Collagen-Carboxymethylcellulose Biocomposite Wound-Dressings with Antimicrobial Activity

Microbial infections associated with skin diseases are frequently investigated since they impact on the progress of pathology and healing. The present work proposes the development of freeze-dried, glutaraldehyde cross-linked, and non-cross-linked biocomposite dressings with a porous structure, which may assist the reepithelization process through the presence of collagen and carboxymethylcellulose, along with a therapeutic antimicrobial effect, due to silver nanoparticles (AgNPs) addition. Phisyco-chemical characterization revealed the porous morphology of the obtained freeze-dried composites, the presence of high crystalline silver nanoparticles with truncated triangular and polyhedral morphologies, as well as the characteristic absorption bands of collagen, silver, and carboxymethylcellulose. In vitro tests also assessed the stability, functionality, and the degradability rate of the obtained wound-dressings. Antimicrobial assay performed on Gram-negative (Escherichia coli), Gram-positive (Staphyloccocus aureus) bacteria, and yeast (Candida albicans) models demonstrated that composite wound dressings based on collagen, carboxymethylcellulose, and AgNPs are suitable for skin lesions because they prevent the risk of infection and have prospective wound healing capacity. Moreover, the cell toxicity studies proved that the obtained materials can be used in long time treatments, with no cytotoxic effects.     

Targeting Janus tyrosine kinase 3 (JAK3) with an inhibitor induces secretion of TGF-β by CD4+ T cells

Regulatory T cells (Tregs) are critical for the peripheral maintenance of the autoreactive T cells in autoimmune disorders such as type 1 diabetes (T1D). Pharmacological inhibition of Janus tyrosine kinase 3 (JAK3) has been proposed as a basis for new treatment modalities against autoimmunity and allogeneic responses. Targeting JAK3 with an inhibitor has previously been shown to exhibit protective action against the development of T1D in non-obese diabetic (NOD) mice. As the mechanism of such preventative action has been unknown, we hypothesized that JAK3 inhibition induces generation of Tregs. Here, we show that the JAK3 inhibitor 4-(4′-hydroxyphenyl)-amino-6,7-dimethoxyquinazoline (WHI-P131) suppresses proliferation of short-term cultured NOD CD4⁺ T cells through induction of apoptosis, while promoting survival of a particular population of long-term cultured cells. It was found that the surviving cells were not of the CD4⁺CD25⁺FoxP3⁺ phenotype. They secreted decreased amounts of IL-10, IL-4 and interferon (IFN)-γ compared to the cells not exposed to the optimal concentrations of JAK3 inhibitor. However, an elevated transforming growth factor (TGF)-β secretion was detected in their supernatants. In vivo treatment of prediabetic NOD mice with WHI-P131 did not affect the frequency and number of splenic and pancreatic lymph node CD4⁺FoxP3⁺ Tregs, while generating an elevated numbers of CD4⁺FoxP3⁻ TGF-β-secreting T cells. In conclusion, our data suggest an induction of TGF-β-secreting CD4⁺ T cells as the underlying mechanism for antidiabetogenic effects obtained by the treatment with a JAK3 inhibitor. To our knowledge, this is the first report of the JAK3 inhibitor activity in the context of the murine Tregs.     

Efficacité sur la croissance et tolérance d’une préparation pour nourrissons à base de protéines de riz hydrolysées

The objective of this study was to assess the efficacy in terms of growth and tolerance of an infant formula based on hydrolyzed rice proteins.Patients and methodsHealthy infants, born at term, less than 1 month old, and exclusively fed an infant formula based on hydrolyzed rice proteins until their diet was diversified, were included in this open-label, multicenter study. The main outcome measure was daily weight gain during the study period. The infant's weight, height, body mass index (BMI), and the data concerning tolerance (digestive disorders, allergy manifestations) were collected at inclusion in the study, at 2 and 4 months, and before diversifying the infant's diet between 4 and 6 months. The growth parameters were compared to the WHO standards by calculating the Z-score.ResultsSeventy-eight infants were included. The mean daily weight gain over 5 months was 23.2 ± 4.3 g/day, identical to the WHO standards (22.2 ± 1.8 g/day, P = 0.09). During the study period, the Z-scores for weight, height, and BMI varied between +1.1 and ?0.5 SD according to the WHO standards. Formula acceptance and tolerance were both good.ConclusionThe infant formula studied, based on hydrolyzed rice proteins, was well tolerated and led to normal growth over the first few months of life, comparable to the WHO standards.     

Two weeks of postsurgical therapy may be enough for high-risk cases of endocarditis caused by Streptococcus viridans or Streptococcus bovis

The duration of antimicrobial therapy after surgery for infective endocarditis (IE) is controversial. A short course of postsurgical therapy is currently accepted only for patients with negative valve culture. We performed a retrospective (1994–2008) analysis of patients who underwent surgery for IE in our hospital and had a high risk of complications (one of more of the following: <2 weeks of antibiotic treatment before surgery; embolism; perivalvular extension; and positive valve culture) to compare outcomes of patients who received short-course antimicrobial therapy (SAT) (median 15 days) or long-course antimicrobial therapy (LAT) (median 32 days), irrespective of the results of valve culture. Our endpoints included length of hospital stay, renal and hepatic failure, relapse, re-infection, and mortality rates 1 year after surgery. During the study period, 140 patients underwent surgery for IE (valve replacement, 87.9%). Of these, 133 fulfilled the high-risk group criteria and 92 completed the antimicrobial schedule. Comparison of patients receiving SAT (37) and LAT (55) showed that the SAT group had a shorter length of hospital stay (29 vs. 40 days, p 0.01), and a trend towards lower frequency of renal failure (5.4% vs. 18.2%, p 0.11) and hepatic failure (5.4% vs. 9.1%, p 0.69), whereas mortality (5.4% vs. 3.6%, p 1), relapse (0% vs. 1.8%, p 1) and re-infection (5.4% vs. 3.6%, p 1) rates were similar between both groups. Multivariate analysis showed that IE caused by Streptococcus viridans or Streptococcus bovis was independently associated with SAT. Postsurgical SAT is safe, especially when IE is caused by Streptococcus viridans or Streptococcus bovis, even in patients at high risk of complications.     

Recent improvements in the management of esophageal anastomotic leak after surgery for cancer

Anastomotic leakage following total gastrectomy or esophagectomy is a significant complication that considerably increases postoperative mortality. The location of the anastomosis together with the anatomy of the esophagus explains the severity of this complication. Surgical knowledge should include general and specific predictive factors of leakage to avoid any technical-related cause of leakage.Clinical presentations may vary from minimally symptomatic to life-threatening situations. Investigations should be undertaken as soon as the diagnosis is suspected because delay greatly worsens the prognosis. CT scans with oral contrast and low insufflation early endoscopy are the preferred diagnostic tools and can also aid in therapeutic procedures.Communication and multidisciplinary teamwork are the cornerstones of treatment. When the leak occurs early with acute and important sepsis, the recommendation is surgical treatment. On the contrary, if the leak is late, non-symptomatic or minimally symptomatic, conservative management with intensive surveillance could be proposed. When the situation is in between these two extremes, endoscopic treatment is often proposed.Based on a review of the literature and experience from high volume centers, in this educational review, we present the incidence, predictive factors, clinical presentations, diagnostic tools, management, and therapeutic algorithms for anastomotic leaks following elective esophagectomy and total gastrectomy for cancer.