The effects of L-cysteine and N-acetyl-L-cysteine on homocysteine metabolism and haemostatic markers, and on cardiac and aortic histology in subchronically methionine-treated Wistar male rats.

Methionine is the precursor of homocysteine, a sulfur amino acid intermediate in the methylation and transsulfuration pathways; methionine-rich diets were used to induce hyperhomocysteinemia, and cardiovascular pathology was often observed. Other sulfur amino acids interfere with this metabolism, i.e., L-cysteine (Cys) and N-aceyl-L-cysteine (NAC), and probably also affect cardiovascular system. Their effects are controversial due to their ability to act both as anti- or pro-oxidant. Thus, this study aimed to elucidate their influence on levels of homocysteine, folate and vitamin B12, levels of different haemostatic parameters (fibrinogen, D-dimer, vWF Ag, vWF Ac) in rat serum or plasma as well as their effects on cardiac and aortic tissue histology in subchronically methionine-treated rats. Wistar albino rats were divided into 4 experimental groups: (a) control group (0.9% sodium chloride 0.1-0.2 mL/day) (n = 10) (K); (b) DL-methionine (0.8 mmol/kg/bw/day) (n = 10) (M); (c) DL-methionine (0.8 mmol/kg/bw/day) + L-cysteine (7 mg/kg/bw/day) (n = 8) (C); (d) DL-methionine (0.8 mmol/ kg/bw/day) + N-acetyl-L-cysteine (50 mg/kg/bw/day) (n = 8) (N). All substances were applied i.p., treatment duration 3 weeks. Lower levels of vitamin B12 in all the groups were found. Folate was reduced only in N group. Decreased fibrinogen was noted in C and N groups and increased D-dimer only in C. VWF activity was reduced in M and C groups. Deleterious effects in heart were observed, especially after Cys and NAC application. Aortic tissue remained unchanged. In conclusion, it could be said that sulfur amino acids have the significant impact on cardiovascular system in subchronically methionine-treated rats. This study points out the relevance of their complex interactions and deleterious effects mediated by either direct influence or procoagulant properties.

Totally implantable central venous catheters of the port-a-cath type: complications due to its use in the treatment of cancer patients.

PURPOSE: A multidisciplinary approach to the treatment of patients with malignant diseases requires adequate venous access in order to safely administer chemotherapy, blood transfusion and blood products, antibiotics, rehydratation and total parenteral nutrition. The insertion of the central venous catheter (CVC), its use and its maintenance can be accompanied by multiple complications. METHODS: Fifty cancer patients were retrospectively enrolled in this study. The obligatory inclusion criterion was an implanted CVC of the port-a-cath type, inserted for chemotherapy administration. This study included patients who had their catheters inserted in the period from 2001 to 2012. RESULTS: The median patient age was 44 years (range 28- 68). Thirty five patients (70%) were female and 15 (30%) male. The port-a-cath had been used from 1 to 40 months (16.8 ± 9 months on average). Breast cancer was the most frequent malignancy (18 patients, 36%). The overall incidence of reported complications was 38%. The most common complications were infections and thromboembolic events, each with an incidence of 10 %. The malposition and disconnection of the port-a-cath were in second place, each with an incidence of 6%. CONCLUSION: Insertion of the CVC carries the possibility of serious complications (thrombosis, infections, occlusions). However, correct implantation and handling performed by experienced and trained surgical and other medical staff significantly decrease the incidence of these complications. The use of the CVC has greatly improved the quality of life and also decreased the morbidity and mortality of the cancer patients in our study.

Trophoblast Cell Function in the Antiphospholipid Syndrome.

Antiphospholipid syndrome (APS) is a complex thrombo-inflammatory autoimmune disease characterized by the presence of antiphospholipid antibodies (aPL). Women with APS are at high risk of recurrent early pregnancy loss as well as late obstetrical complications-premature birth due to placental insufficiency or severe preeclampsia. Accumulating evidence implies that vascular thrombosis is not the only pathogenic mechanism in obstetric APS, and that the direct negative effect of aPL on the placental cells, trophoblast, plays a major role. In this review, we summarize the current findings regarding the potential mechanisms involved in aPL-induced trophoblast dysfunction. Introduction on the APS and aPL is followed by an overview of the effects of aPL on trophoblast-survival, cell function and aPL internalization. Finally, the implication of several non-coding RNAs in pathogenesis of obstetric APS is discussed, with special emphasis of their possible role in trophoblast dysfunction and the associated mechanisms.

Intrauterine Fetal Death in Term Pregnancy-A Single Tertiary Clinic Study.

INTRODUCTION: Intrauterine fetal death (IUFD) is defined as death of the fetus after the 20th week of gestation. Despite regular monitoring the incidence of IUFD remains high. This study aims to assess the incidence and maternal conditions associated with IUFD over term pregnancies in a twelve-year period. MATERIALS AND METHODS: A retrospective descriptive study was conducted on a population of women in whom IUFD was diagnosed in a term pregnancy during the period from January 2010 to December 2022. The study was at the Clinic for Obstetrics and Gynecology, University Clinic Centre of Serbia. The analyses included the number of deliveries, live births, and stillbirths, as well as maternal, fetal, and placental conditions associated with the risk of IUDF. The statistical analysis involved descriptive statistical methods and one sample proportion. RESULTS: The average age of the patients was 30 years. Most patients had secondary and higher education, and 70% of patients had regular pregnancy monitoring; 53.33% were primiparous and pregnancies occurred spontaneously. IUFD mainly occurred in the 39th week of gestation. In total, 38.3% had one to two associated diseases, 5% more than three, and 58.33% were healthy. Recurrence of IUFD was reported by 10% of patients, while 8.33% had a history of spontaneous abortion. Over 80% of placental histopathological findings indicated some pathology (e.g., infarction, infections, placental abruption). CONCLUSIONS: The most significant risk factors for IUFD in term pregnancies in our population during the study period were hypertensive syndrome in pregnancy, obesity and gestational diabetes. Pathological findings on the placenta were more common in our study group than is usually reported with infractions of placental tissue being the most common, even in healthy women.

Caffeic acid protects human trophoblast HTR-8/SVneo cells from H2O2-induced oxidative stress and genotoxicity.

Caffeic acid is highlighted as one of the major phenolic compounds present in foods with known antioxidant activity. This phenolic is among commonly consumed substances in everyday diet of pregnant women. However, there is not enough information on its effects during pregnancy, especially the most vulnerable early stage. Extravillous trophoblast cells are specific cells of the placenta that come in direct contact with maternal uterine tissue. Through this study we investigated the cytoprotective effects of caffeic acid on H2O2-induced oxidative damage in first trimester extravillous trophoblast cell line HTR-8/SVneo. Investigated concentrations (1-100 µM) of caffeic acid showed neither cytotoxic nor genotoxic effects on HTR-8/SVneo cells. The treatment with caffeic acid 100 µM significantly increased the percentage of cells in G2/M phase of the cell cycle, compared to non-treated cells. Pretreatment with caffeic acid (10 and 100 µM) attenuated oxidative DNA damage significantly, reduced cytotoxicity, protein and lipid peroxidation, and restored antioxidant capacity in trophoblast cells following H2O2 exposure. This beneficial outcome is probably mediated by the augmentation of GSH and effective ROS scavenging by caffeic acid. These promising results require further investigations to reveal the additional mechanisms/pathways and confirmation through studies in vivo.

Nutritional status in hospitalized patients in the department of gastroenterohepatology.

BACKGROUND/AIMS: Malnutrition appears to be a major and noticeable problem for hospitalized patients and often present in patients with gastrointestinal diseases. This study attempts to evaluate differences in nutritional status parameters and nutritional state differences among hospitalized patients with various gastrointestinal diseases and disorders. METHODOLOGY: Our study included 154 males and 146 females, aged 18-84 years old, with various gastrointestinal diseases and disorders. All patients underwent baseline nutritional assessment, including subjective global assessment (SGA), anthropometric measurements, bioelectrical impedance analysis (BIA), and biochemical markers. RESULTS: Prevalence of malnutrition was 45.7%. The highest prevalence was detected among patients suffering from gastrointestinal malignancies and chronic pancreatitis. All parameters decreased with malnourishment levels, except CRP and in-hospital stay which rose with malnourishment grade. SGA and length of hospital stay negatively correlated with all analyzed variables of nutritional assessment, except CRP. CONCLUSIONS: Patients suffering from gastrointestinal malignancies, inflammatory bowel disease and peptic ulcer disease have more pronounced level of malnutrition. Body mass index, triceps skin fold thickness, mid-arm circumference, MAMC, wrist circumference, total protein level, albumin, cholesterol, glucose level, lymphocyte count, basal metabolic rate, body fat mass, fat free mass, muscle mass, total body water and resistance appeared to be inversely correlated with malnutrition. However, CRP level correlated positively with the malnutrition severity. SGA malnutrition level is dependent of hospitalization length.

Enhancing the performance of beech-timber concrete hybrids by a wood surface pre-treatment using sol-gel chemistry.

Timber-concrete composites require reliable connections between both components, which are usually obtained by metal fasteners or slots in the wood. In this study, an alternative approach is presented based on a fully glued connection in combination with a primer treated wood surface, to enhance the compatibility and the adhesion properties at the interface between beech wood and concrete. Prior to the gluing and the concrete application in a wet-on-wet process, the wood surface was functionalised with a xerogel obtained by means of a sol-gel process, consisting of two layers of silane nanofilms, with different functional groups, which are capable of undergoing further chemical crosslinking reactions with the adhesive. The coating with its functionalities allows for reducing the penetration of the epoxy adhesives into the wood structure and an additional chemical connection to the adhesive can be established. The main objective of this study was to analyse the effect of the surface treatment on the mechanical properties of such composites in 3-point and 4-point bending tests as well as push-out-tests. The results showed that the pre-treatment can improve the load bearing capacity of the timber-concrete composites, but that a ductile behaviour cannot be achieved with the tested adhesives.

Multivariate analysis of prognostic factors in male breast cancer in Serbia.

BACKGROUND: The aim of this study was to analyze the demographic and clinical characteristics of male breast cancer patients in Serbia, and furthermore to determine overall survival and predictive factors for prognosis. MATERIALS AND METHODS: In the period of 1996-2006 histopathological diagnosis of breast cancer was made in 84 males at the Institute for Oncology and Radiology of Serbia. For statistical analyses the Kaplan-Meier method, long-rank test and Cox proportional hazards regression model were used. RESULTS: The mean age at diagnosis with breast cancer was 64.3±10.5 years with a range from 35-84 years. Nearly 80% of the tumors showed ductal histology. About 44% had early tumor stages (I and II) whereas 46.4% and 9.5% of the male exhibited stages III and IV, respectively. Only 7.1% of male patients were grade one. One-fifth of all patients had tumors measuring ≤2 cm, and 14.3% larger than 5 cm. Lymph node metastasis was recorded in 40.4% patients and 47% relapse. Estrogen and progesterone receptor expression was positive in 66.7% and 58.3%, respectively. Among 14.3% of individuals tumor was HER2 positive. About two-thirds of all male patients had radical mastectomy (66.7%). Adjuvant hormonal (tamoxifene), systematic chemotherapy (CMF or FAC) and adjuvant radiotherapy were given to 59.5%, 35.7% and 29.8% patients respectively. Overall survival rates at five and ten years for male breast cancer were 55.0% and 43.9%, respectively. According to the multivariate Cox regression predictive model, a lower initial disease stage, a lower tumor grade, application of adjuvant hormone therapy and no relapse occurrence were significant independent predictors for good overall survival. CONCLUSIONS: Results of the treatment would be better if disease is discovered earlier and therefore health education and screening are an imperative in solving this problem.

[Evaluation of the efficacy and toxicity of protocol cisplatin, 5-fluorouracil, leucovorin compared to protocol fluorouracil, doxorubicin and mitomycin C in locally advanced and metastatic gastric cancer].

INTRODUCTION: Still there is no consensus on the choice of the most efficient and the least toxic chemotherapy regimen in the treatment of advanced gastric cancer. Nowadays few therapy protocols are available for treating this disease. OBJECTIVE: Study was conducted to compare the efficacy and toxicity of FAM (flurouracil, doxorubicin, mitomycin C) with CDDP and FU/FA (cisplatin, 5-fluorouracil, leucovorin) protocols in patients with locally advanced and metastatic gastric cancer. METHODS: This randomized study involved a group of 50 patients with locally advanced or metastatic gastric cancer, who had not previously undergone chemotherapy treatment. Progression free survival, overall survival and drug toxicity were evaluated. For statistical analysis chi-squaretest, Kaplan-Meier curve and the log rank test were used. RESULTS: The overall response rate was 20% in the group treated with FAM and 24% in the group treated with CDDP, FU/FA (4% of patients from each group had complete response), but without significant statistical difference. Median survival was 10.9 months in the FAM group and 11.8 months in CDDP, FU/FA group, with no statistically significant difference. Non-haematological and haematological toxicities of CDDP, FU/FA were considerably less frequent than of FAM, and there was no treatment related deaths in any of the groups. CONCLUSION: Both investigated regimens demonstrated moderate efficacy. The study shows in favour of justified application of both protocols, while in regard to toxicity CDDP and FU/FA can be recommended as preferable treatment for locally advanced and metastatic gastric cancer. New strategies should be considered for better efficacy in the treatment of advanced gastric cancer. New strategies are necessary with the goal to achieve a better therapeutic effect.

[Neurophysiological evaluation of patients with degenerative diseases of the cervical spine].

BACKGROUND/AIM: Diagnostic protocol for patients with degenerative diseases of the cervical spine demands, in parallel with neuroimaging methods, functional evaluation through neurophysiological methods (somatosensitive and motor evoked potentials and electromyoneurography) aiming to evaluate possible subclinical affection of spinal medula resulting in neurological signs of long tract abnormalities. Considering diversities of clinical outcomes for these patients, complex diagnostic evaluation provides a prognosis of the disease progression. METHODS. The study included 21 patients (48.24 +/- 11.01 years of age) with clinical presentation of cervical spondylarthropathy, without neuroradiological signs of myelopathy. For each patient, in addition to conventional neurophysiological tests (somatisensory evoked potentials--SSEP, motor evoked potentials--MEP, electromyoneurography--EMG, nerve conduction studies), we calculated central motor conduction time (CMCT(F)), as well the same parameter in relation to a different position of the head (maximal anteflexion and retroflexion), so-called dynamic tests. RESULTS: Abnormalities of the peripheral motor neurone by conventional EMNeG was established in 2/3 of the patients, correponding to the findings of root condution time. Prolonged conventional CVMP(F) were found in 29% of the patients, comparing to 43% CVMP(F) abnormalities found with the dynamic tests. In addition, the SSEP findings were abnormal in 38% of the patients with degenerative diseases of the cervical spine. CONCLUSION: An extended neurophysiological protocol of testing corticospinal functions, including dynamic tests of central and periheral motor neurons are relevant for detection of subclinical forms of cervical spondylothic myelopathy, even at early stages. In addition to the conventional neurophysiological tests, we found useful to include the dynamic motor tests and root conduction time measurement in diagnostic evaluation.