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Objective To observe the effect of excess oxygen supply for different time periods on the mitochondrial energy metabolism in alveolar epithelial type Ⅱ cells. Methods Rat RLE-6TN cells were assigned into a control group (21% O2 for 4 h) and excess oxygen supply groups (95% O2 for 1,2,3,and 4 h,res-pectively).The content of adenosine triphosphate (ATP),the activity of mitochondrial respiratory chain complex V,and the mitochondrial membrane potential were determined by luciferase assay,micro-assay,and fluorescent probe JC-1,respectively.Real-time fluorescence quantitative PCR was employed to determine the mRNA levels of NADH dehydrogenase subunit 1 (ND1),cytochrome b (Cytb),cytochrome C oxidase subunit I (COXI),and adenosine triphosphatase 6 (ATPase6) in the core subunits of mitochondrial respiratory chain complexes Ⅰ,Ⅲ,Ⅳ,and Ⅴ,respectively. Results Compared with the control group,excess oxygen supply for 1,2,3,and 4 h down-regulated the mRNA levels of ND1 (q=24.800,P<0.001;q=13.650,P<0.001;q=9.869,P<0.001;q=20.700,P<0.001),COXI (q=16.750,P<0.001;q=10.120,P<0.001;q=8.476,P<0.001;q=14.060,P<0.001),and ATPase6 (q=22.770,P<0.001;q=15.540,P<0.001;q=12.870,P<0.001;q=18.160,P<0.001).Moreover,excess oxygen supply for 1 h and 4 h decreased the ATPase activity (q=9.435,P<0.001;q=11.230,P<0.001) and ATP content (q=5.615,P=0.007;q=5.029,P=0.005).The excess oxygen supply for 2 h and 3 h did not cause significant changes in ATPase activity (q=0.156,P=0.914;q=3.197,P=0.116) and ATP content (q=0.859,P=0.557;q=1.273,P=0.652).There was no significant difference in mitochondrial membrane potential among the groups (F=0.303,P=0.869). Conclusion Short-term excess oxygen supply down-regulates the expression of the core subunits of mitochondrial respiratory chain complexes and reduces the activity of ATPase,leading to the energy metabolism disorder of alveolar epithelial type Ⅱ cells.
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Animais , Ratos , Metabolismo Energético , Trifosfato de Adenosina , Adenosina Trifosfatases , RNA Mensageiro , OxigênioRESUMO
Objective To explore the inhibitory effects and mechanisms of benzodiazepines on Helicobacter pylori (Hp).Methods The Hp international standard strain ATCC43504 was treated with benzodiazepines diazepam,midazolam,and remimazolam,respectively.The treatments with amoxicillin and clarithromycin were taken as the positive controls,and that with water for injection as the negative control.The inhibition zone of each drug was measured by the disk diffusion method.The minimum inhibitory concentration(MIC)and minimum bactericidal concentration(MBC)of each drug against Hp were determined.Hp suspension was configured and treated with diazepam and midazolam,respectively.The bacterial suspension without drug added was used as the control group.The concentration of K+ in each bacterial suspension was measured by an automatic biochemical analyzer before drug intervention(T0)and 1(T1),2(T2),3(T3),4(T4),5(T5),6(T6),and 7 h(T7)after intervention.Hp urease was extracted and treated with 1/2 MIC diazepam,1 MIC diazepam,2 MIC diazepam,1/2 MIC midazolam,1 MIC midazolam,2 MIC midazolam,1 mg/ml acetohydroxamic acid,and water for injection,respectively.The time required for the rise from pH 6.8 to pH 7.7 in each group was determined by the phenol red coloring method.Results The inhibition zones of diazepam,midazolam,remimazolam,amoxicillin,clarithromycin,and water for injection against Hp were 52.3,42.7,6.0,72.3,60.8,and 6.0 mm,respectively.Diazepam and midazolam showed the MIC of 12.5 μg/ml and 25.0 μg/ml and the MBC of 25 μg/ml and 50 μg/ml,respectively,to Hp.The concentrations of K+ in the diazepam,midazolam,and control groups increased during T1-T7 compared with those at T0(all P<0.01).The concentration of K+ in diazepam and midazolam groups during T1-T4 was higher than that in the control group(all P<0.01).The time of inhibiting urease activity in the 1/2 MIC diazepam,1 MIC diazepam,2 MIC diazepam,1/2 MIC midazolam,1 MIC midazolam,and 2 MIC midazolam groups was(39.86±5.11),(36.52±6.65),(38.58±4.83),(39.25±6.19),(36.36±4.61),and(35.81±6.18)min,respectively,which were shorter than that in the acetohydroxamic acid group(all P<0.01)and had no significance differences from that in the water for injection group(all P>0.05).Conclusion Diazepam and midazolam exerted inhibitory effects on Hp,which may be related to the cleavage of Hp cells rather than inhibiting urease.
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Midazolam , Helicobacter pylori , Urease , Claritromicina/farmacologia , Benzodiazepinas/farmacologia , Diazepam/farmacologia , Amoxicilina , Água , Antibacterianos/farmacologiaRESUMO
Parkinson's disease (PD) is the second most common and fastest-growing neurodegenerative disorder. In recent years, it has been recognized that neurotransmitters other than dopamine and neuronal systems outside the basal ganglia are also related to PD pathogenesis. However, little is known about whether and how the caudal zona incerta (ZIc) regulates parkinsonian motor symptoms. Here, we showed that specific glutamatergic but not GABAergic ZIc
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Animais , Camundongos , Neurônios , Doença de Parkinson , Transtornos Parkinsonianos , Substância Negra , Zona IncertaRESUMO
Objective To explore the effect of overwork (OW) on extracellular matrix of arterial vessel wall in rats. Methods Random number grouping method was employed to assign 18 Sprague-Dawley rats into three groups(n=6):the control group(no special treatment),group OW(forced swimming twice a day for 15 days),and sleep deficiency(SD)+OW group(in addition to forced swimming twice a day,the rats were put on the platforms in water to limit sleep for 15 days).On the 16th day,the abdominal aorta and common carotid artery were collected after blood sampling from heart under deep anesthesia.A part of the abdominal aorta sample was taken for Masson staining of collagen fiber,and Verhoeff-Van Gieson staining was carried out for the elastic fiber of common carotid artery.Image J was employed for the quantitative analysis of collagen fiber and elastic fiber content.The expression of collagen 1(Col-1) protein was quantified by immunohistochemistry and the ultrastructure of vascular matrix was examined by transmission electron microscopy.The other part of the abdominal aorta sample was used to determine the mRNA levels of matrix metalloproteinase(MMP)-1,MMP-2,MMP-9,tissue inhibitor of metalloproteinases-1(TIMP-1),and Col-1 by quantitative real-time polymerase chain reaction. Results Compared with that in control group,the content of collagen fiber in groups OW and SD+OW had no significant change(all P>0.05);the content of elastic fiber in groups OW and SD+OW decreased(all P<0.001) and had no significant difference between each other(P>0.05).The vascular vessel wall of group OW showed slight fiber breakage,while that of group SD+OW presented wormhole-like or spongy fiber fragmentation.The mRNA levels of MMP-1 and MMP-2 in groups OW and SD+OW had no significant difference between each other(P>0.05) but were higher than that in control group(all P<0.001).The mRNA levels of MMP-9 and TIMP-1 had no significant difference among the three groups(all P>0.05).Groups OW and SD+OW had lower mRNA level(all P<0.001) and protein level(all P<0.001) of Col-1 than control group,while the mRNA and protein levels of Col-1 had no significant difference between groups OW and SD+OW(P>0.05). Conclusion OW can reduce the content of Col-1 and elastic fibers in the extracellular matrix of arterial vessels,destroy the elastic lamina of vascular wall,up-regulate the expression of MMP-1 and MMP-2,thereby injuring arterial vessels.
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Animais , Ratos , Colágeno Tipo I , Matriz Extracelular/metabolismo , Metaloproteinase 1 da Matriz/metabolismo , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , RNA Mensageiro/genética , Ratos Sprague-Dawley , Inibidor Tecidual de Metaloproteinase-1/metabolismoRESUMO
Re-evaluation of bioequivalence of generic drugs is one of the key research focus currently. As a means to ensure consistency of the therapeutic effectiveness of drug products, clinical bioequivalence has been widely accepted as a gold standard test. In vitro dissolution testing based on the theory of the BCS is the best alternative to in vivo bioequivalence study. In this article, the conventional dissolution method and flow-through cell method were used to investigate the dissolution profiles of domestic amoxicillin capsules in different dissolution media, and the absorption behavior of the drugs with different release rates (t85% = 15-180 min) in the gastrointestinal tract was predicted by Gastro Plus. The flow-through cell method was thought better to reflect the release characteristics in vivo, and amoxicillin capsules with regard to the release rates up to 45 min (t85% = 45 min) were having a satisfied bioequivalence with the oral solution according to the C(max) and AUC. Although two different dissolution profiles of domestic amoxicillin capsules were found by flow-through cell methods, prediction results revealed that domestic capsules were probably bioequivalent to each other.
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Humanos , Amoxicilina , Farmacocinética , Cápsulas , Simulação por Computador , Trato Gastrointestinal , Software , Solubilidade , Equivalência TerapêuticaRESUMO
The applicator therapy is a unique method to treat infant diarrhea in traditional Chinese medicines and widely applied in clinical practice. Currently, many researchers have proved the rationality of the therapy based on the traditional Chinese medicine mechanism and on the data from clinical practice, but its action mechanism is uncertain at present. In this study, with the assistance of pediatric practitioners, the automated ribosomal intergenic-spacer analysis (ARISA) was adopted to study the effect of the adjuvant therapy with Dingguier umbilical paste on intestinal flora of diarrhea infants, in which Dingguier umbilical paste served as the adjuvant therapy in oral traditional Chinese medicines and fecal samples of infants with different diarrhea symptoms were collected and used as the study materials. The results showed that the adjuvant therapy had a significant effect on the shift of intestinal flora, which was associated with the decrease in the similarity difference to the normal control group and the increase in the number of operational taxonomic units (OTUs) shared with the normal control group. Additionally, adjuvant therapy with Dingguier umbilical paste also showed long action duration and increased OTUs number. These results indicated that Dingguier umbilical paste has the effect in restoring the micro-ecosystem of unbalanced intestinal bacteria. Intestinal flora may be one of major targets for the applicator therapy for the infant diarrhea, but not for the single oral traditional Chinese medicine for infant diarrhea.
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Feminino , Humanos , Lactente , Masculino , Adjuvantes Farmacêuticos , Usos Terapêuticos , Diarreia , Tratamento Farmacológico , Microbiologia , Fezes , Microbiologia , Intestinos , Microbiologia , Medicina Tradicional Chinesa , Métodos , Pomadas , Resultado do Tratamento , UmbigoRESUMO
<p><b>OBJECTIVE</b>To observe the therapeutic effect of type II early diabetic nephropathies intervened by acupoint thread embedding for strengthening spleen and benefiting kidney.</p><p><b>METHODS</b>Sixty cases of type II early diabetic nephropathies were randomly divided into an acupoint thread embedding group and a routine therapy group, 30 cases in each group. In routine therapy group, western medicine routine therapy was applied to control blood sugar, blood pressure and blood lipid. In acupoint thread embedding group, besides the western medicine routine therapy, thread embedding intervention was given at Pishu (BL 20), Zusanli (ST 36), Shenshu (BL 23) and Yishu (Extra) on both sides as main acupints, and the treatment course was 3 months. Urinary micro-albumin excretion (UAER), total score of TCM syndrome and monitor control indices (blood sugar, blood pressure, blood lipid, urea nitrogen and serum creatinine) in both groups were observed before and after treatment, and the therapeutic effects in both groups were compared.</p><p><b>RESULTS</b>After treatment, the indices of UAER and total score of TCM syndrome were all reduced (P < 0.001, P < 0.01); the reduction in acupoint thread embedding group was more obvious (P < 0.01, P < 0.05); the total effective rate in acupoint thread embedding group was 76.7% (23/30), superior to that of 63.3% (19/30) in routine therapy group (P < 0.05). The blood sugar, blood pressure and blood lipid in both groups were remarkably improved (all P < 0.001) after treatment; the urea nitrogen and creatinine had no notable variation.</p><p><b>CONCLUSION</b>Acupoint thread embedding combined with western medicine routine therapy can not only reduce the urinary micro-albumin excretion of type II early diabetic nephropathies, but also improve the Chinese medicine symptoms and the therapeutic effect is superior to that of simple western medicine routine therapy.</p>
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Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pontos de Acupuntura , Terapia por Acupuntura , Diabetes Mellitus Tipo 2 , Nefropatias Diabéticas , Terapêutica , Resultado do TratamentoRESUMO
<p><b>OBJECTIVE</b>To investigate the relationship between the human papillomavirus (HPV) and esophageal carcinoma in Baoding City of Hebei Province.</p><p><b>METHODS</b>We detected HPV DNA in 42 formalin-fixed and paraffin-embedded tissues from surgically resected esophageal carcinomas from Baoding City of Hebei Province, by PCR with the general primer set of GP5 + /6 + for HPV L1 gene and type-specific primer sets for HPV16 and 18 as well.</p><p><b>RESULTS</b>37 from 42 esophageal carcinoma samples were HPV positive and the rate was 88.1%. Among the samples detected, 19 were HPV16 E6 positive and rate was 45.2%, eight were HPV18 E6 positive and rate was 19.0%.</p><p><b>CONCLUSION</b>The high rate of HPV in the esophageal carcinoma samples suggested that HPV plays an etiologic role in the development of esophageal cancer in Baoding City of Hebei Province.</p>
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Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma , Virologia , China , Neoplasias Esofágicas , Virologia , Papillomavirus Humano 16 , Genética , Papillomavirus Humano 18 , Genética , Infecções por Papillomavirus , VirologiaRESUMO
<p><b>OBJECTIVE</b>To explore the effect and mechanism of acupoint sticking of Chuanfuling (CFL) in dog-days (the hottest periods of the year) in preventing and treating children asthma in remission stage.</p><p><b>METHODS</b>Ninety patients were divided into three groups, 30 in each. Patients in the CFL group were treated with CFL sticking, in the Western medicine (WM) group treated with Pulmicort inhalation, and in the control group was untreated. The clinical effect and indexes of humoral immunity (IgE, IgA, IgG) and cellular immunity (Eos, IL-4, IFN-gamma) before and after treatment were observed.</p><p><b>RESULTS</b>After treatment in the CFL group all the immune parameters were significantly improved (P<0.05 or P<0.01), all were better than those in the control group (P<0.05 or P<0.01), and the effect on IgA and IgG was better than that in the WM group. In the WM group after treatment, improvement was shown on the IgE and cellular immune parameters with signifian difference (P<0.05 or P<0.01), better than those in the control group (P<0.05 or P<0.01). Besides, significant difference was shown in comparing IL-4 level between the WM group and the CFL group (P<0.05).</p><p><b>CONCLUSION</b>CFL sticking in dog-days could significantly improve the immune function in children with asthma to alleviate and control the attack.</p>