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PubMedDate not supplied

Residual renal function affects lipid profile in patients undergoing continuous ambulatory peritoneal dialysis.

OBJECTIVE: To determine whether lipoprotein abnormalities associated with continuous ambulatory peritoneal dialysis (CAPD) are influenced by residual renal function (RRF). DESIGN: Open, nonrandomized prospective and comparative study. SETTING: Single university teaching hospital dialysis unit and outpatient clinic. PATIENTS: Twenty adult patients on standard CAPD (1-38 months) were divided into two groups: group A (RRF < or = 0.8 mL/min, n = 10) and group B (RRF > or = 1.1 mL/ min, n = 10), Patients in the two groups were matched for age, time on dialysis, body weight, body mass index, serum urea and albumin levels, peritoneal and urinary albumin losses, and peritoneal transport characteristics such as overnight 8-hour peritoneal creatinine and beta 2-microglobulin clearances and overnight B-hour effluent glucose concentrations. RESULTS: The degree of uremia in patients with preserved RRF (group B) was obviously lower than in patients with negligible RRF (group A), that is, patients in group B had significantly lower serum creatinine and beta 2-microglobulin levels and significantly higher weekly KT/V than group A patients. Despite the prevalence of allele 4 of apolipoprotein E genotype in group A patients, their levels of serum total cholesterol, low-density lipoprotein cholesterol, lipoprotein (a) [Lp(a)], apolipoprotein B(ApoB), and apolipoprotein A1 (ApoA1) were significantly lower than those of patients with preserved RRF (group B). The two groups did not differ significantly in the serum levels of triglyceride or high-density lipoprotein cholesterol. Serum concentrations of Lp(a) and ApoA1, as well as ratios of ApoA1 to ApoB, were correlated significantly with RRF (r = 0.63, r = 0.51, and r = 0.61, respectively). CONCLUSIONS: The findings suggest that RRF affects the lipid profile of CAPD patients, especially serum levels of cholesterol-rich lipoproteins.

Adult↗
PubMed1987

Effects of dietary selenium on lipid peroxidation, mitochondrial function and protein profiles in the heart of the myopathic Syrian golden hamster (BIO 14.6).

Male, weanling myopathic Syrian Golden Hamsters (BIO 14.6 strain) were fed a selenium-adequate diet (controls) or this diet supplemented with 1.0 ppm selenium (treated) for 30 days. Se-treated animals exhibited a 50% reduction in lipid peroxidation in heart homogenates relative to controls and a 61% increase in mitochondrial glycerophosphate acyltransferase activity. Gel electrophoresis revealed no alterations in cardiac protein profiles from treated or control animals. These data suggest that the selenium prevents peroxidative injury and maintains mitochondrial function in the absence of alterations in cardiac proteins.

Animals↗
PubMed2006

Profiles of executive function in parents and siblings of individuals with autism spectrum disorders.

Delineation of a cognitive endophenotype for autism is useful both for exploring the genetic mechanisms underlying the disorder and for identifying which cognitive traits may be primary to it. This study investigated whether first-degree relatives of individuals with autism spectrum disorders (ASDs) demonstrate a specific profile of performance on a range of components of executive function (EF), to determine whether EF deficits represent possible endophenotypes for autism. Parents and siblings of ASD and control probands were tested on EF tasks measuring planning, set-shifting, inhibition and generativity. ASD parents showed poorer performance than control parents on a test of ideational fluency or generativity, and ASD fathers demonstrated a weakness in set-shifting to a previously irrelevant dimension. ASD siblings revealed a mild reduction in ideational fluency and a weakness in non-verbal generativity when compared with control siblings. Neither ASD parents nor siblings displayed significant difficulties with planning or inhibition. These results indicated that the broad autism phenotype may not be characterized primarily by impairments in planning and cognitive flexibility, as had been previously proposed. Weaknesses in generativity emerged as stronger potential endophenotypes in this study, suggesting that this aspect of EF should play a central role in cognitive theories of autism. However, discrepancies in the EF profile demonstrated by parents and siblings suggest that factors related to age or parental responsibility may affect the precise pattern of deficits observed.

Adult↗
PubMed2006

Conversion from cyclosporine to tacrolimus improves renal function and lipid profile after cardiac transplantation.

BACKGROUND: Calcineurin inhibitors (CNIs) have become the cornerstone of immunosuppressive regimens following heart transplantation, but their use is associated with nephrotoxicity. The impact on renal function after conversion from cyclosporine (CsA) to tacrolimus (TAC) is reported. PATIENTS AND METHODS: Fifteen patients (men age 42 +/- 11 years) after cardiac transplantation (HTX) were switched from CsA to TAC (mean time after HTX 21 +/- 6 months). There were 13 male and 2 female patients. Mean cholesterol and LDL level at the time of conversion were 217 +/- 65 ml/dl and and 136 +/- 51 mg/100 ml respectively. Indication for HTX was ischemic cardiomyopathy (CMP) in 8, congenital in 3 and dilatative CMP in the remaining 4 patients. RESULTS: Mean tacrolimus level (microg/dl) at 1, 3, 6 and 12 months were 8.6 +/- 3.3, 8.6 +/- 1.4, 9.2 +/- 2.8 and 9.8 +/- 2.5 respectively. There was a statistically significant improvement in creatinine levels at 1, 3, 6 and 12 months after conversion from baseline 1.9 +/- 0.7 mg/dl to 1.4 +/- 0.5 mg/dl, 1.4 +/- 0.4 mg/dl, 1.3 +/- 0.4 mg/dl and 1.2 +/- 0.4 mg/dl, respectively (p < 0.05). Furthermore, TAC decreased cholesterol as well as LDL-levels during this one-year time frame. CONCLUSION: This study shows that conversion from CsA to tacrolimus after orthotopic heart transplantation improves renal function.

Adult↗
PubMed2003

Metabolite profiling as a functional genomics tool.

Plants accumulate a very large number of small molecules (phytochemicals) with important functions in the ecology of plants and in the protection against biotic and abiotic stress conditions. Little is known on how phytochemical biosynthetic pathways are regulated, which is a key step to successfully engineering plant metabolism. Plant natural products are usually not essential, and genetic analyses often fail to identify phenotypes associated with the absence of these compounds. We have investigated the use of metabolite profiling of plant cells in culture to establish the function of transcription factors suspected to control plant metabolic pathways.

Cell Culture Techniques↗
PubMed2005

Coagulation profile and liver function in 102 patients after total cavopulmonary connection at mid term follow up.

OBJECTIVE: To examine coagulation factors and liver function test abnormalities in patients after total cavopulmonary connection (TCPC). DESIGN: Cross sectional study comprising clinical and echocardiographic evaluation, and biochemical and coagulation profile screening. SETTING: Tertiary referral centre. METHODS: 102 patients aged 4-24 years (median 10 years) at one to eight years (median five years) after TCPC were examined. All patients were maintained on a low dose of aspirin. 96% of patients were in a good clinical condition (New York Heart Association class I or II). No intracardiac thrombi were detected on echocardiography and ventricular function was good in 91% of patients. RESULTS: Total bilirubin was increased in 27% and gamma glutamyltransferase in 54% of patients. Serum total protein, albumin, and prealbumin were normal in almost in all patients. Compared with the control group, patients after TCPC had significantly lower fibrinogen, factor V, factor VII, and protein C concentrations, prolonged international normalised ratio, and increased antithrombin III concentration. Factor V concentration was abnormally decreased in 35%, factor VII in 16%, and protein C in 28% of patients. Antithrombin III was increased in 23% of patients. Factor VII, factor V, protein C, and antithrombin III correlated significantly with serum prealbumin. There was also a significant correlation between procoagulant factor VII and both anticoagulant protein C and antithrombin III. CONCLUSIONS: Almost half of patients after TCPC had laboratory signs of mild cholestasis. Decreased liver synthesis of procoagulant and anticoagulant factors was observed but overall coagulation homeostasis appeared to be in balance in this selected group of patients with a good clinical outcome.

Adolescent↗
PubMed2003

Discovery of gene function by expression profiling of the malaria parasite life cycle.

The completion of the genome sequence for Plasmodium falciparum, the species responsible for most malaria human deaths, has the potential to reveal hundreds of new drug targets and proteins involved in pathogenesis. However, only approximately 35% of the genes code for proteins with an identifiable function. The absence of routine genetic tools for studying Plasmodium parasites suggests that this number is unlikely to change quickly if conventional serial methods are used to characterize encoded proteins. Here, we use a high-density oligonucleotide array to generate expression profiles of human and mosquito stages of the malaria parasite's life cycle. Genes with highly correlated levels and temporal patterns of expression were often involved in similar functions or cellular processes.

Animals↗
PubMed2005

Pattern pulses: design of arbitrary excitation profiles as a function of pulse amplitude and offset.

A novel class of pulses is presented which can be regarded as a generalization of both frequency-selective pulses and B1-selective pulses. The excitation profile of these pulses forms a pre-defined pattern in two dimensions, which are spanned by pulse offset and radio-frequency (RF) amplitude. The presented pulses were designed numerically based on principles of optimal control theory. For simple test patterns, we demonstrate the flexibility of this approach by simulations and experiments. This previously unknown flexibility may trigger novel applications in NMR spectroscopy and imaging. As a first practical application, we demonstrate a direct approach for calibrating RF pulses.

Journal Article↗
PubMed2000

Modeling of dose-response-time data: four examples of estimating the turnover parameters and generating kinetic functions from response profiles.

The most common approach to in vivo pharmacokinetic and pharmacodynamic modeling involves sequential analysis of the plasma concentration versus time and then response versus time data, such that the plasma kinetic model provides an independent function, driving the dynamics. However, response versus time data, even in the absence of measured drug concentrations, inherently contain useful information about the turnover characteristics of response (turnover rate, half-life of response), the drug's biophase kinetics (F, half-life) as well as the pharmacodynamic characteristics (potency, intrinsic activity). Previous analyses have assumed linear kinetics, linear dynamics, no time lag between kinetics and dynamics (single-valued response), and time constant parameters. However, this report demonstrates that the drug effect can be indirect (antinociception, cortisol/adrenocorticotropin (ACTH), body temperature), display nonlinear kinetics, display feedback mechanisms (nonstationarity, cortiso/ACTH) and exhibit hysteresis with the drug levels in the biophase (antinociception, body temperature). It is also demonstrated that crucial determinants of the success of modeling dose-response-time data are the dose selection, multiple dosing, and to some extent different input rates and routes. This report exemplifies the possibility of assigning kinetic forcing functions in pharmacodynamic modeling in both preclinical and clinical studies for the purpose of characterizing (discrimination between turnover and drug-specific parameters) response data and optimizing subsequent clinical protocols, and for identification of inter-individual differences.

Animals↗
PubMed1998

Functional characterisation of the human cloned 5-HT7 receptor (long form); antagonist profile of SB-258719.

1. The functional profile of the long form of the human cloned 5-HT7 receptor (designated h5-HT7(a)) was investigated using a number of 5-HT receptor agonists and antagonists and compared with its binding profile. Receptor function was measured using adenylyl cyclase activity in washed membranes from HEK293 cells stably expressing the recombinant h5-HT7(a) receptor. 2. The receptor binding profile, determined by competition with [3H]-5-CT, was consistent with that previously reported for the h5-HT7(a) receptor. The selective 5-HT7 receptor antagonist SB-258719 ((R)-3,N-Dimethyl-N-[1-methyl-3-(4-methylpiperidin-1-yl)propyl]ben zene sulfonamide) displayed high affinity (pKi 7.5) for the receptor. 3. In the adenylyl cyclase functional assay, 5-CT and 8-OH-DPAT were both full agonists compared to 5-HT and the rank order of potency for agonists (5-CT > 5-HT > 8-OH-DPAT) was the same in functional and binding studies. 4. Risperidone, methiothepin, mesulergine, clozapine, olanzapine, ketanserin and SB-258719 antagonised surmountably 5-CT-stimulated adenylyl cyclase activity. Schild analysis of the antagonism by SB-258719 gave a pA2 of 7.2+/-0.2 and slope not significantly different from 1, consistent with competitive antagonism. 5. The same antagonists also inhibited basal adenylyl cyclase activity with a rank order of potency in agreement with those for antagonist potency and binding affinity. Both SB-258719 and mesulergine displayed apparent partial inverse agonist profiles compared to the other antagonists tested. These inhibitory effects of antagonists appear to be 5-HT7 receptor-mediated and to reflect inverse agonism. 6. It is concluded that in this expression system, the h5-HT7(a) receptor shows the expected binding and functional profile and displays constitutive activity, revealing inverse agonist activity for a range of antagonists.

Adenylyl Cyclases↗
PubMed2002

Dyspnea, respiratory function and sputum profile in asthmatic patients during exacerbations.

Dyspnea is often used as a marker of asthma severity although a wide variation in dyspnea perception associated with bronchoconstriction (PB) has been described in asthmatic patients. Our hypothesis is that changes of airway inflammation, airway narrowing and hyperinflation may account for a part of the variability of breathlessness in spontaneous asthma attack. In asthmatic patients with exacerbation of the disease, we evaluated respiratory function, dyspnea (using visual Analogue Scale--VAS) and peak expiratory flow (PEF) values and variability (amplitude % mean), and sputum cellular and biochemical profile before (day I) and after (day II) therapy with i.v. corticosteroids and inhaled beta2-agonists, as appropriate. By day II, forced expiratory volume in 1 s (FEV1), inspiratory capacity (IC), PEF or VAS values and variability, sputum eosinophils and eosinophilic cationic protein (ECP) had improved. Improvement of dyspnea expressed as a decrease in VAS and reduction in variability of dyspnea sensation significantly correlated with increase in FEV1 %predicted value (%pv) (P=0.03; p=0.72 and P=0.02; p=0.74, respectively). No significant correlation was found between IC and VAS either in absolute values or as changes from days I and II, nor between sputum outcomes and PEF or VAS, regardless of how they were measured. We conclude that in acute asthmatic patients, dyspnea measurement, functional measurements and sputum analysis may be useful in monitoring disease activity, response to therapy and can provide different information on the state of the disease.

Acute Disease↗
PubMed2004

[Daily blood pressure profiles and endothelial functions during long-term treatment of arterial hypertension with angiotensin-converting enzyme inhibitors].

Clinical practice has been recently applied new approaches to classifying patients with arterial hypertension (AH), which are based on the determination of the summary risk suggesting the prognosis of the disease. This approach is quite efficient due to the fact that it takes into account a combination of the comparable clinical symptoms of AH, which characterize its course. The paper presents data on the values of blood pressure (BP) in AH and on daily BP profiles (DBPP) in 494 patients with different categories of a risk and on their endothelial function. It also gives the results of achievement of target BP levels in patients with AH having different categories of a risk during long-term (36-month) treatment with enapril and perindopril, as well as data on its impact on endothelial vasomotor function. The findings suggest that the higher the risk is, the more severe the hypertensive syndrome is; that the redistribution of DBPP occurs towards prognostically poor types and endothelial dysfunction (EDF) progresses. Treatment with angiotensin-converting enzyme (ACE) inhibitors results not only to the achievement of target BP levels and to the normalization of DBPP, but also to the amelioration of EDF. Moreover, the co-administration of ACE inhibitors and isosorbide-5-mononitrates causes additional antiischemic effects.

Adolescent↗
PubMed2004

Age-dependent changes in myocardial matrix metalloproteinase/tissue inhibitor of metalloproteinase profiles and fibroblast function.

OBJECTIVE: To evaluate the effects of aging on left ventricular (LV) geometry, collagen levels, matrix metalloproteinase (MMP) and tissue inhibitor of metalloproteinase (TIMP) abundance, and myocardial fibroblast function. METHODS: Young (3-month-old; n=28), middle-aged (MA; 15-month-old; n=17), and old (23-month-old; n=16) CB6F1 mice of both sexes were used in this study. Echocardiographic parameters were measured; collagen, MMP, and TIMP levels were determined for both the soluble and insoluble protein fractions; and fibroblast function was evaluated. RESULTS: LV end-diastolic dimensions and wall thickness increased in both MA and old mice, accompanied by increased soluble protein and decreased insoluble collagen. Immunoblotting revealed differential MMP/TIMP profiles. Compared to MA levels, MMP-3, MMP-8, MMP-9, MMP-12, and MMP-14 increased, and TIMP-3 and TIMP-4 decreased in the insoluble fraction of old mice, suggesting increased extracellular matrix (ECM) degradative capacity. Fibroblast proliferation was blunted with age. CONCLUSION: This study, for the first time, identified specific differences in cellular and extracellular processes that likely contribute to age-dependent ECM remodeling.

Aging↗
PubMed1996

Neonatal phenobarbital-induced persistent alterations in plasma testosterone profiles and testicular function.

Daily sc injections of phenobarbital at anticonvulsant therapeutic doses for the rat (40 mg/kg) for the first 7 days of life resulted in below normal levels of serum testosterone from around birth to before puberty, normal levels during puberty and above normal levels of the androgen after puberty and in adulthood. Cluster analysis of the plasma testosterone secretory profiles obtained at 15-min intervals from phenobarbital-treated rats at 65 and 165 days of age revealed a significant increase in both the peak amplitudes and their durations resulting in a 100% increase in the amount of hormone secreted during the peak periods. In general, most of the rats (control and experimental) secreted testosterone as two large peaks, each 3 to 4 hr in duration, during the 10-hr lights-on collection period. In addition to permanently disrupting the ultradian profiles of plasma testosterone, neonatal exposure to the barbiturate altered testicular responsiveness to steroidogenic regulatory agents. That is, neonatal exposure to phenobarbital enhanced the responsiveness to exogenous hCG as measured by an above-normal increase in testosterone concentration. Moreover, phenobarbital-induced reductions in serum testosterone levels were delayed in adult rats neonatally exposed to the barbiturate. Whereas a single challenge dose of phenobarbital (1 or 10 mg/kg) reduced serum testosterone concentrations in control animals by almost 80% within 3 hr, a decline in serum androgen levels in the neonatally phenobarbital exposed males was not observed until 12 hr after the challenge dose. These results indicate that postpartum exposure to therapeutic levels of phenobarbital can permanently disrupt testosterone secretory profiles and alter pathways regulating testicular steroidogenesis.

Aging↗
PubMed1997

[A forecasting trial of the dento-skeletal and cutaneous facial profile, as a function of sex, in Class II, division 1 malocclusion, using regression analysis of the coordinates].

For a pattern of 36 leucoderm subjects, aged 12 years, with Class II, division 1, prediction of results are been calculated, in each sex, proceeding bony and cutaneous points coordinates, in axis defined by S-N, with "regression" method. Bony, dental and cutaneous profiles expected 3 years afterwards can be established in a personalized way, as well as correspondent security limits. A logical make easy utilisation of this process.

Adolescent↗
PubMed2006

Cross-species transcriptional profiles establish a functional portrait of embryonic stem cells.

An understanding of the regulatory mechanisms responsible for pluripotency in embryonic stem cells (ESCs) is critical for realizing their potential in medicine and science. Significant similarities exist among ESCs harvested from different species, yet major differences have also been observed. Here, by cross-species analysis of a large set of functional categories and all transcription factors and growth factors, we reveal conserved and divergent functional landscapes underlining fundamental and species-specific mechanisms that regulate ESC development. Global transcriptional trends derived from all expressed genes, instead of differentially expressed genes alone, were examined, allowing for a higher discriminating power in the functional portrait. We demonstrate that cross-species correlation of transcriptional changes that occur upon ESC differentiation is a powerful predictor of ESC-important biological pathways and functional cores within a pathway. Hundreds of functional modules, as defined by Gene Ontology, were associated with conserved expression patterns but bear no overt relationship to ESC development, suggestive of new mechanisms critical to ESC pluripotency. Yet other functional modules were not conserved; instead, they were significantly up-regulated in ESCs of either species, suggestive of species-specific regulation. The comparisons of ESCs across species and between human ESCs and embryonal carcinoma stem cells suggest that while pluripotency as an essential function in multicellular organisms is conserved throughout evolution, mechanisms primed for differentiation are less conserved and contribute substantially to the differences among stem cells derived from different tissues or species. Our findings establish a basis for defining the "stemness" properties of ESCs from the perspective of functional conservation and variation. The data and analyses resulting from this study provide a framework for new hypotheses and research directions and a public resource for functional genomics of ESCs.

Animals↗
PubMed2001

Occupational lead exposure and amino acid profiles and liver function tests in industrial workers.

The aim of the present study is to determine the effect of blood lead on the plasma levels of amino acids and serum liver enzymes in industrial workers in United Arab Emirates (UAE). This comparison study consisted of 100 industrial workers (exposed) and 100 non-industrial workers (non-exposed), matched for age, sex and nationality selected from Al-Ain, Abu-Dhabi Emirates. Industrial workers had higher proportion (19%) of smokers than non-industrial workers (11%) which was not considered to be statistically significantly different. Industrial workers had significantly higher mean of blood lead level (77.5 +/- 42.8 miccrog x dl(-1)) than non-industrial workers (19.8 +/- 12.3 microg x dl(-1)). The amino acid analysis showed higher values among industrial than non-industrial workers for histidine, isoleucine, leucine, threonine, lysine, valine, methionine and arginine (essential amino acids, (p<0.0001). Ornithine, taurine, glutamic acid, serine, glycine, proline and alanine (non-essential amino acids) showed significantly higher values in industrial when compared with the non-industrial workers (p<0.0001). Plasma liver function test, cardiac enzymes and renal function test were carried out on industrial and non-industrial workers. The results revealed alkaline phosphatase (p=0.012) and lactate dehydrogenase (p=0.029) were significantly higher in industrial than in non-industrial workers. On the basis of this study, it can be concluded that a substantial difference in amino acid profiles, blood lead and LFT between exposed and non-exposed was found. These results might be related to lead exposure and might have affects on the kidneys or liver.

Adult↗