The flux of arginine after ischemia-reperfusion in the rat kidney

BACKGROUND: Renal arginine synthesis is regulated by arginine plasma levels. The amino acid arginine is synthesized in the proximal tubule of the kidney. Renal ischemia reperfusion (I-R) injury as seen after shock, trauma and major vascular surgery, leading to acute tubular necrosis, might reduce arginine production. METHODS: Wistar rats received either bovine liver arginase (ASE), to lower arginine plasma levels, or saline (SAL). Following the ASE or SAL infusion, rats were randomized to receive a renal artery clamp for 70 minutes, followed by 150 minutes of reperfusion. Renal arteriovenous blood samples were measured and plasma flow was calculated in the I-R kidney (SAL/I-R and ASE/I-R) and the contralateral kidney (SAL/C-L and ASE/C-L) in order to determine renal arginine metabolism. RESULTS: Arginase infusion resulted in lower arginine plasma levels compared to SAL treatment (SAL/I-R vs. ASE/I-R, P < 0.005, and SAL/C-L vs. ASE/C-L, P < 0.005). Renal plasma flow was similar for all groups. The kidney switched from arginine production into arginine uptake after ischemia reperfusion (SAL/I-R vs. SAL/C-L, P < 0.01, and ASE/I-R vs. ASE/C-L, P < 0.01). Renal uptake of glutamine and citrulline increased after ischemia reperfusion (SAL/I-R vs. SAL/C-L and ASE/I-R vs. ASE/C-L, both P < 0.01). Histopathological slices of the kidney showed significantly higher counts of hyperchromasia, pyknosis, nuclear fragmentation and mitoses in individual kidney cells after ischemia reperfusion. CONCLUSION: Decreased renal arginine production is observed with unilateral ischemia-reperfusion, and this change in arginine flux could contribute to or slow the recovery from the low plasma levels of arginine seen in conditions like trauma, shock, or after vascular procedures.     

Abnormal prothrombin in the plasma of rats carrying hepatic tumors

Vitamin K is required for the posttranslational formation of gamma- carboxyglutamyl residues in a number of plasma clotting factors. Interference with vitamin K action results in the appearance of abnormal (des-gamma-carboxy) forms of prothrombin in human plasma. Vitamin K-sufficient patients with primary hepatocellular carcinoma also secrete significant quantities of abnormal prothrombin; this response has now been studied in a rat model. Normal Buffalo strain rats had 9 micrograms/mL of circulating plasma abnormal prothrombin, whereas Buffalo strain rats carrying the transplantable Morris hepatoma tumor no. 7777 had 33 micrograms/mL at 3 weeks after transplant. Vitamin K-dependent carboxylase activity was normal in the liver of these rats, but very low in the tumor tissue. Rats carrying Morris hepatoma tumors no. 9618A and 5123D did not secrete significant amounts of abnormal prothrombin. Carboxylase activity in these tumors was 15 times that of the 7777 tumor. The data suggest that the secretion of abnormal prothrombin by hepatocellular tumors is the result of normal expression of the prothrombin gene by those tumors and a failure of the tumor to express the carboxylase gene.     

Experimental acute tubular necrosis: US appearance

Dichromate-induced acute tubular necrosis (ATN) was created in 16 experimental animals and compared with four controls. An increase in cortical echogenicity, greatest on days 4 and 7 after injection, was noted using both histogram analysis and blinded observer readings. These findings closely correlated with proportional outer cortical blood flow. Good interobserver correlation was noted. Based on this experiment, clinical observations, and the literature, we propose that three different entities with different sonographic appearances are included under the term ATN. Drug-induced nephrotoxicity is associated with increased cortical echogenicity; ischemic ATN leads to no change in cortical echogenicity with normal medullary echogenicity; and precipitation of Tamm-Horsfall protein in the pyramids leads to echogenic pyramids with normal cortical echogenicity.     

The social,economic and political impact of the global HIV/AIDS epidemic

OBJECTIVES: This paper reviews the themes emerging from reports of the many social, economic and political effects of the HIV/AIDS epidemic on individuals, nations and the world. The impact of the global HIV/AIDS epidemic has been felt in every facet of society. APPROACH: The impact of the epidemic is described in five areas: (1) challenges and changes to traditional public health approaches to infectious diseases and sexually transmitted diseases; (2) adjustments to ‘standard’ clinical research and drug regulatory practices; (3) emphasis on the importance of personal behaviors and behavioral approaches in controlling the epidemic; (4) revealing the complexity of and recognizing the need to monitor the impacts of HIV/AIDS; and (5) highlighting the difficulties of, and need for, the international responsiveness to address HIV/AIDS. The oral health community's response to the epidemic is briefly described. CONCLUSIONS: Although in its second decade, the epidemic is still in its early stages of evolution. The challenges lie in the development and perpetual evolution of strategies to respond to the epidemic locally while thinking and acting globally. The international oral health community is one of many that has played and must continue to play an active role in a multi-disciplinary effort needed to curb this epidemic.     

组织多普勒检测心室收缩功能对判断扩张型心肌病患者预后的价值

目的：评价组织多普勒显像（TDI）测定的左右心室长轴方向局部收缩参数在判断扩张型心肌病（DCM）患者预后方面的价值。方法：对48例DCM患者进行常规超声和组织多普勒检查的长期随访。根据预后将患者分为两组：A组为病情加重组（发生各种心脏事件：死亡、心脏移植或因心力衰竭加重住院治疗）21例，B组为病情稳定组（心功能保持稳定或者改善）27例。用TDI方式于心尖四腔观分别检测两组患者左室侧壁（L）、室间隔（S）和右室侧壁（R）的瓣环处（1）、乳头肌水平（3）和二者中点（2）的等容收缩期速度（is）、射血期速度（ez）和左右心室侧壁处的二、三尖瓣环的位移，检测结果进行组间比较，并与患者预后进行相关性分析。结果：TDI检测的A组的R3is、S2ez、S1is、S1ez、L2ez、L1is、右室侧壁三尖瓣位移均低于B组（P均〈0．05），并且对判断DCM患者预后有较高的敏感性和特异性。结论：TDI检测左右心室收缩速度能较准确地判断DCM患者的预后。     

Dose-intensive melphalan with blood stem cell support for the treatment of AL amyloidosis: one-year follow-up in five patients

The morbidity and lethality of AL amyloidosis is caused by the deposition of lg light chains as fibrillar amyloid protein in vital organs, disrupting their function, and not by the generally low burden of clonal plasma cells that produce the paraproteins. Survival of patients with AL amyloidosis is no more than 1 to 2 years from the time of diagnosis with current management approaches. Clearly, more effective therapies are needed for this rapidly lethal disease. Five patients were treated with dose-intensive melphalan and blood stem cell support and followed for a period of 1 year. Patients were diagnosed with AL amyloidosis by tissue biopsy and categorized by performance status and organ involvement. Their plasma cell dyscrasias were evaluated with immunofixation electrophoresis of serum and urine specimens, quantitative serum lgs, and immunohistochemical staining of bone marrow biopsy specimens. After treatment with dose-intensive intravenous melphalan followed by infusion of autologous growth-factor- mobilized blood stem cells, clinical evaluations and plasma cell studies were repeated at 3 and 12 months. Three men and 2 women aged 38 to 53 years were treated. Median performance status (SWOG) was 2 (1 to 3), and clinical presentations included nephrotic syndrome (n = 1), symptomatic cardiomyopathy (n = 1), gastrointestinal involvement with polyneuropathy (n = 2), and hepatomegaly (n = 1). With a median follow- up of 13 months (12 to 17 months), all five patients are well and have shown stable or improved performance status and clinical remission of organ-related dysfunction, including a 50% reduction in daily proteinuria with no change in creatinine, reversal of symptoms of cardiomyopathy and reductions of posterior wall and septal thickening, reversal of polyneuropathy and gastric atony, and resolution of hepatomegaly by computed tomographic scan. In 3 of the 5 patients (60%) at 12 months after treatment, plasma cell dyscrasias could not be detected. Dose-intensive chemotherapy with intravenous melphalan and growth-factor-mobilized blood stem cell support is feasible therapy for patients with AL amyloidosis, even when there is clinical evidence of cardiac involvement. At least some patients with AL amyloidosis achieve complete remission of their plasma cell dyscrasia, improvement in performance status, and clinical remission of organ-specific disease after this form of treatment.     

Early onset of diabetic nephropathy

A 12 year old Asian girl with a four year history of poorly controlled insulin dependent diabetes mellitus developed overt diabetic nephropathy. There were no clinical features of Rabson-Mendenhall syndrome. Screening for microalbuminuria would have identified incipient diabetic nephropathy and highlighted the importance of good glycaemic control. Although screening for microalbuminuria is recommended after five years from diagnosis, it may be appropriate to undertake this annually in those with poor glycaemic control.