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Objective: There have been reports of neuromyelitis optica spectrum disorder (NMOSD) coexisting with connective tissue disorders. The objective of this study was to describe the characteristics of NMOSD coexisting with autoimmune diseases (AID). Methods: This retrospective study evaluated NMOSD patients with and without AID. The enrolled patients had at least one attack, with duration of more than 1 year. Data on the demographics, clinical features, and laboratory findings were assessed. The Poisson model was used to investigate the risk factors associated with the annualized relapse rate (ARR), whereas the Cox model was used to evaluate the risk factors for the first relapse. Results: A total of 180 patients (154 women and 26 men) with NMOSD were identified: 45 had AID and 135 did not. Female patients had a higher prevalence of concomitant AID (p = 0.006) and a greater relapse rate within the first year. There were no statistically significant differences in the characteristics of patients. Kaplan-Meier analysis revealed that NMOSD patients with seropositive aquaporin 4 antibodies (AQP4-Ab; log-rank: p = 0.044), had a shorter time to relapse. Patients seropositive for AQP4-Ab (HR = 2.402, 95%CI = 1.092-5.283, p = 0.029) had a higher risk of suffering a first relapse, according to the Cox model. Patients with and without AID showed a similar declining tendency in terms of change in ARR throughout the first 5 years of the disease. The ARR was greater in the first year [incidence rate ratio (IRR) = 1.534, 95%CI = 1.111-2.118] and the first 2 years (IRR = 1.474, 95%CI = 1.056-2.058) in patients with coexisting AID diagnosis prior to the NMOSD onset. Conclusions: Patients with NMOSD with coexisting AID had similar characteristics when compared with those without AID. NMOSD patients with AID diagnosed before onset had a higher risk of relapse in the early stage of the disease.
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Acuaporina 4 , Enfermedades Autoinmunes , Neuromielitis Óptica , Recurrencia , Humanos , Neuromielitis Óptica/epidemiología , Neuromielitis Óptica/inmunología , Neuromielitis Óptica/diagnóstico , Femenino , Masculino , Adulto , Estudios Retrospectivos , Persona de Mediana Edad , Enfermedades Autoinmunes/epidemiología , Enfermedades Autoinmunes/inmunología , Enfermedades Autoinmunes/complicaciones , Acuaporina 4/inmunología , Autoanticuerpos/sangre , Autoanticuerpos/inmunología , Factores de Riesgo , Anciano , Adulto JovenRESUMEN
BACKGROUNDS: Thrombosis of dural sinuses and/or cerebral veins (CVT) is an uncommon form of cerebrovascular disease. Malnutrition is common in patients with cerebrovascular disease, and early assessment of malnutrition and individualized nutritional treatment have been reported to improve functional outcomes of these patients. As for CVT patients, little is known about whether these patients would suffer from malnutrition. Also, the correlation between malnutrition and cerebral intraparenchymal damage (CID) in CVT patients was rarely studied. METHODS: Patients with CVT were retrospectively included in this observational study. Multivariate logistic regressions were used to investigate the effects of nutritional indexes on the risk of CID. Subsequently, we used the independent risk factors to construct the nomogram model, and the consistency index (C-index), calibration curve and decision curve analysis (DCA) to assess the reliability and applicability of the model. RESULTS: A total of 165 patients were included in the final analysis. Approximately 72.7% of CVT patients were regarded as malnourished by our malnutrition screening tools, and malnutrition is associated with an increased risk of CID. Prognostic Nutritional Index (PNI) (OR = 0.873; CI: 0.791, 0.963, p = 0.007) remained as an independent predictor for CID after adjustment for other risk factors. The nomogram model showed that PNI and gender have a great contribution to prediction. Besides, the nomogram model was consistent with the actual observations of CID risk (C-index = 0.65) and was of clinical significance. CONCLUSIONS: We reported that malnutrition, as indicated by PNI, was associated with a higher incidence of CID in CVT patients. Also, we have constructed a nomogram for predicting the risk of CID in these patients.
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Venas Cerebrales , Trombosis Intracraneal , Desnutrición , Trombosis , Humanos , Estudios Retrospectivos , Reproducibilidad de los Resultados , Trombosis/complicaciones , Desnutrición/complicaciones , Desnutrición/epidemiología , Trombosis Intracraneal/complicacionesRESUMEN
SCOPE: This study aims to investigate the anti-hyperuricemic and nephroprotective effects and the potential mechanisms of the separated gastrointestinal hydrolysates of α-lactalbumin on hyperuricemic mice. METHODS AND RESULTS: The gastrointestinal hydrolysate of α-lactalbumin, the hydrolysate fraction with molecular weight (MW) < 3 kDa (LH-3k), and the fragments with smallest MW among LH-3K harvested through dextran gel chromatography (F5) are used. Hyperuricemia mice are induced via daily oral gavage of potassium oxonate and hypoxanthine. F5 displays the highest in vitro xanthine oxidase (XO) inhibition among all the fractions separated from LH-3k. Oral administration of F5 significantly reduces the levels of serum uric acid (UA), creatinine, and urea nitrogen. F5 treatment could ameliorate kidney injury through alleviating oxidative stress and inflammation. F5 alleviates hyperuricemia in mice by inhibiting hepatic XO activity and regulating the expression of renal urate transporters. Gut microbiota analysis illustrates that F5 administration increases the abundance of some SCFAs producers, and inhibits the growth of hyperuricemia and inflammation associated genera. LH-3k exhibits similar effects but does not show significance as those of the F5 fraction. CONCLUSION: The anti-hyperuricemia and nephroprotective functions of F5 are mediated by inhibiting hepatic XO activity, ameliorating oxidative stress and inflammation, regulating renal urate transporters, and modulating the gut microbiota in hyperuricemic mice.
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Microbioma Gastrointestinal , Hiperuricemia , Ratones , Animales , Ácido Úrico , Lactalbúmina/metabolismo , Hiperuricemia/tratamiento farmacológico , Riñón/metabolismo , Ácido Oxónico/metabolismo , Ácido Oxónico/farmacología , Factores de Transcripción/metabolismo , Inflamación/metabolismo , Hipoxantinas/metabolismo , Hipoxantinas/farmacologíaRESUMEN
VGINYW is a highly active angiotensin I-converting enzyme (ACE) inhibitory peptide discovered from α-lactalbumin by an in vitro-in silico high throughput screening strategy. The aim of this study was to evaluate the antihypertensive effect of the peptide and the α-lactalbumin hydrolysates under 3 kDa (LH-3k), and illustrate the possible mechanism in spontaneously hypertensive rats (SHRs). SHRs were administered with VGINYW and LH-3k at doses of 5 mg per kg BW and 100 mg per kg BW, respectively. VGINYW and LH-3k could markedly decrease the systolic blood pressure (SBP) of the SHRs, and the maximal drops of 21 mmHg (2 h after administration) and 17 mmHg (4 h after administration) were achieved during the 8 hour test, respectively. When the agents were given once per day for 4 weeks, they caused a long-term decrease of 16 mmHg of SBP. VGINYW and LH-3k control the blood pressure through regulating the renin-angiotensin system by inhibiting the ACE activity and diminishing the angiotensin II level, and further upregulating the expression levels of the angiotensin-converting enzyme 2 and angiotensin type 2 receptor, and downregulating the expression of the angiotensin type 1 receptor. VGINYW and LH-3k could notably ameliorate the oxidative stress in the SHR as well. It is more important that the gavage of VGINYW and LH-3k could alleviate hypertension-associated intestinal microbiota dysbiosis by recovering the diversity of the gut microbiota and altering the key floras which are short chain fatty acid producers. In conclusion, VGINYW and LH-3k are effective functional ingredients for blood pressure control.
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Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Antihipertensivos/farmacología , Lactalbúmina , Hidrolisados de Proteína/farmacología , Inhibidores de la Enzima Convertidora de Angiotensina/química , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Animales , Antihipertensivos/química , Antihipertensivos/uso terapéutico , Presión Sanguínea/efectos de los fármacos , Modelos Animales de Enfermedad , Microbioma Gastrointestinal/efectos de los fármacos , Hipertensión/prevención & control , Masculino , Estrés Oxidativo/efectos de los fármacos , Hidrolisados de Proteína/química , Hidrolisados de Proteína/uso terapéutico , Ratas , Ratas Endogámicas SHR , Organismos Libres de Patógenos EspecíficosRESUMEN
OBJECTIVE: The novel biomarker, neutrophil percentage-to-albumin ratio (NPAR), as a prognostic tool for inflammation in relation to all-cause mortality for patients afflicted by strokes has yet to be explored. METHODS: Data sets associated with patient files stored within the MIMIC-III V1.4 database were obtained. Data files from 940-patients were obtained for this retrospective analysis. Clinical endpoints were determined to represent a month (30-), three months (90-) and year (365-) all-cause mortality in stroke patients were determined. In order to determine NPAR and clinical endpoint relationships, Cox proportional hazards models were utilized. RESULTS: For all-cause mortality within a 30-day period, in an unadjusted model, the HR (95% CIs) in group B (NPAR 20.5-25.0) and C (NPAR >25.0) was 1.17 (0.85, 1.63) and 1.55 (1.13, 2.11) compared with group A (NPAR < 20.5). Proceeding adjustment for more confounding factors, higher NPAR still obtained significant predictive power for 30-day all-cause mortality (HR= 1.45, 95% CI: 1.05, 2.00). Statistical significance (P = 0.0196) was also observed for the other time-based subgroupings for all-cause mortality. CONCLUSION: A strong correlation was present between increased levels of the novel biomarker NPAR and increased risk of mortality in stroke patients.
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Objective: Malnutrition has been reported to be related to adverse prognosis in acute ischemic stroke (AIS) patients. Unfortunately, traditional nutritional assessment tools usually increase the workload of neurologists, which makes them unfeasible in the daily clinic work. We aimed to elucidate the association between the prognostic nutritional index (PNI), an easily obtainable baseline nutritional marker, and 3-month outcomes in AIS patients receiving intravenous thrombolysis (IVT). Research methods and procedures: The present study retrospectively included 405 patients. PNI was calculated as 5*lymphocyte count (109 /L) + serum albumin concentration (g/L), and the good prognosis was defined as modified Rankin Scale score of 0-3. The relationship between PNI and clinical parameters was evaluated. The multiple logistic regression model was performed to find out independent predictors of the 3-month outcomes. Results: We found that the patients in the low PNI group had a higher frequency of anemia (12.9 vs. 2.3%, P < 0.001) and a higher level of the Controlling nutritional status (CONUT) score (P < 0.001). The relationship between PNI and nutrition-related factors, such as body mass index (r = 0.208, P = 0.001), age (r = -0.329, P < 0.001), total cholesterol (r = 0.268, P < 0.001) and hemoglobin concentration (r = 0.328, P < 0.001), was significant. Low PNI value (adjusted odds ratio: 2.250, confidence interval: 1.192-4.249, p = 0.012) stayed as an independent predictor for the poor outcome at three months, after adjustment for potential confounders. Conclusions: The PNI was independently associated with 3-month outcomes in AIS patients undergoing IVT. As an easily obtainable nutritional marker, PNI may be a useful nutritional assessment tool in the clinic work.
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A novel prolyl endopeptidase from Stenotrophomonas maltophilia, SmPEP, was discovered and characterized. The specific activity of the recombinant SmPEP expressed by Escherichia coli BL21 (DE3), was 68.3 U/mg at pH 8.0 and 37⯰C. In order to improve the substrate specificity for long-chain peptide, rational design was applied based on the structure constructed by homology modeling. Inter-domain sites within the ß-propeller domain were chosen for the mutation to weaken the inter-domain interaction and form an open conformation for long-chain substrate entering into the active site. The substrate specificity on a designed long-chain substrate, PQPQLPYPQPQLP, of the mutants F263A and E184â¯G increased 8.77 and 5.75 times respectively versus wild-type. After the saturated mutation of the both sites, the reactive rate of mutant F263â¯V on 13-mer peptide was 10.2 times higher than that of the wild-type. Then the mutant F263â¯V was used in the hydrolysis of casein, and the ACE inhibitory activity of the hydrolysate was significantly improved compared with wild type enzyme, which verified the efficiency of the design strategy.
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Prolil Oligopeptidasas/química , Prolil Oligopeptidasas/metabolismo , Stenotrophomonas maltophilia/enzimología , Secuencia de Aminoácidos , Inhibidores de la Enzima Convertidora de Angiotensina/metabolismo , Proteínas Bacterianas/química , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Caseínas/metabolismo , Dominio Catalítico , Escherichia coli/genética , Escherichia coli/metabolismo , Hidrólisis , Modelos Moleculares , Mutación , Péptidos/química , Péptidos/metabolismo , Prolil Oligopeptidasas/genética , Conformación Proteica , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Stenotrophomonas maltophilia/genética , Relación Estructura-Actividad , Especificidad por SustratoRESUMEN
OBJECTIVE: We aimed to investigate whether platelet volume indices (PVIs) were associated with an unfavorable clinical outcome in acute ischemic stroke (AIS) patients undergoing intravenous thrombolysis (IVT). METHODS: We defined a modified Rankin Scale (mRS) score of 3-6 at 90 days as an unfavorable outcome. Logistic regression analysis was performed to find out whether mean platelet volume (MPV), platelet distribution width (PDW), MPV/platelet count (PC) ratio and PDW/PC ratio were associated with poor prognosis. A Spearman correlation test was carried out to assess the relationship between variables. RESULTS: Overall, 183 patients were included in this study. Multivariate logistic regression analysis revealed that MPV (adjusted odds ratio [OR] 1.52, 95% confidence interval [CI]: 1.01-2.29, p = 0.044) and PDW-sd (adjusted OR 1.30, 95% CI: 1.06-1.59, p = 0.011) were independent predictors of the poor outcome. There was a trend of incremental OR when compared higher tertile of MPV with lower ones (second tertile, adjusted OR 2.52,95% CIï¼1.02-6.21, p = 0.045ï¼ third tertile, adjusted OR 2.61, 95% CI: 1.12-6.09, p = 0.027). Besides, we found a significant positive correlation between MPV and PDW-sd (or =0.874, p < 0.001). CONCLUSION: MPV and PDW-sd were independent predictors for 90-day outcomes in stroke patients receiving thrombolysis.
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Isquemia Encefálica/diagnóstico , Isquemia Encefálica/tratamiento farmacológico , Fibrinolíticos/administración & dosificación , Volúmen Plaquetario Medio , Evaluación de Resultado en la Atención de Salud , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Isquemia Encefálica/sangre , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Accidente Cerebrovascular/sangreRESUMEN
PURPOSE: To investigate the clinical character, diagnosis and treatment of chronic inflammatory demyelinating polyneuropathy accompanying myasthenia gravis so as to improve the understanding of such diseases. MATERIALS AND METHODS: A case of chronic inflammatory demyelinating polyneuropathy combined with myasthenia gravis were analyzed retrospectively with review of the literature. RESULTS: This man was presented with chronic progressive sensory symptoms, flaccid tetraparesis, areflexia and protein-cell dissociation of cerebrospinal fluid. Nerve conduction study was indicative of demyelinating neuropathy. He was suspected as chronic inflammatory demyelinating polyneuropathy and treated with high-dose glucocorticoids. However, his condition worsened. Four months later, he was admitted and was diagnosed as combination of chronic inflammatory demyelinating polyneuropathy and myasthenia gravis. Good clinical results were observed after he was treated with pyridostigmine bromide, prednisone and mycophenolate mofetil. CONCLUSIONS: This case warns clinicians to be aware of these two diseases presenting in the same patient, and the possible implications on treatment choices. A common immunological abnormality might exist in this rare association, but it still remains unknown.
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Miastenia Gravis , Polirradiculoneuropatía Crónica Inflamatoria Desmielinizante , Anciano , Humanos , Masculino , Miastenia Gravis/diagnóstico , Miastenia Gravis/tratamiento farmacológico , Miastenia Gravis/fisiopatología , Polirradiculoneuropatía Crónica Inflamatoria Desmielinizante/diagnóstico , Polirradiculoneuropatía Crónica Inflamatoria Desmielinizante/tratamiento farmacológico , Polirradiculoneuropatía Crónica Inflamatoria Desmielinizante/fisiopatologíaRESUMEN
Purpose/Aim of the study: Guillain Barré syndrome (GBS) is a severe peripheral nervous disease that leads to muscle weakness and areflexia. We now commonly accept a synthesis that inflammation and immunity play key role in GBS pathogenesis. Many studies pointed out that neutrophil-to-lymphocyte ratio (NLR) and monocyte-to-lymphocyte ratio (MLR) are novel promising markers of inflammation or immunity. Our study aimed to evaluate whether the NLR and the MLR were associated to GBS or not. MATERIALS AND METHODS: We measured blood cell count in 334 individuals including 117 GBS and 217 healthy controls. RESULTS: Our findings demonstrated that the GBS patients had higher levels of NLR and MLR than the healthy controls. The severe group also had higher levels of NLR and MLR compared to the mild group. We took the method of receiver-operating characteristic curve to find out the cut-off value of NLR for GBS occurrence and severity; it was 2.295 and 3.05, respectively. The cut-off values of MLR for GBS incidence and severity were the same, it was 0.235. CONCLUSION: In the setting of GBS, the NLR and MLR were significantly increased and they may be pathophysiologically and clinically relevant in GBS. The NLR and MLR would be new biomarkers of medical application.
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Síndrome de Guillain-Barré/patología , Linfocitos/patología , Monocitos/patología , Neutrófilos/patología , Adulto , Anciano , Anciano de 80 o más Años , Proteína C-Reactiva/metabolismo , Estudios de Casos y Controles , Femenino , Síndrome de Guillain-Barré/diagnóstico , Humanos , Masculino , Persona de Mediana Edad , Examen Neurológico , Curva ROC , Estudios Retrospectivos , Estadísticas no ParamétricasRESUMEN
Most acute central nervous system (CNS) viral infections lead to either encephalitis or meningitis. Many neurotropic viruses may cause CNS dysfunctions through various mechanisms including oxidative stress. Serum uric acid (SUA) levels, which are associated with oxidative stress and antioxidant status, are reduced in patients with various neurological disorders, including multiple sclerosis. We investigated the possible correlation between SUA levels and clinical disease status in patients with acute CNS viral infections. We measured SUA concentrations in 336 individuals, including 179 healthy individuals and 157 patients with acute CNS viral infections. We found that the patients had lower SUA levels than the healthy individuals did irrespective of sex. Effective therapy significantly increased SUA levels. The patients' SUA levels were correlated inversely with outcomes as measured with the Glasgow Outcome Scale. SUA levels may be a biomarker for predicting treatment outcomes and prognoses for patients with acute CNS viral infections with inflammatory components.
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Enfermedades Virales del Sistema Nervioso Central/sangre , Ácido Úrico/sangre , Adulto , Enfermedades Virales del Sistema Nervioso Central/fisiopatología , Femenino , Escala de Consecuencias de Glasgow , Humanos , Recuento de Leucocitos , Masculino , Persona de Mediana Edad , Estadística como Asunto , Adulto JovenRESUMEN
Acute transverse myelitis (ATM) is a progressive and autoimmune disease with inflammatory cell infiltrates into the spinal cord, and thyroid hormone (TH) level is associated with the oxidative and antioxidant status. Variations in oxidative stress and antioxidant levels are related to the pathogenesis of autoimmune and inflammatory diseases. Our study aimed to investigate the possible correlation between ATM and TH levels of thyroid-stimulating hormone (TSH), free thyroxine (FT4), free triiodothyronine (FT3), and FT4/FT3. We measured serum concentrations of TSH, FT4, and FT3 in 205 individuals, including 42 ATM patients, 49 multiple sclerosis patients, and 114 healthy controls. Our findings show that ATM patients had lower levels of TSH and FT3 and higher levels of FT4 and FT4/FT3 compared with healthy controls, whether male or female. Moreover, levels of TSH and FT3 in patients with ATM were inversely correlated with disease severity measured by the Expanded Disability Status Scale. Variations in TH level may represent the oxidative status and are surrogate biomarkers of the incidence and severity of ATM.