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1.
Am J Physiol Renal Physiol ; 326(4): F669-F679, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38450433

RESUMO

Resuscitative endovascular balloon occlusion of the aorta (REBOA) is used to control noncompressible hemorrhage not addressed with traditional tourniquets. However, REBOA is associated with acute kidney injury (AKI) and subsequent mortality in severely injured trauma patients. Here, we investigated how the degree of aortic occlusion altered the extent of AKI in a porcine model. Female Yorkshire-cross swine (n = 16, 68.1 ± 0.7 kg) were anesthetized and had carotid and bilateral femoral arteries accessed for REBOA insertion and distal and proximal blood pressure monitoring. Through a laparotomy, a 6-cm liver laceration was performed and balloon inflation was performed in zone 1 of the aorta for 90 min, during which animals were randomized to target distal mean arterial pressures of 25 or 45 mmHg via balloon volume adjustment. Blood draws were taken at baseline, end of occlusion, and time of death, at which point renal tissues were harvested 6 h after balloon deflation for histological and molecular analyses. Renal blood flow was lower in the 25-mmHg group (48.5 ± 18.3 mL/min) than in the 45-mmHg group (177.9 ± 27.2 mL/min) during the occlusion phase, which recovered and was not different after balloon deflation. AKI was more severe in the 25-mmHg group, as evidenced by circulating creatinine, blood urea nitrogen, and urinary neutrophil gelatinase-associated lipocalin. The 25-mmHg group had increased tubular necrosis, lower renal citrate synthase activity, increased tissue and circulating syndecan-1, and elevated systemic inflammatory cytokines. The extent of renal ischemia-induced AKI is associated with the magnitude of mitochondrial biomass and systemic inflammation, highlighting potential mechanistic targets to combine with partial REBOA strategies to prevent AKI.NEW & NOTEWORTHY Large animal models of ischemia-reperfusion acute kidney injury (IR-AKI) are lacking. This report establishes a titratable IR-AKI model in swine in which a balloon catheter can be used to alter distal pressures experienced by the kidney, thus controlling renal blood flow. Lower blood flow results in greater renal dysfunction and structural damage, as well as lower mitochondrial biomass, elevated systemic inflammation, and vascular dysfunction.


Assuntos
Injúria Renal Aguda , Oclusão com Balão , Traumatismo por Reperfusão , Choque Hemorrágico , Humanos , Suínos , Feminino , Animais , Modelos Animais de Doenças , Hemorragia/prevenção & controle , Injúria Renal Aguda/etiologia , Isquemia , Inflamação , Oclusão com Balão/métodos , Choque Hemorrágico/terapia
2.
Int J Mol Sci ; 25(8)2024 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-38674120

RESUMO

Hematopoietic acute radiation syndrome (H-ARS) involves injury to multiple organ systems following total body irradiation (TBI). Our laboratory demonstrated that captopril, an angiotensin-converting enzyme inhibitor, mitigates H-ARS in Göttingen minipigs, with improved survival and hematopoietic recovery, as well as the suppression of acute inflammation. However, the effects of captopril on the gastrointestinal (GI) system after TBI are not well known. We used a Göttingen minipig H-ARS model to investigate captopril's effects on the GI following TBI (60Co 1.79 or 1.80 Gy, 0.42-0.48 Gy/min), with endpoints at 6 or 35 days. The vehicle or captopril (0.96 mg/kg) was administered orally twice daily for 12 days, starting 4 h post-irradiation. Ilea were harvested for histological, protein, and RNA analyses. TBI increased congestion and mucosa erosion and hemorrhage, which were modulated by captopril. GPX-4 and SLC7A11 were downregulated post-irradiation, consistent with ferroptosis at 6 and 35 days post-irradiation in all groups. Interestingly, p21/waf1 increased at 6 days in vehicle-treated but not captopril-treated animals. An RT-qPCR analysis showed that radiation increased the gene expression of inflammatory cytokines IL1B, TNFA, CCL2, IL18, and CXCL8, and the inflammasome component NLRP3. Captopril suppressed radiation-induced IL1B and TNFA. Rectal microbiome analysis showed that 1 day of captopril treatment with radiation decreased overall diversity, with increased Proteobacteria phyla and Escherichia genera. By 6 days, captopril increased the relative abundance of Enterococcus, previously associated with improved H-ARS survival in mice. Our data suggest that captopril mitigates senescence, some inflammation, and microbiome alterations, but not ferroptosis markers in the intestine following TBI.


Assuntos
Síndrome Aguda da Radiação , Captopril , Modelos Animais de Doenças , Ferroptose , Microbioma Gastrointestinal , Inflamação , Porco Miniatura , Irradiação Corporal Total , Animais , Síndrome Aguda da Radiação/tratamento farmacológico , Suínos , Inflamação/patologia , Captopril/farmacologia , Irradiação Corporal Total/efeitos adversos , Ferroptose/efeitos dos fármacos , Microbioma Gastrointestinal/efeitos dos fármacos , Intestinos/microbiologia , Intestinos/patologia , Intestinos/efeitos dos fármacos , Intestinos/efeitos da radiação , Masculino , Inibidores da Enzima Conversora de Angiotensina/farmacologia
3.
J Am Chem Soc ; 145(5): 2840-2851, 2023 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-36701177

RESUMO

Despite their inherent instability, 4n π systems have recently received significant attention due to their unique optical and electronic properties. In dibenzopentalene (DBP), benzanellation stabilizes the highly antiaromatic pentalene core, without compromising its amphoteric redox behavior or small HOMO-LUMO energy gap. However, incorporating such molecules in organic devices as discrete small molecules or amorphous polymers can limit the performance (e.g., due to solubility in the battery electrolyte solution or low internal surface area). Covalent organic frameworks (COFs), on the contrary, are highly ordered, porous, and crystalline materials that can provide a platform to align molecules with specific properties in a well-defined, ordered environment. We synthesized the first antiaromatic framework materials and obtained a series of three highly crystalline and porous COFs based on DBP. Potential applications of such antiaromatic bulk materials were explored: COF films show a conductivity of 4 × 10-8 S cm-1 upon doping and exhibit photoconductivity upon irradiation with visible light. Application as positive electrode materials in Li-organic batteries demonstrates a significant enhancement of performance when the antiaromaticity of the DBP unit in the COF is exploited in its redox activity with a discharge capacity of 26 mA h g-1 at a potential of 3.9 V vs. Li/Li+. This work showcases antiaromaticity as a new design principle for functional framework materials.

4.
J Surg Res ; 291: 116-123, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37356340

RESUMO

INTRODUCTION: Vascular reconstruction requires technical expertise and is often time consuming. As a novel alternative to traditional hand-sewn vascular anastomoses, the VasoLock (VL), is a nonabsorbable, sutureless anastomosis device with traction anchors designed to hold free artery ends together. These anchors do not penetrate the vessel wall but adhere by leveraging the elasticity of the vessels to fasten blood vessels together. This pilot study assesses the performance and patency of this novel device in a porcine model of femoral artery injury. METHODS: Female swine (n = 7) underwent femoral artery exposure for a total of 10 VL implanted. Study animals underwent hemodilution to a target hematocrit of 15% and ROTEM was used to assess coagulopathy, followed by an arterial injury via transection. The VL was inserted without any sutures. Flow-probe monitors were positioned proximal and distal to the device and flow rates were measured continuously for a total of 90 min. Flow was analyzed and presented as a ratio of distal to proximal flow with the slope of this ratio across time subsequently determined. Angiographic assessment was completed to evaluate for patency and technical complications after 90 min of implant. RESULTS: The average animal weight was 44.1 ± 3.2 kg. The average mean arterial pressure at the time of implant was 51.2 ± 7.8 mmHg, median heart rate was 77.4 (IQR = 77.25-157.4) beats per minute, and average temperature was 36.1 ± 1.5°C. The baseline hematocrit was 13.5 ± 3.0%, average pH was 7.20 ± 0.1, average clotting time was 154.1 ± 58.7 s and average clot formation time was 103.4 ± 10.9 s all demonstrating the acidotic, hypothermic, and coagulopathic state of the swine at the time of insertion. During the 90-min observation period, the average flow gradient identified across the VL was 0.99 ± 0.24, indicating no significant change in flow across the VL. The average slope of the gradients was 0.0005 (P = 0.22), suggesting the ratio of proximal and distal flow did not change over the 90 min. Following 90 min of dwell time, all VL were patent without technical complication. Angiographic assessment at 90 min demonstrated no evidence of dissection, device migration, arterial extravasation, or thromboembolism with any of the 10 devices. CONCLUSIONS: This pilot study demonstrated technical feasibility of the novel VL device over a 90-min observation period. All VL were patent and no negative events or complications were identified. This technology demonstrated significant promise in a coagulopathic state: additional investigation, involving long-term survival, is warranted for further validation.


Assuntos
Artéria Femoral , Feminino , Animais , Suínos , Estudo de Prova de Conceito , Projetos Piloto , Grau de Desobstrução Vascular , Anastomose Cirúrgica , Artéria Femoral/cirurgia
5.
Chemistry ; 28(33): e202200705, 2022 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-35404526

RESUMO

Semiconducting carbon nitride polymers are used in metal-free photocatalysts and in opto-electronic devices. Conventionally, they are obtained using thermal and ionothermal syntheses in inscrutable, closed systems and therefore, their condensation behavior is poorly understood. Here, the synthetic protocols and properties are compared for two types of carbon nitride materials - 2D layered poly(triazine imide) (PTI) and hydrogen-bonded melem hydrate - obtained from three low-melting salt eutectics taken from the systematic series of the alkali metal halides: LiCl/KCl, LiBr/KBr, and LiI/KI. The size of the anion plays a significant role in the formation process of the condensed carbon nitride polymers, and it suggests a strong templating effect. The smaller anions (chloride and bromide) become incorporated into triazine (C3 N3 )-based PTI frameworks. The larger iodide does not stabilize the formation of a triazine-based polymer, but instead it leads to the formation of the heptazine (C6 N7 )-based hydrogen-bonded melem hydrate as the main crystalline phase. Melem hydrate, obtained as single-crystalline powders, was compared with PTI in photocatalytic hydrogen evolution from water and in an OLED device. Further, the emergence of each carbon nitride species from its corresponding salt eutectic was rationalized via density functional theory calculations. This study highlights the possibilities to further tailor the properties of eutectic salt melts for ionothermal synthesis of organic functional materials.

6.
J Surg Res ; 280: 1-9, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-35939866

RESUMO

INTRODUCTION: Limitations such as time-dependent distal ischemia have slowed the adoption of resuscitative endovascular balloon occlusion of the aorta (REBOA) for noncompressible hemorrhage. Next-generation REBOA technologies may allow for controlled partial flow, known as targeted regional optimization, to reduce distal ischemia. We aimed to characterize the efficacy of one such catheter in a porcine model of lethal hemorrhagic shock. METHODS: Noncompressible hemorrhage from an iliac injury was induced in anesthetized swine (Sus scrofa) (70-90 kg), targeting 30% total blood volume. Animals were then randomized to partial aortic occlusion (PO) with targeted distal mean arterial pressure (MAP) of 35-40 mm of mercury (mm Hg) and complete aortic occlusion (CO) (n = 8 per group) for 90 min. All groups were then resuscitated during a two-h critical care (CC) phase, with flow rate and MAP recorded continuously at the distal infrarenal aorta and proximal carotid artery, and analyzed with two-way repeated measures analysis of variance with S-N-K post-hoc test. RESULTS: During aortic occlusion, MAP distal to the balloon was consistently maintained at 35.8 ± 0.3 mm Hg in the PO group compared to 27.1 ± 0.3 mm Hg in the CO group (P < 0.05), which also corresponded to higher flow rates (202.9 ± 4.8 mL/min PO versus 25.9 ± 0.8 mL/min CO; P < 0.05). MAP proximal to the balloon was significantly higher with CO versus PO (109.2 ± 2.3 mm Hg versus 85.2 ± 2.3 mm Hg; P < 0.05). During the CC phase, distal aortic flow and MAP were not significantly different between groups. However, creatinine returned to baseline levels by the end of the study in the PO group, but not the CO group. One animal died in the CO group, whereas none died in the PO group. CONCLUSIONS: This is the first examination of the next-generation pREBOA-PRO in a porcine model of lethal hemorrhagic shock. We show technical feasibility of this technique to precisely achieve targeted regional optimization without device failure or complication. The ability to titrate balloon inflation and thus distal flow/pressure may extend the therapeutic window of REBOA by mitigating distal ischemia.


Assuntos
Oclusão com Balão , Procedimentos Endovasculares , Mercúrio , Choque Hemorrágico , Animais , Aorta , Oclusão com Balão/métodos , Creatinina , Modelos Animais de Doenças , Procedimentos Endovasculares/métodos , Hemorragia/terapia , Ressuscitação/métodos , Choque Hemorrágico/terapia , Suínos
7.
Chem Soc Rev ; 50(20): 11559-11576, 2021 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-34661213

RESUMO

To this day, the active components of integrated circuits consist mostly of (semi-)metals. Concerns for raw material supply and pricing aside, the overreliance on (semi-)metals in electronics limits our abilities (i) to tune the properties and composition of the active components, (ii) to freely process their physical dimensions, and (iii) to expand their deployment to applications that require optical transparency, mechanical flexibility, and permeability. 2D organic semiconductors match these criteria more closely. In this review, we discuss a number of 2D organic materials that can facilitate charge transport across and in-between their π-conjugated layers as well as the challenges that arise from modulation and processing of organic polymer semiconductors in electronic devices such as organic field-effect transistors.

8.
Angew Chem Int Ed Engl ; 61(3): e202111749, 2022 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-34634165

RESUMO

Poly(triazine imide) (PTI) is a highly crystalline semiconductor, and though no techniques exist that enable synthesis of macroscopic monolayers of PTI, it is possible to study it in thin layer device applications that are compatible with its polycrystalline, nanoscale morphology. We find that the by-product of conventional PTI synthesis is a C-C carbon-rich phase that is detrimental for charge transport and photoluminescence. An optimized synthetic protocol yields a PTI material with an increased quantum yield, enabled photocurrent and electroluminescence. We report that protonation of the PTI structure happens preferentially at the pyridinic N atoms of the triazine rings, is accompanied by exfoliation of PTI layers, and contributes to increases in quantum yield and exciton lifetimes. This study describes structure-property relationships in PTI that link the nature of defects, their formation, and how to avoid them with the optical and electronic performance of PTI. On the basis of our findings, we create an OLED prototype with PTI as the active, metal-free material.

9.
J Surg Res ; 248: 28-37, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31841734

RESUMO

BACKGROUND: The endothelial glycocalyx controls vascular permeability, cellular signaling, blood-endothelial cell adhesion, extravasation, and transmission of shear stress signals. Burn injury compromises integrity of this layer increasing vascular permeability, which is further exacerbated by large volumes of (intravenous) crystalloids. We have shown that enteral resuscitation is able to reverse burn-induced acute kidney injury (AKI), and herein, we present a follow-up examination of the integrity of the glycocalyx layer and its relationship with renal dysfunction after burn injury. MATERIALS AND METHODS: Anesthetized Yorkshire pigs sustained 40% total body surface area full-thickness contact burns and recovered in metabolic cages for one of three treatments: no fluids (oral or intravenous); (n = 6), ad libitum water (n = 6), or volume-matched oral rehydration solution (ORS; n = 6) for 48 h. Urine and blood were collected at baseline (BL), 6, 12, 24, 32, and 48 h after burn at which point kidneys were harvested. RESULTS: In no fluid and water groups (but not ORS), plasma levels of glycosaminoglycans (GAGs) were elevated after burn (P ≤ 0.031). Syndecan-1 was elevated by 6 h after burn in all animals, but levels declined by 24 h with enteral fluids. Urinary GAGs in the no-fluid group were elevated after burn. No differences among treatments were detected in syndecan-1 levels, or glomerular lectin within the kidney. CONCLUSIONS: Collectively, these data demonstrate that ORS prevented increases in circulating GAGs. Furthermore, an inexpensive and simple method for detecting GAGs provides a sensitive measure of endotheliopathy after burn.


Assuntos
Queimaduras/metabolismo , Glicocálix/fisiologia , Glicosaminoglicanos/análise , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/terapia , Animais , Modelos Animais de Doenças , Células Endoteliais/fisiologia , Glicosaminoglicanos/sangue , Glicosaminoglicanos/urina , Túbulos Renais/patologia , Lectinas/análise , Soluções para Reidratação/uso terapêutico , Suínos , Sindecana-1/análise
10.
Ren Fail ; 42(1): 1042-1058, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33043785

RESUMO

While extensive research using animal models has improved the understanding of acute kidney injury (AKI), this knowledge has not been translated into effective treatments. Many promising interventions for AKI identified in mice and rats have not been validated in subsequent clinical trials. As a result, the mortality rate of AKI patients remains high. Inflammation plays a fundamental role in the pathogenesis of AKI, and one reason for the failure to translate promising therapeutics may lie in the profound difference between the immune systems of rodents and humans. The immune systems of large animals such as swine, nonhuman primates, sheep, dogs and cats, more closely resemble the human immune system. Therefore, in the absence of a basic understanding of the pathophysiology of human AKI, large animals are attractive models to test novel interventions. However, there is a lack of reviews on large animal models for AKI in the literature. In this review, we will first highlight differences in innate and adaptive immunities among rodents, large animals, and humans in relation to AKI. After illustrating the potential merits of large animals in testing therapies for AKI, we will summarize the current state of the evidence in terms of what therapeutics have been tested in large animal models. The aim of this review is not to suggest that murine models are not valid to study AKI. Instead, our objective is to demonstrate that large animal models can serve as valuable and complementary tools in translating potential therapeutics into clinical practice.


Assuntos
Injúria Renal Aguda/induzido quimicamente , Cisplatino/farmacologia , Modelos Animais de Doenças , Pesquisa Translacional Biomédica/métodos , Injúria Renal Aguda/imunologia , Injúria Renal Aguda/patologia , Injúria Renal Aguda/terapia , Imunidade Adaptativa , Animais , Gatos , Cães , Imunidade Inata , Inflamação/imunologia , Inflamação/patologia , Camundongos , Ratos , Ovinos , Suínos
11.
Am J Physiol Cell Physiol ; 317(6): C1229-C1238, 2019 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-31532719

RESUMO

Severe burn injury results in systemic disruption of metabolic regulations and impaired cardiac function. Restoration of hemodynamic homeostasis utilizing intravenous (IV) fluids is critical for acute care of the burn victim. However, the effects of burns and resuscitation on cardiomyocyte mitochondria are currently unknown. The purpose of this study is to determine cardiac mitochondrial function in a swine burn model with subsequent resuscitation using either crystalloids or colloids. Anesthetized Yorkshire swine (n = 23) sustained 40% total body surface area burns and received IV crystalloids (n = 11) or colloids (n = 12) after recovery from anesthesia. Non-burned swine served as controls (n = 9). After euthanasia at 48 h, heart tissues were harvested, permeabilized, and analyzed by high-resolution respirometry. Citrate synthase (CS) activity was measured, and Western blots were performed to quantify proteins associated with mitochondrial fusion (OPA1), fission (FIS1), and mitophagy (PINK1). There were no differences in state 2 respiration or maximal oxidative phosphorylation. Coupled complex 1 respiration decreased, while uncoupled state 4O and complex II increased significantly due to burn injury, particularly in animals receiving colloids (P < 0.05). CS activity and electron transfer coupling efficiency were significantly lower in burned animals, particularly with colloid treatment (P < 0.05). Protein analysis revealed increased FIS1 but no differences in mitophagy in cardiac tissue from colloid-treated compared with crystalloid-treated swine. Taken together, severe burns alter mitochondrial respiration in heart tissue, which may be exacerbated by early IV resuscitation with colloids. Early IV burn resuscitation with colloids may require close hemodynamic observation. Mitochondrial stabilizing agents incorporated into resuscitation fluids may help the hemodynamic response to burn injury.


Assuntos
Queimaduras por Corrente Elétrica/terapia , Cardiotônicos/farmacologia , Hidratação/métodos , Coração/efeitos dos fármacos , Mitocôndrias Cardíacas/efeitos dos fármacos , Miócitos Cardíacos/efeitos dos fármacos , Animais , Queimaduras por Corrente Elétrica/genética , Queimaduras por Corrente Elétrica/metabolismo , Queimaduras por Corrente Elétrica/patologia , Cardiotônicos/química , Citrato (si)-Sintase/genética , Citrato (si)-Sintase/metabolismo , Coloides , Cristalização , Complexo de Proteínas da Cadeia de Transporte de Elétrons/genética , Complexo de Proteínas da Cadeia de Transporte de Elétrons/metabolismo , Feminino , GTP Fosfo-Hidrolases/genética , GTP Fosfo-Hidrolases/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Coração/fisiopatologia , Hemodinâmica/efeitos dos fármacos , Mitocôndrias Cardíacas/metabolismo , Mitocôndrias Cardíacas/patologia , Proteínas Mitocondriais/genética , Proteínas Mitocondriais/metabolismo , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Fosforilação Oxidativa/efeitos dos fármacos , Proteínas Quinases/genética , Proteínas Quinases/metabolismo , Ressuscitação/métodos , Pele/efeitos dos fármacos , Pele/lesões , Pele/metabolismo , Suínos
12.
J Emerg Med ; 57(1): 114-117, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31027991

RESUMO

BACKGROUND: Efficacy of medical student substance use interventions in the emergency department (ED) setting remains unstudied. OBJECTIVE: In this pilot study, we set out to determine whether medical students could perform a brief motivational interview for substance use in the ED. METHODS: At two hospitals, medical students utilized motivational interviewing skills taught by their medical school curriculum and administered a substance use intervention to ED patients who met the study definition of unhealthy substance use. RESULTS: In 6 weeks, medical students gave a brief intervention to 102 subjects. The mean age of the subjects was 46.9 (standard deviation 15.6) years. The majority, 86 (86.3%) identified as white. Fifty-four (52.9%) identified as male. Eighty of 102 (78.4%) participants completed a phone follow-up assessment. Of the 69 smokers, 11 (15.9%) reported attempting to quit or quitting completely. Of the 33 with high-risk alcohol use, 11 (33.3%) were abstaining completely from alcohol use and an additional 12 (36.4%) reported a decrease in alcohol daily consumption (measured in drinks per day). Warm hand-off success for street drugs or at-risk alcohol use was 13.6% for those who received an intervention. CONCLUSIONS: It is feasible for medical students to perform a substance use intervention in the ED setting. Medical student contributions as a part of the team response to this public health crisis provide an opportunity for further discussion and research.


Assuntos
Terapia Comportamental/normas , Entrevista Motivacional/normas , Estudantes de Medicina/estatística & dados numéricos , Transtornos Relacionados ao Uso de Substâncias/terapia , Adulto , Idoso , Terapia Comportamental/métodos , Terapia Comportamental/estatística & dados numéricos , Serviço Hospitalar de Emergência/organização & administração , Serviço Hospitalar de Emergência/estatística & dados numéricos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Entrevista Motivacional/métodos , Entrevista Motivacional/estatística & dados numéricos , Projetos Piloto , Transtornos Relacionados ao Uso de Substâncias/psicologia
13.
Int J Mol Sci ; 19(9)2018 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-30208569

RESUMO

The ecological community of microorganisms in/on humans, termed the microbiome, is vital for sustaining homeostasis. While culture-independent techniques have revealed the role of the gut microbiome in human health and disease, the role of the cutaneous microbiome in wound healing is less defined. Skin commensals are essential in the maintenance of the epithelial barrier function, regulation of the host immune system, and protection from invading pathogenic microorganisms. In this review, we summarize the literature derived from pre-clinical and clinical studies on how changes in the microbiome of various acute and chronic skin wounds impact wound healing tissue regeneration. Furthermore, we review the mechanistic insights garnered from model wound healing systems. Finally, in the face of growing concern about antibiotic-resistance, we will discuss alternative strategies for the treatment of infected wounds to improve wound healing and outcomes. Taken together, it has become apparent that commensals, symbionts, and pathogens on human skin have an intimate role in the inflammatory response that highlights several potential strategies to treat infected, non-healing wounds. Despite these promising results, there are some contradictory and controversial findings from existing studies and more research is needed to define the role of the human skin microbiome in acute and chronic wound healing.


Assuntos
Microbiota , Pele/microbiologia , Cicatrização , Infecção dos Ferimentos , Animais , Anti-Infecciosos/uso terapêutico , Humanos , Microbiota/efeitos dos fármacos , Probióticos/uso terapêutico , Cicatrização/efeitos dos fármacos , Infecção dos Ferimentos/tratamento farmacológico , Infecção dos Ferimentos/microbiologia , Infecção dos Ferimentos/terapia
14.
Biochim Biophys Acta Mol Basis Dis ; 1863(10 Pt B): 2661-2671, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28431991

RESUMO

Trauma-induced acute kidney injury (AKI), such as after hemorrhagic shock (HS) or burn, remains a significant problem in the intensive care unit and is associated with increased mortality. The pathophysiology that drives AKI post-trauma is multi-factorial, and includes both inflammatory and metabolic alterations. Identifying the systemic profile that contributes to AKI is crucial not only for early diagnosis, but also for identifying treatments that improve kidney function and maintaining long-term patient health. In an effort to elucidate this molecular pathophysiology researchers have utilized a variety of animal models including chemically-induced (i.e., cisplatin), blocking renal perfusion (i.e., arterial clamping) and inducing burn or HS. As the latter burn and HS models are unequivocally applicable to studying AKI in the context of traumatic injury, this review will summarize the inflammatory and metabolic insights associated with AKI gained with these animal models. Moreover, novel therapeutic strategies brought forth with these models will be discussed.


Assuntos
Injúria Renal Aguda/metabolismo , Modelos Animais de Doenças , Ferimentos e Lesões/metabolismo , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/terapia , Animais , Humanos , Ferimentos e Lesões/complicações , Ferimentos e Lesões/diagnóstico , Ferimentos e Lesões/terapia
15.
Lasers Surg Med ; 49(3): 293-304, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-28220508

RESUMO

BACKGROUND AND OJECTIVES: The current standard for diagnosis of burn severity and subsequent wound healing is through clinical examination, which is highly subjective. Several new technologies are shifting focus to burn care in an attempt to help quantify not only burn depth but also the progress of healing. While accurate early assessment of partial thickness burns is critical for dictating the course of treatment, the ability to quantitatively monitor wound status over time is critical for understanding treatment efficacy. SFDI and LSI are both non-invasive imaging modalities that have been shown to have great diagnostic value for burn severity, but have yet to be tested over the course of wound healing. METHODS: In this study, a hairless rat model (n = 6, 300-450 g) was used with a four pronged comb to create four identical partial thickness burns (superficial n = 3 and deep n = 3) that were used to monitor wound healing over a 28 days period. Weekly biopsies were taken for histological analysis to verify wound progression. Both SFDI and LSI were performed weekly to track the evolution of hemodynamic (blood flow and oxygen saturation) and structural (reduced scattering coefficient) properties for the burns. RESULTS: LSI showed significant changes in blood flow from baseline to 220% in superficial and 165% in deep burns by day 7. In superficial burns, blood flow returned to baseline levels by day 28, but not for deep burns where blood flow remained elevated. Smaller increases in blood flow were also observed in the surrounding tissue over the same time period. Oxygen saturation values measured with SFDI showed a progressive increase from baseline values of 66-74% in superficial burns and 72% in deep burns by day 28. Additionally, SFDI showed significant decreases in the reduced scattering coefficient shortly after the burns were created. The scattering coefficient progressively decreased in the wound area, but returned towards baseline conditions at the end of the 28 days period. Scattering changes in the surrounding tissue remained constant despite the presence of hemodynamic changes. CONCLUSIONS: Here, we show that LSI and SFDI are capable of monitoring changes in hemodynamic and scattering properties in burn wounds over a 28 days period. These results highlight the potential insights that can be gained by using non-invasive imaging technologies to study wound healing. Further development of these technologies could be revolutionary for wound monitoring and studying the efficacy of different treatments. Lasers Surg. Med. 49:293-304, 2017. © 2017 Wiley Periodicals, Inc.


Assuntos
Queimaduras/diagnóstico por imagem , Queimaduras/patologia , Fluxometria por Laser-Doppler/métodos , Cicatrização/fisiologia , Animais , Biópsia por Agulha , Modelos Animais de Doenças , Estudos de Avaliação como Assunto , Imuno-Histoquímica , Escala de Gravidade do Ferimento , Masculino , Consumo de Oxigênio/fisiologia , Fotografação , Distribuição Aleatória , Ratos , Ratos Pelados , Fluxo Sanguíneo Regional/fisiologia , Pigmentação da Pele , Fatores de Tempo
16.
ED Manag ; 29(4): 37-40, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-29160983

RESUMO

With influenza season intensifying, many EDs report strong surges in flu related volume. Although illness severity does not appear to be atypical, hospitals that see high numbers of older patients and the chronically ill face extra challenges meeting the needs of patients who have added susceptibility to flu-related complications. Experts note that all flu strains circulating this year appear to be sensitive to antiviral medications. In mid-February, the CDC reported the number of flu cases was still on the increase in most regions of the country, with 28 states reporting a high incidence of influenza-like illness. Hospitals in Portland, OR, have instituted "zone management" multiple times -- a process whereby ambulances are supervised closely and redirected so that individual hospitals do not become overwhelmed. EDs in both Pennsylvania and Missouri report that flu-related volume is much higher this year than in 2016. The vast majority of flu cases this year involve influenza A (H3N2), although the CDC notes that influenza B viruses also are circulating.


Assuntos
Serviço Hospitalar de Emergência/estatística & dados numéricos , Influenza Humana/epidemiologia , Capacidade de Resposta ante Emergências , Infecção Hospitalar/prevenção & controle , Humanos , Incidência , Controle de Infecções/normas , Vacinas contra Influenza/imunologia , Influenza Humana/imunologia , Estados Unidos/epidemiologia
17.
Wound Repair Regen ; 24(4): 657-68, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27238250

RESUMO

Infection is a leading cause of morbidity and mortality in burn patients. Current therapies include silver-based creams and dressings, which display limited antimicrobial effectiveness and impair healing. The need exists for a topical, point-of-injury antibiotic treatment that provides sustained antimicrobial activity without impeding wound repair. Fitting this description are keratin-based hydrogels, which are fully biocompatible and support the slow-release of antibiotics. Here we develop a porcine model of an infected partial-thickness burn to test the effects of ciprofloxacin-loaded keratin hydrogels on infection and wound healing. Partial-thickness burns were inoculated with either Pseudomonas aeruginosa or Methicillin-resistant Staphylococcus aureus, resulting in infections that persisted for >2 weeks that exceeded 10(5) and 10(6) cfu per gram of tissue, respectively. Compared to silver sulfadiazine, ciprofloxacin-loaded keratin hydrogel treatment significantly reduced the amount of P. aeruginosa and S. aureus in the burn by >99% on days 4, 7, 11, and 15 postinjury. Further, burns treated with ciprofloxacin-loaded keratin hydrogels exhibited similar healing patterns as uninfected burns with regards to reepithelialization, macrophage recruitment, and collagen deposition and remodeling. The ability of keratin hydrogels to deliver antibiotics to fight infection and support healing of partial-thickness burns make them a strong candidate as a first-line burn therapy.


Assuntos
Queimaduras/tratamento farmacológico , Ciprofloxacina/administração & dosagem , Ciprofloxacina/farmacologia , Portadores de Fármacos/administração & dosagem , Hidrogéis/administração & dosagem , Queratinas/administração & dosagem , Cicatrização/efeitos dos fármacos , Infecção dos Ferimentos/tratamento farmacológico , Animais , Queimaduras/microbiologia , Queimaduras/patologia , Ciprofloxacina/uso terapêutico , Modelos Animais de Doenças , Feminino , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Pseudomonas aeruginosa/efeitos dos fármacos , Suínos , Infecção dos Ferimentos/microbiologia
19.
Crit Care ; 19: 243, 2015 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-26067660

RESUMO

Burns are a prevalent and burdensome critical care problem. The priorities of specialized facilities focus on stabilizing the patient, preventing infection, and optimizing functional recovery. Research on burns has generated sustained interest over the past few decades, and several important advancements have resulted in more effective patient stabilization and decreased mortality, especially among young patients and those with burns of intermediate extent. However, for the intensivist, challenges often exist that complicate patient support and stabilization. Furthermore, burn wounds are complex and can present unique difficulties that require late intervention or life-long rehabilitation. In addition to improvements in patient stabilization and care, research in burn wound care has yielded advancements that will continue to improve functional recovery. This article reviews recent advancements in the care of burn patients with a focus on the pathophysiology and treatment of burn wounds.


Assuntos
Queimaduras/terapia , Cicatrização/fisiologia , Bandagens , Biomarcadores/análise , Queimaduras/fisiopatologia , Diagnóstico por Imagem , Edema/fisiopatologia , Hidratação , Humanos , Inflamação/fisiopatologia , Queratinócitos/fisiologia , Queratinócitos/transplante , Apoio Nutricional , Obesidade/complicações , Ressuscitação , Transplante de Pele , Pele Artificial , Transplante de Células-Tronco , Infecção dos Ferimentos/fisiopatologia , Infecção dos Ferimentos/prevenção & controle
20.
BMC Urol ; 15: 103, 2015 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-26463481

RESUMO

BACKGROUND: Restoration of normal bladder volume and function (i.e., bioequivalent bladder) are observed within 8 weeks of performing subtotal cystectomy (STC; removal of ~70 % of the bladder) in 12-week old rats. For analysis of bladder function in rodents, terminal urodynamic approaches are largely utilized. In the current study, we investigated the potential for Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) scans to noninvasively track restoration of structure and function following STC. METHODS: Twelve week old female Fisher F344 rats underwent STC and were scanned via CT and/or MRI 2, 4, 8, and 12 weeks post-STC, followed by urodynamic testing. After euthanasia, bladders were excised for histological processing. RESULTS: MRI scans demonstrated an initial decline followed by a time-dependent increase to normal bladder wall thickness (BWT) by 8 weeks post-STC. Masson's trichrome staining showed a lack of fibrosis post-STC, and also revealed that the percent of smooth muscle in the bladder wall at 2 and 4 weeks positively correlated with pre-operative baseline BWT. Moreover, increased BWT values before STC was predictive of improved bladder compliance at 2 and 4 weeks post-STC. Cystometric studies indicated that repeated MRI manipulation (i.e. bladder emptying) apparently had a negative impact on bladder capacity and compliance. A "window" of bladder volumes was identified 2 weeks post-STC via CT scanning that were commensurate with normal micturition pressures measured in the same animal 6 weeks later. CONCLUSIONS: Taken together, the data indicate some limitations of "non-invasive" imaging to provide insight into bladder regeneration. Specifically, mechanical manipulation of the bladder during MRI appears to negatively impact the regenerative process per se, which highlights the importance of terminal cystometric studies.


Assuntos
Cistectomia/métodos , Imageamento por Ressonância Magnética/métodos , Tomografia Computadorizada por Raios X/métodos , Bexiga Urinária/fisiologia , Bexiga Urinária/cirurgia , Animais , Estudos de Viabilidade , Feminino , Masculino , Ratos , Ratos Endogâmicos F344 , Regeneração/fisiologia , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Cirurgia Assistida por Computador/métodos , Bexiga Urinária/anatomia & histologia
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