Upregulation of BRCA1 and 2 protein expression is associated with dysregulation in amino acids profiles in breast cancer.

BACKGROUND: The prevalence of breast cancer (BC) is high among cancers in Egypt, ranking it the most common cause of cancer mortality in women. BRCA1 and BRCA2 tumor suppressors proteins have a specific relationship with BC. Plasma free amino acids levels (PFAAs) have been reported to exhibit altered profiles among cancer patients. Thus, the present study aims to examine the alteration of the PFAAs profiles and investigate their association with BRCA1 and 2 circulating levels in Egyptian females diagnosed with BC and in females with family history of BC to establish potential early detection strategies for BC. METHODS AND RESULTS: This study included 26 BC patients, 22 females with family history of BC (relatives) in addition to 38 healthy females as control group. Quantitative measurement of PFAAs was determined by the ion exchange separation method through high performance liquid chromatography. BRCA1 and BRCA2 concentrations were determined using ELISA. Our results showed PFAAs profiles in BC patients and in females with BC family history with significant upregulation in mean plasma levels of Alanine, Phenylalanine, Glutamate and Cysteine and downregulation of Taurine, Threonine, Serine, Glycine, Valine, Methionine and Histidine levels compared to controls. Also, a significant positive correlation was observed between plasma BRCA1 and Valine levels while a significant negative correlation was observed between BRCA2 and Lysine plasma levels. CONCLUSION: PFAAs profile can potentially be used in early screening for BC patients and for susceptible females.

Dysregulated miRNA-375, IL-17, TGF-ß, and Microminerals Are Associated with Calpain-10 SNP 19 in Diabetic Patients: Correlation with Diabetic Nephropathy Stages.

Zinc (Zn) and copper (Cu) have been shown to have the potential to improve glucose metabolism through interactions with cytokines and signaling events with multiple genes. miRNA-375 and the Calpin-10 gene are potential genetic biomarkers for the early prediction of diabetic nephropathy (DN). 128 healthy controls and 129 type 2 diabetic (T2DM) participants were matched for age and sex. Three subgroups were identified from the T2DM group: 39 patients had microalbuminuria, 41 had macroalbuminuria, and 49 patients had renal problems. Circulating miR-375 expression levels were measured via qPCR. Calpain-10 SNP 19 (rs3842570) genotyping was assessed with allele-specific PCR in all the included participants. Spectrophotometry was used to measure the concentrations of serum copper, zinc, and magnesium, while ELISA was used to measure the levels of TGF-ß and IL-17. There was significant up-regulation in the expression of miR-375 and serum levels of TGF-ß, IL-17, Cu, and the Cu/Zn ratio, whereas, in contrast to the control group, the Zn and Mg levels were lower in the T2DM group. The DN groups had significantly lower miR-375, TGF-ß, IL-17, Mg, and Zn levels compared with the T2DM without nephropathy group. Furthermore, between TGF-ß, IL-17, and miRNA-375, there were notable correlations. Calpain-10 SNP 19 genotype 22 and allele 2 were linked to a higher incidence of T2DM and DN. Significant TGF-ß, Cu, Cu/Zn ratio, HbAc1, and creatinine levels, but insignificant miRNA-375 levels, were associated with genotype 22 of Calpain-10 SNP 19. interactions between the Calpain-10 SNP 19 genotype 22 and IL-17, TGF-ß, mineral levels, and miRNA-375 might contribute to the aetiology of DN and T2DM and may have clinical implications for diagnosis and management.

Relationship between vitamin D and coronary artery disease in Egyptian patients.

BACKGROUND: Previous studies have reported conflicting results about the association of vitamin D (VD) level with coronary artery disease (CAD). We aimed to study the association of VD with atherosclerotic CAD in Egyptian individuals. RESULTS: We prospectively enrolled 188 consecutive CAD patients with a median age of 55(50-62) years; 151(80.3%) were male. All patients were diagnosed by cardiac catheterization and were compared with 131 healthy controls. VD levels were measured in serum samples of all participants. Compared to controls, CAD patients had a significantly lower median VD level, 14.65 (9.25-21.45) versus 42.0 (32.0-53.0) ng/mL, p < 0.001. VD was correlated with the number of diseased coronary arteries and lipid profile (total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides, p < 0.001 for each). By multivariate analyses, VD was an independent predictor of CAD [OR 1.22 (95% CI 1.07-1.4), p = 0.003, optimal cut-off value 30 ng/mL (AUC 0.92, sensitivity 81% and specificity 81.4%), p < 0.001], and the number of diseased coronary arteries, p < 0.001, especially three-vessel disease [OR 0.83 (95% CI 0.72-0.95), p = 0.008]. CONCLUSIONS: We have shown that low VD should be considered a non-traditional risk factor for CAD in Egyptian individuals. Low VD was correlated with coronary atherosclerosis, especially in patients with multivessel effects.

Circulating Ubiquitin Carboxyl Terminal Hydrolase L1 and Neuroglobin Levels in Traumatic Spinal Cord Injuries: Relation to Severity and Outcomes.

Introduction: Traumatic spinal cord injury (TSCI) is a life-threatening neurological disorder and there is a lack of biomarker research, particularly human studies that could help to categorize the severity and predict the outcome. We aimed to assess the role of serum Ubiquitin C-terminal hydrolase L1 (UCH-L1) and Neuroglobin (NGB) in predicting severity and outcome of TSCI. Methods: This prospective study included 63 participants categorized into 33 patients with various types of TSCI and 30 unrelated healthy volunteers. Neurosurgical [American spinal injury association (ASIA) impairment score (AIS)] and radiological [using spine computed tomography (CT) and magnetic resonance imaging (MRI)] assessments were performed on the included patients to determine the severity and the level of injury with neurological follow-up of patients within 6 months post-injury. Serum UCH-L1 and NGB were measured for all participants using commercially available ELISA assay kits. Results: Of the included patients, 20 (60.60%) had partial SCI and the remaining 13 patients (39.39%) had complete SCI. On follow-up, 19 patients (57.57%) showed improved AIS, while 14 cases (42.42%) did not show any improvement in their AIS scores. There was significantly higher median serum UCHL1 value among cases compared to controls (1723 pg/mL and 657 pg/mL, respectively), p ˂ 0.05. There was an insignificant rise of serum NGB levels among cases in comparison with the controls (15.2pg/mL and 7.52pg/mL, respectively, p ˃ 0.05). Significantly lower initial median serum UCHL1 levels (pg/mL) were observed in patients with improved AIS during the neurological follow-up compared with those who did not show any improvement in their AIS score (1723, and 4700 respectively, p ˂ 0.05), with lack of significant difference in the initial median serum NGB levels, p ˃ 0.05. Conclusion: Initial serum UCHL1 assay could be a helpful marker in reflecting the degree of TSCI and predicting its outcome, though NGB needs further assessment.

Measuring the Systemic Inflammatory Response to On- and Off-Pump Coronary Artery Bypass Graft (CABG) Surgeries Using the Tryptophan/Kynurenine Pathway.

Background: Cardiac surgeries induce many inflammatory responses with remarkable clinical implications. Tryptophan (Trp) is a precursor for serotonin, melatonin and kynurenine (Kyn). Plasma kynurenic acid (Kyna) and Kyn concentrations are thought to be related to the severity of inflammation. Plasma Trp/Kyn ratio is used to measure inflammatory cytokine activity.Methods: We performed the current longitudinal study in a tertiary care center and included 62 patients divided into two groups; group A (on-pump CABG patients) and group B (off-pump CABG patients). Plasma Trp and Kyn were measured using the high-performance liquid chromatography (HPLC) technique. Serum interlukin-6 (IL-6) and white blood cells (WBCs) were measured using ELISA and routine blood count, respectively.Results: The present study revealed that the intraoperative levels of plasma Kyn, IL-6 and WBCs were significantly increased while the plasma Trp/Kyn ratio was significantly decreased in both the groups; however, the changes were more significant in the on-pump CABG group. Moreover, the levels in both the groups returned to preoperative levels 72 h postoperative. Our study has shown that WBCs is positively correlated with IL-6, but has negative correlation with Trp/Kyn ratio.Conclusions: Kyn and Trp/Kyn ratio might be utilized as markers of the severity of inflammation in major surgery. In addition, off-pump CABG might be more preferable than on-pump CABG regarding stress and release of inflammatory markers.

Gephyrin and CYP2C9 Genetic Polymorphisms in Patients with Pharmacoresistant Epilepsy.

PURPOSE: Gephyrin (GPHN) is an essential protein in the regulation of inhibitory postsynaptic density and polymorphism in the corresponding gene may have a role in the development of pharmacoresistant epilepsy (PRE). For the first time, we aimed to evaluate the association of rs928553T/C variants with PRE susceptibility. Moreover, we have analyzed the genetic polymorphism affecting CYP2C9 "rs12782374G/A" in the same population to detect the effect of SNP on the drug-metabolizing ability of patients with PRE. PATIENTS AND METHODS: This case-control study enrolled 100 patients (group A) and 100 healthy, age and sex-matched controls, unrelated to patients (group B). TaqMan™ assays using real-time PCR were run for genotyping of rs928553T/C and rs12782374G/A in all participants. RESULTS: GPHN T>C polymorphism revealed significant risk association with occurrence of PRE using dominant, recessive and codominant models as follows: TT vs (TC+CC): OR 0.23, 95%CI: 0.13-0.43, P<0.001. In addition, (TT+TC vs CC): OR 0.38, 95%CI: 0.18-0.77, P<0.001. Also, T vs C (OR 0.34, 95%CI: 0.22-0.51, P=<0.001). Similarly, CYP2C9 G>A polymorphism showed a significant increased risk of PRE (GG vs (GA+AA): OR 0.11, 95%CI: 0.05-0.23, P<0.001). Furthermore, (GG+GA vs AA): OR 0.18, 95%CI: 0.084-0.39, P<0.001. Also, G vs A (OR 0.24, 95%CI: 0.15-0.366, P=<0.001). CONCLUSION: Mutation of both GPHN (rs928553) and CYP2C9 (rs1278237) genes may be implicated as a genetic mediators of resistance in patients with PRE.

Clinical, Biochemical, Molecular, and Therapeutic Analysis of Maple Syrup Urine Disease in Upper Egypt.

Maple syrup urine disease (MSUD) is an autosomal recessive inherited metabolic disorder caused by mutations in any of the genes encoding for the branched-chain keto dehydrogenase (BCKDH) components. This study screened MSUD patients throughout the whole Upper Egypt describing their symptoms, clinical and laboratory findings, genetic studies, and their treatment, with a 6-month follow-up for their responses. Screening identified three children with MSUD. Homozygous mutation in R195Q single nucleotide polymorphism (SNP) within the BCKDHA gene was found with the second MSUD patient. Follow-up for 6 months to assess the treatment regimens and progression of cases demonstrated that early treatment regimens including a dietary restriction of branched-chain amino acids with L-Carnitine administration could prevent MSUD-associated intellectual disabilities. It was concluded that R195Q SNP is pathogenic, and it may cause inherited forms of MSUD in some patients. MSUD cases have rarely been reported; so these findings will be highly useful for future cases of MSUD in the Upper Egyptian population.

Plasma amino acid metabolomic pattern in heart failure patients with either preserved or reduced ejection fraction: The relation to established risk variables and prognosis.

Communication between amino acids (AAs) and heart failure (HF) is unclear. We evaluate the plasma metabolomic profile of AAs in HF and its subgroups and association with clinical features. This is a case-control study in which 90 patients with HF, 63 with reduced ejection fraction (HFrEF) and 27 with preserved ejection fraction (HFpEF), were compared with 60 controls. The quantitative measurement of plasma concentrations of AA metabolites was performed using an AA analyzer. Compared with controls, HF patients had significantly higher levels of nine AAs and significantly lower levels of seven AAs. Leu, phenylalanine (Phe), and methionine (Met) were the independent predictors of HF that remained significant after adjustment for confounding factors in multivariate analysis. There was a significant difference in 10 AAs and some clinical features between HFpEF and HFrEF. The plasma levels of six AAs were significantly increased across the different New York Heart Association (NYHA) classes, (class II, class III, class IV) but they were not predictor of reduced EF and NYHA in multivariate regression analysis. There were significant associations between Leu, Phe, and Met with cardiovascular risk variables and prognosis. In conclusion, plasma Leu, Phe, and Met provide early prediction and prognostic values of HF. The plasma AAs could have significant impact on the risk-stratifying HFrEF and HFpEF and NYHA functional class but do not predict them.

Functional variants in the promoter region of macrophage migration inhibitory factor rs755622 gene (MIF G173C) among patients with heart failure: Association with echocardiographic indices and disease severity.

BACKGROUND: Heart failure (HF) is a serious public health concern resulting in death. An individual predisposition to HF is determined by relationship between genetic and environmental variables. The macrophage migration inhibitory factor (MIF) is a significant mediator that involved in a variety of inflammatory and cardiovascular diseases. To reveal contribution of MIF rs755622 G173C gene variants in the promoter region towards HF pathogenesis and investigate association between recognized genotype and clinical characteristics. PATIENTS AND METHODS: We recruited 90 patients with HF, 63 with preserved ejection fraction (HFpEF) and 27 with reduced ejection fraction (HFrEF), and 60 age- and sex- matched controls. MIF rs755622 (G>C) single-nucleotide polymorphism was genotyped by PCR-RFLP method. RESULTS: The GG genotype of MIF rs755622 gene polymorphism was more frequent in HF patients than in controls which increased the risk of HF by about 4.25 times (p<0.05). The distribution of the GG, GC and CC genotypes of MIF were 42%, 21% and 0.0% among HFrEF, and 33.3%, 55.6% and 11.1% among HFpEF respectively. Higher frequency of MIF rs755622 G allele among HFrEF (100%) compared to HFpEF (88.9%) (p = 0.007). MIF-GG genotype variant had significantly lower LVEF. In multivariate analysis, MIF-GG genotype was independent risk predictor among HF (OR 4.6). CONCLUSION: MIF rs755622 (GG) could be considered as a probable genotypic risk factor for HF, especially in those with HFrEF which increases the possibility that MIF contribute to HF progression. MIF genotype assay may serve as early predictor and help to recognize those at great risk of developing HF.

Biochemical Assessments of Seminal Plasma Zinc, Testis-Expressed Sequence 101 and Free Amino Acids and Their Correlations with Reproductive Hormones in Male Infertility.

The role of the male factors in the couple's infertility has been significantly increased in recent years due to a sententious assessment of male reproductive functions and enhanced diagnostic tools. We investigated the correlations among the seminal plasma (SP) levels of each of zinc, testis-expressed sequence 101 (TEX101), and free amino acids levels with reproductive hormones in adult fertile and infertile men. The study included 100 infertile men categorized into 50 non-obstructive azoospermic patients and 50 patients with idiopathic oligoasthenoteratozoospermia (iOAT), in addition to 50 fertile controls. Semen analyses, serum ELISA assays for male reproductive hormones (follicle-stimulating hormone (FSH), luteinizing hormone (LH), total testosterone, and prolactin), colorimetric assays of SP zinc and total proteins, SP free amino acids using high-performance liquid chromatography (HPLC), and ELISA assays of SP TEX101 were performed for all subjects. Infertile men with azoospermia had significantly lower SP median levels of zinc, TEX101, and many SP free amino acids compared to both men with iOAT and fertile controls (P Ë‚ 0.05 for all). There were lower SP levels of zinc and some free amino acids among men with iOAT compared to the fertile controls (P Ë‚ 0.05 for all) with non-significant difference regarding to SP TEX101 (P Ëƒ 0.05). Azoospermic men exhibited negative correlations between FSH, LH, and prolactin with some SP free amino acids (P Ë‚ 0.05 for all), and a positive correlation between glycine with total testosterone (P Ë‚ 0.05). Among iOAT patients, LH and FSH were positively correlated with SP zinc, TEX101, and some measured free amino acids (P Ë‚ 0.05 for all). Total testosterone was positively correlated with some amino acids, while prolactin was negatively correlated with glycine (P Ë‚ 0.05 for all). iOAT and azoospermic men exhibited low SP zinc and some free amino acids levels that were more pronounced in azoospermic men and were significantly associated with the reproductive hormones. TEX101 could be a helpful confirmatory test for azoospermia.

Cyclophilin A (CyPA) as a Novel Biomarker for Early Detection of Diabetic Nephropathy in an Animal Model.

BACKGROUND AND AIM: Type 2 diabetes mellitus (DM) is the most common single cause of the end-stage renal disease (ESRD). Cyclophilin A (CyPA) is an 18-kD protein. The connection between diabetic nephropathy (DN) and the secreted form of CyPA (sCyPA) has been elucidated in this study that aims to investigate sCyPA correlation with renal dysfunction. MATERIALS AND METHODS: Thirty-four male adult Wistar rats weighing 180-220 g were used. Animals were divided into a study group and a control group, 17 rats in each. Streptozotocin (STZ) and nicotine amide were used to damage some pancreatic cells for induction of type 2 DM. Comparison was made between the study and the control groups. Moreover, a comparison was made between the members of the study group before and after induction of DN. RESULTS: The rat model that exhibited a higher concentration of urinary sCyPA was detected early in the eighth week. There was a significantly higher level of 24-h urinary CyPA in the study group compared to the control group (p-value=0.004) and there was a significant elevation in the 24-h urinary Cyp-A in the study group after injection of STZ compared to the values before injection (p-value <0.001). Immunohistochemical analysis of renal tissue revealed that the mean expression of CyPA was higher in the study group than in the control group. For the urinary 24-h CYP-A, using a cutoff of 1.15 ng/mL, the accuracy was 72.4%, sensitivity was (77.8%) and specificity was (67%). CONCLUSION: According to this animal study, we proved that CyPA is a valuable marker for DN. It is a more sensitive, noninvasive and rapid biomarker for early detection of any renal affection in human diabetic patients.

Association between circulating microRNAs 486, 146b and 15b and serum betatrophin levels in obese; type 2 diabetic and non-diabetic children.

BACKGROUND: This study tested the association between serum levels of microRNA-486, -146b and -15b and betatrophin in normal and obese children with/without type 2 diabetes mellitus (T2DM). METHODS: the study included 120 children; divided into three groups: G1 (50 healthy), G2 (35 obese) and G3 (35 obese with T2DM). The levels of microRNA-486, 146b and 15b and serum betatrophin were measured by their corresponding methods. RESULTS: serum microRNA-486, -146b, -15b and betatrophin levels were significantly high in G3 followed by G2 then G1 (p = 0.002, > 0.001, > 0.001, and > 0.001, respectively). Especially in G3, these levels correlated positively with the BMI percentile (r = 0.44, 0.58, 0.38, and 0.46, p = 0.007, > 0.001, 0.021, and 0.005, respectively), serum glucose (r = 0.56, 0.49, 0.82, 0.60, and 0.42, p > 0.001, 0.003, > 0.001, and > 0.001, respectively) and HbA1c% (r = 0.56, 0.39, 0.66, and 0.42, p > 0.001, 0.019, > 0.001, and 0.032, respectively) while, showed negative correlations with correlated with serum insulin levels (r = - 0.37, - 0.42, - 0.58, and - 0.41, p = 0.021, 0.012, > 0.001 and 0.013, respectively) and with serum C-peptide levels (r = - 0.76, - 0.50, - 0.35 and - 0.42, p > 0.001, 0.002, 0.036 and 0.011, respectively). Serum betatrophin levels correlated positively with microRNA-486, -146b and -15b levels in G2 (r = 0.35, 0.80, and 0.67, p = 0.036, > 0.001, and,> 0.001, respectively), and in G3 (r = 0.57, 0.36, and 0.38, p > 0.001, 0.029 and, 0.023, respectively). CONCLUSIONS: Circulating microRNA-486, 146b and 15b increase significantly in obese children with T2DM and these levels correlate positively with serum betatrophin levels. Further studies are required to test the role of targeting of these microRNAs and betatrophin in the timely management of obesity and/or T2DM in children.

Assessments of Amino Acids, Ammonia and Oxidative Stress Among Cohort of Egyptian Autistic Children: Correlations with Electroencephalogram and Disease Severity.

OBJECTIVE: The current study aimed to assess the profiles of plasma amino acids, serum ammonia and oxidative stress status among autistic children in terms of electroencephalogram findings and clinical severity among the cohort of autistic Egyptian children. PATIENTS AND METHODS: The present study included 118 Egyptian children categorized into 54 children with autism who were comparable with 64 healthy controls. Clinical assessments of cases were performed using CARS in addition to EEG records. Plasma amino acids were measured using high-performance liquid chromatography (HPLC), while, serum ammonia and oxidative stress markers were measured using colorimetric methods for all included children. RESULTS: The overall results revealed that 37.04% of cases had abnormal EEG findings. Amino acid profile in autistic children showed statistically significant lower levels of aspartic acid, glycine, ß-alanine, tryptophan, lysine and proline amino acids with significantly higher asparagine amino acid derivative levels among autistic patients versus the control group (p˂0.05). There were significantly higher serum ammonia levels with significantly higher total oxidant status (TOS) and oxidative stress index (OSI) values among the included autistic children vs controls (p˂0.05). There were significantly negative correlations between CARS with aspartic acid (r=-0.269, P=0.049), arginine (r= - 0.286, p= 0.036), and TAS (r= -0.341, p= 0.012), and significantly positive correlations between CARS with TOS (r=0.360, p= 0.007) and OSI (r= 0.338, p= 0.013). CONCLUSION: Dysregulated amino acid metabolism, high ammonia and oxidative stress were prevalent among autistic children and should be considered in autism management. Still EEG records were inconclusive among autistic children, although may be helpful in assessment autism severity.

Comparative Protective Effects of N-Acetylcysteine, N-Acetyl Methionine, and N-Acetyl Glucosamine against Paracetamol and Phenacetin Therapeutic Doses-Induced Hepatotoxicity in Rats.

BACKGROUND AND AIMS: Both paracetamol (PA) and phenacetin (PH) are analgesic and antipyretic agents. Part of phenacetin therapeutic activity is attributed to its metabolism into paracetamol. Paracetamol causes direct hepatic oxidative stress damage. The present study aimed to investigate the possible damaging effects of both PA and PH, when used in therapeutic doses, on rat liver and to compare the antioxidant and hepatoprotective effects of N-acetylcysteine (NAC), N-acetyl-methionine (NAM), and N-acetylglucosamine (NAG) against PA- or PH-induced hepatic damage. METHODS: 90 male Wistar albino rats (120-140 gm) were undertaken, categorized randomly into 9 groups of 10 rats each, and administered by gavage for 2 weeks with DMSO 1% (controls), PA, PA+NAC, PA+NAM, PA+NAG, PH, PH+NAC, PH+NAM, and PH+NAG. Biochemical assays of malondialdehyde (MDA), nitric oxide (NO), reduced glutathione (GSH), total thiols, and alpha-fetoprotein (AFP) in liver homogenates and serum assays of ALT, AST, 8-hydroxy guanine (8-OH-Gua), and AFP were done. Also histopathological examinations of liver tissues in various groups were done. RESULTS: PA and PH cause significant increase in hepatic levels of MDA, NO, and AFP and serum ALT, AST, and 8-OH-Gua levels, with significant decrease in hepatic GSH and total thiols. NAG and NAC significantly improve the PA- and PH-induced hepatic and blood, biochemical, and histopathological disturbances, respectively. CONCLUSIONS: Both PA and PH induce oxidative stress in rat liver within their therapeutic doses. NAG and NAC in pharmacological doses can antagonize the oxidative damaging effect of both PA and PH.

Clinical and biochemical study of d-serine metabolism among schizophrenia patients.

BACKGROUND: Schizophrenia is a typical N-methyl-d-aspartate receptor (NMDA-R) hypofunction disorder. Decreased d-serine (d-Ser) levels in the periphery occur in schizophrenia and may reflect decreased availability of d-Ser to activate NMDA-R in the brain. OBJECTIVE: The objective of this study was to investigate the role of d-Ser metabolism in the pathogenesis of schizophrenia via biochemical assays and correlates, the serum level of d-Ser, d-serine racemase (SR) (responsible for its formation from l-serine [l-Ser]) and d-amino acid oxidase (DAAO) (responsible for its catabolism), among different clinical types of schizophrenia patients. PATIENTS AND METHODS: This cross-sectional case-control study was carried out on 100 patients and 50 controls. They were recruited from the outpatients' psychiatric unit of the Neuropsychiatric Department of Assiut University Hospital, Upper Egypt. The type of schizophrenia was determined according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), while the severity of schizophrenia was determined according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). Serum d-Ser levels were estimated using high-performance liquid chromatography (HPLC), while serum SR and DAAO were measured using commercially available enzyme-linked immunosorbent assay kits. RESULTS: There were significantly lower mean serum levels of d-Ser and SR and significantly higher mean serum levels of DAAO (P-value <0.01 for each) among schizophrenia patients when compared with the control group. Paranoid schizophrenia had the highest frequency, with a significantly lower serum levels of d-Ser and SR in the residual type and significantly higher serum levels of DAAO in undifferentiated and catatonic types. Combined receiver-operating characteristic curve for serum d-Ser, SR and DAAO indicated that the best serum level cutoff points at which schizophrenia manifestations started to appear were ≤ 61.4 mg/L for d-Ser, ≤ 15.5 pg/mL for SR and >35.6 pg/mL for DAAO. CONCLUSION: The present study confirms that disturbed d-Ser metabolism could be implicated in the pathogenesis of schizophrenia.

Surfactant protein D, soluble intercellular adhesion molecule-1 and high-sensitivity C-reactive protein as biomarkers of chronic obstructive pulmonary disease.

OBJECTIVE: The aim of this study was to estimate the serum levels of surfactant protein D (SP-D), soluble intercellular adhesion molecule-1 (sICAM-1), and high-sensitivity C-reactive protein (hs-CRP) in patients with chronic obstructive pulmonary disease (COPD) and to assess the correlation of these indices with COPD severity. SUBJECTS AND METHODS: This analytic cross-sectional study was carried out on 64 COPD male patients, and 26 apparently healthy age-matched males as a control. Chest X-ray, spirometry and arterial blood gases were done for only COPD patients. Serum levels of SP-D, sICAM-1 and hs-CRP were determined by enzyme-linked immunosorbent assay in both patient and control groups. RESULTS: The serum levels of SP-D, sICAM-1 and hs-CRP were significantly higher in COPD patients than controls (p < 0.001 for each). Also, these biomarkers were significantly higher in stages III and IV compared to either stage I or II (p < 0.01 for each). SP-D was significantly positively correlated with sICAM-1 and hs-CRP (r = 515, p < 0.001; r = 501, p < 0.001, respectively) and negatively correlated with PaO2 (r = -0.651, p < 0.001) and all parameters of spirometry. CONCLUSION: SP-D, sICAM and hs-CRP were significantly higher in COPD patients in comparison with controls. Moreover, SP-D, sICAM-1, and hs-CRP were significantly negatively correlated with FEV1%. Accordingly, estimation of these biochemical indices may be used as biomarkers for assessment of COPD severity.

Increased circulating ANG II and TNF-α represents important risk factors in obese saudi adults with hypertension irrespective of diabetic status and BMI.

Central adiposity is a significant determinant of obesity-related hypertension risk, which may arise due to the pathogenic inflammatory nature of the abdominal fat depot. However, the influence of pro-inflammatory adipokines on blood pressure in the obese hypertensive phenotype has not been well established in Saudi subjects. As such, our study investigated whether inflammatory factors may represent useful biomarkers to delineate hypertension risk in a Saudi cohort with and without hypertension and/or diabetes mellitus type 2 (DMT2). Subjects were subdivided into four groups: healthy lean controls (age: 47.9±5.1 yr; BMI: 22.9±2.1 Kg/m(2)), non-hypertensive obese (age: 46.1±5.0 yr; BMI: 33.7±4.2 Kg/m(2)), hypertensive obese (age: 48.6±6.1 yr; BMI: 36.5±7.7 Kg/m(2)) and hypertensive obese with DMT2 (age: 50.8±6.0 yr; BMI: 35.3±6.7 Kg/m(2)). Anthropometric data were collected from all subjects and fasting blood samples were utilized for biochemical analysis. Serum angiotensin II (ANG II) levels were elevated in hypertensive obese (p<0.05) and hypertensive obese with DMT2 (p<0.001) compared with normotensive controls. Systolic blood pressure was positively associated with BMI (p<0.001), glucose (p<0.001), insulin (p<0.05), HOMA-IR (p<0.001), leptin (p<0.01), TNF-α (p<0.001) and ANG II (p<0.05). Associations between ANG II and TNF-α with systolic blood pressure remained significant after controlling for BMI. Additionally CRP (p<0.05), leptin (p<0.001) and leptin/adiponectin ratio (p<0.001) were also significantly associated with the hypertension phenotype. In conclusion our data suggests that circulating pro-inflammatory adipokines, particularly ANG II and, TNF-α, represent important factors associated with a hypertension phenotype and may directly contribute to predicting and exacerbating hypertension risk.

Time-dependent morphological and biochemical changes following cutaneous thermal burn injury and their modulation by copper nicotinate complex: an animal model.

BACKGROUND: Thermal tissue injury is partly mediated by reactive oxygen metabolites. Oxygen free radicals are contributory to local tissue damage following thermal injury and accordingly an interventional therapy using antioxidants may be beneficial. Copper nicotinate complex can scavenge reactive oxygen species (i.e., has antioxidant activity). OBJECTIVES: To examine time-related morphological and biochemical changes following skin thermal injury and their modulation by copper nicotinate complex. MATERIALS AND METHODS: An animal model composed of 80 albino rats was established. Ten rats (nonburn group) served as a control group. Seventy rats (burn group) were anesthetized, given a 10% total body surface area, full-thickness burn. Ten rats (from the postburn group) were sacrificed after 24 h (without treatment, i.e., untreated-burn group). The remaining rats were divided into three subgroups (20 rats, each) and were treated topically either with soft paraffin, moist exposed burn ointment (MEBO, a standard therapeutic treatment for burns), or copper nicotinate complex. Five animals from each subgroup were sacrificed every week over a period of 4 weeks. The morphological and biochemical changes were evaluated and compared among the different groups. RESULTS: High levels of the plasma and skin nitiric oxide (marker of oxidative stress) were observed in the untreated-burn group. These levels were significantly low following the application of copper nicotinate complex. Low levels of plasma and skin superoxide dismutase (marker of oxidative stress) and plasma ceruloplasmin were observed in the untreated-burn group. These levels were significantly high following copper nicotinate complex treatment. The total and differential leukocyte counts were low following the onset of the thermal injury. They gradually returned to normal levels over a 4-week period following the application of MEBO or copper nicotinate complex. Compared to untreated-burn group, postburn-healing changes (resolution of the inflammatory reaction, reepithelization of the epidermis, angiogenesis, deposition of collagen fibers, and recovery of the subcellualr organelles) were significantly accelerated following the application of either MEBO or copper nicotinate complex. CONCLUSIONS: Application of copper nicotinate complex was associated with improved healing of the thermal burns of the skin. The underlying molecular changes underlying these effects await further investigations.