神经生长因子对小鼠突触体内Ca^2＋水平的调节作用

观察了多次海马内微注射ＮＧＦ对小鼠突触体内游离钙水平的影响，并在离体情况下观察ＮＧＦ对ＥＧＴＡ和ＣａＣｌ２分别造成突触体内低钙和高钙状态的调节作用。结果如下：（１）在体实验表明，一定剂量的ＮＧＦ可显著降低老年小鼠海马突触体内游离钙水平（Ｐ＜００５）；（２）离体实验表明，当突触体游离钙水平降低时，适当剂量的ＮＧＦ具有升高游离钙水平的作用；而突触体内游离钙水平升高时，则ＮＧＦ有降低游离钙水平的作用。提示ＮＧＦ对游离钙水平的双向调节作用可能是ＮＧＦ改善老年性记忆衰退的作用机制。     

Lung tissue rheology and 1/f noise

The mechanical properties of lung tissue are important contributors to both the elastic and dissipative properties of the entire organ at normal breathing frequencies. A number of detailed studies have shown that the stress adaptation in the tissue of the lung following a step change in volume is very accurately described by the functiont ^−k for some small positive constantk. We applied step increases in length to lung parenchymal strips and found the ensuing stress recovery to be extremely accurately described byt ^−k over almost 3 decades of time, despite the quasi-static stress-length characteristics of the strips being highly nonlinear. The corresponding complex impedance of lung tissue was found to have a magnitude that varied inversely with frequency. We note that this is highly reminiscent of a phenomenon known as 1/f noise, which has been shown to occur ubiquitously throughout the natural world. 1/f noise has been postulated to be a reflection of the complexity of the system that produces it, something like a central limit theorem for dynamic systems. We have therefore developed the hypothesis that thet ^−k nature of lung tissue stress adaptation follows from the fact that lung tissue itself is composed of innumerable components that interact in an extremely rich and varied manner. Thus, although the constantk is no doubt determined by the particular constituents of the tissue, we postulate that the actual functional form of the stress adaptation is not.     

Peritubular capillary loss is associated with chronic tubulointerstitial injury in human kidney: altered expression of vascular endothelial growth factor

Chronic tubulointerstitial injury (CTI) including tubular atrophy and interstitial fibrosis represents one major determinant for the progression of chronic renal disease regardless of cause. Although peritubular capillaries (PTCs) are essential to maintain the normal structure and function of renal tubules, little is known about the role of PTCs in the development of CTI. The integrity of PTCs seems to be regulated by growth factors. Vascular endothelial cell growth factor (VEGF) has recently been recognized as a potent regulator of angiogenesis, vascular survival, and vascular permeability. Knowledge of the role of VEGF in renal disease is still rudimentary, and its role in CTI has not been explored. We analyzed the morphologic changes of PTCs and correlated them with other morphologic parameters of CTI in 32 human kidneys with various types of chronic tubulointerstitial disease. The VEGF expression was immunohistochemically evaluated. Compared with normal kidney, PTC loss (41% to 55% of control) and reduced size of PTCs (55% to 88% of control) were noted in kidneys with CTI. The PTC density was positively correlated with the proximal tubular density (r = 0.66, P <.0001), proximal tubular size (r = 0.54, P <.001), and negatively correlated with interstitial volume (r = -0.84, P <.0001). Compared with normal kidney, where podocytes were the only cell type that constantly expressed VEGF, an interesting pattern of increased VEGF expression by renal tubules, especially morphologically intact or hypertrophic ones, was shared by all cases with CTI. Loss of VEGF in sclerotic glomeruli was noted. PTC injury is pathogenetically linked to tubular atrophy, tubular loss, and interstitial fibrosis in human kidneys with CTI and might be a key factor for the progression of chronic tubulointerstitial disease. The characteristic and uniform pattern of altered VEGF expression in kidneys with CTI may result from ischemia induced by PTC loss and represent a protective mechanism against further PTC injuries. HUM PATHOL 31:1491-1497.     

Diuretic resistance

Resistance to diuretic action is frequently encountered in the clinical setting. This is best managed by systematically optimizing the pharmacodynamic-pharmacokinetic factors that may be involved. Important pharmacodynamic measures include improving the underlying disease state, restriction of salt intake, limiting the use of vasodilators which may cause hypotension, lowering protein excretion, and eliminating drugs which may modify the response to the diuretic. Pharmacokinetic measures include using doses which result in diuretic excretion rates which fall on the steep part of the dose-response curve, sustaining diuretic excretion in this range by frequent drug administration, or constant infusion, using more bioavailable drugs and drugs which have less hepatic elimination, and by increasing the diuretic concentration in blood by coadministration with albumin. Using diuretic combinations to systematically inhibit absorption in the proximal tubule, Henle's loop, distal convoluted tubule, and connecting/collecting tubule will usually effect diuresis in all but the most refractory of cases.     

FK506-associated thrombotic microangiopathy: report of two cases and review of the literature

BACKGROUND: FK506 is a recently developed immunosuppressant that has been useful in improving the survival of transplanted organs. Among the numerous adverse side effects of FK506, thrombotic microangiopathy (TMA) stands out as an infrequent but severe complication. METHODS: We report two cases of FK506-associated TMA and review the 19 previous reported cases. RESULTS: From these 21 cases, the reported incidence of FK506-associated TMA is between 1% and 4.7%. It is more frequent in females, and the mean age at presentation is 47 years. Eighty-one percent of the cases occurred in patients with kidney allografts, and the remaining patients had liver, heart, or bone marrow transplants. Clinically, TMA was diagnosed at an average interval of 9.3 months from the time of transplantation. Patients may be asymptomatic or may present with the full-blown picture of hemolytic uremic syndrome. All patients had an elevated serum creatinine level but did not always show signs of hemolysis. Trough levels of FK506 were not predictive for the development of TMA, but generally a reduction of drug dose correlated with kidney function improvement and disappearance of the hemolytic picture. The renal allograft biopsy provided a conclusive diagnosis in all 17 cases in which this procedure was performed. Treatment, which mainly consisted of reduction or discontinuation of FK506, anticoagulation, and/or plasmapheresis with fresh-frozen plasma exchange, resolved TMA in most patients (57%). However, in one of these patients (5%), the graft was subsequently lost due to causes unrelated to TMA, such as acute or chronic rejection. Despite treatment, one patient (5%) lost the graft due to acute rejection and persistent TMA, and three other patients (14%) who had bone marrow, heart, and liver transplants, died of multiple organ failure, probably unrelated to TMA. In the remaining four patients (19%), response to treatment was not reported. CONCLUSIONS: TMA must be considered in organ transplant patients treated with FK506 whenever kidney function deteriorates, even in the absence of microangiopathic hemolytic anemia. Although TMA usually responds to treatment, it may, in rare cases, lead to loss of kidney function or even the patient's death.     

Renal localization of antiglobulins in glomerulonephritis and after renal transplantation.

Localization of fluorescein-conjugated heat-aggregated IgG (FA IgG) was demonstrated by immunofluorescence in renal glomeruli of 16 of 69 patients with glomerulonephritis. FA IgG bound more frequently in kidney biopsies from patients with diffuse glomerulonephritis and depressed renal function, and localized selectively in glomeruli that contained heavy deposits of IgM, C3, and C4. The factors that caused FA IgG to bind were specifically reactive with the Fc piece of the IgG molecule and were resistant to 56 degrees C heat for 30 minutes. Localization of FA IgG in the kidney did not correlate with the presence of soluble immune complexes or detectable antiglobulin antibodies in the sera. Binding of FA IgG was also seen in glomeruli and arteries of 18 of 21 kidney allografts studied at the time of impending rejection. But the factors responsible for binding FA IgG in the allografts were heat labile and thus could have been C1q. Although the role of these "antiglobulins" in the immunobiology of glomerulonephritis remains unknown, the fact that they occurred mainly in patients with relatively severe glomerular injury suggests that they could play some part in promoting renal glomerular injury.     

The effectiveness of an integrated pain management program for older persons and staff in nursing homes

This study examined the effects of an 8-week integrated pain management program (IPMP) on enhancing the knowledge and attitude toward pain management among staff; and improving the pain, quality of life, physical and psychosocial functions, and use of non-drug therapies for the elderly in nursing homes. Nursing home staff (N=147) and residents (N=535) were recruited from ten nursing homes. Nursing homes were randomly assigned into an experimental group (N=296) with IPMP or control group (N=239) without IPMP. The IPMP consisted of pain education for staff and physical exercise and multisensory stimulation art and craft therapy for residents. Data were collected before and after the IPMP. The staff demonstrated a significant improvement in knowledge and attitude to pain management, with the survey score increasing from 8.46±3.74 to 19.43±4.07 (p<0.001). Among the residents, 74% had experienced pain within the previous 6 months, with pain intensity of 4.10±2.20. Those in the experimental group showed a significantly better reduction in pain scores than the control group, from 4.19±2.25 to 2.67±2.08 (p<0.001). Group differences were also found in psychological well-being, including happiness, loneliness, life satisfaction and depression (p<0.05), and the use of non-drug methods (p<0.05). These results suggested that IPMP is beneficial for staff, and is effective in reducing geriatric pain and negative impacts. Management support and staff involvement in the program are important for its long-term continuation.