Intralesional administration of epidermal growth factor‐based formulation (Heberprot‐P) in chronic diabetic foot ulcer: treatment up to complete wound closure

Previous studies have shown that an epidermal growth factor‐based formulation (Heberprot‐P) can enhance granulation of high‐grade diabetic foot ulcers (DFU). The aim of this study was to explore the clinical effects of this administration up to complete wound closure. A pilot study in 20 diabetic patients with full‐thickness lower extremity ulcers of more than 4 weeks of evolution was performed. Mean ulcer size was 16·3 ± 21·3 cm². Intralesional injections of 75 μg of Heberprot‐P three times per week were given up to complete wound healing. Full granulation response was achieved in all 20 patients in 23·6 ± 3·8 days. Complete wound closure was obtained in 17 (85%) cases in 44·3 ± 8·9 days. Amputation was not necessary in any case and only one relapse was notified. The most frequent adverse events were tremors, chills, pain and ardour at site of administration and local infection. The therapeutic scheme of intralesional Heberprot‐P administration up to complete closure can be safe and suitable to improve the therapeutic goal in terms of healing of chronic DFU.     

Stress urinary incontinence 3 years after pregnancy: correlation to mode of delivery and parity

The aim was to estimate the incidence of stress urinary incontinence 3 years after delivery and its correlation to mode of delivery and parity. A longitudinal cohort study was conducted with 120 women at the Antenatal Clinic at the State University of Campinas. There was a significant difference in the incidence of postpartum stress urinary incontinence (SUI) among patients with SUI during pregnancy (p > 0.0001). Women that were asymptomatic during pregnancy and had vaginal delivery developed SUI 2.4 times more frequently than after c-section (19.2% and 8.0%, respectively). The incidence of SUI after delivery dropped significantly in the primiparous (p = 0.0073) and multiparous 2–3 (p < 0.0001), but not in the multiparous with four or more deliveries (66.7% to 60.0%) (p = 0.5637). A significant correlation has been observed between parity and SUI (p = 0.0299). Pregnancy possibly predisposes to SUI 3 years after delivery as well as parity. No significant correlation has been demonstrated between mode of delivery and SUI.     

Differences in presentation and follow-up between HIV-1 antibody positive teenagers and adults: the need for a more focused approach to care?

Our findings show a high rate of loss to follow-up in HIV-positive teenagers compared with adults. Of concern is the fact that this group also have high rates of sexually transmitted infections, unprotected sex and pregnancy. There is an urgent need to examine the reasons for this and adopt strategies to minimize risk-taking behaviour and to improve access to appropriate healthcare.     

Adriamycin binding assay: a valuable chemosensitivity test in human osteosarcoma

Summary The reliability of a simple method evaluating the pattern of subcellular binding of Adriamycin (Adriamycin binding assay, ABA) as an index of sensitivity was demonstrated in different primary cultures and in sensitive and resistant cell lines of human osteosarcoma. After exposure to Adriamycin (10 g/ml for 30 min at 37°C), living sensitive cells showed selective intranuclear uptake of the drug, whereas in resistant cells no distinct subcellular distribution was observed. The binding pattern of Adriamycin in sensitive and in highly resistant cells was inversely related to the expression of P-glycoprotein. However, low levels of resistance in vitro, not detectable by increased levels of expression of P-glycoprotein, were revealed by ABA. The use of ABA in combination with the estimate of P-glycoprotein expression is recommended in clinical practice as an accurate means for predicting the sensitivity of osteosarcoma to Adriamycin.This study was supported by a grant from the Associazione Italiana per la Ricerca sul Cancro (A.I.R.C.).     

Immune reconstitution complicated by CMV retinitis in a pediatric patient who underwent haploidentical CD34+-selected hematopoietic stem cell transplant for acute lymphoblastic leukemia

We describe two episodes of CMV retinitis in a pediatric patient who underwent a CD34+ selected graft from his haploidentical father. Both recipient and donor were cytomegalovirus (CMV) seropositive. Both episodes occurred late post-grafting during a phase of complete immunological recovery with sufficient numbers of circulating CMV-specific clones. Antiviral treatment with foscarnet and ganciclovir was successful but prolonged treatment was required to prevent relapses. We hypothesize that this complication was more related to an immune reconstitution process than to an immune-deficient state post-grafting. We conclude that CMV retinitis is a late complication of HSCT that can occur despite satisfactory immune reconstitution. Usually, it is responsive to antiviral therapy. Dilated fundoscopic examination is essential both for examining patients with reduced visual acuity and for screening asymptomatic patients.     

Inhibition of influenza A virus replication by resveratrol

We have previously shown that the life cycles of several viruses are influenced by host-cell redox states. Reports of the antioxidant activities of the plant polyphenol resveratrol (RV) prompted us to investigate its effects on influenza virus replication in vitro and in vivo. We found that RV strongly inhibited the replication of influenza virus in MDCK cells but that this activity was not directly related to glutathione-mediated antioxidant activity. Rather, it involved the blockade of the nuclear-cytoplasmic translocation of viral ribonucleoproteins and reduced expression of late viral proteins seemingly related to the inhibition of protein kinase C activity and its dependent pathways. RV also significantly improved survival and decreased pulmonary viral titers in influenza virus-infected mice. No toxic effects were observed in vitro or in vivo. That RV acts by inhibiting a cellular, rather than a viral, function suggests that it could be a particularly valuable anti-influenza drug.     

Phenotypic characterization and predictive analysis of p.Asp47Asn LDL receptor mutation associated with Familial Hypercholesterolemia in a Chilean population

BackgroundFamilial hypercholesterolemia (FH) is an inherited disorder mainly caused by mutations in the LDL receptor (LDL-R) and characterized by elevation of low-density lipoprotein cholesterol (LDL-C) levels and premature cardiovascular disease.ObjectiveIn this study, we evaluated the clinical phenotype of the p.Asp47Asn, described as an uncertain pathogenic variant, and its effect on the structure of LDL-R and ligand interactions with apolipoproteins.Methods27 children and adolescents with suspected FH diagnosis were recruited from a pediatric endocrinology outpatient clinic. Blood samples were collected after 12 h fasting for lipid profile analysis. DNA sequencing was performed for six FH-related genes by Ion Torrent PGM platform and copy number variation by MLPA. For index cases, a familial cascade screening was done restricted to the same mutation found in the index case. In silico analysis were developed to evaluate the binding capacity of LDL-R to apolipoproteins B100 and E.ResultsLipid profile in children and adolescents demonstrated higher LDL-C levels in p.Asp47Asn carriers compared to the wild type genotype. In silico analysis predicted a reduction in the binding capacity of the ligand-binding modules LA1-2 of p.Asp47Asn LDL-R for ApoB100 and ApoE, which was not produced by local structural changes or folding defects but as a consequence of a decreased apparent affinity for both apolipoproteins.ConclusionThe clinical phenotype and the structural effects of p.Asp47Asn LDL-R mutation suggest that this variant associates to FH.