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1.
Clin Pharmacol Ther ; 108(5): 995-1002, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32236953

RESUMO

Treatment with licogliflozin, a dual sodium-glucose co-transporter (SGLT)1/2-inhibitor, is associated with increased stool frequency and loose stools, attributed to SGLT1 inhibition. To investigate the effect of carbohydrate content and supplements on licogliflozin-induced stools, a randomized, open-label, two-part (N = 24/part), three-period crossover study was carried out in overweight or obese adults. Significantly higher (P < 0.01) change from baseline in 3-day total number of bowel movements was observed following 3 days of licogliflozin treatment (50 mg q.d.) together with a 50% carbohydrate meal compared with a 25% and 0% carbohydrate meal. The number of stools with Bristol Stool Chart score of 6 or 7 was also significantly lower following a 0% carbohydrate meal. Supplementation with psyllium 6 g or calcium carbonate 1 g had no effect on stool changes following treatment. Licogliflozin was generally safe and well-tolerated. Loose stool associated with licogliflozin treatment and ingestion of meals can be managed by reducing the carbohydrate content of meals taken with licogliflozin.


Assuntos
Anidridos/uso terapêutico , Defecação/efeitos dos fármacos , Diarreia/prevenção & controle , Dieta com Restrição de Carboidratos , Carboidratos da Dieta/administração & dosagem , Interações Alimento-Droga , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Sorbitol/análogos & derivados , Adulto , Anidridos/efeitos adversos , Desjejum , Estudos Cross-Over , Diarreia/induzido quimicamente , Diarreia/fisiopatologia , Carboidratos da Dieta/efeitos adversos , Suplementos Nutricionais , Feminino , Humanos , Masculino , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Sorbitol/efeitos adversos , Sorbitol/uso terapêutico , Fatores de Tempo , Resultado do Tratamento , Estados Unidos
2.
Am J Perinatol ; 36(13): 1382-1386, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-30620942

RESUMO

OBJECTIVE: Intravenous lipid infusions improve both short- and long-term outcomes of premature neonates. However, prolonged infusion of lipids has been implicated in the development of parenteral nutrition-associated cholestasis (PNAC). We speculated that the multicomponent SMOFlipid would be hepatoprotective against PNAC. STUDY DESIGN: This is a retrospective review comparing the incidence and severity of direct hyperbilirubinemia in preterm infants <1,500 g who were hospitalized for a minimum of 2 weeks during a 20-month period in which all preterm infants on total parenteral nutrition (TPN) received fat as Lipofundin with the following 20-month period in which all preterm infants on TPN received SMOFlipid. RESULTS: Infants in the SMOFlipid period had a lower incidence of PNAC (6 vs. 13%; p = 0.022), lower peak direct bilirubin levels (3.2 vs. 7.1 mg/dL; p = 0.018), and a shorter length of stay (51 vs. 60 days; p = 0.019). The relative risk of developing direct hyperbilirubinemia during the Lipofundin period was 2.22 (1.1-4.3) as compared with period 1; p = 0.018; NNT-14. CONCLUSION: SMOFlipid was hepatoprotective in our population of preterm neonates <1,500 g receiving long-term TPN as compared with those receiving Lipofundin, despite similar levels of exposure to both intravenous lipid load and duration in the two groups.


Assuntos
Colestase/prevenção & controle , Emulsões Gordurosas Intravenosas/uso terapêutico , Óleos de Peixe/uso terapêutico , Hiperbilirrubinemia Neonatal/prevenção & controle , Doenças do Prematuro/prevenção & controle , Azeite de Oliva/uso terapêutico , Nutrição Parenteral Total/efeitos adversos , Fosfolipídeos/efeitos adversos , Sorbitol/efeitos adversos , Óleo de Soja/uso terapêutico , Triglicerídeos/uso terapêutico , Colestase/etiologia , Combinação de Medicamentos , Emulsões Gordurosas Intravenosas/efeitos adversos , Feminino , Humanos , Hiperbilirrubinemia Neonatal/epidemiologia , Hiperbilirrubinemia Neonatal/etiologia , Incidência , Recém-Nascido , Recém-Nascido Prematuro , Masculino , Fosfolipídeos/uso terapêutico , Estudos Retrospectivos , Sorbitol/uso terapêutico
3.
Trials ; 20(1): 808, 2019 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-31888740

RESUMO

BACKGROUND: Home parenteral nutrition (HPN) is a life-preserving therapy for patients with chronic intestinal failure (CIF) indicated for patients who cannot achieve their nutritional requirements by enteral intake. Intravenously administered lipid emulsions (ILEs) are an essential component of HPN, providing energy and essential fatty acids, but can become a risk factor for intestinal-failure-associated liver disease (IFALD). In HPN patients, major effort is taken in the prevention of IFALD. Novel ILEs containing a proportion of omega-3 polyunsaturated fatty acids (n-3 PUFA) could be of benefit, but the data on the use of n-3 PUFA in HPN patients are still limited. METHODS/DESIGN: The HOME study is a prospective, randomized, controlled, double-blind, multicenter, international clinical trial conducted in European hospitals that treat HPN patients. A total of 160 patients (80 per group) will be randomly assigned to receive the n-3 PUFA-enriched medium/long-chain triglyceride (MCT/LCT) ILE (Lipidem/Lipoplus® 200 mg/ml, B. Braun Melsungen AG) or the MCT/LCT ILE (Lipofundin® MCT/LCT/Medialipide® 20%, B. Braun Melsungen AG) for a projected period of 8 weeks. The primary endpoint is the combined change of liver function parameters (total bilirubin, aspartate transaminase and alanine transaminase) from baseline to final visit. Secondary objectives are the further evaluation of the safety and tolerability as well as the efficacy of the ILEs. DISCUSSION: Currently, there are only very few randomized controlled trials (RCTs) investigating the use of ILEs in HPN, and there are very few data at all on the use of n-3 PUFAs. The working hypothesis is that n-3 PUFA-enriched ILE is safe and well-tolerated especially with regard to liver function in patients requiring HPN. The expected outcome is to provide reliable data to support this thesis thanks to a considerable number of CIF patients, consequently to broaden the present evidence on the use of ILEs in HPN. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT03282955. Registered on 14 September 2017.


Assuntos
Emulsões Gordurosas Intravenosas/uso terapêutico , Ácidos Graxos Ômega-3/administração & dosagem , Síndromes de Malabsorção/terapia , Nutrição Parenteral no Domicílio/métodos , Fosfolipídeos/uso terapêutico , Sorbitol/uso terapêutico , Triglicerídeos/administração & dosagem , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Alanina Transaminase/sangue , Aspartato Aminotransferases/sangue , Bilirrubina/sangue , Método Duplo-Cego , Combinação de Medicamentos , Emulsões Gordurosas Intravenosas/efeitos adversos , Feminino , Humanos , Testes de Função Hepática/métodos , Síndromes de Malabsorção/sangue , Masculino , Pessoa de Meia-Idade , Fosfolipídeos/efeitos adversos , Estudos Prospectivos , Sorbitol/efeitos adversos , Resultado do Tratamento , Adulto Jovem
4.
Kidney Int ; 94(3): 524-535, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30045814

RESUMO

Multiple large clinical trials have shown that sodium-glucose cotransporter (SGLT) 2 inhibitors reduce the risk of renal events. However, the mechanism responsible for this outcome remains unknown. Here we investigated the effects of the SGLT2 inhibitor luseogliflozin on the development of renal fibrosis after renal ischemia/reperfusion injury in non-diabetic mice. Luseogliflozin significantly suppressed development of renal fibrosis, prevented peritubular capillary congestion/hemorrhage, attenuated CD31-positive cell loss, suppressed hypoxia, and increased vascular endothelial growth factor (VEGF)-A expression in the kidney after ischemia/reperfusion injury. Luseogliflozin failed to induce the above-mentioned protection in animals co-treated with sunitinib, a VEGF receptor inhibitor. Additionally, luseogliflozin reduced glucose uptake and increased VEGF-A expression in the kidneys of glucose transporter 2 (GLUT2)-downregulated mice following ischemia/reperfusion and in GLUT2-knock-down cells compared with those in normal controls. Withdrawal of glucose from cultured medium, to halt glucose uptake, remarkably increased VEGF-A expression and reversed the luseogliflozin-induced increase in VEGF-A expression in the proximal tubular cells. Thus, luseogliflozin prevented endothelial rarefaction and subsequent renal fibrosis after renal ischemia/reperfusion injury through a VEGF-dependent pathway induced by the dysfunction of proximal tubular glucose uptake in tubules with injury-induced GLUT2 downregulation.


Assuntos
Injúria Renal Aguda/tratamento farmacológico , Túbulos Renais Proximais/patologia , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia , Transportador 2 de Glucose-Sódio/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/patologia , Inibidores da Angiogênese/farmacologia , Animais , Glicemia/metabolismo , Capilares/efeitos dos fármacos , Capilares/metabolismo , Capilares/patologia , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Fibrose , Técnicas de Silenciamento de Genes , Transportador de Glucose Tipo 2/genética , Transportador de Glucose Tipo 2/metabolismo , Humanos , Túbulos Renais Proximais/irrigação sanguínea , Túbulos Renais Proximais/efeitos dos fármacos , Túbulos Renais Proximais/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Receptores de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores , Traumatismo por Reperfusão/complicações , Traumatismo por Reperfusão/patologia , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Sorbitol/análogos & derivados , Sorbitol/farmacologia , Sorbitol/uso terapêutico , Sunitinibe/farmacologia , Resultado do Tratamento
5.
Arch Dermatol Res ; 309(4): 265-274, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28283753

RESUMO

The red maple (Acer rubrum) is a rich source of phenolic compounds which possess galloyl groups attached to different positions of a 1,5-anhydro-D-glucitol core. While these glucitol-core containing gallotannins (GCGs) have reported anti-oxidant and anti-glycative effects, they have not yet been evaluated for their cosmetic applications. Herein, the anti-tyrosinase and anti-melanogenic effects of a proprietary phenolic-enriched red maple leaves extract [Maplifa™; contains ca. 45% ginnalin A (GA) along with other GCGs] were investigated using enzyme and cellular assays. The GCGs showed anti-tyrosinase activity with IC50 values ranging from 101.4 to 1047.3 µM and their mechanism of tyrosinase inhibition (using GA as a representative GCG) was evaluated by chelating and computational/modeling studies. GA reduced melanin content in murine melanoma B16F10 cells by 79.1 and 56.7% (at non-toxic concentrations of 25 and 50 µM, respectively), and its mechanisms of anti-melanogenic effects were evaluated by using methods including fluorescent probe (DCF-DA), real-time PCR, and western blot experiments. These data indicated that GA was able to: (1) reduce the levels of reactive oxygen species, (2) down-regulate the expression of MITF, TYR, TRP-1, and TRP-2 gene levels in a time-dependent manner, and (3) significantly reduce protein expression of the TRP-2 gene. Therefore, the anti-melanogenic effects of red maple GCGs warrant further investigation of this proprietary natural product extract for potential cosmetic applications.


Assuntos
Acer/imunologia , Taninos Hidrolisáveis/uso terapêutico , Oxirredutases Intramoleculares/metabolismo , Melanócitos/efeitos dos fármacos , Extratos Vegetais/uso terapêutico , Neoplasias Cutâneas/tratamento farmacológico , Sorbitol/uso terapêutico , Animais , Proliferação de Células/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Taninos Hidrolisáveis/química , Oxirredutases Intramoleculares/genética , Melaninas/metabolismo , Melanócitos/fisiologia , Melanoma Experimental , Camundongos , Fenóis/química , Extratos Vegetais/química , Folhas de Planta , Sorbitol/química
6.
Acta Paediatr ; 105(6): 689-94, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26948070

RESUMO

AIM: A well-documented, clinically proven per rectum treatment for childhood constipation is needed. This phase two clinical trial evaluated the efficacy of suppositories containing free fatty acids (FFA) compared with Klyx docusate sodium and sorbitol enemas. METHODS: A randomised, controlled, single-blind study was undertaken on 77 children aged between one and 17 who presented to an emergency department in Iceland and were diagnosed with constipation. In stage one, 23 patients were randomised to receive lower dose FFA suppositories or Klyx (n = 33). In stage two, 21 different patients were randomised to receive higher dose suppositories and compared with the same Klyx control subjects. RESULTS: The suppositories were effective at bowel emptying in 39% of the group who received the lower FFA doses and 81% of the group receiving higher doses, compared with 88% in the Klyx control group. Symptom relief was obtained in 30% of the group receiving the lower doses and 71% of the group receiving the higher doses, compared with 73% in the control group. CONCLUSION: The higher dose FFA suppositories were as effective as the Klyx enemas with regard to bowel emptying and symptom relief and might provide an important and less invasive alternative for childhood constipation.


Assuntos
Constipação Intestinal/tratamento farmacológico , Defecação/efeitos dos fármacos , Ácidos Graxos não Esterificados/uso terapêutico , Administração Retal , Catárticos/uso terapêutico , Criança , Pré-Escolar , Ácido Dioctil Sulfossuccínico/uso terapêutico , Enema , Ácidos Graxos não Esterificados/farmacologia , Feminino , Humanos , Lactente , Masculino , Sorbitol/uso terapêutico , Supositórios , Tensoativos/uso terapêutico
7.
Adv Nutr ; 5(1): 82-91, 2014 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-24425726

RESUMO

Parenteral nutrition (PN) is a life-saving nutritional support for a large population of hospitalized infants, and lipids make a substantial contribution to their energy and essential fatty acid (FA) needs. A challenge in the care of these infants is that their metabolic needs require prolonged PN support that increases the risk of PN-associated liver disease (PNALD). In recent years, the emergence of new parenteral lipid emulsions containing different source lipids and FA profiles has created nutritional alternatives to the first-generation, soybean oil-based lipid emulsion Intralipid. The limited U.S. introduction of the new-generation fish-oil emulsion Omegaven has generated promising results in infants with PNALD and spawned a renewed interest in how PN and lipid emulsions, in particular, contribute to this disease. Studies suggest that the lipid load and constituents, such as specific FAs, ratio of n-3 (ω-3) to n-6 (ω-6) long-chain polyunsaturated FAs, phytosterols, and vitamin E content, may be involved. There is an existing literature describing the molecular mechanisms whereby these specific nutrients affect hepatic metabolism and function via lipid and bile acid sensing nuclear receptors, such as peroxisome proliferator-activated receptor α, liver X receptor, and farnesoid X receptor, yet virtually no information as to how they interact and modulate liver function in the context of PN in pediatric patients or animal models. This article will review the recent development of parenteral lipid emulsions and their influence on PNALD and highlight some of the emerging molecular mechanisms that may explain the effects on liver function and disease.


Assuntos
Colestase Intra-Hepática/prevenção & controle , Emulsões Gordurosas Intravenosas/uso terapêutico , Ácidos Graxos Ômega-3/uso terapêutico , Doenças do Prematuro/prevenção & controle , Estresse Oxidativo , Nutrição Parenteral Total/efeitos adversos , Colestase Intra-Hepática/etiologia , Colestase Intra-Hepática/metabolismo , Colestase Intra-Hepática/terapia , Congressos como Assunto , Combinação de Medicamentos , Emulsões Gordurosas Intravenosas/efeitos adversos , Emulsões Gordurosas Intravenosas/metabolismo , Ácidos Graxos Ômega-3/efeitos adversos , Ácidos Graxos Ômega-3/metabolismo , Fatores de Crescimento de Fibroblastos/metabolismo , Óleos de Peixe/efeitos adversos , Óleos de Peixe/metabolismo , Óleos de Peixe/uso terapêutico , Humanos , Recém-Nascido de Baixo Peso , Recém-Nascido , Recém-Nascido Prematuro , Doenças do Prematuro/etiologia , Doenças do Prematuro/metabolismo , Doenças do Prematuro/terapia , Fígado/imunologia , Fígado/metabolismo , Fosfolipídeos/efeitos adversos , Fosfolipídeos/metabolismo , Fosfolipídeos/uso terapêutico , Óleos de Plantas/efeitos adversos , Óleos de Plantas/metabolismo , Óleos de Plantas/uso terapêutico , Receptores Citoplasmáticos e Nucleares/metabolismo , Transdução de Sinais , Sorbitol/efeitos adversos , Sorbitol/metabolismo , Sorbitol/uso terapêutico , Óleo de Soja/efeitos adversos , Óleo de Soja/metabolismo , Óleo de Soja/uso terapêutico , Receptor 4 Toll-Like/metabolismo , Triglicerídeos , Vitamina E/metabolismo
8.
G Ital Dermatol Venereol ; 147(6 Suppl 1): 1-8, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23007324

RESUMO

AIM: Pityriasis alba (PA) is a skin disorder characterized by finely scaly, hypopigmented patches, typical of childhood, that also represents an atopic dermatitis (AD) minor sign according to Hanifin and Rajka criteria. It may be isolated or associated with AD representing, sometimes an atypical manifestation of AD during the long-term follow-up of the disease. Aim of the study was to evaluate of the efficacy and tolerability of AR-GG27® (sorbityl furfural palmitate) cream in the treatment of childhood mild or moderate AD associated with PA. METHODS: The trial is a single center, double-blind, randomized, placebo-controlled study. The study included patients of both sexes, aged between two months and 15 years, suffering from mild and moderate AD always associated with PA. Xerosis was present in all patients. The treatment with topical steroids or topical calcineurin inhibitors (TIMs) had to be suspended for at least 15 days. Any systemic therapy and phototherapy or sun exposure were withdrawn at least 30 days before. Emollients were stopped at least seven days before. During the trial, no other local or systemic treatments were allowed, as well as sun exposure. Patients affected by AD with viral, bacterial or fungal overinfection or patients with diabetes mellitus, severe systemic diseases or intolerance to one or more components of the product were excluded. The primary endpoint was the evaluation of the average change in the Investigator Global Assessment (IGA) after 15 and 30 days of treatment. The second endpoint was the evaluation of severity of three different clinical signs: erythema, excoriation desquamation, using a subjective five-point scale. Changes in pruritus severity was also considered during the entire period of treatment, through the use of a Visual Analogue Scale (VAS). A P<0.05, two tailed was considered as statistically significant. RESULTS: After 15 and 30 days there was a statistically significant difference in the group treated with AR-GG27®, compared to the placebo (respectively, P=0.0007 and P=0.005). After 15 days of treatment, itching was clearly reduced in AR-GG27® treated group compared with the placebo, both in the study population (P=0.01) and in patients where the symptom was present from the beginning (P=0.05). CONCLUSION: AR-GG27® showed a beneficial action associated with high compliance and tolerability in dermatological skin conditions characterized by inflammation and tissue oxidative stress in children, as PA with mild and moderate AD.


Assuntos
Dermatite Atópica/tratamento farmacológico , Fármacos Dermatológicos/administração & dosagem , Furaldeído/administração & dosagem , Hipopigmentação/tratamento farmacológico , Palmitatos/administração & dosagem , Pitiríase/tratamento farmacológico , Sorbitol/administração & dosagem , Administração Cutânea , Adolescente , Algoritmos , Criança , Pré-Escolar , Dermatite Atópica/complicações , Dermatite Atópica/diagnóstico , Fármacos Dermatológicos/uso terapêutico , Diagnóstico Diferencial , Método Duplo-Cego , Combinação de Medicamentos , Feminino , Seguimentos , Humanos , Hipopigmentação/diagnóstico , Hipopigmentação/etiologia , Lactente , Masculino , Palmitatos/síntese química , Palmitatos/uso terapêutico , Pitiríase/classificação , Pitiríase/complicações , Pitiríase/diagnóstico , Estudos de Amostragem , Índice de Gravidade de Doença , Sorbitol/síntese química , Sorbitol/uso terapêutico , Resultado do Tratamento
9.
Clin J Am Soc Nephrol ; 5(10): 1723-6, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20798253

RESUMO

Sodium polystyrene sulfonate (SPS) potassium binding resins increase colonic potassium excretion and are approved by the U.S. Food and Drug Administration (FDA) for the treatment of hyperkalemia. In 2009, the FDA recommended that sorbitol, a cathartic often given with SPS to prevent obstipation, not be added to SPS powder because of associated colonic necrosis. A premixed oral suspension of SPS in 33% sorbitol was not included in this warning. SPS resins increase stool potassium excretion in normokalemic subjects, but proportionately more potassium is excreted due to cathartics when the two are combined. In hyperkalemic patients, oral SPS mixed in water significantly decreases serum potassium within 24 hours. SPS/sorbitol-associated colonic necrosis is most commonly seen in patients who have received enemas in the setting of recent abdominal surgery, bowel injury, or intestinal dysfunction. It is a rare event, on the order of 0.2 to 0.3%, almost exclusively present in patients at risk. The agent most likely associated with colonic necrosis is 70% sorbitol, and animal data support that etiology. There is very little data to suggest that oral SPS given with 33% sorbitol (in the premixed form) or SPS powder in water orally or as an enema causes colonic necrosis. SPS ion-exchange resins are the only agents, other than dialysis and diuretics, available to increase potassium excretion in hyperkalemia, and when used appropriately, they appear to be clinically effective and reasonably safe.


Assuntos
Catárticos/uso terapêutico , Resinas de Troca de Cátion/uso terapêutico , Hiperpotassemia/tratamento farmacológico , Poliestirenos/uso terapêutico , Potássio/sangue , Sorbitol/uso terapêutico , Animais , Catárticos/efeitos adversos , Resinas de Troca de Cátion/efeitos adversos , Colo/efeitos dos fármacos , Colo/patologia , Combinação de Medicamentos , Sinergismo Farmacológico , Medicina Baseada em Evidências , Fezes/química , Humanos , Hiperpotassemia/sangue , Necrose , Poliestirenos/efeitos adversos , Guias de Prática Clínica como Assunto , Medição de Risco , Sorbitol/efeitos adversos , Resultado do Tratamento , Estados Unidos , United States Food and Drug Administration
10.
Biol Pharm Bull ; 32(10): 1803-8, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19801848

RESUMO

The authors previously reported that costunolide, an active compound isolated from the stem bark of Magnolia sieboldii, induced apoptosis via reactive oxygen species (ROS) and Bcl-2-dependent mitochondrial permeability transition in human leukemia cells. In the present study, the authors investigated whether mitogen-activated protein kinases (MAPKs) are involved in the costunolide-induced apoptosis in human promonocytic leukemia U937 cells. Treatment with costunolide resulted in the significant activation of c-Jun N-terminal kinase (JNK), but not of extracellular-signal-related kinase (ERK1/2) or p38. In vitro kinase assays showed that JNK activity was low in untreated cells but increased dramatically after 30 min of costunolide treatment. U937 cells co-treated with costunolide and sorbitol, a JNK activator, exhibited higher levels of cell death. In addition, inhibition of the JNK pathway using a dominant-negative mutation of c-jun and JNK inhibitor SP600125, significantly prevented costunolide-induced apoptosis. Furthermore, pretreatment with the antioxidant NAC (N-acetyl-L-cysteine) blocked the costunolide-stimulated activation of JNK while the overexpression of Bcl-2 failed to reverse JNK activation. Pretreatment with SP600125 recovered the costunolide-suppressed Bcl-2 expression. These results indicate that costunolide-induced JNK activation acts downstream of ROS but upstream of Bcl-2, and suggest that ROS-mediated JNK activation plays a key role in costunolide-induced apoptosis. Moreover, the administration of costunolide (intraperitoneally once a day for 7 d) significantly suppressed tumor growth and increased survival in 3LL Lewis lung carcinoma-bearing model.


Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Apoptose/efeitos dos fármacos , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Leucemia/tratamento farmacológico , Magnolia/química , Extratos Vegetais/uso terapêutico , Sesquiterpenos/uso terapêutico , Acetilcisteína/farmacologia , Animais , Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Carcinoma Pulmonar de Lewis/tratamento farmacológico , Quimioterapia Combinada , Sequestradores de Radicais Livres/farmacologia , Humanos , Leucemia/enzimologia , Leucemia/patologia , Camundongos , Fitoterapia , Casca de Planta , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Caules de Planta , Inibidores de Proteínas Quinases/farmacologia , Proteínas Tirosina Quinases/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Sesquiterpenos/isolamento & purificação , Sesquiterpenos/farmacologia , Transdução de Sinais/efeitos dos fármacos , Sorbitol/farmacologia , Sorbitol/uso terapêutico , Células U937
11.
J Pak Med Assoc ; 59(11): 764-8, 2009 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-20361676

RESUMO

OBJECTIVE: To compare the efficacy, tolerability and compliance of oral iron preparations (iron edetate and iron polymaltose complex) with each other and with intramuscular iron sorbitol in iron deficiency anaemia in children. METHODS: A Randomized Controlled Trial (RCT) was carried out at the Paediatric Department of Combined Military Hospital (CMH) from January 2006 to December 2007. In total 146 children, up to 12 years age having haemoglobin (Hb%) less than 8 gm% were included. They were randomly distributed into three groups. Group A (64 cases) received oral sodium iron edetate (SIE), Group B (40 cases) received oral iron polymaltose complex (IPC) and group C (42cases) received intramuscular iron sorbitol (IS) in recommended dosages. Rise in Hb% > 10gm% was kept as desired target. Maximum duration of treatment planned was 2 weeks for parenteral iron (group C) and 12 weeks for oral iron (groups A and B). Haematological parameters- Hb%, mean corpuscular volum (MCV), mean corpuscuar haemoglobin (MCH), mean corpuscular haemoglobin concentration (MCHC) were measured at induction followed at 2 weeks, 4 weeks, 8 weeks and 12 weeks after start of treatment. Compliance and drop out rates were determined on each visit. Data was analyzed using SPSS version10.ANOVA was used to analyze difference in rise in Hb% at various intervals. RESULTS: Statistically significant increase in mean Hb%, MCV, MCHC after 02 weeks was observed in group C (IS). Rise in these parametes became significant in group A (SIE) and B (IPC) after 04 weeks. Peristent rise was observed in oral groups at 08 and 12 weeks. Rise in Hb% was much faster in group C (IS). It took 2 weeks to achieve mean Hb% > 10gm% and compliance rate was 40.5%, while to achieve same target, duration required was 8 weeks in group A (SIE) and 12 weeks in group B (IPC) and compliance rate was 39% and 30% respectively. Adverse effects were much more common with group A (SIE) as compared to other two groups. CONCLUSION: Intramuscular iron sorbitol is a reliable and faster alternative modality for treatment of iron deficiency anaemia in children. Short duration of treatment, sure rise in Hb% and minimal adverse effects improve compliance as compared to oral preparations. Among oral preparations, rise in Hb% is more rapid with iron edetae. While IPC gives relatively slower rise in Hb% but side effects are much less as compared to SIE.


Assuntos
Anemia Ferropriva/tratamento farmacológico , Ácido Cítrico/uso terapêutico , Compostos Férricos/uso terapêutico , Quelantes de Ferro/uso terapêutico , Sorbitol/uso terapêutico , Administração Oral , Análise de Variância , Criança , Pré-Escolar , Ácido Cítrico/administração & dosagem , Combinação de Medicamentos , Ácido Edético/administração & dosagem , Ácido Edético/uso terapêutico , Feminino , Compostos Férricos/administração & dosagem , Humanos , Injeções , Masculino , Sorbitol/administração & dosagem , Resultado do Tratamento
12.
Eur J Clin Nutr ; 62(9): 1116-22, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-17538537

RESUMO

OBJECTIVE: Fish oil (FO) may attenuate the inflammatory response after major surgery such as abdominal aortic aneurysm (AAA) surgery. We aimed at evaluating the clinical impact and safety aspects of a FO containing parenteral nutrition (PN) after AAA surgery. METHODS: Intervention consisted in 4 days of either standard (STD: Lipofundin medium-chain triglyceride (MCT): long-chain triglyceride (LCT)50%-MCT50%) or FO containing PN (FO: Lipoplus: LCT40%-MCT50%-FO10%). Energy target were set at 1.3 times the preoperative resting energy expenditure by indirect calorimetry. Blood sampling on days 0, 2, 3 and 4. Glucose turnover by the (2)H(2)-glucose method. Muscle microdialysis. CLINICAL DATA: maximal daily T degrees, intensive care unit (ICU) and hospital stay. RESULTS: Both solutions were clinically well tolerated, without any differences in laboratory safety parameters, inflammatory, metabolic data, or in organ failures. Plasma tocopherol increased similarly; with FO, docosahexaenoic and eicosapentaenoic acid increased significantly by day 4 versus baseline or STD. To increased postoperatively, with a trend to lower values in FO group (P=0.09). After FO, a trend toward shorter ICU stay (1.6+/-0.4 versus 2.3+/-0.4), and hospital stay (9.9+/-2.4 versus 11.3+/-2.7 days: P=0.19) was observed. CONCLUSIONS: Both lipid emulsions were well tolerated. FO-PN enhanced the plasma n-3 polyunsaturated fatty acid content, and was associated with trends to lower body temperature and shorter length of stay.


Assuntos
Aneurisma da Aorta Abdominal/cirurgia , Óleos de Peixe/uso terapêutico , Lipídeos/sangue , Fosfolipídeos/uso terapêutico , Cuidados Pós-Operatórios , Sorbitol/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Glicemia/metabolismo , Temperatura Corporal , Método Duplo-Cego , Combinação de Medicamentos , Feminino , Humanos , Lactatos/metabolismo , Masculino , Microdiálise , Pessoa de Meia-Idade , Músculo Esquelético/metabolismo , Nutrição Parenteral
13.
Pharmacotherapy ; 27(3): 459-63, 2007 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-17316157

RESUMO

Dofetilide, a class III antiarrhythmic agent, is prescribed for conversion to and maintenance of normal sinus rhythm in patients with persistent atrial fibrillation or atrial flutter. Most antiarrhythmics have significant toxicities such as torsade de pointes, and patients should be closely monitored while receiving antiarrhythmic therapy. However, we know of no reports concerning management of intentional overdose of dofetilide that have been published. We report the case of a 33-year-old man who was treated for ingestion of approximately 5 mg of dofetilide as a suicide attempt. In addition, he had a known history of cocaine abuse. He came to the emergency department approximately 45 minutes after the ingestion; examination revealed a QTc interval of approximately 570 msec. He was treated with activated charcoal and sorbitol by nasogastric tube and received aggressive supplementation with potassium and magnesium. The patient was monitored by telemetry for several days and responded well. Cardiac toxicity is the utmost concern when treating dofetilide overdose. The mainstay of treatment focuses on supportive care and prevention of drug absorption. Ventricular dysrhythmias or torsade de pointes should be treated according to advanced cardiac life support guidelines.


Assuntos
Antiarrítmicos/toxicidade , Transtornos Relacionados ao Uso de Cocaína , Overdose de Drogas/tratamento farmacológico , Tratamento de Emergência/métodos , Fenetilaminas/toxicidade , Tentativa de Suicídio , Sulfonamidas/toxicidade , Adulto , Carvão Vegetal/uso terapêutico , Monitoramento de Medicamentos , Serviço Hospitalar de Emergência , Humanos , Masculino , Sorbitol/uso terapêutico
14.
J Am Med Dir Assoc ; 6(3 Suppl): S32-4, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-15890292

RESUMO

OBJECTIVE: The objective of this report is to describe a cost-effective strategy for management of constipation in nursing home residents with dementia. DESIGN: We conducted a prospective observational quality improvement study of 41 residents with chronic constipation and receiving an osmotic laxative. Sorbitol was substituted for lactulose. SETTING: The study was conducted at a dementia special care unit at a Veterans Administration hospital. MEASUREMENT: We measured the number and amount of laxative use over a period of 4 weeks that were required to maintain regular bowel function. RESULTS: There was no difference in efficacy of lactulose and sorbitol. Use of additional laxatives was infrequent: Milk of Magnesia on approximately 10% of days/patient, bisacodyl suppository on 2% to 4% of days/patient, and Fleet enema only on 3 occasions. The cost of constipation management using routine administration of sorbitol and as-needed use of other laxatives was 27% to 55% lower than the cost of other constipation management strategies reported in the literature. CONCLUSION: Substitution of sorbitol for lactulose does not change efficacy of the treatment and decreases cost. Regular use of an osmotic laxative avoids the costs and discomforts of rectal laxatives.


Assuntos
Catárticos/economia , Constipação Intestinal/tratamento farmacológico , Demência/complicações , Custos de Medicamentos , Sorbitol/economia , Idoso , Idoso de 80 Anos ou mais , Catárticos/uso terapêutico , Doença Crônica , Constipação Intestinal/complicações , Análise Custo-Benefício , Humanos , Lactulose/economia , Lactulose/uso terapêutico , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Sorbitol/uso terapêutico , Estados Unidos , Veteranos
15.
Int Immunopharmacol ; 3(13-14): 1743-9, 2003 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-14636825

RESUMO

The effects of ferric-sorbitol-citrate and ferric-citrate on the severity of experimental arthritis, TNF-alpha secretion and the immune status were examined in mice. Arthritis was induced by footpad injection of methylated BSA and intraperitoneal injection of Bordetella pertussis. Joint and footpad swelling were measured weekly by a caliper. TNF-alpha serum levels were measured by ELISA. The immune status was determined by the response of mouse lymphocytes to ConA in vitro and by the antigen-presenting cell assay. Experimental arthritis was aggravated by ferric-citrate, whereas ferric-sorbitol-citrate did not promote it. If applied to normal (non-arthritic) mice three times a week for 4 weeks, ferric-sorbitol-citrate stimulated isolated splenocytes to increase production of TNF-alpha, the function of antigen-presenting cells and lymphocyte proliferation in response to ConA in vitro. TNF-alpha production by cultured splenocytes was also stimulated. In mice with antigen-induced arthritis, iron compounds did not additionally stimulate TNF-alpha production. Thus, we have shown that ferric-sorbitol-citrate stimulated TNF-alpha production, antigen-presenting cell activity and cellular immune response. Development of antigen-induced arthritis and TNF-alpha production in arthritic mice were not stimulated.


Assuntos
Artrite Experimental/tratamento farmacológico , Autoimunidade/imunologia , Compostos de Ferro/uso terapêutico , Fator de Necrose Tumoral alfa/imunologia , Animais , Artrite Experimental/induzido quimicamente , Artrite Experimental/imunologia , Autoimunidade/efeitos dos fármacos , Divisão Celular/efeitos dos fármacos , Células Cultivadas , Ácido Cítrico/administração & dosagem , Ácido Cítrico/farmacocinética , Ácido Cítrico/uso terapêutico , Modelos Animais de Doenças , Esquema de Medicação , Combinação de Medicamentos , Compostos Férricos/administração & dosagem , Compostos Férricos/efeitos adversos , Compostos Férricos/farmacocinética , Injeções Intramusculares , Compostos de Ferro/administração & dosagem , Compostos de Ferro/química , Lipopolissacarídeos/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos NOD , Soroalbumina Bovina/administração & dosagem , Soroalbumina Bovina/imunologia , Sorbitol/administração & dosagem , Sorbitol/farmacocinética , Sorbitol/uso terapêutico , Baço/citologia , Baço/efeitos dos fármacos , Timo/citologia , Timo/efeitos dos fármacos , Fator de Necrose Tumoral alfa/efeitos dos fármacos , Fator de Necrose Tumoral alfa/metabolismo
16.
J Toxicol Clin Toxicol ; 37(1): 103-7, 1999.
Artigo em Inglês | MEDLINE | ID: mdl-10078167

RESUMO

BACKGROUND: Ingestion of small amounts of elemental mercury is generally thought to be harmless. However, in 4 previously reported cases, ingested mercury became sequestered in the appendix, causing appendicitis in one. We present a case in which elemental mercury was administered as a Mexican-American folk remedy for abdominal pain and became sequestered in the appendix. CASE REPORT: A 10-year-old Hispanic male presented with 3 days of right-sided abdominal pain, diarrhea, fever, and malaise. On admission, his temperature was 41.5 degrees C and he had right abdominal tenderness. Urinalysis showed 3 WBCs, 9 RBCs, occasional bacteria, and 1+ protein. An abdominal CT scan suggested right focal pyelonephritis, but also showed multiple intraabdominal metallic densities. On further questioning, the family admitted giving him elemental mercury as a remedy for "empacho." He was treated with intravenous ampicillin/sulbactam and gentamicin for a focal pyelonephritis. Because of mercury remaining in the gastrointestinal tract, activated charcoal and sorbitol were given. By hospital day 3, mercury filled the appendix as shown by abdominal radiograph. He was placed in the left lateral decubitus position overnight, and by the next morning, the mercury partially emptied from the appendix. By hospital day 8, his symptoms had resolved and mercury was no longer seen in the appendix. There were only minimal increases in urine mercury levels (18 mg/L). At 5-month follow-up, he has remained asymptomatic.


Assuntos
Apendicite/induzido quimicamente , Apêndice/metabolismo , Medicina Tradicional , Mercúrio/efeitos adversos , Dor Abdominal/tratamento farmacológico , Antídotos/uso terapêutico , Apendicite/metabolismo , Apendicite/fisiopatologia , Catárticos/uso terapêutico , Carvão Vegetal/uso terapêutico , Criança , Humanos , Masculino , Mercúrio/metabolismo , Mercúrio/uso terapêutico , México , Pielonefrite/induzido quimicamente , Pielonefrite/patologia , Sorbitol/uso terapêutico
17.
Acta Odontol Scand ; 56(3): 148-56, 1998 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-9688223

RESUMO

A previous clinical trial showed that long-term use of saliva-stimulating polyol (xylitol and sorbitol) chewing gums was associated with arrest of dental caries in young subjects. After a 20-22-month intervention (when the subjects were 8 years old), a total of 23 primary teeth with extensive dentin caries lesions whose surface in clinical examination was found to be totally rehardened (remineralized) could be removed because the teeth were near their physiologic exfoliation time. These teeth were subjected to histologic, microhardness, and electron microscopic tests. The majority of the specimens had been remineralized from the surface by a non-cellular-mediated process within the remaining collapsed, organic extracellular matrix associated with the remaining dentinal surface. Many of the underlying dentinal tubules were filled with a matrix that had been subsequently mineralized. Dental microanalyses showed that the topmost (outer) 20-microm-thick rehardened layer of the lesions exhibited the highest Ca:P ratio, which leveled off at a depth of approximately 150 microm. The rehardened surface layer (normally <0.1 mm in thickness) was significantly (P < 0.001) harder than sound dentin and nearly as hard as sound enamel. Although the main source of the mineral present in the rehardened layer was most likely of salivary origin, some extracellular remineralization was probably mediated by odontoblasts. The results complete the dinical diagnoses of the original trial and suggest that regular use of polyol chewing gums may induce changes in dentin caries lesions, which in histologic and physiochemical studies show typical characteristics of rehardening and mineralization.


Assuntos
Goma de Mascar , Cárie Dentária/patologia , Dentina/ultraestrutura , Sorbitol/uso terapêutico , Edulcorantes/uso terapêutico , Remineralização Dentária , Dente Decíduo/ultraestrutura , Xilitol/uso terapêutico , Cálcio/análise , Criança , Cárie Dentária/metabolismo , Cárie Dentária/prevenção & controle , Esmalte Dentário/química , Esmalte Dentário/ultraestrutura , Dentina/química , Microanálise por Sonda Eletrônica , Matriz Extracelular/química , Matriz Extracelular/ultraestrutura , Dureza , Humanos , Microscopia Eletrônica de Varredura , Minerais/análise , Odontoblastos/metabolismo , Fósforo/análise , Saliva/química , Esfoliação de Dente , Dente Decíduo/química
18.
Medicentro ; 2(Supl 2)1998.
Artigo em Espanhol | CUMED | ID: cum-20611

RESUMO

Se realizó un ensayo clínico en 100 pacientes con gingivitis crónica adematosa y fibroedematosa en edades de 18 a 31 años. Fueron divididos en dos grupos (estudio y control) de 50 pacientes cada uno y subdivididos en gingivitis leve y moderada. Ambos recibieron el control mecánico de la placa, donde se comprobó la evolución con el índice de Análisis de la Higiene de Love. Al grupo estudio se le indicó, además, los enjuagatorios bucales de Cumbopogon citratus más sorbitol y se investigaron las posibles reacciones adversas. Se afectuaron dos mediciones clínicas: antes del tratamiento y al mes de comienzo del mismo, mediante los criterios del índice gingival, índice de placa y profundidad del sondeo. En ambos grupos disminuyeron las variables y se observaron mejores resultados en el grupo estudio por lo que se comprobó la eficacia de este enjuagatorio en el tratamiento de la gingivitis crónica. No se produjeron reacciones adversas


Assuntos
Gengivite/terapia , Sorbitol/uso terapêutico , Plantas Medicinais
19.
J Appl Toxicol ; 16(4): 317-24, 1996.
Artigo em Inglês | MEDLINE | ID: mdl-8854218

RESUMO

N-Benzyl-D-glucaminedithiocarbamate (BGD), diethyldithiocarbamate (DDTC), dihydroxyethyldithiocarbamate (DHED), trans-1,2-cyclohexanediamine N,N,N',N'-tetraacetic acid (CDTA) and meso-2,3-dimercaptosuccinic acid (DMSA) were studied for their protective effects against the pulmonary toxicity in mice induced by acute exposure to nickel. Nickel injection increased lipid peroxidation, lactate dehydrogenase (LDH) activity and the concentrations of protein, phospholipids (PL) and essential metals such as Ca, Fe and Zn and decreased the reduced glutathione (GSH) concentration and alkaline phosphatase (ALP) activity in the lungs. At 30 min after Ni treatment, DMSA, BGD and DDTC effectively depressed Ni concentration in the lungs. At 24 h after Ni treatment, DMSA and BGD were effective in mobilizing Ni from the lungs. Both DMSA and BGD significantly prevented increases in lipid peroxidation and in the concentrations of PL, Ca, Fe and Zn, and decreases in GSH concentration and ALP activity in the lungs of mice caused by Ni injection. Treatment with DMSA or BGD was more effective than that with other chelating agents in decreasing the pulmonary Ni concentration and preventing other changes caused by acute exposure to Ni, resulting in effective protection against Ni-induced pulmonary damage.


Assuntos
Quelantes/uso terapêutico , Pneumopatias/induzido quimicamente , Pneumopatias/prevenção & controle , Pulmão/efeitos dos fármacos , Níquel/toxicidade , Fosfatase Alcalina/análise , Animais , Líquido da Lavagem Broncoalveolar/química , Ácido Edético/análogos & derivados , Ácido Edético/uso terapêutico , Glutationa/análise , Injeções Intraperitoneais , L-Lactato Desidrogenase/análise , Peroxidação de Lipídeos/efeitos dos fármacos , Pulmão/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos ICR , Níquel/análise , Sorbitol/análogos & derivados , Sorbitol/uso terapêutico , Succímero/uso terapêutico , Tiocarbamatos/uso terapêutico
20.
Nutr Hosp ; 10(2): 74-80, 1995.
Artigo em Espanhol | MEDLINE | ID: mdl-7756393

RESUMO

Among the general complications caused by total parenteral nutrition (TPN), the hematological alterations play an important role, and they have been related to the lipid emulsions. With the objective of studying the influence of two lipid emulsions on the hemocoagulation of patients with TPN, we have done a prospective and double blind study in which 21 patients were randomized into two groups to receive TPN which included lipid emulsions and other components, Group I (n = 10) received a 20% LCT lipid emulsion with the TPN, and group II (n = 11) received a 20% MCT-LCT (50-50) lipid emulsion with the TPN. The following were then studied: activated cephalin time, prothrombin time, percentage of prothrombin time, thrombin and fibrinogen time, hemogram, and proteinogram. The basal values of both groups were similar and after eight days there were no differences in any of the variables when comparing the two groups. We came to the conclusion that both lipid emulsions behaved in a similar fashion, both were clinically well tolerated and neither produced by alteration in hemocoagulation.


Assuntos
Coagulação Sanguínea/efeitos dos fármacos , Emulsões Gordurosas Intravenosas/uso terapêutico , Nutrição Parenteral Total/efeitos adversos , Fosfolipídeos/uso terapêutico , Sorbitol/uso terapêutico , Adulto , Idoso , Método Duplo-Cego , Combinação de Medicamentos , Emulsões Gordurosas Intravenosas/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fosfolipídeos/efeitos adversos , Estudos Prospectivos , Sorbitol/efeitos adversos , Fatores de Tempo
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