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1.
Crit Care ; 28(1): 134, 2024 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-38654351

RESUMO

BACKGROUND: In this study, the concentrations of inflammatory cytokines were measured in the bronchial epithelial lining fluid (ELF) and plasma in patients with acute hypoxemic respiratory failure (AHRF) secondary to severe coronavirus disease 2019 (COVID-19). METHODS: We comprehensively analyzed the concentrations of 25 cytokines in the ELF and plasma of 27 COVID-19 AHRF patients. ELF was collected using the bronchial microsampling method through an endotracheal tube just after patients were intubated for mechanical ventilation. RESULTS: Compared with those in healthy volunteers, the concentrations of interleukin (IL)-6 (median 27.6 pmol/L), IL-8 (1045.1 pmol/L), IL-17A (0.8 pmol/L), IL-25 (1.5 pmol/L), and IL-31 (42.3 pmol/L) were significantly greater in the ELF of COVID-19 patients than in that of volunteers. The concentrations of MCP-1 and MIP-1ß were significantly greater in the plasma of COVID-19 patients than in that of volunteers. The ELF/plasma ratio of IL-8 was the highest among the 25 cytokines, with a median of 737, and the ELF/plasma ratio of IL-6 (median: 218), IL-1ß (202), IL-31 (169), MCP-1 (81), MIP-1ß (55), and TNF-α (47) were lower. CONCLUSIONS: The ELF concentrations of IL-6, IL-8, IL-17A, IL-25, and IL-31 were significantly increased in COVID-19 patients. Although high levels of MIP-1 and MIP-1ß were also detected in the blood samples collected simultaneously with the ELF samples, the results indicated that lung inflammation was highly compartmentalized. Our study demonstrated that a comprehensive analysis of cytokines in the ELF is a feasible approach for understanding lung inflammation and systemic interactions in patients with severe pneumonia.


Assuntos
COVID-19 , Citocinas , Insuficiência Respiratória , Humanos , COVID-19/sangue , COVID-19/complicações , COVID-19/imunologia , Citocinas/sangue , Citocinas/análise , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Insuficiência Respiratória/terapia , Insuficiência Respiratória/sangue , Adulto , Brônquios , Líquido da Lavagem Broncoalveolar/química
2.
J Infect Chemother ; 30(5): 406-416, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-37984540

RESUMO

INTRODUCTION: In treating acute hypoxemic respiratory failure (AHRF) caused by coronavirus disease 2019 (COVID-19), clinicians choose respiratory therapies such as low-flow nasal cannula oxygenation, high-flow nasal cannula oxygenation, or mechanical ventilation after assessment of the patient's condition. Chest computed tomography (CT) imaging contributes significantly to diagnosing COVID-19 pneumonia. However, the costs and potential harm to patients from radiation exposure need to be considered. This study was performed to predict the quantitative extent of COVID-19 acute lung injury using clinical indicators such as an oxygenation index and blood test results. METHODS: We analyzed data from 192 patients with COVID-19 AHRF. Multiple logistic regression was used to determine correlations between the lung infiltration volume (LIV) and other pathophysiological or biochemical laboratory parameters. RESULTS: Among 13 clinical parameters, we identified the oxygen saturation/fraction of inspired oxygen ratio (SF ratio) and serum lactate dehydrogenase (LD) concentration as factors associated with the LIV. In the binary classification of an LIV of ≥20 % or not and with the borderline LD = 2.2 × [SF ratio]-182.4, the accuracy, precision, diagnostic odds ratio, and area under the summary receiver operating characteristic curve were 0.828, 0.818, 23.400, and 0.870, respectively. CONCLUSIONS: These data suggest that acute lung injury due to COVID-19 pneumonia can be estimated using the SF ratio and LD concentration without a CT scan. These findings may provide significant clinical benefit by allowing clinicians to predict acute lung injury levels using simple, minimally invasive assessment of oxygenation capacity and biochemical blood tests.


Assuntos
Lesão Pulmonar Aguda , COVID-19 , Pneumonia , Insuficiência Respiratória , Humanos , COVID-19/diagnóstico por imagem , Oxigênio , SARS-CoV-2 , Saturação de Oxigênio , Tomografia Computadorizada por Raios X , Lactato Desidrogenases , Estudos Retrospectivos
3.
J Craniofac Surg ; 33(4): 1222-1226, 2022 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-34802020

RESUMO

ABSTRACT: End-to-side anastomosis requires highly specialized techniques. An easy end-to-side anastomosis technique enables anastomosis of vessels with different diameters and under various situations. We invented T-shaped metal stents and evaluated novel methods of end-to-side sutureless anastomosis, confirming their safety, effectiveness, and operability. We performed 8 end-to-side sutureless anastomoses in 4 7- to 11-month-old, male Mexican hairless piglets. After induction of anesthesia, the left femoral artery was resected by approximately 8 cm, and the superior and posterior stumps of the resected femoral artery underwent an end-to-side anastomosis with the right femoral artery by the placement of the metal stents with subsequent use of adhesive for the circumferential area. The patency of blood vessels and the presence of thrombosis were evaluated by ultrasonography or contrast-enhanced computed tomography and histology 4 weeks postoperatively. All the animals survived the procedure; no thrombosis was identified in any of the 8 anastomosis sites according to imaging studies performed 4 weeks postoperatively. Histological examination confirmed the probe patency of blood vessels and neointimal cell proliferation around stent branches. End-to-side anastomosis is possible with T-shaped metal stents. In the future, we aim for the practical application of these stents by improving their operability.


Assuntos
Artéria Femoral , Stents , Anastomose Cirúrgica/métodos , Animais , Cães , Artéria Femoral/cirurgia , Masculino , Microcirurgia/métodos , Suínos , Grau de Desobstrução Vascular
4.
J Infect Chemother ; 26(3): 257-265, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31680038

RESUMO

The secondary in-hospital epidemiological investigation for drug-resistant Pseudomonas aeruginosa infections was conducted to evaluate the in-hospital situation and identify any associations between exoenzyme genotypes and other genotypes and antimicrobial resistance characteristics, at the University Hospital in Kyoto, Japan, following a reported outbreak of antimicrobial-resistant P. aeruginosa ST357 between 2005 and 2014. Twelve of the 546 P. aeruginosa isolates collected during the follow-up period were resistant to more than two classes of antimicrobials. All isolates were resistant to fluoroquinolones and 8 (66.7%) showed carbapenem resistance. None of the isolates fulfilled the clinical criteria for multidrug-resistant P. aeruginosa. All isolates were metallo-ß-lactamase test-negative. Among five exoS (-)exoU (+) isolates, three possessing a class 1 integron with gene cassette aadB + cmlA6 were classified as ST357, and one isolate containing a class 1 integron with aacA31 was ST235. Collectively, the second survey results confirm that the initial outbreak is currently undergoing convergence. By combining data from the first and second surveys, we showed that prevalent STs such as ST357 and ST235 are associated with fluoroquinolone resistance, class 1 integron-associated resistance to ß-lactams and aminoglycosides, and cytotoxic exoU (+) genotypes. With the current worldwide spread of ST357 and ST235 isolates, it is important to evaluate epidemiological trends for high-risk P. aeruginosa isolates by continuous hospital monitoring.


Assuntos
Infecção Hospitalar , Surtos de Doenças/estatística & dados numéricos , Infecções por Pseudomonas , Pseudomonas aeruginosa/efeitos dos fármacos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/microbiologia , Farmacorresistência Bacteriana , Feminino , Fluoroquinolonas/farmacologia , Hospitais , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Tipagem de Sequências Multilocus , Infecções por Pseudomonas/epidemiologia , Infecções por Pseudomonas/microbiologia , Pseudomonas aeruginosa/genética , Estudos Retrospectivos , Adulto Jovem
5.
Biosci Biotechnol Biochem ; 82(3): 476-483, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29400146

RESUMO

The creaming effects, mechanical properties and microstructures of processed cheeses were investigated under different emulsifying conditions using a rapid visco-analyzer, and the changes in protein network related to the creaming effect and the occurrence of yielding points were discussed. The higher stirring speed affected the fat globules to be smaller, and gave the processed cheese more firmness at fixed stirring time. The longer stirring time caused the protein network to become fine-stranded. A fine-stranded structure promoted the creaming effect, and hence the formation of yielding point in the mechanical properties. The emulsifying salts had active effects on the creaming effect and mechanical properties at longer stirring time. The fine-stranded structures were shown in the cases of a binary mixture of polyphosphate and disodium phosphate (PDSP), polyphosphate (PP), and trisodium citrate (TSC). Monophosphate (MP) showed the lowest ability to alter the protein network, but was assisted at the higher stirring speed.


Assuntos
Queijo , Fenômenos Mecânicos , Emulsões , Manipulação de Alimentos , Teste de Materiais , Viscosidade
6.
J Infect Chemother ; 24(8): 615-622, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29628388

RESUMO

Antimicrobial-resistant isolates of Pseudomonas aeruginosa collected from 2005 to 2014 in a university hospital in Kyoto, Japan, were retrospectively analyzed by multilocus sequence typing (MLST), exoenzyme genotype determination, integron characterization, and clinical associations. During the study, 1573 P. aeruginosa isolates were detected, and 41 of these were resistant to more than two classes of antimicrobial agents. Twenty-five (61.0%) isolates were collected from urine. All isolates were resistant to ciprofloxacin, 8 (19.5%) isolates showed resistance to imipenem/cilastatin, and 8 (19.5%) isolates showed resistance to meropenem. None of the isolates fulfilled the clinical criteria for multidrug-resistant P. aeruginosa. All isolates were negative in the metallo-ß lactamase test. Thirty-six (87.8%) isolates were of the exoS-exoU+ genotype and 5 (12.2%) isolates were of the exoS+exoU- genotype. Among 36 exoS-exoU+ isolates, 33 (80.5%) were ST357, and 3 (7.3%) were ST235. Five isolates of exoS+exoU- were ST186, ST244, ST314, ST508, and ST512. Thirty-three isolates were positive for class 1 integrons and four different class 1 integrons were detected: aminoglycoside (2') adenyltransferase and chloramphenicol transporter (AadB+CmlA6), OXA-4 ß-lactamase and aminoglycoside 3'-adenyltransferase (OXA4+AadA2), AadB alone, and aminoglycoside acetyltransferase alone (AacA31). Among the 41 patients from which the isolates originated, the most common underlying disease was cancer in 16 patients (39%), and 9 patients (22.0%) died during the hospitalization period. There was no statistical correlation between MLST, exoenzyme genotype, and patient mortality. The results indicated outbreaks of fluoroquinolone-resistant P. aeruginosa in immunocompromised patients mainly due to the propagation of potentially virulent ST357 isolates possessing the exoU+ genotype.


Assuntos
Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Surtos de Doenças , Farmacorresistência Bacteriana/genética , Fluoroquinolonas/farmacologia , Infecções por Pseudomonas/epidemiologia , Pseudomonas aeruginosa/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Aminoglicosídeos/farmacologia , Aminoglicosídeos/uso terapêutico , Antibacterianos/uso terapêutico , Feminino , Fluoroquinolonas/uso terapêutico , Genótipo , Humanos , Hospedeiro Imunocomprometido , Integrons/genética , Japão/epidemiologia , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Tipagem de Sequências Multilocus , Infecções por Pseudomonas/imunologia , Infecções por Pseudomonas/microbiologia , Pseudomonas aeruginosa/isolamento & purificação , Pseudomonas aeruginosa/patogenicidade , Adulto Jovem
7.
Environ Health Prev Med ; 23(1): 16, 2018 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-29724162

RESUMO

BACKGROUND: Hepatocyte growth factor (HGF) may act as a possible biochemical index for vascular damage, although evidence for the association between HGF and carotid intima-media thickness (CIMT) is limited. Since both HGF and circulating CD34-positive cells play an important role in endothelial repair, circulating CD34-positive cell levels may influence the association between HGF and CIMT. METHODS: We conducted a cross-sectional study of 269 elderly Japanese men aged 60-69 years who had undertaken an annual medical checkup from 2014 to 2015. RESULTS: The median value for circulating CD34-positive cells was 0.93 cells/µL. Among the study population, 135 men showed low circulating CD34-positive cell levels (≤ 0.93 cells/µL). By multivariable linear regression analysis, HGF was found to be significantly positively associated with CIMT only to participants with low circulating CD34-positive cell levels, with a multi-adjusted ß of 0.26 (p = 0.005) and 0.002 (0.986) for low and high circulating CD34-positive cell levels, respectively. In addition, a significant interaction was observed between HGF and circulating CD34-positive cell levels (low and high) on CIMT (multivariable p value of 0.049). A positive association exists between HGF and CIMT in elderly Japanese men, limited to participants with low circulating CD34-positive cell levels. CONCLUSION: A positive association exists between HGF and CIMT in community-dwelling elderly Japanese men, which is limited to participants with low numbers of circulating CD34-positive cells. Our findings indicate that circulating CD34-positive cell levels could determine the influence of HGF on CIMT in elderly Japanese men.


Assuntos
Antígenos CD34/sangue , Espessura Intima-Media Carotídea , Fator de Crescimento de Hepatócito/metabolismo , Idoso , Biomarcadores/sangue , Estudos Transversais , Humanos , Japão , Masculino , Pessoa de Meia-Idade
8.
Angew Chem Int Ed Engl ; 56(27): 7863-7866, 2017 06 26.
Artigo em Inglês | MEDLINE | ID: mdl-28510344

RESUMO

A series of anionic Fries-type rearrangements of carbamoyl-substituted aryllithium intermediates were controlled by using flow microreactor systems. For the [1,4] and [1,5] rearrangements, the aryllithium intermediate formed before carbamoyl migration and the lithium alkoxide formed after carbamoyl migration can be selectively subjected to subsequent reactions with electrophiles by precisely controlling the residence time and temperature (-25 to -50 °C). In contrast, the [1,6] rearrangement is rather slow even at -25 °C. The absence of crossover products indicates the intramolecular nature of the carbamoyl group migration.

9.
Cancer Sci ; 106(2): 143-50, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25492592

RESUMO

Local recurrence is a major clinical issue following surgical resection in head and neck cancer, and the dissemination and lymph node metastasis of minimal residual disease is relatively difficult to treat due to the lack of suitable therapeutic approaches. In the present study, we developed and evaluated a novel immunotherapy using a skin flap transfer treated with sensitized dendritic cells (DC), termed the "immuno-flap," in a rat tumor model. After the local round area of skin was resected, SCC-158 cells (a rat head and neck cancer cell line) were inoculated into the muscle surface; lastly, the groin skin flap injected with mature DC was overlaid. Two weeks after the second DC injection, systemic immunological reactions and tumor size were measured. The DC-treated group showed a significant reduction in tumor size compared with the control. Although the induction of CTL activity in spleen cells was marginal, Th1 cytokines such as interleukin-2 and interferon-γ were elevated in the DC-treated group. These results suggest that a novel immunotherapy based on the immuno-flap method has the potential for clinical application to prevent the local recurrence of head and neck cancer patients.


Assuntos
Vacinas Anticâncer/imunologia , Células Dendríticas/imunologia , Neoplasias de Cabeça e Pescoço/imunologia , Pele/imunologia , Animais , Linhagem Celular Tumoral , Modelos Animais de Doenças , Feminino , Imunoterapia/métodos , Interferon gama/imunologia , Interleucina-2/imunologia , Recidiva Local de Neoplasia/imunologia , Ratos , Baço/imunologia , Linfócitos T Citotóxicos/imunologia , Células Th1/imunologia
11.
Kansenshogaku Zasshi ; 88(5): 704-7, 2014 Sep.
Artigo em Japonês | MEDLINE | ID: mdl-25672142

RESUMO

We report herein on the case of a 71-year-old woman hospitalized for continued postauricular pain of unknown origin with tongue deviation. In view of the severe inflammatory reaction and multiple nodular shadows of the lungs, the existence of infectious disease was indicated. A contrast-enhanced CT scan of the neck revealed a thrombosis of the right internal jugular vein, osteomyelitis of right temporal-occipital bone and upper cervical spine, and cellulitis of the adjacent soft tissue. Multiple nodular shadows of the lungs were suspected to be the result of a metastatic septic embolism. Hence, she was diagnosed with Lemierre syndrome. Following treatment with long course of antimicrobial therapy including beta-lactams and clindamycin, complete recovery in this patient was achieved.


Assuntos
Síndrome de Lemierre/complicações , Osteomielite/etiologia , Idoso , Feminino , Humanos , Distúrbios da Fala/etiologia , Tomografia Computadorizada por Raios X
12.
Cureus ; 16(5): e61390, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38947646

RESUMO

This case report discusses the management of anti-neutrophil cytoplasmic antibodies (ANCA)-negative rapid progressive glomerulonephritis (RPGN) in a 68-year-old man with a complex medical history, presenting with fatigue, edema, and acute renal failure. Despite the absence of positive biomarkers for specific RPGN types, the clinical progression suggested microscopic polyangiitis, leading to intensive immunosuppressive therapy with cyclophosphamide and rituximab. The patient's condition was further complicated by the coexistence of nephritic and nephrotic syndromes, requiring nuanced management strategies, including prolonged hemodialysis. After initial treatment failure, remission was eventually achieved, allowing cessation of dialysis and significant recovery of renal function. This case highlights the challenges of diagnosing and managing ANCA-negative RPGN, particularly the importance of a tailored, dynamic approach to treatment in resource-limited settings. The recovery observed underscores the potential for renal function improvement even after prolonged periods of intensive therapy, reinforcing the need for persistence and adaptability in managing complex RPGN cases.

13.
Vaccines (Basel) ; 12(4)2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38675726

RESUMO

In novel coronavirus infection (COVID-19), the outbreak of acute lung injury due to trans-airway infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the starting point of severe disease. The COVID-19 pandemic highlights the need for a vaccine that prevents not only the disease but also its infection. Currently, the SARS-CoV-2 vaccine is administered via intramuscular injection and is generally not immunogenic to the mucosa. As a result, current vaccinations fail to reduce viral shedding and transmission and ultimately do not prevent infection. We established a mouse vaccine model in which a single dose of S1 protein and aluminum oxide gel (alum) subcutaneous vaccine was followed by a booster dose of S1 protein and CpG oligodeoxynucleotide intranasal vaccine. The group that received two doses of the intranasal vaccine booster showed a significant increase in IgG and IgA antibody titers against S1 and RBD in serum and BAL, and a significant difference in neutralizing antibody titers, particularly in BAL. One intranasal vaccine booster did not induce sufficient immunity, and the vaccine strategy with two booster intranasal doses produced systemic neutralizing antibodies and mucus-neutralizing antibodies against SARS-CoV-2. It will be an important tool against the emergence of new viruses and the next pandemic.

14.
Cureus ; 15(1): e34174, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36843816

RESUMO

Right upper quadrant pain can originate from the liver, cholecystic duct, gallbladder, pancreas, or surrounding organs. Peritonitis in the right upper quadrant of the abdomen can be caused by lesions in these organs as well as the adjacent organs, such as the kidney and colon. The kidneys are surrounded by Gerota's fascia and fat; therefore, mild local inflammation may not cause peritonitis. Herein, we report the case of a 72-year-old woman with right-sided abdominal pain who was diagnosed with urinary extravasation due to a ureteral stone. Urinary extravasations can present with peritonitis. For effective diagnosis, prompt physical examination and abdominal ultrasound are essential, with the extent of extravasation being key to effective management. Therefore, general physicians should consider urinary extravasation, which is typically caused by kidney and urinary stones, in patients with right upper quadrant pain.

15.
Cureus ; 15(5): e38850, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37303320

RESUMO

Although cytomegalovirus (CMV) usually colonizes the human body without causing symptoms, CMV infections often develop in immunocompromised hosts. Immunosuppression can trigger CMV infection, and its prediction is essential; however, this is challenging without specific criteria. We present the case of an 87-year-old male patient who visited a rural community hospital with the chief complaint of persistent cough, productive of bloody sputum. Initially, the patient developed thrombocytopenia without any abnormalities of liver function; however, a positive myeloperoxidase antineutrophil cytoplasmic antibody (ANCA) test and the presence of alveolar hemorrhage and glomerulonephritis confirmed ANCA-associated vasculitis. The patient's symptoms and thrombocytopenia resolved transiently after treatment with prednisolone and rituximab. However, the recurrence of thrombocytopenia and the appearance of urinary intracytoplasmic inclusion bodies during the treatment course were investigated using an antigenemia test, which ultimately confirmed CMV viremia. Valganciclovir treatment resolved all the symptoms. This case report showed that thrombocytopenia might indicate the presence of CMV infection in ANCA-associated vasculitis and that intracytoplasmic inclusion bodies in immunosuppressed patients require investigation of CMV infection for effective treatment.

16.
PeerJ ; 11: e15174, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37065694

RESUMO

Background: In the treatment of acute hypoxemic respiratory failure (AHRF) due to coronavirus 2019 (COVID-19), physicians choose respiratory management ranging from low-flow oxygen therapy to more invasive methods, depending on the severity of the patient's symptoms. Recently, the ratio of oxygen saturation (ROX) index has been proposed as a clinical indicator to support the decision for either high-flow nasal cannulation (HFNC) or mechanical ventilation (MV). However, the reported cut-off value of the ROX index ranges widely from 2.7 to 5.9. The objective of this study was to identify indices to achieve empirical physician decisions for MV initiation, providing insights to shorten the delay from HFNC to MV. We retrospectively analyzed the ROX index 6 hours after initiating HFNC and lung infiltration volume (LIV) calculated from chest computed tomography (CT) images in COVID-19 patients with AHRF. Methods: We retrospectively analyzed the data for 59 COVID-19 patients with AHRF in our facility to determine the cut-off value of the ROX index for respiratory therapeutic decisions and the significance of radiological evaluation of pneumonia severity. The physicians chose either HFNC or MV, and the outcomes were retrospectively analyzed using the ROX index for initiating HFNC. LIV was calculated using chest CT images at admission. Results: Among the 59 patients who required high-flow oxygen therapy with HFNC at admission, 24 were later transitioned to MV; the remaining 35 patients recovered. Four of the 24 patients in the MV group died, and the ROX index values of these patients were 9.8, 7.3, 5.4, and 3.0, respectively. These index values indicated that the ROX index of half of the patients who died was higher than the reported cut-off values of the ROX index, which range from 2.7-5.99. The cut-off value of the ROX index 6 hours after the start of HFNC, which was used to classify the management of HFNC or MV as a physician's clinical decision, was approximately 6.1. The LIV cut-off value on chest CT between HFNC and MV was 35.5%. Using both the ROX index and LIV, the cut-off classifying HFNC or MV was obtained using the equation, LIV = 4.26 × (ROX index) + 7.89. The area under the receiver operating characteristic curve, as an evaluation metric of the classification, improved to 0.94 with a sensitivity of 0.79 and specificity of 0.91 using both the ROX index and LIV. Conclusion: Physicians' empirical decisions associated with the choice of respiratory therapy for HFNC oxygen therapy or MV can be supported by the combination of the ROX index and the LIV index calculated from chest CT images.


Assuntos
COVID-19 , Insuficiência Respiratória , Humanos , Estudos Retrospectivos , COVID-19/terapia , Insuficiência Respiratória/terapia , Oxigênio , Oxigenoterapia/métodos
17.
Vaccines (Basel) ; 11(6)2023 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-37376477

RESUMO

An effective vaccine against Pseudomonas aeruginosa would benefit people susceptible to severe infection. Vaccination targeting V antigen (PcrV) of the P. aeruginosa type III secretion system is a potential prophylactic strategy for reducing P. aeruginosa-induced acute lung injury and acute mortality. We created a recombinant protein (designated POmT) comprising three antigens: full-length PcrV (PcrV#1-#294), the outer membrane domain (#190-342) of OprF (OprF#190-#342), and a non-catalytic mutant of the carboxyl domain (#406-613) of exotoxin A (mToxA#406-#613(E553Δ)). In the combination of PcrV and OprF, mToxA, the efficacy of POmT was compared with that of single-antigen vaccines, two-antigen mixed vaccines, and a three-antigen mixed vaccine in a murine model of P. aeruginosa pneumonia. As a result, the 24 h-survival rates were 79%, 78%, 21%, 7%, and 36% in the POmT, PcrV, OprF, mTox, and alum-alone groups, respectively. Significant improvement in acute lung injury and reduction in acute mortality within 24 h after infection was observed in the POmT and PcrV groups than in the other groups. Overall, the POmT vaccine exhibited efficacy comparable to that of the PcrV vaccine. The future goal is to prove the efficacy of the POmT vaccine against various P. aeruginosa strains.

18.
Vaccines (Basel) ; 12(1)2023 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-38276664

RESUMO

The new coronavirus infection causes severe respiratory failure following respiratory tract infection with severe acute respiratory syndrome-related coronavirus (SARS-CoV-2). All currently approved vaccines are administered intramuscularly; however, intranasal administration enhances mucosal immunity, facilitating the production of a less invasive vaccine with fewer adverse events. Herein, a recombinant vaccine combining the SARS-CoV-2 spike protein receptor-binding domain (RBD), or S1 protein, with CpG-deoxyoligonucleotide (ODN) or aluminum hydroxide (alum) adjuvants was administered intranasally or subcutaneously to mice. Serum-specific IgG titers, IgA titers in the alveolar lavage fluid, and neutralizing antibody titers were analyzed. The nasal administration of RBD protein did not increase serum IgG or IgA titers in the alveolar lavage fluid. However, a significant increase in serum IgG was observed in the intranasal group administered with S1 protein with CpG-ODN and the subcutaneous group administered with S1 protein with alum. The IgA and IgG levels increased significantly in the alveolar lavage fluid only after the intranasal administration of the S1 protein with CpG-ODN. The neutralizing antibody titers in serum and bronchoalveolar lavage were significantly higher in the intranasal S1-CpG group than in every other group. Hence, the nasal administration of the S1 protein vaccine with CpG adjuvant might represent an effective vaccine candidate.

19.
Am J Pathol ; 178(5): 2322-32, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21514444

RESUMO

Based on the analysis of exudates from injured adipose tissue, we prepared a mixture containing the injury-associated growth factors at the same proportion as the exudates, named adipose injury cocktail (AIC). We hypothesized that AIC induces a series of regenerating and angiogenic processes without actual wounding. The purpose of this study is to elucidate the therapeutic potentials of AIC. AIC preferentially activated adipose-derived stem/progenitor/stromal cells (ASCs) to proliferate, migrate, and form networks compared with vascular endothelial cells, whereas vascular endothelial growth factor did not induce mitogenesis or chemotaxis in human ASCs. Each component growth factor of AIC was differently responsible for the ASC activation. AIC-treated ASCs tended to differentiate into adipocytes or vessel-constituting cells rather than into other cell types. In ischemic adipose tissues of mice, induced by either a surgical intervention or diabetes, AIC administration enhanced proliferation, especially of CD31(-)/CD34(+) ASCs, and mitigated tissue hypoxia by increasing capillary density and reducing fibrogenesis. These results suggest that AIC may have therapeutic potentials for various ischemic/hypoxic conditions by inducing adipose remodeling and neovascularization through activation of ASCs and other cells. Treatment with AIC has many advantages over cell-based therapies regarding morbidity, cost, and physical risks and may be used as an alternative therapy for improving tissue oxygen.


Assuntos
Tecido Adiposo/metabolismo , Hipóxia/prevenção & controle , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Isquemia/prevenção & controle , Células-Tronco Mesenquimais/citologia , Neovascularização Fisiológica/fisiologia , Tecido Adiposo/lesões , Adulto , Animais , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/fisiologia , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Separação Celular , Citometria de Fluxo , Humanos , Hipóxia/metabolismo , Imuno-Histoquímica , Peptídeos e Proteínas de Sinalização Intercelular/farmacologia , Isquemia/metabolismo , Masculino , Células-Tronco Mesenquimais/efeitos dos fármacos , Camundongos , Neovascularização Fisiológica/efeitos dos fármacos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Células Estromais/citologia , Células Estromais/efeitos dos fármacos
20.
Cureus ; 14(1): e21578, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35228937

RESUMO

Fatal ureteral bleeding is rare among elderly individuals. One cause of bleeding can be a fistula between the arteries and urinary organs, such as a common iliac arterio-ureteral fistula. However, the clinical presentation of fistulas can vary. As microscopic hematuria can be an initial finding, detecting the fistula without gross hematuria may be difficult. Here, we report a case of microhematuria that progressed to massive hematuria caused by a common iliac arterio-ureteral fistula. The patient was an 86-year-old man with a chief complaint of cardiopulmonary arrest. He was resuscitated in the previous condition. He had microscopic hematuria. One month later, the patient underwent rehabilitation. He was in hemorrhagic shock with massive hematuria. Further investigation revealed a right common iliac arterio-ureteral fistula. This case demonstrates the importance of investigating anemia in the elderly, including anemia of urinary origin, despite it being rare.

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