Urographic Changes in Acute Papillary Necrosis in the Rat

Intravenous high-dosage urography was performed in rats which had renal papillary necrosis induced with ethyleneimine or renal tubular necrosis produced with mercuric chloride. In both groups, nephrograms were abnormally persistent. In animals treated with ethyleneimine dense selective opacification of the necrotic renal pyramid occurred. It is suggested that this selective opacification may be a valuable radiological sign of recent renal papillary necrosis.     

I. Recognition of the problem of analgesic nephropathy

The incidence of renal impairment secondary to the abuse of analgesic compounds now accounts for a significant proportion of patients requiring renal replacement therapy. The clinical features of 100 cases of analgesic nephropathy are described; essentially these consist of otherwise unexplained renal impairment, urinary tract symptoms, radiological changes and sterile pyuria, often associated with dyspepsia, anemia and psychiatric disturbances. The classical pathological changes consist of interstitial nephritis and progressive reduction in renal size, secondary to repeated episodes of papillary necrosis. Cessation of analgesic abuse usually arrests the deterioration in renal function, and indeed some recovery of function may occur.     

Prolonged Oliguria with Survival in Acute Bilateral Cortical Necrosis

Survival is uncommon in cases of acute bilateral cortical necrosis. Three cases admitted to the renal unit at Newcastle have regained useful renal function after oliguric phases of 38, 46, and 120 days.Prolonged periods of intermittent dialysis are justified in patients in whom a firm diagnosis of acute cortical necrosis is made.     

CT平扫对肠坏死诊断价值

目的:探讨CT平扫对肠坏死诊断价值,总结肠管坏死征象。方法:分析98例可疑肠坏死患者CT平扫图像,所有患者均经手术证实或未能及时治疗死亡患者CT平扫影像,总结、分析影像特点。结果:全部患者中40例患者存在肠坏死,肠壁厚度改变,包括29例肠壁增厚,8例肠壁菲薄,5例表现为肠壁密度减低,3例表现为肠壁密度增加,25例表现肠管扩张,8例表现肠管塌陷,36例肠管内积液,其中34例见气液平面,4例仅见积气,5例肠壁内见气泡影,38例见腹腔积液,10例见系膜水肿,2例见肠系膜血管密度增高,1例肠系膜静脉内气体,1例门静脉内气体,5例见腹腔游离气体。结论:多排螺旋CT平扫对肠坏死部位及范围的评价有较高的价值,同时CT平扫能明确病因,为及早治疗打下良好基础。     

The Sequence of Events in the Development of Bilateral Renal Cortical Necrosis Accompanying the Generalized Shwartzman Reaction

The generalized Shwartzman reaction, or Shwartzman-like conditions, were induced in a variety of experimental mammalian species by systemic injections of disintegrated cells of Gram negative bacteria, live Salmonella cholerae-suis or Liquoid. A comparative study of the renal lesions showed that the initial step in the development of bilateral cortical necrosis is stagnation and disintegration of red cells in glomerular capillaries. The glomerular “microthrombi” consist mainly of erythrocytic debris, which frequently has staining properties akin to those of fibrin; even wide-spread glomerular “thrombosis” is not accompanied by obvious destruction of renal parenchyma. A second step is necrotic mural lesions in afferent arteries, with ensuing thrombosis. These vascular lesions lead to the formation of individual infarcts which fuse to form total bilateral cortical necrosis in fulminant cases of the generalized Shwartzman reaction.     

Six year follow up of infants with bacteriuria on screening.

OBJECTIVE--To determine the value of screening for bacteriuria in infants with special emphasis on the natural course of untreated asymptomatic bacteriuria, renal growth, and renal damage. DESIGN--Prospective six year follow up of infants with bacteriuria on screening in an unselected infant population. SETTING--Paediatric outpatient clinic. PATIENTS--50 Infants (14 girls, 36 boys) with bacteriuria on screening verified by suprapubic aspiration from an unselected population of 3581 infants in a defined area of Gothenburg. INTERVENTIONS--Children with asymptomatic bacteriuria and normal findings on initial urography were untreated, although other infections were treated. MAIN OUTCOME MEASURES--Culture of urine and determination of C reactive protein concentration every six weeks for the first six months after diagnosis, every three months from six months to two years, and every six months between two and three years; thereafter yearly urine culture. Evaluation of renal concentrating capacity with a desmopressin test; radiological examination, including first and follow up urography and micturition cystourethrography without antibiotic cover; and measurement of renal parenchymal thickness and renal surface area. RESULTS--Of the original 50 infants, 37 (12 girls, 25 boys) were followed up for at least six years. Two infants developed pyelonephritis within two weeks after bacteriuria was diagnosed; the others remained free of symptoms. 45 Infants were untreated; the bacteriuria cleared spontaneously in 36 and in response to antibiotics given for infections in the respiratory tract in eight. Recurrences of bacteriuria were observed in 10 of the 50 children, of whom one had pyelonephritis. No child had more than one recurrence. At follow up urography in 36 of the 50 children (9 girls, 27 boys) after a median of 32 months no child had developed renal damage. First samples tested for renal concentrating capacity showed significantly higher values than those from a reference population (mean SD score 0.50, 95% confidence interval 0.21 to 0.79; p less than 0.001), but the last samples showed no significant difference (mean SD score 0.08, -0.24 to 0.40; p greater than 0.05). CONCLUSIONS--Mass screening for bacteriuria in infancy results primarily in detection of innocent bacteriuric episodes and is not recommended.     

Controlled Necrosis

Some necrosis mechanisms are considered. Although traditionally necrosis is considered as an uncontrolled and catastrophic cell death caused by intense damaging impacts, last data have shown that necrosis may occur in some physiological processes. Moreover, necrosis may be controlled by the intracellular signaling processes. For example, experiments with photodynamic treatment of neurons and surrounding glial cells have shown that increase in plasma membrane permeability leading to necrosis is controlled by neurotrophins, Ca²⁺-, cAMP-, and cGMP-dependent signaling pathways. An assortment of signaling proteins involved in these responses are different in neurons and glial cells. Thus, necrosis is uncontrolled under very strong impacts. However, necrotic processes induced by moderate impacts may be controlled by the cellular signaling system. Moreover, in some physiological situations necrosis may be performed according to the predetermined program.     

Renal disease,epidermal necrosis,and epithelial cell antibodies.

OBJECTIVE--To describe the association between epithelial cell IgM, which has previously been associated with an increased incidence of loss of renal graft in children, with a novel cutaneous eruption and unexplained native renal disease. DESIGN--Observational study on children with epithelial cell antibody presenting with unexplained renal or skin disease. SETTING--General paediatric department and regional paediatric nephrology unit. PATIENTS--Six children (five girls, one boy), who presented to the unit in 1989-90. RESULTS--Three children, two of whom had a history of a hyperpigmented rash, presented with hypertension, proteinuria, and impaired renal function. Renal biopsy specimens from two of these children showed severe arteriolar endothelial cell swelling with arteriolar occlusion. These children fully recovered after treatment with antihypertensive drugs. The third child developed end stage renal failure and required dialysis. Three other children presented with an unusual cutaneous eruption but no evidence of renal disease. Histology of the skin lesions showed acute epidermal necrosis and features consistent with a viral infection. CONCLUSIONS--The aetiology and pathogenesis of the epithelial cell antibody are unknown. These cases indicate that it may have a role in native kidney disease and focal epidermal necrosis. Clinical and histological features suggest that the antibody may be associated with a viral infection.     

Papillary Necrosis in Rats Caused by Aspirin and Aspirin-containing Mixtures

Nearly half the rats gavage-fed with aspirin and aspirin-containing mixtures developed papillary necrosis in 20 weeks. This incidence is similar to that found in rats on A.P.C. mixtures with high and low concentrations of p-chloracetanilide, an impurity of phenacetin. Aspirin alone produced necrosis in 7 out of 19 rats (36·8%) whereas phenacetin in the same dose had failed to cause any renal damage over six to nine months. If these results also apply to man they suggest that aspirin and not phenacetin may be the major factor in analgesic nephropathy in patients taking A.P.C. mixtures. An augmented clearance of aspirin appeared to afford some protection to the medulla, and it is suggested that this observation may have important clinical and epidemiological applications.     

Necrosis and necroptosis in germ cell depletion from mammalian ovary

The maximum number of germ cells is present during the fetal life in mammals. Follicular atresia results in rapid depletion of germ cells from the cohort of the ovary. At the time of puberty, only a few hundred (<1%) germ cells are either culminated into oocytes or further get eliminated during the reproductive life. Although apoptosis plays a major role, necrosis as well as necroptosis, might also be involved in germ cell elimination from the mammalian ovary. Both necrosis and necroptosis show similar morphological features and are characterized by an increase in cell volume, cell membrane permeabilization, and rupture that lead to cellular demise. Necroptosis is initiated by tumor necrosis factor and operated through receptor interacting protein kinase as well as mixed lineage kinase domain-like protein. The acetylcholinesterase, cytokines, starvation, and oxidative stress play important roles in necroptosis-mediated granulosa cell death. The granulosa cell necroptosis directly or indirectly induces susceptibility toward necroptotic or apoptotic cell death in oocytes. Indeed, prevention of necrosis and necroptosis pathways using their specific inhibitors could enhance growth/differentiation factor-9 expression, improve survivability as well as the meiotic competency of oocytes, and prevent decline of reproductive potential in several mammalian species and early onset of menopause in women. This study updates the information and focuses on the possible involvement of necrosis and necroptosis in germ cell depletion from the mammalian ovary.     

Poly[ADP-Ribose] Polymerase-1 Expression Is Related To Cold Ischemia,Acute Tubular Necrosis,and Delayed Renal Function In Kidney Transplantation

Cold ischemia time especially impacts on outcomes of expanded-criteria donor (ECD) transplantation. Ischemia-reperfusion (IR) injury produces excessive poly[ADP-Ribose] Polymerase-1 (PARP-1) activation. The present study explored the hypothesis that increased tubular expression of PARP-1 contributes to delayed renal function in suboptimal ECD kidney allografts and in non-ECD allografts that develop posttransplant acute tubular necrosis (ATN).

Materials and Methods

Nuclear PARP-1 immunohistochemical expression was studied in 326 paraffin-embedded renal allograft biopsies (193 with different degrees of ATN and 133 controls) and in murine Parp-1 knockout model of IR injury.

Results

PARP-1 expression showed a significant relationship with cold ischemia time (r coefficient = 0.603), time to effective diuresis (r = 0.770), serum creatinine levels at biopsy (r = 0.649), and degree of ATN (r = 0.810) (p = 0.001, Pearson test). In the murine IR model, western blot showed an increase in PARP-1 that was blocked by Parp-1 inhibitor. Immunohistochemical study of PARP-1 in kidney allograft biopsies would allow early detection of possible delayed renal function, and the administration of PARP-1 inhibitors may offer a therapeutic option to reduce damage from IR in donor kidneys by preventing or minimizing ATN. In summary, these results suggest a pivotal role for PARP-1 in the ATN of renal transplantation. We propose the immunohistochemical assessment of PARP-1 in kidney allograft biopsies for early detection of a possible delayed renal function.     

Necrosis in yeast

Necrosis was long regarded as an accidental cell death process resulting from overwhelming cellular injury such as chemical or physical disruption of the plasma membrane. Such a definition, however, proved to be inapplicable to many necrotic scenarios. The discovery that genetic manipulation of several proteins either protected or enhanced necrotic cell death argued in favor of a regulated and hence programmed process, as it is the case for apoptosis. For more than a decade, yeast has served as a model for apoptosis research; recently, evidence accumulated that it also harbors a necrotic program. Here, we summarize the current knowledge about factors that control necrotic cell death in yeast. Mitochondria, aging and a low pH are positive regulators of this process while cellular polyamines (e.g. spermidine) and endonuclease G as well as homeostatic organelles like the vacuole or peroxisomes are potent inhibitors of necrosis. Physiological necrosis may stimulate intercellular signaling via the release of necrotic factors that promote viability of healthy cells and, thus, assure survival of the clone. Together, the data obtained in yeast argue for the existence of a necrotic program, which controls longevity and whose physiological function may thus be aging.     

一种研究和鉴别悬浮培养红豆杉细胞凋亡与坏死的新方法

将在动物细胞凋亡研究中应用的Hoechst-PI双重荧光染色法与琥珀酸脱氢酶(SDH)染色法相结合,建立了一种更加完善的、能同时鉴别和研究悬浮培养的植物细胞凋亡及坏死的新方法——Hoechst-PI-SDH三重染色法(H-P-S法)。该方法可直接用于红豆杉悬浮培养细胞,无需对细胞进行去壁、固定及切片等其它方法所必需的步骤,在荧光显微镜下可鉴别活细胞、死细胞及凋亡细胞,并可同时观测细胞凋亡的全部过程。该方法简单、快速、准确,而且克服了因细胞膜通透性差异引起的对死、活细胞判断的困难,可在植物细胞凋亡的研究中广泛应用。     

非创伤性股骨头坏死的机制及早期治疗的研究进展

非创伤性股骨头坏死(NONFH)是临床常见的骨科难治性疾病之一,本文就其发病机制和临床治疗研究的相关进展和问题展开综述,旨在进一步提高对NONFH的临床认识和治疗水平。股骨头坏死的机制仍然没有统一的定论,但各种机制最终归于股骨头供血区域血液瘀滞,导致股骨头发生缺血坏死虽然目前还没有一种治疗方法达到理想的治疗效果,髓心减压仍然是应用最为广泛的早期治疗手段,各种改进手术如骨移植、钽棒移植、骨髓干细胞移植和生长因子移植是今后的主要趋势。     

Papillary Necrosis in Experimental Analgesic Nephropathy

A proprietary aspirin, phenacetin, and caffeine preparation given to rats in a dose equivalent to that taken by patients with analgesic nephropathy produced papillary necrosis in 55%. There was a higher incidence in rats deprived of fluids overnight.Papillary necrosis was not noted in rats receiving twice as much phenacetin.These findings support the argument that phenacetin should not be singled out as the substance responsible for analgesic nephropathy in man.     

Genetically determined gout: characteristics of the course

Analysis of clinical-roentgen-laboratory features of the course of hereditarily determined gout in 74 patients is represented. It is exhibited that hereditarily induced gout begins at the young age and is accompanied by the acute disturbance of purine exchange resulting in serious relapsing course of the articular (with availability of radiological attributes of osteal destruction) and the renal syndromes (urate nephrolithiasis, immune complex glomerulonephritis, tubulointerstitional nephritis) as well as in the early occurrence and rapidly progressing chronic renal insufficiency. The disease is accompanied by high frequency of the cardiovascular pathologies negatively influencing the mean lifetime of patients.     

Necrosis of thyroid nodules after fine needle aspiration

In a series of 200 fine needle aspirations (FNA) of the thyroid, necrosis around the needle tract was histologically evident in 2 of 30 cases with surgical follow-up. In one case of a differentiated thyroid carcinoma, necrosis with involution of the nodule was the dominant finding. This suggests that FNA can induce necrosis and apparent clinical regression of thyroid neoplasms. We believe, however, that a positive cytologic diagnosis coupled with a clinical suspicion of neoplasm should lead to surgical intervention, despite clinical regression following FNA.     

水杨酸和乙烯对依赖于Cf基因的过敏坏死的调控作用

通过农杆菌(Agrobacterium tumefaciens)介导的方法将互补Aνr/Cf基因对同时在烟草叶片中表达,可以导致过敏性坏死反应。以水杨酸积累缸失型nahC和乙烯不应型etr1-1转基因烟草植株为材料,对水杨酸和乙烯在依赖于番茄Cf-4和Cf—9基因的过敏坏死中的调控作用进行了比较研究。结果表明,nahG植株产生的依赖于Cf-4的过敏坏死反应强度与野生型相似,依赖于Cf—9的坏死反应则明显轻于野生型。转etr1—1基因植株产生的依赖于Cf-4和Cf—9的坏死反应均轻于野生型,与依赖于Cf-4的坏死反应相比,转基因植株中依赖于Cf—9的坏死反应比野生型的减轻程度更显著。这些结果说明水杨酸可能对依赖于Cf—9的过敏坏死起重要调控作用,但对依赖于Cf-4的无此作用;而乙烯则对两者依赖性过敏坏死均起调控作用。     

Fueling the Flames: Mammalian Programmed Necrosis in Inflammatory Diseases

Programmed necrosis or necroptosis is an inflammatory form of cell death driven by TNF-like death cytokines, toll-like receptors, and antigen receptors. Unlike necrosis induced by physical trauma, a dedicated pathway is involved in programmed necrosis. In particular, a kinase complex composed of the receptor interacting protein kinase 1 (RIPK1) and RIPK3 is a central step in necrotic cell death. Assembly and activation of this RIPK1–RIPK3 “necrosome” is critically controlled by protein ubiquitination, phosphorylation, and caspase-mediated cleavage events. The molecular signals cumulate in formation of intracellular vacuoles, organelle swelling, internal membrane leakage, and eventually plasma membrane rupture. These morphological changes can result in spillage of intracellular adjuvants to promote inflammation and further exacerbate tissue injury. Because of the inflammatory nature of necrosis, it is an attractive pathway for therapeutic intervention in acute inflammatory diseases.Necrosis and tissue inflammation are two tightly linked phenomena. Cell injury induced by excessive trauma such as heat shock and osmotic shock can result in cell death with “necrotic morphology.” These relatively nonspecific means to trigger necrosis have contributed to the notion that necrosis is caused by excessive insults and does not involve elaborate intracellular signaling pathways. In contrast to the notion that necrosis is associated with harmful pathologies, recent work indicates that necrosis can have beneficial roles in certain biological responses. Proteomic approaches and RNA interference screens have identified several crucial regulators of necrosis induced by TNF-like death cytokines. Because a dedicated molecular circuitry is involved, the terms “programmed necrosis” and “necroptosis” have been used to distinguish these types of necrotic cell death from necrosis induced by physical trauma or insults. Here I will discuss the molecular pathway that regulates programmed necrosis/necroptosis. For the sake of simplicity, we will use the term necrosis to refer to programmed necrosis induced by defined death cytokines.     

Sulfur-containing amino acids that increase renal glutathione protect the kidney against papillary necrosis induced by 2-bromoethylamine

Papillary necrosis was observed in the kidneys of rats, 72 h after receiving a single injection of bromoethylamine (BEA). This effect was associated with renal glutathione (GSH) depletion 1 h after the administration of BEA. Stimulation of renal GSH synthesis by pretreatment of the animals either with glutamine + glycine + cystine or N-acetyl-L-cysteine was attempted. Low doses of these precursors administered previously to BEA, respectively, decreased or abolished the GSH depletion. Nevertheless, both pretreatments failed to modify the magnitude of renal papillary necrosis. High doses of these precursors did not modify the BEA-induced GSH depletion, but they significantly increased GSH levels 24 h after BEA administration. At this time, although a smaller intensity of renal papillary necrosis was observed with the amino acid mixture pretreatment, N-acetyl-L-cysteine pretreated rats showed no papillary necrosis. It is suggested that the observed protective effects against BEA-induced renal papillary injury may be ascribed in some measure, to a mechanism independent of GSH.