Synthesis of MnCoO/CNT nanoflakes for the photocatalytic degradation of methyl orange dye and the evaluation of their activity against Culex pipiens larvae in the purification of fresh water.

Researchers worldwide have been looking forward to using novel ways to purify fresh water containing pollutants and disease vectors. In the current work, nanoparticles were introduced as a promising technique for cleaning water and saving human health and living organisms. The nanocomposites, MnCoO and MnCoO/CNTs, were fabricated by a cost-effective co-precipitation method. Phase and molecular structures were investigated by XRD and Raman spectroscopy. The samples exhibited polycrystalline nature of binary phase and weak crystallinity. The elemental composition was recorded by EDX spectra, revealing the purity of the nanoparticles. The surface morphology and particle distribution were described using SEM and TEM micrographs, indicating that MnCoO/CNTs are nanoflakes with a large surface area. The optical parameters include α, E g, n, k, which were identified from T% and R% measurements, suggesting that MnCoO has a direct band gap that reduced with the CNT support. The photocatalytic activity of MnCoO/CNTs was examined for the degradation of methyl orange dye with an efficiency of ∼90.97% over 0.6 g L-1 within 50 min under UV irradiation. In the larvicidal activity, the micrograph images revealed the impact of the nanoflake particles on the 4th instar larvae, where the enzymatic activity of esterases acetylcholinesterase, α- and ß-carboxylesterase, and transaminases drastically decreased with the MnCoO/CNT ratio.

Body mass index stratification in hospitalized Italian adults with congenital heart disease in relation to complexity, diagnosis, sex and age.

BACKGROUND AND AIMS: Adults with congenital heart disease (ACHD) are at risk of overweight and obesity, two major health problems, though underweight can be a negative prognostic factor too. Awareness of the body mass index (BMI) in ACHD is very limited. The present study describes the use and prevalence of BMI in Italian symptomatic hospitalized ACHD patients in relation to complexity by Bethesda system classification, diagnosis, sex and age. METHODS AND RESULTS: We classified 1388 ACHD patients, aged 18-69 years, on the basis of their BMI, and compared them to the Italian reference population. In our total ACHD population we found a significantly higher prevalence of underweight compared to the Italian reference population (6.34% vs 3.20%). ACHD women were more underweight than men. Underweight decreased with age. Overweight was significantly less frequent in the total ACHD population (26.73% compared to 31.70%) in the Italian reference population. Men were more likely to be overweight than women. In statistical terms obesity was similar in the Italian reference population (10.50%) and our ACHD population (9.58%). Both overweight and obesity increased with age. Results were comparable using a diagnostic anatomical-functional classification and the Bethesda system classification. CONCLUSIONS: In our cohort of ACHD the prevalence of underweight was double that of the Italian reference population. The prevalence of overweight was lower, while obesity was similar. Since BMI does not account for differences in body fat distribution, a future aim will be to quantify the visceral component of the adipose tissue in ACHD patients and examine their body composition in order to reflect their risk of acquired cardiovascular disease better, and either to maintain or achieve an adequate visceral component.

Estrogenic Activity Including Bone Enhancement and Effect on Lipid Profile of Luteolin-7-O-glucoside Isolated from Trifolium alexandrinum L. in Ovariectomized Rats.

Luteolin-7-O-glycoside (LG), an abundant component in many edible plants, was found to be one of the major constituents of the aqueous methanol extract of Trifolium alexandrinum L. family Fabaceae, a fodder plant widely cultivated in Egypt. The estrogenic activity of LG concerning the effect on uterotrophy, lipid profile, weight gain and bone enhancement activity was determined in ovariectomized rat model at a dose of 5 mg/kg. Luteolin-7-O-glycoside showed significant estrogenic effect through the preservation of normal uterine weight and plasma estradiol level. It also significantly inhibited the bone turnover markers plasma bone-specific alkaline phosphatase, plasma osteocalsin, type I procollagen N-terminal, and C-telopeptide of type II collagen levels. It induced a significant improvement in plasma lipid profile. The effect of LG was comparable with estradiol with lower effect on uterine weight. Liver and kidney functions revealed a wide safety of LG at this dose level. The present study revealed that LG may be a promising hormone replacement therapy after being examined thoroughly on human. Copyright © 2016 John Wiley & Sons, Ltd.

Activation of migration of endogenous stem cells by erythropoietin as potential rescue for neurodegenerative diseases.

UNLABELLED: Neurodegenerative disorders such as Alzheimer's disease (AD) are characterized by progressive cognitive dysfunction and memory loss. There is deposition of amyloid plaques in the brain and subsequent neuronal loss. Neuroinflammation plays a key role in the pathogenesis of AD. There is still no effective curative therapy for these patients. One promising strategy involves the stimulation of endogenous stem cells. This study investigated the therapeutic effect of erythropoietin (EPO) in neurogenesis, and proved its manipulation of the endogenous mesenchymal stem cells in model of lipopolysaccharide (LPS)-induced neuroinflammation. METHODS: Forty five adult male mice were divided equally into 3 groups: Group I (control), group II (LPS untreated group): mice were injected with single dose of lipopolysaccharide (LPS) 0.8 mg/kg intraperitoneally (ip) to induce neuroinflammation, group III (EPO treated group): in addition to (LPS) mice were further injected with EPO in dose of 40 µg/kg of body weight three times weekly for 5 consecutive weeks. Groups were tested for their locomotor activity and memory using open field test and Y-maze. Cerebral specimens were subjected to histological and morphometric studies. Glial fibrillary acidic protein (GFAP) and mesenchymal stem cell marker CD44 were assessed using immunostaining. Gene expression of brain derived neurotrophic factor (BDNF) was examined in brain tissue. RESULTS: LPS decreased locomotor activity and percentage of correct choices in Y-maze test. Cerebral sections of LPS treated mice showed increased percentage area of dark nuclei and amyloid plaques. Multiple GFAP positive astrocytes were detected in affected cerebral sections. In addition, decrease BDNF gene expression was noted. On the other hand, EPO treated group, showed improvement in locomotor and cognitive function. Examination of the cerebral sections showed multiple neurons exhibiting less dark nuclei and less amyloid plaques in comparison to the untreated group. GFAP positive astrocytes were also reduced. Cerebral sections of the EPO treated group showed multiple branched and spindle CD44 positive cells inside and around blood vessels more than in LPS group. This immunostaining was negative in the control group. EPO administration increased BDNF gene expression. CONCLUSION: This study proved that EPO provides excellent neuroprotective and neurotrophic effects in vivo model of LPS induced neuroinflammation. It enhances brain tissue regeneration via stimulation of endogenous mesenchymal stem cells proliferation and their migration to the site of inflammation. EPO also up regulates cerebral BDNF expression and production, which might contributes to EPO mediated neurogenesis. It also attenuates reactive gliosis thus reduces neuroinflammation. These encouraging results obtained with the use of EPO proved that it may be a promising candidate for future clinical application and treatment of neurodegenerative diseases.

The hematopoietic growth factor "erythropoietin" enhances the therapeutic effect of mesenchymal stem cells in Alzheimer's disease.

Alzheimer's disease is a neurodegenerative disorder clinically characterized by cognitive dysfunction and by deposition of amyloid plaques, neurofibrillary tangles in the brain. The study investigated the therapeutic effect of combined mesenchymal stem cells and erythropoietin on Alzheimer's disease. Five groups of mice were used: control group, Alzheimer's disease was induced in four groups by a single intraperitoneal injection of 0.8 mg kg(-1) lipopolysaccharide and divided as follows: Alzheimer's disease group, mesenchymal stem cells treated group by injecting mesenchymal stem cells into the tail vein (2 x 10(6) cells), erythropoietin treated group (40 microg kg(-1) b.wt.) injected intraperitoneally 3 times/week for 5 weeks and mesenchymal stem cells and erythropoietin treated group. Locomotor activity and memory were tested using open field and Y-maze. Histological, histochemical, immunohistochemical studies, morphometric measurements were examined in brain sections of all groups. Choline transferase activity, brain derived neurotrophic factor expression and mitochondrial swellings were assessed in cerebral specimens. Lipopolysaccharide decreased locomotor activity, memory, choline transferase activity and brain derived neurotrophic factor. It increased mitochondrial swelling, apoptotic index and amyloid deposition. Combined mesenchymal stem cells and erythropoietin markedly improved all these parameters. This study proved the effective role of mesenchymal stem cells in relieving Alzheimer's disease symptoms and manifestations; it highlighted the important role of erythropoietin in the treatment of Alzheimer's disease.

Genome-wide association study meta-analysis of European and Asian-ancestry samples identifies three novel loci associated with bipolar disorder.

Meta-analyses of bipolar disorder (BD) genome-wide association studies (GWAS) have identified several genome-wide significant signals in European-ancestry samples, but so far account for little of the inherited risk. We performed a meta-analysis of ∼750,000 high-quality genetic markers on a combined sample of ∼14,000 subjects of European and Asian-ancestry (phase I). The most significant findings were further tested in an extended sample of ∼17,700 cases and controls (phase II). The results suggest novel association findings near the genes TRANK1 (LBA1), LMAN2L and PTGFR. In phase I, the most significant single nucleotide polymorphism (SNP), rs9834970 near TRANK1, was significant at the P=2.4 × 10(-11) level, with no heterogeneity. Supportive evidence for prior association findings near ANK3 and a locus on chromosome 3p21.1 was also observed. The phase II results were similar, although the heterogeneity test became significant for several SNPs. On the basis of these results and other established risk loci, we used the method developed by Park et al. to estimate the number, and the effect size distribution, of BD risk loci that could still be found by GWAS methods. We estimate that >63,000 case-control samples would be needed to identify the ∼105 BD risk loci discoverable by GWAS, and that these will together explain <6% of the inherited risk. These results support previous GWAS findings and identify three new candidate genes for BD. Further studies are needed to replicate these findings and may potentially lead to identification of functional variants. Sample size will remain a limiting factor in the discovery of common alleles associated with BD.

Mechanisms of vincristine-induced neurotoxicity: Possible reversal by erythropoietin.

Vincristine (VCR) is a potent anticancer drug, but neurotoxicity is one of its most important dose-limiting toxicities. In this study, we investigated the neurotoxic effect of VCR, the possible mechanisms and the role of erythropoietin (EPO) in the protection against VCR-induced neurotoxicity in a rat model. The neurotoxicity of VCR and protective effect of EPO were examined using the tail flick test and by recording electrophysiological characteristics in isolated sciatic nerve. To elucidate the underlying mechanisms, mRNA expression of N-methyl-D-aspartate (NMDA) receptor, an index of glutamate excitotoxicity, and calcitonin gene-related peptide (CGRP), an important regulator of vascular tone, were measured in both spinal cord and sciatic nerves using an RT-PCR method. After intraperitoneal injection at a dose of 150 µg/kg three times weekly for five consecutive weeks, VCR significantly decreased the latency of tail withdrawal reflex, the amplitude of maximum compound action potential (MCAP) and chronaxie, and prolonged the duration of action potential (AP) and relative refractory period (RRP), but it had no effect on conduction velocity. VCR increased NMDA receptor expression and decreased CGRP expression. Forty µg/kg of EPO improved all VCR-induced changes, except chronaxie, while a higher dose of 80 µg/kg reversed all parameters and its effect was more prominent on tail flick test latency and NMDA receptor expression. These results suggested that VCR might cause increased nerve excitability and induce a state of glutamate excitotoxicity through enhancing NMDA receptor expression and diminishing CGRP expression, thus resulting in axonal degeneration. EPO had an obvious neuroprotective effect probably through decreasing NMDA receptor expression and increasing CGRP expression both centrally and peripherally.

Family risk and related education and counseling needs: perceptions of adults with bipolar disorder and siblings of adults with bipolar disorder.

Genetics and mental health professionals increasingly provide education and counseling related to risk for psychiatric illness, but there is insufficient evidence about patient perceptions and needs to guide such interventions. Affected individuals and relatives may perceive increased family risk and have interest in genetic education and counseling. Our objectives were to explore perceptions of family vulnerability, perceived control, and coping strategies related to familial risk and needs from genetic counseling. Our methods included conducting semi-structured interviews (n = 48) with individuals with bipolar disorder (BPD) and unaffected siblings. Content analysis generated descriptive data that provide guidance for clinical interventions and themes to evaluate in future studies. The results showed that participants perceived increased personal and family risk, attributing BPD to genes and family environment. Causal attributions were often uncertain and at times inconsistent. Participants wished to modify psychiatric risk to relatives, but were uncertain how to do so; despite the uncertainty, most parents reported risk-modification efforts. Efforts to cope with family vulnerability included monitoring and cognitive distancing. Participants endorsed the usefulness of education and psychological support, but described more ambivalence about receiving risk assessment. Educational and supportive interventions around family risk for BPD should focus on perceptions of cause and vulnerability, reproductive decision-making, and early intervention and risk modification in young relatives. Psychological support is an important component. Providers should evaluate patient coping strategies, which could facilitate or hinder genetic counseling interventions, and should not assume interest in quantitative risk assessment.

Two variants in Ankyrin 3 (ANK3) are independent genetic risk factors for bipolar disorder.

Two recent reports have highlighted ANK3 as a susceptibility gene for bipolar disorder (BD). We first reported association between BD and the ANK3 marker rs9804190 in a genome-wide association study (GWAS) of two independent samples (Baum et al., 2008). Subsequently, a meta-analysis of GWAS data based on samples from the US and the UK reported association with a different ANK3 marker, rs10994336 (Ferreira et al., 2008). The markers lie about 340 kb apart in the gene. Here, we test both markers in additional samples and characterize the contribution of each marker to BD risk. Our previously reported findings at rs9804190, which had been based on DNA pooling, were confirmed by individual genotyping in the National Institute of Mental Health (NIMH) waves 1-4 (P=0.05; odds ratio (OR)=1.24) and German (P=0.0006; OR=1.34) samples. This association was replicated in an independent US sample known as NIMH wave 5 (466 cases, 212 controls; P=0.017; OR=1.38). A random-effects meta-analysis of all three samples was significant (P=3 x 10(-6); OR=1.32), with no heterogeneity. Individual genotyping of rs10994336 revealed a significant association in the German sample (P=0.0001; OR=1.70), and similar ORs in the NIMH 1-4 and NIMH 5 samples that were not significant at the P<0.05 level. Meta-analysis of all three samples supported an association with rs10994336 (P=1.7 x 10(-5); OR=1.54), again with no heterogeneity. There was little linkage disequilibrium between the two markers. Further analysis suggested that each marker contributed independently to BD, with no significant marker x marker interaction. Our findings strongly support ANK3 as a BD susceptibility gene and suggest true allelic heterogeneity.

Thymoquinone triggers anti-apoptotic signaling targeting death ligand and apoptotic regulators in a model of hepatic ischemia reperfusion injury.

Thymoquinone (TQ) has been reported as a potent inducer of apoptosis in cancer cells. However, the role of TQ as an apoptotic or antiapoptotic has not been established yet in other types of cell injuries. Our objective was to explore whether TQ exerts a hepatoprotective effect against hepatic ischemia reperfusion injury (I/R) and to identify its potential effect on apoptotic pathways. Rats were divided into eight groups: group I: shamoperated; group II: I/R (45 min ischemia-60 min reperfusion). The other six groups were given PO administration of TQ aqueous solution at 5, 20, and 50 mg/kg/day dose levels for 10 days. At the end of treatment three groups were not subjected to any intervention (groups III, IV, and V: TQ control groups) or subjected to 45 min ischemia followed by one-hour reperfusion as in group II (groups VI, VII, and VIII: TQ pretreated I/R groups). Serum levels of liver enzymes, tissue levels of malondialdehyde (MDA), reduced glutathione (GSH) and TNF-α were measured. Activities of caspases 8, 9, and 3 were determined. Cytochrome c in cytosol was determined by solid phase ELISA. Expression of anti-apoptotic Bcl-2 and pro-apoptotic Bax proteins as well as nuclear factor κB (NF-κB) were assessed using polymerase chain reaction. Apoptosis end point was detected using electrophoresis for analysis of DNA fragmentation. TQ administration before I/R resulted in a significant decrease in liver enzymes, MDA and TNF-α tissue levels with increased GSH content. It also inhibited cytochrome c release into the cytosol, down regulated the expression of NF-κB and Bax and up regulated the Bcl-2 proteins. Hepatic apoptosis was significantly attenuated as indicated by a significant decrease in all caspase activities and by DNA fragmentation. In conclusion, TQ exerts an antiapoptotic effect through attenuating oxidative stress and inhibiting TNF-α induced NF-κB activation. Furthermore, it regulates the Bcl-2/Bax ratio and inhibits downstream caspases in this I/R model.

Promising therapy for Alzheimer's disease targeting angiotensinconverting enzyme and the cyclooxygense-2 isoform.

Deposition of ß-amyloid in brain is one of the pathological hallmarks of Alzheimer's disease (AD) that is often associated with inflammatory response. Much evidence also points to a link between the renin-angiotensin system, hypertension and dementia. Accordingly, the potential use of anti-inflammatory and antihypertensives might be beneficial agents in AD therapy. In this study, we investigated the possible mechanisms of Celecoxib (cyclooxygenase-2 (COX-2) inhibitor), Perindopril (angiotensin converting enzyme (ACE) inhibitor) and their combination in a lipopolysaccharide (LPS) model of AD. Mice were injected with LPS (0.8 mg/ kg, i.p.) once then divided into three groups: the first was treated with Celecoxib (30 mg/kg/day, i.p.), the second with Perindopril (0.5 mg/kg/day, i.p.) and the last group with a combination of both drugs. Learning and memory function were tested using a Y-maze and locomotor activity was assessed using an open-field test. Cerebral specimens were subjected to histopathological studies. Brain tumor necrosis factor alpha (TNF-α), and interleukin (IL)-1ß levels were measured. LPS decreased locomotor activity and percentage of correct choices in the Y-maze test. It also produced a significant increase in the percentage area of vascular angiopathy, area of lamellated plaques, and apoptotic index. These were associated with increased TNF-α and IL-1ß. Administration of either Celecoxib or Perindopril partially improved cognitive impairment, decreased inflammatory cytokines and amyloid deposition. Combined therapy of both drugs completely prevented LPS induced neurodegenerative and cognitive changes. In conclusion, these findings establish a link between COX-2, ACE activity and cognitive impairment in AD and provided a promising strategy for the complete cure of AD.

Antioxidant activity and two new flavonoids from Washingtonia filifera.

Two new flavonoids, 8-hydroxyisoscoparin (1) and luteolin 7-O-glucoside 4''-sulfate (2), along with eight known flavonoids, including luteolin 7-O-glucoside 2''-sulfate, were isolated and identified from Washingtonia filifera. All compounds were characterized by (1)H-NMR, (13)C-NMR, CI-MS, FABMS and UV. The antioxidant activities of various W. filifera extracts were determined.

The impact of maternal history and behavior upon foster placement and adjustment in sexually abused girls.

This study investigated the impact of the nonoffending mother's childhood history and current functioning upon the psychological status and placement decisions for 68 sexually abused girls. Maternal history of abuse and/or poor childhood attachment relationships were significantly related to current maternal substance abuse. Maternal substance abuse and dissatisfaction with social support were significantly associated with lack of maternal support to the child and more abuse incidents, which in turn were related to more sexual abuse-related symptomatology and placement in foster care. The findings are congruent with studies indicating that intergenerational transmission of abuse is not inevitable, and suggest that maternal substance abuse and social isolation are important mediating variables between maternal history of sexual abuse and response to the abused child. The findings suggest that interventions targeted to the nonoffending mothers may be important in reducing child dysfunction and placement in foster care in the aftermath of sexual abuse.

Rorschach assessment of psychological functioning in sexually abused girls.

We measured psychological functioning in a group of 79 Black females between the ages of 5 and 16 and a comparison group of nonabused girls using the Rorschach. In addition to Exner's (1985) Comprehensive System, the Elizur (1949) Rorschach Content Test Scale (RCT), the Mutuality of Autonomy Scale (MOA; Urist, 1977; Urist & Shill, 1982), and the Barrier and Penetration Scales (Fisher & Cleveland, 1968) were used. Sexually abused girls were found to show more disturbed thinking, to experience a higher level of stress relative to their adaptive abilities, to describe human relationships more negatively, and to show more preoccupation with sexuality than the comparison group. The distress experienced by the victimized children was more related to internal mediating variables then to abuse characteristics. Sexually abused girls who are cognitively and emotionally active also experienced high levels of distress compared to abused girls who are psychologically constricted.

Interleukins 1 alpha and 6 and tumor necrosis factor-alpha are paracrine inhibitors of human melanocyte proliferation and melanogenesis.

Interleukin (IL)-1 alpha, IL-6, and tumor necrosis factor (TNF)-alpha are epidermal cytokines that produce many similar biologic effects. We have investigated the possibility that these cytokines act as regulators of melanization and proliferation of cultured normal human melanocytes (NHM). All three cytokines elicited a dose-dependent decrease in the activity of the enzyme tyrosinase after 48 h of treatment. IL-1 alpha had the greatest inhibitory effect, resulting in a 22% inhibition of tyrosinase activity at a concentration of 3 x 10(-14) M. An equivalent effect was elicited by 4 x 10(-11) M IL-6 and 10(-11) M TNF-alpha. All three cytokines also inhibited melanocyte proliferation, as measured by a decrease in the rate of 3H-thymidine incorporation and an increase in doubling time. IL-1 alpha at 6 x 10(-14) M, 6 x 10(-13) M, and 3 x 10(-12) M, TNF-alpha at 10(-10) M, 10(-9) M, and 10(-8) M, and IL-6 at 4 x 10(-10) and 1.2 x 10(-9) M produced a dose-dependent inhibition of 3H-thymidine incorporation. The effects of IL-1 alpha, TNF-alpha, and IL-6 were cytostatic, not cytotoxic, because melanocytes remained viable following several treatments with the cytokines. Also, melanocytes treated with IL-1 alpha and TNF-alpha recovered and resumed proliferation after cessation of treatment. These effects of IL-1 alpha, IL-6 and TNF-alpha do not seem to be mediated by stimulation of eicosanoid production, because inhibition of arachidonic acid (AA) metabolism by indomethacin, a cyclooxygenase inhibitor, and nordihydroguaiaretic acid, a lipoxygenase inhibitor, did not reverse the inhibitory effects on either proliferation or tyrosinase activity of NHM. This is the first demonstration that NHM respond to epidermal cytokines, and suggests a role for paracrine and possibly autocrine regulation of melanocytes by immune modulators.

Multimethod assessment of depression in sexually abused girls.

This study measured depression in sexually abused Black girls using the Children's Depression Inventory (Kovacs & A. T. Beck, 1977), the Internalization scale of the Child Behavior Checklist (Achenbach & Edelbrock, 1983), and the Rorschach Depression Index (Exner, 1986). There were no significant correlations between these self-report, behavior observation (by parental report), and projective measures. The abused subjects had high scores on the behavior observation and Rorschach scales. Consistent with past research, negative results were obtained with the self-report instrument. We suggest that the low scores on self-report measures of distress produced by sexually abused children may be the result of guardedness or defensiveness rather than a genuinely low level of dysphoria in this population. There were no significant relations between abuse characteristics and scores on the depression measures. Scores on Rorschach measures of organizational activity (Zf) and available coping resources (EA) were generally positively related to depression within the abuse group and negatively related to depression within the control group.