Predictors of Serum 25-Hydroxyvitamin D Concentrations among a Sample of Egyptian Schoolchildren.

OBJECTIVE: To assess the level of 25-hydroxyvitamin D status among a sample of Egyptian schoolchildren and to evaluate predictors of deficiency and insufficiency. SUBJECTS AND METHODS: A cross-sectional study comprising 200 prepubescent schoolchildren aged from 9 to 11 years was performed. A questionnaire including frequency of midday sun exposure, milk intake, physical activity, and level of maternal education was taken. Body mass index (BMI) was calculated; serum 25-hydroxyvitamin D [25(OH)D], serum calcium, phosphorus, and parathyroid hormone were measured. RESULTS: Vitamin D deficiency [serum 25(OH)D < 20 ng/mL] was detected in 11.5% of subjects while its insufficiency (serum 25(OH)D is between 20 and 29.9 ng/mL) was detected in 15%. Results revealed that obesity, low physical activity, low sun exposure, and low maternal education level are significant predictors of insufficiency, though female gender, low maternal education level, and low milk intake are significant predictors of deficiency. Lower serum phosphorus and higher serum parathyroid hormone were significantly associated with both deficiency and insufficiency (p < 0.05). CONCLUSION: Vitamin D deficiency and insufficiency are common among schoolchildren in Egypt. Food fortification, vitamin D supplementation, and increasing maternal awareness about the importance of physical activity and exposure of their children to ultraviolet light may help to overcome this problem.

Selenium and antioxidant levels in children with intractable epilepsy receiving ketogenic diet.

Ketogenic diet is a high-fat, low-carbohydrate, and adequate-protein diet. It is well-established as a treatment option for drug-resistant childhood epilepsies. Our study aimed to evaluate Selenium levels and oxidative stress in children receiving ketogenic diet for intractable seizures for 6 months. This is a comparative case-control study included 90 children under 6 years age. They were subdivided into three groups. Group I: Thirty patients with drug-resistant epilepsy under antiepileptic drugs only. Group II: Thirty patients with drug-resistant epilepsy under treatment with ketogenic diet for 6 months and antiepileptic drugs. Group III: Thirty age and sex-matched healthy children as controls. Full history taking with special emphasis on severity and frequency of seizures, neurological examination, anthropometric measurements and laboratory analysis for serum Malonaldehyde, and total antioxidant capacity and Selenium were done for all participants. The frequency and severity of seizures were significantly lower in group II receiving ketogenic diet than group I on antiepileptic drugs only. Selenium levels were significantly lower in epileptic patients in comparison to controls. However, it was markedly lower in the ketogenic diet group. Malonaldehyde levels were significantly higher in epileptic children in comparison to controls, with lower values among ketogenic diet group when compared to patients on antiepileptic drugs only. Total antioxidant capacity levels were significantly lower in epileptic patients in comparison to controls, with higher values among ketogenic diet group as compared to epileptic patients on pharmacological treatment. Ketogenic diet is an effective treatment for refractory epilepsy for its anti-epileptic mechanism. It also may exert antioxidant effects. The nutrient content of the ketogenic diet may not meet the recommended daily allowance for selenium. So, this should be taken into consideration for supplementation of minerals in adequate amounts for patients receiving this diet.

Blueberry-induced changes in spatial working memory correlate with changes in hippocampal CREB phosphorylation and brain-derived neurotrophic factor (BDNF) levels.

Phytochemical-rich foods have been shown to be effective at reversing age-related deficits in memory in both animals and humans. We show that a supplementation with a blueberry diet (2% w/w) for 12 weeks improves the performance of aged animals in spatial working memory tasks. This improvement emerged within 3 weeks and persisted for the remainder of the testing period. Memory performance correlated well with the activation of cAMP-response element-binding protein (CREB) and increases in both pro- and mature levels of brain-derived neurotrophic factor (BDNF) in the hippocampus. Changes in CREB and BDNF in aged and blueberry-supplemented animals were accompanied by increases in the phosphorylation state of extracellular signal-related kinase (ERK1/2), rather than that of calcium calmodulin kinase (CaMKII and CaMKIV) or protein kinase A. Furthermore, age and blueberry supplementation were linked to changes in the activation state of Akt, mTOR, and the levels of Arc/Arg3.1 in the hippocampus, suggesting that pathways involved in de novo protein synthesis may be involved. Although causal relationships cannot be made among supplementation, behavior, and biochemical parameters, the measurement of anthocyanins and flavanols in the brain following blueberry supplementation may indicate that changes in spatial working memory in aged animals are linked to the effects of flavonoids on the ERK-CREB-BDNF pathway.

Evaluation of interleukin 23 (IL-23) as a non-invasive test of disease severity in patients with ulcerative colitis.

BACKGROUND AND STUDY AIMS: Studies have found increased expression of IL-23 in inflamed and non-inflamed mucosa of patients with ulcerative colitis (UC). We hypothesized that serum interleukin-23 as a non-invasive test has a role in pathogenesis of ulcerative colitis disease and correlates with the disease severity. PATIENTS AND METHODS: Forty patients with biopsy proven ulcerative colitis, recruited from Ain Shams University hospitals were included. Forty healthy subjects matched in age and gender were also included in the study as a control group. Serum IL-23 level was quantified using quantitative ELISA technique (Enzyme linked Immunosorbent Assay). RESULTS: Patients with UC had higher level of interleukin 23 (234.5 ±â€¯161 pg/mL) compared to control subjects (54.2 ±â€¯15 pg/mL) and the level of IL-23 correlated with the disease severity. Cut off value of IL-23 at 68 pg/mL was the best to differentiate between cases and control subjects. Receiver operating characteristic curve (ROC) revealed that the best cut off for IL-23 to detect mild cases of ulcerative colitis was at105 pg/mL, to detect moderate cases at 200 pg/mL and to detect severe cases was at 270 pg/mL with sensitivity 80% to mild cases, 60% to moderate cases and 81% to severe cases. CONCLUSION: Our findings confirm the suggestion that IL-23 level measurement may be of value as a non-invasive test in the diagnosis and disease severity assessment in patients with UC.

Multidrug-resistant organisms in neonatal sepsis in two tertiary neonatal ICUs, Egypt.

BACKGROUND: Neonatal sepsis remains a serious problem in any neonatal intensive care unit (NICU). Bacterial organisms have developed increased resistance to commonly used antibiotics. Because not enough data are available from Egypt, the aim of the present study was to determine the causative bacteria and the level of their resistance to commonly used antibiotics in tertiary NICUs in Cairo, Egypt. MATERIALS AND METHODS: A 3.5-year retrospective study was carried out at NICUs of the Children's Hospital of Ain Shams University and that of El-Hussein Hospital, Al-Azhar University, Egypt. Records of neonates were reviewed. All neonates with culture-proven sepsis were included in the study. RESULTS: Almost one-third of the admitted neonates (33.4%) were diagnosed as having neonatal sepsis, 32.25% of them culture-proven. Early/late onset sepsis was found in 35.4 and 64.6%, respectively. Gram-negative/gram-positive bacteria was found in 68 to 25.6%. Fungal infection was detected in 9% of the isolates. Escherichia coli was the main pathogen isolated in both early-onset sepsis (41.2%) and late-onset sepsis (24.5%). Overall, 77% of the isolates were multidrug-resistant (60% of gram-positive bacteria and 83.4% of gram-negative bacteria). Nearly 80% (79%) of mortality was caused by multidrug-resistant organisms. Gram-positive and gram-negative bacteria showed high resistance against commonly used antibiotics such as ampicillin, amoxicillin, cefotaxime, ceftriaxone, and gentamicin. CONCLUSION AND RECOMMENDATIONS: There is an alarming increase in antibiotic resistance to the commonly used antibiotics. Continuous surveillance for antibiotic susceptibility is needed to ensure proper empirical therapy. Improvement of infection control practices, avoidance of irrational use of antibiotics, and revision of the protocols are mandatory in the prevention of neonatal sepsis.

Study of Serum Hepcidin as a Potential Mediator of the Disrupted Iron Metabolism in Obese Adolescents.

BACKGROUND & AIMS: The prevalence of obesity continues to rise in both developed and developing nations. An association between iron status and obesity has been described in children and adults. We aimed to study the relation between serum hepcidin level and both iron as well as high sensitive CRP status in obese adolescents. MATERIALS & METHODS: This work was conducted on 80 adolescents aging 12-14 years old, divided into two equal groups; obese and non-obese. Anthropometric measurements, determination of haemoglobin, serum iron, total iron binding capacity (TIBC), transferrin saturation, serum ferritin, soluble serum transferrin receptor (sTfR), high sensitive CRP (hs -CRP) and serum hepcidin were performed. RESULTS: Obese adolescents showed significantly lower levels of haemoglobin, serum iron, serum ferritin and transferrin saturation. Significant higher diastolic blood pressure, higher mean TIBC, sTfR, serum hepcidin and hs -CRP were also found. Serum hepcidin level correlated positively with BMI and hs- CRP, but negatively with iron level in obese group. CONCLUSION: These data suggest that hepcidin is an important modulator of anemia in obese patients. Obesity can be considered as a low grade inflammatory state, that stimulates the production of inflammatory markers such as CRP which can up-regulate hepcidin synthesis.

Uptake and metabolism of epicatechin and its access to the brain after oral ingestion.

Epicatechin is a flavan-3-ol that is commonly present in green teas, red wine, cocoa products, and many fruits, such as apples. There is considerable interest in the bioavailability of epicatechin after oral ingestion. In vivo studies have shown that low levels of epicatechin are absorbed and found in the circulation as glucuronides, methylated and sulfated forms. Recent research has demonstrated protective effects of epicatechin and one of its in vivo metabolites, 3'-O-methyl epicatechin, against neuronal cell death induced by oxidative stress. Thus, we are interested in the ability of ingested epicatechin to cross the blood brain barrier and target the brain. Rats were administered 100 mg/kg body weight/d epicatechin orally for 1, 5, and 10 d. Plasma and brain extracts were analyzed by HPLC with photodiode array detection and LC-MS/MS. This study reports the presence of the epicatechin glucuronide and 3'-O-methyl epicatechin glucuronide formed after oral ingestion in the rat brain tissue.

The differential tissue distribution of the citrus flavanone naringenin following gastric instillation.

Citrus flavonoids have been investigated for their biological activity, with both anti-inflammatory and -carcinogenic effects being reported. However, little information is known on the bioavailability of these compounds in vivo. The objectives of this study were to determine the tissue distribution of naringenin after gastric gavage of [3H]-naringenin to rats. Unlabelled naringenin was also used to quantify the levels of naringenin and its major metabolites in tissues and eliminated in the urine and faeces. Significant radioactivity was detected in the plasma as well as all tissues examined 2h post-gavage. After 18h, higher levels of radioactivity were retained in plasma and tissues (55% of the administered radioactivity). Investigation of the nature of metabolites, using unlabelled naringenin, revealed that the glucuronides were the major components in plasma, tissues and urine, in addition to the colonic metabolite 3-(4-hydroxyphenyl) propionic acid, detected in the urine. The aglycone was the form extensively retained in tissues after 18h post-gavage. Total identified metabolites detected after 18h in most tissues were only 1-5% of the levels detected after 2h. However, the brain, lungs and heart retained 27, 20 and 11%, respectively, relative to the total metabolites detected at 2h. While radioactive detection suggests increased levels of breakdown products of naringenin after 18 h versus 2 h, the products identified using unlabelled naringenin are not consistent with this, suggesting that a predominant proportion of the naringenin breakdown products at 18 h are retained as smaller decomposition molecules which cannot yet be identified.

Serum level of brain derived neurotrophic factor (BDNF) among patients with bipolar disorder.

BACKGROUND: There is a growing body of evidence that serum brain derived neurotrophic factor (BDNF) is altered during the episodes of bipolar disorder. The aim of this study was to investigate serum BDNF levels in bipolar disorder patients during manic and depressive episodes and its clinical utility in bipolar disorder compared to other psychiatric disorders. METHODS: The study was conducted on 80 Egyptian patients, who were classified into 4 groups: group Ia (25 patients with depressive episodes), group Ib (25 patients with manic episodes), group II (15 patients having Schizophrenia) as pathological controls and group III (15 healthy subjects) as controls. All subjects were diagnosed according to DSM-IV, assessed using the Hamilton Rating Scale for depression (HAM-D), and the Young Mania Rating Scale (YMRS). sBDNF concentrations were measured using the quantitative sandwich enzyme immunoassay technique. RESULTS: sBDNF showed significantly lower levels in patients with depressive episodes or manic episodes. The best cut-off for sBDNF in discriminating depressed patient from healthy control was ≤33,000pg/ml (AUC=0.891, sensitivity of 84%, and specificity of 80%). Moreover, the best cut-off for sBDNF in discriminating mania patients׳ group from healthy control was ≤29,500pg/ml, (AUC=0.984, asensitivity of 96%, and specificity of 86.7%). LIMITATIONS: Only a small sample size was considered which included only drug free patients. BDNF was measured in serum not in CSF or brain tissue. CONCLUSIONS: Low sBDNF levels are strongly associated with active phases of bipolar disorder, in depressive and manic episodes.

Histological study on effect of mesenchymal stem cell therapy on experimental renal injury induced by ischemia/reperfusion in male albino rat.

BACKGROUND AND OBJECTIVES: Acute kidney injury (AKI) represents a major clinical problem with high mortality and limited treatment protocols. This study was planned to evaluate the therapeutic effectiveness of bone marrow - derived mesenchymal stem cells (BM-MSCs) in a rat model of ischemia/reperfusion (I/R) AKI. METHODS AND RESULTS: This study was carried out on thirty adult male albino rats. Animals were divided equally into three groups. Group I (control sham-operated group) (n=10), were subdivided equally into two subgroups; Ia and Ib. The experimental group (n=20) were all subjected to I/R injury by clamping both renal pedicles for 40 minutes. Half of the I/R animals did not receive MSC therapy (group II) [non-MSC treated group]. The other half of the I/R animals received single intravenous injection of PKH26 labelled BM-MSCs immediately after removal of the clamps and visual confirmation of reflow (group III) [MSC treated group]. Animals were sacrificed 24 hrs (subgroups IIa & IIIa) and 72 hrs (subgroups IIb & IIIb) after intervention. Serological measurements included serum urea and creatinine. Kidney specimens were processed for H&E, PAS and PCNA. Mean % of renal corpuscles with affected glomeruli, mean % of affected tubules, mean area % of PAS-positive reaction and mean area % of PCNA immunoreactivity were measured by histomorphometric studies and statistically compared. MSCs-treated group exhibited protection against renal injury serologically and histologically. CONCLUSIONS: Results of the present study suggest a potential reno-protective capacity of MSCs which could be of considerable therapeutic promise for cell-based management of clinical AKI.

Biomarkers of the intake of dietary polyphenols: strengths, limitations and application in nutrition research.

In order to establish firm evidence for the health effects of dietary polyphenol consumption, it is essential to have quantitative information regarding their dietary intake. The usefulness of the current methods, which rely mainly on the assessment of polyphenol intake using food records and food composition tables, is limited as they fail to assess total intake accurately. This review highlights the problems associated with such methods with regard to polyphenol-intake predictions. We suggest that the development of biological biomarkers, measured in both blood and urine, are essential for making accurate estimates of polyphenol intake. However, the relationship between dietary intakes and nutritional biomarkers are often highly complex. This review identifies the criteria that must be considered in the development of such biomarkers. In addition, we provide an assessment of the limited number of potential biomarkers of polyphenol intake currently available.

Absorption, tissue distribution and excretion of pelargonidin and its metabolites following oral administration to rats.

Recent reports have demonstrated various cardiovascular and neurological benefits associated with the consumption of foods rich in anthocyanidins. However, information regarding absorption, metabolism, and especially, tissue distribution are only beginning to accumulate. In the present study, we investigated the occurrence and the kinetics of various circulating pelargonidin metabolites, and we aimed at providing initial information with regard to tissue distribution. Based on HPLC and LC-MS analyses we demonstrate that pelargonidin is absorbed and present in plasma following oral gavage to rats. In addition, the main structurally related pelargonidin metabolite identified in plasma and urine was pelargonidin glucuronide. Furthermore, p-hydroxybenzoic acid, a ring fission product of pelargonidin, was detected in plasma and urine samples obtained at 2 and 18 h after ingestion. At 2 h post-gavage, pelargonidin glucuronide was the major metabolite detected in kidney and liver, with levels reaching 0.5 and 0.15 nmol pelargonidin equivalents/g tissue, respectively. Brain and lung tissues contained detectable levels of the aglycone, with the glucuronide also present in the lungs. Other tissues, including spleen and heart, did not contain detectable levels of pelargonidin or ensuing metabolites. At 18 h post-gavage, tissue analyses did not reveal detectable levels of the aglycone nor of pelargonidin glucuronides. Taken together, our results demonstrate that the overall uptake of the administered pelargonidin was 18 % after 2 h, with the majority of the detected levels located in the stomach. However, the amounts recovered dropped to 1.2 % only 18 h post-gavage, with the urine and faecal content constituting almost 90 % of the total recovered pelargonidin.

Distribution of [3H]trans-resveratrol in rat tissues following oral administration.

Resveratrol has been widely investigated for its potential health properties, although little is known about its metabolism in vivo. Here we investigated the distribution of metabolic products of [3H]trans-resveratrol, following gastric administration. At 2 h, plasma concentrations reached 1.7 % of the administered dose, whilst liver and kidney concentrations achieved 1.0 and 0.6 %, respectively. Concentrations detected at 18 h were lower, being only 0.5 % in plasma and a total of 0.35 % in tissues. Furthermore, whilst kidney and liver concentrations fell to 10 and 25 %, respectively, of concentrations at 2 h, the brain retained 43 % of that measured at 2 h. Resveratrol-glucuronide was identified as the major metabolite, reaching 7 microm in plasma at 2 h. However, at 18 h the main form identified in liver, heart, lung and brain was native resveratrol aglycone, indicating that it is the main form retained in the tissues. No phenolic degradation products were detected in urine or tissues, indicating that, unlike flavonoids, resveratrol does not appear to serve as a substrate for colonic microflora. The present study provides additional information about the nature of resveratrol metabolites and which forms might be responsible for its in vivo biological effects.

Age-associated changes in protein oxidation and proteasome activities in rat brain: modulation by antioxidants.

The free radical theory of ageing postulates that age-associated neurodegeneration is caused by an imbalance between pro-oxidants and antioxidants resulting in oxidative stress. The current study showed regional variation in brain susceptibility to age-associated oxidative stress as shown by increased lipofuscin deposition and protein carbonyl levels in male rats of age 15-16 months compared to control ones (3-5 months). The hippocampus is the area most vulnerable to change compared to the cortex and cerebellum. However, proteasomal enzyme activity was not affected by age in any of the brain regions studied. Treatment with melatonin or coenzyme Q10 for 4 weeks reduced the lipofuscin content of the hippocampus and carbonyl level. However, both melatonin and coenzyme Q10 treatments inhibited beta-glutamyl peptide hydrolase activity. This suggests that these molecules can alter proteasome function independently of their antioxidant actions.

Cellular uptake and metabolism of flavonoids and their metabolites: implications for their bioactivity.

Flavonoids have been proposed to act as beneficial agents in a multitude of disease states, including cancer, cardiovascular disease, and neurodegenerative disorders. The biological effect of these polyphenols and their in vivo circulating metabolites will ultimately depend on the extent to which they associate with cells, either by interactions at the membrane or more importantly their uptake. This review summarises the current knowledge on the cellular uptake of flavonoids and their metabolites with particular relevance to further intracellular metabolism and the generation of potential new bioactive forms. Uptake and metabolism of the circulating forms of flavanols, flavonols, and flavanones into cells of the skin, the brain, and cancer cells is reviewed and potential biological relevance to intracellular formed metabolites is discussed.