Advanced glycated albumin impairs protein degradation in the kidney proximal tubules cell line LLC-PK1

Advanced glycation end-products (AGEs) are assumed to play a major role in the genesis of diabetic nephropathy and other diabetic complications. We studied the potential effect of AGEs on protein turnover and lysosomal proteinase activities in LLC-PK1 cells, a pig kidney proximal tubules cell line. Advanced glycated bovine serum albumin (AGE-BSA) was used as a model of AGEs and its action was compared to that of nonglycated BSA. AGE-BSA but not BSA (50 micromol/l) induced a significant increase in cell volume (BSA: 4870.6 +/- 74.8 fl, AGE-BSA: 5718.0 +/- 20.7 fl, p<0.01). Protein degradation rate was decreased by 13.8% after 48 hrs. incubation with AGE-BSA (p<0.01) while protein synthesis increased by 19,1%, (p<0.01). After incubation with AGE-BSA but not BSA activities of lysosomal cathepsins (B, L+B and H) decreased in a time- and dose-dependent fashion. This decline was neither caused by a shift in lysosomal pH outside the optimal range for cathepsins, nor by a direct inhibitory effect of AGEs modified proteins or peptides but most probably by inhibition of cathepsin B expression as measured by RT-PCR. It is supposed that impaired protease activities participated in decreased protein breakdown and cell enlargement. For the first time our data provide the evidence that AGEs induce hypertrophy of LLC-PK1 cells due to decreased protein breakdown resulting from reduced lysosomal proteinase activities with a concomitant stimulation of protein synthesis.     

Decision support issues using a physiology based score

OBJECTIVE: As physiology based assessments of mortality risk become more accurate, their potential utility in clinical decision support and resource rationing decisions increases. Before these prediction models can be used, however, their performance must be statistically evaluated and interpreted in a clinical context. We examine the issues of confidence intervals (as estimates of survival ranges) and confidence levels (as estimates of clinical certainty) by applying Pediatric Risk of Mortality III (PRISM III) in two scenarios: (1) survival prediction for individual patients and (2) resource rationing. DESIGN: A non-concurrent cohort study. SETTING: 32 pediatric intensive care units (PICUs). PATIENTS: 10608 consecutive patients (571 deaths). INTERVENTIONS: None. MEASUREMENTS AND RESULTS: For the individual patient application, we investigated the observed survival rates for patients with low survival predictions and the confidence intervals associated with these predictions. For the resource rationing application, we investigated the maximum error rate of a policy which would limit therapy for patients with scores exceeding a very high threshold. For both applications, we also investigated how the confidence intervals change as the confidence levels change. The observed survival in the PRISM III groups >28, >35, and >42 were 6.3, 5.3, and 0%, with 95% upper confidence interval bounds of 10.5, 13.0, and 13.3%, respectively. Changing the confidence level altered the survival range by more than 300% in the highest risk group, indicating the importance of clinical certainty provisions in prognostic estimates. The maximum error rates for resource allocation decisions were low (e. g., 29 per 100000 at a 95% certainty level), equivalent to many of the risks of daily living. Changes in confidence level had relatively little effect on this result. CONCLUSIONS: Predictions for an individual patient's risk of death with a high PRISM score are statistically not precise by virtue of the small number of patients in these groups and the resulting wide confidence intervals. Clinical certainty (confidence level) issues substantially influence outcome ranges for individual patients, directly affecting the utility of scores for individual patient use. However, sample sizes are sufficient for rationing decisions for many groups with higher certainty levels. Before there can be widespread acceptance of this type of decision support, physicians and families must confront what they believe is adequate certainty.     

Cytokine activation leads to acidification and increases maturation of Mycobacterium avium-containing phagosomes in murine macrophages

Mycobacterium avium (MAC) organisms multiply in phagosomes that have restricted fusigenicity with lysosomes, do not acidify due to a paucity of vacuolar proton-ATPases, yet remain accessible to recycling endosomes. During the course of mycobacterial infections, IFN-gamma-mediated activation of host and bystander macrophages is a key mechanism in the regulation of bacterial growth. Here we demonstrate that in keeping with earlier studies, cytokine activation of host macrophages leads to a decrease in MAC viability, demonstrable by bacterial esterase staining with fluorescein diacetate as well as colony-forming unit counts from infected cells. Analysis of the pH of MAC phagosomes demonstrated that the vacuoles in activated macrophages equilibrate to pH 5.2, in contrast to pH 6.3 in resting phagocytes. Biochemical analysis of MAC phagosomes from both resting and activated macrophages confirmed that the lower intraphagosomal pH correlated with an increased accumulation of proton-ATPases. Furthermore, the lower pH is reflected in the transition of MAC phagosomes to a point no longer accessible to transferrin, a marker of the recycling endosomal system. These alterations parallel the coalescence of bacterial vacuoles from individual bacilli in single vacuoles to communal vacuoles with multiple bacilli. These data demonstrate that bacteriostatic and bactericidal activities of activated macrophages are concomitant with alterations in the physiology of the mycobacterial phagosome.     

LD􀀁PSD􀀁直角棱镜同轴度测量技术研究

半导体激光准直光源(LD)和光斑位置传感器(PSD)固定在从动轴上,直角棱镜固定在主动轴上.并根据该结构建立了测量过程的数学模型,讨论了所存在的主要系统误差以及为消除系统误差的影响所应采取的措施.结论:若激光器不存在安装倾斜误差,PSD传感器也不存在安装平移误差,则在任意两个转角位置进行测量均可得到4个同轴度偏差参数,否则要在任意四个转角位置进行测量方能消除激光器和PSD传感器的安装误差对测量结果的影响.     

Reforming the health care system: the universal dilemma

This Article surveys alternative approaches by which the advanced industrialized nations seek to cope with the twin problems that health care poses everywhere: the provision of universal access to health care and the control of national spending on health care. Although approaches to these twin problems vary considerably among nations at this time, there may well be a convergence toward a common approach in the next century. Under that approach, all health care systems will be subject to top-down global budgets and will put their health care providers into "statistical fishbowls" that reveal just how effectively these providers allocate the global budgets at their disposal.     

Quality in consumer-driven health systems

Recent animal work suggests that gamma-linolenic acid (GLA) and eicosapentaenoic acid (EPA) enhance calcium absorption, reduce excretion and increase calcium deposition in bone. A pilot study was set up to test the interactions between calcium and GLA + EPA in humans. Sixty-five women (mean age 79.5), taking a background diet low in calcium, were randomly assigned to GLA + EPA or coconut oil placebo capsules; in addition, all received 600 mg/day calcium as the carbonate. Markers of bone formation/degradation and bone mineral density (BMD) were measured at baseline, 6, 12 and 18 months. Twenty-one patients were continued on treatment for a second period of 18 months, after which BMD (36 months) was measured. At 18 months, osteocalcin and deoxypyridinoline levels fell significantly in both groups, indicating a decrease in bone turnover, whereas bone specific alkaline phosphatase rose indicating beneficial effects of calcium given to all the patients. Lumbar and femoral BMD, in contrast, showed different effects in the two groups. Over the first 18 months, lumbar spine density remained the same in the treatment group, but decreased 3.2% in the placebo group. Femoral bone density increased 1.3% in the treatment group, but decreased 2.1% in the placebo group. During the second period of 18 months with all patients now on active treatment, lumbar spine density increased 3.1% in patients who remained on active treatment, and 2.3% in patients who switched from placebo to active treatment; femoral BMD in the latter group showed an increase of 4.7%. This pilot controlled study suggests that GLA and EPA have beneficial effects on bone in this group of elderly patients, and that they are safe to administer for prolonged periods of time.     

The reaction to nailing or cementing of the femur in rats. A microangiographic and fluorescence study

Bone reaction to cement and to a cementless stem was studied in the rat femur with histological fluorescence and microangiographic techniques. Periosteal and endosteal apposition, and consequent remodelling, appeared as a reaction to reaming rather than caused by cement or a cementless stem. Every change in bone began with proliferation, progression and orientation of the vessels. Endosteal apposition was absent in cemented femurs because the entire medulla was occupied by the acrylic cement, but remodelling of the subendosteal cortex followed medullary revascularisation which was far advanced after 90 days. In cementless stems, endosteal apposition of primary woven bone and remodelling was the basis for bony ingrowth and anchorage through bony bridges. Our results suggest that the pattern of blood supply is relevant to the structural organisation of mature lamellar bone around the implant. Cemented stems have maximum anchorage and stability as soon as they are inserted, but this decreases with time as revascularisation occurs. Cementless stems can reach maximum integration later after insertion, and revascularisation is less critical because they usually do not fill the canal completely.     

Childhood burns in south eastern Nigeria

A case has been presented in this article of congenital absence of bilateral inferior rectus muscles combined with restriction of the lateral rectus muscle and malinsertion of the inferior oblique muscle to the lateral rectus muscle. The surgical procedures for correction of the absence of the inferior rectus muscle and embryogenesis of extraocular muscles were also reviewed.     

Acute complications and restenosis in women undergoing percutaneous transluminal coronary angioplasty. Is it possible to define sex differences and to determine risk factors?

BACKGROUND: Several investigators report a sex bias in the treatment of coronary artery disease. This study attempts to define sex differences in the outcome of percutaneous transluminal coronary angioplasty (PTCA) and to determine risk factors contributing to these results. RESULTS: Data were collected from 1082 patients (887 men and 195 women). In women, the risk of abrupt vessel closure (8.1% versus 2.5%, odds ratio 3.46) and of myocardial infarction (6.2% versus 1.2%, odds ratio 5.58) following PTCA for stable angina pectoris was significantly increased. History of myocardial infarction and PTCA of a vessel of less than 3.0 mm diameter predicted abrupt vessel closure in women. Age and cardiovascular risk factors were not predictors. The incidence of restenosis did not differ significantly (angiographic restenosis in women 36.1% versus 40.8% in men, P=0.34). CONCLUSIONS: A significantly increased risk of acute complications could only be documented in women undergoing PTCA for stable angina pectoris and not in acute coronary syndrome. Long-term outcome was similar between the two sexes.