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1.
Artículo en Inglés | MEDLINE | ID: mdl-37360909

RESUMEN

The current work presents a systematic study of two alloy compositions (RR3010 and CMSX-4) and two types of coatings: inward grown (pack) and outward grown (vapour) deposited aluminides, exposed to 98Na2SO4-2NaCl mixture. Grit blasting was used on some of the samples, prior to coating, to mimic in-service procedures and remove oxides from the surface prior to coating. Two-point bend tests were then performed on the coated samples, with and without applied salt at 550 °C for 100 hours. Samples were pre-strained at 0.6 pct strain to deliberately pre-crack the coating and then strained at 0.3 pct for the heat treatment. Exposure to 98Na2SO4-2NaCl under applied stress of vapour-aluminide coated samples of both alloys, revealed significant coating damage in the form of secondary cracks in the intermetallic-rich inter-diffusion zone, although only CMSX-4 exhibited cracks propagating further into the bulk alloy while RR3010 proved more resistant. The pack-aluminide coating proved more protective for both alloys, with cracks propagating only into the coating and never into the underlying alloy. In addition, grit blasting proved beneficial in reducing spallation and cracking for both types of coating. The findings were used to propose a mechanism based on thermodynamic reactions, to explain the crack width changes through the formation of volatile AlCl3 in the cracks.

2.
Sci Total Environ ; 806(Pt 1): 150127, 2022 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-34583076

RESUMEN

The four-year continuous measurements of CO, NOx, NH3, SO2, and O3 were carried at a high altitude site (32.12°N, 76.56°E at 1347 m AMSL) of the Indian Western Himalayan area to study the mixing ratios of these gases for understanding the changing trends of these trace gases over the region. Each of these trace gases showed significant daily and monthly variabilities. The highest variability was recorded in the monthly mean values of O3 as it varied from 10 to 63 ppb during the study period. All the trace gases except CO showed maximum variability in the pre-monsoon seasons due to the strong advection and vertical circulation of air masses at the site. The seasonal mean maxima of CO were recorded during the monsoon season, while the mean maxima of NH3 were recorded during the post-monsoon seasons. The meteorological parameters have been found to influence the mixing ratios of trace gases. The least variability in the mean seasonal mixing ratios of SO2 during the study period indicated the constant point source of SO2 near the site. The trajectories analysis revealed that the area receives maximum air masses from the southeast to the west directions where a number of the coal-based thermal power plants, industries, cement plants, and agricultural fields are also located. The influence of valley-to-mountain circulations was also observed at the site, resulting in the transport of pollutant-rich air masses from local and distant sources to the site. A comparison of the mixing ratios of different trace gases obtained in the present study is also made with the values reported for other high altitude stations in the world.


Asunto(s)
Contaminantes Atmosféricos , Contaminación del Aire , Ozono , Contaminantes Atmosféricos/análisis , Monitoreo del Ambiente , Gases , Meteorología , Ozono/análisis , Estaciones del Año
4.
J Endocrinol Invest ; 43(4): 515-528, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-31691259

RESUMEN

PURPOSE: The present study was aimed to demonstrate the recuperative effect of nesfatin-1 on testicular dysfunction in the high-fat diet (HFD)/streptozotocin (STZ)-induced type-2 diabetes mellitus (T2DM) mice. METHOD AND RESULTS: Three experimental groups were formed: (1) vehicle control (VC), (2) T2DM mice, (3) T2DM + nesf-1. The mice with blood glucose level higher than 300 mg/dL following HFD and a single dose of STZ were used for the experiment. The T2DM mice showed increases in body mass, blood glucose and insulin levels, reductions in spermatogenesis and steroidogenesis, production of antioxidative enzymes, and disturbed lipid profile. These alterations were all ameliorated by administration of nesfatin-1 at 20 µg/Kg BW for 15 days. Nesfatin-1 treatment also increased the production of testosterone (T), improved insulin sensitivity, and effectively ameliorated the testicular aberrations, and increased spermatogenesis and steroidogenesis. In addition, nesfatin-1 treatment upregulated the PCNA and Bcl2 expression and inhibited the caspase-3 and prohibitin expression in T2DM mice. Nesfatin-1 increased insulin receptor (IR) and GLUT8 expressions, and lactate production, the changes that further substantiate the increase of energy influx to the testis. CONCLUSION: Altogether, the results suggest the ameliorative effect of nesfatin-1 against T2DM-associated testicular dysfunctions and improved insulin sensitivity along with promoting T production and fertility in T2DM mice.


Asunto(s)
Diabetes Mellitus Experimental/fisiopatología , Diabetes Mellitus Tipo 2/fisiopatología , Nucleobindinas/farmacología , Reproducción/efectos de los fármacos , Espermatogénesis/efectos de los fármacos , Testículo/efectos de los fármacos , Animales , Glucemia , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Insulina/sangre , Resistencia a la Insulina , Masculino , Ratones , Proteínas Proto-Oncogénicas c-bcl-2/genética , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Receptor de Insulina/genética , Receptor de Insulina/metabolismo , Regulación hacia Arriba/efectos de los fármacos
5.
Rev Sci Instrum ; 90(7): 073701, 2019 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-31370442

RESUMEN

In Conduction Atomic Force Microscopy (CAFM), it is sometimes required to monitor electrical data at a single location over an extended period of time. However, thermal drift of the microscope will cause the tip to move with respect to the sample and thus limit the collection of data. We investigate a method to prolong the time a tip dwells at a location by choosing the AFM cantilever to have small spring constants in the lateral directions. The basis of the approach is that the tip can only move (or slip) once the lateral forces caused by drift overcome the friction force pinning the tip to the surface. We demonstrate the effect experimentally using platinum wire tips and diamond coated tips on SiO2 and HfO2 dielectric films. Simultaneous measurement of the current flow and lateral force signals show that the onset of tip slipping correlates with the beginning of a decrease in the measured current flow, and the onset of slip is prolonged for blunt tips or cantilevers having soft lateral spring constants. The approach not only provides a way to improve the CAFM method for time dependent measurements but also assists in interpreting CAFM data in the presence of drift.

6.
Sci Rep ; 8(1): 2854, 2018 02 12.
Artículo en Inglés | MEDLINE | ID: mdl-29434292

RESUMEN

This study investigates the resistive switching characteristics and underlying mechanism in 2D layered hexagonal boron nitride (h-BN) dielectric films using conductive atomic force microscopy. A combination of bipolar and threshold resistive switching is observed consistently on multi-layer h-BN/Cu stacks in the low power regime with current compliance (I comp ) of less than 100 nA. Standard random telegraph noise signatures were observed in the low resistance state (LRS), similar to the trends in oxygen vacancy-based RRAM devices. While h-BN appears to be a good candidate in terms of switching performance and endurance, it performs poorly in terms of retention lifetime due to the self-recovery of LRS state (similar to recovery of soft breakdown in oxide-based dielectrics) that is consistently observed at all locations without requiring any change in the voltage polarity for I comp ~1-100 nA.

7.
Diabetes Metab Res Rev ; 34(3)2018 03.
Artículo en Inglés | MEDLINE | ID: mdl-29135074

RESUMEN

Because ethanol is thought to be a risk factor for severe hypoglycemia, patients with type 1 diabetes (T1D) are recommended to limit ethanol intake. However, little is known on how ethanol affects plasma glucose and how ethanol-induced hypoglycemia can be prevented. In this study, we systematically reviewed the literature for ethanol effects on plasma glucose and for prevention strategies on ethanol-induced hypoglycemia. Electronic searches on PubMed and Google were conducted in February 2017. Randomized clinical trials and observational studies were included. Studies involved patients with T1D with no history of ethanol abuse. The primary aims were changes in plasma glucose after ethanol intake and prevention strategies for ethanol-induced hypoglycemia. Quality of the studies was assessed by GRADE. Additionally, we searched for guidelines from diabetes associations on their suggested prevention strategies. We included 13 studies. Eight studies reported that ethanol, regardless of administration intravenously or orally, were associated with an increased risk of hypoglycemia due to decrease in plasma glucose, impaired counter-regulatory response, awareness of hypoglycemia, and cognitive function. Five studies did not report an increased risk of hypoglycemia. None of the studies investigated prevention strategies for ethanol-induced hypoglycemia. Recommendations from 13 diabetes associations were included. All associations recommend that ethanol should only be consumed with food intake. The majority of included studies showed that ethanol intake increased the risk of hypoglycemia in patients with T1D. However, the evidence for how to prevent ethanol-induced hypoglycemia is sparse, and further investigations are needed to establish evidence-based recommendations.


Asunto(s)
Glucemia/metabolismo , Depresores del Sistema Nervioso Central/efectos adversos , Diabetes Mellitus Tipo 1/fisiopatología , Etanol/efectos adversos , Hipoglucemia/prevención & control , Hipoglucemiantes/efectos adversos , Glucemia/efectos de los fármacos , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Humanos , Hipoglucemia/inducido químicamente
8.
J Nanomed Nanotechnol ; 8(4)2017 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-29034126

RESUMEN

Glioblastoma (GBM) is an aggressive, grade IV brain tumor that develops from astrocytes located within the cerebrum, resulting in poor prognosis and survival rates following an accepted treatment regimen of surgery, radiation, and temozolomide. Thus, development of new therapeutics is necessary. During the last two decades, methylene blue (MB) has received increased attention as a potential neurotherapeutic due to its duality in brain cancers and neurodegenerative diseases. While MB is capable of easily permeating the blood-brain barrier, its therapeutic concentrations in GBM are known to induce off-target cytotoxicity and thus, another mode of drug delivery must be considered. To this end, encapsulation of formerly unusable compounds into nanoparticles (NPs) made from the biodegradable/biocompatible, FDA approved co-polymer poly (lactide-co-glycolide) (PLGA) has been more commonplace when developing novel therapeutics. In this study, we formulated and characterized Pluronic F68-coated PLGA NPs containing a sodium oleate conjugate of MB (MBOS) via solvent displacement. Conjugation of sodium oleate to MB was shown to reduce its release from PLGA NPs compared to unmodified MB, leading to potential improvements in drug accumulation and therapeutic effectiveness. Our drug-loaded NP preparations, which were ~170 nm in size and had drug loading values of ~2%, were shown to reduce cell viability and cell compartment-specific, as well as overall cell, functions equivalenty, if not more so, when compared to free drug in two GBM cell lines. Following bio-distribution analysis of free MBOS compared to its nano-encapsulated counterpart, drug-loaded NPs were shown to more effectively permeate the BBB, which could lead to improvements in therapeutic effectiveness upon further examination in a tumor-bearing mouse model. Based on these results, we believe that the further development and eventual utilization of this nanoformulation could lead to an effective GBM therapy that could extend patient survival rates.

9.
AJNR Am J Neuroradiol ; 38(7): 1343-1347, 2017 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-28495941

RESUMEN

BACKGROUND AND PURPOSE: The MR Parkinsonism index helps in differentiating progressive supranuclear palsy from Parkinson disease and multisystem atrophy. Pontomesencephalic involvement is common in neurologic Wilson disease, but there is no prior study evaluating the MR Parkinsonism index and its indices in Wilson disease. We report the MR Parkinsonism index and its indices in Wilson disease and correlate these changes with clinical severity and postural reflex. MATERIALS AND METHODS: Thirteen individuals with neurologic Wilson disease were included, and their clinical details, including neurologic severity, postural reflex abnormality, and location of signal changes on MR imaging, were noted. The 3D BRAVO T1 sequence was used for measurement of the MR Parkinsonism index and its indices. The MR Parkinsonism index and its indices were also obtained in 6 age- and sex-matched controls. The morphometric parameters in Wilson disease were compared with those in with healthy controls and among the patients with and without abnormal postural reflex. RESULTS: The midbrain area was reduced in patients with Wilson disease compared with controls (112.08 ± 27.94 versus 171.95 ± 23.66 mm2, P = .002). The patients with an abnormal postural reflex had an increased MR Parkinsonism index and pons-to-midbrain ratio compared with controls, whereas these parameters were equivalent in patients with normal postural reflex and controls. The patients with abnormal postural reflex had more severe illness, evidenced by higher Burke-Fahn-Marsden scores (51.0 ± 32.27 versus 13.75 ± 12.37, P = .04) and neurologic severity grades (2.57 ± 0.53 versus 1.67 ± 0.82, P = .04). CONCLUSIONS: An increase in the MR Parkinsonism index in Wilson disease is mainly due to midbrain atrophy and it correlates with neurologic severity and abnormal postural reflex.


Asunto(s)
Degeneración Hepatolenticular/diagnóstico por imagen , Mesencéfalo/diagnóstico por imagen , Puente/diagnóstico por imagen , Adolescente , Adulto , Anciano , Atrofia/patología , Cerebelo/diagnóstico por imagen , Cerebelo/patología , Cobre/metabolismo , Femenino , Degeneración Hepatolenticular/patología , Degeneración Hepatolenticular/fisiopatología , Humanos , Imagen por Resonancia Magnética , Masculino , Mesencéfalo/patología , Persona de Mediana Edad , Trastornos Parkinsonianos/diagnóstico por imagen , Trastornos Parkinsonianos/patología , Trastornos Parkinsonianos/fisiopatología , Puente/patología , Estudios Prospectivos , Reflejo , Parálisis Supranuclear Progresiva/diagnóstico por imagen , Parálisis Supranuclear Progresiva/patología , Adulto Joven
10.
Diabetes Obes Metab ; 18(4): 410-8, 2016 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-26743775

RESUMEN

AIM: To investigate the dose-response relationship of subcutaneous (s.c.) glucagon administration on plasma glucose and on counter-regulatory hormone responses during s.c. insulin-induced mild hypoglycaemia in patients with type 1 diabetes treated with insulin pumps. METHODS: Eight insulin pump-treated patients completed a blinded, randomized, placebo-controlled study. Hypoglycaemia was induced in the fasting state by an s.c. insulin bolus and, when plasma glucose reached 3.4 mmol/l [95% confidence interval (CI) 3.2-3.5], an s.c. bolus of either 100, 200, 300 µg glucagon or saline was administered. Plasma glucose, counter-regulatory hormones, haemodynamic variables and side effects were measured throughout each study day. Peak plasma glucose level was the primary endpoint. RESULTS: Plasma glucose level increased significantly by a mean (95% CI) of 2.3 (1.7-3.0), 4.2 (3.5-4.8) and 5.0 (4.3-5.6) mmol/l to 6.1 (4.9-7.4), 7.9 (6.4-9.3) and 8.7 (7.8-9.5) vs 3.6 (3.4-3.9) mmol/l (p < 0.001) after the three different glucagon doses as compared with saline, and the increase was neither correlated with weight nor insulin levels. Area under the plasma glucose curve, peak plasma glucose, time to peak plasma glucose and duration of plasma glucose level above baseline were significantly enhanced with increasing glucagon doses; however, these were not significantly different between 200 and 300 µg glucagon. Free fatty acids and heart rates were significantly lower initially after glucagon than after saline injection. Other haemodynamic variables, counter-regulatory hormones and side effects did not differ between interventions. CONCLUSIONS: An s.c. low-dose glucagon bolus effectively restores plasma glucose after insulin overdosing. Further research is needed to investigate whether low-dose glucagon may be an alternative treatment to oral carbohydrate intake for mild hypoglycaemia in patients with type 1 diabetes.


Asunto(s)
Diabetes Mellitus Tipo 1/tratamiento farmacológico , Glucagón/administración & dosificación , Hipoglucemia/prevención & control , Hipoglucemiantes/efectos adversos , Antagonistas de Insulina/administración & dosificación , Insulina Aspart/efectos adversos , Adulto , Anciano , Glucemia/análisis , Péptido C/sangre , Diabetes Mellitus Tipo 1/sangre , Relación Dosis-Respuesta a Droga , Femenino , Glucagón/efectos adversos , Glucagón/farmacocinética , Glucagón/uso terapéutico , Humanos , Hipoglucemia/inducido químicamente , Hipoglucemia/fisiopatología , Hipoglucemiantes/administración & dosificación , Hipoglucemiantes/farmacocinética , Hipoglucemiantes/uso terapéutico , Inyecciones Subcutáneas , Antagonistas de Insulina/efectos adversos , Antagonistas de Insulina/farmacocinética , Antagonistas de Insulina/uso terapéutico , Insulina Aspart/administración & dosificación , Insulina Aspart/farmacocinética , Insulina Aspart/uso terapéutico , Sistemas de Infusión de Insulina , Masculino , Persona de Mediana Edad , Índice de Severidad de la Enfermedad , Método Simple Ciego , Adulto Joven
11.
QJM ; 109(5): 319-23, 2016 May.
Artículo en Inglés | MEDLINE | ID: mdl-26475599

RESUMEN

BACKGROUND AND AIMS: To evaluate the outcome of patients with Guillain -: Barre syndrome (GBS) having respiratory failure treated with modified intubation policy. DESIGN AND METHODS: Consecutive patients with GBS having single breath count below 12 and respiratory rate >30/min were included and their clinical details noted. The patients were intubated and mechanically ventilated (MV) if their PaO2 was <60 mmHg on venturi mask, PaCo2 > 50 mmHg or pH < 7.3. Their electrophysiological subtypes and complications were noted. The hospital mortality and 3 months outcome were compared in MV and those could be managed without MV even with respiratory compromise. RESULTS: Out of 369 patients, 102 (27.6%) patients had respiratory compromise who were included in this study. Of the patients with respiratory compromise, 44 (43.1%) were intubated and mechanically ventilated after a median of 4 days of hospitalization. The median duration of MV was 21 (range 1-88) days. The patients with autonomic dysfunction (56.8% vs. 19%), facial weakness (78% vs. 36.2%), bulbar weakness (81.8% vs. 31%), severe weakness (63.8% vs. 31%) and high transaminase level (47.7% vs. 25.9%) needed MV more frequently. In our study, 6.8% patients died and 26.6% had poor outcome which was similar between MV and non-MV patients. The MV patients had longer hospitalization and more complications compared with non-MV group. CONCLUSION: In GBS patients with respiratory compromise, conservative intubation does not increase mortality and disability.


Asunto(s)
Cuidados Críticos , Síndrome de Guillain-Barré/fisiopatología , Síndrome de Guillain-Barré/terapia , Intubación Intratraqueal/métodos , Respiración Artificial , Parálisis Respiratoria/fisiopatología , Parálisis Respiratoria/terapia , Adolescente , Adulto , Anciano , Niño , Preescolar , Progresión de la Enfermedad , Femenino , Síndrome de Guillain-Barré/complicaciones , Síndrome de Guillain-Barré/mortalidad , Mortalidad Hospitalaria , Humanos , Intubación Intratraqueal/efectos adversos , Tiempo de Internación/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Respiración Artificial/métodos , Parálisis Respiratoria/etiología , Parálisis Respiratoria/mortalidad , Estudios Retrospectivos , Factores de Riesgo , Resultado del Tratamiento , Capacidad Vital , Adulto Joven
12.
Public Health Action ; 5(1): 59-64, 2015 Mar 21.
Artículo en Inglés | MEDLINE | ID: mdl-26400602

RESUMEN

SETTING: All multidrug-resistant tuberculosis (MDR-TB) patients who had completed 6 months of treatment under the Revised National Tuberculosis Control Programme (RNTCP) in Uttar Pradesh, the largest state in northern India. OBJECTIVE: To determine the proportion of MDR-TB patients with regular follow-up examinations, and underlying provider and patient perspectives of follow-up services. METHODS: A retrospective cohort study was undertaken involving record reviews of 64 eligible MDR-TB patients registered during April-June 2013 in 11 districts of the state. Patients and programme personnel from the selected districts were interviewed using a semi-structured questionnaire. RESULTS: A total of 34 (53.1%) patients underwent follow-up sputum culture at month 3, 43 (67.2%) at month 4, 36 (56.3%) at month 5 and 37 (57.8%) at month 6. Themes associated with irregular follow-up that emerged from the interviews were multiple visits, long travel distances, shortages of equipment at the facility and lack of knowledge among patients regarding the follow-up schedule. CONCLUSION: The majority of the MDR-TB patients had irregular follow-up visits. Provider-related factors outweigh patient-related factors on the poor follow-up examinations. The programme should focus on the decentralisation of follow-up services and ensure logistics and patient-centred counselling to improve the regularisation of follow up.


Contexte : Tous les patients atteints de tuberculose multirésistante (TB-MDR) qui avaient achevé 6 mois de traitement dans le cadre du Programme National Révisé de Lutte contre la Tuberculose (RNTCP) dans l'Uttar Pradesh, le plus grand état dans le nord de l'Inde.Objectif : Déterminer la proportion de patients TB-MDR bénéficiant d'examens de suivi régulier et la vision des prestataires et des patients sur ces services de suivi.Méthodes : Une étude rétrospective de cohorte a été réalisée grâce à la revue des dossiers de 64 patients TB-MDR éligibles enregistrés entre avril et juin 2013 dans 11 districts de l'état. Les patients et le personnel du RNTCP des districts sélectionnés ont également été interviewés grâce à un questionnaire semi-structuré.Résultats : Au total, 34 (53,1%) patients ont bénéficié d'examens de culture de crachats au 3e mois, 43 (67,2%) au 4e mois, 36 (56,3%) au 5e mois et 37 (57,8%) au 6e mois. Les principaux facteurs associés à un suivi irrégulier émanant des entretiens étaient le nombre élevé de consultations, la distance à parcourir, les ruptures de stock dans les structures et le manque de connaissances des patients vis-à-vis du programme de suivi.Conclusion : La majorité des patients TB-MDR ont eu un suivi irrégulier. Les facteurs liés aux prestataires dépassent ceux liés aux patients en matière d'examens de suivi médiocres. Le RNTCP devrait se concentrer sur la décentralisation des services de suivi, assurer la logistique et le conseil centré sur le patient afin d'accroitre la régularité du suivi.


Marco de referencia: Todos los pacientes con diagnóstico de tuberculosis multidrogorresistente (TB-MDR) después de haber completado los 6 meses de tratamiento en el contexto del Programa Nacional de Control de la Tuberculosis (RNTCP) en Uttar Pradesh, la provincia más grande del norte de la India.Objetivo: Determinar la proporción de pacientes con TB-MDR en quienes se practicaron exámenes periódicos de seguimiento y conocer las opiniones de los profesionales y de los pacientes sobre los servicios de seguimiento.Métodos: Se llevó a cabo un estudio de cohortes retrospectivo a partir del examen de las historias clínicas de 64 pacientes con diagnóstico de TB-MDR, que cumplían con los requisitos de inclusión, registrados entre abril y junio del 2013 en 11 distritos del estado. Se realizaron además entrevistas a los pacientes y al personal del RNTCP de algunos distritos mediante un cuestionario semi-estructurado.Resultados: En 34 pacientes se practicó el seguimiento del cultivo de esputo al tercer mes (53,1%), en 43 casos al cuarto mes (67,2%), en 36 al quinto mes (56,3%) y en 37 pacientes al sexto mes de tratamiento (57,8%). Los principales factores asociados con la irregularidad del seguimiento que revelaron las entrevistas fueron la multiplicidad de las citas, la larga distancia de los desplazamientos, la carencia de insumos en los centros y el desconocimiento del calendario del seguimiento por parte de los pacientes.Conclusión: El seguimiento de la mayoría de los pacientes con diagnóstico de TB-MDR fue irregular. En las causas de la deficiencia del seguimiento predominaron los factores dependientes de los profesionales en comparación con los factores propios a los pacientes. El RNTCP debe considerar seriamente la descentralización de los servicios de seguimiento, suministrarlos materiales necesarios y proveer una orientación centrada en los pacientes con el objeto de mejorar la regularidad de los seguimientos.

13.
Clin Neurol Neurosurg ; 138: 31-6, 2015 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-26278999

RESUMEN

OBJECTIVE: To evaluate the sensitivity of different MRI sequences in Wilson disease (WD) with neurological manifestations and its correlation with clinical features and outcome. METHODS: 34 WD patients with neurological manifestation with a median age of 14 years were included. Their Mini Mental State Examination (MMSE) score, movement disorders and laboratory findings were noted. Cranial MRI in T1, T2, FLAIR and DW sequences were done. Outcome at 6 months was categorized into improved (>1 grade improvement), static or worsening. RESULTS: MRI was abnormal in all and revealed involvement of putamen in 29 (85.3%), caudate in 23 (67.6%), brainstem and globus pallidus in 21 (61.8%) each, thalamus in 20 (58.8%), cerebral cortex in 9 (26.5%), subcortical white matter in 8 (23.5%), and cerebellum in 2 (5.9%) patients. The overall sensitivity of T2 and FLAIR was 97.1% each, DWI 38.2% and T1 31.4%. None had contrast enhancement and 4 had reduced ADC value. Choreoathetosis correlated with thalamic, pallidal and putaminal lesions; MMSE with subcortical white mater. MRI load correlated with age, tremor, psychiatric disorder, choreoathetosis, and severity of WD. At 6 months 9 (26.5%) patients improved, 18 (52.9%) remained static and 6 (17.6%) deteriorated. CONCLUSION: In neurologic WD, putaminal involvement is the commonest; T2 and FLAIR sequences have similar sensitivity and number of MRI lesions correlated with disease severity but not with outcome.


Asunto(s)
Degeneración Hepatolenticular/patología , Imagen por Resonancia Magnética , Sustancia Blanca/patología , Adolescente , Adulto , Núcleo Caudado/patología , Niño , Femenino , Globo Pálido/patología , Degeneración Hepatolenticular/complicaciones , Humanos , Masculino , Trastornos del Movimiento/etiología , Estudios Prospectivos , Putamen/patología , Estudios Retrospectivos , Adulto Joven
14.
Neurotoxicology ; 49: 45-9, 2015 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-26004675

RESUMEN

BACKGROUND AND AIM: There is no report of MRI correlation with neurological worsening following chelating treatment in Wilson disease with neurological manifestation (WDN). We report radiological changes in four patients with WDN who worsen after penicillamine. METHODS: WDN was diagnosed on the basis of clinical, KF ring, serum ceruloplasmin and 24h urinary copper. Hematological, biochemical and cranial MRI were repeated at the time of clinical deterioration following chelating treatment. RESULTS: Four WDN patients had neurological deterioration within 4-8 weeks of penicillamine therapy. This was associated with new lesions in white matter, thalamus, pons and mid brain and these lesions showed diffusion restriction. The neurologic deterioration was associated with increased free serum copper and malanodialdehyde and reduced glutathione. Clinical conditions stabilized after few weeks of penicillamine discontinuation. CONCLUSION: Neurological worsening was associated with new lesions on MRI which revealed diffusion restriction. Increased free copper induced oxidative stress may be responsible for these changes.


Asunto(s)
Antídotos/efectos adversos , Degeneración Hepatolenticular/tratamiento farmacológico , Enfermedades del Sistema Nervioso/inducido químicamente , Enfermedades del Sistema Nervioso/patología , Estrés Oxidativo/efectos de los fármacos , Penicilamina/efectos adversos , Adulto , Niño , Degeneración Hepatolenticular/complicaciones , Humanos , Imagen por Resonancia Magnética , Masculino , Enfermedades del Sistema Nervioso/etiología , Factores de Tiempo , Adulto Joven
15.
Diabetes Metab Res Rev ; 31(7): 672-9, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-25533565

RESUMEN

Intensive insulin treatment in type 1 diabetes reduces the incidence and slows the progression of microvascular and macrovascular complications; however, it is associated with an increased risk of hypoglycaemia and weight gain. In this review, we propose dual-hormone treatment with insulin and glucagon as a method for achieving near normalization of blood glucose levels without increasing hypoglycaemia frequency and weight gain. We briefly summarize glucagon pathophysiology in type 1 diabetes as well as the current applications of glucagon for the treatment of hypoglycaemia. Until now, the use of glucagon has been limited by the need for reconstitution immediately before use, because of instability of the available compounds; however, stabile compounds are soon to be launched and will render long-term intensive dual-hormone treatment in type 1 diabetes possible.


Asunto(s)
Diabetes Mellitus Tipo 1/tratamiento farmacológico , Glucagón/uso terapéutico , Terapia de Reemplazo de Hormonas/métodos , Hormonas/uso terapéutico , Hipoglucemiantes/uso terapéutico , Insulina/uso terapéutico , Quimioterapia Combinada , Humanos , Hipoglucemia/inducido químicamente , Hipoglucemia/prevención & control , Aumento de Peso
16.
Pharm Res ; 31(11): 3120-6, 2014 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-24852892

RESUMEN

PURPOSE: The objectives of this study were to: 1) determine if mild hyperthermia (40-42°C) can sensitize tumor cells for more effective proton beam radiotherapy (PBRT); 2) characterize the survival fraction of cells exposed to PBRT; and 3) characterize release of the drug doxorubicin (Dox) from low temperature sensitive liposomes (LTSLs) without exposure to mild hyperthermia in combination with PBRT. METHODS: Dox was actively loaded in LTSLs. A549 monolayer cells were incubated with 100-200 nM of Dox-LTSL (±mild hyperthermia). Cell irradiation (0-6 Gy) was performed by placing the cell culture plates inside a solid water phantom and using a clinical proton treatment beam with energy of 150 MeV. End points were survival fraction, radiation-mediated Dox release, and reactive oxygen species (ROS) production. RESULTS: Hyperthermia effectively sensitized cells for PBRT and lowered the cell survival fraction (SF) by an average of 9.5%. The combination of 100 nM Dox-LTSL and PBRT (1-6 Gy) achieved additive to synergistic response at various dose combinations. At higher radiation doses (>3 Gy), the SF in the Dox and Dox-LTSL groups was similar (~20%), even in the absence of hyperthermia. In addition, 30% of the Dox was released from LTSLs and a 1.3-1.6 fold increase in ROS level occurred compared to LTSL alone therapy. CONCLUSIONS: The combination of LTSLs and PBRT achieves additive to synergistic effect at various dose combinations in vitro. Concurrent PBRT and Dox-LTSL treatment significantly improved the cytotoxic outcomes of the treatment compared to PBRT and Dox chemotherapy without LTSLs. We hypothesize that PBRT may induce drug release from LTSL in the absence of hyperthermia.


Asunto(s)
Antineoplásicos/farmacología , Liberación de Fármacos/efectos de los fármacos , Liposomas/farmacología , Terapia de Protones , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Terapia Combinada/métodos , Doxorrubicina/farmacología , Humanos , Hipertermia Inducida/métodos , Temperatura
17.
Indian Pediatr ; 51(1): 21-5, 2014 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-24277964

RESUMEN

OBJECTIVE: To assess the effectiveness of facility-based care for children with severe acute malnutrition (SAM) in Nutrition Rehabilitation Centers (NRC). DESIGN: Review of data. SETTING: 12 NRCs in Uttar Pradesh, India. PARTICIPANTS: Children admitted to NRCs (Jan 1, 2010 - Dec 31, 2011). INTERVENTION: Detection and treatment of SAM with locally-adapted protocols. OUTCOMES: Survival, default, discharge, and recovery rates. RESULTS: 54.6% of the total 1,229 children admitted were boys, 81.6% were in the age group 6-23 months old, 86% belonged to scheduled tribes, scheduled castes, or other backward castes, and 42% had edema or medical complications. Of the 1,181 program exits, 14 (1.2%) children died, 657 (47.2%) children defaulted, and 610 (51.7%) children were discharged The average (SD) weight gain was 12.1 (7.3)g/kg body weight/day and the average (SD) length of stay was 13.2 (5.6) days. 206 (46.8%) children were discharged after recovery (weight gain >15%) while 324 (53.2%) were discharged, non-recovered (weight gain <15%). CONCLUSIONS: NRCs provide life-saving care for children with SAM; however, the protocols and therapeutic foods currently used need to be improved to ensure the full recovery of all children admitted.


Asunto(s)
Desnutrición Proteico-Calórica/terapia , Preescolar , Femenino , Humanos , India , Lactante , Masculino , Aumento de Peso
18.
Nepal J Ophthalmol ; 5(2): 242-5, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-24172562

RESUMEN

INTRODUCTION: Calcium carbide used in fruit ripening industry as a cheap alternative to natural plant hormone ethylene produces highly inflammable acetylene gas. Inadvertent ignition of this gas can cause severe ocular burn injury with unilateral or bilateral blindness. OBJECTIVE: To determine the characteristics and visual outcome of ocular burn injuries from calcium carbide during mango ripening season of West Bengal, eastern India. MATERIALS AND METHODS: A prospective study of all cases of calcium carbide related ocular burn injury attending a tertiary care hospital during mango ripening season was carried out. The demographic features, characteristics of the injury, management and outcomes were recorded. RESULTS: Fifty five eyes of 33 patients were studied. Males were more commonly affected (20 patients, 60.6%) than females. The injury was bilateral in 22 patients (66.66%). Seventeen patients (51.51%) were below 20 years of age. Ten eyes had open globe injuries and 45 eyes had closed globe injuries. One eye of a patient had to be enucleated (3%). Children below 14 years of age were mainly injured while playing with indigenous fireworks of shooting carbide. Middle aged women were affected particularly during ignition of evening lamps. Carbide lamp was another source of injury. CONCLUSION: Males are more commonly affected by calcium carbide related ocular injuries. Children and young adults are the common victims. Such injuries can involve both the eyes and cause a permanent visual disability.


Asunto(s)
Acetileno/análogos & derivados , Agricultura , Quemaduras Químicas/etiología , Quemaduras Oculares/etiología , Mangifera , Traumatismos Ocupacionales/etiología , Acetileno/efectos adversos , Adolescente , Ceguera/inducido químicamente , Niño , Femenino , Humanos , India , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Adulto Joven
19.
Clin Genet ; 83(2): 99-107, 2013 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-23094849

RESUMEN

This systematic review investigated the inheritance of the classical chronic myeloproliferative neoplasms (MPNs) including polycythemia vera (PV), essential thrombocythemia (ET), primary myelofibrosis (PMF) and chronic myelogenous leukemia (CML). Sixty-one articles were included and provided 135 families with a total of 341 participants distributed to various subtypes of MPN: 50% PV, 23% ET, 14% PMF, 10% CML and 3% non-MPN hematological disorder. Women developed the disease earlier than men (43.1 years vs 47.3 years; p = 0.074), while the general average age of onset was 46 years, notably younger than sporadic cases. The clinical phenotype of the families showed a homogenous (67%) and a heterogeneous (33%) pattern, with the majority being PV-PV pairs (36%) and PV-PMF pairs (17%), respectively. This observation suggests that the susceptibility gene (or genes) is not restricted to one subtype supporting the hypothesis of a mutation in an early multipotent stem cell. Furthermore, a major subgroup of families provided evidence of an autosomal dominant (AD) inheritance with reduced penetrance. This study suggests that the origin of MPNs may occur in at least three different settings: (i) a sporadic, (ii) genetic heterogeneity with polygenetic and environmental impact and (iii) a familial phenotype following an AD inheritance.


Asunto(s)
Trastornos Mieloproliferativos/genética , Enfermedad Crónica , Femenino , Predisposición Genética a la Enfermedad , Humanos , Patrón de Herencia , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Masculino , Policitemia Vera/genética , Mielofibrosis Primaria/genética , Trombocitemia Esencial/genética
20.
Vet Q ; 32(3-4): 145-50, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-23078207

RESUMEN

Cattle can synthesize L-ascorbic acid (or Vitamin C) from either D-glucose or D-galactose through glucuronic acid pathway in the liver. L-Ascorbic acid present in cattle diet is almost totally destroyed by rumen microorganisms making them essentially dependent on its endogenous synthesis, which is assumed sufficient to meet the physiological requirement. Therefore, the role of vitamin C in cattle health and disease has remained widely overlooked. However, there is mounting evidence that the level of L-ascorbic acid in blood and other tissues decreases in association with stress and disease, and Vitamin C supplementation revealed favorable response as evident from early recovery. The present review is an attempt to summarize the existing literature pertaining to the physiological role of L-ascorbic acid and the scope of its supplementation in the prevention and treatment of diseases in cattle. It should be realized that the aqueous solution of vitamin C is highly acidic and subcutaneous or intramuscular administration may cause tissue irritation and inflammation, whereas the sodium ascorbate solution is less acidic and might be used for intramuscular administration.


Asunto(s)
Ácido Ascórbico/metabolismo , Ácido Ascórbico/uso terapéutico , Enfermedades de los Bovinos/dietoterapia , Enfermedades de los Bovinos/prevención & control , Bovinos/fisiología , Fenómenos Fisiológicos Nutricionales de los Animales , Animales , Ácido Ascórbico/biosíntesis , Ácido Ascórbico/inmunología , Dieta/veterinaria , Suplementos Dietéticos/análisis , Reproducción
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