Evaluation of the effects of different treatment modalities on angiogenesis in heart failure patients with reduced/mid-range ejection fraction via VEGF and sVEGFR-1.

OBJECTIVES: To investigate the clinical significance of VEGF, sVEGFR-1 in heart failure reduced ejection fraction (HFrEF) and heart failure mid-range ejection fraction (HFmrEF) patients. Methods: A total of 104 people consisting of HFrEF and HFmrEF patients (n=54) and healthy (n=50) subjects were included in this comparative cross-sectional study. The study took place in Gulhane Training and Research Hospital, Ankara, Turkey, between  2011 and 2013. Serum VEGF, sVEGFR-1, plasma pro-BNP analysis and transthoracic echocardiography were performed.  Results: The average sVEGFR-1 level of the HFrEF and HFmrEF patients was significantly higher than the control group (0.185±0.122; 0.141±0.120; p=0.013). The average sVEGFR-1 level of the HFrEF and HFmrEF patients using beta-blocker was significantly higher than the HFrEF and HFmrEF patients not using it (p=0.015). There was a significant and positive correlation between sVEGFR-1 and N-terminal pro-brain natriuretic peptide (pro-BNP)  levels in the group with HF (r=0.211, p=0.044). Conclusion: It increases awareness about the role of sVEGFR-1 in HFrEF anf HFmrEF patients and the need for further studies. Beta-blocker may have a negative effect on angiogenesis in HFrEF and HFmrEF via increasing sVEGFR-1 levels. Additionally, Pro-BNP may contribute to inhibiting angiogenesis by increasing sVEGFR-1 levels and sVEGFR-1 may be an important biomarker in HFrEF and HFmrEF.

NFU1 gene mutation and mitochondrial disorders.

Mitochondrial respiratory chains consist of approximately 100 structural proteins. Thirteen of these structural proteins are encoded by mitochondrial DNA (mtDNA), and the others by nuclear DNA (nDNA). Mutation in any of the mitochondrial structural-protein related genes, regardless of whether they are in the nDNA or mtDNA, might cause mitochondrial disorders. In the recent past, new nuclear genes required for assembly, maintenance, and translation of respiratory chain proteins have been found. Mutation in these genes might also cause mitochondrial disorders (MD). NFU1 gene is one of such genes and has a role in the assembly of iron-sulfur cluster (ISC). ISCs are included in a variety of metalloproteins, such as the ferredoxins, as well as in enzymatic reactions and have been first identified in the oxidation-reduction reactions of mitochondrial electron transport. It is important to be aware of NFU1 gene mutations that may cause severe mitochondrial respiratory chain defects, mitochondrial encephalomyopathies and death, early in life.

Two cases of the same family with the unusual elevation of CA19-9 levels.

INTRODUCTION: Serum carbohydrate associated antigen (CA19-9) is widely used marker in clinical practice and shows small increases in a few benign diseases. Here we report two cases, a mother and her daughter with slightly elevated CA19-9 levels not accompanied by any clinical pathology. CASE PRESENTATION: The mother with elevated CA19-9 level (89.90 U/mL; upper limit of normal range (ULNR) < 37 U/mL) was referred to our department for evaluation. Similar increase was determined in her daughter incidentally. Daughter's CA19-9 level was 123.92 U/mL. Extensive laboratory data, imaging procedures and clinical evaluations were within the normal ranges except elevated CA19- 9 levels for both. Also, any pathology compatible with the elevated CA19-9 level couldn't be determined. In order to avoid laboratory errors and interferences, we measured the samples at four different immunoassay platforms twice. CONCLUSION: Healthy people can be in excess of the ULNR. Therefore, clinicians need to be aware of these rare situations without missing the malignant disorders.

Introdução: O antigénio carbohidrato (CA19-9) presente no soro é um marcador amplamente utilizado na prática clínica e apresenta pequenos aumentos em algumas doenças benignas. Aqui relatamos dois casos saudáveis, uma mãe e a sua filha, com níveis CA19-9 um pouco elevados.Casos Clínicos: A mãe, com um nível CA19-9 elevado (89,90 U/mL; limite superior do intervalo normal (ULNR) < 37 U/mL) foi encaminhada ao nosso departamento para avaliação. Um aumento semelhante foi incidentalmente determinado na sua filha. O nível de CA19-9 da filha era 123,92 U/mL. Os restantes parametros laboratoriais avaliados, estudos imagiológicos e avaliações clínicas revelaram-se dentro dos limites da normalidade. Não foi encontrada, qualquer patologia que justifique elevado nível de CA19-9. A fim de evitar erros de laboratório ou possíveis interferências, as amostras foram analisadas em quatro plataformas de imunoensaios diferentes, em duplicado.Conclusão: As pessoas saudáveis podem ter níveis da CA19-9 superiores aos limites de referência. Portanto, os médicos precisam estar cientes dessas situações raras, sem falhar o diagnóstico de doenças malignas.

Pentraxin 3 as a potential biomarker of acetaminophen-induced liver injury.

OBJECTIVE: Overdose of acetaminophen (APAP) can lead to severe liver injury in humans and experimental animals. Pentraxin-3 (PTX-3) is produced and released by several cell types. In this study, we aimed to evaluate whether PTX-3 is a potential biomarker in the identification of APAP-induced liver injury. MATERIALS AND METHODS: Thirty adult male Wistar rats were randomly divided into three groups: control, APAP-1 and APAP-2 groups. APAP-1 (1 g/kg) and APAP-2 (2 g/kg) group rats were given APAP by gastric tube. Liver tissues and blood samples were obtained for biochemical and histopathological analysis. Biochemical parameters, plasma and liver PTX-3 levels and degree of liver necrosis were measured in all groups. RESULTS: APAP treatments caused necrosis in liver and accompanied by elevated liver PTX-3 levels after 48 h. In APAP-1 and APAP-2 groups when compared with control group (7.5±3.3 ng/mg protein), mean liver PTX-3 concentrations were 14.1±3.0 (p=0.032) and 28.5±8.2 (p<0.001) ng/mg protein, respectively. All rats (100%) in the APAP-2 group had the degree 3 liver necrosis. However 10%, 40% and 50% of rats had the degree 1, the degree 2 and the degree 3 liver necrosis in the APAP-1 group, respectively. The degrees of liver necrosis of the APAP-1 and APAP-2 groups were higher than the group of control (p<0.001 and p<0.001, respectively). CONCLUSIONS: PTX-3 may have a role in the APAP-induced liver injury in the rats. The elevated liver PTX-3 in the APAP-induced hepatic necrosis might be a marker of acute histological liver damage. Further prospective studies are necessary to clarify the prognostic value of liver PTX-3 for prediction of histological hepatic necrosis in the APAP-induced liver injury.

The association between neopterin and acetaminophen-induced nephrotoxicity.

INTRODUCTION: In large dosages, acetaminophen (APAP) produces acute kidney necrosis in most mammalian species. High neopterin levels have been accepted as strong indicators for the clinical severity of some diseases. In this study, we aimed to evaluate whether neopterin is a biomarker in the identification of APAP-induced nephrotoxicity. MATERIALS AND METHODS: Thirty adult male Wistar rats were randomly divided into three groups: control, APAP-1, and APAP-2 groups. APAP-1 and APAP-2 group rats were given a single dose of 1 and 2 g/kg body weight of APAP by gastric tube, respectively. Kidney tissues and blood samples were obtained for biochemical and histopathological analyses. Biochemical parameters, serum and kidney neopterin levels, and the grade of tubular injury were compared in the control, APAP-1, and APAP-2 group animals. RESULTS: APAP treatments caused tubular necrosis in the kidney and increase in serum creatinine concentrations accompanied by elevated serum and kidney neopterin levels. In the rats of groups APAP-1 and APAP-2 when compared with that of the control group (109.1 pmol/mg protein), median kidney neopterin concentrations were 162.1 (p = 0.089) and 222.2 (p < 0.001) pmol/mg protein, respectively. The grade of tubular injury of the APAP-1 and APAP-2 groups was higher than the group of control (both p < 0.001). CONCLUSIONS: Serum and kidney neopterin levels could be sensible alternative to evaluate the risk to have nephrotoxicity because of APAP overdose. The elevated serum and kidney neopterin in the APAP-induced tubular necrosis might be a marker of acute histological kidney injury.