Sulfate homeostasis. I. Effect of salicylic acid and its metabolites on inorganic sulfate in rats

Homeostasis of inorganic sulfate, a physiologic anion necessary for both detoxification and biosynthetic reactions, involves predominantly capacity-limited renal clearance mechanisms. The objective of this investigation was to examine the effect of salicylic acid (SA) and its major metabolites, salicyluric acid and salicyl phenolic glucuronide, on the serum concentrations and renal clearance of inorganic sulfate in rats. Animals were studied using a crossover design in which they received a bolus i.v. injection (75 mg/kg) and infusion (approximately 0.26 mg/min/kg) of SA or the same volume of saline (the vehicle). Blood samples were collected at 2, 3 and 4 hr after administration and urine between 2 and 4 hr. The renal clearance of sulfate and creatinine were examined at mean steady-state SA serum concentrations of 249 micrograms/ml. Although no changes in the serum concentrations and renal clearance of creatinine were observed, the renal clearance of inorganic sulfate was increased significantly (2.13 +/- 0.74 vs. 1.09 +/- 0.54 ml/min/kg in controls, mean +/- S.D., n = 7) and its serum concentration decreased (0.55 +/- 0.12 vs. 1.04 +/- 0.23 mM in controls). These changes were not due to alterations in uric acid concentrations as uric acid serum concentrations and renal clearance were unchanged when examined at similar steady-state SA serum concentrations in a subsequent study. The effects on sulfate disposition also were probably not due to the major metabolites of SA: no changes in the serum concentrations or renal clearance of sulfate were observed at mean steady-state concentrations of 52 micrograms/ml of salicyluric acid or 73.7 micrograms/ml of salicyl phenolic glucuronide after their direct administration.(ABSTRACT TRUNCATED AT 250 WORDS)     

Genomic organization of the mouse pore-forming protein (perforin) gene and localization to chromosome 10. Similarities to and differences from C9

Genomic clones encompassing the entire coding region of the mouse lymphocyte pore-forming protein gene (Pfp) have been isolated and used to determine its intron-exon organization. In contrast to C9, Pfp has a simple structure, consisting of only three exons (two of which encode polypeptide), a large 5' intron, and a single, smaller intron that is situated approximately one-third of the way through the protein-coding portions of the gene. The regions encoding the homologous domains of PFP and C9 are encoded on exons 7, 8, 9, and 10 of C9, but form only approximately half of the open reading frame of exon III in Pfp. Although encoding polypeptides with related functions, the two genes possess such sharply contrasting structures as to suggest that their analogous regions may have risen independently, by a process of convergent evolution. Using a panel of somatic cell hybrid cell lines, Pfp has been mapped to chromosome 10.     

FK506 in combination with methotrexate for the prevention of graft- versus-host disease after marrow transplantation from matched unrelated donors

The safety and potential efficacy of FK506 in combination with a short course of methotrexate (MTX) for the prevention of acute graft-versus- host disease (GVHD) after marrow transplantation from HLA-matched unrelated donors was evaluated in a single-arm Phase II study conducted at two centers. Forty-three patients, 15 to 54 (median 41) years of age, were transplanted for hematologic malignancies. Thirty-seven of 43 evaluable patients had evidence of sustained marrow engraftment. Five patients died before day 17 after transplantation. The median time to an absolute neutrophil count of > 0.5 x 10(5)/L was 21 (range, 14 to 30) days. Nephrotoxicity (serum creatinine concentration > 2 mg/dL or doubling of baseline) occurred in 32 patients (74% cumulative incidence during the first 100 days after transplant). Other adverse effects included hypertension (n = 27), hyperglycemia (n = 27), neurotoxicity (n = 9) and thrombotic thrombocytopenic purpura (n = 2). Severe veno- occlusive disease of the liver occurred in 9 (21%) of the 43 patients. Eighteen patients (42%) developed grades II to IV acute GVHD and five (12%) developed grades III to IV acute GVHD. Twelve of 25 evaluable patients developed extensive chronic GVHD within 1 year of marrow transplantation resulting in an estimate of the probability of developing this complication of 48%. The cumulative incidence of transplant-related mortality during the first 100 days was 37%. Kaplan- Meier estimates of disease-free survival at 2 years for good-risk, poor- risk, and all patients were 65%, 4%, and 32%, respectively. FK506 in combination with a short course of MTX appears active in preventing acute GVHD after marrow transplantation from unrelated donors. Further studies comparing the combination of FK506 and MTX with cyclosporine and MTX for the prevention of acute GVHD are warranted.     

A case of colon obstruction developed during the recovery period of acute pancreatitis]

Complications of acute pancreatitis usually occur in pancreas and its contiguous organs. The prevalence of colonic invasion is rare, however, the consequence is fatal, with mortality above 50%. The initial symptoms and onset times are variable and major affected sites are transverse colon and splenic flexure. The spread of inflammatory exudates into the colon is the main mechanism of colonic invasion. If the colonic stenosis develops, it is necessary to manage it surgically. We report a case who arrived at the hospital with watery diarrhea and abdominal distension in the recovery period of acute alcoholic pancreatitis and was diagnosed as a colonic obstruction in the splenic flexure. The patient underwent loop ileostomy instead of the resection of the lesion because of severe adhesion around the splenic flexure. The patient died due to sepsis 5 days after the operation.     

The Relationship of Abdominal Muscles Balance and Body Balance

This study aimed to identify what impact the thickness differences between the leftside and rightside transversus abdominis (TrA), internal obliquus (IO) and external obliquus (EO) have on balance ability in the abdominal drawing-in maneuver (ADIM) and resting postures. [Subjects and Methods] In this study, 41 young adults were asked to adopt a resting posture and to perform ADIM. The thicknesses of the abdominal muscles (TrA, IO, EO) were measured using ultrasound imaging, Then balance ability was measured, so that a comparative analysis could be carried out. [Results] According to the results, the thicknesses of TrA and IO very significantly increased when ADIM was performed. The changes in thickness of the muscles on the left and right sides showed no significant correlations with balance ability. [Conclusion] According to the study results, the difference in thickness between the left and right side muscles in a normal person is small (symmetric), and the differences in the thickness of TrA and IO on the left and right side reduced when the ADIM, which is a re-education method for abdominal muscles was performed. Therefore, we consider that the ADIM should be used in future clinical trials to induce symmetric contraction of the abdominal muscles. Also, the correlation results of muscle balance and body balance can be used as empirical data.Key words: Ultrasound, Abdominal muscle, Imbalance     

Continuous Long-Term Entecavir Therapy in Na?ve Chronic Hepatitis B Patients Showing Partial Virologic Response

Background/Aims

We investigated the efficacy of continuous long-term entecavir 0.5 mg treatment in naïve chronic hepatitis B patients showing a partial virologic response (PVR).

Methods

A total of 227 patients were included. PVR was defined as a more than 1 log₁₀ IU/mL decline in detectable serum hepatitis B virus (HBV) DNA by polymerase chain reaction (PCR; ≥20 IU/mL) at week 48. A complete virologic response (CVR) was defined as undetectable serum HBV DNA by PCR (<20 IU/mL) at week 48.

Results

At week 48, the rate of the PVR was 64/227 (28.2%). Among patients with PVR, the cumulative rates of virologic response (serum HBV DNA <20 IU/mL) at weeks 96 and 144 were 45.2% and 73.8%, respectively. The cumulative rates of genotypic resistance were not significantly different between patients with a PVR and patients with a CVR (p=0.057). However, the cumulative rates of virologic breakthrough were higher in patients with PVR than in patients with CVR (4% vs 0% and 11.2% vs 0% at weeks 96 and 144, respectively; p<0.001).

Conclusions

Long-term continuous entecavir 0.5 mg treatment in patients with a PVR resulted in an additional virologic response without a significant increase in genotypic resistance. However, the rate of virologic breakthrough was higher in the partial responders.     

Comparison of long-term clinical outcomes of external and internal pancreatic stents in pancreaticoduodenectomy: randomized controlled study

Background

To determine the most appropriate pancreatic drainage method, by investigating differences in 12-month clinical outcomes in patients implanted with external and internal pancreatic stents as an extension to a previous study on short-term outcome.

Prognostic factors and causes of death in Korean patients with idiopathic pulmonary fibrosis

The purpose of this study was to investigate the prognostic factors at initial presentation and the causes of death in Korean patients with idiopathic pulmonary fibrosis (IPF), which might be different report wise, in comparison to the western countries. A retrospective review of 88 patients (mean 60.3 years, 69 male) was carried out and they were diagnosed as IPF positive. After diagnosis, the survival rate was 57% and 41% for third and fifth year, respectively (mean follow-up 39.1 months). Mortality was closely correlated with severe dyspnea at presentation (Hazard Ratio [HR], 2.6 per grade; p=0.015), lower initial forced vital capacity (HR, 1.7 per 10% predicted; p=0.004) and lower initial diffusing capacity of the lung (HR, 1.5 per 10% predicted; p=0.033). Treatment with specific drugs was ineffective against the survival when compared with symptomatic supportive care. Thirty-four patients (68%) died of worsened respiratory failure, seven (14%) died of infection and only one patient showed cardiovascular death. In conclusion, our study suggests that the severity of dyspnea and lung function tests at the time of diagnosis are the predictive factors for the survival of patients with IPF. In comparison to the reports from western countries, we observed that respiratory failure and pulmonary infection were more frequent causes of death, while cardiovascular death was rare in Korean patients with IPF.     

肠息肉发生的细胞和分子生物学研究进展

肠息肉是一类从黏膜表面突出到肠腔内的隆起状病变的临床诊断．在最近的研究中陆续证实,其发生和发展的原因和机制,是由于Bmprla,APC,SMAD4,PTEN,STK11等基强突变而使各种细胞信号分子通过影响BMP信号通路,PTEN信号通路及Wnt信号通路所组成的生长信号调控网络,造成β-catenin在肠干细胞中的过度积聚,使得肠干细胞功能紊乱,导致其自我更新、克隆增殖、分化和凋亡失去平衡的结果．     

The xanthine oxidase–NFAT5 pathway regulates macrophage activation and TLR‐induced inflammatory arthritis

NFAT5 (nuclear factor of activated T cells), a well‐known osmoprotective factor, can be activated by isotonic stimuli such as Toll‐like receptor (TLR) triggering. However, it is unclear how NFAT5 discriminates between isotonic and hypertonic stimuli to produce different functional and molecular outcomes. Here, we identified a novel XO–ROS–p38 MAPK–NFAT5 pathway (XO is xanthine oxidase, ROS is reactive oxygen species) that is activated in RAW 264.7 macrophages upon isotonic TLR stimulation. Unlike what is seen under hypertonic conditions, XO‐derived ROS were selectively required for the TLR‐induced NFAT5 activation and NFAT5 binding to the IL‐6 promoter in RAW 264.7 macrophages under isotonic conditions. In mouse peritoneal macrophages and human macrophages, TLR ligation also induced NFAT5 activation, which was dependent on XO and p38 kinase. The involvement of XO in NFAT5 activation by TLR was confirmed in RAW 264.7 macrophages implanted in BALB/c mice. Moreover, allopurinol, an XO inhibitor, suppressed arthritis severity and decreased the expression of NFAT5 and IL‐6 in splenic macrophages in C57BL/6 mice. Collectively, these data support a novel function of the XO–NFAT5 axis in macrophage activation and TLR‐induced arthritis, and suggest that XO inhibitor(s) could serve as a therapeutic agent for chronic inflammatory arthritis.