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2.
Beijing Da Xue Xue Bao Yi Xue Ban ; 52(5): 952-958, 2020 Oct 18.
Artigo em Chinês | MEDLINE | ID: mdl-33047736

RESUMO

OBJECTIVE: To prepare and evaluate the basic properties in vitro of a novel small intestinal submucosa (SIS) sponge, and to describe the bone formation ability of the SIS sponge in vivo. METHODS: The SIS sponge was prepared by freeze-drying method. To evaluate the physicochemical properties of the sponge, electron microscope observation, porosity test, water absorption ability and mechanical property were conducted in vitro. The cytotoxicity of the SIS sponge was performed by cell counting kit-8 method. In vivo experiments, eighteen extraction sockets of premolar of three Beagle dogs were randomly divided into three groups: SIS sponge group (SIS sponge), positive control group (Bio-Oss granules and Bio-Gide membrane) and control group(no treatment). The animals were sacrificed 4 weeks and 12 weeks after operation, and micro computed tomography (Micro-CT) was applied to measure the bone volume fraction (BV/TV) and bone mineralized density (BMD). The data were analyzed with one-way ANOVA. RESULTS: The average pore diameter of the SIS sponge was (194.90±30.39) µm, the porosity was 92.31%±0.24%, the water absorption rate was 771.50%±40.90%, and the compressive elastic modulus was (2.20±0.19) kPa. There was no significant difference in cell proliferation ability between SIS sponge and control group (P>0.05). Micro-CT quantitative results showed that BV/TV of SIS sponge group (52.81%±3.21%) and positive control group (58.30%±9.36%) were significantly higher than that of control group (38.65%±4.80%) 4 weeks after operation (P < 0.05). The BMD of SIS sponge group [(887.09±61.02) mg/cm3], positive control group [(952.05±132.78) mg/cm3] and control group [(879.29±74.27) mg/cm3] showed no statistical difference 4 weeks after operation (P>0.05). The BV/TV of positive control group (60.57%± 6.56%) was significantly higher than that of SIS sponge group (47.89%±3.59%) and control group (42.99%±2.54%) 12 weeks after operation (P < 0.05). BMD of SIS sponge group [(1047±89.95) mg/cm3] and positive control group [(1101.37±98.85) mg/cm3] were significantly higher than that of control group [(890.36±79.79) mg/cm3] 12 weeks after operation (P < 0.05). CONCLUSION: The SIS sponge has satisfying physicochemical properties and biocompatibility. The SIS sponge significantly increased bone volume fraction in the early stage of bone formation (4 weeks) and bone mineralized density in the late stage of bone formation (12 weeks).


Assuntos
Osteogênese , Animais , Cães , Microtomografia por Raio-X
5.
J Spec Oper Med ; 20(3): 103-108, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32969012

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARSCov- 2) is hypothesized to have originated from a spillover event from an animal reservoir. This has raised many questions, with an important one being whether the widely disseminated coronavirus disease 2019 (COVID-19) is transmissible to other animal species. SARS-CoV-2 is primarily transmitted person to person. K9-to-human transmission, although theoretically possible via fomites, is considered minimal, if at all, and there have been no reported cases of K9-to-human transmission. Human-to-K9 transmission, although rare, seems more likely; however, in only one case has a K9 been suspected to have displayed symptoms of COVID-19. Preparation, decontamination, hand hygiene, and distancing remain the key factors in reducing transmission of the virus. The information presented is applicable to personnel operating within the military conventional and Special Operation Forces as well as civilian Tactical Emergency Medical Services communities who may have the responsibility of supporting an operational K9.


Assuntos
Infecções por Coronavirus/transmissão , Infecções por Coronavirus/veterinária , Cães/virologia , Militares , Pandemias/veterinária , Pneumonia Viral/transmissão , Pneumonia Viral/veterinária , Animais , Betacoronavirus , Infecções por Coronavirus/prevenção & controle , Humanos , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle
6.
Am J Vet Res ; 81(10): 804-809, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32969728

RESUMO

OBJECTIVE: To investigate whether an actual improvement in gait could be differentiated from physiologic differences or habituation effects during gait analysis of dogs. ANIMALS: 11 healthy dogs. PROCEDURES: On 4 examination days, kinetic parameters were measured while dogs were walking on a treadmill. Differences in mean parameter values and habituation effects (ie, effect sizes) were quantified and compared among examination days. Coefficients of variation for repeated measurements were calculated to determine measurement reproducibility, and minimum differences were calculated to distinguish between physiologic fluctuation and an actual change in gait pattern. RESULTS: Among the 4 examination days, mean absolute differences in peak vertical force and vertical impulse (VI) varied from 1.5% to 5.3% of body weight (BW) and 0.9% to 1.8% of BW·s, respectively. Mean absolute differences in the percentage of stance-phase duration (%SPD) and relative stride length (RSL) varied from 0.9% to 3.2% and 1.7% to 3.0%, respectively. Reproducibility of parameter measurements was good. Values for %SPD had the lowest amount of dispersion and largest effect size, suggesting a habituation effect for this parameter. Calculated minimum differences among the days for peak vertical force, VI, %SPD, and RSL did not exceed 9.9% of BW, 3.3% of BW·s, 5.8 percentage points, and 5.2 percentage points, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: The %SPD of healthy dogs walking on a treadmill was the most sensitive and diagnostically reliable of the measured kinetic parameters, in contrast to VI and RSL. Findings suggested that actual changes can be distinguished from random physiologic fluctuations during gait analysis of dogs.


Assuntos
Teste de Esforço/veterinária , Caminhada , Animais , Fenômenos Biomecânicos , Cães , Marcha , Cinética , Reprodutibilidade dos Testes
7.
Am J Vet Res ; 81(10): 790-795, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32969729

RESUMO

OBJECTIVE: To use the small data approach of the Clinical and Laboratory Standards Institute (CLSI) to evaluate the transferability of reference intervals (RIs) for kinetic variables obtained with instrumented gait analysis (IGA) in dogs from an RI-originator laboratory to another laboratory that used the same data acquisition and analytic techniques for IGA in walking dogs. ANIMALS: 27 adult client-owned dogs without evidence of lameness. PROCEDURES: Dogs were individually walked at their preferred velocity on a pressure-sensing walkway for IGA at the Colorado State University Animal Gait Laboratory (CSU-AGL), and 6 valid trials were analyzed for each dog. The small data approach of the CLSI was then used to evaluate transferability of RIs previously established at the Purdue University Animal Gait Laboratory (PU-AGL). A linear model was used to establish weight-dependent RIs for peak vertical force (PVF). RESULTS: Results indicated that RIs of dynamic weight distribution (DWD), DWD symmetry index, DWD coefficient of variation, PVF symmetry index, and PVF coefficient of variation were transferable from PU-AGL to CSU-AGL, whereas the weight-dependent RIs for PVF were not. Regression slopes for PVF versus body weight were greater for all limbs in dogs tested at the CSU-AGL, compared with historic results for dogs tested at the PU-AGL. CONCLUSIONS AND CLINICAL RELEVANCE: Use of the small data approach method of the CLSI to validate transference of RIs for IGA kinetic variables in walking dogs was simple and efficient to perform and may help facilitate clinical and research collaborations on gait analysis.


Assuntos
Análise da Marcha , Caminhada , Animais , Fenômenos Biomecânicos , Cães , Marcha , Cinética
8.
Am J Vet Res ; 81(10): 827-831, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32969730

RESUMO

OBJECTIVE: To compare initial leak pressure (ILP) between cadaveric canine and synthetic small intestinal segments that did and did not undergo enterotomy. SAMPLE: Eight 8-cm grossly normal jejunal segments from 1 canine cadaver and eight 8-cm synthetic small intestinal segments. PROCEDURES: Intestinal segments were randomly assigned to undergo enterotomy (6 cadaveric and 6 synthetic segments) or serve as untreated controls (2 cadaveric and 2 synthetic segments). For segments designated for enterotomy, a 2-cm full-thickness incision was created along the antimesenteric border. The incision was closed in a single layer with 4-0 suture in a simple continuous pattern. Leak testing was performed with intestinal segments occluded at both ends and infused with dilute dye solution (999 mL/h) until the solution was observed leaking from the suture line or serosal tearing occurred. Intraluminal pressure was continuously monitored. The ILP at construct failure was compared between cadaveric and synthetic control segments and between cadaveric and synthetic enterotomy segments. RESULTS: Mean ± SD ILP did not differ significantly between cadaveric (345.11 ± 2.15 mm Hg) and synthetic (329.04 ± 24.69 mm Hg) control segments but was significantly greater for cadaveric enterotomy segments (60.77 ± 15.81 mm Hg), compared with synthetic enterotomy segments (15.03 ± 6.41 mm Hg). CONCLUSIONS AND CLINICAL RELEVANCE: Leak testing should not be used to assess the accuracy or security of enterotomy suture lines in synthetic intestinal tissue. Synthetic intestinal tissue is best used for students to gain confidence and proficiency in performing enterotomies before performing the procedure on live animals.


Assuntos
Procedimentos Cirúrgicos do Sistema Digestório/veterinária , Doenças do Cão , Anastomose Cirúrgica/veterinária , Animais , Cadáver , Cães , Pressão , Técnicas de Sutura/veterinária , Suturas
9.
PLoS Pathog ; 16(8): e1008775, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32866218

RESUMO

Small RNA viruses only have a very limited coding capacity, thus most viral proteins have evolved to fulfill multiple functions. The highly conserved matrix protein 1 (M1) of influenza A viruses is a prime example for such a multifunctional protein, as it acts as a master regulator of virus replication whose different functions have to be tightly regulated. The underlying mechanisms, however, are still incompletely understood. Increasing evidence points towards an involvement of posttranslational modifications in the spatio-temporal regulation of M1 functions. Here, we analyzed the role of M1 tyrosine phosphorylation in genuine infection by using recombinant viruses expressing M1 phosphomutants. Presence of M1 Y132A led to significantly decreased viral replication compared to wildtype and M1 Y10F. Characterization of phosphorylation dynamics by mass spectrometry revealed the presence of Y132 phosphorylation in M1 incorporated into virions that is most likely mediated by membrane-associated Janus kinases late upon infection. Molecular dynamics simulations unraveled a potential phosphorylation-induced exposure of the positively charged linker domain between helices 4 and 5, supposably acting as interaction platform during viral assembly. Consistently, M1 Y132A showed a defect in lipid raft localization due to reduced interaction with viral HA protein resulting in a diminished structural stability of viral progeny and the formation of filamentous particles. Importantly, reduced M1-RNA binding affinity resulted in an inefficient viral genome incorporation and the production of non-infectious virions that interferes with virus pathogenicity in mice. This study advances our understanding of the importance of dynamic phosphorylation as a so far underestimated level of regulation of multifunctional viral proteins and emphasizes the potential feasibility of targeting posttranslational modifications of M1 as a novel antiviral intervention.


Assuntos
Vírus da Influenza A/metabolismo , Mutação de Sentido Incorreto , Proteínas da Matriz Viral/metabolismo , Células A549 , Substituição de Aminoácidos , Animais , Cães , Feminino , Células HEK293 , Humanos , Vírus da Influenza A/genética , Células Madin Darby de Rim Canino , Masculino , Camundongos , Camundongos Transgênicos , Fosforilação , Proteínas da Matriz Viral/genética
10.
PLoS Pathog ; 16(9): e1008841, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32881973

RESUMO

The influenza virus polymerase transcribes and replicates the viral genome. The proper timing and balance of polymerase activity is important for successful replication. Genome replication is controlled in part by phosphorylation of NP that regulates assembly of the replication machinery. However, it remains unclear whether phosphorylation directly regulated polymerase activity. Here we identified polymerase phosphosites that control its function. Mutating phosphosites in the catalytic subunit PB1 altered polymerase activity and virus replication. Biochemical analyses revealed phosphorylation events that disrupted global polymerase function by blocking the NTP entry channel or preventing RNA binding. We also identified a regulatory site that split polymerase function by specifically suppressing transcription. These experiments show that host kinases phospho-regulate viral RNA synthesis directly by modulating polymerase activity and indirectly by controlling assembly of replication machinery. Further, they suggest polymerase phosphorylation may bias replication versus transcription at discrete times or locations during the infectious cycle.


Assuntos
Vírus da Influenza A/fisiologia , RNA Viral/biossíntese , Transcrição Genética , Proteínas Virais/metabolismo , Replicação Viral , Células A549 , Animais , Cães , Células HEK293 , Humanos , Células Madin Darby de Rim Canino , Fosforilação , RNA Viral/genética , Proteínas Virais/genética
11.
Sci Rep ; 10(1): 15917, 2020 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-32985513

RESUMO

SARS-CoV-2 is the novel coronavirus responsible for the outbreak of COVID-19, a disease that has spread to over 100 countries and, as of the 26th July 2020, has infected over 16 million people. Despite the urgent need to find effective therapeutics, research on SARS-CoV-2 has been affected by a lack of suitable animal models. To facilitate the development of medical approaches and novel treatments, we compared the ACE2 receptor, and TMPRSS2 and Furin proteases usage of the SARS-CoV-2 Spike glycoprotein in human and in a panel of animal models, i.e. guinea pig, dog, cat, rat, rabbit, ferret, mouse, hamster and macaque. Here we showed that ACE2, but not TMPRSS2 or Furin, has a higher level of sequence variability in the Spike protein interaction surface, which greatly influences Spike protein binding mode. Using molecular docking simulations we compared the SARS-CoV and SARS-CoV-2 Spike proteins in complex with the ACE2 receptor and showed that the SARS-CoV-2 Spike glycoprotein is compatible to bind the human ACE2 with high specificity. In contrast, TMPRSS2 and Furin are sufficiently similar in the considered hosts not to drive susceptibility differences. Computational analysis of binding modes and protein contacts indicates that macaque, ferrets and hamster are the most suitable models for the study of inhibitory antibodies and small molecules targeting the SARS-CoV-2 Spike protein interaction with ACE2. Since TMPRSS2 and Furin are similar across species, our data also suggest that transgenic animal models expressing human ACE2, such as the hACE2 transgenic mouse, are also likely to be useful models for studies investigating viral entry.


Assuntos
Betacoronavirus/genética , Infecções por Coronavirus/veterinária , Pandemias/veterinária , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/veterinária , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/metabolismo , Sequência de Aminoácidos/genética , Animais , Gatos , Biologia Computacional/métodos , Infecções por Coronavirus/patologia , Cricetinae , Modelos Animais de Doenças , Cães , Furões , Furina/genética , Furina/metabolismo , Cobaias , Humanos , Macaca fascicularis , Camundongos , Simulação de Acoplamento Molecular , Peptidil Dipeptidase A/genética , Pneumonia Viral/patologia , Coelhos , Ratos , Serina Endopeptidases/genética , Serina Endopeptidases/metabolismo
12.
Am J Vet Res ; 81(10): 810-820, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32969725

RESUMO

OBJECTIVE: To characterize the biochemical, functional, and histopathologic changes associated with lomustine-induced liver injury in dogs. ANIMALS: I0 healthy purpose-bred sexually intact female hounds. PROCEDURES: Dogs were randomly assigned to receive lomustine (approx 75 mg/m2, PO, q 21 d for 5 doses) alone (n = 5) or with prednisone (approx 1.5 mg/kg, PO, q 24 h for 12 weeks; 5). For each dog, a CBC, serum biochemical analysis, liver function testing, urinalysis, and ultrasonographic examination of the liver with acquisition of liver biopsy specimens were performed before and at predetermined times during and after lomustine administration. Results were compared between dogs that did and did not receive prednisone. RESULTS: 7 of the I0 dogs developed clinical signs of liver failure. For all dogs, serum alanine aminotransferase (ALT) and alkaline phosphatase (ALP) activities, bile acid concentrations, and liver histologic score increased and hepatic reduced glutathione content decreased over time. Peak serum ALT (r = 0.79) and ALP (r = 0.90) activities and bile acid concentration (r = 0.68) were positively correlated with the final histologic score. Prednisone did not appear to have a protective effect on histologic score. CONCLUSIONS AND CLINICAL RELEVANCE: In dogs, liver enzyme activities, particularly ALT and ALP activities, should be closely monitored during lomustine treatment and acute increases in those activities may warrant discontinuation of lomustine to mitigate liver injury. Nonspecific ultrasonographic findings and abnormal increases in liver function tests were not detected until the onset of clinical liver failure. Glutathione depletion may have a role in lomustine-induced hepatopathy and warrants further investigation.


Assuntos
Doença Hepática Crônica Induzida por Substâncias e Drogas/veterinária , Doenças do Cão/induzido quimicamente , Doenças do Cão/tratamento farmacológico , Lomustina , Alanina Transaminase , Fosfatase Alcalina , Animais , Cães , Feminino , Fígado , Lomustina/efeitos adversos
13.
Vet Res ; 51(1): 110, 2020 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-32883344

RESUMO

Canine parvovirus (CPV) can cause acute and highly contagious bloody enteritis in dog. To obtain antibodies against CPV, hens were immunized with virus-like particles (VLP) of CPV-VP2. The IgY single chain fragment variables (scFv) were generated by T7 phage display system and expressed in E. coli system. The titer of the primary scFv library reached to 1.5 × 106 pfu/mL, and 95% of the phages contained the target fragments. The CPV-VLP and CPV-VP2 protein showed similar reaction values to the purified scFv in the ELISA test, and the results of ELISA analysis using IgY-scFv toward CPV clinical samples were consistent with commercial immunochromatographic assay (ICA) and PCR detection, the scFv did not show cross reactivity with canine distemper virus (CDV) and canine coronavirus (CCV). IgY-scFv was successfully expressed in CRFK cells, and in the virus suppression assay, 55% of CPV infections were eliminated within 24 h. Docking results demonstrated that the number of amino acids of the binding sides between scFv and VP2 were AA37 and AA40, respectively. This study revealed the feasibility of a novel functional antibody fragment development strategy by generating diversified avian IgY-scFv libraries towards the pathogenic target of interest for both detection and therapeutic purposes in veterinary medicine.


Assuntos
Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Proteínas do Capsídeo/imunologia , Doenças do Cão/virologia , Imunoglobulinas/imunologia , Infecções por Parvoviridae/veterinária , Parvovirus Canino/imunologia , Anticorpos de Cadeia Única/imunologia , Animais , Galinhas/imunologia , Doenças do Cão/diagnóstico , Doenças do Cão/imunologia , Cães , Ensaio de Imunoadsorção Enzimática/veterinária , Feminino , Simulação de Acoplamento Molecular , Infecções por Parvoviridae/diagnóstico , Infecções por Parvoviridae/imunologia , Infecções por Parvoviridae/virologia , Anticorpos de Cadeia Única/genética
14.
Sci Adv ; 6(35): eaba7910, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32923629

RESUMO

Targeting a universal host protein exploited by most viruses would be a game-changing strategy that offers broad-spectrum solution and rapid pandemic control including the current COVID-19. Here, we found a common YxxØ-motif of multiple viruses that exploits host AP2M1 for intracellular trafficking. A library chemical, N-(p-amylcinnamoyl)anthranilic acid (ACA), was identified to interrupt AP2M1-virus interaction and exhibit potent antiviral efficacy against a number of viruses in vitro and in vivo, including the influenza A viruses (IAVs), Zika virus (ZIKV), human immunodeficiency virus, and coronaviruses including MERS-CoV and SARS-CoV-2. YxxØ mutation, AP2M1 depletion, or disruption by ACA causes incorrect localization of viral proteins, which is exemplified by the failure of nuclear import of IAV nucleoprotein and diminished endoplasmic reticulum localization of ZIKV-NS3 and enterovirus-A71-2C proteins, thereby suppressing viral replication. Our study reveals an evolutionarily conserved mechanism of protein-protein interaction between host and virus that can serve as a broad-spectrum antiviral target.


Assuntos
Proteínas Adaptadoras de Transporte Vesicular/metabolismo , Antivirais/farmacologia , Cinamatos/farmacologia , Infecções por Coronavirus/tratamento farmacológico , Infecções por HIV/tratamento farmacológico , Influenza Humana/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , ortoaminobenzoatos/farmacologia , Células A549 , Animais , Betacoronavirus/efeitos dos fármacos , Sítios de Ligação/genética , Linhagem Celular Tumoral , Chlorocebus aethiops , Infecções por Coronavirus/patologia , Cães , Células HEK293 , Infecções por HIV/patologia , HIV-1/efeitos dos fármacos , Interações Hospedeiro-Patógeno/efeitos dos fármacos , Humanos , Vírus da Influenza A/efeitos dos fármacos , Influenza Humana/patologia , Células Madin Darby de Rim Canino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Knockout , Coronavírus da Síndrome Respiratória do Oriente Médio/efeitos dos fármacos , Pandemias , Pneumonia Viral/patologia , Ligação Proteica/genética , Transporte Proteico/efeitos dos fármacos , RNA Viral/genética , Receptor de Interferon alfa e beta/genética , Fator de Crescimento Transformador beta1/metabolismo , Células Vero , Replicação Viral/efeitos dos fármacos , Zika virus/efeitos dos fármacos , Infecção por Zika virus/patologia
15.
J Transl Med ; 18(1): 358, 2020 09 21.
Artigo em Inglês | MEDLINE | ID: mdl-32957995

RESUMO

COVID-19 caused by a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) originated in Wuhan (Hubei province, China) during late 2019. It has spread across the globe affecting nearly 21 million people with a toll of 0.75 million deaths and restricting the movement of most of the world population during the past 6 months. COVID-19 became the leading health, economic, and humanitarian challenge of the twenty-first century. In addition to the considerable COVID-19 cases, hospitalizations, and deaths in humans, several cases of SARS-CoV-2 infections in animal hosts (dog, cat, tiger, lion, and mink) have been reported. Thus, the concern of pet owners is increasing. Moreover, the dynamics of the disease requires further explanation, mainly concerning the transmission of the virus from humans to animals and vice versa. Therefore, this study aimed to gather information about the reported cases of COVID-19 transmission in animals through a literary review of works published in scientific journals and perform genomic and phylogenetic analyses of SARS-CoV-2 isolated from animal hosts. Although many instances of transmission of the SARS-CoV-2 have been reported, caution and further studies are necessary to avoid the occurrence of maltreatment in animals, and to achieve a better understanding of the dynamics of the disease in the environment, humans, and animals. Future research in the animal-human interface can help formulate and implement preventive measures to combat the further transmission of COVID-19.


Assuntos
Betacoronavirus , Infecções por Coronavirus/veterinária , Pandemias/veterinária , Pneumonia Viral/veterinária , Zoonoses/transmissão , Criação de Animais Domésticos , Animais , Betacoronavirus/classificação , Betacoronavirus/genética , Betacoronavirus/patogenicidade , Gatos , Coronavirus/classificação , Coronavirus/genética , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/transmissão , Reservatórios de Doenças/veterinária , Reservatórios de Doenças/virologia , Cães , Genoma Viral , Humanos , Vison/virologia , Países Baixos/epidemiologia , Exposição Ocupacional , Animais de Estimação/virologia , Filogenia , Pneumonia Viral/epidemiologia , Pneumonia Viral/transmissão , Glicoproteína da Espícula de Coronavírus/genética , Pesquisa Médica Translacional , Zoonoses/epidemiologia
16.
J Endod ; 46(9S): S135-S142, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32950185

RESUMO

We showed the safety and efficacy of pulp regenerative therapy by the autologous transplantation of mobilized dental pulp stem cells with granulocyte colony-stimulating factor in a pilot clinical study of young and middle-aged pulpectomized teeth. An experimental study in dogs further demonstrated an age-dependent decline in the amount of regenerated pulp tissue. In our society, in which people will soon live beyond 100 years, this therapy should be efficacious for contributing to the functional survival and endurance of the tooth not only for pulpectomized young teeth but also for aged teeth with periapical disease. However, there are 2 challenges: 1 is enhancing pulp regeneration in aged teeth, and another is complete disinfection before cell transplantation. Thus, this review presents trypsin pretreatment for the former and a novel irrigant, nanobubbles with antibacterial nanopolymers, for the latter, thus demonstrating potential utility for pulp regenerative therapy in aged teeth with periapical disease.


Assuntos
Polpa Dentária , Transplante de Células-Tronco , Envelhecimento , Animais , Cães , Regeneração
17.
Yonsei Med J ; 61(9): 797-804, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32882764

RESUMO

PURPOSE: Climate and lifestyle changes increase an individual's susceptibility to various allergens and also the incidence of allergic diseases. We aimed to examine the changes in sensitization rate for aeroallergens over a 10-year period in Korean children. MATERIALS AND METHODS: We retrospectively reviewed the medical records of 4493 children who visited the allergy clinic at a tertiary hospital in Korea for allergic rhinitis or asthma from January 2009 to December 2018. The serum specific immunoglobulin E (IgE) levels were measured to confirm the sensitization against Dermatophagoides farinae (D. farinae), Alternaria, weed and tree pollen mixtures, as well as cat and dog dander through ImmunoCAP test. RESULTS: D. farinae was the most common sensitizing aeroallergen (45.9%) during the 10-year span. The sensitization rate for tree pollen mixture (p for trend <0.001), weed pollen mixtures (p for trend <0.001), dog dander (p for trend=0.025), and cat dander (p for trend=0.003) showed ascending trends during the 10-year study period. Furthermore, the sensitization rate for multiple allergens (≥2) in 2018 increased significantly compared to that in 2009 (p for trend=0.013). Compared with children without sensitization to D. farinae, those with sensitization to D. farinae showed higher sensitization rates to other aeroallergens (p for interaction <0.001). CONCLUSION: Children's sensitization rate to cat and dog dander and weed and tree pollen mixtures significantly increased during the 10-year period in Korea. Children with sensitization to D. farinae are likely to be sensitized to other aeroallergens as well.


Assuntos
Alérgenos/imunologia , Asma/imunologia , Hipersensibilidade/diagnóstico , Imunoglobulina E/sangue , Rinite Alérgica/imunologia , Alérgenos/efeitos adversos , Animais , Asma/diagnóstico , Asma/epidemiologia , Gatos , Criança , Dermatophagoides farinae , Cães , Feminino , Humanos , Hipersensibilidade/imunologia , Masculino , Pólen/imunologia , República da Coreia/epidemiologia , Estudos Retrospectivos , Rinite Alérgica/diagnóstico
18.
Pharm Res ; 37(10): 194, 2020 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-32918191

RESUMO

PURPOSE: We characterized three canine P-gp (cP-gp) deficient MDCKII cell lines. Their relevance for identifying efflux transporter substrates and predicting limitation of brain penetration were evaluated. In addition, we discuss how compound selection can be done in drug discovery by using these cell systems. METHOD: hMDR1, hBCRP-transfected, and non-transfected MDCKII ZFN cells (all with knock-down of endogenous cP-gp) were used for measuring permeability and efflux ratios for substrates. The compounds were also tested in MDR1_Caco-2 and BCRP_Caco-2, each with a double knock-out of BCRP/MRP2 or MDR1/MRP2 transporters respectively. Efflux results were compared between the MDCK and Caco-2 models. Furthermore, in vitro MDR1_ZFN efflux data were correlated with in vivo unbound drug brain-to-plasma partition coefficient (Kp,uu). RESULTS: MDR1 and BCRP substrates are correctly classified and robust transporter affinities with control substrates are shown. Cell passage mildly influenced mRNA levels of transfected transporters, but the transporter activity was proven stable for several years. The MDCK and Caco-2 models were in high consensus classifying same efflux substrates. Approx. 80% of enlisted substances were correctly predicted with the MDR1_ZFN model for brain penetration. CONCLUSION: cP-gp deficient MDCKII ZFN models are reliable tools to identify MDR1 and BCRP substrates and useful for predicting efflux liability for brain penetration.


Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/deficiência , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/metabolismo , Avaliação Pré-Clínica de Medicamentos/métodos , Proteínas de Neoplasias/metabolismo , Farmacocinética , Subfamília B de Transportador de Cassetes de Ligação de ATP/antagonistas & inibidores , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Subfamília B de Transportador de Cassetes de Ligação de ATP/metabolismo , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/antagonistas & inibidores , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/genética , Animais , Barreira Hematoencefálica/metabolismo , Encéfalo/metabolismo , Células CACO-2 , Permeabilidade da Membrana Celular , Dibenzocicloeptenos/farmacologia , Dicetopiperazinas/farmacologia , Cães , Compostos Heterocíclicos de 4 ou mais Anéis/farmacologia , Humanos , Células Madin Darby de Rim Canino , Proteínas de Neoplasias/antagonistas & inibidores , Proteínas de Neoplasias/genética , Prazosina/farmacocinética , Quinidina/farmacocinética , Quinolinas/farmacologia , Especificidade por Substrato , Transfecção
19.
Ther Umsch ; 77(7): 289-296, 2020 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-32996428

RESUMO

The Discovery of Insulin Abstract. The initiative for the work that led to the discovery of insulin in Toronto in 1921 came from Frederik G. Banting. He worked under the direction of John J. R. Macleod in the Institute of Physiology at the University of Toronto. In his experimental program he was assisted by the student Charles H. Best. On dogs with experimental diabetes they demonstrated the blood sugar-lowering effect of pancreatic extracts. Thanks to collaboration with Macleod and James B. Collip, a biochemist from the University of Alberta who was on sabbatical in Toronto, the work was quickly crowned with success and the first clinical applications of the extracts became possible in early 1922. As early as 1923, Banting and Macleod were awarded the Nobel Prize for Physiology or Medicine. Banting shared his half of the prize with Best, while Macleod shared his half with Collip. That their research was crowned with success is probably due in large part to Banting's abilities as a surgeon, Best's enthusiasm as a student, Collip's abilities as a biochemist and Macleod's prudence in bringing the group together and providing it with the necessary resources. In the 1950s, important advances were made in insulin research that were to spur further research in diabetology. These included the clarification of insulin structure and the possibility of measuring insulin in the blood. These two discoveries were awarded the Nobel Prize for Chemistry (see Kasten 1). In the 1960s-70s, insulin manufacturers developed ever better purification methods, which eventually led to preparations with very good tolerability and only very rare allergies. Later, in the 1980s, the possibility of biotechnological production of insulin led to an ever-increasing spread of human insulin. Based on the same technology, insulin analogues were produced in the 1990s and then in the new millennium, which, as "designer insulins" so to speak, enabled new clinically interesting active profiles. Today's variety of available insulins, modern forms of insulin application (insulin pens, insulin pumps) and blood glucose self-monitoring or continuous glucose monitoring form the basis of modern intensive insulin therapy.


Assuntos
Automonitorização da Glicemia , Insulina , Animais , Glicemia , Cães , Emoções , Humanos , Prêmio Nobel
20.
MMWR Morb Mortal Wkly Rep ; 69(38): 1374-1377, 2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-32970659

RESUMO

Although canine rabies virus variant (CRVV) was successfully eliminated from the United States after approximately 6 decades of vaccination campaigns, licensing requirements, and stray animal control, dogs remain the principal source of human rabies infections worldwide. A rabies vaccination certificate is required for dogs entering the United States from approximately 100 countries with endemic CRVV, including Egypt (1). On February 25, 2019, rabies was diagnosed in a dog imported from Egypt, representing the third canine rabies case imported from Egypt in 4 years (2,3). This dog and 25 others were imported by a pet rescue organization in the Kansas City metropolitan area on January 29. Upon entry into the United States, all 26 dogs had certificates of veterinary inspection, rabies vaccination certificates, and documentation of serologic conversion from a government-affiliated rabies laboratory in Egypt. CDC confirmed that the dog was infected with a CRVV that circulates in Egypt, underscoring the continued risk for CRVV reintroduction and concern regarding the legitimacy of vaccine documentation of dogs imported from countries considered at high risk for CRVV. Vaccination documentation of dogs imported from these countries should be critically evaluated before entry into the United States is permitted, and public health should be consulted upon suspicion of questionable documents.


Assuntos
Doenças Transmissíveis Importadas/veterinária , Doenças do Cão/diagnóstico , Raiva/veterinária , Animais , Doenças Transmissíveis Importadas/diagnóstico , Cães , Egito , Kansas , Raiva/diagnóstico
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