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Introduction Methods Results Conclusions Carotid sinus syndrome (CSS), characterized by exaggerated vagal responses leading to asystolic pauses with carotid sinus massage (CSM), often necessitates pacemaker implantation. This study investigates cardioneuroablation (CNA) as an alternative strategy for CSS.Prospective study of consecutive patients referred for CNA due to CSS. All patients underwent CSM, atropine test and 24‐h Holter monitoring before the procedure and at 6 months. The primary objective was the absence of any cardioinhibitory response to CSM following CNA. Secondary objectives included the combined endpoint of syncope and presyncope‐free survival, pacemaker‐free survival, differences in heart rate variation (HRV), as well as differences in the pre‐ and postprocedure atropine tests and in the SF‐36 quality‐of‐life questionnaire.A total of 13 consecutive patients (84.6% male, mean age 63.8 ± 12.3 years) were included. CSM revealed a symptomatic asystolic pause in all patients before CNA (7.3 [5.6–10.5] s). After the procedure, all the patients had a negative CSM, and only one patient (7.7%) had a positive CSM at 6 months. After a median follow‐up of 11.2 (10.6–16.3) months, syncope or presyncope‐free survival was 84.6%, and none required pacemaker implantation. There was an improvement in the energy and health change items in the SF‐36 questionnaire. There was a reduction in HR increase in the atropine test at 6 months (pre‐CNA: 66% [52–84] vs. post‐CNA 26.0% (19.8–29.3]; p = .008) and in HRV parameters.In this proof‐of‐efficacy study, performed in patients affected by asystolic CSS, CNA was effective in reducing the rate of cardioinhibitory responses, suggesting a potential efficacy in also reducing syncopal recurrences. Controlled trials are warranted to corroborate clinical findings. [ABSTRACT FROM AUTHOR]

This study aimed to assess the incidence of post‐discharge nausea and vomiting (PDNV) following sedation with nalbuphine and etomidate and to evaluate the prophylactic effects of scopolamine in reducing PDNV. A two‐stage prospective clinical trial was conducted. The first part involved an observational study of 77 subjects to assess the PDNV incidence post‐sedation with nalbuphine, etomidate, and propofol. The second part compared the effectiveness of palonosetron 0.075 mg (P group), scopolamine 0.1 mg (S group), and their combination (PS group) in reducing PDNV. The primary endpoint was the incidence of PDNV within 8 h post‐sedation. Secondary outcomes included PDNV frequency and severity at 8–24, 0–24, and 24–48 h and side effects of medications. The incidence of PDNV within 8 h post‐sedation was 37.66% (29/77). The PS group showed a significantly lower PDNV rate of 2.56% within 8 h, compared to the P group (35.71%, P < .001), S group (19.64%, P < .001), and control group (38.39%, P < .001), respectively. The S group (19.64%) also had a lower rate than the P group (35.71%, P = .007) and the control group (38.39%, P = .002). Subgroup analysis suggested a potential differential effect of palonosetron in reducing vomiting among male patients undergoing gastrointestinal procedures. The combination therapy was also associated with fewer cases of mild or no nausea and vomiting. In summary, the incidence of PDNV following sedation with nalbuphine and etomidate was notably high. The combination of scopolamine and palonosetron was more effective in preventing PDNV, with implications for improved post‐sedation care. [ABSTRACT FROM AUTHOR]

BACKGROUND: Our objective in this study was to evaluate the effectiveness of oligosaccharides extracted from black ginseng (OSBG), innovatively prepared by a low‐temperature steam‐heating process, in the improvement of learning and memory impairment in mice, as well as the mechanism(s). RESULTS: Eight carbohydrates involving isomaltose and maltotetraose were detected in black gensing; monosaccharide residues including mannose and rhamnose were also discovered. OSBG‐treated mice showed significant amelioration in recognition and spatial memory deficits compared to the scopolamine group. OSBG could decrease acetylcholinesterase activity in a tissue‐dependent fashion but not in a dose‐dependent manner. Furthermore, in contrast, OSBG administration resulted in significant upregulation superoxide dismutase, glutathione, glutathione peroxidase (GPx), and Kelch‐like ECH‐associated protein 1, downregulation of malondialdehyde and nuclear factor erythroid 2‐related factor 2 in the tissues. Finally, at the genus level, we observed that the OSBG interventions increased the relative abundance of probiotics (e.g., Barnesiella, Staphylococcus, Clostridium_XlVb) and decreased pernicious bacteria such as Eisenbergiella and Intestinimonas, compared to the Alzheimer's disease mouse model group. Herein, our results demonstrate that OSBG restores the composition of the scopolamine‐induced intestinal microbiota in mice, providing homeostasis of gut microbiota and providing evidence for microbiota‐regulated therapeutic potential. CONCLUSION: Our results showed for the first time a clear role for OSBG in improving scopolamine‐induced memory impairment by inhibiting cholinergic dysfunction in a tissue‐dependent manner. Additionally, OSBG administration relieved oxidative stress by activating the Keap‐1/Nrf2 pathway and modulating the gut microbiota. Collectively, OSBG may be a promising target for neuroprotective antioxidants for improving memory and cognition in Alzheimer's disease patients. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

BACKGROUND: Cognitive impairment (CI) is a significant public health concern, and bioactive peptides have shown potential as therapeutic agents. However, information about their synergistic effects on cognitive function is still limited. Here, we investigated the synergistic effects of tilapia head protein hydrolysate (THPH) and walnut protein hydrolysate (WPH) in mitigating CI induced by scopolamine in mice. RESULTS: The results showed that the combined supplementation of THPH and WPH (mass ratio, 1:1) was superior to either individual supplement in enhancing spatial memory and object recognition abilities in CI mice, and significantly lessened brain injury in CI mice by alleviating neuronal damage, reducing oxidative stress and stabilizing the cholinergic system. In addition, the combined supplementation was found to be more conducive to remodeling the gut microbiota structure in CI mice by not only remarkably reducing the ratio of Firmicutes to Bacteroidota, but also specifically enriching the genus Roseburia. On the other hand, the combined supplementation regulated the disorders of sphingolipid and amino acid metabolism in CI mice, particularly upregulating glutathione and histidine metabolism, and displayed a stronger ability to increase the expression of genes and proteins related to the brain‐derived neurotrophic factor (BDNF)/TrkB/CrEB signaling pathway in the brain. CONCLUSION: These findings demonstrate that tilapia head and walnut‐derived protein hydrolysates exerted synergistic effects in ameliorating CI, which was achieved through modulation of gut microbiota, serum metabolic pathways and BDNF signaling pathways. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

The morbidity and mortality associated with type 2 diabetes mellitus (T2DM) have grown exponentially over the last 30 years. Together with its associated complications, the mortality rates have increased. One important complication in those living with T2DM is the acceleration of age‐related cognitive decline. T2DM‐induced cognitive impairment seriously affects memory, executive function, and quality of life. However, there is a lack of effective treatment for both diabetes and cognitive decline. Thus, finding novel treatments which are cheap, effective in both diabetes and cognitive impairment, are easily accessible, are needed to reduce impact on patients with diabetes and health‐care systems. Carnosine, a histidine containing dipeptide, plays a protective role in cognitive diseases due to its antioxidant, anti‐inflammation, and anti‐glycation properties, all of which may slow the development of neurodegenerative diseases and ischemic injury. Furthermore, carnosine is also involved in regulating glucose and insulin in diabetes. Herein, we discuss the neuroprotective role of carnosine and its mechanisms in T2DM‐induced cognitive impairment, which may provide a theoretical basis and evidence base to evaluate whether carnosine has therapeutic effects in alleviating cognitive dysfunction in T2DM patients. [ABSTRACT FROM AUTHOR]

The role of neuromodulators in the cerebellum is not well understood. In particular, the behavioural significance of the cholinergic system in the cerebellum is unknown. To investigate the importance of cerebellar cholinergic signalling in behaviour, we infused acetylcholine receptor antagonists, scopolamine and mecamylamine, bilaterally into the rat cerebellum (centred on interpositus nucleus) and observed the motor effects through a battery of behavioural tests. These tests included unrewarded behaviour during open field exploration and a horizontal ladder walking task and reward‐based beam walking and pellet reaching tasks. Infusion of a mix of the antagonists did not impair motor learning in the horizontal ladder walking or the reaching task but reduced spontaneous movement during open field exploration, impaired coordination during beam walking and ladder walking, led to fewer reaches in the pellet reaching task, slowed goal‐directed reaching behaviour and reduced reward pellet consumption in a free access to food task. Infusion of the muscarinic antagonist scopolamine on its own resulted in deficits in motor performance and a reduction in the number of reward pellets consumed in the free access to food task. By contrast, infusion of the nicotinic antagonist mecamylamine on its own had no significant effect on any task, except beam walking traversal time, which was reduced. Together, these data suggest that acetylcholine in the cerebellar interpositus nucleus is important for the execution and coordination of voluntary movements mainly via muscarinic receptor signalling, especially in relation to reward‐related behaviour. [ABSTRACT FROM AUTHOR]

Rich in unsaturated fatty acids, walnut oil provides a number of physiological benefits, including a reduction in the risk of cardiovascular disease and a delay in the aging process. In this work, walnut oil was prepared using the aqueous enzyme process and cold pressing method, and it was then analyzed using HPLC and FTIR. The characterization results show that the walnut oil extracted by the aqueous enzyme method outperformed the pressing oil in content of LLL by 11.64%, LLLn by 9.16% and OLL by 4.08%. But this oil had significantly less OLnLn (‐) than the pressing oil (7.90%). The Morris water maze and shuttle box tests of ICR mice revealed a notable improvement in the memory of the animals administered walnut oil. Among them, mice fed the walnut oil extracted by aqueous enzyme method showed a much shorter escape latency and a significantly higher rate of active avoidance reaction (p < 0.05, p < 0.01) than mice fed cold pressing method. With the prolongation of time, the mice even performed better than the positive control PIR group in all aspects. In summary, the quality of walnut oil extracted by aqueous enzyme method is better than that by cold pressing method. Practical Applications: Walnut oil prepared by aqueous enzymatic extraction can improve learning ability, is healthy and pollution‐free, and can be utilized as a dietary supplement in ordinary life. [ABSTRACT FROM AUTHOR]

Introduction: Alzheimer's disease (AD) is a neurodegenerative condition characterized by gradual loss of cognitive abilities (dementia) and is a major public health problem. Here, we aimed at investigating the effects of Rosa damascena essential oil (RDEO) on learning and memory functions in a rat model of amnesia induced by scopolamine, as well as on changes in acetylcholinesterase (AChE) activity, M1 muscarinic acetylcholine receptor (mAChR) expression, and brain‐derived neurotrophic factor (BDNF) levels in the extracted brain tissues. Methods: The control, amnesia (scopolamine, 1 mg/kg/i.p.) and treatment (RDEO, 100 μL/kg/p.o. or galantamine, 1.5 mg/kg/i.p.) groups were subjected to Morris water maze and new object recognition tests. AChE activity was assayed by ELISA, and M1 mAChR and BDNF concentration changes were determined by western blotting. Also, using computational tools, human M1 mAChR was modeled in an active conformation, and the major components of RDEO were docked onto this receptor. Results: According to our behavioral tests, RDEO was able to mitigate the learning and memory impairments caused by scopolamine in vivo. Our in vitro assays showed that the observed positive effects correlated well with a decrease in AChE activity and an increase in M1 mAChR and BDNF levels in amnestic rat brains. We also demonstrated in an in silico setting that the major components of RDEO, specifically ‐citronellol, geraniol, and nerol, could be accommodated favorably within the allosteric binding pocket of active‐state human M1 mAChR and anchored here chiefly by hydrogen‐bonding and alkyl–π interactions. Conclusion: Our findings offer a solid experimental foundation for future RDEO‐based medicinal product development for patients suffering from AD. [ABSTRACT FROM AUTHOR]

This document contains abstracts from various scientific studies covering a range of topics in biology and related disciplines. The studies investigate maternal overnutrition and its potential link to liver disease and cancer in offspring, the inhibition of NLRP1 inflammasome activation for neuroprotection, the effects of a nicotinic intermediate on Alzheimer's disease, the use of artificial thymic organoids to study T-cell development, the inhibition of siderophore biosynthesis for Mycobacterium abscessus infections, machine learning for early prediction of ovarian cancer, transcriptomic study of nicotine catabolism, natural variation and cellular morphology patterns in epithelial cysts, new treatments for cell quiescence in acute myeloid leukemia, the impact of endocrine disruptors on cortical development, and more. These summaries provide a brief overview of the research findings and can serve as a starting point for library patrons conducting research in these areas. [Extracted from the article]

Strobilanthes cordifolia has emerged as a promising material in traditional medicine. In this study, we have made an attempt to synthesize zinc oxide nanoparticles derived from S. cordifolia leaf. The team employed a wide range of techniques including UV, FT‐IR, XRD, FE‐SEM with EDAX, HR‐TEM with SAED, DLS, Zeta potential, BET and PZC analysis to thoroughly examine the properties of the NPs. FTIR analysis provided evidence of various functional groups within the NPs. XRD analysis demonstrated the crystal nature and phase purity of the NPs. SEM analysis showcased the spherical shape of the particles, while TEM revealed their rod‐like shape with sizes averaging at approximately 10 nm. DLS analysis indicated the average particle size, and the high zeta potential value confirmed the stability and BET analysis deciphered the specific surface area of the biosynthesized NPs. The NPs confirmed strong antioxidant properties with DPPH, ABTS, and hydroxyl radicals. Enzyme studies confirmed good anti‐cholinergic activity and anti‐inflammatory efficacy, highlighting their potential therapeutic benefits. The NPs demonstrated promising wound healing properties. Overall, this research study sheds light on the medicinal aspects of zinc oxide nanoparticles from S. cordifolia leaf extract and it offers exciting prospects for future exploration and development in this field. [ABSTRACT FROM AUTHOR]

The series of N‐methylpiperazinyl and piperdinylalkyl‐O‐chalcone derivatives as potential polyfuctional agents against Alzheimer's disease that have been designed, synthesized and then evaluated biologically using in vitro assays for the inhibition of acetylcholinesterase (AChE) activity, AGEs, and free radical formation. The majority of synthesized compounds inhibited AChE & AGEs with additional free radical scavenging activities at nanomolar concentrations. Among these, compound 5k was found to have potent AChE inhibitory activity (IC50 = 11.6 nM), superior than the reference compound donepezil (15.68 nM) along with the good anti‐AGEs and free radical formation effect. Its potency was justified by docking studies that revealed its dual binding characteristic with both catalytic active site and peripheral anionic site of AChE, simultaneously. Furthermore, the in vivo evaluation of 5k against streptozotocin (STZ)‐induced dementia in rats also showed improvement of memory functions (Morris water maze test) in animals. Also, 5k inhibited STZ‐inudced brain AChE activity and oxidative stress which further strengthen the observed in vitro effects. The stability of the ligand‐protein complex was then analyzed using a simulation‐based interaction protocol. The results revealed that these N‐methylpiperazinyl and piperdinylalkyl‐O‐chalcone derivatives could be considered for potential polyfunctional anti‐Alzheimer's molecules. [ABSTRACT FROM AUTHOR]

Tropane alkaloids constitute a compound‐class which is structurally defined by a central 8‐azabicyclo[3.2.1]octane core. A diverse bioactivity profile combined with an unusual aza‐bridged bicyclic framework has made tropanes molecules‐of‐interest within organic chemistry. Enantioselective examples of (5+2) cycloadditions between 3‐oxidopyridinium betaines and olefins remain unexplored, despite 3‐oxidopyridinium betaines being useful reagents in organic synthesis. The first asymmetric (5+2) cycloaddition of 3‐oxidopyridinium betaines is reported, affording tropane derivatives in up to quantitative yield and with excellent control of peri‐, regio‐, diastereo‐, and enantioselectivity. The reactivity is enabled by dienamine‐activation of α,β‐unsaturated aldehydes combined with in situ formation of the pyridinium reaction‐partner. A simple N‐deprotection protocol allows for liberation of the tropane alkaloid motif, and synthetic elaborations of the cycloadducts demonstrate their synthetic utility to achieve highly diastereoselective modification around the bicyclic framework. DFT computations suggest a stepwise mechanism where regio‐ and stereoselectivity are defined during the first bond‐forming step in which the pyridinium dipole exerts critical conformational control over its dienamine partner. In the second bond‐forming step, a kinetic preference toward an initial (5+4) cycloadduct was identified; however, a lack of catalyst turn‐over, reversibility, and thermodynamic bias favoring a (5+2) cycloadduct rendered the reaction fully periselective. [ABSTRACT FROM AUTHOR]

Twenty novel phthalazinone‐based compounds were designed as acetylcholinesterase (hAChE) inhibitors. Compounds 7e and 17c demonstrated comparable or superior activity compared to donepezil, respectively, in in vitro enzyme assay. Moreover, both compounds 7e and 17c possess minimal toxicity on hepatic and neuroblastoma cell lines. Besides, it was proved that compounds 7e and 17c have percentage alternations and a transfer latency time comparable to donepezil and can alleviate the cognitive impairment caused by the scopolamine‐induced model in mice. The kinetic analysis for compound 17c suggested this compound as a mixed‐type inhibitor that could bind to both the peripheral (PAS) and the catalytic site (CAS) of the hAChE enzyme. The synthesized molecules were subjected to in silico analyses, including molecular docking studies, and the outcomes were consistent with the in vitro findings. [ABSTRACT FROM AUTHOR]

Erucic acid is a single unsaturated fatty acid that falls under the omega‐9 fatty acid family. It was suggested to treat Wistar rats with lipopolysaccharide (LPS)‐induced memory impairment and minimize cognitive impairment. A total of 30 animals were randomized: group I was normally treated group, group II was administered with LPS, group III was treated with LPS along with erucic acid at the dose of 10 mg kg–1 p.o.–1, group IV was treated with LPS along with erucic acid at 20 mg kg–1 p.o.–1 and group V was the erucic acid per se group provided at the dose of 20 mg kg–1 p.o.–1 per se. Behavioral tests were evaluated by using the Morris water maze and Y‐maze. Biochemical analysis including acetylcholine esterase (AChE), choline acetyltransferase (ChAT), glutathione (GSH), catalase activity (CAT), superoxide dismutase (SOD), and nitric oxide (NO) along with proinflammatory mediators tumor necrosis factor‐α (TNF‐α), interleukin‐1β (IL‐1β), caspase 3, and neuroinflammatory biomarker (nuclear factor kappa B‐NF‐κB) were measured. Erucic acid produced substantial behavioral improvement in the Y‐maze test, including spontaneous alterations and reduced latency time during acquisition, and a longer duration of time in the consolidation phase undergoing the MWM test. Furthermore, erucic acid improved the AChE, proinflammatory markers, and oxidative stress as well as restoring endogenous antioxidant levels, ChAT, caspase 3, and NF‐κB levels. Erucic acid may be a therapeutic component for conditions related to memory disorders such as memory impairment, enhances memory functioning, and protects against neuronal damage. [ABSTRACT FROM AUTHOR]

Live imaging of microglia behavior across the life stages of the brain: From neonatal to agin... VanessaCoelho-Santos 1, Taryn Tieu 1, Anne-Jolene N. Cruz 1, Andy Y. Shih 1,2,3 1 Seattle Children's Research Institute, Center for Developmental Biology and Regenerative Me... Microglia are brain resident immune cells with important functions across the lifespan. YMS04-04 Microglia in brain organoids exhibit different immune responses if developed innately versus... Tyler J. Wenzel, Joseph D. Desjarlais, Darrell D. Mousseau University of Saskatchewan, Psychiatry, College of Medicine, Saskatoon, Canada Microglia are the innate immune cells of the brain and help maintain homeostasis, regulate synaptic development as well as facilitate the maturation of other brain cell types. Finally, we show activated OPCs and microglia/macrophages express fractalkine receptor CX3CR1 in vivo, and that in OPC-microglia co-cultures fractalkine increases in vitro oligodendrocyte differentiation by modulating both OPC and microglia biology. YMS04-02 R- and S-Ketamine modulate microglia reactivity and gene expression in lipopolysaccharide (LP... AdrianoChaves-Filho 1,2, Michele V. Soares 1, Paloma M. Jucá 1, Tatiana de Queiroz 1, Da... 1 Federal University of Ceará, Physiology and Pharmacology, Fortaleza, Brazil; 2 University o... Microglia, the brain resident immune cells, play a major role in supporting synaptic plasticity in the adult hippocampus. [Extracted from the article]

In the present study, we examined the antinociceptive and anti‐inflammatory activities of a guanylhydrazone derivative, (E)‐(3,5‐di‐tert‐butyl‐4‐hydroxybenzylidene)‐2‐guanylhydrazone hydrochloride (LQM10), in mice. The antinociceptive effect was determined by assessing behavioural responses in different pain models, while anti‐inflammatory activity was examined in carrageenan‐induced pleurisy. Intraperitoneal LQM10 administration reduced the acetic acid‐induced nociceptive behaviour, a phenomenon that was unaltered by pretreatment with yohimbine, atropine, naloxone or glibenclamide. In the formalin assay, LQM10 reduced nociceptive behaviour only in the second phase, indicating an inhibitory effect on inflammatory pain. LQM10 did not alter the pain latency in the hot plate assay and did not impact the locomotor activity of mice in the rotarod assay. In the carrageenan‐induced pleurisy assay, LQM10 treatment inhibited critical events involved in inflammatory responses, namely, leucocyte recruitment, plasma leakage and increased inflammatory mediators (tumour necrosis factor Like Properties of Chalchones and Flavonoid Derivatives [TNF]‐α and interleukin [IL]‐1β) in the pleural exudate. Overall, these results indicate that LQM10 exhibits antinociceptive effects associated with peripheral mechanisms and anti‐inflammatory activity mediated via a reduction in leucocyte migration and proinflammatory mediators, rendering this compound a promising candidate for treating pain and inflammatory process. [ABSTRACT FROM AUTHOR]

This study presents an attempt has been carried out to fabricate ion‐selective electrodes (ISEs) for the determination of Atropine sulfate (AT) in pharmaceutical formulas. Three plasticizers; namely, di‐n‐butyl phthalate (DBP), bis (2‐ethyl hexyl) phthalate (BEP), nitrobenzene (NB), and tetrahydrofuran (THF) were used in the fabrication of the three ion selective electrodes after incorporating into polyvinyl chloride (PVC) and symbolized as E1, E2, and E3, respectively. Beyond evaluation of the three ISEs, it has been confirmed that one with DBP experienced the most Nernstian behaviour. For the electrode of interest, the slope and detection limit are 55.02 mV/decade and 1.1×10−6 M, respectively. The linear range was 1.0×10−2–1.0×10−5 M (R2=0.9999) with recording 5 s and 45 days; sequentially, for the response time and shelf life of E1 electrode. The sensor has experienced high selectivity for atropine sulfate, verifying from the selectivity coefficient data for a number of potential interferences. The statistical analysis using t‐test and F‐test indicates the eligibility of constructed electrode for utilization in field of pharmaceutical analysis. A satisfactory accordance has been obtained between the proposed electrode for atropine sulfate and the standard method. This methodology is supposed to be applicable in quality control and even clinical diagnosis. [ABSTRACT FROM AUTHOR]

Several types of Quantum Dots (QDs) (CdS, CdSe and InP, as well as core‐shell QDs such as type I InP‐ZnS, quasi type‐II CdSe‐CdS and inverted type‐I CdS‐CdSe) were considered for generating α‐aminoalkyl free radicals. The feasibility of the oxidation of the N‐aryl amines and the generation of the desired radical was evidenced experimentally by quenching of the photoluminescence of the QDs and by testing a vinylation reaction using an alkenylsulfone radical trap. The QDs were tested in a radical [3+3]‐annulation reaction giving access to tropane skeletons and that requires the completion of two consecutive catalytic cycles. Several QDs such as CdS core, CdSe core and inverted type I CdS‐CdSe core‐shell proved to be efficient photocatalysts for this reaction. Interestingly, the addition of a second shorter chain ligand to the QDs appeared to be essential to complete the second catalytic cycle and to obtain the desired bicyclic tropane derivatives. Finally, the scope of the [3+3]‐annulation reaction was explored for the best performing QDs and isolated yields that compare well with classical iridium photocatalysis were obtained. [ABSTRACT FROM AUTHOR]

There is substantial evidence for the modulatory role of cyclic guanosine monophosphate (cGMP)‐specific phosphodiesterases (PDEs) in memory and synaptic plasticity, and an increase in intracellular cGMP facilitates these processes. The present study was aimed at the neuropharmacological investigations of tadalafil (TAD 5, 10, and 20 mg/kg, p.o.) and further involvement of nitric oxide (NO)‐cGMP in its effects. The effects of tadalafil and its combination with NG‐nitro‐L‐arginine methyl ester (L‐NAME) were investigated in scopolamine‐ and diabetes‐induced cognitive dysfunction using elevated plus maze (EPM) and object recognition (ORT) tests. The results of EPM revealed that the scopolamine‐ and diabetes‐induced learning and memory deficit was dose dependently attenuated after administration of TAD (TAD 10 and 20 mg/kg, p.o.) in both paradigms studied. Administration of L‐NAME (20 mg/kg) aggravated scopolamine‐ and diabetes‐induced learning and memory deficit. Co‐administration of L‐NAME (20 mg/kg) after TAD (20 mg/kg) produced significant increase in cognitive performance as compared to scopolamine‐ and diabetic‐ control group. This showed that L‐NAME (20 mg/kg) aggravated scopolamine‐ and diabetes‐induced learning and memory deficit was significantly reversed by TAD (20 mg/kg). The results of the present study revealed that tadalafil by inhibiting PDE5 possibly elevated the cGMP level that through a diversity of its substrates produced neuropharmacological effects in cognitive dysfunction. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a complex neurodegenerative disease. There is epidemiological evidence that heart failure (HF) patients are at higher risk of developing AD, and the impact of sacubitril/valsartan, the first angiotensin receptor‐neprilysin inhibitor (ARNI) approved for HF, on cognitive functions is still controversial. To investigate the effect of sacubitril/valsartan on cognitive functions in colchicine‐induced AD rat model. Forty adult male Wistar rats were equally allocated into four groups (each of 10 rats): Group I: normal control, Group II: intracerebroventricular injection of colchicine (15 μg/5 μl/bilaterally), Group III: colchicine (15 μg/5 μl/bilaterally, icv) + oral sacubitril/valsartan (100 mg/kg/day) for 25 days, and Group IV: colchicine (15 μg/5 μl/bilaterally, icv) + oral valsartan (50 mg/kg/day) for 25 days. Behavioral assessment was done using Morris water maze and passive avoidance tasks. Biochemically, β‐amyloid (1–40 and 1–42) peptides, oxidative stress (malondialdehyde and superoxide dismutase) and inflammatory (tumor necrosis factor‐alpha) parameters were measured in hippocampus and prefrontal cortex. Sacubitril/valsartan exaggerated colchicine‐induced cognitive impairment in both Morris water maze and passive avoidance tasks and was associated with significant increase in β‐amyloid accumulation, oxidative stress, and inflammation versus valsartan. Sacubitril/valsartan caused deleterious effect on cognitive impairment and biochemical alterations in colchicine‐induced AD rat model. Hence, special caution should be taken following long‐term intake of ARNI on cognitive functions. [ABSTRACT FROM AUTHOR]

Background: Laser Doppler flowmetry (LDF) is a noninvasive method of measuring regional blood flow in humans. However, this method has not been widely applied to measure blood flow in dogs. Hypothesis/Objectives: We hypothesised that LDF can measure changes in blood flow in canine pinnae accurately. The objectives were to determine whether LDF could accurately detect dermal blood flow changes in canine pinnae caused by haemodynamic drugs and characterize the dermal blood flow in dogs with pinnal alopecia. Animals: Sixteen laboratory‐owned healthy dogs, 25 client‐owned healthy control dogs and six dogs with pinnal alopecia suspected to be secondary to ischaemic dermatoses. Materials and Methods: Clinical doses of the haemodynamic drugs atropine, medetomidine and dibutyryl cyclic adenosine monophosphate (dBcAMP), as well as topical dBcAMP, were administered to healthy beagles. Subsequently, an LDF apparatus was attached to the pinnae to analyse changes in dermal blood flow. Finally, LDF was used to measure auricular dermal blood flow in dogs with pinnal alopecia compared to healthy dogs. Results: Dermal blood flow increased after atropine injection, during dBcAMP infusion and after topical dBcAMP ointment application, and decreased after medetomidine injection. Auricular dermal blood flow (in mL/min/100 g tissue) was significantly (p < 0.05) lower in dogs with pinnal alopecia than in healthy dogs. Conclusions and Clinical Relevance: Laser Doppler flowmetry is useful for measuring dermal blood flow in canine pinnae; it can be a noninvasive method to monitor ischaemic conditions of dog skin. [ABSTRACT FROM AUTHOR]

Synthetic cathinones comprise a large amount of substances present on the dark market, which creates an undeniably worldwide problem and still is posing a threat. A 22‐year‐old man was brought to the Emergency Room from a party, where he had ingested orally 20 g of mephedrone. The man exhibited a disorder of consciousness with no logical verbal contact and dilated pupils. Moreover, a metabolic acidosis was present. The patient died after an hour from an admission to the ER. Blood and vitreous humor collected during an autopsy were analyzed with the use of an ultra‐high‐performance liquid chromatography‐tandem mass spectrometry (UHPLC‐QqQ‐MS/MS) with the use of C18 column in multiple reaction monitoring (MRM) mode. Both biological specimens were prepared using liquid–liquid extraction (LLE) with the use of ethyl acetate and 0.5 M ammonium carbonate water solution (pH 9). The limit of quantification (LOQ) of the method was 0.5 ng/ml in both matrices; precision and accuracy values did not exceed ±15%. Recovery of the method was in the range of 86.1%–102.7%. Determined concentrations of 4‐CMC were 8542 and 9874 ng/ml in blood and vitreous humor, respectively. Other substances present in both biological materials were: atropine, diazepam, lidocaine, and its metabolite norlidocaine, as well as methcathinone and ethyl alcohol. The concentration presented in here described case is the highest ever reported 4‐CMC concentration. Important aspect is also receiving other NPS by recreational users than intended, which lead to accidental poisoning (in presented case user assumed 4‐CMC was 4‐MMC). [ABSTRACT FROM AUTHOR]

"In the land of the blind, the one-eyed man is king."[7] More drug programs would be improved or saved, thereby fundamentally shifting CNS drug R&D economics relative to pharmaceutical companies that do not fully integrate QSP computational modeling. B Pharmaceutical research and development (R&D) relies on developing good systemic hypotheses about the effect of novel drug mechanisms on pathophysiology. Even if these isolated questions could be satisfactorily answered via QSP computational modeling, a broader application of the modeling to more general questions about the disease is not initiated, and single, isolated modeling attempts prevail. [Extracted from the article]

Recycled polyvinyl butyral film (RPVB) is reactive blending with different dosages of styrene‐maleic anhydride copolymer (SMA) in a torque rheometer. The shape memory properties of the RPVB/SMA blends are studied. The cross‐linked reaction between RPVB and SMA is the main factor affecting the shape memory properties of the binary blends. When the RPVB and SMA blending ratios are 3:1 and 4:1, both blends exhibit superior shape memory properties (the shape fixation ratios are above 96% at room temperature, and the shape recovery ratios are over 99% at 80°C). Furthermore, the RPVB/SMA/NRGO composites are prepared by adding the NH2‐functionalized reduced graphene oxide (NRGO) with an excellent thermal stability. The introduction of NRGO not only improves the tensile properties of the composites, but also endows them with an excellent light‐induced shape memory function. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a neurodegenerative disease in elderly population. Pterostilbene (PTS) is a resveratrol analog with neuroprotective activity. However, the biological mechanisms of PTS in AD progression are largely uncertain. An animal model of AD was established using streptozotocin (STZ)‐treated C57BL/6J mice. Monoamine oxidase B (MAOB) expression was analyzed by bioinformatics analysis and detected by western blotting assay. The memory impairment was investigated by Morris water maze test. The levels of Tau hyperphosphorylation and death‐related proteins were detected by western blotting analysis. The levels of amyloid β (Aβ)1–42 accumulation, oxidative stress‐related markers (ROS, MDA, SOD, and GSH), and inflammation‐relative markers (TNF‐α, IL‐1β, IL‐6, and p‐NF‐κB) were measured by ELISA. MAOB expression was increased in hippocampus of AD mice, and it was decreased by PTS. PTS attenuated STZ‐induced body weight loss and memory impairment by regulating MAOB. PTS mitigated Aβ1–42 accumulation and Tau hyperphosphorylation by regulating MAOB in STZ‐treated mice. PTS attenuated neuronal death by decreasing cleaved caspase‐3 and Bax levels and increasing Bcl2 expression in hippocampus by regulating MAOB in STZ‐treated mice. PTS weakened STZ‐induced oxidative stress in hippocampus by decreasing ROS and MDA levels and increasing SOD and GSH levels by regulating MAOB. PTS protected against STZ‐induced neuroinflammation in hippocampus by inhibiting TNF‐α, IL‐1β, IL‐6, and p‐NF‐κB levels through regulating MAOB. In conclusion, PTS alleviates STZ‐induced memory impairment, Aβ1–42 accumulation, Tau hyperphosphorylation, neuronal death, oxidative stress, and inflammation by decreasing MAOB in AD mice, proving anti‐AD potential of PTS. The biological mechanisms of pterostilbene (PTS) in Alzheimer's disease (AD) progression are largely uncertain. PTS alleviates streptozotocin (STZ)‐induced memory impairment, Aβ1–42 accumulation, Tau hyperphosphorylation, neuronal death, oxidative stress, and inflammation by decreasing MAOB in AD mice. This study might provide new pharmacological activity of PTS in treating AD. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a complex, degenerative condition linked to memory loss and cognitive degradation. The phenyl sulfonyl‐pyrimidine derivatives containing dimethoxy‐chloro substituent (BS‐10 and BS‐22) were previously recognized as multitarget‐directed ligands (MTDLs) due to their ability to inhibit acetylcholinesterase (AChE) at low nanomolar concentrations (IC50=47.33±0.02 and 51.36±0.04 nM respectively) while also reducing amyloid beta (Aβ) aggregation. In the current investigation, we investigated the in vivo and ex‐vivo effects of BS‐10 and BS‐22 chemicals on cognition and the cholinergic system. We have used scopolamine and Aβ1‐42 models of cognitive impairment which were measured during Y‐maze and passive avoidance apparatus. Results showed that BS‐10 at 10 mg/kg compared to BS‐22 at 20 mg/kg rescued memory impairment more significantly. Moreover, ex‐vivo and biochemical studies exhibited both compounds improved the hippocampal acetylcholine (Ach) level by reducing AChE activity as well as antioxidant properties. In addition, BS‐10 and BS‐22 attenuated Aβ1‐42 induced cognitive deficiency in rats during Y‐maze tests and significantly restored mitochondrial membrane potential and reduced the tau protein level in rats (p<0.05). In summary, our results indicated that MTDLs BS‐10 and BS‐22 would be a promising therapeutic approach in AD. [ABSTRACT FROM AUTHOR]

We present the development of novel ion‐selective electrodes for tropane, atropine, and scopolamine, as a general model for tropane alkaloids and drugs such as e. g. cocaine. These potentiometric sensors rely either on a metallocarborane or tetraphenylborate complex as recognition element and led to systems with a near‐Nernstian behaviour in the range of 10−5–10−2 mol/L and detection limits around 2 ⋅ 10−5 mol/L. Selectivity studies with commonly used drug additives (caffeine, phenacetin) and closely related tropane derivatives show very low influence of the additives and a structure dependent interference for the derivatives. Beside this, a hydrogel‐based concept with a similar performance was developed, which could be used for on‐site measurement of solid samples. The developed sensors therefore demonstrated their suitability and might be used to enable the development of portable sensor arrays for the quantification of a wide range of tropane alkaloids. [ABSTRACT FROM AUTHOR]

To investigate the expression and significance of pyruvate carboxylase (PC) for astrocytes cells, we evaluated the effect of the PC inhibition on survival of cultured human astrocytes cells and the expression of PC in cultured astrocytes cells as well as among human brain cortex samples by immunoprobing methods. Our experimental results showed that the combination of andrographolide and 6-shogaol exhibited the most prominent NO inhibitory effect in lipopolysaccharide (LPS)-activated microglia N11 cells with IC SB 50 sb value of 6.10 M. This combination continued to show a promising effect in LPS activated tri-culture system (microglia N11, endothelial bEnd3 cells, and neuron N2A cells) that reduced NO production and enhanced neuronal survival. WTH10-19 Influence of curcumin on choliensterase activity and gene expression in brain of scopolamine-... Odunayo Oluokun SP 1,2 sp , Omodesola Ogunruku SP 4 sp , Haruna Umar SP 1 sp , Ganiyu Oboh SP 1,2 sp SP 1 sp The Federal University of Technology Akure, Department of Biochemistry, Akure, Nigeria; SP 2 sp The Federal University of Technology Akure, Drosophila Research Lab, Functional Foods and Nutraceuticals Unit, Department of Biochemistry, Akure, Nigeria; SP 3 sp The Federal University of Technology Akure, Department of Biomedical Technology, School of Basic Medical Sciences, Akure, Nigeria; SP 4 sp ObafemiAwolowo University, Department of Biochemistry and Molecular Biology, Ile-Ife, Nigeria Combination therapies involving cholinesterase inhibitors with other therapeutic agents have been found to have better effects in the management of dementia related diseases but there has been a dearth of information on their synergistic effects with dietary polyphenols. Meta-analysis of seven deep datasets reveals 2698 differentially expressed (DE) proteins in the landscape of AD brain proteome ( I n i = 12,017 proteins/genes), covering 35 reported AD genes and risk loci. [Extracted from the article]

Background and Purpose: Gastric pacemaker cells, interstitial cells of Cajal (ICC), are believed to initiate myogenic (non‐neuronal) contractions. These become damaged in gastroparesis, associated with dysrhythmic electrical activity and nausea. We utilised mouse isolated stomach to model myogenic contractions and investigate their origin and actions of interstitial cells of Cajal modulators. Experimental Approach Intraluminal pressure was recorded following distension with a physiological volume; tone, contraction amplitude and frequency were quantified. Compounds were bath applied. Key Results: The stomach exhibited regular large amplitude contractions (median amplitude 9.0 [4.7–14.8] cmH2O, frequency 2.9 [2.5–3.4] c.p.m; n = 20), appearing to progress aborally. Tetrodotoxin (TTX, 10−6 M) had no effect on tone, frequency or amplitude but blocked responses to nerve stimulation. ω‐conotoxin GVIA (10−7 M) ± TTX was without effect on baseline motility. In the presence of TTX, (1) atropine (10−10–10−6 M) reduced contraction amplitude and frequency in a concentration‐related manner (pIC50 7.5 ± 0.3 M for amplitude), (2) CaCC channel (previously ANO1) inhibitors MONNA and CaCCinh‐A01 reduced contraction amplitude (significant at 10−5, 10−4 M respectively) and frequency (significant at 10−5 M), and (3), neostigmine (10−5 M) evoked a large, variable, increase in contraction amplitude, reduced by atropine (10−8–10−6 M) but unaffected (exploratory study) by the H1 receptor antagonist mepyramine (10−6 M). Conclusions and Implications: The distended mouse stomach exhibited myogenic contractions, resistant to blockade of neural activity by TTX. In the presence of TTX, these contractions were prevented or reduced by compounds blocking interstitial cells of Cajal activity or by atropine and enhanced by neostigmine (antagonised by atropine), suggesting involvement of non‐neuronal ACh in their regulation. [ABSTRACT FROM AUTHOR]

Atropine eye drops are frequently used in the treatment of keratitis and during ophthalmic surgery. We described a rare complication of central anticholinergic syndrome secondary to atropine eye drops. [ABSTRACT FROM AUTHOR]

Oxidative stress is the critical marker of neurological complications such as Alzheimer's disease (AD). Apple cider vinegar (ACV) is known to have health benefits due to its antidiabetic, anti‐inflammatory, and high antioxidant properties. Therefore, we hypothesized that regular consumption of ACV would protect against AD‐like neurological diseases via inhibition of oxidative stress. Authors have compared the efficacy of ACV with that of Chrysin and Rivastigmine in cellular and animal studies. In the cellular study, oxidative stress was induced in Neuro2A cells (1 × 107) via H2O2 (50 μM) treatment. Subsequently, acetylcholinesterase (AChE) activity was performed, and cell viability, SOD, GSH, lipid peroxidation (MDA) levels were measured. Similarly, in the animal study, oxidative stress was introduced in Swiss albino mice (10–11 weeks old, 20–25 g, n = 30) via scopolamine (1 mg/kg). Subsequently, histopathological experiments were performed; cognitive ability, AChE activity, and SOD, GSH, and MDA levels were measured. The in vitro results indicated that ACV (2 μM) provided better protection than Chrysin and Rivstigmine in cell viability. ACV has also performed better in restoring the antioxidants markers (SOD, GSH levels) and reducing MDA and AChE levels. In the in vivo study, test compounds (ACV, Chrysin, and Rivastigmine) improved cognitive impairment, increased the SOD and GSH level, reduced the MDA level and AChE activity, and protected the cortex‐hippocampal neurons from degeneration. Here also, ACV (0.7%) showed better neuroprotection than the other two compounds. Therefore, these results supported our hypothesis that moderate consumption of ACV might prove to be beneficial prophylaxis against AD‐like neurological diseases. [ABSTRACT FROM AUTHOR]

Bisphenol A (BPA) is a raw material of polycarbonate and epoxy resin. It is used for various household electrical appliances, electronic equipment, office automation equipment, medical equipment, mobile phones, paints for automobiles, internal surface coating of cans, and adhesives for civil engineering and construction. BPA is a well‐known endocrine‐disrupting chemical, and it was reported that BPA has an adverse effect on the nervous and immune systems. However, BPA‐induced memory impairment and changes in neuroimmune biomarkers in the allergic asthmatic subject are not known yet. We aim to investigate the dietary exposure effect of BPA on brain function and biomarkers using allergic an asthmatic mouse model. Five‐week‐old male C3H/HeJSlc mice were fed two doses of BPA [0.901, 9.01 μg/kg/day] contained chow diet from 5 to 11 weeks old and ovalbumin (OVA) was given by intratracheal instillation every 2 weeks. Memory function was determined by a novel object recognition test. Genes related to memory and immune markers in the hippocampus were investigated with the real‐time polymerase chain reaction (RT‐PCR) method. In this study, impaired novel object recognition occurred in BPA‐exposed mice in the presence of an allergen. Moreover, upregulation of expression level of neuroimmune biomarkers such as N‐methyl‐D‐aspartate receptor, tumor necrosis factor‐α, ionized calcium‐binding adapter molecule‐1, cyclooxygenase‐2, and heme oxygenase‐1 in the hippocampus was observed in BPA‐exposed allergic asthmatic mice. These findings show that BPA exposure can induce neuroinflammation and which triggers impairment of memory function in mice with allergic asthma. Our study indicated that dietary exposure to BPA may affect higher brain functions by modulating neuroimmune biomarkers in allergic asthmatic subjects. Dietary BPA exposure affects neuroimmune biomarkers. Dietary BPA exposure impaired memory in allergic asthmatic mice. Neuroimmune activation was observed in BPA in the presence of allergen. [ABSTRACT FROM AUTHOR]

Hypobaric hypoxia at higher altitudes usually impairs cognitive function. Previous studies suggested that epigenetic modifications are the culprits for this condition. Here, we set out to determine how hypobaric hypoxia mediates epigenetic modifications and how this condition worsens neurodegeneration and memory loss in rats. In the current study, different duration of hypobaric hypoxia exposure showed a discrete pattern of histone acetyltransferases and histone deacetylases (HDACs) gene expression in the hippocampus when compared with control rat brains. The level of acetylation sites in histone H2A, H3 and H4 was significantly decreased under hypobaric hypoxia exposure compared to the control rat's hippocampus. Additionally, inhibiting the HDAC family with sodium butyrate administration (1.2 g/kg body weight) attenuated neurodegeneration and memory loss in hypobaric hypoxia‐exposed rats. Moreover, histone acetylation increased at the promoter regions of brain‐derived neurotrophic factor (BDNF); thereby its protein expression was enhanced significantly in hypobaric hypoxia exposed rats treated with HDAC inhibitor compared with hypoxic rats. Thus, BDNF expression upregulated cAMP‐response element binding protein (CREB) phosphorylation by stimulation of PI3K/GSK3β/CREB axis, which counteracts hypobaric hypoxia‐induced spatial memory impairment. In conclusion, these results suggested that sodium butyrate is a novel therapeutic agent for the treatment of spatial memory loss associated with hypobaric hypoxia, and also further studies are warranted to explore specific HDAC inhibitors in this condition. [ABSTRACT FROM AUTHOR]

Hyoscyamine (HYO) and scopolamine (SCO) are tropane alkaloids acting as anticholinergic factors on the parasympathetic nervous system in humans and are produced by Solanaceous plants. Two strains of Agrobacterium rhizogenes, A4 and LBA9402, were used to infect Atropa acuminata Royle ex Miers and Atropa belladonna L. leaf explants. A. acuminata was inoculated either by direct infection or sonicated‐assisted A. rhizogenes‐mediated transformation (SAAT) was performed. A. belladonna was inoculated with the A4 strain using a direct method. The selected hairy root lines of both species were elicited with 50 mM methyl‐β‐cyclodextrin (β‐CD), 0.5 μM coronatine (Cor) or 50 mM β‐CD + 0.5 μM Cor on Day 14 of culture. The elicitor effect on growth and HYO and SCO content was analyzed after one (T1) and two (T2) weeks of treatment. In A. acuminata explants, the highest transformation percentage (T%) was obtained with strain A4 and the SAAT method (T%: 96.43). Cor significantly reduced the growth of A. acuminata hairy roots (fresh weight and dry weight [DW]: 2.52 and 0.3 g, respectively), whereas β‐CD increased their DW (0.4 g). Also, the combined β‐CD + Cor treatment had a positive significant effect on the DW of A. belladonna hairy roots (0.41 g). In A. acuminata hairy roots, the HYO level was lower under Cor treatment than in the control at both sampling times. In contrast, the SCO content was increased 10‐fold by Cor elicitation at T1 compared to the control (10.95 mg g−1 DW) and was also positively affected by β‐CD + Cor. In A. belladonna hairy roots, all the elicitors had a negative effect on both HYO and SCO production. This report is the first assessment of the effect of β‐CD and Cor elicitors on tropane alkaloid production. [ABSTRACT FROM AUTHOR]

Sialorrhea is a troublesome and disabling symptom defined by the unintentional loss of saliva from the mouth, usually associated with swallowing disorders. Today there is no consensus about the management of sialorrhoea, but off‐label use of ophthalmic atropine eyedrop administered sublingually may offer benefits, despite limited safety data. We report 2 cases of atropine overdose after sublingual administration illustrating that atropine can expose to severe adverse effects when administered sublingually. The noncompartmental pharmacokinetic study of atropine performed in 1 patient highlighted that systemic absorption of sublingual atropine was effective (Cmax [1 h] = 2.2 ng mL−1; approximately) after a single dose of 1 mg. [ABSTRACT FROM AUTHOR]

The present study investigates the effect of ozagrel, a selective thromboxane A2 (TXA2) inhibitor, in rat model of hyperhomocysteinemia (HHcy)‐induced vascular cognitive impairment and dementia (VCID). Wistar rats were administered L‐methionine (1.7 g/kg/day; p.o. × 8 weeks) to induce VCID. Morris water maze (MWM) test was employed to assess learning and memory. Endothelial dysfunction was assessed in the isolated aorta by observing endothelial‐dependent vasorelaxation and levels of serum nitrite. Various biochemical and histopathological estimations were also performed. L‐methionine produced significant impairment in endothelium‐dependent vasorelaxation and decreases serum nitrite levels indicating endothelial dysfunction. Further, these animals performed poorly on MWM, depicting impairment of learning and memory. Further, a significant rise in brain oxidative stress level (indicated by increase in brain thiobarbituric acid‐reactive species and decrease in reduced glutathione levels), brain acetylcholinesterase activity, brain myeloperoxidase activity, brain TNF‐α and IL‐6 levels, and brain leukocyte (neutrophil) infiltration was also observed. Treatment of ozagrel (10 and 20 mg/kg, p. o.)/donepezil (0.5 mg/kg, i.p., serving as standard) ameliorated L‐methionine‐induced endothelial dysfunction, memory deficits, and biochemical and histopathological changes. It may be concluded that ozagrel markedly improved endothelial dysfunction, learning and memory, and biochemical and histopathological alteration associated with L‐methionine‐induced VCID and that TXA2 can be considered as an important therapeutic target for the management of VCID. [ABSTRACT FROM AUTHOR]

Purpose: Atropine at a low concentration is considered a safe and effective treatment to mitigate myopia progression. However, the potential unwanted side effects of administering atropine at a low dose on visual functions other than best corrected visual acuity has not been investigated. In this study, we investigate the short‐term (12, 16, and 20 h) and long‐term (1, 2, and 4 weeks) effects of 0.01% atropine (i.e., 0.1 mg/ml) on contrast sensitivity (CS) in patients with myopia. Methods: Thirty adults (23.33 ± 2.93 years old) with myopia between −1.00 and −6.00 diopters (D), astigmatism of −1.50 D or less, and anisometropia of 1.00 D or less, participated in this prospective, masked, placebo‐controlled, randomized study. The participants were randomly assigned to receive 0.01% atropine or polyvinyl alcohol eye drops once nightly to both eyes for four weeks. CS was measured binocularly at baseline and 12, 16, 20 h, 1, 2, and 4 weeks after the first use of the eye drops. Results: There was no statistically significant differences of CS found between atropine and placebo‐controlled groups in both short‐term and long‐term. There was no statistically significant interaction effect found between the time and group. Conclusion: We demonstrated no significant deleterious effect of 0.01% atropine on adult myopes' CS. [ABSTRACT FROM AUTHOR]

Aims: Dietary Mg2+ deficiency (MgD) impairs hippocampus‐dependent memory in mice; however, the molecular mechanisms underlying MgD‐induced memory impairments are unclear. Here, we investigated the molecular signatures in the hippocampus of MgD mice by analyzing the hippocampal transcriptome. Methods: We performed RNA‐sequencing of the hippocampal transcriptome of MgD mice. We used gene ontology analyses and quantitative real‐time PCR to validate the RNA‐sequencing results. Results: mRNAs for neuroinflammation‐related genes were upregulated in the hippocampus and cortex of MgD mice. Conclusion: MgD induces neuroinflammation in the mouse brain, including the hippocampus and cortex. Our findings suggest that MgD‐induced neuroinflammation triggers the impairments of hippocampus‐dependent memory. [ABSTRACT FROM AUTHOR]

We have optimized a synthetic approach to (±)‐Ferrugine in 8 steps starting from 5‐aminocyclohept‐1‐ene and using the Brønsted acid‐catalyzed pseudotransannular ring‐opening of the epoxide derived from this cycloheptene as the key step for the construction of the 8‐azabicyclo[3.2.1]octane central core. While attempting the enantioselective synthesis of this natural product from enantiopure 2‐hydroxy‐8‐azabicyclo[3.2.1]octane we have found that this compound shows a pronounced tendency to racemize via an achiral symmetric aziridinium intermediate. This racemization side process has been studied in detail using both experimental and computational methods. [ABSTRACT FROM AUTHOR]

The authors of the document respond to comments made by Mr. Rottenberg regarding their case report and CPR practices. They explain that the resuscitation of the dog in the case report followed the recommendations outlined in the 2012 Reassessment Campaign on Veterinary Resuscitation (RECOVER) clinical guidelines. These guidelines group CPR interventions into basic and advanced life support, with advanced interventions informed by cardiac arrest rhythm diagnoses. The administration of epinephrine is recommended for animals with a nonshockable cardiac arrest rhythm, such as asystole. The authors also mention that the use of extracorporeal membrane oxygenation (ECMO) in conjunction with abdominal compression-only CPR is a compelling technique, but its use may be limited by availability and cost. They justify the routine incorporation of epinephrine and atropine in their institution's treatment of cardiopulmonary arrest patients based on the available evidence. [Extracted from the article]

Recent studies raise the possibility that donepezil can delay the progression of Alzheimer's disease (AD). This research evaluated the efficacy of donepezil in an animal model with brain insulin resistance and AD‐like alterations. Rats were fed with high‐fat/high‐fructose (HF/Hfr) diet during the study period (17 weeks) and received one injection of streptozotocin (STZ) (25 mg/kg) after 8 weeks of starting the study. Diabetic (T2D) rats were treated with donepezil (4 mg/kg; p.o.) or vehicle for 8 weeks after STZ injection. The influence of donepezil on AD‐related behavioral, biochemical, and neuropathological changes was investigated in T2D rats. Treatment of diabetic rats with donepezil led to a significant decrease in both amyloid‐β deposition and the raised hippocampal activity of cholinesterase (ChE). It significantly increased the suppressed glutamate receptor expression (AMPA GluR1 subunit and NMDA receptor subunits NR1, NR2A, NR2B). It also improved cognitive dysfunction in the passive avoidance and the Morris water maze tests. However, donepezil treatment did not significantly decrease the elevated levels of P‐tau, caspase‐3, GSK‐3β, MDA, TNF‐α, and IL‐1β in the hippocampus of diabetic rats. Also, it did not restore the suppressed levels of glutathione and superoxide dismutase in the brain of these rats. Moreover, donepezil did not alter the elevated serum level of glucose, insulin, and total cholesterol. These findings suggest that donepezil treatment could ameliorate learning and memory impairment in T2D rats through reversal of some of the AD‐related alterations, including reduction of amyloid‐β burden and ChE activity as well as restoration of glutamate receptor expression. However, lack of any significant effect on P‐tau load, oxidative stress, neuroinflammation, and insulin resistance raises the question about the ability of donepezil to delay the development or arrest the progression of T2D‐induced AD and it is still a matter of debate that requires further studies. [ABSTRACT FROM AUTHOR]

The synthesis of tropanes via a microwave‐assisted, stereoselective 6π‐electrocyclic ring‐opening/ Huisgen [3+2]‐cycloaddition cascade of cyclopropanated pyrrole and furan derivatives with electron‐deficient dipolarophiles is demonstrated. Starting from furans or pyrroles, 8‐aza‐ and 8‐oxabicyclo[3.2.1]octanes are accessible in two steps in dia‐ and enantioselective pure form, being versatile building blocks for the synthesis of pharmaceutically relevant targets, especially for new cocaine analogues bearing various substituents at the C‐6/C‐7 positions of the tropane ring system. Moreover, the 2‐azabicyclo[2.2.2]octane core (isoquinuclidines), being prominently represented in many natural and pharmaceutical products, is accessible via this approach. [ABSTRACT FROM AUTHOR]

d‐Ribose‐l‐cysteine (DRLC) is an analogue of cysteine that has been shown to boost cellular antioxidant capacity by enhancing intracellular biosynthesis of glutathione (GSH). Deficiency of GSH has been implicated in the pathogenesis of Alzheimer's disease (AD), a neurodegenerative disorder associated with loss of memory. Thus, the use of antioxidants to prevent or retard the progression of memory deteriorations in persons with AD has been the focus of intense investigations. This study was carried out to evaluate the effects of DRLC on memory and scopolamine‐induced amnesia, acetyl‐cholinesterase activity, and oxidative stress in mice. Male Swiss mice were given oral administration of saline (10 ml/kg), DRLC (25, 50, and 100 mg/kg) or donepezil (1 mg/kg) 30 min before testing for memory performance using Y‐maze and object recognition models. Another set of mice were also pretreated orally with saline, DRLC (25, 50, and 100 mg/kg) or donepezil (1 mg/kg) but in combination with scopolamine (3 mg/kg, i.p.) daily for 7 days. Thirty minutes after treatment on Day 7, memory function was then evaluated. The brain levels of acetyl‐cholinesterase and oxidative stress parameters were assayed. DRLC significantly (p <.05) enhanced memory performance and attenuated scopolamine‐induced amnesia. Increased acetyl‐cholinesterase activity and oxidative stress, as shown by decreased antioxidant substrates (glutathione and catalase) and elevated malondialdehyde contents in mice with scopolamine amnesia were also attenuated by DRLC. Our findings suggest that inhibition of oxidative stress and acetyl‐cholinesterase activity might contribute to the potential benefit of DRLC in persons with amnesia. [ABSTRACT FROM AUTHOR]

Background and Purpose: Alzheimer's disease (AD) is the most prevalent disease associated with cognitive dysfunction. Current AD therapeutic agents have several gastrointestinal or psychological adverse effects and therefore, novel therapeutic agents with fewer adverse effects must be developed. Previously, we demonstrated that oleanolic acid, which is similar in chemical structure to maslinic acid, ameliorates cognitive impairment through the activation of tropomyosin receptor kinase (TrkB)-ERK-cAMP response element-binding protein (CREB) phosphorylation and increased levels of brain-derived neurotrophic factor (BDNF). In the present study, we investigate the effect of maslinic acid on cholinergic blockade-induced memory impairment in mice.Methods and Key Results: Maslinic acid reversed scopolamine-induced memory impairment, as determined by the Y-maze, passive avoidance and Morris water maze tests. In addition, we also observed that ERK-CREB, PI3K and PKB (Akt) phosphorylation levels were increased by maslinic acid administration in the mouse hippocampus. Moreover, we determined that the effects of maslinic acid on scopolamine-induced memory impairment in the passive avoidance test were abolished by a specific TrkB receptor antagonist (ANA-12). Additionally, we observed similar temporal changes in the expression levels between BDNF and tissue plasminogen activator in the hippocampus.Conclusion and Implications: These findings suggest that maslinic acid enhances cognitive function through the activation of BDNF and its downstream pathway signalling in the hippocampus and that it might be a potential therapeutic agent for cognitive decline, such as that observed in AD. [ABSTRACT FROM AUTHOR]

The enantioselective synthesis of tropanols has been accomplished through chiral phosphoric acid catalyzed pseudotransannular ring opening of 1‐aminocyclohept‐4‐ene‐derived epoxides. The reaction proceeds together with the desymmetrization of the starting material and leads to the direct formation of the 8‐azabicyclo[3.2.1]octane scaffold with excellent stereoselectivity. The synthetic applicability of the reaction was demonstrated by the enantioselective synthesis of the two natural products (−)‐α‐tropanol and (+)‐ferruginine. [ABSTRACT FROM AUTHOR]

A Pd/C‐catalyzed cascade approach for the synthesis of attractive benzo‐fused tropanes was developed. The reaction proceeds through a sequential Pd/C‐catalyzed dehydrogenative formation of azomethine ylides from amines and 1,3‐dipolar cycloaddition. It allows the generation of structurally complex benzo‐fused tropanes in good yields with excellent diastereoselectivities under mild reaction conditions. Preliminary results of asymmetric version of the reaction reveal that the copper catalyst and chiral monophosphoramidite ligand can furnish optically active products with moderate ee. Described is a Pd/C‐catalyzed dehydrogenative [3+2] cycloaddition for the synthesis of benzo‐fused tropanes. The reaction proceeds through a sequential Pd/C‐catalyzed dehydrogenative formation of azomethine ylides from amines and 1,3‐dipolar cycloaddition. [ABSTRACT FROM AUTHOR]

Abstract: A novel strategy for constructing tropanes via [3+3] annulation of cyclic azomethine ylides with substituted 2‐vinylindoles and 2‐vinylpyrroles in the presence of in‐house Cu(II)/N,O‐ligand complex has been developed. The reaction was achieved via a tandem copper(II)‐catalyzed Michael addition/BF3 ⋅ Et2O promoted intramolecular aza‐Friedel‐Crafts reaction of indoles or pyrroles with non‐activated ketimines, providing indole or pyrrole‐annulated tropanes in high yields (up to 87%) and excellent stereoselectivities (>99:1 dr in all cases, up to >99% ee). [ABSTRACT FROM AUTHOR]

Abstract: A new method has been developed for the simultaneous determination of 13 tropane alkaloids in tea and herbal teas using high‐performance liquid chromatography coupled to an Exactive‐Orbitrap analyzer. A mixture of methanol, water, and formic acid was used for the extraction of the target compounds followed by a solid‐phase extraction step. The validated method provided recoveries from 75 to 128% with intra‐ and interday precision lower than or equal to 24% (except for apoatropine). Limits of quantification ranged from 5 to 20 μg/kg. Eleven tea and herbal tea samples and two contaminated samples with Datura stramonium seeds were analyzed. Tropane alkaloids were detected in six samples with concentrations from 5 (apoatropine) to 4340 μg/kg (sum of physoperuvine, pseudotropine, and tropine), whereas concentrations from 5 (apoatropine) to 1725 μg/kg (sum of physoperuvine, pseudotropine, and tropine) were found in the contaminated samples. [ABSTRACT FROM AUTHOR]

BACKGROUND Tropane alkaloids are known to play a role in plant defence. By blocking acetylcholine receptors, they exert insecticidal and deterrent effects against herbivore insects. Carbamates are an important class of chemical insecticides that also inhibit acetyl cholinesterase. The objective of this work was to synthesise a series of tropane alkaloids bearing a carbamate group, and to evaluate their effects against the pest Ascia monuste. The effects of the most active compounds were evaluated on the A. monuste predator Solenopsis saevissima and on the pollinator Tetragonisca angustula. RESULTS The synthesis of carbamate-tropane alkaloids was accomplished in 4-5 steps from commercially available ketones. Results from bioassays showed that compounds 6a, 10a and 14a presented higher activities against second-instar larvae of A. monuste, with LD50 values of 1.01, 3.76 and 1.92 µg substance mg−1 insect, and TL50 values of 7.0, 15.0 and 5.0 h respectively. These compounds were also tested for their selectivity in favour of S. saevissima and T. angustula. Compound 6a, which showed the highest activity against A. monuste, also showed lower toxicity against S. saevissima. CONCLUSION Tropane alkaloid derivatives bearing a carbamate group show potential for the development of novel insecticides against A. monuste. © 2017 Society of Chemical Industry [ABSTRACT FROM AUTHOR]

Background Voxel-wise comparison of [123I]-2β-carbomethoxy-3beta-(4-iodophenyl)tropane ([123I]β- CIT) radioligand distribution measured by single-photon emission computed tomography ( SPECT) revealed distinct patterns of reduced dopamine transporter ( DAT) availability in the Parkinson's variant of MSA ( MSA-P). The aim of this study was to identify the monoamine transporter distribution pattern in patients with the cerebellar variant of MSA ( MSA-C). Additionally, monoamine transporter availability was investigated in a small cohort of patients with sporadic adult-onset ataxia ( SAOA). Methods [123I]β- CIT SPECT was performed in patients with MSA-C (n = 12), MSA-P (n = 14), SAOA (n = 5), and controls (n = 15) matched for age. Parametric images of [123I]β- CIT binding potential ( BPND) were generated and analyzed by statistical parametric mapping ( SPM) and region of interest ( ROI) analysis. Results SPM localized significant reductions of [123I]β- CIT BPND in the striatum, midbrain, and pons in MSA-C compared to controls. When compared with MSA-P, the striatal DAT decline was significantly less affected in MSA-C. ROI analysis revealed reductions of striatal and midbrain [123I]β- CIT binding in MSA-C compared to SAOA, whereas no significant difference was apparent between the SAOA and control groups. Conclusions Midbrain and pontine monoaminergic transporter binding was severely impaired in MSA-C, matching the underlying pathological features. Striatal DAT availability was relatively less affected in MSA-C compared to MSA-P, reflecting measureable, but less-profound, degeneration of the nigrostriatal dopaminergic projections. Preliminary results of reduced striatal and midbrain [123I]β- CIT binding in MSA-C, compared to SAOA, suggest that the potential of DAT- SPECT as a surrogate marker in the diagnostic workup of patients with adult-onset cerebellar ataxia should be further investigated. [ABSTRACT FROM AUTHOR]