2,2′-dithienyl diselenide,an organoselenium compound,elicits antioxidant action and inhibits monoamine oxidase activity in vitro

Context: Organoselenium compounds have been described as antioxidant and neuroprotective agents.

Objective: To evaluate the antioxidant action of 2,2′-dithienyl diselenide (DTDS) and its effects in brain monoamine oxidase (MAO) activity in vitro.

Materials and methods: Assays for reactive species (RS), lipid peroxidation, protein oxidation, MAO A and B activities in rat brain homogenate as well as mimetic dehydroascorbate reductase and glutathione S-transferase activities were performed using DTDS (μM range).

Results: DTDS was effective in decreasing the levels of RS as well as lipid peroxidation induced by malonate, sodium nitroprusside or FeCl₂/EDTA and protein carbonyl in the rat brain homogenate. DTDS elicited dehydroascorbate reductase-like and glutathione S-transferase-like activities. DTDS was effective in inhibiting both MAO-A and MAO-B activities.

Discussion: The results demonstrated that DTDS is an antioxidant agent with non-selective inhibitory effect on MAO activity.

Conclusion: DTDS is a promising molecule to be evaluated in experimental models of neurological diseases.     

Ganoderma lucidum total triterpenes prevent γ-radiation induced oxidative stress in Swiss albino mice in vivo

Objectives: The in vivo radio-protective effect of total triterpenes isolated from Ganoderma lucidum (Fr.) P. Karst was evaluated using Swiss albino mice, by pre-treatment with total triterpenes for 14 days, followed by a whole body exposure to γ-radiation.

Methods: The activities of the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), and the level of reduced glutathione (GSH) were analysed in liver and brain homogenates. The extent of lipid and protein peroxidation was also estimated in liver and brain homogenates after irradiation. Protection of radiation-induced DNA strand breaks in peripheral blood lymphocytes and bone marrow cells was assessed using the comet assay.

Results: Total triterpenes were highly effective in reducing the levels of lipid peroxidation and protein oxidation to near normal values in both liver and brain tissues. Total triterpenes, when administered in vivo, were also found to be successful in restoring the antioxidant enzyme activities and GSH level in liver and brain of irradiated mice. Administration of total triterpenes, prior to radiation exposure, significantly decreased the DNA strand breaks.

Discussion: The results of the present study thus revealed the potential therapeutic use of Ganoderma total triterpenes as an adjuvant in radiation therapy.     

THE BIRDS OF LIVINGSTONE TOWNSHIP,NORTHERN RHODESIA, 1942–1950

Summary

Clark, R. A. 1979. DDT contamination of the Sacred Ibis. Ostrich 50:134-138.

Samples of fat and brain from Sacred Ibises Threskiornis aethiopicus in Pretoria, Transvaal, were analyzed for organochlorine insecticides. Except for traces of p,p'-DDT only p,p'-DDE was found to occur (means of 28,35 mg/kg wet fat and 0,22 mg/kg wet brain). There was a significant correlation between the concentrations of DDE in the fat and brain of birds (r = 0,53; p ? 0,01). In the period when Sacred Ibises mobilized their fat reserves there was no significant correlation between the level of body fat and the concentration of DDE in either the brain or the remaining body fat.     

Building Biosynthetic Schools: Reviewing Compartmentation of CNS Taurine Synthesis

Taurine is one of the mammalian brain's most abundant and indispensable amino acids. Considerable strides have been made in understanding taurine biosynthesis within the brain, but many disputed issues nonetheless remain. Heading the list is the cellular origin of biosynthetically derived taurine: glial or neuronal? This article reviews the competing theories surrounding cellular compartmentation of taurine biosynthesis in the brain. It concludes that while in vitro systems clearly show astrocytes to be fully capable of taurine synthesis and neurons to be limited to synthesizing taurine from hypotaurine, there is insufficient evidence to attribute these processes to any one cell type in vivo. Instead, there is a growing body of evidence that suggests brain taurine biosynthesis is occurring via a more cooperative metabolic interaction between astrocytes and neurons.

     

Usefulness of parathyroid hormone as a predictor of heart failure with preserved ejection fraction

Objective: To investigate the relation between parathyroid hormone (PTH) and heart failure with preserved ejection fraction (HF-PEF) in outpatients.

Methods: One hundred consecutive patients who had preserved left ventricular (LV) ejection fraction and heart failure (HF) symptoms, were enrolled. Echocardiography, assessing the diastolic functions was performed. Blood samples were collected for intact PTH and brain natriuretic peptide (BNP).

Results: Significant correlations between PTH level and predictors of advanced HF-PEF were found (p < 0.05). PTH level and left atrium diameter were found to be independent predictors of DHF.

Conclusion: Measurement of serum PTH provides complementary information for the diagnosis and prognosis of HF-PEF.     

Caprylic acid ameliorates rotenone induced inflammation and oxidative stress in the gut-brain axis in Zebrafish

Background

Dysfunction of the gastrointestinal tract (GIT) is one of the most common non-motor symptom of Parkinson’s Disease (PD). Pathological processes causing PD were suggested to initiate in the enteric nervous system (ENS) and proceed to the central nervous system (CNS). There are studies showing that low-carbohydrate ketogenic diets can improve motor symptoms of PD. Caprylic acid (C8) is the principal fatty acid component of the medium-chain triglycerides in the ketogenic diets. In this study, we aimed to evaluate the effects of caprylic acid, in neurotoxin exposed zebrafish focusing on the relationship between intestinal and brain oxidative stress and inflammation.

Methods

Adult zebrafish were exposed to rotenone (5 μg/L) (R group) and caprylic acid (20 and 60 mg/mL) (L?+?HDCA and R?+?HDCA groups) for 30 days. At the end of 30 days locomotor activities were determined. Levels of lipid peroxidation (LPO), nitric oxide, glutathione and superoxide dismutase and glutathione S-transferase activities were determined by spectrophotometric methods and gene expressions of tnf?, il1, il6, il21, ifn? and bdnf were evaluated by RT-PCR in the brain and intestinal tissues of zebrafish.

Results

Caprylic acid ameliorated LPO, NO, SOD and the expressions of tnf?, il1, il6, il21, ifn? and bdnf in brain and intestines. Locomotor activities were only ameliorated in high dose R?+?HDCA group.

Conclusions

Caprylic acid ameliorated the neurotoxin-induced oxidative stress and inflammation both in the brain and intestines and enhanced locomotor activity in zebrafish.

Graphical abstract

     

iTRAQ-based proteomics reveals novel biomarkers of osteoarthritis

Abstract

Objective: We performed comprehensive proteomic analyses of articular cartilage by using the isobaric tags for relative and absolute quantitation (iTRAQ) method, and searched for candidate biomarkers for osteoarthritis (OA).

Methods: Articular cartilage was collected from patients with OA or femoral neck fracture for the control group. Molecular variations were detected by the iTRAQ method, and quantitative analyses were performed by western blot.

Results: Using the iTRAQ method, we identified 76 proteins with different expression levels in OA patients and the control group. Among these proteins, we selected LECT2 (leukocyte cell-derived chemotaxin-2), BAALC (brain and acute leukemia, cytoplasmic), and PRDX6 (peroxiredoxin-6), which had not been reported as biomarkers for OA.

Conclusions: Use of these proteins in combination with conventional OA biomarkers may better reflect the grade and prognosis of OA.     

Making a family decision to donate the brain for genomic research: lessons from the genotype-tissue expression project (GTEx)

This study sheds light on the attitudes and circumstances that influence decisions by families to donate the brain of a deceased family member for research. This study, a part of the Genotype-Tissue Expression (GTEx) project, interviewed families of patients who had authorized organ and/or tissue donation for transplantation. A total of 384 family decision makers (FDMs) who decided to donate organs and/or tissues for transplantation were also asked to donate to GTEx. Of these, 297 families were asked to donate their loved one’s whole brain and 87 families responded to a hypothetical request for brain donation. The decision to donate the brain to GTEx, actually or hypothetically, was the major outcome measure. The majority of the FDMs would choose to donate the brain, 78%. Unwillingness to donate the brain was associated with four attitudes: (1) the FDM unwillingness to donate their own tissues for research (OR 1.91, 95% CI .67 to 2.96; p?=?.05), (2) concern with potential for-profit use of tissues (OR 2.12, 95% CI 1.2 to 3.7; p?=?.008), (3) reported squeamishness about tissue donation (OR 1.34, 95% CI 1.1 to 1.7;?p?=?.006), and (4) belief that FDMs should have a say in how the donated tissues are used (OR 1.36, 95% CI 1.13 to 1.5;?p?=?.01). Organ and tissue donors may present a plenteous source of brains for research. Family concerns about tissue use and collection should be addressed by requesters.

     

Hippocampal Up-Regulation of Apolipoprotein D in a Rat Model of Maternal Hypo- and Hyperthyroidism: Implication of Oxidative Stress

Thyroid disorders impair various functions of the hippocampus where thyroid hormone receptors are localized in the brain. Hyper and hypothyroidism are associated with large changes in brain oxidative stress. Apolipoprotein D (APOD) is a conserved glycoprotein that increased in response to oxidative stress in the brain and has been suggested function as an antioxidant in the brain. Thus, the goal of this work was to explore the effect of maternal hypo- and hyperthyroidism on the Apod expression in the pup’s brain regarding changes in oxidative stress. For induction hypo and hyperthyroidism in adult female rats, 100 ppm propylthiouracil (PTU) and 8 ppm levothyroxine administrated 1 month before copulation to the week 3 after delivery in drinking water. The hippocampal region of rat pups was isolated and used for immunohistochemistry and quantitative RT-PCR on postnatal day (PND)5, PND10 and PND20. Results revealed that APOD over-expressed in both hypo- and hyperthyroid groups on PND5, PND10, and PND20. There was a proportional increase between the Apod expression and oxidative stress in the hyperthyroid group but not the hypothyroid in different days. Regarding the wide functions of thyroid hormones, oxidative stress does not suggest to be the only mechanism that involves Apod gene expression in thyroid disturbances.

     

Nanostructured cubosomes in an in situ nasal gel system: an alternative approach for the controlled delivery of donepezil HCl to brain

Abstract

The purpose of this research was to develop cubosomal mucoadhesive in situ nasal gel to enhance the donepezil HCl delivery to the brain. Glycerol mono-oleate (GMO) and surfactant poloxamer 407 were used to prepare cubosomes. The developed formulations were characterized for particle size (PS), poly dispersity index (PDI), zeta potential (ZP), entrapment efficiency (EE), transmission electron microscopy (TEM), in vitro drug release and in vivo bio-distribution study in blood and brain tissue. Central composite design was used for the optimization purpose and the selected formulation (containing GMO 2?g and poloxamer 1.5%) was prepared in presence of gellan gum and konjac gum as gelling agent and mucoadhesive agent respectively. The optimal cubosomal dispersion and optimal cubosomal mucoadhesive in situ nasal gel were subjected to in vivo bio-distribution studies in rat model. It showed significantly higher transnasal permeation and better distribution to the brain, when compared to the drug solution. Thus, the formulated cubosomal mucoadhesive in situ gel could be considered as a promising carrier for brain targeting of CNS acting drugs through the transnasal route.     

Brain glycogen during non-diapausing and diapausing development of Pieris brassicae larvae and pupae

Summary

Histological and cytological localization of glycogen was studied in the brain of Pieris brassicae larvae and pupae by histochemistry and electron microscopy. The major glycogen deposits were observed in glial cells located between the cortex and the neuropile and also in perineurial cells. The concentrations of brain glycogen were measured in the larvae and the pupae during non-diapausing and diapausing development. In addition, we demonstrated that starvation reduces the density of the brain glycogen deposits as well as the concentrations of glycogen.     

Protective effect of polysaccharide-protein complex from a polypore mushroom,Phellinus rimosus against radiation-induced oxidative stress

Abstract

Objectives

Ionizing radiation induces severe oxidative stress in the body resulting an imbalance in prooxidant and antioxidant status in the cell. The aim of the present study is to investigate the protective effect of polysaccharide protein complex (PPC-Pr) isolated from the mushroom Phellinus rimosus against the oxidative stress induced by gamma radiation.

Methodology

PPC-Pr complex was isolated from the aqueous extracts of P. rimosus. The complex was administered to Swiss albino mice at a concentration of 5 and 10 mg/kg body weight intraperitoneally for 5 days consecutively and exposed to 4 Gy of gamma irradiation. Animals were sacrificed 1 day after irradiation and the antioxidant parameters such as glutathione, glutathione peroxidase, superoxide dismutase, catalase, glutathione reductase as well as lipid peroxidation were evaluated in both liver and brain tissues to evaluate oxidative stress. Amifostine, a standard radioprotective agent, was used as a positive control. In vitro DNA damage was assessed using the comet assay. Survival studies were also carried out to determine the protective role of PPC-Pr against radiation-induced delayed oxidative stress.

Results

PPC-Pr treatment enhanced the declined levels of antioxidants and comet parameters to a significant level, indicating its antioxidant as well as DNA protecting potential. Significant increase in the survival rate of animals was also observed in irradiated animals treated with PPC-Pr complex. The results were comparable to the standard drug amifostine.

Discussion

The results indicate profound effects of PPC-Pr against radiation-induced oxidative stress. The findings suggest potential therapeutic use of PPC-Pr in radiotherapy.     

Comparison of β2-microglobulin serum level between Alzheimer’s patients,cognitive healthy and mild cognitive impaired individuals

Background: Several studies performed in the last years on the brain, showed that beta2-microglobulin (β2m) and MHC can act independently of their canonical immune function to regulate normal brain development, synaptic plasticity and behaviour. Increased systemic levels of soluble β2m have been implicated in cognitive impairments like that associated with chronic haemodialysis, or aortic valve replacement. Increased soluble β2m has also been detected in the cerebral spinal fluid (CSF) of patients with HIV-associated dementia and Alzheimer’s disease (AD).

Objective: To compare plasma β2m levels in healthy subjects and subjects with dementia or cognitive impairment.

Methods: We measured the concentration of β2m in a cohort of 245 individuals and compared sex matched, cognitive healthy individuals.

Results: We found higher levels of β2m in AD patients compared to non-AD MCI and healthy controls (2063?ng/mL ±852 versus 1613?±?503 and 1832?±?382?ng/mL, pp?>?0.05).

Conclusions: Our data confirm that β2m could play a role in AD. However, a replication study in an independent cohort would be necessary to confirm our preliminary results.     

Ceramic sculpture of Russell Aitken

Abstract

Pongioli's blowing, and the scraping of the anonymous fiddlers had shaken the air in the great hall. This moved the air in Lord Edward's membrana tympani; the interlocked malleus, incus, and stirrup bones were set in motion so as to agitate the membrana of the oval window and raise an infinitesimal storm in the fluid of the labyrinth. The hairy endings of the auditory nerve shuddered like weeds in a rough sea; a vast number of obscure miracles were performed in the brain, and Lord Edward ecstatically whispered ‘Bach!’—Aldous Huxley, Point Counterpoint

Music is the supreme mystery of human knowledge.—Claude Levi-Strauss     

Neuroglobin and Nogo-a as biomarkers for the severity and prognosis of traumatic brain injury

Abstract

Objective: To identify the early changes of serum neuroglobin and Nogo-A concentrations and the relations to traumatic brain injury (TBI) severity and prognosis.

Methods: Serum samples were obtained and analyzed from 34 patients with TBI within the first 96?h after injury. Comparative analysis combined with Glasgow Coma Scale (GCS) scores and the 6-month prognosis of these patients was performed.

Results: Significant correlations were found between peak serum neuroglobin and Nogo-A concentrations and a patient’s GCS score on admission (p?<?0.001). The mean peak serum neuroglobin and Nogo-A concentrations were both significantly higher in patients with an unfavorable outcome at 6 months after injury (p?<?0.05).

Conclusions: Serum neuroglobin and Nogo-A levels could be suggested as biomarkers for predicting TBI severity and prognosis.

Trial registration: ClinicalTrials.gov identifier: NCT02229643.     

Production of Monoclonal Antibodies Against Corpora Cardiaca Extracts of Locusta Migratoria: A Potential Tool for the Isolation of Insect Neurohormones

Summary

Corpora cardiaca of Locusta migratoria, contain the axon endings of the neurosecretory cells of the brain and store in neurosecretory granules a variety of mostly unidentified neurohormones. Homogenates of corpora cardiaca served to generate a battery of monoclonal antibodies screened by their immunoreactivity to antigenic determinants present in the neurosecretory cells of the pars intercerebralis in the brain. The results are illustrated with three selected monoclonal antibodies which recognize antigens located within the neurosecretory granules of the pericarya of the pars intercerebralis, the cerebro-cardiac axon tracts and the axonic endings in the neurohaemal part of the corpora cardiaca. The apparent molecular weights of these antigenes were determined by Western blotting. We discuss the potential of these monoclonal antibodies for the isolation and structure determination of neuropeptides.     

Dichloroacetate (DCA) reduces brain lactate but increases brain glutamine in experimental cerebral malaria: a 1H-NMR study

Abstract

Recent findings that levels of brain lactate and alanine were elevated in murine cerebral malaria led us to investigate the effect of dichloroacetate (DCA; 60 mg/kg), an activator of pyruvate dehydrogenase, on the levels of brain metabolites, and on the survival of mice infected with Plasmodium berghei ANKA which normally causes lethal cerebral malaria. DCA significantly reduced brain lactate and alanine levels when administered to infected mice, had no effect on the TCA cycle-related metabolites glutamate, GABA and aspartate and was associated with increased brain glutamine levels: 40% of mice thus treated survived the normally lethal infection.     

Changes in S-(2-succinyl)cysteine and advanced glycation end-products levels in mouse tissues associated with aging

Cysteine is non-enzymatically modified by fumarate, which is an intermediate of the tricarboxylic acid cycle, leading to the formation of S-(2-succinyl)cysteine (2SC). Post-translational modification of physiological proteins by fumarate causes enzyme dysfunction. The aim of the study was to evaluate the changes in 2SC accumulation in physiological tissues associated with aging. Brain, liver, kidney, and serum samples were collected from 4-, 12-, and 96-week-old male C57BL/6J mice, and the level of 2SC was determined by liquid chromatography–tandem mass spectrometry (LC–MS/MS) after pretreatment, including delipidation, protein precipitation, and hydrolysis using hydrochloric acid. The 2SC level in the brain was higher than that in other tissues, and its accumulation significantly increased with age. Similarly, N^ε-(carboxymethyl)lysine levels, an advanced glycation end-products (AGEs) that accumulates in tissues in an age-dependent manner, was found to be increased in the brain and kidneys of elderly mice. Accumulation of N^δ-(5-hydro-5-methyl-4-imidazolone-2-yl)-ornithine increased significantly with age, but only in the kidneys. The fumarate content in the brain was similar to that in the liver and kidney at 4 and 12 weeks of age. Furthermore, fumarate contents increased in the liver and kidney at 96 weeks of age, whereas its level did not change in the brain. Our results demonstrated that the changes in 2SC and AGEs levels in tissues reflected differing metabolism and enhanced oxidative stress in each organ; in particular, the metabolism in the brain and kidneys is highly affected by aging.

     

Prothoracicotropic hormone bioassay: Bombyx larva assay

Summary

An assay for the prothoracicotropic hormone (PTTH) has been established using in situ activation of the prothoracic glands (PG) of Bombyx mori in its larva-to-larva development. The timing of PTTH release was estimated by examining developmental response of 4th instar larvae to brain removal and neck ligation, and changes in the haemolymph ecdysteroid titer and ecdysone-releasing activity of PG in vitro during the development. Injection of Bombyx brain extracts into 4th instar larvae neck-ligated shortly before full activation of PG elicited larval moulting rather than precocious pupation in headless larvae. This developmental shift was regarded as due to the action of PTTH, and the PTTH unit has been defined from a linear log dose-response relationship. Materials chromatographically fractionated from Bombyx brain extracts were examined for the presence of stage- and species-specific PTTH molecules by using this Bombyx larva assay and Bombyx and Samia pupa assays previously developed. The same fractions were active when assayed by Bombyx larva and pupa assays.     

Excessive hydrogen sulfide causes lung and brain tissue damage by promoting PARP1/Bax and C9 and inhibiting LAMB1

Excessive hydrogen sulfide (H₂S) causes serious damage to human organs and tissues. In this study, we aimed to explore the role and underlying mechanism of excessive H₂S in brain and lung tissues. A H₂S concentration of 100–800 pm promotes apoptosis and inflammation of brain and lung cells in ICR mice. Mechanistically, a H₂S concentration of 100–800 pm upregulates PARP1 and Bax expression in a dose-dependent manner in vivo and in vitro, and functional gain-and-loss experiments verified that an excessive amount of H₂S plays a pro-apoptotic role in HT22 and MML1 cells via regulation of PARP1 and Bax in vitro. By combining animal and cell experiments, we clarified that excess H₂S promotes the inflammatory response of mouse brain and lung cells by promoting the expression of C9. In addition, the downregulation of LAMB1 by an excessive H₂S concentration was confirmed using mass spectrometry and western blotting in vivo and in vitro. Combined with in vitro experiments, we found that an excessive H₂S concentration promotes the expression of STAT1 and EGFR in HT22 and MML1 cells by inhibiting the expression of LAMB1. In summary, 100–800 pm H₂S causes the brain and lung tissue damage in ICR mice, the underlying mechanisms include H₂S induced apoptosis and inflammation of mouse brain and lung cells by upregulation of PARP1/Bax and C9, respectively, and H₂S might induce fibrosis of mouse brain and lung cells by downregulation of LAMB1.