RESUMO
This study aimed to evaluate the levels of eicosanoids derived from arachidonic acid (ARA) in the lungs of asthmatic rats supplemented with fish oil. The present data gives insight into the action of fish oil in asthma, related to its inability to modify the contractile capacity of tracheal smooth muscle reported previously in a model of asthma in rats. Male Wistar rats were supplemented daily with 1 g of fish oil/kg of body weight for 21 days. They were exposed to ovalbumin (OVA) after previous sensitization with OVA to induce asthma. Pulmonary levels of five eicosanoids were measured using immunoassay kits: PGE2, TXB2, LTB4, LXA4, and 8-iso PGF2α. In asthmatic rats, supplementation with fish oil resulted in lower concentrations of lung eicosanoids produced by cyclooxygenase-2 and 15-lipoxygenase: PGE2, TXB2, and LXA4, respectively. Fish oil supplementation also decreased the non-enzymatically produced eicosanoid 8-iso PGF2α. Fish oil supplementation did not affect LTB4, a metabolite of 5-lipoxygenase. The limited efficacy of fish oil supplementation in asthmatic rats is associated with a lack of action in reducing the levels of LTB4 in the lungs. Thus, fish oil differentially modulates the concentrations of eicosanoids derived from ARA via specific pathways in an animal model of asthma.
RESUMO
OBJECTIVES: This study objectives to investigate the influence of average energy intake at 1 week of hospitalization on prognosis for older adults with pneumonia. DESIGN: Retrospective observational cohort study. SETTING: The Japan Rehabilitation Nutrition Database comprise those with pneumonia in acute care hospitals. PARTICIPANTS: The study included 329 pneumonia patients (aged over 65 years) who entered into the Japan Rehabilitation Nutrition Database (JRND) from November 2015 to March 2018. MEASUREMENTS: Logistic regression analysis was performed to confirm the relationship of energy intake with the rate of mortality, discharge home, and pneumonia recurrence during hospitalization. Variables included in the multiple regression analysis model were age, sex, Mini Nutritional Assessment-Short Form score (MNA-SF) at hospitalization, A-DROP, Charlson comorbidity index (CCI), and presence or absence of rehabilitation. RESULTS: Of 315 patients with pneumonia (median age 85 years), 63.8% were men. 57.7% were assigned to the lack of energy intake (LEI) at 1 week after admission. Patients in the LEI group were older (p = 0.033), had higher A-DROP score (p < 0.001), and showed higher malnutrition rate in MNA-SF at hospitalization (p < 0.001) than those in the control group. Mortality, pneumonia recurrence (p = 0.001), median body mass index (p = 0.012), and low malnutrition in MNA-SF (p < 0.001) at discharge were significantly higher in the LEI group than in the control group. Logistic regression analysis showed that LEI was an independent risk factor for mortality (Odds ratio: 5.07, p = 0.002), discharge home (Odds ratio: 0.33, p = 0.007), and pneumonia recurrence (Odds ratio: 3.26, p = 0.007). CONCLUSIONS: LEI at 1 week after hospitalization in older adults with pneumonia was an independent risk factor for mortality, difficult at-home recovery, and pneumonia recurrence. These findings suggest the importance of adequate energy intake from the early days of hospitalization.
Assuntos
Ingestão de Energia/fisiologia , Avaliação Nutricional , Estado Nutricional/fisiologia , Pneumonia/reabilitação , Idoso , Idoso de 80 Anos ou mais , Índice de Massa Corporal , Estudos de Coortes , Feminino , Hospitalização , Humanos , Japão , Masculino , Desnutrição/mortalidade , Desnutrição/fisiopatologia , Pneumonia/mortalidade , Prognóstico , Recidiva , Estudos Retrospectivos , Fatores de RiscoRESUMO
We showed recently that increasing kidney epoxyeicosatrienoic acids (EETs) by blocking soluble epoxide hydrolase (sEH), an enzyme responsible for EETs degradation, retarded the development of renal dysfunction and progression of aorto-caval fistula(ACF)-induced congestive heart failure (CHF) in Ren-2 transgenic hypertensive rats (TGR). In that study the final survival rate of untreated ACF TGR was only 14 % but increased to 41 % after sEH blockade. Here we examined if sEH inhibition added to renin-angiotensin system (RAS) blockade would further enhance protection against ACF-induced CHF in TGR. The treatment regimens were started one week after ACF creation and the follow-up period was 50 weeks. RAS was blocked using angiotensin-converting enzyme inhibitor (ACEi, trandolapril, 6 mg/l) and sEH with an sEH inhibitor (sEHi, c-AUCB, 3 mg/l). Renal hemodynamics and excretory function were determined two weeks post-ACF, just before the onset of decompensated phase of CHF. 29 weeks post-ACF no untreated animal survived. ACEi treatment greatly improved the survival rate, to 84 % at the end of study. Surprisingly, combined treatment with ACEi and sEHi worsened the rate (53 %). Untreated ACF TGR exhibited marked impairment of renal function and the treatment with ACEi alone or combined with sEH inhibition did not prevent it. In conclusion, addition of sEHi to ACEi treatment does not provide better protection against CHF progression and does not increase the survival rate in ACF TGR: indeed, the rate decreases significantly. Thus, combined treatment with sEHi and ACEi is not a promising approach to further attenuate renal dysfunction and retard progression of CHF.
Assuntos
Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Benzoatos/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Indóis/uso terapêutico , Insuficiência Renal/prevenção & controle , Ureia/análogos & derivados , Animais , Fístula Arteriovenosa , Benzoatos/farmacologia , Avaliação Pré-Clínica de Medicamentos , Quimioterapia Combinada , Epóxido Hidrolases/antagonistas & inibidores , Feminino , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/mortalidade , Masculino , Ratos , Ratos Sprague-Dawley , Ratos Transgênicos , Insuficiência Renal/etiologia , Ureia/farmacologia , Ureia/uso terapêuticoRESUMO
Various stimuli to the exposed surface of dentin induce changes in the hydrodynamic force inside the dentinal tubules resulting in dentinal pain. Recent evidences indicate that mechano-sensor channels, such as the transient receptor potential channels, in odontoblasts receive these hydrodynamic forces and trigger the release of ATP to the pulpal neurons, to generate dentinal pain. A recent study, however, has shown that odontoblasts also express glutamate receptors (GluRs). This implies that cells in the dental pulp tissue have the ability to release glutamate, which acts as a functional intercellular mediator to establish inter-odontoblast and odontoblast-trigeminal ganglion (TG) neuron signal communication. To investigate the intercellular signal communication, we applied mechanical stimulation to odontoblasts and measured the intracellular free Ca2+ concentration ([Ca2+]i). During mechanical stimulation in the presence of extracellular Ca2+, we observed a transient [Ca2+]i increase not only in single stimulated odontoblasts, but also in adjacent odontoblasts. We could not observe these responses in the absence of extracellular Ca2+. [Ca2+]i increases in the neighboring odontoblasts during mechanical stimulation of single odontoblasts were inhibited by antagonists of metabotropic glutamate receptors (mGluRs) as well as glutamate-permeable anion channels. In the odontoblast-TG neuron coculture, we observed an increase in [Ca2+]i in the stimulated odontoblasts and TG neurons, in response to direct mechanical stimulation of single odontoblasts. These [Ca2+]i increases in the neighboring TG neurons were inhibited by antagonists for mGluRs. The [Ca2+]i increases in the stimulated odontoblasts were also inhibited by mGluRs antagonists. We further confirmed that the odontoblasts express group I, II, and III mGluRs. However, we could not record any currents evoked from odontoblasts near the mechanically stimulated odontoblast, with or without extracellular Mg2+, indicating that N-methyl-d-aspartic acid receptor does not contribute to inter-odontoblast signal communication. The results suggest that a mechanically stimulated odontoblast is capable of releasing glutamate into the extracellular space via glutamate-permeable anion channels. The released glutamate activates mGluRs on the odontoblasts in an autocrine/paracrine manner, forming an inter-odontoblasts communication, which drives dentin formation via odontoblast-odontoblast signal communication. Glutamate and mGluRs also mediate neurotransmission between the odontoblasts and neurons in the dental pulp to modulate sensory signal transmission for dentinal sensitivity.
Assuntos
Comunicação Celular , Ácido Glutâmico/metabolismo , Neurônios/metabolismo , Odontoblastos/metabolismo , Transdução de Sinais , Gânglio Trigeminal/citologia , Gânglio Trigeminal/metabolismo , Animais , Células Cultivadas , Feminino , Masculino , Camundongos , Camundongos Endogâmicos BALB CRESUMO
BACKGROUND: Post-transplantation de novo and recurrent immunoglobulin A (IgA) deposition (IgAD) in the allograft is commonly observed. However, the association between post-transplantation IgAD and reduced allograft function has not been determined. We therefore investigated the association between reduced allograft function and post-transplantation IgAD using serial allograft biopsies. METHODS: IgAD was retrospectively analyzed in 45 adults who underwent kidney transplantation for chronic glomerulonephritis, including IgA nephropathy, at Kagawa University Hospital. Allograft biopsy samples were obtained from per protocol biopsies obtained 1 and 3 years after transplantation, as well as from episode biopsies. Factors contributing to post-transplantation IgAD were assessed by calculating adjusted odds ratios (AORs) using logistic regression analysis. RESULTS: Of the 45 recipients, 18 had post-transplantation allograft IgAD. The estimated glomerular filtration rates (eGFR) 1, 2, and 3 years after transplantation were lower in the recipients with than without IgAD. Urinalysis was normal in 61% of recipients with IgAD. Reduced allograft function (eGFR <40 mL/min/1.73 m(2)) 1 year after transplantation was significantly associated with post-transplantation IgAD (AOR = 34.4 [95% CI = 2.35-502], P = .01). Conversely, blood concentrations of mycophenolic acid and latent IgAD from donor kidneys were not significantly associated with post-transplantation IgAD. CONCLUSION: Reduced allograft function may be associated with post-transplantation IgAD in the allograft.
Assuntos
Aloenxertos/patologia , Glomerulonefrite por IGA/etiologia , Glomerulonefrite por IGA/patologia , Imunoglobulina A , Transplante de Rim , Adulto , Biópsia , Feminino , Taxa de Filtração Glomerular , Mesângio Glomerular/patologia , Glomerulonefrite por IGA/cirurgia , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Recidiva , Estudos Retrospectivos , Fatores de RiscoRESUMO
Dietary fish oil supplementation increases the content of n-3 polyunsaturated fatty acids (PUFA) in cellular membranes. The highly unsaturated nature of n-3 PUFA could result in an enhanced lipid peroxidation in the oxidative environment characteristic of asthma. The oxidative reaction cascade culminates in an increased production of components associated to oxidative stress and of an important proinflammatory mediator platelet-activating factor (PAF)-like lipid. We evaluated the effect of fish oil supplementation in asthmatic rats upon the PAF bioactivity and parameters related to oxidative stress in the lung. Fish oil supplementation of asthmatic rats resulted in lower concentrations of nitrite (1.719 ± 0.137 vs. 2.454 ± 0.163 nmol/mL) and lipid hydroperoxide (72.190 ± 7.327 vs. 120.200 ± 11.270 nmol/mg protein). In asthmatic animals, fish oil increased the activities of superoxide dismutase (EC 1.15.1.1) (33.910 ± 2.325 vs. 24.110 ± 0.618 U/mg protein) and glutathione peroxidase (EC 1.11.1.9) (164.100 ± 31.250 vs. 12.590 ± 5.234 U/mg protein). However, fish oil did not affect PAF bioactivity in lung tissue of asthmatic rats (0.545 ± 0.098 340/380 vs. 0.669 ± 0.101 340/380 nm ratio). Considering the two-step process--oxidative stress and PAF bioactivity--fish oil exhibited a divergent action on these aspects of asthmatic inflammation, since the supplement lowered oxidative stress in the lungs of asthmatic rats, presenting an antioxidant effect, but did not affect PAF bioactivity. This suggests a dual effect of fish oil on oxidative stress and inflammation in asthma.
Assuntos
Asma/metabolismo , Suplementos Nutricionais , Óleos de Peixe/farmacologia , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Fator de Ativação de Plaquetas/metabolismo , Animais , Asma/patologia , Óleos de Peixe/administração & dosagem , Pulmão/patologia , Masculino , Ratos , Ratos WistarRESUMO
Glaucoma is conventionally defined as a chronic optic neuropathy characterized by progressive loss of retinal ganglion cells (RGCs) and optic nerve fibers. Although glaucoma is often associated with elevated intraocular pressure (IOP), significant IOP reduction does not prevent progression of the disease in some glaucoma patients. Thus, exploring IOP-independent mechanisms of RGC loss is important. We describe chronic systemic administration of aldosterone and evaluate its effect on RGCs in rat. Aldosterone was administered via an osmotic minipump that was implanted subcutaneously into the mid-scapular region. Although systemic administration of aldosterone caused RGC loss associated with thinning of the retinal nerve fiber layer without elevated IOP, the other cell layers appeared to be unaffected. After chronic administration of aldosterone, RGC loss was observed at 2 weeks in the peripheral retina and at 4 weeks in the central retina. However, administration of mineralocorticoid receptor blocker prevented RGC loss. These results demonstrate aldosterone is a critical mediator of RGC loss that is independent of IOP. We believe this rat normal-tension glaucoma (NTG) animal model not only offers a powerful system for investigating the mechanism of neurodegeneration in NTG, but can also be used to develop therapies directed at IOP-independent mechanisms of RGC loss.
Assuntos
Aldosterona/fisiologia , Apoptose , Glaucoma/metabolismo , Células Ganglionares da Retina/fisiologia , Animais , Sobrevivência Celular/efeitos dos fármacos , Glaucoma/patologia , Glaucoma/fisiopatologia , Pressão Intraocular , Masculino , Antagonistas de Receptores de Mineralocorticoides/farmacologia , Degeneração Neural/metabolismo , Nervo Óptico/patologia , Ratos Sprague-Dawley , Retina/patologia , Retina/fisiopatologia , Espironolactona/farmacologiaRESUMO
Episodes of acute exacerbation are the major clinical feature of asthma and therefore represent an important focus for developing novel therapies for this disease. There are many reports that the n-3 fatty acids found in fish oil exert anti-inflammatory effects, but there are few studies of the action of fish oil on airway smooth muscle (ASM) function. In the present investigation, we evaluated the effect of fish oil supplementation on smooth muscle force of contraction in ovalbumin-induced asthmatic Wistar rats, and its consequences on static lung compliance, mucus production, leukocyte chemotaxis and production of proinflammatory cytokines. Fish oil supplementation suppressed the infiltration of inflammatory cells into the lung in asthmatic animals (2.04 ± 0.19 × 10(6) cells vs. 3.33 ± 0.43 × 10(6) cells in the control asthmatic group; P < 0.05). Static lung compliance increased with fish oil supplementation in asthmatic rats (0.640 ± 0.053 mL/cm H2O vs. 0.399 ± 0.043 mL/cm H2O; P < 0.05). However, fish oil did not prevent asthma-associated lung eosinophilia and did not affect the concentrations of tumor necrosis factor-α and interleukin-1ß in lung tissue or the proportion of the airways obliterated with mucus. Fish oil had no effect on the force of contraction in asthmatic rats in response to acetylcholine (3.026 ± 0.274 mN vs. 2.813 ± 0.364 mN in the control asthmatic group). In conclusion, although fish oil exerts some benefits in this model of asthma, its effectiveness appears to be limited by an inefficient action on airway smooth muscle function.
Assuntos
Asma/fisiopatologia , Óleos de Peixe/farmacologia , Músculo Liso/efeitos dos fármacos , Traqueia/efeitos dos fármacos , Acetilcolina/farmacologia , Análise de Variância , Animais , Asma/induzido quimicamente , Líquido da Lavagem Broncoalveolar/citologia , Broncodilatadores/farmacologia , Suplementos Nutricionais , Eosinófilos/efeitos dos fármacos , Eosinófilos/patologia , Óleos de Peixe/administração & dosagem , Técnicas In Vitro , Interleucina-1beta/metabolismo , Isoproterenol/farmacologia , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Pulmão/patologia , Complacência Pulmonar/efeitos dos fármacos , Linfócitos/efeitos dos fármacos , Linfócitos/patologia , Macrófagos/efeitos dos fármacos , Macrófagos/patologia , Masculino , Músculo Liso/fisiopatologia , Neutrófilos/efeitos dos fármacos , Neutrófilos/patologia , Ovalbumina , Ratos , Ratos Wistar , Traqueia/fisiopatologia , Fator de Necrose Tumoral alfa/metabolismo , Vasodilatadores/farmacologiaRESUMO
We have previously reported that intrarenal angiotensin II (Ang II) levels are increased long before diabetes becomes apparent in obese Otsuka-Long-Evans-Tokushima-Fatty (OLETF) rats, a model of type 2 diabetes. In this study, we examined the changes in intrarenal renin-angiotensin system (RAS) activity in the developing kidneys of OLETF rats. Ang II contents and mRNA levels of RAS components were measured in male OLETF and control Long-Evans Tokushima (LETO) rats at postnatal days (PND) 1, 5, and 15, and at 4-30 weeks of age. In both LETO and OLETF rats, kidney Ang II levels peaked at PND 1, then decreased during the pre- and post-weaning periods. However, Ang II levels and gene expression of RAS components, including angiotensinogen (AGT), renin, and angiotensin-converting enzyme (ACE), were not significantly different between LETO and OLETF rats. Intrarenal Ang IIcontents further decreased during puberty (from 7 to 11 weeks of age) in LETO rats, bur not in OLETF rats. At 11 weeks of age, kidney Ang II levels, urinary AGT excretion, and mRNA levels of AGT and renin were higher in OLETF rats than in LETO rats, while blood glucose levels were not significantly different between these groups of rats. These data indicate that continued intrarenal expression of Ang II during pubescence contributes to the increases in intrarenal Ang II levels in prediabetic OLETF rats, and is associated with increased intrarenal AGT and renin expression. Inappropriate activation of the intrarenal RAS in the prediabetic stage may facilitate the onset and development of diabetic nephropathy in later life.
Assuntos
Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Rim/crescimento & desenvolvimento , Rim/metabolismo , Sistema Renina-Angiotensina , Albuminúria/complicações , Angiotensina II/metabolismo , Angiotensinogênio/metabolismo , Animais , Glicemia/metabolismo , Pressão Sanguínea , Peso Corporal , Colágeno/genética , Colágeno/metabolismo , Fator de Crescimento do Tecido Conjuntivo/genética , Fator de Crescimento do Tecido Conjuntivo/metabolismo , Creatinina/urina , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/urina , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/urina , Feminino , Regulação da Expressão Gênica , Tamanho do Órgão , Peptidil Dipeptidase A/metabolismo , Ratos , Ratos Endogâmicos OLETF , Receptores de Angiotensina/metabolismo , Renina/metabolismo , Fatores de Tempo , Fator de Crescimento Transformador beta/genética , Fator de Crescimento Transformador beta/metabolismoRESUMO
BACKGROUND: Acute exacerbation (AE) of idiopathic pulmonary fibrosis (IPF) has an extremely poor prognosis. Direct hemoperfusion with a polymyxin B-immobilized fiber column (PMX-DHP) has been used to improve oxygenation for acute respiratory distress syndrome. The study aim was to retrospectively determine the predictive factors affecting the prognosis of AE of IPF treated with PMX-DHP. METHODS: We studied patients suffering from AE of IPF, treated with PMX-DHP combined with high-dose corticosteroid therapy. Stored serum taken before and after PMX-DHP therapy was analyzed for 27 cytokines and chemokines. RESULTS: Nineteen patients with AE of IPF were studied. The median survival time after diagnosis of AE was 22 days. Survival rates after diagnosis of AE were 47.4% at 30 days, 31.6% at 60 days, and 26.3% at 90 days. Serum levels of Interleukin (IL)-7, an anti-fibrotic cytokine, in survivors at day 30 following PMX-DHP therapy ('Survivors') significantly increased after the treatment, compared to serum levels of non-survivors at day 30 after the therapy ('Nonsurvivors'), which did not demonstrate a significant change. Serum levels of IL-1beta, interferon-y and chemokine ligand (CCL) 2 levels were not significantly altered in 'Survivors', but were significantly changed in 'Nonsurvivors.' Multivariate Cox proportional-hazards analysis showed that an increase in IL-7 levels after PMX-DHP therapy and treatment without intubation (other than invasive positive-pressure ventilation) were significantly better prognostic factors. CONCLUSION: The results suggest that serum IL-7 may be a useful prognostic factor for patients with AE of IPF treated with PMX-DHP, possibly reflecting underlying anti-fibrotic mechanisms.
Assuntos
Hemoperfusão/métodos , Fibrose Pulmonar Idiopática/terapia , Interleucina-17/sangue , Polimixina B/uso terapêutico , Corticosteroides/administração & dosagem , Biomarcadores/sangue , Distribuição de Qui-Quadrado , Terapia Combinada , Hemoperfusão/efeitos adversos , Humanos , Fibrose Pulmonar Idiopática/diagnóstico por imagem , Fibrose Pulmonar Idiopática/imunologia , Fibrose Pulmonar Idiopática/mortalidade , Japão , Estimativa de Kaplan-Meier , Polimixina B/efeitos adversos , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Taxa de Sobrevida , Fatores de Tempo , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
Rho/Rho kinase (ROCK) pathway plays an important role in pathological cardiovascular conditions. In the present study, the effect of a subdose of fasudil, a selective ROCK inhibitor, on systemic hypertension and myocardium fibrosis induced by aldosterone was investigated in uninephrectomized Sprague-Dawley rats (SD). Treatment with a fasudil (10 mg/kg x day, s.c.) for 5 weeks decreased the activity of ROCK activity for more than 53% as determined by the expression of phosphorylated Myosin phosphatase target subunit 1 (MYPT1). Although this dose of fasudil did not signifantly prevent hypertension, it remarkably alleviated myocardium hypertrophy and fibrosis. The elevated transcriptional expression of transforming growth factors beta1 (TGF-beta1), atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and collagen I and III was also decreased. These results demonstrated that fasudil can protect the myocardium from injury by aldosterone at a subhypertensive dose.
Assuntos
1-(5-Isoquinolinasulfonil)-2-Metilpiperazina/análogos & derivados , Aldosterona , Anti-Hipertensivos/farmacologia , Bloqueadores dos Canais de Cálcio/farmacologia , Cardiomiopatias/prevenção & controle , Nefrectomia , Cloreto de Sódio , 1-(5-Isoquinolinasulfonil)-2-Metilpiperazina/administração & dosagem , 1-(5-Isoquinolinasulfonil)-2-Metilpiperazina/farmacologia , Animais , Anti-Hipertensivos/administração & dosagem , Biomarcadores , Pressão Sanguínea/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Bloqueadores dos Canais de Cálcio/administração & dosagem , Cardiomiopatias/induzido quimicamente , Primers do DNA , Fibrose , Hemodinâmica/efeitos dos fármacos , Hipertensão/induzido quimicamente , Hipertensão/prevenção & controle , Hipertensão Renal/prevenção & controle , Hipertrofia Ventricular Esquerda/induzido quimicamente , Hipertrofia Ventricular Esquerda/prevenção & controle , Masculino , Fosforilação , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase Via Transcriptase ReversaAssuntos
Vírus da Influenza A Subtipo H1N1 , Influenza Humana/diagnóstico , Tireotropina/sangue , Reação de Fase Aguda , Antivirais/administração & dosagem , Biomarcadores/sangue , Criança , Humanos , Influenza Humana/tratamento farmacológico , Masculino , Metilprednisolona/administração & dosagem , Oseltamivir/administração & dosagem , Pulsoterapia , Hormônio Liberador de Tireotropina/administração & dosagemRESUMO
BACKGROUND: Inflammatory airway disease (IAD) is prevalent in young racehorses during training, being the 2nd most commonly diagnosed ailment interrupting training of 2-year-old Thoroughbred racehorses. HYPOTHESIS: That stabling and exercise cause oxidative stress, release of platelet-activating factor (PAF) and inflammation in airways of Thoroughbred colts. ANIMALS: Colts in breeding farms (NC, n = 45), stabled for 30 days (EC, n = 40), and race trained (EX, n = 34). METHODS: Cytological profile and parameters of bronchoalveolar lavage fluid (BALF) related to oxidative stress, bioactivity of the proinflammatory mediator PAF, catalase activity, and alveolar macrophage function. RESULTS: Percentages of neutrophils and eosinophils in the BALF of the EX group were higher (5.4 +/- 6.4% versus 0.9 +/- 1.2%) than the upper limits for normal horses (3-5%). BALF from the EX group (45.6 +/- 2.8 cells/microL of BALF) also displayed significantly (P = .017) higher total nucleated cell count. PAF bioactivity and the total protein concentration in the BALF were higher in the EX group (0.0683 +/- 0.076 versus 0.0056 +/- 0.007 340 : 380 nm ratio P = .0039, 0.36 +/- 0.30 versus 0.14 +/- 0.15 mg of proteins/mL of BALF P < .001). Concentration of BALF hydroperoxides was higher in the EC group (104.7 +/- 80.0 versus 35.2 +/- 28.0 nmol/mg of proteins, P = .013) and catalase activity was higher in the EX group (0.24 +/- 0.16 versus 0.06 +/- 0.02 micromol H2O2/min/mg of proteins, P = .0021). Alveolar macrophage phagocytosis (P = .048) as well as production of superoxide anion (P = .0014) and hydrogen peroxide (P = .0011) were significantly lower in EX group. CONCLUSIONS AND CLINICAL IMPORTANCE: Further studies should be performed to elucidate the role of PAF in the pathophysiology of IAD. Its presence in bronchoalveolar fluid of young athletic horses makes it a potential therapeutic target to be investigated.
Assuntos
Líquido da Lavagem Broncoalveolar/química , Cavalos/fisiologia , Estresse Oxidativo/fisiologia , Fator de Ativação de Plaquetas/análise , Animais , Líquido da Lavagem Broncoalveolar/citologia , Macrófagos Alveolares/fisiologia , Masculino , Condicionamento Físico Animal , Fator de Ativação de Plaquetas/metabolismo , Sistema Respiratório , EsportesRESUMO
To determine the effects of saturated and unsaturated fatty acids in phosphatidylcholine (PC) on macrophage activity, peritoneal lavage cells were cultured in the presence of phosphatidylcholine rich in saturated or unsaturated fatty acids (sat PC and unsatPC, respectively), both used at concentrations of 32 and 64 ìM. The treatment of peritoneal macrophages with 64 ìM unsat PC increased the production of hydrogen peroxide by 48.3% compared to control (148.3 ± 16.3 vs 100.0 ± 1.8%, N = 15), and both doses of unsat PC increased adhesion capacity by nearly 50%. Moreover, 64 ìM unsat PC decreased neutral red uptake by lysosomes by 32.5% compared to the untreated group (67.5 ± 6.8 vs 100.0 ± 5.5%, N = 15), while both 32 and 64 ìM unsat PC decreased the production of lipopolysaccharide-elicited nitric oxide by 30.4% (13.5 ± 2.6 vs 19.4 ± 2.5 ìM) and 46.4% (10.4 ± 3.1 vs 19.4 ± 2.5 ìM), respectively. Unsat PC did not affect anion production in non-stimulated cells or phagocytosis of unopsonized zymosan particles. A different result pattern was obtained for macrophages treated with sat PC. Phorbol 12-miristate 13-acetate-elicited superoxide production and neutral red uptake were decreased by nearly 25% by 32 and 64 ìM sat PC, respectively. Sat PC did not affect nitric oxide or hydrogen peroxide production, adhesion capacity or zymosan phagocytosis. Thus, PC modifies macrophage activity, but this effect depends on cell activation state, fatty acid saturation and esterification to PC molecule and PC concentration. Taken together, these results indicate that the fatty acid moiety of PC modulates macrophage activity and, consequently, is likely to affect immune system regulation in vivo.
Assuntos
Animais , Masculino , Ratos , Ácidos Linoleicos/farmacologia , Macrófagos Peritoneais/efeitos dos fármacos , Fagocitose/efeitos dos fármacos , Fosfatidilcolinas/farmacologia , Adesão Celular/efeitos dos fármacos , Adesão Celular/fisiologia , Peróxido de Hidrogênio/metabolismo , Macrófagos Peritoneais/fisiologia , Óxido Nítrico Sintase/metabolismo , Óxido Nítrico/metabolismo , Fagocitose/fisiologia , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismoRESUMO
To determine the effects of saturated and unsaturated fatty acids in phosphatidylcholine (PC) on macrophage activity, peritoneal lavage cells were cultured in the presence of phosphatidylcholine rich in saturated or unsaturated fatty acids (sat PC and unsat PC, respectively), both used at concentrations of 32 and 64 microM. The treatment of peritoneal macrophages with 64 microM unsat PC increased the production of hydrogen peroxide by 48.3% compared to control (148.3 +/- 16.3 vs 100.0 +/- 1.8%, N = 15), and both doses of unsat PC increased adhesion capacity by nearly 50%. Moreover, 64 microM unsat PC decreased neutral red uptake by lysosomes by 32.5% compared to the untreated group (67.5 +/- 6.8 vs 100.0 +/- 5.5%, N = 15), while both 32 and 64 microM unsat PC decreased the production of lipopolysaccharide-elicited nitric oxide by 30.4% (13.5 +/- 2.6 vs 19.4 +/- 2.5 microM) and 46.4% (10.4 +/- 3.1 vs 19.4 +/- 2.5 microM), respectively. Unsat PC did not affect anion production in non-stimulated cells or phagocytosis of unopsonized zymosan particles. A different result pattern was obtained for macrophages treated with sat PC. Phorbol 12-miristate 13-acetate-elicited superoxide production and neutral red uptake were decreased by nearly 25% by 32 and 64 microM sat PC, respectively. Sat PC did not affect nitric oxide or hydrogen peroxide production, adhesion capacity or zymosan phagocytosis. Thus, PC modifies macrophage activity, but this effect depends on cell activation state, fatty acid saturation and esterification to PC molecule and PC concentration. Taken together, these results indicate that the fatty acid moiety of PC modulates macrophage activity and, consequently, is likely to affect immune system regulation in vivo.
Assuntos
Ácidos Linoleicos/farmacologia , Macrófagos Peritoneais/efeitos dos fármacos , Fagocitose/efeitos dos fármacos , Fosfatidilcolinas/farmacologia , Animais , Adesão Celular/efeitos dos fármacos , Adesão Celular/fisiologia , Peróxido de Hidrogênio/metabolismo , Macrófagos Peritoneais/fisiologia , Masculino , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase/metabolismo , Fagocitose/fisiologia , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismoRESUMO
The aim of this study was to explore the relationship between patterns of missing occlusal units (OUs) and oral health-related quality of life (OHRQoL) in subjects with the shortened dental arches (SDAs). Subjects with SDAs were recruited consecutively for 1 month from six university-based prosthodontic clinics. In total, 115 SDA subjects participated (mean age, 58.5 +/- 10.0 years; 71% female). The location and number of missing teeth were examined and the number of missing OUs was calculated. To evaluate OHRQoL, the Japanese version of the Oral Health Impact Profile (OHIP-J) was administered and the summary score of OHIP-J was calculated. The SDA subjects were categorized depending upon the anterior-posterior lengths of the missing or remaining OUs. Regression analyses were performed to investigate the OHIP-J differences between groups of subjects with various anterior-posterior SDA lengths. The analyses revealed that subjects who only lost the second molar contact exhibited significantly better OHRQoL than those who lost more teeth [coefficient: 11.1, 95% confidence interval (CI): 2.8-19.2, P = 0.02]. Furthermore a statistically significant group difference was observed between the groups with and without the first molar occlusal contact (coefficient: 12.8, 95% CI: 1.4 to 24.1, P = 0.03). In conclusion, although our results are of exploratory nature and need validation, patterns of missing OUs are likely to be related to the OHRQoL impairment in SDA subjects with the presence of first molar contact having a particularly important role.
Assuntos
Arco Dental/fisiopatologia , Dor Facial/etiologia , Qualidade de Vida , Perda de Dente/complicações , Inquéritos de Saúde Bucal , Dor Facial/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Saúde Bucal/normas , Qualidade de Vida/psicologia , Perfil de Impacto da Doença , Classe Social , Perda de Dente/psicologiaRESUMO
Secondary alterations in splicing have been reported to produce semi-functional mRNA from several nonsense mutations in the dystrophin gene. Disruptions of exonic splicing enhancers by single nucleotide changes are thought to underlie such alterations. The precise frequencies of such nonsense mutation-dependent splicing alterations, however, remain unknown. Here we analyzed the splicing patterns of dystrophin mRNA in lymphocytes from 38 patients with dystrophinopathies due to nonsense mutations in the dystrophin gene. In seven of the cases (18%), we observed partial skipping of the nonsense-encoding exon. Two of the seven cases, however, exhibited complex activation of a nonsense mutation-created splice site, which resulted in the generation of novel transcripts. Examination of cis-regulatory splicing elements through calculation of splicing probability scores and identification of potential splicing enhancer or silencer sequences failed to disclose a single cause for exon skipping. Remarkably, individual differences in splicing patterns were observed for cells from patients with identical nonsense mutations (C.5899C>T). Although five cases produced semi-functional dystrophin mRNAs, only one of these exhibited a mild clinical course. These results provide important insights about targets for exon skipping induced by candidate antisense oligonucleotides and for ribosomal read-through of nonsense mutations.
Assuntos
Códon sem Sentido , Distrofina/genética , Linfócitos/metabolismo , Distrofias Musculares/genética , Adolescente , Adulto , Criança , Pré-Escolar , Análise Mutacional de DNA , Humanos , Japão , Splicing de RNARESUMO
Designs of removable partial dentures are suggested to affect the mobility of abutment teeth and removable partial denture (RPD) during oral functions. This study aimed to examine the effect of direct retainer and major connector designs on RPD dynamics under simulated loading. Six different Kennedy class II maxillary RPDs were fabricated on a maxillary model. These dentures involved 3 different direct retainers (wrought-wire clasp, RPA clasp, and conical crown telescopic retainer) and 2 different major connectors (Co-Cr major connector and heat-cured acrylic resin with a metal strengthener). Using an experimental model with simulated periodontal ligaments and mucosa that were fabricated using silicone impression material, three-dimensional displacements of the RPDs were measured under a simulated 30-N loading with a displacement transducer type M-3. Significant effects of "direct retainer design" on bucco-palatal displacements and "major connector" on mesio-distal displacements were revealed by 2 x 3 two-way analysis of variance of abutment teeth movements (P < 0.001 and P = 0.002, respectively). Additionally, analysis of variance of RPD displacements revealed significant effects of "direct retainer design" on corono-apical displacements and "major connector" on mesio-distal displacements (P = 0.001 and P = 0.028, respectively). Rigid direct retainers and rigid major connectors decrease the movements of both abutment tooth and RPD.