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1.
Air Med J ; 43(2): 151-156, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38490779

RESUMO

OBJECTIVE: The use of traditional inhaled pulmonary vasodilators, such as nitric oxide, to treat symptomatic pulmonary edema is not practical in the air medical or prehospital environment because of difficulty with administration. A hospital-based critical care air medical transport service initiated a pilot study to investigate the use of inhaled nitroglycerin (iNTG) as an alternative pulmonary vasodilator. METHODS: For this pilot study, iNTG was administered using a jet nebulizer setup and concentrated nitroglycerin, both of which are widely available in acute care settings. In conjunction with medical oversight, transport personnel identified patients with respiratory distress secondary to pulmonary edema. Twenty-two months after initiating the protocol, a retrospective chart review was conducted. Data for patients receiving iNTG were retrospectively abstracted through a medical record search and manual chart review. RESULTS: Twelve patients received iNTG during the pilot study. Basic demographics, medical comorbidities, concurrent medications, laboratory values, and radiographic studies were collected for each patient. Basic statistics were performed to identify any potential trends. CONCLUSION: The administration of iNTG is feasible in an air medical transport setting and may provide a useful adjunct to treating patients with pulmonary edema and respiratory distress. Because iNTG delivery targets the pulmonary vasculature, this may be of particular benefit in patients with a poor hemodynamic profile. Larger randomized controlled or cohort studies are needed to specifically analyze and compare hemodynamics, diagnostics, and patient outcomes.


Assuntos
Edema Pulmonar , Síndrome do Desconforto Respiratório , Humanos , Nitroglicerina/uso terapêutico , Estudos Retrospectivos , Projetos Piloto , Edema Pulmonar/tratamento farmacológico , Vasodilatadores/uso terapêutico , Dispneia
2.
Physiol Behav ; 260: 114063, 2023 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-36563734

RESUMO

Some γ-glutamyl peptides including glutathione (γ-Glu-Cys-Gly) and γ-glutamyl-valyl-glycine (γ-Glu-Val-Gly= γ-EVG) are reported to increase the intensity of basic tastes, such as salty, sweet, and umami, although they have no taste themselves at tested concentrations. The mechanism of action of γ-glutamyl peptides is not clearly understood, but the calcium sensing receptor (CaSR) may be involved. Glutathione and γ-EVG enhance the pungency of some spices, and the present study investigated the effects of γ-EVG on the responses of trigeminal ganglion (TG) cells to thermosensitiveTRP channel agonists. Single-cell RT-PCR revealed that most CaSR-expressing cells co-expressed TRPV1 (sensitive to capsaicin) and TRPA1 (sensitive to allyl isothiocyanate= AITC). Intracellular Ca2+ imaging showed that pretreatment with γ-EVG excited 7% of trigeminal ganglion (TG) cells and increased the amplitude of their responses to AITC, but not to capsaicin or menthol. The enhancing effect of γ-EVG was prevented by a CaSR inhibitor. The results indicate that γ-EVG increases AITC pungency by activating a subset of trigeminal ganglion cells that co-express CaSR and TRPA1.


Assuntos
Capsaicina , Receptores de Detecção de Cálcio , Camundongos , Animais , Receptores de Detecção de Cálcio/agonistas , Receptores de Detecção de Cálcio/metabolismo , Capsaicina/farmacologia , Gânglio Trigeminal/metabolismo , Glutationa , Canal de Cátion TRPA1
4.
Sci Transl Med ; 10(440)2018 05 09.
Artigo em Inglês | MEDLINE | ID: mdl-29743351

RESUMO

The use of autologous (or syngeneic) cells derived from induced pluripotent stem cells (iPSCs) holds great promise for future clinical use in a wide range of diseases and injuries. It is expected that cell replacement therapies using autologous cells would forego the need for immunosuppression, otherwise required in allogeneic transplantations. However, recent studies have shown the unexpected immune rejection of undifferentiated autologous mouse iPSCs after transplantation. Whether similar immunogenic properties are maintained in iPSC-derived lineage-committed cells (such as neural precursors) is relatively unknown. We demonstrate that syngeneic porcine iPSC-derived neural precursor cell (NPC) transplantation to the spinal cord in the absence of immunosuppression is associated with long-term survival and neuronal and glial differentiation. No tumor formation was noted. Similar cell engraftment and differentiation were shown in spinally injured transiently immunosuppressed swine leukocyte antigen (SLA)-mismatched allogeneic pigs. These data demonstrate that iPSC-NPCs can be grafted into syngeneic recipients in the absence of immunosuppression and that temporary immunosuppression is sufficient to induce long-term immune tolerance after NPC engraftment into spinally injured allogeneic recipients. Collectively, our results show that iPSC-NPCs represent an alternative source of transplantable NPCs for the treatment of a variety of disorders affecting the spinal cord, including trauma, ischemia, or amyotrophic lateral sclerosis.


Assuntos
Células-Tronco Pluripotentes Induzidas/citologia , Células-Tronco Neurais/transplante , Medula Espinal/transplante , Envelhecimento , Animais , Diferenciação Celular , Reprogramação Celular , Doença Crônica , Fibroblastos/citologia , Regulação da Expressão Gênica , Tolerância Imunológica , Imunidade Humoral , Terapia de Imunossupressão , Neostriado/patologia , Células-Tronco Neurais/citologia , Neurônios/citologia , Ratos , Pele/citologia , Traumatismos da Medula Espinal/patologia , Traumatismos da Medula Espinal/terapia , Análise de Sobrevida , Suínos , Porco Miniatura , Transplante Homólogo , Transplante Isogênico
7.
J Comp Neurol ; 524(2): 244-56, 2016 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-26099199

RESUMO

Itch is relayed to higher centers by projection neurons in the spinal and medullary dorsal horn. We employed a double-label method to map the ascending projections of pruriceptive and nociceptive trigeminal and spinal neurons. The retrograde tracer fluorogold (FG) was stereotaxically injected into the right thalamus or lateral parabrachial area (LPb) in mice. Seven days later, mice received intradermal (id) microinjection of histamine, chloroquine, capsaicin, or vehicle into the left cheek. Histamine, chloroquine, and capsaicin intradermally elicited similar distributions of Fos-positive neurons in the medial aspect of the superficial medullary and spinal dorsal horn from the trigeminal subnucleus caudalis to C2. Among neurons retrogradely labeled from the thalamus, 43%, 8%, and 22% were Fos-positive following id histamine, chloroquine, or capsaicin. Among the Fos-positive neurons following pruritic or capsaicin stimuli, ∼1-2% were retrogradely labeled with FG. Trigeminoparabrachial projection neurons exhibited a higher incidence of double labeling in the superficial dorsal horn. Among the neurons retrogradely labeled from LPb, 36%, 29%, and 33% were Fos positive following id injection of histamine, chloroquine, and capsaicin, respectively. Among Fos-positive neurons elicited by id histamine, chloroquine, and capsaicin, respectively, 3.7%, 4.3%, and 4.1% were retrogradely labeled from LPb. The present results indicate that, overall, relatively small subpopulations of pruriceptive and/or nociceptive neurons innervating the cheek project to thalamus or LPb. These results imply that the vast majority of pruritogen- and algogen-responsive spinal neurons are likely to function as interneurons relaying information to projection neurons and/or participating in segmental nocifensive circuits.


Assuntos
Neurônios/fisiologia , Núcleos Parabraquiais/fisiologia , Tálamo/citologia , Núcleo Espinal do Trigêmeo/fisiologia , Animais , Antipruriginosos/farmacologia , Mapeamento Encefálico , Capsaicina/farmacologia , Cloroquina/farmacologia , Histamina/farmacologia , Agonistas dos Receptores Histamínicos/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neurônios/efeitos dos fármacos , Proteínas Oncogênicas v-fos/metabolismo , Células do Corno Posterior/efeitos dos fármacos , Células do Corno Posterior/metabolismo , Estilbamidinas
9.
Gen Dent ; 63(3): 8, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25945754
10.
Pain ; 156(7): 1240-1246, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25830923

RESUMO

We investigated roles for spinal neurons expressing the neurokinin-1 receptor (NK1R) and/or gastrin-releasing peptide receptor (GRPR) in a mouse model of ovalbumin (OVA)-induced chronic atopic dermatitis. Mice receiving repeated topical application of OVA exhibited atopic-like skin lesions and behavioral signs of chronic itch including spontaneous scratching, touch-evoked scratching (alloknesis), and enhancement of chloroquine-evoked scratching (hyperknesis). Substance P-saporin (SP-SAP) and bombesin-saporin (BB-SAP) were intrathecally injected into OVA-sensitized mice to neurotoxically ablate NK1R- or GRPR-expressing spinal neurons, respectively. SP-SAP diminished the expression of NK1R in the superficial spinal dorsal horn and significantly attenuated all behavioral signs of chronic itch. BB-SAP reduced the spinal dorsal horn expression of GRPR and significantly attenuated hyperknesis, with no effect on spontaneous scratching or alloknesis. To investigate whether NK1R-expressing spinal neurons project in ascending somatosensory pathways, we performed a double-label study. The retrograde tracer, Fluorogold (FG), was injected into either the somatosensory thalamus or lateral parabrachial nucleus. In the upper cervical (C1-2) spinal cord, most neurons retrogradely labeled with FG were located in the dorsomedial aspect of the superficial dorsal horn. Of FG-labeled spinal neurons, 89% to 94% were double labeled for NK1R. These results indicate that NK1R-expressing spinal neurons play a major role in the expression of symptoms of chronic itch and give rise to ascending somatosensory projections. Gastrin-releasing peptide receptor-expressing spinal neurons contribute to hyperknesis but not to alloknesis or ongoing itch. NK1R-expressing spinal neurons represent a potential target to treat chronic itch.


Assuntos
Células do Corno Posterior/fisiologia , Prurido/metabolismo , Receptores da Neurocinina-1/biossíntese , Animais , Doença Crônica , Regulação da Expressão Gênica , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Prurido/etiologia , Receptores da Neurocinina-1/genética
12.
Gen Dent ; 62(5): 8, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25184705
16.
J Am Coll Dent ; 80(1): 45-8, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23767246

RESUMO

Narrative medicine seeks to improve clinical effectiveness through narrative training in reading and writing. Stories give meaning to experience and encourage communication between doctors and patients by honoring the basic human need to recognize and be recognized. Learning how to receive and tell stories, practiced through close reading, group discussion, and written response, may also facilitate ethical reflection and inquiry.


Assuntos
Assistência Odontológica/ética , Ética Odontológica , Narração , Anedotas como Assunto , Comunicação , Relações Dentista-Paciente/ética , Educação em Odontologia , Ética Odontológica/educação , Humanos , Relações Profissional-Paciente/ética , Leitura , Redação
18.
J Am Coll Dent ; 79(4): 64-71, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23654166
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