Is it time for the practical application of biomarkers in chronic heart failure management?

Chronic heart failure is a complex clinical syndrome with increasing significance in the ageing societies of developed countries. Recent advances in both medical and instrumental therapy improve the prognosis of heart failure patients which, nevertheless, remains poor. Patients suffer from progressive pump failure reflected in increasing incidence of hospital admissions as well as sudden death due to electrical imbalance of diseased myocardium. AIM: The aim of the study was to review of current data on some most promising heart failure biomarkers. MATERIALS AND METHODS: To realize the aim of the work we analyzed papers published in recent years in medical journals indexed in PubMed and Google Scholar. RESULTS: Currently, only natriuretic peptides, reflecting pressure overload of the heart, and cardiac troponins, are recognized and used in practice diagnostic biomarkers of heart failure. Numerous plasma substances are being studied such as: galectin-3, ST-2 protein, MR-proADM, GDF- 15, uric acid and other. Among them, especially cardiac interstitial fibrosis markers seem to have the biggest prognostic value in heart failure patients. CONCLUSIONS: There is a growing number of indices with scientifically proven association with clinical outcome of heart failure patients. Large, randomized trials investigating the impact of biomarkers-guided clinical decisions on patients outcome are certainly needed.

Rare Case of a Young Male Presented with Abdominal Pain, Solid Colon Tumors, and Eosinophilia, Followed by Tremendous Thromboembolic Complications and Eventually Diagnosed with Idiopathic Hypereosinophilic Syndrome.

Hypereosinophilic syndrome (HES) is a rare condition characterized by profound peripheral eosinophilia and various organ dysfunction. Diagnostic criteria and classification of this challenging medical entity changed over time. Elevated absolute eosinophil count with extensive tissue infiltration and signs of organ damage of unknown origin is termed idiopathic HES. Hypereosinophilia is a highly hypercoagulable state; thus, a variety of thromboembolic complications may occur. Only a few reports of idiopathic HES patients with different forms of thrombosis are being published. We document a case of a young male presented with persistent abdominal pain with two eosinophilic colon tumors. The patient suffered from phlegmasia cerulea dolens and portal vein thrombosis, followed by pulmonary embolism and overt disseminated intravascular coagulation (DIC). Corticosteroids successfully reduced and controlled eosinophil level while skilled anticoagulation and supportive management overcome DIC-associated complications.

[Mutations of tumor suppressor gemne TP53 in tobacco smoke-associated tumors]. / Mutacje supresorowego genu przeciwnowotworowego TP53w nowotworach tytonio-zaleznych.

Tumour suppressor gene TP53 is a subject of frequent lesions and mutations in a majority of cancer types that is followed by its dysfunction in regulation of cell proliferation, apoptosin and DNA repair. Mutation profile reflects the presence of mutagen-vulnerable sites (including tobacco smoke carcinogens) in its structure. A number of mutations in tobacco smoke-associated cancers are higher than in other types. Particularly, G > T mutation is recognized a signature to benzo(a)pyrene exposure. Further, a mutation profile is dependent on cancer anatomic localization and histological type. There were put forward suggestions concerning estimation of cancer risk and disease prognosis basing of TP53 gene status and expression. The protocols of gene therapy involving TP53 gene are still not satisfactory.

Expression of neuromedins S and U and their receptors in the hypothalamus and endocrine glands of the rat.

Neuromedin S (NMS) and neuromedin U (NMU) are regulatory peptides that share the C-terminal amino-acid sequence and act via common G protein-coupled receptors called NMUR1 and NMUR2. Semiquantitative real time-PCR showed that in the rat hypothalamus and testis NMS gene expression was markedly higher than that of the NMU gene, while the reverse occurred in the anterior pituitary and thyroid gland. Low expression of both genes was detected in the thymus, adrenal gland and ovary, whereas in the pancreatic islets only the expression of NMU mRNA was detected. In the rat hypothalamus the expression of the NMUR2 gene was strikingly higher than that of the NMUR1 gene; in contrast, in the testis and ovary the very low expression of NMUR2 contrasted with the relatively high expression of the NMUR1 gene. In the other glands examined only expression of the NMUR1 gene was found. The marked differences in the level of expression of NMU, NMS and their receptors in the hypothalamus and endocrine glands of the rat suggest that in this species such neuromedins may play different roles in the functional regulation of neuroendocrine axes.

ZFP91-a newly described gene potentially involved in prostate pathology.

In search for novel molecular targets in benign prostate hyperplasia (BPH), a PCR Array based screening of 84 genes was performed. Of those, expression of ZFP91 (ZFP91 zinc finger protein) was notably upregulated. Limited data concerning the function of ZFP91 product show that it is a potential transcription factor upregulated in human acute myelogenous leukemia and most recently found to be the non-canonical NF-κB pathway regulator. In order to test this finding on a larger number of samples, prostate specimens were obtained from patients undergoing adenomectomy for BPH (n = 21), and as a control, from patients undergoing radical cystectomy for bladder cancer (prostates unchanged pathologically, n = 18). Similar studies were performed on cultured human prostate cancer cell lines: LNCaP, DU145, 22Rv1, PC-3; as well as normal prostate epithelial cells-PrEC. Methods employed included: Human Obesity PCR Array (Qiagen), QPCR and Western blotting. QPCR studies confirmed significant overexpression of ZFP91 in BPH samples. On a protein level, however, comparison between normal and BPH prostates revealed insignificant differences. As for prostate cell lines examined, all expressed ZFP91 mRNA. Western blotting analysis showed markedly higher protein levels of ZFP91 in all cancer cell lines in comparison with normal (PrEC) cells. In conclusion, the upregulated ZFP91 mRNA in BPH, not accompanied by parallel changes in ZFP91 protein levels, together with ZFP91 protein abundance in prostate cancer cell lines suggest ZFP91 involvement in these prostate diseases.

Adiponectin and adiponectin receptor system in the rat adrenal gland: ontogenetic and physiologic regulation, and its involvement in regulating adrenocortical growth and steroidogenesis.

Adiponectin (ADN) is a regulatory peptide secreted mostly by adipose tissue and acting via two receptors: AdipoR1 and AdipoR2. Our aim was to investigate expression of adiponectin system genes in the rat adrenal gland as well as its ontogenetic and physiological control. Furthermore, we examined the effects of acute and prolonged activation of HPA axis on ADN system in adipose tissue. By means of QPCR, ADN and AdipoR1 expression was demonstrated in rat adrenal cortex both at mRNA and protein levels, while AdipoR2 could only be detected at mRNA levels. ADN expression level was significantly upregulated in a developing and regenerating adrenal cortex. Globular domain of adiponectin at 10(-9) M stimulated corticosterone output and BrdU incorporation by cultured rat adrenocortical cells. Moreover, both acute (ACTH and ether stress) and prolonged (ACTH) adrenal stimulation resulted in lowered ADN levels, while expression of AdipoR1 and AdipoR2 was upregulated by the acute treatment. Depending on its site of origin, visceral (VAT) or subcutaneous (SAT) adipose tissue responded differently to alterations in HPA axis. VAT expression of ADN and its receptors remained almost unchanged by experimental manipulations. In SAT, on the other hand, expression of ADN and AdipoR2 was markedly increased by ACTH treatment and stress, while dexamethasone suppressed ADN and AdipoR1 mRNA levels. The results of this study provide new evidence for direct and indirect interactions between adipokines and HPA axis.

Contribution of polymorphism in codon 72 of TP53 gene to laryngeal cancer in Polish patients.

The amino acid substitution Arg72Pro in the TP53 protein has an impact on the biochemical and biological activity of this protein, and is associated with several types of cancers. However, the Arg72Pro polymorphism exhibits inconsistent contribution as a risk factor in various cancer types. Therefore, using PCR-RFLPs, we investigated the distribution of Arg72Pro genotypes and alleles in patients with laryngeal cancer (n=123) and controls (n=300) in Poland. We observed that patients with the Pro/Pro and Arg/Pro TP53 genotypes displayed a 1.755-fold increased risk of laryngeal cancer (95% CI=1.149-2.680, P=0.0099). However, we did not find a significant increase in laryngeal cancer risk for the homozygous Pro/Pro TP53 genotype OR=2.093 (95% CI=1.046-4.192, P=0.0530). This result suggests that the TP53Pro variant may contribute to the risk of laryngeal cancer development in Polish patients.