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OBJECTIVE: To report on the feasibility of establishing a regional prenatal referral network for critical congenital heart defects (CHDs) and its impact on perinatal outcome of fetuses with transposition of the great arteries and intact ventricular septum (TGA-IVS) in low-resource settings. METHODS: This was a retrospective study of consecutive fetuses with a diagnosis of TGA-IVS between January 2011 and December 2019 in Kochi, Kerala, India. A regional network for prenatal diagnosis and referral of patients with critical CHDs was initiated in 2011. Pregnancy and early neonatal outcomes were reported. The impact of the timing of diagnosis (prenatal or after birth) on age at surgery, perinatal mortality and postoperative recovery was evaluated. RESULTS: A total of 82 fetuses with TGA-IVS were included. Diagnosis typically occurred later on in gestation, at a median of 25 (interquartile range (IQR), 21-32) weeks. The majority (78.0%) of affected pregnancies resulted in live birth, most (84.4%) of which occurred in a specialist pediatric cardiac centers. Delivery in a specialist center, compared with delivery in a local maternity center, was associated with a significantly higher rate of surgical correction (98.1% vs 70.0%; P = 0.01) and overall lower neonatal mortality (3.7% vs 50%; P = 0.001). The proportion of cases undergoing arterial switch operation after prenatal diagnosis of TGA-IVS increased significantly, along with the prenatal detection rate, over the study period (2011-2015, 11.1% vs 2016-2019, 29.4%; P = 0.001). Median age at surgery was significantly lower in the prenatally diagnosed group than that in the postnatally diagnosed group (4 days (IQR, 1-23 days) vs 10 days (IQR, 1-91 days); P < 0.001). There was no significant difference in postoperative mortality (2.0% vs 3.6%; P = 0.49) between the two groups. CONCLUSIONS: This study demonstrates the feasibility of creating a network for prenatal diagnosis and referral of patients with critical CHDs, such as TGA, in low-resource settings, that enables planned peripartum care in specialist pediatric cardiac centers and improved neonatal survival. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.
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Cardiología/métodos , Recursos en Salud/provisión & distribución , Atención Perinatal/métodos , Perinatología/métodos , Transposición de los Grandes Vasos/diagnóstico , Adulto , Estudios de Factibilidad , Femenino , Edad Gestacional , Humanos , India , Recién Nacido , Nacimiento Vivo , Mortalidad Perinatal , Embarazo , Evaluación de Programas y Proyectos de Salud , Derivación y Consulta/estadística & datos numéricos , Estudios Retrospectivos , Transposición de los Grandes Vasos/embriología , Transposición de los Grandes Vasos/mortalidad , Tabique Interventricular/embriología , Tabique Interventricular/patologíaRESUMEN
High levels of ambient environmental particulate matter (PM10 i.e. < 10 µm median aerodynamic diameter) have been linked to acute exacerbations of asthma. We examined the effects of delivering a single dose of Sydney PM10 by intranasal instillation to BALB/c mice that had been sensitized to ovalbumin and challenged repeatedly with a low (≈3 mg/m(3)) mass concentration of aerosolized ovalbumin for 4 weeks. Responses were compared to animals administered carbon black as a negative control, or a moderate (≈30 mg/m(3)) concentration of ovalbumin to simulate an allergen-induced acute exacerbation of airway inflammation. Delivery of PM10 to mice, in which experimental mild chronic asthma had previously been established, elicited characteristic features of enhanced allergic inflammation of the airways, including eosinophil and neutrophil recruitment, similar to that in the allergen-induced exacerbation. In parallel, there was increased expression of mRNA for interleukin (IL)-33 in airway tissues and an increased concentration of IL-33 in bronchoalveolar lavage fluid. Administration of a monoclonal neutralizing anti-mouse IL-33 antibody prior to delivery of particulates significantly suppressed the inflammatory response induced by Sydney PM10, as well as the levels of associated proinflammatory cytokines in lavage fluid. We conclude that IL-33 plays a key role in driving airway inflammation in this novel experimental model of an acute exacerbation of chronic allergic asthma induced by exposure to PM10.
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Alérgenos/inmunología , Asma/inmunología , Asma/metabolismo , Interleucinas/metabolismo , Material Particulado/efectos adversos , Animales , Anticuerpos Monoclonales/farmacología , Líquido del Lavado Bronquioalveolar/inmunología , Citocinas/biosíntesis , Modelos Animales de Enfermedad , Femenino , Inflamación/inmunología , Inflamación/metabolismo , Interleucina-33 , Interleucina-4/metabolismo , Interleucinas/antagonistas & inhibidores , Ratones , Ovalbúmina/efectos adversosRESUMEN
Nanoparticles prepared from bio-reduction agents are of keen interest to researchers around the globe due to their ability to mitigate the harmful effects of chemicals. In this regard, the present study aims to synthesize copper oxide nanoparticles (CuO NPs). CuNPs show a characteristic absorption peak at 347 nm, while SEM reveals the spherical but agglomerated shape of CuNPs of the size within the range of 51.26-56.66 nm. The crystallite size measured by using XRD was found to be within a range of 23.38-46.64 nm for ginger-doped CuO and 26-56 nm for garlic-doped CuO. The X-ray diffraction analysis shows the crystalline structure of copper nanoparticles with prominent peaks. Bragg's reflection of copper nanoparticles shows diffraction peaks around 2θ =43.4°, 50.3°, and 74.39°, representing [111], [200], and [220] crystallographic planes of face-centered cubic (fcc). The synthesized CuO NPs tested antibacterial properties against various strains of microorganisms, including Escherichia coli, 25 µg/mL 2.3 ± 0.21 and 100 µg/mL 6.5 ± 0.17, Staphylococcus aureus, 25 µg/mL 2.3 ± 0.29 and 100 µg/mL 11.5 ± 1.17, Streptococcus mutans, 25 µg/mL 01.05 ± 0.21 and 100 µg/mL 15.8 ± 0.17, Enterococcus faecalis). The short novelty of Azadirachta indica lies in its potential relevance to human health, as it has been found to possess bioactive compounds with various medicinal properties, such as antimicrobial, antioxidant, and anti-inflammatory activities, making it a promising natural resource for therapeutic applications.
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Electrochemical affinity biosensors have the potential to facilitate the development of multiplexed point-of-care diagnostics in complex biological fluids. However, their commercial viability has been hindered by challenges such as electrode biofouling and the lack of inherent redox properties. To address this unmet need, we have developed a universal nanocomposite coating which is unique in its ability to not only allow oriented conjugation of the biorecognition element but also specific detection directly in complex biological fluids like serum and urine owing to its built-in antifouling and redox capabilities, thus improving suitability for point of care testing. This multifunctional coating comprises a 3D porous crosslinked bovine serum albumin matrix for oriented conjugation and antifouling properties with embedded graphene nanosheets modified with amino-ferrocene for enhanced conductivity and mediator-free biosensing. The coating showed minimal signal degradation despite prolonged exposure to 1% bovine serum albumin, artificial urine and untreated human serum for up to 30 days. To demonstrate its utility, we fabricated and tested proof-of-concept electrochemical immunosensors for bladder cancer protein biomarkers, specifically interleukin-8 (IL-8) and vascular endothelial growth factor (VEGF). The practical feasibility was highlighted by the excellent sensitivity and specificity observed for IL-8 and VEGF with a limit of detection of 41 pg mL-1 and 67 pg mL-1, respectively. Consequently, this universal nanocomposite-based electrochemical biosensing platform can be extended to the point of care testing of a broad spectrum of biomarkers present in complex biological fluids, thus enabling reliable and early diagnostics.
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Técnicas Biosensibles , Técnicas Electroquímicas , Grafito , Metalocenos , Nanocompuestos , Oxidación-Reducción , Albúmina Sérica Bovina , Técnicas Biosensibles/métodos , Nanocompuestos/química , Humanos , Técnicas Electroquímicas/métodos , Técnicas Electroquímicas/instrumentación , Grafito/química , Albúmina Sérica Bovina/química , Factor A de Crecimiento Endotelial Vascular/sangre , Factor A de Crecimiento Endotelial Vascular/orina , Interleucina-8/sangre , Interleucina-8/orina , Interleucina-8/análisis , Incrustaciones Biológicas/prevención & control , Animales , Neoplasias de la Vejiga Urinaria/orina , Biomarcadores de Tumor/sangre , Biomarcadores de Tumor/orina , Compuestos Ferrosos/química , BovinosRESUMEN
AIM: The purpose of the present in vivo study was to measure the efficacy of different gingival displacement materials in achieving gingival tissue displacement and to compare the efficacy of Expasyl displacement paste (Pierre Rolland, France) and gingival displacement cord for gingival displacement. MATERIALS AND METHODS: Sixteen subjects were included in the study. Premolars were prepared to receive full veneer crown, gingival displacement was carried using gingival retraction cord and gingival displacement paste. Impression of the gingival sulcus was made. Sulcus width after displacement was measured under magnification. RESULTS: The mean displacement value of sulcus width was 0.21 ± 0.01 mm for the gingival retraction cord and 0.26 ± 0.02 mm for the gingival displacement paste. 'F' test was used for statistical analysis. Difference among the two test agents was statistically significant (p < 0.01). CONCLUSION: Gingival displacement paste showed better response in achieving horizontal displacement of the gingival sulcus than gingival retraction cord. CLINICAL SIGNIFICANCE: Gingival displacement helps in recording the unprepared tooth surface adjacent to the finish line in the impression being made, thereby helping a better marginal adaptation and emergence profile in the extracoronal restoration.
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Encía/anatomía & histología , Técnicas de Retracción Gingival/instrumentación , Cloruro de Aluminio , Compuestos de Aluminio/uso terapéutico , Astringentes/uso terapéutico , Diente Premolar/anatomía & histología , Cloruros/uso terapéutico , Coronas , Materiales de Impresión Dental/química , Técnica de Impresión Dental , Coronas con Frente Estético , Compuestos Férricos/uso terapéutico , Hemostáticos/uso terapéutico , Humanos , Caolín/uso terapéutico , Pomadas/química , Polivinilos/química , Siloxanos/química , Preparación Protodóncica del Diente/métodosRESUMEN
In this study, polyethylene glycol (PEG) and polyurethane (PU)-based shape-stabilized copolymer nanocomposites were synthesized and utilized for developing low-cost and flexible temperature sensors. PU was utilized as a flexible structural material for loading a thermosensitive phase change PEG polymer by means of physical mixing and chemical crosslinking. Furthermore, the introduction of multi-walled carbon nanotubes (MWCNT) as a conductive filler in the PEG-PU copolymer resulted in a nanocomposite with thermoresistive properties. MWCNT loading concentrations from 2 wt.% to 10 wt.% were investigated, to attain the optimum conductivity of the nanocomposite. Additionally, the effect of MWCNT loading concentration on the thermosensitive behavior of the nanocomposite was analyzed in the temperature range 25 °C to 50 °C. The thermosensitive properties of the physically mixed and crosslinked polymeric nanocomposites were compared by spin coating the respective nanocomposites on screen printed interdigitated (IDT) electrodes, to fabricate the temperature sensor. The chemically crosslinked MWCNT-PEG-PU polymeric nanocomposite showed an improved thermosensitive behavior in the range 25 °C to 50 °C, compared to the physically mixed nanocomposite. The detailed structural, morphological, thermal, and phase transition properties of the nanocomposites were investigated using XRD, FTIR, and DSC analysis. XRD and FTIR were used to analyze the crystallinity and PEG-PU bonding of the copolymer nanocomposite, respectively; while the dual phase (solid-liquid) transition of PEG was analyzed using DSC. The proposed nanocomposite-based flexible temperature sensor demonstrated excellent sensitivity, reliability and shows promise for a wide range of bio-robotic and healthcare applications.
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Owing to their excellent sensitivity, stretchability, flexibility and conductivity, polymeric nanocomposites with conductive fillers have shown promise for a wide range of applications in bioelectronics and wearable devices. Herein, we report on the development of a flexible and biocompatible polymeric nanocomposite comprising ultra-long Ag-Au core-sheath nanowires (Au@AgNWs) dispersed in elastomeric media to fabricate a high-resolution wearable temperature sensor. Ultra-long AgNWs with an aspect ratio of about 1500 were synthesized using a Ca2+ ion-mediated facile one-pot polyol process. To enhance the biocompatibility and anti-oxidative property of the AgNWs, a 10-20 nm gold (Au) layer was conformably deposited without affecting the original nanowire morphology. The core-sheath structure of Au@AgNWs was characterized using HRTEM and EDS elemental mapping while the biocompatibility and anti-oxidative properties were tested using hydrogen peroxide (H2O2) etching in solution phase. Finally, the fabricated nanowires were used to prepare the Au@AgNW-poly-ethylene glycol (PEG)-polyurethane (PU)-based nanocomposite ink which can be printed on interdigitated electrodes to fabricate a thermoresistive temperature sensor with negative temperature coefficient (NTC) of resistance and quick response time (<100 s). The Au@AgNW-PEG-PU nanocomposite was characterized in detail and a novel temperature sensing mechanism based on controlling the internanowire distance of the PEG coated Au@AgNWs percolation by means of capillarity force among the nanowires as a result of the glass transition temperature of thermosensitive PEG was demonstrated. The proposed printable temperature sensor is flexible and biocompatible and shows promise for a range of wearable applications.
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Nanocompuestos , Nanocables , Peróxido de Hidrógeno , Plata , TemperaturaRESUMEN
Breath monitoring and pulmonary function analysis have been the prime focus of wearable smart sensors owing to the COVID-19 outbreak. Currently used lung function meters in hospitals are prone to spread the virus and can result in the transmission of the disease. Herein, we have reported the first-ever wearable patch-type strain sensor for enabling real-time lung function measurements (such as forced volume capacity (FVC) and forced expiratory volume (FEV) along with breath monitoring), which can avoid the spread of the virus. The noninvasive and highly sensitive strain sensor utilizes the synergistic effect of two-dimensional (2D) silver flakes (AgFs) and one-dimensional (1D) silver nanowires (AgNWs), where AgFs create multiple electron transmission paths and AgNWs generate percolation networks in the nanocomposite. The nanocomposite-based strain sensor possesses a high optimized conductivity of 7721 Sm-1 (and a maximum conductivity of 83,836 Sm-1), excellent stretchability (>1000%), and ultrasensitivity (GFs of 35 and 87 when stretched 0-20 and 20-50%, respectively), thus enabling reliable detection of small strains produced by the body during breathing and other motions. The sensor patching site was optimized to accurately discriminate between normal breathing, quick breathing, and deep breathing and analyze numerous pulmonary functions, including the respiratory rate, peak flow, FVC, and FEV. Finally, the observed measurements for different pulmonary functions were compared with a commercial peak flow meter and a spirometer, and a high correlation was observed, which highlights the practical feasibility of continuous respiratory monitoring and pulmonary function analysis.
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COVID-19 , Nanocompuestos , Nanocables , Humanos , Plata , PulmónRESUMEN
Early-life respiratory viral infections are linked to subsequent development of allergic asthma in children. We assessed the underlying immunological mechanisms in a novel model of the induction phase of childhood asthma. BALB/c mice were infected neonatally with pneumonia virus of mice, then sensitized intranasally with ovalbumin following recovery. Animals were challenged with low levels of aerosolized ovalbumin for 4 weeks to induce changes of chronic asthma, then received a single moderate-level challenge to elicit mild acute allergic inflammation. To inhibit the initial induction of a T helper type 2 (Th2) response, we administered neutralizing antibodies against interleukin (IL)-4 or IL-25, then assessed development of airway inflammation and remodelling. Anti-IL-4 administered during chronic challenge prevented development of chronic and acute allergic inflammation, as well as goblet cell hyperplasia/metaplasia, but features of remodelling such as subepithelial fibrosis and epithelial hypertrophy were unaffected. In contrast, anti-IL-25 had limited effects on the airway inflammatory response but prevented key changes of remodelling, although it had no effect on goblet cells. Both antibodies suppressed development of a Th2 response, while anti-IL-25 also promoted a Th17 response. In further experiments, anti-IL-25 was administered in early life alone, and again had limited effects on airway inflammation, but prevented development of airway wall remodelling. We conclude that in this murine model of childhood asthma, administration of anti-IL-4 or anti-IL-25 prevents development of some key features of asthma, suggesting that suppression of development of a Th2 response during the neonatal period or later in childhood could be effective for primary prevention.
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Asma/inmunología , Células Caliciformes/metabolismo , Virus de la Neumonía Murina/inmunología , Infecciones por Pneumovirus/inmunología , Células Th2/metabolismo , Remodelación de las Vías Aéreas (Respiratorias)/efectos de los fármacos , Alérgenos/inmunología , Animales , Animales Recién Nacidos , Anticuerpos Bloqueadores/administración & dosificación , Asma/fisiopatología , Asma/prevención & control , Células Cultivadas , Niño , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Células Caliciformes/efectos de los fármacos , Células Caliciformes/inmunología , Células Caliciformes/patología , Humanos , Hiperplasia/prevención & control , Interleucina-4/inmunología , Interleucinas/inmunología , Ratones , Ratones Endogámicos BALB C , Virus de la Neumonía Murina/patogenicidad , Ovalbúmina/inmunología , Neumonía/prevención & control , Infecciones por Pneumovirus/fisiopatología , Infecciones por Pneumovirus/prevención & control , Células Th2/efectos de los fármacos , Células Th2/inmunología , Células Th2/patologíaRESUMEN
Creatinine biosensing is a rapidly developing field owing to the clinical relevance of creatinine as a vital biomarker for several diseases associated with renal, thyroidal, and muscular dysfunctions. Over the years, we have observed numerous creatinine biosensing strategies, including the most widely studied enzymatic creatinine biosensors. Though the enzymatic approach provides excellent selectivity and reliability, it has certain drawbacks, which include high fabrication cost and poor storage stability (that is inherent to every enzyme-based biosensors). This has led to the development of non-enzymatic creatinine biosensors, of which electrochemical sensors are the most promising for point-of-care applications. However, only a limited number of studies have been conducted and there is a lack of reviews addressing the recent advances in this research area. Herein, we present for the first time, a review with a prime focus on the various strategies implemented in non-enzymatic electrochemical creatinine biosensing. We aim to offer a comprehensive context on the achievements and limitations of currently available non-enzymatic electrochemical creatinine biosensors and address the underlying factors pertaining to the interplay of modification/fabrication techniques with the sensitivity, selectivity, interferences, and long-term storage stability of the biosensor. We hope that this work shall prove to be seminal in the conception and advancement of future non-enzymatic electrochemical creatinine biosensors.
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Técnicas Biosensibles , Creatinina , Sistemas de Atención de Punto , Reproducibilidad de los ResultadosRESUMEN
Perivascular adipose tissue (PVAT) is protective and reduces contraction of blood vessels in health. PVAT is composed of adipocytes, multiple types of immune cells and stromal cells. Interleukin (IL)-10, an anti-inflammatory cytokine usually produced by T cells, B cells and macrophages, was identified as one of the highly expressed (mRNA) cytokines in the mesenteric PVAT of healthy rats. One report suggested that exogenous IL-10 causes relaxation of mouse mesenteric arteries, also suggesting that IL-10 maybe a potential anti-contractile factor. Hence, we hypothesized that PVAT-derived IL-10 causes vasorelaxation and/or reduces vasoconstriction, thus contributing to the anti-contractile nature of PVAT in health. Mesenteric arteries from rats and mice expressed the receptor for IL-10 (in tunica intima and media) as determined by immunohistochemistry. Mesenteric resistance arteries for rats and superior mesenteric artery for mice were used for isometric contractility studies. Increasing concentrations [0.4-100 ng/mL] of recombinant rat/mouse (rr/mr) IL-10 or vehicle was directly added to half-maximally constricted (phenylephrine, PE) vessels (without PVAT, with endothelium). IL-10 did not cause a direct vasorelaxation. Further, the ability of rrIL-10 to cause a rightward or downward shift of a vasoconstriction-response curve was tested in the rat. The vessels were incubated with rrIL-10 [100 ng/mL or 10 ng/mL] or vehicle for 1.5 h in the tissue bath followed by a cumulative PE [10-8-10-4 M] or U46619 [10-10-10-5 M] response curve. The maximal contractions and EC50 values were similar in IL-10 incubated vessels vs vehicle. Thus, acute exposure of exogenous IL-10 did not reduce local vasoconstriction. To further test if endogenous IL-10 from PVAT was anti-contractile, superior mesenteric arteries from IL-10 WT and KO mice, with and without PVAT, were subjected to increasing concentrations of PE. The anti-contractile nature of PVAT was preserved with both short-term and prolonged depletion (using younger and older mice, respectively) of endogenous IL-10 in males and females. Contrary to our hypothesis, PVAT-derived IL-10 neither caused vasorelaxation nor reduced local vasoconstriction directly/indirectly. Therefore, IL-10 does not contribute to the anti-contractile nature of PVAT in healthy rodents.
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Tejido Adiposo/metabolismo , Interleucina-10/metabolismo , Arterias Mesentéricas/metabolismo , Vasoconstricción , Vasodilatación , Animales , Células Cultivadas , Femenino , Interleucina-10/genética , Interleucina-10/farmacología , Masculino , Arterias Mesentéricas/efectos de los fármacos , Ratones Endogámicos C57BL , Ratones Noqueados , Comunicación Paracrina , Ratas Sprague-Dawley , Receptores de Interleucina-10/metabolismo , Transducción de Señal , Vasoconstricción/efectos de los fármacos , Vasodilatación/efectos de los fármacosRESUMEN
BACKGROUND: Airway hyperresponsiveness (AHR) in asthmatics includes a variable component that persists following an allergen challenge. This may be dissociated from inflammatory cell recruitment, implying a role for resident pulmonary cells in regulating the response. OBJECTIVE: Using improved methods of assessing AHR in a mouse model of allergic airway disease, to investigate the basis of the development of prolonged AHR. METHOD: BALB/c mice were systemically sensitized and then challenged with aerosolized ovalbumin (OVA). Airway and tissue responsiveness were measured at baseline and at 1 day, and 1, 2 and 3 weeks after the last OVA challenge. Inflammatory cell numbers in BALF and levels of mRNA for eotaxin-1 and -2, IFN-gamma, IL-5 and -13 in the lung were measured at each time-point. In further experiments, the roles of IFN-gamma and of CCR3(+) and CD4(+) cells in the development of prolonged AHR were assessed by blockade or depletion with monoclonal antibodies. The role of pulmonary macrophages was assessed by selective chemical depletion of these cells. RESULTS: Airway responsiveness was increased above baseline at 1 day after the last OVA challenge, and this was sustained for 1 week. In contrast, tissue-specific responsiveness was only significantly increased above baseline at 1 day. Development of prolonged AHR was inhibited by neutralization of IFN-gamma or by depletion of pulmonary macrophages, but not by depletion of either CD4(+) T cells or CCR3(+) eosinophils. CONCLUSION: An interaction between IFN-gamma and pulmonary macrophages contributed to the prolongation of airway hyperresponsiveness. In contrast, T cells and eosinophils did not contribute to prolongation of AHR. These findings emphasize the importance of the innate host response in the development of manifestations of asthma, as well as its potential relevance as a target for therapeutic intervention.
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Alérgenos/inmunología , Hiperreactividad Bronquial/inmunología , Interferón gamma/inmunología , Macrófagos Alveolares/inmunología , Animales , Modelos Animales de Enfermedad , Inmunización , Ratones , Ratones Endogámicos BALB C , Ovalbúmina/inmunologíaRESUMEN
STUDY DESIGN: Cross sectional follow-sup survey. OBJECTIVE: To ascertain the factors influencing community reintegration, of individuals with spinal cord injury living in rural environment, and to suggest measures to enhance community participation. SETTING: Bangalore, Karnataka, India. METHODS: Thirty-five individuals who were admitted under Physical Medicine and Rehabilitation Department of St Johns Medical College Hospital and rehabilitated to their functional level based on their level of injury; individuals living in rural environment were included in the study. The study was conducted by means of a standardized questionnaire and environmental and home assessments carried out during follow-up home visits after 12 months of discharge from the hospital. The main outcome measures were Craig Handicap Assessment and Reporting Technique (CHART) and Craig Hospital Inventory of Environmental Factors (CHIEF). The home visits and assessments were carried out by a rehabilitation team, which consisted of community-based rehabilitation worker, medico-social worker, physiotherapist and occupational therapist, and headed by a physiatrist. RESULTS: The findings of the study indicate a general decline in community re integration in terms of physical independence, mobility, occupation and social integration. Mobility issues were the greatest perceived barrier and economic issues also significantly influenced the community participation. CONCLUSION: Our study showed significant decline in community reintegration in subjects living in rural south India. Architectural and environmental barriers, poor socio-economic status and comorbidities significantly affected the level of community participation.
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Servicios de Salud Comunitaria/métodos , Vida Independiente/lesiones , Apoyo Social , Traumatismos de la Médula Espinal/psicología , Traumatismos de la Médula Espinal/rehabilitación , Adulto , Servicios de Salud Comunitaria/normas , Estudios Transversales , Evaluación de la Discapacidad , Femenino , Estado de Salud , Humanos , Vida Independiente/normas , India/epidemiología , Masculino , Persona de Mediana Edad , Población Rural/tendencias , Traumatismos de la Médula Espinal/epidemiología , Encuestas y CuestionariosRESUMEN
BACKGROUND: In a mouse model of mild chronic asthma, both inflammation and remodelling can be suppressed by dexamethasone (a glucocorticoid) and roflumilast (a selective phosphodiesterase-4 inhibitor). OBJECTIVE: To better understand the underlying molecular mechanisms, we investigated the effects of treatment on airway expression of inflammation-related cytokines, as well as on epithelial expression of growth factors. METHODS: BALB/c mice systemically sensitized to ovalbumin were challenged with aerosolized antigen for 6 weeks and treated with roflumilast or dexamethasone during the final 2 weeks. Expression of mRNA, for a variety of cytokines and growth factors, was assessed in selectively dissected proximal airways or in airway epithelium obtained by laser capture microdissection. RESULTS: In the airway wall of vehicle-treated challenged animals, there was significantly elevated expression of mRNA for a variety of pro-inflammatory and T helper type 2 cytokines, as well as for IFN-gamma. All these cytokines were suppressed by dexamethasone. Treatment with roflumilast reduced expression of IL-17A, TNF-alpha, granulocyte-macrophage colony-stimulating factor and IL-6, but did not inhibit other cytokines. Both drugs suppressed the enhanced expression of mRNA for growth factors such as TGF-beta1 and FGF-2 in airway epithelium. CONCLUSIONS: Whereas dexamethasone non-specifically inhibits numerous mediators involved in inflammation and the immune response, roflumilast selectively inhibits a subset of pro-inflammatory cytokines and growth factors. These mediators and/or the cells that produce them may have critical roles in the pathogenesis of the lesions of chronic asthma.
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Aminopiridinas/uso terapéutico , Antiasmáticos/uso terapéutico , Asma/tratamiento farmacológico , Benzamidas/uso terapéutico , Citocinas/antagonistas & inhibidores , Dexametasona/uso terapéutico , Modelos Animales de Enfermedad , Inhibidores de Fosfodiesterasa/uso terapéutico , Aminopiridinas/farmacología , Animales , Antiasmáticos/farmacología , Asma/inmunología , Benzamidas/farmacología , Bronquios/efectos de los fármacos , Bronquios/patología , Enfermedad Crónica , Ciclopropanos/farmacología , Ciclopropanos/uso terapéutico , Citocinas/metabolismo , Dexametasona/farmacología , Femenino , Humanos , Inflamación/tratamiento farmacológico , Inflamación/inmunología , Ratones , Ratones Endogámicos BALB C , Inhibidores de Fosfodiesterasa 4 , Organismos Libres de Patógenos EspecíficosRESUMEN
Measurement of grip force is important for both exercise training and assessment of the hand during physical rehabilitation. The standard method uses a grip dynamometer which measures the force between the fingers and opposing thumb. The primary limitation of the grip dynamometer is the restriction of measurement to cylindrical grasps. Any deformation of the hand due to muscular or skeletal disease makes the grip dynamometer difficult or impossible to use. An alternative to the grip dynamometer is a sealed pneumatic object that can be gripped by the hand. Measurement of the internal pressure in the object can be related to the grip force. In this paper, we analyze such a pneumatic pressure sensing object for hand grip assessment and also describe an easy fabrication of the grip sensor. The instrumented object presented in this paper is designed to assess both the maximal voluntary grip forces and continuous grip force to monitor control of hand function during exercise under instruction from a therapist. Potential uses of such a pneumatic pressure sensing object for hand grip are in physical rehabilitation of patients following paralysing illnesses like stroke and spinal cord injury.
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Prueba de Esfuerzo/instrumentación , Terapia por Ejercicio/instrumentación , Fuerza de la Mano , Calibración , Diseño de Equipo , Humanos , Modelos Teóricos , PresiónRESUMEN
The measurement of hand kinematics is important for the assessment and rehabilitation of the paralysed hand. The traditional method of hand function assessment uses a mechanical or electronic goniometer placed across the joint of interest to measure the range of joint movement. Mechanical goniometers are imprecise and lack the ability to provide a dynamic measurement; electronic goniometers are expensive and cumbersome to use during therapy. An alternative to the goniometric based assessment is to use inertial motion sensors to monitor the hand movement-these can be incorporated in a glove. In this paper, we present the design of an instrumented glove equipped with Magnetic, Angular Rate and Gravity (MARG) sensors for the objective evaluation of hand function. The instrumented glove presented in this paper is designed to assess the range of movement of the hand and also monitor the hand function during the course of hand rehabilitation. Static and dynamic calibrations were performed for the Euler angles calculated from the MARG sensors. The results are also presented for physiological flexion/extension of the wrist (relative roll), flexion/extension of elbow (relative pitch), and internal rotation/external rotation (relative yaw). The static calibration results gave mean absolute errors of 4.1° for roll, 4.0° for pitch, and 4.6° for yaw. From the dynamic calibration, the speed of response to a step change gave a convergence time of 0.4 s; sinusoidally oscillating movement gave good tracking at 0.2 Hz but exhibits overshoot errors at higher frequencies which were tested to be 1 Hz. We present the results of the calibration of the instrumented glove (one sensor pair measuring one joint angle) measuring anatomical joint angles-mean absolute errors during static calibration: 6.3° for a relative roll (wrist flexion/extension), 5.0° for relative pitch (elbow flexion/extension), and 4.5° for relative yaw (shoulder internal rotation/external rotation). The experimental results from the instrumented glove are promising, and it can be used as an alternative to the traditional goniometer based hand function assessments.
Asunto(s)
Mano/fisiología , Monitoreo Fisiológico/instrumentación , Dispositivos Electrónicos Vestibles , Acelerometría/instrumentación , Fenómenos Biomecánicos , Calibración , Humanos , Fenómenos Magnéticos , Movimiento , Rango del Movimiento Articular , Temblor/fisiopatologíaRESUMEN
The properties of a factor responsible for immunosuppressive activity in the plasma of inbred SJL/J mice bearing transplanted lymphomas were investigated. Suppressive activity was not due to an intact virus but resided in a soluble molecule characterized as a nonimmunoglobulin protein of molecular weight 68,000-88,000. The plasma suppressor factor was relatively stable and was neither directly cytotoxic nor complement-dependent. The degree of suppression of in vitro lymphocyte proliferative responses depended on the time of addition of plasma to cultures. Suppression was reversible if cells exposed to plasma were washed before mitogen stimulation, but stimulated cells exposed to the suppressor factor were irreversibly inhibited. The suppressor factor was partially species-specific. Supernatants from short-term cultures of tumor cells from lymph nodes of SJL/L mice contained a similar suppressor factor, indicating that the plasma factor was probably a product of tumor cells.
Asunto(s)
Inmunosupresores/sangre , Linfoma/inmunología , Animales , Células Cultivadas , Femenino , Humanos , Tolerancia Inmunológica , Inmunosupresores/farmacología , Activación de Linfocitos/efectos de los fármacos , Linfoma/sangre , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos , Peso Molecular , Neoplasias Experimentales/inmunología , Fitohemaglutininas/farmacología , Ratas , Ratas Endogámicas , Especificidad de la EspecieRESUMEN
The proliferative responses of peripheral blood lymphocytes of inbred SJL/J mice to the mitogens phytohemagglutinin and concanavalin A were evaluated serially in individual animals before and after induction of lymphomas by transplantation. Tumor-bearing mice exhibited marked suppression of mitogen responsiveness. Proliferative responses in mixed lymphocyte-tumor cell culture and mixed lymphocyte culture were also suppressed. Suppression of responses was tumor related, and responsiveness was restored in animals whose tumors regressed. There was no deficiency of responder T-cells in the peripheral blood of tumor-bearing animals, and suppressor cell activity was not demonstrable in a number of in vitro assays. However, plasma from tumor-bearing animals exhibited potent immunosuppressive activity. The presence of plasma suppressive activity was similarly tumor related. Thus this study demonstrates nonspecific suppression of cell-mediated immune responses following tumor induction, apparently mediated by a plasma suppressor factor.
Asunto(s)
Tolerancia Inmunológica , Inmunidad Celular , Linfoma/inmunología , Animales , Concanavalina A/farmacología , Femenino , Activación de Linfocitos , Prueba de Cultivo Mixto de Linfocitos , Linfoma/sangre , Ratones , Ratones Endogámicos , Trasplante de Neoplasias , Neoplasias Experimentales/inmunología , Fitohemaglutininas/farmacología , Linfocitos T Reguladores/inmunologíaRESUMEN
Desferal, a siderophore of microbial origin is the only drug currently used for clinical treatment of a genetic disorder, thalassemia. By using a combination of HPLC and 31P-NMR, it is demonstrated that the Cu complex of desferal cleaves DNA, the primary site of hydroxyl radical attack being the sugar C1' in the minor groove, which leads to production of 5-methylene furanone. While no C5'-oxidation was observed, a minor process involving C4'-attack accompanies the above cleavage path. The oxidative cleavage of DNA observed with CuDFO may have implications in the emerging applications of desferal as a drug delivery agent and an antimalarial.