Acanthocheilonema viteae in Mastomys coucha : Combination Effect of An Immunostimulator (CDRI compound 86/448) and Antifilarial agents on Establishment of Infection

Effect of two antifilarials ivermectin (microfilaricidal) and CDRI Comp. 82/437 (macrofilaricidal) in combination with immunostimulator (CDRI Comp. 86/448) was evaluated on establishment of Acanthocheilonema viteae infection in Mastomys coucha. The immunostimulator along with the antifilarials was administered on single occasion (Day 0 of larval exposure). Immunostimulator when given in combination with macrofilaricidal agent (82/437), revealed significantly less percentage of worm recovery over untreated control as well as over treated (with either immunostimulator or antifilarial alone) infected controls. It is, thus surmised that establishment of filarial infection is affected by immunostimulant along with antifilarial agent

Neuroprotective effect of peroxiredoxin 6 against hypoxia-induced retinal ganglion cell damage

Abstract Background The ability to respond to changes in the extra-intracellular environment is prerequisite for cell survival. Cellular responses to the environment include elevating defense systems, such as the antioxidant defense system. Hypoxia-evoked reactive oxygen species (ROS)-driven oxidative stress is an underlying mechanism of retinal ganglion cell (RGC) death that leads to blinding disorders. The protein peroxiredoxin 6 (PRDX6) plays a pleiotropic role in negatively regulating death signaling in response to stressors, and thereby stabilizes cellular homeostasis. Results We have shown that RGCs exposed to hypoxia (1%) or hypoxia mimetic cobalt chloride display reduced expression of PRDX6 with higher ROS expression and activation of NF-κB. These cells undergo apoptosis, while cells with over-expression of PRDX6 demonstrate resistance against hypoxia-driven RGC death. The RGCs exposed to hypoxia either with 1% oxygen or cobalt chloride (0-400 μM), revealed ~30%-70% apoptotic cell death after 48 and 72 h of exposure. Western analysis and real-time PCR showed elevated expression of PRDX6 during hypoxia at 24 h, while PRDX6 protein and mRNA expression declined from 48 h onwards following hypoxia exposure. Concomitant with this, RGCs showed increased ROS expression and activation of NF-κB with IkB phosphorylation/degradation, as examined with H2DCF-DA and transactivation assays. These hypoxia-induced adverse reactions could be reversed by over-expression of PRDX6. Conclusion Because an abundance of PRDX6 in cells was able to attenuate hypoxia-induced RGC death, the protein could possibly be developed as a novel therapeutic agent acting to postpone RGC injury and delay the progression of glaucoma and other disorders caused by the increased-ROS-generated death signaling related to hypoxia.Peer Reviewe

Adsorption challenge in the PDMS-based microfluidic systems for drug screening application

Drug screening is one of the demand areas due to close and direct dependency on human health. On the other hand, recently microfluidic systems have been increasingly used for drug development and screening purposes. However, this system has some challenges such as adsorption issue which can effect pharmacokinetic-pharmacodynamic (PK-PD) of the drugs. Thus, in this research, the issue was characterized and evaluated by UV-Vis spectrophotometry and FTIR spectroscopy devices as a model drug of cisplatin. Despite of strong relationship between logP and adsorption, and the very low value of logP in the drug candidate, the results for both apical and basal planes of the microfluidic chip confirmed the adsorption. In the UV-Vis spectrophotometry, the basal plane show 5%, and 10% higher adsorption compared to apical and control polydimethylsiloxane (PDMS)-based microfluidic. Additionally, the FTIR patterns were a good coincide with UV-Vis results

Cellular distribution of lens epithelium-derived growth factor (LEDGF) in the rat eye: loss of LEDGF from nuclei of differentiating cells

Lens epithelium-derived growth factor (LEDGF) enhances the survival and growth of cells. To understand LEDGF's spatial localization and its putative function(s) during proliferation and differentiation, we localized LEDGF during terminal differentiation in whole rat lenses, lens epithelial cell (LEC) explants stimulated with FGF-2, and insulin, iris, human LECs with lentoids. In addition, intracellular localization of LEDGF was performed in other ocular tissues: ciliary body, retina, and cornea. We found the immunopositivity of nuclear LEDGF decreased in LECs of the equatorial region. In contrast, immunopositivity of LEDGF was detected in the cytoplasm of LECs and superficial fiber cells. After treating LEC explants with FGF-2 and insulin, which are known to be differentiating factors for LECs, the nuclei of these cells showed no LEDGF immunopositivity, but explants did express p57 kip2 , a differentiation marker protein. Also, immunopositive LEDGF was not detected in the nuclei of differentiated cells, lentoid body, and corneal epithelial cells. This demonstrated that the loss of LEDGF from the nucleus may be associated with the process of terminal differentiation that might be in some way common with the biochemical mechanisms of apoptosis. The spatial and temporal distribution of LEDGF in the present study also provides a vision for further investigation as to how this protein is involved in cell fate determination.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/42235/1/s00418-003-0518-3.pd

Anion-Sensitive Regions of L-Type CaV1.2 Calcium Channels Expressed in HEK293 Cells

L-type calcium currents (ICa) are influenced by changes in extracellular chloride, but sites of anion effects have not been identified. Our experiments showed that CaV1.2 currents expressed in HEK293 cells are strongly inhibited by replacing extracellular chloride with gluconate or perchlorate. Variance-mean analysis of ICa and cell-attached patch single channel recordings indicate that gluconate-induced inhibition is due to intracellular anion effects on Ca2+ channel open probability, not conductance. Inhibition of CaV1.2 currents produced by replacing chloride with gluconate was reduced from ∼75%–80% to ∼50% by omitting β subunits but unaffected by omitting α2δ subunits. Similarly, gluconate inhibition was reduced to ∼50% by deleting an α1 subunit N-terminal region of 15 residues critical for β subunit interactions regulating open probability. Omitting β subunits with this mutant α1 subunit did not further diminish inhibition. Gluconate inhibition was unchanged with expression of different β subunits. Truncating the C terminus at AA1665 reduced gluconate inhibition from ∼75%–80% to ∼50% whereas truncating it at AA1700 had no effect. Neutralizing arginines at AA1696 and 1697 by replacement with glutamines reduced gluconate inhibition to ∼60% indicating these residues are particularly important for anion effects. Expressing CaV1.2 channels that lacked both N and C termini reduced gluconate inhibition to ∼25% consistent with additive interactions between the two tail regions. Our results suggest that modest changes in intracellular anion concentration can produce significant effects on CaV1.2 currents mediated by changes in channel open probability involving β subunit interactions with the N terminus and a short C terminal region

Acanthocheilonema viteae in Mastomys coucha : Combination Effect of An Immunostimulator (CDRI compound 86/448) and Antifilarial agents on Establishment of Infection

Effect of two antifilarials ivermectin (microfilaricidal) and CDRI Comp. 82/437 (macrofilaricidal) in combination with immunostimulator (CDRI Comp. 86/448) was evaluated on establishment of Acanthocheilonema viteae infection in Mastomys coucha. The immunostimulator along with the antifilarials was administered on single occasion (Day 0 of larval exposure). Immunostimulator when given in combination with macrofilaricidal agent (82/437), revealed significantly less percentage of worm recovery over untreated control as well as over treated (with either immunostimulator or antifilarial alone) infected controls. It is, thus surmised that establishment of filarial infection is affected by immunostimulant along with antifilarial agent

Determination of Fear of Birth in Individuals During The Covid-19 (Coronavirus) Pandemic Process Covid-19 (Koronavirüs) Pandemi Sürecinde Bireylerde Doğum Korkusunun Belirlenmesi

Background: The Covid-19 pandemic process has affected individuals’ thoughts on pregnancy and having a child, as in many areas. Objective: It was aimed to examine the fear of childbirth in individualsin the pre-pregnancy period during the pandemic process in this research. Method: The research is of descriptive-cross-sectional type. A total of 385 participants who were of reproductive age (18-49 years old), did not have children, and were planning/desiring to have children in the future were included in the study. In the data collection form, there are questions about the socio-demographic characteristics of the participants,their planning of pregnancy and childbearing during the pandemic process and the “Childbirth Fear-Prior to Pregnancy Scale (CF-PPS)”. Results: While 72.2% of the participants were afraid of the future birth/birth of their spouse; 41% stated that this fear increased during the pandemic process. The total mean score of the participants’ CF-PPS scale was 40.49 ± 11.10. It has been determined that the fear of childbirth differs according to gender, marital status, working in an income generating job and income status. It was determined that those who have fear of future birth/birth of their spouse and those who have increased fear of childbirth/birth of their spouse during the pandemic process have a significantly higher mean score of CF-PPS. Conclusion: The pandemic process has led to an increase in the fear of birth of individuals. Most of the participants stated that they do not plan to have children during the pandemic period