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1.
Cochrane Database Syst Rev ; 6: CD013468, 2024 06 05.
Artigo em Inglês | MEDLINE | ID: mdl-38837237

RESUMO

BACKGROUND: Postburn pruritus (itch) is a common and distressing symptom experienced on healing or healed burn or donor site wounds. Topical, systemic, and physical treatments are available to control postburn pruritus; however, it remains unclear how effective these are. OBJECTIVES: To assess the effects of interventions for treating postburn pruritus in any care setting. SEARCH METHODS: In September 2022, we searched the Cochrane Wounds Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), Ovid MEDLINE (including In-Process & Other Non-Indexed Citations), Ovid Embase, and EBSCO CINAHL Plus. We also searched clinical trials registries and scanned references of relevant publications to identify eligible trials. There were no restrictions with respect to language, publication date, or study setting. SELECTION CRITERIA: Randomised controlled trials (RCTs) that enrolled people with postburn pruritus to compare an intervention for postburn pruritus with any other intervention, placebo or sham intervention, or no intervention. DATA COLLECTION AND ANALYSIS: We used the standard methodological procedures expected by Cochrane. We used GRADE to assess the certainty of the evidence. MAIN RESULTS: We included 25 RCTs assessing 21 interventions with 1166 randomised participants. These 21 interventions can be grouped into six categories: neuromodulatory agents (such as doxepin, gabapentin, pregabalin, ondansetron), topical therapies (such as CQ-01 hydrogel, silicone gel, enalapril ointment, Provase moisturiser, beeswax and herbal oil cream), physical modalities (such as massage therapy, therapeutic touch, extracorporeal shock wave therapy, enhanced education about silicone gel sheeting), laser scar revision (pulsed dye laser, pulsed high-intensity laser, fractional CO2 laser), electrical stimulation (transcutaneous electrical nerve stimulation, transcranial direct current stimulation), and other therapies (cetirizine/cimetidine combination, lemon balm tea). Most RCTs were conducted at academic hospitals and were at a high risk of performance, attrition, and detection bias. While 24 out of 25 included studies reported change in burn-related pruritus, secondary outcomes such as cost-effectiveness, pain, patient perception, wound healing, and participant health-related quality of life were not reported or were reported incompletely. Neuromodulatory agents versus antihistamines or placebo There is low-certainty evidence that doxepin cream may reduce burn-related pruritus compared with oral antihistamine (mean difference (MD) -2.60 on a 0 to 10 visual analogue scale (VAS), 95% confidence interval (CI) -3.79 to -1.42; 2 studies, 49 participants). A change of 2 points represents a minimal clinically important difference (MCID). Due to very low-certainty evidence, it is uncertain whether doxepin cream impacts the incidence of somnolence as an adverse event compared to oral antihistamine (risk ratio (RR) 0.64, 95% CI 0.32 to 1.25; 1 study, 24 participants). No data were reported on pain in the included study. There is low-certainty evidence that gabapentin may reduce burn-related pruritus compared with cetirizine (MD -2.40 VAS, 95% CI -4.14 to -0.66; 1 study, 40 participants). A change of 2 points represents a MCID. There is low-certainty evidence that gabapentin reduces the incidence of somnolence compared to cetirizine (RR 0.02, 95% CI 0.00 to 0.38; 1 study, 40 participants). No data were reported on pain in the included study. There is low-certainty evidence that pregabalin may result in a reduction in burn-related pruritus intensity compared with cetirizine with pheniramine maleate (MD -0.80 VAS, 95% CI -1.24 to -0.36; 1 study, 40 participants). A change of 2 points represents a MCID. There is low-certainty evidence that pregabalin reduces the incidence of somnolence compared to cetirizine (RR 0.04, 95% CI 0.00 to 0.69; 1 study, 40 participants). No data were reported on pain in the included study. There is moderate-certainty evidence that ondansetron probably results in a reduction in burn-related pruritus intensity compared with diphenhydramine (MD -0.76 on a 0 to 10 numeric analogue scale (NAS), 95% CI -1.50 to -0.02; 1 study, 38 participants). A change of 2 points represents a MCID. No data were reported on pain and adverse events in the included study. Topical therapies versus relevant comparators There is moderate-certainty evidence that enalapril ointment probably decreases mean burn-related pruritus compared with placebo control (MD -0.70 on a 0 to 4 scoring table for itching, 95% CI -1.04 to -0.36; 1 study, 60 participants). No data were reported on pain and adverse events in the included study. Physical modalities versus relevant comparators Compared with standard care, there is low-certainty evidence that massage may reduce burn-related pruritus (standardised mean difference (SMD) -0.86, 95% CI -1.45 to -0.27; 2 studies, 166 participants) and pain (SMD -1.32, 95% CI -1.66 to -0.98). These SMDs equate to a 4.60-point reduction in pruritus and a 3.74-point reduction in pain on a 10-point VAS. A change of 2 VAS points in itch represents a MCID. No data were reported on adverse events in the included studies. There is low-certainty evidence that extracorporeal shock wave therapy (ESWT) may reduce burn-related pruritus compared with sham stimulation (SMD -1.20, 95% CI -1.65 to -0.75; 2 studies, 91 participants). This equates to a 5.93-point reduction in pruritus on a 22-point 12-item Pruritus Severity Scale. There is low-certainty evidence that ESWT may reduce pain compared with sham stimulation (MD 2.96 on a 0 to 25 pressure pain threshold (PPT), 95% CI 1.76 to 4.16; 1 study, 45 participants). No data were reported on adverse events in the included studies. Laser scar revision versus untreated or placebo controls There is moderate-certainty evidence that pulsed high-intensity laser probably results in a reduction in burn-related pruritus intensity compared with placebo laser (MD -0.51 on a 0 to 1 Itch Severity Scale (ISS), 95% CI -0.64 to -0.38; 1 study, 49 participants). There is moderate-certainty evidence that pulsed high-intensity laser probably reduces pain compared with placebo laser (MD -3.23 VAS, 95% CI -5.41 to -1.05; 1 study, 49 participants). No data were reported on adverse events in the included studies. AUTHORS' CONCLUSIONS: There is moderate to low-certainty evidence on the effects of 21 interventions. Most studies were small and at a high risk of bias related to blinding and incomplete outcome data. Where there is moderate-certainty evidence, practitioners should consider the applicability of the evidence for their patients.


Assuntos
Queimaduras , Prurido , Ensaios Clínicos Controlados Aleatórios como Assunto , Humanos , Prurido/etiologia , Prurido/terapia , Queimaduras/complicações , Queimaduras/terapia , Viés , Antipruriginosos/uso terapêutico
2.
Indian J Plast Surg ; 54(3): 253-256, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34667507
3.
Indian J Cancer ; 58(3): 441-444, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34380853

RESUMO

Pseudomyogenic hemangioendothelioma (PHE) is a soft-tissue tumor of intermediate malignant potential, recognized as a separate entity in the WHO (World Health Organization) classification of tumors of soft tissue and bone, in 2013. This is a case report of a 33-year-old man with intraosseous scapular PHE reported on small biopsy and immunohistochemistry. The patient presented with local recurrence and metastases even after wide local excision and adjuvant radiotherapy after 14 months. The rarity of this lesion at this site and morphologic clues to diagnosis are important for optimizing the treatment protocol.


Assuntos
Hemangioendotelioma/diagnóstico , Escápula/patologia , Adulto , Biópsia , Humanos , Masculino
4.
Pharmacotherapy ; 41(7): 634-640, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33934388

RESUMO

Enteral tubes are necessary for certain patients; however, medication absorption can be affected by this route of administration potentially resulting in decreased efficacy. All first-line treatments for Hepatitis C Virus (HCV) infection are only available as tablets and may have decreased absorption if administered via an enteral tube. This report describes the first case of a pegylated interferon and ribavirin treatment-experienced patient who successfully achieved HCV cure after 12 weeks of elbasvir/grazoprevir administered via percutaneous gastrostomy tube. We further review the available pharmacokinetic and clinical literature regarding administration via enteral feeding tubes for all first-line direct-acting antivirals (DAAs). The literature suggests that crushed administration can be considered for DAAs in patients with gastric access. However, caution should be exercised in patients with extragastric enteral tubes and in those with altered gastrointestinal tract anatomy.


Assuntos
Amidas , Benzofuranos , Carbamatos , Ciclopropanos , Hepatite C Crônica , Imidazóis , Quinoxalinas , Sulfonamidas , Amidas/administração & dosagem , Antivirais/administração & dosagem , Benzofuranos/administração & dosagem , Carbamatos/administração & dosagem , Ciclopropanos/administração & dosagem , Quimioterapia Combinada , Gastrostomia , Hepatite C Crônica/tratamento farmacológico , Humanos , Imidazóis/administração & dosagem , Quinoxalinas/administração & dosagem , Sulfonamidas/administração & dosagem , Resposta Viral Sustentada , Resultado do Tratamento
5.
J Occup Environ Hyg ; 18(sup1): S25-S34, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33822697

RESUMO

RESUMENLa etiqueta para la tos y la higiene respiratoria son formas de control de la fuente de emisión cuyo uso se alienta para evitar la propagación de infecciones respiratorias. El uso de mascarillas quirúrgicas como medio de control de la fuente en términos de reducción de la exposición de terceros no se ha investigado. En este estudio diseñamos un modelo in vitro utilizando varias mascarillas faciales con el fin de evaluar su aporte a la reducción de la exposición cuando son utilizadas en la fuente infecciosa (Fuente) en comparación con la reducción proporcionada por las mascarillas usadas para la protección primaria (Receptor), así como los factores que contribuyen a cada una. En una cámara con diversos flujos de aire se exhalaron aerosoles radiomarcados desde una cabeza de maniquí de cara blanda ventilada, utilizando respiración periódica y tos (Fuente). En otro maniquí, al que se le colocó un filtro, se cuantificó la exposición del Receptor. Se probaron una mascarilla quirúrgica de ajuste natural, una mascarilla quirúrgica de ajuste seguro (SecureFit) y una mascarilla respiratoria autofiltrante de clase N95 (comúnmente conocida como "mascarilla autofiltrante N95") con y sin sello de vaselina. Con la tos, el control de la fuente (mascarilla quirúrgica/autofiltrante colocada en la Fuente) fue estadísticamente superior a la protección brindada por la mascarilla quirúrgica/mascarilla autofiltrante sin sellar en el Receptor (protección del Receptor) en todos los entornos. Para igualar el control de la fuente durante la tos, la mascarilla autofiltrante N95 debe estar sellada con vaselina. Durante la respiración periódica, el control de la fuente fue comparable o superior a la protección brindada por la mascarilla quirúrgica/autofiltrante en el Receptor. El control de la fuente mediante mascarillas quirúrgicas puede ser una importante defensa adicional contra la propagación de infecciones respiratorias. El ajuste de la mascarilla quirúrgica/autofiltrante combinado con los patrones de flujo de aire en un entorno determinado contribuye de manera significativa a la eficacia del control de la fuente. Los futuros ensayos clínicos deberían incluir un brazo de control de la fuente con mascarilla quirúrgica a fin de evaluar el aporte realizado por el control de la fuente a la protección general contra infecciones de transmisión aérea.

6.
Crit Care Clin ; 37(1): 205-219, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33190771

RESUMO

The importance of evaluating and adjusting the nutritional state of critically ill patients has become a core principle of care. This article focuses on tools for the nutritional assessment of geriatric intensive care unit patients, including a review of imaging and other standardized techniques for evaluation of muscle mass, an indicator of malnutrition and sarcopenia. It concludes with a discussion of the interplay of malnutrition, reduced muscle mass/sarcopenia, and frailty. The goal of this multidimensional assessment is to identify those at risk and thereby initiate interventions to improve outcomes.


Assuntos
Desnutrição , Sarcopenia , Idoso , Avaliação Geriátrica , Humanos , Unidades de Terapia Intensiva , Desnutrição/diagnóstico , Avaliação Nutricional , Sarcopenia/diagnóstico
7.
Burns Trauma ; 8: tkaa019, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33123605

RESUMO

Currently, there are no harmonized guidelines which govern skin banking in the Asia Pacific region. Therefore, skin banks are either unregulated or rely on their nation's legislation or international accreditation to uphold their quality standards. A new set of skin banking guidelines was developed through a comprehensive review and collation of best international practices for the Asia Pacific Burn Association (APBA) members, from donor screening and testing, to skin recovery, processing, storage and distribution, and quality assurance. National regulatory requirements reviewed include the European directives, Australia's Therapeutic Goods Administration and Singapore's tissue banking standards. Further technical and quality management recommendations are referenced from the American Association of Tissue Banks (AATB), the United States Food and Drug Administration standards and guidance documents, various relevant European guides, Japanese Society of Tissue Transplantation guidelines and the Asia Pacific Association of Surgical Tissue Banking. Adapted mainly from the AATB standards, the new Asia Pacific Burn Association Guidelines for Skin Banking in Therapeutic Applications offer a comprehensive manual, addressing: governance and contracts; staff responsibilities; quality management; facilities, equipment and supplies management; donor consent and testing; and recommendations of good practices pertaining to skin recovery, processing, storage and distribution. Besides complementing current generic regulations, they provide technical specifications of major aspects unaddressed in most legislations. This inaugural set of new regional skin banking guidelines would be a start for regional members of the APBA to adopt, and will hopefully culminate in a set of standards so that, in the long run, skin allografts from this region can be of similar quality, which can simplify import process and facilitate the exchange of allografts between members.

8.
Crit Care Explor ; 2(7): e0160, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32766557

RESUMO

Preventing exposure of virulent pathogens during aerosolizing procedures such as intubations has been a cause of concern during the coronavirus pandemic. As such, protocols have been adjusted and precautions implemented in order to minimize the risk to the proceduralist. As patients improve, we face another high-risk aerosolizing procedure-extubation. We illustrate a protocol to help minimize the exposure risk during extubation. We describe a barrier technique during extubation which contained aerosolized particulates into a non-rebreather mask at time of extubation. Our protocol allows providers to perform extubations while minimizing exposure to aerosolized particles.

10.
ACS Omega ; 4(2): 3684-3689, 2019 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-31459581

RESUMO

Feasibility of performing multiple coulometric titrations in a single course of electrolysis is presented. In these titrations, three pairs of cathode and anode compartments were connected with a network of electrodes and salt bridges. Passage of current through the cell caused concurrent electrolysis in cathode and anode compartments. Electrogenerated reagents produced in these compartments were used as titrants for quantifying the analyte samples. Endpoints of the titrations were determined from the visual color change of an indicator. The charge passing through the cell was monitored and Faraday's laws of electrolysis were applied to assess the quantitative relation between the charge and analyte concentration. Experimentally determined coulombs required to titrate aqueous potassium hydrogen phthalate, MnO4 -, OH-, and S2O3 2- were 0.100, 0.466, 0.103, and 0.0934 C, respectively. These results matched with estimated values of 0.0965, 0.482, 0.0965, and 0.0965 C, respectively. Agreement between the coulombs determined from experimental results and reaction stoichiometry suggests a feasible application of concurrent coulometric titrations. Efficacy of the method was tested for determining the active ingredients in household vinegar and vitamin C dietary supplement tablets. Quantities of acetic acid and ascorbic acid in these products were 5.1% and 980 mg, respectively, agreeing with the quantities determined from volumetric titrations (5.1% and 990 mg) and manufacturer's label (5.0% and 1000 mg).

11.
J Anal Methods Chem ; 2018: 2681796, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29629210

RESUMO

A gravimetric method for the quantitative assessment of the products of electrolysis of water is presented. In this approach, the electrolysis cell was directly powered by 9 V batteries. Prior to electrolysis, a known amount of potassium hydrogen phthalate (KHP) was added to the cathode compartment, and an excess amount of KHCO3 was added to the anode compartment electrolyte. During electrolysis, cathode and anode compartments produced OH-(aq) and H+(aq) ions, respectively. Electrolytically produced OH-(aq) neutralized the KHP, and the completion of this neutralization was detected by a visual indicator color change. Electrolytically produced H+(aq) reacted with HCO3-(aq) liberating CO2(g) from the anode compartment. Concurrent liberation of H2(g) and O2(g) at the cathode and anode, respectively, resulted in a decrease in the mass of the cell. Mass of the electrolysis cell was monitored. Liberation of CO2(g) resulted in a pronounced effect of a decrease in mass. Experimentally determined decrease in mass (53.7 g/Faraday) agreed with that predicted from Faraday's laws of electrolysis (53.0 g/Faraday). The efficacy of the cell was tested to quantify the acid content in household vinegar samples. Accurate results were obtained for vinegar analysis with a precision better than 5% in most cases. The cell offers the advantages of coulometric method and additionally simplifies the circuitry by eliminating the use of a constant current power source or a coulometer.

12.
Sci Rep ; 7(1): 3756, 2017 06 16.
Artigo em Inglês | MEDLINE | ID: mdl-28623364

RESUMO

The peptide HsTX1[R14A] is a potent and selective blocker of the voltage-gated potassium channel Kv1.3, which is a highly promising target for the treatment of autoimmune diseases and other conditions. In order to assess the biodistribution of this peptide, it was conjugated with NOTA and radiolabelled with copper-64. [64Cu]Cu-NOTA-HsTX1[R14A] was synthesised in high radiochemical purity and yield. The radiotracer was evaluated in vitro and in vivo. The biodistribution and PET studies after intravenous and subcutaneous injections showed similar patterns and kinetics. The hydrophilic peptide was rapidly distributed, showed low accumulation in most of the organs and tissues, and demonstrated high molecular stability in vitro and in vivo. The most prominent accumulation occurred in the epiphyseal plates of trabecular bones. The high stability and bioavailability, low normal-tissue uptake of [64Cu]Cu-NOTA-HsTX1[R14A], and accumulation in regions of up-regulated Kv channels both in vitro and in vivo demonstrate that HsTX1[R14A] represents a valuable lead for conditions treatable by blockade of the voltage-gated potassium channel Kv1.3. The pharmacokinetics shows that both intravenous and subcutaneous applications are viable routes for the delivery of this potent peptide.


Assuntos
Canal de Potássio Kv1.3/antagonistas & inibidores , Peptídeos , Bloqueadores dos Canais de Potássio , Administração Intravenosa , Animais , Linhagem Celular , Injeções Subcutâneas , Masculino , Camundongos , Peptídeos/farmacocinética , Peptídeos/farmacologia , Bloqueadores dos Canais de Potássio/farmacocinética , Bloqueadores dos Canais de Potássio/farmacologia , Ratos , Ratos Wistar
13.
Burns Trauma ; 5: 13, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28473994

RESUMO

Contractures of the axilla and elbow can produce a significant impact on quality of life by reducing the ability to perform activities of daily living. Varieties of techniques are available for resurfacing defects following contracture release but graft or flap loss, donor-site morbidity, esthetics, and recurrences are still challenges for reconstructive surgeons. Central axis "propeller" flaps based on a random, subcutaneous pedicle were first described for axillary and elbow contractures to deploy the unburnt skin of axillary dome in type I and II contractures (Kurtzman and Stern) by moving them 90° to straddle the contracting bands. This strategy provided better esthetics and avoided prolonged splinting. Over more than two decades, there have been several design modifications of these flaps with extended applications to cubital fossa. A comprehensive review of published literature on the topic is presented to discuss classifications, design modifications, and applications of such flaps in managing axillary and elbow contractures.

14.
Clin Immunol ; 180: 45-57, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28389388

RESUMO

Effector memory T lymphocytes (TEM cells) that lack expression of CCR7 are major drivers of inflammation in a number of autoimmune diseases, including multiple sclerosis and rheumatoid arthritis. The Kv1.3 potassium channel is a key regulator of CCR7- TEM cell activation. Blocking Kv1.3 inhibits TEM cell activation and attenuates inflammation in autoimmunity, and as such, Kv1.3 has emerged as a promising target for the treatment of TEM cell-mediated autoimmune diseases. The scorpion venom-derived peptide HsTX1 and its analog HsTX1[R14A] are potent Kv1.3 blockers and HsTX1[R14A] is selective for Kv1.3 over closely-related Kv1 channels. PEGylation of HsTX1[R14A] to create a Kv1.3 blocker with a long circulating half-life reduced its affinity but not its selectivity for Kv1.3, dramatically reduced its adsorption to inert surfaces, and enhanced its circulating half-life in rats. PEG-HsTX1[R14A] is equipotent to HsTX1[R14A] in preferential inhibition of human and rat CCR7- TEM cell proliferation, leaving CCR7+ naïve and central memory T cells able to proliferate. It reduced inflammation in an active delayed-type hypersensitivity model and in the pristane-induced arthritis (PIA) model of rheumatoid arthritis (RA). Importantly, a single subcutaneous dose of PEG-HsTX1[R14A] reduced inflammation in PIA for a longer period of time than the non-PEGylated HsTX1[R14A]. Together, these data indicate that HsTX1[R14A] and PEG-HsTX1[R14A] are effective in a model of RA and are therefore potential therapeutics for TEM cell-mediated autoimmune diseases. PEG-HsTX1[R14A] has the additional advantages of reduced non-specific adsorption to inert surfaces and enhanced circulating half-life.


Assuntos
Canal de Potássio Kv1.3/antagonistas & inibidores , Peptídeos/farmacologia , Polietilenoglicóis/farmacologia , Bloqueadores dos Canais de Potássio/farmacologia , Venenos de Escorpião/farmacologia , Adulto , Alérgenos/imunologia , Animais , Artrite Experimental/induzido quimicamente , Artrite Experimental/patologia , Artrite Reumatoide/induzido quimicamente , Artrite Reumatoide/patologia , Linhagem Celular , Células Cultivadas , Feminino , Humanos , Hipersensibilidade Tardia/imunologia , Imunomodulação/efeitos dos fármacos , Leucócitos Mononucleares , Camundongos , Pessoa de Meia-Idade , Ovalbumina/imunologia , Peptídeos/química , Peptídeos/farmacocinética , Polietilenoglicóis/química , Polietilenoglicóis/farmacocinética , Bloqueadores dos Canais de Potássio/química , Bloqueadores dos Canais de Potássio/farmacocinética , Ratos , Ratos Endogâmicos Lew , Venenos de Escorpião/química , Venenos de Escorpião/farmacocinética , Baço/citologia , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia , Terpenos , Adulto Jovem
15.
Methods Mol Biol ; 1579: 231-244, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28299740

RESUMO

Matrix metalloproteinases (MMPs) represent more than 20 zinc-containing endopeptidases that cleave internal peptide bonds, leading to protein degradation. They play a critical role in many physiological cell functions, including tissue remodeling, embryogenesis, and angiogenesis. They are also involved in the pathogenesis of a vast array of diseases, including but not limited to systemic inflammation, various cancers, and cardiovascular, neurological, and autoimmune diseases. Here, we describe gel zymography to detect MMPs in cell and tissue samples and in cell culture supernatants.


Assuntos
Eletroforese em Gel de Poliacrilamida/métodos , Metaloproteinases da Matriz/análise , Animais , Células Cultivadas , Humanos
16.
Cell Death Dis ; 7(10): e2426, 2016 10 20.
Artigo em Inglês | MEDLINE | ID: mdl-27763639

RESUMO

Myoblasts are mononucleated precursors of myofibers; they persist in mature skeletal muscles for growth and regeneration post injury. During myotonic dystrophy type 1 (DM1), a complex autosomal-dominant neuromuscular disease, the differentiation of skeletal myoblasts into functional myotubes is impaired, resulting in muscle wasting and weakness. The mechanisms leading to this altered differentiation are not fully understood. Here, we demonstrate that the calcium- and voltage-dependent potassium channel, KCa1.1 (BK, Slo1, KCNMA1), regulates myoblast proliferation, migration, and fusion. We also show a loss of plasma membrane expression of the pore-forming α subunit of KCa1.1 in DM1 myoblasts. Inhibiting the function of KCa1.1 in healthy myoblasts induced an increase in cytosolic calcium levels and altered nuclear factor kappa B (NFκB) levels without affecting cell survival. In these normal cells, KCa1.1 block resulted in enhanced proliferation and decreased matrix metalloproteinase secretion, migration, and myotube fusion, phenotypes all observed in DM1 myoblasts and associated with disease pathogenesis. In contrast, introducing functional KCa1.1 α-subunits into DM1 myoblasts normalized their proliferation and rescued expression of the late myogenic marker Mef2. Our results identify KCa1.1 channels as crucial regulators of skeletal myogenesis and suggest these channels as novel therapeutic targets in DM1.


Assuntos
Diferenciação Celular , Movimento Celular , Subunidades alfa do Canal de Potássio Ativado por Cálcio de Condutância Alta/metabolismo , Mioblastos Esqueléticos/citologia , Mioblastos Esqueléticos/metabolismo , Cálcio/metabolismo , Fusão Celular , Membrana Celular/metabolismo , Proliferação de Células , Células Cultivadas , Humanos , Espaço Intracelular/metabolismo , Metaloproteinase 2 da Matriz/metabolismo , Fibras Musculares Esqueléticas/citologia , Fibras Musculares Esqueléticas/metabolismo , Distrofia Miotônica/patologia , NF-kappa B/metabolismo
17.
Sci Rep ; 6: 33808, 2016 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-27654170

RESUMO

Autoimmune diseases mediated by a type of white blood cell-T lymphocytes-are currently treated using mainly broad-spectrum immunosuppressants that can lead to adverse side effects. Antioxidants represent an alternative approach for therapy of autoimmune disorders; however, dietary antioxidants are insufficient to play this role. Antioxidant carbon nanoparticles scavenge reactive oxygen species (ROS) with higher efficacy than dietary and endogenous antioxidants. Furthermore, the affinity of carbon nanoparticles for specific cell types represents an emerging tactic for cell-targeted therapy. Here, we report that nontoxic poly(ethylene glycol)-functionalized hydrophilic carbon clusters (PEG-HCCs), known scavengers of the ROS superoxide (O2•-) and hydroxyl radical, are preferentially internalized by T lymphocytes over other splenic immune cells. We use this selectivity to inhibit T cell activation without affecting major functions of macrophages, antigen-presenting cells that are crucial for T cell activation. We also demonstrate the in vivo effectiveness of PEG-HCCs in reducing T lymphocyte-mediated inflammation in delayed-type hypersensitivity and in experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis. Our results suggest the preferential targeting of PEG-HCCs to T lymphocytes as a novel approach for T lymphocyte immunomodulation in autoimmune diseases without affecting other immune cells.

18.
Burns ; 42(8): 1693-1698, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27633687

RESUMO

INTRODUCTION: Morbidity and mortality from venous thrombo-embolism (VTE) remains a significant problem for trauma and medical patients and there are established guidelines for prophylaxis in these patients. However, the efficacy and safety of VTE prophylaxis in thermally injured patients continue to be elusive as it has never been studied in a prospective, randomized fashion. Selective use of VTE prophylaxis, for high risk patients, is practiced by some burn units even if objective evidence is lacking for majority of risk factors enunciated in burn patients. Differing demographics and wound management techniques are other confounding factors mandating more prospective studies to evaluate the need and role of chemoprophylaxis for deep vein thrombosis (DVT) prevention in burn patients. Ours is the first prospective, randomized, controlled study which seeks to identify risk factors for DVT in our patients, and evaluate the role of routine chemoprophylaxis and its complications. METHODS: The study design (sample size, inclusion/exclusion criteria, randomization, methodology and statistical methods) is detailed in part-1 of this two part manuscript. RESULTS: Doppler ultrasound (DUS) identified DVT in four out of 50 patients (8% incidence) forming the control group. DVT was not detected in any of the patients on prophylaxis (0% incidence). This difference was found to be statistically significant (p value-0.021). Patients with DVT had significantly higher %TBSA, prolonged immobility and a longer duration of stay as compared to patients without DVT in the control group. Only one patient on enoxaparin prophylaxis developed mild epistaxis which resolved spontaneously. Fifteen patients died during the study out of which two had DVT but none showed autopsy evidence of pulmonary embolism. CONCLUSION: With a moderate risk of developing DVT (8%) and a complication rate of only 2% with chemoprophylaxis, we feel that routine prophylaxis has the potential to decrease the incidence of VTE, without associated complications, in the moderate to high risk category.


Assuntos
Queimaduras/terapia , Enoxaparina/uso terapêutico , Fibrinolíticos/uso terapêutico , Tempo de Internação/estatística & dados numéricos , Limitação da Mobilidade , Trombose Venosa/prevenção & controle , Adolescente , Adulto , Superfície Corporal , Queimaduras/complicações , Gerenciamento Clínico , Epistaxe/induzido quimicamente , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Fatores de Tempo , Índices de Gravidade do Trauma , Ultrassonografia Doppler , Trombose Venosa/complicações , Trombose Venosa/diagnóstico por imagem , Adulto Jovem
19.
Burns ; 42(8): 1686-1692, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27639819

RESUMO

INTRODUCTION: The high prevalence of deep vein thrombosis (DVT) reported in prospective studies and the unreliability of clinical diagnosis mandates prospective screening for DVT in burn patients. Our study seeks to compare D-dimer and Doppler ultrasound (DUS) in search for a practical, inexpensive and a reliable screening tool. METHODS: One hundred burn patients (inclusion criteria: 30-60% TBSA burn, >18 years of age, admitted within 48h of burn) were computer randomized into two equal groups. The study (prophylaxis) group received low molecular weight heparin (LMWH) (0.5mg/kg, twice daily-max 60mg/day) from day one, till discharge. Screening D-dimer assays and DUS of the lower extremities were performed on all 100 patients on day five, and then weekly, till discharge. RESULTS: Signs and symptoms simulating DVT (pain, swelling, redness, warmth, positive Homans' and Moses' sign) were present in majority of patients with lower limb burns. 43/50 patients (86%) in the control group and 38/50 patients (76%) in the study (prophylaxis) group had positive D-dimer values (>0.5µg/ml) on the 5th post-burn day. D-dimer was positive in all the four patients identified with DVT. However, only 4/100 patients enrolled in the study demonstrated DVT on DUS. Thus, the specificity of the D-dimer assay was only 20% with a positive predictive value of 5%. Absolute D-dimer values were found to have no correlation to the extent of burns. CONCLUSION: We conclude that D-dimer is not a useful screening tool for DVT in burns contrary to its accepted value in general trauma and medical patients.


Assuntos
Queimaduras/terapia , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Trombose Venosa/diagnóstico por imagem , Adolescente , Adulto , Superfície Corporal , Queimaduras/complicações , Queimaduras/metabolismo , Gerenciamento Clínico , Enoxaparina/uso terapêutico , Feminino , Fibrinolíticos/uso terapêutico , Humanos , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Sensibilidade e Especificidade , Índices de Gravidade do Trauma , Ultrassonografia Doppler , Trombose Venosa/complicações , Trombose Venosa/metabolismo , Trombose Venosa/prevenção & controle , Adulto Jovem
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