SYNERGISM BETWEEN PROBIOTICS AND HERBS TO MANAGE TYPE 2 DIABETES IN RATS

Objective: This study aims to explore the adjuvant effect of multi-strain probiotics with either saffron, cardamom, ginger, or cinnamon herbs to achieve synergistic management for controlling type 2 diabetes (T2D). Methods: Eighty-eight adult male, Wistar rats were used. Eight rats were kept as healthy control. Eighty rats were used to induce type 2 diabetic rats (T2DR) and were randomly assigned to ten groups. One group was an offer to 0.2 ml multi-strain probiotics orally. The rest of T2DR were gavage with 100 mg/kg aqueous extract of saffron, cardamom, ginger, or cinnamon without or with 0.2 ml multi-strain probiotics orally. Bodyweight gain (BWG), and feed efficiency ratio (FER) were recorded. Determination of oral glucose tolerance test (OGTT), serum insulin, C-peptide, HDL, LDL, HDL/total cholesterol ratio were performed. Serum antioxidant activity, Th1and Th2 cytokines and histopathology of the pancreas were done. Results: Comparable with T2DR, solely multi-strain probiotics or with herbs caused a significant reduction in BWG (P<0.05). Groups fed saffron, cardamom, and ginger and enriched with multi-strain probiotic showed significant improvement in OGTT, serum insulin, C-peptide and lipid abnormalities (P<0.05) compared to T2DR. Besides, they had antioxidant and anti-inflammatory effects. The group received ginger alone exerted anti-hyperglycemia and anti-inflammatory effects. However, cinnamon had a moderate anti-diabetic effect and solely probiotics did not show a significant benefit for all parameters except BWG. Conclusion: Cardamom, saffron, and ginger enriched with multi-strain probiotics achieve a synergistic relationship for managing T2D. This finding exhibits a possible new hypothesis to manage diabetes that needs further study

A comparison of the early motor repertoire of very preterm infants and term infants

OBJECTIVE: To obtain reference data on the early motor repertoire of very preterm infants compared with healthy term infants at three months' post-term age. STUDY DESIGN: In this observational study, using Prechtl's method on the assessment of the early motor repertoire, we compared the quality of fidgety movements and the concurrent motor optimality score - revised of infants with a gestational age <30 weeks and/or a birth weight <1000 g with healthy infants with a gestational age of 37-42 weeks. RESULTS: One hundred eighty very preterm and 180 healthy term infants participated. The median motor optimality scores - revised of very preterm infants were significantly lower in comparison to those of term infants, with scores of 24 (25th-75th percentiles: 23-26) and 26 (25th-75th percentiles: 26-28), respectively. Fidgety movements were aberrant (abnormal or absent) more often in very preterm infants than in term infants. The odds ratio was 4.59 (95% CI, 1.51-13.92). Compared with term infants, very preterm infants had poorer scores on the subscales age-adequate movement repertoire, observed postural patterns, and movement character with odds ratios ≥2.97. We found no differences regarding observed movement patterns. CONCLUSION: This study provides reference data on the early motor repertoire of very preterm and healthy term infants. It demonstrates that the early motor repertoire of very preterm infants is poorer than that of term infants, a finding consistent with existing knowledge that prematurity increases the risk of poor neurodevelopment

CYP1B1 and myocilin gene mutations in Egyptian patients with primary congenital glaucoma

Purpose: Primary congenital glaucoma (PCG) accounts for 26–29% of childhood blindness in Egypt. The identification of disease causing mutations has not been extensively investigated. We aimed to examine the frequency of CYP1B1 and MYOC mutations in PCG Egyptian patients, and study a possible genotype/phenotype correlation.Methods: Ninety-eight patients with PCG diagnosed at the Ophthalmology department ofAlexandria Main University Hospital were enrolled. Demographic and phenotypic characteristics were recorded. Patients and 100 healthy subjects (control group) were screened for two mutations in CYP1B1 gene (G61E, R368H) and one mutation in MYOC gene (Gln48His) using polymerase chain reaction/restriction fragment length polymorphism (PCR/RFLP). Phenotypic characteristics pertaining to disease severity were compared.Results: Nineteen patients (19%) with PCG were found positive for one or more of the mutations screened for. Seven patients (7%) were homozygous for the G61E mutation. Ten patients (10%) were heterozygous; 6 for the G61E mutation, 2 for the R368H mutation and 2 for the Gln48His mutation. Two patients (2%) were double heterozygotes harboring a R368H as well as a Gln48His mutation. The most common mutation observed was the G61E in 13 patients; 7 homozygotes and 6 heterozygotes for the mutation. The control group were negative for all mutations screened for. No significant correlations between the mutations and phenotype severity were detected. A statistically significant positive correlation however was found between the different mutations andeach of the IOP and the cup/disk ratio.Conclusion: The current study further endorses the role of CYP1B1 mutations in the etiology of PCG among Egyptian patients and is the first study to report MYOC gene mutation in Egyptian patients with PCG

Fetal Brain-Sparing, Postnatal Cerebral Oxygenation, and Neurodevelopment at 4 Years of Age Following Fetal Growth Restriction

Objectives: To assess the role of fetal brain-sparing and postnatal cerebral oxygen saturation (r cSO 2) as determinants of long-term neurodevelopmental outcome following fetal growth restriction (FGR). Methods: This was a prospective follow-up study of an FGR cohort of 41 children. Prenatally, the presence of fetal brain-sparing (cerebroplacental ratio < 1) was assessed by Doppler ultrasound. During the first two days after birth, r cSO 2 was measured with near-infrared spectroscopy. At 4 years of age, intelligence (IQ points), behavior (T-scores), and executive function (T-scores) were assessed using the Wechsler Preschool and Primary Scale of Intelligence, Child Behavior Checklist, and Behavior Rating Inventory of Executive Function—Preschool Version, respectively. Using linear regression analyses, we tested the association (p < 0.05) between brain-sparing/r cSO 2 and normed neurodevelopmental scores. Results: Twenty-six children (gestational age ranging from 28.0 to 39.9 weeks) participated in the follow-up at a median age of 4.3 (range: 3.6 to 4.4) years. Autism spectrum disorder was reported in three children (11.5%). Fetal brain-sparing was associated with better total and externalizing behavior (betas: −0.519 and −0.494, respectively). R cSO 2 levels above the lowest quartile, particularly on postnatal day 2 (≥ 77%), were associated with better total and internalizing behavior and executive functioning (betas: −0.582, −0.489, and −0.467, respectively), but also lower performance IQ (beta: −0.530). Brain-sparing mediated some but not all of these associations. Conclusions: In this FGR cohort, fetal brain-sparing and high postnatal r cSO 2 were—independently, but also as a reflection of the same mechanism—associated with better behavior and executive function. Postnatal cerebral hyperoxia, however, was negatively associated with brain functions responsible for performance IQ

Cellular, molecular and functional characterisation of YAC transgenic mouse models of Friedreich Ataxia

Copyright © 2014 Anjomani Virmouni et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.This article has been made available through the Brunel Open Access Publishing Fund.Background - Friedreich ataxia (FRDA) is an autosomal recessive neurodegenerative disorder, caused by a GAA repeat expansion mutation within intron 1 of the FXN gene. We have previously established and performed preliminary characterisation of several human FXN yeast artificial chromosome (YAC) transgenic FRDA mouse models containing GAA repeat expansions, Y47R (9 GAA repeats), YG8R (90 and 190 GAA repeats) and YG22R (190 GAA repeats). Methodology/Principal Findings - We now report extended cellular, molecular and functional characterisation of these FXN YAC transgenic mouse models. FXN transgene copy number analysis of the FRDA mice demonstrated that the YG22R and Y47R lines each have a single copy of the FXN transgene while the YG8R line has two copies. Single integration sites of all transgenes were confirmed by fluorescence in situ hybridisation (FISH) analysis of metaphase and interphase chromosomes. We identified significant functional deficits, together with a degree of glucose intolerance and insulin hypersensitivity, in YG8R and YG22R FRDA mice compared to Y47R and wild-type control mice. We also confirmed increased somatic GAA repeat instability in the cerebellum and brain of YG22R and YG8R mice, together with significantly reduced levels of FXN mRNA and protein in the brain and liver of YG8R and YG22R compared to Y47R. Conclusions/Significance - Together these studies provide a detailed characterisation of our GAA repeat expansion-based YAC transgenic FRDA mouse models that will help investigations of FRDA disease mechanisms and therapy.European Union, Ataxia UK and FARA

Organ-specific toxicity evaluation of stearamidopropyl dimethylamine (SAPDMA) surfactant using zebrafish embryos

Surfactants are widely used in the industry of detergents, household products, and cosmetics. SAPDMA is a cationic surfactant that is used mostly in cosmetics, conditioning agents and has recently gained attention as a corrosion inhibitor in the sea pipelines industry. In this regard, literature concerning the ecotoxicological classification of SAPDMA on aquatic animals is lacking. This study aims to evaluate the potential ecotoxicity of SAPDMA using the aquatic zebrafish embryo model. The potential toxic effects of SAPDMA were assessed by different assays. This includes (i) mortality/survival assay to assess the median lethal concentration (LC50); (ii) teratogenicity assay to assess the no observed effect concentration (NOEC); (iii) organ-specific toxicity assays including cardiotoxicity, neurotoxicity (using locomotion assay), hematopoietic toxicity (hemoglobin synthesis using o-dianisidine staining), hepatotoxicity (liver steatosis and yolk retention using Oil Red O (ORO) stain); (iv) cellular cytotoxicity (mitochondrial membrane potential) by measuring the accumulation of JC-1 dye into mitochondria. Exposure of embryos to SAPDMA caused mortality in a dose-dependent manner with a calculated LC50 of 2.3 mg/L. Thus, based on the LC50 value and according to the Fish and Wildlife Service (FWS) Acute Toxicity Rating Scale, SAPDMA is classified as “moderately toxic”. The No Observed Effect Concentration (NOEC) concerning a set of parameters including scoliosis, changes in body length, yolk, and eye sizes was 0.1 mg/L. At the same NOEC concentration (0.1 mg/L), no organ-specific toxicity was detected in fish treated with SAPDMA, except hepatomegaly with no associated liver dysfunctions. However, higher SAPDMA concentrations (0.8 mg/L) have dramatic effects on zebrafish organ development (eye, heart, and liver development). Our data recommend a re-evaluation of the SAPDMA employment in the industry setting and its strictly monitoring by environmental and public health agencies

Annona Muricata L. extract restores renal function, oxidative stress, immunohistochemical structure, and gene expression of TNF-α, IL-β1, and CYP2E1 in the kidney of DMBA-intoxicated rats

Introduction: 7,12-dimethylbenz (a) anthracene (DMBA) is a harmful polycyclic aromatic hydrocarbon derivative known for its cytotoxic, carcinogenic, and mutagenic effects in mammals and other species. Annona muricata, L. (Graviola; GRV) is a tropical fruit tree traditionally well-documented for its various medicinal benefits. This investigation is the first report on the potential antioxidant and antinfammatory reno-protective impact of GRV against DMBA-induced nephrotoxicity in rats.Methods: Forty male albino rats were allocated into four equal groups (n = 10). The 1st group served as the control, the 2nd group (GRV) was gastro-gavaged with GRV (200 mg/kg b.wt), the 3rd group (DMBA) was treated with a single dose of DMBA (15 mg/kg body weight), and the 4th group (DMBA + GRV) was gastro-gavaged with a single dose of DMBA, followed by GRV (200 mg/kg b.wt). The GRV administration was continued for 8 weeks.Results and Discussion: Results revealed a significant improvement in renal function, represented by a decrease in urea, creatinine, and uric acid (UA) in the DMBA + GRV group. The antioxidant potential of GRV was confirmed in the DMBA + GRV group by a significant decline in malondialdehyde (MDA) and a significant increase in catalase (CAT), superoxide dismutase (SOD), glutathione S transferase (GST), and reduced glutathione (GSH) compared to DMBA-intoxicated rats; however, it was not identical to the control. Additionally, the antiinflammatory role of GRV was suggested by a significant decline in mRNA expression of cytochrome P450, family 2, subfamily e, polypeptide 1 (CYP2E1), tumor necrosis factor-alpha (TNF-α), and interleukin 1 beta (IL-1β) in the DMBA + GRV group. Moreover, GRV improved the histopathologic and immunohistochemical expression of TNF-α, CYP450, and IL1β in DMBA-intoxicated kidney tissue. Conclusively, GRV is a natural medicinal product that can alleviate the renal injury resulting from environmental exposure to DMBA. The reno-protective effects of GRV may involve its anti-inflammatory and/or antioxidant properties, which are based on the presence of phytochemical compounds such as acetogenins, alkaloids, and flavonoids

Generation and characterisation of Friedreich ataxia YG8R mouse fibroblast and neural stem cell models

This article has been made available through the Brunel Open Access Publishing Fund.Background: Friedreich ataxia (FRDA) is an autosomal recessive neurodegenerative disease caused by GAA repeat expansion in the first intron of the FXN gene, which encodes frataxin, an essential mitochondrial protein. To further characterise the molecular abnormalities associated with FRDA pathogenesis and to hasten drug screening, the development and use of animal and cellular models is considered essential. Studies of lower organisms have already contributed to understanding FRDA disease pathology, but mammalian cells are more related to FRDA patient cells in physiological terms. Methodology/Principal Findings: We have generated fibroblast cells and neural stem cells (NSCs) from control Y47R mice (9 GAA repeats) and GAA repeat expansion YG8R mice (190+120 GAA repeats). We then differentiated the NSCs in to neurons, oligodendrocytes and astrocytes as confirmed by immunocytochemical analysis of cell specific markers. The three YG8R mouse cell types (fibroblasts, NSCs and differentiated NSCs) exhibit GAA repeat stability, together with reduced expression of frataxin and reduced aconitase activity compared to control Y47R cells. Furthermore, YG8R cells also show increased sensitivity to oxidative stress and downregulation of Pgc-1α and antioxidant gene expression levels, especially Sod2. We also analysed various DNA mismatch repair (MMR) gene expression levels and found that YG8R cells displayed significant reduction in expression of several MMR genes, which may contribute to the GAA repeat stability. Conclusions/Significance: We describe the first fibroblast and NSC models from YG8R FRDA mice and we confirm that the NSCs can be differentiated into neurons and glia. These novel FRDA mouse cell models, which exhibit a FRDA-like cellular and molecular phenotype, will be valuable resources to further study FRDA molecular pathogenesis. They will also provide very useful tools for preclinical testing of frataxin-increasing compounds for FRDA drug therapy, for gene therapy, and as a source of cells for cell therapy testing in FRDA mice. © 2014 Sandi et al

AEO-7 surfactant is “super toxic” and induces severe cardiac, liver and locomotion damage in zebrafish embryos

© 2020, The Author(s). Background: Fatty alcohol polyoxyethylene ether-7 (AEO-7), a non-ionic surfactant, has recently been receiving extensive attention from the ocean pipeline industry for its ability to inhibit corrosion. However, the present lack of information concerning the potential environmental toxicity of AEO-7, especially towards aquatic organisms, is a major impediment to its wider application. Here, we assess potential adverse effects of AEO-7 on zebrafish embryos employing a variety of assays, including (i) a mortality/survival assay which allowed the median lethal concentration (LC50) to be calculated; (ii) a teratogenicity assay on the basis of which the no observed effect concentration (NOEC) was determined; and (iii) specific assays of cardiotoxicity, neurotoxicity (based on locomotion), hematopoietic toxicity (the level of hemoglobin as revealed by o-dianisidine staining) and hepatotoxicity (liver steatosis and yolk retention examined by staining with Oil Red O). Results: AEO-7 caused mortality with a calculated LC50 of 15.35 μg/L, which, according to the U.S. Fish and Wildlife Service (USFWS) Acute Toxicity Rating scale, should be considered “super toxic”. Although at its NOEC (0.8 μg/L), there were no signs of significant teratogenicity, cardiotoxicity, or hemopoiesis toxicity, 3.2 µg/L AEO-7 exerted dramatic detrimental effects on organ development. Conclusion: On the basis of these findings, we recommend that the industrial usage and environmental impact of AEO-7 be re-evaluated and strictly monitored by environmental and public health organizations

Sloan Digital Sky Survey Imaging of Low Galactic Latitude Fields: Technical Summary and Data Release

The Sloan Digital Sky Survey (SDSS) mosaic camera and telescope have obtained five-band optical-wavelength imaging near the Galactic plane outside of the nominal survey boundaries. These additional data were obtained during commissioning and subsequent testing of the SDSS observing system, and they provide unique wide-area imaging data in regions of high obscuration and star formation, including numerous young stellar objects, Herbig-Haro objects and young star clusters. Because these data are outside the Survey regions in the Galactic caps, they are not part of the standard SDSS data releases. This paper presents imaging data for 832 square degrees of sky (including repeats), in the star-forming regions of Orion, Taurus, and Cygnus. About 470 square degrees are now released to the public, with the remainder to follow at the time of SDSS Data Release 4. The public data in Orion include the star-forming region NGC 2068/NGC 2071/HH24 and a large part of Barnard's loop.Comment: 31 pages, 9 figures (3 missing to save space), accepted by AJ, in press, see http://photo.astro.princeton.edu/oriondatarelease for data and paper with all figure