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Tuberculosis (TB), caused by Mycobacterium tuberculosis, is a significant global health problem. In immunocompetent individuals, the microorganism can remain in a latent, non-contagious form, however, it may become active under conditions of immunosuppression. Tumour necrosis factor (TNF) inhibitors, which are frequently used for the management of immune-mediated disorders like psoriasis, have been associated with a significantly increased risk of reactivating latent TB. Consequently, international guidelines recommend TB screening and preventive treatment before starting anti-TNF therapy. These recommendations have extended to IL-12/23, IL-17, IL-23 and TYK2 inhibitors under a caution principle, despite their different mechanisms of action. However, current evidence suggests that some of these agents are arguably not associated with an increased risk of TB reactivation or development of TB disease after infection, which calls for a critical reassessment of these guidelines. We have conducted a literature search evaluating the risk of TB reactivation associated with these innovative therapies, integrating findings from both randomized clinical trials and real-world evidence. The identified evidence is limited but the low number of identified cases of reactivation with IL-17 and IL-23 inhibitors prompts reconsidering the need for preventive treatment for latent TB in all cases, regardless of biologic class or individual patient's risk of TB reactivation or drug toxicity. This review, along with the clinical insight of a panel of experts on behalf of the SPIN-FRT, led to the development of these consensus recommendations for managing psoriasis treatment in patients with latent TB infection or at risk of TB infection, who are receiving or are intended to receive biologic and non-biologic targeted therapies. These recommendations highlight the need for updates to the existing guidelines, aiming to provide a more differentiated approach that reflects the evolving landscape of psoriasis treatment and its implications for TB management.
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AIMS: Impairment of blood-brain barrier (BBB) is involved in numerous neurological diseases from developmental to aging stages. Reliable imaging of increased BBB permeability is therefore crucial for basic research and preclinical studies. Today, the analysis of extravasation of exogenous dyes is the principal method to study BBB leakage. However, these procedures are challenging to apply in pups and embryos and may appear difficult to interpret. Here we introduce a novel approach based on agonist-induced internalization of a neuronal G protein-coupled receptor widely distributed in the mammalian brain, the somatostatin receptor type 2 (SST2). METHODS: The clinically approved SST2 agonist octreotide (1 kDa), when injected intraperitoneally does not cross an intact BBB. At sites of BBB permeability, however, OCT extravasates and induces SST2 internalization from the neuronal membrane into perinuclear compartments. This allows an unambiguous localization of increased BBB permeability by classical immunohistochemical procedures using specific antibodies against the receptor. RESULTS: We first validated our approach in sensory circumventricular organs which display permissive vascular permeability. Through SST2 internalization, we next monitored BBB opening induced by magnetic resonance imaging-guided focused ultrasound in murine cerebral cortex. Finally, we proved that after intraperitoneal agonist injection in pregnant mice, SST2 receptor internalization permits analysis of BBB integrity in embryos during brain development. CONCLUSIONS: This approach provides an alternative and simple manner to assess BBB dysfunction and development in different physiological and pathological conditions.
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Barreira Hematoencefálica/patologia , Permeabilidade Capilar , Imuno-Histoquímica/métodos , Receptores de Somatostatina/análise , Receptores de Somatostatina/metabolismo , Animais , Anticorpos Monoclonais , Camundongos , Camundongos Endogâmicos C57BL , Octreotida/metabolismo , Ratos , Ratos WistarRESUMO
BACKGROUND: The treatment of tuberculosis (TB) in solid organ transplant (SOT) recipients is challenging owing to interactions between rifampin and immunosuppressive drugs. Rifabutin, a rifamycin with excellent activity against Mycobacterium tuberculosis and that induces cytochrome p450 less, may facilitate treatment. We report our experience with rifabutin for treating TB in SOT recipients and review the available literature. METHODS: A retrospective observational study of all SOT recipients with TB between January 2000 and December 2019. The clinical characteristics and outcomes of patients treated with and without rifabutin-containing regimens were compared and a literature review was conducted. RESULTS: We included 31 SOT recipients with TB, among whom 22 (71%) were men and the median age was 62 years (interquartile range 50-20). There were no significant differences between patients treated with rifabutin (n = 12), rifampin (n = 14), and non-rifamycins (n = 5) in clinical cure rates (83.3%, 64.3%, and 100%, respectively; P = .21), side effects (25%, 37.5%, and 20%, respectively; P = .74), or mortality (16.7%, 35.7%, and 0%, respectively; P = .21). Only one patient, treated with rifampin, suffered graft rejection. The literature review identified 59 SOT recipients with TB treated with rifabutin-containing regimens from 8 publications. Overall, the clinical cure, graft rejection, and mortality rates were 93.2%, 5.1%, and 6.8%, respectively. CONCLUSIONS: Rifabutin-containing regimens offer a reliable alternative to rifampin when treating TB in SOT recipients.
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Mycobacterium tuberculosis , Transplante de Órgãos , Tuberculose , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Observacionais como Assunto , Rifabutina , Rifampina , TransplantadosRESUMO
BACKGROUND AND RATIONALE: Histopathological studies revealed degeneration of the dorsal motor nucleus of the vagus nerve (VN) early in the course of idiopathic Parkinson's disease (IPD). Degeneration of VN axons should be detectable by high-resolution ultrasound (HRUS) as a thinning of the nerve trunk. In order to establish if the VN exhibits sonographic signs of atrophy in IPD, we examined patients with IPD compared with age-matched controls. MATERIAL AND METHODS: We measured the caliber (cross-sectional area, CSA) and perimeter of the VN in 20 outpatients with IPD (8 females and 12 males; mean age 73.0 + 8.6 years) and in age-matched controls using HRUS. Evaluation was performed by blinded raters using an Esaote MyLab Gamma device in conventional B-Mode with an 8-19 MHz probe. RESULTS: In both sides, the VN CSA was significantly smaller in IPD outpatients than in controls (right 2.37 + 0.91, left 1.87 + 1.35 mm2 versus 6.0 + 1.33, 5.6 + 1.26 mm2; p <0.001), as well as the perimeter (right 5.06 + 0.85, left 4.78 + 1.74 mm versus 8.87 + 0.86, 8.58 + 0.97 mm; p <0.001). There were no significant correlations between VN CSA and age, the Hoehn and Yahr scale, L-dopa therapy, and disease duration. CONCLUSION: Our findings provide evidence of atrophy of the VNs in IPD patients by HRUS. Moreover, HRUS of the VN represent a non-invasive easy imaging modality of screening in IPD patients independent of disease stage and duration and an interesting possible additional index of disease.
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Doença de Parkinson , Idoso , Idoso de 80 Anos ou mais , Atrofia , Feminino , Humanos , Levodopa , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/diagnóstico por imagem , Ultrassonografia , Nervo Vago/diagnóstico por imagemRESUMO
Background: In the case of a degenerated intervertebral disc (IVD), even though spinal fusion has provided good short-term clinical results, an alteration of the spine stability has been demonstrated by long-term studies. In this context, different designs of IVD prostheses have been proposed as alternative to spinal fusion. However, over the past few years, much of the recent research has been devoted to IVD tissue engineering, even if several limitations related to the complex structure of IVD are still presented.Purpose/Aim: Accordingly, the aim of the current paper was to develop a strategy in designing customised multiphasic nucleus/annulus scaffolds for IVD tissue engineering, benefiting from the great potential of reverse engineering, additive manufacturing and gels technology.Materials and Methods: The device consisted of a customised additive-manufactured poly(ε-caprolactone) scaffold with tailored architectural features as annulus and a cell-laden collagen-low molecular weight hyaluronic acid-based material as nucleus with specific rheological and functional properties. To this aim, injectability and viscoelastic properties of the hydrogel were analyzed. Furthermore, a mechanical and biological characterization of cell-laden multiphasic nucleus/annulus scaffold was performed.Results and Conclusions: Analyses on the developed devices demonstrated appropriate viscoelastic and mechanical properties. As evidenced by rheological tests, the hydrogel showed a shear-thinning behaviour, supporting the possibility to inject the material. The mechanical characterization highlighted a compressive modulus which falls in the range of lumbar discs, with the typical initial J-shaped stress-strain curve of natural IVDs. Furthermore, preliminary biological tests showed that human mesenchymal stem cells were viable over the culture period.
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Degeneração do Disco Intervertebral/terapia , Núcleo Pulposo/fisiologia , Regeneração , Alicerces Teciduais/química , Animais , Colágeno/química , Humanos , Hidrogéis/químicaRESUMO
The objective of this study was to evaluate management practices and environmental factors associated with cryptosporidiosis and giardiasis in preweaned heifer calves on US dairy operations. This study was conducted as part of the calf component of the National Animal Health Monitoring System's Dairy 2014 study. The calf component included 104 dairy operations in 13 states and was an 18-mo longitudinal study focused on dairy heifer calves from birth to weaning. Fecal samples were collected from 2,249 calves: 839 calves in the West region (California, Colorado, and Washington) and 1,410 calves in the East region (Iowa, Michigan, Minnesota, Missouri, New York, Ohio, Pennsylvania, Vermont, Virginia, and Wisconsin). Fecal samples were collected only once from calves during the preweaning period. Samples were collected from calves 3 to 66 d of age, with a mean of 22 d. Overall, Cryptosporidium and Giardia were detected in 43.1 and 30.5% of fecal samples, respectively. Backward elimination logistic model selection was used after univariate screening to determine which management practices and environmental factors significantly affected the presence of Cryptosporidium or Giardia. The final Cryptosporidium model included herd size, days of age at fecal collection, and average temperature-humidity index for the month of fecal collection (fTHI). Cryptosporidium was found on a higher percentage of large operations (≥500 cows) than small operations (30 to 99 cows). Younger calves were more likely to have a fecal sample positive for Cryptosporidium than samples from older calves. Fecal samples from calves during the warmer parts of the year (fTHI >70) were more likely to be positive for Cryptosporidium than samples collected in colder months (fTHI <20). The final Giardia model included herd size, days of age at fecal collection, average fTHI, failure of passive transfer status, and average daily gain (kg/d) during the preweaning period. Giardia was isolated more frequently from calves on small operations than on large operations and from calves that were older compared with younger calves. Giardia was more frequently isolated in warmer months. Samples from calves with failure of passive transfer were more likely to have Giardia than calves with adequate passive transfer (>10 g/L IgG). Average daily gain during the preweaning period was lower in calves from which Giardia was isolated. These results highlight the factors associated with the presence of Cryptosporidium and Giardia in preweaned dairy heifer calves.
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Doenças dos Bovinos/epidemiologia , Criptosporidiose/epidemiologia , Fezes/parasitologia , Giardíase/veterinária , Animais , Animais Lactentes , Bovinos , Doenças dos Bovinos/parasitologia , Cryptosporidium/isolamento & purificação , Feminino , Giardia/isolamento & purificação , Giardíase/epidemiologia , Estudos LongitudinaisRESUMO
The study objective was to evaluate average daily gain (ADG) in dairy heifer calves based on health, feeding, management practices, and environmental factors. This study included 102 operations in 13 states that participated in the calf component of the National Animal Health Monitoring System's Dairy 2014 study. This 18-mo longitudinal study included 1,410 Holstein heifer calves monitored from birth to weaning. The mean ADG from birth to final weight was 0.74 kg/d. Backward elimination model selection in Proc Mixed after univariate screening determined factors that significantly affected ADG. The final model included dam lactation number, singleton versus twin birth, bedding type, Giardia and Cryptosporidium fecal shedding, disease events, a categorized average temperature-humidity index for the preweaning period (pTHI), amount of protein in the liquid diet (kg/d), milk pasteurization, direct-fed microbials, and the interaction between milk pasteurization and direct-fed microbials. After controlling for other independent variables in the model, calves born to first-lactation dams gained less (0.60 kg/d) than calves from second- (0.65 kg/d) or third- or greater-lactation (0.64 kg/d) dams. Singleton calves gained 0.07 kg/d more than twins. Calves bedded with sand or no bedding gained less (0.49 kg/d) than calves on all other bedding types. Calves negative for Cryptosporidium or Giardia at the time of sampling gained 0.03 or 0.02 kg/d more, respectively, than calves that were positive for Cryptosporidium or Giardia. Calves with no disease events gained 0.07 kg/d more than calves with one or more disease events. Calves experiencing an average pTHI <50 gained more (0.67 kg/d) than calves experiencing an average pTHI from 50 to 69 (0.62 kg/d), or ≥70 (0.59 kg/d). Within the range of observed kilograms of protein fed per day in the liquid diet, every additional 0.1 kg of protein fed per day equated to 0.02 kg/d of gain. Calves fed milk replacer with a direct-fed microbial gained less (0.44 kg/d) than calves fed milk replacer without a direct-fed microbial (0.60 kg/d) and calves fed pasteurized or unpasteurized milk regardless of direct-fed microbial use. These results highlight the importance of feeding a quantity and quality of a liquid diet to achieve optimal growth, keeping calves free of disease, the type or status of bedding, and mitigating the effects of temperature and humidity on preweaning ADG.
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Animais Lactentes/crescimento & desenvolvimento , Bovinos/crescimento & desenvolvimento , Ração Animal , Animais , Dieta , Feminino , Estudos Longitudinais , Leite , DesmameRESUMO
The basal ganglia are key structures for motor, cognitive and behavioral functions. They undergo several changes with aging and disease, such as Parkinson's or Huntington's disease, for example. Iron accumulation in basal ganglia is often related to these diseases, which is conventionally monitored by the transverse relaxation rate (R2 *). Quantitative susceptibility mapping (QSM) is a novel contrast mechanism in MRI produced by adding information taken from the phase of the MR signal to its magnitude. It has been shown to be more sensitive to subtle changes in Parkinson's disease. In order to be applied widely to various pathologies, its reproducibility must be evaluated in order to assess intra-subject variability and to disseminate into clinical and pharmaceutical studies. In this work, we studied the reproducibility and sensitivity of several QSM techniques. Fourteen subjects were scanned four times, and QSM and R2 * images were reconstructed and registered. An atlas of the basal ganglia was used to automatically define regions of interest. We found that QSM measurements are indeed reproducible in the basal ganglia of healthy subjects and can be widely used as a replacement for R2 * mapping in iron-rich regions. This reproducibility study could lead to several lines of research in relaxometry and susceptibility measurements, in vivo iron load evaluation as well as pharmacological assessment and biomarker development. Copyright © 2016 John Wiley & Sons, Ltd.
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Algoritmos , Gânglios da Base/diagnóstico por imagem , Gânglios da Base/metabolismo , Interpretação de Imagem Assistida por Computador/métodos , Ferro/metabolismo , Imageamento por Ressonância Magnética/métodos , Imagem Molecular/métodos , Adulto , Biomarcadores/metabolismo , Feminino , Humanos , Masculino , Valores de Referência , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Adulto JovemRESUMO
To determine trends in incidence and clinical relevance of rapidly growing mycobacteria (RGM) in a low-prevalence region of non-tuberculous mycobacteria. We retrospectively identified all patients with RGM-positive cultures between January 1994 and December 2015. Trends in incidence, clinical significance, and outcomes were assessed. One hundred and forty patients had RGM-positive cultures (116 respiratory and 24 extra-respiratory sources). The incidence of RGM isolates increased steadily from 2003 (0.34 per 100,000) to 2015 (1.73 per 100,000), with an average annual increase of 8.3%. Thirty-two patients (22.9%) had clinical disease, which trended to cluster in the second half of the study period. A positive acid-fast bacilli smear (odds ratio [OR] 97.7, 95 % CI 13.8-689.4), the presence of extra-respiratory isolates (OR 19.4, 95 % CI 5.2-72.7), and female gender (OR 5.9, 95 % CI 1.9-19.1) were independently associated with clinical disease. Cure rates were 73.3 and 87.5% for pulmonary and extra-pulmonary disease respectively. Although the burden of disease remains low, the presence of RGM isolates is increasing in our geographical setting. Whether this rise will be sustained over time and will coincide with an increase in clinical disease, or whether it is merely a cycle in the poorly understood epidemiological behaviour of environmental mycobacteria, will be seen in the near future.
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Infecções por Mycobacterium não Tuberculosas/epidemiologia , Micobactérias não Tuberculosas/isolamento & purificação , Idoso , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Infecções por Mycobacterium não Tuberculosas/patologia , Estudos Retrospectivos , Fatores de Risco , Fatores Sexuais , Resultado do TratamentoRESUMO
Glucagon-like peptide 2 (GLP-2) therapy was shown previously to reduce inflammation-related gut damage from coccidiosis in dairy calves, and feeding of artificial sweetener stimulates GLP-2 secretion from intestinal L cells. The purpose of this study was to determine whether GLP-2 treatment or artificial sweetener feeding beginning 1 wk before an experimental inoculation with the coccidian parasite Cryptosporidium parvum can reduce infection-related intestinal damage in Holstein bull calves. Newborn calves were assigned to 1 of 4 treatment groups of 6 calves each, including noninfected control calves injected s.c. every 12 h with control buffer (CON), infected control calves injected s.c. every 12 h with control buffer (INF), infected calves injected s.c. every 12 h with 50 µg/kg of body weight of GLP-2 (GLP2), and infected calves injected s.c. every 12 h with control buffer and supplemented in the diet with Sucram (Pancosma, Geneva, Switzerland) at 400 mg/kg of dry matter of milk replacer (SUC). Treatments were initiated on d 1, and calves in INF, GLP2, and SUC were orally dosed on d 8 with 12,500 C. parvum oocysts. Fecal scores were recorded daily, plasma was collected on d 1, 8, 12, 15, and 18 to evaluate markers of inflammation, and fecal samples were collected on d 1, 8, and every other day thereafter to determine the presence of oocysts. Calves were euthanized on d 18 for collection of intestinal tissues and histological and gene expression analyses. Relative to CON, calves in INF exhibited an increase in diarrhea severity, increased plasma serum amyloid A concentration on d 15 and 18, reduced intestinal villus height, increased villus apoptosis and crypt cell proliferation, and increased intestinal mRNA expression of MARVELD2 and GPX2. However, calves in SUC and GLP2 had reduced diarrhea severity and fecal C. parvum oocyst shedding, reduced plasma serum amyloid A concentration on d 15 and 18, and, depending on the intestinal segment, increased villus height, reduced crypt cell proliferation, and reduced mRNA expression of MARVELD2, GPX2, and other tight junction proteins relative to INF. Lastly, GLP2 and SUC exhibited increased intestinal mass-to-length ratio and decreased length-to-empty body weight ratio relative to INF. Our findings suggest that GLP-2 and Sucram treatments administered before a low-level C. parvum exposure may contribute to fewer effects on intestinal integrity, morphology, and inflammation in response to infection, and shorter, denser intestines.
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Cryptosporidium parvum , Peptídeo 2 Semelhante ao Glucagon , Animais , Bovinos , Doenças dos Bovinos/prevenção & controle , Criptosporidiose , Masculino , EdulcorantesRESUMO
The purpose of this study was to develop and utilize semi-quantitative RT-PCR and PCR assays for measuring the level of Cryspovirus, the viral symbiont of Cryptosporidium parvum, during in vitro development of the protozoan. Cultures of human carcinoma cells (HCT-8) were inoculated with excysting C. parvum sporozoites, followed by harvest of cells and culture medium at 2-, 24-, 48-, and 72-h post-infection. Changes in viral RNA levels were detected by RT-PCR using primers specific for RNA encoding the 40-kDa capsid protein (CP) or RNA-dependent RNA polymerase (RdRp). Parasite or host DNA was quantified by PCR specific for C. parvum or human glyceraldehyde-3-phosphate dehydrogenase (HuGAPDH). An internal standard (competitor) was incorporated into all assays as a control for PCR inhibition. Intracellular levels of C. parvum DNA increased between 2- and 48-h post-infection, and then decreased at 72 h. Culture medium overlying these C. parvum-infected cells displayed a similar increase in CP and RdRp signal, reaching peak levels at 48 h. However, the CP and RdRp levels in cellular RNA displayed only a modest increase between 2 and 48 h, and exhibited no change (CP) or decreased (RdRp) at 72 h. These data suggest that during the first 48 h of C. parvum in vitro development, Cryspovirus is released into the media overlying cells but remains at fairly constant levels within infected cells.
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Cryptosporidium parvum/virologia , Vírus de RNA/isolamento & purificação , Linhagem Celular Tumoral , Cryptosporidium parvum/crescimento & desenvolvimento , Humanos , Reação em Cadeia da Polimerase , RNA Viral/genéticaRESUMO
Blastocystis has been reported in pig feces but the sites of development in the gastrointestinal tract are unknown. The present study was undertaken to determine predilection sites of Blastocystis in 11 naturally infected pigs examined at 20 weeks of age. At necropsy, feces and contents of the duodenum, jejunum, ileum, and cecum were examined by immunofluorescence (IFA) microscopy and PCR and tissues from these sites as well as the proximal and distal colon were processed for histology from pigs 1 to 5. Feces were examined by IFA microscopy, and segments from the jejunum and ileum were processed for histology from pigs 6 to 11. Multiple sections were cut from each tissue segment, and each was stained with the following: hematoxylin and eosin, polyclonal rabbit antibody to Blastocystis, and ParaFlor B monoclonal antibody to Blastocystis. Blastocystis was detected in feces of all 11 pigs by IFA microscopy and determined by PCR and gene sequencing to be subtype 5 for pigs 1-5. Blastocystis was also detected in the lumen contents removed from the cecum of pigs 1-5 examined by IFA microscopy and in the cecum of pigs 4 and 5 by PCR. Blastocystis was also observed in tissue sections from the jejunum of 7 of the 11 pigs, in the proximal and distal colon of pigs 1-5, and in the cecum of 4 of these 5 pigs but was not detected in the duodenum or ileum of any pigs. In tissue sections, Blastocystis was found primarily in the lumen usually associated with digested food debris, sometimes in close proximity or appearing to adhere to the epithelium, but no stages were found to penetrate the epithelium or the lamina propria.
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Blastocystis/crescimento & desenvolvimento , Intestinos/parasitologia , Sus scrofa/parasitologia , Animais , Ceco/parasitologia , Ceco/patologia , Colo/parasitologia , Colo/patologia , Duodeno/parasitologia , Duodeno/patologia , Fezes/parasitologia , Conteúdo Gastrointestinal/parasitologia , Íleo/parasitologia , Íleo/patologia , Intestinos/patologia , Jejuno/parasitologia , Jejuno/patologia , TropismoRESUMO
Chronic and acute wounds can be quickly contaminated and infected by microorganisms such as bacteria, multi-resistant organisms or fungi. The introduction of silver as anti-microbial agent into wound management has widely been demonstrated to be effective and contribute to wound healing. As a consequence, many approaches and different materials have been employed to synthesize antibacterial silver-hydrogels. In this work the introduction of silver particles into the fibrillar structure of self-assembling aromatic di-phenylalanine derivatives modified with aromatic groups such as 9-fluorenylmethoxycarbonyl is proposed to produce antibacterial wound dressings. Hydrogels doped with increasing amounts of silver were tested and adopted to modify flax textiles. The influence of silver on the structure of hydrogels was studied using light and confocal microscopy, while SEM-EDX allowed the characterization of the hydrogel coating on the surface of the textile substrates as well as the identification and distribution of silver nanoparticles. The antibacterial potential of the treated flax was demonstrated through microbiological tests on Staphylococcus aureus. The combination of the physico-chemical and anti-bacterial properties, together with the ease of preparation of these biomaterials, fulfils the requirement of clinically-effective wound dressings.
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Anti-Infecciosos/química , Bandagens , Materiais Biocompatíveis/química , Hidrogéis/química , Fenilalanina/química , Prata/química , Cicatrização/efeitos dos fármacos , Antibacterianos/química , Biofilmes , Cromatografia Líquida de Alta Pressão , Fluorenos/química , Géis , Espectrometria de Massas , Microscopia Confocal , Microscopia Eletrônica de Varredura , Peptídeos/química , Compostos de Prata/química , Staphylococcus aureus/efeitos dos fármacosRESUMO
Nonsteroidal anti-inflammatory drugs (NSAIDs) are frequently used to reduce pain and inflammation. However, their effect on bone metabolisms is not well known, and results in the literature are contradictory. The present study focusses on the effect of dexketoprofen, ketorolac, metamizole, and acetylsalicylic acid, at therapeutic doses, on different biochemical and phenotypic pathways in human osteoblast-like cells. Osteoblasts (MG-63 cell line) were incubated in culture medium with 1-10 µM of dexketoprofen, ketorolac, metamizole, and acetylsalicylic acid. Flow cytometry was used to study antigenic profile and phagocytic activity. The osteoblastic differentiation was evaluated by mineralization and synthesis of collagen fibers by microscopy and alkaline phosphatase activity (ALP) by spectrophotometric assay. Short-term treatment with therapeutic doses of NSAIDs modulated differentiation, antigenic profile, and phagocyte activity of osteoblast-like cells. The treatment reduced ALP synthesis and matrix mineralization. However, nonsignificant differences were observed on collagen syntheses after treatments. The percentage of CD54 expression was increased with all treatments. CD80, CD86, and HLA-DR showed a decreased expression, which depended on NSAID and the dose applied. The treatments also decreased phagocyte activity in this cellular population. The results of this paper provide evidences that NSAIDs inhibit the osteoblast differentiation process thus reducing their ability to produce new bone mineralized extracellular matrix.
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Anti-Inflamatórios não Esteroides/farmacologia , Neoplasias Ósseas/patologia , Osteoblastos/efeitos dos fármacos , Osteossarcoma/patologia , Fosfatase Alcalina/análise , Antígenos de Diferenciação/análise , Aspirina/farmacologia , Remodelação Óssea/efeitos dos fármacos , Calcificação Fisiológica/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Colágeno/biossíntese , Meios de Cultura/farmacologia , Dipirona/farmacologia , Matriz Extracelular/metabolismo , Citometria de Fluxo , Humanos , Cetoprofeno/análogos & derivados , Cetoprofeno/farmacologia , Cetorolaco/farmacologia , Minerais/metabolismo , Fagocitose/efeitos dos fármacos , Trometamina/farmacologiaRESUMO
BACKGROUND: The End TB Strategy calls for the global scale-up of treatment for latent TB infection (LTBI). We aimed to evaluate a nurse-led care programme for LTBI by identifying gaps in the care cascade in a low-incidence TB setting.METHODS: We included people at risk of TB over a 15-year period. We define three main outcomes in the LTBI care cascade: 1) attendance at the first appointment, 2) completion of the evaluation process, and 3) completion of treatment.RESULTS: We identified 6,126 individuals (2,369 TB contacts, 1,749 biological therapy candidates, and 2,008 transplant candidates). Overall, 5,938 (96.9%) attended, 5,872/5,938 (98.9%) completed the evaluation and 1,624/1,847 (87.9%) completed treatment. Pre-biological (aOR 2.32, 95% CI 1.54-3.49) and pre-transplant (aOR 1.82, 95% CI 1.20-2.76) candidates were more likely to attend the first appointment, while age was associated with completing the evaluation process (aOR 1.02, 95% CI 1.003-1.04). Female sex (aOR 1.47, 95% CI 1.08-1.99) was associated with completing the treatment.CONCLUSION: Successful assessment and treatment of LTBI is achievable when delivered as a part of a comprehensive, nurse-led, patient-centred programme in specialist TB clinics.
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Tuberculose Latente , Tuberculose , Humanos , Feminino , Tuberculose Latente/diagnóstico , Tuberculose Latente/tratamento farmacológico , Tuberculose Latente/epidemiologia , IncidênciaRESUMO
Parasites, including helminths and protists, are pathogens responsible for waterborne and foodborne illnesses in both developed and developing countries. Their global incidence is difficult to estimate, but the World Health Organization (WHO) has indicated the global disease burden of 11 waterborne and foodborne parasitic diseases, is responsible for causing over 407 million illnesses resulting in an estimated of 94 K deaths and 11 million disability-adjusted life years (DALYs). Nevertheless, compared with bacteria and viruses, parasites are often overlooked as etiological agents of foodborne or waterborne disease; this is due to a variety of reasons, including the difficulty of their identification in environmental matrices and because many have a prolonged period between infection and symptoms, making it difficult to implicate infection vehicles. This Special Issue comprises 17 articles that include the more significant waterborne and foodborne parasites of zoonotic importance due to their relevance, with all groups of parasites (protist, cestodes, trematodes, and nematodes) being represented. Each chapter covers relevant aspects regarding -the importance of the parasite in food and water, including an overview of outbreaks where relevant, information on fundamental epidemiological aspects such as transmission, lifecycle and host range, clinical aspects such as pathogenesis, diagnosis and treatment, a summary of prospects for control in water or the food chain, and, finally, providing the authors' opinions regarding future research or studies required to improve control of transmission to people via food or water.
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Surtos de Doenças , Parasitologia de Alimentos , Doenças Transmitidas por Alimentos/epidemiologia , Parasitos/fisiologia , Doenças Parasitárias em Animais/epidemiologia , Água/parasitologia , Animais , Doenças Transmitidas por Alimentos/parasitologia , Doenças Transmitidas por Alimentos/prevenção & controle , Humanos , Incidência , Doenças Parasitárias em Animais/parasitologia , Doenças Parasitárias em Animais/prevenção & controle , Médicos Veterinários , ZoonosesRESUMO
Nanotechnology-based health products are providing innovative solutions in health technologies and the pharmaceutical field, responding to unmet clinical needs. However, suitable standardised methods need to be available for quality and safety assessments of these innovative products prior to their translation into the clinic and for monitoring their performance when manufacturing processes are changed. The question arises which technological solutions are currently available within the scientific community to support the requested characterisation of nanotechnology-based products, and which methodological developments should be prioritized to support product developers in their regulatory assessment. To this end, the work presented here explored the state-of-the-art methods to identify methodological gaps associated with the preclinical characterisation of nanotechnology-based medicinal products and medical devices. The regulatory information needs, as expressed by regulatory authorities, were extracted from the guidance documents released so far for nanotechnology-based health products and mapped against available methods, thus allowing an analysis of methodological gaps and needs. In the first step, only standardised methods were considered, leading to the identification of methodological needs in five areas of characterisation, including: (i) surface properties, (ii) drug loading and release, (iii) kinetic properties in complex biological media, (iv) ADME (absorption, distribution, metabolism and excretion) parameters and (v) interaction with blood and the immune system. In the second step, a detailed gap analysis included analytical approaches in earlier stages of development, and standardised test methods from outside of the nanotechnology field that could address the identified areas of gaps. Based on this analysis, three categories of methodological needs were identified, including (i) method optimisation/adaptation to nanotechnological platforms, (ii) method validation/standardisation and (iii) method development for those areas where no technological solutions currently exist. The results of the analysis presented in this work should raise awareness within the scientific community on existing and emerging methodological needs, setting priorities for the development and standardisation of relevant analytical and toxicological methods allowing the development of a robust testing strategy for nanotechnology-based health products.
Assuntos
Nanomedicina , Nanotecnologia , Padrões de ReferênciaRESUMO
This work combines modeling and experiment to assess encapsulated microbubble oscillations associated with broadband pressure peaks detected after microbubble excitation (postexcitation signals). Data were acquired from albumin-shelled and phospholipid-shelled microbubbles using a passive cavitation detector consisting of a confocally aligned 2.8-MHz transmitter and 13-MHz receiver. Microbubbles in weak solutions were insonified with a 5-cycle pulse at a peak rarefactional pressure of 2.0+/-0.2 MPa. For each microbubble type, at least 100 received signals were identified as individual-microbubble responses. The average broadband noise from signals with postexcitation response was 4.2-7.2 dB higher than from signals without postexcitation. Pressure-time responses for each microbubble type were simulated using the model by Marmottant et al. [J. Acoust. Soc. Am. 118, 3499-3505 (2005)], with insonification conditions matching the experiment. Increased broadband noise predicted for microbubbles with postexcitation response was consistent with that observed experimentally (4.0-8.9 dB). The model predicted that postexcitation signals occur only when the radial oscillation exceeds both the shell break-up threshold and twice the initial radius (free bubble inertial cavitation threshold).
Assuntos
Meios de Contraste , Microbolhas , Periodicidade , Pressão , Ultrassom , Albuminas , Algoritmos , Simulação por Computador , Fluorocarbonos , Humanos , Modelos Teóricos , Fosfolipídeos , Hexafluoreto de Enxofre , Fatores de TempoRESUMO
OBJECTIVE: Structural epilepsy related to cerebral arteriovenous malformation (AVM) suggests different epileptogenic mechanisms. The aim of our study was to determine factors associated with epilepsy into a retrospective cohort of AVM patients. PATIENTS AND METHODS: Ruptured and unruptured AVM data retrieved from a prospective single center registry (2009-2016) were retrospectively assessed. Demographic, clinical and radiological features were identified in AVM patients with or without epilepsy according to the International League Against Epilepsy classification. RESULTS: Epilepsy concerned 22 out of 80 consecutive patients with AVM (27.5%). Univariate analysis comparing both groups revealed a significant association of different variables with the structural epilepsy: young age (P=0.02), large nidus size (P=0.02), venous dilation (P=0.02), posterior cerebral artery (PCA) feeder (P<0.001) and Spetzler-Martin grade (P=0.02). Based on multivariate analysis, only the PCA feeder was identified (OR=5.2 [95% CI 1.1-24,5], P=0.04). CONCLUSION: PCA feeder for cerebral AVM was significantly associated with structural epilepsy. The hypothesis of a vascular steal phenomenon to the detriment of internal temporal lobe vascularization could be related to the development of epilepsy.