Valutazione tossicologica di due nuovi inibitori della DHFR del P. falciparum e del P. vivax

Secondo una segnalazione del 2004 dell'UNiCEF "La malaria uccide più di un milionedi persone all'anno". Gli antifolato sono una classe di antimalarici cheagiscono sulla via biosintetica del folato dei vari Plasmodi inibendo gli enzimi in essacoinvolti. Sono farmaci estremamente sfruttati e, per questo motivo spesso inefficaci acausa dell'insorgenza di ceppi di Plasmodium divenuti resistenti. Oltre a ciò, nostri studirecenti in vitro hanno evidenziato la capacità di alcuni antimalarici di interferire con lareplicazione di cellule sane e cellule tumorali. Per lapresenza di gravi effetti collaterali e di ceppi resistenti, diviene sempre piiì urgente lanecessità di disporre di nuovi farmaci antimalarici. Nel presente studio sono state utilizzatedue molecole di nuova sintesi non analoghe del folato, ma in grado di inibire la DHFR(diidrofolato reduttasi) del Plasmodium falciparum e del Plasmodium vivax con una IC50compresa nel range micromolare e sub-micromolare. I composti, siglati come 1B e 6G sonorispettivamente una molecola N-idrossiamidina simile e un derivato della tiourea e sonostati saggiati in modo comparativo con l'antifolato pirimetamina nei confronti di celluleVERO e cellule MCF-7 (tumore mammario). Le cellule sono state coltivate sterilmente inpiastre con terreno EMEM arricchito. Al raggiungimento della semiconfluenza, sono stateaggiunte alle colture concentrazioni crescenti di 1B, 6G e pirimetamina (1,56-3,125-6,25-12,5-25-50 mg/l). Dopo 48 ore di incubazione sono stati eseguiti test: MTT e WesternBlotting. I risultati preliminari indicano che il composto 1B non interferisce in alcun modosulla crescita delle cellule sane o tumorali, mentre il derivato tioureico (6G) esercita unsignificativo stimolo sulla crescita delle cellule VERO (+ 60%), ma non sulle MCF-7. Ilfarmaco di riferimento pirimetamina stimola in modo dose dipendente la replicazione deileMCF-7. L'espressione delle proteine p53 e p21 immodificata nelle colture di MCF-7trattate con le due nuove molecole ne conferma l'assenza di tossicità. Questi risultatipreliminari, associati alla conferma che le due molecole sono attive specialmente verso iceppi di Plasmodium multiresistenti sono incoraggianti per il proseguimento dello studio dinuovi strumenti terapeutici caratterizzati anche da scarsa citotossicità

Epidemiology and Treatment of Surgical Infection after Ankle Arthroscopy: A Systematic Review

Background: Ankle arthroscopy is indicated for both diagnosis and treatment of a large spectrum of common ankle disorders. It has certain advantages over the open procedure; however, it is important to recognize that there are some complications associated with it. Infections after this procedure are quite uncommon, with an overall estimated incidence of 2%. Given the low incidence of infections after ankle arthroscopy, not a great deal of literature on the topic has been published. The present review aims to provide an overview of the incidence, diagnosis, and treatment of infections after ankle arthroscopy. Methods: A systematic review of the literature indexed in the PubMed, MEDLINE, and Cochrane Library databases using search term “ankle arthroscopy infections” was performed in November 2023. No restrictions were applied concerning the date of publication. The Preferred reporting items for systematic reviews and meta-analyses (PRISMA) were followed. Among all surgical operations for the treatment of ankle and foot pathologies, we included articles with a described superficial or deep infection after ankle arthroscopy. Results: The search resulted in 201 studies. Only 21 studies met our inclusion criteria, and they were included in this systematic review. We evaluated 1706 patients who underwent 1720 arthroscopic tibiotalar procedures at an average age of 42 years old. Out of the 1720 procedures, 41 (2%) were complicated by infection. We divided infectious complications into superficial (68%; 28/41) and deep (32%; 13/41) infections. The most common pathogen isolated was Staphylococcus aureus. Arthroscopic arthrodesis was found to be the most affected by deep infections. Conclusions: Infection after ankle arthroscopy is an uncommon complication. Superficial infections were successfully treated with antibiotics, while surgical debridement, arthroscopic drainage, and intravenous antibiotics were necessary in cases of deep infections. Considering the amount of information on pathogens associated with knee and shoulder infections, there is still a lack of literature on pathogens associated with ankle infections, which makes their management difficulty

Neurodevelopmental Profile in Children Affected by Ocular Albinism

Aim The aim of this study was to detail the neurodevelopmental profile of subjects affected by ocular albinism (OA) and to collect data on GPR143 gene analysis.Design The design of the study involves a retrospective longitudinal observational case series.Methods We collected data on the neurodevelopmental profile of 13 children affected by OA from clinical annual assessments conducted for a period of 6 years after the first evaluation. We described visual profile, neuromotor development and neurological examination, cognitive profile, communication and language skills and behavioral characteristics. The GPR143 gene analysis was performed as well.Results Children presented a variable combination of ocular and oculomotor disorders unchanged during the follow-up, a deficit in visual acuity and in contrast sensitivity that progressively improved. Abnormalities in pattern visual evoked potential were found. No deficits were detected at neurological examination and neuromotor development except for a mild impairment in hand-eye coordination observed in five cases. A language delay was observed in five cases, two of whom had also a developmental quotient delay at 2 years evolving to a borderline/deficit cognitive level at preschool age, difficulties in adaptive behavior and autistic-like features were found. Mutations in the GPR143 gene were identified in the two patients who presented the most severe clinical phenotype.Conclusion Children with OA may share, in addition to a variable combination of ocular signs and symptoms, a neurodevelopment impairment regarding mostly the cognitive, communicative, and social area, especially those with GPR143 mutation