The aim of this study was to evaluate the biopharmaceutical behavior of colistin methanesulfonate (CMS) with special focus on colistin presystemic formation after CMS nebulization in rats. CMS was administered (15 mg ⅐ kg ؊1 of body weight) either intravenously for systemic pharmacokinetic studies (n ؍ 6) or as an intratracheal nebulization for systemic pharmacokinetic studies (n ؍ 5) or for CMS and colistin concentration measurements in epithelial lining fluid (ELF) at 30, 120, and 240 min after nebulization (n ؍ 14). CMS and colistin concentrations were determined by a new liquid chromatography (LC)-tandem mass spectrometry (MS/MS) assay. Pharmacokinetic parameters were estimated by noncompartmental analysis. CMS and colistin pharmacokinetic data were consistent with previously published values when comparisons were possible. The fraction of the CMS dose converted systematically into colistin after intravenous CMS administration was estimated to be 12.5% on average. After CMS nebulization it was estimated that about two-thirds of the dose was directly absorbed within the systemic circulation, whereas one-third was first converted into active colistin, which was eventually absorbed. As a consequence, the colistin area under curve (AUC) reflecting systemic availability was about 4-fold greater after CMS intratracheal nebulization (607 ؎ 240 g ⅐ min ⅐ ml ؊1 ) than after CMS intravenous administration (160 ؎ 20 g ⅐ min ⅐ ml ؊1 ). CMS concentrations in ELF at 30 min and 120 min postnebulization were very high (in the order of several mg/ml) due to the limited volume of ELF but were considerably reduced at 240 min. Although lower (15% ؎ 5% at 120 min) in relative terms, colistin concentrations in ELF could be high enough for being active against microorganisms following CMS nebulization.
More than two years after the start of COVID-19 pandemic, Africa still lags behind in terms vaccine distribution. This highlights the predicament of Africa in terms of vaccine development, deployment, and sustainability, not only for COVID-19, but for other major infectious diseases that plague the continent. This opinion discusses the challenges Africa faces in its race to vaccinate its people, and offers recommendations on the way forward. Specifically, to get out of the ongoing vaccine shortage trap, Africa needs to diversify investment not only to COVID-19 but also other diseases that burden the population. The continent needs to increase its capacity to acquire vaccines more equitably, improve access to technologies to enable local manufacture of vaccines, increase awareness on vaccines both in rural and urban areas to significantly reduce disease incidence of COVID-19 and as well as other prevalent diseases on the African continent such as HIV and TB. Such efforts will go a long way to reduce the disease burden in Africa.
Introduction Kaposi sarcoma is an angioproliferative disorder that requires infection with human herpesvirus 8 (HHV-8) for its development. The majority of cases are associated with HIV infection or other immunocompromising conditions. Thymomas are occasionally associated to cytopenia, which may alter the patients' immune responses. Methods Case report using clinical records. Results Case report of a 46-year-old male patient diagnosed with thymoma and myasthenia gravis. The patient was referred to an otolaryngology consultation with complaints of facial pain in the right malar region, interpreted as an acute sinusitis. Following examination, an expansive maxillary sinus mass was found, and endoscopic surgery was undertaken. After careful investigation, it was diagnosed as a Kaposi sarcoma. Conclusions It is thought to be the first described case of a maxillary sinus Kaposi sarcoma in an HIV-negative patient. Thus, this entity has to be considered in the differential diagnosis of sinus masses, even in non-HIV patients.
Maria do Carmo Bezerra & Mona-Lisa Choas artigo 39 integração de modeloS de SimUlação em Sig: aplicação ao caSo da drenagem de ágUaS plUviaiS UrBanaS.
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