Aptamers are short nucleic acids or peptides that strongly bind to a protein of interest and functionally inhibit a given target protein at the intracellular level. Besides high affinity and specificity, aptamers have...Aptamers are short nucleic acids or peptides that strongly bind to a protein of interest and functionally inhibit a given target protein at the intracellular level. Besides high affinity and specificity, aptamers have several advantages over traditional antibodies. Hence, they have been broadly selected to develop antiviral agents for therapeutic applications against hepatitis B and C viruses (HBV, HCV). This review provides a summary of in vitro selection and characterization of aptamers against viral hepatitis, which is of practical significance in drug discovery.展开更多
AIM: To investigate the possible relationships between gastric autoimmune phenomena and clinical presentations of this disorder, in consecutive atrophic body gastritis patients. METHODS: A total of 140 atrophic body...AIM: To investigate the possible relationships between gastric autoimmune phenomena and clinical presentations of this disorder, in consecutive atrophic body gastritis patients. METHODS: A total of 140 atrophic body gastritis patients, diagnosed as consecutive outpatients presenting with macrocytic or iron deficiency anemia, or longstanding dyspepsia underwent gastroscopy with antral and body biopsies, assay of intrinsic factor, parietal cells and Helicobacter pylori ( H pylon) antibodies. Gastritis was assessed according to Sydney System. RESULTS: Parietal cell antibodies were equally distributed in all clinical presentations, whereas the positivity of intrinsic factor antibodies (49/140, 35%) was significantly higher in pernicious anemia patients (49.2%) than in iron deficiency (21.1%) and dyspeptic patients (27.8%). No specific pattern of autoantibodies was related to the clinical presentations of atrophic body gastritis. A positive correlation was obtained between the body atrophy score and the intrinsic factor antibody levels (r=0.2216, P=0.0085). Associated autoimmune diseases were present in 25/140 (17.9%) patients, but the prevalence of autoimmune diseases was comparable, irrespective of the clinical presentations. CONCLUSION: The so-called hallmarks of gastric autoimmunity, particularly in intrinsic factor antibody cannot be usefully employed in defining an autoimmune pattern in the clinical presentations of ABG.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
AIM: To assess the incidence and analyze the risk factors for Clostridium difficile-associated diarrhea (CDAD)after living donor liver transplantation (LDLT) in adult.METHODS: The micobiological data and medical...AIM: To assess the incidence and analyze the risk factors for Clostridium difficile-associated diarrhea (CDAD)after living donor liver transplantation (LDLT) in adult.METHODS: The micobiological data and medical records of 242 adult recipients that underwent LDLT at the Tokyo University Hospital were analyzed retrospectively. The independent risk factors for postoperative CDAD were identified.RESULTS: Postoperative CDAD occurred in 11 (5%)patients. Median onset of CDAD was postoperative d 19(range, 5-54). In the multivariate analyses, male gender (odds ratio, 4.56) and serum creatinine (≥ 1.5 mg/dL,odds ratio, 16.0) independently predicted postoperative CDAD.CONCLUSION: CDAD should be considered in the differential diagnosis of patients with postoperative diarrhea after LDLT.展开更多
Diarrhoea is an alteration of normal bowel movement characterized by an increase in the water content, volume, or frequency of stools. Diarrhoea needs to be classified according to the trends over time (acute or chro...Diarrhoea is an alteration of normal bowel movement characterized by an increase in the water content, volume, or frequency of stools. Diarrhoea needs to be classified according to the trends over time (acute or chronic) and to the characteristics of the stools (watery, fatty, inflammatory). Secretory diarrhoeas, mostly acute and of viral aetiology in more than 70% of cases, are by far the most important subtype of diarrhoeas in terms of frequency, incidence and mortality (over 2.5 million deaths/year in developing countries). Natural and synthetic opiates such as morphine, codeine, and Ioperamide which react with endogenous opiates (enkephalins, beta-endorphins, dynorphins) mainly act on intestinal motility and slow down transit. An antidiarrhoeal drug developed in recent years, racecadotril, acts as an enkephalinase inhibitor. Clinical studies have shown that it is just as effective as ioperamide in resolving acute diarrhoea but with greater reduction in pain and abdominal distension. Some studies have explored the prevalence of diarrhoea in old age. An epidemiological study carried out in Italy by 133 General Practitioners on 5515 elderly outpatients reported a prevalence of diarrhoea, defined according to the Rome criteria, of 9.1%. Infectious diseases (19%) and drug use (16%) were the most common causes of diarrhoea in old age. Regardless of the cause, the treatment of elderly patients with diarrhoea must include rehydration and nutritional support. Every year, more than 50 million tourists travel from industrialized countries to places where hygiene levels are pool. At least 75% of those travelling for short periods mention health problems, and in particular traveller's diarrhoea.展开更多
Previous studies have shown that expression of the interferon-sensitive gene (ISG)15 protease UBP43 is increased in the liver biopsy specimens of patients who do not respond to interferon (IFN)-α therapy. We hypo...Previous studies have shown that expression of the interferon-sensitive gene (ISG)15 protease UBP43 is increased in the liver biopsy specimens of patients who do not respond to interferon (IFN)-α therapy. We hypothesized that UBP43 might hinder the ability of IFN to inhibit HBV replication. In this study, we investigated whether vector-based siRNA promoted by HI (psiUBP43) could enhance IFN inhibiting HBV replication in cell culture. UBP43 was specifically silenced using shRNA. In HepG2.2.15 cells, the HBeAg and HBV DNA levels were significantly reduced by IFN after transfection of shRNA, imphicated that vector-based siRNA promoted by H1 (psiUBP43) could enhance IFN inhibiting HBV replication in cell culture. These data suggest that UBP43 modulates the anti-HBV type I IFN response, and is a possible therapeutic target for the treatment of HBV infection.展开更多
AIM: To investigate the feasibility of compression anastomosis clip (CAC) for gastrointestinal anastomosis proximal to the ileocecal junction. METHODS: Sixty-six patients undergoing gastrointe-stinal anastomosis proxi...AIM: To investigate the feasibility of compression anastomosis clip (CAC) for gastrointestinal anastomosis proximal to the ileocecal junction. METHODS: Sixty-six patients undergoing gastrointe-stinal anastomosis proximal to the ileocecal junction were randomized into two groups according to the anastomotic method, CAC or stapler. RESULTS: The postoperative recovery of patients in CAC and stapled anastomosis groups was similar. No postoperative complication related to the anastomotic method was found in either group. Both upper gastrointestinal contrast radiography at the early postoperative course and endoscopic examination after a 6-mo follow-up showed a better healing at the compression anastomosis. CONCLUSION: CAC can be used not only in colonic surgery but also in gastrointestinal anastomosis. Our result strongly suggests that CAC anastomosis is safe in various complication circumstances. However, it should be further conf irmed with a larger patient sample.展开更多
Recent advances in the management of lupus nephritis, together with earlier renal biopsy and selective use of aggressive immunosuppressive therapy, have contribut-ed to a favorable outcome in children and adolescents ...Recent advances in the management of lupus nephritis, together with earlier renal biopsy and selective use of aggressive immunosuppressive therapy, have contribut-ed to a favorable outcome in children and adolescents with systemic lupus erythematosus (SLE). Neverthe-less, we believe that a more effective and less toxic treatment is needed to attain an optimal control of the activity of lupus nephritis. Recent published papers and our experiences regarding treatment of young patients with lupus nephritis using calcineurin inhibitors are re-viewed. Although it has been reported that intermittent monthly pulses of intravenous cyclophosphamide (IVCY) are effective for preserving renal function in adult pa-tients, CPA is a potent immunosuppressive agent thatinduces severe toxicity, including myelo- and gonadal toxicity, and increases the risk of secondary malig-nancy. Thus, treatment for controlling lupus nephritis activity, especially in children and adolescents, remains challenging. Cyclosporine A (CsA) and tacrolimus (Tac) are T-cell-specific calcineurin inhibitors that prevent the activation of helper T cells, thereby inhibiting thetranscription of the early activation genes of interleu-kin (IL)-2 and suppressing T cell-induced activation of tumor necrosis factor-α, IL-1β and IL-6. Therefore, both drugs, which we believe may be less cytotoxic, are attractive therapeutic options for young patients with lupus nephritis. Recently, a multidrug regimen of prednisolone (PDN), Tac, and mycophenolate mofetile (MMF) has been found effective and relatively safe in adult lupus nephritis. Since the mechanisms of action of MMF and Tac are probably complementary, multidrug therapy for lupus nephritis may be useful. We propose as an alternative to IVCY, a multidrug therapy with mizoribine, which acts very similarly to MMF, and Tac, which has a different mode of action, combined with PDN for pediatric-onset lupus nephritis. We also believe that a multidrug therapy including CsA and Tac may bean attractive option for young patients with SLE and lupus nephritis展开更多
Several cardiovascular(CV)risk factors may explain the high rate of CV death among patients with chronic kidney disease(CKD).Among them both traditional and uremia-related risk factors are implicated and,moreover,the ...Several cardiovascular(CV)risk factors may explain the high rate of CV death among patients with chronic kidney disease(CKD).Among them both traditional and uremia-related risk factors are implicated and,moreover,the presence of kidney disease represents"per se"a multiplier of CV risk.Plasma lipid and lipoprotein profiles are changed in quantitative,but above all in qualitative,structural,and functional ways,and lipoprotein metabolism is influenced by the progressive loss of renal function.Statin therapy significantly reduces cholesterol synthesis and both CV morbidity and mortality either directly,by reducing the lipid profile,or via pleiotropic effects;it is supposed to be able to reduce both the progression of CKD and also proteinuria.These observations derive from a post-hoc analysis of large trials conducted in the general population,but not in CKD patients.However,the recently published SHARP trial,including over 9200 patients,either on dialysis or pre-dialysis,showed that simvastatin plus ezetimibe,compared with placebo,was associated with a significant low-density lipoprotein cholesterol reduction and a 17%reduction in major atherosclerotic events.However,no benefit was observed in overall survival nor in preserving renal function in patients treated.These re-cent data reinforce the conviction among nephrologists to consider their patients at high CV risk and that lipid lowering drugs such as statins may represent an important tool in reducing atheromatous coronary disease which,however,represents only a third of CV deaths in patients with CKD.Therefore,statins have no protective effect among the remaining two-thirds of patients who suffer from sudden cardiac death due to arrhythmia or heart failure,prevalent among CKD patients.The safety of statins is demonstrated in CKD by several trials and recently confirmed by the largest SHARP trial,in terms of no increase in cancer incidence,muscle pain,creatine kinase levels,severe rhabdomyolysis,hepatitis,gallstones and pancreatitis;thus confirming the handiness of statins in CKD patients.Here we will review the latest data available concerning the effectiveness and safety of statin therapy in CKD patients.展开更多
Vascular calcification(VC) is common among patientswith chronic kidney disease(CKD).The severity of VC is associated with increased risk of cardiovascular events and mortality.Risk factors for VC include traditional c...Vascular calcification(VC) is common among patientswith chronic kidney disease(CKD).The severity of VC is associated with increased risk of cardiovascular events and mortality.Risk factors for VC include traditional cardiovascular risk factors as well as CKD-related risk factors such as increased calcium and phosphate load.VC is observed in arteries of all sizes from small arterioles to aorta,both in the intima and the media of arterial wall.Several imaging techniques have been utilized in the evaluation of the extent and the severity of VC.Plain radiographs are simple and readily available but with the limitation of decreased sensitivity and subjective and semi-quantitative quantification methods.Mammography,especially useful among women,offers a unique way to study breast arterial calcification,which is largely a medial-type calcification.Ultrasonography is suitable for calcification in superficial arteries.Analyses of wall thickness and lumen size are also possible.Computed tomography(CT) scan,the gold standard,is the most sensitive technique for evaluation of VC.CT scan of coronary artery calcification is not only useful for cardiovascular risk stratification but also offers an accurate and an objective analysis of the severity and progression.展开更多
基金Program of Chinese Academy of Sciences (0802021SA1)
文摘Aptamers are short nucleic acids or peptides that strongly bind to a protein of interest and functionally inhibit a given target protein at the intracellular level. Besides high affinity and specificity, aptamers have several advantages over traditional antibodies. Hence, they have been broadly selected to develop antiviral agents for therapeutic applications against hepatitis B and C viruses (HBV, HCV). This review provides a summary of in vitro selection and characterization of aptamers against viral hepatitis, which is of practical significance in drug discovery.
基金Supported by Grants From the Italian Ministry for the University (MIUR), No. 02/12/01/10 1999-2002 and No. 8.111.126.5
文摘AIM: To investigate the possible relationships between gastric autoimmune phenomena and clinical presentations of this disorder, in consecutive atrophic body gastritis patients. METHODS: A total of 140 atrophic body gastritis patients, diagnosed as consecutive outpatients presenting with macrocytic or iron deficiency anemia, or longstanding dyspepsia underwent gastroscopy with antral and body biopsies, assay of intrinsic factor, parietal cells and Helicobacter pylori ( H pylon) antibodies. Gastritis was assessed according to Sydney System. RESULTS: Parietal cell antibodies were equally distributed in all clinical presentations, whereas the positivity of intrinsic factor antibodies (49/140, 35%) was significantly higher in pernicious anemia patients (49.2%) than in iron deficiency (21.1%) and dyspeptic patients (27.8%). No specific pattern of autoantibodies was related to the clinical presentations of atrophic body gastritis. A positive correlation was obtained between the body atrophy score and the intrinsic factor antibody levels (r=0.2216, P=0.0085). Associated autoimmune diseases were present in 25/140 (17.9%) patients, but the prevalence of autoimmune diseases was comparable, irrespective of the clinical presentations. CONCLUSION: The so-called hallmarks of gastric autoimmunity, particularly in intrinsic factor antibody cannot be usefully employed in defining an autoimmune pattern in the clinical presentations of ABG.
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.
基金Supported by a Grant-in-aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology of Japan and Grants-in-aid for Research on HIV/AIDS, a multicenter pilot clinical study to compare the safety and efficacy of a steroid and steroid free immunosuppression protocol with monoclonal anti-IL2R antibody in HCV positive living donor liver transplantation and Research on Measures for Intractable Diseases from the Ministry of Health, Labor and Welfare of Japan
文摘AIM: To assess the incidence and analyze the risk factors for Clostridium difficile-associated diarrhea (CDAD)after living donor liver transplantation (LDLT) in adult.METHODS: The micobiological data and medical records of 242 adult recipients that underwent LDLT at the Tokyo University Hospital were analyzed retrospectively. The independent risk factors for postoperative CDAD were identified.RESULTS: Postoperative CDAD occurred in 11 (5%)patients. Median onset of CDAD was postoperative d 19(range, 5-54). In the multivariate analyses, male gender (odds ratio, 4.56) and serum creatinine (≥ 1.5 mg/dL,odds ratio, 16.0) independently predicted postoperative CDAD.CONCLUSION: CDAD should be considered in the differential diagnosis of patients with postoperative diarrhea after LDLT.
文摘Diarrhoea is an alteration of normal bowel movement characterized by an increase in the water content, volume, or frequency of stools. Diarrhoea needs to be classified according to the trends over time (acute or chronic) and to the characteristics of the stools (watery, fatty, inflammatory). Secretory diarrhoeas, mostly acute and of viral aetiology in more than 70% of cases, are by far the most important subtype of diarrhoeas in terms of frequency, incidence and mortality (over 2.5 million deaths/year in developing countries). Natural and synthetic opiates such as morphine, codeine, and Ioperamide which react with endogenous opiates (enkephalins, beta-endorphins, dynorphins) mainly act on intestinal motility and slow down transit. An antidiarrhoeal drug developed in recent years, racecadotril, acts as an enkephalinase inhibitor. Clinical studies have shown that it is just as effective as ioperamide in resolving acute diarrhoea but with greater reduction in pain and abdominal distension. Some studies have explored the prevalence of diarrhoea in old age. An epidemiological study carried out in Italy by 133 General Practitioners on 5515 elderly outpatients reported a prevalence of diarrhoea, defined according to the Rome criteria, of 9.1%. Infectious diseases (19%) and drug use (16%) were the most common causes of diarrhoea in old age. Regardless of the cause, the treatment of elderly patients with diarrhoea must include rehydration and nutritional support. Every year, more than 50 million tourists travel from industrialized countries to places where hygiene levels are pool. At least 75% of those travelling for short periods mention health problems, and in particular traveller's diarrhoea.
基金National Science Foundation of China (30271170National Hish Technology Research and Douelopment program of China (2006AA02Z128)
文摘Previous studies have shown that expression of the interferon-sensitive gene (ISG)15 protease UBP43 is increased in the liver biopsy specimens of patients who do not respond to interferon (IFN)-α therapy. We hypothesized that UBP43 might hinder the ability of IFN to inhibit HBV replication. In this study, we investigated whether vector-based siRNA promoted by HI (psiUBP43) could enhance IFN inhibiting HBV replication in cell culture. UBP43 was specifically silenced using shRNA. In HepG2.2.15 cells, the HBeAg and HBV DNA levels were significantly reduced by IFN after transfection of shRNA, imphicated that vector-based siRNA promoted by H1 (psiUBP43) could enhance IFN inhibiting HBV replication in cell culture. These data suggest that UBP43 modulates the anti-HBV type I IFN response, and is a possible therapeutic target for the treatment of HBV infection.
文摘AIM: To investigate the feasibility of compression anastomosis clip (CAC) for gastrointestinal anastomosis proximal to the ileocecal junction. METHODS: Sixty-six patients undergoing gastrointe-stinal anastomosis proximal to the ileocecal junction were randomized into two groups according to the anastomotic method, CAC or stapler. RESULTS: The postoperative recovery of patients in CAC and stapled anastomosis groups was similar. No postoperative complication related to the anastomotic method was found in either group. Both upper gastrointestinal contrast radiography at the early postoperative course and endoscopic examination after a 6-mo follow-up showed a better healing at the compression anastomosis. CONCLUSION: CAC can be used not only in colonic surgery but also in gastrointestinal anastomosis. Our result strongly suggests that CAC anastomosis is safe in various complication circumstances. However, it should be further conf irmed with a larger patient sample.
文摘Recent advances in the management of lupus nephritis, together with earlier renal biopsy and selective use of aggressive immunosuppressive therapy, have contribut-ed to a favorable outcome in children and adolescents with systemic lupus erythematosus (SLE). Neverthe-less, we believe that a more effective and less toxic treatment is needed to attain an optimal control of the activity of lupus nephritis. Recent published papers and our experiences regarding treatment of young patients with lupus nephritis using calcineurin inhibitors are re-viewed. Although it has been reported that intermittent monthly pulses of intravenous cyclophosphamide (IVCY) are effective for preserving renal function in adult pa-tients, CPA is a potent immunosuppressive agent thatinduces severe toxicity, including myelo- and gonadal toxicity, and increases the risk of secondary malig-nancy. Thus, treatment for controlling lupus nephritis activity, especially in children and adolescents, remains challenging. Cyclosporine A (CsA) and tacrolimus (Tac) are T-cell-specific calcineurin inhibitors that prevent the activation of helper T cells, thereby inhibiting thetranscription of the early activation genes of interleu-kin (IL)-2 and suppressing T cell-induced activation of tumor necrosis factor-α, IL-1β and IL-6. Therefore, both drugs, which we believe may be less cytotoxic, are attractive therapeutic options for young patients with lupus nephritis. Recently, a multidrug regimen of prednisolone (PDN), Tac, and mycophenolate mofetile (MMF) has been found effective and relatively safe in adult lupus nephritis. Since the mechanisms of action of MMF and Tac are probably complementary, multidrug therapy for lupus nephritis may be useful. We propose as an alternative to IVCY, a multidrug therapy with mizoribine, which acts very similarly to MMF, and Tac, which has a different mode of action, combined with PDN for pediatric-onset lupus nephritis. We also believe that a multidrug therapy including CsA and Tac may bean attractive option for young patients with SLE and lupus nephritis
文摘Several cardiovascular(CV)risk factors may explain the high rate of CV death among patients with chronic kidney disease(CKD).Among them both traditional and uremia-related risk factors are implicated and,moreover,the presence of kidney disease represents"per se"a multiplier of CV risk.Plasma lipid and lipoprotein profiles are changed in quantitative,but above all in qualitative,structural,and functional ways,and lipoprotein metabolism is influenced by the progressive loss of renal function.Statin therapy significantly reduces cholesterol synthesis and both CV morbidity and mortality either directly,by reducing the lipid profile,or via pleiotropic effects;it is supposed to be able to reduce both the progression of CKD and also proteinuria.These observations derive from a post-hoc analysis of large trials conducted in the general population,but not in CKD patients.However,the recently published SHARP trial,including over 9200 patients,either on dialysis or pre-dialysis,showed that simvastatin plus ezetimibe,compared with placebo,was associated with a significant low-density lipoprotein cholesterol reduction and a 17%reduction in major atherosclerotic events.However,no benefit was observed in overall survival nor in preserving renal function in patients treated.These re-cent data reinforce the conviction among nephrologists to consider their patients at high CV risk and that lipid lowering drugs such as statins may represent an important tool in reducing atheromatous coronary disease which,however,represents only a third of CV deaths in patients with CKD.Therefore,statins have no protective effect among the remaining two-thirds of patients who suffer from sudden cardiac death due to arrhythmia or heart failure,prevalent among CKD patients.The safety of statins is demonstrated in CKD by several trials and recently confirmed by the largest SHARP trial,in terms of no increase in cancer incidence,muscle pain,creatine kinase levels,severe rhabdomyolysis,hepatitis,gallstones and pancreatitis;thus confirming the handiness of statins in CKD patients.Here we will review the latest data available concerning the effectiveness and safety of statin therapy in CKD patients.
文摘Vascular calcification(VC) is common among patientswith chronic kidney disease(CKD).The severity of VC is associated with increased risk of cardiovascular events and mortality.Risk factors for VC include traditional cardiovascular risk factors as well as CKD-related risk factors such as increased calcium and phosphate load.VC is observed in arteries of all sizes from small arterioles to aorta,both in the intima and the media of arterial wall.Several imaging techniques have been utilized in the evaluation of the extent and the severity of VC.Plain radiographs are simple and readily available but with the limitation of decreased sensitivity and subjective and semi-quantitative quantification methods.Mammography,especially useful among women,offers a unique way to study breast arterial calcification,which is largely a medial-type calcification.Ultrasonography is suitable for calcification in superficial arteries.Analyses of wall thickness and lumen size are also possible.Computed tomography(CT) scan,the gold standard,is the most sensitive technique for evaluation of VC.CT scan of coronary artery calcification is not only useful for cardiovascular risk stratification but also offers an accurate and an objective analysis of the severity and progression.