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Background: Hearing loss, occurring in 1-3/1,000 newborns in the well-babies population, is one of the most common congenital diseases, and hearing screening at birth still represents the only means for its early detection. Since 2011 the Emilia Romagna Regional Health Agency has recommended Newborn Hearing Screening for all babies at its birth points and for newborns moving to the region. The aims of this study are to analyze the results of this regional-based Newborn Hearing Screening program and to discuss the impact of the legislative endorsement on the organization. Material and methods: This is an observational retrospective chart study. The recordings of well-babies and babies at Neonatal Intensive Care Units were collected during the period from January 1st 2015 to December 31st 2020. The following data were included: Newborn Hearing Screening coverage, percentage of refer at otoacoustic emissions, prevalence and entity of hearing loss, unilateral/bilateral rate, presence of audiological risk factors. Results: More than 99% of a total of 198,396 newborns underwent the Newborn Hearing Screening test during the period January 1st 2015 to December 31st 2020, with a coverage ranging between 99.6% and 99.9%. Overall, the percentage of confirmed hearing loss cases was about 17-30 % of refer cases, 745 children received a diagnosis of hearing loss (prevalence 3.7/1,000). Considering profound hearing loss cases, these represent 13% of bilateral hearing loss. Conclusion: A regional-based Newborn Hearing Screening program is valuable and cost-effective. In our experience, the centralization of the data system and of the data control is crucial in order to implement its efficiency and effectiveness. Healthcare policies, tracking systems and public awareness are decisive for a successful programme implementation.
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Potenciales Evocados Auditivos del Tronco Encefálico , Pérdida Auditiva , Lactante , Niño , Recién Nacido , Humanos , Estudios Retrospectivos , Pérdida Auditiva/diagnóstico , Pérdida Auditiva/epidemiología , Pruebas Auditivas/métodos , Emisiones Otoacústicas Espontáneas , Tamizaje Neonatal/métodosRESUMEN
OBJECTIVE: Summarize and compare the available evidence on the reactivation times in patients with age-related macular degeneration treated with Ranibizumab (RNB). METHOD: Systematic review of studies that reported the reactivation time of patients (direct method) or the number of injections received in a certain period of follow-up (indirect method). RESULTS: Only 18 of 89 selected studies reported the average reactivation time of patients in a manifest form, without the need of any calculation. The average calculated, weighted reactivation time was 101.8 days with the direct method and 99.8 days in the indirect method (84 studies included). With both methods, it was found that the average reactivation time of the RCTs was between 2 and 3 weeks less than the average time identified in the observational studies. These differences are also reflected in the clinical results, there being a correlation between the number of doses received and the change in BCVA. The analysis of 11 comparative studies showed a difference in reactivation times between patients treated with RNB or Bevacizumab (BVZ). CONCLUSION: There are few direct studies of reactivation time, but calculation from the PRN dose number turns out to be a good approximation for retrospective study of the variable. The use of the PRN, with criteria not based on optical coherence tomography scans, delays the application of doses between 2 or 3 weeks, and patients suffer loss of clinical benefits. RNB enables patients to receive less injections than BVZ throughout treatment.
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Ranibizumab/administración & dosificación , Tomografía de Coherencia Óptica/métodos , Agudeza Visual , Degeneración Macular Húmeda , Inhibidores de la Angiogénesis/administración & dosificación , Humanos , Inyecciones Intravítreas , Mácula Lútea/patología , Factores de Tiempo , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Degeneración Macular Húmeda/diagnóstico , Degeneración Macular Húmeda/tratamiento farmacológico , Degeneración Macular Húmeda/fisiopatologíaRESUMEN
Ivermectin (IVM) is probably one of the most widely used antiparasitic drugs worldwide, and its efficacy is well established. However, slight differences in formulation may change the plasma kinetics, the biodistribution, and in consequence, the efficacy of this compound. The present study focuses on the development of a novel nanocarrier for the delivery of lipophilic drugs such as IVM and its potential application in antiparasitic control. Lipid nanocapsules (LNC) were prepared by a new phase inversion procedure and characterized in terms of size, surface potential, encapsulation efficiency, and physical stability. A complement activation assay (CH50) and uptake experiments by THP-1 macrophage cells were used to assess the stealth properties of this nanocarrier in vitro. Finally, a pharmacokinetics and biodistribution study was carried out as a proof of concept after subcutaneous (SC) injection in a rat model. The final IVM-LNC suspension displayed a narrow size distribution and an encapsulation rate higher than 90 % constant over the evaluated time (60 days). Through flow cytometry and blood permanence measurements, it was possible to confirm the ability of these particles to avoid the macrophage uptake. Moreover, the systemic disposition of IVM in the LNC administered by the SC route was higher (p < 0.05) (1367 ng h/ml) compared to treatment with a commercial formulation (CF) (1193 ng.h/ml), but no significant differences in the biodistribution pattern were found. In conclusion, this new carrier seems to be a promising therapeutic approach in antiparasitic control and to delay the appearance of resistance.
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Antiparasitarios/uso terapéutico , Ivermectina/administración & dosificación , Lípidos/química , Nanocápsulas/química , Animales , Vías de Administración de Medicamentos , Portadores de Fármacos , Inyecciones Subcutáneas , Ivermectina/sangre , Ivermectina/farmacocinética , Macrófagos/metabolismo , Ratas , Distribución TisularRESUMEN
BACKGROUND: IgG4 related disease rarely affects the salivary glands and clinically is often confused with salivary gland malignancy. METHOD: This is a retrospective study comprising 137 cases of chronic sialadenitis diagnosed in a histopathology department over 4 years. The morphology was assessed by reviewing the histology slides and the incidence of IgG4 related sclerosing sialadenitis was calculated. IgG and IgG4 immunohistochemistry was performed and mean IgG4 count/hpf and IgG4/IgG ratio were determined. Clinical findings were obtained from medical records. RESULTS: Of the 137 cases reviewed, 3 cases showed diagnostic histological features of IgG4 related sialadenitis, these being: a prominent lymphoplasmacytic infiltrate, lobular fibrosis, acinar atrophy, obliterative phlebitis and mean IgG4 count of 86/hpf with mean IgG4/IgG ratio 65%. No further disease was documented at follow-up which ranged from 24 to 36 months. CONCLUSION: The incidence of IgG4 related sialadenitis in the present study is 2%, indicating that it is a rare condition. Since there is no non-invasive diagnostic modality, either core biopsy or surgical excision is required for definitive histological diagnosis.
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Enfermedades del Sistema Inmune/inmunología , Inmunoglobulina G , Sialadenitis/inmunología , Anciano , Humanos , Enfermedades del Sistema Inmune/epidemiología , Enfermedades del Sistema Inmune/patología , Inmunohistoquímica , Incidencia , Masculino , Estudios Retrospectivos , Sialadenitis/epidemiología , Sialadenitis/patologíaRESUMEN
The objective of our study was to review retrospectively the clinical, radiological and therapeutic findings in 62 adults with acute mastoiditis treated at the ENT Department of Ferrara from 1992 to 2010. 62 adult cases fulfilled the following inclusion criteria: otoscopical evidence of co-existent or recent otitis media; postauricular swelling, erythema or tenderness; protrusion of the auricle; fever and/or significant radiological findings of mastoiditis. Conservative treatment comprehended antibiotic ± ventilation tube. Surgical procedures comprehended mastoidectomy or mastoido-tympanoplasty. The incidence of adult's mastoiditis in our district (0.99 cases/year/100.000 inhabitants) has maintained quite stable during the considered 19-year period. The typical clinical presentation was observed in 48% of cases. Complications were meningitis (15 cases), meningo-encephalitis (1), meningitis associated with lateral sinus thrombosis (1), facial nerve paralysis (11), and labyrinthitis (8). In all cases except one, the facial palsy recovered completely and no mortality was observed due to these complications. Complete cure was obtained with conservative treatment in 69% of uncomplicated cases and in 24% of patients with intracranial complications. Mastoiditis in adults may present as the acute classical form, as well as latent forms which often have prolonged and insidious development followed by a rapid clinical deterioration. Clinical features are frequently atypical, while incidence of meningitis and other complications is still high particularly in the most elderly. Thus, great care is required from clinicians to make an early diagnosis in order to promote adequate treatment.
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Mastoiditis/diagnóstico , Centros Médicos Académicos , Enfermedad Aguda , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antibacterianos/uso terapéutico , Parálisis Facial/etiología , Femenino , Estudios de Seguimiento , Humanos , Italia , Laberintitis/etiología , Trombosis del Seno Lateral/etiología , Masculino , Apófisis Mastoides/cirugía , Mastoiditis/complicaciones , Mastoiditis/terapia , Meningitis/etiología , Persona de Mediana Edad , Ventilación del Oído Medio , Otoscopía , Tomografía Computarizada por Rayos X , Resultado del Tratamiento , Timpanoplastia , Adulto JovenRESUMEN
An important frontier in the administration of therapeutic drugs to veterinary species is the use of different polymers as drug delivery platforms. The usefulness of polymers as platforms for the administration of pharmaceutical and agricultural agents has been clearly recognized in the recent decades. The chemical versatility of polymers and the wide range of developed controlled-release strategies enhance the possibilities for the formulation of active molecules. In particular, the veterinary area offers opportunities for the development of novel controlled-release drug delivery technologies adapted to livestock or companion animal health needs. In some cases, it also allows to improve profitability in meat production or to meet the safety criteria related to drug residues. A number of factors affect the selection of polymers and subsequent properties of the controlled-release drug delivery system. However, their selection also dictates the release kinetics of the drug from the delivery system. Such choices are therefore crucial as they affect the success and potential of the delivery system for achieving the therapeutic goals of the veterinarian. It is the intention of this review to give an overview of the most relevant polymers, which are used or have been tested as drug delivery release rate modifiers in the veterinary field. The article highlights some recent developments focusing on their advantages and applications and analyzes the future direction of the scientific and technological advancements in this area.
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Polímeros/química , Drogas Veterinarias/administración & dosificación , Medicina Veterinaria/métodos , Animales , Formas de DosificaciónRESUMEN
Following the extraction of oil for biodiesel production, oilseed press cakes are high in fat. As the dietary supplementation of fat is currently considered the most promising strategy of consistently depressing methanogenesis, it follows that oilseed press cakes may have a similar potential for CH4 abatement. As such, this study aimed to characterise the nutritive value of several oilseed press cakes, glycerine and soybean meal (SBM) and to examine their effects on in vitro ruminal fermentation, digestion kinetics and CH4 production. Moringa press oil seeds exhibited the greatest in sacco effective degradability (ED) of DM and CP (p<0.05). In vitro gas production (ml/g digested DM) was not affected (p = 0.70) by supplement at 48 h of incubation. In vitro DMD was increased with the supplementation of glycerine and SBM at all levels of inclusion. Moringa oilseed press cakes produced the lowest CH4 (mg/g digested DM) at 6 and 12 h of incubation (p<0.05). The findings suggest that moringa oilseed press cake at 400 g/kg DM has the greatest potential of the oilseed press cakes examined in this study, to reduce CH4 production, without adversely affecting nutrient degradability.
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New therapeutic strategies based on the search of alternative formulations of albendazole (ABZ) and albendazole sulphoxide (ABZSO) are under current development to optimize posology and antiparasite efficacy in dogs. In an incomplete block design, nine dogs were randomly divided into three groups (n = 6). Treatments were carried out in two phases as follows. Phase I: Group I (treatment A), animals received ABZ at 25 mg/kg of conventional formulation. Group II (treatment B), dogs received 25 mg/kg of a modified poloxamer-ABZ formulation. Group III (treatment C), animals were treated with ABZSO in equimolar amount to ABZ doses. After 21 days of wash-out period the experiment was repeated (Phase II). Blood samples were collected over 24 h and subsequently analysed by high performance liquid chromatography. ABZSO and ABZSO(2) were the analytes recovered in plasma. Significant higher (P < 0.001) ABZSO area under the concentration-time curve (+500%) and C(max) (+487%) values were obtained for the treatment C in comparison with treatments A and B. However, no statistical differences on pharmacokinetic parameters were found between formulations A and B. In conclusion, the enhanced plasma concentration profile obtained for the ABZSO formulation used in treatment C may contribute to optimize the anthelmintic control in dogs.
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Albendazol/análogos & derivados , Antihelmínticos/farmacocinética , Perros/metabolismo , Albendazol/administración & dosificación , Albendazol/sangre , Albendazol/farmacocinética , Animales , Antihelmínticos/administración & dosificación , Antihelmínticos/sangre , Área Bajo la Curva , Cromatografía Líquida de Alta Presión , Femenino , MasculinoRESUMEN
Scleromyxedema--the generalized form of lichen myxedematosus, a primary mucinosis--is a rare disease in human patients. It is characterized by dermal mucin deposits, increased numbers of fibroblasts, and variable fibrosis in the absence of thyroid disease. It is accompanied in 80% of cases by a monoclonal gammopathy. To date, scleromyxedema with systemic involvement has not been documented in domestic animals. This is the first report of a scleromyxedema-like syndrome in a cat, which had a substantial deposition of mucin in the dermis of the head and paws with a mild gammaglobulinemia of 2.25 g/dl (reference range, 1.39-2.22 g/dl). At necropsy, multiple nodules of connective tissue intermingled with mucin deposits were conspicuous on the surface of thoracic and abdominal organs. Such severe systemic accumulations of mucin have not been reported in human or veterinary medicine.
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Enfermedades de los Gatos/patología , Escleromixedema/veterinaria , Enfermedades de la Piel/veterinaria , Animales , Gatos , Resultado Fatal , Femenino , Inmunohistoquímica/veterinaria , Escleromixedema/patología , Enfermedades de la Piel/patologíaRESUMEN
Tumour-to-tumour metastasis is a rare phenomenon. It occurs when a primary tumour is a recipient of a separate tumour within the same individual. We present a case of a 66-year-old woman with known breast cancer who presented with one-sided nasal symptoms. Examination and imaging revealed a unilateral polyp arising from the skull base. She underwent endoscopic polypectomy with the histology demonstrating tumour-to-tumour metastasis from a breast carcinoma to an olfactory neuroblastoma, a rare sinonasal tumour. Clinicians should be cautious of distant metastases in any patient presenting with head and neck symptoms and a known primary tumour. This is the first documented case of this type.
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Neoplasias de la Mama/patología , Carcinoma Lobular/secundario , Estesioneuroblastoma Olfatorio/diagnóstico , Neoplasias Complejas y Mixtas/diagnóstico , Neoplasias Primarias Secundarias/diagnóstico , Neoplasias Nasales/diagnóstico , Anciano , Neoplasias de la Mama/terapia , Carcinoma Lobular/diagnóstico , Carcinoma Lobular/cirugía , Quimioterapia Adyuvante/métodos , Estesioneuroblastoma Olfatorio/patología , Estesioneuroblastoma Olfatorio/cirugía , Femenino , Humanos , Imagen por Resonancia Magnética , Mastectomía , Hueso Nasal/diagnóstico por imagen , Hueso Nasal/patología , Hueso Nasal/cirugía , Cavidad Nasal/diagnóstico por imagen , Terapia Neoadyuvante/métodos , Neoplasias Complejas y Mixtas/patología , Neoplasias Complejas y Mixtas/cirugía , Neoplasias Primarias Secundarias/patología , Neoplasias Primarias Secundarias/cirugía , Neoplasias Nasales/patología , Neoplasias Nasales/cirugía , Tomografía Computarizada por Rayos XRESUMEN
OBJECTIVES: To estimate the direct medical costs associated with the management of patients with primary open-angle glaucoma and to compare the costs of patients according to the degree of severity. METHODS: A longitudinal retrospective study was carried out using all patients with primary open-angle glaucoma that recorded follow-up from May 2010 to June 2013 at the Hospital Privado de Córdoba. We estimated the cost of the disease from the perspectives of the institution, with a bottom-up approach. RESULTS: The three-year follow-up after treatment of 104 patients revealed that the average cost of care for a patient with primary open-angle glaucoma was US$2746 ± 1560. The first year of treatment was significantly more expensive than subsequent ones (US$1100-$810-$827). Cost was related to the degree of severity of glaucoma; patients in "Stage 0" had significantly lower costs than those in other groups (Kruskal-Wallis test, p < 0.01). This was a consequence of lower costs associated with medication and a lower percentage of patients undergoing surgery. DISCUSSION: The direct medical costs of a patient with primary open-angle glaucoma vary according to the severity of their disease and the year of treatment. We found that costs increased with disease severity, but decreased over time.
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Glaucoma de Ángulo Abierto/economía , Costos de la Atención en Salud/estadística & datos numéricos , Índice de Severidad de la Enfermedad , Anciano , Anciano de 80 o más Años , Progresión de la Enfermedad , Femenino , Glaucoma de Ángulo Abierto/terapia , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
Triamcinolone acetonide (TA) is an effective drug widely (off-label) used in the treatment of several ocular diseases involving inflammation and angiogenic processes. However, the use of TA ocular presents some limitations mainly related to its excipient composition, as in the case of benzyl alcohol. Thus, the aim of this work was to obtain an alternative TA formulation based on lipid nanocapsules (LNCs). Triamcinolone acetonide-loaded lipid nanocapsules (TA-LNCs) were obtained by the phase inversion temperature process without the use of irritating excipients, by combining lipids and surfactants generally recognized as safe. Pre-formulation studies were carried out to evaluate the TA solubility in different co-surfactants and to optimize the lipid core composition in order to enhance the drug loading and encapsulation rate in the LNCs. A stable final TA-LNC formulation was obtained with a mean particle size (MPS) of below 50â¯nm, a narrow size distribution (PDIâ¯<â¯0.2), a negative zeta potential (ZP) and a high encapsulation efficiency (%EEâ¯>â¯98%). In vitro cellular viability assays revealed that blank LNCs and TA-LNCs at 0.1⯵g/mL did not affect the viability of the human corneal epithelial (HCE) cells. TA-LNCs showed a high anti-inflammatory activity below the toxicity level, with a reduction of 30% in interleukin (IL)-6 secretion observed in an in vitro model using the same cell line. More importantly, the TA-LNCs revealed a therapeutic efficacy in the endotoxin-induced uveitis (EIU) rabbit model with a significant attenuation of clinical signs of an inflammatory response. These findings make the TA-LNCs a safer and more efficient alternative for the treatment of eye disorders.
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Antiinflamatorios/administración & dosificación , Lípidos/química , Triamcinolona Acetonida/administración & dosificación , Uveítis/tratamiento farmacológico , Administración Oftálmica , Animales , Antiinflamatorios/farmacología , Línea Celular , Modelos Animales de Enfermedad , Estabilidad de Medicamentos , Epitelio Corneal/citología , Epitelio Corneal/efectos de los fármacos , Humanos , Masculino , Nanocápsulas , Tamaño de la Partícula , Conejos , Solubilidad , Tensoactivos/química , Temperatura , Triamcinolona Acetonida/farmacologíaRESUMEN
OBJECTIVES: To describe the clinicopathological and genetic characteristics of mast cell tumours in dogs less than 12 months old. MATERIALS AND METHODS: Retrospective review of dogs aged less than 12 months when diagnosed with mast cell tumours at three referral hospitals in the UK. RESULTS: Sixteen pure-bred dogs were included, of which 11 were female. The median age at first presentation and diagnosis were 7.6 and 9 months, respectively. In 13 dogs the mast cell tumours were cutaneous and in three they were subcutaneous. Four cutaneous mast cell tumours were described as high-grade (Patnaik or Kiupel) and nine were Patnaik grade II; three had mitotic index of >5 in 10 high-power fields. Of the three subcutaneous tumours, two had an infiltrative growth pattern and one had mitotic index of 10 per 10 high-power fields. Of 10 tested dogs, seven had c-kit mutations in exon 11 and Ki-67 score was above the cut-off value in nine. Four of 12 cases showed evidence of metastasis in the regional lymph nodes. After varying treatment protocols, all patients were alive and disease free at a median of 1115 days after diagnosis. CLINICAL SIGNIFICANCE: The prognosis of mast cell tumours in dogs less than a year old appears better than the adult counterparts, even without extensive treatment.
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Enfermedades de los Perros , Neoplasias Cutáneas/veterinaria , Animales , Perros , Femenino , Mastocitos , Índice Mitótico/veterinaria , Pronóstico , Estudios RetrospectivosRESUMEN
The current standard of care for locally advanced rectal cancer (RC) is neoadjuvant radio-chemotherapy (NRC) with 5-fluorouracil (5Fu) as the main drug, followed by surgery and adjuvant chemotherapy. While a group of patients will achieve a pathological complete response, a significant percentage will not respond to the treatment. The Unfolding Protein Response (UPR) pathway is generally activated in tumors and results in resistance to radio-chemotherapy. We previously showed that RHBDD2 gene is overexpressed in the advanced stages of colorectal cancer (CRC) and that it could modulate the UPR pathway. Moreover, RHBDD2 expression is induced by 5Fu. In this study, we demonstrate that the overexpression of RHBDD2 in CACO2 cell line confers resistance to 5Fu, favors cell migration, adhesion and proliferation and has a profound impact on the expression of both, the UPR genes BiP, PERK and CHOP, and on the cell adhesion genes FAK and PXN. We also determined that RHBDD2 binds to BiP protein, the master UPR regulator. Finally, we confirmed that a high expression of RHBDD2 in RC tumors after NRC treatment is associated with the development of local or distant metastases. The collected evidence positions RHBDD2 as a promising prognostic biomarker to predict the response to neoadjuvant therapy in patients with RC.
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Resistencia a Antineoplásicos/genética , Regulación Neoplásica de la Expresión Génica , Proteínas de la Membrana/genética , Neoplasias del Recto/terapia , Respuesta de Proteína Desplegada/efectos de los fármacos , Antimetabolitos Antineoplásicos/farmacología , Células CACO-2 , Adhesión Celular/efectos de los fármacos , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Chaperón BiP del Retículo Endoplásmico , Fluorouracilo/farmacología , Quinasa 1 de Adhesión Focal/genética , Quinasa 1 de Adhesión Focal/metabolismo , Adhesiones Focales/efectos de los fármacos , Células HCT116 , Proteínas de Choque Térmico/genética , Proteínas de Choque Térmico/metabolismo , Humanos , Metástasis Linfática , Proteínas de la Membrana/metabolismo , Terapia Neoadyuvante/métodos , Paxillin/genética , Paxillin/metabolismo , Unión Proteica , Neoplasias del Recto/genética , Neoplasias del Recto/metabolismo , Neoplasias del Recto/patología , Transducción de Señal , Factor de Transcripción CHOP/genética , Factor de Transcripción CHOP/metabolismo , eIF-2 Quinasa/genética , eIF-2 Quinasa/metabolismoRESUMEN
The fast and non-invasive detection of odors and volatile organic compounds (VOCs) by gas sensors and electronic noses is a growing field of interest, mostly due to a large scope of potential applications. Additional drivers for the expansion of the field include the development of alternative and sustainable sensing materials. The discovery that isolated cross-linked polymeric structures of suberin spontaneously self-assemble as a film inspired us to develop new sensing composite materials consisting of suberin and a liquid crystal (LC). Due to their stimuli-responsive and optically active nature, liquid crystals are interesting probes in gas sensing. Herein, we report the isolation and the chemical characterization of two suberin types (from cork and from potato peels) resorting to analyses of gas chromatography-mass spectrometry (GC-MS), solution nuclear magnetic resonance (NMR), and X-ray photoelectron spectroscopy (XPS). The collected data highlighted their compositional and structural differences. Cork suberin showed a higher proportion of longer aliphatic constituents and is more esterified than potato suberin. Accordingly, when casted it formed films with larger surface irregularities and a higher C/O ratio. When either type of suberin was combined with the liquid crystal 5CB, the ensuing hybrid materials showed distinctive morphological and sensing properties towards a set of 12 VOCs (comprising heptane, hexane, chloroform, toluene, dichlormethane, diethylether, ethyl acetate, acetonitrile, acetone, ethanol, methanol, and acetic acid). The optical responses generated by the materials are reversible and reproducible, showing stability for 3 weeks. The individual VOC-sensing responses of the two hybrid materials are discussed taking as basis the chemistry of each suberin type. A support vector machines (SVM) algorithm based on the features of the optical responses was implemented to assess the VOC identification ability of the materials, revealing that the two distinct suberin-based sensors complement each other, since they selectively identify distinct VOCs or VOC groups. It is expected that such new environmentally-friendly gas sensing materials derived from natural diversity can be combined in arrays to enlarge selectivity and sensing capacity.
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Oxidative stress seems to play a major role in the pathogenesis of neurodegeneration. In Parkinson's disease (PD) patients, the dopaminergic neurons are subjected to oxidative stress resulting from reduced levels of antioxidant defenses such as glutathione and high amount of intracellular iron. Levodopa (LD) is widely used for the symptomatic treatment of PD, but its role in oxidative damage control is still unclear. The aim of this study was to analyze the presence of DNA damage in peripheral blood lymphocytes (PBL) of PD patients, during a washout and a controlled LD dosage and to evaluate the oxidative damage fluctuation after LD intake. The standard and the Fpg-modified version of Comet assay were applied in analyzing DNA damage in PBL from blood samples of nine PD patients and nine matched controls. Due to the limited number of patients we cannot reach definite conclusions even if our data confirm the accumulation of DNA lesions in PD patients; these lesions decrease after LD intake.
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Antiparkinsonianos/farmacología , Células Sanguíneas/efectos de los fármacos , Daño del ADN/efectos de los fármacos , Levodopa/farmacología , Enfermedad de Parkinson/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Antiparkinsonianos/uso terapéutico , Células Sanguíneas/metabolismo , Ensayo Cometa , Femenino , Humanos , Técnicas In Vitro , Levodopa/uso terapéutico , Masculino , Persona de Mediana Edad , Estrés OxidativoRESUMEN
Humoral immunological defects are frequent and important causes of hypogammaglobulinemia, leading to recurrent infections, autoimmunity, allergies, and neoplasias. Usually, its onset occurs in childhood or during the second and third decades of life; however, the diagnosis is made, on average, 6 to 7 years afterwards. As a consequence, antibody defects can lead to sequelae. Here we describe the clinical-laboratory characteristics, treatment, and prognoses of patients with hypogammaglobulinemia. An observational, cross-sectional, and retrospective study of patients attending the recently established outpatient group of Clinical Immunology between 2013 and 2018 was carried out. Patients with IgG levels below 2 standard deviations from the mean values for the age and/or impaired antibody response were included. Eight patients (3 F and 5 M; median age=41 years (16-65), average symptom onset at 25 years (1-59), and time to diagnosis of 10 years were included. The main infections were: sinusitis in 7/8, pneumonia in 6/8, otitis in 2/8, tonsillitis and diarrhea in 2/8, and diarrhea in 2/8 patients. Hypothyroidism was identified in 4/8 (50%) patients. Rhinitis was found in 7/8 (87.5%) and asthma in 3/8 (37.5%) patients. The tomographic findings were consolidations, atelectasis, emphysema, ground glass opacity, budding tree, bronchial thickening, and bronchiectasis. Immunoglobulin reposition was used between 466 and 600 mg/kg monthly (514.3 mg·kg-1·dose-1). Prophylactic antibiotic therapy was included in 7/8 (87.5%) patients. Airway manifestations prevailed in patients with hypogammaglobulinemia. There is a need for educational work to reduce the time of diagnosis and initiation of treatment, avoiding sequelae.
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Agammaglobulinemia/diagnóstico , Inmunoglobulinas Intravenosas/administración & dosificación , Adolescente , Adulto , Agammaglobulinemia/tratamiento farmacológico , Anciano , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Tiempo , Adulto JovenRESUMEN
AIMS: To describe three cases of purely in situ salivary duct carcinoma, so as better to define the entity. METHODS AND RESULTS: Three primary tumours of the parotid gland are presented, in each case composed of cysts and ducts and lined by high nuclear grade epithelial cells. All parts of each tumour were surrounded by a myoepithelial cell rim and there was no evidence of invasion. The tumour cells expressed immunohistochemical markers seen in invasive salivary duct carcinoma of usual (high-grade) type. In two cases the androgen receptor (AR) reaction was strong, but there was no immunohistochemical expression of HER2 protein or gene amplification by in situ hybridization. In the remaining case, fewer nuclei stained for AR, but both HER2 protein and gene amplification were demonstrated. CONCLUSIONS: Salivary duct carcinoma in situ is morphologically similar to breast ductal carcinoma in situ and, although our cases are few, salivary duct carcinoma in situ can possibly be subdivided into luminal and non-luminal cell types, as can analogous mammary neoplasms. The present study cannot determine whether low-grade cribriform cystadenocarcinoma, architecturally similar but immunohistochemically different, is part of the spectrum of salivary duct carcinoma in situ, or whether it represents a separate entity.
Asunto(s)
Carcinoma in Situ/metabolismo , Carcinoma in Situ/patología , Glándula Parótida/patología , Neoplasias de la Parótida/metabolismo , Neoplasias de la Parótida/patología , Adenocarcinoma/metabolismo , Adenocarcinoma/patología , Biomarcadores de Tumor/metabolismo , Humanos , Inmunohistoquímica , Hibridación in Situ , Receptor ErbB-2/metabolismo , Receptores Androgénicos/metabolismo , Conductos Salivales/patologíaRESUMEN
The purpose of this study was to compare the in vivo efficacy of several timolol (TM)-loaded liposomal formulations with current TM antiglaucoma treatment (aqueous 0.5% w/v eye drops). In this study, conventional liposomes (CL) and deformable liposomes, without (DL1) and with ethanol (DL2) were prepared and characterized. In addition, in vitro release and permeation studies, as well as in vivo lowering intraocular pressure (IOP) and biocompatibility studies were performed. It was found that the quali and quantitative lipid bilayer composition played a significant role in modifying the physical properties of vesicles. The deformability study and electronic microscopy images revealed that membrane elasticity of DL1 and DL2 was much higher than CL. However, in vitro permeation results showed that the flux and permeability coefficient were significantly higher in CL compared to DL. The IOP study revealed that TM-loaded CL showed the best pharmacological activity, in comparison to deformable vesicles. Compared to the eye drops, CL formulation could equally reduce the IOP but using a concentration 10-fold lower, whereas the effective time was significantly longer. In addition, the formulations showed no irritant effects after instillation on the ocular surface.
Asunto(s)
Antagonistas Adrenérgicos beta/administración & dosificación , Liposomas/química , Nanoestructuras/química , Timolol/administración & dosificación , Administración Oftálmica , Antagonistas Adrenérgicos beta/farmacocinética , Animales , Relación Dosis-Respuesta a Droga , Etanol/efectos adversos , Etanol/química , Liposomas/efectos adversos , Masculino , Nanoestructuras/efectos adversos , Soluciones Oftálmicas , Conejos , Tensoactivos/efectos adversos , Tensoactivos/química , Timolol/farmacocinéticaRESUMEN
Hereditary angioedema (HAE) is a rare autosomal dominant disease due to C1 esterase inhibitor deficiency (C1-INH). The disease is characterized by subcutaneous and submucosal edema in the absence of urticaria due to the accumulation of bradykinin. This descriptive study aimed to evaluate the clinical characteristics of patients with a confirmed diagnosis of HAE referred to our Outpatient Clinic between December 2009 and November 2017. Fifty-one patients (38 F, 13 M) with a mean age of 32 years (range: 7-70 y) were included. Family history of HAE was reported in 70% (36/51) of the cases; 33/46 patients became symptomatic by 18 years of age. The median time between onset of symptoms and diagnosis was 13 years (3 mo-50 y). The most frequent triggering factors for attacks were stress (74.4%), trauma (56.4%), and hormonal variations (56%). The main symptoms were subcutaneous edema in 93.5% (43/46) of patients, gastrointestinal symptoms in 84.8% (39/46), and obstruction in the upper airways in 34.8% (16/46). Hospitalization occurred in 65.2%, of whom 13.3% had to be transferred to the Intensive Care Unit. Prophylactic treatment was instituted in 87% (40/46) of patients, and 56.5% (26/46) required additional treatment to control attacks. Owing to our data collection over a period of 8 years, a significant number of patients were identified by this HAE reference center. Despite early recognition and prophylactic treatment, a high percentage of patients were hospitalized. HAE is still diagnosed late, reinforcing the need for more reference centers specialized in diagnosis and educational projects for health professionals.