Understanding osteomyelitis and its treatment through local drug delivery system.

A osteomielite e um processo inflamatorio do tecido osseo, de origem infecciosa, que resulta em destruicao inflamatoria, necrose e formacao de novo osso. Pode aparecer em qualquer idade, afetar qualquer osso e tornar-se uma doenca cronica com morbidade persistente. Apesar dos progressos na quimioterapia infecciosa, o tratamento da osteomielite e caro e dificil, em particular quando associada a presenca de biofilmes bacterianos, especialmente de Staphylococcus aureus e Staphylococcus epidermidis. O tratamento da osteomielite inclui a administracao de doses elevadas de antibioticos (AB) por via endovenosa e oral, durante um periodo de pelo menos 6 semanas. Os sistemas de veiculacao localizada de farmacos, utilizando materiais nao biodegradaveis (polimetilmetacrilato) ou biodegradaveis e osteoativos como os cimentos osseos de ortofosfatos de calcio e vidro bioativo, surgiram como uma alternativa promissora para o tratamento da osteomielite. Estes sistemas permitem a veiculacao de AB in situ com concentracoes bactericidas por longos periodos de tempo e sem a toxicidade associada as outras vias de administracao. O presente trabalho propoe uma revisao da literatura relativa as causas, a patogenia e ao tratamento farmacologico da osteomielite. A metodologia do estudo da revisao consistiu numa pesquisa bibliografica, nas bases de dados Google Scholar, Science Direct, Pubmed, Springer link, B-on. Foram revistos e analisados diversos artigos publicados desde o ano de 1979.

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Osteomyelitis: an overview of antimicrobial therapy

A sensitive, selective, economic, and validated spectrofluorimetric method was developed for the determination of clindamycin hydrochloride in pharmaceutical preparations, depending on the reaction of its tertiary amino group with eosin Y. The proposed method involves quantitative fluorescence quenching of eosin Y measured at 555 nm after excitation at 482 nm upon addition of the studied drug, where the decrease in fluorescence intensity was directly proportional to the concentration of CLD over the concentration range of 0.2–2.0 μg mL−1, with a LOD of 0.13 μg mL−1 and a LOQ of 0.18 μg mL−1. The proposed method was successfully applied to the determination of the studied compound in its dosage forms. The results obtained were in good agreement with those obtained by the official method. Judging from the effects of temperature according to Stern–Volmer plots, the quenching of fluorescence of EY is a static quenching process, resulting from electrostatic attraction and aromatic stacking interactions.

Application of the Stern–Volmer equation for studying the spectrofluorimetric quenching reaction of eosin with clindamycin hydrochloride in its pure form and pharmaceutical preparations

A method of microwave (MW) assisted synthesis was employed to prepare cadmium sulfide (CdS) quantum dots (QDs) in dimethylformamide in the presence of poly(methyl methacrylate) (PMMA). The MW irradiation was carried out for a fixed time of 20–30 s and the size of QDs varied from 2.9–5.5 nm. Before each irradiation the solution was cooled down to ambient temperature and the irradiation process was repeated six times. An increase in the intensity and red shift of the characteristic UV-vis absorption peak originating from CdS QDs were observed with repeated MW irradiation, suggesting that the amount of generated CdS QDs increased within the PMMA network and aggregated with repeated MW irradiation. MW irradiation could influence selectively the nucleation and growing rates of PMMA–CdS QDs systems. The broadness and large Stokes shift of the emission from Cd2+-rich PMMA–CdS QDs was due to the surface trap state photoluminescence. The recombination of shallow trapped electrons and shallow trapped holes has been considered as the primary source of the surface trap state photoluminescence in Cd2+-rich PMMA–CdS QDs. The photoluminescence lifetime was observed to be decreased sharply when the amount of QDs was less, showing the emission decay was dependent on the surface property of PMMA–CdS QDs. The origin of the longer lifetime was due to the involvement of surface trap states and dependent on the amount of CdS QDs present within PMMA and its environment. The effect of the concentration of Cd2+, S2− and PMMA on the generation of CdS QDs within PMMA and the effect of repeated MW irradiation on the optical properties was studied and the results are discussed in this article.

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Controlled surface trap state photoluminescence from CdS QDs impregnated in poly(methyl methacrylate).

Different graphitic carbon-based electrode materials were evaluated for direct electro-oxidation of clindamycin and electroanalytical parameters such as sensitivity, residual background current, and signal-tobackground current ratio were compared to select the best one for the clindamycin electroanalysis. Such electrode materials include glassy carbon, carbon paste, pyrolytic graphite (edge-plane and basal-plane), carbon nanotube, reduced graphene oxide, and carbon black. The edge-plane pyrolytic graphite electrode after a simple and fast electrochemical pretreatment showed superior performance compared with the other carbon electrodes. Raman and Fourier transform infrared spectroscopy were employed to analyze the surface microstructure and chemical bonding of the carbon materials and scanning electron microscopy was used to study their surface morphologic features. The applicability of the electrochemically activated edge-plane pyrolytic graphite electrode for the determination of clindamycin in pharmaceutical formulations and human urine samples was evaluated.

Application of anodized edge-plane pyrolytic graphite electrode for analysis of clindamycin in pharmaceutical formulations and human urine samples

Aim: To investigate the serum circulating DPP4 activity in patients with COVID-19 disease. Materials & methods: Serum samples from 102 hospitalized COVID-19 patients and 43 post-COVID-19 plasma donors and 39 SARS-CoV-2 naive controls and their medical data were used. Circulating DPP4 activities according to different COVID-19 disease peak severity (WHO) groups at sampling and at peak were assessed. Results: A significant decrease (p < 0.0001) in serum DPP4 activity was found in study groups of higher disease severity. When the circulating DPP4 activity was assessed as a prognostic marker, the logistic regression (p = 0.0023) indicated that the enzyme activity is a predictor of mortality (median 9.5 days before death) with receiver operating characteristic area under the curves of 73.33% (p[area = 0.5] < 0.0001) as single predictor and 83.45% (p[area = 0.5] < 0.0001) in combination with age among hospitalized patients with COVID-19. Conclusion: Decreased circulating DPP4 activity is associated with severe COVID-19 disease and is a strong prognostic biomarker of mortality.

Decreased circulating dipeptidyl peptidase-4 enzyme activity is prognostic for severe outcomes in COVID-19 inpatients

Osteomyelitis continues to be a severe problem worldwide, causing plenty of hospital admissions and entailing vast expenses. Previously, we developed a low-cost polymethyl-methacrylate (PMMA)-sorbitol based capsule system for local long-term drug delivery. In the present study we aimed to test the in vitro release of clindamycin capsules by high performance liquid chromatography. By the end of the clinically relevant period (42 days), the capsules released 70-100% of their load. Furthermore, the release kinetics suggested that an effective antimicrobial concentration may be maintained within the target area. Our findings indicate that these newly developed capsules may be a versatile device for local clindamycin delivery by providing efficient release and reducing financial burdens.

Clindamycin release determined by high performance liquid chromatography from a novel low-cost local drug delivery system: a new potential treatment option for chronic osteomyelitis.

Gellért Cseh

Papers

Decreased circulating dipeptidyl peptidase-4 enzyme activity is prognostic for severe outcomes in COVID-19 inpatients

Clindamycin release determined by high performance liquid chromatography from a novel low-cost local drug delivery system: a new potential treatment option for chronic osteomyelitis.

Polymethyl-methacrylate-sorbitol-based capsules as local drug delivery vehicles: a preliminary study.

Polymethyl-methacrylate—sorbitol-based capsules as local drug delivery vehicles: an in vitro antibiotic elution study