An evaluation of transition in functional states among the elderly in Beijing, China

Objectives The goal of the present study was to describe the changes in activities of daily living (ADL) of community-dwelling Beijing elderly people (n=3,257), observed for 8 years, and to identify the demographic characteristic that predict the functional change. Methods Two sets of interview data (1992 and 2000) were used to evaluate changes among the elderly in reports of limitation in ADL management. Results The prevalence of disability increased over 8 years both in IADL and BADL disability. The patterns of ADLs change were bi-directional. A large proportion (74.7%) of the elderly were found to remain active in their functional states, 20.4% of the elderly declined, 3.4% of the elderly remained disabled, and 1.5% showed improvement in functional states. The transition rates from non-disability and disability states to various functional states showed different characteristic, a high disability rate accompanied a high mortality rate. The demographic factors that affected the level of disability among different kinds of population manifested similar trends. Conclusion Age was the most significant predictor for functional limitations. In addition, demographic variables played an important role in estimating functional outcomes. It is recommended that the demarcation factor for the evaluation of ADLs should be 75 years of age.     

Interleukin-1beta converting enzyme (caspase-1) in intestinal inflammation

An imbalance of T helper cell type 1 (Th1) versus type 2 (Th2) polarization in favor of Th1 cell subsets appears to be a key pathogenic mechanism in chronic inflammatory bowel disease (IBD), in particular in Crohn's disease. The interferon gamma-inducing factor interleukin (IL)-18 acts in strong synergism with the Th1 polarizing cytokine IL-12. Recent studies provide evidence for the participation of IL-18 in the pathogenesis of IBD: IL-18 expression is increased in inflamed lesions of Crohn's disease patients and neutralization of IL-18 in different models of experimental colitis resulted in a dramatic amelioration of disease severity. IL-18 and IL-1beta are cleaved and thereby activated by the interleukin-1beta converting enzyme (ICE). Activation of ICE also occurs during different types of infectious colitis, and ICE expression and subsequent release of IL-1beta and IL-18 significantly contribute to intestinal inflammation. ICE knockout mice as well as mice treated with the ICE inhibitor pralnacasan are protected against experimental mucosal inflammation. Thus, inhibition of ICE represents an intriguing new target that requires further investigation in animal models.     

Synthesis and antimicrobial activities of N-substituted imides

In the field of our research programs concerning novel antimicrobial agents, a series of N-substituted imides was synthesized. These compounds were obtained by cyclization of amido-acids in acetic anhydride/sodium acetate or hexamethyldisilazane/zinc bromide for the hydroxy-aromatic derivatives. The hydroxy-alkyl maleimides were directly prepared by condensation of the corresponding amino-alcohol with maleic anhydride in boiling toluene. Most of N-substituted maleimides showed an interesting antimicrobial activity towards bacteria from the ATCC collection (Staphylococcus aureus ATCC 25923, Enterococcus faecalis ATCC 29212, Escherichia coli ATCC 25922 and Pseudomonas aeruginosa ATCC 27853) but the MIC values for P. aeruginosa were always high (128 microg/ml). The imides with alkyl substituents showed higher activities than aromatic analogues with MIC values in the range of 8-32 microg/ml. Comparatively, succinimides were practically inactive.     

Comparative effects of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers on blood pressure and the kidney

Many clinicians are uncomfortable about using angiotensin-converting enzyme (ACE) inhibitors or angiotensin II type 1 receptor blockers (AT(1)-blockers) to treat patients with renal disease because of concerns about increasing serum creatinine levels. However, the benefits of these medications, particularly their efficacy in slowing the progression of renal disease, outweigh such concerns. ACE inhibitors are effective in patients with type 1 diabetes and renal disease, as well as in those with nondiabetic renal disease and proteinuria >0.5 g/d. AT(1)-blockers slow the progression of diabetic nephropathy in patients with type 2 diabetes. Although these classes of medications should not be used in patients with severe renal insufficiency (e.g., glomerular filtration rate <20 mL/min), they may be beneficial in patients with mild-to-moderate renal insufficiency. Nonetheless, caution should be exercised in those with a glomerular filtration rate <30 mL/min, and serum creatinine and potassium levels should be checked approximately 1 week after starting treatment. There is also evidence suggesting that these medications lead to greater reductions in blood pressure and proteinuria when used in combination than when alone. The purpose of this paper is to review the mechanisms of action of these two classes of medication, as well as the experimental and clinical evidence that they slow the progression of renal disease.     

VALsartan In Acute myocardial iNfarcTion (VALIANT) trial: baseline characteristics in context

BACKGROUND: The VALsartan In Acute myocardial iNfarcTion (VALIANT) trial compared outcomes with: (1) angiotensin-converting enzyme inhibition (ACEI) with the reference agent captopril; (2) angiotensin-receptor blockade (ARB) with valsartan; or (3) both in patients with heart failure (HF) and/or left ventricular systolic dysfunction (LVSD) after myocardial infarction (MI). AIMS: a goal of this active-control trial was to simulate conditions that would lead current practitioners to use ACEIs. Thus, we compared characteristics of VALIANT patients with those of patients in placebo-controlled trials that established ACEIs as standard treatment. METHODS AND RESULTS: We collected demographic, clinical, medication and imaging information from 14703 patients in 24 countries. This high-risk population was a median 65.8 years old, and 31.1% were female. Most (51.8%) showed imaging evidence of LVSD at enrollment. Most (72%) had Killip class>/=II HF. Patients received evidence-based therapies at rates similar to those of contemporary MI trials and at an improved rate compared with prior placebo-controlled ACEI trials. CONCLUSION: VALIANT represents the largest globally representative cohort enrolled with HF and/or LVSD after MI. Patients were similar to those in placebo-controlled ACEI trials while reflecting improvements in evidence-based care. With enrollment complete, VALIANT is poised to define the optimal strategy for renin-angiotensin system blockade after MI to improve cardiovascular outcomes.     

Plasma thrombopoietin levels in patients with aplastic anemia and idiopathic t hrombocytopenic purpura

目的　为了研究血小板生成素 (TPO)在慢性血小板减少性疾病中的病理变化。方法　我们用敏感的双抗体夹心法酶联免疫吸附试验 (ELISA)检测了 4 0例再生障碍性贫血 (AA)和 32例特发性血小板减少性紫癜 (ITP)病人的血浆TPO的浓度。结果　AA患者血浆TPO浓度 (774± 393pg/ml)明显高于正常人 (5 5± 34pg/ml,P <0 0 0 1) ,并且与血小板计数呈负相关 ;ITP患者血浆TPO水平正常或仅轻度增高 (73± 36pg/ml) ,与正常人相比无显著性差异 (P >0 0 5 ) ,其血浆TPO浓度与血小板计数间也无相关性。结论　AA和ITP患者血浆TPO含量不仅受到外周血血小板同时也受到骨髓巨核细胞的调节。血浆TPO含量的检测有助于血小板减少性疾病的诊断及病理研究。     

Effects of AT1 receptor antagonist therapy in patients with severe heart failure pretreated with angiotensin-converting enzyme inhibitors

BACKGROUND:

The efficacy of angiotensin-converting enzyme (ACE) inhibitors is well documented in the treatment of chronic severe heart failure. Because pharmacological mechanisms of angiotensin II type 1 (AT1) receptor antagonists differ from the effects of ACE inhibitors, an additional positive effect can be expected by combining these drugs.

METHODS:

Sixty patients (mean age 68.3±10.0 years) with severe chronic heart failure receiving long term medication with digitalis, diuretics, ACE inhibitors and in part beta-blockers (68.3%) were randomly assigned after clinical recompensation to three groups: additional therapy with eprosartan (477.5±143.7 mg/day), telmisartan (65.9±17.7 mg/day) and control group according to a prospective study design. Hemodynamic measurements by impedance cardiography were performed before and during the observation period (9.6±3.4 days).

RESULTS:

Additional sartan treatment resulted in an improvement in cardiac output from 2.32±0.69 L/min to 3.12±1.24 L/min (P=0.003) in the eprosartan group and from 2.24±0.59 L/min to 2.76±0.91 L/min (P=0.001) in the telmisartan group; cardiac output in the control group did not increase. Furthermore, a significant decrease in total peripheral resistance was observed during treatment with eprosartan (23%, P=0.002) and telmisartan (18%, P=0.002). In the subgroup receiving combined therapy with beta-blockers, ACE inhibitors and AT1 antagonists, a significant increase in cardiac output was also observed.

CONCLUSIONS:

The additional treatment with AT1 receptor antagonists resulted in an increase in the cardiac output and a decrease in the peripheral resistance. This beneficial effect may be due to the additional property of sartans to block the interaction of locally and non-ACE-generated angiotensin II with their respective vascular and myocardial AT1 receptors.     

Decrease of 1-methyl-1,2,3,4-tetrahydroisoquinoline synthesizing enzyme activity in the brain areas of aged rat

1-Methyl-1,2,3,4-tetrahydroisoquinoline (1-MeTIQ), an endogenous monoamine, which prevents the neurotoxic effect of 1-methyl-4-phenylpyridinium ion (MPP(+)) and other endogenous neurotoxins, has been described as being enzymatically formed in the brain by the 1-MeTIQ synthesizing enzyme (1-MeTIQse). In this paper, we report the brain's regional distribution of this enzyme in 3- and 24-month-old rats. The results show that the activity is spread throughout the brain, the highest activity being in the dopaminergic areas (striatum and substantia nigra) and in the cortex. During aging there was a 1-MeTIQse activity reduction ( approximately 50%) in the areas implicated in the ethyology of Parkinson disease (substantia nigra, striatum) and in the cerebral cortex.     

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目的探讨肥胖是否会引起儿童体内的氧化应激加剧以及可能的机制.方法浙江大学医学院附属第二医院等单位于2004年10月至2005年3月,采用病例对照研究设计,用分光光度分析法检测浙江大学附属第二医院确诊的80例肥胖儿童(OCs)和浙江大学附属儿童医院80例健康儿童(HCs)的血浆维生素C(VC)、维生素E(VE)、β-胡萝卜素(β-CAR)水平以及红细胞超氧化物歧化酶(SOD)、过氧化氢酶(CAT)活性和红细胞丙二醛(MDA)水平.结果与HCs组VC、VE、β-CAR、SOD、CAT和MDA均值比较,OCs的VC、VE、β-CAR、SOD和CAT均值均显著降低(P<0.001),MDA均值显著增高(P<0.001);对80例肥胖儿童控制年龄和肥胖病程的偏相关分析提示,随着BMI升高,VC、VE、β-CAR、SOD和CAT值逐渐降低(P<0.05～0.01),MDA值逐渐增高(P<0.001);对反映肥胖儿童氧化应激加剧的可靠性分析表明,6项生化指标的可靠性系数为0.7152,P<0.001,标化可靠性系数为0.9018,P<0.001.结论肥胖儿童体内存在着氧化应激加剧,此氧化应激加剧与体重指数(BMI)密切相关.