Enas A. Hamed

Vascular Risk Factors, Endothelial Function, and Carotid Thickness in Patients with Migraine: Relationship to Atherosclerosis

Recent studies indicated that migraine is associated with specific vascular risk profile. However, the functional and structural vascular abnormalities in migraine are rarely addressed. We evaluated the vascular risk factors, endothelial function, and carotid artery (CA)-intima-media thickness (IMT), segregators of preclinical atherosclerosis, in migraineurs. This preliminary study included 63 adults with headache (migraine with aura [n=14], migraine without aura [n=24], transformed migraine [n=6], and tension headache [n=19]) and 35 matched healthy subjects. The following vascular risks were assessed: body mass index (BMI), systolic blood pressure (SBP) and diastolic blood pressures (DBP), serum levels of C-reactive protein, fasting glucose, fasting insulin, total cholesterol, and triglycerides. Plasma endothelin (ET)-1, a vasoactive peptide produced by vascular smooth muscle cells and marker for endothelial injury and atherosclerosis, was measured. Endothelial-dependent vasoreactivity was assessed using brachial artery flow-mediated dilatation (FMD) in response to hyperemia. CA-IMT, structural marker of early atherosclerosis, was measured. Compared with control subjects, SBP, DBP, glucose, insulin, ET-1, and CA-IMT were elevated with migraine. FMD% was inversely correlated with SBP (P < .001), DBP (P < .01), glucose (P < .001), and insulin levels (P < .01). CA-IMT was correlated with BMI (P < .05), SBP (P < .01), total cholesterol (P < .01), triglycerides (P < .001), glucose (P < .001), insulin (P < .01), and FMD% (P < .05). In multivariate analysis, ET-1 was correlated with duration of illness, SBP, DBP, glucose, insulin, IMT, and FMD%. We conclude that endothelial injury, impaired endothelial vasoreactivity, and increased CA-IMT occur with migraine and are associated with vascular risk factors that strongly suggest that migraine could be a risk for atherosclerosis.

States of serum leptin and insulin in children with epilepsy: Risk predictors of weight gain

BACKGROUND AND OBJECTIVES Weight gain is an adverse metabolic effect in some children with epilepsy. The studies done to detect the effect of antiepileptic drugs and weight homeostatic hormones, insulin and leptin, were limited and controversial. MATERIALS AND METHODS We evaluated the serum leptin and insulin as predictors of weight gain in children receiving long-term treatment with valproate (VPA), carbamazepine (CBZ), lamotrigine (LTG). This study included 90 patients (treated: 70; untreated: 20). Serum lipid profile, insulin and leptin were measured. RESULTS BMI, serum leptin and insulin were significantly elevated in VPA compared with controls, untreated patients and those treated with CBZ, LTG and combined therapy with LTG. Girls on VPA had higher BMI and leptin levels than boys. With VPA, serum insulin was correlated with BMI (r=0.625, p<0.01), leptin (r=0.823, p<0.001), treatment duration (r=0.775, p<0.01) and VPA dose (r=0.975, p<0.0001). Serum leptin was correlated with age (r=0.980, p<0.0001), BMI (r=0.704, p<0.01), serum insulin (r=0.823, p<0.001), LDL-c (r=0.630, p<0.01), HDL-c (r=-0.880, p<0.001), treatment duration (r=0.770, p<0.01) and VPA dose (r=0.970, p<0.001). BMI is correlated with serum insulin, leptin, LDL-c (r=0.835, p<0.001) and HDL-c (r=-0.955, p<0.0001). CONCLUSION Hyperinsulinemia and hyperleptinemia are common with VPA and marked among epileptic children who gained weight suggesting states of insulin and leptin resistances. These alterations were not demonstrated with CBZ or LTG. The relationship between VPA, leptin and weight seems to be gender specific. Serum leptin may serve as a sensitive parameter for weight gain and reduction with intervention programs during follow-up of girls with epilepsy.

Serum thyroid hormone balance and lipid profile in patients with epilepsy

PURPOSE Patients with epilepsy may exhibit changes in thyroid hormone balance, lipids and lipoproteins concentrations. The suggestion that lipid abnormalities are associated with subclinical thyroid dysfunction remains controversial. The aim of this study was to analyze whether thyroid dysfunction encountered in patients with epilepsy would also be associated with abnormal lipid profile. METHODS Eighty-eight patients with epilepsy and 30 control subjects were included in the study. A fasting blood sample for thyroid hormones, lipid profile and GGT determination was obtained. RESULTS The serum levels of FT3 was elevated in 10.2% of patients, FT4 was low in 28.4%, TSH was high in 4.6% and low in 2.3%. 13.6% of patients had high TC, 17.1% had high LDL-c, 60.2% had marked reduction of HDL-c levels (P<0.0001) and only 2.3% had high TG levels. Abnormalities were predominated in CBZ-treated patients. 27.3% patients with abnormal hormones had abnormal lipid profile. Significant association was identified between the serum TC, LDL-c, TG, GGT and EIAEDs and between the duration of illness and TG (r=-0.411; P=0.017), and FT4 (r=-0.412; P=0.018). HDL was higher in women than men (r=0.416; P<0.002). However, changes in HDL-c levels associated neither with duration of illness, type or serum levels of AEDs nor with age or degree of control on AEDs. CONCLUSIONS Our results support that (1) altered lipid metabolism might be associated but not solely influenced by thyroid hormones and (2) enzyme induction is not the main or only reason for altered thyroid function or HDL-c among patients with epilepsy. Hypothalamic/pituitary dysregulation by precisely mechanism caused by epilepsy itself or AEDs seems possible and (3) it is important to recognize that patients with epilepsy are at great risk for atherosclerosis, hence monitoring and correction of the culprit risks are mandatory.

Renal functions in pediatric patients with beta-thalassemia major: relation to chelation therapy: original prospective study.

BackgroundIn β-thalassemia, profound anemia and severe hemosiderosis cause functional and physiological abnormalities in various organ systems. In recent years, there have been few published studies mainly in adult demonstrating renal involvement in β-thalassemia. This prospective study was aimed to investigate renal involvement in pediatric patients with transfusion dependant beta-thalassemia major (TD-βTM), using both conventional and early markers of glomerular and tubular dysfunctions, and to correlate findings to oxidative stress and iron chelation therapy.MethodsSixty-nine TD-βTM patients (aged 1-16 years) and 15 healthy controls (aged 3-14 years) were enrolled in this study. Based on receiving chelation therapy (deferoxamine, DFO), patients were divided into two groups: group [I] with chelation (n = 34) and group [II] without chelation (n = 35). Levels of creatinine (Cr), calcium (Ca), inorganic phosphorus (PO4), uric acid (UA) and albumin were measured by spectrophotometer. Serum (S) levels of cystatin-C (SCysC) and total antioxidant capacity (STAC) and urinary (U) levels of β2-microglobulin (Uβ2MG) were measured by immunosorbent assay (ELISA). Urinary N-acetyl-beta-D-glucosaminidase (UNAG) activity and malondialdehyde (UMDA) were measured by chemical methods. Estimated glomerular filtration rate (eGFR) was determined from serum creatinine.ResultsIn patient with and without chelation, glomerular [elevated SCysC, SCr, Ualbumin/Cr and diminished eGFR]; and tubular dysfunctions [elevated SUA, SPO4, UNAG/Cr, Uβ2MG/Cr] and oxidative stress marker disturbances [diminished STAC and elevated UMDA/Cr] were reported than controls. In patients with chelation, SCysC was significantly higher while, STAC was significantly lower than those without chelation. In all patients, SCysC showed significant positive correlation with SCr and negative correlation with eGFR; STAC showed significant positive correlation with eGFR and negative correlation with SCysC, SCr, UNAG/Cr; UMDA/Cr showed significant positive correlation with Ualbumin/Cr, Uβ2MG/Cr, UNAG/Cr.ConclusionsOur data confirm high frequency of glomerular and tubular dysfunctions in TD-βTM pediatric patients which could be attributed to oxidative stress and DFO therapy.

The sexual and reproductive health in men with generalized epilepsy: a multidisciplinary evaluation

This study was specifically aimed to evaluate the sexual and reproductive health in a group of men with generalized epilepsy. In total, 44 men with generalized epilepsy were included in this study, their ages between 18 and 48 years (29.2±9.9) and duration of illness between 2 and 35 years (11.2±7.4); 34 patients were treated with conventional antiepileptic drugs (AEDs). Sexological and psychological interviews together with serum total testosterone, E2, FSH, LH and prolactin were determined. Hyposexuality was diagnosed in 61.4%. Erectile dysfunction (ED) and premature ejaculation represented 70.4 and 66.7%, respectively. Variables such as hyposexuality, seizure duration and its poor control on AEDs were significantly associated with depressive symptoms. Compared to the normal control group, all patients reported elevated E2 levels (P<0.001), 10 had FSH (n=4) and LH (n=6) levels exceeding that of the normal range for controls and two had hyperprolactinemia. Although the patients’ mean value of total testosterone remained within the normal range, but it was significantly lower in hyposexual men compared to nonhyposexual (P<0.002), only two epileptic patients had markedly reduced level of total testosterone beyond normal control levels. This study strongly supports that: (1) The risk of hyposexuality and reproductive disturbances is high in epileptic patients with GTC convulsions despite the AEDs utilized. The risk for SD is further increased by poor seizure control and the frequently accompanied depressive manifestations. (2) It is possible that elevated E2 could increase the risk of SD by reducing active testosterone through negative feedback and the reduction of active testosterone could increase seizure intractability to antiepileptic medications.

Parathormone – 25(OH)-vitamin D axis and bone status in children and adolescents with type 1 diabetes mellitus

Hamed EA, Abu Faddan NH, Adb Elhafeez HA, Sayed D. Parathormone – 25(OH)‐vitamin D axis and bone status in children and adolescents with type 1 diabetes mellitus.

Circulating leptin and insulin in obese patients with and without type 2 diabetes mellitus: relation to ghrelin and oxidative stress.

AIM This case control study aimed to investigate relationship between appetite hormones (ghrelin and leptin) and body mass index (BMI), insulin and oxidative stress in simple obese and type 2 diabetes (T2DM) obese patients. METHODS Thirty healthy controls; 30 simple obese and 30 T2DM obese patients were enrolled. Demographic and clinical data of all participants were reported. Serum levels of fasting blood glucose (FBG), postprandial blood glucose (PBG), lipid peroxide (LPO) and nitric oxide (NO) were measured by chemical methods while, insulin, leptin and ghrelin by ELISA kits. RESULTS Serum levels of insulin, leptin, LPO were significantly higher while, ghrelin was significantly lower in simple obese and obese patients with diabetes versus controls. Insulin resistance was found in 76.67% simple obese and 93.33% obese patients with diabetes. Ghrelin showed a positive correlation with PBG in controls; but negative correlation with BMI in simple obese and with NO in obese patients with diabetes. Positive correlations were found between LPO and FBG, insulin, homeostasis model assessment of insulin resistance (HOMA-IR) and between leptin and FBG in obese patients with diabetes. CONCLUSIONS Our results suggested that hyperinsulinemia and hyperleptinemia may be most important mechanisms in decreasing ghrelin and inducing oxidative stress in simple obese and T2DM obese patients.

Septic encephalopathy: relationship to serum and cerebrospinal fluid levels of adhesion molecules, lipid peroxides and S-100B protein.

Severe septic illness is often associated with cerebral manifestations such was disturbed consciousness and delirium. Little was known about its effect on the CNS. This is the first study in children that has assessed the direct mediators of brain inflammation and injury with sepsis. The serum and CSF concentrations of soluble intracellular adhesion molecule-1 (sICAM-1) (marker of endothelium-leukocyte interaction), nitric oxide (NO) and lipid peroxide (LPO) (markers for lipid peroxidation) and S-100B protein (marker of astrocytes activation and injury), were measured in 40 children with sepsis of whom 40% had moderate to severe septic encephalopathy. Serum from 25 normal children was used for comparison. Serum values of sICAM-1, NO, LPO and S100B were elevated in patients compared to controls. The greater elevation of the CSF:serum albumin ratio suggests loss of blood-brain barrier integrity. After normalising for CSF:serum albumin ratio, we demonstrated a significant intrathecal synthesis of NO, LPO and S100B. Patients with encephalopathy had elevated serum and CSF levels of sICAM-1, NO, LPO and S100B compared to sepsis only. This study indicates that the brain is vulnerable in children with sepsis. It also suggests that coordinated interactions between immune system, vascular endothelial cells, CNS barriers, astrocytes and brain lipid peroxides, may contribute to septic encephalopathy.

Oxidative stress and S-100B protein in children with bacterial meningitis

BackgroundBacterial meningitis is often associated with cerebral compromise which may be responsible for neurological sequelae in nearly half of the survivors. Little is known about the mechanisms of CNS involvement in bacterial meningitis. Several studies have provided substantial evidence for the key role of nitric oxide (NO) and reactive oxygen species in the complex pathophysiology of bacterial meningitis.MethodsIn the present study, serum and CSF levels of NO, lipid peroxide (LPO) (mediators for oxidative stress and lipid peroxidation); total thiol, superoxide dismutase (SOD) (antioxidant mediators) and S-100B protein (mediator of astrocytes activation and injury), were investigated in children with bacterial meningitis (n = 40). Albumin ratio (CSF/serum) is a marker of blood-CSF barriers integrity, while mediator index (mediator ratio/albumin ratio) is indicative of intrathecal synthesis.ResultsCompared to normal children (n = 20), patients had lower serum albumin but higher NO, LPO, total thiol, SOD and S-100B. The ratios and indices of NO and LPO indicate blood-CSF barriers dysfunction, while the ratio of S-100B indicates intrathecal synthesis. Changes were marked among patients with positive culture and those with neurological complications. Positive correlation was found between NO index with CSF WBCs (r = 0.319, p < 0.05); CSF-LPO with CSF-protein (r = 0.423, p < 0.01); total thiol with LPO indices (r = 0.725, p < 0.0001); S-100B and Pediatric Glasow Coma Scores (0.608, p < 0.0001); CSF-LPO with CSF-S-100B (r = 0.482, p < 0.002); serum-total thiol with serum S-100B (r = 0.423, p < 0.01).ConclusionThis study suggests that loss of integrity of brain-CSF barriers, oxidative stress and S-100B may contribute to the severity and neurological complications of bacterial meningitis.

Role of some vasoactive mediators in patients with erectile dysfunction: their relationship with angiotensin-converting enzyme and growth hormone

The imbalance between vasoconstrictors and vasodilators may play an important role in the pathogenesis of erectile dysfunction (ED). A total of 36 patients with ED, organogenic [diabetic (n=12) and nondiabetic (n=12)] and psychogenic (n=12) etiology, and 12 healthy adult men as controls were included. The levels of endothelin-1 (ET-1), growth hormone (GH), angiotensin-converting enzyme activity (ACE), nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) were determined in the flaccid penis cavernosal blood of patients and in cubital blood of patients and controls. In psychogenic ED, systemic ACE activity was elevated compared to controls (P<0.05). In diabetic and nondiabetic ED patients, systemic levels of ET-1 (P<0.0001 for both) and ACE activity (P<0.01 and <0.05) were higher while GH (P<0.0001 and <0.001), NO (P<0.0001 for both) and cGMP (P<0.01 for both) levels were lower compared to controls. In diabetic patients, systemic and cavernosal ET-1 levels (P<0.0001 for both) and cavernosal ACE activity levels (P<0.05) were significantly elevated while systemic and cavernosal NO (P<0.0001 for both) and GH (<0.001 and <0.05) levels were declined compared to psychogenic. In nondiabetic patients, systemic and cavernosal ET-1 levels (P<0.0001 for both) were significantly elevated while systemic and cavernosal NO (P<0.0001 for both) and systemic GH levels (P<0.05) were declined compared to psychogenic. Systemic NO was positively correlated with GH in psychogenic (r=0.616, P<0.05), diabetic (r=0.583, P<0.05) and nondiabetic (r=0.615, P<0.05) patients and correlated positively with cGMP (r=0.605, P<0.05) but negatively with ACE activities (r=−0.585, P<0.05) in diabetic patients. In conclusion, plasma levels of ET-1, ACE activities are elevated and associated with reduction of GH, NO and cGMP levels in the systemic and cavernous blood of ED patients. This disturbance may indicate endothelial dysfunction that may hind at their significance in the pathophysiology of ED.