Ethanol is the most commonly used toxic chemical in human cultures. Ethanol predominantly damages the brain causing various neurological disorders. Astrocytes are important cellular targets of ...ethanol in the brain and are involved in alcoholic symptoms. Recent studies have revealed the diversity of astrocyte populations in the brain. However, it is unclear how the different astrocyte populations respond to an excess of ethanol. Here we examined the effect of binge ethanol levels on astrocytes in the mouse brainstem and cerebellum. Ethanol administration for four consecutive days increased the glial fibrillary acidic protein (GFAP)-immunoreactive signals in the spinal tract of the trigeminal nerve (stTN) and reticular nucleus (RN). Another astrocyte marker, aquaporin 4 (AQP4), was also increased in the stTN with a pattern similar to that of GFAP. However, in the RN, the immunoreactive signals of AQP4 were different from that of GFAP and were not changed by ethanol administration. In the cerebellum, GFAP-positive signals were found in all four astrocytic populations, and those in the Bergmann glia were selectively eliminated by ethanol administration. We next examined the effect of estradiol on the ethanol-induced changes in astrocytic immunoreactive signals. The administration of estradiol alone increased the AQP4-immunoreactivity in the stTN with a pattern similar to that of ethanol, whereas the co-administration of estradiol and ethanol suppressed the intensity of the AQP4-positive signals. Thus, binge levels of ethanol intake selectively affect astrocyte populations in the brainstem and cerebellum. Sex hormones can affect the ethanol-induced neurotoxicity via modulation of astrocyte reactivity.
Abstract only
Introduction:
The entrainment rule by which the site of entrainment has no effect on the orthodromic conduction time across the reentry circuit immediately after cessation of pacing has ...not been unequivocally verified in atypical atrioventricular nodal reentrant tachycardia (AVNRT). We have recently observed a unique electrophysiological response upon atrial induction of fast-slow (F/S-) AVNRT, characterized by a shortening of the retrograde conduction time across the slow pathway (SP) (retro-SP-time).
Hypothesis:
Atrial entrainment pacing (EP) of a) the common-type (com-) F/S-AVNRT using a typical SP, or b) the superior-type (sup-) F/S-AVNRT using a superior SP, both might modify the retro-SP-time immediately after termination of EP.
Methods:
In 16 patients of com-F/S-AVNRT and 11 patients of sup-F/S-AVNRT in whom successful EP from the high right atrium (EP-HRA) and the proximal coronary sinus (EP-CS) was obtained at 2±2 rates, we evaluated the difference in the His-atrial (HA) interval measured immediately after cessation of each EP attempt (HA difference) between EP-HRA and EP-CS (HA1-HRA and HA1-CS, respectively) and also measured atrial-His and HA intervals in the 1st and 2nd cycles immediately after the EP, and during tachycardia stabilized.
Results:
>20 ms HA difference, defined as an atypical difference, at ≥1 rates of EP was observed in 16 patients (56%), including 7 with com- and 9 with sup-F/S-AVNRT. Irrespective of the EP rate, the atypical response of com-F/S-AVNRT was always due to a shorter HA1-CS than HA1-HRA, with a 39±22 ms HA difference, whereas the atypical response of sup-F/S-AVNRT was always due to a longer HA1-CS than HA1-HRA, with a 51±26 ms HA difference. Moreover, the atypical response disappeared within 2 cycles after the cessation of EP. The atypical difference, although its exact mechanism remains unclear, might attribute to a shortening of the retro-SP-time according to decremental properties of the SP with deeper antidromic penetration during EP provoked depending on the site and rate of pacing.
Conclusions:
We have identified a little-known pacing site- and pacing rate-dependent shortening of the retro-SP-time. This phenomenon may affect an interpretation of post-pacing interval after EP of F/S-AVNRT.
Recovery of precious metals (PMs: AuIII and PtIV) from waste resources is of high importance due to the environmental concern and imbalance in the supply-demand ratio. A new approach has been ...explored for the recovery of PM using earlier developed bio-adsorbent, dithiocarbamate-modified cellulose (DMC). The adsorbent exhibits excellent adsorption efficiency (~99%) over a wide range of pH (< 1–6) and high selectivity towards AuIII and PtIV extraction from acidic solutions (H+: ≥ 0.2 mol L–1). The adsorption capacity (mmol g–1; AuIII: 5.07, PtIV: 2.41) and rate to reach equilibrium (≤ 30 min) were significantly higher than most of the reported bio-adsorbents. The AuIII or PtIV, after captured in DMC, was subsequently recovered as Au0 and Pt0 (yield > 99%) via incineration. The protocol was verified using real waste samples containing AuIII and PtIV in a mixed matrix of base metal ions, and a quantitative (~100%) and selective extraction of AuIII and PtIV were observed. The proposed technique is more effective and straightforward than the typical adsorption-desorption-reduction based method, because of the advantages like no-use of toxic eluents, and no-addition of any reductants to collect the PMs in elemental form.
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•New bio-adsorbent (DMC) for selective AuIII or PtIV extraction from acidic waste.•The high adsorption capacity of DMC assists rapid capture of AuIII or PtIV.•The adsorption of AuIII or PtIV onto DMC follows a complexation-reduction mechanism.•A straightforward pathway for the recovery of the metals as Au0 and Pt0 is proposed.•No toxic eluents or reductants were used in the proposed recovery technique.
Copper (Cu) and zinc (Zn) are essential nutrients and cofactors of enzymatic reactions with their binding partner. Metallothionein (MT) plays an important role in protecting against heavy metals and ...oxidative injury, however it may also portend drug resistance and a worse prognosis for hepatocellular carcinoma (HCC) patients. The aim of this study was to determine the amount of Cu, Zn, Cu/Zn and MT in evaluating a group of patients with HCC, including those treated with lenvatinib. We enrolled 175 patients with HCC (139 men, 36 women; mean age 71.1 years; hepatitis C virus n = 85, hepatitis B virus n = 19, hepatitis C virus and hepatitis B virus n = 2, non-alcoholic steatohepatitis n = 39, alcohol n = 25, others n = 5; Child-Pugh A n = 141, Child-Pugh B n = 30, Child-Pugh C n = 4; Barcelona clinic liver cancer (BCLC) stage 0 n = 38, stage A n = 56, stage B n = 39, stage C n = 38, stage D n = 4). We evaluated the associations between Cu, Zn and MT. The study outcome was liver cancer-specific survival. Moreover, we treated 12 HCC patients with lenvatinib and investigated the changes in MT during lenvatinib therapy. The serum level of Cu was positively correlated with alanine aminotransferase and the BCLC stage. The serum level of Zn decreased concordant with liver disease progression. Patients with a Cu/Zn ratiogreater than or equal to0.999 had significantly improved rates of survival when compared to patients with a Cu/Zn ratio<0.999 (45.3 vs. 30.1 months, p<0.001). MT was significantly correlated with the Cu/Zn ratio and increased after the administration of lenvatinib. Using multivariate Cox regression analyses, it was determined that the Cu/Zn ratio (hazard ratio HR: 1.442, p = 0.008), alpha-fetoprotein (HR: 1.000, p<0.001) and BCLC stage (HR: 2.087, p<0.001) were independent predictors of survival. The Cu/Zn ratio could serve as a useful predictive marker for survival in cases of HCC. MT levels increased in HCC patients receiving lenvatinib therapy, and maybe a predictor of reduced survival.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The occurrence, distribution, speciation, and biotransformation of arsenic in aquatic environment (marine and freshwater) have been studied extensively by several research groups during last couple ...of decades. However, most of those studies have been conducted in marine waters, and the results are available in a number of reviews. Speciation, bioaccumulation, and biotransformation of arsenic in freshwaters have been studied in recent years. Although inorganic arsenic (iAs) species dominates in both marine and freshwaters, it is biotransformed to methyl and organoarsenic species by aquatic organisms. Phytoplankton is considered as a major food source for the organisms of higher trophic levels in the aquatic food chain, and this autotrophic organism plays important role in biotransformation and distribution of arsenic species in the aquatic environment. Bioaccumulation and biotransformation of arsenic by phytoplankton, and trophic transfer of arsenic in marine and freshwater food chains have been important concerns because of possible human health effects of the toxic metalloid from dietary intake. To-date, most of the studies on arsenic biotransformation, speciation, and trophic transfer have focused on marine environments; little is known about these processes in freshwater systems. This article has been reviewed the bioaccumulation, biotransformation, and trophic transfer of arsenic in marine and freshwater food chain.
Multiple external and internal factors have been reported to induce thymic involution. Involution involves dramatic reduction in size and function of the thymus, leading to various ...immunodeficiency-related disorders. Therefore, clarifying and manipulating molecular mechanisms governing thymic involution are clinically important, although only a few studies have dealt with this issue. In the present study, we investigated the molecular mechanisms underlying thymic involution using a murine acute diet-restriction model. Gene expression analyses indicated that the expression of T helper 1 (Th1)-producing cytokines, namely interferon-γ and interleukin (IL)-2, was down-regulated, while that of Th2-producing IL-5, IL-6, IL-10 and IL-13 was up-regulated, suggesting that acute diet-restriction regulates the polarization of naïve T cells to a Th2-like phenotype during thymic involution. mRNAs for prostanoid biosynthetic enzymes were up-regulated by acute diet-restriction. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) analyses detected the increased production of prostanoids, particularly prostaglandin D2 and thromboxane B2, a metabolite of thromboxane A2, in the diet-restricted thymus. Administration of non-steroidal anti-inflammatory drugs, namely aspirin and etodolac, to inhibit prostanoid synthesis suppressed the biased expression of Th1- and Th2-cytokines as well as molecular markers of Th1 and Th2 cells in the diet-restricted thymus, without affecting the reduction of thymus size. In vitro stimulation of thymocytes with phorbol myristate acetate (PMA)/ionomycin confirmed the polarization of thymocytes from diet-restricted mice toward Th2 cells. These results indicated that the induced production of prostanoids during diet-restriction-induced thymic involution is involved in the polarization of naïve T cells in the thymus.
Immune suppression in elderly individuals is one of the most important hygienic problems in aged societies. The primary immune organ thymus is histologically and functionally reduced by aging, which ...is known as thymic involution. The thymus is also involuted by nutritional deficiency, which frequently occurs in elderly individuals. However, there is no information on the thymic changes caused by nutritional deficiency with aging. Therefore, this study was conducted to examine the histological and molecular responses of the thymus to nutritional deficiency in young and aged mice. The thymic size was significantly smaller in 16- or 18-week-old aged mice than in 7-week-old young mice. Dietary restriction for 48 h reduced the thymic size in young mice, but not in aged mice. Immunostaining with anti-keratin 5 antibody revealed that the integrity of the corticomedullary boundary was maintained in the aged thymus, whereas dietary restriction induced its disorganization in both young and aged thymus. The numbers of immunoglobulin G (IgG)-positive cells were increased upon dietary restriction in aged, but not in young, thymus. Dietary restriction, but not aging, upregulated the mRNA levels of T-helper 2 (Th2)-related Il5, Il6, and Il10, whereas aging increased that of Th1-related interferon-γ (Ifng). The dietary restriction–induced upregulation of prostanoid-synthesizing enzymes was clearly observed in the young thymus but attenuated in the aged thymus. Thus, nutritional deficiency and aging cause an involuted thymus with different properties. Moreover, the thymus in aged mice does not show further reduction in size by nutritional deficiency but still responds differently compared with that in young mice.
Excessive intake of ethanol is associated with severe brain dysfunction, and the subsequent neurological and behavioral abnormalities are well-established social risks. Many research studies have ...addressed how ethanol induces neurological toxicity. However, the underlying mechanisms with which ethanol induces neurological toxicity are still obscure, perhaps due to the variety and complexity of these mechanisms. Epithelial cells are in direct contact with blood and can thus mediate ethanol neurotoxicity. Ethanol activates the endothelial cells of blood vessels, as well as lymphatic vessels, in a concentration-dependent manner. Among various signaling mediators, nitric oxide plays important roles in response to ethanol. Endothelial and inducible nitric oxide synthases (eNOS and iNOS) are upregulated and activated by ethanol and enhance neuroinflammation. On the other hand, angiogenesis and blood vessel remodeling are both affected by ethanol intake, altering blood supply and releasing angiocrine factors to regulate neuronal functions. Thus, ethanol directly acts on endothelial cells, yet the molecular target(s) on endothelial cells remain unknown. Previous studies on neurons and glial cells have validated the potential contribution of membrane lipids and some specific proteins as ethanol targets, which may also be the case in endothelial cells. Future studies, based on current knowledge, will allow for a greater understanding of the contribution and underlying mechanisms of endothelial cells in ethanol-induced neurological toxicity, protecting neurological health against ethanol toxicity.
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