A Single-Arm, Proof-Of-Concept Trial of Lopimune (Lopinavir/Ritonavir) as a Treatment for HPV-Related Pre-Invasive Cervical Disease

BACKGROUND: Cervical cancer is the most common female malignancy in the developing nations and the third most common cancer in women globally. An effective, inexpensive and self-applied topical treatment would be an ideal solution for treatment of screen-detected, pre-invasive cervical disease in low resource settings. METHODS: Between 01/03/2013 and 01/08/2013, women attending Kenyatta National Hospital's Family Planning and Gynaecology Outpatients clinics were tested for HIV, HPV (Cervista®) and liquid based cervical cytology (LBC -ThinPrep®). HIV negative women diagnosed as high-risk HPV positive with high grade squamous intraepithelial lesions (HSIL) were examined by colposcopy and given a 2 week course of 1 capsule of Lopimune (CIPLA) twice daily, to be self-applied as a vaginal pessary. Colposcopy, HPV testing and LBC were repeated at 4 and 12 weeks post-start of treatment with a final punch biopsy at 3 months for histology. Primary outcome measures were acceptability of treatment with efficacy as a secondary consideration. RESULTS: A total of 23 women with HSIL were treated with Lopimune during which time no adverse reactions were reported. A maximum concentration of 10 ng/ml of lopinavir was detected in patient plasma 1 week after starting treatment. HPV was no longer detected in 12/23 (52.2%, 95%CI: 30.6-73.2%). Post-treatment cytology at 12 weeks on women with HSIL, showed 14/22 (63.6%, 95%CI: 40.6-82.8%) had no dysplasia and 4/22 (18.2%, 95%CI: 9.9-65.1%) were now low grade demonstrating a combined positive response in 81.8% of women of which 77.8% was confirmed by histology. These data are supported by colposcopic images, which show regression of cervical lesions. CONCLUSIONS: These results demonstrate the potential of Lopimune as a self-applied therapy for HPV infection and related cervical lesions. Since there were no serious adverse events or detectable post-treatment morbidity, this study indicates that further trials are clearly justified to define optimal regimes and the overall benefit of this therapy. TRIAL REGISTRATION: ISRCTN Registry 48776874

Conséquences cardiovasculaires de l’insuffisance rénale chronique, intérêt d’une modulation des acides époxyeicosatriénoïques

International audienceCardiovascular events are more prevalent in chronic kidney disease than in the general population, being the main cause of morbi-mortality. The physiopathology explaining this association remains complex. Thus, research for new therapies to prevent cardiovascular events in chronic kidney disease is a major issue. Epoxyeicosatrienoic acids, products of the arachidonic acid metabolism, are endothelium-derived hyperpolarizing factors with vasodilatory, anti-inflammatory, thrombolytic, pro-angiogenic and anti-apoptotic properties. A decrease in the bioavailability of epoxyeicosatrienoic acids has been observed in many cardiovascular diseases such as hypertension, myocardial infarction or diabetes. Moreover, human studies of genetic polymorphisms of soluble epoxide hydrolase, the enzyme degrading epoxyeicoatrienoic acids, have shown that allelic variants related to an increase in its activity is associated with higher risk of cardiovascular events. Modulation of epoxyeicosatrienoic acids by soluble epoxide hydrolase inhibitors in some cardiovascular diseases induces structural improvements in the heart, vessels and kidneys, including decrease in cardiomyocyte hypertrophy, reduction in cardiac and renal interstitial fibrosis, improvement in renal hemodynamics, and prevention of endothelial dysfunction. In this context, increasing the bioavailability of epoxyeicosatrienoic acids appears to be an interesting therapeutic option in the prevention of cardiovascular events related to chronic kidney disease

First plasma and tissue pharmacikinetic study of the YSNSG cyclopeptide, a new integrin antagonist, using microdialysis.

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Décaler la palette cutanée dans une contre-incision améliore le résultat : étude d’une série de 82 reconstructions mammaires par grand dorsal avec prothèses à 10 ans

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New in vivo model to analyse the expression of angiogenic genes in the borders of a cleft lip

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