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1.
J Vis Exp ; (206)2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38709055

RESUMO

Mechanical ventilation is widely used and requires specific knowledge for understanding and management. Health professionals in this field may feel insecure and lack knowledge because of inadequate training and teaching methods. Therefore, the objective of this article is to outline the steps involved in generating an ex vivo porcine lung model to be used in the future, to study and teach lung mechanics. To generate the model, five porcine lungs were carefully removed from the thorax following the guidelines of the Animal Research Ethics Committee with adequate care and were connected to the mechanical ventilator through a tracheal cannula. These lungs were then subjected to the alveolar recruitment maneuver. Respiratory mechanics parameters were recorded, and video cameras were used to obtain videos of the lungs during this process. This process was repeated for five consecutive days. When not used, the lungs were kept refrigerated. The model showed different lung mechanics after the alveolar recruitment maneuver every day; not being influenced by the days, only by the maneuver. Therefore, we conclude that the ex vivo lung model can provide a better understanding of lung mechanics and its effects, and even of the alveolar recruitment maneuver through visual feedback during all stages of the process.


Assuntos
Pulmão , Mecânica Respiratória , Animais , Suínos , Pulmão/fisiologia , Mecânica Respiratória/fisiologia , Modelos Animais , Respiração Artificial/métodos
2.
J Vis Exp ; (206)2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38709079

RESUMO

Laboratory stocks of the lower dipteran fly, Bradysia (Sciara) coprophila, have been maintained for over a century. Protocols for laboratory upkeep of B. coprophila are presented here. These protocols will be useful for the rapidly increasing number of laboratories studying B. coprophila to take advantage of its unique biological features, which include (1) a monopolar spindle in male meiosis I; (2) non-disjunction of the X dyad in male meiosis II; (3) chromosome imprinting to distinguish maternal from paternal homologs; (4) germ line-limited (L) chromosomes; (5) chromosome elimination (paternal chromosomes in male meiosis I; one to two X chromosomes in early embryos; L chromosomes from the soma in early embryos); (6) sex determination by the mother (there is no Y chromosome); and (7) developmentally regulated DNA amplification at the DNA puff loci in larval salivary gland polytene chromosomes. It is now possible to explore these many unique features of chromosome mechanics by using the recent advances in sequencing and assembly of the B. coprophila genome and the development of transformation methodology for genomic engineering. The growing scientific community that uses B. coprophila for research will benefit from the protocols described here for mating the flies (phenotypic markers for mothers that will have only sons or only daughters; details of mass mating for biochemical experiments), checking embryo hatch, feeding larvae, and other comments on its rearing.


Assuntos
Dípteros , Animais , Dípteros/genética , Dípteros/fisiologia , Feminino , Masculino , Modelos Animais
3.
Eur Radiol Exp ; 8(1): 55, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38705940

RESUMO

BACKGROUND: To evaluate the reproducibility of a vessel-specific minimum cost path (MCP) technique used for lobar segmentation on noncontrast computed tomography (CT). METHODS: Sixteen Yorkshire swine (49.9 ± 4.7 kg, mean ± standard deviation) underwent a total of 46 noncontrast helical CT scans from November 2020 to May 2022 using a 320-slice scanner. A semiautomatic algorithm was employed by three readers to segment the lung tissue and pulmonary arterial tree. The centerline of the arterial tree was extracted and partitioned into six subtrees for lobar assignment. The MCP technique was implemented to assign lobar territories by assigning lung tissue voxels to the nearest arterial tree segment. MCP-derived lobar mass and volume were then compared between two acquisitions, using linear regression, root mean square error (RMSE), and paired sample t-tests. An interobserver and intraobserver analysis of the lobar measurements was also performed. RESULTS: The average whole lung mass and volume was 663.7 ± 103.7 g and 1,444.22 ± 309.1 mL, respectively. The lobar mass measurements from the initial (MLobe1) and subsequent (MLobe2) acquisitions were correlated by MLobe1 = 0.99 MLobe2 + 1.76 (r = 0.99, p = 0.120, RMSE = 7.99 g). The lobar volume measurements from the initial (VLobe1) and subsequent (VLobe2) acquisitions were correlated by VLobe1 = 0.98VLobe2 + 2.66 (r = 0.99, p = 0.160, RSME = 15.26 mL). CONCLUSIONS: The lobar mass and volume measurements showed excellent reproducibility through a vessel-specific assignment technique. This technique may serve for automated lung lobar segmentation, facilitating clinical regional pulmonary analysis. RELEVANCE STATEMENT: Assessment of lobar mass or volume in the lung lobes using noncontrast CT may allow for efficient region-specific treatment strategies for diseases such as pulmonary embolism and chronic thromboembolic pulmonary hypertension. KEY POINTS: • Lobar segmentation is essential for precise disease assessment and treatment planning. • Current methods for segmentation using fissure lines are problematic. • The minimum-cost-path technique here is proposed and a swine model showed excellent reproducibility for lobar mass measurements. • Interobserver agreement was excellent, with intraclass correlation coefficients greater than 0.90.


Assuntos
Pulmão , Animais , Suínos , Pulmão/diagnóstico por imagem , Reprodutibilidade dos Testes , Tomografia Computadorizada por Raios X/métodos , Modelos Animais , Algoritmos
4.
Arq Bras Cir Dig ; 37: e1800, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38716920

RESUMO

BACKGROUND: One of the primary complications associated with large incisions in abdominal surgery is the increased risk of fascial closure rupture and incisional hernia development. The choice of the fascial closure method and closing with minimal tension and trauma is crucial for optimal results, emphasizing the importance of uniform pressure along the suture line to withstand intra-abdominal pressure. AIMS: To evaluate the resistance to pressure and tension of stapled and sutured hand-sewn fascial closure in the abdominal wall. METHODS: Nine abdominal wall flaps from human cadavers and 12 pigs were used for the experimentation. An abdominal defect was induced after the resection of the abdominal wall and the creation of a flap in the cadaveric model and after performing a midline incision in the porcine models. The models were randomized into three groups. Group 1 was treated with a one-layer hand-sewn small bite suture, Group 2 was treated with a two-layer hand-sewn small bite suture, and Group 3 was treated with a two-layer stapled closure. Tension measurements were assessed in cadaveric models, and intra-abdominal pressure was measured in porcine models. RESULTS: In the human cadaveric model, the median threshold for fascial rupture was 300N (300-350) in Group 1, 400N (350-500) in Group 2, and 350N (300-380) in Group 3. Statistical comparisons revealed non-significant differences between Group 1 and Group 2 (p=0.072, p>0.05), Group 1 and Group 3 (p=0.346, p>0.05), and Group 2 and Group 3 (p=0.184, p>0.05). For porcine subjects, Group 1 showed a median pressure of 80 mmHg (85-105), Group 2 had a median of 92.5 mmHg (65-95), and Group 3 had a median of 102.5 mmHg (80-135). Statistical comparisons indicated non-significant differences between Group 1 and Group 2 (p=0.243, p>0.05), Group 1 and Group 3 (p=0.468, p>0.05), and Group 2 and Group 3 (p=0.083, p>0.05). CONCLUSIONS: Stapled and conventional suturing resist similar pressure and tension thresholds.


Assuntos
Parede Abdominal , Cadáver , Técnicas de Sutura , Humanos , Animais , Suínos , Parede Abdominal/cirurgia , Técnicas de Fechamento de Ferimentos Abdominais , Grampeamento Cirúrgico , Modelos Animais , Fasciotomia/métodos , Feminino , Masculino
5.
J Exp Med ; 221(7)2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38713202

RESUMO

A method to precisely determine which cells respond to chemokines in vivo is currently lacking. A novel class of dual fluorescence reporter mice could help identify cells that produce and/or sense a given chemokine in vitro and in vivo (Rodrigo et al. 2024. J. Exp. Med.https://doi.org/10.1084/jem.20231814).


Assuntos
Quimiocinas , Animais , Camundongos , Quimiocinas/metabolismo , Modelos Animais
6.
Sci Rep ; 14(1): 10060, 2024 05 02.
Artigo em Inglês | MEDLINE | ID: mdl-38698246

RESUMO

This study aimed to evaluate the safety and efficiency of hybrid endoscopic submucosal dissection (H-ESD) using a newly developed ALL IN ONE (AIO) snare. This was a matched control study in a porcine model. Five paired simulated stomach lesions 2-2.5 cm in size were removed by H-ESD using an AIO snare or conventional ESD (C-ESD) using an endoscopic knife. The outcomes of the two procedures were compared, including en-bloc resection rates, procedure times, intraprocedural bleeding volumes, muscular injuries, perforations, thicknesses of the submucosal layer in resected specimens, and stomach defects. All simulated lesions were resected en-bloc. Specimens resected by H-ESD and C-ESD were similar in size (7.68 ± 2.92 vs. 8.42 ± 2.42 cm2; P = 0.676). H-ESD required a significantly shorter procedure time (13.39 ± 3.78 vs. 25.99 ± 4.52 min; P = 0.031) and submucosal dissection time (3.99 ± 1.73 vs. 13.1 ± 4.58 min; P = 0.003) versus C-ESD; H-ESD also yielded a faster dissection speed (241.37 ± 156.84 vs. 68.56 ± 28.53 mm2/min; P = 0.042) and caused fewer intraprocedural bleeding events (0.40 ± 0.55 vs. 3.40 ± 1.95 times/per lesion; P = 0.016) than C-ESD. The thicknesses of the submucosal layer of the resected specimen (1190.98 ± 134.07 vs. 1055.90 ± 151.76 µm; P = 0.174) and the residual submucosal layer of the stomach defect (1607.94 ± 1026.74 vs. 985.98 ± 445.58 µm; P = 0.249) were similar with both procedures. The AIO snare is a safe and effective device for H-ESD and improves the treatment outcomes of gastric lesions by shortening the procedure time.


Assuntos
Ressecção Endoscópica de Mucosa , Mucosa Gástrica , Animais , Ressecção Endoscópica de Mucosa/métodos , Ressecção Endoscópica de Mucosa/efeitos adversos , Ressecção Endoscópica de Mucosa/instrumentação , Suínos , Mucosa Gástrica/cirurgia , Gastroscopia/métodos , Duração da Cirurgia , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/patologia , Estômago/cirurgia , Modelos Animais
7.
Gut Microbes ; 16(1): 2351520, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38717832

RESUMO

Links between the gut microbiota and human health have been supported throughout numerous studies, such as the development of neurological disease disorders. This link is referred to as the "microbiota-gut-brain axis" and is the focus of an emerging field of research. Microbial-derived metabolites and gut and neuro-immunological metabolites regulate this axis in health and many diseases. Indeed, assessing these signals, whether induced by microbial metabolites or neuro-immune mediators, could significantly increase our knowledge of the microbiota-gut-brain axis. However, this will require the development of appropriate techniques and potential models. Methods for studying the induced signals originating from the microbiota remain crucial in this field. This review discusses the methods and techniques available for studies of microbiota-gut-brain interactions. We highlight several much-debated elements of these methodologies, including the widely used in vivo and in vitro models, their implications, and perspectives in the field based on a systematic review of PubMed. Applications of various animal models (zebrafish, mouse, canine, rat, rabbit) to microbiota-gut-brain axis research with practical examples of in vitro methods and innovative approaches to studying gut-brain communications are highlighted. In particular, we extensively discuss the potential of "organ-on-a-chip" devices and their applications in this field. Overall, this review sheds light on the most widely used models and methods, guiding researchers in the rational choice of strategies for studies of microbiota-gut-brain interactions.


Assuntos
Eixo Encéfalo-Intestino , Microbioma Gastrointestinal , Interações entre Hospedeiro e Microrganismos , Animais , Microbioma Gastrointestinal/fisiologia , Eixo Encéfalo-Intestino/fisiologia , Humanos , Encéfalo/microbiologia , Encéfalo/metabolismo , Encéfalo/fisiologia , Trato Gastrointestinal/microbiologia , Trato Gastrointestinal/metabolismo , Modelos Animais , Camundongos
8.
Sci Rep ; 14(1): 10636, 2024 05 09.
Artigo em Inglês | MEDLINE | ID: mdl-38724644

RESUMO

Gene-knockout animal models with organ-deficient phenotypes used for blastocyst complementation are generally not viable. Animals need to be maintained as heterozygous mutants, and homozygous mutant embryos yield only one-fourth of all embryos. In this study, we generated organ-deficient embryos using the CRISPR-Cas9-sgRNAms system that induces cell death with a single-guide RNA (sgRNAms) targeting multiple sites in the genome. The Cas9-sgRNAms system interrupted cell proliferation and induced cell ablation in vitro. The mouse model had Cas9 driven by the Foxn1 promoter with a ubiquitous expression cassette of sgRNAms at the Rosa26 locus (Foxn1Cas9; Rosa26_ms). It showed an athymic phenotype similar to that of nude mice but was not hairless. Eventually, a rat cell-derived thymus in an interspecies chimera was generated by blastocyst complementation of Foxn1Cas9; Rosa26_ms mouse embryos with rat embryonic stem cells. Theoretically, a half of the total embryos has the Cas9-sgRNAms system because Rosa26_ms could be maintained as homozygous.


Assuntos
Sistemas CRISPR-Cas , Fatores de Transcrição Forkhead , RNA Guia de Sistemas CRISPR-Cas , Animais , Camundongos , Ratos , RNA Guia de Sistemas CRISPR-Cas/genética , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/metabolismo , Timo/metabolismo , Modelos Animais , Blastocisto/metabolismo
9.
Neurología (Barc., Ed. impr.) ; 39(4): 329-339, May. 2024. ilus, tab, graf
Artigo em Inglês | IBECS | ID: ibc-232515

RESUMO

Introduction: In the present study, anticonvulsant effects of aqueous extract (AE), hydro-alcoholic crude extract (HE), and its fractions (F-CHCl3, F-EtOAc, F-MeOH) of Paeonia daurica subsp. macrophylla (P. daurica ssp. macrophylla) root examined by using a pentylenetetrazol-induced model (PTZ) on mice. Methods: HE and its fractions as well as AE, in concentrations of (100, 200 and 400 mg/kg), valproate (Val) (100 and 200 mg/kg), and saline (negative control) (10 mg/kg) were injected intraperitoneally (i.p.) 30 min before PTZ (80 mg/kg, i.p.). The time taken before the onset of myoclonic convulsions (MC), MC duration, time taken before the onset of generalized tonic-clonic seizures (GTCS), the duration of GTCS, and the percentage of GTCS and mortality protection recorded. The plant's anticonvulsant mechanisms were assessed using flumazenil (5 mg/kg, i.p.) before AE (100, 200, and 400 mg/kg, i.p.) injection. GraphPad Prism software was used to compare the differences between various treatment groups with one-way analysis of variance (ANOVA) followed by Tukey–Krammer multiple comparison tests. Results: All the plant samples except F-EtOAc significantly delayed the onset and decreased the duration of PTZ-induced MCS and GTCS, and significantly reduced the GTCS and mortality rate. Pretreatment with flumazenil diminished the significant anticonvulsant effects of AE against PTZ-induced seizures. Conclusions: It can report that extract of P. daurica ssp. macrophylla might be a helpful guide for future studies in the treatment of epilepsy.(AU)


Introducción: Epilepsia es el término usado para un grupo de trastornos caracterizado por las convulsiones espontáneas recurrentes. Un estudio enfocado en los productos naturales de los recursos tradicionales ofrece ventajas significativas que se están utilizando de manera más amplia en modelos animales de epilepsia y candidatos a mayor desarrollo clínico y sus fracciones (F-CHCl3, F-EtOAc, F-MeOH) de Paeonia daurica subsp. macrophylla (P. daurica ssp. macrophylla) raíz examinada utilizando un modelo inducido por pentilentetrazol (PTZ) en ratones. Métodos: La maceración dinámica utilizada para extraer HE de la planta y técnica de cromatografía en columna de sílice utilizada para obtener F-CHCl3, F-EtOAc, así como fracciones de F-MeOH. La extracción de raíces secas se utilizó con agua destilada y se provocó AE. Las muestras de plantas (100, 200 y 400 mg/kg), valproato (Val) (100 y 200 mg/kg) y suero (control negativo) se inyectaron por vía intraperitoneal (ip) 30 min antes de PTZ (80 mg/kg, ip). El tiempo transcurrido antes del comienzo de convulsiones mioclónicas (MC), duración de las MC, tiempo transcurrido antes del comienzo de convulsiones tónico-clónicas generalizadas (GTCS), la duración de GTCS, así como el porcentaje de GTCS y protección contra la mortalidad registrada. Los mecanismos anticonvulsivos de planta fueron evaluados mediante el uso de flumazenil (5 mg/kg, ip) antes de AE (100, 200 y 400 mg/kg, ip) inyección. Se utilizaba el software GraphPad Prism® comparando las diferencias entre varios grupos de tratamiento con un análisis unilateral de variación (ANOVA) seguido por las pruebas de comparación múltiple de Tukey's Krammer. Resultados: Todas las muestras de plantas, excepto F-EtOAc, retrasaron de manera considerable el inicio, y disminuyeron la duración de PTZ inducidos por MCS y GTCS, y redujo significativamente el GTCS, así como la tasa de mortalidad...(AU)


Assuntos
Animais , Anticonvulsivantes , Convulsões , Epilepsia/tratamento farmacológico , Flumazenil/uso terapêutico , Receptores de GABA , Paeonia , Neurologia , Doenças do Sistema Nervoso , Modelos Animais
10.
Methods Mol Biol ; 2794: 331-340, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38630242

RESUMO

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder characterized by social deficits and stereotyped, repetitive patterns of behaviors, limited interests, and cognitive impairment. Especially, social deficit has been considered a core feature of ASD. Because of the limitations of the experimental approach in humans, valid animal models are essential in an effort to identify novel therapeutics for social deficits in ASD. The genetic and environmental factors are clinically relevant to the pathophysiology of ASD. Epidemiological studies demonstrate environmental interventions such as prenatal exposure to valproic acid (VPA). Prenatal exposure to VPA represents a robust model of ASD exhibiting face, construct, and predictive validity. Here, we introduce protocols of the social interaction test and the three-chamber test for evaluating social deficits in mice prenatally exposed to VPA.


Assuntos
Transtorno do Espectro Autista , Disfunção Cognitiva , Efeitos Tardios da Exposição Pré-Natal , Humanos , Feminino , Gravidez , Animais , Camundongos , Transtorno do Espectro Autista/genética , Comportamento Social , Modelos Animais , Ácido Valproico/uso terapêutico
11.
World J Gastroenterol ; 30(10): 1420-1430, 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38596496

RESUMO

BACKGROUND: Various animal models have been used to explore the pathogenesis of choledochal cysts (CCs), but with little convincing results. Current surgical techniques can achieve satisfactory outcomes for treatment of CCs. Consequently, recent studies have focused more on clinical issues rather than basic research. Therefore, we need appropriate animal models to further basic research. AIM: To establish an appropriate animal model that may contribute to the investigation of the pathogenesis of CCs. METHODS: Eighty-four specific pathogen-free female Sprague-Dawley rats were randomly allocated to a surgical group, sham surgical group, or control group. A rat model of CC was established by partial ligation of the bile duct. The reliability of the model was confirmed by measurements of serum biochemical indices, morphology of common bile ducts of the rats as well as molecular biology experiments in rat and human tissues. RESULTS: Dilation classified as mild (diameter, ≥ 1 mm to < 3 mm), moderate (≥ 3 mm to < 10 mm), and severe (≥ 10 mm) was observed in 17, 17, and 2 rats in the surgical group, respectively, while no dilation was observed in the control and sham surgical groups. Serum levels of alanine aminotransferase, aspartate aminotransferase, total bilirubin, direct bilirubin, and total bile acids were significantly elevated in the surgical group as compared to the control group 7 d after surgery, while direct bilirubin, total bilirubin, and gamma-glutamyltransferase were further increased 14 d after surgery. Most of the biochemical indices gradually decreased to normal ranges 28 d after surgery. The protein expression trend of signal transducer and activator of transcription 3 in rat model was consistent with the human CC tissues. CONCLUSION: The model of partial ligation of the bile duct of juvenile rats could morphologically simulate the cystic or fusiform CC, which may contribute to investigating the pathogenesis of CC.


Assuntos
Cisto do Colédoco , Humanos , Feminino , Ratos , Animais , Cisto do Colédoco/cirurgia , Reprodutibilidade dos Testes , Ratos Sprague-Dawley , Modelos Animais , Dilatação Patológica , Bilirrubina , Modelos Animais de Doenças
12.
Int J Mol Sci ; 25(7)2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38612647

RESUMO

Impaired healing wounds do not proceed through the normal healing processes in a timely and orderly manner, and while they do eventually heal, their healing is not optimal. Chronic wounds, on the other hand, remain unhealed for weeks or months. In the US alone, chronic wounds impact ~8.5 million people and cost ~USD 28-90 billion per year, not accounting for the psychological and physical pain and emotional suffering that patients endure. These numbers are only expected to rise in the future as the elderly populations and the incidence of comorbidities such as diabetes, hypertension, and obesity increase. Over the last few decades, scientists have used a variety of approaches to treat chronic wounds, but unfortunately, to date, there is no effective treatment. Indeed, while there are thousands of drugs to combat cancer, there is only one single drug approved for the treatment of chronic wounds. This is in part because wound healing is a very complex process involving many phases that must occur sequentially and in a timely manner. Furthermore, models that fully mimic human chronic wounds have not been developed. In this review, we assess various models currently being used to study the biology of impaired healing and chronic non-healing wounds. Among them, this paper also highlights one model which shows significant promise; this model uses aged and obese db/db-/- mice and the chronic wounds that develop show characteristics of human chronic wounds that include increased oxidative stress, chronic inflammation, damaged microvasculature, abnormal collagen matrix deposition, a lack of re-epithelialization, and the spontaneous development of multi-bacterial biofilm. We also discuss how important it is that we continue to develop chronic wound models that more closely mimic those of humans and that can be used to test potential treatments to heal chronic wounds.


Assuntos
Ansiedade , Cicatrização , Animais , Idoso , Camundongos , Humanos , Biofilmes , Emoções , Modelos Animais , Obesidade
13.
Cell Rep Med ; 5(4): 101490, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38574736

RESUMO

While neurodegeneration underlies the pathological basis for permanent disability in multiple sclerosis (MS), predictive biomarkers for progression are lacking. Using an animal model of chronic MS, we find that synaptic injury precedes neuronal loss and identify thinning of the inner plexiform layer (IPL) as an early feature of inflammatory demyelination-prior to symptom onset. As neuronal domains are anatomically segregated in the retina and can be monitored longitudinally, we hypothesize that thinning of the IPL could represent a biomarker for progression in MS. Leveraging our dataset with over 800 participants enrolled for more than 12 years, we find that IPL atrophy directly precedes progression and propose that synaptic loss is predictive of functional decline. Using a blood proteome-wide analysis, we demonstrate a strong correlation between demyelination, glial activation, and synapse loss independent of neuroaxonal injury. In summary, monitoring synaptic injury is a biologically relevant approach that reflects a potential driver of progression.


Assuntos
Esclerose Múltipla , Animais , Humanos , Esclerose Múltipla/patologia , Retina/patologia , Neurônios/patologia , Modelos Animais , Atrofia/patologia
14.
PLoS One ; 19(4): e0300360, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38626145

RESUMO

Bisphosphonates are commonly used to treat and prevent bone loss, but their effects in active, juvenile populations are unknown. This study examined the effects of intramuscular clodronate disodium (CLO) on bone turnover, serum bone biomarkers (SBB), bone mineral density (BMD), bone microstructure, biomechanical testing (BT), and cartilage glycosaminoglycan content (GAG) over 165 days. Forty juvenile sheep (253 ± 6 days of age) were divided into four groups: Control (saline), T0 (0.6 mg/kg CLO on day 0), T84 (0.6 mg/kg CLO on day 84), and T0+84 (0.6 mg/kg CLO on days 0 and 84). Sheep were exercised 4 days/week and underwent physical and lameness examinations every 14 days. Blood samples were collected for SBB every 28 days. Microstructure and BMD were calculated from tuber coxae (TC) biopsies (days 84 and 165) and bone healing was assessed by examining the prior biopsy site. BT and GAG were evaluated postmortem. Data, except lameness data, were analyzed using a mixed-effects model; lameness data were analyzed as ordinal data using a cumulative logistic model. CLO did not have any measurable effects on the skeleton of sheep. SBB showed changes over time (p ≤ 0.03), with increases in bone formation and decreases in some bone resorption markers. TC biopsies showed increasing bone volume fraction, trabecular spacing and thickness, and reduced trabecular number on day 165 versus day 84 (p ≤ 0.04). These changes may be attributed to exercise or growth. The absence of a treatment effect may be explained by the lower CLO dose used in large animals compared to humans. Further research is needed to examine whether low doses of bisphosphonates may be used in active juvenile populations for analgesia without evidence of bone changes.


Assuntos
Ácido Clodrônico , Coxeadura Animal , Humanos , Animais , Ovinos , Ácido Clodrônico/farmacologia , Coxeadura Animal/tratamento farmacológico , Densidade Óssea , Difosfonatos/farmacologia , Modelos Animais
16.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 49(1): 47-53, 2024 Jan 28.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-38615165

RESUMO

Trigeminal neuralgia is a manifestation of orofacial neuropathic pain disorder, always deemed to be an insurmountable peak in the field of pain research and treatment. The pain is recurrent, abrupt in onset and termination similar to an electric shock or described as shooting. A poor quality of life has been attributed to trigeminal neuralgia, as the paroxysms of pain may be triggered by innocuous stimuli on the face or inside the oral cavity, such as talking, washing face, chewing and brushing teeth in daily life. The pathogenesis of trigeminal neuralgia has not been fully elucidated, although the microvascular compression in the trigeminal root entry zone is generally considered to be involved in the emergence and progression of the pain disorder. In addition, orofacial neuropathic pain restricted to one or more divisions of the trigeminal nerve might be secondary to peripheral nerve injury. Based on current hypotheses regarding the potential causes, a variety of animal models have been designed to simulate the pathogenesis of trigeminal neuralgia, including models of compression applied to the trigeminal nerve root or trigeminal ganglion, chronic peripheral nerve injury, peripheral inflammatory pain and center-induced pain. However, it has not yet been possible to determine which model can be perfectly employed to explain the mechanisms. The selection of appropriate animal models is of great significance for the study of trigeminal neuralgia. Therefore, it is necessary to discuss the characteristics of the animal models in terms of animal strains, materials, operation methods and behavior observation, in order to gain insight into the research progress in animal models of trigeminal neuralgia. In the future, animal models that closely resemble the features of human trigeminal neuralgia pathogenesis need to be developed, with the aim of making valuable contributions to the relevant basic and translational medical research.


Assuntos
Neuralgia , Traumatismos dos Nervos Periféricos , Neuralgia do Trigêmeo , Animais , Humanos , Qualidade de Vida , Mastigação , Modelos Animais
17.
Int J Med Sci ; 21(5): 958-964, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38617003

RESUMO

Nowadays dog bite is becoming a world public health problem. Therefore, the study aimed to develop a dog bite animal model that is helpful to solve these problems. In this study, the skull of an adult dog was scanned. The three-dimensional model of the dog maxillofacial bones and dentition was built by MIMICS. Next, the model was printed with Co-Cr alloy by using selective laser sintering technology to develop the dog bite simulation pliers. Then, to simulate dog bite to most, the maximum bite force of the pliers was measured and actions contained in dog bite process was analyzed. Afterwards, according to action analysis results, rabbits were bitten by the prepared instrument in actions that simulate dog's bite. Finally, the reproducibility and controllability of this animal model of dog bite injuries was validated in an in vivo study. The results showed a reliable animal model of dog bite injuries has been developed in this study. The sites and severities of the injuries could be adjusted as the operator wishes and the animal model of dog bite injuries was highly repeatable. This study also indicates the feasibility of using digital technology in establishing animal bite models.


Assuntos
Mordeduras e Picadas , Crânio , Cães , Animais , Coelhos , Reprodutibilidade dos Testes , Ligas , Modelos Animais
18.
J Clin Invest ; 134(8)2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38618955

RESUMO

Capillary malformation (CM), or port wine birthmark, is a cutaneous congenital vascular anomaly that occurs in 0.1%-2% of newborns. Patients with a CM localized on the forehead have an increased risk of developing a neurocutaneous disorder called encephalotrigeminal angiomatosis or Sturge-Weber syndrome (SWS), with complications including seizure, developmental delay, glaucoma, and vision loss. In 2013, a groundbreaking study revealed causative activating somatic mutations in the gene (GNAQ) encoding guanine nucleotide-binding protein Q subunit α (Gαq) in CM and SWS patient tissues. In this Review, we discuss the disease phenotype, the causative GNAQ mutations, and their cellular origin. We also present the endothelial Gαq-related signaling pathways, the current animal models to study CM and its complications, and future options for therapeutic treatment. Further work remains to fully elucidate the cellular and molecular mechanisms underlying the formation and maintenance of the abnormal vessels.


Assuntos
Capilares/anormalidades , Glaucoma , Malformações Vasculares , Recém-Nascido , Animais , Humanos , Modelos Animais , Mutação
19.
J Int Med Res ; 52(4): 3000605241245293, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38619175

RESUMO

In recent years, the incidence of autism spectrum disorder (ASD) has increased, but the etiology and pathogenesis remain unclear. In this narrative review, we review and systematically summarize the methods used to construct animal models to study ASD and the related behavioral studies based on recent literature. Utilization of various ASD animal models can complement research on the etiology, pathogenesis, and core behaviors of ASD, providing information and a foundation for further basic research and clinical treatment of ASD.


Assuntos
Transtorno do Espectro Autista , Animais , Transtorno do Espectro Autista/genética , Modelos Animais
20.
Cell Stem Cell ; 31(4): 435-436, 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38579680

RESUMO

Lee et al.1 analyzed the impacts of lentiviral vector transduction and CRISPR-Cas9/homology-directed repair editing on hematopoietic stem and progenitor cell (HSPC) engraftment and clonal dynamics. The study suggests that relative to lentiviral-vector-mediated gene addition, homology-directed repair editing is inefficient in vivo and might impair the engraftment and differentiation of HSPCs.


Assuntos
Edição de Genes , Transplante de Células-Tronco Hematopoéticas , Animais , Humanos , Células-Tronco Hematopoéticas/metabolismo , Modelos Animais , Sistemas CRISPR-Cas/genética
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