The Phototoxicity of Fluvastatin, an HMG-CoA Reductase Inhibitor, Is Mediated by the formation of a Benzocarbazole-Like Photoproduct

In this paper, we have investigated the mechanism of phototoxicity of fluvastatin, an 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, in human keratinocytes cell line NCTC-2544. Fluvastatin underwent rapid photodegradation upon Ultraviolet-A (UVA) irradiation in buffered aqueous solution as shown by the changes in absorption spectra. Interestingly, no isosbestic points were observed but only a fast appearance of a spectral change, indicative of the formation of a new chromophore. The isolation and characterization of the main photoproduct revealed the formation of a polycyclic compound with a benzocarbazole-like structure. This product was also evaluated for its phototoxic potential. Cell phototoxicity was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyl tetrazolium bromide test after 72 h from the irradiation in the presence of fluvastatin. The results showed a reduction of the cell viability in a concentration and UVA dose-dependent manner. Surprisingly, the photoproduct showed a dramatic decrease of the cell viability that occurred at concentrations of an order of magnitude lower than the parent compound. Flow cytometric analysis indicated that fluvastatin and its main photoproduct induced principally necrosis as revealed by the large appearance of propidium iodide-positive cells and confirmed also by the rapid drop in cellular adenosine triphosphate levels. Interestingly, a rapid increase of intracellular calcium followed by an extensive cell lipid membrane peroxidation and a significant oxidation of model proteins were induced by fluvastatin and its photoproduct, suggesting that these compounds exerted their toxic effect mainly in the cellular membranes. On the basis of our results, the phototoxicity of fluvastatin may be mediated by the formation of benzocarbazole-like photoproduct that acts as strong photosensitizer

New insights into SARS-CoV-2 Lumipulse G salivary antigen testing: accuracy, safety and short TAT enhance surveillance

Objectives The rapid, accurate and safe detection of SARS-CoV-2 is the key to improving surveillance and infection containment. The aim of the present study was to ascertain whether, after heat/chemical inactivation, SARS-CoV-2 N antigen chemiluminescence (CLEIA) assay in saliva remains a valid alternative to molecular testing. Methods In 2022, 139 COVID-19 inpatients and 467 healthcare workers were enrolled. In 606 self-collected saliva samples (Salivette), SARS-CoV-2 was detected by molecular (TaqPath rRT-PCR) and chemiluminescent Ag assays (Lumipulse G). The effect of sample pre-treatment (extraction solution-ES or heating) on antigen recovery was verified. Results Salivary SARS-CoV-2 antigen assay was highly accurate (AUC=0.959, 95% CI: 0.943-0.974), with 90% sensitivity and 92% specificity. Of the 254 antigen positive samples, 29 were false positives. We demonstrated that heterophilic antibodies could be a cause of false positive results. A significant antigen concentration decrease was observed after ES treatment (p=0.0026), with misclassification of 43 samples. Heat had a minimal impact, after treatment the correct classification of cases was maintained. Conclusions CLEIA SARS-CoV-2 salivary antigen provides accurate, timely and high-throughput results that remain accurate also after heat inactivation, thus ensuring a safer work environment. This supports the use of salivary antigen detection by CLEIA in surveillance programs

Intra-hospital acquisition of colonization and infection by Klebsiella pneumoniae strains producing carbapenemases and carriage evolution: A longitudinal analysis in an Italian teaching hospital from January 2017 to August 2019

Abstract Objectives We present an updated picture (1/1/2017–31/08/2019) of the frequency of carbapenemase producing Klebsiella pneumoniae (CPKP) in surveillance rectal swabs (SRS) and in clinical samples (CS) of patients admitted to a tertiary level hospital, focusing on longitudinal evolution of CPKP detected in SRS and on colistin resistant strains. Methods Retrospective longitudinal analysis. Only the first positive CPKP strain isolated from each patient was included. Results 638 CPKP strains were identified (471 in SRS and 167 in CS). SRS frequency increased over time in the medical department, remained high in the surgical department (SD) and decreased in the intensive care department. Most SRS–71.3%–and 49.1% of CS had nosocomial origin; about half of the SRS were identified in the SD. Regarding SRS evolution, carriage was confirmed in 39.5% of patients, no more testing in 25.5%, clinical involvement in 24.8 %, and negative result in 10.2%. Rates of colistin resistance were 20.1% in 2017, 31.2% in 2018 and 26.9% in 2019. Conclusions CPKP diffusion is still an important issue despite the surveillance program. It is vital to enhance medical staff's awareness on this because most CPKP first detections in SRS occurred during hospital stay due to a nosocomial acquisition with a comparable picture over time. Colistin resistance is increasing

Effect of MTA-based sealer on the healing of periapical lesions

Some manufacturers have recently added specific components to improve the ease of handling and insertion material properties of MTA in order to create MTA-based sealers. Objective The aim of this study was to evaluate the healing of periapical lesions in canine teeth after a single session of endodontic treatment with MTA Fillapex® compared with Sealapex® or Endo-CPM-Sealer®. Material and Methods Sixty-two root canals were performed on two 1-year-old male dogs. After coronal access and pulp extirpation, the canals were exposed to the oral cavity for 6 months in order to induce periapical lesions. The root canals were prepared, irrigated with a solution of 2.5% sodium hypochlorite and filled with gutta-percha and different sealers, according to the following groups: 1) Sealapex®; 2) Endo-CPM-Sealer®; and 3) MTA Fillapex®. Some teeth with periapical lesions were left untreated for use as positive controls. Healthy teeth were used as negative controls. After 6 months, the animals were sacrificed and serial sections from the roots were prepared for histomorphologic analysis and stained with hematoxylin and eosin and the Brown and Brenn technique. The lesions were scored according to pre-established histomorphologic parameters and the scores statistically analyzed using the Kruskal-Wallis test. Results All 3 materials produced similar patterns of healing (p>;0.05); in particular, persistent inflammation and absence of complete periapical tissue healing were consistently noted. Conclusions Preparation of the infected root canals followed by filling with the materials studied was insufficient to provide complete healing of the periapical tissues

Liver stiffness is not associated with short- and long-term plasma HIV RNA replication in immunocompetent patients with HIV infection and with HIV/HCV coinfection

Background:Human immunodeficiency virus (HIV) may be directly responsible for liver damage but there are contrasting data regarding the influence of detectable plasma viremia. We analyzed the influence of plasma HIV RNA (pHIV) detectability and of other clinical and viro-immunological variables on liver stiffness (LS) measurement in adult immunocompetent HIV-monoinfected patients and in patients coinfected with hepatitis C virus (HCV). Methods: Logistic regression analysis was performed using the value of LS>7.1 kPa as the dependent variable. A linear regression model was applied using LS measurement after log 10 transformation (lkpa) as the dependent variable and we analyzed the predicted values versus the observed lkpa values; pHIV was classified as detectable or undetectable in the 12- and 36-month study periods before LS measurement. Results: We studied 251 patients (178 with HIV monoinfection), most of whom were on antiviral treatment; 36-month study time was available for 154 subjects. The mean CD4+ cell count was 634 cells/mm3 in HIV-monoinfected patients and 606 cells/mm3 in coinfected patients. No difference in LS was found between patients with detectable or undetectable pHIV in either the 12- or the 36-month study period before transient elastography. The mean LS was higher in HIV/HCV coinfected patients (P<0.0001) than in the HIV-monoinfected subjects; lkpa was positively correlated with HCV coinfection (P<0.0001) and aspartate aminotransferase levels (P<0.0001). Detectable pHIV failed to reach significance. Eight HIV-monoinfected patients had a predicted LS measurement lower than the observed one, while eight patients had the opposite result. Conclusion: LS was not correlated with ongoing HIV replication during the 12- and 36-month study periods in immunocompetent HIV-monoinfected and HIV/HCV-coinfected patients

Intrusão dentária associada ao uso de abridor de boca do tipo molt em paciente com paralisia cerebral: relato de caso / Dental intrusion associated with the use of molt mouth opener in a patient with cerebral palsy – a case report

Introdução: O uso de abridores de boca pode ser necessário para o atendimento de pacientes com deficiência, como a paralisia cerebral. Acidentes com o deslocamento do elemento dental para dentro do seio maxilar são relativamente comuns na prática odontológica, porém não há relatos que relacionam esta complicação ao uso de abridores de boca. Objetivo: Apresentar um caso clínico de intrusão de primeiro molar permanente no seio maxilar, em paciente com paralisia cerebral, associado ao uso de abridor de boca do tipo Molt. Relato do caso: Paciente de 29 anos, sexo masculino, com paralisia cerebral espástica e deficiência mental, foi encaminhado ao Centro de Especialidades Odontológicas da Unioeste (Universidade Estadual do Oeste do Paraná) para tratamento. Durante a realização de uma restauração com auxílio de abridor de boca do tipo Molt, houve a intrusão do elemento 26, em decorrência de apertamentos bruscos e repetidos sobre o abridor. Foi realizada uma cirurgia exploratória através do próprio alvéolo para a remoção do dente, o qual apresentava todas as raízes fusionadas. O alvéolo foi fechado por primeira intenção com um retalho lateral tracionado para o rebordo alveolar e suturado sem tensão. O paciente recebeu as recomendações pós-operatórias e foi medicado. O processo de cicatrização apresentou-se normal após 14 dias. Conclusão: Conclui-se que, apesar de muito importante para o atendimento de pacientes com deficiência, o uso de abridores de boca deve ser cuidadoso para evitar possíveis acidentes e complicações

Childhood Cancer patients and dentist registers from a hospital: a 15-year study / Pacientes com câncer na infância e registos dentários de um hospital: um estudo de 15 anos

Os efeitos colaterais da terapia antineoplásica na mucosa bucal podem afetar a qualidade de vida dos pacientes, principalmente em crianças e adolescentes. Este estudo transversal avaliou a frequência de pacientes de até 19 anos atendidos no Hospital de Câncer de Cascavel - UOPECCAN (Hospital do Câncer de Cascavel) entre 2000-2014, apenas aqueles atendidos pelo dentista da instituição. Neoplasia, tratamento e as manifestações orais foram determinados. Os registros médicos enfocavam sexo, idade, classificação do câncer e tratamento. Exames odontológicos e anos de assistência também foram cobrados. De 100 pacientes que atenderam aos critérios, os resultados foram: masculino (57%), feminino (43%), &lt;1 ano de idade (5%), 1-4 (42%), 5-9 (25%), 10 -14 (23%) e 15-19 (5%). Leucemia (48%), rabdomiossarcoma (10%) e neuroblastoma (7%) foram os mais prevalentes, assim como a quimioterapia (55%). Oito e seis pessoas desenvolveram manifestações orais: mucosite (34%), gengivite (9%), cárie (33%), gengivoestomatite herpética (11%), herpes labial (7%), candidíase (9%) e outro estágio de dentição mista relacionados (esfoliação de dente decíduo e edema - 8%). O setor odontológico aumentou o número de atendimentos ao longo dos anos. O dentista atendeu metade dos pacientes. A maioria deles eram crianças menores de 4 anos. Leucemia e quimioterapia foram mais prevalentes e 86% da amostra desenvolveu manifestação oral. A maioria deles eram crianças menores de 4 anos. Leucemia e quimioterapia foram mais prevalentes e 86% da amostra desenvolveu manifestação oral. A maioria deles eram crianças menores de 4 anos. Leucemia e quimioterapia foram mais prevalentes e 86% da amostra desenvolveu manifestação oral