Galectin-3 as a Prognostic Biomarker in Patients with First Acute Myocardial Infarction without Heart Failure.

BACKGROUND: Galectin-3 (Gal-3) is a biomarker involved in a wide range of diseases including cardiac remodeling following acute myocardial infarction (AMI). Identification of prognostic markers in patients with AMI can guide strategies towards improved survival and quality of life. METHODS: Our study included 59 patients with AMI and a preserved ejection fraction. We determined the Gal-3 plasma concentration within 24 h of chest pain onset from the aortic root, femoral/radial artery, coronary sinus and cubital vein. Major adverse cardiovascular events (MACEs) were evaluated at six months follow-up. RESULTS: MACE at six months post-AMI was recorded in 20 patients (34%). The Gal-3 plasma concentration from the aortic root and the femoral/radial artery were independent predictors of MACE at six months follow-up after the first AMI (OR 1.228; 95%CI: 1.011-1.491; p = 0.038; OR 3.438; 95%CI: 1.275-9.265; p = 0.015). ROC analysis identifies the Gal-3 plasma concentration from the aortic root as a better predictor of MACE or death (cut-off ≥ 10.86 ng/mL; AUC 0.858; 95%CI: 0.744-0.973; p < 0.001) than Gal-3 plasma concentration from the femoral/radial artery (cut-off ≥ 10.18 ng/mL; AUC 0.742; 95%CI: 0.596-0.888; p = 0.006). CONCLUSION: the Gal-3 plasma concentration in patients with AMI determined during coronary angiography, especially from the aortic root, within 24 h after chest pain onset is a valuable biomarker of prognosis at six months follow-up.

Interaction of thrombophilic SNPs in patients with unexplained infertility-multifactor dimensionality reduction (MDR) model analysis.

PURPOSE: Our aim was to evaluate the frequency and SNP-SNP interactions between factor V Leiden (FVL) G1691A, prothrombin G20210A mutation, and C677T MTHFR and PAI-1 4G/5G gene polymorphisms in female IVF patients with unexplained infertility (UI) by using a multifactor dimensionality reduction (MDR) model analysis. METHODS: A total of 225 subjects were enrolled in the study. There were 105 females in UI group and 120 healthy controls. Designated SNPs were determined by using allele-specific PCR methods. The difference in thrombophilia prevalence was assessed by a chi-square test and logistic regression analysis. Four-locus SNP interaction model was tested using the MDR approach. A ten-fold cross-validation consistency (CVC) and permutation testing were performed. RESULTS: There was a significant difference of MTHFR C677T polymorphism frequency between the groups. Significantly less UI patients had MTHFR CC genotype (p = 0.005), while the risk allele T was more frequent (OR = 1.83, p = 0.0018). Logistic regression determined a significant association only for MTHFR C677T in our patients (TT genotype OR = 2.99). The MDR analysis confirmed the significance of a single-locus model for MTHFR C677T polymorphism (p = 0.015; OR = 2.93). However, the best, significant predictive model was the two-locus model comprising MTHFR C677T and FVL (CVC = 10/10, testing accuracy = 60.95%, p = 0.013; OR = 3.02). CONCLUSION: The MTHFR C677T polymorphism was significantly associated with UI, with minor allele T being more frequent. Additionally, there was a significantly increased presence of MTHFR C677T with FVL mutation in these patients. Therefore, MTHFR and its interaction with FVL should be recognized as contributing factors in the pathogenesis of infertility.

Oral supplementation with melatonin reduces oxidative damage and concentrations of inducible nitric oxide synthase, VEGF and matrix metalloproteinase 9 in the retina of rats with streptozotocin/nicotinamide induced pre-diabetes.

Hyperglycemia mediated oxidative stress and pro-angiogenic molecules such as vascular endothelial growth factor (VEGF) and matrix metalloproteinase 9 (MMP9) are considered important for diabetic retinopathy onset and progression. Melatonin is a pineal hormone that regulates circadian and seasonal rhythms and most likely is involved in regulating glucose metabolism. We aimed to evaluate the potential benefit of melatonin supplementation to the pre-diabetic retina by assessing melatonin effects on lipid peroxidation (thiobarbituric acid reactive substances, TBARS), protein oxidation (advanced oxidation protein products, AOPP) and concentrations of inducible nitric oxide synthase (iNOS), VEGF and MMP9 in the retina of rats with pre-diabetes. Pre-diabetes was induced by streptozotocin (45 mg/kg, i.p.) following nicotinamide injection (110 mg/kg, i.p.). Beside mild hyperglycemia, lower serum insulin, increased fructosamine and lower HDL cholesterol, the present study demonstrated decreased serum melatonin in pre-diabetic rats, as well as, increased concentration of retinal TBARS, AOPP, iNOS, VEGF, and MMP9. Oral supplementation with melatonin (85 µg/animal/day) caused melatonin and HDL cholesterol levels to rise in treated rats and reduced levels of fasting serum glucose and fructosamine. It also affected serum insulin and quantitative insulin sensitivity check index (QUICKI) in treated groups but had no significant effect on non-fasting glucose. Finally, supplementation with melatonin reduced concentrations of TBARS, AOPP, iNOS, VEGF, and MMP9 in significant level, thereby exerting an overall positive effect on oxidative stress and pro-angiogenic signaling in the pre-diabetic retina. Thus, oral melatonin might be considered in an early treatment or in the prevention of retinal changes associated with pre-diabetes.

Association of tumor necrosis factor-α (G-308A) genetic variant with matrix metalloproteinase-9 activity and joint destruction in early rheumatoid arthritis.

Matrix metalloproteinases (MMPs) are the key enzymes responsible for the joint destruction. Their activity is regulated by the level of proinflammatory cytokines. The aim of this study was to examine the impact of TNF-α G-308A polymorphism on MMP-9 levels in blood plasma (BP) and synovial fluid (SF) of patients with rheumatoid arthritis (RA) and their role in progression of joint destruction. One hundred thirty-four subjects were enrolled in this study. TNF-α G-308A polymorphism was determined using PCR-RFLP method. ELISA assay was used for the detection of MMP-9 activity in BP and SF. Joint damage was estimated by hands and feet radiography. Larsen score and annual changes in LS were used for quantitative evaluation of joint destruction and radiographic progression of disease. MMP-9 activity in BP and SF was significantly higher in RA compared to controls, as well as in SF of patients with erosive compared to nonerosive RA. Faster radiographic progression and increased MMP-9 activity in BP and SF were detected in the group A (GA or AA genotype carriers) compared to the group G (GG genotype carriers). However, statistical significance was revealed only for MMP-9 activity in SF (p < 0.05). MMP-9 activity in BP and SF is significantly higher in RA patients compared to patients with osteoarthritis. The presence of TNF-α-308A allele is associated with increased MMP-9 activity in SF of patients with early RA and may be a predictor of rapid radiographic progression of disease.

Boerhaave syndrome - case report / Síndrome de Boerhaave - relato de caso

ABSTRACT CONTEXT: Boerhaave syndrome consists of spontaneous longitudinal transmural rupture of the esophagus, usually in its distal part. It generally develops during or after persistent vomiting as a consequence of a sudden increase in intraluminal pressure in the esophagus. It is extremely rare in clinical practice. In 50% of the cases, it is manifested by Mackler's triad: vomiting, lower thoracic pain and subcutaneous emphysema. Hematemesis is an uncommon yet challenging presentation of Boerhaave's syndrome. Compared with ruptures of other parts of the digestive tract, spontaneous rupture is characterized by a higher mortality rate. CASE REPORT: This paper presents a 64-year-old female patient whose vomit was black four days before examination and became bloody on the day of the examination. Her symptoms included epigastric pain and suffocation. Physical examination showed hypotension, tachycardia, dyspnea and a swollen and painful abdomen. Auscultation showed lateral crackling sounds on inspiration. Ultrasound examination showed a distended stomach filled with fluid. Over 1000 ml of fresh blood was extracted by means of nasogastric suction. Esophagogastroduodenoscopy was discontinued immediately upon entering the proximal esophagus, where a large amount of fresh blood was observed. The patient was sent for emergency abdominal surgery, during which she died. An autopsy established a diagnosis of Boerhaave syndrome and ulceration in the duodenal bulb. CONCLUSION: Boerhaave syndrome should be considered in all cases with a combination of gastrointestinal symptoms (especially epigastric pain and vomiting) and pulmonary signs and symptoms (especially suffocation).

RESUMO CONTEXTO: A síndrome de Boerhaave é uma ruptura longitudinal transmural espontânea do esôfago, normalmente da parte distal. Ela geralmente se desenvolve durante ou após vômitos persistentes como consequência do aumento repentino da pressão intraluminal no esôfago. É extremamente rara na prática clínica. Em 50% dos casos, manifesta-se pela tríade de Mackler: vômitos, dor torácica inferior, enfisema subcutâneo. Hematêmese é uma apresentação incomum porém desafiadora da síndrome de Boerhaave. Em comparação com rupturas de outras partes do tubo digestivo, a ruptura espontânea é caracterizada pela taxa de mortalidade mais elevada. RELATO DO CASO: O artigo apresenta uma paciente do sexo feminino de 64 anos de idade, cujo vômito era preto, quatro dias antes do exame, e continha sangue no dia do exame. Os sintomas incluíam dor epigástrica e sufocação. No exame físico, foi verificada hipotensão, taquicardia, dispneia e abdômen inchado e doloroso. Ausculta revelou estertores laterais na inspiração. A ultrassonografia mostrou estômago dilatado, preenchido com conteúdo líquido. Sucção nasogástrica evacuou mais de 1.000 ml de sangue fresco. Esofagogastroduodenoscopia foi abortada imediatamente ao se entrar no esôfago proximal, onde foi observada grande quantidade de sangue fresco. A paciente foi encaminhada com urgência para cirurgia abdominal, durante a qual faleceu. Autópsia estabeleceu diagnóstico de síndrome de Boerhaave e úlcera no bulbo-duodenal. CONCLUSÃO: A síndrome Boerhaave deve ser considerada em todos os casos com uma combinação de sintomas gastrointestinais (especialmente dor epigástrica e vómitos) e sintomas e sinais pulmonares (especialmente sufocação).

Boerhaave syndrome - case report.

CONTEXT:: Boerhaave syndrome consists of spontaneous longitudinal transmural rupture of the esophagus, usually in its distal part. It generally develops during or after persistent vomiting as a consequence of a sudden increase in intraluminal pressure in the esophagus. It is extremely rare in clinical practice. In 50% of the cases, it is manifested by Mackler's triad: vomiting, lower thoracic pain and subcutaneous emphysema. Hematemesis is an uncommon yet challenging presentation of Boerhaave's syndrome. Compared with ruptures of other parts of the digestive tract, spontaneous rupture is characterized by a higher mortality rate. CASE REPORT:: This paper presents a 64-year-old female patient whose vomit was black four days before examination and became bloody on the day of the examination. Her symptoms included epigastric pain and suffocation. Physical examination showed hypotension, tachycardia, dyspnea and a swollen and painful abdomen. Auscultation showed lateral crackling sounds on inspiration. Ultrasound examination showed a distended stomach filled with fluid. Over 1000 ml of fresh blood was extracted by means of nasogastric suction. Esophagogastroduodenoscopy was discontinued immediately upon entering the proximal esophagus, where a large amount of fresh blood was observed. The patient was sent for emergency abdominal surgery, during which she died. An autopsy established a diagnosis of Boerhaave syndrome and ulceration in the duodenal bulb. CONCLUSION:: Boerhaave syndrome should be considered in all cases with a combination of gastrointestinal symptoms (especially epigastric pain and vomiting) and pulmonary signs and symptoms (especially suffocation).

Global and specific histone acetylation pattern in patients with Balkan endemic nephropathy, a worldwide disease.

UNLABELLED: Abstract Background: Balkan endemic nephropathy (BEN) is a chronic tubulointerstitial nephropathy present in the Danube river regions in several Balkan countries. There appears to be a polygenic susceptibility to the disease in interaction with multiple environmental factors (aristolochic acid, ochratoxin A). In a previous study SEC61G, IL17RA, HDAC11 proved to be differently methylated throughout all patient-control pairs of BEN patients from Serbia and Bulgaria. Emerging connections between DNA methylation and histone acetylation prompted the present study on histone acetylation in patients with BEN. METHODS: The study involved 39 patients with BEN, and 39 controls collected from non-endemic regions in Serbia. The EpiSeeker Histone H3 and H4 Total Acetylation Detection colorimetric Kits and specific acetylated at lysine 18 H3K18 and H3K36 acetylated at lysine 36 detection kits were used. RESULTS: It was documented that total H4 histone acetylation level was increased significantly, while total H3 histone acetylation did not differ significantly. Specific histone structure and functional properties may be affected by the observed derangement of H3 histone acetylation pattern, since H3K36 site was significantly more acetylated, while H3K18 tended to be less acetylated than in control subjects. Multiple regression analysis revealed a statistically significant relationship between H4, H3T and H3K36 in BEN patients. CONCLUSION: This preliminary study suggests that the acetylation of histone lysine residues was detectable and found increased at specific sites of H3 and total H4 histones isolated from urothelial cells of patients with BEN. Having in mind a possible mechanism and biological role of epigenetic chromatin modification in urothelial tumor development they obtained results may open opportunity for selective therapeutic interventions in patients with BEN.

Tumor necrosis factor alpha gene polymorphism in serbian patients with sarcoidosis.

INTRODUCTION: Sarcoidosis is a multisystemic disease of unknown etiology. Genetic factors play a considerable role in the onset of the disease. Tumor necrosis factor alpha (TNF-a) is a proinflammatory cytokine which plays an important role in the pathogenesis of the disease and the formation of granuloma by regulating cellular proliferation and apoptosis. OBJECTIVE: The aim of this study was to investigate the role of TNF-alpha-308 G/A polymorphism in the development of sarcoidosis and to evaluate the association between the aforementioned type of polymorphism and the clinical course of the disease. METHODS: Seventy patients with sarcoidosis and 50 healthy volunteers were genotyped for the TNF-alpha-308G/A polymorphism. Polymorphism variants were examined by PCR-RFLP (polymerase chain reaction-restriction fragment length polymorphism) on the DNA isolated from blood leukocytes. RESULTS: There were no significant differences in TNF-alpha-308A allele frequency distribution between sarcoidosis patients and the control group, but the TNF-alpha-308A allele was observed significantly more frequently in the sarcoidosis patients with Löfgren's syndrome when compared with non-Löfgren's patients. CONCLUSION: We have found that the TNF-alpha-308A variant is associated with Löfgren's syndrome in Serbian patients with sarcoidosis.