Oxidative stress induced by administration of the neuroleptic drug haloperidol is attenuated by higher doses of haloperidol

The effect of haloperidol administration on lipid peroxidation and glutathione/protein thiol homeostasis in the brain was examined 4 h following subcutaneous administration of a single dose of haloperidol; 1.0, 1.5, 2.0 or 2.5 mg/kg b.wt. Glutathione (GSH) levels decreased significantly in cortex, striatum and midbrain after haloperidol administration. Maximal decreases of GSH was observed in the striatum. The depleted GSH was recoverable as protein glutathione mixed disulfide (Pr-SSG) with concomitant loss of protein thiols (Pr-SH) in all the regions of the brain examined. Administration of 1.5 mg/kg b.wt of haloperidol resulted in significant depletion of GSH in striatum and midbrain as compared to that after administration of the lower dose of 1.0 mg/kg b.wt. of haloperidol. However, administration of higher doses of haloperidol (2.0 and 2.5 mg/kg b.wt.) did not result in greater depletion of GSH; the GSH levels were not significantly different from that observed following the administration of 1.5 mg/kg b.wt. of haloperidol. However, Pr-SSG levels increased dose-dependently following haloperidol administration. The total GSH recovered as sum of GSH and Pr-SSG was significantly higher than controls in striatum and midbrain following administration of higher doses of haloperidol, namely, 2.0 and 2.5 mg/kg b.wt. The depleted GSH was not recoverable as glutathione disulfide (GSSG), GSSG levels were not significantly different from controls 4 h after administration of 1.5 mg/kg b.wt. of haloperidol. The levels of malondialdehyde (indicative of lipid peroxidation) increased significantly as compared to control levels (280-220%) following administration of 1.0 and 1.5 mg/kg b.wt. of haloperidol. Thereafter, the malondialdehyde levels in brain regions decreased and were only (186-150%) of control levels after administration of 2.0 and 2.5 mg/kg b.wt. of haloperidol, respectively. The present study demonstrates that administration of low doses of haloperidol results in depletion of GSH and increased levels of malondialdehyde. However, administration of higher doses of haloperidol results in attenuation of peroxidative damage with concomitant increase in the total GSH recovered as sum of free GSH and GSH bound to protein thiols (Pr-SSG)

Low glutathione levels in brain regions of aged rats

Glutathione (GSH) was measured in 6 regions of brain and liver of young adult, middle-aged and aged rats. GSH levels were significantly lower in cortex, cerebellum, striatum, thalamus and hippocampus of aged rats, while no changes were observed in liver as compared to young adult rats. On the other hand, lipid peroxidation as measured by thiobarbituric acid-reactive products increased significantly in all the regions of brain examined and in the liver of aged rats. Since GSH plays an important role as a cellular protectant against oxygen radical-mediated injury, decreased levels of GSH in aged rat brain are indicative of the vulnerability of the aged cerebral tissue to oxidative injury

Growing of Chlorella, Scenedesmus and Botryococus in sewage water for biodiesel production

Algae grown on wastewater media are a potential source of low-​cost lipids for prodn. of liq. biofuels. This study was aimed to est. the effect of Physico-​chem. characteristics of normal and sewage water (pH 7.60 and 6.60, EC 15.97 and 12.36 μmol, free Co2 1.48 and 0.74, nitrogen 0.90 and 0.50 mg​/l, potassium 168.11 and 54.63 mg​/l, calcium 249.52 and 112.21 mg​/l, magnesium 104.91 and 51.19 mg​/l, sulfate 57.08 and 28.35 mg​/l, chloride 98.00 and 84.63 mg​/l, carbonates 362.18 and 32.64 mg​/l and bicarbonates 1138.30 and 253.33 mg​/l in sewage and normal water resp.) on Chlorella, Scenedesmus and Botryococus. The highest biomass (4.533 mg ml-​1)​, chlorophyll (15.56 μg ml-​1)​, lipid (49 %)​, acid value (0.52 mg KOH​/g)​, d. (0.885 g​/cm3)​, iodine value (75 mg​/g)​, sapon. value (0.125 mg KOH​/g)​, viscosity (4.8 mm2​/s)​, myristic acid (9.0​%)​, oleic acid (9.3​%)​, linolenic acid (20.1​%)​, palmitic acid (35.3​%)​, stearic acid (6.1​%) was obsd. in Scenedesmus than Botryococus and Chlorella. The properties of algal oil meet all the properties given by American society for testing and materials (ASTM) D6751, ISO 15607 and EN14214- Europe. Hence, it is concluded that algae can be grown better in sewage water than normal water for their oil and used as a potential feedstock for liq. biofuel prodn

A Method to Identify and Isolate Pluripotent Human Stem Cells and Mouse Epiblast Stem Cells Using Lipid Body-Associated Retinyl Ester Fluorescence.

We describe the use of a characteristic blue fluorescence to identify and isolate pluripotent human embryonic stem cells and human-induced pluripotent stem cells. The blue fluorescence emission (450–500 nm) is readily observed by fluorescence microscopy and correlates with the expression of pluripotency markers (OCT4, SOX2, and NANOG). It allows easy identification and isolation of undifferentiated human pluripotent stem cells, high-throughput fluorescence sorting and subsequent propagation. The fluorescence appears early during somatic reprogramming. We show that the blue fluorescence arises from the sequestration of retinyl esters in cytoplasmic lipid bodies. The retinoid-sequestering lipid bodies are specific to human and mouse pluripotent stem cells of the primed or epiblast-like state and absent in naive mouse embryonic stem cells. Retinol, present in widely used stem cell culture media, is sequestered as retinyl ester specifically by primed pluripotent cells and also can induce the formation of these lipid bodies

Identification of potential serum biomarkers of glioblastoma: serum osteopontin levels correlate with poor prognosis

Background: The aim of this study is to identify serum biomarkers with classification and prognosis utility for astrocytoma, in particular glioblastoma (GBM). Methods: Our previous glioma microarray database was mined to identify genes that encode secreted or membrane-localized proteins. Subsequent analysis was done using significant analysis of microarrays, followed by reverse transcription-quantitative PCR (RT-qPCR) and immunohistochemical validation in tumor tissues, ELISA and Western blot validation in sera, and correlation with survival of GBM patients. Results: Significant analysis of microarrays identified 31 upregulated and 3 downregulated genes specifically in GBMs. RT-qPCR validation on an independent set of samples confirmed the GBM-specific differential expression of several genes, including three upregulated (CALU, CXCL9, and TIMP1) and two downregulated (GPX3 and TIMP3) novel genes. With respect to osteopontin (OPN), we show the GBM-specific upregulation by RT-qPCR and immunohistochemical staining of tumor tissues. Elevated serum OPN levels in GBM patients were also shown by ELISA and Western blot. GBM patients with high serum OPN levels had poorer survival than those with low serum OPN levels (median survival 9 versus 22 months respectively; P = 0.0001). Further, we also show high serum TIMP1 levels in GBM patients compared with grade II/III patients by ELISA and downregulation of serum GPX3 and TIMP3 proteins in GBMs compared with normal control by Western blot analysis. Conclusions: Several novel potential serum biomarkers of GBM are identified and validated. High serum OPN level is found as a poor prognostic indicator in GBMs. Impact: Identified serum biomarkers may have potential utility in astrocytoma classification and GBM prognosis

What makes the pregnant women revisit public hospitals for research? Participant engagement and retention trial in a public hospital (PERTH): an RCT protocol.

BACKGROUND: Cohort studies have public health importance as they effectively provide evidence on determinants of health from a life course perspective. Researchers often confront the poor follow-up rates as a major challenge in the successful conduct of cohort studies. We are currently recruiting in a birth cohort study, titled as "Maternal Antecedents of Adiposity and Studying the Transgenerational role of Hyperglycemia and Insulin" (MAASTHI) in a public hospital; with the aim of assessing maternal glycemic levels on the risk of adverse fetal outcomes. Nested within the ongoing cohort, the proposed trial aims to evaluate the effectiveness of two interventions in improving the follow-up in the cohort study in a public hospital. METHODS: A randomized trial of 795 pregnant women, with 265 women each in three arms observed through pregnancy, until their baby is 14 weeks old. The comparator group receives a standard leaflet, with details on the importance of glucose testing and regular follow up in pregnancy. Intervention arm-1 will receive the standard leaflet plus individualized messages, through an Interactive Voice Response (IVR) system; a type of computer-linked telephone intervention system to remind the participants about the lab test and follow-up dates. Intervention arm- 2 will have the opportunity to attend Mother and Baby Affairs (MBA) workshops, which will provide information on Gestational Diabetes Mellitus (GDM) screening and management to pregnant women and personalized counselling services. The outcome of interest is the difference in the proportion of participants completing follow-up at different points in time, among three arms. DISCUSSION: Between the two interventions (IVR and MBA), the study results would uncover the contextually specific, timely intervention, which can increase the proportion of pregnant women followed up in public hospitals. If effective, this study will provide information on an effective intervention, useful in ensuring the success of longitudinal follow-up in the public hospitals. TRIAL REGISTRATION: NCT03088501 , Date Registered: 16/03/2017

Stabilnost amlodipin besilata i atenolola u jednoslojnim i dvoslojnim tabletama

Multi-drug tablets of amlodipine besylate and atenolol were prepared as either mono-layer (mixed matrix) or bi-layer tablets containing each drug in a separate layer by using similar excipients and processing. Each tablet batch was packed in strip and blister packs and kept under accelerated temperature and humidity conditions. The stability of two tablet and packaging types was compared by HPLC analysis after 0, 1, 3 and 4.5 months and expressed as the content of intact amlodipine and atenolol. The content of atenolol did not decline regardless of tablet and packaging type. Amlodipine content in bi-layer tablets decreased to about 95 and 88% when packed in strips and blisters, respectively. When prepared as mono-layer tablets, the content decreased to 72 and 32%, respectively. The study revealed that the bi-layer tablet formulation was more stable than the mono-layer type. Further, the stability was increased when the tablets were packed in aluminium strips as compared to PVC blisters.Tablete s amlodipinom i atenololom pripremljene su ili u obliku jednoslojne tablete (miješani matriks) ili kao dvoslojne tablete (lijekovi u zasebnim slojevima) koristeći slične pomoćne tvari i uvjete tabletiranja. Tablete su pakirane u dvije vrste pakiranja, aluminijske folije (strip) ili PVC (blister) i čuvane u uvjetima ubrzanog starenja. Stabilnost je određivana pomoću HPLC metode nakon 0, 1, 2, 3 i 4,5 mjeseci i izražena kao sadržaj intaktnog lijeka. Sadržaj atenolola nije se značajno promijenio bez obzira na tip tablete ili pakiranje. Sadržaj amlodipina u dvoslojnim tabletama smanjio se na 95 % (tablete u strip pakiranju) i 88 % (tablete u blister pakiranju). Istodobno, u jednoslojnom tipu kombiniranih tableta sadržaj se smanjio na 72 % (strip pakiranje) i 32 % (blister pakiranje). Rezultati pokazuju da su dvoslojne tablete s amlodipinom i atenololom stabilnije od jednoslojnih. Štoviše, pakiranje tableta u aluminijsku foliju u obliku strip pakiranja povećava njihovu stabilnost u usporedbi s PVC pakirnim materijalom (blister)

Multimessenger search for sources of gravitational waves and high-energy neutrinos: Initial results for LIGO-Virgo and IceCub

We report the results of a multimessenger search for coincident signals from the LIGO and Virgo gravitational-wave observatories and the partially completed IceCube high-energy neutrino detector, including periods of joint operation between 2007–2010. These include parts of the 2005–2007 run and the 2009–2010 run for LIGO-Virgo, and IceCube’s observation periods with 22, 59 and 79 strings. We find no significant coincident events, and use the search results to derive upper limits on the rate of joint sources for a range of source emission parameters. For the optimistic assumption of gravitational-wave emission energy of 10−2  M⊙c2 at ∼150  Hz with ∼60  ms duration, and high-energy neutrino emission of 1051  erg comparable to the isotropic gamma-ray energy of gamma-ray bursts, we limit the source rate below 1.6×10−2  Mpc−3 yr−1. We also examine how combining information from gravitational waves and neutrinos will aid discovery in the advanced gravitational-wave detector era