Estimation of tissue and serum lipocalin-2 in psoriasis vulgaris and its relation to metabolic syndrome.

Adipose tissue is now considered an endocrine organ secreting different cytokines known as adipocytokines. Lipocalin-2 has been recently identified as an adipokine present in the circulation, it is related to insulin resistance, obesity, atherosclerotic diseases and type 2 diabetes. Lipocalin-2 and psoriasis are assumed to be closely associated with the metabolic syndrome. The aim of the present study is to estimate the level of lipocalin-2 in the serum and tissue of psoriatic patients and to correlate these levels with markers of metabolic syndrome, CRP and disease severity. This study was done on 30 patients of psoriasis and 30 healthy controls. All patients and controls were subjected to clinical examination. Serum, tissue levels of lipocalin-2 and C-reactive protein (CRP) were measured by enzyme linked immunosorbent assay technique. Metabolic syndrome parameters including anthropometric measures, lipid profiles, blood sugar and blood pressure were studied. Patients with psoriasis showed significant association with metabolic syndrome parameters than controls. Tissue lipocalin-2 was significantly higher than serum levels in psoriasis patients. A significant difference was detected in tissue levels of lipocalin-2 and not in the serum between patients and controls. Both tissue and serum lipocalin-2 correlated with CRP. Although there was a correlation between tissue and serum levels of lipocalin-2 in patients, there was no correlation between both of them with metabolic syndrome and related disorders. Our results revealed that patients with psoriasis are at increased risk of metabolic and cardiovascular complications, tissue lipocalin-2 is more specific to psoriasis than serum lipocalin-2. Lipocalin-2 has no role in determining severity of the disease. Neither tissue nor serum lipocalin-2 conveys cardiovascular risk in psoriasis patients.

Detection of myxovirus resistance protein A in lichen planus lesions and its relationship to hepatitis C virus.

BACKGROUND: Lichen planus (LP) is an inflammatory disease of the skin and oral mucosa. Studies suggested that type I interferons (IFNs) could play an important role in the cytotoxic inflammation in LP. Type I IFNs stimulate the production of several IFN-induced proteins including myxovirus resistance protein A (MxA protein). The association of LP and chronic hepatitis C is well established, with variable prevalence rates among different populations. Many authors have considered hepatitis C virus (HCV) as a possible antigen for inducing cytotoxic immune response in LP. OBJECTIVES: To investigate the role of type I IFNs in LP through the detection of MxA protein, and to compare the expression of MxA protein between HCV-positive and HCV-negative patients with LP in an attempt to clarify the role of HCV in the pathogenesis of LP. METHODS: The study included 33 skin biopsies from patients with LP and 10 control biopsies. MxA mRNA was detected by reverse transcription-polymerase chain reaction. HCV-specific antibodies were detected in patient sera by enzyme-linked immunosorbent assay. RESULTS: Our analysis revealed a significantly higher level of MxA protein in all the LP skin biopsies compared with controls. The expression was significantly higher in HCV-positive patients than in HCV-negative patients. CONCLUSIONS: Type I IFNs play a role in the pathogenesis of LP, and HCV could induce LP through increasing the production of type I IFNs.

The role of heat shock protein 60, vascular endothelial growth factor and antiphospholipid antibodies in Behçet disease.

BACKGROUND: Behçet disease is a systemic inflammatory disease of unknown aetiology. T cells in this disease proliferate vigorously in response to a specific peptide of heat shock protein (HSP) 60 in an antigen-specific fashion. Vascular endothelial cell growth factor (VEGF) is a cytokine participating in the inflammatory process. One of the prominent features of Behçet disease is vasculitis as a result of endothelial dysfunction. Antiphospholipid antibodies (APA) may play a role in the development of thrombosis by inhibiting production of prostacyclin by endothelial cells. OBJECTIVES: To investigate the role of HSP60, VEGF and APA in Behçet disease and their relation to clinical manifestations and disease activity. METHODS: Thirty patients with Behçet disease were included; 17 were in the active stage and 13 were in the inactive. Fifteen age- and sex-matched healthy subjects served as controls. Complete clinical examination and Doppler examination were done. Serum levels of HSP60, VEGF and APA were performed. RESULTS: Serum levels of HSP60, VEGF and APA were significantly higher in patients than in controls; however, their level did not correlate with disease activity. The serum level of VEGF correlated significantly with the presence of vascular manifestations and ocular involvement. The serum level of APA was greater in patients with thrombosis. HSP60 has an important role in aetiopathogenesis of Behçet disease, which sheds new light on its autoimmune nature. CONCLUSIONS: An elevated serum level of VEGF may be a risk factor for the development of ocular disease contributing to poor visual outcome.

Evaluation of anti-thrombomodulin antibody as a tumor marker for vascular neoplasms.

BACKGROUND: Various endothelial markers are available for the evaluation of vascular tumors and malformations, including anti CD34, anti-CD31, von Willebrand factor (vWF), and anti-thrombomodulin (anti-TM) antibodies. All have their limitations, and we sought to compare the utility of anti-TM antibody as a marker for several types of vascular neoplasms vs. previously established endothelial markers. METHODS: We examined immunostaining profiles of 30 capillary hemangiomas, 10 pyogenic granulomas, five tufted angiomas, 17 Kaposi's sarcomas, and nine angiosarcomas. Immunostains for TM, CD34, and vWF were carried out using a labeled streptavidin-biotin peroxidase detection system. RESULTS: Anti-TM antibody showed moderately intense immunostaining in 89% of benign and malignant vascular neoplasms. Anti-CD34 antibody showed moderate to diffuse immunostaining in 98% of vascular neoplasms, and vWF showed weak focal staining in 84% of all vascular neoplasms examined. CONCLUSION: Anti-TM antibody proved to be a sensitive marker for both benign and malignant vascular neoplasms. While not as sensitive as anti-CD34, it may have some advantages in specificity that would make it a more reliable vascular tumor marker in certain situations.

Association of polycystic ovaries with the use of valproic Acid in jordanian epileptic patients.

OBJECTIVE: To investigate the frequency of occurrence of polycystic ovaries (PCO) in women taking valproic acid (VPA) as monotherapy for epilepsy. STUDY DESIGN AND PATIENTS: 163 epileptic patients were seen at the outpatient neurology clinic at Princess's Basma Teaching Hospital, Irbid, and Basheer Hospital, Amman, Jordan. A detailed medical history was taken from the patients followed by a clinical examination and vaginal ultrasonography of the ovaries. RESULTS: 102 patients (62.5%) had primary generalised seizures, 46 patients (28.2%) had partial seizures and 15 patients (9.2%) had partial secondary generalised seizures. Mean age +/- standard error of the mean (SEM) was 29.8 +/- 0.97 years. The duration of epilepsy and treatment with VPA were (mean +/- SD) 9.1 +/- 0.48 and 7.9 +/- 0.4 years, respectively. The dose and serum concentrations of VPA were (mean +/- SD) 983.9 +/- 101.96mg and 52.7 +/- 4.7 mg/L, respectively. Mean body mass index (BMI) was 25.6 +/- 0.92 kg/m(2). The mean weight gain was 6.6 +/- 1.3kg (range 2-24kg). Menstrual abnormalities were detected in 58 (35.6%) patients. Twelve patients (7.4%) had PCO; these patients were compared with 17 patients without PCO selected randomly. There was a statistically significant difference in testosterone level and BMI values in patients with PCO compared with those without negative PCO. Patients with PCO had a mean +/- SEM serum testosterone level of 1.2 +/- 0.18 mug/L and BMI values of 29.24 +/- 1.75 kg/m(2). However, patients without PCO had a serum testosterone level of 0.61 +/- 0.1 mug/L and a BMI of 21.91 +/- 0.7 kg/m(2). Menstrual abnormalities were detected in all patients with PCO and in eight patients without PCO. Hirsutism was found in four cases with PCO and in one case with no PCO. There were no statistically significant differences in the duration of therapy, doses and serum concentrations of VPA in patients with PCO compared with those without PCO. CONCLUSION: These results suggest an association between the use of VPA and PCO, hyperandrogenism, obesity and menstrual abnormalities. For women receiving VPA therapy, clinicians should consider performing an assessment of ovarian structure and function, especially if these patients develop menstrual cycle disturbances during treatment.

Evaluation of drug use in Jordan using WHO patient care and health facility indicators.

We prospectively studied current drug use in Jordan in 21 primary health care facilities in northern Jordan over a three-month period, using World Health Organization-recommended indicators. Both the mean time spent on physician-patient consultations (3.9 +/- 3.5 minutes) and mean pharmacy dispensing time (28.8 +/- 23.7 seconds) were short, resulting in a mean patient knowledge of prescribed drug dose of 77.7%. No centre had an essential drugs list and/or formulary available. An average of 80% of key drugs were available at centres. Baseline data gathered by this study can be used by researchers and policymakers to monitor and improve pharmaceutical prescribing and consumption practices in Jordan.

Evaluation of drug use in Jordan using WHO prescribing indicators.

Patterns of prescribing and use of pharmaceuticals by physicians and patients in Jordan have not previously been studied. We retrospectively evaluated pharmaceutical drug prescribing practices in 21 primary health care facilities in Irbid governorate, northern Jordan using World Health Organization-recommended core indicators. The mean number of drugs prescribed was 2.3 overall, ranging from 1.9 to 3.0. The percentage of drugs prescribed by generic name was very low, as was the percentage of prescriptions involving injections. The percentages of prescriptions involving antibiotics and drugs from the essential drugs list averaged 60.9% and 93% respectively. We conclude that the prescribing and use of drugs in Jordan requires rationalization, particularly the over-prescribing of antibiotics and the under-prescribing of generic drugs.

Evaluation of drug use in Jordan using WHO patient care and health facility indicators

We prospectively studied current drug use in Jordan in 21 primary health care facilities in northern Jordan over a three-month period, using World Health Organization-recommended indicators. Both the mean time spent on physician-patient consultations [3.9 +/- 3.5 minutes] and mean pharmacy dispensing time [28.8 +/- 23.7 seconds] were short, resulting in a mean patient knowledge of prescribed drug dose of 77.7%. No centre had an essential drugs list and/or formulary available. An average of 80% of key drugs were available at centres. Baseline data gathered by this study can be used by researchers and policymakers to monitor and improve pharmaceutical prescribing and consumption practices in Jordan

Evaluation of drug use in Jordan using WHO prescribing indicators

Patterns of prescribing and use of pharmaceuticals by physicians and patients in Jordan have not previously been studied. We retrospectively evaluated pharmaceutical drug prescribing practices in 21 primary health care facilities in Irbid governorate, northern Jordan using World Health Organization-recommended core indicators.The mean number of drugs prescribed was 2.3 overall, ranging from 1.9 to 3.0. The percentage of drugs prescribed by generic name was very low, as was the percentage of prescriptions involving injections. The percentages of prescriptions involving antibiotics and drugs from the essential drugs list averaged 60.9% and 93% respectively. We conclude that the prescribing and use of drugs in Jordan requires rationalization, particularly the over-prescribing of antibiotics and the under-prescribing of generic drugs

Allelic association between the DRD2 TaqI A polymorphism and Parkinson's disease.

Genes encoding proteins involved in dopaminergic transmission have been of special interest during the evaluation of candidate genes for Parkinson's disease (PD). The dopamine D2 receptor gene (DRD2) is located on chromosome 11 q22-q23, and several polymorphisms of the gene have been described. The DRD2 gene has a TaqI A restriction fragment length polymorphism that is located in the untranslated region, approximately 10 kilobases from the 3' end of the gene. This polymorphism creates the two alleles A1 (variant) and A2. In this study, we investigated the hypothesis that a TaqI repeat fragment length polymorphism in the dopamine D2 receptor gene may be associated with PD. DNA from 72 patients with PD, classified as definite, probable, or atypical PD, and from 81 controls was genotyped by polymerase chain reaction and gel electrophoresis for the presence of the TaqI A1 polymorphism. The controls were matched for age, race, and geographic origin. There were significant differences in allelic distribution between the overall PD group and control groups (chi2 = 5.009, p = 0.025). When only patients with definite PD were considered an even more significant association was found (chi2 = 8.2121, p = 0.004). Among the overall PD group, the odds ratio for having the variant allele A1 was found to be 2.2 (95% confidence interval, [1.1; 4.4]), whereas it was calculated to be 3.0 (95% confidence interval, [1.4; 6.4]) when only patients with definite PD were considered. The current study showed that there is a statistically significant association between the DRD2 variant allele A1 and PD. This association is most pronounced in patients with definite PD and becomes nonsignificant when the clinical picture is classified as atypical PD.

Variability of coumarin 7- and 3-hydroxylation in a Jordanian population is suggestive of a functional polymorphism in cytochrome P450 CYP2A6.

OBJECTIVE: To determine the variability of coumarin 7- and 3-hydroxylation in a human population and to evaluate the evidence for the existence of genetic polymorphism in these pathways. 7-Hydroxylation of coumarin is considered to be a detoxication pathway, whilst 3-hydroxylation, which predominates in rats, leads to hepatotoxicity in the rat. Coumarin metabolic phenotypes could aid in refining the risk evaluation for humans of dietary and environmental exposure to coumarin and for the chronic use of coumarin in high doses as a drug to treat lymphoedema and certain cancers. METHODS: Healthy male and female Jordanian volunteers (n = 103) were administered 2 mg coumarin by mouth and collected their 0-8-h urines. These, together with pre-dose blank urines, were analysed by selected-ion monitoring gas chromatography mass spectrometry for their content of the coumarin metabolites 7-hydroxycoumarin (70HC) and 2-hydroxyphenylacetic acid (2OHPAA), the latter arising from the 3-hydroxylation pathway. RESULTS: After coumarin administration, excretion of both 70HC and 2OHPAA was highly variable. A coumarin metabolic ratio (2OHPAA/7OHC) was suggestive of polymorphism. At least one subject had a metabolic response similar to an individual known to be both phenotypically and genotypically (CYP2A6 gene) 7-hydroxylation-deficient. CONCLUSION: In the light of the finding of high variability and possible polymorphism in both the 7- and 3-hydroxylation of coumarin in a human population. we recommend a reappraisal of the risk evaluation of human exposure to coumarin, particularly in pharmaceutical doses.

A single amino acid substitution (Leu160His) in cytochrome P450 CYP2A6 causes switching from 7-hydroxylation to 3-hydroxylation of coumarin.

Human populations are thought to metabolize coumarin almost exclusively by 7-hydroxylation. We have identified an individual who is homozygous for a single amino acid substitution (Leu160His) in the cytochrome P450 CYP2A6 arising from the variant CYP2A6*2 allele. On administration of coumarin (2 mg orally) no detectable 7-hydroxycoumarin was excreted in the 0-8-hr urine, rather, approximately 50% of the dose was eliminated as 2-hydroxyphenylacetic acid, the end-product of coumarin 3-hydroxylation. His immediate family members, who were heterozygous for the CYP2A6*2 allele, excreted little 2-hydroxyphenylacetic acid and mainly 7-hydroxycoumarin, when similarly tested. These findings raise a question regarding human risk evaluations for environmental coumarin exposures, since 7-hydroxylation is regarded as a detoxication pathway, but 3-hydroxylation as the process required to lead to macromolecular covalent binding of coumarin. Persons homozygous for the CYP2A6*2 allele may constitute 1-25% of various populations.

Dextromethorphan metabolism in Jordanians: dissociation of dextromethorphan O-demethylation from debrisoquine 4-hydroxylation.

The concentrations of dextromethorphan (DM) and its metabolites dextrorphan (DRP), 3-methoxymorphinan (MM) and 3-hydroxymorphinan (HM) were measured in 8 h urine samples from 266 unrelated healthy Jordanian subjects following oral administration of 30 mg dextromethorphan hydrobromide and using a rapid, sensitive and precise HPLC method with fluorometric detection. The frequency of the 'poor' metabolizer status of DM-O-demethylation as judged by log DM/DRP was found to be 6.8% with a 95% confidence interval of 3.8-9.8%. There was a strong correlation between log DM/DRP and log total non-O-demethylated compounds (NODM)/total O-demethylated metabolites (ODM) metabolic ratios (r = 0.96, P < 0.01). However, one subject with log DM/DRP of 0.05 that classifies him as a poor metabolizer was found to have a log NODM/ODM of -0.73 which is in the range of extensive metabolizer status suggesting the presence of another cytochrome P450 isoenzyme involved in dextromethorphan O-demethylation. Dextromethorphan N-demethylation to 3-methoxymorphinan was detected in 55.3% of individuals. Furthermore, a dissociation between dextromethorphan O-demethylation and debrisoquine (D) 4-hydroxylation has been observed. Among the 116 subjects phenotyped with both dextromethorphan and debrisoquine, 7 were poor metabolizers of both, three were poor metabolizers of debrisoquine and extensive metabolizers of dextromethorphan whilst 4 were poor metabolizers of dextromethorphan and extensive metabolizers of debrisoquine, one of whom was reclassified as an extensive metabolizer of dextromethorphan using log NODM/ODM to characterize dextromethorphan metabolizer status.

The effects of diclofenac on cryo-induced miosis.

The maintenance of pupil dilation is necessary for the success of scleral buckling procedures and in prophylactic transconjuctival cryopexy. To assess the miotic effect that is induced by cryotherapy and the ability of diclofenac sodium 0.1% (a potent prostaglandin synthetase inhibitor) to overcome such an effect, we conducted a randomized, masked and controlled experiment on 18 rabbits. These were divided into three groups; each group had their eyes treated by cryotherapy in a controlled fashion. Two groups were treated preoperatively with dilating drops: a solution without diclofenac in one group and one with diclofenac drops in the second. Pupil diameters were measured with Castroviejo's calipers by an independent observer at regular intervals. A third group had no drops and were treated as a control. A highly statistical difference was observed in the reduction of the miotic effect of cryotherapy in those eyes treated by diclofenac.

S-mephenytoin hydroxylation phenotypes in a Jordanian population.

We tested the ability of 194 unrelated, healthy Jordanian volunteers to metabolize S-mephenytoin. Mephenytoin (100 mg) was coadministered with debrisoquin (10 mg) orally and urine was collected for 8 hours. Mephenytoin metabolism was tested according to three measures: the amount of 4-hydroxymephenytoin, the S/R enantiomeric ratio, and the presence of a polar, acid-labile metabolite in urine collected for 8 hours after the dose. The S/R ratio and the presence of the acid-labile metabolite were determined in the urine of 16 patients who had low amounts of 4-hydroxymephenytoin (log hydroxylation index > or = 1). On examination of these three parameters of oxidation status, nine subjects were found to be poor metabolizers of mephenytoin by all three parameters. Thus 4.6% (95% confidence interval of 1.6% to 7.6%) of Jordanian subjects studied were poor metabolizers of mephenytoin. According to the Hardy-Weinberg Law, the frequency of the recessive autosomal gene controlling the poor metabolizer status of mephenytoin was predicted to be 0.215% (95% confidence interval of 0.146% to 0.283%). These results are on the same order of magnitude as those determined in European white populations and constitute the first report in Arab populations.

The N-oxidation of trimethylamine in a Jordanian population.

The ability to oxidise trimethylamine (TMA) to trimethylamine N-oxide (TMAO) is distributed polymorphically within a British white population with the majority of individuals excreting greater than 90% of total urinary TMA as TMAO. The opposite extreme is characterised by a rare inborn error of TMA N-oxidation known as the fish-odour syndrome. However there is a lack of information regarding inter-individual variability in the N-oxidation of TMA in other ethnic groups. In this study the urinary excretion of TMA and TMAO was determined over a period of 24 h in 82 Jordanian subjects. A frequency distribution histogram of % of total urinary TMA excreted as TMAO revealed that the majority of subjects excreted greater than 80% of the total urinary TMA as TMAO, however eight subjects (9.7%) excreted less than 80% of the total TMA as TMAO. In a previous study of 169 white British subjects only one (0.6%) excreted less than 80% of the total TMA as TMAO. The results suggest that the prevalence of compromised ability to N-oxidise TMA may be higher in a Jordanian population than in a British population.

Metoprolol alpha-hydroxylation is a poor probe for debrizoquine oxidation (CYP2D6) polymorphism in Jordanians.

The frequency distribution of the 8-h urinary ratio of log metoprolol/alpha-hydroxymetoprolol was assessed in 65 healthy, unrelated Jordanian volunteers. There was no apparent bimodality in the frequency distribution of this ratio among the subjects studied. The frequency of the poor metabolizer phenotype of metoprolol alpha-hydroxylation was 1.5% (one subject). There was a significant correlation (r = 0.61, P < 0.05, n = 39) between the log metoprolol/alpha-hydroxymetoprolol and the log debrisoquine/4-hydroxydebrisoquine ratios. However, the frequency of poor metabolizer status of debrisoquine among the 39 subjects was 7.7% (three subjects). Only one of the poor metabolizer of metoprolol alpha-hydroxylation. These findings indicate that metoprolol alpha-hydroxylation by CYP2D6 represents a poor probe for studying debrisoquine polymorphism in Jordanians.