Dependence of the escape from an axially symmetric galaxy on the energy.

The escape of a particle from a dynamical system depends on the intersection between the ingoing and outgoing asymptotic trajectories to certain periodic orbits placed at the openings of the curves of zero velocity of the system. Although many efforts have been devoted to the analysis of the escape from potentials presenting multiple openings, there are still few studies on potentials with only one opening. In this article, we clarify the way in which the energy affects the escape in this type of systems, showing that, contrary to what one could expect, there are several bifurcations for certain values of the energy.

On the escape from potentials with two exit channels.

The aim of this paper is to investigate the escape dynamics in a Hamiltonian system describing the motion of stars in a galaxy with two exit channels through the analysis of the successive intersections of the stable and unstable manifolds to the main unstable periodic orbits with an adequate surface of section. We describe in detail the origin of the spirals shapes of the windows through which stars escape.

Dietary Quality and Adherence to Dietary Recommendations in Patients Undergoing Hemodialysis.

BACKGROUND: The multiple dietary restrictions recommended to hemodialysis patients may be difficult to achieve and, at the same time, may result in nutritional deficiencies rendering a poor dietary quality. We here assess the dietary quality and adherence to renal-specific guideline recommendations among hemodialysis patients from a single center in Canary Islands, Spain. METHODS: Cross-sectional study, including 91 patients undergoing maintenance hemodialysis. Clinical data and 3-day dietary records were collected. We compared patient's reported nutrients intake with guideline recommendations. We also evaluated their alignment with current American Heart Association dietary guidelines for cardiovascular prevention. RESULTS: Seventy-seven percent and 50% of patients consumed less than the recommended daily energy and protein, respectively. Although half of the patients met the recommendations for dietary fat intake, this was accounted by an excess of saturated fat in 92% of them. Only 22% consumed sufficient fiber. A very small proportion of patients (less than 50%) met the requirements for vitamins and other micronutrients. Insufficient dietary intake was observed in most patients for all vitamins except for cobalamin. Similarly, inadequate dietary intake was observed for many minerals, by both excess (phosphorus, calcium, sodium, and potassium) and defect (magnesium). Most patients met the recommendations for iron and zinc in their diets. CONCLUSIONS: A large proportion of hemodialysis patients at our center did not meet current renal-specific dietary recommendations. The quality of the diet was considered poor and proatherogenic according to American Heart Association guidelines.

Identification of permissive insertion sites for generating functional fluorescent mineralocorticoid receptors.

The mineralocorticoid receptor (MR), a member of the nuclear receptor superfamily of transcription factors, is activated by aldosterone and mediates its natriferic action in tight epithelia. MR is also expressed in nonepithelial tissues. Importantly, it mediates the deleterious effects of inappropriately high aldosterone levels in the heart, in which it induces the development of cardiac fibrosis. Antagonism of MR in humans is useful in the treatment of severe cardiac failure and some forms of hypertension. Despite the important pathophysiological and pharmacological role of this receptor, many important questions about its cellular biology and functional roles remain unanswered. A major challenge in the study of MR is the unavailability of fully functional fluorescent derivatives of the receptor. In this study we have created a library of MR mutants with insertions of the yellow fluorescent protein in various internal locations in the receptor using a random-insertion transposon-based technique. Screening of this library using a transactivation assay allowed us to identify several fluorescent constructs that retain functionality. Detailed characterization of one of these construct showed that it induces aldosterone-target genes such as the epithelial Na(+) channel subunits and the serum and glucocorticoid-induced kinase 1 at physiological concentrations of aldosterone to an equal extent than the wild-type receptor. Furthermore, aldosterone affinity, hormone-induced nuclear translocation, DNA binding and regulation of nongenomic pathways are all indistinguishable from the wild-type receptor. This new set of fluorescent MR derivatives provides a useful tool for studying the cell biology of the receptor.

Influence of renal involvement on peripheral blood mononuclear cell expression behaviour of tumour necrosis factor-alpha and interleukin-6 in type 2 diabetic patients.

BACKGROUND: Type 2 diabetes is associated with a high cardiovascular risk, which is even increased if renal damage is superimposed. Peripheral blood mononuclear cells (PBMCs) and pro-inflammatory cytokines are key factors linking type 2 diabetes and atherosclerosis. We investigated the influence of renal damage on serum, urinary and PBMCs expression behavior of TNF-alpha and IL-6 in these patients. METHODS: PBMCs were isolated by density gradient centrifugation (Ficoll-Paque method) from fasting blood samples of 22 non-diabetic control subjects and 78 diabetic patients with normal renal function and different stages of diabetic nephropathy (18 with normoalbuminuria, 29 with microalbuminuria and 31 with macroalbuminuria). Expression levels of TNF-alpha and IL-6 were analyzed by real-time quantitative RT-PCR. Serum and urinary TNF-alpha and IL-6 concentrations were measured by a solid-phase, chemiluminescent immunometric assay. RESULTS: The mean percent increases in the serum and urinary levels of TNF-alpha and IL-6 in diabetic patients with respect to control subjects were 176% (P < 0.0001), 250% (P < 0.0001), 114% (P < 0.0001) and 39.6% (P = 0.01), respectively. The mRNA expression level of TNF-alpha was higher by 68.8% (P < 0.001) and IL-6 mRNA levels were higher by 64.1% (P < 0.001) with respect to non-diabetic controls. TNF-alpha mRNA expression in patients with macroalbuminuria was higher by 84.8% with respect to subjects with normalbuminuria (P < 0.001) and by 29% with respect to individuals with microalbuminuria (P < 0.05). Likewise, microalbuminuric patients showed a 44.5% increase in TNF-alpha mRNA expression compared to subjects with normoalbuminuria (P < 0.05). Concerning IL-6, the mRNA expression levels of this cytokine was higher by 63.1% with respect to normoalbuminuric subjects (P < 0.01), and by 23.1% with respect to patients with microalbuminuria (P < 0.05). However, with respect to controls, diabetic patients with normoalbuminuria had similar serum TNF-alpha and urinary excretion of IL-6, without any differences in the mRNA expression levels of these cytokines in PBMCs. Partial correlation and multiple regression analysis using TNF-alpha and IL-6 mRNA levels as the dependent variables showed that urinary albumin excretion (UAE) was direct and independently associated with the expression profile of these pro-inflammatory cytokines in PBMCs. CONCLUSIONS: These data show for the first time the relationship between inflammatory activation of PBMCs (reflected by enhanced mRNA expression of TNF-alpha and IL-6) and renal involvement (reflected by increased UAE) in type 2 diabetic patients. These results provide potential insights for the increased inflammation, accelerated atherosclerosis and cardiovascular risk associated with nephropathy in type 2 diabetes.

Hypercalciuria in pediatric patients with ureteropelvic junction obstruction is of genetic origin.

OBJECTIVE: Genitourinary tract malformations are associated with urolithiasis. Hypercalciuria has been described in children with ureteropelvic junction obstruction (UPJO), although the etiology of this metabolic abnormality remains unknown. This study was conducted to find out whether children with UPJO have a higher prevalence of hypercalciuria and whether their family members are affected by hypercalciuria and/or urolithiasis. MATERIAL AND METHODS: We studied the prevalence of hypercalciuria and urolithiasis in 27 children (14 males, 13 females) with UPJO and their parents. RESULTS: One patient had a history of renal colic, whereas imaging studies showed macroscopic renal lithiasis in two patients and calyceal microlithiasis in four. Hypercalciuria was found in 17/27 children (63%), 15 of whom (88%) had a familial history of urolithiasis: seven families in first-degree relatives, six in second-degree relatives and two in other relatives. Concerning the 10 children without hypercalciuria, seven of them (70%) had a family history of urolithiasis: four in first-degree relatives and three in second-degree relatives. The prevalences of both urolithiasis and hypercalciuria were not influenced by gender. CONCLUSIONS: Urolithiasis is associated with hypercalciuria in patients with UPJO. In accordance with previous data, our results show that the prevalence of hypercalciuria is greater in pediatric patients with UPJO than in the general population. Likewise, the prevalence of urolithiasis in the families of these children is also higher than that in the general population. Hypercalciuria was inherited as an autosomal dominant trait.

Renal pro-inflammatory cytokine gene expression in diabetic nephropathy: effect of angiotensin-converting enzyme inhibition and pentoxifylline administration.

BACKGROUND: Recent studies have shown a role for inflammation in the pathogenesis of diabetic nephropathy (DN). Tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 and IL-6 are cytokines with a prevalent pro-inflammatory activity. Our objective was to study the renal gene expression of TNF-alpha, IL-1 and IL-6 in DN and their relationship with renal damage assessed by urinary albumin excretion (UAE). In addition, we also investigated the effect of angiotensin-converting enzyme inhibition and pentoxifylline (PTF) administration on these parameters. METHODS: After streptozotocin-induced diabetes, rats received either no treatment or therapy with enalapril (EN) or PTF for 8 weeks. Renal expression of pro-inflammatory cytokines was evaluated by real-time polymerase chain reaction. Urinary cytokine excretion and albuminuria were also evaluated. RESULTS: Renal cortical mRNA expression for TNF-alpha, IL-1 and IL-6 in untreated diabetic rats was 2.4-, 1.2- and 3.4-fold higher than in non-diabetic rats. Kidney weight and UAE were significantly associated with renal mRNA expression of TNF-alpha and IL-6. Both EN and PTF administration virtually abrogated the overexpression of TNF-alpha, IL-1 and IL-6, which was associated with a reduction in kidney weight and urinary albumin excretion. CONCLUSION: The renal expression of the main pro-inflammatory cytokines TNF-alpha, IL-1 and IL-6 is increased in DN, which is significantly associated with UAE. EN and PTF administration prevented this enhanced expression, leading to a decrease in urinary cytokine excretion and a reduction in albuminuria. These findings provide novel insight into the pathogenic mechanisms of DN, supporting the hypothesis that inflammatory mechanisms play a role in the renal injury secondary to diabetes mellitus.

The role of TNF-alpha in diabetic nephropathy: pathogenic and therapeutic implications.

Diabetes mellitus and its complications are a public health problem. Diabetic nephropathy has become the main cause of renal failure, and furthermore is associated with a dramatic increase in cardiovascular risk. Unfortunately, the mechanisms leading to the development and progression of renal injury in diabetes are not yet fully known. There is now evidence that activated innate immunity and inflammation are relevant factors in the pathogenesis of diabetes. Furthermore, different inflammatory molecules, including pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha), play a critical role in the development of microvascular diabetic complications, including nephropathy. This review discusses the role of TNF-alpha as a pathogenic factor in renal injury, focusing on diabetic nephropathy, and describes potential treatment strategies based on modulation of TNF-alpha activity.

Inflammation and diabetic nephropathy.

Diabetic nephropathy has become the main cause of renal failure, but unfortunately the intimate mechanisms leading to the development and progression of renal injury are not yet fully known. Activated innate immunity and inflammation are relevant factors in the pathogenesis of diabetes. Moreover, different inflammatory molecules, including chemokines, adhesion molecules, and proinflammatory cytokines, may be critical factors in the development of microvascular diabetic complications, including nephropathy. This new pathogenic perspective leads to important therapeutic considerations, with new pathogenic pathways becoming important therapeutic targets that can be translated into clinical treatments for diabetic nephropathy.

Diabetes, inflammation, proinflammatory cytokines, and diabetic nephropathy.

Diabetes and its complications have become a public health problem. Diabetic nephropathy is the main cause of renal failure. In spite of our higher knowledge on this complication, the intimate mechanisms leading to the development and progression of renal injury are not yet fully known. Activated innate immunity and inflammation are relevant factors in the pathogenesis of diabetes. Moreover, inflammation, and more specifically proinflammatory cytokines and other molecules with a relevant role within the inflammatory process, may be critical factors in the development of microvascular diabetic complications, including nephropathy. This new pathogenic perspective may lead to important new therapeutic considerations and new therapeutic goals for the treatment of diabetic nephropathy.

Urinary tumour necrosis factor-alpha excretion independently correlates with clinical markers of glomerular and tubulointerstitial injury in type 2 diabetic patients.

BACKGROUND: Inflammation is a potential factor in the development and progression of diabetic nephropathy. The aim of this study was to analyse the relationship between the pro-inflammatory cytokine tumour necrosis factor-alpha (TNFalpha) and clinical markers of glomerular and tubulointerstitial damage [urinary albumin excretion (UAE) and urinary N-acetyl-beta-glucosaminidase (UNAG), respectively] in a large group of type 2 diabetic patients. METHODS: A total of 160 diabetic patients and 32 healthy controls were included in the study. High-sensitive C-reactive protein (hs-CRP) as well as serum and urinary levels of TNFalpha were measured. UAE and UNAG were determined by 24-h urine collection. RESULTS: Serum hs-CRP and TNFalpha were significantly higher in diabetic than in control subjects, as well as UAE and UNAG. Diabetic patients had increased urinary TNFalpha compared to non-diabetics [14.5 (2-29) vs 4 (0.8-12), P < 0.001]. Serum hs-CRP and TNFalpha in diabetics with increased UAE were elevated compared to diabetics having normoalbuminuria. Urinary TNFalpha was also higher in diabetic subjects with micro- or macroalbuminuria than in patients with normal UAE [10.5 (4-20) and 18 (9-29) vs 7 (2-18) pg/mg, P < 0.0001, respectively]. Multiple regression analysis showed that urinary TNFalpha (P < 0.0001), hs-CRP (P < 0.0001), serum TNFalpha (P < 0.01) and HbA1c (P < 0.05) were independent of and significantly associated with UAE, whereas duration of diabetes (P < 0.001), urinary TNFalpha (P < 0.01), HbA1c (P = 0.01), hs-CRP (P < 0.05) and serum creatinine (P < 0.05) were associated with UNAG. CONCLUSIONS: In patients with type 2 diabetes, urinary TNFalpha excretion is elevated and correlates with severity of renal disease in terms of both glomerular and tubulointerstitial damage, suggesting a significant role for TNFalpha in the pathogenesis and progression of renal injury in diabetes mellitus.

Tumor necrosis factor-alpha gene expression in diabetic nephropathy: relationship with urinary albumin excretion and effect of angiotensin-converting enzyme inhibition.

BACKGROUND: The pathogenic mechanisms and molecular events involved in the development and progression of diabetic nephropathy (DN) are not completely known. Recent data indicate that diabetes includes an inflammatory component that is related to diabetic complications. Tumor necrosis factor (TNF)-alpha, a cytokine with mainly proinflammatory activity, may be synthesized by renal cells. Our objective was to analyze intrarenal TNF-alpha gene expression and its relationship with urinary albumin excretion (UAE). We also investigated the effect of inhibition of angiotensin-converting enzyme on TNF-alpha expression and UAE. METHODS: Streptozotocin-induced diabetic rats received either no treatment or an angiotensin-converting enzyme inhibitor (enalapril). After eight weeks, renal expression of TNF-alpha was evaluated by real-time polymerase chain reaction. RESULTS: Renal cortical messenger RNA levels of TNF-alpha increased significantly and were twice as high in diabetic rats than in nondiabetic control rats. Enalapril administration nearly completely abolished the increase in TNF-alpha messenger RNA expression to the level observed in control rats. UAE was significantly correlated with urinary levels of TNF-alpha (r=0.68, P<0.05) and with renal TNF-alpha expression (r=0.51, P<0.05). CONCLUSION: DN was associated with increased renal expression of TNF-alpha and UAE. Enalapril administration prevented this enhanced expression of TNF-alpha and decreased urinary cytokine excretion and albuminuria. These data provide a novel insight into the pathogenic mechanisms of DN, and support the hypothesis that inflammatory mechanisms may play a significant role in the development and progression of renal injury secondary to diabetes mellitus.

Additive antiproteinuric effect of pentoxifylline in patients with type 2 diabetes under angiotensin II receptor blockade: a short-term, randomized, controlled trial.

Despite the beneficial effects of blockade of the renin-angiotensin system in diabetic nephropathy (DN), albuminuria and progression of renal disease are not completely halted by these agents. Therefore, it is necessary to explore potential antiproteinuric and renoprotective effects of innovative therapeutic approaches. This study tested the hypothesis that the combination of pentoxifylline (PTF) with angiotensin II receptor blockers in normotensive patients with type 2 diabetes produces an additive antiproteinuric effect. Sixty-one patients with DN and residual albuminuria despite treatment with the recommended doses of ARB for >1 yr were randomly assigned to receive the addition of 1200 mg of PTF daily (n = 30) or to a control group (n = 31). Baseline characteristics were similar between groups, and correlation analysis showed a significant association between urinary albumin excretion (UAE) and urinary TNF-alpha (R = 0.53, P < 0.001). After 4 mo, albuminuria showed a significant decrease in patients who received PTF, from 900 mg/24 h (466 to 1542 mg/d) to 791 mg/24 h (309 to 1400 mg/d; P < 0.001), whereas no significant changes were observed in the control group: 920 mg/24 h (450 to 1489 mg/d) at baseline, and 900 mg/24 h (428 to 1800 mg/d) at the end of the study. The mean percentage variation of UAE in the treatment and control groups was -16.7 and 5.5%, respectively (between-group comparison, P < 0.001). This additive antiproteinuric effect was not dependent on changes in BP or metabolic control. However, both serum and urinary levels of TNF-alpha also decreased in patients who received PTF, from 6.4 pg/ml (2.1 to 9.7) and 16 pg/mg (8 to 29) at baseline to 4.6 pg/ml (0.4 to 9) and 14.2 pg/mg (3 to 26) at the end of the study, respectively (P < 0.01), without significant variations in control patients. Moreover, regression analysis at the end of the study showed a correlation between the change in UAE and the change in urinary TNF-alpha in patients who were treated with PTF (R = 0.49, P < 0.001). In conclusion, administration of PTF to patients who have type 2 diabetes and are under long-term treatment with an ARB produces a significant additive antiproteinuric effect associated with a reduction of urinary TNF-alpha excretion.

Effects of atorvastatin on lipid profile and non-traditional cardiovascular risk factors in diabetic patients on hemodialysis.

BACKGROUND/AIMS: Dyslipidemia and non-traditional cardiovascular (CV) risk factors, such as lipoprotein(a) (Lp(a)), homocysteine, oxidative stress and inflammation, are important determinants in the increased CV risk of hemodialysis (HD) patients. The aim of our study was to evaluate the effects of atorvastatin on these parameters in one of the groups with the highest CV risk: diabetic patients with end-stage renal disease under HD therapy. METHODS: Twenty maintenance HD diabetic patients (mean age 64 +/- 10 years, mean time on HD 25 +/- 11 months) with low-density lipoprotein cholesterol (LDL-C) >2.59 mmol/l received atorvastatin (10 mg/day) for 4 months. Lipid profile, including total cholesterol (TC), LDL-C, high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), apolipoproteins A1 and B (Apo-A and Apo-B), and the non-traditional risk factors Lp(a), homocysteine, autoantibodies against oxidized LDL-C (anti-LDLox), total antioxidant status (TAS), and high sensitive C-reactive protein (hs-CRP), were measured at baseline and at the end of the study. Safety was assessed by clinical and laboratory (liver and muscle enzymes) monitoring once a month. RESULTS: Mean percent reductions for TC, LDL-C and TG were 18.5% (p < 0.001), 22% (p < 0.001) and 19% (p < 0.01), respectively. The ratios of TC/HDL-C and LDL-C/HDL-C decreased after treatment (p < 0.05), whereas the ratios of LDL-C/Apo-B (p < 0.01) and Apo-A/Apo-B (p < 0.001) increased. No significant changes were observed in HDL-C. Concerning the non-traditional risk factors, levels of homocysteine, Lp(a), anti-LDLox and TAS did not change significantly. However, hs-CRP decreased from 5.4 (range 0.9-67.8) to 2.3 mg/l (range 0.4-21) (p < 0.01), whereas a concomitant increase in serum albumin was observed (from 38 +/- 2 to 40 +/- 1.7 g/l, p < 0.01). At baseline, hs-CRP was inversely associated with HDL-C and Apo-A, and directly related to Lp(a). The change in hs-CRP was inversely associated with the change of HDL-C, whereas a direct correlation was found with the change of TG. CONCLUSIONS: Atorvastatin administration to diabetic patients on HD is associated with improvement of lipid profile and reduction of hs-CRP. These effects may be critical for the reduction of CV risk and mortality in HD population.

Bone mineral density in girls and their mothers with idiopathic hypercalciuria.

BACKGROUND/AIMS: Idiopathic hypercalciuria (IH) is associated with a decreased bone mineral density (BMD) both in children and adults. It is being increasingly recognized that IH may be a contributing factor to osteopenia and/or osteoporosis in adults. We studied BMD in girls with IH and in their mothers, also affected with IH, in order to evaluate the influence of genetic background on bone mass in the setting of IH. METHODS: BMD was evaluated in 40 girls with IH and in their premenopausal mothers from whom they had inherited this disease. Urinary creatinine and calcium were measured by standard laboratory methods. BMD was determined by dual X-ray absorptiometry scanning of the lumbar spine (LS) and the femoral neck (FN), and values are expressed as Z- and T-scores. RESULTS: A Z-score of <-1 at the LS was found in 42.5% of the girls, whilst in the mothers, a Z score of <-1 at the LS and/or FN was observed in 47.5% and a T-score of <-1 at the LS and/or FN in 62.5%. The Z-score at the LS was significantly lower in girls and their mothers compared to controls, although this finding did not apply for the Z-score at the FN in the mothers. Z-scores in the girls of mothers with osteopenia were significantly lower or there was a trend for the score to be lower than in the girls of mothers with normal BMD. There was a significant relationship between the Z-score of the girls and the T-score at the LS in the mothers (r = 0.32, p < 0.05). CONCLUSION: We have observed a high prevalence of osteopenia in our population affected by IH, both in girls and in their mothers. We suggest that BMD should be measured during the third or fourth decades of life in those individuals with nephrolithiasis or with children diagnosed as having IH.