RESUMEN
OBJECTIVES: Our team previously showed that like the experience of the rubber hand illusion (RHI) in people with schizophrenia and their offspring¸ dexamphetamine administration to healthy volunteers increases the stimulus binding windows (BWs) in RHI. It is not clear if similar expansions of BWs are present for unimodal illusions. Studies have also shown that subjective or objective effects of amphetamine would be linked to between-person variations in personality measures. Therefore, we aimed to examine the effect of dexamphetamine (DEX), a dopamine-releasing stimulant, on illusory perception using unimodal sensory stimuli (Tactile Funneling Illusion [TFI]) across both temporal and spatial variables. We further examined the relationship between changes in psychometric scores and changes in illusion perception induced by dexamphetamine. METHODS: Healthy subjects (N = 20) participated in a randomized, double-blind, counter-balanced, placebo-controlled, cross-over study. The effects of dexamphetamine (0.45 mg/kg, PO, q.d.) on funneling and error of spatial localization (EL) were examined using TFI. Psychotomimetic effects were assessed using a battery of psychological measures. RESULTS: Dexamphetamine did not significantly increased the funneling illusion (p = 0.88) or EL (p = 0.5), relative to placebo. However, the degree of change in psychometric scores following dexamphetamine positively correlated with changes in funneling (ρ = 0.48, p = 0.03, n = 20), mainly at 0 ms delay condition (ρ = 0.6, p = 0.004, n = 20). CONCLUSION: Unlike multimodal illusions, alteration of BWs does not occur for unimodal illusions after administration of a dopamine-releasing agent. However, our findings indicate that moderate release of dopamine, through its psychotomimetic effect, indirectly influences unimodal illusion.
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Ilusiones , Percepción del Tacto , Humanos , Estudios Cruzados , Dopamina/farmacología , Psicometría , Dextroanfetamina/farmacología , Percepción VisualRESUMEN
An investigation of the problems of X-ray imaging of dentinal tubules is presented. Two main points are addressed. In the first part of this paper, the problem of computer simulating tubule images recorded in a coherent synchrotron radiation (SR) beam has been discussed. A phantom material which involved a two-dimensional lattice of the tubules with parameters similar to those of dentin was considered. By a comparative examination of two approximations, it was found that the method of phase-contrast imaging is valid if the number of tubules along the beam is less than 100. Calculated images from a lattice of 50â ×â 50 tubules are periodic in free space but depend strongly on the distance between the specimen and the detector. In the second part, SR microtomographic experiments with millimetre-sized dentin samples in a partially coherent beam have been described. Tomograms were reconstructed from experimental projections using a technique for incoherent radiation. The main result of this part is the three-dimensional rendering of the directions of the tubules in a volume of the samples. Generation of the directions is possible because a tomogram shows the positions of the tubules. However, a detailed tubule cross-section structure cannot be restored.
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Dentina/ultraestructura , Sincrotrones , Simulación por Computador , Humanos , Microscopía de Contraste de Fase , Fotones , Microtomografía por Rayos X , Rayos XRESUMEN
BACKGROUND: Allergic respiratory conditions have been associated with increased susceptibility to viral infection due to impaired interferon (IFN)-related immune responses, but the mechanisms for reinforcement of mucosal immunity against viral infection in allergic diseases are largely unknown. OBJECTIVES: To determine whether IFN induction would be impaired in allergic nasal mucosa and to identify whether higher loads of influenza A virus (IAV) in allergic nasal mucosa could be controlled with IFN treatment. METHODS: Influenza A virus mRNA, viral titres and IFN expression were compared in IAV-infected normal human nasal epithelial (NHNE, N = 10) and allergic rhinitis nasal epithelial (ARNE, N = 10) cells. We used in vivo model of allergic rhinitis (BALB/c mice, N = 10) and human nasal mucosa from healthy volunteers (N = 72) and allergic rhinitis patients (N = 29) to assess the induction of IFNs after IAV infection. RESULTS: Influenza A virus mRNA levels and viral titres were significantly higher in ARNE compared with NHNE cells. IFN-ß and IFN-λs were induced in NHNE and ARNE cells up to 3 days after IAV infection. Interestingly, induction of IFN-λs mRNA levels and the amount of secreted proteins were considerably lower in ARNE cells. The mean IFN-λs mRNA level was also significantly lower in the nasal mucosa of AR patients, and we found that recombinant IFN-λ treatment attenuated viral mRNA levels and viral titres in IAV-infected ARNE cells. In vivoAR mouse exhibited higher viral load after IAV infection, but intranasal inoculation of IFN-λ completely decreased IAV protein expression and viral titre in nasal mucosa of IAV-infected AR mouse. CONCLUSION: Higher susceptibility of the allergic nasal mucosa to IAV may depend on impairment of type III IFN induction, and type III IFN is a key mechanistic link between higher viral loads and control of IAV infection in allergic nasal mucosa.
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Gripe Humana/inmunología , Interferones/inmunología , Mucosa Nasal/inmunología , Rinitis Alérgica/inmunología , Adulto , Animales , Femenino , Humanos , Virus de la Influenza A/inmunología , Masculino , Ratones , Ratones Endogámicos BALB C , Persona de Mediana Edad , Mucosa Nasal/virología , Rinitis Alérgica/virología , Carga Viral/inmunología , Adulto Joven , Interferón lambdaRESUMEN
BACKGROUND: Hypohidrosis is defined as diminished sweating in response to an appropriate thermal or sympathetic stimulus. When encountered in a clinical setting, it necessitates an accurate documentation of its pattern and extent to prognosticate the risk of associated heat-related illnesses. This can be achieved by thermoregulatory sweat testing which includes a starch-iodine sweat test that can be administered via various methods. OBJECTIVE: To describe and evaluate the effectiveness and safety of a novel method of using an atomizer spray gun in administering the starch-iodine test. METHODS: We describe the administration of the starch-iodine test via an atomizer spray gun (Series 700 Lab Model; Mitsuba Systems, Mumbai, India). The method was utilized for the evaluation of 30 individuals who presented with symptoms of hypohidrosis. RESULTS: Application of iodinated starch powder prepared in-house with the atomizer spray gun achieved a lightweight and homogeneous coat on our patients' skin which allowed for clear visualization of the sweating pattern in areas of anhidrosis. The sharp demarcation of the pathological regions enabled the precise calculation of the affected body surface area of impaired sweating. Unlike the starch-iodine tests using the Minor and Wada methods, neither staining of the skin nor irritation was detected in this method. CONCLUSION: We report a novel method of using an atomizer spray gun to perform the starch-iodine test in a rapid, reproducible, effective, and safe manner suitable for use in the clinical evaluation of hypohidrosis.
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Dermoscopía/métodos , Hipohidrosis/diagnóstico , Hipohidrosis/patología , Nebulizadores y Vaporizadores , Piel/efectos de los fármacos , Almidón/análogos & derivados , Administración Cutánea , Adulto , Aerosoles/administración & dosificación , Aerosoles/síntesis química , Diseño de Equipo , Análisis de Falla de Equipo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Polvos , Embarazo , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Almidón/administración & dosificación , Almidón/síntesis químicaRESUMEN
BACKGROUND: The optimal duration of antiviral therapy for kidney transplant recipients (KTR) with chronic hepatitis B virus (HBV) infection remains unclear. We reported the long-term outcomes after withdrawal of antiviral agent in KTR with chronic HBV infection. METHODS: We retrospectively investigated the hepatitis B surface antigen (HBsAg)-positive KTR with antiviral agents between January 2002 and January 2012. Antiviral treatments were withdrawn in patients who met all of the following 7 criteria: (i) no clinical and histologic evidence of cirrhosis, (ii) normal liver biochemistry, (iii) negative for both HBV DNA and hepatitis B envelope antigen (HBeAg), (iv) no resistance to antiviral agent, (v) antiviral therapy > 9 months, (vi) maintenance dosage of immunosuppressant for > 3 months, and (vii) no history of acute rejection during recent 6 months. All patients were followed regularly at approximately 3-6 months for liver enzyme, viral markers, and HBV DNA level after antiviral withdrawal. RESULTS: Among a total of 445 KTR, 14 HBsAg-positive patients were included in this study. Antiviral agents were used, with lamivudine in 11 patients, and with adefovir, entecavir, and telbivudine in 3 patients, respectively. Discontinuation of antiviral agent was attempted in 6 (42.9%) of 14 patients who satisfied the criteria. The median duration of antiviral therapy before withdrawal was 14.3 months (range, 9-24 months). Four (66.7%) of 6 patients were successfully withdrawn and remained negative for HBV DNA for a median 60.5 months (range, 47-82 months). The baseline HBV DNA level was not related to maintenance of remission after withdrawal. Two reactivated patients resumed antiviral treatment immediately, with subsequent normalization of HBV DNA. During the follow-up, 1 patient developed hepatocellular carcinoma; however, no patient death or graft failure was reported for all HBsAg-positive KTR. CONCLUSIONS: Antiviral therapy can be discontinued successfully and safely in selected KTR with chronic HBV infection, after complete suppression of HBV and sufficient duration of antiviral therapy.
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Antivirales/uso terapéutico , ADN Viral/sangre , Virus de la Hepatitis B/fisiología , Hepatitis B Crónica/tratamiento farmacológico , Trasplante de Riñón , Privación de Tratamiento , Adenina/análogos & derivados , Adenina/uso terapéutico , Adulto , Alanina Transaminasa/sangre , Femenino , Estudios de Seguimiento , Guanina/análogos & derivados , Guanina/uso terapéutico , Antígenos de Superficie de la Hepatitis B/sangre , Antígenos e de la Hepatitis B/sangre , Virus de la Hepatitis B/inmunología , Hepatitis B Crónica/sangre , Humanos , Inmunosupresores/administración & dosificación , Lamivudine/uso terapéutico , Masculino , Persona de Mediana Edad , Organofosfonatos/uso terapéutico , Estudios Retrospectivos , Telbivudina , Timidina/análogos & derivados , Timidina/uso terapéutico , Factores de Tiempo , Activación ViralRESUMEN
AIMS/HYPOTHESIS: Many of the effects of resveratrol are consistent with the activation of AMP-activated protein kinase (AMPK), silent information regulator T1 (SIRT1) and peroxisome proliferator-activated receptor (PPAR)γ co-activator 1α (PGC-1α), which play key roles in the regulation of lipid and glucose homeostasis, and in the control of oxidative stress. We investigated whether resveratrol has protective effects on the kidney in type 2 diabetes. METHODS: Four groups of male C57BLKS/J db/m and db/db mice were used in this study. Resveratrol was administered via gavage to diabetic and non-diabetic mice, starting at 8 weeks of age, for 12 weeks. RESULTS: The db/db mice treated with resveratrol had decreased albuminuria. Resveratrol ameliorated glomerular matrix expansion and inflammation. Resveratrol also lowered the NEFA and triacylglycerol content of the kidney, and this action was related to increases in the phosphorylation of AMPK and the activation of SIRT1-PGC-1α signalling and of the key downstream effectors, the PPARα-oestrogen-related receptor (ERR)-1α-sterol regulatory element-binding protein 1 (SREBP1). Furthermore, resveratrol decreased the activity of phosphatidylinositol-3 kinase (PI3K)-Akt phosphorylation and class O forkhead box (FOXO)3a phosphorylation, which resulted in a decrease in B cell leukaemia/lymphoma 2 (BCL-2)-associated X protein (BAX) and increases in BCL-2, superoxide dismutase (SOD)1 and SOD2 production. Consequently, resveratrol reversed the increase in renal apoptotic cells and oxidative stress, as reflected by renal 8-hydroxy-deoxyguanosine (8-OH-dG), urinary 8-OH-dG and isoprostane concentrations. Resveratrol prevented high-glucose-induced oxidative stress and apoptosis in cultured mesangial cells through the phosphorylation of AMPK and activation of SIRT1-PGC-1α signalling and the downstream effectors, PPARα-ERR-1α-SREBP1. CONCLUSIONS/INTERPRETATION: The results suggest that resveratrol prevents diabetic nephropathy in db/db mice by the phosphorylation of AMPK and activation of SIRT1-PGC-1α signalling, which appear to prevent lipotoxicity-related apoptosis and oxidative stress in the kidney.
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Diabetes Mellitus Tipo 2/tratamiento farmacológico , Nefropatías Diabéticas/prevención & control , Riñón/efectos de los fármacos , Células Mesangiales/efectos de los fármacos , Sustancias Protectoras/uso terapéutico , Transducción de Señal/efectos de los fármacos , Estilbenos/uso terapéutico , Proteínas Quinasas Activadas por AMP/antagonistas & inhibidores , Proteínas Quinasas Activadas por AMP/química , Proteínas Quinasas Activadas por AMP/genética , Proteínas Quinasas Activadas por AMP/metabolismo , Animales , Células Cultivadas , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patología , Activación Enzimática/efectos de los fármacos , Riñón/metabolismo , Riñón/patología , Riñón/fisiopatología , Metabolismo de los Lípidos/efectos de los fármacos , Lipotrópicos/farmacología , Lipotrópicos/uso terapéutico , Masculino , Células Mesangiales/metabolismo , Células Mesangiales/patología , Ratones , Ratones Endogámicos C57BL , Ratones Mutantes , Estrés Oxidativo/efectos de los fármacos , Sustancias Protectoras/farmacología , Procesamiento Proteico-Postraduccional/efectos de los fármacos , Interferencia de ARN , Resveratrol , Sirtuina 1/antagonistas & inhibidores , Sirtuina 1/química , Sirtuina 1/genética , Sirtuina 1/metabolismo , Estilbenos/farmacología , Factores de Transcripción/agonistas , Factores de Transcripción/metabolismoRESUMEN
Hypermucoviscous (HV) isolates of Klebsiella pneumoniae have been linked to virulence potential in experimental infections. We examined 33 isolates of K. pneumoniae from patients with bacteraemia for the HV phenotype on agar culture, and determined their virulence potential by screening for capsular (K) serotype by polymerase chain reaction and the presence of seven virulence factor genes. Fourteen (42·4%) isolates expressed the HV phenotype and 11 of these were serotype K1 or K2; these serotypes were not identified in HV-negative isolates. The genes rmpA, rmpA2, aerobactin, wabG and allS were significantly more frequent in HV than non-HV isolates. Multilocus sequence typing identified 21 sequence types (ST), eight of which were found in HV-positive isolates and the clonal relatedness of isolates of the most frequent types (ST23 and ST11) from different hospitals was confirmed by pulsed-field gel electrophoresis. The HV phenotype was more associated with community-acquired infection with a lower frequency of fatal underlying illness, but with significantly more focal infections, notably liver abscesses. Clinicians should be aware of such clinical impacts of the HV phenotype.
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Antiinfecciosos/farmacología , Bacteriemia/genética , Farmacorresistencia Microbiana/genética , Infecciones por Klebsiella/genética , Klebsiella pneumoniae , Fenotipo , Factores de Virulencia/genética , Bacteriemia/microbiología , Infección Hospitalaria/etiología , Electroforesis en Gel de Campo Pulsado , Humanos , Infecciones por Klebsiella/microbiología , Klebsiella pneumoniae/clasificación , Klebsiella pneumoniae/genética , Klebsiella pneumoniae/patogenicidad , Absceso Hepático/etiología , Tipificación de Secuencias Multilocus/métodos , Reacción en Cadena de la Polimerasa , República de Corea , Estudios Retrospectivos , Serotipificación/métodos , Centros de Atención TerciariaRESUMEN
UNLABELLED: Korean kimchi is known for its myriad of lactic acid bacteria (LAB) with diverse bioactive compounds. This study was undertaken to isolate an efficient antifungal LAB strain among the isolated kimchi LABs. One thousand and four hundred LABs isolated from different kimchi samples were initially screened against Aspergillus niger. The strain exhibiting the highest antifungal activity was identified as Lactobacillus plantarum YML007 by 16S rRNA sequencing and biochemical assays using API 50 CHL kit. Lact. plantarum YML007 was further screened against Aspergillus oryzae, Aspergillus flavus, Fusarium oxysporum and other pathogenic bacteria. The morphological changes during the inhibition were assessed by scanning electron microscopy. Preliminary studies on the antifungal compound demonstrated its proteinaceous nature with a molecular weight of 1256·617 Da, analysed by matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-TOF). The biopreservative activity of Lact. plantarum YML007 was evaluated using dried soybeans. Spores of A. niger were observed in the negative control after 15 days of incubation. However, fungal growth was not observed in the soybeans treated with fivefold concentrated cell-free supernatant of Lact. plantarum YML007. The broad activity of Lact. plantarum YML007 against various food spoilage moulds and bacteria suggests its scope as a food preservative. SIGNIFICANCE AND IMPACT OF THE STUDY: After screening 1400 kimchi bacterial isolates, strain Lactobacillus plantarum YML007 was selected with strong antifungal activity against various foodborne pathogens. From the preliminary studies, it was found that the bioactive compound is a low molecular weight novel protein of 1256·617 Da. Biopreservative potential of Lact. plantarum YML007 was demonstrated on soybean grains, and the results point out YML007 as a potent biopreservative having broad antimicrobial activity against various foodborne pathogens.
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Antifúngicos/aislamiento & purificación , Antifúngicos/farmacología , Aspergillus/efectos de los fármacos , Microbiología de Alimentos , Conservantes de Alimentos/aislamiento & purificación , Conservantes de Alimentos/farmacología , Lactobacillus plantarum/química , Antifúngicos/química , Conservantes de Alimentos/química , Fusarium/efectos de los fármacos , Lactobacillaceae/química , Lactobacillaceae/aislamiento & purificación , Lactobacillus plantarum/genética , Lactobacillus plantarum/aislamiento & purificación , Lactobacillus plantarum/metabolismo , Glycine max/microbiologíaRESUMEN
Studies that examined the effect of amphetamine or caffeine on spatial working memory (SWM) and verbal working memory (VWM) have used various tasks. However, there are no studies that have used spatial span tasks (SSTs) to assess the SWM effect of amphetamine and caffeine, although some studies have used digit span tasks (DST) to assess VWM. Previous reports also showed that increasing dopamine increases psychosis-like experiences (PLE, or schizotypy) scores which are in turn negatively associated with WM performance in people with high schizotypy and people with schizophrenia. Therefore, the present study aimed to examine the influence of d-amphetamine (0.45 mg/kg, PO), a dopamine releasing stimulant, on SST, DST, and on PLE in healthy volunteers. In a separate study, we examined the effect of caffeine, a nonspecific adenosine receptor antagonist with stimulant properties, on similar tasks. METHODS: Healthy participants (N = 40) took part in two randomized, double-blind, counter-balanced placebo-controlled cross-over pilot studies: The first group (N = 20) with d-amphetamine (0.45 mg/kg, PO) and the second group (N = 20) with caffeine (200 mg, PO). Spatial span and digit span were examined under four delay conditions (0, 2, 4, 8 s). PLE were assessed using several scales measuring various aspects of psychosis and schizotypy. RESULTS: We failed to find an effect of d-amphetamine or caffeine on SWM or VWM, relative to placebo. However, d-amphetamine increased a composite score of psychosis-like experiences (p = 0.0005), specifically: Scores on Brief Psychiatric Rating Scale, Perceptual Aberrations Scale, and Magical Ideation Scale were increased following d-amphetamine. The degree of change in PLE following d-amphetamine negatively and significantly correlated with changes in SWM, mainly at the longest delay condition of 8 s (r = -0.58, p = 0.006). CONCLUSION: The present results showed that moderate-high dose of d-amphetamine and moderate dose of caffeine do not directly affect performances on DST or SST. However, the results indicate that d-amphetamine indirectly influences SWM, through its effect on psychosis-like experiences. CLINICAL TRIAL REGISTRATION NUMBER: CT-2018-CTN-02561 (Therapeutic Goods Administration Clinical Trial Registry) and ACTRN12618001292268 (The Australian New Zealand Clinical Trials Registry) for caffeine study, and ACTRN12608000610336 for d-amphetamine study.
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Cafeína , Dextroanfetamina , Humanos , Dextroanfetamina/farmacología , Cafeína/farmacología , Voluntarios Sanos , Dopamina , Australia , Anfetamina/farmacología , Método Doble CiegoRESUMEN
AIM: The aims of the study were to isolate anti-H9N2 bacteria from Korean Kimchi isolates and to evaluate its performance in cell line, egg and in specific pathogen-free (SPF) chickens. METHODS AND RESULTS: Using Madin-Darby canine kidney (MDCK) cell line, 220 bacterial isolates were screened and the isolate YML003 was selected having pronounced antiviral activity against H9N2 virus. This isolate was identified as Leuconostoc mesenteroides by 16S rRNA gene sequencing. Anti-H9N2 activity of the strain was also evaluated by hemagglutination assay. Leuconostoc mesenteroides YML003 was assessed for its survival in gastric juice and 5% bile acid and the antibiotic susceptibility. Both live and heat-killed cells were selected for in vivo chicken feeding experiment. Body weight, immune index, serobiochemical parameters and splenic IFN-γ production were assessed during selected intervals. Viral population in the trachea and cloacae were calculated by quantitative real-time reverse transcriptase PCR (qRT-PCR). CONCLUSIONS: Leuconostoc mesenteroides YML003 exhibited anti-H9N2 activity both in in vitro cell line as well as in vivo SPF chickens. SIGNIFICANCE AND IMPACT OF THE STUDY: This is a primary report on the anti-H9N2 activity by a Leuconostoc strain. Amid the increasing reports of avian influenza virus occurrence resulting in severe losses to the poultry industry, prophylactic administration of such probiotic strains are highly significant.
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Pollos/virología , Subtipo H9N2 del Virus de la Influenza A/patogenicidad , Gripe Aviar/prevención & control , Leuconostoc , Probióticos/farmacología , Animales , Brassica/microbiología , Cloaca/virología , Perros , Pruebas de Hemaglutinación , Interferón gamma/metabolismo , Leuconostoc/genética , Leuconostoc/aislamiento & purificación , Células de Riñón Canino Madin Darby , Óvulo/virología , ARN Ribosómico 16S/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Organismos Libres de Patógenos Específicos , Bazo/inmunología , Tráquea/virología , Verduras/microbiologíaRESUMEN
BACKGROUND: Placental hypoxia has been implicated in the pathogenesis of pre-eclampsia. Hypoxia inducible factor-1α (HIF-1α) is activated by low oxygen tension and is a key regulator of genes involved in the cellular responses to hypoxia. AIM: We determined whether maternal blood c.1722C>T (Pro582Ser) and c.1790G>A (Ala588Thr) polymorphisms in exon 12 of the HIF-1α gene are associated with pre-eclampsia. SUBJECTS AND METHODS: Subjects included 163 pre-eclamptic patients (48 mild and 115 severe preeclampsia) and 194 healthy pregnant women. Polymorphisms were genotyped by PCR and direct DNA sequencing. RESULTS: There were no significant differences in genotype or allele frequencies of the c.1772C>T and c.1790G>A polymorphisms of the HIF-1α gene among the study groups. Moreover, subgroup analysis according to pre-eclampsia severity revealed no significant differences in genotype or allele frequencies of the HIF-1α c.1772C>T and c.1790G>A polymorphism in mild pre-eclamptic compared to severe pre-eclamptic group. In addition, there were no significant differences in the frequencies of 3 haplotypes (C-G,-G, T-G, and C-A) between the control and pre-eclamptic groups. CONCLUSIONS: Our results suggest that the HIF-1α gene polymorphisms are not associated with the development of pre-eclampsia in the studied Korean women population.
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Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Polimorfismo de Nucleótido Simple , Preeclampsia/genética , Adulto , Sustitución de Aminoácidos , Exones , Femenino , Frecuencia de los Genes , Estudios de Asociación Genética , Haplotipos , Hospitales Generales , Hospitales Urbanos , Humanos , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Preeclampsia/metabolismo , Preeclampsia/fisiopatología , Embarazo , Estudios Prospectivos , República de Corea , Índice de Severidad de la EnfermedadRESUMEN
AIMS/HYPOTHESIS: Lon protease degrades oxidatively damaged proteins in mitochondrial matrix. To examine the relationships between mitochondrial quality control, mitochondrial functions and diabetes, we investigated whether lon protease deficiency influences insulin resistance by affecting mitochondrial function. METHODS: Lon protease-specific small interfering RNA (siRNA) was transfected into human liver SK-HEP-1 cells and changes in molecules related to insulin resistance were analysed. RESULTS: Reduction in lon protease was achieved using specific siRNA-induced mitochondrial dysfunction in human liver SK-HEP-1 cells. Concurrently, insulin signalling and subsequent insulin action were impaired and levels of gluconeogenic enzymes were increased by lon protein deficiency. Moreover, the activity of mitogen-activated protein kinases and transcription factors related to hepatic gluconeogenesis were elevated in LON (also known as LONP1) siRNA-transfected cells via increased intracellular reactive oxygen species production. Overproduction of lon protease restored mitochondrial function and also diminished the insulin resistance induced by treatment with cholesterol and palmitate. In addition, levels of lon protease decreased dramatically in livers of diabetic db/db mice compared with their lean mice counterparts. CONCLUSIONS/INTERPRETATION: Here we have demonstrated that reduction of lon protease induced hepatic insulin resistance by lowering mitochondrial function. This is the first study to report that defects in mitochondrial protein quality control could cause insulin resistance and diabetes.
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Proteasas ATP-Dependientes/deficiencia , Regulación hacia Abajo/fisiología , Hepatocitos/fisiología , Resistencia a la Insulina/fisiología , Mitocondrias Hepáticas/enzimología , Mitocondrias Hepáticas/fisiología , Proteínas Mitocondriales/deficiencia , Proteasa La/deficiencia , Proteasas ATP-Dependientes/metabolismo , Animales , Línea Celular , Diabetes Mellitus/metabolismo , Diabetes Mellitus/patología , Modelos Animales de Enfermedad , Gluconeogénesis/fisiología , Hepatocitos/patología , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Mutantes , Proteínas Mitocondriales/metabolismo , Proteasa La/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal/fisiología , Factores de Transcripción/metabolismoRESUMEN
Bartter syndrome (BS) Type IV, associated with a G47R mutation in the BSND gene, is known to result in a mild renal phenotype. However, we report here on three brothers with varying degrees of renal dysfunction from mild to end-stage renal disease associated with renal barttin and ClC-K expression. The brothers had histories of polyhydramnios, prematurity, polyuria, deafness, and small body size. Laboratory findings showed hypokalemic metabolic alkalosis, normotensive hyperreninemic hyperaldosteronism, and an increased urinary excretion of sodium, potassium and chloride, consistent with BS Type IV. Microscopic examination of renal tissue showed hyperplasia of cells at the juxtaglomerular apparatus with dilated atrophic tubules and tubulointerstitial fibrosis. A weak barttin signal related to CIC-K expression in the cytoplasm of tubule cells, but not the basement membrane, was noted. A sequence analysis of the BSND gene showed that the affected males were homozygous for a missense G47R mutation in exon 1 of BSND. These findings suggest that the G47R mutation results in a dramatic decrease in barttin expression, which appears to be related to the location of CIC-K being changed from the basement membrane to the cytoplasm in the tubule and might have varying effects on renal function associated with factors other than this gene.
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Síndrome de Bartter/genética , Canales de Cloruro/genética , Fallo Renal Crónico/genética , Riñón/fisiopatología , Mutación Missense , Adulto , Síndrome de Bartter/metabolismo , Síndrome de Bartter/patología , Síndrome de Bartter/fisiopatología , Biopsia , Canales de Cloruro/metabolismo , Análisis Mutacional de ADN , Exones , Predisposición Genética a la Enfermedad , Homocigoto , Humanos , Hiperplasia , Riñón/metabolismo , Riñón/patología , Fallo Renal Crónico/metabolismo , Fallo Renal Crónico/patología , Fallo Renal Crónico/fisiopatología , Masculino , Persona de Mediana Edad , Linaje , Fenotipo , Índice de Severidad de la EnfermedadRESUMEN
OBJECTIVE: Increased inhibin A serum and plasma levels in the second trimester are significantly associated with the development of preeclampsia. The measurement of inhibin A during early pregnancies may be helpful to predict those at risk of this disorder. The purpose of this study was to determine whether the 769G>A variant of the inhibin alpha (INHalpha) gene was associated with preeclampsia. PATIENTS AND METHODS: We screened the 769G>A variation in 162 preeclamptic patients and in 202 normal pregnancies. The 769G>A variant of the INHalpha gene was determined by the PCR-based restriction fragment length polymorphism analysis and DNA sequencing. RESULTS: We found no variation between the normal subjects and the preeclamptic patients. CONCLUSION: The 769G>A variant of the INHalpha gene may be rare in Korean patients with preeclampsia.
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Inhibinas/genética , Polimorfismo de Longitud del Fragmento de Restricción , Preeclampsia/genética , Adulto , Secuencia de Bases , Análisis Mutacional de ADN , Femenino , Frecuencia de los Genes , Humanos , Corea (Geográfico) , Edad Materna , Datos de Secuencia Molecular , Mutación Puntual , EmbarazoRESUMEN
The acaricidal activities of compounds derived from Thymus vulgaris (thyme) oil against Tyrophagus putrescentiae were assessed using an impregnated fabric disk bioassay, and were compared with those of the synthetic acaricides, benzyl benzoate and N,N-diethyl-m-toluamide. The observed responses differed according to dosage and chemical components. The 50% lethal dose (LD50) value of the T. vulgaris oil against T. putrescentiae was 10.2 microg/cm2. Biologically active constituents derived from T. vulgaris oil were purified by using silica gel chromatography and high-performance liquid chromatography. The structures of acaricidal components were analyzed by gas chromatography-mass spectrometry, 1H nuclear magnetic resonance (NMR), 13C NMR, 1H-13C COSY-NMR, and DEPT-NMR spectra, and were subsequently identified as carvacrol and thymol. Carvacrol was the most toxic compound with LD50 values (4.5 microg/cm2) significantly different from thymol (11.1 microg/cm2), benzyl benzoate (11.3 microg/cm2), and N,N-diethyl-m-toluamide (13.9 microg/cm2). Linalool was as toxic as was N,N-diethyl-m-toluamide. The lower LD50 of carvacrol indicates that it may be the major contributor of the toxicity of T. vulagaris oil against the stored food mite, although it only constitutes 14.2% of the oil. From this point of view, carvacrol and thymol can be very useful as potential control agents against stored food mite.
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Conservación de Alimentos/métodos , Insecticidas/farmacología , Ácaros/efectos de los fármacos , Aceites de Plantas/farmacología , Thymus (Planta)/química , Animales , Bioensayo , Cromatografía en Gel , Cromatografía Líquida de Alta Presión , Cimenos , Relación Dosis-Respuesta a Droga , Microbiología de Alimentos , Cromatografía de Gases y Espectrometría de Masas , Dosificación Letal Mediana , Monoterpenos/farmacología , Control Biológico de Vectores/métodos , Timol/farmacologíaRESUMEN
INTRODUCTION: To investigate the correlation between serum anti-ABO immunoglobulin G (IgG) and IgG subclasses, anti-ABO IgG subclasses were measured by flow cytometry (FCM) in ABO-incompatible (ABOi) kidney transplant recipients. We also evaluated baseline anti-ABO C1q antibody. METHOD: Baseline anti-ABO IgG titers were measured by both FCM and column agglutination technique methods in 18 ABOi kidney transplant recipients. The mean florescence intensity (MFI) ratios of baseline anti-ABO IgG subclasses and anti-ABO C1q antibody were obtained by FCM and followed-up after rituximab treatment, each plasmapheresis (PP) session, and kidney transplantation. Correlation between the values of IgG subclass and total IgG titer was analyzed. RESULTS: The baseline MFI ratios of total IgG, IgG1, IgG2, IgG3, and IgG4 were 202.46, 62.41, 30.01, 1.04, and 1.13, respectively. The MFI ratios of IgG1, IgG2, and total IgG measured at baseline and pre-PP were positively correlated with the baseline ABO titer was measured using the column agglutination technique. The numbers of PP sessions to reach the target titer were correlated with the baseline IgG and IgG1 levels. IgG1 and IgG2 as well as total IgG were removed effectively after serial PP. Anti-ABO C1q antibody was neither detected nor correlated with total IgG and any IgG subclasses. CONCLUSIONS: Our findings suggest that IgG1 and IgG2 are the dominant IgG subclass in ABOi kidney transplant recipients. Baseline levels of IgG1 and IgG2 were correlated with baseline total IgG titer. However, anti-ABO C1q antibody was not detected in the present study.
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Incompatibilidad de Grupos Sanguíneos/inmunología , Inmunoglobulina G/inmunología , Trasplante de Riñón , Antígenos de Grupos Sanguíneos/inmunología , Complemento C1q/inmunología , Desensibilización Inmunológica , Femenino , Citometría de Flujo , Rechazo de Injerto/inmunología , Rechazo de Injerto/prevención & control , Humanos , Factores Inmunológicos/uso terapéutico , Masculino , Metilprednisolona/uso terapéutico , Ácido Micofenólico/uso terapéutico , Plasmaféresis , Rituximab/uso terapéutico , Tacrolimus/uso terapéuticoRESUMEN
The preprotein translocase of the yeast mitochondrial outer membrane (TOM) consists of the initial import receptors Tom70 and Tom20 and a approximately 400-kDa (400 K) general import pore (GIP) complex that includes the central receptor Tom22, the channel Tom40, and the three small Tom proteins Tom7, Tom6, and Tom5. We report that the GIP complex is a highly stable complex with an unusual resistance to urea and alkaline pH. Under mild conditions for mitochondrial lysis, the receptor Tom20, but not Tom70, is quantitatively associated with the GIP complex, forming a 500K to 600K TOM complex. A preprotein, stably arrested in the GIP complex, is released by urea but not high salt, indicating that ionic interactions are not essential for keeping the preprotein in the GIP complex. Under more stringent detergent conditions, however, Tom20 and all three small Tom proteins are released, while the preprotein remains in the GIP complex. Moreover, purified outer membrane vesicles devoid of translocase components of the intermembrane space and inner membrane efficiently accumulate the preprotein in the GIP complex. Together, Tom40 and Tom22 thus represent the functional core unit that stably holds accumulated preproteins. The GIP complex isolated from outer membranes exhibits characteristic TOM channel activity with two coupled conductance states, each corresponding to the activity of purified Tom40, suggesting that the complex contains two simultaneously active and coupled channel pores.
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Canales Iónicos/metabolismo , Proteínas de la Membrana/metabolismo , Proteínas de Transporte de Membrana , Mitocondrias/metabolismo , Receptores Citoplasmáticos y Nucleares , Proteínas de Saccharomyces cerevisiae , Proteínas Fúngicas/metabolismo , Membranas Intracelulares/metabolismo , Proteínas de Transporte de Membrana Mitocondrial , Proteínas del Complejo de Importación de Proteínas Precursoras Mitocondriales , Saccharomyces cerevisiae , Transducción de SeñalRESUMEN
The center of pressure (COP) position reflects a combination of proprioceptive, motor and mechanical function. As such, it can be used to quantify and characterize neurologic dysfunction. The aim of this study was to describe and quantify the movement of COP and its variability in healthy chondrodystrophoid dogs while walking to provide a baseline for comparison to dogs with spinal cord injury due to acute intervertebral disc herniations. Fifteen healthy adult chondrodystrophoid dogs were walked on an instrumented treadmill that recorded the location of each dog's COP as it walked. Center of pressure (COP) was referenced from an anatomical marker on the dogs' back. The root mean squared (RMS) values of changes in COP location in the sagittal (y) and horizontal (x) directions were calculated to determine the range of COP variability. Three dogs would not walk on the treadmill. One dog was too small to collect interpretable data. From the remaining 11 dogs, 206 trials were analyzed. Mean RMS for change in COPx per trial was 0.0138 (standard deviation, SD 0.0047) and for COPy was 0.0185 (SD 0.0071). Walking speed but not limb length had a significant effect on COP RMS. Repeat measurements in six dogs had high test retest consistency in the x and fair consistency in the y direction. In conclusion, COP variability can be measured consistently in dogs, and a range of COP variability for normal chondrodystrophoid dogs has been determined to provide a baseline for future studies on dogs with spinal cord injury.
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Perros/fisiología , Marcha , Animales , Fenómenos Biomecánicos , Cartílago/crecimiento & desarrollo , Enfermedades de los Perros/fisiopatología , Perros/anatomía & histología , Especificidad de la Especie , Traumatismos de la Médula Espinal/fisiopatología , Traumatismos de la Médula Espinal/veterinariaRESUMEN
The synthesis of new 1beta-methylcarbapenems 1a-d bearing aminopyrimidinylthioether moiety at C-5 position of pyrrolidine ring and their antibacterial activities are described. All the compounds exhibited potent antibacterial activity. Of these carbapenems, 1d showed the best combination of antibacterial activity and stability to dehydropeptidase-I (DHP-I).
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Antibacterianos/síntesis química , Carbapenémicos/síntesis química , Pirimidinas/síntesis química , Sulfuros/síntesis química , Antibacterianos/química , Antibacterianos/metabolismo , Antibacterianos/farmacología , Carbapenémicos/química , Carbapenémicos/metabolismo , Carbapenémicos/farmacología , Dipeptidasas/metabolismo , Espectroscopía de Resonancia Magnética , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Pirimidinas/química , Pirimidinas/metabolismo , Pirimidinas/farmacología , Sulfuros/química , Sulfuros/metabolismo , Sulfuros/farmacologíaRESUMEN
The activities of benzaldehyde isolated from Prunus persica seeds and of commercially available aldehydes against Tyrophagus putrescentiae (a stored-food mite) adults were examined and compared with those of the synthetic acaricides benzyl benzoate and N,N-diethyl-m-toluamide. On the basis of the 50% lethal dose (LD50), the compound most toxic to T. putrescentiae adults was salicylaldehyde (LD50 of 1.02 microg/cm2) followed by cinnamaldehyde (1.66 microg/cm2), benzaldehyde (4.23 microg/cm2), phthaldialdehyde (5.16 microg/cm2), benzyl benzoate (9.75 microg/cm2), and N,N-diethyl-m-toluamide (16.26 micorg/cm2). Benzaldehyde was about 2.3 and 3.8 times more toxic than benzyl benzoate and N,N-diethyl-m-toluamide, respectively, against T. putrescentiae adults. These results indicated that benzaldehyde isolated from P. persica seeds and the three aldehydes (cinnamaldehyde, salicylaldehyde, and phthaldialdehyde) are useful as lead compounds for developing acaricidal agents against T. putrescentiae adults. The color of the T. putrescentiae cuticle was changed by treatment with cinnamaldehyde, salicylaldehyde, and phthaldialdehyde.