New model of liver regeneration induced through use of vascular endothelial growth factor

INTRODUCTION: Vascular endothelial growth factor (VEGF) is an endothelial cell mitogen. The objective of this study was to verify the proregenerative effects of VEGF in an experimental model of acute liver failure. MATERIALS AND METHODS: Sixty four rats that underwent intraperitoneal injection of carbon tetrachloride (CCl(4)) were randomly divided into two groups: group B animals received intravenous injection of VEGF(164) 1 hour following CCl(4) poisoning. Group A hosts were untreated. To obtain daily liver function tests (LFTs) and histological samples, on each day up to 8 days we sacrificed four rats in each group. RESULTS: The laboratory examinations showed notable alteration of LFTs in group A, while group B revealed only slight changes. The histological examination showed greater liver damage in group A compared with group B. CONCLUSION: Our results suggest that administration of exogenous VEGF protects the liver from CCl(4)-induced acute hepatic failure. Further studies are underway to assess whether exogenous VEGF is effective in other liver injuries.     

Study of thrombinic activation indexes, in patients with lower limb critic ischaemia, before and after prostaglandin E1 therapy.

BACKGROUND: In this study the action of a prostaglandin, PGE1, was studied in a group of patients with peripheral arterial occlusive disease (PAOD). METHODS: In 16 patients (14 men and 2 women, aged 47-70 years, mean 57 +/- 7) with PAOD, Fontaine stage IIb and III in critical ischemia, the effects on two indexes of thrombin generation and action of the endovenous administration (2 hours) of 60 micrograms of Alprostadil-PGE1 for four weeks were evaluated. In all artheriopathic patients, before and after pharmacological treatment, the following haemostatic parameters were evaluated: the prothrombin fragment 1 + 2 (F1 + 2) and the fibrinopeptide A(FPA). RESULTS: The patients showed plasma levels of FPA significantly decreased at the end of the treatment. On the other hand, no significant difference in plasma F1 + 2 levels was observed after treatment. CONCLUSIONS: These results seem to indicate that plasma F1 + 2 levels are significantly elevated, as a marker of thrombosis status, in patients with PAOD before and after treatment with PGE1.     

Intercalated Chemotherapy and Epidermal Growth Factor Receptor Inhibitors for Patients With Advanced Non–Small-cell Lung Cancer: A Systematic Review and Meta-analysis

Randomized clinical trials (RCTs) of concurrent epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) plus chemotherapy for unselected patients with advanced non–small-cell lung cancer (NSCLC) produced negative results. Intercalated administration could avoid the reduction of chemotherapy activity due to G₁ cell-cycle arrest from EGFR-TKIs. A PubMed search was performed in December 2015 and updated in February 2016. The references from the selected studies were also checked to identify additional eligible trials. Furthermore, the proceedings of the main international meetings were searched from 2010 onward. We included RCTs comparing chemotherapy intercalated with an EGFR-TKI versus chemotherapy alone for patients with advanced NSCLC. Ten RCTs were eligible (6 with erlotinib, 4 with gefitinib): 39% of patients had a known EGFR mutational status, 43% of whom EGFR mutation positive. The intercalated combination was associated with a significant improvement in overall survival (OS; hazard ratio [HR], 0.82; 95% confidence interval [CI], 0.71-0.95; P = .01), progression-free survival (PFS; HR, 0.60; 95% CI, 0.53-0.68; P < .00001), and objective response rate (ORR; odds ratio [OR], 2.70; 95% CI, 2.08-3.49; P < .00001). Considering only first-line trials, similar differences were found in OS (HR, 0.85; 95% CI, 0.72-1.00; P = .05), PFS (HR, 0.63; 95% CI, 0.55-0.73; P < .00001), and ORR (OR, 2.21; 95% CI, 1.65-2.95; P < .00001). In EGFR mutation-positive patients, the addition of an intercalated EGFR-TKI produced a significant benefit in PFS (129 patients; HR, 0.24; 95% CI, 0.16-0.37; P < .00001) and ORR (168 patients; OR, 11.59; 95% CI, 5.54-24.25; P < .00001). In patients with advanced NSCLC, chemotherapy plus intercalated EGFR-TKIs was superior to chemotherapy alone, although a definitive interpretation was jeopardized by the variable proportion of patients with EGFR mutation-positive tumors included.     

Design, synthesis, biological activity, and ADME properties of pyrazolo[3,4-d]pyrimidines active in hypoxic human leukemia cells: a lead optimization study

A family of dual Src/Abl inhibitors characterized by a substituted pyrazolo[3,4-d]pyrimidine scaffold was previously reported by us and proved to be active against several tumor cell lines. Among these compounds, a promising antileukemia lead (1) has been recently identified, but, unfortunately, it suffers from substandard pharmaceutical properties. Accordingly, an approach for the optimization of the lead 1 is described in the present work. A series of more soluble pyrazolo[3,4-d]pyrimidine derivatives were rationally designed and proved to maintain the dual Src/Abl activity of the lead. Selected compounds showed an interesting activity profile against three different leukemic cells also in hypoxic conditions, which are usually characterized by imatinib-resistance. Finally, in vitro ADME properties (PAMPA permeation, water solubility, microsomal stability) for the most promising inhibitors were also evaluated, thus allowing the identification of a few optimized analogues of lead 1 as promising antileukemia agents.     

SIEDY Scale 3, a New Instrument to Detect Psychological Component in Subjects with Erectile Dysfunction

IntroductionWe previously developed and validated a structured interview (SIEDY) dealing with the organic (Scale 1), relational (Scale 2), and psychological (Scale 3) components of erectile dysfunction (ED).AimTo identify a pathological threshold for SIEDY Scale 3 and to analyze Scale 3 score with biological and psychological correlates in subjects with sexual dysfunction.MethodA pathological threshold of SIEDY Scale 3 score in predicting subjects with a medical history of psychopathology and using psychiatric drugs was identified through receiver operating characteristic (ROC) curve analysis in a sample of 484 patients (Sample A).Main Outcome MeasureSensitivity and specificity, along with possible interactions with biological and psychological (Middlesex Hospital Questionnaire, MHQ‐score) correlates were verified in a further sample of 1,275 patients (Sample B).ResultsIn sample A, 39 (8%) and 60 (12.4%) subjects reported a positive medical history for psychiatric disturbances or for the use of psychotropic medication, respectively. The association with both conditions was present in 28 (5.8%) subjects. ROC curve showed that SIEDY Scale 3 score predicts psychopathology with an accuracy of 69.5 ± 5.9% (P < 0.002), when a threshold of 3 was chosen. When the same threshold was applied in Sample B, it identified a higher ranking in MHQ‐A (free‐floating anxiety), MHQ‐S (somatized anxiety) and MHQ‐D (depressive symptoms) subscales, even after adjustment for age and Σ‐MHQ (a broader index of general psychopathology). In the same sample, we also confirmed that pathological Scale 3 score was related to a higher risk of psychopathology at medical history or to the use of psychotropic drugs as well as with risky lifestyle behaviors, including smoking and alcohol abuse, and elevated BMI.ConclusionsSIEDY represents an easy tool for the identification of patients with a relevant intra‐psychic component who should be considered for psychological/psychiatric treatment. Corona G, Ricca V, Bandini E, Rastrelli G, Casale H, Jannini EA, Sforza A, Forti G, Mannucci E, and Maggi M. SIEDY Scale 3, a new instrument to detect psychological component in subjects with erectile dysfunction. J Sex Med 2012;9:2017–2026.