Differential effects of insulin-like growth factor binding proteins-1, -2, -3, and -6 on cultured growth plate chondrocytes

Differential effects of insulin-like growth factor binding proteins-1, -2, -3, and -6 on cultured growth plate chondrocytes.BackgroundIn children with chronic renal failure (CRF), impairment of longitudinal growth is in part due to excess amounts of circulating high-affinity insulin-like growth factor binding proteins (IGFBPs) that might decrease or prevent insulin-like growth factor (IGF) binding to its signaling receptor. However, it appears from the clinical studies that various IGFBPs may have contrasting effects on longitudinal growth. Because of the potential importance of the IGFBPs as modulators of longitudinal growth in pediatric CRF, the aim of the present study was to investigate the biological effects of IGFBP-1, -2, -3, and -6 on cultured growth plate chondrocytes that express the type 1 IGF receptor.MethodsThe effects of exogenous IGFBPs on IGF-independent and IGF-dependent proliferation of rat growth plate chondrocytes in primary culture were investigated. Proliferation was assessed by colony formation of agarose-stabilized long-term suspension cultures and by the [3H]thymidine assay. The effects of IGFBPs on IGF-I binding and the binding of IGFBPs to chondrocytes were assessed by binding studies with radiolabeled proteins in monolayer culture.ResultsIntact IGFBP-1, IGFBP-2 and IGFBP-6 inhibited in equimolar concentration the IGF-I- and IGF-II-stimulated DNA synthesis and cell proliferation, whereas the biological activity of IGFBP-3 was complex. It had an IGF-independent antiproliferative effect and also inhibited IGF-dependent chondrocyte proliferation under coincubation conditions, whereas under preincubation conditions IGFBP-3 enhanced IGF-I-responsiveness. Studies on the mechanism by which IGFBP-3 potentiated IGF activity demonstrated that under preincubation conditions IGFBP-3 is capable to associate with the cell membrane and to facilitate IGF-I cell surface binding.ConclusionsIntact IGFBP-1, IGFBP-2 and IGFBP-6 act exclusively as growth inhibitors on IGF-dependent proliferation of growth plate chondrocytes. IGFBP-3, however, can either inhibit IGF-independent and IGF-dependent cell proliferation, or enhance IGF responsiveness of chondrocytes dependent on the temporal relationship to the IGF exposure

Fractal nature in fat crystal networks

The determination of the mechanical and rheological characteristics of several plastic fats requires a detailed understanding of the microstructure of the fat crystal network aggregates. The fractal approach is useful for the characterization of this microstructure. This review begins with information on fractality and statistical self-similar structure. Estimations for fractal dimension by means of equations relating the volume fraction of solid fat to shear elastic modulus G’ in linear region are described. The influence of interesterification on fractal dimension decrease (from 2,46 to 2,15) for butterfat-canola oil blends is notable. This influence is not significant for fat blends without butterfat. The need for an increase in research concerning the relationship between fractality and rheology in plastic fats is emphasized.La determinación de las características mecánicas y reológicas de ciertas grasas plásticas requiere conocimientos detallados sobre las microestructuras de los agregados que forman la red de cristales grasos. El estudio de la naturaleza fractal de estas microestructuras resulta útil para su carac­terización. Este artículo de información se inicia con descripciones de la dimensión fractal y de la "autosimilitud estadística". A continuación se describe el cálculo de la dimensión fractal mediante ecuaciones que relacionan la fracción en volumen de grasa sólida con el módulo de recuperación (G') dentro de un comportamiento viscoelástico lineal. Se destaca la influencia que la interesterificación ejerce sobre la dimensión fractal de una mezcla de grasa láctea y aceite de canola (que pasa de 2,64 a 2,15). Esta influencia no se presenta en mezclas sin grasa láctea. Se insiste sobre la necesidad de incrementar las investi­gaciones sobre la relación entre reología y estructura fractal en grasas plásticas.Peer reviewe

Миграция и эмиграция поволжских немцев

This article presents an overview of current simulation methods describing the interaction of grinding process and grinding machine structure, e.g., vibrations, deflections, or thermal deformations. Innovative process models which describe the effects of the grinding wheel–workpiece interaction inside the contact zone are shown in detail. Furthermore, simulation models representing the static and dynamic behaviour of a grinding machine and its components are discussed. Machine tool components with a high influence on the process results are modelled more detailed than those with low influence. The key issue of the paper is the coupling of process and machine tool models for predicting the interactions of process and machine. Several coupling methods are introduced and the improvements of the simulation results are documented. On the basis of the presented simulation approaches, grinding processes and machines can be designed more effectively resulting in higher workpiece quality and process stability

Hypertension in children with chronic kidney disease: pathophysiology and management

Arterial hypertension is very common in children with all stages of chronic kidney disease (CKD). While fluid overload and activation of the renin–angiotensin system have long been recognized as crucial pathophysiological pathways, sympathetic hyperactivation, endothelial dysfunction and chronic hyperparathyroidism have more recently been identified as important factors contributing to CKD-associated hypertension. Moreover, several drugs commonly administered in CKD, such as erythropoietin, glucocorticoids and cyclosporine A, independently raise blood pressure in a dose-dependent fashion. Because of the deleterious consequences of hypertension on the progression of renal disease and cardiovascular outcomes, an active screening approach should be adapted in patients with all stages of CKD. Before one starts antihypertensive treatment, non-pharmacological options should be explored. In hemodialysis patients a low salt diet, low dialysate sodium and stricter dialysis towards dry weight can often achieve adequate blood pressure control. Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers are first-line therapy for patients with proteinuria, due to their additional anti-proteinuric properties. Diuretics are a useful alternative for non-proteinuric patients or as an add-on to renin–angiotensin system blockade. Multiple drug therapy is often needed to maintain blood pressure below the 90th percentile target, but adequate blood pressure control is essential for better renal and cardiovascular long-term outcomes

The use of mycophenolate mofetil suspension in pediatric renal allograft recipients

Mycophenolate mofetil (MMF) is widely used to prevent acute rejection in adults after renal, cardiac, and liver transplantation. This study investigated the safety, tolerability, and pharmacokinetics of MMF suspension in pediatric renal allograft recipients. One hundred renal allograft recipients were enrolled into three age groups (33 patients, 3 months to <6 years; 34 patients, 6 to <12 years; 33 patients, 12 to 18 years). Patients received MMF 600 mg/m 2 b.i.d. concomitantly with cyclosporine and corticosteroids with or without antilymphocyte antibody induction. One year after transplantation, patient and graft survival (including death) were 98% and 93%, respectively. Twenty-five patients (25%) experienced a biopsy-proven (Banff grade borderline or higher) or presumptive acute rejection within the first 6 months post-transplantation. Analysis of pharmacokinetic parameters for mycophenolic acid (MPA) and mycophenolic acid glucuronide showed no clinically significant differences among the age groups. The dosing regimen of MMF 600 mg/m 2 b.i.d. achieved the targeted early post-transplantation MPA 12-h area under concentration-time curve (AUC 0–12 ) of 27.2 µg h per ml. Adverse events had similar frequencies among the age groups (with the exception of diarrhea, leukopenia, sepsis, and anemia, which were more frequent in the <6 years age group) and led to withdrawal of MMF in about 10% of patients. Administration of MMF 600 mg/m 2 b.i.d. is effective in prevention of acute rejection, provides predictable pharmacokinetics, and is associated with an acceptable safety profile in pediatric renal transplant recipients.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/42304/1/467-16-12-978_10160978.pd

Refining Kidney Survival in 383 Genetically Characterized Patients With Nephronophthisis

Introduction: Nephronophthisis (NPH) comprises a group of rare disorders accounting for up to 10% of end-stage kidney disease (ESKD) in children. Prediction of kidney prognosis poses a major challenge. We assessed differences in kidney survival, impact of variant type, and the association of clinical characteristics with declining kidney function. Methods: Data was obtained from 3 independent sources, namely the network for early onset cystic kidney diseases clinical registry (n = 105), an online survey sent out to the European Reference Network for Rare Kidney Diseases (n = 60), and a literature search (n = 218). Results: A total of 383 individuals were available for analysis: 116 NPHP1, 101 NPHP3, 81 NPHP4 and 85 NPHP11/TMEM67 patients. Kidney survival differed between the 4 cohorts with a highly variable median age at onset of ESKD as follows: NPHP3, 4.0 years (interquartile range 0.3–12.0); NPHP1, 13.5 years (interquartile range 10.5–16.5); NPHP4, 16.0 years (interquartile range 11.0–25.0); and NPHP11/TMEM67, 19.0 years (interquartile range 8.7–28.0). Kidney survival was significantly associated with the underlying variant type for NPHP1, NPHP3, and NPHP4. Multivariate analysis for the NPHP1 cohort revealed growth retardation (hazard ratio 3.5) and angiotensin-converting enzyme inhibitor (ACEI) treatment (hazard ratio 2.8) as 2 independent factors associated with an earlier onset of ESKD, whereas arterial hypertension was linked to an accelerated glomerular filtration rate (GFR) decline. Conclusion: The presented data will enable clinicians to better estimate kidney prognosis of distinct patients with NPH and thereby allow personalized counseling

Estudo experimental do uso de rebolos convencionais na usinagem do aço VP-50 utilizado na retificação cilíndrica, por meio de diferentes métodos de lubrirrefrigeração

A retificação é um processo de usinagem preciso, sendo uma das etapas mais caras na fabricação dos moldes para injeção de termoplásticos. Na retificação o rebolo é a ferramenta abrasiva responsável pela retirada do material. O número de tipos de abrasivos e granulometrias disponíveis são bastante grandes e junto com a quantidade de ligas possíveis, estruturas e durezas, além dos formatos, fazem com que se chegue a um número enorme de produtos. O conhecimento das suas características técnicas, vantagens, defeitos e condições de trabalho são fundamentais para os engenheiros de produto, de processos e, naturalmente, para os gerentes de área industrial, identificarem qual o rebolo mais indicado para realização do processo de retificação. Dentre os aços utilizados na fabricação de moldes para injeção de termoplásticos destaca-se o aço VP-50, o qual foi o aço usado neste experimento, sendo usinado pelo processo de retificação cilíndrica. No processo de retificação, também foi adotado para fins de experimento dois métodos de lubrirrefrigeração, sendo eles o método convencional com lubrirrefrigeração abundante e o MQL que é a técnica com mínima quantidade de lubrirrefrigeração. O objetivo deste trabalho foi analisar de forma comparativa o desempenho de corte executado com três tipos de rebolos convencionais: rebolo de óxido de alumínio branco, rebolo de carbureto de silício verde e rebolo de carbureto de silício preto com óxido de alumínio branco. Os resultados foram analisados e comparados pelas variáveis de saída dos três tipos de rebolos, tipo de refrigeração e espessura equivalente de corte