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BACKGROUND AND AIM: Fibroblast growth factor 19 (FGF19) is an intestinal-derived factor that plays a role in metabolic diseases. We performed a differential study of circulating FGF19 levels and investigated the causal effects of FGF19 on metabolic diseases using Mendelian randomization (MR). METHODS: Firstly, 958 subjects were included in the physical examination center of affiliated hospital from January 2019 to January 2021. Dividing the subjects into different subgroups to compare FGF19 levels. We conducted a two-sample MR analysis of genetically predicted circulating FGF19 in relation to alcohol, cardiovascular and metabolic biomarkers and diseases, and liver function biomarkers using publicly available genome-wide association study summary statistics data. RESULTS: The circulating FGF19 levels in nonalcoholic fatty liver disease (NAFLD) patients were lower than those without NAFLD (P < 0.001). The FGF19 levels in participants with obese were lower than those without obese (P < 0.001). In two-sample MR analyses, genetically predicted higher circulating FGF19 levels was significantly associated with lower aspartate aminotransferase, γ-glutamyltransferase, triglycerides, total cholesterol, low-density lipoprotein, and C-reactive protein concentrations (P < 0.05) and a negative correlation with cardiovascular disease and cirrhosis whereas a positive association with type 2 diabetes mellitus (P < 0.05). CONCLUSIONS: Our study found that circulating FGF19 levels were lower in NAFLD and obese populations. Additionally, our MR research results support the causal effects of FGF19 on improved liver function, lipids, and reduced the occurrence of inflammation, cardiovascular disease, and cirrhosis. We found a positive correlation with diabetes, which may indicate a compensatory increase in regulating above FGF19 resistance states in humans.
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BACKGROUND: The evaluation of patients with fatty liver as defined by metabolic dysfunction-associated fatty liver disease (MAFLD) in the real world remains poorly researched. This study aimed to analyse the clinical and histological features of patients with MAFLD and nonalcoholic fatty liver disease (NAFLD) and to characterize each metabolic subgroup of MAFLD. METHODS: A total of 2563 patients with fatty liver confirmed by ultrasonography and/or magnetic resonance tomography and/or liver biopsy-proven from three hospitals in China were included in the study. Patients were divided into different groups according to diagnostic criteria for MAFLD and NAFLD, and MAFLD into different subgroups. RESULTS: There were 2337 (91.2%) patients fitting the MAFLD criteria, and 2095 (81.7%) fitting the NAFLD criteria. Compared to patients with NAFLD, those with MAFLD were more likely to be male, had more metabolic traits, higher liver enzyme levels, and noninvasive fibrosis scores. Among the patients with liver biopsy, the extent of advanced fibrosis in cases with MAFLD was significantly higher than those with NAFLD, 31.8% versus 5.2% (P < .001); there was no significant difference in advanced fibrosis between obese cases and lean individuals in MAFLD (P > .05); MAFLD complicated with diabetes had significantly higher advanced fibrosis than those without diabetes (43.3% and 17.2%, respectively; P < .001). CONCLUSIONS: Patients with MAFLD have a higher degree of liver fibrosis than NAFLD patients. In addition, diabetic patients should be screened for fatty liver and liver fibrosis degree.
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Hepatopatia Gordurosa não Alcoólica , Humanos , Masculino , Feminino , Estudos Transversais , Hepatopatia Gordurosa não Alcoólica/patologia , Hepatopatia Gordurosa não Alcoólica/complicações , Pessoa de Meia-Idade , China/epidemiologia , Biópsia , Adulto , Fígado Gorduroso/patologia , Cirrose Hepática/patologia , Ultrassonografia , Fígado/patologia , Fígado/diagnóstico por imagem , Imageamento por Ressonância MagnéticaRESUMO
We report epidemiologic, laboratory, and clinical findings for 7 patients with 2019 novel coronavirus disease in a 2-family cluster. Our study confirms asymptomatic and human-to-human transmission through close contacts in familial and hospital settings. These findings might also serve as a practical reference for clinical diagnosis and medical treatment.
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Doenças Assintomáticas , Betacoronavirus , Infecções por Coronavirus/transmissão , Pneumonia Viral/transmissão , Adulto , COVID-19 , Família , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , SARS-CoV-2RESUMO
Although motion of the head and body has been suspected or known as the provocative cause for the production of motion sickness for centuries, it is only within the last 20 yr that the source of the signal generating motion sickness and its neural basis has been firmly established. Here, we briefly review the source of the conflicts that cause the body to generate the autonomic signs and symptoms that constitute motion sickness and provide a summary of the experimental data that have led to an understanding of how motion sickness is generated and can be controlled. Activity and structures that produce motion sickness include vestibular input through the semicircular canals, the otolith organs, and the velocity storage integrator in the vestibular nuclei. Velocity storage is produced through activity of vestibular-only (VO) neurons under control of neural structures in the nodulus of the vestibulo-cerebellum. Separate groups of nodular neurons sense orientation to gravity, roll/tilt, and translation, which provide strong inhibitory control of the VO neurons. Additionally, there are acetylcholinergic projections from the nodulus to the stomach, which along with other serotonergic inputs from the vestibular nuclei, could induce nausea and vomiting. Major inhibition is produced by the GABAB receptors, which modulate and suppress activity in the velocity storage integrator. Ingestion of the GABAB agonist baclofen causes suppression of motion sickness. Hopefully, a better understanding of the source of sensory conflict will lead to better ways to avoid and treat the autonomic signs and symptoms that constitute the syndrome.
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Enjoo devido ao Movimento/fisiopatologia , Animais , Baclofeno/uso terapêutico , Agonistas dos Receptores de GABA-B/uso terapêutico , Humanos , Enjoo devido ao Movimento/tratamento farmacológico , Núcleos Vestibulares/fisiologia , Núcleos Vestibulares/fisiopatologia , Vestíbulo do Labirinto/fisiologia , Vestíbulo do Labirinto/fisiopatologiaRESUMO
The first NS3/4A hepatitis C virus (HCV) protease inhibitors telaprevir and boceprevir were approved in 2011, and both NS5A and NS5B polymerase inhibitors were launched. Recently, direct-acting antivirals (DAAs) have had a major impact on patients infected with HCV. HCV DAAs are highly effective antivirals with fewer side effects. DAAs have been developed for the treatment of HCV infection in combination with PEG-IFN-α/RBV as well as in IFN-free regimens. However, some drug resistance mutations occur when a single oral DAA is used for treatment, which indicates that there is a low-frequency drug resistance mutation in HCV patients before the application of antiviral drugs. Our research showed that natural resistance to HCV DAAs was found in treatment-naive CHC patients and that the drug resistance mutation rates differ in various HCV genotypes. Many challenges posed by natural resistance should be considered in the context of DAA therapies.
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Antivirais/farmacologia , Farmacorresistência Viral , Hepacivirus/genética , Hepatite C Crônica/tratamento farmacológico , Mutação , Inibidores de Proteases/farmacologia , Adulto , Antivirais/uso terapêutico , Feminino , Genótipo , Hepacivirus/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores de Proteases/uso terapêutico , Serina Proteases , Proteínas não Estruturais Virais/antagonistas & inibidoresRESUMO
Trains that tilt on curves can go faster, but passengers complain of motion sickness. We studied the control signals and tilts to determine why this occurs and how to maintain speed while eliminating motion sickness. Accelerometers and gyros monitored train and passenger yaw and roll, and a survey evaluated motion sickness. The experimental train had 3 control configurations: an untilted mode, a reactive mode that detected curves from sensors on the front wheel set, and a predictive mode that determined curves from the train's position on the tracks. No motion sickness was induced in the untilted mode, but the train ran 21% slower than when it tilted 8° in either the reactive or predictive modes (113 vs. 137 km/h). Roll velocities rose and fell faster in the predictive than the reactive mode when entering and leaving turns (0.4 vs. 0.8 s for a 4°/s roll tilt, P<0.001). Concurrently, motion sickness was greater (P<0.001) in the reactive mode. We conclude that the slower rise in roll velocity during yaw rotations on entering and leaving curves had induced the motion sickness. Adequate synchronization of roll tilt with yaw velocity on curves will reduce motion sickness and improve passenger comfort on tilting trains.
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Aceleração/efeitos adversos , Enjoo devido ao Movimento/etiologia , Meios de Transporte , Humanos , Enjoo devido ao Movimento/fisiopatologia , MovimentoRESUMO
The angular vestibulo-ocular reflex (aVOR) and optokinetic nystagmus (OKN) were elicited simultaneously at low frequencies to study effects of habituation of the velocity storage time constant in the vestibular system on motion sickness. Twenty-nine subjects, eleven of whom were susceptible to motion sickness from common transportation, were habituated by sinusoidal rotation at 0.017 Hz at peak velocities from 5 to 20°/s, while they watched a full-field OKN stimulus. The OKN stripes rotated in the same direction and at the same frequency as the subjects, but at a higher velocity. This produced an OKN opposite in direction to the aVOR response. Motion sickness sensitivity was evaluated with off-vertical axis rotation (OVAR) and by the response to transportation before and after 5 days of visual-vestibular habituation. Habituation did not induce motion sickness or change the aVOR gains, but it shortened the vestibular time constants in all subjects. This greatly reduced motion sickness produced by OVAR and sensitivity to common transport in the motion susceptible subjects, which persisted for up to 18 weeks. Two motion susceptible subjects who only had aVOR/OKN habituation without being tested with OVAR also became asymptomatic. Normal subjects who were not habituated had no reduction in either their aVOR time constants or motion sickness sensitivity. The opposing aVOR/OKN stimulation, which has not been studied before, was well tolerated, and for the first time was an effective technique for rapid and prolonged habituation of motion sickness without exposure to drugs or other nauseating habituation stimuli.
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Suscetibilidade a Doenças , Movimentos Oculares/fisiologia , Enjoo devido ao Movimento/patologia , Nistagmo Optocinético/fisiologia , Reflexo Vestíbulo-Ocular/fisiologia , Adulto , Feminino , Habituação Psicofisiológica/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Enjoo devido ao Movimento/fisiopatologia , Rotação , Limiar Sensorial/fisiologia , Fatores de TempoRESUMO
We investigated spatial responses of the aVOR to small and large accelerations in six canal-plugged and lateral canal nerve-sectioned monkeys. The aim was to determine whether there was spatial adaptation after partial and complete loss of all inputs in a canal plane. Impulses of torques generated head thrusts of ≈ 3,000°/s². Smaller accelerations of ≈ 300°/s² initiated the steps of velocity (60°/s). Animals were rotated about a spatial vertical axis while upright (0°) or statically tilted fore-aft up to ± 90°. Temporal aVOR yaw and roll gains were computed at every head orientation and were fit with a sinusoid to obtain the spatial gains and phases. Spatial gains peaked at ≈ 0° for yaw and ≈ 90° for roll in normal animals. After bilateral lateral canal nerve section, the spatial yaw and roll gains peaked when animals were tilted back ≈ 50°, to bring the intact vertical canals in the plane of rotation. Yaw and roll gains were identical in the lateral canal nerve-sectioned monkeys tested with both low- and high-acceleration stimuli. The responses were close to normal for high-acceleration thrusts in canal-plugged animals, but were significantly reduced when these animals were given step stimuli. Thus, high accelerations adequately activated the plugged canals, whereas yaw and roll spatial aVOR gains were produced only by the intact vertical canals after total loss of lateral canal input. We conclude that there is no spatial adaptation of the aVOR even after complete loss of specific semicircular canal input.
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Adaptação Fisiológica/fisiologia , Orientação , Reflexo Vestíbulo-Ocular/fisiologia , Canais Semicirculares/fisiologia , Percepção Espacial/fisiologia , Nervo Vestibular/fisiologia , Animais , Movimentos Oculares/fisiologia , Lateralidade Funcional/fisiologia , Macaca fascicularis , Modelos Biológicos , Canais Semicirculares/cirurgia , Nervo Vestibular/cirurgiaRESUMO
BACKGROUND: The coronavirus disease 2019 (COVID-19) is spreading rapidly across countries and has infected tens of millions of people all over the world. So far, the pandemic is ongoing globally, and the situation is still worsening. METHODS: In this retrospective, single-center cohort analysis, we included 25 adult inpatients with laboratory confirmed COVID-19 disease from the affiliated hospital of Xuzhou Medical University (Xuzhou, China). Epidemiological characterizations, clinical findings, and medical treatments were all reported. In addition, laboratory markers were investigated in terms of course of treatment. RESULTS: Epidemiological features and clinical findings were present for all 25 patients. Laboratory markers were identified due to temporal changes. After medical treatment, all patients were discharged home and recovering from the infection. CONCLUSIONS: This study provides a comprehensive overview of patients with COVID-19 disease in a single hospital. Some of the laboratory markers were statistically different during the course of the disease, which might serve as indicators in identifying patients with COVID-19 disease at an early stage of the infection.
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We tested the hypothesis that motion sickness is produced by an integration of the disparity between eye velocity and the yaw-axis orientation vector of velocity storage. Disparity was defined as the magnitude of the cross product between these two vectors. OVAR, which is known to produce motion sickness, generates horizontal eye velocity with a bias level related to velocity storage, as well as cyclic modulations due to re-orientation of the head re gravity. On average, the orientation vector is close to the spatial vertical. Thus, disparity can be related to the bias and tilt angle. Motion sickness sensitivity was defined as a ratio of maximum motion sickness score to the number of revolutions, allowing disparity and motion sickness sensitivity to be correlated. Nine subjects were rotated around axes tilted 10 degrees-30 degrees from the spatial vertical at 30 degrees/s-120 degrees/s. Motion sickness sensitivity increased monotonically with increases in the disparity due to changes in rotational velocity and tilt angle. Maximal motion sickness sensitivity and bias (6.8 degrees/s) occurred when rotating at 60 degrees/s about an axis tilted 30 degrees. Modulations in eye velocity during OVAR were unrelated to motion sickness sensitivity. The data were predicted by a model incorporating an estimate of head velocity from otolith activation, which activated velocity storage, followed by an orientation disparity comparator that activated a motion sickness integrator. These results suggest that the sensory-motor conflict that produces motion sickness involves coding of the spatial vertical by the otolith organs and body tilt receptors and processing of eye velocity through velocity storage.
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Percepção de Movimento/fisiologia , Enjoo devido ao Movimento/fisiopatologia , Reflexo Vestíbulo-Ocular/fisiologia , Adulto , Tontura/fisiopatologia , Movimentos Oculares/fisiologia , Feminino , Movimentos da Cabeça/fisiologia , Humanos , Masculino , Náusea/fisiopatologia , Nistagmo Fisiológico/fisiologia , Orientação/fisiologia , Membrana dos Otólitos/fisiologia , Rotação , Percepção Espacial/fisiologia , Vestíbulo do Labirinto/fisiologiaRESUMO
Head movements in a rotating frame of reference are commonly encountered, but their long term effects on the angular vestibulo-ocular reflex (aVOR) are not well understood. To study this, monkeys were oscillated about a naso-occipital (roll) axis for several hours while rotating about a spatial vertical axis (roll-while-rotating, RWR). This induced oscillations in roll and pitch eye velocity and continuous horizontal (yaw) nystagmus. For several hours thereafter, simple roll in darkness induced horizontal nystagmus and pitch and roll oscillations. The rising and falling time constants of the horizontal velocity indicated that the nystagmus arose in velocity storage. The continuous nystagmus was correlated with a phase shift of vertical eye velocity from 90 degrees to 0 degrees re head position. As the phases reverted toward pre-adaptive values, the horizontal velocity declined. Similar yaw nystagmus and pitch and roll velocities were produced by oscillation in roll after adaptation with roll and horizontal optokinetic nystagmus (OKN), but not after adaptation with pitch-while-rotating (PWR). Findings were explained by a model that shifted the roll orientation vector of velocity storage toward the pitch axis during adaptation with RWR and Roll & OKN. This shift produced modulation in vertical eye velocity in the post adaptive state, which was approximately in phase with roll head position, generating horizontal nystagmus. Similar orientation changes to prolonged exposure to complex motion environments may be responsible for producing post-stimulus motion sickness and/or mal de debarquement.
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Adaptação Biológica/fisiologia , Movimentos da Cabeça/fisiologia , Percepção de Movimento/fisiologia , Orientação/fisiologia , Reflexo Vestíbulo-Ocular/fisiologia , Rotação/efeitos adversos , Animais , Encéfalo/fisiologia , Macaca , Enjoo devido ao Movimento/etiologia , Enjoo devido ao Movimento/fisiopatologia , Nistagmo Fisiológico/fisiologia , Músculos Oculomotores/inervação , Músculos Oculomotores/fisiologia , Estimulação Física , Percepção Espacial/fisiologia , Vestíbulo do Labirinto/fisiologiaRESUMO
Klotho beta (KLB) mediates binding of fibroblast growth factor (FGF) 21 to the FGF receptor (FGFR). FGF21-KLB-FGFR signaling regulates multiple metabolic systems in the liver, and we hypothesized that FGF21, KLB and FGFR single-nucleotide polymorphisms (SNPs) are involved in hepatic lipid accumulation. The SNPs were detected in 1688 individuals divided into four groups: non-obese without non-alcoholic fatty liver disease (NAFLD), obese without NAFLD, non-obese with NAFLD, and obese with NAFLD. The A-allele of KLB SNP rs7670903 correlated with higher body mass index (P = 0.0005), and the A-allele frequency was higher in the obese than non-obese group (P = 0.003). The G-allele frequency of KLB rs7674434 and T-allele frequency of rs12152703 were higher in the obese with NAFLD than obese without NAFLD group (P = 0.004 and P = 0.006), but the genotype distribution between two non-obese groups did not differ. KLB rs7674434 and rs12152703 had associations with alanine aminotransferase (ALT) (P = 0.03 and P = 0.04, respectively) and gamma-glutamyltransferase (P = 0.03 and P = 0.02, respectively) levels in all subjects, but the associations were especially strong with ALT in the NAFLD group (P = 0.005 and P = 0.008, respectively). These findings suggest that KLB SNPs are related to obesity and hepatic inflammation and that they may be involved in the pathogenesis of NAFLD.
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Predisposição Genética para Doença , Proteínas de Membrana/genética , Hepatopatia Gordurosa não Alcoólica/genética , Obesidade/genética , Polimorfismo de Nucleotídeo Único , Adulto , Alelos , Povo Asiático/genética , Índice de Massa Corporal , China , Feminino , Frequência do Gene , Estudos de Associação Genética , Genótipo , Humanos , Proteínas Klotho , Masculino , Pessoa de Meia-IdadeRESUMO
Hepatitis C virus (HCV)infected liver cells sensitize host cells to tumor necrosis factor (TNF)related apoptosisinducing ligand (TRAIL)induced cell apoptosis; however, the precise mechanisms are unknown. In the present study, flow cytometry demonstrated that the Annexin Vpositive Huh7 cell number was higher in groups transfected with core proteins when compared with the pcDNA3.1 group. The mRNA and protein expression levels of Bcell lymphoma 2 (Bcl2) were negatively associated, while Bcl2associated X protein (Bax) were positively correlated, with cell apoptotic rate, which, were verified by reverse transcriptionquantitative polymerase chain reaction (RTqPCR) and western blotting. There were no signiï¬cant differences in the expressions of casein kinase 1 (CK1)ε, CK1γ or CK1δ; however, the mRNA and protein levels of CK1α were markedly higher in groups transfected with the T (those derived from the HCVJ6 strain), NT (those derived from nontumor tissues) and C191 (those derived from tumor tissues) HCV core proteins than in mock group. When compared with the Mock and Negative Control (control knowndown) groups, the mRNA and protein levels of CK1α were lower in the CK1α knowndown group, and there were no marked Huh7 cell morphological changes among the 3 groups. There was more sensitivity to cell apoptosis in CK1αsilenced, however, not in nonCK1αsilenced, Huh7 cells. BH3 interactingdomain death agonist (Bid) protein levels in CK1αsilenced Huh7 cells were higher when compared with nonCK1αsilenced Huh7 cells, and the level of p53 that translocated to the nucleus increased. Chromatin immunoprecipitationPCR demonstrated that p53 bound to human Bid gene promoter. The level of the Bid promoter in CK1αsilenced Huh7 cells was significantly higher than in the nonCK1αsilenced Huh7 cells. Electron microscopy indicated that p53 knockdown decreased HCV core protein and TRAILinduced cell apoptosis. Bid/caspase8 protein levels in CK1αsilenced Huh7 cells that were transfected with p53 siRNA were lower than in the control group. The present study demonstrated that HCV core proteins sensitize host cells to TRAILinduced cell apoptosis by activating the CK1αp53Bid dependent pathway.
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Apoptose , Caseína Quinase Ialfa/metabolismo , Hepacivirus/fisiologia , Transdução de Sinais , Proteína Supressora de Tumor p53/metabolismo , Proteínas do Core Viral/metabolismo , Apoptose/efeitos dos fármacos , Apoptose/genética , Caseína Quinase Ialfa/genética , Linhagem Celular Tumoral , Técnicas de Silenciamento de Genes , Hepatite C/metabolismo , Hepatite C/virologia , Humanos , Ligante Indutor de Apoptose Relacionado a TNF/metabolismo , Ligante Indutor de Apoptose Relacionado a TNF/farmacologiaRESUMO
INTRODUCTION: Mal de Debarquement Syndrome (MdDS) is a condition characterized by a persistent perception of self-motion, in most cases triggered from exposure to passive motion (e.g., boat travel, a car ride, flights). Patients whose onset was triggered in this way are categorized as Motion-Triggered (MT) subtype or onset group. However, the same syndrome can occur spontaneously or after non-motion events, such as childbirth, high stress, surgery, etc. Patients who were triggered in this way are categorized as being of the Spontaneous/Other (SO) subtype or onset group. The underlying pathophysiology of MdDS is unknown and there has been some speculation that the two onset groups are separate entities. However, despite the differences in onset between the subtypes, symptoms are parallel and a significant female predominance has been shown. To date, the role of gonadal hormones in MdDS pathophysiology has not been investigated. This study aimed to evaluate the hormonal profile of MdDS patients, the presence of hormonal conditions, the influence of hormones on symptomatology and to assess possible hormonal differences between onset groups. In addition, the prevalence of migraine and motion sickness and their relation to MdDS were assessed. METHOD: Retrospective online surveys were performed in 370 MdDS patients from both onset groups. Data were analyzed using Fisher's exact test or Fisher-Freeman-Hanlon exact test. When possible, data were compared with normative statistical data from the wider literature. RESULTS: From the data collected, it was evident that naturally cycling female respondents from the MT group were significantly more likely to report an aggravation of MdDS symptoms during menses and mid-cycle (p < 0.001). A few preliminary differences between the onset groups were highlighted such as in regular menstrual cycling (p = 0.028), reporting menses during onset (p < 0.016), and migraine susceptibility after onset (p = 0.044). CONCLUSION: These results demonstrate a potential relation between hormone fluctuations and symptom aggravation in the MT group. This study is an important first step to suggest a hormonal involvement in the pathophysiology of MdDS and provides a base for further hormonal investigation. Future prospective studies should expand upon these results and explore the implications for treatment.
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The mal de debarquement syndrome (MdDS) is a movement disorder, occurring predominantly in women, is most often induced by passive transport on water or in the air (classic MdDS), or can occur spontaneously. MdDS likely originates in the vestibular system and is unfamiliar to many physicians. The first successful treatment was devised by Dai et al. (1), and over 330 MdDS patients have now been treated. Here, we report the outcomes of 141 patients (122 females and 19 males) treated 1 year or more ago. We examine the patient's rocking frequency, body drifting, and nystagmus. The patients are then treated according to these findings for 4-5 days. During treatment, patients' heads were rolled while watching a rotating full-field visual surround (1). Their symptom severity after the initial treatment and at the follow-up was assessed using a subjective 10-point scale. Objective measures, taken before and at the end of the week of treatment, included static posturography. Significant improvement was a reduction in symptom severity by more than 50%. Objective measures were not possible during the follow-up because of the wide geographic distribution of the patients. The treatment group consisted of 120 classic and 21 spontaneous MdDS patients. The initial rate of significant improvement after a week of treatment was 78% in classic and 48% in spontaneous patients. One year later, significant improvement was maintained in 52% of classic and 48% of spontaneous subjects. There was complete remission of symptoms in 27% (32) of classic and 19% (4) of spontaneous patients. Although about half of them did not achieve a 50% improvement, most reported fewer and milder symptoms than before. The success of the treatment was generally inversely correlated with the duration of the MdDS symptoms and with the patients' ages. Prolonged travel by air or car on the way home most likely contributed to the symptomatic reversion from the initial successful treatment. Our results indicate that early diagnosis and treatment can significantly improve results, and the prevention of symptomatic reversion will increase the long-term benefit in this disabling disorder.
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Interleukin-35 is a novel inhibition cytokine secreted by CD4+CD25+ regulatory T-cells (Treg) in murine. However, it is disputed whether IL-35 could be secreted by Treg cells in humans. In this study, the levels of IL-35 were detected, and its relationship with regulatory T-cells in chronic hepatitis B (CHB) patients was investigated. It was shown that the levels of IL-35 in CHB patients were higher than those in normal controls, and the levels increased gradually, accompanied with the severe liver inflammation and necrosis and poor synthesis function. Treg cells may secrete IL-35, whose levels would become higher, accompanied by a longer activated time. Thus, IL-35 as a cytokine secreted by Treg cells may accelerate liver inflammation and necrosis, and inhibit the synthesis function.
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Hepatite B Crônica/imunologia , Interleucinas/sangue , Linfócitos T Reguladores/imunologia , Animais , Hepatite B Crônica/patologia , Humanos , Fígado/patologia , CamundongosRESUMO
We propose that motion sickness is mediated through the orientation properties of velocity storage in the vestibular system that tend to align eye velocity produced by the angular vestibulo-ocular reflex (aVOR) with gravito-inertial acceleration (GIA). (GIA is the sum of the linear accelerations acting on the head. In the absence of translational accelerations, gravity is the GIA.) We further postulate that motion sickness produced by cross-coupled vestibular stimulation can be characterized by a metric composed of the disparity between the axis of eye rotation and the GIA, the strength of the response to angular motion, and the response duration, as determined by the central vestibular time constant, that is, by the time constant of velocity storage. The nodulus and uvula of the vestibulocerebellum are likely to be the central sites where the disparity is sensed, where the vestibular time constants are habituated, and where links are made to the autonomic system to produce the symptoms and signs.
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Movimentos Oculares/fisiologia , Movimentos da Cabeça/fisiologia , Percepção de Movimento/fisiologia , Enjoo devido ao Movimento/fisiopatologia , Reflexo Vestíbulo-Ocular/fisiologia , Adulto , Estudos Cross-Over , Tontura/fisiopatologia , Método Duplo-Cego , Feminino , Antagonistas dos Receptores Histamínicos H1/administração & dosagem , Humanos , Masculino , Enjoo devido ao Movimento/prevenção & controle , Náusea/fisiopatologia , Nistagmo Fisiológico/fisiologia , Prometazina/administração & dosagem , RotaçãoRESUMO
The spatial orientation of the slow-phase eye velocity of caloric nystagmus was investigated in cynomolgus monkeys after all six semicircular canals had been plugged. Normal animals generate responses that have dominant convective components produced by movement of the endolymph in the lateral canal toward or away from gravity. As a result, the direction of horizontal slow-phase velocity induced by cold-water irrigation changes direction with changes in head position with regard to gravity. Plugging produced a dense overgrowth of bone that blocked the flow of endolymph, but the end organs were intact. Robust caloric nystagmus was elicited after recovery, but the horizontal (yaw) component was now always toward the stimulated (ipsilateral) side, regardless of head position re gravity. The induced caloric nystagmus had strong spatial orientation properties after canal plugging. With animals upright, the three-dimensional velocity vector of the caloric nystagmus was close to the yaw axis with small vertical and roll components. Roll components became stronger in supine and prone positions and vertical components were enhanced in the right- and left-side down positions. In each instance, the addition of the roll and vertical components moved the velocity vector of the nystagmus closer to the spatial vertical. Modeling supported the postulate that the caloric nystagmus after canal plugging is influenced by three factors: (1) a reduction in neural activity in the ampullary nerves on the stimulated side due to cooling of the nerves; (2) contraction of the endolymph in the closed space between the cupula and the plug due to cooling, which resulted in deflection of the cupula and hair cells toward the plug (ampullofugal deflection); and (3) alignment of eye velocity to gravity due to the orientation properties of velocity storage. Although convection is the most prominent factor in producing caloric responses in the normal state, our results suggest that alteration of nerve activity due to thermal effects, endolymph contraction or expansion, and velocity storage are also likely to contribute to the total response.
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Nistagmo Fisiológico/fisiologia , Animais , Orelha Interna/fisiologia , Lateralidade Funcional , Macaca fascicularis , Orientação/fisiologia , Reflexo Vestíbulo-Ocular/fisiologia , Percepção Espacial/fisiologiaRESUMO
The mal de debarquement syndrome (MdDS), a continuous feeling of swaying, rocking, and/or bobbing, generally follows travel on the sea. The associated symptoms cause considerable distress. The underlying neural mechanisms are unknown, and to date there have been no effective treatments for this condition. Results in monkeys and humans suggested that MdDS was caused by maladaptation of the vestibulo-ocular reflex (VOR) to roll of the head during rotation. We studied 24 subjects with persistent MdDS (3 males, 21 females; 19.1 ± 33 months). Physical findings included body oscillation at 0.2 Hz, oscillating vertical nystagmus when the head was rolled from side-to-side in darkness, and unilateral rotation during the Fukuda stepping test. We posited that the maladapted rocking and the physical symptoms could be diminished or extinguished by readapting the VOR. Subjects were treated by rolling the head from side-to-side while watching a rotating full-field visual stimulus. Seventeen of the 24 subjects had a complete or substantial recovery on average for approximately 1 year. Six were initially better, but the symptoms recurred. One subject did not respond to treatment. Thus, readaptation of the VOR has led to a cure or substantial improvement in 70% of the subjects with MdDS. We conclude that the adaptive processes associated with roll-while-rotating are responsible for producing MdDS, and that the symptoms can be reduced or resolved by readapting the VOR.