Gheita, T. A., S. A. B. Kenawy, R. W. El Sisi, H. A. Gheita, and H. Khalil, "Subclinical reduced G6PD activity in rheumatoid arthritis and Sjögren's Syndrome patients: relation to clinical characteristics, disease activity and metabolic syndrome.", Modern rheumatology, vol. 24, issue 4, pp. 612-7, 2014. Abstract

OBJECTIVE: Glucose-6-phosphate dehydrogenase (G6PD) is an important site of metabolic control in the pentose phosphate pathway. The purpose of this study was to investigate the enzyme activity of G6PD in Rheumatoid Arthritis (RA) and Sjögren's Syndrome (SS) patients not known to be deficient in this enzyme. It was also within the scope of the aim to find the relation of G6PD to the presence of metabolic syndrome (MetS) in these patients.

METHODS: Erythrocyte G6PD activity was evaluated in 40 RA patients, 30 SS patients and in 30 age- and sex-matched control. The clinical characteristics, disease activity score (DAS28), SS disease activity (SSDAI) and damage (SSDDI) indices and presence of MetS of the included patients were analyzed in relation to the enzyme level.

RESULTS: The G6PD activity in RA patients (7.72 ± 3.57 U/g Hb) was significantly reduced compared to that in the SS patients (11.55 ± 3.14 U/g Hb) and control (13.23 ± 3.34 U/g Hb) especially those with MetS (4.61 ± 1.84 U/g Hb) (p < 0.001). There was a significant negative correlation of the G6PD activity with the disease duration and DAS28 (p < 0.001).

CONCLUSION: The results of this study, suggest that G6PD not only does not protect against MetS in RA, but may even be considered a risk factor for the development of this disorder. The identification of regulatory tools for G6PD activity may prove promising for treating the associated metabolic disorders and chronic inflammation in RA.

Gheita, T. A., I. I. El Gazzar, H. S. El-Fishawy, M. A. Aboul-Ezz, and S. A. Kenawy, "Involvement of IL-23 in enteropathic arthritis patients with inflammatory bowel disease: preliminary results.", Clinical rheumatology, vol. 33, issue 5, pp. 713-7, 2014. Abstract

The role of interleukin (IL)-23 in the pathogenesis of inflammatory bowel disease (IBD) remains unclear. The aim of this work was to study the serum level of IL-23 in IBD with and without arthritis and determine its relation to the subsets and clinical features of the disease. Thirty-seven patients with IBD including 11 with arthritis were included in the study with a mean age of 30.86 ± 4.66 years. Twenty healthy subjects served as control. Seronegative spondyloarthropathy was present in 11 (29.73 %) of the IBD patients; Crohn's disease (CD) was present in 23 and 14 had ulcerative colitis (UC). Serum level of IL-23 was measured in all patients and control by ELISA. IL-23 was significantly higher in IBD patients (46.24 ± 27.19 pg/ml) compared to control (24.1 ± 2.31 pg/ml) (p < 0.0001) being higher in CD patients (52.57 ± 32.78 pg/ml) compared to those with UC (35.86 ± 6.41 pg/ml) (p = 0.026). Furthermore, it was significantly higher in those with peripheral and/or axial arthritis (67.73 ± 40.85 pg/ml) compared to patients without (37.15 ± 10.37 pg/ml) (p = 0.03). There was a tendency to a higher level in males (49.15 ± 30.97 pg/ml) compared to females (38.4 ± 9.54 pg/ml). Serum IL-23 is increased in IBD especially those with CD associated with arthritis and sacroiliitis. The IL-23 could be added to the biomarkers of development of arthritis in IBD patients. These results also confirm the findings of previous studies on the critical role played by IL-23 in the pathogenesis of IBD making it an important new therapeutic target for these patients.

Gheita, T. A., and S. A. Kenawy, "Measurement of malondialdehyde, glutathione, and glutathione peroxidase in SLE patients.", Methods in molecular biology (Clifton, N.J.), vol. 1134, pp. 193-9, 2014. Abstract

Oxidative stress contributes to chronic inflammation of tissues and plays a central role in immunomodulation, which may lead to autoimmune diseases such as systemic lupus erythematosus (SLE) and antiphospholipid syndrome. Markers of oxidative damage include malondialdehyde (MDA), antioxidant scavengers as glutathione (GSH), and glutathione peroxidase (GSH Px), which all correlate well with SLE disease activity. Amelioration of some clinical manifestations of SLE may be expected by targeting lipid peroxidation with dietary or pharmacological antioxidants. Here, we describe the detection of the key players of oxidant/antioxidant imbalance in SLE.

El-Meligy, R. M., A. S. Awaad, G. A. Soliman, A. B. Bacha, A. M. Alafeefy, and S. A. Kenawy, "Prophylactic and curative anti-ulcerative colitis activity and the possible mechanisms of action of some desert plants.", Journal of enzyme inhibition and medicinal chemistry, vol. 30, issue 2, pp. 250-8, 2015. Abstract

The aim of the present study was to evaluate both prophylactic and curative anti-ulcerative colitis activity and the possible mechanism of action of seven desert plant extracts. Seven desert plants from different families; Conyza dioscoridis (L.) Desf. (Asteraceae), Euphorbia hirta L. (Euphorpiaceae), Origanum syriacum L. and Salvia lanigera L. (Lamiaceae), Sisymbrium irio L., Solanum nigrum Linn. (Solanaceae) and Solenostemma arghel (Del.) Hayne. (Asclepiadaceae) were separately evaluated at three doses (125, 250, and 500 mg/kg) using the acetic acid-induced colitis model. The investigated extracts possessed prophylactic and curative anti-ulcerative colitis activities in a dose-dependent manner, where Salvia lanigera (87.9) and Solenostemma arghel (89.2) were the most effective extracts whereas the dexamesathone produced 68%. These extracts were further investigated for estimation of their mechanism of action. The in vitro potential radical (DPPH) scavenging activities of the investigated extracts were well supported with the reduction of colonic MDA content for both extracts. Suppression of the inflammatory mediator TNF-α and inhibition of both PLA2 and protease enzymes may play an important role in the anti-ulcerative colitis activities. The investigated extracts were safe for use up to 5 g/kg and the total alcohol extracts of Salvia lanigera and Solenostemma arghel (400 mg/kg for 35 d) showed no alteration on liver and kidney functions. Phytochemical screening of the investigated extracts revealed the presence of flavonoids, tannins, unsaturated sterols, and proteins which could be responsible for the activities.

Gheita, T. A., S. Sayed, H. A. Gheita, and S. A. Kenawy, "Vitamin D status in rheumatoid arthritis patients: relation to clinical manifestations, disease activity, quality of life and fibromyalgia syndrome.", International journal of rheumatic diseases, vol. 19, issue 3, pp. 294-9, 2016. Abstract

AIM: To assess vitamin D levels in rheumatoid arthritis (RA) patients and to find their relation to clinical parameters, fibromyalgia syndrome (FMS), quality of life (QoL) and disease activity.

METHODS: The study included 63 RA patients and 62 controls. Clinical examination and laboratory investigations were performed. For patients, the Disease Activity Score (DAS-28), QoL index, Health Assessment Questionnaire II (HAQ II) and Modified Larsen score were calculated. 25-OH-vitamin D was measured in patients and controls.

RESULTS: The patients' mean age was 41.59 ± 9.69 years and disease duration 5.89 ± 3.67 years. The level of vitamin D in RA patients was significantly lower (23.11 ± 12.71 ng/mL) than that in the controls (32.59 ± 13.06 ng/mL) (P = 0.005) being deficient in 50.8%, insufficient in 23.8% and normal in 25.4%. The RA patients with FMS (n = 33) had significantly lower levels of vitamin D (19.08 ± 10.59 ng/mL) than those without (27.55 ± 13.51 ng/mL) (P = 0.008). The difference was significant on comparing those receiving hydroxychloroquine (17.39 ± 7.84 ng/mL) to those not (31.85 ± 13.85 ng/mL) (P < 0.001). Vitamin D significantly correlated with QoL index (r = 0.58, P < 0.001) and negatively with HAQ II (r = -0.36, P = 0.004) and BMI (r = -0.39, P = 0.001).

CONCLUSION: Special attention is required regarding vitamin D levels in RA patients with FMS and decreased QoL. Vitamin D should be corrected and supplementation considered among the RA management armamentarium.

Gheita, T. A., H. Ammar, and S. A. Kenawy, "Potential effect of Sildenafil beyond pulmonary hypertension in a patient with diffuse systemic sclerosis and cryoglobulinemic vasculitis.", SpringerPlus, vol. 3, pp. 559, 2014. Abstract

INTRODUCTION: Pulmonary arterial hypertension (PAH) is a serious complication of systemic sclerosis (SSc), has a dramatic impact on prognosis and survival and is a leading cause of death.

CASE DESCRIPTION: A 40 years old female patient with difuse cutaneous SSc (dcSSc) presented with progressive dyspnea, choking sensation, cough, abdominal distension, constipation and dysphagia to solids. The muscle power was mildly reduced and multiple purpuric eruptions were present on the legs of variable sizes. The patient was ANCA negative and had positive cryoglobulinemia. The hepatitis C virus test was positive and the skin biopsy histopathology proved small vessel (leucocytoclastic) vasculitis. The modified Rodnan total skin score (MRSS) was 37. There was deterioration of the pulmonary function tests and transesophageal echocardiography revealed PAH (RVSP 60 mmHg). Sildenafil 50 mg/day resulted in a remarkable improvement of the dyspnea and Raynauds' with a significant improvement of the skin tightness as the MRSS became 22. The small vessel vasculitic rash remarkably improved and the RVSP became 34 mmHg with a dramatic improvement of the PAH.

DISCUSSION AND EVALUATION: Sildenafil enhances vasodilatation, has antiproliferative effects and is effective in the treatment of PAH. The remarkable improvement in the vasculitic skin lesions in this case after sildenafil is the second report after the described dramatic improvement of small vessel vasculitis in a case with Takayasu arteritis. The emerging trends make it necessary to exploit the full therapeutic potential of Sildenafil in scleroderma and PAH with other extrapulmonary manifestations.

CONCLUSION: We report a very rare association of dcSSc with small vessel cryoglobulinemic vasculitis with a remarkable improvement after sildenafil.

El-Marasy, S. A., H. M. I. Abdallah, S. M. El-Shenawy, A. S. El-Khatib, O. A. El-Shabrawy, and S. A. Kenawy, "Anti-depressant effect of hesperidin in diabetic rats.", Canadian journal of physiology and pharmacology, vol. 92, issue 11, pp. 945-52, 2014. Abstract

This study aimed to investigate the anti-depressant effect of hesperidin (Hsp) in streptozotocin (STZ)-induced diabetic rats. Additionally, the effect of Hsp on hyperglycaemia, oxidative stress, inflammation, brain-derived neurotrophic factor (BDNF), and brain monoamines in diabetic rats was also assessed. The Wistar rats in the experimental groups were rendered hyperglycaemic with a single dose of STZ (52.5 mg·(kg body mass)(-1), by intraperitoneal injection). The normal group received the vehicle only. Hyperglycaemic rats were treated with Hsp (25.0, 50.0, or 100.0 mg·(kg body mass)(-1)·day(-1), per oral) and fluoxetine (Flu) (5.0 mg·(kg body mass)(-1)·day(-1), per oral) 48 h after the STZ injection, for 21 consecutive days. The normal and STZ control groups received the vehicle (distilled water). Behavioral and biochemical parameters were then assessed. When Hsp was administered to the STZ-treated rats, this reversed the STZ-induced increase in immobility duration in the forced swimming test (FST) and attenuated hyperglycaemia, decreased malondialdehyde (MDA), increased reduced glutathione (GSH) decreased interleukin-6 (IL-6), and increased BDNF levels in the brain. Treatment with Hsp attenuated STZ-induced neurochemical alterations, as indicated by increased levels of monoamines in the brain, namely, norepinephrine (NE), dopamine (DA), and serotonin (5-hydroxytryptamine; 5-HT). All of these effects of Hsp were similar to those observed with the established anti-depressant Flu. This study shows that Hsp exerted anti-depressant effect in diabetic rats, which may have been partly mediated by its amelioration of hyperglycaemia as well as its anti-oxidant and anti-inflammatory activities, the enhancement of neurogenesis, and changes in the levels of monoamines in the brain.

Asaad, M., R. M. Abdelsalam, S. A. Kenawy, and A. S. Attia, "Montelukast, a cysteinyl leukotriene receptor-1 antagonist protects against hippocampal injury induced by transient global cerebral ischemia and reperfusion in rats.", Neurochemical research, vol. 40, issue 1, pp. 139-50, 2015. Abstract

Cysteinyl leukotrienes (CysLTs) are potent pro-inflammatory and immune modulating lipid mediators involved in inflammatory diseases and were boosted in human brain after acute phase of cerebral ischemia. The antagonism of CysLTs receptors may offer protection against ischemic damage. Therefore it seemed interesting to study the possible neuroprotective effect of Montelukast, a CysLTR1 antagonist in global cerebral ischemia/reperfusion (IR) injury in rats. Global cerebral ischemia-reperfusion was induced by bilateral carotid artery occlusion for 15 min followed by 60 min reperfusion period. Animals were randomly allocated into three groups (n = 30 per group): Sham operated, I/R control and rats treated with montelukast (0.5 mg/kg, po) daily for 7 days then I/R was induced 1 h after the last dose of montelukast. After reperfusion rats were killed by decapitation, brains were removed and both hippocampi separated and the following biochemical parameters were estimated; lactate dehydrogenase activity, oxidative stress markers (lipid peroxides, nitric oxide and reduced glutathione), inflammatory markers (myeloperoxidase, tumor necrosis factor-alpha, nuclear factor kappa-B, interleukin-6 and interleukin-10), apoptotic biomarkers (caspase 3 and cytochrome C), neurotransmitters (glutamate, gamma aminobutyric acid), Cys-LTs contents and CysLT1 receptor expression; as well as total brain infarct size and histopathological examination of the hippocampus were assessed. Montelukast protected hippocampal tissue by reducing oxidative stress, inflammatory and apoptotic markers. Furthermore, it reduced glutamate and lactate dehydrogenase activity as well as infarct size elevated by I/R. These results were consistent with the histopathological findings. Montelukast showed a neuroprotective effects through antioxidant, anti-inflammatory and antiapoptotic mechanisms.

Sayed, R. H., W. K. B. Khalil, H. A. Salem, S. A. Kenawy, and B. M. El-Sayeh, "Sulforaphane increases the survival rate in rats with fulminant hepatic failure induced by D-galactosamine and lipopolysaccharide.", Nutrition research (New York, N.Y.), vol. 34, issue 11, pp. 982-9, 2014. Abstract

Fulminant hepatic failure (FHF) is a life-threatening clinical syndrome, with liver transplantation being the only effective therapy. Sulforaphane (SFN) is a natural compound that is extracted from cruciferous vegetables and possesses potent anti-inflammatory, antioxidant, and anticancer activities. This study was designed to test the hypothesis that SFN (3 mg/kg) may protect against FHF induced in rats by administering a combination of D-galactosamine (GalN; 300 mg/kg) and lipopolysaccharide (LPS; 30 μg/kg). The rats were given a single intraperitoneal injection of SFN, 1 hour before the FHF induction. Sulforaphane reduced the mortality and alleviated the pathological liver injury. In addition, SFN significantly reduced the increase in serum aminotransferase activities and lipid peroxidation. The glutathione content decreased in the GalN/LPS group, and this decrease was attenuated by SFN. Increases in serum tumor necrosis factor α, interleukin-6, and interleukin-10, which were observed in GalN/LPS-treated rats, were significantly reduced after using SFN. The GalN/LPS treatment increased the expression of superoxide dismutase-1, glutathione peroxidase 2, catalase, and heme oxygenase-1 genes. Sulforaphane inhibited the induction of reactive oxygen species scavenging proteins. Moreover, SFN inhibited GalN/LPS-induced caspase-3 activation and suppressed FAS and FASL expression. These findings suggest that SFN alleviates GalN/LPS-induced liver injury, possibly by exerting antioxidant, anti-inflammatory, and antiapoptotic effects and modulating certain antioxidant defense enzymes.

Gheita, T. A., G. S. Azkalany, S. A. Kenawy, and A. A. Kandeel, "Bone scintigraphy in axial seronegative spondyloarthritis patients: role in detection of subclinical peripheral arthritis and disease activity.", International journal of rheumatic diseases, vol. 18, issue 5, pp. 553-9, 2015. Abstract

AIM: To detect subclinical peripheral arthritis and disease activity in axial seronegative spondyloarthritis (SpA) patients using bone scintigraphy.

METHODS: Seronegative SpA patients with an established diagnosis and no clinically evident arthritis at the time of the study were included. After excluding symptomatic cases, 20 patients were recruited; 18 with ankylosing spondylitis (AS) and another two with psoriatic arthritis (PsA). Conventional bone scintigraphy was performed to detect the distribution of increased uptake, blood vascular pool (vascularity) and activity.

RESULTS: The peripheral joints in all the patients were asymptomatic with no signs of arthritis on clinical examination. Disease activity was higher in those with hypervascularity and activity (75%) detected by scintigraphy. Scintigraphic activity of the sacroiliac joints was found in 10 patients (50%) with a mean sacroiliac joint index of 2.4 ± 0.6. Subclinical involvement of the hips, knees, shoulders, ankles, small joints of the hands, ankles and sternoclavicular joints, as well as the small joints of the feet were detected with descending frequencies (25%, 25%, 20%, 20%, 15%, 10% and 10%, respectively). Dorsal spine increased uptake was found in 35% and hypervascularity of the skull in two cases. Avascular necrosis of the hip was present in one case with hypovascularity.

CONCLUSION: The spectrum of joint involvement in seronegative SpAs should not be limited to sacroiliitis. Bone scintigraphy provides a cost-effective method for detecting the extent of involvement in this group of autoimmune systemic diseases (axial SpA) without clinical evidence of peripheral arthritis.

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