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BACKGROUND: A dedicated intensive care dietitian, as part of the intensive care unit (ICU) multidisciplinary team, contributes to improved delivery of nutrition support. The Paediatric Critical Care Society recommends a minimum dietetic staffing to critical-care bed ratio of 1:10, led by an Agenda for Change (AfC) Band 7. METHODS: A cross-sectional study was conducted using an electronic survey that was available for 12 weeks. The Paediatric Intensive Care Audit Network database was used to identify all hospitals with paediatric intensive care unit (PICU) beds (n = 28). RESULTS: Only 14% (n = 4/28) of trusts met the recommended 1:10 dietitian to bed ratio. PICU dietetic whole time equivalent was 0.7 ± 0.4, with a staff to bed ratio of 1:23.7 ± 10.7, compared to adult staff to bed ratio of 1:24.7. Some 92.8% (n = 26/28) had a AfC Band 7 Lead and only 7% (n = 2/28) had an AfC Band 8a Lead compared to adult services where 12.5% (n = 15/122) had an AfC Band 8a (p < 0.05). CONCLUSIONS: There is a significant disparity between adult versus paediatric services with regard to seniority of dietitians. Dietitians in well-resourced centres were more likely to review patients without the need for a referral, which may improve nutrition outcomes.
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Dietética , Humanos , Enfermedad Crítica/terapia , Estudios Transversales , Irlanda , Reino UnidoRESUMEN
The possibility of inclusion of agro-industrial by-products in the diet of small ruminants represents both an economical and an environmental strategy for reducing waste management by industries and the cost of feeding as well as the impact of livestock farming. Large amounts of wastes from the cocoa industry are annually produced with a considerable part represented by cocoa bean shells, considered a suitable ingredient to be included in the diet of ruminants within the limits established by European legislation. The aim of this study was to assess the effect of including cocoa bean shells in the diet of dairy sheep on the sensory, volatile, and antioxidant properties of cheese. To this purpose, 20 Comisana lactating ewes were randomly assigned to 2 experimental groups: control (CTRL) and cocoa bean shells (CBS), and received alfalfa hay ad libitum and 800g of conventional (CTRL) or experimental (CBS) concentrate containing 11.7% CBS to partially replace corn and barley of the CTRL concentrate. Bulk milk collected from each group was used to produce a total of 15 cheeses per group, obtained in 5 different days of cheese-making (3 cheeses a day per group). After 60 d of aging, each cheese of each experimental group was sampled for the analyses. The results on chemical composition revealed a greater monounsaturated fatty acids content and an increase in the nutritional indices suggesting a favorable role of cocoa bean shells dietary inclusion on the nutritive value of the cheese. The cheese sensory profile was affected by the cocoa bean shells inclusion, with more pronounced appearance, odor, aroma, and taste attributes in the product. The volatile profile showed only a few significant differences, mainly related to the cheese ripening process, and no differences were found in α-tocopherol contents in cheese fat between the 2 groups. Therefore, the coca bean shells inclusion in the diet of dairy sheep allowed to obtain a good quality cheese, without altering the characteristics associated with the typical profiles of sheep cheese. Furthermore, the use of this by-product could contribute to decrease feed costs and waste management, representing a good practice for increasing the sustainability of dairy products.
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Alkaline phosphatase (ALP) is a native raw-milk enzyme used in many countries as the standard assay for rapidly validating the milk pasteurization process. Due to the increased restrictions on the production or import of cheeses produced from unpasteurized milk, ALP activity (<10 mU/g) in cheese was measured as a simple and reliable method to check proper milk pasteurization in cheese for both safety inspection and trading controls. In Sicily, the artisanal cheesemaking of the Protected Denomination of Origin (PDO) semi-hard cheeses made with raw sheep milk, includes the cooking of the curd, after whey separation, in a wooden vat under hot Scotta whey (≥80°C), for 3 to 4 h, and finally is left to cool at ambient temperature. Thus, the temperatures adopted during cheesemaking may inactivate the ALP enzyme. To this purpose, the aim of this study was to demonstrate how different temperatures of Scotta whey (35°C [T35], 60°C [T60], 70°C [T70], 80°C [T80], 90°C [T90], and 100°C [T100]) used during the second cooking of Pecorino cheeses after molding for 3 h, influence the ALP activity in fresh and 3-mo aged cheese, both at core and outside. The results highlight that the rate of reduction of ALP was greater with increasing temperature of the second cooking, in particular for T 80°C curd, indicating that the use of Scotta whey >80°C could be a breakpoint able to reduce the ALP activity to values <10 mU/g. Different effects between the core and the outside portions of the experimental cheeses were found, with a decrease in ALP activity more on the outside than in the core portions, in both fresh and 3-mo aged cheeses, for T80, T90, and T100 treatments. Care must be taken in using ALP to control the use of pasteurized milk in the production of PDO cheeses without considering the cheesemaking processes, such as the second cooking, which could be equal to pasteurization, and an adequate interaction of time and temperature can reduce the ALP activity to values comparable with cheeses produced with pasteurized milk.
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The prevention of canine leishmaniosis in healthy dogs requires a multimodal approach combining repellents with an effective vaccine. A vaccine that modulates the cell-mediated immune response against the protozoan has been available in Europe since 2012 (CaniLeish®, Virbac, France). The aim of the present study was to monitor dogs vaccinated with CaniLeish® to examine the kinetics of the antibody response and the safety and tolerance of CaniLeish®. Dogs vaccinated with CaniLeish® were monitored for 12 months. In follow-up visits at baseline (primovaccination or annual booster) (Visit 1, V1), and 1 (V2), 4 (V3), 8 (V4) and 12 (V5) months later, we examined antibody response kinetics using two serology techniques (IFAT and Speed Leish K™). Tolerance to CaniLeish® and its safety were also monitored. Anti-L. infantum IgG antibodies were determined in 242 dogs (125 dogs after primovaccination (Group P) and 117 dogs after booster vaccination (Group B). In addition, 46, 22 and 19 dogs were followed for 2, 3 and 4 years, respectively. At baseline, 100% of dogs in Group P returned negative IFAT and Speed Leish K™ test results while 9.4% (11/117) in Group B tested IFAT positive though Speed Leish K™ negative. In subsequent visits, seropositivity was detected by IFAT in 31.2% (Group P) and 41% (Group B) of the dogs in V2; 16.8% (Group P) and 10.2% (Group B) in V3; 6.4% (Group P) and 8.5% (Group B) in V4; and 3.2% (Group P) and 5.9% (Group B) in V5. All dogs tested Speed Leish K™ negative except two, in which it was later confirmed by molecular testing that they were not infected. Adverse events that could be associated with the vaccine were detected in 20 out of 314 dogs (6.4%). The good clinical status of all dogs was confirmed in an exhaustive clinical exam and haemato-biochemical profile. The Canileish® vaccine was well-tolerated with exceptions that did not appear to be related to age, sex, race or size of vaccinated dogs. Anti-L. infantum antibodies were detected by IFAT in 31.9-40.3% of the dogs 1 month after vaccination, and these antibodies could still be detected in 3.2% of the dogs 1 year later. This means that veterinarians need to use other tools (eg. PCR) to correctly diagnose seropositive dogs.
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Enfermedades de los Perros/prevención & control , Leishmania infantum/inmunología , Leishmaniasis Visceral/veterinaria , Vacunas Antiprotozoos/inmunología , Vacunación/veterinaria , Animales , Anticuerpos Antiprotozoarios/sangre , Enfermedades de los Perros/parasitología , Perros , Femenino , Técnica del Anticuerpo Fluorescente Indirecta/veterinaria , Estudios de Seguimiento , Leishmaniasis Visceral/prevención & control , Masculino , Reacción en Cadena de la Polimerasa , Vacunas Antiprotozoos/normas , EspañaRESUMEN
This entomological survey examines the spatial and seasonal distribution patterns of flea species infesting dogs in Spain. Bioclimatic zones covering broad climate and vegetation ranges were surveyed according to size. In a cross-sectional spatial survey carried out from late May 2013 to mid-July 2015, 1084 dogs from 42 different locations were examined. A total of 3032 fleas were collected and identified as belonging to the following species: Ctenocephalides felis (Siphonaptera: Pulicidae) (81.7%, 2476 fleas); Ctenocephalides canis (11.4%, 347 fleas); Pulex irritans (Siphonaptera: Pulicidae) (6.9%, 208 fleas), and Echidnophaga gallinacea (Siphonaptera: Pulicidae) (0.03%, one flea). Variables observed to have effects on flea abundance were animal weight, sex, length of hair and habitat. In the seasonal survey conducted from June 2014 to June 2015, 1014 fleas were collected from 239 dogs at 30 veterinary practices across Spain. Peaks in C. felis abundance were observed in early summer and late autumn, whereas high numbers of P. irritans and C. canis were recorded in autumn. Numbers of fleas detected in winter were low overall. Based on these findings, the present study updates the spatial and seasonal distributions of flea species in Spain and assesses the impacts of host and habitat variables on flea infestation.
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Distribución Animal , Enfermedades de los Perros/epidemiología , Ecosistema , Infestaciones por Pulgas/veterinaria , Siphonaptera/fisiología , Animales , Biota , Estudios Transversales , Enfermedades de los Perros/parasitología , Perros , Infestaciones por Pulgas/epidemiología , Infestaciones por Pulgas/parasitología , Incidencia , Prevalencia , Estaciones del Año , Siphonaptera/clasificación , España/epidemiologíaRESUMEN
OBJECTIVES: To specify the topography and variations in lymphatic drainage of the right lung to the mediastinum and their therapeutic implications in non-small cell lung cancers (NSCLC). MATERIALS AND METHOD: We injected a dye into the subpleural lymphatic vessels in 65 right lung segments, followed by dissection in 22 subjects. RESULTS: At the upper lobe, we had injected 32 segments. We noted extrasegmental overflow in one case; extrasegmental and extralobar drainage in two cases; drainage to the lymph nodes of another lobe in one case. Fifty-six percent of the segments drained directly (skipping intrapulmonary and hilar lymph nodes) into the right paratracheal lymph nodes, and one dorsal segment drained into the thoracic duct. A ventral segment drained into the inferior tracheobronchial lymph nodes. A contralateral drainage to the recurrent chain was observed in two cases. Sixteen segments of the middle lobe were injected and mainly drained into the inferior tracheobronchial lymph nodes with six direct paths; one medial segment drained into the right anterior mediastinal chain. We noted three contralateral drainages and eight downward abdominal drainages. Out of the 17 segments of the lower lobe injected, 6 segments drained into the lymph nodes of another lobe, 5 segments showed a direct route to the lower quadrant chains. We noted one time a drainage into the paraesophageal lymph nodes. CONCLUSION: The variations in lymphatic drainage of the right lung require to carry out systematically a radical mediastinal lymphadenectomy during the removal of non-small cell lung cancers and to associate an adjuvant treatment.
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Variación Anatómica , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Neoplasias Pulmonares/cirugía , Pulmón/anatomía & histología , Ganglios Linfáticos/anatomía & histología , Vasos Linfáticos/anatomía & histología , Anciano , Anciano de 80 o más Años , Cadáver , Colorantes , Disección , Femenino , Humanos , Inyecciones Intralinfáticas , Metástasis Linfática , Masculino , MediastinoRESUMEN
In rodent models of inflammatory arthritis, bone erosion has been non-invasively assessed by micro-computed tomography (micro-CT). However, non-invasive assessments of paw swelling (oedema) are still based on clinical grading by visual evaluation, or measurements by callipers, not always reliable for the tiny mouse paws. The aim of this work was to demonstrate a novel straightforward 3D micro-CT analysis protocol capable of quantifying not only joint bone erosion, but also soft tissue swelling, from the same scans, in a rodent inflammatory arthritis model. Balb/c mice were divided into two groups: collagen antibody-induced arthritis (CAIA) and CAIA treated with prednisolone, the latter reflecting an established treatment in human rheumatoid arthritis. Clinical paw scores were recorded. On day 10, front paws were assessed by micro-CT and histology. Micro-CT measurements included paw volume (bone and soft tissue together) and bone volume at the radiocarpal joint, and bone volume from the radiocarpal to the metacarpophalangeal joint. Micro-CT analysis revealed significantly lower paw volume (-36%, P < 0.01) and higher bone volume (+17%, P < 0.05) in prednisolone-treated CAIA mice compared with untreated CAIA mice. Paw volume and bone volume assessed by micro-CT correlated significantly with clinical and histological scores (|r| > 0.5, P < 0.01). Untreated CAIA mice showed significantly higher clinical scores, higher inflammation levels histologically, cartilage and bone degradation, and pannus formation, compared with treated mice (P < 0.01). The presented novel micro-CT analysis protocol enables 3D-quantification of paw swelling at the micrometre level, along with the typically assessed bone erosion, using the same images/scans, without altering the scanning procedure or using contrast agents.
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Artritis Experimental/diagnóstico por imagen , Resorción Ósea/diagnóstico por imagen , Enfermedades del Tejido Conjuntivo/diagnóstico por imagen , Edema/diagnóstico por imagen , Microtomografía por Rayos X/métodos , Animales , Antiinflamatorios/farmacología , Artritis Experimental/diagnóstico , Artritis Experimental/tratamiento farmacológico , Artritis Reumatoide/tratamiento farmacológico , Resorción Ósea/diagnóstico , Articulaciones del Carpo/diagnóstico por imagen , Articulaciones del Carpo/efectos de los fármacos , Enfermedades del Tejido Conjuntivo/diagnóstico , Modelos Animales de Enfermedad , Edema/diagnóstico , Femenino , Miembro Anterior/diagnóstico por imagen , Miembro Anterior/efectos de los fármacos , Humanos , Articulación Metacarpofalángica/diagnóstico por imagen , Articulación Metacarpofalángica/efectos de los fármacos , Ratones Endogámicos BALB C , Prednisolona/farmacología , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Factores de Tiempo , Resultado del TratamientoRESUMEN
Particle-induced bone loss by osteoclasts is a common cause of aseptic loosening around implants. This study investigates whether caffeic acid phenethyl ester (CAPE), a potent and specific inhibitor of nuclear factor of activated T cells, cytoplasmic, calcineurin-dependent 1 and nuclear factor kappa B, at a low dose reduces bone resorption in a murine calvarial model of polyethylene (PE) particle-induced osteolysis. The effects of particles and CAPE treatment on gastrointestinal tract (GIT) histopathology were also evaluated. Mice were scanned using in vivo animal micro-computed tomography (µCT) as a baseline measurement. PE particles (2.82 × 10(9) particles/mL) were implanted over the calvariae on day 0. CAPE was administered subcutaneously (1 mg/kg/day) at days 0, 4, 7 and 10. Mice were killed at day 14 and serum was analysed for Type-1 carboxyterminal collagen crosslinks (CTX)-1 and osteoclast-associated receptor (OSCAR) levels. Ex vivo µCT scans were conducted to assess bone volume (BV) change and percentage area of calvarial surface resorbed. Calvarial and GIT tissue was processed for histopathology. By day 14, PE particles significantly induced calvarial bone loss compared with control animals as evidenced by resorption areas adjacent to the implanted PE in three-dimensional µCT images, an increase in percentage of resorbed area (p = 0.0022), reduction in BV (p = 0.0012) and increased Tartrate-resistant acid phosphatase positive cells. Serum CTX-1 (p = 0.0495) and OSCAR levels (p = 0.0006) significantly increased in the PE implant group. CAPE significantly inhibited PE particle-induced calvarial osteolysis, as evidenced by a significant reduction in surface bone resorption (p = 0.0012) and volumetric change (p = 0.0154) compared with PE only, but had no effect on systemic CTX-1. Neither particles nor CAPE had an effect on GIT histopathology.
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Resorción Ósea/prevención & control , Ácidos Cafeicos/farmacología , Osteólisis/prevención & control , Alcohol Feniletílico/análogos & derivados , Cráneo/diagnóstico por imagen , Animales , Modelos Animales de Enfermedad , Femenino , Ratones , Alcohol Feniletílico/farmacología , Polietileno/toxicidad , Cráneo/efectos de los fármacos , Microtomografía por Rayos XRESUMEN
OBJECTIVES: The aim of this paper is to analyse the use of anti-TNF drugs in current Italian practice, evaluate clinical responses to treatment, and identify possible predictors of negative response in patients with rheumatoid arthritis (RA). METHODS: DOSE is a non-interventional, prospective study of patients with active RA treated for the first time with anti-TNF agents in 21 Italian hospitals. Demographic and clinical characteristics of patients, treatments and outcome measures were assessed. Outcome measures used were EULAR response, DAS28 remission and HAQ remission at 12 months. A stepwise logistic regression model was used to study the predictors of non-response. RESULTS: Of 299 RA patients (mean 53.8 ± 12.8 years, 76.1% female), DAS28 was >5.1 in 60.5% of patients and HAQ was >1 in 65.9%. Etanercept was the most prescribed anti-TNF. DMARDs were used in 77.6% of patients (methotrexate in 59.2%). Significant improvements in clinical and laboratory parameters were observed at 12 months. The proportion of patients classed as non-responders remained high, and varied according to assessment criteria. The main predictors independently and significantly associated with a high risk of non-response were: age and female gender for all outcome criteria; high DAS28 value for disease remission; and HAQ >1 for disability remission. CONCLUSIONS: In Italian anti-TNF treatment for RA, age, gender, and high values of both disease activity and disability were predictors of non-response to first-line therapy with anti-TNF drugs. Future studies should consider optimal second-line therapies for RA patients who do not achieve remission to their first anti-TNF treatment.
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Adalimumab , Antirreumáticos , Artritis Reumatoide , Etanercept , Infliximab , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Adalimumab/administración & dosificación , Adalimumab/efectos adversos , Adulto , Factores de Edad , Anciano , Antirreumáticos/administración & dosificación , Antirreumáticos/efectos adversos , Artritis Reumatoide/diagnóstico , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/epidemiología , Evaluación de la Discapacidad , Monitoreo de Drogas , Resistencia a Medicamentos , Quimioterapia Combinada , Etanercept/administración & dosificación , Etanercept/efectos adversos , Femenino , Humanos , Infliximab/administración & dosificación , Infliximab/efectos adversos , Italia/epidemiología , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Índice de Severidad de la Enfermedad , Factores Sexuales , Resultado del TratamientoRESUMEN
BACKGROUND: Pruritus is a clinically important symptom of psoriasis that has a major impact on quality of life (QoL). OBJECTIVE: The objective of this study was to examine pruritus and QoL in patients with moderate-to-severe psoriasis treated with etanercept (ETN) in the PRISTINE clinical trial. METHODS: Patients were randomized (1 : 1, double-blind) to ETN 50 mg QW or 50 mg BIW for 12 weeks, followed by 50 mg QW for 12 weeks. Pruritus was reported as 0 (no itching) to 5 (severe itching). Associations were examined between pruritus and Psoriasis Area and Severity Index, Dermatology Life Quality Index (DLQI), Hospital Anxiety and Depression Screening (HADS), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue), Euro-Qol 5D (EQ-5D) and Medical Outcomes Study (MOS) Sleep Index II. RESULTS: At baseline, patients (n = 270) had a mean pruritus level of 3.6. Itching (level ≥1) was reported by 96% of patients, 62% of whom had severe itching (level ≥4) and 26% had the highest level of itching. DLQI, HADS-Anxiety, HADS-Depression, FACIT-Fatigue, EQ-5D visual analog scale, and MOS Sleep Index II were significantly associated with itch. At week 12, mean pruritus improvement in the ETN BIW/QW group was greater than in the QW/QW group (2.4 vs. 1.6, P < 0.001), but not at week 24 (2.2 vs. 2.0, P = 0.180). Patients with the most severe itching at baseline (score of 5) had a mean score of 1.7 at week 24. Overall, patients with clinically meaningful pruritus improvement at week 24 reported greater improvement in QoL measures than other patients. CONCLUSION: Most patients with moderate-to-severe psoriasis in this study (96%) reported pruritus. Pruritus improved significantly with ETN therapy and was strongly associated with improvements in QoL. These data support the clinical relevance of pruritus as an important symptom of patients with moderate/severe psoriasis.
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Etanercept/uso terapéutico , Inmunosupresores/uso terapéutico , Prurito/psicología , Psoriasis/tratamiento farmacológico , Psoriasis/psicología , Calidad de Vida , Adulto , Ansiedad/etiología , Depresión/etiología , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Prurito/complicaciones , Prurito/tratamiento farmacológico , Psoriasis/complicaciones , Índice de Severidad de la EnfermedadRESUMEN
OBJECTIVES: This study was conducted to compare the surface scratch resistance of titanium implant abutments and cementum to evaluate the impact of scaling with metal curettes on both surfaces. MATERIALS AND METHODS: A standard in vitro force of 14 N was used to assess the scratch width and depth created by curettes on extracted human tooth roots and titanium implant abutments. Scratch width and depth were analysed using a stereomicroscope and non-contact surface profilometry. RESULTS: The mean force applied during test scaling procedures by experienced volunteer operators was 14 N. Mechanical scaling using this force in vitro of cementum produced a mean scratch width of 59.4 ± 1.9 µm, N = 20, and scratch depth of 0.86 ± 0.03 µm, N = 20, compared to the titanium abutments' mean scratch width of 30.8 ± 1.9 µm, N = 6, and scratch depth of 0.34 ± 0.02 µm, N = 6. These differences were statistically significant (P < 0.05). CONCLUSIONS: Although there a number of factors in the clinical situation which are not easily reproducible in vitro, this proof-of-principle in vitro study is the first to confirm quantitatively that titanium abutments had a significantly greater scratch resistance than cementum when metal curettes were used on these surfaces. This information should be considered, especially if there is a preferred choice of metal instruments for effective dental prophylactic procedures for the maintenance of titanium dental implants. CLINICAL RELEVANCE: Clinical dogma suggests that titanium implant abutment surfaces should not be instrumented with metal instruments due to scratching of the surface. However, since cementum is softer than titanium, the logic of this tenet seems flawed. This study demonstrated for the first time that titanium abutments undergo less scratch damage during scaling with metal curettes than does cementum. Metal curettes may be used on titanium abutments with as much confidence as for root planing on natural teeth.
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Pilares Dentales , Cemento Dental , Implantes Dentales , Titanio/química , Propiedades de SuperficieRESUMEN
Ocular trauma is the leading cause of acquired monocular blindness, accounting for 1.97-6% of such cases. Particularly, penetrating ocular injuries are among the most common eye injuries with this kind of outcome. Early diagnosis and prompt management are crucial to avoid complications, and the especially dreaded enucleation. In this article, the authors describe the clinical management, and evaluate the visual and anatomical results obtained in a case of ocular injury with retained intraocular foreign body (IOFB) in a 20-year old female patient. The course of treatment involved a combination of penetrating keratoplasty with a temporary keratoprosthesis, phacoemulsification with intraocular lens implantation and pars plana vitrectomy. At three years from the initial injury, the patient was able to count fingers at 30 centimetres and anatomical restitutio ad integrum of the globe had been achieved.
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BACKGROUND AND OBJECTIVE: The complex microenvironment of the periodontal wound creates many challenges associated with multitissue regeneration of periodontal lesions. Recent characterization of mesenchymal stem cell-like populations residing in periodontal ligament tissues has shown that these cells exhibit features of postnatal stem cells. Despite these advances, a lack of consistency in design of preclinical studies and a limited study of allogeneic transplantation applications has restricted our understanding of their clinical utility in the treatment of periodontal disease. The aim of this study was to assess the regenerative potential of allogeneic periodontal ligament stem cells (PDLSCs) in a rat periodontal fenestration defect mode and to identify an optimal end time-point suitable for quantitative assessment of tissue regeneration. MATERIAL AND METHODS: Periodontal fenestration defects, created in Sprague Dawley rats, were treated with allogeneic PDLSCs seeded onto Gelfoam(®) (Absorbable gelatin sponge; Pharmacia Corporation, Kalamazoo, MI, USA) or with Gelfoam(®) alone, or remained untreated. Experimental rats were killed at 7, 14, 21 or 28 d after surgery and the tissues were processed for immunohistochemical and histomorphometric examination. RESULTS: Defects treated with PDLSCs showed significantly greater percentage bone fill and length of new bone bridge compared with the untreated group or the group treated with Gelfoam(®) alone on days 14 and 21. Similarly, a statistically significant difference was achieved within specimens retrieved on day 21 for analysis of regeneration of cementum/periodontal ligament (PDL)-like structures. CONCLUSION: The present investigation shows that allogeneic PDLSCs have a marked ability to repair periodontal defects by forming bone, PDL and cementum-like tissue in vivo. The results suggest that treatment periods of 14 and 21 d are optimal end time-points for quantitative assessment of periodontal regeneration within the rodent fenestration-defect model utilized in the present study.
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Aloinjertos/trasplante , Pérdida de Hueso Alveolar/terapia , Ligamento Periodontal/citología , Regeneración/fisiología , Trasplante de Células Madre/métodos , Proceso Alveolar/patología , Animales , Regeneración Ósea/fisiología , Diferenciación Celular/fisiología , Separación Celular/métodos , Cementogénesis/fisiología , Colágeno/ultraestructura , Tejido Conectivo/patología , Modelos Animales de Enfermedad , Femenino , Citometría de Flujo , Esponja de Gelatina Absorbible/química , Regeneración Tisular Guiada Periodontal/métodos , Osteogénesis/fisiología , Ligamento Periodontal/patología , Ratas , Ratas Sprague-Dawley , Ingeniería de Tejidos/métodos , Andamios del Tejido/químicaRESUMEN
We have previously demonstrated that tyrosine phosphorylation of STAT1/3 and p38 mitogen-activated protein kinase (p38 MAPK) activation are involved in the apoptotic response triggered by a chimeric cyclic peptide of the interferon-α2b (IFN-α2b) in WISH cells. Since the peptide also induced serine phosphorylation of STAT proteins, in the present study we examined the kinase involved in serine STAT1 phosphorylation and the signaling effectors acting upstream such activation. We first found that p38 MAPK is involved in serine STAT1 phosphorylation, since a reduction of phophoserine-STAT1 levels was evident after incubating WISH cells with cyclic peptide in the presence of a p38 pharmacological inhibitor or a dominant-negative p38 mutant. Next, we demonstrated that the peptide induced activation of protein kinase Cδ (PKCδ). Based on this finding, the role of this kinase was then evaluated. After incubating WISH cells with a PKCδ inhibitor or after decreasing PKCδ expression levels by RNA interference, both peptide-induced serine STAT1 and p38 phosphorylation levels were significantly decreased, indicating that PKCδ functions as an upstream regulator of p38. We also showed that PKCδ and p38 activation stimulated by the peptide was inhibited by a specific pharmacological inhibitor of phosphatidylinositol 3-kinase (PI3K) or by a dominant-negative p85 PI3K-regulatory subunit, suggesting that PI3K is upstream in the signaling cascade. In addition, the role of PI3K and PKCδ in cyclic peptide-induced apoptosis was examined. Both signaling effectors were found to regulate the antiproliferative activity and the apoptotic response triggered by the cyclic peptide in WISH cells. In conclusion, we herein demonstrated that STAT1 serine phosphorylation is mediated by the sequential activation of PI3K, PKCδ and p38 MAPK. This signaling cascade contributes to the antitumor effect induced by the chimeric IFN-α2b cyclic peptide in WISH cells.
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Apoptosis , Interferón-alfa/farmacología , Proteína Quinasa C-delta/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Antineoplásicos/farmacología , Línea Celular Tumoral/efectos de los fármacos , Proliferación Celular , Activación Enzimática , Humanos , Imidazoles/farmacología , Interferón alfa-2 , Péptidos Cíclicos/farmacología , Fosfatidilinositol 3-Quinasas/metabolismo , Inhibidores de las Quinasa Fosfoinosítidos-3 , Fosforilación , Proteína Quinasa C-delta/genética , Piridinas/farmacología , Interferencia de ARN , ARN Interferente Pequeño/genética , ARN Interferente Pequeño/metabolismo , Proteínas Recombinantes/farmacología , Factor de Transcripción STAT1/genética , Factor de Transcripción STAT1/metabolismo , Serina/metabolismo , Transducción de Señal , Proteínas Quinasas p38 Activadas por Mitógenos/antagonistas & inhibidores , Proteínas Quinasas p38 Activadas por Mitógenos/genéticaRESUMEN
This study was performed to evaluate α-tocopherol and ß-carotene contents of pasture milk under ordinary Sicilian farming conditions. Fourteen dairy farms were allocated into 2 balanced groups on the basis of cultivated (CULT) or spontaneous (SPO) pasture type feeding. Bulk milk per farm was collected 4 times from February through April at 3-wk intervals. Pasture botanical and diet composition, diet nutritional quality, milk yield and composition were estimated each time. Pasture intake levels were calculated based on feed analyses, hay and concentrate amounts fed, and milk yield and chemical composition. According to pasture intake, the farms were split into low pasture intake (LPI; <29.5% of dry matter) and high pasture intake (HPI; >29.5% of dry matter) groups. Milk samples per farm were analyzed for α-tocopherol and ß-carotene contents by HPLC. The SPO group had higher levels of α-tocopherol and ß-carotene in milk (0.7 and 0.3 mg/L, respectively) and milk fat (19.0 and 7.5 mg/kg fat, respectively) compared with the CULT group in milk (0.5 and 0.2 mg/L, respectively) and milk fat (14.6 and 4.9 mg/kg, respectively). High pasture intake compared with LPI increased α-tocopherol in milk fat (18.0 and 16.0 mg/kg of fat, respectively). However, only in the SPO (not in CULT), HPI compared with LPI increased milk α-tocopherol (0.8 vs. 0.6 mg/L, respectively), milk ß-carotene (0.3 vs. 0.2 mg/L, respectively), and milk fat ß-carotene (8.4 vs. 6.6 mg/kg, respectively). Results may be related to the different botanical composition of the respective pasture types and pasture intake. Spontaneous pasture compared with CULT contained a higher mass proportion of Asteraceae, Fabaceae, Cruciferae, Euphorbiaceae, and Malvaceae plants. Milk and milk fat α-tocopherol levels were higher on test-days (TD)-1, TD-2, and TD-4 compared with TD-3. For HPI farms, milk fat ß-carotene content was higher on the first 2 TD compared with the last 2 TD. These differences could be related to plant biological stage. On Sicilian dairy farms, the highest milk α-tocopherol and ß-carotene contents may be obtained feeding high levels of SPO pasture in the spring.
Asunto(s)
Bovinos/fisiología , Leche/química , alfa-Tocoferol/análisis , beta Caroteno/análisis , Alimentación Animal , Crianza de Animales Domésticos , Fenómenos Fisiológicos Nutricionales de los Animales , Animales , Dieta/veterinaria , Femenino , Sicilia , beta Caroteno/metabolismoRESUMEN
BACKGROUND: Nail psoriasis is common in patients with psoriasis and can seriously affect their quality of life. Current treatments are limited and there is no standard course of therapy. OBJECTIVES: To assess the efficacy and safety of etanercept (ETN) on nail psoriasis in patients with moderate-to-severe psoriasis. METHODS: Patients with moderate-to-severe plaque psoriasis, who had previously failed at least one form of systemic therapy for nail psoriasis, were randomized to receive open-label ETN 50 mg twice weekly (BIW) for 12 weeks followed by once weekly (QW) for 12 weeks (BIW/QW group) or ETN 50 mg QW for 24 weeks (QW/QW group). The primary endpoint was the mean improvement in the Nail Psoriasis Severity Index (NAPSI; score range 0-8) over 24 weeks in the target fingernail with the most severe abnormalities. RESULTS: Seventy-two patients received one or more doses of ETN (38 BIW/QW; 34 QW/QW) and 69 patients were included in the modified intent-to-treat population. At baseline, mean (standard error) target fingernail NAPSI score was 6.0 (0.3) in the BIW/QW group and 5.8 (0.3) in the QW/QW group. At week 24, mean target fingernail NAPSI score had decreased significantly by -4.3 [95% confidence interval (CI) -4.9 to -3.7; P < 0.0001] in the BIW/QW group and by -4.4 (95% CI -5.0 to -3.7; P < 0.0001) in the QW/QW group. Improvement in NAPSI showed significant correlation with Psoriasis Area and Severity Index improvement. ETN was well tolerated with no unexpected safety findings. CONCLUSIONS: Both ETN regimens were effective at treating nail psoriasis in this patient population.
Asunto(s)
Inmunoglobulina G/administración & dosificación , Inmunosupresores/administración & dosificación , Enfermedades de la Uña/tratamiento farmacológico , Psoriasis/tratamiento farmacológico , Receptores del Factor de Necrosis Tumoral/administración & dosificación , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Adulto , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Etanercept , Femenino , Humanos , Inmunoglobulina G/efectos adversos , Inmunosupresores/efectos adversos , Masculino , Persona de Mediana Edad , Uñas , Índice de Severidad de la Enfermedad , Factores de Tiempo , Resultado del TratamientoRESUMEN
The aim of this study was to determine whether hydroxyapatite ß-tricalcium phosphate (HA-TCP) either alone or coated with Emdogain (EMD) or recombinant human platelet-derived growth factor-BB (rhPDGF-BB) becomes osteoinductive in the murine thigh muscle model for osteoinduction. Twenty CD1 adult male mice had gelatin capsules implanted into the thigh muscle of both hind limbs. The capsules were either empty or contained one of the following: uncoated particulate HA-TCP, EMD-coated HA-TCP or rhPDGF-BB-coated HA-TCP. The implant sites were assessed histologically at 4 and 8 weeks. A semi-quantitative histological examination was performed to assess the inflammatory changes, reparative processes and osteoinduction within the graft site. At both 4 and 8 weeks, histological analysis failed to demonstrate any osteoinductive activity in any of the specimens from the experimental groups. A minimal chronic inflammatory response and foreign body reaction around the implanted materials was seen which reduced over time. The HA-TCP particles were embedded within fibrous connective tissue and were encapsulated by a dense cellular layer consisting of active fibroblasts and occasional macrophages with the thickness of this layer decreasing over time. The results of this study suggest that the use of commercially available HA-TCP alone or in combination with EMD or rhPDGF-BB is biocompatible but not osteoinductive in the murine thigh muscle model of osteoinduction. Coating HA-TCP with EMD or rhPDGF-BB does not enhance its osteoinductive potential.
Asunto(s)
Materiales Biocompatibles/farmacología , Materiales Biocompatibles Revestidos/farmacología , Proteínas del Esmalte Dental/farmacología , Hidroxiapatitas/farmacología , Osteogénesis/efectos de los fármacos , Proteínas Proto-Oncogénicas c-sis/farmacología , Animales , Becaplermina , Tejido Conectivo/patología , Fibroblastos/patología , Fibrosis , Reacción a Cuerpo Extraño/patología , Células Gigantes/patología , Humanos , Inflamación/patología , Macrófagos/patología , Masculino , Ratones , Ratones Endogámicos , Músculo Cuádriceps/patología , Proteínas Recombinantes , Factores de TiempoRESUMEN
BACKGROUND AND OBJECTIVE: Bone loss caused by enhanced osteoclast activity is a significant feature of periodontitis. Histone deacetylase inhibitors (HDACi) can suppress osteoclast-mediated bone loss in vitro and in vivo. This study investigated whether HDACi can suppress bone loss in experimental periodontitis. MATERIAL AND METHODS: Experimental periodontitis was induced in mice by oral inoculation with Porphyromonas gingivalis bacteria. Mice were treated orally with olive oil alone, with olive oil and a novel compound - 1179.4b - which targets both Class I and Class II histone deacetylases (HDACs) or with olive oil and MS-275, which targets Class I HDACs. Micro-computed tomography scans of live mice, stereo imaging and histological analyses were used to detect changes in bone. RESULTS: In the absence of treatment there was a 13.2% increase in bone volume in controls compared with a 7.4% decrease in P. gingivalis-inoculated mice. 1179.4b significantly reduced bone loss, with a 3.4% increase in bone volume (p < 0.01). MS-275 did not have a significant effect on P. gingivalis-induced bone loss. Histological analysis revealed that 1179.4b reduced bone loss despite having no effect on inflammation. CONCLUSION: HDACi were found to effectively suppress bone loss in the mouse model of periodontitis. 1179.4b - the inhibitor of Class I and Class II HDACs - was more effective at suppressing bone loss than MS-275, which targets Class I HDACs only. These compounds may therefore have the potential to be used for the management of periodontitis.
Asunto(s)
Pérdida de Hueso Alveolar/enzimología , Pérdida de Hueso Alveolar/prevención & control , Inhibidores de Histona Desacetilasas/uso terapéutico , Pérdida de Hueso Alveolar/diagnóstico por imagen , Aminoquinolinas/uso terapéutico , Animales , Benzamidas/uso terapéutico , Densidad Ósea , Femenino , Ácidos Hidroxámicos/uso terapéutico , Imagenología Tridimensional , Ratones , Ratones Endogámicos BALB C , Aceite de Oliva , Osteoclastos/patología , Periodontitis/enzimología , Aceites de Plantas/uso terapéutico , Porphyromonas gingivalis , Piridinas/uso terapéutico , Microtomografía por Rayos XRESUMEN
OBJECTIVES: To assess the relationship between smooth and roughened implant surfaces of straight and narrow configurations with respect to microdamage of the bone surface during placement of dental implants. MATERIALS AND METHODS: Straight and tapered, rough and smooth surface Nobel Biocare implants were placed into sheep mandibles. Microdamage within the bone adjacent to the implant surface was quantitated using a semi-automated digitized histomorphometric method. RESULTS: Independent of implant type, microdamage, microcracks, cross-hatch damage and diffuse damage were significantly higher close to the implants compared with far from the implants. Microcracks and cross-hatch damage were higher for the rough cylindrical implants than all the other implant types. CONCLUSIONS: Insertion of a rough cylindrical implant type results in an increased fraction of microdamaged bone matrix in comparison to rough tapered, smooth cylindrical and smooth tapered implants.
Asunto(s)
Implantes Dentales , Materiales Dentales/química , Diseño de Prótesis Dental , Mandíbula/cirugía , Titanio/química , Animales , Fenómenos Biomecánicos , Matriz Ósea/patología , Matriz Ósea/cirugía , Colorantes , Procesamiento de Imagen Asistido por Computador/métodos , Masculino , Mandíbula/patología , Microscopía Fluorescente , Osteotomía/instrumentación , Colorantes de Rosanilina , Ovinos , Estrés Mecánico , Propiedades de Superficie , TorqueRESUMEN
AIM: The aim of this study was to determine whether or not cardiac resynchronization therapy (CRT) has a favourable effect on the incidence of new-onset atrial fibrillation (AF) in a homogeneous population of patients with non-ischaemic idiopathic-dilated cardiomyopathy and severe heart failure. METHODS: We designed a single-centre prospective study and enrolled 58 patients AF naïve when received CRT. After 1 year of follow-up our population was subdivided into responders (72.4%) and non-responders (27.6%), so as to compare the incidence of AF after 1, 2 and 3 years of follow-up in these two groups. RESULTS: Already after 1 year, there was a significant (p < 0.05) difference in new-onset AF in non-responder patients with respect to responders (18.2% vs. 3.3%). These data were confirmed at 2 years (33.3% vs. 12.2%) and 3 years (50.0% vs. 15.0%) follow-up. In particular, 3 years after device implantation non-responders had an increased risk to develop new-onset AF (OR = 5.67). CONCLUSIONS: This is the first study analysing long-term effects of CRT in a homogeneous population of patients with non-ischaemic dilated cardiomyopathy, indicating the favourable role of this non-pharmacological therapy on the prevention of AF.