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Biomedical subjects

A Kamel

Publications and source records attributed to A Kamel.

At least 19 recordsLinked to original sources
PubMed2003

Endoscopic-assisted microsurgery: microsurgery in the new millennium? A comparative experimental study.

Endoscopes are already present in almost all plastic surgery departments. The operating microscope is currently an essential piece of equipment for performing microsurgical anastomoses; however, microsurgery could be conducted using other equipment, including the endoscope. By performing 60 vessel and nerve repairs in rats under the operating microscope and the same number using the endoscope as a visual aid, we investigated the technical and clinical differences between the two instruments. We recorded significantly shorter operative, vascular preparation and anastomotic times in the endoscopically assisted group. Based on the data collected during this study, we conclude that microsurgery is possible with the aid of an endoscope. Using the endoscope may make prolonged microvascular procedures shorter and less physically demanding and may increase the comfort level of both the surgeon and the assistant.

Anastomosis, Surgical↗
PubMed2002

In vitro effects of leptin on human adipocyte metabolism.

OBJECTIVE: Leptin receptors are expressed in adipocytes, suggesting potential autocrine/paracrine effects. Studies on the direct effects of leptin on adipose tissue metabolism in different species have yielded controversial data. To assess the in vitro effects of leptin on human adipocyte metabolism: lipolysis, the insulin-induced inhibition of lipolysis and lipogenesis were studied in adipocytes obtained from infants and adults. METHODS: Lipolysis was studied by incubating adipocytes with increasing concentrations of leptin or isoprenaline. Glycerol in the incubation medium was measured as an indicator of lipolysis. For the lipogenesis and insulin-induced inhibition of lipolysis experiments, the cells were preincubated with 0, 25, or 250 ng/ml of leptin for 2 h. RESULTS: Leptin did not stimulate lipolysis in human adipocytes, either in children or adults. Preincubation with leptin did not affect the insulin-induced inhibition of lipolysis, but decreased the insulin-induced lipogenesis (p < 0.05). CONCLUSIONS: This study shows that leptin has no direct lipolytic effect in human adipocytes. The lack of effect on the insulin-induced inhibition of lipolysis and the negative effect on lipogenesis indicates that the effect of leptin is not at the proximal insulin-signalling pathway but further downstream.

Adipocytes↗
PubMed2001

Upregulation of uncoupling protein homologues in skeletal muscle but not adipose tissue in posttraumatic insulin resistance.

Metabolic alterations after surgical stress include peripheral insulin resistance and increased utilization of fat as a fuel substrate. An up-regulation of skeletal muscle uncoupling proteins (UCPs) has been associated with physiologic states of insulin resistance and enhanced fat metabolism in rodents. We examined whether posttraumatic insulin resistance induced the UCPs in gastrocnemius and soleus muscle and white adipose tissue in an experimental model of surgical trauma. Insulin sensitivity was significantly reduced in isolated soleus muscles but unchanged in adipocytes after trauma. In traumatized rats, mRNA and protein contents of UCP2 and UCP3 and were significantly increased in both muscle types. UCP2 protein content in adipose tissue was unaltered by surgical stress. Circulating NEFAs and glycerol were reduced after surgical trauma. We hypothesize that the changes in UCP2 and UCP3 gene and protein expression are involved in the regulation of substrate utilization in posttraumatic insulin resistance.

Adipocytes↗
PubMed2000

Narrow-bore high-performance liquid chromatography in combination with ionspray tandem mass spectrometry for the determination of the substance P receptor antagonist ezlopitant and its two active metabolites in plasma.

A simple, but highly sensitive and specific, assay was developed for the quantitative determination of ezlopitant and its two active metabolites in human plasma using narrow-bore reversed-phase high-performance liquid chromatography (HPLC) coupled with electrospray tandem mass spectrometry (ES-MS-MS). Ezlopitant, its two pharmacologically active metabolites, an alkene analogue (CJ-12 458) and a benzyl alcohol analogue (CJ-12 764), and their corresponding trideuterated internal standards (I.S.), were extracted from plasma with methyl tert.-butyl ether (MTBE). The dried MTBE extracts were reconstituted and analyzed using a narrow-bore (2.1 mm I.D.) YMC basic HPLC column and a mobile phase of acetonitrile-20 mM ammonium acetate, pH 5 (60:40, v/v). Column effluent was monitored by pneumatically assisted electrospray tandem mass spectrometry. Multiple reaction monitoring (MRM) using the parent to product ions was used to quantify ezlopitant and its two active metabolites. The assay exhibited a linear dynamic range of 0.1-100 ng/ml. Average absolute recoveries from plasma were approximately 71, 80 and 99% for ezlopitant and its two active metabolites CJ-12 485 and CJ-12 764, respectively. The precision (RSD %) and accuracy (Deviation %) values for the method were within +/- 12% and +/- 15%, respectively, for all analytes. Sample analysis times were less than 5 min from one injection to the next. The assay proved to be suitable for pharmacokinetics studies.

Benzylamines↗
PubMed2000

Insulin-degrading enzyme identified as a candidate diabetes susceptibility gene in GK rats.

Genetic analysis of the diabetic GK rat has revealed several diabetes susceptibility loci. Congenic strains have been established for the major diabetes locus, Niddm1, by transfer of GK alleles onto the genome of the normoglycemic F344 rat. Niddm1 was dissected into two subloci, physically separated in the congenic strains Niddm1b and Niddm1i, each with at least one disease susceptibility gene. Here we have mapped Niddm1b to 1 cM by genetic and pathophysiological characterization of new congenic substrains for the locus. The gene encoding insulin-degrading enzyme (IDE:) was located to this 1 cM region, and the two amino acid substitutions (H18R and A890V) identified in the GK allele reduced insulin-degrading activity by 31% in transfected cells. However, when the H18R and A890V variants were studied separately, no effects were observed, demonstrating a synergistic effect of the two variants on insulin degradation. No effect on insulin degradation was observed in cell lysates, indicating that the effect is coupled to receptor-mediated internalization of insulin. Congenic rats with the IDE: GK allele displayed post-prandial hyperglycemia, reduced lipogenesis in fat cells, blunted insulin-stimulated glucose transmembrane uptake and reduced insulin degradation in isolated muscle. Analysis of additional rat strains demonstrated that the dysfunctional IDE: allele was unique to GK. These data point to an important role for IDE: in the diabetic phenotype in GK.

Alleles↗
PubMed2000

Identification of the major human liver cytochrome P450 isoform(s) responsible for the formation of the primary metabolites of ziprasidone and prediction of possible drug interactions.

AIMS: To identify the cytochrome P450 (CYP) isoform(s) responsible for the formation of the primary metabolite of ziprasidone (ziprasidone sulphoxide), to determine the kinetics of its formation and to predict possible drug interactions by investigating CYP isoform inhibition in an in vitro study. METHODS: In vitro metabolism of [14C]-ziprasidone was studied using human liver microsomes. The metabolites were identified using mass spectrometry. The kinetics of metabolite formation were determined using [14C]-ziprasidone (10-200 microM) over 5 min, and Km and Vmax were estimated from Lineweaver-Burk plots. IC50 values for the inhibition of specific probe substrates for CYP1A2, CYP2C9, CYP2C19, CYP2D6 and CYP3A4, by ziprasidone, risperidone and 9-hydroxyrisperidone were also determined using human liver microsomes from three subjects. Mean Ki values were calculated. RESULTS: Three CYP-mediated metabolites - ziprasidone sulphoxide, ziprasidone sulphone and oxindole acetic acid - were identified. The apparent Km and Vmax values for the formation of the major metabolite, ziprasidone sulphoxide (measured as the sum of sulphoxide and sulphone) were 235 microM and 1.14 nmol mg(-1) protein min(-1), respectively. Isoform-selective inhibitors and recombinant enzymes indicated that CYP3A4 is responsible for the formation of ziprasidone metabolites. Ziprasidone was not a substrate for the other isoforms studied. Similar in vitro inhibition of CYP2D6 (Ki 6.9-16 microM) and CYP3A4 (Ki 64-80 microM) was obtained with ziprasidone, risperidone and 9-hydroxyrisperidone. The in vivo free drug concentrations associated with clinically effective doses of ziprasidone are at least 1500-fold lower than the mean Ki for either CYP2D6 inhibition or CYP3A4 inhibition. CONCLUSIONS: Ziprasidone is predominantly metabolized by CYP3A4 in human liver microsomes and is not expected to mediate drug interactions with coadministered CYP substrates, at clinically effective doses.

Antipsychotic Agents↗
PubMed2000

Otogenic intracranial inflammations: role of magnetic resonance imaging.

The clinical course of acute otitis media is usually short, and the process terminates because of the host's immune system, the infection-resistant properties of the mucosal linings, and the susceptibility of the major organisms (beta-hemolytic streptococcus or pneumococcus) to penicillin. However, a small proportion (1% to 5%) of untreated or inadequately treated patients may experience complications. Prior to the development of an intracranial complication of otomastoiditis, warning symptoms or signs may be evident; these include severe earache, severe headache, vertigo, chills and fever, and meningeal symptoms and signs. Increasing headache, particularly temporoparietal headache near the affected ear, often indicates an impending intracranial complication. This symptom, often the only indication of an epidural abscess, demands prompt investigation and medical and surgical intervention. In our experience, computed tomography (CT) permits accurate diagnosis of acute coalescent or latent (masked) mastoiditis and its associated complications. However, magnetic resonance imaging (MRI) remains the study of choice to evaluate otogenic intracranial complications. This article demonstrates the important role of MRI in diagnosing various stages of acute otomastoiditis and its associated complications.

Brain Diseases↗
PubMed2000

Effects of growth hormone treatment in obese prepubertal boys.

Childhood obesity is associated with several abnormalities of the GH axis, including decreased spontaneous secretion, decreased response to exogenous secretagogues, and altered pulsatile pattern of secretion. In adults, GH treatment reduces abdominal obesity and improves insulin sensitivity, as well as blood lipid profiles. Whether GH has similar effects in obese children has not been investigated previously. In this study, seven prepubertal severely obese boys aged 10-12 yr were treated with GH for 6 months and followed for an additional 6 months. No diet or exercise modifications were initiated. Body fat percentage decreased from 51.3% to 46.1% after treatment (P = 0.03). Frequently sampled iv glucose tolerance tests revealed an increased responsivity of the acute insulin secretion (P = 0.04) and a nonsignificant trend toward improved insulin sensitivity. In isolated adipocytes, the maximum isoprenaline- and terbutaline-induced lipolysis were increased approximately 2.5-fold (P = 0.02). The sensitivity of the adipocytes to isoprenaline was unchanged, whereas the sensitivity to terbutaline was increased (P = 0.04). No effect was observed on basal or insulin-stimulated lipogenesis. In conclusion, GH treatment for 6 months of obese prepubertal boys reduces body fat, possibly, via stimulation of catecholamine-induced lipolysis, without negative effects on glucose homeostasis.

Adipocytes↗
PubMed1999

Peripheral blood vs bone marrow as a source for allogeneic hematopoietic stem cell transplantation.

In this randomized prospective study, we included 30 patients with different hematological diseases (acute myeloid leukemia, acute lymphoblastic leukemia, chronic myeloid leukemia, myelodysplastic syndrome or severe aplastic anemia) to compare peripheral blood stem cells (PBSC) (15 patients; mean age 23) and bone marrow (BM) (15 patients; mean age 21.8) as a source for allogeneic transplantation regarding the tempo of hematopoietic recovery and the incidence of acute graft-versus-host disease (GVHD). In the BM group, the median nucleated cell count harvested was 1.3 x 10(10), while in the PBSC group, the aphereses contained a median of 4.4 x 10(6) CD34+/kg recipient weight. PBSC transplantation (PBSCT) was associated with faster hematopoietic reconstitution measured as absolute neutrophil count (ANC) >0.5 x 10(9)/l (log-rank P value <0.0018) and platelet count >25 x 10(9)/l (log-rank P value <0.0098). Seven patients (46.7%) in the BM group vs only one patient (6.7%) in the PBSC group developed acute GVHD (P = 0.013). Therefore, we conclude that PBSCT is associated with faster hematopoietic recovery and the incidence of acute GVHD does not exceed that seen with BMT.

Adult↗
PubMed1999

Insulin induced hypoglycaemia: comparison of glucose and glycerol concentrations in plasma and microdialysate from subcutaneous adipose tissue.

AIMS: To investigate the dynamics between plasma and dialysate glucose during hypoglycaemia in children. STUDY DESIGN: Six children in prepuberty or early puberty were investigated by multiple blood sampling and microdialysis of subcutaneous adipose tissue during a standard arginine-insulin tolerance test. Glucose and glycerol, as an index of lipolysis, were measured in samples from both compartments. Plasma concentrations of insulin and the main counterregulatory hormones were also measured. RESULTS: Plasma and dialysate glucose concentrations were very similar at baseline and increased in concert after infusion of arginine, probably in response to glucagon release. After insulin injection, glucose in both plasma and dialysate fell in parallel. The subsequent hypoglycaemic stress response induced a rapid rebound in the plasma concentration with a mean (SD) delay in the dialysate of 16 (3) minutes. Plasma glycerol was approximately fivefold lower than in the dialysate and did not fluctuate significantly. Dialysate glycerol decreased with arginine infusion and reached a nadir immediately following insulin administration. Subsequently, the antilipolytic effect of insulin was overcome by the hypoglycaemic stress response, and lipolysis prevailed in spite of hyperinsulinaemia. CONCLUSION: After rapidly induced hypoglycaemia, rebound of interstitial glucose concentrations is significantly delayed compared with plasma concentrations, and the antilipolytic effect of hyperinsulinaemia is opposed possibly by the hypoglycaemic stress response.

Adipose Tissue↗
PubMed1999

Growth hormone treatment downregulates serum leptin levels in children independent of changes in body mass index.

The changes in serum leptin levels during growth hormone (GH) treatment were studied in 27 children, 17 with GH deficiency (GHD), 10 with idiopathic short stature (ISS), and 9 with Prader-Willi syndrome (PWS). Within 1 month of GH treatment, serum leptin levels decreased by 40% in the GHD children (p < 0.01). There was no significant change in serum leptin level in the children with ISS. In children with PWS, the mean serum leptin level decreased by almost 60% after 3 months of treatment (p < 0.001). Thereafter, no further decline was observed in any of the 3 groups. Changes in body composition became evident first after the 3 months of treatment. In the GHD children, the BMI was unchanged while the mean body fat percentage was 2.7% lower after 1 year of GH treatment (p < 0.05). In the ISS children, neither BMI nor body fat percentage were significantly changed during treatment. The PWS children exhibited a significant decrease in BMI after 6 months of GH treatment without any further change during the remaining period of treatment. In this group, the mean body fat percentage decreased from 42 +/- 2.4 to 28 +/- 2.2% after treatment (p < 0.001). The finding that the fall in leptin occurs before changes in body composition become detectable suggests a direct effect of GH on leptin production, metabolism, or clearance.

Body Composition↗
PubMed1999

Pathophysiological and genetic characterization of the major diabetes locus in GK rats.

Genetic studies of the type 2 diabetes-like GK rat have revealed several susceptibility loci for the compound diabetes phenotype. Congenic strains were established for Niddm1, the major quantitative trait locus (QTL) for postprandial glucose levels, by transfer of GK alleles onto the genome of the normoglycemic F344 rat. Despite the polygenic nature of diabetes in GK, the locus-specific diabetes phenotype was retained in the congenic strain Niddmla, containing a GK-derived genomic fragment of 52 cM from the Niddm1 locus. Furthermore, Niddm1 was divided into two non-overlapping loci, physically separated in the two congenic strains Niddmlb and Niddm1i with distinct metabolic phenotypes. Both strains displayed postprandial hyperglycemia and reduced insulin action in isolated adipose cells. Furthermore, Niddm1i already exhibits a pronounced in vivo insulin secretion defect at 65 days, while Niddm1b develops a relative insulin secretory defect at 95 days. This suggests that Niddm1i impairs mechanisms common to insulin secretion in pancreatic B-cells and insulin action in adipocytes. Niddm1b rats show signs of increasing insulin resistance with age associated with obesity, hyperinsulinemia, and dyslipidemia. Moreover, the data indicated nonallelic interaction (epistasis) between Niddm1b and Niddm1i on the postprandial glucose levels. These data emphasize the pathophysiological complexity of diabetes, even within an apparently single QTL, and demonstrate the potential of the GK model in transforming the multifactorial diabetes phenotype into single traits, suitable for positional cloning.

Adipose Tissue↗
PubMed1998

Penetration of household insecticides through different types of textile fabrics.

Six different types of fabrics were compared for their ability to protect against human exposure to three different commercial household aerosol insecticides. Fabrics used in this investigation were, 100% cotton, cotton-polyester thermal underwear, cotton-polyester blend (twill), 100% acrylic, 100% wool and artificial silk (rayon). The household insecticides were, Black Flag (Ant and Roach Killer), Raid (Ant and Roach Killer) and Hot Shot (Wasp and Hornet Killer) containing propoxur, permethrin/pyrethrins and chlorpyrifos/allethrins as their active ingredients respectively. A fluorescent tracer, 4-methyl-7-diethyl amino coumarin was mixed with the aerosol (or equivalent aliquot) and sprayed onto cloth squares fitted on Whatman paper patches. The percentage of penetration through the cloth was quantified by the intensity of the fluorescence spectrum of each patch extract and the amount of the tracer recovered was calculated. The extract was concentrated to 1/10th of the volume to measure the content of each of the insecticides by supercritical fluid chromatography (SFC) using electron capture (ECD) and diode array detectors. Scanning electron microscope (SEM) images of the fabrics showed the geometry of the yarn. The results obtained from the fluorescence spectra, SFC and SEM showed that cotton-polyester (twill), cotton, wool and cotton thermal underwear were the least penetrable materials for the aerosols. On the other hand, acrylic and artificial silk (rayon) were the most penetrable cloth types.

Aerosols↗
PubMed1998

Mother's milk protein profile, a possible biomarker for human exposure to persistent insecticides.

The electrophoretic protein profile and residue levels of selected persistent insecticides were investigated in 160 mother's milk samples representing 20 different locations in Egypt. Nine major protein bands were detected in all of the samples. These protein bands were designated as lactoferrin, albumin, SIgA heavy chain, casein I, casein II, SIgA light chain, casein III, lysozyme and alpha-lactalbumin. Residue levels of DDT and its metabolites as well as lindane and its other hexachlorocyclohexane isomers were determined using electron capture gas chromatography and confirmed by gas chromatography/mass spectrometric analysis. Samples containing relatively higher residue levels of the DDT group (DDT, DDE and DDD) showed significant effects on the levels of lysozyme and alpha-lactalbumin bands relative to samples with low or no residue levels. On the other hand, the casein subunits were mostly affected by the residue levels of hexachlorocyclohexane isomers (alpha, beta, gamma and delta isomers). The two patterns showed characteristic dose response correlation suggesting that the protein profile of human milk may serve as a quick biomarker for exposure to persistent insecticides.

Albumins↗
PubMed1998

Effect of growth hormone treatment on insulin action in adipocytes from children with Prader-Willi syndrome.

OBJECTIVE: To study the effect of growth hormone (GH) treatment (2-4 months) on insulin action in adipocytes isolated from children with Prader-Willi syndrome (PWS), in whom GH deficiency appears to be a primary defect. We investigated the complex effects of GH on carbohydrate metabolism, as part of a current clinical trial of GH treatment in children with PWS. METHODS: Biopsies of subcutaneous abdominal adipose tissue were obtained from 12 children with PWS before and after 2-4 months of GH treatment. Lipogenesis was determined by the incorporation of radiolabelled glucose into lipids in isolated adipocytes, and glycerol release to the incubation medium was used as an index of lipolysis. GLUT4 RNA was measured by solution hybridization. RESULTS: With low glucose concentrations, at which glucose transport is rate-limiting, maximal insulin-induced lipogenesis was increased by 120% after GH treatment (P < 0.05), but the sensitivity to insulin (half-maximum effective hormone concentration) was unchanged. This was not accompanied by a significant change in the RNA expression of GLUT4. Neither responsiveness (maximum effect) nor sensitivity of insulin-induced inhibition of lipolysis was affected by GH treatment. CONCLUSIONS: GH treatment of children with PWS results in an upregulation of insulin-induced lipogenesis in isolated adipocytes, with no effect on insulin-induced inhibition of lipolysis. The data suggest that the site of the effect of GH on lipogenesis is distal to the insulin hormone-receptor interaction, but does not involve altered GLUT4 expression.

Adipocytes↗
PubMed1997

Determination of the substance P receptor antagonist CP-122,721 in plasma by narrow-bore high-performance liquid chromatography-ionspray tandem mass spectrometry.

A simple, highly sensitive and specific LC-MS-MS assay was developed for the determination of CP-122,721 (I) in rat and human plasma. I and a structural analog, CP-129,943 (II, internal standard), were extracted from plasma with methyl tert.-butyl ether (MTBE). The dried MTBE extracts were reconstituted and analyzed using a narrow-bore (2.1 mm I.D.) YMC basic HPLC column and a mobile phase of acetonitrile-20 mM ammonium acetate, pH 5 (50:50, v/v). Column effluents were monitored by ionspray tandem mass spectrometry. Multiple reaction monitoring (MRM) using the parent to product ion combinations of m/z 381-->205 and 395-->219 was used to quantitate I and II, respectively. The assay exhibited a linear dynamic range of 0.2-100 ng/ml. Absolute recoveries from plasma were above 80% for both I and II. The precision and accuracy values for the method were within +/-3 and +/-9%, respectively. Sample analysis times were less than 5 min from one injection to the next. The assay has proved to be applicable to the pharmacokinetic study of I in rats.

Animals↗
PubMed1997

Antilipolytic effect of insulin and insulin receptor messenger RNA expression in adipocytes of infants, children, and adults.

Human adipose tissue exhibits marked age-dependent differences in morphology and regulation of lipolysis. The mechanism behind this phenomenon is poorly characterized. The aim of the present investigation was to evaluate the antilipolytic effect of insulin and the expression of insulin receptor mRNA in human adipose tissue during development. To study the antilipolytic effect of insulin, lipolysis was induced with submaximal effective concentrations of isoprenaline or forskolin in adipocytes from five infants below 2 mo of age, five infants above 2 mo of age, six children, and five adults. Isoprenaline was equally effective in stimulating lipolysis in all age groups, whereas forskolin was significantly more effective in adipocytes isolated from adults than from infants and children. Increasing the concentration of insulin during the incubation allowed construction of dose-response curves of insulin inhibition of lipolysis. Maximal inhibition was observed with 30 microU/mL of insulin in the presence of either isoprenaline or forskolin. No differences in the maximal antilipolytic effect of insulin or in the insulin sensitivity expressed as ED50 were observed. Furthermore, the expression of insulin receptor mRNA in adipocytes did not differ from six infants, five children, and six adults as determined with a solution hybridization RNase protection assay. Thus, age-dependent variations in the regulation of lipolysis do not appear to be accompanied by variations in insulin action and insulin receptor gene expression in isolated adipocytes.

Adipocytes↗