AIM:Cardiovascular autonomic and peripheral sensoryneuropathy is a known complication of chronic alcoholicand non-alcoholic liver diseases.We aimed to assess theprevalence and risk factors for peripheral sensory nerve...AIM:Cardiovascular autonomic and peripheral sensoryneuropathy is a known complication of chronic alcoholicand non-alcoholic liver diseases.We aimed to assess theprevalence and risk factors for peripheral sensory nerveand autonomic dysfunction using sensitive methods inpatients with primary biliary cirrhosis (PBC).METHODS:Twenty-four AMA M2 positive female patientswith clinical,biochemical and histological evidence of PBCand 20 age matched healthy female subjects were studied.Five standard cardiovascular reflex tests and 2d-h heartrate variability(HRV)analysis were performed to defineautonomic function.Peripheral sensory nerve function onmedian and peroneal nerves was characterized by currentperception threshold(CPT),measured by a neuroselectivediagnostic stimulator(Neurotron,Baltimore,MD).RESULTS:Fourteen of 24 patients(58%)had at least oneabnormal cardiovascular reflex test and thirteen(54%)had peripheral sensory neuropathy.Lower heart rateresponse to deep breathing(P=0.001),standing(P=0.03)and Valsalva manoeuvre(P=0.01),and more profounddecrease of blood pressure after standing(P=0.03)wasfound in PBC patients than in controls.As a novel findingwe proved that both time domain and frequency domainparameters of 24-h HRV were significantly reduced in PBCpatients compared to controls.Each patient had at leastone abnormal parameter of HRV.Lower CPT values indicatedhyperaesthesia as a characteristic feature at peronealnerve testing at three frequencies(2000 Hz:P=0.005;250 Hz:P=0.002;5 Hz:P=0.004)in PBC compared tocontrols.Correlation of autonomic dysfunction with theseverity and duration of the disease was observed.Lowertotal power of HRV correlated with lower CPT values atmedian nerve testing at 250 Hz(P=0.0001)and at 5 Hz(P=0.002),as well as with those at peroneal nerve testingat 2000 Hz(P=0.01).CONCLUSION:Autonomic and sensory nerve dysfunctionsare frequent in PBC.Twenty-four-hour HRV analysis is moresensitive than standard cardiovascular tests for detectingof both parasympathetic and sympathetic impairments.Ournovel data suggest that hyperaesthesia is a characteristicfeature of peripheral sensory neuropathy and mightcontribute to itching in PBC.Autonomic dysfunction is relatedto the duration and severity of PBC.展开更多
AIM:To examine the activation of the Nalp3 inflammasome and its downstream targets following lipopolysaccharide(LPS) -induced stimulation in the liver. METHODS:Six-to-eight-week-old C57BL/6 chow fed mice were injected...AIM:To examine the activation of the Nalp3 inflammasome and its downstream targets following lipopolysaccharide(LPS) -induced stimulation in the liver. METHODS:Six-to-eight-week-old C57BL/6 chow fed mice were injected intraperitoneally with 0.5μg/g bodyweight LPS and sacrificed 2,4,6,18 or 24 h later. LPS-induced liver damage was confirmed by a biochemical assay to detect alanine aminotransferase(ALT) levels.To determine if LPS stimulation in the liver led to activation of the inflammasome,real-time quantitative polymerase chain reaction was used to evaluate the mRNA expression of components of the Nalp3 inflammasome.Enzyme-linked immunosorbent assays were used to determine the protein expression levels of several downstream targets of the Nalp3 inflammasome,including caspase-1 and two cytokine targets of caspase-1,interleukin(IL) -1βand IL-18. RESULTS:We found that LPS injection resulted in liver damage as indicated by elevated ALT levels.This was associated with a significant increase in both mRNA and protein levels of the proinflammatory cy-tokine tumor necrosis factor(TNF) -αin the liver,as well as increased levels of TNFs in serum.We showed that LPS stimulation led to upregulation of mRNA levels in the liver for all the receptor components of the inflammasome,including Nalp3,Nalp1,pannexin-1 and the adaptor molecule apoptosis-associated specklike,caspase recruitment domain-domain containing protein.We also found increased levels of mRNA and protein for caspase-1,a downstream target of the inflammasome.In addition,LPS challenge led to increased levels of both mRNA and protein in the liver for two cytokine targets of caspase-1,IL-1βand IL-18. Interestingly,substantial baseline expression of pre-IL1βand pre-IL-18 was found in the liver.Inflammasome and caspase-1 activation was indicated by the significant increase in the active forms of IL-1βand IL-18 after LPS stimulation. CONCLUSION:Our results show that the Nalp3 inflammasome is upregulated and activated in the liver in response to LPS stimulation.展开更多
A 35-year-old female patient presented with the following symptoms of Holmes-Adie syndrome： photophobia, enlargement of the left pupil unresponsive to light, Achilles areflexia. The pilocarpine test was positive. No ...A 35-year-old female patient presented with the following symptoms of Holmes-Adie syndrome： photophobia, enlargement of the left pupil unresponsive to light, Achilles areflexia. The pilocarpine test was positive. No tumor or other neurological abnormality was found. She had a 19-year history of autoimmune hepatitis. Flares up were observed following each 3 deliveries. At age of 31 she presented with diarrhea and weight loss. Abdominal tumor was detected by ultrasound. The surgically removed tumor was histologically a benign mesenteric multicystic lymphangioma. Simultaneously, celiac disease was diagnosed. Gluten-free diet resulted in a significant improvement of celiac disease, but not of autoimmune hepatitis. Autonomic neuropathy was proven by standard cardiovascular tests. The patient was a homozygous carrier for HLA DQ2 antigen characteristic for celiac disease and heterozygous for HLA DR3 B8 frequent in autoimmune liver diseases. Our novel observation on association of Holmes-Adie syndrome with autoimmune hepatitis and celiac disease is suggestive for a common immunological background for all three entities present in a patient with mesenteric multicystic lymphangioma.展开更多
文摘AIM:Cardiovascular autonomic and peripheral sensoryneuropathy is a known complication of chronic alcoholicand non-alcoholic liver diseases.We aimed to assess theprevalence and risk factors for peripheral sensory nerveand autonomic dysfunction using sensitive methods inpatients with primary biliary cirrhosis (PBC).METHODS:Twenty-four AMA M2 positive female patientswith clinical,biochemical and histological evidence of PBCand 20 age matched healthy female subjects were studied.Five standard cardiovascular reflex tests and 2d-h heartrate variability(HRV)analysis were performed to defineautonomic function.Peripheral sensory nerve function onmedian and peroneal nerves was characterized by currentperception threshold(CPT),measured by a neuroselectivediagnostic stimulator(Neurotron,Baltimore,MD).RESULTS:Fourteen of 24 patients(58%)had at least oneabnormal cardiovascular reflex test and thirteen(54%)had peripheral sensory neuropathy.Lower heart rateresponse to deep breathing(P=0.001),standing(P=0.03)and Valsalva manoeuvre(P=0.01),and more profounddecrease of blood pressure after standing(P=0.03)wasfound in PBC patients than in controls.As a novel findingwe proved that both time domain and frequency domainparameters of 24-h HRV were significantly reduced in PBCpatients compared to controls.Each patient had at leastone abnormal parameter of HRV.Lower CPT values indicatedhyperaesthesia as a characteristic feature at peronealnerve testing at three frequencies(2000 Hz:P=0.005;250 Hz:P=0.002;5 Hz:P=0.004)in PBC compared tocontrols.Correlation of autonomic dysfunction with theseverity and duration of the disease was observed.Lowertotal power of HRV correlated with lower CPT values atmedian nerve testing at 250 Hz(P=0.0001)and at 5 Hz(P=0.002),as well as with those at peroneal nerve testingat 2000 Hz(P=0.01).CONCLUSION:Autonomic and sensory nerve dysfunctionsare frequent in PBC.Twenty-four-hour HRV analysis is moresensitive than standard cardiovascular tests for detectingof both parasympathetic and sympathetic impairments.Ournovel data suggest that hyperaesthesia is a characteristicfeature of peripheral sensory neuropathy and mightcontribute to itching in PBC.Autonomic dysfunction is relatedto the duration and severity of PBC.
文摘AIM:To examine the activation of the Nalp3 inflammasome and its downstream targets following lipopolysaccharide(LPS) -induced stimulation in the liver. METHODS:Six-to-eight-week-old C57BL/6 chow fed mice were injected intraperitoneally with 0.5μg/g bodyweight LPS and sacrificed 2,4,6,18 or 24 h later. LPS-induced liver damage was confirmed by a biochemical assay to detect alanine aminotransferase(ALT) levels.To determine if LPS stimulation in the liver led to activation of the inflammasome,real-time quantitative polymerase chain reaction was used to evaluate the mRNA expression of components of the Nalp3 inflammasome.Enzyme-linked immunosorbent assays were used to determine the protein expression levels of several downstream targets of the Nalp3 inflammasome,including caspase-1 and two cytokine targets of caspase-1,interleukin(IL) -1βand IL-18. RESULTS:We found that LPS injection resulted in liver damage as indicated by elevated ALT levels.This was associated with a significant increase in both mRNA and protein levels of the proinflammatory cy-tokine tumor necrosis factor(TNF) -αin the liver,as well as increased levels of TNFs in serum.We showed that LPS stimulation led to upregulation of mRNA levels in the liver for all the receptor components of the inflammasome,including Nalp3,Nalp1,pannexin-1 and the adaptor molecule apoptosis-associated specklike,caspase recruitment domain-domain containing protein.We also found increased levels of mRNA and protein for caspase-1,a downstream target of the inflammasome.In addition,LPS challenge led to increased levels of both mRNA and protein in the liver for two cytokine targets of caspase-1,IL-1βand IL-18. Interestingly,substantial baseline expression of pre-IL1βand pre-IL-18 was found in the liver.Inflammasome and caspase-1 activation was indicated by the significant increase in the active forms of IL-1βand IL-18 after LPS stimulation. CONCLUSION:Our results show that the Nalp3 inflammasome is upregulated and activated in the liver in response to LPS stimulation.
文摘A 35-year-old female patient presented with the following symptoms of Holmes-Adie syndrome： photophobia, enlargement of the left pupil unresponsive to light, Achilles areflexia. The pilocarpine test was positive. No tumor or other neurological abnormality was found. She had a 19-year history of autoimmune hepatitis. Flares up were observed following each 3 deliveries. At age of 31 she presented with diarrhea and weight loss. Abdominal tumor was detected by ultrasound. The surgically removed tumor was histologically a benign mesenteric multicystic lymphangioma. Simultaneously, celiac disease was diagnosed. Gluten-free diet resulted in a significant improvement of celiac disease, but not of autoimmune hepatitis. Autonomic neuropathy was proven by standard cardiovascular tests. The patient was a homozygous carrier for HLA DQ2 antigen characteristic for celiac disease and heterozygous for HLA DR3 B8 frequent in autoimmune liver diseases. Our novel observation on association of Holmes-Adie syndrome with autoimmune hepatitis and celiac disease is suggestive for a common immunological background for all three entities present in a patient with mesenteric multicystic lymphangioma.
