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Biomedical subjects

S Madani

Publications and source records attributed to S Madani.

At least 19 recordsLinked to original sources

Antioxidant status and levels of different vitamins determined by high performance liquid chromatography in diabetic subjects with multiple complications.

Plasma vitamin A, C and E levels and erythrocyte antioxidant enzyme activities were investigated in type I and type II diabetic subjects with and without complications, i.e., hypertension, coronary artery disease and renal failure. Reverse phase HPLC was used to quantify vitamin A and E levels. We observed that the vitamin C levels were not significantly different between control and diabetic subjects. However, vitamin A and E levels were significantly lower in type I and type II diabetic subjects compared to controls. Superoxide dismutase (SOD) activity was significantly lower in type II, but not in type I, diabetic patients compared to controls. Interestingly, glutathione reductase and peroxidase activities were diminished in type I, but not in type II, diabetic subjects as compared to controls. Catalase activity was lower in both types of diabetic patients in comparison with their respective controls. Altogether these results suggest that diabetes mellitus may be associated with altered antioxidant status regardless to various complications.

Adult↗

Implication of acyl chain of diacylglycerols in activation of different isoforms of protein kinase C.

We synthesized diacylglycerols (DAGs) containing omega-6 or omega-3 polyunsaturated fatty acids [i.e., 1-stearoyl-2-arachidonoyl-sn-glycerol (SAG), 1-stearoyl-2-docosahexaenoyl-sn-glycerol (SDG), and 1-stearoyl-2-eicosapentaenoyl-sn-glycerol (SEG)] and assessed their efficiency on activation of conventional (alpha, beta I, gamma) and novel (epsilon, delta) protein kinase C (PKC). SAG exerted significantly higher stimulatory effects than SDG and SEG on activation of PKC alpha and PKC delta. Activation of PKC beta I by SEG and SDG was higher than that by SAG. Activation of PKC gamma did not differ significantly among DAG molecular species. Addition of SAG to assays containing SEG and SDG exerted additive effects on activation of alpha and epsilon, but not on beta I and gamma, isoforms of PKC. SDG- and SEG-induced activation of PKC delta was significantly curtailed by the addition of SAG. Three DAG species significantly curtailed the PMA-induced activation of beta Iota, gamma, and delta, but not of alpha and epsilon, isoforms of PKC. Our study demonstrates for the first time that in vitro activation of different PKC isoenzymes vary in response to different DAG species, and one can envisage that this differential regulation may be responsible for their in vivo effects on target organs.

Diglycerides↗

Age-related changes in cholesterol metabolism in macrosomic offspring of rats with streptozotocin-induced diabetes.

The aim of this study was to determine the impact of diabetic macrosomia on cholesterol and lipoprotein metabolism. Age-related changes in the activities of serum LCAT, hepatic HMG-CoA reductase, cholesterol 7alpha-hydroxylase, and ACAT, the major enzymes involved in cholesterol metabolism, were determined in macrosomic offspring of streptozotocin-induced diabetic rats. Hepatic, serum, and lipoprotein cholesterol contents were also examined. Mild hyperglycemia in pregnant rats was induced by intraperitoneal injection of streptozotocin (40 mg/kg body weight) on day 5 of gestation. Control pregnant rats were injected with citrate buffer. At birth, macrosomic pups had higher serum, LDL-HDL(1), and HDL(2-3) cholesterol levels (P < 0.05) associated with increased LCAT activity (+57%) compared with control values. At 1 and 2 months of life, serum and lipoprotein cholesterol concentrations in macrosomic rats were similar to those of controls, whereas LCAT activity remained elevated about 1.5-fold. In addition, there was no change in hepatic cholesterol contents but hepatic HMG-CoA reductase, cholesterol 7alpha-hydroxylase, and ACAT activities were higher in both macrosomic males and females than in their respective controls (P < 0.01). By 3 months, macrosomic rats had developed hypercholesterolemia with a rise in all lipoproteins. Enzyme activities were still increased in these mature macrosomic rats, and hepatic cholesteryl esters were higher only in macrosomic females. These data demonstrate an overproduction, combined with overutilization, of cholesterol during the phase of rapid growth in macrosomic rats. However, cholesterol oversynthesis exceeded its removal and was a major contributor to hypercholesterolemia in adult macrosomic rats. In conclusion, macrosomia was associated with alterations in cholesterol metabolism through adulthood.

Acetyl-CoA C-Acyltransferase↗

Analysis of hydroxylated and N-dealkylated metabolites of terfenadine in microsomal incubates by liquid chromatography--mass spectrometry.

This report describes an assay for the H(1)-receptor antagonist, terfenadine, and its two primary metabolites, terfenadine alcohol (TOH) and azacyclonol (AZ), using positive-ion, electrospray ionization-liquid chromatography-mass spectrometry. The assay was developed in support of kinetic studies of terfenadine oxidative metabolism in human liver and intestinal microsomes, which required quantification of incubate metabolites at low nanomolar concentrations. Terfenadine metabolites were extracted from basified microsomal incubates into methylene chloride. Reconstituted extracts were subject to liquid chromatographic separation on a cyano-reverse phase column. The [M+H]+ ions of terfenadine, terfenadine metabolites, and internal standard were monitored in the effluent by quadrupole mass spectrometry. The assay demonstrated linearity over an incubate concentration range of 5-250 and 12.5-1250 ng/ml for the metabolites and the parent drug, respectively. The respective limits of detection and quantitation for all three analytes were 1.5 and 5 ng/ml of microsomal incubate. Replicate analysis of quality control samples exhibited intra-day coefficients of variation ranging from 3.3% to 7.8% for the three analytes. The corresponding inter-day coefficients of variation ranged from 4.2% to 8.6%. The reproducibility and sensitivity of the assay, combined with the selectivity of mass spectrometric detection, should allow an accurate kinetic characterization of terfenadine oxidation mediated by the high affinity CYP3A enzymes in human liver and intestinal microsomes.

Alkylation↗

Pseudopelade of Brocq in beard area.

Pseudopelade is a rare self-limited hair disorder, resulting in cicatricial alopecia. It presents with skin-colored alopecic patches primarily involving the parietal and vertex portions of the scalp. This is a case report of a patient with pseudopelade that involves both his scalp and beard area.

Adult↗

Dietary protein level and origin (casein and highly purified soybean protein) affect hepatic storage, plasma lipid transport, and antioxidative defense status in the rat.

The effects of different proportions (10, 20, and 30%) of dietary casein or highly purified soybean protein on lipid metabolism were studied in growing Wistar rats. Hepatic, plasma and lipoprotein lipid, and protein concentrations, plasma thiobarbituric acid-reactive substance (TBARS) levels, and resistance of red blood cells against free-radical attack were determined after a 4-wk dietary regimen. Compared with the 20% casein diet, the 20% soybean protein diet exhibited similar cholesterolemia but lower plasma triacylglycerol concentrations and very-low-density lipoprotein (VLDL) particle number, as measured by diminished contents of VLDL-triacylglycerol, VLDL-protein, and VLDL-apolipoprotein (Apo) B (B-100 and B-48). The soybean protein diet raised high-density lipoprotein (HDL)(2-3) particle number, as measured by enhanced concentrations of HDL(2-3) cholesterol, HDL-phospholipid, and HDL-ApoA-I. Increasing casein or soybean protein level (from 10 to 30%) in the diet involved higher VLDL-ApoB (B-100 and B-48), indicating an increase in the number of VLDL particles. Feeding the 30% casein or 30% soybean protein diet enhanced LDL-HDL(1) cholesterol contents. Despite similar HDL(2-3)-ApoA-I levels, the 30% casein diet enhanced the HDL(2-3) mass and its cholesterol concentrations. In contrast, feeding either the 10 or 30% soybean protein diet significantly lowered HDL(2-3) cholesterol and ApoA-I levels. These effects on cholesterol distribution in lipoprotein fractions occurred despite unchanged total cholesterol concentrations in plasma. Feeding 20% soybean protein versus 20% casein involved lower plasma TBARS concentrations. Decreasing casein or soybean protein levels in the diet were associated with higher plasma TBARS concentrations and had a lower resistance of red blood cells against free-radical attack. The present study shows that dietary protein level and origin play an important role in lipoprotein metabolism and the antioxidative defense status but do not affect total cholesterol concentrations in plasma.

Animals↗

Diagnosis of Helicobacter pylori infection from antral biopsies in pediatric patients is urease test that reliable?

Our objectives were to determine if the urease (CLO) test alone is a reliable diagnostic test for H. pylori gastritis in children and if the density of H. pylori influences the CLO test result. We performed a combined retrospective and prospective study reviewing the results of CLO-test and histology of gastric mucosal biopsy from 67 patients (35 females) with H. pylori gastritis. Two antral biopsies were inoculated on the CLO-test and two processed for histology to grade the severity of gastritis and H. pylori density. The mean age of patients was 11 years (SD +/- 4.53). Only 50 patients tested positive for H. pylori on CLO-test, whereas all patients were positive on histology. The sensitivity of the CLO-test was 75%. There was a significant association between CLO-test positivity and the density of H. pylori organisms on histology (P < 0.01), and with the severity of gastritis (P < 0.001) by the Pearson chi-square test. However, there was no association between the density of H. pylori and severity of gastritis. In conclusion, the CLO-test is not reliable as a sole diagnostic test for H. pylori gastritis in children because of a significant number of false negatives. Histologic examination of gastric mucosal biopsy is superior to the CLO-test in diagnosing H. pylori infection.

Adolescent↗

Time course of changes in serum glucose, insulin, lipids and tissue lipase activities in macrosomic offspring of rats with streptozotocin-induced diabetes.

The aim of this investigation was to determine the time course of changes in serum glucose, insulin and lipid levels, as well as lipid and protein content and lipolytic activities in insulin target organs (liver, adipose tissue and muscle), in macrosomic offspring of streptozotocin-induced mildly hyperglycaemic rats. Food intake and nutritional efficiency were also evaluated. Mild hyperglycaemia in pregnant rats was induced by intraperitoneal injection of streptozotocin (40 mg/kg body weight) on day 5 of gestation. Control pregnant rats were injected with citrate buffer. At birth, macrosomic pups (birth weight >1.7 S.D. greater than the mean value for the control pups) had higher serum insulin, glucose and lipid levels than control pups. These macrosomic rats maintained accelerated postnatal growth combined with high adipose tissue weight up to 12 weeks of age. These rats were not hyperphagic; however, they had higher food efficiency and fat storage capacity with higher adipocyte lipoprotein lipase activity, which contributed to persisting obesity. Hepatic lipase activity was increased in macrosomic rats at all ages. Moreover, macrosomia was associated with metabolic disturbances that varied according to age and sex. After 1 month, several alterations observed at birth had disappeared. Serum glucose, insulin and lipid levels in male and female macrosomic rats became similar to those of their respective controls. At 2 months of age, hepatic and serum triacylglycerol levels were higher in macrosomic females than in controls. By 3 months, macrosomic rats (both males and females) had developed insulin resistance with hyperinsulinaemia, hyperglycaemia, and higher serum and hepatic lipids. In conclusion, macrosomia was associated with alterations in glucose and lipid metabolism through to adulthood. It should be considered as an important potential risk factor for obesity and its metabolic complications.

Adipose Tissue↗

Unplanned incomplete Mohs micrographic surgery.

BACKGROUND: Incomplete Mohs micrographic surgery (MMS) is the cessation of MMS while the tumor margins are known to be still positive. OBJECTIVE: Our purpose was to examine the factors behind unplanned incomplete MMS and to identify means of avoiding and managing this situation when it arises. METHODS: We performed a retrospective case review examining clinical presentations, histologic features, and management of incomplete MMS. RESULTS: Fifteen of 10,346 procedures (0.15%) were identified as incomplete MMS. Complete records were available in 14 cases. The age range was 30 to 90 years; the study comprised 10 men and 4 women. The tumors included 9 basal cell and 4 squamous cell carcinomas and 1 dermatofibrosarcoma protuberans. The sites involved were nose, medial canthus, ear, scalp, and lower eyelid. Twelve cases dealt with unresectable disease, whereas two patients were unable to tolerate further surgery. Of the unresectable cases, MMS was terminated because of ongoing multifocal positive skin margins, bony invasion, or extension of tumor to other locations. Surgical defects were repaired, whereas residual disease was managed with a variety of methods. CONCLUSION: Incomplete MMS is a rare problem of either unresectable disease or inability of the patient to tolerate the procedure. Preoperative planning may help to identify both subgroups of patients. A multispecialty approach to managing these cases is often necessary.

Adult↗

Maternal and fetal serum lipid and lipoprotein concentrations and compositions in type 1 diabetic pregnancy: relationship with maternal glycemic control.

The aim of this study was to determine maternal and fetal lipoprotein profiles in type 1 diabetic pregnancies differing in glycemic control. Serum lipid, apolipoprotein, and lipoprotein lipid concentrations were investigated in mothers with poorly controlled or well-controlled type 1 diabetes as reflected by hemoglobin A1c(HbA1c) concentrations performed by isolab column chromatography and in their macrosomic (body wt = 4650 +/- 90 g) or appropriate-for-gestational-age newborns (body wt = 3616 +/- 68 g), and these levels were compared with those in healthy mothers and in their control newborns (body wt = 3290 +/- 45 g). In mothers with well-controlled diabetes and in their infants, serum lipid, apolipoprotein, and lipoprotein lipid concentrations were comparable to those in control mothers and in their control newborns. Mothers with poorly controlled diabetes presented higher serum triglyceride and apoprotein B-100 (apo B-100) levels but lower apo A-I and HDL3 cholesterol and phospholipid levels as compared with control values. In their macrosomic newborns, all serum lipid, apolipoprotein, and lipoprotein lipid levels were higher than those in control newborns. Maternal HbA1c and triglyceride levels in late gestation were significant predictors of fetal lipids and lipoproteins in the poorly controlled diabetes group. In conclusion, when under good metabolic control, type 1 diabetes did not affect maternal and fetal lipid levels. However, when under poor metabolic control, type 1 diabetes is associated with maternal and fetal lipoprotein abnormalities.

Adult↗

Fetal macrosomia related to maternal poorly controlled type 1 diabetes strongly impairs serum lipoprotein concentrations and composition.

AIMS: To determine the effects of fetal macrosomia related to maternal type 1 diabetes on the lipid transport system. METHODS: Serum lipoprotein concentrations and composition and lecithin:cholesterol acyltransferase (LCAT) activity were investigated in macrosomic newborns (mean birth weight, 4650 g; SEM, 90) and their mothers with poorly controlled type 1 diabetes, in appropriate for gestational age newborns (mean birth weight, 3616 g; SEM, 68) and their mothers with well controlled type 1 diabetes, and macrosomic (mean birth weight, 4555 g; SEM, 86) or appropriate for gestational age (mean birth weight, 3290 g; SEM, 45) newborns and their healthy mothers. RESULTS: In mothers with well controlled type 1 diabetes, serum lipids, apolipoproteins, and lipoproteins were comparable with those of healthy mothers. Similarly, in their infants, these parameters did not differ from those of appropriate for gestational age newborns. Serum triglyceride, very low density lipoprotein (VLDL), apolipoprotein B100 (apo B100), and high density lipoprotein (HDL) triglyceride concentrations were higher, whereas serum apo A-I and HDL3 concentrations were lower in mothers with diabetes and poor glycaemic control than in healthy mothers. Their macrosomic newborns had higher concentrations in all serum lipids and lipoproteins, with high apo A-I and apo B100 values compared with appropriate for gestational age newborns. In macrosomic infants of healthy mothers, there were no significant differences in lipoprotein profiles compared with those of appropriate for gestational age infants. LCAT activity was similar in both groups of mothers and newborns. CONCLUSION: Poorly controlled maternal type 1 diabetes and fetal macrosomia were associated with lipoprotein abnormalities. Macrosomic lipoprotein profiles related to poor metabolic control of type 1 diabetes appear to have implications for later metabolic diseases.

Adult↗

Alopecia areata update.

Alopecia areata (AA) is a nonscarring hair loss condition. Among the many factors under investigation in the pathogenesis of AA, the main areas of concentration have been genetic constitution as well as nonspecific immune and organ-specific autoimmune reactions. Treatment with intralesional corticosteroid injections for localized patchy AA and topical immunotherapy for extensive AA have proven successful in the majority of patients, although all treatments are palliative and do not change the prognosis of the disease.

Administration, Topical↗

Changes in serum lipid and lipoprotein concentrations and compositions at birth and after 1 month of life in macrosomic infants of insulin-dependent diabetic mothers.

The aim of this study was to determine whether macrosomia related to maternal diabetes alters lipoprotein metabolism and whether these abnormalities still persist or regress after 1 month of life. Serum lipoprotein compositions and concentrations as well as serum lipid fatty acid compositions were investigated in macrosomic infants (birth weight = 4840 +/- 105 g at term) of insulin-dependent diabetic mothers at birth and after 1 month of life, and were compared to those of control infants (birth weight = 3400 +/- 198 g at term) of healthy mothers. Compared to controls, at birth, macrosomic newborns had higher serum lipids, apolipoprotein A-I and B-100, and lipoprotein (very low density lipoprotein, low density lipoprotein, high density lipoprotein-2 and high density lipoprotein-3) levels. Higher percentages of C18:2n-6 in serum triacylglycerols, phospholipids and cholesteryl esters were also observed. At day 30, in macrosomics, serum triacylglycerol, apo B-100, very low density lipoprotein and low density lipoprotein levels were still significantly higher. C18:2n-6 and C18:3n-3 contents in serum phospholipids, triacylglycerols and cholesteryl esters were reduced while C20:4n-6 and C22:6n-3 contents in serum phospholipids and cholesteryl esters were enhanced, compared to control values. Macrosomia was associated with alterations in lipoprotein compositions and concentrations at birth, some of which persisted after 1 month of life, and might play a role in the pathogenesis of diabetes and atherosclerosis in adult life.

Case-Control Studies↗

Comparison of CYP2D6 content and metoprolol oxidation between microsomes isolated from human livers and small intestines.

PURPOSE: To assess the role of intestinal CYP2D6 in oral first-pass drug clearance by comparing the enzyme content and catalytic activity of a prototype CYP2D6 substrate, metoprolol, between microsomes prepared from human intestinal mucosa and from human livers. METHODS: Microsomes were prepared from a panel of 31 human livers and 19 human intestinal jejunal mucosa. Microsomes were also obtained from the jejunum, duodenum and ileum of four other human intestines to assess regional distribution of intestinal CYP2D6. CYP2D6 content (pmole/mg microsomal protein) was determined by Western blot. CYP2D6 activity was measured by alpha-hydroxylation and O-demethylation of metoprolol. RESULTS: Kinetic studies with microsomes from select livers (n = 6) and jejunal mucosa (n = 5) yielded K(M) estimates of 26 +/- 9 microM and 44 +/- 17 microM, respectively. The mean Vmax (per mg protein) for total formation of alpha-OH-M and ODM was 14-fold higher for the liver microsomes compared to the jejunal microsomes. Comparisons across intestinal regions showed that CYP2D6 protein content and catalytic activity were in the order ofjejunum > duodenum > ileum. Excluding the poor metabolizer genotype donors, CYP2D6 content varied 13- and 100-fold across the panels of human livers (n = 31) and jejunal mucosa (n = 19), respectively. Metoprolol alpha-hydroxylation activity and CYP2D6 content were highly correlated in the liver microsomes (r = 0.84, p < 0.001) and jejunal microsomes (r = 0.75, p < 0.05). Using the well-stirred model, the mean microsomal intrinsic clearance (i.e., Vmax/K(M)) for the livers and jejunum were scaled to predict their respective in vivo organ intrinsic clearance and first-pass extraction ratio. Hepatic and intestinal first-pass extractions of metoprolol were predicted to be 48% and 0.85%, respectively. CONCLUSIONS: A much lower abundance and activity of CYP2D6 are present in human intestinal mucosa than in human liver. Intestinal mucosal metabolism contributes minimally to the first-pass effect of orally administered CYP2D6 substrates, unless they have exceptionally high microsomal intrinsic clearances and/or long residence time in the intestinal epithelium.

Adrenergic beta-Antagonists↗

The scalp biopsy: making it more efficient.

BACKGROUND: The scalp biopsy plays an important role in diagnosis and subsequent management of many scalp disorders. This simple diagnostic procedure can be time-consuming and frustrating for most dermatologists. OBJECTIVE: To outline an efficient technique for performing a scalp biopsy. METHODS: The technique of performing a scalp biopsy is reviewed and suggestions are made to make this time-consuming procedure more efficient. RESULTS: Sufficient specimen for histopathologic evaluation in a short perid of time is obtained. CONCLUSION: Attention to specific details in performing a scalp biopsy allows the physician to obtain a quick and histopathologically informative scalp biopsy.

Biopsy↗