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1.
J Am Pharm Assoc (2003) ; 62(2): 461-467.e1, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34799259

RESUMO

BACKGROUND: For a vaccine to be successful, communities must perceive it as important, safe, effective, and necessary. However, there are many barriers and hesitancies to vaccination. Underserved patient populations may face additional challenges related to access and cost. Because community pharmacists improve vaccine access and increase vaccination rates, it is beneficial for pharmacists to understand perceptions and barriers to vaccinations in their community to increase vaccine confidence. OBJECTIVES: This study aims to assess and compare barriers and perceptions of the annual influenza to the coronavirus disease 2019 (COVID-19) vaccine for underserved patients of a charitable pharmacy. METHODS: Patients who qualified to receive medications from an outpatient charitable pharmacy took an electronic survey when receiving medications. The survey incorporated questions developed by the World Health Organization's Strategic Advisory Group of Experts on Vaccine Hesitancy on a 5-point Likert scale. Questions about the influenza and COVID-19 vaccines mirrored one another. Demographic data such as age, race, sex, and education level were also collected. RESULTS: Of the 189 patients surveyed at the charitable pharmacy, 71.7% were 55 years old and older and 58.9% were female. Of note, 78% and 77% of participants agreed or strongly agreed that the influenza and COVID-19 vaccines, respectively, were important for the health of others in their community. Adverse effects and the cost of the COVID-19 vaccine were noted to be statistically significantly more of a concern with the COVID-19 vaccine than that of the influenza vaccine (P < 0.001). CONCLUSION: Ensuring equitable vaccine access, promoting the COVID-19 vaccine as free, and eliciting and addressing individual persons' concerns related to vaccine safety and adverse effects are all important ways pharmacists and other health care providers and community stakeholders can help promote vaccine confidence within the populations they serve.


Assuntos
COVID-19 , Vacinas contra Influenza , Influenza Humana , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , Vacinas contra COVID-19/uso terapêutico , Feminino , Humanos , Vacinas contra Influenza/efeitos adversos , Vacinas contra Influenza/uso terapêutico , Influenza Humana/prevenção & controle , Masculino , Pessoa de Meia-Idade , Vacinação/efeitos adversos , Populações Vulneráveis
2.
J Health Care Poor Underserved ; 32(3): 1493-1513, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34421045

RESUMO

While prior research has shown that food insecurity and malnutrition worsen health outcomes and increase health care costs, nutrition risk is rarely assessed in the community setting. Tools exist to screen for food insecurity and malnutrition individually, but none screen for both. This study aimed to implement a dual-purpose screening tool to identify nutrition risk in a community setting, to characterize nutrition risk in a charitable pharmacy population, and to identify patients who screen positive for nutrition risk and connect them to community nutrition resources. Of the 221 patients screened during their initial and annual qualification interview at the Charitable Pharmacy of Central Ohio, 140 (63%) screened positive for nutrition risk. There were 84 (38%) patients positive for food insecurity, 14 (6%) positive for malnutrition risk, and 42 (19%) positive for both. Patients at nutrition risk were referred to nutrition resources, including food pantries, home-delivered meals, and SNAP.


Assuntos
Desnutrição , Assistência Farmacêutica , Farmácias , Farmácia , Abastecimento de Alimentos , Humanos , Desnutrição/epidemiologia , Estado Nutricional
3.
Mol Neurobiol ; 57(5): 2220-2231, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31989383

RESUMO

Mevalonate pathway inhibitors have been extensively studied for their roles in cholesterol depletion and for inhibiting the prenylation and activation of various proteins. Inhibition of protein prenylation has potential therapeutic uses against neurological disorders, like neural cancers, neurodegeneration, and neurotramatic lesions. Protection against neurodegeneration and promotion of neuronal regeneration is regulated in large part by Ras superfamily small guanosine triphosphatases (GTPases), particularly the Ras, Rho, and Rab subfamilies. These proteins are prenylated to target them to cellular membranes. Prenylation can be specifically inhibited through altering the function of enzymes of the mevalonate pathway necessary for isoprenoid production and attachment to target proteins to elicit a variety of effects on neural cells. However, this approach does not address how prenylation affects a specific protein. This review focuses on the regulation of small GTPase prenylation, the different techniques to inhibit prenylation, and how this inhibition has affected neural cell processes.


Assuntos
GTP Fosfo-Hidrolases/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Prenilação de Proteína/fisiologia , Acil Coenzima A/metabolismo , Motivos de Aminoácidos/efeitos dos fármacos , Animais , Vias Biossintéticas/efeitos dos fármacos , Membrana Celular/metabolismo , Dimetilaliltranstransferase/metabolismo , Ativação Enzimática , Humanos , Metilação , Ácido Mevalônico/metabolismo , Ligação Proteica , Terpenos/metabolismo
4.
J Am Pharm Assoc (2003) ; 59(4S): S19-S24, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31080150

RESUMO

OBJECTIVES: The objectives of this study were to assess how a charitable pharmacy model affects patient perception of health care insecurity, physical and emotional functioning, and medication access in an underserved population. METHODS: New patients presenting for medication at their initial pharmacy visit at Charitable Pharmacy of Central Ohio were screened for eligibility during a 12-week enrollment period. Participants completed a baseline survey containing the Health Care Insecurity Measure (HCIM), Veterans RAND 12-Item Health Survey (VR-12), and medication access questions. The follow-up survey, which contained the HCIM and VR-12 only, was administered during a pharmacy visit at least 14 days after the patient's initial visit. Survey data were analyzed with the use of descriptive statistics. RESULTS: A total of 105 patients met eligibility criteria, and 17 patients declined to participate. Of the 88 remaining participants, 33 (38%) completed the study (both baseline and follow-up survey). Of the 33 participants who completed the study, there was a statistically significant decrease from the baseline health care insecurity score (23.2 ± 11.1) to the follow-up score (17.9 ± 8.5; P = 0.0031). CONCLUSION: This study demonstrated that pharmacists working in a charitable pharmacy can have a positive impact on the sense of security patients feel about their health care and can better understand their medication-related needs.


Assuntos
Serviços Comunitários de Farmácia/estatística & dados numéricos , Farmácias/estatística & dados numéricos , Populações Vulneráveis/estatística & dados numéricos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ohio , Farmacêuticos/estatística & dados numéricos , Inquéritos e Questionários
5.
J Neurotrauma ; 35(12): 1319-1328, 2018 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-29295647

RESUMO

Spinal cord injury (SCI) without radiographical abnormalities (SCIWORA) presents a significant challenge because of the loss of function despite an apparent normal anatomy. The cause of dysfunction is not understood, and specific treatment options are lacking. Some scoliosis corrective surgeries result in SCIWORA, where stretching of the spinal cord can lead to vascular compromise and hypoxia. The iatrogenic nature of this injury allows for the implantation of neuroprotective strategies that are designed to prevent damage. We utilized a model of atraumatic SCI to evaluate the efficacy of the sodium-channel blocker, riluzole, as a prophylactic neuroprotectant. As expected, the stretch injury caused a significant reduction in intraparenchymal oxygen in distraction (-53.09 ± 22.23%) and riluzole pre-treated distraction animals (-43.04 ± 22.86%). However, in contrast to the oxidative stress and metabolic impairments observed in vehicle-treated distraction animals, in which protein carbonylation increased significantly (5.88 ± 1.3 nmol/mL), riluzole kept these levels within the normal range (1.8 ± 1.0 nmol/mL). This neurprotection also prevented ventral motor neuron hypoplasia and pyknosis, characteristic features of this atraumatic SCI model, and maintained normal gait function (e.g., stride length and stance time). This study provides evidence for the use of prophylactic neuroprotective strategies in which thoracic or spine surgeries present the risk of causing atraumatic SCI.


Assuntos
Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Riluzol/farmacologia , Traumatismos da Medula Espinal/patologia , Animais , Feminino , Neurônios Motores/metabolismo , Neurônios Motores/patologia , Ratos , Ratos Long-Evans , Traumatismos da Medula Espinal/metabolismo
6.
J Am Pharm Assoc (2003) ; 57(3S): S203-S210.e3, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28400250

RESUMO

OBJECTIVES: This descriptive study explored whether patients with mental health conditions engage in personal medicine (self-care activities) as part of their treatment regimen. Personal medicine is patient-identified and -initiated activities of self-care that can improve mental health through various means, including physical activity, social engagement, and spiritual connectedness. The purpose of this study was to explore patient engagement in personal medicine within an underserved population and to evaluate the impact self-care might have on self-reported medication use and adherence and patient perception of mental health control. DESIGN: Cross-sectional study design with a face-to-face verbally administered survey assessing medication adherence, engagement in self-care activities, perception of self-care, and mental health control. SETTING: The study site was a nonprofit charitable pharmacy in an urban setting. The pharmacy provides medications and pharmacy services at no charge, including disease state education, point-of-care testing, and medication therapy management. PARTICIPANTS: Study participants included those who fill medications for mental health conditions and who are age 18 years and older. MAIN OUTCOME MEASURES: Main outcomes included engagement in self-care and self-reported medication adherence. Additional measures included stratification of dimensions of self-care, perception of mental health control, and patient knowledge of community resources. RESULTS: Overall, 81.7% of participants engaged in activities of self-care, with 98.3% recognizing self-care as important to improving and maintaining their mental health. Greater self-reported adherence rates and mental health control were seen with patients who participate in self-care. CONCLUSION: Participants who identify and engage in personal medicine recognize its value and are willing to incorporate it into their treatment regimen. As accessible and trusted health care providers, pharmacists can encourage patients to identify and use personal medicine to aid in the improvement of their mental health condition.


Assuntos
Adesão à Medicação/estatística & dados numéricos , Saúde Mental/estatística & dados numéricos , Autocuidado/estatística & dados numéricos , Serviços Comunitários de Farmácia/estatística & dados numéricos , Estudos Transversais , Feminino , Humanos , Masculino , Conduta do Tratamento Medicamentoso/estatística & dados numéricos , Transtornos Mentais/terapia , Pessoa de Meia-Idade , Participação do Paciente/estatística & dados numéricos , Farmacêuticos/estatística & dados numéricos , Testes Imediatos/estatística & dados numéricos
7.
J Neurotrauma ; 34(12): 2034-2044, 2017 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-28125935

RESUMO

Corrective forces during spine deformity surgery, including distraction, impart significant stresses to the spinal cord that may result in permanent injury. Intraoperative neuromonitoring is commonly used by surgeons to recognize possible damage to the spinal cord in cases of evident traumatic or vascular damage to the spinal cord. However, mild insult to the spinal cord that does not result in obvious trauma or electrophysiological changes present a major clinical challenge as the mechanisms of this type of spinal cord injury (SCI) remain largely unknown, and thus preventive strategies are lacking. We used a sustained bidirectional spinal distraction animal model to determine the role of stretch-induced hypoxia in mild SCI. Direct measurement of intraparenchymal oxygen revealed an immediate decrease in partial pressure (47.08 ± 5.79% pO2) distal to the injury site following a 5-mm distraction. This hypoxic insult induced mitochondrial dysfunction as evidenced by an acute increase (216%) in protein oxidation 30 min post-injury, as well as a 37% decrease in perikaryal size and a 42% decrease in nuclear area (pyknosis) in ventral motor neurons at the injury site. These results indicate that hypoxic events during mild spine distraction may lead to cellular metabolic impairments and permanent functional deficits. The development of strategies targeting the prevention of hypoxic injury during spine distraction may be useful in protecting the cellular metabolic damage that may occur during spine surgery in the absence of overt mechanical or vascular SCI.


Assuntos
Mitocôndrias/metabolismo , Neurônios Motores/metabolismo , Procedimentos Neurocirúrgicos/efeitos adversos , Traumatismos da Medula Espinal/cirurgia , Medula Espinal/metabolismo , Tração/efeitos adversos , Animais , Modelos Animais de Doenças , Feminino , Ratos , Ratos Long-Evans
8.
Med Eng Phys ; 38(2): 87-96, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26678325

RESUMO

Intraoperative neurophysiological monitoring (IONM) is utilized to minimize neurological morbidity during spine surgery. Transcranial motor evoked potentials (TcMEPs) are principal IONM signals in which the motor cortex of the subject is stimulated with electrical pulses and the evoked potentials are recorded from the muscles of interest. Currently available monitoring systems require the connection of 40-60 lengthy lead wires to the patient. These wires contribute to a crowded and cluttered surgical environment, and limit the maneuverability of the surgical team. In this work, it was demonstrated that the cumbersome wired system is vulnerable to electromagnetic interference (EMI) produced by operating room (OR) equipment. It was hypothesized that eliminating the lengthy recording wires can remove the EMI induced in the IONM signals. Hence, a wireless system to acquire TcMEPs was developed and validated through bench-top and animal experiments. Side-by-side TcMEPs acquisition from the wired and wireless systems in animal experiments under controlled conditions (absence of EMI from OR equipment) showed comparable magnitudes and waveforms, thus demonstrating the fidelity in the signal acquisition of the wireless solution. The robustness of the wireless system to minimize EMI was compared with a wired-system under identical conditions. Unlike the wired-system, the wireless system was not influenced by the electromagnetic waves from the C-Arm X-ray machine and temperature management system in the OR.


Assuntos
Artefatos , Fenômenos Eletromagnéticos , Potencial Evocado Motor , Monitorização Intraoperatória/instrumentação , Tecnologia sem Fio , Animais , Feminino , Salas Cirúrgicas , Ratos , Processamento de Sinais Assistido por Computador , Razão Sinal-Ruído , Fatores de Tempo
9.
J Am Pharm Assoc (2003) ; 55(1): 59-66, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25575150

RESUMO

OBJECTIVE: To evaluate the impact that Charitable Pharmacy of Central Ohio (CPCO), a pharmacy providing free pharmacy services and medications, had on an indigent patient population by determining the change in patient-reported hospital use, ability to access medications, and perception of health status after receiving CPCO services. DESIGN: Cross-sectional study with face-to-face interviews using a convenience sample. SETTING: Columbus, OH, in January to March 2013. PATIENTS: 206 English-speaking patients 18 years or older at CPCO. INTERVENTION: Free pharmacy services and medications provided by CPCO. MAIN OUTCOMES MEASURES: Number of patient-reported hospital visits before and after CPCO use. RESULTS: In the year before using CPCO, patients reported using the hospital a mean of 2.36 (median, 2.00) times per year versus 1.33 (median, 0.67) times per year after, a decrease of 1.03 hospital visits per year per patient. Before coming to CPCO, 41% of patients were able to have all of their prescribed medications filled; this rose to 85% after using CPCO. A total of 89% of patients reported that not only was their overall health was better, but they also had a better understanding of their medications and believed they were in more control of their own health since receiving CPCO services. CONCLUSION: A charitable pharmacy model has the potential to decrease health care costs and empower patients to be more in control of their health.


Assuntos
Instituições de Caridade , Serviços Comunitários de Farmácia/provisão & distribuição , Acessibilidade aos Serviços de Saúde , Nível de Saúde , Hospitalização , Preparações Farmacêuticas/provisão & distribuição , Adulto , Idoso , Idoso de 80 Anos ou mais , Instituições de Caridade/economia , Instituições de Caridade/tendências , Serviços Comunitários de Farmácia/economia , Serviços Comunitários de Farmácia/tendências , Estudos Transversais , Custos de Medicamentos , Prescrições de Medicamentos , Feminino , Pesquisas sobre Atenção à Saúde , Conhecimentos, Atitudes e Prática em Saúde , Acessibilidade aos Serviços de Saúde/economia , Acessibilidade aos Serviços de Saúde/tendências , Hospitalização/economia , Hospitalização/tendências , Humanos , Entrevistas como Assunto , Masculino , Indigência Médica , Pessoa de Meia-Idade , Ohio , Participação do Paciente , Percepção , Preparações Farmacêuticas/economia , Poder Psicológico , Avaliação de Programas e Projetos de Saúde , Fatores de Tempo , Adulto Jovem
10.
IEEE Trans Neural Syst Rehabil Eng ; 20(2): 220-7, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22203723

RESUMO

Clinical use of neurally controlled prosthetics has advanced in recent years, but limitations still remain, including lacking fine motor control and sensory feedback. Indwelling multi-electrode arrays, cuff electrodes, and regenerative sieve electrodes have been reported to serve as peripheral neural interfaces, though long-term stability of the nerve-electrode interface has remained a formidable challenge. We recently developed a regenerative multi-electrode interface (REMI) that is able to record neural activity as early as seven days post-implantation. While this activity might represent normal neural depolarization during axonal regrowth, it can also be the result of altered nerve regeneration around the REMI. This study evaluated high-throughput expression levels of 84 genes involved in nerve injury and repair, and the histological changes that occur in parallel to this early neural activity. Animals exhibiting spike activity increased from 29% to 57% from 7 to 14 days following REMI implantation with a corresponding increase in firing rate of 113%. Two weeks after implantation, numbers of neurofilament-positive axons in the control and REMI implanted nerves were comparable, and in both cases the number of myelinated axons was low. During this time, expression levels of genes related to nerve injury and repair were similar in regenerated nerves, both in the presence or absence of the electrode array. Together, these results indicate that the early neural activity is intrinsic to the regenerating axons, and not induced by the REMI neurointerface.


Assuntos
Bainha de Mielina/fisiologia , Regeneração Nervosa/fisiologia , Nervos Periféricos/fisiologia , Interface Usuário-Computador , Animais , Axônios/fisiologia , Eletrodos Implantados , Fenômenos Eletrofisiológicos , Feminino , Expressão Gênica/fisiologia , Proteínas de Neurofilamentos/metabolismo , RNA/biossíntese , RNA/isolamento & purificação , Ratos , Ratos Endogâmicos Lew , Reação em Cadeia da Polimerase em Tempo Real , Nervo Isquiático/fisiologia , Cicatrização
11.
Ann Biomed Eng ; 39(1): 517-23, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-20824343

RESUMO

Intraoperative neurophysiological monitoring (IONM) is commonly used as an attempt to minimize neurological morbidity from operative manipulations. The goal of IONM is to identify changes in the central and peripheral nervous system function prior to irreversible damage. Intraoperative monitoring also has been effective in localizing anatomical structures, including peripheral nerves and sensorimotor cortex, which helps guide the surgeon during dissection. As part of IONM, transcranial motor evoked potentials (TcMEPs), and somatosensory evoked potentials (SSEPs) are routinely monitored. However, current wired systems are cumbersome as the wires contribute to the crowded conditions in the operating room and in doing so not only it limits the maneuverability of the surgeon and assistants, but also places certain demand in the total anesthesia required during surgery, due to setup preoperative time needed for proper electrode placement, due to the number and length of the wires, and critical identification of the lead wires needed for stimulation and recording. To address these limitations, we have developed a wireless TcMEP IONM system as a first step toward a multimodality IONM system. Bench-top and animal experiments in rodents demonstrated that the wireless method reproduced with high fidelity, and even increased the frequency bandwidth of the TcMEP signals, compared to wired systems. This wireless system will reduce the preoperative time required for IONM setup, add convenience for surgical staff, and reduce wire-related risks for patients during the operation.


Assuntos
Eletroencefalografia/instrumentação , Potencial Evocado Motor/fisiologia , Monitorização Ambulatorial/instrumentação , Córtex Motor/fisiologia , Telemetria/instrumentação , Animais , Desenho de Equipamento , Análise de Falha de Equipamento , Feminino , Humanos , Ratos , Ratos Long-Evans
12.
Neurosci Lett ; 450(2): 176-80, 2009 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-19027829

RESUMO

The Rho guanine nucleotide triphosphatases (GTPases) Rac1 and RhoA are important regulators of axon growth. However, the specific roles each plays are complicated by implications that each is involved in promoting and inhibiting neurite outgrowth. Differential regulation of Rac1 and RhoA activation in cell bodies and growth cones may be important in directing axon growth. To test this, we separated neuroblastoma cells into growth cone and cell body fractions and assessed Rac1 and RhoA activation in response to outgrowth promoters, serum withdrawal and 8-bromoadeosine-5',3'-cyclic monophosphate (8-Br-cAMP), and outgrowth inhibitors, chondroitin sulfate proteoglycans (CSPGs) or semaphorin 3A (Sema 3A). In whole cell lysates, serum withdrawal decreased and CSPGs or Sema 3A increased RhoA activity, but no treatments affected Rac1 activity. In growth cones, serum withdrawal or 8-Br-cAMP increased Rac1 activation and serum withdrawal decreased RhoA activation. Conversely, outgrowth inhibitors decreased Rac1 activity. Additionally, 8-Br-cAMP reversed increases in RhoA activity induced by Sema 3A in whole cell lysates and CSPGs in growth cones. These data suggest that activation of RhoA and Rac1 is differentially regulated in specific cellular regions, perhaps contributing to the complexity of Rho GTPase-mediated axon growth.


Assuntos
Neuroblastoma/metabolismo , Proteínas rac1 de Ligação ao GTP/metabolismo , Proteína rhoA de Ligação ao GTP/metabolismo , 8-Bromo Monofosfato de Adenosina Cíclica/farmacologia , Animais , Linhagem Celular Tumoral , Proteoglicanas de Sulfatos de Condroitina/farmacologia , Meios de Cultura Livres de Soro/farmacologia , Cones de Crescimento/efeitos dos fármacos , Cones de Crescimento/metabolismo , Lamina Tipo A/genética , Lamina Tipo A/metabolismo , Neuroblastoma/ultraestrutura , Ratos , Semaforina-3A/farmacologia , Frações Subcelulares/efeitos dos fármacos , Frações Subcelulares/metabolismo
13.
J Am Chem Soc ; 127(16): 5750-1, 2005 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-15839648

RESUMO

The physiological electron-transfer (ET) partners, cytochrome c peroxidase (CcP) and cytochrome c (Cc)1, can be modified to exhibit photoinitiated ET through substitution of Zn (or Mg) for Fe in either partner. Laser excitation of the Zn-porphyrin (ZnP) to its triplet excited state (3ZnP) initiates direct heme-heme ET to the ferriheme center of its partner across the protein-protein interface. This photoinitiated ET produces the charge-separated intermediate, I = [ZnP+CcP, Fe2+Cc], with a metalloporphyrin pi-cation radical (ZnP+) in the donor protein and a ferroheme acceptor protein. I, in general, is thought to return to the ground state by a thermal ET process that involves direct heme-heme back-ET to complete a simple photocycle. We here contrast intracomplex ET between yeast iso-1 Cc and ZnCcP(WT) (wild-type) with that for two ZnCcP(X) variants: X = W191F, with redox-active W191 replaced by Phe; WYM4, a W191F mutant with further replacement of four other potentially redox-active sites (W51F, Y187F, Y229F, and Y236F). The results show that W191 acts as an ET mediator, which "short-circuits" the direct heme-heme back-ET through a two-step, hopping process in which the ZnP+ cation radical formed by photoinitiated ET rapidly oxidizes W191, and the resultant W191+, in turn, rapidly oxidizes Fe2+Cc.


Assuntos
Citocromo-c Peroxidase/química , Citocromos c/química , Zinco/química , Citocromo-c Peroxidase/metabolismo , Citocromos c/metabolismo , Heme/química , Heme/metabolismo , Cinética , Oxirredução , Fotoquímica , Zinco/metabolismo
14.
Proc Natl Acad Sci U S A ; 102(10): 3564-9, 2005 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-15738411

RESUMO

We propose that the forward and reverse halves of a flash-induced protein-protein electron transfer (ET) photocycle should exhibit differential responses to dynamic interconversion of configurations when the most stable configuration is not the most reactive, because the reactants exist in different initial configurations: the flash-photoinitiated forward ET process begins with the protein partners in an equilibrium ensemble of configurations, many of which have little or no reactivity, whereas the reactant of the thermal back ET (the charge-separated intermediate) is formed in a nonequilibrium, "activated" protein configuration. We report evidence for this proposal in measurements on (i) mixed-metal hemoglobin hybrids, (ii) the complex between cytochrome c peroxidase and cytochrome c, and (iii and iv) the complexes of myoglobin and isolated hemoglobin alpha-chains with cytochrome b(5). For all three systems, forward and reverse ET does respond differently to modulation of dynamic processes; further, the response to changes in viscosity is different for each system.


Assuntos
Transporte de Elétrons , Proteínas/química , Citocromo-c Peroxidase/química , Citocromos c/química , Hemoglobinas/química , Humanos , Mioglobina/química , Conformação Proteica , Viscosidade
15.
J Am Chem Soc ; 124(32): 9404-11, 2002 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-12167035

RESUMO

In this paper, we describe the first observations of photoinitiated interprotein electron transfer (ET) within sol-gels. We have encapsulated three protein-protein complexes, specifically selected because they represent a full range of affinities, are sensitive to different types of dynamic processes, and thus are expected to respond differently to sol-gel encapsulation. The three systems are (i) the [Zn, Fe(3+)L] mixed-metal hemoglobin hybrids, where the alpha(1)-Zn and beta(2)-Fe subunits correspond to a "predocked" protein-protein complex with a crystallographically defined interface (Natan, M. J.; Baxter, W. W.; Kuila, D.; Gingrich, D. J.; Martin, G. S.; Hoffman, B. M. Adv. Chem. Ser. 1991, 228 (Electron-Transfer Inorg., Org., Biol. Syst.), 201-213), (ii) the Zn-cytochrome c peroxidase complex with cytochrome c, [ZnCcP, Fe(3+)Cc], having an intermediate affinity between its partners (Nocek, J. M.; Zhou, J. S.; De Forest, S.; Priyadarshy, S.; Beratan, D. N.; Onuchic, J. N.; Hoffman, B. M. Chem. Rev. 1996, 96, 2459-2489), and (iii) the [Zn-deuteromyoglobin, ferricytochrome b(5)] complex, [ZnDMb, Fe(3+)b(5)], which is loosely bound and highly dynamic (Liang, Z.-X.; Nocek, J.; Huang, K.; Hayes, R. T.; Kurnikov, I. V.; Beratan, D. N.; Hoffman, B. M. J. Am. Chem. Soc. 2002, 124, 6849-6859. Intersubunit ET within the hybrid does not involve second-order processes or subunit rearrangements, and thus is influenced only by perturbations of high-frequency motions coupled to ET. For the latter two complexes, sol-gel encapsulation eliminates second-order processes: protein partners encapsulated as a complex must stay together throughout a photoinitiated ET cycle, while proteins encapsulated alone cannot acquire a partner. It further modulates intracomplex motions of the two partners.


Assuntos
Hemoglobinas/química , Cristalografia , Transporte de Elétrons , Géis , Humanos , Cinética
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