AIM: To study isolation and chemical characterization of pectin derived from the common cranberry Vaccin/um oxycoccos L. (oxycoccusan OP) and the testing of its preventive effect on experimental colitis. METHODS: ...AIM: To study isolation and chemical characterization of pectin derived from the common cranberry Vaccin/um oxycoccos L. (oxycoccusan OP) and the testing of its preventive effect on experimental colitis. METHODS: Mice were administrated orally with OP two days prior to a rectal injection of 5% acetic acid and examined for colonic damage 24 h later. Colonic inflammation was characterized by macroscopical injury and enhanced levels of myeloperoxidase activity measured spectrophotometrically with o-phenylene diamine as the substrate. The mucus contents of the colon were determined by the Alcian blue dye binding method. Vascular permeability was estimated using 4% Evans blue passage after i.p. injection of 0.05 mol/L acetic acid. RESULTS: In the mice treated with OP, colonic macroscopic scores (1.1 ± 0.4 vs 2.7, P 〈 0.01) and the total square area of damage (10 ± 2 vs 21 ± 7, P 〈 0.01) were significantly reduced when compared with the vehicle-treated colitis group. OP was shown to decrease the tissue myeloperoxidase activity in colons (42 ± 11 vs 112 ± 40, P 〈 0.01) and enhance the amount of mucus of colitis mice (0.9 ± 0.1 vs 0.4 ± 0.1, P 〈 0.01). The level of colonic malondialdehyde was noted to decrease in OP-pretreated mice (3.6 ± 0.7 vs 5.1 ± 0.8, P 〈 0.01). OP was found to decrease the inflammatory status of mice as was determined by reduction of vascular permeability (161 ± 34 vs 241 ± 21, P 〈 0.01). Adhesion of peritoneal neutrophils and macrophages was also shown to decrease after administration of OP (141 ± 50 vs 235 ± 37, P 〈 0.05). CONCLUSION: Thus, a preventive effect of pectin from the common cranberry, namely oxycoccusan OP, on acetic acid-induced colitis in mice was detected. A reduction of neutrophil infiltration and antioxidant action may be implicated in the protective effect of oxycoccusan.展开更多
Object: To examine the effect of astragalus polysaccharide (APS) on kidney status and fibrosis indices of rats withdiabetic nephropathy. Methods: 72 male rats were randomly divided into three groups: negative con...Object: To examine the effect of astragalus polysaccharide (APS) on kidney status and fibrosis indices of rats withdiabetic nephropathy. Methods: 72 male rats were randomly divided into three groups: negative control group (NC, n =24); diabetic nephropathy model group (DNM, n = 24); and diabetic nephropathy model with APS group (DNM + APS,n = 24). Rats of the DNM and DNM + APS groups were subjected to both unilateral nephrectomy and administeredstreptozotocin (STZ) injection (65 mg/kg). DNM + APS group rats were administered 50 IU/kg/d APS by subcutaneousinjection from the first week after operation until death. The NC and DNM group rats were subcutaneously injected withan identical volume of physiological saline. At weeks 3, 8, and 13 after the operation, 6 rats from each group wererandomly sacrificed and blood was collected to measure serum creatinine and blood urea nitrogen. On the day beforesacrifice, the rats were placed in a metabolic cage for 24 h to collect urine. At week 14 after the operation, 6 rats fromeach group were randomly selected to measure body weight and kidney index. Blood was collected to measure bloodglucose. The kidneys were harvested to detect pathological changes by hematoxylin and eosin staining. Results:Histological assessment of DNM rats suggested damage symptoms as evidenced by hyperplasia of the glomerularmesangial matrix, atrophia of the kidney tubules, and thickening of the basement membrane. In contrast, STZ-induceddiabetic nephropathy rats treated with APS (50 IU/kg/d) showed significantly improved histological results, suggestingthat APS has beneficial effect on renal tissues in STZ-induced DNM rats. Our results also indicated that APS relievedrenal injury and effectively improved body weight in DNM rats. The ratio of kidney weight to body weight was reducedand the early stage of renal function damage was improved after APS treatment. In the later stages of the disease, the 24h urinary protein significantly decreased. Moreover, APS down-regulated TGF-β1 and α-SMA expression of the kidney.Conclusion: APS significantly improved renal tubular interstitial injury in DNM rats and the early stage of renalfunction damage. The mechanism may be related to downregulation of the expression of TGF-β1 and α-SMA whichdelays the progression of renal interstitial fibrosis in DNM rats.展开更多
AIM: To study whether N-acetyltransferase 2 (NAT2) genotypes and phenotypes are associated with increased risk factor for gastric cancer in Omani patients and to study the clinico-pathological correlations and the ...AIM: To study whether N-acetyltransferase 2 (NAT2) genotypes and phenotypes are associated with increased risk factor for gastric cancer in Omani patients and to study the clinico-pathological correlations and the prognostic significance of NAT2. METHODS: Genomic DNA was extracted from peripheral blood of 100 gastric cancer patients and 100 control subjects. NAT2 genotyping was performed using DNA sequencing. The prognostic significance of NAT2 and other clinicopathological features was assessed by univariate and multivariate analyses. RESULTS: We observed no significant association between NAT2 genotypes and phenotypes and gastric cancer risk. The IVAT2 phenotype polymorphisms and gastric cancer risk predisposition were not modified by concomitant Hpylori infection and smoking. There was no significant association between NAT2 and clinicopathological features, and NAT2 had no independent prognostic significance. CONCLUSION: In the current study, NAT2 genotypes and phenotypes are not associated with gastric cancer risk predisposition. Moreover NAT2 phenotypes had no clinicopathological associations or prognostic significance.展开更多
Non-alcoholic fatty liver disease(NAFLD) has a prevalence of approximately 30% in western countries, and is emerging as the first cause of liver cirrhosis and hepatocellular carcinoma(HCC). Therefore, risk stratificat...Non-alcoholic fatty liver disease(NAFLD) has a prevalence of approximately 30% in western countries, and is emerging as the first cause of liver cirrhosis and hepatocellular carcinoma(HCC). Therefore, risk stratification emerges as fundamental in order to optimize human and economic resources, and genetics displays intrinsic characteristics suitable to fulfill this task. According to the available data, heritability estimates for hepatic fat content range from 20% to 70%, and an almost 80% of shared heritability has been found between hepatic fat content and fibrosis. The rs738409 single nucleotide polymorphism(SNP) in patatin-like phospholipase domain-containing protein 3 gene and the rs58542926 SNP in transmembrane 6 superfamily member 2 gene have been robustly associated with NAFLD and with its progression, but promising results have been obtained with many other SNPs. Moreover, there has been proof of the additive role of the different SNPs in determining liver damage, and there have been preliminary experiences in which risk scores created through a few genetic variants, alone or in combination with clinical variables, were associated with a strongly potentiated risk of NAFLD, non-alcoholic steatohepatitis(NASH), NASH fibrosis or NAFLD-HCC. However, to date, clinical translation of genetics in the field of NAFLD has been poor or absent. Fortunately, the research we have done seems to have placed us on the right path: We should rely on longitudinal rather than on cross-sectional studies; we should focus on relevant outcomes rather than on simple liver fat accumulation; and we should put together the genetic and clinical information. The hope is that combined genetic/clinical scores, derived from longitudinal studies and built on a few strong genetic variants and relevant clinical variables, will reach a significant predictive power, such as to have clinical utility for risk stratification at the single patient level and even to esteem the impact of intervention on the risk of disease-related outcomes. Well-structured future studies would demonstrate if this vision can become a reality.展开更多
To get a better understanding of the location,pathophysiology,etiology and prognosis of multiple malignant tumors (MPMT),we evaluated the medical records of 22 patients with MPMT.Our results suggested that radiotherap...To get a better understanding of the location,pathophysiology,etiology and prognosis of multiple malignant tumors (MPMT),we evaluated the medical records of 22 patients with MPMT.Our results suggested that radiotherapy and chemotherapy might play an important role in the pathogenesis of MPMT and follow up is important in detecting a secondary primary malignant tumor (PMT) at an early stage.Surgical removal of tumors is the first choice therapy for MPMT.展开更多
Parkinson disease(PD) is characterized by the selective loss of dopaminergic neurons in the substantia nigra. Although investigation in mammalian animal models of PD has enhanced our understanding of PD, the complexit...Parkinson disease(PD) is characterized by the selective loss of dopaminergic neurons in the substantia nigra. Although investigation in mammalian animal models of PD has enhanced our understanding of PD, the complexity of the mammalian nervous system and our inability to visualize DA neurons in vivo restricts the advances in elucidating the molecular mechanisms of PD. Conservation between C. elegans and mammals in genomic, biosynthetic and metabolic pathways as well as the advantages of observing DA neurons morphology in vivo and the ease of transgenic and genetic manipulation make C. elegans an excellent model organism for PD.展开更多
Autosomal dominant polycystic kidney disease (ADPKD), the most frequent cause of genetic renal disease affecting approximately 4 to 7 million individuals worldwide and accounting for 7%-15% of patients on renal repl...Autosomal dominant polycystic kidney disease (ADPKD), the most frequent cause of genetic renal disease affecting approximately 4 to 7 million individuals worldwide and accounting for 7%-15% of patients on renal replacement therapy, is a systemic disorder mainly involving the kidney but cysts can also occur in other organs such as the liver, pancreas, arachnoid membrane and seminal vesicles. Though computed tomography and magnetic resonance imaging (MRI) were similar in evaluating 81% of cystic lesions of the kidney, MRI may depict septa, wall thickening or enhancement leading to upgrade in cyst classification that can affect management. A screening strategy for intracranial aneurysms would provide 1.0 additional year of life without neurological disability to a 20-year-old patient with ADPKD and reduce the fnancial impact on society of the disease. Current treatment strategies include reducing: cyclic adenosine monophosphate levels, cell proliferation and fluid secretion. Several randomised clinical trials (RCT) including mammalian target of rapamycin inhibitors, somatostatin analoguesand a vasopressin V2 receptor antagonist have beenperformed to study the effect of diverse drugs ongrowth of renal and hepatic cysts, and on deteriorationof renal function. Prophylactic native nephrectomy isindicated in patients with a history of cyst infection orecurrent haemorrhage or to those in whom space musbe made to implant the graft. The absence of largeRCT on various aspects of the disease and its treatmen leaves considerable uncertainty and ambiguity in many aspects of ADPKD patient care as it relates to end stage renal disease (ESRD). The outlook of patients with ADPKD is improving and is in fact much better than that for patients in ESRD due to other causes. This review highlights the need for well-structured RCTs as a frst step towards trying newer interventions so as to develop updated clinical management guidelines.展开更多
AIM: To identify clinical parameters, and develop an Upper Gastrointesinal Bleeding (UGIB) Etiology Score for predicting the types of UGIB and validate the score. METHODS: Patients with UGIB who underwent endoscop...AIM: To identify clinical parameters, and develop an Upper Gastrointesinal Bleeding (UGIB) Etiology Score for predicting the types of UGIB and validate the score. METHODS: Patients with UGIB who underwent endoscopy within 72 h were enrolled. Clinical and basic laboratory parameters were prospectively collected. Predictive factors for the types of UGIB were identified by univariate and multivariate analyses and were used to generate the UGIB Etiology Score. The best cutoff of the score was defined from the receiver operating curve and prospectively validated in another set of patients with UGIB. RESULTS: Among 261 patients with UGIB, 47 (18%) had variceal and 214 (82%) had non-variceal bleeding. Univariate analysis identified 27 distinct parameters significantly associated with the types of UGIB. Logistic regression analysis identified only 3 independent factors for predicting variceal bleeding; previous diagnosis of cirrhosis or signs of chronic liver disease (OR 22.4, 95% CI 8.3-60.4, P 〈 0.001), red vomitus (OR 4.6, 95% CI 1.8-11.9, P = 0.02), and red nasogastric (NG) aspirate (OR 3.3, 95% CI 1.3-8.3, P = 0.011). The UGIB Etiology Score was calculated from (3.1× previous diagnosis of cirrhosis or signs of chronic liver disease) + (1.5× red vomitus) + (1.2× red NG aspirate), when 1 and 0 are used for the presence and absence of each factor, respectively. Using a cutoff ≥ 3.1, the sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) in predicting variceal bleeding were 85%, 81%, 82%, 50%, and 96%, respectively. The score was prospectively validated in cases (46 variceal and 149 another set of 195 UGIB non-variceal bleeding). The PPV and NPV of a score ≥ 3.1 for variceal bleeding were 79% and 97%, respectively. CONCLUSION: The UGIB Etiology Score, composed of 3 parameters, using a cutoff ≥ 3.1 accurately predicted variceal bleeding and may help to guide the choice of initial therapy for UGIB before endoscopy.展开更多
AIM: To determine the temporal expression and pattern of Rel/nuclear factor (NF)-κB proteins in renal tissue in polycystic kidney disease (PKD). METHODS: The renal expression of Rel/NF-κB proteins was determin...AIM: To determine the temporal expression and pattern of Rel/nuclear factor (NF)-κB proteins in renal tissue in polycystic kidney disease (PKD). METHODS: The renal expression of Rel/NF-κB proteins was determined by immunohistochemistry, immunofuorescence and immunoblot analysis in Lewis polycystic kidney rats (LPK, a genetic ortholog of human nephronopthsis-9) from postnatal weeks 3 to 20. At each timepoint, renal disease progression and the mRNA expression of NF-κB-dependent genes (TNFa and CCL2) were determined. NF-κB was also histologically assessed in human PKD tissue.RESULTS: Progressive kidney enlargement in LPK rats was accompanied by increased renal cell proliferation and interstitial monocyte accumulation (peaking at weeks 3 and 10 respectively), and progressive interstitial fibrosis (with a smooth muscle actin and Sirius Red deposition significantly increased compared to Lewis kidneys from weeks 3 to 6 onwards). Rel/NF-κB proteins (phosphorylated-p105, p65, p50, c-Rel and RelB) were expressed in cystic epithelial cells (CECs) of LPK kidneys as early as postnatal week 3 and sustained until late-stage disease at week 20. From weeks 10 to 20, nuclear p65, p50, RelB and cytoplasmic IκBa protein levels, and TNFa and CCL2 expression, were upregulated in LPK compared to Lewis kidneys. NF-κB proteins were consistently expressed in CECs of human PKD. The DNA damage marker γ-H2AX was also identifed in the CECs of LPK and human polycystic kidneys. CONCLUSION: Several NF-κB proteins are consistently expressed in CECs in human and experimental PKD. These data suggest that the upregulation of both the canonical and non-canonical pathways of NF-κB signaling may be a constitutive and early pathological feature of cystic renal diseases.展开更多
AIM: To evaluate the feasibility of a new clinical rating scale for a standardized assessment of cirrhosis-associated neuro-psychiatric symptoms. METHODS: Forty patients with liver cirrhosis (LC, with or without lo...AIM: To evaluate the feasibility of a new clinical rating scale for a standardized assessment of cirrhosis-associated neuro-psychiatric symptoms. METHODS: Forty patients with liver cirrhosis (LC, with or without low-grade hepatic encephalopathy) were investigated using a clinical neuro-psychiatric rating scale based on a comprehensive list of neurological, psychomotor, cognitive, affective, behavioral symptoms, and symptoms of disturbed bioregulation. RESULTS: The analysis revealed that the majodty of cirrhotic patients showed, besides characteristic neurological symptoms of hepatic encephalopathy, various psychomotor, affective and bioregulatory symptoms (disturbed sleep and sexual dysfunction). Patients were impaired in the following subscales: sleep and biorhythm disorder (75.0% of patients), Parkinsonoid symptoms (25.0%), affective symptoms (17.5%), and psychomotor retardation (12.5%). The increase of total neuro-psychiatric clinical score was significantly associated with the degree of hepatic encephalopathy. CONCLUSION: This study suggests that a substantial number of patients with LC and low-grade hepatic encephalopathy manifest various clinical neuro-psychiatric symptoms. The use of a rating scale, which explores clinical dimensions of hepatic encephalopathy, would improve the management of patients with LC.展开更多
This paper reports a familial amyloid polyneuropathy (FAP) family in China. This family being investigated had 69 members of five generations. From the third generation, there have been 16 patients. The age of onset w...This paper reports a familial amyloid polyneuropathy (FAP) family in China. This family being investigated had 69 members of five generations. From the third generation, there have been 16 patients. The age of onset was about 3 to 5 decades. The initial symptoms were autonomic nerve symptoms, such as impotence, dyspepsia and diarrhoea, associated with the sensory loss of lower extremities. As the disease progressed, the upper extremities and motor ability were also involved. The duration of disease course was about 8-10 years, most patients died of infection and cachexia. Sural biopsy in 3 patients had showed positive Congo red staining. From the clinical view, this FAP family is similar to FAP I found in Japan. The true classification, however, should be confirmed by further genetic analysis.展开更多
A 27-year-old male started to have his ankles swollen during his military service. He was examined at a military hospital where electromyoneurography showed the signs of distal sensory-motor polyneuropathy with axon d...A 27-year-old male started to have his ankles swollen during his military service. He was examined at a military hospital where electromyoneurography showed the signs of distal sensory-motor polyneuropathy with axon demyelinization and weak myopathic changes, whereas histopathological examination of gastrocnemius muscle biopsy revealed some mild and nonspecific myopathy. Besides, he was found to have subcutaneous ankle tissue edemas and hypertransaminasemia. Due to these reasons, he was dismissed from the military service and examined at another hospital where bone osteodensitometry revealed low bone mineral density of the spine. However, his medical problems were not resolved and after the second discharge from hospital he was desperately seeing doctors from time to time. Finally, at our institution he was shown to have celiac disease (CD) by positive serology (antitissue transglutaminase and antiendomysial antibodies) and small bowel mucosal histopathological examination, which showed total small bowel villous atrophy. Three months after the initiation of gluten-free diet, his ankle edema disappeared, electromyoneurographic signs of polyneuropathy improved and liver aminotransferases normalized. Good knowledge of CD extraintestinal signs and serologic screening are essential for early CD recognition and therapy.展开更多
AIM:To develop a novel endoscopic severity model of intestinal Behcet's disease(BD) and to evaluate its feasibility by comparing it with the actual disease activity index for intestinal Behcet's disease(DAIBD)...AIM:To develop a novel endoscopic severity model of intestinal Behcet's disease(BD) and to evaluate its feasibility by comparing it with the actual disease activity index for intestinal Behcet's disease(DAIBD).METHODS:We reviewed the medical records of 167 intestinal BD patients between March 1986 and April 2011.We also investigated the endoscopic parameters including ulcer locations,distribution,number,depth,shape,size and margin to identify independent factors associated with DAIBD.An endoscopic severity model was developed using significant colonoscopic variables identified by multivariate regression analysis and its correlation with the DAIBD was evaluated.To determine factors related to the discrepancy between endoscopic severity and clinical activity,clinical characteristics and laboratory markers of the patients were analyzed.RESULTS:A multivariate regression analysis revealed that the number of intestinal ulcers(≥ 2,P = 0.031) and volcanoshaped ulcers(P = 0.001) were predictive factors for the DAIBD.An endoscopic severity model(Y) was developed based on selected endoscopic variables as follows:Y = 47.44 + 9.04 × non-Ileocecal area + 11.85 ×≥ 2 of intestinal ulcers + 5.03 × shallow ulcers + 12.76 × deep ulcers + 4.47 × geographicshaped ulcers + 26.93 × volcano-shaped ulcers + 8.65 ×≥ 20 mm of intestinal ulcers.However,endoscopic parameters used in the multivariate analysis explained only 18.9% of the DAIBD variance.Patients with severe DAIBD scores but with moderately predicted disease activity by the endoscopic severity model had more symptoms of irritable bowel syndrome(21.4% vs 4.9%,P = 0.026) and a lower rate of corticosteroid use(50.0% vs 75.6%,P = 0.016) than those with severe DAIBD scores and accurately predicted disease by the model.CONCLUSION:Our study showed that the number of intestinal ulcers and volcano-shaped ulcers were predictive factors for severe DAIBD scores.However,the correlation between endoscopic severity and DAIBD(r = 0.434) was weak.展开更多
AIM:To evaluate the clinical relevance of each cofactor on clinical presentation of chronic hepatitis B.METHODS:Out of 1366 hepatitis B surface antigen(HBsAg) positive subjects consecutively observed in 79 Italian hos...AIM:To evaluate the clinical relevance of each cofactor on clinical presentation of chronic hepatitis B.METHODS:Out of 1366 hepatitis B surface antigen(HBsAg) positive subjects consecutively observed in 79 Italian hospitals,53(4.3%) showed as the only cofactor hepatitis D virus(HDV) infection [hepatitis B virus(HBV)/HDV group],130(9.5%) hepatitis C virus(HCV)(group HBV/HCV),6(0.4%) human immunodeficiencyvirus(HIV)(group HBV/HIV),138(10.2%) alcohol abuse(group HBV/alcohol);109(8.0%) subjects had at least two cofactors and 924 were in the cofactor-free(CF) group.RESULTS:Compared with patients in group CF those in group HBV/alcohol were older and more frequently had cirrhosis(P < 0.001),those in group HBV/HDV were younger(P < 0.001),more frequently resided in the south of the country and had cirrhosis(P <0.001),those in group HBV/HCV were older(P < 0.001) and more frequently had cirrhosis(P < 0.001).These cofactors were all independent predictors of liver cirrhosis in HBsAg positive patients.Multivariate analysis showed that an older age [odds ratio(OR) 1.06,95% CI:1.05-1.08],alcohol abuse with more than 8 drinks daily(OR 2.89,95% CI:1.81-4.62) and anti-HDV positivity(OR 3.48,95% CI:2.16-5.58) are all independently associated with liver cirrhosis.This association was found also for anti-HCV positivity in univariate analysis,but it was no longer associated(OR 1.23,95% CI:0.84-1.80) at multivariate analysis.CONCLUSION:Older age,HDV infection and alcohol abuse are the major determinants of severe liver disease in chronic HBV infection,while HCV replication plays a lesser role in the severity of hepatic damage.展开更多
ATP Binding Cassette sub-family B member 1 (ABCB1) affects disposition of many drugs and thus affects the pharmacokinetics of drugs and ultimately treatment response. Polymorphisms of ABCB 1 especially ABCB 1 C3435T...ATP Binding Cassette sub-family B member 1 (ABCB1) affects disposition of many drugs and thus affects the pharmacokinetics of drugs and ultimately treatment response. Polymorphisms of ABCB 1 especially ABCB 1 C3435T polymorphism may thus affect pharmacokinetics of antiretroviral drugs and hence CD4 treatment response and other clinical outcomes of HIV patients. Methods: The study design was a historical cohort study and entailed collection of patient data. PureLink genomic DNA extraction mini kit was used for the extraction and purification of genomic DNA. TaqMan drug genotyping assay and protocol was used in the DNA amplification and genotyping. Data analysis was done using STATA software version 10. Results: Study participants with the CT genotype had lower creatinine levels after 6 months on lopinavir-based regimens compared with those with the CC genotype (p = 0.001). In addition, the study participants with the CT genotype had consistently higher CD4 cell counts compared with those with the CC genotype from the time of ART switch but this was not statistically significant. However, there was no significant association between the ABCB 1 C3435T genotypes and haemoglobin and ALT levels. Conclusion: There was a significant association between ABCB1 C3435T polymorphism and creatinine levels 6 months after therapy on lopinavir-based regimens.展开更多
Clinical trials have demonstrated the capacity for dopamine neurons, transplanted ectopicaUy into the striatum, to structurally inte- grate, restore dopamine transmission, and induce long-term functional benefits for ...Clinical trials have demonstrated the capacity for dopamine neurons, transplanted ectopicaUy into the striatum, to structurally inte- grate, restore dopamine transmission, and induce long-term functional benefits for Parkinson's disease (PD) patients. Despite this proof of principle, a number of limitations have hindered the development of cell replacement therapy over the past 20 years, particu- larly tissue availability, graft survival, and adequate reinnervation of the host brain. With a greater understanding of failure in prior clinical trials, increased knowledge of midbrain dopamine development (now including Wnts), and the development of pluripotent stem cell technologies, we are better equipped than ever to re-address a number of these challenges. This review summarizes the trials, tribulations, and progress in cell replacement therapy for PD. We discuss the prospects of modulating canonical and non-canon- ical Wnt signalingto improve cell therapy based upon their roles in dopamine neural development and the adult brain. This will include the potential of Wnts to (i) expand fetaUy derived tissue in vitro and foUowing transplantation, (ii) promote the differentiation of pluripotent stem cells, (iii) increase graft integration and restoration of neural circuitry, and finally (iv) enhance graft survival.展开更多
基金the Program of Presidium of the Russian Acad.Sci. <>, the Russian Fund forBasic Research, No. 06-04-48079 the Program for LeadingScientific Schools, No. 5796.2006.4
文摘AIM: To study isolation and chemical characterization of pectin derived from the common cranberry Vaccin/um oxycoccos L. (oxycoccusan OP) and the testing of its preventive effect on experimental colitis. METHODS: Mice were administrated orally with OP two days prior to a rectal injection of 5% acetic acid and examined for colonic damage 24 h later. Colonic inflammation was characterized by macroscopical injury and enhanced levels of myeloperoxidase activity measured spectrophotometrically with o-phenylene diamine as the substrate. The mucus contents of the colon were determined by the Alcian blue dye binding method. Vascular permeability was estimated using 4% Evans blue passage after i.p. injection of 0.05 mol/L acetic acid. RESULTS: In the mice treated with OP, colonic macroscopic scores (1.1 ± 0.4 vs 2.7, P 〈 0.01) and the total square area of damage (10 ± 2 vs 21 ± 7, P 〈 0.01) were significantly reduced when compared with the vehicle-treated colitis group. OP was shown to decrease the tissue myeloperoxidase activity in colons (42 ± 11 vs 112 ± 40, P 〈 0.01) and enhance the amount of mucus of colitis mice (0.9 ± 0.1 vs 0.4 ± 0.1, P 〈 0.01). The level of colonic malondialdehyde was noted to decrease in OP-pretreated mice (3.6 ± 0.7 vs 5.1 ± 0.8, P 〈 0.01). OP was found to decrease the inflammatory status of mice as was determined by reduction of vascular permeability (161 ± 34 vs 241 ± 21, P 〈 0.01). Adhesion of peritoneal neutrophils and macrophages was also shown to decrease after administration of OP (141 ± 50 vs 235 ± 37, P 〈 0.05). CONCLUSION: Thus, a preventive effect of pectin from the common cranberry, namely oxycoccusan OP, on acetic acid-induced colitis in mice was detected. A reduction of neutrophil infiltration and antioxidant action may be implicated in the protective effect of oxycoccusan.
文摘Object: To examine the effect of astragalus polysaccharide (APS) on kidney status and fibrosis indices of rats withdiabetic nephropathy. Methods: 72 male rats were randomly divided into three groups: negative control group (NC, n =24); diabetic nephropathy model group (DNM, n = 24); and diabetic nephropathy model with APS group (DNM + APS,n = 24). Rats of the DNM and DNM + APS groups were subjected to both unilateral nephrectomy and administeredstreptozotocin (STZ) injection (65 mg/kg). DNM + APS group rats were administered 50 IU/kg/d APS by subcutaneousinjection from the first week after operation until death. The NC and DNM group rats were subcutaneously injected withan identical volume of physiological saline. At weeks 3, 8, and 13 after the operation, 6 rats from each group wererandomly sacrificed and blood was collected to measure serum creatinine and blood urea nitrogen. On the day beforesacrifice, the rats were placed in a metabolic cage for 24 h to collect urine. At week 14 after the operation, 6 rats fromeach group were randomly selected to measure body weight and kidney index. Blood was collected to measure bloodglucose. The kidneys were harvested to detect pathological changes by hematoxylin and eosin staining. Results:Histological assessment of DNM rats suggested damage symptoms as evidenced by hyperplasia of the glomerularmesangial matrix, atrophia of the kidney tubules, and thickening of the basement membrane. In contrast, STZ-induceddiabetic nephropathy rats treated with APS (50 IU/kg/d) showed significantly improved histological results, suggestingthat APS has beneficial effect on renal tissues in STZ-induced DNM rats. Our results also indicated that APS relievedrenal injury and effectively improved body weight in DNM rats. The ratio of kidney weight to body weight was reducedand the early stage of renal function damage was improved after APS treatment. In the later stages of the disease, the 24h urinary protein significantly decreased. Moreover, APS down-regulated TGF-β1 and α-SMA expression of the kidney.Conclusion: APS significantly improved renal tubular interstitial injury in DNM rats and the early stage of renalfunction damage. The mechanism may be related to downregulation of the expression of TGF-β1 and α-SMA whichdelays the progression of renal interstitial fibrosis in DNM rats.
文摘AIM: To study whether N-acetyltransferase 2 (NAT2) genotypes and phenotypes are associated with increased risk factor for gastric cancer in Omani patients and to study the clinico-pathological correlations and the prognostic significance of NAT2. METHODS: Genomic DNA was extracted from peripheral blood of 100 gastric cancer patients and 100 control subjects. NAT2 genotyping was performed using DNA sequencing. The prognostic significance of NAT2 and other clinicopathological features was assessed by univariate and multivariate analyses. RESULTS: We observed no significant association between NAT2 genotypes and phenotypes and gastric cancer risk. The IVAT2 phenotype polymorphisms and gastric cancer risk predisposition were not modified by concomitant Hpylori infection and smoking. There was no significant association between NAT2 and clinicopathological features, and NAT2 had no independent prognostic significance. CONCLUSION: In the current study, NAT2 genotypes and phenotypes are not associated with gastric cancer risk predisposition. Moreover NAT2 phenotypes had no clinicopathological associations or prognostic significance.
文摘Non-alcoholic fatty liver disease(NAFLD) has a prevalence of approximately 30% in western countries, and is emerging as the first cause of liver cirrhosis and hepatocellular carcinoma(HCC). Therefore, risk stratification emerges as fundamental in order to optimize human and economic resources, and genetics displays intrinsic characteristics suitable to fulfill this task. According to the available data, heritability estimates for hepatic fat content range from 20% to 70%, and an almost 80% of shared heritability has been found between hepatic fat content and fibrosis. The rs738409 single nucleotide polymorphism(SNP) in patatin-like phospholipase domain-containing protein 3 gene and the rs58542926 SNP in transmembrane 6 superfamily member 2 gene have been robustly associated with NAFLD and with its progression, but promising results have been obtained with many other SNPs. Moreover, there has been proof of the additive role of the different SNPs in determining liver damage, and there have been preliminary experiences in which risk scores created through a few genetic variants, alone or in combination with clinical variables, were associated with a strongly potentiated risk of NAFLD, non-alcoholic steatohepatitis(NASH), NASH fibrosis or NAFLD-HCC. However, to date, clinical translation of genetics in the field of NAFLD has been poor or absent. Fortunately, the research we have done seems to have placed us on the right path: We should rely on longitudinal rather than on cross-sectional studies; we should focus on relevant outcomes rather than on simple liver fat accumulation; and we should put together the genetic and clinical information. The hope is that combined genetic/clinical scores, derived from longitudinal studies and built on a few strong genetic variants and relevant clinical variables, will reach a significant predictive power, such as to have clinical utility for risk stratification at the single patient level and even to esteem the impact of intervention on the risk of disease-related outcomes. Well-structured future studies would demonstrate if this vision can become a reality.
文摘To get a better understanding of the location,pathophysiology,etiology and prognosis of multiple malignant tumors (MPMT),we evaluated the medical records of 22 patients with MPMT.Our results suggested that radiotherapy and chemotherapy might play an important role in the pathogenesis of MPMT and follow up is important in detecting a secondary primary malignant tumor (PMT) at an early stage.Surgical removal of tumors is the first choice therapy for MPMT.
文摘Parkinson disease(PD) is characterized by the selective loss of dopaminergic neurons in the substantia nigra. Although investigation in mammalian animal models of PD has enhanced our understanding of PD, the complexity of the mammalian nervous system and our inability to visualize DA neurons in vivo restricts the advances in elucidating the molecular mechanisms of PD. Conservation between C. elegans and mammals in genomic, biosynthetic and metabolic pathways as well as the advantages of observing DA neurons morphology in vivo and the ease of transgenic and genetic manipulation make C. elegans an excellent model organism for PD.
文摘Autosomal dominant polycystic kidney disease (ADPKD), the most frequent cause of genetic renal disease affecting approximately 4 to 7 million individuals worldwide and accounting for 7%-15% of patients on renal replacement therapy, is a systemic disorder mainly involving the kidney but cysts can also occur in other organs such as the liver, pancreas, arachnoid membrane and seminal vesicles. Though computed tomography and magnetic resonance imaging (MRI) were similar in evaluating 81% of cystic lesions of the kidney, MRI may depict septa, wall thickening or enhancement leading to upgrade in cyst classification that can affect management. A screening strategy for intracranial aneurysms would provide 1.0 additional year of life without neurological disability to a 20-year-old patient with ADPKD and reduce the fnancial impact on society of the disease. Current treatment strategies include reducing: cyclic adenosine monophosphate levels, cell proliferation and fluid secretion. Several randomised clinical trials (RCT) including mammalian target of rapamycin inhibitors, somatostatin analoguesand a vasopressin V2 receptor antagonist have beenperformed to study the effect of diverse drugs ongrowth of renal and hepatic cysts, and on deteriorationof renal function. Prophylactic native nephrectomy isindicated in patients with a history of cyst infection orecurrent haemorrhage or to those in whom space musbe made to implant the graft. The absence of largeRCT on various aspects of the disease and its treatmen leaves considerable uncertainty and ambiguity in many aspects of ADPKD patient care as it relates to end stage renal disease (ESRD). The outlook of patients with ADPKD is improving and is in fact much better than that for patients in ESRD due to other causes. This review highlights the need for well-structured RCTs as a frst step towards trying newer interventions so as to develop updated clinical management guidelines.
文摘AIM: To identify clinical parameters, and develop an Upper Gastrointesinal Bleeding (UGIB) Etiology Score for predicting the types of UGIB and validate the score. METHODS: Patients with UGIB who underwent endoscopy within 72 h were enrolled. Clinical and basic laboratory parameters were prospectively collected. Predictive factors for the types of UGIB were identified by univariate and multivariate analyses and were used to generate the UGIB Etiology Score. The best cutoff of the score was defined from the receiver operating curve and prospectively validated in another set of patients with UGIB. RESULTS: Among 261 patients with UGIB, 47 (18%) had variceal and 214 (82%) had non-variceal bleeding. Univariate analysis identified 27 distinct parameters significantly associated with the types of UGIB. Logistic regression analysis identified only 3 independent factors for predicting variceal bleeding; previous diagnosis of cirrhosis or signs of chronic liver disease (OR 22.4, 95% CI 8.3-60.4, P 〈 0.001), red vomitus (OR 4.6, 95% CI 1.8-11.9, P = 0.02), and red nasogastric (NG) aspirate (OR 3.3, 95% CI 1.3-8.3, P = 0.011). The UGIB Etiology Score was calculated from (3.1× previous diagnosis of cirrhosis or signs of chronic liver disease) + (1.5× red vomitus) + (1.2× red NG aspirate), when 1 and 0 are used for the presence and absence of each factor, respectively. Using a cutoff ≥ 3.1, the sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) in predicting variceal bleeding were 85%, 81%, 82%, 50%, and 96%, respectively. The score was prospectively validated in cases (46 variceal and 149 another set of 195 UGIB non-variceal bleeding). The PPV and NPV of a score ≥ 3.1 for variceal bleeding were 79% and 97%, respectively. CONCLUSION: The UGIB Etiology Score, composed of 3 parameters, using a cutoff ≥ 3.1 accurately predicted variceal bleeding and may help to guide the choice of initial therapy for UGIB before endoscopy.
基金Supported by Funding from the National Health and Medical Research Council of Australia,Nos.457575 and 632647 to Rangan GKthe Baltimore Polycystic Kidney Disease Research and Clinical Core Center,No.P30DK090868+2 种基金DK095036 to Watnick Tsupported by an Australian Postgraduate Award(University of Sydney)the Michael Stern Polycystic Kidney Disease Research Fellowship
文摘AIM: To determine the temporal expression and pattern of Rel/nuclear factor (NF)-κB proteins in renal tissue in polycystic kidney disease (PKD). METHODS: The renal expression of Rel/NF-κB proteins was determined by immunohistochemistry, immunofuorescence and immunoblot analysis in Lewis polycystic kidney rats (LPK, a genetic ortholog of human nephronopthsis-9) from postnatal weeks 3 to 20. At each timepoint, renal disease progression and the mRNA expression of NF-κB-dependent genes (TNFa and CCL2) were determined. NF-κB was also histologically assessed in human PKD tissue.RESULTS: Progressive kidney enlargement in LPK rats was accompanied by increased renal cell proliferation and interstitial monocyte accumulation (peaking at weeks 3 and 10 respectively), and progressive interstitial fibrosis (with a smooth muscle actin and Sirius Red deposition significantly increased compared to Lewis kidneys from weeks 3 to 6 onwards). Rel/NF-κB proteins (phosphorylated-p105, p65, p50, c-Rel and RelB) were expressed in cystic epithelial cells (CECs) of LPK kidneys as early as postnatal week 3 and sustained until late-stage disease at week 20. From weeks 10 to 20, nuclear p65, p50, RelB and cytoplasmic IκBa protein levels, and TNFa and CCL2 expression, were upregulated in LPK compared to Lewis kidneys. NF-κB proteins were consistently expressed in CECs of human PKD. The DNA damage marker γ-H2AX was also identifed in the CECs of LPK and human polycystic kidneys. CONCLUSION: Several NF-κB proteins are consistently expressed in CECs in human and experimental PKD. These data suggest that the upregulation of both the canonical and non-canonical pathways of NF-κB signaling may be a constitutive and early pathological feature of cystic renal diseases.
文摘AIM: To evaluate the feasibility of a new clinical rating scale for a standardized assessment of cirrhosis-associated neuro-psychiatric symptoms. METHODS: Forty patients with liver cirrhosis (LC, with or without low-grade hepatic encephalopathy) were investigated using a clinical neuro-psychiatric rating scale based on a comprehensive list of neurological, psychomotor, cognitive, affective, behavioral symptoms, and symptoms of disturbed bioregulation. RESULTS: The analysis revealed that the majodty of cirrhotic patients showed, besides characteristic neurological symptoms of hepatic encephalopathy, various psychomotor, affective and bioregulatory symptoms (disturbed sleep and sexual dysfunction). Patients were impaired in the following subscales: sleep and biorhythm disorder (75.0% of patients), Parkinsonoid symptoms (25.0%), affective symptoms (17.5%), and psychomotor retardation (12.5%). The increase of total neuro-psychiatric clinical score was significantly associated with the degree of hepatic encephalopathy. CONCLUSION: This study suggests that a substantial number of patients with LC and low-grade hepatic encephalopathy manifest various clinical neuro-psychiatric symptoms. The use of a rating scale, which explores clinical dimensions of hepatic encephalopathy, would improve the management of patients with LC.
文摘This paper reports a familial amyloid polyneuropathy (FAP) family in China. This family being investigated had 69 members of five generations. From the third generation, there have been 16 patients. The age of onset was about 3 to 5 decades. The initial symptoms were autonomic nerve symptoms, such as impotence, dyspepsia and diarrhoea, associated with the sensory loss of lower extremities. As the disease progressed, the upper extremities and motor ability were also involved. The duration of disease course was about 8-10 years, most patients died of infection and cachexia. Sural biopsy in 3 patients had showed positive Congo red staining. From the clinical view, this FAP family is similar to FAP I found in Japan. The true classification, however, should be confirmed by further genetic analysis.
文摘A 27-year-old male started to have his ankles swollen during his military service. He was examined at a military hospital where electromyoneurography showed the signs of distal sensory-motor polyneuropathy with axon demyelinization and weak myopathic changes, whereas histopathological examination of gastrocnemius muscle biopsy revealed some mild and nonspecific myopathy. Besides, he was found to have subcutaneous ankle tissue edemas and hypertransaminasemia. Due to these reasons, he was dismissed from the military service and examined at another hospital where bone osteodensitometry revealed low bone mineral density of the spine. However, his medical problems were not resolved and after the second discharge from hospital he was desperately seeing doctors from time to time. Finally, at our institution he was shown to have celiac disease (CD) by positive serology (antitissue transglutaminase and antiendomysial antibodies) and small bowel mucosal histopathological examination, which showed total small bowel villous atrophy. Three months after the initiation of gluten-free diet, his ankle edema disappeared, electromyoneurographic signs of polyneuropathy improved and liver aminotransferases normalized. Good knowledge of CD extraintestinal signs and serologic screening are essential for early CD recognition and therapy.
文摘AIM:To develop a novel endoscopic severity model of intestinal Behcet's disease(BD) and to evaluate its feasibility by comparing it with the actual disease activity index for intestinal Behcet's disease(DAIBD).METHODS:We reviewed the medical records of 167 intestinal BD patients between March 1986 and April 2011.We also investigated the endoscopic parameters including ulcer locations,distribution,number,depth,shape,size and margin to identify independent factors associated with DAIBD.An endoscopic severity model was developed using significant colonoscopic variables identified by multivariate regression analysis and its correlation with the DAIBD was evaluated.To determine factors related to the discrepancy between endoscopic severity and clinical activity,clinical characteristics and laboratory markers of the patients were analyzed.RESULTS:A multivariate regression analysis revealed that the number of intestinal ulcers(≥ 2,P = 0.031) and volcanoshaped ulcers(P = 0.001) were predictive factors for the DAIBD.An endoscopic severity model(Y) was developed based on selected endoscopic variables as follows:Y = 47.44 + 9.04 × non-Ileocecal area + 11.85 ×≥ 2 of intestinal ulcers + 5.03 × shallow ulcers + 12.76 × deep ulcers + 4.47 × geographicshaped ulcers + 26.93 × volcano-shaped ulcers + 8.65 ×≥ 20 mm of intestinal ulcers.However,endoscopic parameters used in the multivariate analysis explained only 18.9% of the DAIBD variance.Patients with severe DAIBD scores but with moderately predicted disease activity by the endoscopic severity model had more symptoms of irritable bowel syndrome(21.4% vs 4.9%,P = 0.026) and a lower rate of corticosteroid use(50.0% vs 75.6%,P = 0.016) than those with severe DAIBD scores and accurately predicted disease by the model.CONCLUSION:Our study showed that the number of intestinal ulcers and volcano-shaped ulcers were predictive factors for severe DAIBD scores.However,the correlation between endoscopic severity and DAIBD(r = 0.434) was weak.
基金Supported by A grant from the Progetto di Ricerca di Interesse Nazionale 2000in part with a grant from the Viral Hepatitis ProjectIstituto Superiore di Sanità,D.leg.vo 30/12/1992 n.502
文摘AIM:To evaluate the clinical relevance of each cofactor on clinical presentation of chronic hepatitis B.METHODS:Out of 1366 hepatitis B surface antigen(HBsAg) positive subjects consecutively observed in 79 Italian hospitals,53(4.3%) showed as the only cofactor hepatitis D virus(HDV) infection [hepatitis B virus(HBV)/HDV group],130(9.5%) hepatitis C virus(HCV)(group HBV/HCV),6(0.4%) human immunodeficiencyvirus(HIV)(group HBV/HIV),138(10.2%) alcohol abuse(group HBV/alcohol);109(8.0%) subjects had at least two cofactors and 924 were in the cofactor-free(CF) group.RESULTS:Compared with patients in group CF those in group HBV/alcohol were older and more frequently had cirrhosis(P < 0.001),those in group HBV/HDV were younger(P < 0.001),more frequently resided in the south of the country and had cirrhosis(P <0.001),those in group HBV/HCV were older(P < 0.001) and more frequently had cirrhosis(P < 0.001).These cofactors were all independent predictors of liver cirrhosis in HBsAg positive patients.Multivariate analysis showed that an older age [odds ratio(OR) 1.06,95% CI:1.05-1.08],alcohol abuse with more than 8 drinks daily(OR 2.89,95% CI:1.81-4.62) and anti-HDV positivity(OR 3.48,95% CI:2.16-5.58) are all independently associated with liver cirrhosis.This association was found also for anti-HCV positivity in univariate analysis,but it was no longer associated(OR 1.23,95% CI:0.84-1.80) at multivariate analysis.CONCLUSION:Older age,HDV infection and alcohol abuse are the major determinants of severe liver disease in chronic HBV infection,while HCV replication plays a lesser role in the severity of hepatic damage.
文摘ATP Binding Cassette sub-family B member 1 (ABCB1) affects disposition of many drugs and thus affects the pharmacokinetics of drugs and ultimately treatment response. Polymorphisms of ABCB 1 especially ABCB 1 C3435T polymorphism may thus affect pharmacokinetics of antiretroviral drugs and hence CD4 treatment response and other clinical outcomes of HIV patients. Methods: The study design was a historical cohort study and entailed collection of patient data. PureLink genomic DNA extraction mini kit was used for the extraction and purification of genomic DNA. TaqMan drug genotyping assay and protocol was used in the DNA amplification and genotyping. Data analysis was done using STATA software version 10. Results: Study participants with the CT genotype had lower creatinine levels after 6 months on lopinavir-based regimens compared with those with the CC genotype (p = 0.001). In addition, the study participants with the CT genotype had consistently higher CD4 cell counts compared with those with the CC genotype from the time of ART switch but this was not statistically significant. However, there was no significant association between the ABCB 1 C3435T genotypes and haemoglobin and ALT levels. Conclusion: There was a significant association between ABCB1 C3435T polymorphism and creatinine levels 6 months after therapy on lopinavir-based regimens.
文摘Clinical trials have demonstrated the capacity for dopamine neurons, transplanted ectopicaUy into the striatum, to structurally inte- grate, restore dopamine transmission, and induce long-term functional benefits for Parkinson's disease (PD) patients. Despite this proof of principle, a number of limitations have hindered the development of cell replacement therapy over the past 20 years, particu- larly tissue availability, graft survival, and adequate reinnervation of the host brain. With a greater understanding of failure in prior clinical trials, increased knowledge of midbrain dopamine development (now including Wnts), and the development of pluripotent stem cell technologies, we are better equipped than ever to re-address a number of these challenges. This review summarizes the trials, tribulations, and progress in cell replacement therapy for PD. We discuss the prospects of modulating canonical and non-canon- ical Wnt signalingto improve cell therapy based upon their roles in dopamine neural development and the adult brain. This will include the potential of Wnts to (i) expand fetaUy derived tissue in vitro and foUowing transplantation, (ii) promote the differentiation of pluripotent stem cells, (iii) increase graft integration and restoration of neural circuitry, and finally (iv) enhance graft survival.