Chitosan-clodronate nanoparticles loaded in poloxamer gel for intra-articular administration.

This work was based on the study of an intra-articular delivery system constituted by a poloxamer gel vehiculating clodronate in chitosan nanoparticles. This system has been conceived to obtain a specific and controlled release of clodronate in the joints to reduce the arthritis rheumatoid degenerative effect. Clodronate (CLO) is a first-generation bisphosphonate with anti-inflammatory properties, inhibiting the cytokine and NO secretion from macrophages, therefore causing apoptosis in these cells. This is related to its ability to be metabolized by cells and converted into a cytotoxic intermediate as a non-hydrolysable analogue of ATP. Chitosan (CHI) was used to develop nanosystems, by ionotropic gelation induced by clodronate itself. A fractional factorial experimental design allowed us to obtain nanoparticles, the diameter of which ranged from 200 to 300nm. Glutaraldehyde was used to increase nanoparticle stability and modify the drug release profile. The zeta potential value of crosslinked nanopaparticles was 21.0mV±1.3, while drug loading was 31.0%±5.4 w/w; nanoparticle yield was 18.2%±1.8 w/w, the encapsulation efficiency was 48.8%±9.9 w/w. Nanoparticles were homogenously loaded in a poloxamer sol, and the drug delivery system is produced in-situ after local administration, when sol become gel at physiological temperature. The properties of poloxamer gels containing CHI-CLO nanoparticles, such as viscosity, gelation temperature and drug release properties, were evaluated. In vitro studies were conducted to evaluate the effects of these nanoparticles on a human monocytic cell line (THP1). The results showed that this drug delivery system is more efficient, with respect to the free drug, to counteract the inflammatory process characteristic of several degenerative diseases.

Ambulatory heart failure management in private practice in France.

UNLABELLED: Management of ambulatory heart failure was assessed in a group of 600 patients, mean age 73, 64% males, NYHA I: 9%; II: 52%; III: 33%; IV: 6%; followed up by a representative sample of private cardiologists. Fifty-two percent of patients had been previously hospitalised for worsening heart failure with a mean duration of stay of 13.1 days, for those hospitalised in the year preceding the survey (26%). First diagnosis of heart failure had been performed by a cardiologist (57%), a general practitioner (37%) or another category of physician (6%). Seventy percent of patients received three or more different classes of heart failure medications. Diuretics were prescribed to 71%, angiotensin converting enzyme inhibitors to 54% and digitalis to 35% of the population. Beta-blockers were given to only 14% of the patients. In patients aged over 80 years, only 45% received angiotensin converting enzyme inhibitors. CONCLUSION: This survey of ambulatory heart failure patients confirms that the disease is predominantly observed in elderly patients, and associated with prolonged and recurrent hospitalisations. The underuse of recommended therapeutic classes including angiotensin converting enzyme inhibitors and beta-blockers deserves further investigation.

[Observations on the management of cardiac failure in ambulatory patients. Results of a survey of cardiologists]. / Observatoire de la prise en charge de l'insuffisance cardiaque en ambulatoire. Enquête auprès des cardiologues.

An enquiry was undertaken amongst 71 cardiologists in 1999 evaluating 600 ambulatory patients with cardiac failure (64% men; mean age 73 years; NYHA Class I: 9%, Class II: 52%, Class III: 33%, Class IV: 6%). Cardiac failure is commoner in men (81%) before the age of 70. After the age of 80, the tendency is inversed (53% of women). Fifty-two per cent of patients had a history of hospital admission for cardiac failure: 26% in the year before the enquiry (on average 13.1 days' hospital stay). On inclusion, the diagnosis was made 4.2 +/- 4.6 years previously and the patients had been followed up for an average of 3.04 +/- 3.3 years. The diagnosis of cardiac failure was made by the cardiologist (57%), the general practitioner (37%), or another category of physician (6%). Eight per cent of patients were treated with a single drug before inclusion, 22% had a bi-therapy and 70% a polytherapy. The most frequently prescribed drugs were: diuretics (71%), angiotensin converting enzyme (ACE) inhibitors (54%) and digitalis (35%). The prescription of betablockers was only reported in 14% of the population. In the over-80's, only 45% of patients were prescribed ACE inhibitors. These results confirm that ambulatory patients with cardiac failure are mainly in NYHA Classes II and III, that the pathology concerns elderly patients and that it is the cause of recurrent hospital admission. The prescription of diuretics is the main therapy in all NYHA Classes. ACE inhibitors were only prescribed in 2/3 of patients and in less than half of patients over 80 years of age. The prescription of betablockers remains marginal. The reason for the underprescription of recommended drugs (International Recommendations) would justify further investigation.

[The estimation of cardiovascular risk in hypertensive patients is not modified by management of the hypertension]. / L'estimation du risque cardiovasculaire chez des patients hypertendus ne modifie pas la prise en charge de l'HTA.

OBJECTIVES: To compare antihypertensive therapeutic strategies and efficacy whether the physicians were aware or not of the calculated cardiovascular risk at 10 years obtained from the Framingham equation. It was also possible to evaluate the concordance of the general physicians estimation of the cardiovascular risk with the calculated percentage. METHODS: The participation of 953 general physicians to the study allowed to achieve an estimation of the absolute cardiovascular risk for 1,243 hypertensives. Patients were randomised in 2 groups according to the knowledge or not by the physicians of the calculated risk. The therapeutic strategy included a monotherapy (Fosinopril 20 mg/days) for a follow up of 8 weeks, with the possibility to increase the treatment after 4 weeks (Fosinopril + hydrochlorotiazide). To be included, patients had to be more than 18 and less than 75 years, and a blood pressure above 140/90 mmHg. Estimated and calculated cardiovascular risk at 10 years, were classified according to the 1999 WHO-ISH guidelines: low risk < 15%, medium risk 15-20%, high risk 20-30%, very high risk > 30%. RESULTS: In this population, aged 60 +/- 10 years, with 54% of men, the concordance between estimated risk and calculated risk was of 35%. This concordance was better for the "low risk" and "very high risk", but remains inferior to 50%. The determinants of concordance were: gender (male), smoking and a low HDL cholesterol. After 8 weeks of treatment, no difference was observed between the 2 groups concerning final blood pressure level, percentage of normalised patients and number of patients with bi-therapy. CONCLUSIONS: General physicians estimation of cardiovascular risk at 10 years of hypertensive subjects has a bad concordance with the calculated risk according to Framingham equation. The results of this study indicate that the estimation of cardiovascular risk of hypertensive subjects does not modify the management of hypertension.