Chlorpromazine Protects Against Apoptosis Induced by Exogenous Stimuli in the Developing Rat Brain

Background: Chlorpromazine (CPZ), a commonly used antipsychotic drug, was found to play a neuroprotective role in various models of toxicity. However, whether CPZ has the potential to affect brain apoptosis in vivo is still unknown. The purpose of this study was to investigate the potential effect of CPZ on the apoptosis induced by exogenous stimuli. Methodology: The ethanol treated infant rat was utilized as a valid apoptotic model, which is commonly used and could trigger robust apoptosis in brain tissue. Prior to the induction of apoptosis by subcutaneous injection of ethanol, 7-day-old rats were treated with CPZ at several doses (5 mg/kg, 10 mg/kg and 20 mg/kg) by intraperitoneal injection. Apoptotic cells in the brain were measured using TUNEL analysis, and the levels of cleaved caspase-3, cytochrome c, the pro-apoptotic factor Bax and the anti-apoptotic factor Bcl-2 were assessed by immunostaining or western blot. Findings: Compared to the group injected with ethanol only, the brains of the CPZ-pretreated rats had fewer apoptotic cells, lower expression of cleaved caspase-3, cytochrome c and Bax, and higher expression of Bcl-2. These results demonstrate that CPZ could prevent apoptosis in the brain by regulating the mitochondrial pathway. Conclusions: CPZ exerts an inhibitory effect on apoptosis induced by ethanol in the rat brain, intimating that it may offer

Role of Novelty Seeking Personality Traits as Mediator of the Association between COMT and Onset Age of Drug Use in Chinese Heroin Dependent Patients

Personality traits such as novelty seeking (NS) are associated with substance dependence but the mechanism underlying this association remains uncertain. Previous studies have focused on the role of the dopamine pathway.Examine the relationships between allelic variants of the catechol-O-methyltransferase (COMT) gene, NS personality traits, and age of onset of drug use in heroin-dependent subjects in China.The 478 heroin dependent subjects from four drug rehabilitation centers in Shanghai who were genotyped for eight tagging single nucleotide polymorphisms (SNP) on the COMT gene completed the NS subscale from the Temperament and Character Inventory. Multivariate analyses were used to assess the potential mediating role of NS personality traits in the association between COMT gene variants and the age of onset of heroin use.In the univariate analysis the COMT rs737866 gene variants were independently associated with both NS and age of onset of drug use: those with the TT genotype had higher NS subscale scores and an earlier onset age of heroin use than individuals with CT or CC genotypes. In the multivariate analysis the inclusion of the NS subscore variable weakened the relationship between the COMT rs737866 TT genotype and an earlier age of onset of drug use. Our findings that COMT is associated with both NS personality traits and with the age of onset of heroin use helps to clarify the complex relationship between genetic and psychological factors in the development of substance abuse

An adaptive nonlocal filtering for low-dose CT in both image and projection domains

An important problem in low-dose CT is the image quality degradation caused by photon starvation. There are a lot of algorithms in sinogram domain or image domain to solve this problem. In view of strong self-similarity contained in the special sinusoid-like strip data in the sinogram space, we propose a novel non-local filtering, whose average weights are related to both the image FBP (filtered backprojection) reconstructed from restored sinogram data and the image directly FBP reconstructed from noisy sinogram data. In the process of sinogram restoration, we apply a non-local method with smoothness parameters adjusted adaptively to the variance of noisy sinogram data, which makes the method much effective for noise reduction in sinogram domain. Simulation experiments show that our proposed method by filtering in both image and projection domains has a better performance in noise reduction and details preservation in reconstructed images

Analytical analyses of the effect of filled karst cavern on tunnel lining structure under complex geological conditions

In this study, based on the elastic foundation beam theory, a local elastic foundation model has been developed. Using the model, the mechanical characteristics of the effect of tunnel-filled karst on the lining structure has been investigated. Incorporating the characteristic of the karst area, the formulas for the displacement, bending moment, and shear force of an equivalent beam have been derived. By applying the formulas to a beam under different working conditions, such as different cavern sizes and different compression modulus ratios of the filling media, analyses of the mechanical states have been carried out. The results show that if the compression modulus ratio of different filling media is close to unity, the effect of the cave on the lining structure is very small. On the other hand, if the ratio is much less than unity, the effect is more significant. The effect on the stability of the lining structure is greater for the larger caves, and smaller for the smaller caves. For the tunnel bottom equivalent beam, its bending point is at the point where the cave is in contact with the surrounding rock. Further, the maximum shear force is at the contact surface. For a beam that is closer to the karst, the displacement is larger. Under this situation, the beam section is in an adverse force state and prone to cracks. The results from this study can be used as a significant guide for the design, maintenance and construction of a tunnel which has a cavern at the base of the tunnel

Impact of terminal tip location of midline catheters on catheter‐related complications and indwelling duration in elderly patients

Abstract Aim To investigate the relationship between the position of the midline catheter tip and the frequency and type of complications associated with its placement. Design A cohort study was performed on patients between May 2018 and December 2021 who underwent midline catheter placement at our institution. Patients were divided into two groups, superficial implementation and deep implementation, based on the midline catheter tip location relative to the clavicle. Methods Clinical data and outcome parameters, including the numbers and types of midline catheter‐related complications, day of occurrence and catheter indwell duration, were recorded. Results Catheter‐related complications occurred in 14 individuals. Compared with the superficial implementation group, the incidence of complications in the deep catheterization group was significantly reduced, with a delayed first occurrence time, and a prolonged catheter indwelling time. The results suggested that locating the midline catheter tip in the distal segment of the axillary vein may reduce catheter‐related complication incidence and prolong the indwelling duration

Sigma-1 receptors amplify dopamine D1 receptor signaling at presynaptic sites in the prelimbic cortex

AbstractSigma-1 receptors are highly expressed in the brain. The downstream signaling mechanisms associated with the sigma-1 receptor activation have been shown to involve the activation of protein kinase C (PKC), the control of Ca2 homoeostasis and the regulation of voltage- and ligand-gated ion channels. But few studies examined the regulatory effect of sigma-1 receptors on metabotropic receptor signaling. The present paper studied the regulatory effect of sigma-1 receptors on the signaling of dopamine D1 receptors, one of metabotropic receptors, by examining the effect of sigma-1 receptor agonists on the D1 receptor agonist-induced cAMP-dependent protein kinase (PKA) activation at presynaptic sites using the synaptosomes from the prelimbic cortex. The results showed that sigma-1 receptor agonists alone had no effects on the PKA activity, but could amplify the D1 receptor agonist-induced PKA activation. The sigma-1 receptor agonist also amplified the membrane-permeable analog of cAMP- and the adenylyl cyclase (AC) activator-induced PKA activation, but did not on the D1 receptor agonist-induced AC activation. The conventional PKC (cPKC), especially the PKCβI, and the extracellular Ca2+ influx through L-type Ca2+ channels might play key roles in the amplifying effect of the sigma-1 receptor agonists. The activation of PKC by sigma-1 receptor agonists was the upstream event of the increase in the intrasynaptosomal Ca2+ concentration. These results suggest that sigma-1 receptors may amplify the D1 receptor agonist-induced PKA activation by sigma-1 receptors - cPKC (especially the PKCβI) - L-type Ca2+ channels - Ca2+ - AC and/or cAMP signaling pathway