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1.
Biology (Basel) ; 13(5)2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38785793

RESUMO

Previous reports have shown that various oral pulmonary vasodilators are effective against canine pulmonary hypertension (PH). However, no studies have compared their hemodynamic effects. We aimed to compare the hemodynamic effects of 15 µg/kg beraprost sodium, 1.0 mg/kg sildenafil, and their combination, in dogs with experimentally induced mitral regurgitation. This experimental crossover study evaluated the hemodynamic and functional effects of oral pulmonary vasodilators by application of right-sided heart catheterization and echocardiography. Beraprost significantly decreased pulmonary and systemic vascular resistance. Additionally, beraprost increased right-ventricular stroke volume and left-ventricular cardiac output without worsening left-heart size and left-atrial pressure. The pulmonary vasodilatory effects of sildenafil were stronger, and its systemic vasodilatory effects were weaker than those of beraprost. However, sildenafil significantly increased the left-ventricular volume, left-atrial pressure indicator, and right-ventricular cardiac output. Combination therapy resulted in the strongest pulmonary and systemic vasodilating effects without worsening the left-heart size and left-atrial pressure indicators. Both beraprost and sildenafil were effective against canine PH; however, sildenafil was associated with the risk of worsening left-heart loading. Combination therapy with beraprost and sildenafil synergistically dilated pulmonary and systemic vessels, indicating a more potent treatment option for severe PH cases.

2.
J Vet Intern Med ; 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38662965

RESUMO

An 8-year-old Leonberger receiving immunosuppressive treatment with clinical signs of acute dyspnea, cyanosis, and difficulty standing was referred to our institution (Day 1). Treatment including oxygen, clopidogrel, and low-molecular-weight heparin was initiated for suspected pulmonary thrombosis. However, exertional dyspnea persisted until Day 10, and increased tricuspid regurgitation velocity, pulmonary vascular resistance, and McConnell's signs also were observed. Thus, beraprost sodium was administered PO on Day 11 to treat suspected pulmonary hypertension. On Day 13, contrast-enhanced computed tomography identified extensive contrast defects in the pulmonary arteries, and IV monteplase was administered on Days 14 and 18, with marked improvement in respiratory status and exertional dyspnea on Day 20. Right ventricular function and McConnell signs also improved, and tricuspid regurgitation velocity and pulmonary vascular resistance decreased. On Day 250, echocardiography indicated further improvement in pulmonary hypertension pathophysiology. The patient was still progressing well with antithrombotic and pulmonary vasodilator treatment 400 days later.

3.
Int J Mol Sci ; 24(24)2023 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-38139314

RESUMO

Mesenchymal stem cells (MSCs) are a promising cell source for stem cell therapy of intractable diseases in veterinary medicine, but donor-dependent cellular heterogeneity is an issue that influences therapeutic efficacy. Thus, we previously established immortalized cells that maintain the fundamental properties of primary cells, but functional evaluation had not been performed. Therefore, we evaluated the immunomodulatory capacity of the immortalized canine adipose-derived MSCs (cADSCs) in vitro and in vivo to investigate whether they maintain primary cell functions. C57BL/6J mice were treated with dextran sulfate sodium (DSS) to induce colitis, injected intraperitoneally with immortalized or primary cADSCs on day 2 of DSS treatment, and observed for 10 days. Administration of immortalized cADSCs improved body weight loss and the disease activity index (DAI) in DSS-induced colitic mice by shifting peritoneal macrophage polarity from the M1 to M2 phenotype, suppressing T helper (Th) 1/Th17 cell responses and inducing regulatory T (Treg) cells. They also inhibited the proliferation of mouse and canine T cells in vitro. These immunomodulatory effects were comparable with primary cells. These results highlight the feasibility of our immortalized cADSCs as a cell source for stem cell therapy with stable therapeutic efficacy because they maintain the immunomodulatory capacity of primary cells.


Assuntos
Colite , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Camundongos , Animais , Cães , Citocinas/genética , Camundongos Endogâmicos C57BL , Colite/induzido quimicamente , Colite/terapia , Linhagem Celular , Transplante de Células-Tronco Mesenquimais/métodos , Sulfato de Dextrana/toxicidade , Modelos Animais de Doenças
4.
J Vet Intern Med ; 37(5): 1656-1666, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37593765

RESUMO

BACKGROUND: Pulmonary hypertension (PH) secondary to respiratory disease is caused by pulmonary vascular remodeling and hypoxia. Severe PH can induce various clinical signs, including syncope and right-sided heart failure. HYPOTHESIS/OBJECTIVES: To investigate the echocardiographic characteristics in dogs with PH secondary to respiratory diseases. ANIMALS: Thirty-one dogs with respiratory diseases with or without PH and 15 healthy dogs. METHODS: Prospective cross-sectional study. Dogs were classified according to respiratory disease (obstructive airway/lung disease [OALD] or restrictive lung disease [RLD]) and PH-relevant signs. The association between echocardiographic variables and PH (classified by respiratory disease and PH-relevant signs) was investigated. RESULTS: Twenty-one dogs were diagnosed with PH; of these, 11 showed PH-related signs (OALD, n = 2; RLD, n = 9), 14 had right ventricular hypertrophy, and 19 had pulmonary arterial enlargement. Right ventricular dysfunction and dilatation were observed only in dogs with PH-related signs (n = 10). Left and right ventricular stroke volumes were significantly lower in dogs with PH (median [interquartile range]: 17.2 [12.4-20.8] and 16.8 [15.3-29.5] mL/m2 , respectively). Dogs with RLD had higher echocardiography-estimated pulmonary vascular resistance than those with OALD (median [interquartile range]: 3.1 [1.9-3.3] and 1.6 [1.3-2.2], respectively). CONCLUSIONS AND CLINICAL IMPORTANCE: Pulmonary arterial enlargement was the most common echocardiographic finding in dogs with PH secondary to respiratory diseases. Right ventricular dysfunction, dilatation, and decreased left and right ventricular stroke volume were significantly associated with the PH-related signs, indicating that comprehensive echocardiography is recommended in dogs with respiratory disease. Restricted lung disease might induce more severe PH than OALD.


Assuntos
Doenças do Cão , Hipertensão Pulmonar , Pneumopatias , Disfunção Ventricular Direita , Cães , Animais , Hipertensão Pulmonar/diagnóstico por imagem , Hipertensão Pulmonar/veterinária , Hipertensão Pulmonar/complicações , Disfunção Ventricular Direita/veterinária , Estudos Prospectivos , Estudos Transversais , Ecocardiografia/veterinária , Pneumopatias/complicações , Pneumopatias/diagnóstico por imagem , Pneumopatias/veterinária , Doenças do Cão/diagnóstico por imagem
5.
Front Vet Sci ; 10: 1191211, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37426078

RESUMO

In recent years, hypertrophic cardiomyopathy (HCM) in cats has become much more common in clinical practice due to improvements in diagnostic techniques and equipment performance. One phenotype is obstructive HCM with left ventricular (LV) outflow tract obstruction (DLVOTO). It has been reported that the presence or absence of DLVOTO does not affect long-term prognosis in cats with HCM. In this study, we evaluated and compared myocardial function in HCM-affected cats with and without DLVOTO using the two-dimensional speckle-tracking echocardiography. LV longitudinal strain of the endocardial, epicardial, and whole layer and LV circumferential strain of the epicardium were significantly decreased in all HCM-affected cats compared to healthy cats. However, these values were not significantly different between those with and without DLVOTO. In contrast, the endocardial and whole layers of LV circumferential strain were only significantly decreased in HCM-affected cats with DLVOTO compared to healthy cats. This could be attributed to the fact that the LV pressure load associated with DLVOTO affected the endocardial myocardium more in the LV endocardial layer, and that lower values of LV endocardial strain lowered the values of LV strain in the whole layer. In conclusion, our results suggest that LV myocardial function may have been more compromised in the HCM-affected cats with DLVOTO.

6.
J Clin Neurosci ; 115: 71-76, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37499322

RESUMO

Drooling represents a common and noteworthy symptom in patients with intractable neuromuscular disease (IND) and cerebral palsy (CP) and can lead to poor quality of life (QOL) and higher incidence of death due to aspiration of saliva. Identifying the factors affecting drooling is crucial to improving QOL and improving the poor prognosis of patients with IND and CP. This study sought to assess the prevalence of drooling and to elucidate the associated factors, drugs, and differences between patients with IND and CP. We included hospitalized patients with IND and CP. Among the 269 patients, 69 of 162 patients with IND (42.6%) and 75 of 107 patients with CP (70.1%) exhibited drooling. Drooling in IND was significantly higher in patients with tube feeding and those who had a previous stroke than in patients with potential oral intake and those having no history of stroke. In individuals with CP, drooling was significantly negatively associated with age. Taltirelin in patients with IND had a significant positive association with drooling, and antipsychotics and centrally acting muscle relaxants in those with CP had a significant negative association with drooling. Our results suggest that the factors associated with frequent drooling differ between IND and CP cases, and patients who should be screened for drooling are those with decreased swallowing function, those with IND who have had a previous stroke, and young patients with CP. Moreover, clinicians should consider the impact of drugs on drooling in IND and CP cases.


Assuntos
Paralisia Cerebral , Doenças Neuromusculares , Sialorreia , Acidente Vascular Cerebral , Humanos , Paralisia Cerebral/complicações , Doenças Neuromusculares/complicações , Prevalência , Qualidade de Vida , Sialorreia/epidemiologia , Sialorreia/etiologia , Acidente Vascular Cerebral/complicações
7.
Biol Pharm Bull ; 46(4): 614-620, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37005306

RESUMO

Digoxin toxicity (plasma digoxin concentration ≥0.9 ng/mL) is associated with worsening heart failure (HF). Decision tree (DT) analysis, a machine learning method, has a flowchart-like model where users can easily predict the risk of adverse drug reactions. The present study aimed to construct a flowchart using DT analysis that can be used by medical staff to predict digoxin toxicity. We conducted a multicenter retrospective study involving 333 adult patients with HF who received oral digoxin treatment. In this study, we employed a chi-squared automatic interaction detection algorithm to construct DT models. The dependent variable was set as the plasma digoxin concentration (≥ 0.9 ng/mL) in the trough during the steady state, and factors with p < 0.2 in the univariate analysis were set as the explanatory variables. Multivariate logistic regression analysis was conducted to validate the DT model. The accuracy and misclassification rates of the model were evaluated. In the DT analysis, patients with creatinine clearance <32 mL/min, daily digoxin dose ≥1.6 µg/kg, and left ventricular ejection fraction ≥50% showed a high incidence of digoxin toxicity (91.8%; 45/49). Multivariate logistic regression analysis revealed that creatinine clearance <32 mL/min and daily digoxin dose ≥1.6 µg/kg were independent risk factors. The accuracy and misclassification rates of the DT model were 88.2 and 46.2 ± 2.7%, respectively. Although the flowchart created in this study needs further validation, it is straightforward and potentially useful for medical staff in determining the initial dose of digoxin in patients with HF.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Insuficiência Cardíaca , Adulto , Humanos , Estudos Retrospectivos , Volume Sistólico , Creatinina , Função Ventricular Esquerda , Digoxina/efeitos adversos , Insuficiência Cardíaca/induzido quimicamente , Aprendizado de Máquina , Cardiotônicos/efeitos adversos
8.
Auris Nasus Larynx ; 50(6): 904-910, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37012135

RESUMO

OBJECTIVE: Detailed quantitative studies on olfaction remain inadequate in patients with paediatric allergic rhinitis (AR). This study examined olfactory dysfunction in children with AR. METHODS: From July 2016 to November 2018, children aged 6-9 years were recruited and grouped as AR (n = 30) or without AR (control group, n = 10). Odour identification was evaluated by the Universal Sniff (U-Sniff) test and the Open Essence (OE). The results were compared between the AR and control groups. Intranasal mucosa findings, nasal smear eosinophil counts, blood eosinophil counts, total immunoglobulin E (IgE) levels, Japanese cedar-specific IgE and Dermatophagoides pteronyssinus-specific IgE were evaluated in all participants. Additionally, the presence of sinusitis and adenoid hypertrophy in patients with AR was also evaluated by sinus X-ray examinations. RESULTS: The median U-Sniff test scores were not significantly different between the AR and control groups (9.0 vs. 10.0, respectively; p = 0.107). The OE score was significantly lower in the AR group than in the control group (4.0 vs. 8.0; p = 0.007, respectively), especially in the moderate-to-severe AR group versus the control group (4.0 vs. 8.0; p = 0.004). Furthermore, in the OE, the correct answer rates for 'wood', 'cooking gas' and 'sweaty socks' were significantly lower in the AR group than in the control group. CONCLUSIONS: Paediatric AR patients can reduce olfactory identification ability, and the degree may be associated with the severity of AR in nasal mucosal findings. Furthermore, olfactory dysfunction may slow down the response to 'emergency situations', such as gas leak.


Assuntos
Transtornos do Olfato , Seios Paranasais , Rinite Alérgica , Humanos , Criança , Olfato , Rinite Alérgica/complicações , Imunoglobulina E
9.
Insect Mol Biol ; 32(4): 424-435, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37017304

RESUMO

Termites have an elaborate social system that involves cooperation and division of labour among colony members. Although this social system is regulated by chemical signals produced in the colony, it remains unclear how these signals are perceived by other members. Signal transduction is well known to be triggered by the reception of odorant molecules by some binding proteins in the antennae, after which, a signal is transmitted to chemosensory receptors. However, there is insufficient information on the role of chemosensory genes involved in signal transduction in termites. Here, we identified the genes involved in chemosensory reception in the termite Reticulitermes speratus and performed a genome-wide comparative transcriptome analysis of worker and soldier antennae. First, we identified 31 odorant-binding proteins (OBPs), and three chemosensory protein A (CheA) from the genome data. Thereafter, we performed RNA sequencing to compare the expression levels of OBPs, CheAs, and previously identified chemosensory receptor genes between worker and soldier antennae. There were no receptor genes with significant differences in expression between castes. However, the expression levels of three non-receptor odorant-detection/binding proteins (OBP, CheA, and Sensory neuron membrane protein) were significantly different between castes. Real-time qPCR (RT-qPCR) analysis using antennae and other head parts confirmed that these genes were highly expressed in soldier antennae. Finally, independent RT-qPCR analysis showed that the expression patterns of these genes were altered in soldiers from different social contexts. Present results suggest that gene expression levels of some non-receptors are affected by both castes and behavioural interactions among colony members in termites.


Assuntos
Isópteros , Receptores Odorantes , Animais , Transcriptoma , Isópteros/genética , Isópteros/metabolismo , Análise de Sequência de RNA , Células Receptoras Sensoriais , Receptores Odorantes/metabolismo , Antenas de Artrópodes/metabolismo , Perfilação da Expressão Gênica , Proteínas de Insetos/metabolismo , Filogenia
10.
Vet Sci ; 10(4)2023 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-37104457

RESUMO

Pulmonary hypertension (PH) is a life-threatening complication in dogs with cardiopulmonary disease. Epoprostenol is an intravenous pulmonary vasodilator used to treat PH in humans; however, its efficacy in dogs remains unknown. We investigated the cardiovascular effects of epoprostenol and several cardiac agents for acute heart failure in canine models of chronic PH. Six dogs with chronic PH were anesthetized and underwent right heart catheterization and echocardiography before and after infusion of epoprostenol, dobutamine, dopamine and pimobendane. (The drug administration order was the same for all dogs). High-dose epoprostenol (15-20 ng/kg/min) tended to decrease pulmonary arterial pressure (PAP) while significantly decreasing pulmonary and systemic vascular resistance and increasing left and right ventricular (LV and RV, respectively) function. Pimobendan significantly increased LV and RV functions without increasing PAP. Conversely, dobutamine and dopamine significantly increased LV and RV function as well as PAP. This study revealed the efficacy of epoprostenol in treating canine PH through its pulmonary and systemic vasodilating effects. Although catecholamines improve LV and RV function, they might worsen PH pathophysiology, and careful monitoring may be necessary when using these drugs. Pimobendan improved LV and RV function without increasing PAP; however, a stronger vasodilating effect was observed with epoprostenol.

11.
PLoS One ; 18(4): e0283433, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37071642

RESUMO

Hypertrophic cardiomyopathy (HCM) is the most common heart disease in cats with a suspected genetic origin. Previous studies have identified five HCM-associated variants in three genes (Myosin binding protein C3: MYBPC3 p.A31P, p.A74T, p.R820W; Myosin heavy chain 7: MYH7 p.E1883K; Alstrom syndrome protein 1: ALMS1 p.G3376R). These variants are considered breed-specific, with the exception of MYBPC3 p.A74T, and have rarely been found in other breeds. However, genetic studies on HCM-associated variants across breeds are still insufficient because of population and breed bias caused by differences in genetic background. This study investigates the ubiquitous occurrence of HCM-associated genetic variants among cat breeds, using 57 HCM-affected, 19 HCM-unaffected, and 227 non-examined cats from the Japanese population. Genotyping of the five variants revealed the presence of MYBPC3 p.A31P and ALMS1 p.G3376R in two (Munchkin and Scottish Fold) and five non-specific breeds (American Shorthair, Exotic Shorthair, Minuet, Munchkin and Scottish Fold), respectively, in which the variants had not been identified previously. In addition, our results indicate that the ALMS1 variants identified in the Sphynx breed might not be Sphynx-specific. Overall, our results suggest that these two specific variants may still be found in other cat breeds and should be examined in detail in a population-driven manner. Furthermore, applying genetic testing to Munchkin and Scottish Fold, the breeds with both MYBPC3 and ALMS1 variants, will help prevent the development of new HCM-affected cat colonies.


Assuntos
Cardiomiopatia Hipertrófica , Proteínas de Transporte , Gatos , Animais , Japão , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Cardiomiopatia Hipertrófica/genética , Cardiomiopatia Hipertrófica/veterinária , Proteínas do Citoesqueleto/genética , Nível de Saúde , Mutação
12.
J Vet Intern Med ; 37(3): 856-865, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36994902

RESUMO

BACKGROUND: Progression to combined post- and pre-capillary pulmonary hypertension (PH) provides prognostic information in human patients with post-capillary PH. Pulmonary vascular resistance estimated by echocardiography (PVRecho) is useful for the stratification of dogs with myxomatous mitral valve disease (MMVD) and detectable tricuspid regurgitation. OBJECTIVES: To evaluate the prognostic value of PVRecho in dogs with MMVD. ANIMALS: Fifty-four dogs with MMVD and detectable tricuspid regurgitation. METHODS: Prospective cohort study. All dogs underwent echocardiography. The PVRecho was calculated based on tricuspid regurgitation and the velocity-time integral of the pulmonary artery flow. To evaluate the influence of echocardiographic variables on cardiac-related deaths, Cox proportional hazard analysis was performed. Additionally, Kaplan-Meier curves classified by PVRecho tertiles were made and compared using log-rank tests to evaluate the influence of PVRecho on all-cause mortality and cardiac-related death. RESULTS: The median follow-up time was 579 days. Forty-one dogs with MMVD (PH severity [number]: no or mild, 21/33; moderate, 11/11; severe, 9/10) died during the study. In the multivariable Cox proportional hazard analysis adjusted for age, sildenafil administration, and American College of Veterinary Internal Medicine stage of MMVD, left atrial to aortic diameter ratio and PVRecho remained significant (adjusted hazard ratio [95% confidence interval]: 1.2 [1.1-1.3] and 2.1 [1.6-3.0], respectively). Higher PVRecho showed a significant association with lower survival rates. CONCLUSIONS AND CLINICAL IMPORTANCE: Left atrial enlargement and high PVRecho were independent prognostic factors in dogs with MMVD and detectable tricuspid regurgitation.


Assuntos
Fibrilação Atrial , Doenças do Cão , Doenças das Valvas Cardíacas , Hipertensão Pulmonar , Insuficiência da Valva Tricúspide , Humanos , Cães , Animais , Valva Mitral/diagnóstico por imagem , Prognóstico , Hipertensão Pulmonar/diagnóstico por imagem , Hipertensão Pulmonar/veterinária , Hipertensão Pulmonar/complicações , Insuficiência da Valva Tricúspide/diagnóstico por imagem , Insuficiência da Valva Tricúspide/veterinária , Estudos Prospectivos , Fibrilação Atrial/veterinária , Doenças das Valvas Cardíacas/veterinária , Ecocardiografia/veterinária , Resistência Vascular
13.
Vet Sci ; 10(3)2023 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-36977271

RESUMO

Cats urgently visit emergency hospitals due to respiratory distress, and the chief cause is cardiogenic pulmonary edema (CPE). Although cats with CPE were frequently encountered in clinics, the prognostic factors were poorly reported. The objective of this retrospective study was to investigate the association of physical examination and venous blood gas parameters with the survival of cats with CPE in an emergency hospital. Thirty-six cats with CPE were ultimately included in the present study, and eight of them died within 12 h after their presentation to our hospital. Statistical analyses of clinical parameters between cats that died within 12 h and those that survived for 12 h were conducted using Mann-Whitney U test with Bonferroni correction. Cats that died within 12 h had significantly lower rectal temperatures and higher PvCO2 than those that did not die within 12 h. Moreover, hypotension and vasoconstrictor use were related to death within 12 h of presentation and higher PvCO2. These findings indicated the prognostic utility of body temperature and PvCO2, and the association between hypercapnia and the severity of CPE or hypotension. A large number of prospective studies should be performed to validate these results.

14.
Int J Mol Sci ; 24(3)2023 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-36768587

RESUMO

Mesenchymal stem cells are expected to be a cell source for stem cell therapy of various diseases in veterinary medicine. However, donor-dependent cell heterogenicity has been a cause of inconsistent therapeutic efficiency. Therefore, we established immortalized cells from canine adipose tissue-derived mesenchymal stem cells (ADSCs) to minimize cellular heterogeneity by reducing the number of donors, evaluated their properties, and compared them to the primary cells with RNA-sequencing. Immortalized canine ADSCs were established by transduction with combinations of the R24C mutation of human cyclin-dependent kinase 4 (CDKR24C), canine cyclin D1, and canine TERT. The ADSCs transduced with CDK4R24C, cyclin D1, and TERT (ADSC-K4DT) or with CDK4R24C and cyclin D1 (ADSC-K4D) showed a dramatic increase in proliferation (population doubling level >100) without cellular senescence compared to the primary ADSCs. The cell surface markers, except for CD90 of the ADSC-K4DT and ADSC-K4D cells, were similar to those of the primary ADSCs. The ADSC-K4DT and ADSC-K4D cells maintained their trilineage differentiation capacity and chromosome condition, and did not have a tumorigenic development. The ability to inhibit lymphocyte proliferation by the ADSC-K4D cells was enhanced compared with the primary ADSCs and ADSC-K4DT cells. The pathway analysis based on RNA-sequencing revealed changes in the pathways mainly related to the cell cycle and telomerase. The ADSC-K4DT and ADSC-K4D cells had decreased CD90 expression, but there were no obvious defects associated with the decreased CD90 expression in this study. Our results suggest that ADSC-K4DT and ADSC-K4D cells are a potential novel cell source for mesenchymal stem cell therapy.


Assuntos
Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Animais , Cães , Humanos , Ciclina D1/metabolismo , Células-Tronco Mesenquimais/metabolismo , Diferenciação Celular , Proteínas/metabolismo , RNA/metabolismo , Tecido Adiposo/metabolismo
15.
Cancer Sci ; 114(1): 321-338, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36136061

RESUMO

Important roles of humoral tumor immunity are often pointed out; however, precise profiles of dominant antigens and developmental mechanisms remain elusive. We systematically investigated the humoral antigens of dominant intratumor immunoglobulin clones found in human cancers. We found that approximately half of the corresponding antigens were restricted to strongly and densely negatively charged polymers, resulting in simultaneous reactivities of the antibodies to both densely sulfated glycosaminoglycans (dsGAGs) and nucleic acids (NAs). These anti-dsGAG/NA antibodies matured and expanded via intratumoral immunological driving force of innate immunity via NAs. These human cancer-derived antibodies exhibited acidic pH-selective affinity across both antigens and showed specific reactivity to diverse spectrums of human tumor cells. The antibody-drug conjugate exerted therapeutic effects against multiple cancers in vivo by targeting cell surface dsGAG antigens. This study reveals that intratumoral immunological reactions propagate tumor-oriented immunoglobulin clones and demonstrates a new therapeutic modality for the universal treatment of human malignancies.


Assuntos
Neoplasias , Ácidos Nucleicos , Humanos , Epitopos , Antígenos , Neoplasias/terapia , Anticorpos , Antígenos de Superfície , Concentração de Íons de Hidrogênio
16.
Front Insect Sci ; 3: 1188343, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38469474

RESUMO

Unveiling the proximate mechanism of caste differentiation is crucial for understanding insect social evolution, and gene function analysis is an important tool in this endeavor. The RNA interference (RNAi) technique is useful in termites, but its knockdown effects may differ among species. One of the most important model species in the field of termite sociogenomics is Reticulitermes speratus Kolbe (Isoptera: Rhinotermitidae). Presoldier and worker differentiation of this species can be artificially induced by juvenile hormone and 20-hydroxyecdysone application, respectively. However, appropriate RNAi technique of genes expressed during caste differentiation has never been considered. To clarify this issue, first, we injected nine different volumes of nuclease-free water (NFW, 0-404.8 nL) into workers and found that survival and caste differentiation rates were strongly reduced by the application of the top three largest volumes. Second, we injected double-stranded (ds) RNA of ecdysone receptor homolog (RsEcR) (2.0 µg/151.8 nL NFW) into workers with hormone treatments. The expression levels of RsEcR were significantly reduced at 9 days after dsRNA injection. RsEcR RNAi strongly affected both molting events during presoldier and worker differentiation induced by hormone treatments. The present results highlight the need for caution regarding injection volumes for RNAi experiments using hormone treatments. We suggest that the injection of dsRNA solution (2 µg; approximately 100-200 nL) is suitable for RNAi experiments during caste differentiation induced by hormone application in R. speratus.

17.
Int J Mol Sci ; 23(23)2022 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-36499004

RESUMO

Mesenchymal stem cells (MSC) are currently being investigated for their therapeutic applications in a wide range of diseases. Although many studies examined peripheral venous administration of MSC, few have investigated the detailed intravenous administration procedures of MSC from their preparation until they enter the body. The current study therefore aimed to explore the most efficient infusion procedure for MSC delivery by preparing and infusing them under various conditions. Canine adipose-derived mesenchymal stem cells (cADSC) were infused using different infusion apparatuses, suspension solutions, allogenic serum supplementation, infusion time and rates, and cell densities, respectively. Live and dead cell counts were then assessed by manual measurements and flow cytometry. Efficiency of live- and dead-cell infusion and cell viability were calculated from the measured cell counts and compared under each condition. Efficiency of live-cell infusion differed significantly according to the infusion apparatus, infusion rate, and combination of cell density and serum supplementation. Cell viability after infusion differed significantly between the infusion apparatuses. The optimal infusion procedure resulting in the highest cell delivery and viability involved suspending cADSC in normal saline supplemented with 5% allogenic serum at a density of 5 × 105 cells/mL, and infusing them using an automatic infusion device for 15 min. This procedure is therefore recommended as the standard procedure for the intravenous administration of ADSC in terms of cell-delivery efficiency.


Assuntos
Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Animais , Cães , Transplante de Células-Tronco Mesenquimais/métodos , Administração Intravenosa , Infusões Intravenosas
18.
J Pharm Health Care Sci ; 8(1): 37, 2022 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-36510270

RESUMO

BACKGROUND: The number of medications, number of administrations per day, dosing frequency on indicated day, and medication from multiple prescriptions are the medication factors prone to medication errors in self-management that have been previously reported. However, whether pharmacists actually intervene in medication factors that affect medication error occurrences in self-management is unclear. Therefore, we conducted this study to clarify these issues. METHOD: This study included patients who underwent self-management in the rehabilitation ward of Higashinagoya National Hospital. From April 2019 to March 2020, a one-pharmacist period existed, and from April 2020 to March 2021, a two-pharmacist period existed. The number of patient instructions and interventions were expected to increase with an increase in the number of pharmacists. Considering this to be an environment of differential interventions by pharmacists, a pre-post-test design was conducted with all self-managed patients in both the time periods. The primary and secondary endpoints were the proportion of medication error occurrences and proportion of pharmacist's interventions in medication factors, respectively. RESULT: The proportions of medication error occurrences during the one-pharmacist and two-pharmacist periods were 41% (71/173) and 28% (51/180) (relative risk 0.690, 95% confidential interval 0.515-0.925), respectively. The proportion of pharmacist's interventions in medication factors in the one-pharmacist period was 13% (22/173) and 22% (40/180) in the two-pharmacist period; there was an increase in the proportion of pharmacist's interventions in medication factors in the two-pharmacist period. CONCLUSION: The proportion of medication error occurrences was significantly lower in the two-pharmacist period than that in the one-pharmacist period. This can be attributed to the increase in the proportion of pharmacist's interventions in medication factors. Therefore, an environment in which pharmacists could intervene in the medication factors to prevent medication errors in advance is necessary.

19.
Vet Sci ; 9(11)2022 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-36356070

RESUMO

An 11-year-old intact female Papillion weighing 2.1 kg was referred to our institution with the main complaint of shallow, rapid breathing. At the first visit (day 0), although clinical signs improved due to the use of medication from the primary hospital, transthoracic radiography and echocardiography revealed left heart enlargement and left ventricular dysfunction. A clinical diagnosis of dilated cardiomyopathy (DCM) was made and oral administration of pimobendan, temocapril, and taurine was initiated. However, on day 10, the respiratory status worsened and furosemide was prescribed. On day 54, no significant improvement in heart size was observed. Additionally, the diet that this patient received met the recommendation for diet-related DCM by the U.S. Food and Drug Administration, and the patient's diet was changed from a grain-free diet to a grain-containing diet. On day 1191, the patient's respiratory status was stable and no clinical signs were observed. Transthoracic radiography and echocardiography revealed an improvement in left heart size. Additionally, improvements in the left and right ventricular myocardial strains were observed after changing the diet. We suggest that it may be necessary to suspect a dietary association with dilated cardiomyopathy, and a good prognosis might be expected by dietary modification, even in small-breed dogs.

20.
Medicine (Baltimore) ; 101(33): e30122, 2022 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-35984141

RESUMO

Medication errors, including overdose and underdose, have a significant impact on patients and the medical economy. We need to prevent or avoid recurring medication errors. Therefore, we conducted a survey to identify medication and prescription background risk factors contributing to the administration of medication by nurses. This study surveyed cases of medication administration errors. This study was conducted at Higashinagoya National Hospital from April 1, 2018, to October 31, 2019. Patients' backgrounds and medication and prescription background risk factors were investigated. Three control cases were randomly selected for each medication error case. We defined the group of medication error cases as the medication error group and the group of control cases as the no-medication-error group. A logistic regression analysis was performed for factors related to medication errors. A total of 202 patients were included in the medication error group. The median age and number of medications were 78 years and 7, respectively. A total of 606 cases were included in the no-medication-error group. The median age and number of medications were 77 years and 6, respectively. The factors that exhibited a relationship with the medication error group were the number of administrations per day, dosing frequency on indicated days, prescription and start dates were the same, medications from multiple prescriptions, and continuous use of a medication received prior to admission. This study identified existing medication and prescription background risk factors. Overlapping risk factors from these groups might contribute to medication administration errors. Therefore, reviewing these factors is necessary to avoid recurring medication administration errors.


Assuntos
Prescrições de Medicamentos , Erros de Medicação , Estudos de Casos e Controles , Hospitalização , Humanos , Fatores de Risco
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