Case Report: Inferior Vena Cava Agenesia in a Young Male Patient Presenting With Bilateral Iliac Veins Thrombosis.

Introduction: Anomalies in inferior vena cava represent an uncommon finding with a prevalence of 0. 3 to 0.5% among healthy patients. Specifically, the condition characterized by the agenesis of the inferior vena cava (IVC; AIVC) has been observed among the 0.0005 to 1% of the general population. AIVC is strongly related to deep vein thrombosis (DVT) of the lower limb and pelvic district, especially in young patients. The rarity of the presented condition could relate to an underestimation of its impact on a particular clinical setting leading to a delayed diagnosis and inaccurate early- and long-term management. Report: We presented a case of this anomaly regarding a 31-year-old man presenting with bilateral symptomatic proximal DVT. Duplex vascular ultrasound and subsequent CT-angiography revealed the complete occlusion of the right external and common iliac vein, as well as partial occlusion of the contralateral external iliac vein, in the patient. The exam also revealed the interruption of IVC in its infrarenal part. At the level of renal veins coalescence, IVC appeared again in its usual position. A dilatated portal system, hepatic veins, and azygos and hemiazygos systems were also highlighted. Anticoagulation was promptly started with the administration of Fondaparinux (7.5 mg/die). In addition, compression stocking was initiated within 24 h from diagnosis. After 3 weeks, the anticoagulation regimen was shifted toward the administration of a direct oral anticoagulant (Apixaban; 5 mg two times a day). At 1-month follow-up, a vascular duplex ultrasound revealed a complete resolution of the iliac veins' thrombosis. Conclusion: It is important to consider the eventuality of IVC anomalies in a young adult presenting with unexplained, extensive, or bilateral DVT. Accurate diagnostic evaluation is necessary to fully identify this condition that could represent a real challenge.

SAR evolution towards potent C-terminal carboxamide peptide inhibitors of Zika virus NS2B-NS3 protease.

Zika virus (ZIKV) is a member of the Flaviviridae family that can cause neurological disorders and congenital malformations. The NS2B-NS3 viral serine protease is an attractive target for the development of new antiviral agents against ZIKV. We report here a SAR study on a series of substrate-like linear tripeptides that inhibit in a non-covalent manner the NS2B-NS3 protease. Optimization of the residues at positions P1, P2, P3 and of the N-terminal and C-terminal portions of the tripeptide allowed the identification of inhibitors with sub-micromolar potency with phenylglycine as arginine-mimicking group and benzylamide as C-terminal fragment. Further SAR exploration and application of these structural changes to a series of peptides having a 4-substituted phenylglycine residue at the P1 position led to potent compounds showing double digit nanomolar inhibition of the Zika protease (IC50 = 30 nM) with high selectivity against trypsin-like proteases and the proteases of other flavivirus, such as Dengue 2 virus (DEN2V) and West Nile virus (WNV).

Functional Selectivity Revealed by N-Methylation Scanning of Human Urotensin II and Related Peptides.

In accordance with their common but also divergent physiological actions, human urotensin II (1) and urotensin II-related peptide (2) could stabilize specific urotensin II receptor (UTR) conformations, thereby activating different signaling pathways, a feature referred to as biased agonism or functional selectivity. Sequential N-methylation of the amides in the conserved core sequence of 1, 2, and fragment U-II4-11 (3) shed light on structural requirements involved in their functional selectivity. Thus, 18 N-methylated UTR ligands were synthesized and their biological profiles evaluated using in vitro competition binding assays, ex vivo rat aortic ring bioassays and BRET-based biosensor experiments. Biological activity diverged from that of the parent structures contingent on the location of amide methylation, indicating relevant hydrogen-bond interactions for the function of the endogenous peptides. Conformational analysis of selected N-methyl analogs indicated the importance of specific amide residues of 2 for the distinct pharmacology relative to 1 and 3.

Heart failure with preserved systolic function: prevalence and clinical features in a cohort of patients admitted to internal medicine units. The study PRESYF-HF Tuscany.

BACKGROUND: There is uncertainty about the prevalence and clinical characteristics of heart failure (HF) patients with preserved systolic function (PRESYF). AIM: To analyze the prevalence and clinical characteristics of patients with PRESYF in an unselected cohort of subjects consecutively hospitalized for HF. METHODS: The study cohort included 338 patients consecutively admitted for HF at 24 Internal Medicine units homogeneously settled in Tuscany area (Italy). We did not have any criteria for exclusion. All patients had an echocardiographic measure of left ventricular ejection fraction (LVEF) within 72 hours from hospital admission. Patients with LVEF > or = 50% were considered to have PRESYF. RESULTS: The patients with PRESYF were 112 (33.1%), those with depressed systolic function (DESYF) 226 (66.9%). In the group PRESYF were prevalent female sex, hypertensive etiology, and elevated BMI. The distribution for classes of age shows a great frequency of PRESYF in the elderly. CONCLUSION: About one third of patients admitted for HF have a PRESYF. They are different compared to those with DESYF. A correct identification of this form of HF may be important in clinical practice for more targeted therapeutic options and for prognostic implications.

Heart failure, oxidative stress and allopurinol.

Oxidative stress is one of the new and most intriguing pathogenetic hypotheses of heart failure; it involves various mechanisms such as endothelial dysfunction, mechano-energetic uncoupling and apoptosis. Xanthine oxidase, a key enzyme in purine catabolism, is overexpressed in patients with heart failure, and it is also an important source of oxidizing activity molecules (free radicals, superoxide anion, oxygen peroxide, etc...). Allopurinol competitively inhibits the action of xanthine oxidase and effectively counters oxidative stress. It could thus prove useful in the treatment of heart failure: in fact it is the only drug that has been proven able to lower O2 consumption of dysfunctioning myocardium. The Authors briefly review the xanthine oxido-reductase enzyme system and in particular analyse the latest evidence reported in the literature on allopurinol in the treatment of heart failure.