The protective effect of arbutin against potassium bromate-induced oxidative damage in the rat brain

This study aimed to investigate the protective effects of arbutin (ARB) against brain injury induced in rats with potassium bromate (KBrO₃). The rats were divided into four groups as Group 1: Control (0.9% NaCl ml/kg/day p.), Group 2: KBrO₃ (100 mg/kg (gavage), Group 3: ARB (50 mg/kg/day p.), and Group 4: KBrO₃ + ARB (100 mg/kg (gavage) + 50 mg/kg/day p.). At the end of the fifth day of the study, the rats in all groups were killed, and their brain tissues were collected. In the collected brain tissues, malondialdehyde (MDA), superoxide dismutase (SOD), and catalase (CAT) levels were measured, and routine histopathological examinations were made. The MDA levels in the group that was exposed to KBrO₃ were significantly higher than those in the control group (p ˂ 0.001). In comparison to the KBrO₃ group, the MDA levels in the KBrO₃ + ARB group were significantly lower (p ˂ 0.001). It was observed that SOD and CAT enzyme activity levels were significantly lower in the KBrO₃ group compared to the control group (p ˂ 0.001), while these levels were significantly higher in the KBrO₃ + ARB group than in the KBrO₃ group (p ˂ 0.001). Additionally, the group that was subjected to KBrO₃ toxicity, as well as ARB administration, had much lower levels of histopathologic signs than the group that was subjected to KBrO₃ toxicity only. Consequently, it was found that KBrO₃ exposure led to injury in the brain tissues of the rats, and using ARB was effective in preventing this injury.     

Dieckol,a natural polyphenolic drug,inhibits the proliferation and migration of colon cancer cells by inhibiting PI3K,AKT, and mTOR phosphorylation

This study investigated that dieckol (DKL), a natural drug, inhibits colon cancer cell proliferation and migration by inhibiting phosphoinositide-3-kinase (PI3K), protein kinase B (AKT), and mammalian target of rapamycin (mTOR) phosphorylation in HCT-116 cells. The cells were treated with DKL in various concentrations (32 and 50 μM) for 24 h and then analyzed for various experiments. MTT (tetrazolium bromide) and crystal violet assay investigated DKL-mediated cytotoxicity. Dichlorodihydrofluorescein diacetate staining was used to assess the reactive oxygen species (ROS) measurement, and apoptotic changes were studied by dual acridine orange and ethidium bromide staining. Protein expression of cell survival, cell cycle, proliferation, and apoptosis protein was evaluated by western blot analysis. Results indicated that DKL produces significant cytotoxicity in HCT-116, and the half-maximal inhibitory concentration was found to be 32 μM for 24-h incubation. Moreover, effective production of ROS and enhanced apoptotic signs were observed upon DKL treatment in HCT-116. DKL induces the expression of phosphorylated PI3K, AKT, and mToR-associated enhanced expression of cyclin-D1, proliferating cell nuclear antigen, cyclin-dependent kinase (CDK)-4, CDK-6, and Bcl-2 in HCT-116. In addition, proapoptotic proteins such as Bax, caspase-9, and caspase-3 were significantly enhanced by DKL treatment in HCT-116. Hence, DKL has been considered a chemotherapeutic drug by impeding the expression of PI3K-, AKT-, and mTOR-mediated inhibition of proliferation and cell cycle-regulating proteins.     

Three-dimensional species distribution modelling reveals the realized spatial niche for coral recruitment on contemporary Caribbean reefs

The three-dimensional structure of habitats is a critical component of species' niches driving coexistence in species-rich ecosystems. However, its influence on structuring and partitioning recruitment niches has not been widely addressed. We developed a new method to combine species distribution modelling and structure from motion, and characterized three-dimensional recruitment niches of two ecosystem engineers on Caribbean coral reefs, scleractinian corals and gorgonians. Fine-scale roughness was the most important predictor of suitable habitat for both taxa, and their niches largely overlapped, primarily due to scleractinians' broader niche breadth. Crevices and holes at mm scales on calcareous rock with low coral cover were more suitable for octocorals than for scleractinian recruits, suggesting that the decline in scleractinian corals is facilitating the recruitment of octocorals on contemporary Caribbean reefs. However, the relative abundances of the taxa were independent of the amount of suitable habitat on the reef, emphasizing that niche processes alone do not predict recruitment rates.     

Clinical pharmacology of the new COMT inhibitor CGP 28 014

CGP 28 014 is a specific inhibitor of catechol-O-methyltransferase (COMT) in vivo. In humans, the inhibition was assessed by measuring urinary excretion of isoquinolines and with the levodopa test. Following administration of CGP 28 014, urinary excretion of isoquinolines was significantly increased. In rats, CGP 28 014 reduced plasma and striatal concentrations of 3-O-methyldopa (30MD) in a dose-dependent manner. Acute and subchronic administration of CGP 28 014 alone or in combination with the peripherally acting decarboxylase inhibitor benserazide decreased plasma 30MD as an index of COMT inhibition by about 50%. There seems to be a close relationship between the time-course of plasma concentrations of CGP 28 014 and the extent of COMT inhibition assessed by the 30MD/DOPA ratio in plasma.     

Nerve growth factor antibodies recognize neurotrophin-3

The immunological properties of the neurotrophins NGF, BDNF, and NT-3 were compared using polyclonal and monoclonal antibodies against the subunit of mouse NGF. Affinity-purified anti-NGF IgG consistently recognized NGF and NT-3 on Western blots, and inhibited the trophic activity of NGF and NT-3 but not BDNF. In contrast, anti-NGF monoclonal antibodies did not block the trophic activity of either NT-3 or BDNF. These results are consistent with the greater structural overlap between NGF and NT-3 than between NGF and BDNF.     

Specific bindings of [3H](+)PN200-110 and [125I]ω-conotoxin to crude membranes from differentiated NG108-15 cells

The characteristics of the specific bindings of [³H](+)PN200-110 (PN: L-type Ca channel antagonist) and [¹²⁵I]-conotoxin G VI A (-CgTX: neuronal L-or N-type Ca channel antagonist) to crude membranes from undifferentiated neuroblastoma x glioma hybrid NG108-15 (NG108-15) cells and differentiated cells induced with dibutyryl cAMP (Bt₂cAMP) were examined, because we have already observed that the magnitude and rate of KCL-stimulated⁴⁵Ca uptake by NG108-15 cells increased progressively during differentiation of the cells induced with Bt₂cAMP (unpublished results). The specific binding of [³H](+)PN to these crude membranes was saturable at various concentrations of 2.5–5.0 nM [³H](+)PN. Scatchard analysis showed that the specific binding of [³H](+)PN at equilibrium was significantly increased after differentiation of the NG108-15 cells with Bt₂cAMP, but that the apparent Kd value for the specific binding of [³H](+)PN was not influenced by treatment with Bt₂cAMP. The specific binding of [³H](+)PN to crude membranes from Bt₂cAMP-treated NG108-15 cells was inhibited by a calcium agonist and antagonists, the order of their inhibitory potencies being (+)PN>nitrendipine>(–)PNBay K 8644diltiazem = verapamil. Thus, PNs showed significant stereoselective inhibition of the specific binding of [³H(+)PN. On the other hand, [¹²⁵I]-CgTX at concentrations of 0.075–0.6 nM showed scarcely any specific binding to these crude membranes, although at 0.6 nM it showed specific binding to crude membranes from rat brain in the same experimental conditions. These results suggest that the increase in magnitude or rate of KCl-stimulated⁴⁵Ca uptake during differentiation of NG108-15 cells is partially due to quantitative alteration of voltage-sensitive Ca channels in the cells, and that there are scarcely any specific binding sites for [¹²⁵I]-CgTX on Bt₂cAMP-treated or untreated NG108-15 cells.     

Trace amines and Tourette's syndrome

There has been considerable interest in recent years in possible neurochemical abnormalities in Tourette's Syndrome (TS). In studies combining neuropsychological and neurochemical measurements, we have investigated the possible roles of trace amines in this disorder. Urinary levels of free -phenylethylamine (PEA) and plasma levels of its precursor amino acid phenylalanine were decreased in TS patients when compared to values in normal children. These urinary PEA levels in TS patients were inversely related to several scores from the Tourette's Syndrome Global Scale (TSGS). Further investigation of the group of subjects with low urinary PEA indicated that they also had low levels of MHPG, normetanephrine, 5-HT andm- andp-tyramine. Patients with low PEA were also compared on an extensive battery of neuropsychological measures and observed to perform significantly worse than TS patients with normal urinary PEA levels. Biochemical measurements also suggest a possible abnormality in tryptamine turnover in TS since urinary levels of indole-3-acetic acid (IAA; the acid metabolite of tryptamine) are significantly lower in TS patients than in normal controls.     

Asymmetric distribution and down-regulation of the muscarinic acetylcholine receptor in rat cerebral cortex

The distribution and down-regulation of the muscarinic acetylcholine receptor (mAChR) were studied in dissociated cells from right (RCC) and left (LCC) cerebral cortex. For this purpose [³H]quinuclidinyl benzilate (QNB) and [³H]pirenzepine (Pz), two muscarinic antagonists, were used. The mAChR binding sites detected with [³H]QNB were asymmetrically distributed between the two hemispheres, the majority being found in the RCC. Asymmetry was also evident in the distribution of the mAChR subtypes (M₁ and M₂) detected with [³H]Pz. Under basal conditions the RCC had roughly 50% more M₁ subtype than the LCC. The pharmacological and kinetic parameters were similar for both antagonists in RCC and LCC, indicating that the observed lateralization was due to a different density of the receptor rather than to different kinetics of binding of the two radioligands. After sustained stimulation with the agonist carbamoylcholine, the receptor sites detected with [³H]Pz, i.e. the M₁ subtype of mAChR, decreased at a higher rate in the RCC (44%) than in the LCC (25% of controls), demonstrating that the down-regulation process is more active in the right than in the left cortex, and thus implying that there is better coupling between the stimulated mAChR and its effector system in the former.     

缺氧与复氧对不同血管α_1肾上腺素受体收缩效应的影响

本实验观察离体大鼠肾动脉(含α_(1V)亚型)、主动脉(含α_(1B)亚型)和肺动脉(含α_(1V)和α_(1B)亚型)在缺氧与复氧时由α_1肾上腺素受体激动所致收缩效应的改变。结果显示肾动脉在缺氧时pD值增大,最大收缩效应降低,复氧时pD值恢复;主动脉在缺氧时pD值减小,最大收缩效应不变,复氧时pD值不恢复:而肺动脉的改变为上述两者的综合。提示σ_1受体不同亚型在缺氧与复氧时发生的变化不同,这可能是不同血管对缺氧、复氧反应不同的机制之一。