Effects of catch-up growth and intrauterine growth retardation on proliferation,differentiation and function of adipocytes in rats

目的 探讨宫内生长迟缓(IUGR)生长追赶对大鼠脂肪细胞增殖分化及功能的影响.方法 母鼠孕期饥饿法建立IUGR模型,仔鼠出生后减少每窝仔鼠数以实现生长追赶;大鼠4周时取肾周白色脂肪组织进行前脂肪细胞和成熟脂肪细胞培养并诱导分化.测定前脂肪细胞增殖能力,成熟脂肪细胞脂联素分泌水平、葡萄糖摄取率,以及各前脂肪细胞及成熟脂肪细胞的二酰基甘油酰基转移酶(DGAT)、脂蛋白脂肪酶(LPL)、胰岛素受体底物1和2(IRS1、IRS2)、磷脂酰肌醇3-激酶(P13K)mRNA表达水平.结果 IUGR大鼠前脂肪细胞的后期增殖能力高于对照组(P<0.05);IUGR大鼠成熟脂肪细胞的脂联索分泌水平低于对照组(P<0.01),葡萄糖摄取率无变化(P>0.05).IUGR大鼠前脂肪细胞,成熟细胞的DGAT、LPLmRNA表达水平高于对照组(P0.05).结论 IUGR可能在大鼠胎儿期即引起脂肪组织多基因改变,影响前脂肪细胞的增殖分化,改变成熟脂肪细胞的糖脂代谢功能,进而造成生后生长追赶者胰岛素抵抗的易感性.     

Autochthonous male urothelial carcinoma immune competent model: from induction to BCG transurethral treatment

Objective: To describe a new animal model of autochthonous urothelial cancer (UC) accessible by transurethral catheter in males, from induction to treatment. Seven-week-old male Fischer 344 rats were used. The first 10 animals were used to overcome and standardize the technical challenges of safe transurethral catheterization of male rats. The remaining 14 animals underwent intravesical N-Methyl-Nitrosourea (MNU) instillation for UC induction, of which six were randomized to undergo intravesical BCG treatment. The stretched male rat urethra travels 35 mm in a tortuous “S” shaped trajectory with a 180° angle behind the pubic bone, safely traversed by a 20G 36” 0.8 mm epidural catheter in a stretched, straightened urethra inserted after anterior dilation of the penile urethra with a 24G IV catheter. Histopathologic analysis of the urinary bladder demonstrated Stage pT1, pTa, and pTis lesions in the 8 controls, all with increased cell proliferation by Ki-67 expression and no pT1 or pTis in the animals 6 treated with BCG. This pioneering study describes an autochthonous, effective, and accessible transurethral animal model of immune-competent UC in males, and may help with understanding of the biology, immunology, and treatment of UC, which predominates in males.     

What can nephrologists learn from epidemiology?

During the last decade, epidemiology has played an increasing role in the study of renal diseases. In the fields of drug-nephrotoxicity and occupational renal failure, epidemiological research has made an important contribution. In recent years, the specific role of epidemiology in outcome research has gained recognition. Epidemiology is based on observations under real-life conditions using a representative sample of renal patients. Methods range from simple clinical observations and cross-sectional studies to case-control and prospective cohort studies. Contributions and limitations of the different epidemiological approaches are illustrated using the example of the nephrotoxicity of 5-aminosalicylic acid in patients with inflammatory bowel disease.     

Renal osteopontin protein and mRNA upregulation during acute nephrotoxicity in the rat.

BACKGROUND: The effect of segment-specific proximal tubular injury on spatio-temporal osteopontin (OPN) distribution was determined in two different nephrotoxic rat models to evaluate its conceivability with a possible role for OPN in acute renal failure (ARF). OPN gene expression was further determined in proximal and distal tubular cells to investigate the origin of increased renal OPN. METHODS: Renal OPN protein and mRNA expression were compared in the rat during mercuric-chloride- vs gentamicin-induced ARF using immunohistochemistry and in situ hybridization. RESULTS: Mercuric chloride primarily induced tubular injury and subsequent cell proliferation in proximal straight tubules (PST), whereas gentamicin predominantly injured proximal convoluted tubules (PCT). In both models, the distribution of OPN protein was associated with increased OPN mRNA levels in proximal as well as distal tubular cells. However, upregulation was delayed in the proximal tubular segment suffering most from injury, i.e. PCT in gentamicin ARF vs PST in mercuric-chloride ARF. OPN immunostaining at the apical cell membrane from distal tubules was in contrast to perinuclear vesicular staining in proximal tubular cells. CONCLUSIONS: OPN gene and protein expression is induced in both proximal and distal tubular cells during rat toxic ARF. The distinct subcellular localization in proximal vs distal tubular cells indicates differences in OPN processing and/or handling. The spatio-temporal distribution is consistent with a possible role in renal injury and regeneration.     

Predicting Fractures Using Bone Mineral Density: A Prospective Study of Long-Term Care Residents

Bone mineral density (BMD) has been shown to predict fracture risk in community-dwelling older persons; however, no comparable prospective study has been performed in the long-term care setting where the role of BMD testing is uncertain. To determine the ability of a single BMD measurement to predict the risk of subsequent fracture in long-term care residents, we designed a prospective study in a 725-bed long-term care facility. A total of 252 Caucasian nursing home residents (mean age 88 years, 74% women) were recruited between 1992 and 1998. BMD of the hip, radius or both sites was measured using dual-energy X-ray absorptiometry. Participants were followed through September 1999 for the occurrence of fracture. Cox proportional hazards regression models were constructed to determine the relationship between BMD and the risk of fracture controlling for potentially confounding variables. Sixty-three incident osteoporotic fractures occurred during a median follow-up time of 2.3 years. The multivariate-adjusted risk of fracture for each standard deviation decrease in BMD was 2.82 (95% CI 1.81–4.42) at the total hip, 2.79 (95% CI 1.69–4.61) at the femoral neck, 2.26 (95% CI 1.51–3.38) at the trochanter, 1.83 (95% CI 1.14–2.94) at the radial shaft and 1.84 (95% CI 1.21–2.80) at the ultradistal radius. Subjects in the lowest age-specific quartile of femoral neck BMD had over 4 times the incidence of fracture compared with those in the highest quartile. BMD at either hip or radius was a predictor of osteoporotic fracture, although in women, radial BMD did not predict fracture. Knowledge of BMD in long-term care residents provides important information on subsequent fracture risk. Received: 3 December 1999 / Accepted: 17 March 2000     

Aluminum, iron, lead, cadmium, copper, zinc, chromium, magnesium, strontium, and calcium content in bone of end-stage renal failure patients.

BACKGROUND: Little is known about trace metal alterations in the bones of dialysis patients or whether particular types of renal osteodystrophy are associated with either increased or decreased skeletal concentrations of trace elements. Because these patients are at risk for alterations of trace elements as well as for morbidity from skeletal disorders, we measured trace elements in bone of patients with end-stage renal disease. METHODS: We analyzed bone biopsies of 100 end-stage renal failure patients enrolled in a hemodialysis program. The trace metal contents of bone biopsies with histological features of either osteomalacia, adynamic bone disease, mixed lesion, normal histology, or hyperparathyroidism were compared with each other and with the trace metal contents of bone of subjects with normal renal function. Trace metals were measured by atomic absorption spectrometry. RESULTS: The concentrations of aluminum, chromium, and cadmium were increased in bone of end-stage renal failure patients. Comparing the trace metal/calcium ratio, significantly higher values were found for the bone chromium/calcium, aluminum/calcium, zinc/calcium, magnesium/calcium, and strontium/calcium ratios. Among types of renal osteodystrophy, increased bone aluminum, lead, and strontium concentrations and strontium/calcium and aluminum/calcium ratios were found in dialysis patients with osteomalacia vs the other types of renal osteodystrophy considered as one group. Moreover, the concentrations of several trace elements in bone were significantly correlated with each other. Bone aluminum was correlated with the time on dialysis, whereas bone iron, aluminum, magnesium, and strontium tended to be associated with patient age. Bone trace metal concentrations did not depend on vitamin D intake nor on the patients' gender. CONCLUSIONS: The concentration of several trace elements in bone of end-stage renal failure patients is disturbed, and some of the trace metals under study might share pathways of absorption, distribution, and accumulation. The clinical significance of the increased/decreased concentrations of several trace elements other than aluminum in bone of dialysis patients deserves further investigation.     

An 18q- syndrome breakpoint resides between the duplicated serpins SCCA1 and SCCA2 and arises via a cryptic rearrangement with satellite III DNA

The 18q-syndrome is representative of a group of terminal deficiency or macrodeletion syndromes characterized by mental retardation and congenital malformations. To gain insight into the mechanism of chromosomal loss and stabilization in these disorders, we cloned a putative terminal deletion breakpoint from an 18q-syndrome patient. The 18q21.3 breakpoint occurred between two nearly identical serine protease inhibitor (serpin) genes, SCCA1 and SCCA2. Although cytogenetic studies suggested that this chromosomal aberration was formed by a simple terminal deletion, DNA sequence analysis, pulsed- field gel electrophoresis and fluorescence in situ hybridization showed that the breakpoint was contiguous with a 35 bp filler sequence followed by a satellite III DNA-containing telomeric fragment of 475- 1000 kb. This type of satellite III DNA sequence was not detected on the normal chromosome 18, but was highly homologous with types of satellite III DNA sequences normally located on the short arms (p11) of the acrocentric chromosomes and other heterochromatic regions. This DNA sequence analysis suggested that the terminal deficiency in this 18q- syndrome patient arose via illegitimate (non-homologous) recombination. Moreover, these data raise the possibility that a subset of chromosomal aberrations appearing cytogenetically and molecularly as simple terminal truncations or deletions are caused by small (<1000 kb) cryptic rearrangements.      

Differences in osteopontin up-regulation between proximal and distal tubules after renal ischemia/reperfusion.

BACKGROUND: Osteopontin (OPN) is a highly acidic phosphoprotein containing an arginine-glycine-aspartic acid (RGD) cell adhesion motif. High OPN expression has been found in tissues with high cell turnover, and OPN up-regulation has been demonstrated in several models of renal injury, suggesting a possible role in tissue remodeling and repair. However, its exact function in the kidney remains unknown. In this study, the possible contribution of OPN to regeneration and repair in the kidney was explored by studying the time course and subcellular localization of OPN up-regulation after renal ischemia/reperfusion injury in different nephron segments and by investigating its relationship with tubular morphology. METHODS: Rats that underwent 60 minutes of left renal ischemia and a right nephrectomy sacrificed at 10 different time points (from 1 hr to 10 days after reperfusion) were compared with uninephrectomized rats at each time point. In renal tissue sections immunostained for OPN, proximal (PTs) and distal tubules (DTs) in both the renal cortex and outer stripe of the outer medulla (OSOM) were scored for the degree of OPN expression and tubular morphology. RESULTS: Kidneys of uninephrectomized rats showed no injury, and the localization and intensity of their OPN expression remained unaltered compared with normal rats. After ischemia/reperfusion, morphological damage was most severe in PTs of the OSOM, but all examined nephron segments showed a significant increase in OPN expression. The time course of OPN up-regulation was different in PTs and DTs. DTs in both cortex and OSOM rapidly increased their OPN expression, with a maximum at 24 hours after reperfusion followed by a slow decrease. In contrast, PTs showed a delayed increase in OPN staining, with a maximum after five to seven days, higher in the OSOM than in the cortex. In OSOM PTs, OPN expression was predominantly associated with morphological regeneration, whereas DTs showed a substantial OPN up-regulation without major morphological damage. PTs and DTs displayed a different subcellular OPN staining pattern: OPN staining in DTs was located to the apical side of the cell; PTs, however, presented a vesicular, perinuclear staining pattern. CONCLUSIONS: Our study found a different pattern of OPN up-regulation after renal ischemia/reperfusion in PTs versus DTs, both with regard to time course and subcellular localization. DTs show an early and persistent increase in OPN staining in the absence of major morphological injury, whereas OPN staining in PTs is delayed and is mostly associated with morphological regeneration. PTs show a vesicular, perinuclear OPN staining pattern, whereas DTs show OPN staining at the apical cell side.     

Spermatic vein embolization as a treatment for symptomatic varicocele

IntroductionVaricocele is a relatively common condition in men that causes pain in approximately 10% of cases. There have been few studies to date assessing the improvements in both pain and quality of life parameters associated with spermatic vein embolization (SVE) as a treatment for patients with symptomatic varicocele, so we aimed to assess this.MethodsA review was carried out of consecutive SVE procedures performed at our institution from 2013–2019. Only patients with painful varicocele were included after other causes of testicular pain were excluded. The technique employed was a combination of distal coil embolization of the spermatic vein with 4–6 mm coils at the level of the inguinal canal, as well as sclerotherapy to prevent reflux of sclerosant. Furthermore, a prospective validated Pain Impact Questionnaire-6 (PIQ-6) was performed to assess for improvement in quality of life. A matched pair Student two-tailed t-test was used to compare mean scores pre- and post-treatment, with 95% confidence intervals presented as T scores and their associated p-values.ResultsOver six years, 62 SVE procedures were performed for symptomatic varicocele. Success rate was 95%, with a median followup of nine months. Two patients had a failed procedure on two occasions requiring subsequent surgical ligation. There was one clinically significant recurrence. All components of PIQ-6 score showed a statistically significant reduction post-SVE, most noticeably pain severity and impact on leisure activities.ConclusionsSVE is a safe, effective, and well-tolerated treatment for symptomatic varicocele, improving pain and quality of life.     

Further data on the validity of the informant questionnaire on cognitive decline in the elderly (IQCODE)

The validity of the long and short forms of the IQCODE was studied in a group of 144 elderly ex-servicemen whose wives served as informants. The study examined the association of the IQCODE with clinical diagnosis of dementia, a battery of neuropsychological and psychological tests, CT scan findings and psychosocial characteristics of informants. For comparison, the validity of the Mini-Mental State Examination was also examined using the same standards. The IQCODE was found to perform as well as the Mini-Mental as a screening test for dementia. Unlike the Mini-Mental, it was not influenced by premorbid intelligence or education. However, it was influenced by other non-cognitive factors: the affective state and personality of the subject, the affective state of the informant and the quality of the relationship between the subject and the informant. The short and long forms of the IQCODE were highly correlated and had equal validity.