Home About us Contact
|
Home About us Contact | ||
|
|
||
Metabolic Evaluation (metabolic + evaluation)
Selected Abstracts2-Acylaminopyridin-4-ylimidazoles as p38 MAP Kinase Inhibitors: Design, Synthesis, and Biological and Metabolic EvaluationsCHEMMEDCHEM, Issue 11 2009Katharina Ziegler Dr. Abstract Targeting cytokines has become an important focus in the treatment of many inflammatory disorders. p38 MAP kinase (MAPK) is the key enzyme in regulating the biosynthesis and release of pro-inflammatory cytokines such as IL-1, and TNF,. Inhibition of p38 MAPK results in decreased expression of these cytokines. Tri- and tetrasubstituted pyridinylimidazoles are potent inhibitors of p38 MAPK. Substitution on the pyridinyl moiety allows the design of inhibitors that show increased selectivity and activity by targeting the enzyme's hydrophobic region,II. The objective of this study was to synthesize novel 1,2,4,5-tetrasubstituted imidazole derivates and to characterize them not only for their ability to inhibit p38 MAPK and modulate cytokine release in human whole blood, but also to evaluate their metabolic stability. Biological data and metabolic studies demonstrate that the introduction of a 2-acylamino function at C2 of the pyridine results in highly efficient and metabolically stable inhibitors relative to C2-alkylamino derivatives. A series of novel candidates was investigated for metabolic stability in human liver microsomes and in human whole blood. Additionally, metabolic S-oxidation was investigated, and possible metabolites were synthesized. [source] Etiologic yield of autistic spectrum disorders: A prospective studyAMERICAN JOURNAL OF MEDICAL GENETICS, Issue 1 2006Agatino Battaglia Abstract Studies addressing etiologic yield in childhood developmental disabilities have mainly looked at individuals with developmental delay/mental retardation. The few studies addressing the question of etiologic yield in patients with pervasive developmental disorders (PDDs) had a major drawback, in that the enrolled subjects were diagnosed as having the autistic spectrum disorders based only on history and clinical examination, and/or on unspecified instruments. In addition, only some of these patients underwent a complete laboratory evaluation. To investigate the etiologic yield of PDDs, we undertook a large prospective study on subjects selected according to very strict criteria and diagnosed as having PDD based on the present "gold standard" (ADI-R and ADOS-G), and a clinical diagnosis made by a child psychiatrist. Eighty-five (85) patients with PDD and their first degree relatives participated in this study. These patients were selected from a sample of 236 subjects who had received a clinical diagnosis of PDD at the Stella Maris Institute between March 2002 and 2005. Selection criteria for entering the study were: (1) a diagnosis of PDD (with exclusion of the Rett syndrome) confirmed after the administration of the ADI-R (autism diagnostic interview-revised) and the ADOS-G (autism diagnostic observation schedule-generic). In addition, a clinical diagnosis was made by the child psychiatrist, on the basis of presence or absence of DSM-IV symptoms of autism; (2) chronological age between 4 and 18 years; (3) IQ>30; (4) availability of both biologic parents. Patients, 65/85 (76.5%), had autism, 18/85 (21.2%) had PDD-NOS, and the remaining 2/85 (2.3%) had Asperger syndrome. Ages varied between 4 years 2 months and 12 years 5 months (mean 7.6 years), and there was a marked male preponderance (68/85). All subjects underwent various laboratory studies and neuroimaging. With respect to possible etiologic determination, a detailed history and physical examination in this group of patients with PDD was informative in 10.5% (9/85). HRB karyotype was diagnostic in one, and molecular fragile X studies in one child. Brain MRI was informative in two children (2.3%) with relative macrocrania but no neurological features; and EEG was helpful in one child, identifying a Landau,Kleffner disorder. Audiometry and brainstem auditory evoked potentials (BAEPs) showed a bilateral sensorineural loss in another child. Metabolic evaluation gave normal results in all subjects. The results suggest an evaluation paradigm with reference to etiologic determination for individuals with PDDs that does not presently justify metabolic or neuroimaging on a screening basis. Recurrence risk, treatment implications, and significant and long-lasting emotional relief for the parents suggest that serious consideration be given to clinical genetic examination, genetic testing, EEG study (during wakefulness and sleep), and audiometry, despite a relatively low yield. © 2006 Wiley-Liss, Inc. [source] Metabolic evaluation of cooled equine spermatozoaANDROLOGIA, Issue 2 2010A. B. Vasconcelos Summary Microscopy has been used in the routine evaluation of sperm metabolism. Nevertheless, it has limited capacity to preview male fertility. As calorimetry may be used to evaluate directly the metabolic activity of a biological system, the aim of this study was to use microcalorimetry as an additive method for sperm metabolism evaluation of cooled equine semen. Two ejaculates of four stallions were collected and motility, viability (eosin 3%) and membrane functional integrity (hyposmotic swelling test) of spermatozoa were evaluated. Sperm samples were processed following different protocols and the metabolism of these samples was accessed by calorimetry. Centrifugation is part of some of these processing protocols and although this procedure has been deleterious for sperm viability and plasma membrane integrity, no decrease in sperm motility was observed. Microcalorimetry was capable of detecting the positive effect of re-suspending the sperm pellet with Kenney extender. Thus, the use of microcalorimetry offered additional information for equine sperm metabolism evaluation and was efficient in detecting important information from sperm cell metabolism. [source] Metabolic evaluation in neurodevelopmental disabilities,ANNALS OF NEUROLOGY, Issue 4 2009FRCP(c), Michael Shevell MD No abstract is available for this article. [source] The management of paediatric urolithiasisBJU INTERNATIONAL, Issue 7 2000S. Choong Objective To evaluate the efficacy and safety of the management of paediatric urolithiasis by extracorporeal shock wave lithotripsy (ESWL), endoscopic ureterolithotomy, percutaneous nephrolithotomy (PCNL) and open nephrolithotomy. Patients and methods In a 3-year period (1997,1999), 59 children were treated for urolithiasis and underwent a total of 79 procedures. Thirty-two ESWL sessions were performed in 23 children (mean age 7.4 years, median 6.0). PCNL was undertaken in 30 renal units in 25 children (mean age 6.4 years, median 4.0). Eight patients (mean age 7.8 years, median 5) underwent 17 ureteroscopic procedures, six of which involved the use of a holmium laser. Three children with staghorn calculi underwent open nephrolithotomy under conditions of renal ischaemia and hypothermia. Results Of the 23 children treated using ESWL, 21 (91%) became stone-free; 17 underwent one ESWL session (74%), three had two sessions and three (13%) had three sessions. All eight patients who underwent ureteroscopy became stone-free. Four patients in whom the stone could not be reached by ureteroscopy initially had a JJ stent inserted, and the stone and stent subsequently removed. Stones were cleared using PCNL in 27 of 30 renal units (90%); three patients who had residual stone fragments were rendered stone-free by ESWL. Two of three children undergoing open nephrolithotomy were stone-free after surgery and the remaining one rendered stone-free with ESWL. Metabolic evaluation showed that 25 of 45 children (55%) had a urinary infection, eight (18%) had hyperoxaluria, three (7%) had hypercalciuria, two (4%) had cystinuria, and no identifiable cause was found in seven (16%). Treatment by a single modality rendered 52 of the 59 children (88%) stone-free; when the different modalities were combined, 57 of 59 patients (97%) were cleared of their stones. Conclusions Technological advances in ESWL, ureteroscopy and PCNL have had a significant effect on the management of urolithiasis in children, allowing a safe and successful outcome. The comprehensive care of children with urolithiasis should include a full metabolic evaluation. Anatomical anomalies contribute to the complexity of many cases, necessitating a close liaison between adult and paediatric urologists, nephrologists and radiologists to optimize stone management in children. [source] Clinical and metabolic evaluation of subjects with erectile dysfunction: a review with a proposal flowchartINTERNATIONAL JOURNAL OF ANDROLOGY, Issue 3 2009C. Foresta Summary Erectile function is a haemodynamic phenomenon depending on the integrity of neurological, vascular, endocrinological, tissue (corpora cavernosa), psychological and relational factors; changes in any one of these components may lead to erectile dysfunction (ED). ED and its comorbid conditions share common risk factors such as endothelial dysfunction, atherosclerosis and metabolic and hormonal abnormalities. Furthermore, although cross-sectional studies have shown a clear age-dependent association between ED, diabetes mellitus, hypertension, metabolic syndrome (MetS) and cardiovascular diseases, longitudinal evidence has recently emphasized that ED could be an early marker of these conditions. Recently, the European Association of Urology and American Urology Association provided consensus guidelines for the management of ED patients. However, the metabolic aspect of ED is rather neglected or not sufficiently treated. In this study, more emphasis will be placed on the presence of ED comorbid metabolic factors. The primary and secondary goals of therapy, according to current guidelines and to prevent their clinical evolution, will also be provided. We review the concepts of metabolic diseases related to ED and their treatment. Criteria for the diagnosis and treatment of hypogonadism, metabolic and vascular disease related to ED were analysed. ED can mark the starting point for the evaluation and prevention of significant severe diseases (such as diabetes, MetS, dyslipidaemia, arteriosclerosis, hypertension, ischaemic cardiopathy, neuropathy, etc.) hitherto unknown by the patients. Most widely used criteria for the diagnosis and treatment of these diseases were reported. We suggest a clinical approach which allows the identification of metabolic and others systemic pathologies contributing to the development of ED. This approach may constitute an improvement in disease prognosis and either induce a spontaneous reduction of ED or facilitate its specific therapy. [source] Methods for metabolic evaluation of prostate cancer cells using proton and 13C HR-MAS spectroscopy and [3- 13C] pyruvate as a metabolic substrateMAGNETIC RESONANCE IN MEDICINE, Issue 5 2009Yakir S. Levin Abstract Prostate cancer has been shown to undergo unique metabolic changes associated with neoplastic transformation, with associated changes in citrate, alanine, and lactate concentrations. 13C high resolution-magic angle spinning (HR-MAS) spectroscopy provides an opportunity to simultaneously investigate the metabolic pathways implicated in these changes by using 13C-labeled substrates as metabolic probes. In this work, a method to reproducibly interrogate metabolism in prostate cancer cells in primary culture was developed using HR-MAS spectroscopy. Optimization of cell culture protocols, labeling parameters, harvesting, storage, and transfer was performed. Using [3- 13C] pyruvate as a metabolic probe, 1H and 13C HR-MAS spectroscopy was used to quantify the net amount and fractional enrichment of several labeled metabolites that evolved in multiple cell samples from each of five different prostate cancers. Average enrichment across all cancers was 32.4 ± 5.4% for [3- 13C] alanine, 24.5 ± 5.4% for [4- 13C] glutamate, 9.1 ± 2.5% for [3- 13C] glutamate, 25.2 ± 5.7% for [3- 13C] aspartate, and 4.2 ± 1.0% for [3- 13C] lactate. Cell samples from the same parent population demonstrated reproducible fractional enrichments of alanine, glutamate, and aspartate to within 12%, 10%, and 10%, respectively. Furthermore, the cells produced a significant amount of [4- 13C] glutamate, which supports the bioenergetic theory for prostate cancer. These methods will allow further characterization of metabolic properties of prostate cancer cells in the future. Magn Reson Med, 2009. © 2009 Wiley-Liss, Inc. [source] The management of paediatric urolithiasisBJU INTERNATIONAL, Issue 7 2000S. Choong Objective To evaluate the efficacy and safety of the management of paediatric urolithiasis by extracorporeal shock wave lithotripsy (ESWL), endoscopic ureterolithotomy, percutaneous nephrolithotomy (PCNL) and open nephrolithotomy. Patients and methods In a 3-year period (1997,1999), 59 children were treated for urolithiasis and underwent a total of 79 procedures. Thirty-two ESWL sessions were performed in 23 children (mean age 7.4 years, median 6.0). PCNL was undertaken in 30 renal units in 25 children (mean age 6.4 years, median 4.0). Eight patients (mean age 7.8 years, median 5) underwent 17 ureteroscopic procedures, six of which involved the use of a holmium laser. Three children with staghorn calculi underwent open nephrolithotomy under conditions of renal ischaemia and hypothermia. Results Of the 23 children treated using ESWL, 21 (91%) became stone-free; 17 underwent one ESWL session (74%), three had two sessions and three (13%) had three sessions. All eight patients who underwent ureteroscopy became stone-free. Four patients in whom the stone could not be reached by ureteroscopy initially had a JJ stent inserted, and the stone and stent subsequently removed. Stones were cleared using PCNL in 27 of 30 renal units (90%); three patients who had residual stone fragments were rendered stone-free by ESWL. Two of three children undergoing open nephrolithotomy were stone-free after surgery and the remaining one rendered stone-free with ESWL. Metabolic evaluation showed that 25 of 45 children (55%) had a urinary infection, eight (18%) had hyperoxaluria, three (7%) had hypercalciuria, two (4%) had cystinuria, and no identifiable cause was found in seven (16%). Treatment by a single modality rendered 52 of the 59 children (88%) stone-free; when the different modalities were combined, 57 of 59 patients (97%) were cleared of their stones. Conclusions Technological advances in ESWL, ureteroscopy and PCNL have had a significant effect on the management of urolithiasis in children, allowing a safe and successful outcome. The comprehensive care of children with urolithiasis should include a full metabolic evaluation. Anatomical anomalies contribute to the complexity of many cases, necessitating a close liaison between adult and paediatric urologists, nephrologists and radiologists to optimize stone management in children. [source] | ||||||||||