resonance imaging has high potential for tissue differentiation and multidetector computed tomography determines precisely degree of stenosis and presence of ulceration and calcifications. The three noninvasive imaging modalities are complementary for optimal evaluation of the morphology of carotid plaque. This will help to determine the risk of stroke and to decide on the best treatment – carotid endarterectomy or carotid stenting.

237-240

Authors: Vlora Ademi Ibishi, Rozalinda Dusan Isjanovska

BACKGROUND: Pre-labour Rupture of Membranes (PROM) is an important cause of maternal and fetal morbidity and increased rate of cesarean section delivery. AIM: The aim of this study is to investigate the clinical characteristics, PROM-delivery interval, mode of delivery, and early maternal neonatal outcome among pregnant patients presenting with pre-labour rupture of membranes. MATERIAL AND METHODS: This prospective case control study is implemented at the Obstetric and Gynecology Clinic of the University Clinical Center of Kosovo. The study included 100 pregnant patients presenting with prelabour rupture of membranes of which 63 were primigravida and 37 patients were multigravida. RESULTS: The incidence of cesarean section in this study is 28 % and the most common indications for cesarean delivery were fetal distress, malpresentation, cephalopelvic disproportion, and failed induction. The most common maternal complications in this study are chorioamnionitis, retained placenta and postpartum hemorrhage. Neonatal infectious morbidity was present in 16 % of cases. CONCLUSION: PROM is a significant issue for obstetricians and an important cause of maternal and neonatal morbidity and increased rate of cesarean section delivery.

245-249

Authors: Howayda E. Gomaa, Mohamed Mahmoud, Nevine E. Saad, Amal S. Saad-Hussein, Somaia Ismail, Eman H. Thabet, Hebatallah Farouk, Dina Kandil, Ahmed Heba, Wael Hafez

AIM: We examined the role that immunoglobulin GM 23 and KM allotypes—genetic markers of γ and κ chains, respectively—play in response to treatment of hepatitis C virus (HCV) infection in Egyptian patients. MATERIAL AND METHODS: A total of 120 persons who had responded to HCV treatment and 125 with persistent HCV infection were genotyped for the presence of GM23 and KM determinants. HLA –C genotyping was also done. RESULTS: Association of GM 23+ and KM3 was significantly associated with non response to treatment (P < 0.0001). Individuals who lacked this GM genotype (but were positive for KM1,2 and 3) were likely to respond to treatment (P=0.045). Association of heterozygous GM23 (+/-) with KM 1,2 and 3 or KM3 alone was significantly associated with SVR (P = 0.001) and (P = 0.0001) respectively. Particular combinations of HLA and GM genotypes were associated significantly with the response to HCV treatment. The combination of HLAC2C2 and GM23+ was associated with persistence of infection (P = 0.027) while the association of HLAC2C2 and heterozygous GM23+/- was associated with SVR (P = 0.001).The association of HLAC1C1 and heterozygous GM23+/- was significantly associated with SVR (P = 0.001) and also subjects with HLA C1/C2 and heterozygous GM23+/- were likely to respond to treatment (P = 0.003) while subjects with HLA C1/C2 and GM23+ show tendency to resist to treatment (P = 0.0001). CONCLUSION: Our results didn’t support a role for KM allotypes, GM23 allotype plays a role in the persistence of HCV infection in the presence or absence of KM1,3. Interaction between certain GM and HLA-C genotypes may favor adequate response to interferon based therapies.

256-261

Authors: Rada Miskovic, Aleksandra Plavsic, Sanvila Raskovic, Zikica Jovicic, Jasna Bolpacic

BACKGROUND: Numerous studies indicate potential role of vitamin D as an important factor in the development of many autoimmune diseases including systemic lupus erythematosus (SLE). Patients with SLE are especially prone to the development of vitamin D deficiency due to the nature of their illness. AIM: The aims of our study were to determine the prevalence of vitamin D insufficiency and deficiency in patients with SLE in Serbia, to identify clinical variables associated with vitamin D status and to examine the impact of vitamin D status on disease activity and presence of specific lupus autoantibodies. MATERIAL AND METHODS: The study included 46 patients with SLE. Serum 25(OH)D concentration was measured by electrohemiluminiscent immunoassay. RESULTS: The mean serum concentration of 25(OH)D was 11.9 ± 7.3 ng/ml. The prevalence of insufficiency was 32.6%, while the prevalence of deficiency was 67.4%. There was no association between vitamin D status and photosensitivity, skin lesions, arthritis and lupus nephritis. Vitamin D status was not associated with the presence of specific autoantibodies. There was no correlation between disease activity assessed by SLEDAI scale with the concentration of 25(OH)D. Patients who used vitamin D supplements and calcium did not have a significantly higher concentration of 25(OH)D. CONCLUSION: In conclusion, vitamin D deficiency is common in patients with SLE.

268-272

Authors: Elena Jovanovska Janeva, Zlatica Goseva, Angjelko Gjorchev, Angela Debreslioska, Mirko Spiroski, Beti Zafirova, Magdalena Genadieva Dimitrova

BACKGROUND: IL-13 is one of many cytokines responsible for the chronic inflammation of asthma. AIM: The aim of this study was to determine the effect of combined therapy ICS/LABA and ICS/LABA plus Montelukast in patients with uncontrolled severe persistent asthma by analyzing of serum IL-13 and FEV1 before the treatment and after 6 months of therapy. MATERIAL AND METHODS: In study we included two groups. First group with 27 patients were treated with ICS/LABA. Second group with 29 patients were treated with ICS/LABA plus Montelukast. In each of them were measured serum IL-13 levels by the ELISA method and FEV1 before and after 6 months of treatment. Results were statistically analyzed according to the Wilcoxon Pairs Test and T-test. RESULTS: The obtained results in both groups showed that the serum IL-13 before the start of therapy were much higher and after 6 months of treatment significantly reduces their value, which in the second group were more expressed. The difference in the average value of FEV1 in both groups before and after therapy was statistically significant. CONCLUSION: Treatment with ICS/LABA plus Montelukast proved superior compared to therapy of ICS/LABA in patients with uncontrolled severe persistent asthma and allows achievement of well controlled of asthma with subjective clinical improvement.

278-282

Authors: Svetla Nikolova, Vasil Yablanski, Evgeni Vlaev, Luben Stokov, Alexey Savov, Ivo Kremensky

BACKGROUND: The current consensus on idiopathic scoliosis maintains that it has a multifactorial etiology with genetic predisposing factors. AIM: Estrogen receptor alpha gene has been considered as candidate gene of idiopathic scoliosis. MATERIAL AND METHODS: We conducted a case-control study of Bulgarian population samples (eighty patients with idiopathic scoliosis and one hundred-sixty healthy unrelated gender-matched controls) trying to investigate the association between common genetic polymorphisms of estrogen receptor alpha and the susceptibility to idiopathic scoliosis. Molecular detection of the restriction polymorphisms XbaI and PvuII was performed by polymerase chain reaction following by restriction fragment length polymorphism. The statistical analysis was performed by Pearson's chi-squared test. RESULTS: Our case-control study showed statistically significant association between the PvuII polymorphism and susceptibility to idiopathic scoliosis and curve progression. No genotype or allele of XbaI polymorphism was found to be correlated with the onset or severity of the disease. CONCLUSIONS: The identification of molecular markers with diagnostic and prognostic value could be useful for early detection of children at risk for the development of scoliosis and for prognosis of the risk for a rapid deformity progression. That would facilitate the therapy decisions and early stage treatment of the patient with the least invasive procedures.

287-292

Authors: Khaled M. Salama, Ola M. Ibrahim, Ahmed M. Kaddah, Samia Boseila, Leila Abu Ismail, May M. Abdel Hamid

BACKGROUND: Beta Thalassemia is the most common chronic hemolytic anemia in Egypt (85.1%) with an estimated carrier rate of 9-10.2%. Injury to the liver, whether acute or chronic, eventually results in an increase in serum concentrations of Alanine transaminase (ALT) and Aspartate transaminase (AST). AIM: Evaluating the potentiating effect of iron overload & viral hepatitis infection on the liver enzymes. PATIENTS AND METHODS: Eighty (80) thalassemia major patients were studied with respect to liver enzymes, ferritin, transferrin saturation, HBsAg, anti-HCV antibody and HCV-PCR for anti-HCV positive patients. RESULTS: Fifty % of the patients were anti-HCV positive and 55% of them were HCV-PCR positive. Patients with elevated ALT and AST levels had significantly higher mean serum ferritin than those with normal levels. Anti-HCV positive patients had higher mean serum ferritin, serum ALT, AST and GGT levels and higher age and duration of blood transfusion than the negative group. HCV-PCR positive patients had higher mean serum ferritin and serum ALT and also higher age and duration of blood transfusion than the negative group. CONCLUSION: Iron overload is a main leading cause of elevated liver enzymes, and presence of HCV infection is significantly related to the increased iron overload.

298-302

Authors: Ahmed Salman, Mona Hegazy, Soheir AbdElfadl

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) has become the most prevalent cause of liver disease, nonalcoholic steatohepatitis (NASH) and fibrosis in obese patients identifies the risk group with increased incidence of liver-related deaths. AIM: To clarify the role of serum adiponectin and its receptor liver gene expression in the progression of liver damage in NAFLD. METHODS: Fifty four (54) obese patients with NAFLD preliminary diagnosed by liver ultra-sound were recruited. Full medical history, anthropometric measurement, biochemical studies, serum adiponectin level, liver biopsy for histological examination and NAS score to identify NASH patients, and assessment of adiponectin receptor gene expression by RT-PCR, were conducted for each patients. Fifteen ages matched average weight healthy adult had been chosen as a control for serum adiponectin level. RESULTS: According to NAS score, patients were divided into non- NASH (8 patients), and NASH (46 patients). Serum adiponectin level was significantly lower in NAFLD patients compared to normal participants (p < 0.004). Serum adiponectin level was lower in NASH patients (4.437 ± 2.569 ng/dl in NASH vs. 5.138 ± 2.841 ng/dl in non-NASH). Adiponectin receptor liver gene expression was lower in NASH patients (0.8459 ± 0.4671 vs. 1.0688 ± 0.3965 in non-NASH). CONCLUSION: Both adiponectin deficiency and resistance had a role in progression of simple liver steatosis to severe injury in obese patients.

307-309

Authors: Irfan Ahmeti, Lliljana Simonovska, Branka Krstevska, Nevena Ristevska

AIM: To estimate suspect nodule for benign or malignant characteristics, and to verify cytological features of the node with the fine needle aspiration (FNA) under ultrasound. DESIGN: A total of 106 patients were analyzed. FNA biopsy was performed at outpatient clinic via ultrasound. Inform consent was signed for each patient. Preparation of procedure with local anaesthesia was made by assistant nurse. PROCEDURE: Parallel approach of ultrasound guided fine needle aspiration (USGFNA) was used for each patient. This approach allows the operator to observe needle penetration, location and pathway of the entire needle within the neck, thyroid and nodule, which remain visible on the monitor. As a side effect commonly noticed mild pain and dizziness were recorded. RESULTS: General findings: According the gender, 96 (90.5%) of them were women and 10 (9.5%) men. Median age was 47 ± 9 years. Cytological findings: 5 patients were with papillary carcinoma, 3 with Hurtle cell metaplasia, 1 follicular tumour and 1 with unclear differentiation. CONCLUSION: Close collaboration between endocrinologists, morphologists and surgeons in a multidisciplinary frame is the key to correct preoperative thyroid cancer diagnosis and optimal treatment. FNA biopsy remains the most accurate diagnostic method in detecting thyroid cancer.

315-321

Authors: Yusr M. I. Kazem, Salwa M. El Shebini, Maha I. A. Moaty, Suzanne Fouad, Salwa T. Tapozada

AIM: To study the interaction between sleep deprivation, obesity and cognitive functions, and the effect of following a balanced low caloric diet and increasing sleep duration on those variables. SUBJECTS AND METHODS: Ninety two obese females with mean age 47.00 ± 2.00 years and body mass index (BMI) 36.14 ± 3.00 kg/m² were divided into 3 groups according to their sleeping hours. They followed balanced low-caloric diet and were instructed to increase sleeping hours. Full clinical examination, 24 hours dietary intake recall, anthropometric measurements, mini mental state test, questionnaire for subjective sleep and life style evaluation were performed at baseline and after 2 months. Serum visfatin, fasting blood glucose and C-peptide were assessed; Modified homeostatic model assessment of insulin resistance was calculated. RESULTS: About one third of our sample slept less than 6 hours daily, group (1), all patients had elevated visfatin serum level (33.87 ± 2.8 ng/ml) with the highest level in group (1). At base line, group (1) showed the highest BMI, lowest cognitive functions, highest visfatin level and highest insulin resistance (P < 0.05). After 2 months of intervention, improvement was recorded in all variables, with the best improvement in group (1) after extending sleep duration (P < 0.05). CONCLUSION: Sleep deprivation may be a modifiable risk factor for obesity, cognitive impairment and visfatin elevation.

326-330

Authors: Aleksandra Plavsic, Rada Miskovic, Jasna Bolpacic, Branka Šuštran, Aleksandra Peric-Popadic, Mirjana Bogic

Sjögren’s syndrome is an autoimmune disease of unknown etiology where immune response to self-antigens is believed to result from interactions between genetic and environmental factors. We describe the case of a patient who has been diagnosed with Sjögren’s syndrome based on typical clinical and immunological parameters. The clinical picture was dominated by the respiratory symptoms, and radiographic and multislice computed tomography examination of the chest showed certain changes characteristic of pneumoconiosis. Given that the patient has worked in a foundry where he has been exposed to the silica dust, he was subject to examination by occupational health specialists under the suspicion of lung silicosis, who confirmed the silicosis. This case report points to the possible connection between a professional exposure to silica and Sjögren’s syndrome. Occupational exposure to silica is a possible risk factor for the development of autoimmune diseases, and in the evaluation of patients with connective tissue diseases it is important to consider work-related history.

337-340

Authors: Ljiljana Simonovska, Biljana Ilievska-Popovska

BACKGROUND: The successful treatment of patients with active tuberculosis is one of the priorities in the Tuberculosis Control Programs. AIM: The aim was to establish whether there was a statistically significant difference in the treatment outcome in patients with tuberculosis who began their initial treatment phase and/or pursued it as inpatient, as opposed to patients with tuberculosis who underwent their entire treatment regime as outpatient. Moreover, our goal was to determine whether there is a statistically significant difference in the outcome from the treatment between patients with tuberculosis who were hospitalized up to one month, two months, or more than two months. MATERIALS AND METHOD: The study includes 355 patients, divided into two groups. The first group, which consists of 219 patients, began their initial treatment phase as inpatient, and then they continued the treatment as outpatient. The second group, 136 patients, underwent their entire treatment as outpatient. The treatment outcome is determined with every patient (cured, treatment completed, treatment default, treatment failed, died, treatment in progress). For the statistical data analysis and for establishing the significance of the findings regarding the differences between the two groups we used the Pearson Chi-Square Test and the Yates Corrected Test. RESULTS: The statistical analysis with the Pearson Chi-Square Test showed that the treatment outcome does not significantly depend on the model of treatment (p = 0.31). The statistical data analysis showed that there is no statistically significant difference in the achievement of conversion of the bacterial result of the sputum at the end of the initial phase of treatment regarding the studied groups (p = 0.89). The statistical data analysis showed that the length of inpatient treatment affects the outcome of the treatment and that the difference is statistically highly significant (p < 0.00005). CONCLUSION: There are no statistically significant differences in the sputum conversion and the treatment outcome among inpatient/outpatient with tuberculosis or outpatient only; however, the length of inpatient treatment is statistically significant regarding its effect on the treatment outcome.

345-355

Authors: Adnan Tutic, Srecko Novakovic, Mitar Lutovac, Rade Biocanin, Sonja Ketin, Nusret Omerovic

The metal is a chemical element that conducts electricity well and heat, and the nonferrous metals builds cations and ionic bonds. Heavy metals include metals whose density is higher than 5 g/cm3. The whole range of the metal is in the form of essential trace elements, essential for a number of functions in the human body, and its deficiency results in a lack of occurrence of a serious symptom. The best examples are anemia lack of iron, lack of chromium in diabetes, growth problems in lack of nickel. Other elements such as lead, cadmium, mercury, arsenic and molybdenum have been shown to exhibit large quantities of toxic effects. The paper examines the problem of heavy metals originating from agriculture on agroecosystems. This group of pollutants is considered the most important cause of degradation of soil quality, surface and groundwater and direct causal adverse effects on human and animal health. In order to complete the environmental monitoring of pollutants, these main categories, origins, and possible negative impacts of the basic principles of preventing their toxic effects were examined.

363-369

Authors: Basak Kucukcakan, Zehra Hayrulai-Musliu

Aflatoxins (AFT) are poisonous substances which are classified in Group 1 carcinogenic agents to humans by International Agency for Research on Cancer (IARC). AFT can occur naturally in food commodities (maize, corn, rice) as a result of fungal contamination in hot and humid environments. In the food, toxin contamination can remain during manufacturing and long after fungi have stopped being biologically active. Aflatoxin B1 (AFB1) is the most dominant and potent agent from all AFT. In developing countries, high exposure to AFB1 can cause chronic toxicity and usually increases the incidence of Hepatocellular Carcinoma (HCC). However, in these regions hepatitis B is the most common risk factor for HCC cases. Many researches were aimed to enlighten the mechanism and the role of two etiological agents on risk of HCC, but the obtained data was conflicting with each other. It was uncertain that the indicators/biomarkers might be the contribution of the carcinogenic status of the patient; and, the biomarker samples from the subject may only reflect the recent effects of the toxin exposure after consumption of AFB1 contaminated commodities. The studies were facing with the errors of methods which were un-fit to enlighten the possible interaction between Hepatitis B and AFB1 on contribution to HCC. It was pivotal to understand the effect of each risk factor in order to prevent and improve public health in poor and undeveloped regions. Although some of the studies evaluate AFB1 alone as a considerable factor on HCC risk, according to this review it was concluded vice versa. This study was aimed to clarify the main etiological agent of HCC where AFB1 and HBV are endangering public health. In additionally, the purpose was to enlighten the possible synergistic effect between these two factors among HCC pathogenesis. Hence forth, appropriate and right applications could be conducted in undeveloped countries in order to protect public health.