MBOAT7 expression is associated with disease progression in COVID-19 patients.

BACKGROUND AND AIM: The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in late 2019 caused a pandemic of acute respiratory disease, named coronavirus disease 2019 (COVID-19). COVID-19 became one of the most challenging health emergencies, hence the necessity to find different prognostic factors for disease progression, and severity. Membrane bound O-acyltransferase domain containing 7 (MBOAT7) demonstrates anti-inflammatory effects through acting as a fine-tune regulator of the amount of cellular free arachidonic acid. We aimed in this study to evaluate MBOAT7 expression in COVID-19 patients and to correlate it with disease severity and outcomes. METHODS: This case-control study included 56 patients with confirmed SARS-CoV-2 diagnosis and 28 control subjects. Patients were further classified into moderate (n = 28) and severe (n = 28) cases. MBOAT7, tumor necrosis factor-α (TNF-α), and interleukin-1ß (IL-1ß) mRNA levels were evaluated in peripheral blood mononuclear cells (PBMC) samples isolated from patients and control subjects by real time quantitative polymerase chain reaction (RT-qPCR). In addition, circulating MBOAT7 protein levels were assayed by enzyme-linked immunosorbent assay (ELISA). RESULTS: Significant lower levels of circulating MBOAT7 mRNA and protein were observed in COVID-19 patients compared to control subjects with severe COVID-19 cases showing significant lower levels compared to moderate cases. Moreover, severe cases showed a significant upregulation of TNF-α and IL-1ß mRNA. MBOAT7 mRNA and protein levels were significantly correlated with inflammatory markers (TNF-α, IL-1ß, C-reactive protein (CRP), and ferritin), liver enzymes, severity, and oxygen saturation levels. CONCLUSION: COVID-19 is associated with downregulation of MBAOT7, which correlates with disease severity.

Antiapoptotic and chemotaxis-stimulating effects of poly (D, L-lactide-co-glycolide)-chitosan and whey proteins against aflatoxicosis-induced splenic and thymic atrophy.

BACKGROUND: Aflatoxin B (AFB) induces toxicological effects on the liver and immune organs. The whey proteins can modulate the immune response during aflatoxicosis. Our work evaluates the novel polylactic acid-glycolic acid-chitosan-encapsulated bovine and camel whey proteins against AFB-induced thymic and splenic atrophy in rats. METHODS AND RESULTS: Seventy adult male Wister albino rats were divided into a control healthy group (G1) and six AFB1-intoxicated groups (G2-G7). One of the following supplements: distilled water, camel whey proteins (CWP), bovine whey proteins, poly (D, L-lactide-co-glycolide) (PLGA)- chitosan-loaded with camel whey protein microparticles (CMP), PLGA-chitosan loaded with bovine whey protein microparticles (BMP), and PLGA-chitosan nanoparticles were administered as prophylactic supplements to AFB1-intoxicated groups. The AFB-treated group showed significantly higher hepatic levels of oxidative stress and lower levels of antioxidants. In the aflatoxicated group, atrophy of the splenic lymphatic nodules and disfigurement in the organisation with an apparent decrease in the thickness of the cortex in the thymus were observed, as well as a decrease in splenic and thymic CD4+T and CD8+T lymphocytes. Moreover, CXCL12 levels were downregulated, whereas tumour necrosis factor-alpha, nuclear factor kappa B, and cleaved caspase-3 levels were upregulated. CWP, BMP, and CMP supplements markedly decreased oxidative stress, inflammation, and apoptosis, as well as significantly raised CXCL12, CD4+T, and CD8+T cells. CONCLUSIONS: The CWP, BMP, and CMP supplements rescue the liver and immune tissues from the toxic effects of AFB through their antioxidant, antiapoptotic, anti-inflammatory, and chemotaxis-enhancing roles.

Validity of Serum Zinc/Copper Ratio as a Potential Novel Biomarker in Childhood Epilepsy.

BACKGROUND: Alterations in zinc and copper homeostasis may contribute to seizure susceptibility, development, termination, and response to antiepileptic medications. The current study examined the profile of zinc, copper, and their ratio in childhood epilepsy and its pharmacological variants (pharmacoresistant and pharmacoresponsive). METHODS: The study included 100 epileptic children (50 pharmacoresistant and 50 pharmacoresponsive) and 50 healthy, age- and gender-matched controls. History, clinical examination, and assays of serum zinc and copper were performed. Zinc/copper ratio was calculated. RESULTS: Serum zinc and the zinc/copper ratio were significantly lower in epileptic children than in controls (p < 0.001). Significantly lower zinc and zinc/copper ratio and higher copper levels were found in children treated with levetiracetam/sodium valproate/oxcarbazepine than those treated with levetiracetam alone or combined with sodium valproate (p < 0.05 for all). Epileptic children, particularly pharmacoresistant, exhibited significant negative correlations between the serum levels of zinc and copper (r = -0.279, p = 0.005, and r = -0.363 and p = 0.010, respectively). At cutoff value of zinc/copper ratio < 1.118 in diagnosing children with epilepsy, it gives a sensitivity of 64% and a specificity of 85% with the AUC = 0.8092. At cutoff value of zinc/copper ratio ≤ 0.7826 in distinguishing pharmacoresistant epilepsy, it produced 52% sensitivity, 64% specificity with AUC = 0.576 Conclusions: Low zinc and high copper levels were associated with childhood epilepsy especially those with pharmacoresistant type and treated with Oxcarbazepine. Zinc/copper ratio might be a potential biomarker in diagnosing childhood epilepsy and to some extent in predicting pharmacoresistant type.

Serum vascular endothelial growth factor, transforming growth factor ß1, and nitric oxide levels in patients with psoriasis vulgaris: their correlation to disease severity.

BACKGROUND: Vascular endothelial growth factor (VEGF), transforming growth factor ß1 (TGF-ß1), and nitric oxide (NO) have been reported to be contributory factors to the pathogenesis of psoriasis vulgaris. In the current study, we aimed to investigate the association between the levels of VEGF, TGF-ß1, and NO and psoriasis severity (as expressed by psoriasis area severity index, PASI). METHODS: Fifty-eight patients with psoriasis vulgaris and twenty-two controls were included in the study. The serum levels of VEGF and TGF-ß1 were estimated by ELISA technique. The serum levels of NO were determined by colorimetric method. RESULTS: The serum levels of VEGF, TGF-ß1, and NO were significantly higher in patients than controls. Moreover, the serum levels of the studied biochemical variables in patients with severe disease activity were significantly higher than mild cases. The duration of disease showed significant positive correlations with each VEGF (r = 0.35, P < 0.01) and TGF-ß1 (r = 0.41, P < 0.05). In addition, the PASI score was significantly positively correlated with VEGF (r = 0.65, P < 0.001), TGF-ß1 (r = 0.31, P < 0.05), and NO (r = 0.51, P < 0.001). CONCLUSION: These findings suggest an association between psoriasis disease severity and serum levels of VEGF, TGF-ß1, and NO, which can be recognized as markers of the psoriasis severity. The modulation of their production may represent a therapeutic potential strategy for psoriasis.

Pharmacogenetic study of phosphatase and tensin homolog polymorphism (rs701848) in childhood epilepsy: relation to circulating Wnt signaling.

OBJECTIVE: The present study aimed at evaluating the potential contribution of Phosphatase and Tensin Homolog (PTEN) and its gene polymorphism (PTEN rs701848 T/C) in relation to Wingless/integrase-1 (Wnt) signaling in childhood epilepsy and the impact of antiepileptic medications on their serum levels. METHODS: This study included 100 children with epilepsy (50 pharmacoresistant and 50 pharmacoresponsive) and 50 matched controls. All subjects had their genotypes for the PTEN rs701848T/C polymorphism assessed using TaqManTM assays and real-time PCR. By using the sandwich ELISA technique, the blood concentrations of PTEN and Wnt3a were measured. RESULTS: Serum Wnt3a levels in epileptic patients were significantly higher than in the control group, p < 0.001. Children with epilepsy who received oxcarbazepine had considerably lower serum Wnt3a levels than those who didn't, p < 0.001.With an AUC of 0.71, the cutoff value for diagnosing epilepsy as serum Wnt3a > 6.2 ng/mL has a sensitivity of 55% and a specificity of 80%. When compared to controls, epileptic children had considerably more (TT) genotype and less (TC and CC) genotypes, p < 0.05 for all. Epileptic children had significantly higher (T) allele frequency than controls, p = 0.006 with OR (95%CI) = 1.962(1.206-3.192). Pharmacoresistant epileptic children had significantly higher (TT) genotype compared to pharmacoresponsive type (p = 0.020). CONCLUSION: We originally found a strong association between PTEN rs701848 T/C and childhood epilepsy, in particular pharmacoresistant type. Serum Wnt3a levels increased in epilepsy, but were not significantly different between different alleles of PTEN. In pharmaco-responsive children Wnt3a levels differed significantly between the different PTEN genotypes. Antiepileptics may affect Wnt3a levels.

The significance of PCSK-9's level and polymorphism in premature coronary artery disease: Relation to risk and severity.

BACKGROUND: Proprotein convertase subtilisin/kexin type 9 (PCSK-9) is a circulating protein that plays an important role in lipid metabolism and is linked to inflammation, which has implications for atherosclerosis and its severe cardiac effects. We studied the potential association of the PCSK-9 gene single nucleotide polymorphism (SNP), Oxidized low-density lipoprotein receptor 1- (OLR-1), and caspase-3 serum levels with the risk and severity of premature coronary artery disease (PCAD). The potential contribution of PCSK-9 serum level to the severity of PCAD patients was also assessed. METHOD: This case-control study included 120 PCAD patients (age < 45), and 60 age matched healthy controls. Serum PCSK-9 and caspase-3 levels and clinical characteristics were recorded. SYNTAX score was calculated to estimate the severity of the coronary artery lesions. The SNP rs2483205 of the PCSK-9 gene and the rs11053646 of the OLR-1gene were genotyped in all participants. RESULTS: Serum PCSK-9 levels were higher in PCAD patients and were significantly different among the three SYNTAX score groups (SS ≤ 12, 12 < SS ≤ 21.5, and SS > 21.5). The diagnostic cutoff values of PCSK-9 and caspase-3 levels for PCAD were > 3.2 ng/mL for both, yielding an area under the curve (AUC) of 0.98 and 0.92, sensitivity of 85 %, 98 %, and specificity of 99.5 %, 93 % for PCSK-9 and caspase-3, respectively. The genotypes TT + CT vs. CC of PCSK-9's rs2483205 SNP presented a higher risk for PCAD and higher SYNTAX scores. Furthermore, the rs11053646 SNP of OLR-1 presented the CG genotype as more risky and having higher SYNTAX scores. CONCLUSION: Circulating PCSK9 and caspase-3 concentrations were higher in PCAD patients and were associated with CAD severity. The SNPs of PCSK-9 (rs2483205) and OLR-1 (rs11053646) were associated with PCAD and its severity.

Biochemical markers of oxidative and nitrosative stress in acne vulgaris: correlation with disease activity.

BACKGROUND: Acne vulgaris is a multifactorial skin disorder of unknown etiology. Free radical-mediated reactions have been implicated but their role in eliciting this response and contributing to disease progress remains unexplored. This study was undertaken to investigate the status and contribution of oxidative/nitrosative stress in patients with acne vulgaris. METHODS: Sera from 50 acne vulgaris with varying levels of disease activity (mild, moderate, and severe) according to the Global Acne Grading System (GAGS) and 40 age- and sex-matched controls were evaluated for serum levels of oxidative/nitrosative stress markers, including protein oxidation, lipid peroxidation and nitric oxide (NO), superoxide dismutase (SOD), and glutathione (GSH). RESULTS: Serum analysis showed significantly higher levels of carbonyl contents, malondialdehyde (MDA) and NO, in acne patients compared with healthy controls (P < 0.05). Interestingly, not only there were an increased number of subjects positive for carbonyl contents, but also the levels of these oxidants were significantly increased with the increase of the disease activity (P < 0.05). In addition, a significant correlation was observed between the levels of carbonyl contents and the GAGS scores (r = 0.341, r = 0.355, and r = 0.299, respectively). Furthermore, sera from acne patients had lower levels of SOD and GSH compared with healthy control sera. CONCLUSION: These findings support an association between oxidative/nitrosative stress and acne. The stronger response observed in serum samples from patients with higher GAGS scores suggests that markers of oxidative/nitrosative stress may be useful in evaluating the progression of acne and in elucidating the mechanisms of disease pathogenesis.

Copeptin, miRNA-208, and miRNA-499 as New Biomarkers for Early Detection of Acute Coronary Syndrome.

cTn and CK-MB are gold standard biomarkers for acute coronary syndrome (ACS) but are less sensitive in the first 3 h after onset of symptoms. A need thus exists for novel biomarkers for early detection of ACS. We evaluated circulating copeptin, miRNA-208, and miRNA-499 as possible biomarkers for early detection of unstable angina (UA) and non-ST-segment elevation myocardial infarction (NSTEMI). Sixty-five patients with probable ACS that presented within 4 h of the onset of chest pain (23 UA and 42 NSTEMI) and 25 apparently healthy individuals were studied. Two sets of blood samples collected in the first 3 h and at 6 h after onset were analyzed for copeptin levels via ELISA and miRNA-208 and miRNA-499 expression via real-time PCR. Copeptin, miRNA-208, and miRNA-499 expression levels were significantly increased in UA and NSTEMI patients compared with controls (p < 0.001) and in NSTEMT compared with UA patients (p < 0.001). Levels were also significantly elevated in UA and NSTEMI patients with negative cardiac troponin in the first 3 h (p < 0.001). ROC curves displayed AUC for prediction of ACS of 0.96 for copeptin, 0.97 for miRNA-208, and 0.97 for miRNA-499. Their combination improved AUC to 0.98. Copeptin and miRNA-208 and miRNA-499 expression are promising biomarkers for UA and NSTEMI that present in the first 3 h of pain onset. A combination of these markers with cTn may increase the accuracy of diagnosis by avoiding the gray zone of cTn as a biomarker.

Protective effect of green tea on lead-induced oxidative damage in rat's blood and brain tissue homogenates.

Recent studies have shown that lead (Pb) could disrupt tissue prooxidant/antioxidant balance which lead to physiological dysfunction. Natural antioxidants are particularly useful in such situation. Current study was designed to investigate efficacy of green tea extract (GTE), on oxidative status in brain tissue and blood caused by chronic oral Pb administration in rats. Four groups of adult male rats (each 15 rats) were utilized: control group; GTE-group (oral 1.5% w/v GTE for 6 weeks); Pb-group (oral 0.4% lead acetate for 6 weeks), and Pb+GTE-group (1.5% GTE and 0.4% lead acetate for 6 weeks). Levels of prooxidant/antioxidant parameters [lipid peroxides (LPO), nitric oxides (NO), total antioxidant capacity (TAC), glutathione (GSH), glutathione-S-transferase (GST), superoxide dismutase (SOD)] in plasma, erythrocytes, and brain tissue homogenate were measured using colorimetric methods. Pb concentrations in whole blood and brain tissue homogenate were measured by atomic absorption. In Pb-group, levels of LPO were higher while NO and GSH were lower in plasma, erythrocytes, and brain tissue than controls. TAC in plasma, SOD in erythrocytes, and GST in brain tissue homogenate were lower in Pb-group versus control. GTE co-administrated with Pb-reduced Pb contents, increased antioxidant status than Pb-group. In erythrocytes, Pb correlated positively with LPO and negatively with NO, GSH, SOD, and Hb. In brain tissue homogenate, Pb correlated positively with LPO and negatively with GSH. This study suggests that lead induce toxicity by interfering balance between prooxidant/antioxidant. Treatment of rats with GTE combined with Pb enhances antioxidant/ detoxification system which reduced oxidative stress. These observations suggest that GTE is a potential complementary agent in treatment of chronic lead intoxication.

Effect of green tea extract and vitamin C on oxidant or antioxidant status of rheumatoid arthritis rat model.

Elevated free radical generation in inflamed joints and impaired antioxidant system has been implicated in rheumatoid arthritis (RA). Green tea extracts (GTE) have been shown to reduce inflammation in inflammatory arthritis murine model. This study investigates possible mechanisms by which vitamin C and GTE protect joints in RA rat model. This study included forty adult male rats that were divided into four groups (10 rats each); control group, collagen II induced RA group (CII), CII treated with vitamin C (CII + Vit C) and CII treated with GTE (CII + GTE) in physiology laboratory, Assiut University, Egypt. After 45 days of treatment, plasma levels of lipid peroxides (LPO), nitric oxide (NO), ceruloplasmin (CP), superoxide dismutase (SOD), uric acid (UA) and glutathione (GSH) were detected using colorimetric methods, PGE(2) using ELISA and copper (Cu) and zinc (Zn) using spectrometer. In CII group, levels of LPO, NO, PGE(2), UA, CP, Cu were higher while SOD, GSH, Zn were lower than controls. In groups treated with vitamin C and GTE, levels of SOD, GSH were increased while levels of LPO, NO, PGE(2), Cu, CP were decreased compared with CII group. Levels of UA were decreased and Zn increased in GTE treated group compared with CII group. GTE treated group showed higher Zn and low Cu levels compared with vitamin C treated group. This study suggests proper GTE and vitamin C intake may effectively normalize the impaired oxidant/antioxidant system and delaying complication of RA.

Myocardial injury induced by scorpion sting envenoming and evidence of oxidative stress in Egyptian children.

In the present study, 45 children in Upper Egypt (less than 16 years old) were admitted to the Pediatric Intensive Care Unit for scorpion envenomation (SE). They were compared with 30 apparently healthy children of matching age and sex as controls. Out of the studied victims, 35 children (78%) showed signs of severe envenomation, while 10 victims (22%) showed signs of mild envenomation. The case fatality was 33%. The serum levels of cardiac markers, cardiac troponin T (cTnT) and I (cTnI), as well as the enzymatic activities of creatine kinase-MB (CPK-MB) and lactate dehydrogenase (LDH) were determined for both victims and controls. In addition, the serum levels of oxidative stress markers, nitric oxide (NO), malondialdehyde (MDA), superoxide dismutase (SOD), reduced glutathione (GSH) and zinc (Zn) were measured. Electrocardiography and echocardiography were done. All the envenomed victims showed significantly higher mean values of cTnT, cTnI, CPK-MB and LDH than control group. These cardiac markers were elevated in severe cases and in non survivors in comparison with mild cases and survivors respectively. Furthermore, the serum levels of NO and MDA were significantly higher while the serum levels of SOD, GSH and Zn were significantly lower in all envenomed victims than the controls (p < 0.05 for all). There were no significant differences in the serum levels of oxidative stress markers among severe and mild cases or between survivors and non survivors victims. There were no significant correlations between the serum levels of cardiac markers and the oxidative stress markers in envenomed victims. In conclusions, oxidative stress occurs in scorpion envenomed children, but does not determine prognosis. Cardiac markers, but not the oxidative stress, remain the most important determining factor for the severity and the outcome of SE.

Role of some vasoactive mediators in scorpion envenomed children: Possible relation to envenoming outcome.

Scorpion envenomation causes an autonomic storm resulting in changes in the vasoactive mediators' levels which lead to myocardial damage, cardiovascular disturbances, peripheral circulatory failure, pulmonary edema, multi-system-organ-failure and death. The study aimed to determine the circulating levels of adrenaline, noradrenaline, angiotensin converting enzyme (ACE), Angiotensin II (Ang II), kallikrein enzyme, nitric oxide (NO), aldosterone, and electrolytes Na+, K+ and Ca+2 in scorpion envenomed children and to evaluate the potential relation between these vasoactive mediators, the severity of scorpion envenoming and the clinical outcome of envenomed children. Forty envenomed children (22 mild and 18 severe cases) along with 10 healthy control children were enrolled in the study. The circulating levels of adrenaline, noradrenaline, Ang II, ACE, kallikrein enzyme, and NO were determined by ELISA, and spectrophotometric assays on admission and 24 h later. On admission, serum aldosterone, and electrolytes; Na+, K+ and Ca+2 were determined by RIA, Flame photometer and Flame atomic absorption respectively. All envenomed children showed significant surge of adrenaline, noradrenaline, ACE, Ang II, aldosterone, NO and Na+, that concomitantly faced by significant reduction in kallikrein, K+ and Ca+2 on admission. Twenty four hours later, all envenomed children continued to show significant elevation of ACE, Ang II and NO. The severely envenomed children showed considerable reduction in circulating levels of adrenaline, noradrenaline, ACE and Ang II, while dramatic increase in kallikrein activity was reported in comparison to mildly envenomed children after 24 h of medical care. Also, NO exhibited considerable accumulation in non survivors, on admission, that was persistent for the subsequent 24 h and was accompanied by high kallikrein, low catecholamines and Ang II levels compared to survivors. Finally, the hypertensive cases showed substantial higher levels of catecholamine, ACE and Ang II, 24 h after admission. These findings indicated that, disturbances of the studied vasoactive mediators were common in scorpion envenomed children and may account for several inflammatory manifestations and clinical outcome. ACE inhibitors could be considered as possible therapeutic agent in victims with prominent increase in ACE and Ang II while kallikrein inhibitor and antioxidants may be effective in the treatment of late hypotensive ones.

Serum levels of IL-6 and its soluble receptor, TNF-alpha and chemokine RANTES in scorpion envenomed children: their relation to scorpion envenomation outcome.

During the present study, 30 children in Upper Egypt (less than 12 years old) were admitted to Pediatric Intensive Care Unit because of scorpion envenomation. They were compared with 20 apparently normal children of matching age and sex as controls. The victims and controls were subjected to complete clinical examination and full blood picture. The serum levels of interleukin-6 (IL-6), soluble IL-6 receptor (sIL-6R), regulated upon activation normal T cells expressed and secreted (RANTES ) and tumour necrosis factor-alpha (TNF-alpha) were determined once for the controls and twice for the victims, the first sample on admission and the second sample after 24h. All victims showed significantly higher mean values of IL-6, sIL-6R, RANTES, TNF-alpha, and leucocytic count both on admission and on the follow up when compared with controls. According to the clinical manifestations of envenomation, 40% of the victims had a mild envenomation manifestation, while 60% of them had severe manifestations. The severely envenomed children showed significantly higher mean values of IL-6, sIL-6R, TNF-alpha, RANTES and leucocytic count both on admission and on the follow up samples when compared with the mild cases. The non-survival victims (five victims) showed significantly higher mean values of IL-6, sIL-6R, TNF-alpha, RANTES and leucocytic count both on admission and on the follow up samples in comparison to the survivals. Furthermore, those fatal cases showed a non-significant decline in the serum levels of IL-6, sIL-6R, TNF-alpha, RANTES and leucocytic count on the following up samples, while the survivals showed a significant decline in the serum levels of these parameters on the following up samples. In conclusion, these data revealed that IL-6, sIL-6R, TNF-alpha and chemokine, RANTES are involved in the pathogenesis of scorpion envenomation and correlated with its severity.

Vascular endothelial growth factor and insulin-like growth factor-1 in polycystic ovary syndrome and their relation to ovarian blood flow.

OBJECTIVES: (1) To determine the serum levels of vascular endothelial growth factor (VEGF) and insulin-like growth factor-1 (IGF-1) in women with polycystic ovary syndrome (PCOS). (2) To study Doppler blood flow changes within the ovarian stroma of women with PCOS. (3) To evaluate the relationship between VEGF and IGF-1 and Doppler indices as well as hormonal profile. SETTING: Department of Obstetrics and Gynecology, and Department of Biochemistry, Faculty of Medicine, Assiut University, Egypt. DESIGN: Cross-sectional study. PATIENTS AND METHODS: Fifty infertile women with PCOS diagnosed by ultrasound examination and a history of oligomenorrhea, hirsutism and obesity were studied. Serum levels of vascular endothelial growth factor (VEGF), insulin-like growth factor-1 (IGF-1) and hormonal profile were measured. Doppler blood flow velocity waveforms analysis in both right and left intraovarian arteries was done. Twenty healthy and fertile women with regular menstrual cycles served as a comparison group were similarly studied at the third day of the cycle. RESULTS: The serum levels of VEGF, IGF-1 (4.79 +/- 0.91, 253.15 +/- 70.07 versus 2.39 +/- 0.42, 186.65 +/- 42.7) were significantly elevated (P <0.001 and P <0.01, respectively) in women with PCOS compared with control. Doppler indices, PI (2.01 +/- 0.77, 2.66 +/- 1.00 versus 2.98 +/- 0.77, 3.75 +/- 0.98) and RI (0.77 +/- 0.12, 0.82 +/- 0.09 versus 0.87 +/- 0.09, 0.89 +/- 0.09) in both right and left intraovarian vessels were significantly lower in the patients than controls. The VEGF and IGF-1 levels were negatively correlated with RI and PI in the uterine and intraovarian arteries. VEGF level was positively correlated with IGF-1 (r=0.41, P <0.05) in women with PCOS. CONCLUSIONS: Higher serum levels of VEGF and IGF-1 in PCOS women may be related to the increased vascularity that underlies the increased blood flow demonstrated by Doppler blood flow measurements in these women.

Evaluation of the impact of laparoscopic ovarian drilling on Doppler indices of ovarian stromal blood flow, serum vascular endothelial growth factor, and insulin-like growth factor-1 in women with polycystic ovary syndrome.

OBJECTIVE: To study the serum levels and correlation of vascular endothelial growth factor (VEGF), insulin-like growth factor 1 (IGF-1), hormonal profile, and Doppler blood flow changes within the ovarian stroma before and after laparoscopic ovarian drilling (LOD) in women with clomiphene-resistant polycystic ovary syndrome (PCOS). DESIGN: Prospective controlled study. SETTING: University teaching hospital. PATIENT(S): Twenty-five women with clomiphene-resistant PCOS (group 1) and 20 women with regular menstrual cycles as a comparison group (group 2). INTERVENTION(S): Laparoscopic ovarian drilling. MAIN OUTCOME MEASURE(S): Serum levels of VEGF, IGF-1, and Doppler indices of ovarian stromal blood flow. RESULT(S): The serum levels of VEGF, IGF-1, T, and LH were significantly higher in group 1 before LOD than in group 2. The Doppler indices (pulsatility index and resistance index) of ovarian stromal blood flow were also significantly lower in group 1 before LOD than in group 2. The serum levels of VEGF, T, and LH were significantly reduced in group 1 after LOD compared with in group 1 before LOD. Doppler indices (pulsatility index and resistance index) of ovarian stromal blood flow were significantly increased after LOD. The VEGF levels before LOD were positively correlated with IGF-1, LH, and T. After LOD, the VEGF levels were positively correlated with LH and T. CONCLUSION(S): Higher serum levels of VEGF and IGF-1 may explain the increased vascularity that was demonstrated by Doppler blood flow measurements in PCOS. Laparoscopic ovarian drilling reduced serum VEGF, IGF-1, T, and LH and reduced ovarian blood flow velocities, which may explain the reduction of ovarian hyperstimulation syndrome in women with PCOS after LOD.

Caspase-3 and heat shock protein-70 in rat liver treated with aflatoxin B1: effect of melatonin.

In the present study, caspase-3 enzyme activity (apoptotic marker) and heat shock protein-70 (HSP70) expression in male rat liver after aflatoxin B1 (AFB1) treatment and the effect of melatonin (MEL) were investigated. Four groups of 20 rats each were used: controls, MEL-treated rats (MEL dose, 5 mg/kg body wt), AFB1-treated rats (50 microg/kg body wt) and MEL+AFB1-treated rats. After 8 weeks of daily treatment, biochemical assays in liver homogenates were done. The caspase-3 enzyme activity was measured using colorimetric method while the level of HSP70 expression was determined using dot blot analysis. In addition, the tissue levels of lipid peroxides (LPO), nitric oxide (NO), glutathione (GSH) and the enzyme activities of glutathione reductase (GR) and glutathione peroxidase (GSPx) were determined using colorimetric methods. The levels of caspase-3 activities and HSP70 level in AFB1 group were significantly higher than control group. Concomitantly, the levels of oxidative stress indices, LPO and NO, were significantly increased while the levels of antioxidants, GSH, GSPx and GR in AFB1 group were significantly decreased compared to their levels in controls. Caspase-3 activity was positively correlated with LPO while negatively correlated with GSH in rat livers treated with AFB1. The levels of caspase-3 activity, LPO, NO and HSP70 expression were significantly lower while the levels of GSH, GSPx and GR activities were significantly higher in MEL+AFB1 group than AFB1 group. In conclusion, higher levels of caspase-3 activity and HSP70 expression were associated with oxidative stress in rat liver treated with AFB1. The increased HSP70 expression in liver of AFB1 group may be due to a compensatory defense mechanism. MEL may effectively normalize the impaired antioxidants status, which consequently reduce both expression of HSP70 and apoptotic dysregulation in the liver. Thus, clinical application of MEL as therapy may benefit in cases of aflatoxicosis.

Ameliorated effects of green tea extract on lead induced liver toxicity in rats.

In the present study, the effect of green tea extract (GTE) on lead induced toxicity was studied in Sprague-Dawley rats. Four groups of rats were used in the study. Lead and GTE was given orally to the rats with drinking water for 8 weeks. Lead concentration in the digested tissues of liver was detected using atomic absorption spectroscopy. The activities of glutathione-S-transferase (GST) and superoxide dismutase (SOD) were used as markers to evaluate the anti oxidant status of tissues. Lead exposure was found to attenuate the antioxidant potential of liver, which was however augmented when supplemented with green tea extract. Liver enzymes ALT, AST and ALP and serum protein determinations indicated the protective effects of green tea extract. Histopathological studies of liver revealed that supplementation of green tea extract resulted in mild degeneration and congestion of the blood vessels and an enhanced regenerative capacity.

Association of Blood Lead level with Elevated Blood Pressure in Hypertensive Patients.

BACKGROUND: Lead is a metal with many important industrial uses. The relationship between lead exposure and the rise of blood pressure has received a great deal of attention as it was implicated that the mortality from cardiovascular diseases might be reduced by lowering lead levels in the environment. OBJECTIVES: The study was to investigate the correlation between the blood lead (B-Pb) levels and the values of blood pressure in hypertensive patients. Moreover, the plasma activities of angiotensin converting enzyme (ACE), plasma levels of nitric oxide (NO), total antioxidants (TAOX) and malondialdehyde (MDA) were estimated to investigate the correlations between the measured parameters and B-Pb levels in hypertensive patients. METHODS: Fifty-five hypertensive patients were compared with fifty-three age and sex matched control group. The B-Pb levels were detected by flame atomic absorption spectrometry. The plasma levels of ACE activities, NO, TAOX and MDA were measured by colorimetric methods. RESULTS: In the hypertensive patients, B-Pb levels were significantly higher than controls. Concomitantly, the plasma levels of ACE activities and MDA were significantly increased while the plasma levels of NO and TAOX were significantly reduced in the hypertensive patients in comparison with controls. There were significant positive correlations between B-Pb and each of MDA, and systolic as well as diastolic blood pressure. Conversely, a significant negative correlation was found between B-Pb and NO. CONCLUSIONS: Our study indicated that a positive relationship exists between blood pressure and B-Pb levels. The increased B-Pb levels were associated with oxidative stress. Moreover, The B-Pb level was negatively correlated with NO and this may clarify the implication of Pb as leading risk factor for the cardiovascular diseases and hypertension. These findings provide support for continued efforts to reduce lead concentration in the population at Qassim region.

The biochemical and morphological alterations following administration of melatonin, retinoic acid and Nigella sativa in mammary carcinoma: an animal model.

Worldwide, breast cancer is the second leading cause of cancer death among women and the third most common cancer. Although our understanding of the molecular basis of this fatal disease has improved, this malignancy remains elusive. Melatonin (Mel), retinoic acid (RA) and Nigella sativa (NS) are substances with anticancer effects. To date, our understanding of the mechanisms of therapeutic effects of these products in mammary cancer is still marginal. To look at the preventive and therapeutic values of these products, we carried out this investigation. An animal model formed of 80 rats was established. The animals were divided into eight groups of 10 animals each: (a) control group injected with the same vehicle used for treatments in the relevant dosages and routes; (b) carcinogen group injected with the known carcinogenic substance 7,12-di-methylbenz(a)anthracene (DMBA) that induces mammary carcinoma; (c) three prophylactic (Pro) groups (Mel-Pro, RA-Pro and NS-Pro) injected with test substances (Mel, RA and NS, respectively) 14 days before the intake of the carcinogenic substance DMBA and then continued until the end of the experiments; and (d) three treated (Tr) groups (Mel-Tr, RA-Tr and NS-Tr) injected with the vehicles after the intake of DMBA. In both the Pro and Tr groups, the drugs were daily administered for 3 months. The animals were killed, and their serum and tissues were evaluated for (a) markers of tumorigenicity [serum levels of total sialic acid (TSA) and lipid-bound sialic acid (LSA)], (b) markers of endocrine derangement (serum prolactin, estradiol and progesterone levels), (c) apoptotic changes [serum tumour necrosis factor (TNF)-alpha, tissue caspase-3 activity, percentage of DNA fragmentation and ultrastructural features of apoptosis] and (d) markers of oxidative stress (tissue levels of lipid peroxides and nitric oxide). Carcinoma was absent both in the control and in the NS-Pro groups. Mammary carcinoma occurred in DMBA and other Pro and Tr groups. The frequency of mammary carcinoma was high in the carcinogen DMBA group (60%), followed by the Tr (56%) and finally the Pro groups (33%). These tumours included papillary, comedo and cribriform carcinomas. As compared with the control group, the development of carcinoma in the carcinogen DMBA group was associated with increased levels of (a) markers of tumorigenicity (77.0 +/- 3.3 vs. 209.0 +/- 5.6 and P < 0.05 for TSA; 28.7 +/- 1.7 vs. 41.8 +/- 1.2 and P < 0.01 for LSA), (b) markers of endocrine derangement (2.5 +/- 0.1 vs. 3.6 +/- 0.3 and P < 0.05 for prolactin; 39.6 +/- 1.3 vs. 24.8 +/- 2.1 and P < 0.01 for progesterone and 31.0 +/- 0.7 vs. 51.1 +/- 3.4 and P < 0.01 for estradiol) and (c) markers of oxidative stress (2.3 +/- 0.2 vs. 5.2 +/- 0.7 and P < 0.01 for lipid peroxides and 4.4 +/- 0.2 vs. 7.6 +/- 0.8 and P < 0.01 for nitric oxide). Also, it was associated with decreased levels of markers of apoptotic activity (20.8 +/- 1.1 vs. 13.4 +/- 0.7 and P < 0.01 for caspase-3; 29.0 +/- 1.7 vs. 20.9 +/- 1.3 and P < 0.05 for percentage of DNA fragmentation; and 9.4 +/- 0.8 vs. 52.1 +/- 3.3 and P < 0.01 for TNF-alpha). When compared with the carcinogen DMBA group, the development of carcinoma in the Pro and Tr groups was associated with decreased levels of (a) markers of tumorigenicity, (b) markers of endocrine derangement and (c) markers of oxidative stress. Alternatively, carcinogenicity was associated with statistically significant (P < 0.01) increased levels of markers of apoptotic activity. To conclude, the administration of Mel, RA and NS reduced the carcinogenic effects of DMBA, suggesting a protective role. The possible underlying mechanisms of these effects await further investigations.