Effect of Bilastine on Diabetic Nephropathy in DBA2/J Mice.

Diabetic nephropathy is an unmet therapeutic need, and the search for new therapeutic strategies is warranted. Previous data point to histamine H1 receptor as a possible target for glomerular dysfunction associated with long term hyperglycaemia. Therefore, this study investigated the effects of the H1 receptor antagonist bilastine on renal morphology and function in a murine model of streptozotocin-induced diabetes. Diabetes was induced in DBA2/J male mice and, from diabetes onset (glycaemia ≥200 mg/dL), mice received bilastine (1-30 mg/kg/day) by oral gavage for 14 consecutive weeks. At the end of the experimental protocol, diabetic mice showed polyuria (+195.5%), increase in Albumin-to-Creatine Ratio (ACR, +284.7%), and a significant drop in creatinine clearance (p < 0.05). Bilastine prevented ACR increase and restored creatinine clearance in a dose-dependent manner, suggesting a positive effect on glomerular filtration. The ultrastructural analysis showed a preserved junctional integrity. Preservation of the basal nephrin, P-cadherin, and synaptopodin expression could explain this effect. In conclusion, the H1 receptor could contribute to the glomerular damage occurring in diabetic nephropathy. Bilastine preserved the glomerular junctional integrity, leading to the hypothesis of anti-H1 antihistamines as a possible add-on therapy for diabetic nephropathy.

The Interplay between Histamine H4 Receptor and the Kidney Function: The Lesson from H4 Receptor Knockout Mice.

Previous studies implicated the histamine H4 receptor in renal pathophysiology. The aim here is to elucidate the role of this receptor on renal function using H4 receptor knockout mice (H4R-/-). Healthy and diabetic H4R-/- mice compared to their C57BL/6J wild-type counterpart for renal function and the expression of crucial tubular proteins. H4R-/- and wild-type mice, matched for ages, showed comparable weight gain curves reaching similar median weight at the end of the study. However, H4R-/- mice displayed a higher basal glycemia. H4R-/- mice showed a lower urine 24 h outflow, and albumin-to-creatinine ratio (ACR) compared to wild-type mice. Consistently, H4R-/- mice presented a higher expression of megalin and a lower basal expression of the sodium-hydrogen exchanger (NHE)3 and aquaporin (AQP)2. According to these basal differences, diabetic H4R-/- mice developed more severe hyperglycemia and a higher 24 h urine volume, but a lower increase in ACR and decrease in urine pH were observed. These events were paralleled by a reduced NHE3 over-expression and megalin loss in diabetic H4R-/- mice. The AQP1 and AQP7 patterns were also different between H4R-/- and wild-type diabetic mice. The collected results highlight the role of the histamine H4 receptor in the control of renal reabsorption processes, particularly albumin uptake.

Ethical issues associated with in-hospital emergency from the Medical Emergency Team's perspective: a national survey.

BACKGROUND: Medical Emergency Teams (METs) are frequently involved in ethical issues associated to in-hospital emergencies, like decisions about end-of-life care and intensive care unit (ICU) admission. MET involvement offers both advantages and disadvantages, especially when an immediate decision must be made. We performed a survey among Italian intensivists/anesthesiologists evaluating MET's perspective on the most relevant ethical aspects faced in daily practice. METHODS: A questionnaire was developed on behalf of the Italian scientific society of anesthesia and intensive care (SIAARTI) and administered to its members. Decision making criteria applied by respondents when dealing with ethical aspects, the estimated incidence of conflicts due to ethical issues and the impact on the respondents' emotional and moral distress were explored. RESULTS: The questionnaire was completed by 327 intensivists/anesthesiologists. Patient life-expectancy, wishes, and the quality of life were the factors most considered for decisions. Conflicts with ward physicians were reported by most respondents; disagreement on appropriateness of ICU admission and family unpreparedness to the imminent patient death were the most frequent reasons. Half of respondents considered that in case of conflicts the final decision should be made by the MET. Conflicts were generally recognized as causing increased and moral distress within the MET members. Few respondents reported that dedicated protocols or training were locally available. CONCLUSION: Italian intensivists/anesthesiologists reported that ethical issues associated with in-hospital emergencies are occurring commonly and are having a significant negative impact on MET well-being. Conflicts with ward physicians happen frequently. They also conveyed that hospitals don't offer ethics training and have no protocols in place to address ethical issues.

Factors affecting attitudes and barriers to a medical emergency team among nurses and medical doctors: a multi-centre survey.

AIM: To identify factors underlying attitudes towards the medical emergency team (MET) and barriers to its utilisation among ward nurses and physicians. METHODS: Multicentre survey using an anonymous questionnaire in hospitals with a fully operational MET system in the Piedmont Region, Italy. Response to questions was scored on a 5-point Likert-type agreement scale. Dichotomised results were included in a logistic regression model. RESULTS: Among 2279 staff members who were contacted, 1812 (79.6%) completed the survey. The vast majority of respondents valued the MET. Working in a surgical vs. medical ward and having participated in either the MET educational programme (METal course) or MET interventions were associated with better acceptance of the MET system. Reluctance by nurses to call the covering doctor first instead of the MET for deteriorating patients (62%) was significantly less likely in those working in surgical vs. medical wards or having a higher seniority or a METal certification (OR 0.51 [0.4-0.65], 0.69 [0.47-0.99], and 0.6 [0.46-0.79], respectively). Reluctance to call the MET in a patient fulfilling calling criteria (21%), was less likely to occur in medical doctors vs. nurses and in surgical vs. medical ward staff, and it was unaffected by the METal certification. CONCLUSIONS: The MET was well accepted in participating hospitals. Nurse referral to the covering physician was the major barrier to MET activation. Medical status, working in surgical vs. medical wards, seniority and participation in the METal educational programme were associated with lower likelihood of showing barriers to MET activation.