Losartan improves intestinal mucositis induced by 5-fluorouracil in mice

Intestinal mucositis (IM) is a common side effect of 5-fluorouracil (5-FU)-based chemotherapy, which negatively impacts therapeutic outcomes and delays subsequent cycles of chemotherapy resulting in dose reductions and treatment discontinuation. In search of new pharmacological alternatives that minimize your symptoms, this work set out to study the effect of losartan (LOS), a receptor type I (AT1) angiotensin II antagonist, on intestinal mucositis induced by 5-FU. Intestinal mucositis was induced by a single intraperitoneal administration of 5-FU (450 mg/kg) in Swiss mice. Losartan (5, 25 or 50 mg/kg) or saline was orally administered 30 min before 5-FU and daily for 4 days. On 4th day, the animals were euthanized and segments of small intestine were collected to evaluate histopathological alterations (morphometric analysis), concentration of inflammatory cytokines, oxidative stress markers and genic expression of NF-κB p65, Fn-14 and TWEAK. Weight evaluation and changes in leukogram were also analyzed. 5-FU induced intense weight loss, leukopenia and reduction in villus height compared to saline group. Losartan (50 mg/kg) prevented 5-FU-induced inflammation by decreasing in the analyzed parameters compared to the 5-FU group. Our findings suggest that 50 mg/kg of losartan prevents the effects of 5-FU on intestinal mucosa in mice.

Formulation and Evaluation of Valsartan Solid Lipid Nanoparticles

Valsartan is a potent and specific competitive angiotensin II antagonist which is used in the management of hypertension. It is well absorbed following oral administration, with rather poor bioavailability of about 25 %. Peak plasma concentration of valsartan occurs 2-4 hours after ingestion. Optimized VAL_SLNS are prepared by hot homogenization method and spray dried to improve handling processing and stability. Solid state studies such as FTIR indicated absence of any chemical interaction between valsartan and the lipid. The mean particles size, Polydispersity index (PDI) and entrapment efficiency of optimized formulation (F-05) was found to be 136.5 nm, 0.424, 80.98% respectively. The drug release study from the nano formulation was studied in Phosphate buffer 6.8 for all the formulations F1 F2 F3 F4 and F5. The results demonstrated that V-SLN formulation (F-5) showed biphasic behaviour with an initial burst release followed by a sustained release maximum up to 72-79% till 12 hours. The release curve was found to follow Korsmeyer Peppas model (R2=0.98). Keywords: hot homogenization, hydrogenated soya phosphatidyl choline, sustained release

Acute coronary syndromes in chronic kidney disease patients: the good, the bad or the ugly?

Background Patients with chronic kidney disease (CKD) are at increased risk of composite cardiovascular (CV) events and all-cause mortality. However, current aggressiveness of therapeutic strategies may minimize the course of the disease. Aim To assess the prognostic impact of optimized medical treatment in a CKD population with acute coronary syndrome (ACS). Methods 355 ACS patients admitted to a single coronary care with CKD who were discharged from hospital were included. Those with end-stage renal disease were excluded. Three groups were created based on the KDIGO classification: Group A (Stage 3A, eGFR [estimated glomerular filtration rate] 45–59mL/min/1.73 m2) N=190; Group B (Stage 3B, eGFR 30–44mL/min/1.73 m2) N=113; and Group C (Stage 3B, eGFR 15–29mL/min/1.73 m2) N=52. The primary endpoint was long-term all-cause mortality. Kaplan-Meyer survival curves and Cox regression were done. The median of follow-up was 32 (IQ 15–70) months. Results Groups were similar regarding demographics, CV risk factors, ACS type, heart failure diagnosis, left ventricular (LV) systolic function, peak troponin, multivessel disease, treatment option (PCI, CABG or OMT) and medical therapy at discharge. More advance renal failure patients had a higher prevalence of diabetes mellitus (DM), a lower haemoglobin, a higher NT-proBNP and were less likely to receive ACE inhibitors/angiotensin II antagonist at discharge. 170 patients met the primary outcome. Kaplan-Meyer curves showed decreased survival with worse renal function (Group A 68% vs Group B 57% vs Group C 37%, Log Rank P=0.006 – Figure 1). After adjustment for age, DM, haemoglobin, NT-proBNP, LV systolic function and ACE inhibitors/angiotensin II antagonist at discharge, eGFR was not associated with increased death (HR 1.00, 95% CI 0.98–1.01). In this model, only age (HR 1.04, 95% CI 1.01–1.07), haemoglobin (HR 0.86, 95% CI 0.979–0.94), Nt-proBNP (HR 1.00, 95% CI 1.00–1.00) and impaired LV function (LV ejection fraction 40–49%: HR 2.95, 95% CI 1.89–4.81; LV ejection fraction <40%: HR 2.15, 95% CI 1.44–3.21) remained associated with the outcome. Conclusion The worse outcome attributed to CKD after an ACS seems to be related not the eGFR itself but to associated comorbidities such as age, anaemia, fluid overload and impaired LV function. The fact that some of these comorbidities may be altered by intensive therapy indicates that CKD patients should also be candidates to optimized medical treatment. Funding Acknowledgement Type of funding source: None