A S Alhomida

King Saud University, Ar Riyāḑ, Ar Riyāḑ, Saudi Arabia

Are you A S Alhomida?

Claim your profile

Publications (93)143.88 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Diabetic retinopathy is widely recognized as a neurodegenerative disease of the eye. Increased oxidative stress has been considered the central factor in damaging neural retina in diabetes. Flavonoids, being powerful antioxidants, play protective roles in several oxidative stress-mediated neurodegenerative diseases. In this study, we analyzed the neuroprotective effects of a potential flavonoid, rutin, in the diabetic rat retina. Diabetes was induced in male Wistar rats by single injection of streptozotocin (65 mg/kg). In age-matched control (non-diabetic) and 1 week of diabetic rats, rutin (100 mg/kg/day) was orally administered and continued for 5 weeks. In another group of diabetic rats, only saline was supplemented. After treatments, retinas from all the groups were isolated and analyzed for potential neurotrophic factors and apoptotic and oxidative stress markers using biochemical and immunoblotting techniques. Our results indicate that rutin possesses antidiabetic activity, as blood glucose level decreased and insulin level increased in diabetic rats. In the diabetic retina, rutin supplementation enhanced the reduced levels of brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), and glutathione (GSH) (P < 0.05), and reduced the level of thiobarbituric acid-reactive substances (TBARS) (P < 0.05). In addition, rutin treatment showed antiapoptotic activity by decreasing the level of caspase-3 and increasing the level of Bcl-2 in the diabetic retina. These results suggest the effectiveness of rutin in ameliorating the levels of neuroprotective factors in diabetic retina. Therefore, rutin might be a potential flavonoid that can prevent the retinal damage and subsequently the development of diabetic retinopathy.
    Journal of Molecular Neuroscience 05/2015; 56(2). DOI:10.1007/s12031-015-0561-2
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Objective: To determine high sensitivity C-reactive protein (hsCRP) levels in patients with acute myocardial infarction (AMI) and its correlation with classical enzyme markers of myocardial damage. Study Design: Observational study. Place and Duration of Study: Department of Emergency Medicine at King Khalid University Hospital, King Saud University, Riyadh and Department of Physiology, from August 2010 to December 2011. Methodology: Consecutive eligible patients with either ST elevation myocardial infarction (STEMI) or non-ST elevation myocardial infarction (NSTEMI) who were admitted to the Emergency Department of King Khalid University Hospital were recruited. A total of 71 subjects were finally selected for the study. The hsCRP, Troponin I (Trop I), creatine kinase myocardial bound (CK-MB), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) concentrations of all patients with an acute myocardial infarction (AMI) were measured. Results: Among all patients 34 (47.9%) patients had diabetes mellitus, 21 (29.6%) were hypertensive, and 16 (22.5%) had no associated illness. Patients with STEMI had significantly higher levels of CKMB (p=0.0348), LDH (p=0.0471) and hsCRP (p=0.0231) compared to NSTEMI patients. While the differences were non-significant for Trop I (p=0.7022), AST (p=0.9729) and Lp(a) (p=0.5985). Spearman's correlations revealed that CRP correlated significantly with Trop I, CK-MB and LDH. There was a significant predictive relationship of hsCRP with Trop I, LDH and CK-MB while with AST it was nonsignificant. Conclusion: High sensitivity CRP levels is a significant predictor of standard markers for myocardial damage and it may be a useful prognostic marker in acute coronary syndromes.
    Journal of the College of Physicians and Surgeons--Pakistan: JCPSP 06/2014; 24(6):387-91.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Intravenous tissue plasminogen activator (TPA) infusion is one of the effective therapeutic approaches for acute myocardial infarction (AMI). Plasminogen activator inhibitor-1 (PAI-1) functions as a principal inhibitor of TPA and hence counteracts fibrinolysis. The overall fibrinolytic activity is mainly determined by the balance between TPA and PAI-1 levels. Considering the important role of these biomarkers in thrombotic pathway, we determined the levels of TPA and PAI-1 in sera of 50 AMI patients, 100 patients with associated risk factors and 100 healthy controls. Our results showed significantly higher levels of both TPA and PAI-1 in sera of AMI patients whereas the risk group patients (dyslipidemia and hypertension) showed only non-significant increases as compared with control gorup. Both these markers were not correlated with body mass index (BMI) however TPA showed significant correlation with age and PAI-1 with systolic blood pressure. In conclusion, a combination of these markers could provide a useful tool to assess the prognosis of AMI.
    "5th international conference on Bio marker & clinical research" university of oxford, UK; 02/2014
  • 29 th annual meeting of the Saudi Biological Society; 01/2014
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Diabetes-induced damages in brain are known as diabetic encephalopathy, which is well characterized by cellular, molecular and functional changes in the brain of diabetic subjects and rodents. However, little is known about the mechanism of damages and the therapeutic strategies in ameliorating those damages in the diabetic brain. In this study, we utilized a flavonoid, morin which is emerging as a potent drug against a wide range of free radical-mediated as well as neurodegenerative diseases. Morin (15 and 30 mg/kg body weight/day) was orally administered to two different groups of rats after 1 week of diabetes induction, and continued for five consecutive weeks. Two other untreated groups of diabetic and non-diabetic rats were used to compare with drug-treated groups. After drug treatments, cerebral cortex of the brain harvested and analyzed for different factors. Morin supplementation especially at high dose increased the levels of insulin, reduced glutathione, superoxide dismutase and catalase activities, and decreased fasting glucose and thiobarbituric acid reactive substances in the diabetic brain compared to untreated diabetic rats (P < 0.05). Morin also significantly decreased the level of inflammatory markers (TNFα, IL1β, IL-6) in the diabetic brain compared to untreated diabetic rats. Furthermore, the drug influenced an increase in the level of neurotrophic factors (BDNF, NGF and IGF-1) in the diabetic brain compared to untreated diabetic rats (P < 0.05). Thus, our results indicate a beneficial effect of morin by decreasing oxidative stress, inflammation and increasing the neurotrophic support in the diabetic brain, which may ameliorate diabetic encephalopathy.
    Neurological Sciences 01/2014; 35(7). DOI:10.1007/s10072-014-1628-5
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Tissue plasminogen activator (TPA) and plasminogen activator inhibitor-1 (PAI-1) have pro- and anti-fibrinolytic activities respectively. The net fibrinolytic activity is mainly determined by the balance between TPA and PAI-1 levels. Considering the important role of these markers in thrombotic pathway, we determined the levels of TPA and PAI-1 in sera of 50 AMI patients, 100 patients with associated risk factors (dyslipidemia and high blood pressure) and 100 healthy controls. The findings showed significantly high levels of TPA and PAI-1 in AMI patients as compared to control subjects. Both these markers were only non-significantly increased in the risk group. There was no correlation between body mass index and these markers however TPA and PAI-1 were significantly correlated with age and systolic blood pressure, respectively. In conclusion, a combination of these markers could provide a useful tool to assess the prognosis of AMI.
    International Journal of Clinical and Experimental Medicine 01/2014; 7(4):1059-63.
  • [Show abstract] [Hide abstract]
    ABSTRACT: Abstract Recently, American Diabetic Association has recommended glycated hemoglobin (HbA1c ≥6.5%) as an alternate to fasting plasma glucose (FPG ≥7.0 mmol/L) for diagnosis of diabetes. However, studies from different groups showed inconsistent results with the use of HbA1c criteria. We examined the validity of HbA1c cut-point of 6.5% for diagnosis of diabetes. A total of 12 785 male diabetic patients (FGP ≥7.0 mmol/L), aged 56.27 ± 13.32 years were included. The average values of FPG and HbA1c of all the 12 785 patients were 10.127 ± 0.026 mmol/L and 8.729 ± 0.013%, respectively. Sub-grouping of patients into different age categories showed significantly high levels of FPG (10.934 ± 0.123 mmol/L) in the youngest group (age, ≥20-35 years) as compared to FPG (ranged from 10.021 ± 0.052 to 10.190 ± 0.050 mmol/L) in patients with other age categories. The level of HbA1c was highest in the youngest group (8.809 ± 0.056%) and lowest in the oldest group (8.653 ± 0.082%). There was a significant correlation between FPG and HbA1c (R = 0.571, p < 0.001). There were 484 patients below the diagnostic threshold (HbA1c <6.5%), resulting in 3.78% false negative predictions. Majority of the false negative patients were in the age group of 40-75 years and had borderline FPG (7.0-8.0 mmol/L) and HbA1c (6.0-6.5%). These findings suggest that Saudi individuals with HbA1c between 6.0% and 6.5% may be considered as "probable diabetic" and their status should be verified by combined FPG and HbA1c criteria.
    Endocrine Research 09/2013; DOI:10.3109/07435800.2013.828740
  • [Show abstract] [Hide abstract]
    ABSTRACT: Earlier studies have suggested an important role of carnitine pathway in cardiovascular pathology. However, the redistribution of carnitine and acylcarnitine pools, as a result of altered carnitine metabolism, is not clearly known in patients with acute myocardial infarction (AMI). We compared the carnitine and acylcarnitine profiles of 65 AMI patients, including 26 ST-elevated myocardial infarction (STEMI) and 39 non-ST-elevated myocardial infarction (NSTEMI), 28 patients with chest pain and 154 normal controls. The levels of carnitine and acylcarnitines in the blood spots were determined using LC-MS/MS. Total and free carnitine levels were significantly higher in all the patient groups in the following order: STEMI > NSTEMI > chest pain. The levels of short- and medium-chain acylcarnitines were significantly higher in patient groups. Among the long-chain acylcarnitines, C14:2 and C16:1 levels were significantly increased in STEMI and NSTEMI. The ratio of free carnitine to short-chain or medium-chain acylcarnitines was significantly decreased in STEMI, NSTEMI and chest pain patients however a significant increase was observed in the ratio of carnitine to long-chain acylcarnitines in all the patient groups as compared to normal controls. In conclusion, alterations in carnitine and acylcarnitine levels in the blood of AMI patients indicate the possibility of impaired carnitine homeostasis in ischemic myocardium. The clinical implications of these findings for the risk screening or diagnosis and prognosis of AMI require additional follow-up studies on large number of patients. We also suggest that a dual-marker strategy using carnitine (longer plasma half-life) in combination with troponin (shorter plasma half-life) could be a more promising biomarker strategy in risk stratification of patients.
    Metabolomics 08/2013; 9(4):828-838. DOI:10.1007/s11306-013-0505-1
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The data on the biocompatibility of naked gold nanoparticles (GNPs) are scarce, and their interpretation is controversial. We studied the acute (1 day) and subchronic (5 days) effects of GNPs (10 and 50 nm diameter) on expression of interleukin-1 beta (IL-1 β ), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF- α ) in the liver and kidneys of rats. In the liver, the GNPs of both sizes (10 and 50 nm) significantly increased the cytokines gene expression on day 1 which was subsided on day 5; the GNPs of 50 nm size produced more severe inflammatory response as compared to smaller sized GNPs. In the kidney, the GNPs did not produce any significant change in the expression of IL-1 β . Although the gene expression of IL-6 and TNF- α was not affected by GNPs of 10 nm size, 50 nm GNPs significantly increased the expression of IL-6 and TNF- α in the kidneys of rats on day 1 after treatment which returned to normalcy on day 5. These findings indicate the possible immunocompatibility of medium sized GNPs as they caused only a transient acute phase increase in proinflammatory cytokines expression followed by their normalcy during the repeated exposure.
    05/2013; 2013:590730. DOI:10.1155/2013/590730
  • [Show abstract] [Hide abstract]
    ABSTRACT: Neurodegeneration is an early event in the diabetic retina which may lead to diabetic retinopathy. One of the potential pathways in damaging retinal neurons is the activation of renin angiotensin system including angiotensin II type 1 receptor (AT1R) in the diabetic retina. The purpose of this study was to determine the effect of telmisartan, an AT1R blocker on retinal level of brain derived neurotrophic factor (BDNF), ciliary neurotrophic factor (CNTF) and tyrosine hydroxylase (TH), glutathione (GSH) and caspase activity in the diabetic rats. The dysregulated levels of these factors are known to cause neurodegeneration in diabetic retina. Three weeks streptozotocin induced diabetic rats were orally treated or untreated with telmisartan (10 mg/kg/day). After 4 weeks of treatments, the levels of BDNF and GSH were found to be increased systemically in the sera as well as in the retina of diabetic rats compared to untreated rats as measured by enzyme-linked immunosorbent assay and biochemical techniques (p < 0.05). The caspase-3 activity in the telmisartan treated diabetic retina was decreased compared to untreated diabetic rats (p < 0.05). Western blotting experiments showed the expression levels of BDNF, CNTF and TH were increased compared to untreated diabetic rats (p < 0.05). Thus, our findings show a beneficial effect of AT1R blocker telmisartan in efficiently increasing neurotrophic support, endogenous antioxidant GSH content, and decreasing signs of apoptosis in diabetic retina.
    Neurochemical Research 04/2013; 38(8). DOI:10.1007/s11064-013-1058-4
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Diabetic retinopathy (DR) is the most common complication of diabetes. It causes vision loss, and the incidence is increasing with the growth of the diabetes epidemic worldwide. Over the past few decades a number of clinical trials have confirmed that careful control of glycemia and blood pressure can reduce the risk of developing DR and control its progression. In recent years, many treatment options have been developed for clinical management of the complications of DR (e.g., proliferative DR and macular edema) using laser-based therapies, intravitreal corticosteroids and anti-vascular endothelial growth factors, and vitrectomy to remove scarring and hemorrhage, but all these have limited benefits. In this review, we highlight and discuss potential molecular targets and new approaches that have shown great promise for the treatment of DR. New drugs and strategies are based on targeting a number of hyperglycemia-induced metabolic stress pathways, oxidative stress and inflammatory pathways, the renin-angiotensin system, and neurodegeneration, in addition to the use of stem cells and ribonucleic acid interference (RNAi) technologies. At present, clinical trials of some of these newer drugs in humans are yet to begin or are in early stages. Together, the new therapeutic drugs and approaches discussed may control the incidence and progression of DR with greater efficacy and safety.
    Medical science monitor: international medical journal of experimental and clinical research 04/2013; 19:300-8. DOI:10.12659/MSM.883895
  • [Show abstract] [Hide abstract]
    ABSTRACT: Brain iron accumulation and oxidative stress are common features of many neurodegenerative diseases, and could be due in part to increased iron influx across the blood–brain interface. The iron transport protein, divalent metal transporter 1 (DMT1) is found in reactive astrocytes of the lesioned hippocampal CA fields after excitotoxicity induced by the glutamate analog kainate (KA), but in order for iron to be transported by DMT1, it must be converted from the ferric to the ferrous form. The present study was carried out to investigate the expression of a ferric reductase, duodenal cytochrome b (DCYTB), in the rat hippocampus after KA injury. Quantitative reverse transcriptase-polymerase chain reaction showed significant increases in DCYTB mRNA expression of 2.5, 2.7, and 5.2-fold in the hippocampus at 1 week, 2 weeks and 1 month post-KA lesions respectively compared to untreated controls, and 3.0-fold compared to 1 month post-saline injection. DCYTB-positive cells were double labeled with glial fibrillary acidic protein, and electron microscopy showed that the DCYTB-positive cells had dense bundles of glial filaments, characteristic of astrocytes, and were present as end-feet around unlabeled brain capillary endothelial cells. DMT1 labeling in astrocytes and increased iron staining were also observed in the lesioned hippocampus. Together, the present findings of DCYTB and DMT1 localization in astrocytes suggest that DCYTB is a ferric reductase for reduction of ferric iron, for transport by DMT1 into the brain. We postulate that the coordinated action of these two proteins could be important in iron influx across the blood–brain interface, in areas undergoing neurodegeneration.
    Neuroscience 04/2013; 245:179–190. DOI:10.1016/j.neuroscience.2013.04.008
  • Haseeb Ahmad Khan, Abdullah Saleh Alhomida
    [Show abstract] [Hide abstract]
    ABSTRACT: Ischemic and reperfusion injuries in acute myocardial infarction (AMI) lead to mitochondrial dysfunction in heart cells. Lipid metabolism takes place in mitochondria where carnitine palmitoyltransferase (CPT) enzyme system facilitates the transport of long-chain fatty acids into matrix to provide substrates for beta-oxidation. We sequenced the coding regions of CPT1B and CPT2 genes to identify the single nucleotide polymorphism (SNP) in 23 AMI patients and 23 normal subjects. We also determined blood carnitine levels in these samples to study the impact of these SNPs on carnitine homeostasis. The sequencing of coding regions revealed 4 novel variants in CPT1B gene (G320D, S427C, E531K, and A627E) and 2 variants in CPT2 gene (V368I and M647V). There were significant increases in total carnitine (54.18 ± 3.11 versus 21.49 ± 1.03μmol/l) and free carnitine (37.78 ± 1.87 versus 10.06 ± 0.80μmol/l) levels in AMI patients as compared to normal subjects. CPT1B heterozygous variants of G320D and S427C among control subjects showed significantly higher levels of total and free carnitine in the blood. The homozygous genotype (AA) of CPT2 variant V368I had significantly less blood carnitine in AMI patients. Serum troponin T was significantly less in GG genotype of CPT1B variant S427C whereas the genotype AA of CPT2 variant V368I showed significantly higher serum troponin T levels. Further studies on large number of patients are necessary to confirm the role of CPT1B and CPT2 polymorphism in AMI.
    Gene 04/2013; 523(1). DOI:10.1016/j.gene.2013.03.086
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Diabetic retinopathy is widely considered to be a neurovascular disease. This is in contrast to its previous identity as solely a vascular disease. Early in the disease progression of diabetes, the major cells in the neuronal component of the retina consist of retinal ganglion cells and glial cells, both of which have been found to be compromised. A number of retinal function tests also indicated a functional deficit in diabetic retina, which further supports dysfunction of neuronal cells. As an endocrinological disorder, diabetes alters metabolism both systemically and locally in several body organs, including the retina. A growing body of evidences indicates increased levels of excitotoxic metabolites, including glutamate, branched chain amino acids and homocysteine in cases of diabetic retinopathy. Also present, early in the disease, are decreased levels of folic acid and vitamin-B12, which are potential metabolites capable of damaging neurons. These altered levels of metabolites are found to activate several metabolic pathways, leading to increases in oxidative stress and decreases in the level of neurotrophic factors. As a consequence, they may damage retinal neurons in diabetic patients. In this review, we have discussed those potential excitotoxic metabolites and their implications in neuronal damage. Possible therapeutic targets to protect neurons are also discussed. However, further research is needed to understand the exact molecular mechanism of neurodegeneration so that effective neuroprotection strategies can be developed. By protecting retinal neurons early in diabetic retinopathy cases, damage of retinal vessels can be protected, thereby helping to ameliorate the progression of diabetic retinopathy, a leading cause of blindness worldwide.
    International Journal of Molecular Sciences 02/2013; 14(2):2559-72. DOI:10.3390/ijms14022559
  • [Show abstract] [Hide abstract]
    ABSTRACT: Phospholipases A(2) (PLA(2)) are enzymes that cleave the sn-2 bond of membrane phospholipids to yield free fatty acids and lysophospholipids. Secretory PLA(2)-III (sPLA(2)-III) has been suggested to be important for neuronal differentiation, growth and survival, and is highly expressed in the spinal cord. The aim of this study is to elucidate its expression and distribution in different regions of the adult rat CNS. Quantitative RT-PCR analyses showed high levels of sPLA(2)-III mRNA expression in the brainstem and spinal cord and low expression in the olfactory bulb. Western blot analyses showed high level of expression in the brainstem, spinal cord and cerebral neocortex. A dense band corresponding to the catalytically active, mature/cleaved form, and a faint band corresponding to the full length sPLA(2)-III were detected in post-mitochondrial supernatants, from different parts of the CNS. Subcellular fractionation of spinal cord homogenates showed that sPLA(2)-III protein is present in the 'light membrane/cytosol' fraction, but not the nucleus, synaptosomal membrane or synaptic vesicle-enriched fractions. sPLA(2)-III was immunolocalized to neurons in the cerebral neocortex, Purkinje neurons in the cerebellar cortex, periaqueductal gray, red nucleus, spinal trigeminal nucleus and dorsal horn of the spinal cord. Electron microscopy of the spinal cord and cerebral neocortex showed that sPLA(2)-III was localized in dendrites or dendritic spines, that formed asymmetrical synapses with unlabeled, putatively glutamatergic, axon terminals. The localization of mature/cleaved form of sPLA(2)-III in postsynaptic structures suggest a physiological role of the enzyme in neurotransmission or synaptic plasticity.
    Neurochemical Research 01/2013; 38(4). DOI:10.1007/s11064-013-0974-7
  • Source
    Haseeb A Khan, Abdullah Saleh Alhomida, Samia Hasan Sobki
    [Show abstract] [Hide abstract]
    ABSTRACT: The biomarker potential of using various lipids fractions for predicting risk of acute myocardial infarction (AMI) is controversial. We therefore compared the lipid profiles, including serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL), high-density lipoprotein cholesterol (HDL) and triglycerides (TG), in 67 AMI patients. Patients included 28 STEMI (ST-elevated myocardial infarction) patients, 39 NSTEMI (non-ST-elevated myocardial infarction) patients and 25 patients with chest pain. Control group included 54 age- and gender-matched normal subjects. We also studied the correlation between lipid profile and systemic inflammation in these subjects. There were significant decreases in TC, LDL and HDL levels in both STEMI and NSTEMI patients as compared to normal subjects; however, patients with chest pain did not show any significant change in these lipids. Serum TG levels did not differ significantly among the study groups. There were significant increases in serum high-sensitive C-reactive protein (hs-CRP) levels in STEMI and NSTEMI patients, as compared to control group. Serum hs-CRP showed significant inverse correlation with HDL; however, hs-CRP was not correlated with TC, LDL, and TG. In conclusion, our findings suggest that reduction in serum TC does not prevent the risk of AMI, whereas a decrease in serum HDL and increase in hs-CRP strongly predisposes the risky individuals to an AMI event. We emphasize the importance of HDL and CRP measurements for the assessment of a combined lipid-inflammation risk factor that could be a useful predictor of high risk individuals, as well as a prognostic marker in AMI patients.
    Biomarker insights 01/2013; 8:1-7. DOI:10.4137/BMI.S11015
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Prothrombin time (PT) and activated partial thromboplastin time (aPTT) respectively measures the extrinsic and intrinsic pathways of coagulation and are used to determine the bleeding or clotting tendency of blood. We compared PT and aPTT levels in acute myocardial infarction (AMI) patients and normal subjects. There were significant increases in PT levels in patients with STEMI (15.98 ± 0.96 s), NSTEMI (16.03 ± 0.97 s) and chest pain (15.02 ± 0.54 s) as compared to control group (8.86 ± 0.08 s). The level of aPTT in control subjects was 31.35 ± 0.48 s. Patients with STEMI (40.79 ± 1.83 s), NSTEMI (41.33 ± 2.06) and chest pain (37.84 ± 1.66 s) showed significantly higher levels of aPTT. There was a significant correlation between PT and aPTT levels. Both PT and aPTT were significantly correlated with age however there was no correlation between these coagulation markers and gender or body mass index. In conclusion, both PT and aPTT are significantly increased in AMI patients on anticoagulation therapy. The elevations in PT values were more than 2.5-fold greater than aPTT suggesting a high potential of PT for predicting blood clotting tendency in patients receiving anticoagulation therapy.
    International Journal of Clinical and Experimental Medicine 01/2013; 6(4):294-7.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Most studies have used in vitro systems to test inflammatory responses of nanoparticles; these may not reflect the real biological response of body organs. In fact, certain nanoparticles have provoked opposite effects under in vitro and in vivo conditions. Current understanding of the biocompatibility of gold nanoparticles is controversial. We studied the acute (1 day) and sub-chronic (5 days) effects of gold nanoparticles (10 and 50 nm in diameter) on expression of interleukin-1 beta (IL-1β), IL-6 and tumor necrosis factor alpha (TNF-α) in rat liver. Real-time PCR analysis showed that gold nanoparticles of both sizes significantly increased cytokine gene expression on day 1; this had subsided by day 5. The 50-nm gold nanoparticle produced more severe inflammation than the smaller gold nanoparticle. These findings indicate a possible biocompatibility of medium-sized gold nanoparticles, as they caused only a transient increase in proinflammatory cytokines, followed by normalization during sub-chronic repeated exposure.
    Genetics and molecular research: GMR 01/2013; 12(4):5851-7. DOI:10.4238/2013.November.22.12
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Diabetic retinopathy (DR) is widely recognized as a neurovascular disease. Retina, being a neuronal tissue of the eye, produces neurotrophic factors for its maintenance. However, diabetes dysregulates their levels and thereby may damage the retina. Among neurotrophins, brain derived neurotrophic factor (BDNF) is the most abundant in the retina. In this study, we investigated the level of BDNF in the serum of patients with DR and also in the serum and retina of streptozotocin-induced diabetic rats. The level of BDNF was significantly decreased in the serum of proliferative diabetic retinopathy patients as compared to that of non-diabetic healthy controls (25.5 ± 8.5-10.0 ± 8.1 ng/ml, p < 0.001) as well as compared to that of diabetic patients with no retinopathy (21.8 ± 4.7-10.0 ± 8.1 ng/ml, p < 0.001), as measured by ELISA techniques. The levels of BDNF in the serum and retina of diabetic rats were also significantly reduced compared to that of non-diabetic controls (p < 0.05). In addition, the expression level of tropomyosin-related kinase B (TrkB) was significantly decreased in diabetic rat retina compared to that of non-diabetic controls as determined by Western blotting technique. Caspase-3 activity was increased in diabetic rat retina after 3 weeks of diabetes and remained elevated until 10 weeks, which negatively correlated with the level of BDNF (r = -0.544, p = 0.013). Our results indicate that reduced levels of BDNF in diabetes may cause apoptosis and neurodegeneration early in diabetic retina, which may lead to neuro-vascular damage later in DR.
    Cellular and Molecular Neurobiology 12/2012; DOI:10.1007/s10571-012-9901-8
  • [Show abstract] [Hide abstract]
    ABSTRACT: The phospholipase A2 (PLA2) family members are critical regulators of membrane structure and lipid composition and have been implicated in neuroinflammation, oxidative stress and neurodegeneration. Here, we review the published data describing regulation of cPLA2 and iPLA2 gene expression. Based on promoter sequence, cPLA2 expression can be regulated by glucocorticoid and pro-inflammatory cytokines, whereas transcription of iPLA2 can be controlled in response to sterol level. RNA degradation in 3′ UTR and epigenetic mechanisms may be involved in the regulation of cPLA2 and iPLA2 expression, respectively. MicroRNA target sequences lie within cPLA2 and iPLA2 mRNAs. Together, these findings indicate differential regulation of cPLA2 and iPLA2 expression. It is hoped that determination of diverse regulatory mechanisms of the PLA2 family may open new doors for development of novel therapeutic compounds that modulate PLA2 expression and function in the treatment of brain diseases.
    12/2012; 7(6). DOI:10.1007/s11515-012-9247-0