Perioperative latex allergy.

The prevalence of latex allergy varies greatly depending on the population studied and the methods used to detect sensitization. Subjects considered to be at high risk for latex allergy are rubber industry workers, children with spina bifida and urological abnormalities, children undergoing multiple surgical procedures and with urinary catheterization, health care workers and people with food allergy (latex fruit syndrome). In this paper we report a review of latex proteins, the symptoms of latex allergy, diagnosis and management in subjects with latex allergy

Perioperative allergy: therapy.

Perioperative allergic reactions manifest in various ways. The majority of systemic reactions occur during anesthesia within minutes of intravenous induction; however, agents which are administered via other routes may cause reactions after more than 15 minutes. Anaphylaxis during anesthesia may present in many different ways and the signs and symptoms, which do not vary from those of anaphylactic reactions in general, may be masked by hypovolemia, light, deep anesthesia or extensive regional blockade. Recommendations for treatment are based on available evidence in the literature. A treatment algorithm is suggested, with emphasis on the incremental titration of adrenaline and fluid therapy as first-line treatment. Increased focus on this subject will hopefully lead to prompt diagnosis and rapid, correct treatment

Simulated microgravity promotes the formation of tridimensional cultures and stimulates pluripotency and a glycolytic metabolism in human hepatic and biliary tree stem/progenitor cells

Many pivotal biological cell processes are affected by gravity. The aim of our study was to evaluate biological and functional effects, differentiation potential and exo-metabolome profile of simulated microgravity (SMG) on human hepatic cell line (HepG2) and human biliary tree stem/progenitor cells (hBTSCs). Both hBTSCs and HepG2 were cultured in a weightless and protected environment SGM produced by the Rotary Cell Culture System (Synthecon) and control condition in normal gravity (NG). Self-replication and differentiation toward mature cells were determined by culturing hBTSCs in Kubota's Medium (KM) and in hormonally defined medium (HDM) tailored for hepatocyte differentiation. The effects on the expression and cell exo-metabolome profiles of SMG versus NG cultures were analyzed. SMG promotes tridimensional (3D) cultures of hBTSCs and HepG2. Significative increase of stemness gene expression (p < 0.05) has been observed in hBTSCs cultured in SMG when compared to NG condition. At the same time, the expression of hepatocyte lineage markers in hBTSCs differentiated by HDM was significantly lower (p < 0.05) in SMG compared to NG, demonstrating an impaired capability of hBTSCs to differentiate in vitro toward mature hepatocytes when cultured in SMG condition. Furthermore, in HepG2 cells the SMG caused a lower (p < 0.05 vs controls) transcription of CYP3A4, a marker of late-stage (i.e. Zone 3) hepatocytes. Exo-metabolome NMR-analysis showed that both cell cultures consumed a higher amount of glucose and lower glutamate in SMG respect to NG (p < 0.05). Moreover, hBTSCs media cultures resulted richer of released fermentation (lactate, acetate) and ketogenesis products (B-hydroxybutyrate) in SGM (p < 0.05) than NG. While, HepG2 cells showed higher consumption of amino acids and release of ketoacids (3-Methyl-2-oxovalerate, 2-oxo-4-methyl-valerate) and formiate with respect to normogravity condition (p < 0.05). Based on our results, SMG could be helpful for developing hBTSCs-derived liver devices. In conclusion, SMG favored the formation of hBTSCs and HepG2 3D cultures and the maintenance of stemness contrasting cell differentiation; these effects being associated with stimulation of glycolytic metabolism. Interestingly, the impact of SMG on stem cell biology should be taken into consideration for workers involved in space medicine programs

Cryopreservation protocol for human biliary tree stem/progenitors, hepatic and pancreatic precursors

Human biliary tree stem/progenitor cells (hBTSCs) are being used for cell therapies of patients with liver cirrhosis. A cryopreservation method was established to optimize sourcing of hBTSCs for these clinical programs and that comprises serum-free Kubota's Medium (KM) supplemented with 10% dimethyl sulfoxide (DMSO), 15% human serum albumin (HSA) and 0.1% hyaluronans. Cryopreserved versus freshly isolated hBTSCs were similar in vitro with respect to self-replication, stemness traits, and multipotency. They were able to differentiate to functional hepatocytes,cholangiocytes or pancreatic islets, yielding similar levels of secretion of albumin or of glucose-inducible levels of insulin. Cryopreserved versus freshly isolated hBTSCs were equally able to engraft into immunocompromised mice yielding cells with human-specific gene expression and human albumin levels in murine serum that were higher for cryopreserved than for freshly isolated hBTSCs. The successful cryopreservation of hBTSCs facilitates establishment of hBTSCs cell banking offering logistical advantages for clinical programs for treatment of liver diseases

Treating Pediatric Asthma According Guidelines

Asthma is a common chronic inflammatory disorder of the lower respiratory airways in childhood. The management of asthma exacerbations and the disease control are major concerns for clinical practice. The Global Strategy for Asthma Management and Prevention, published by GINA, updated in 2017, the British Thoracic Society/Scottish Intercollegiate Guideline Network, revised in 2016, the National Institute for Health and Care Excellence asthma guideline consultation, available in 2017, are widely accepted documents, frequently implemented, with conflicting advices, and different conclusion on asthma definition and treatment. An International Consensus on Pediatric Asthma was carried out in 2012 by a Committee with expertise in the field, to critically review differences on current guidelines. In addition, the specific issue of treating severe and difficult asthma has been recently highlighted throughout the International European Respiratory Society/American Thoracic Society guidelines on severe asthma. The aim of this paper is to describe conventional treatments and some new therapeutic approaches to pediatric asthma according to guidelines, highlighting key aspects, and differences on proposed clinical recommendations for asthma management. Age specific therapy are proposed in steps, according to clinical severity and the level of disease control. If control is not achieved within 3 months, stepping-up should be considered; otherwise, if control is achieved after 3 months, stepping down may be considered. The most used drug classes of asthma medications are beta-2 adrenergic agonists, corticosteroids, and leukotriene modifiers. Intramuscolar triamcinolone has been used for severe asthma treatment. Chromones and xanthines have been extensively used in the past, but they have shown limits related to their efficacy and safety profile. Omalizumab, a monoclonal antibody against IgE, is an immunomodulatory biological agent, used as new drug in patients with confirmed IgE-mediated allergic asthma, only for patient's specific range of total IgE level. There are low evidences in the efficacy of metotrexate, as well as macrolide antibiotics in children with asthma. Antifungal agents are also not recommended in asthmatic patients. Non-pharmacological measures that may improve patient's quality of life should also be attempted. We conclude that treatment decisions on childhood asthma management should be critically made, pondering the differences suggested by agreed international consensus documents

SIAIP position paper: provocation challenge to antibiotics and non-steroidal anti-inflammatory drugs in children

Drug hypersensitivity reactions (DHRs) in childhood are mainly caused by betalactam or non-betalactam antibiotics, and non-steroidal anti-inflammatory drugs (NSAIDs). Laboratory tests for identifying children who are allergic to drugs have low diagnostic accuracy and predictive value. The gold standard to diagnose DHR is represented by the drug provocation test (DPT), that aims of ascertaining the causative role of an allergen and evaluating the tolerance to the suspected drug. Different protocols through the administration of divided increasing doses have been postulated according to the type of drug and the onset of the reaction (immediate or non immediate reactions). DPT protocols differ in doses and time interval between doses. In this position paper, the Italian Pediatric Society for Allergy and Immunology provides a practical guide for provocation test to antibiotics and NSAIDs in children and adolescents

Hyaluronan coating improves liver engraftment of transplanted human biliary tree stem/progenitor cells

BACKGROUND: Cell therapy of liver diseases with human biliary tree stem cells (hBTSCs) is biased by low engraftment efficiency. Coating the hBTSCs with hyaluronans (HAs), the primary constituents of all stem cell niches, could facilitate cell survival, proliferation, and, specifically, liver engraftment given that HAs are cleared selectively by the liver. METHODS: We developed a fast and easy method to coat hBTSCs with HA and assessed the effects of HA-coating on cell properties in vitro and in vivo. RESULTS: The HA coating markedly improved the viability, colony formation, and population doubling of hBTSCs in primary cultures, and resulted in a higher expression of integrins that mediate cell attachment to matrix components. When HA-coated hBTSCs were transplanted via the spleen into the liver of immunocompromised mice, the engraftment efficiency increased to 11% with respect to 3% of uncoated cells. Notably, HA-coated hBTSC transplantation in mice resulted in a 10-fold increase of human albumin gene expression in the liver and in a 2-fold increase of human albumin serum levels with respect to uncoated cells. Studies in distant organs showed minimal ectopic cell distribution without differences between HA-coated and uncoated hBTSCs and, specifically, cell seeding in the kidney was excluded. CONCLUSIONS: A ready and economical procedure of HA cell coating greatly enhanced the liver engraftment of transplanted hBTSCs and improved their differentiation toward mature hepatocytes. HA coating could improve outcomes of stem cell therapies of liver diseases and could be immediately translated into the clinic given that GMP-grade HAs are already available for clinical use