RESUMO
BACKGROUND: Maternal supplementation with omega-3 polyunsaturated fatty acids (n-3 PUFA) may modulate immune responses and allergy in neonates and children. OBJECTIVE: To determine if n-3 PUFA supplementation during pregnancy and lactation reduces risk for childhood allergic disease. SEARCH STRATEGY: We searched Medline and all evidence-based medicine reviews for randomised controlled trials comparing the effects of n-3 PUFA and placebo supplementation during pregnancy and/or lactation on childhood allergic diseases and inflammatory cytokines. SELECTION CRITERIA: We included studies reporting on food allergy, response to the egg skin prick test (SPT), atopy and asthma in infancy and childhood as well as production of interleukin-13 and interferon-gamma, two cytokines involved in the pathogenesis of asthma. For assessment of inclusion, two authors reviewed all abstracts for suitability and independently extracted data. DATA COLLECTION AND ANALYSIS: Two-by-two tables were constructed and odds ratios (OR) were calculated for the outcomes: response to the SPT, food allergy, atopy and asthma in childhood. The assays differed so data on inflammatory markers were reported in narrative form. MAIN RESULTS: Five randomised controlled trials (n = 949) were included. n-3 PUFA supplementation during pregnancy reduced 12-month prevalence of positive egg SPT (two trials, 12/87 versus 32/100, OR 0.33, 95% CI 0.16, 0.70) and childhood asthma (two trials, 10/303 versus 17/179, OR 0.349, 95% CI 0.154, 0.788) and significantly reduced cord blood interleukin-13 levels. Supplementation during lactation did not prevent asthma, food allergy or atopy. CONCLUSION: n-3 PUFA supplementation during pregnancy decreases childhood asthma and response to SPT.
Assuntos
Ácidos Graxos Ômega-3/administração & dosagem , Ácidos Graxos Ômega-3/farmacologia , Hipersensibilidade/prevenção & controle , Assistência Perinatal , Asma/prevenção & controle , Biomarcadores/sangue , Aleitamento Materno , Dermatite Atópica/prevenção & controle , Feminino , Hipersensibilidade Alimentar/prevenção & controle , Humanos , Hipersensibilidade/sangue , Recém-Nascido , Interferon gama/sangue , Interferon gama/efeitos dos fármacos , Interleucina-13/sangue , Razão de Chances , Assistência Perinatal/métodos , Gravidez , Ensaios Clínicos Controlados Aleatórios como Assunto , Testes CutâneosRESUMO
Primary snoring is mainly the bed partner's problem and not that of the snorer. The request for treatment arises from how annoying the snoring is and how sensitive the bed partner is to noise. In addition to a thorough medical history and an ENT examination, a polysomnography should be always performed to differentiate between primary snoring, upper airway resistance and obstructive sleep apnoea syndromes. Primarily weight loss and avoidance of alcohol in the evening as well as devices and surgery are used in the treatment of snoring.
Assuntos
Ronco/terapia , Consumo de Bebidas Alcoólicas/efeitos adversos , Diagnóstico Diferencial , Eletrocirurgia , Humanos , Placas Oclusais , Palato Mole/cirurgia , Faringe/cirurgia , Apneia Obstrutiva do Sono/diagnóstico , Ronco/etiologia , Tonsilectomia , Resultado do Tratamento , Úvula/cirurgia , Redução de PesoRESUMO
BACKGROUND AND PURPOSE: Fluoxetine (Prozac) is a widely prescribed drug in adults and children, and it has an active metabolite, norfluoxetine, with a prolonged elimination time. Although uncommon, Prozac causes QT interval prolongation and arrhythmias; a patient who took an overdose of Prozac exhibited a prolonged QT interval (QTc 625 msec). We looked for possible mechanisms underlying this clinical finding by analysing the effects of fluoxetine and norfluoxetine on ion channels in vitro. EXPERIMENTAL APPROACH: We studied the effects of fluoxetine and norfluoxetine on the electrophysiology and cellular trafficking of hERG K+ and SCN5A Na+ channels heterologously expressed in HEK293 cells. KEY RESULTS: Voltage clamp analyses employing square pulse or ventricular action potential waveform protocols showed that fluoxetine and norfluoxetine caused direct, concentration-dependent, block of hERG current (IhERG). Biochemical studies showed that both compounds also caused concentration-dependent reductions in the trafficking of hERG channel protein into the cell surface membrane. Fluoxetine had no effect on SCN5A channel or HEK293 cell endogenous current. Mutations in the hERG channel drug binding domain reduced fluoxetine block of IhERG but did not alter fluoxetine's effect on hERG channel protein trafficking. CONCLUSIONS AND IMPLICATIONS: Our findings show that both fluoxetine and norfluoxetine at similar concentrations selectively reduce IhERG by two mechanisms, (1) direct channel block, and (2) indirectly by disrupting channel protein trafficking. These two effects are not mediated by a single drug binding site. Our findings add complexity to understanding the mechanisms that cause drug-induced long QT syndrome.
Assuntos
Canais de Potássio Éter-A-Go-Go/metabolismo , Fluoxetina/efeitos adversos , Síndrome do QT Longo/induzido quimicamente , Adulto , Antidepressivos de Segunda Geração/efeitos adversos , Antidepressivos de Segunda Geração/farmacologia , Western Blotting , Linhagem Celular , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Membrana Celular/fisiologia , Cisaprida/farmacologia , Relação Dose-Resposta a Droga , Overdose de Drogas , Canais de Potássio Éter-A-Go-Go/antagonistas & inibidores , Canais de Potássio Éter-A-Go-Go/genética , Feminino , Fluoxetina/análogos & derivados , Fluoxetina/farmacologia , Humanos , Síndrome do QT Longo/metabolismo , Síndrome do QT Longo/fisiopatologia , Potenciais da Membrana/efeitos dos fármacos , Proteínas Musculares/antagonistas & inibidores , Proteínas Musculares/genética , Proteínas Musculares/metabolismo , Mutação/genética , Canal de Sódio Disparado por Voltagem NAV1.5 , Técnicas de Patch-Clamp , Piperidinas/farmacologia , Transporte Proteico/efeitos dos fármacos , Piridinas/farmacologia , Canais de Sódio/genética , Canais de Sódio/metabolismo , Fatores de Tempo , TransfecçãoRESUMO
The case of a 31-year-old man (smoker) with a progressively enlarging swelling and reddening in the region of the nasal vestibule is discussed. Before he was seen by us, he had been repeatedly treated with antibiotics, but to no avail. A deep excisional biopsy was obtained, and the histopathological work-up revealed a squamous cell carcinoma. Thereupon, complete surgical ablation in healthy tissue was carried out. This case shows that in chronic inflammation of the nasal vestibule that fails to respond to antibiotic treatment differential diagnostic consideration must be given to the possibility of a malignancy.
Assuntos
Carcinoma de Células Escamosas/diagnóstico , Furunculose/diagnóstico , Doenças Nasais/diagnóstico , Neoplasias Nasais/diagnóstico , Adulto , Biópsia , Carcinoma de Células Escamosas/patologia , Erros de Diagnóstico , Furunculose/patologia , Humanos , Masculino , Mucosa Nasal/patologia , Estadiamento de Neoplasias , Doenças Nasais/patologia , Neoplasias Nasais/patologia , Encaminhamento e Consulta , Tomografia Computadorizada por Raios XRESUMO
Subtotal pancreatectomy (90%) in Lewis rats induces chronic islet inflammation and tissue damage in the remaining pancreas 4 months after surgery. Concomitantly, significant enlargement of the islets of Langerhans was observed (90% pancreatectomy: islet/pancreas area: 25.6 +/- 9.6 x 10(-3), beta-cell/pancreas area: 12.4 +/- 4.4 x 10(-3); n = 4; controls without pancreatectomy: islet/pancreas area: 5.5 +/- 1.7 x 10(-3), beta-cell/pancreas area: 4.6 +/- 1.5 x 10(-3); n = 4; p < 0.05, respectively). Islet growth is mainly due to an increase in beta-cell mass. Beta-cell regeneration was not caused by the surgical manipulations or by metabolic stress. The former was ruled out by performing 10% pancreatectomy which did not cause islet enlargement after 4 months (islet/pancreas area: 13.6 +/- 11.3 x 10(-3), beta-cell/pancreas area: 7.1 +/- 2.0 x 10(-3); n = 3). An influence of metabolic stress was excluded by continuous substitution of syngenic islet antigens, which inhibits insulitis. In the absence of islet inflammation, despite persistent metabolic stress, beta-cell regeneration did not occur (islet/pancreas area: 7.0 +/- 5.5 x 10(-3), beta-cell/pancreas area: 5.5 +/- 4.1 x 10(-3); n = 4). Continuous treatment of animals after 90% pancreatectomy by insulin implants (1.5 U/day) avoided insulitis and beta-cell growth (islet/pancreas area: 9.2 +/- 1.1 x 10(-3), beta-cell/pancreas area: 6.8 +/- 1.0 x 10(-3), n = 3): All enlarged islets observed 4 months after 90% pancreatectomy without further treatment were infiltrated. Thus, beta-cell growth appears to be a response to insulitis. The stimulus for beta-cell growth could result from tissue damage caused by infiltrating cells or from cytokines secreted by the infiltrating cells, or both.
Assuntos
Ilhotas Pancreáticas/patologia , Ilhotas Pancreáticas/fisiologia , Pancreatite/patologia , Animais , Feminino , Imuno-Histoquímica , Pancreatectomia , Ratos , Ratos Endogâmicos Lew , Regeneração , Estresse Fisiológico/patologiaRESUMO
Laser-assisted surgery is a valid option for the treatment of respiratory sleep disorders and complements established therapies. Laser-surgery of the inferior turbinates can improve nasal obstruction and amend or eliminate primary snoring. LAUP is as well an ambulant therapeutic method for snoring, but it is leading to strong post-operative pain and should exclusively be applied to patients with small tonsils or who already underwent tonsillectomy. OSAS can be worsened by LAUP and should therefore be excluded before the operation. In childhood OSAS laser tonsillotomy leads to a distinct improvement of sleep-disordered breathing with normalisation of the sleeping profile; it is less painful than tonsillectomy and a part of the tonsil is left to continue to exercise its function in the immune system.
Assuntos
Terapia a Laser , Tonsila Palatina/cirurgia , Síndromes da Apneia do Sono/cirurgia , Ronco/cirurgia , Conchas Nasais/cirurgia , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/complicações , Palato Mole/cirurgia , Úvula/cirurgiaRESUMO
The risk for lethal ventricular arrhythmias is increased in individuals who carry mutations in genes that encode cardiac ion channels. Loss-of-function mutations in SCN5A, the gene encoding the cardiac sodium channel, are linked to Brugada syndrome (BrS). Arrhythmias in BrS are often preceded by coved-type ST-segment elevation in the right-precordial leads V1 and V2. Loss-of-function mutations in KCNH2, the gene encoding the cardiac ion channel that is responsible for the rapidly activating delayed rectifying potassium current, are linked to long-QT syndrome type 2 (LQT-2). LQT-2 is characterised by delayed cardiac repolarisation and rate-corrected QT interval (QTc) prolongation. Here, we report that the risk for ventricular arrhythmias in BrS and LQT-2 is further increased during fever. Moreover, we demonstrate that fever may aggravate coved-type ST-segment elevation in BrS, and cause QTc lengthening in LQT-2. Finally, we describe molecular mechanisms that may underlie the proarrhythmic effects of fever in BrS and LQT-2. (Neth Heart J 2010;18:165-9.).
RESUMO
BACKGROUND: Sulfido-Leukotrienes are important inflammatory mediators of bronchial asthma, intolerance of acetylsalicylic acid (ASA), polyposis nasi and allergic rhinitis. Receptorantagonists like Montelukast constitute a well-established asthma- and ASA intolerance-therapy. The aim of our study was to evaluate changes in patients Health-Related-Quality-of-Life (HRQL) during Montelukast-monotherapy of nasal polyposis. METHODS: The study was performed in a prospective, double blind and placebo-controlled matter. The study included 30 patients of our ENT outpatient's dept. (77 % male, mean age 49 yrs), suffering from nasal polyposis grade II to IV. Polyps were endoscopically graded, nasal Eosinophilic Cationic Protein (ECP) was measured, and HRQL-score was taken prior to and four weeks after Montelukast-(0 - 0 - 10 mg) compared to placebo. An established HRQL-questionnaire - including 25 items, summarized in 6 symptom-groups - was used. Given was a symptom-score of 1 (not troubled) to 4 (extremely troubled). RESULTS: Patients treated with Montelukast improved their nasal symptoms (Delta HRQL-score 0.58 +/- 0.94, P < 0.01), practical problems (Delta HRQL-score 0.42 +/- 0.71, P < 0.05), headaches (Delta HRQL-score 0.38 +/- 0.56, P < 0.05), non-nasal symptoms (Delta HRQL-score 0.35 +/- 0.92, P < 0.05), sleep (Delta HRQL-score 0.26 +/- 0.71) and emotional problems (Delta HRQL-score 0.18 +/- 0.75). Intranasal ECP (Delta 210.67 ng/ml +/- 332.68) and polyp grading (Delta 0.72 +/- 1.77) tended to improve as well, but did not reach statistical significance. Patients treated with placebo revealed no significant changes neither in HRQL-score, ECP, nor polyp grading. CONCLUSIONS: Montelukast-therapy of nasal polyposis significantly improved patient's HRQL in 4 out of 6 symptom-groups. Measuring HRQL proofed to constitute a more sensitive tool than looking at eosinophilic parameters of inflammation or polyp size.
Assuntos
Acetatos/uso terapêutico , Antagonistas de Leucotrienos/uso terapêutico , Pólipos Nasais/tratamento farmacológico , Qualidade de Vida , Quinolinas/uso terapêutico , Acetatos/administração & dosagem , Ciclopropanos , Interpretação Estatística de Dados , Método Duplo-Cego , Proteína Catiônica de Eosinófilo/análise , Feminino , Seguimentos , Humanos , Antagonistas de Leucotrienos/administração & dosagem , Masculino , Pessoa de Meia-Idade , Mucosa Nasal/metabolismo , Pólipos Nasais/classificação , Pólipos Nasais/diagnóstico , Placebos , Estudos Prospectivos , Quinolinas/administração & dosagem , Sensibilidade e Especificidade , Sulfetos , Inquéritos e Questionários , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Depending on age and gender up to 60 % of the population snore regularly. As simple snoring is more a social than a medical problem, unlike OSAS, CPAP-therapy or multilevel surgery are not appropriate therapies for snoring. But alternative therapies, such as laser-assisted uvulopalatoplasty (LAUP) or uvulopalatopharyngoplasty (UPPP) address distinct sites of the pharynx. Therefore a correct identification of the snoring-source should optimise the selection of patients and improve the outcome of therapy. As there is no commonly recommended tool for identifying the snoring-source, the use of a new technique, based on pharyngeal pressure measurement, was tested. METHODS: 25 patients with suspected OSAS had standard polysomnography recordings during two nights with esophagopharyngeal pressure measurement on the second night. The pressure probe had 5 pharyngeal and 1 esophageal transducers. The curves of the pharyngeal pressure were examined for quick pressure changes superimposed on the slow pressure-changes caused by breathing. The appearance of these quick pressure changes was documented for each transducer throughout the whole night. RESULTS: The average (+/- SD) Apnea-Hypopnea-Index in the patients was 28.3 +/- 24.8. 17 patients (68 %) had an AHI of more than 10. All patients showed heavy snoring. 23 patients (92 %) showed a high frequency, sawtooth-pattern, superimposed on the slow breathing rhythm in at least one channel and in association with snoring. 91 % of the patients showed a sawtooth pattern in more than one channel, but the pattern was always more pronounced in one channel compared to others. The sawtooth-pattern of the highest amplitude was seen in the pressure curves from the velum in 56 % of the patients, from the tonsils in 24 %, and from the tonguebase in 12 % of the patients. CONCLUSIONS: Quick pressure changes from distinctive pharyngeal pressure transducers during snoring are common in OSAS patients and may indicate the source of snoring. Further investigations have to show whether this assumption is correct, and whether the quick pressure changes are also apparent in simple snorers.
Assuntos
Manometria , Faringe/fisiologia , Polissonografia , Ronco/fisiopatologia , Adulto , Feminino , Humanos , Masculino , Manometria/instrumentação , Pessoa de Meia-Idade , Seleção de Pacientes , Pressão , Síndromes da Apneia do Sono/fisiopatologia , Ronco/cirurgia , TransdutoresRESUMO
Sepsis is a state of high turnover of bone-marrow cells. Nitric oxide (NO) is reported to be involved in cell proliferation and demise. Murine bone-marrow cells were incubated with lipopolysaccharide together with tumor necrosis factor alpha, interferon gamma and interleukin-1 beta for 48 h. The basal proliferation rate of the cells remained unchanged, but granulocyte-macrophage colony stimulating factor-induced proliferation was suppressed and the percentage of apoptotic cells significantly raised. Levels of nitrite in the culture supernatants were inversely correlated with the suppression of proliferation, but directly correlated with apoptosis. The NO synthesis inhibitor N-methyl-arginine inhibited the suppression of proliferation as well as the induction of apoptosis and NO synthesis. Our results indicate that NO is a negative feedback regulator of cell turnover in sepsis, which limits growth-factor-induced proliferation and induces apoptosis of bone marrow cells.
Assuntos
Células da Medula Óssea/citologia , Óxido Nítrico/fisiologia , Sepse/metabolismo , Animais , Apoptose/efeitos dos fármacos , Divisão Celular/efeitos dos fármacos , Feminino , Mediadores da Inflamação/farmacologia , Lipopolissacarídeos/farmacologia , Camundongos , Camundongos Endogâmicos BALB C , Óxido Nítrico/biossínteseRESUMO
We studied the effect of severe reduction of beta-cell mass by 90% pancreatectomy on the immune tolerance to the endocrine pancreas. Four months after subtotal pancreatectomy all LEW.Han rats had developed mononuclear infiltration of islets and 9 of 14 rats were positive for islet-cell antibodies. Electron microscopy revealed lymphocytic invasion of endocrine tissue, lysis of beta cells and phagocytotic macrophages. None of these changes were seen 2 weeks after 90% pancreatectomy or 4 months after 10% pancreatectomy. Weekly substitution of islet antigens in the form of a homogenate of 100 islets into 90% pancreatectomized LEW.Han rats almost completely prevented the development of insulitis and autoantibodies. The dependence of insulitis on T cells was shown when 90% pancreatectomy in LEW.rnu rats (i.e., the congenic athymic nude strain), did not result in islet infiltration. The exocrine tissue remained normal in all experimental groups. During the observation period insulitis was not associated with overt diabetes but was accompanied by substantial enlargement of islets and of beta-cell mass, as shown by morphometry. Suppression of islet inflammation by injection of islet antigens abolished beta-cell regeneration, despite continuing metabolic stress in rats with 90% pancreatectomy. The findings indicate induction of islet autoimmunity in response to 90% but not to 10% pancreatectomy. We conclude that severe reduction of the islet-antigen mass allows the development of T-cell-dependent islet autoimmunity which indicates a loss of immune tolerance. In addition, the data suggest the existence of islet-antigen autoreactive immune cells in rats not genetically predisposed to autoimmune diabetes. Finally, we conclude that selective beta-cell regeneration occurs in association with insulitis.