RESUMO
Mouse senile amyloidosis is a disorder in which apolipoprotein A-II deposits extracellularly in many organs as amyloid fibrils (AApoAII). In this study, we intravenously injected 1 µg of isolated AApoAII fibrils into R1.P1-Apoa2(c) mice, to induce AApoAII amyloidosis. We observed that the unfolded protein response was induced by deposition of AApoAII amyloid. We found that the mRNA and the protein expression levels of heat shock protein A5 (HSPA5; also known as glucose-regulated protein 78) were increased in the liver with AApoAII amyloid deposits. Immunohistochemistry showed that HSPA5 was only detected in hepatocytes close to AApoAII amyloid deposits. Furthermore, gene transcription of several endoplasmic reticulum (ER) stress-related proteins increased, including eukaryotic translation initiation factor 2 alpha kinase 3 (Eif2ak3), activating transcription factor 6 (Atf6), activating transcription factor 4 (Atf4), X-box-binding protein 1 splicing (Xbp1s), DNA-damage inducible transcript 3 (Ddit3), and autophagy protein 5 (Atg5). Moreover, apoptosis-positive cells were increased in the liver. Similar results were seen in the kidney but not in the heart. Our study indicates that ER stress responses differed among tissues with extracellular AApoAII amyloid fibril deposition. Although upregulated HSPA5 and the activated unfolded protein response might have roles in protecting tissues against aggregated extracellular AApoAII amyloid deposition, prolonged ER stress induced apoptosis in the liver and the kidney.
Assuntos
Amiloide/metabolismo , Apolipoproteína A-II/metabolismo , Rim/metabolismo , Fígado/metabolismo , Miocárdio/metabolismo , Resposta a Proteínas não Dobradas , Amiloidose/metabolismo , Animais , Apoptose , Western Blotting , Chaperona BiP do Retículo Endoplasmático , Estresse do Retículo Endoplasmático , Espaço Extracelular/metabolismo , Expressão Gênica , Proteínas de Choque Térmico/genética , Proteínas de Choque Térmico/metabolismo , Hepatócitos/metabolismo , Hepatócitos/patologia , Imuno-Histoquímica , Túbulos Renais/metabolismo , Túbulos Renais/patologia , Camundongos , Especificidade de Órgãos , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
BACKGROUND: Postinfectious cough (PIC) is a common symptom following a respiratory tract infection. Xingbei Zhike (XBZK) granules, a Chinese patent medicine, has been widely used for PIC in clinics. However, there is a lack of evidence on the effectiveness. PURPOSE: To investigate whether treatment with XBZK granules is effective for PIC. STUDY DESIGN: A multicenter, randomized, double-blinded, placebo-controlled trial. METHODS: Eligible participants from fourteen hospitals were randomly assigned in 3:1 ratio to receive either XBZK granules or placebo for 14 days. The primary outcome was the area under the curve (AUC) of a visual analogue scale (VAS) for cough symptoms. Secondary outcomes included cough symptom score (CSS), time and probability of recovery from cough, traditional Chinese medicine (TCM) syndrome score, relief rates of individual symptoms, Leicester Cough Questionnaire (LCQ) score, and the use of reliever drug. RESULTS: A total of 235 patients (176 in XBZK and 59 in placebo groups) were included in the analysis. The AUC for cough VAS scores was lower in the XBZK than placebo group (-8.10, 95 % CI -14.12 to -2.07, p = 0.009), indicating superiority. XBZK decreased CSS (-0.68 points, 95 % CI -1.13 to -0.22, p = 0.01), shortened time to cough recovery (-2 days, hazard ratio [HR] 1.48, 95 % CI 1.03 to 2.13, p = 0.02), enhanced the probability of cough recovery (risk ratio [RR] 1.66, 95 % CI 1.07 to 2.58, p = 0.03), lowered TCM syndrome score (-0.99 points, 95 % CI -1.58 to -0.40, p = 0.004), increased the rate of daytime (RR 1.84, 95 % CI 1.07 to 3.15, p = 0.02) and nighttime (RR 2.07, 95 % CI 1.29 to 3.35, p = 0.004) cough recovery, and reduced the viscosity of sputum (RR 2.92, 95 % CI 1.66 to 5.13, p < 0.001) compared to placebo. There were no significant differences in LCQ scores and taking reliever drugs between groups. No severe adverse events were reported in either group. CONCLUSIONS: XBZK granules are a promising therapy against PIC, effective in lowering the overall severity of cough, shortening the time to cough recovery, and reducing the viscosity of sputum.
Assuntos
Medicamentos de Ervas Chinesas , Infecções Respiratórias , Humanos , Tosse/tratamento farmacológico , Medicina Tradicional Chinesa , Infecções Respiratórias/tratamento farmacológico , Resultado do Tratamento , Método Duplo-Cego , Medicamentos de Ervas Chinesas/efeitos adversosRESUMO
Apolipoprotein A-II (apoA-II) is the second major apolipoprotein following apolipoprotein A-I (apoA-I) in HDL. ApoA-II has multiple physiological functions and can form senile amyloid fibrils (AApoAII) in mice. Most circulating apoA-II is present in lipoprotein A-I/A-II. To study the influence of apoA-I on apoA-II and AApoAII amyloidosis, apoA-I-deficient (C57BL/6J.Apoa1â»/â») mice were used. Apoa1â»/â» mice showed the expected significant reduction in total cholesterol (TC), HDL cholesterol (HDL-C), and triglyceride (TG) plasma levels. Unexpectedly, we found that apoA-I deficiency led to redistribution of apoA-II in HDL and an age-related increase in apoA-II levels, accompanied by larger HDL particle size and an age-related increase in TC, HDL-C, and TG. Aggravated AApoAII amyloidosis was induced in Apoa1â»/â» mice systemically, especially in the heart. These results indicate that apoA-I plays key roles in maintaining apoA-II distribution and HDL particle size. Furthermore, apoA-II redistribution may be the main reason for aggravated AApoAII amyloidosis in Apoa1â»/â» mice. These results may shed new light on the relationship between apoA-I and apoA-II as well as provide new information concerning amyloidosis mechanism and therapy.
Assuntos
Amiloide/biossíntese , Amiloidose , Apolipoproteína A-II , Apolipoproteína A-I , HDL-Colesterol/sangue , Envelhecimento , Amiloidose/metabolismo , Amiloidose/patologia , Amiloidose/fisiopatologia , Animais , Apolipoproteína A-I/deficiência , Apolipoproteína A-I/genética , Apolipoproteína A-II/sangue , Apolipoproteína A-II/genética , Feminino , Deleção de Genes , Fígado/química , Fígado/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Miocárdio/química , Miocárdio/metabolismo , Tamanho da Partícula , RNA Mensageiro/análise , RNA Mensageiro/biossíntese , Triglicerídeos/sangueRESUMO
OBJECTIVE: To observe the effect of tracheotomy high-flow oxygen therapy (THFO) on the clinical efficacy of non-mechanically ventilated patients undergoing a tracheotomy. METHODS: Sixty adult patients with tracheotomy and non-mechanical ventilation who were diagnosed and treated from January 2019 to December 2020 in Fenyang Hospital of Shanxi Province were enrolled. According to the random number table, the patients were divided into Venturi oxygen therapy group and THFO group, 30 cases in each group. The THFO group was given oxygen therapy with THFO; the Venturi group (without mask) was given Venturi connected the MR850 base and the ventilator tube. Observe the changes of two groups at 7 AM within 5 days, including body temperature which was 1 centigrade higher than the baseline, white blood cell count (WBC) which was 2×109/L higher than baseline, oxygenation index (PaO2/FiO2) < 300 mmHg (1 mmHg = 0.133 kPa), the occurrence of lower respiratory tract infections (based on radiography), and changes in sputum indexing and sputum formation. RESULTS: Compared with the Venturi oxygen therapy group, the body temperature increased > 1 centigrade, WBC increased by 2×109/L, PaO2/FiO2 < 300 mmHg, and the proportion of lower respiratory tract infection in THFO group decreased significantly [body temperature increased > 1 centigrade: 10.0% (3/30) vs. 13.3% (4/30), WBC increased by 2×109/L: 10.0% (3/30) vs. 30.0% (9/30), PaO2/FiO2 < 300 mmHg: 3.3% (1/30) vs. 10.0% (3/30), the proportion of lower respiratory tract infection: 6.7% (2/30) vs. 13.3% (4/30), all P < 0.05]. The proportion of patients with sputum scab formation and sputum viscosity of I degree were significantly increased [sputum scab formation: 16.7% (5/30) vs. 6.7% (2/30), sputum viscosity of I degree: 30.0% (9/30) vs. 20.0% (6/30), both P < 0.05]. CONCLUSIONS: THFO during non-mechanical ventilation of adult patients with tracheotomy can maintain a higher oxygen partial pressure and ideally control the temperature and humidity of the inhaled gas, promote the discharge of sputum with degree I and II viscosity, thereby reducing the tracheotomy complications such as lower respiratory tract infections.
Assuntos
Oxigenoterapia , Traqueotomia , Gasometria , Humanos , Oxigênio , TraqueostomiaRESUMO
Introduction: With the emergence of novel coronavirus disease 2019 (COVID-19) in many countries, medical resources currently focus on the treatment of confirmed patients and screening of suspected cases. Asymptomatic patients may be contagious, which makes epidemic control difficult. We describe an asymptomatic patient with a positive real-time polymerase chain reaction (RT-PCR) test in urine.Case report: An asymptomatic girl was identified during the epidemiological investigation of a confirmed COVID-19 patient. When admitted to the hospital on 24 February 2020, she had no clinical manifestations. A throat swab was negative for RT-PCR, but urine was positive. She was given antiviral and symptomatic supportive treatment. On 26 February, a throat swab RT-PCR was positive. RT-PCR in throat swabs and urine were negative on 3 and 5 March, and on 9 and 12 March, throat swabs were still negative. At follow-up on 26 March, she felt well, throat swab RT-PCR was negative, and isolation was lifted.Conclusion: The urine of asymptomatic patients may be contagious. RT-PCR in urine might be a useful supplement in screening when the RT-PCR is negative in throat swabs.
Assuntos
Infecções Assintomáticas , Betacoronavirus/isolamento & purificação , Técnicas de Laboratório Clínico/métodos , Infecções por Coronavirus/urina , Pneumonia Viral/urina , Adolescente , Betacoronavirus/genética , COVID-19 , Teste para COVID-19 , Vacinas contra COVID-19 , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/virologia , Feminino , Humanos , Pandemias , Pneumonia Viral/virologia , Reação em Cadeia da Polimerase em Tempo Real/métodos , SARS-CoV-2 , Urina/virologiaRESUMO
OBJECTIVE: To investigate the effect of oxygen therapy with Venturi combined with MR850 heating humidifier on patients without mechanical ventilation after tracheotomy. METHODS: Eighty patients (≥ 18 years old) who had undergone tracheotomy and without mechanical ventilation admitted to Fenyang Hospital of Shanxi Province from June 2016 to December 2017 were enrolled, and they were divided into control group and observation group according to random number table method, with 40 patients in each group. The observation group was given Venturi (removed the mask) combined with MR850 device active warm and humid oxygen therapy; the control group was given one-off ordinary flow device and warm and humid exchanger (artificial nose, HME) passive humid oxygen therapy. Body temperature increased by 1 centigrade above basal body temperature, white blood cell count (WBC) increased 2×109/L than the base value, oxygenation index (PaO2/FiO2) < 300 mmHg (1 mmHg = 0.133 kPa), airway mucosal hemorrhage, pulmonary infection and sputum viscosity were observed in the two groups for 5 days after oxygen therapy. RESULTS: Among the 80 patients, there were 46 males and 34 females, with an average age of (67.7±12.2) years. Compared with the control group, the incidence of increased body temperature (5.0% vs. 20.0%), the incidence of increased WBC (7.5% vs. 35.0%), the incidence of low PaO2/FiO2 (2.5% vs. 7.5%), the incidence of airway mucosal bleeding (5.0 % vs. 15.0%) and the incidence of pulmonary infection (2.5% vs. 10.0%) were significantly decreased in the observation group (all P < 0.01), and the proportion of sputum viscosity I degree of patients was significantly increased (57.5% vs. 12.5%, P < 0.01). CONCLUSIONS: Venturi combined with MR850 device can effectively control airway temperature and humidity, promote sputum dilution and conducive to drainage, reduce pulmonary infection in adults patients without mechanical ventilation after tracheotomy, thereby reducing postoperative complications of tracheotomy.
Assuntos
Oxigenoterapia/métodos , Traqueotomia , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Respiração Artificial , Resultado do TratamentoRESUMO
AIM: The present study was conducted to define the relationship between the anti-aging effect of ubiquinol-10 supplementation and mitochondrial activation in senescence-accelerated mouse prone 1 (SAMP1) mice. RESULTS: Here, we report that dietary supplementation with ubiquinol-10 prevents age-related decreases in the expression of sirtuin gene family members, which results in the activation of peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), a major factor that controls mitochondrial biogenesis and respiration, as well as superoxide dismutase 2 (SOD2) and isocitrate dehydrogenase 2 (IDH2), which are major mitochondrial antioxidant enzymes. Ubiquinol-10 supplementation can also increase mitochondrial complex I activity and decrease levels of oxidative stress markers, including protein carbonyls, apurinic/apyrimidinic sites, malondialdehydes, and increase the reduced glutathione/oxidized glutathione ratio. Furthermore, ubiquinol-10 may activate Sirt1 and PGC-1α by increasing cyclic adenosine monophosphate (cAMP) levels that, in turn, activate cAMP response element-binding protein (CREB) and AMP-activated protein kinase (AMPK). INNOVATION AND CONCLUSION: These results show that ubiquinol-10 may enhance mitochondrial activity by increasing levels of SIRT1, PGC-1α, and SIRT3 that slow the rate of age-related hearing loss and protect against the progression of aging and symptoms of age-related diseases.