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Targeting harmful effects of non-excitatory amino acids as an alternative therapeutic strategy to reduce ischemic damage

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Neural Regeneration Research 2025年第9期20卷 2454-2463页

作者： Victoria Jiménez Carretero IrisÁlvarez-Merz jorge Hernández-Campano Sergei A.Kirov Jesús M.Hernández-Guijo department of Pharmacology and Therapeutic School of MedicineUniv.Autónoma de MadridMadridSpain Ramón y Cajal Institute for Health Research(IRYCIS) Neurobiology-Research ServiceHospital Ramón y CajalMadridSpain Institute of Neurobiology Faculty of Mathematics and Natural SciencesHeinrich Heine University DüsseldorfDüsseldorfGermany department of Neuroscience and Regenerative Medicine&department of Neurosurgery Medical College of Georgia at Augusta UniversityAugustaGAUSA

The involvement of the excitatory amino acids glutamate and aspartate in ce rebral ischemia and excitotoxicity is ***,the role of non-excitatory amino acids in brain damage following a stroke or brain trauma remains largely *** release of amino acids by necrotic cells in the ischemic core may contribute to the expansion of the *** findings indicated that the reversible loss of field excitato ry postsynaptic potentials caused by transient hypoxia became irreversible when exposed to a mixture of just four non-excitatory amino acids(L-alanine,glycine,L-glutamine,and L-serine)at their plasma *** amino acids induce swelling in the somas of neurons and astrocytes during hypoxia,along with permanent dendritic damage mediated by N-methyl-d-aspartate *** N-methyl-d-aspartate receptors prevented neuronal damage in the presence of these amino acids during *** is likely that astroglial swelling caused by the accumulation of these amino acids via the alanine-serine-cysteine transporter 2 exchanger and system N transporters activates volume-regulated anion channels,leading to the release of excitotoxins and subsequent neuronal damage through N-methyl-d-aspartate receptor ***,previously unrecognized mechanisms involving non-excitatory amino acids may contribute to the progression and expansion of brain injury in neurological emergencies such as stroke and traumatic brain *** these pathways co uld highlight new therapeutic targets to mitigate brain injury.

关键词： cell swelling N-methyl-d-aspartate receptor non-excitatory amino acids stroke synaptic transmission

The sexually dimorphic expression of glutamate transporters and their implication in pain after spinal cord injury

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Neural Regeneration Research 2025年第11期20卷 3317-3329页

作者： Jennifer M.Colón-Mercado Aranza I.Torrado-Tapias Iris K.Salgado Jose M.Santiago Samuel E.Ocasio Rivera dina P.Bracho-Rincon Luis H.Pagan Rivera jorge d.Miranda department of Physiology University of Puerto RicoMedical Sciences CampusSan JuanPRUSA National Institutes of Health National Human Genome Research InstituteBethesdaMDUSA Universidad Central del Caribe School of MedicineBayamónPRUSA University of Puerto Rico Carolina CampusCarolinaPRUSA Institute of Neurobiology San JuanPRUSA

In addition to the loss of motor function,~60% of patients develop pain after spinal cord *** cellular-molecular mechanisms are not well understood,but the data suggests that plasticity within the rostral,epicenter,and caudal penumbra of the injury site initiates a cellularmolecular interplay that acts as a rewiring mechanism leading to central neuropathic *** can lead to the formation of new connections triggering abnormal sensory *** excitatory glutamate transporters are responsible for the reuptake of extracellular glutamate which makes them a critical target to prevent neuronal hyperexcitability and *** previous studies showed a sexually dimorphic therapeutic window for spinal cord injury after treatment with the selective estrogen receptor modulator *** this study,we investigated the anti-allodynic effects of tamoxifen in male and female rats with spinal cord *** hypothesized that tamoxifen exerts anti-allodynic effects by increasing the expression of glutamate transporters,leading to reduced hyperexcitability of the secondary neuron or by decreasing aberrant *** and female rats received a moderate contusion to the thoracic spinal cord followed by subcutaneous slow-release treatment of tamoxifen or matrix pellets as a control(placebo).We used von Frey monofilaments and the“up-down method”to evaluate mechanical *** treatment decreased allodynia only in female rats with spinal cord injury revealing a sexdependent *** expression profile of glutamatergic transporters(excitatory amino acid transporter 1/glutamate aspartate transporter and excitatory amino acid transporter 2/glutamate transporter-1)revealed a sexual dimorphism in the rostral,epicenter,and caudal areas of the spinal cord with a pattern of expression primarily on *** rodents showed a significantly higher level of excitatory amino acid transporter-1 expression while male rodents showed increased

关键词： allodynia central neuropathic pain EAAT-1/GLAST EAAT-2/GLT-1 glutamate transporters selective estrogen receptor modulator sexual dimorphism spinal cord injury trauma

TLR8： the forgotten relative revindicated

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Cellular & Molecular Immunology 2012年第6期9卷 434-438页

作者： jorge L Cervantes Bennett Weinerman Chaitali Basole Juan C salazar department of Pediatrics Immunology University of Connecticut Health Center Farmington CT USA division of Pediatric Infectious diseases Connecticut Children's Medical Center Hartford USA Parmington CT 06030 USA

The endosomal Toll-like receptors （TLRs） TLR3, TLR7, TLR8 and TLR9 are important in sensing foreign nucleic acids encountered by phagocytes. Because TLR8 was initially thought to be non-functional in mice, less is known about TLR8 than the genetically and functionally related TLR7. Originally associated with the recognition of single-stranded RNA of viral origin, there is now evidence that human TLR8 is also able to sense bacterial RNA released within phagosomal vacuoles, inducing the production of both nuclear factor （NF）-κB-dependent cytokines and type I interferons （IFNs）, such as IFN-β. The functions of TLR8 extend beyond the recognition of foreign pathogens and include cross-talk with other endosomal TLRs, a process that may also have a role in the generation of autoimmunity.

关键词： human monocytes TLR8 type I interferon

Clinical pharmacology relevant to older adults with cardiovascular disease

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Journal of Geriatric Cardiology 2015年第3期12卷 192-195页

作者： jorge A Brenes-salazar Laith Alshawabkeh Kenneth E Schmader Joseph T Hanlon daniel E Forman department of Medicine Division of Cardiovascular Diseases Mayo Clinic Rochester MN USA department of Medicine Division of Cardiovascular Medicine University of lowa Iowa City IA USA department of Medicine Division of Geriatrics Duke University School of Medicine Durham NC USA departments of Medicine (division of Geriatric Medicine) Pharmacy and Epidemiology University of Pittsburgh Geriatric Research Education and Clini- cal Center and Center for Health Equity Research and Promotion VA Pittsburgh Health System Pittsburgh PA USA department of Medicine (divisions of Geriatric Medicine and Cardiology) University of Pittsburgh Medical Center Geriatric Research Education and Clinical Center VA Pittsburgh Health System Pittsburgh PA USA

1 Introduction Although older adults are generally among the highest users of cardiovascular medications, they are typically underrepresented or excluded from most efficacy and safety trials. drug developers are usually reluctant to include many senior adults in randomized controlled clinical trials in part due to their high prevalence of multiple comorbidities, frailty, and polypharmacy; and to age-related pharmacokinetic and pharmacodynamic complexities. Consequently, there is often insufficient high quality evidence-based data to inform pharmacologic management of common cardiovascular conditions on older adults. In the absence of data, clinicians often rely on conceptual principles regarding metabolism and drug-drug interactions to minimize adverse drug events, but this is often not well-substantiated or standardized. A related challenge is poor cardiovascular medication adherence among older adults, and its detrimental impact on their health outcomes. In this brief review we highlight some aspects of these topics.

关键词： Metabolism Pharmacokinetics Pharmacodynamics Polypharmacy

Cardiovascular physiology in the older adults

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Journal of Geriatric Cardiology 2015年第3期12卷 196-201页

作者： Xuming dai Scott L Hummel jorge B salazar George E Taffet Susan Zieman Janice B Schwartz division of Cardiology University of North Carolina at Chapel Hill Chapel Hill NC USA division of Cardiovascular Medicine Department of Medicine University of Michigan Ann Arbor Ml Ann Arbor Veterans Affairs Health System Ann Arbor M1 USA division of Cardiology Mayo Clinic Rochester MN USA division of Geriatrics Geriatrics and Cardiovascular Sciences Houston Methodist Hospital Baylor College of'Medicine Houston TX USA division of Geriatrics and Clinical Gerontology National Institute of Aging Bethesda ME) USA divisions of Geriatrics and Clinical Pharmacology Department of Medicine University of California San Francisco CA USA

1 Introduction In an aging society with persistent high prevalence of cardiovascular disease （CVd） in the elderly population, the health care system is facing an increasing challenge to effectively care for these patients. However, due to the under-representation of CVd patients over 75 years of age in clinical trials, assessing safety and efficacy of diagnostic and therapeutic approaches, the evidence for managing elderly CVd patients is especially limited. Physiological changes of aging intertwined with pathophysiology of CVd, and comorbid conditions often complicate clinical management.

关键词： Aging Cardiovascular disease Left ventricular

Echocardiography in centenarians： characteristics, utility and follow-up

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Journal of Geriatric Cardiology 2018年第5期15卷 328-333页

作者： jorge A Brenes-salazar Jaime de la Fuente Punnaiah Marella Hari Chaliki Christopher Scott Heidi M Connolly Roger L Click department of Cardiovascular diseases Mayo Clinic Rochester USA department of Internal Medicine Mayo Clinic Rochester USA department of Cardiovascular diseases Mayo Clinic Arizona USA division of Biostatistics Mayo Clinic Rochester USA

Background Echocardiography has been shown to be a valuable resource in the diagnosis of many cardiac conditions, and can be used in all age groups, from the fetus to the oldest old. In the context of an increasingly aging population, the impact and utility of echocar- diography in centenarians is largely unknown. This study is to determine whether echocardiography in centenarians aids in making clinical patient management decisions. Methods A retrospective review of echocardiograms from 1986 to 2014, at two affiliated tertiary centers, in individuals who were 100 years or older at the time of the examination. Patient and echocardiogram characteristics, management decisions based on echocardiography, and mortality were documented. Results 114 centenarians had echocardiograms, with ages ranging from 100 to 107 years （101 - 1.4 years）. In 82 of the centenarians evaluated （72%）, no changes in management occurred as a consequence of the echocardiogram. From all management changes directly related to the echocardiogram, 81% （n = 26） of these corresponded to medication adjustments; interventional or surgical procedures followed the echocardiogram only in 4% （n = 5） of the total number of centenarians. Echocardiogram-based changes in management were only significant in patients that were referred for congestive heart failure （P = 0.02）. After the echocardiogram was performed, 1-month and 1-year mortality were 15% and 47%, respectively. The median survival after the echocardiogram was obtained was 13 months （range 0.03 to 145 months）, with no difference if there was a change or no change in manage- ment （P = 0.21）. Conclusions Among centenarians undergoing echocardiography, despite additional diagnostic information, echocardio- grams in centenarians influence management in a minority of cases, most commonly in the form of medication changes for treatment of heart failure. A significant proportion of centenarians are deceased within a year of undergoing echocardiographic ass

关键词： Centenarian Echocardiography Geriatric

Combination of hydrotreating and delayed coking technologies for conversion of residue

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Chinese Journal of Chemical Engineering 2023年第11期63卷 209-219页

作者： José A.d.Munoz Gabriel Páez jorge Ancheyta Instituto Mexicano del Petróleo Eje Central Lázaro Cárdenas Norte 152Col.San Bartolo AtepehuacanMéxico City 07730México

Residue conversion by combining catalytic hydrotreating and delayed coking has been evaluated comparatively with both processes *** operating conditions are defined to achieve the greatest economic benefit for upgrading an atmospheric residue from a heavy crude oil.A literature model was adapted to simulate the hydrotreating reactor,and for delayed coking,correlations reported in the literature were *** results with both approaches were employed to calculate the techno-economic feasibility of the combined process *** combination of hydrotreating and delayed coking presented an increase in light fractions of 29% and a reduction in coke production of 47.8%.Based on the calculated net benefit values,it was demonstrated that the combination of hydrotreating and delayed coking is technically and economically better than using each process alone,with highest benefit of 57.7 USd·m^(-3).

关键词： Economic benefit Heavy oil Hydrotreating delayed coking

Openwork Walls and Their Solar Applicability Range jorge Hernan salazar Trujillo

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Journal of Civil Engineering and Architecture 2015年第4期9卷 373-383页

作者： jorge Hernan salazar Trujillo Faculty of Architecture Universidad Nacional de Colombia (National University of Colombia) Medellin Colombia

The environmental potential of perforated surfaces in the tropics is noticeable. They allow obtaining higher attenuation and spatial dispersion of both direct and diffuse lighting in indoor spaces, whereas in outdoor areas, the openwork elements reduce surfaces temperature and mitigate the characteristic glare of smooth surfaces when exposed to sunlight. Openwork walls have an immense sustainability potential in modern tropical buildings： they limit the solar rays＇ admission, as well as provide an advantageous use of natural light and cross ventilation, but the research on their solar behavior is scarce. In order to obtain suitable levels of solar gain, relationships among shape, proportion, thickness and partitions composing openwork elements must be studied. This research evaluates solar gain in perforated surfaces by defining the ＂solar applicability range＂, a property useful to identify intervals of guidance where a perforated pattern shape will present a definite solar gain, giving valuable input in the geometric design of openwork elements and introducing shade performance in the design of openwork walls. Results give geometric guidelines that allow to widen the solar applicability range of a perforation pattern and to define two perforation features that have impact on the solar performance of perforated surfaces： focalization and solar performance shift.

关键词： Openwork bricks openwork walls solar performance shadow tropic architecture.

Corneal collagen cross‑linking epithelium‑on ***‑off:a systematic review and meta‑analysis

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Eye and Vision 2021年第6期8卷 338-352页

作者： Francesco d’Oria Antonio Palazón jorge L.Alio Vissum Innovation c/Cabañal103016 AlicanteSpain division of Ophthalmology Universidad Miguel HernándezAlicanteSpain Section of Ophthalmology Department of Basic Medical ScienceNeuroscience and Sense OrgansUniversity of BariBariItaly department of Clinical Medicine Miguel Hernández UniversitySan Juan de AlicanteSpain

Background:The purpose of the study was to determine the advantages and disadvantages of epi-on corneal crosslinking(CXL)techniques compared with standard epi-off ***:We searched MEdLINE and EMBASE for randomized controlled trials(RCTs)and non-randomized studies of interventions(NRSIs)and we evaluated the selected papers according to the Cochrane risk of bias *** considered,as primary outcomes,average Kmax flattening,changes in uncorrected and corrected distance visual acuity(UdVA and CdVA);as secondary outcomes,we considered changes in pachymetry values and endothelial cell density(ECd).We also investigated adverse events related to the treatments and treatment ***-analysis was conducted with a fixed or random-effects model using weighted mean difference(Md)with 95%confidence interval(CI)as the effect ***:A total of 15 studies were included and among these 15 trials,9 were RCTs and 6 were NRSIs,but only 4 studies showed no high risk of bias and were included in this *** analysis revealed significant postoperative differences in CdVA(Md=0.07;95%CI 0.04 to 0.10;Pd no significative differences in UdVA,Kmax,central corneal thickness(CCT)and ECd(P>0.05).Epi-on CXL protocol was found to be significantly less prompt to have risks of delay in epithelial healing(P=0.035)and persistent stromal haze(P=0.026).Conclusion:Epi-on CXL is as effective as epi-off *** for a higher significant improvement in CdVA with current epi-on protocols,our meta-analysis demonstrates that epi-on and epi-off CXL have comparable effects on visual,topographic,pachymetric,and endothelial ***-on CXL has clinical advantages in terms of comfort and avoidance of complications as it reduces the risk of developing delay in epithelial healing and persistent stromal haze.

关键词： Corneal collagen cross-linking Keratoconus Transepithelial CXL Epithelium-off CXL Epithelium-on CXL Iontophoresis