Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 22.602
Filtrar
1.
Vet J ; 282: 105829, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35462036

RESUMO

Pelvic limb movement disorders unrelated to lameness or proprioceptive ataxia have been described in horses for centuries. The two best described are Shivering and Stringhalt. Shivering is unique in that it is primarily apparent when horses are asked to walk backward, without affecting forward gaits until quite advanced. Horses exhibit abduction and either hyperflexion or marked hyperextension of one or both pelvic limbs when walking backward, resulting in a pause at the peak of the stride cycle and reluctance to move backward. Generally, Stringhalt differs from Shivering in that it produces consistent hyperflexion without abduction in forward gaits including walk and trot. This review will focus on the two most common pelvic limb movement disorders, Shivering and Stringhalt, their clinical presentation, differential diagnosis, etiopathology, and treatment.


Assuntos
Doenças dos Cavalos , Transtornos dos Movimentos , Animais , Fenômenos Biomecânicos , Membro Anterior/patologia , Marcha , Membro Posterior , Doenças dos Cavalos/diagnóstico , Doenças dos Cavalos/patologia , Doenças dos Cavalos/terapia , Cavalos , Coxeadura Animal/diagnóstico , Coxeadura Animal/etiologia , Coxeadura Animal/terapia , Transtornos dos Movimentos/patologia , Transtornos dos Movimentos/veterinária , Tremor por Sensação de Frio , Caminhada
2.
J Vis Exp ; (181)2022 03 16.
Artigo em Inglês | MEDLINE | ID: mdl-35377355

RESUMO

Peripheral arterial disease (PAD) is a significant cause of morbidity resulting from chronic exposure to atherosclerotic risk factors. Patients suffering from its most severe form, chronic limb-threatening ischemia (CLTI), face substantial impairments to daily living, including chronic pain, limited walking distance without pain, and nonhealing wounds. Preclinical models have been developed in various animals to study PAD, but mouse hindlimb ischemia remains the most widely used. There can be significant variation in response to ischemic insult in these models depending on the mouse strain used and the site, number, and means of arterial disruption. This protocol describes a unique method combining femoral artery and vein electrocoagulation with the administration of a nitric oxide synthase (NOS) inhibitor to reliably induce footpad gangrene in Friend Virus B (FVB) mice that resembles the tissue loss of CLTI. While traditional means of assessing reperfusion such as laser Doppler perfusion imaging (LDPI) are still recommended, intracardiac perfusion of the lipophilic dye 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI) is used to label the vasculature. Subsequent whole-mount confocal laser scanning microscopy allows for high-resolution, three-dimensional (3D) reconstruction of footpad vascular networks that complements traditional means of assessing reperfusion in hindlimb ischemia models.


Assuntos
Gangrena , Imageamento Tridimensional , Animais , Artéria Femoral , Gangrena/diagnóstico por imagem , Membro Posterior/irrigação sanguínea , Membro Posterior/diagnóstico por imagem , Humanos , Extremidade Inferior , Camundongos
3.
J Exp Biol ; 225(8)2022 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-35363299

RESUMO

Animals rely on their ability to perform certain tasks sufficiently well to survive, secure mates and reproduce. Performance traits depend on morphology, and so morphological traits should predict performance, yet this relationship is often confounded by multiple competing performance demands. Males and females experience different selection pressures on performance, and the consequent sexual conflict over performance expression can either constrain performance evolution or drive sexual dimorphism in both size and shape. Furthermore, change in a single morphological trait may benefit some performance traits at the expense of others, resulting in functional trade-offs. Identifying general or sex-specific relationships between morphology and performance at the organismal level thus requires a multivariate approach, as individuals are products of both an integrated phenotype and the ecological environment in which they have developed and evolved. We estimated the multivariate morphology→performance gradient in wild-caught, green anoles (Anolis carolinensis) by measuring external morphology and forelimb and hindlimb musculature, and mapping these morphological traits to seven measured performance traits that cover the broad range of ecological challenges faced by these animals (sprint speed, endurance, exertion distance, climbing power, jump power, cling force and bite force). We demonstrate that males and females differ in their multivariate mapping of traits on performance, indicating that sex-specific ecological demands likely shape these relationships, but do not differ in performance integration.


Assuntos
Lagartos , Animais , Evolução Biológica , Força de Mordida , Feminino , Membro Anterior , Membro Posterior/anatomia & histologia , Lagartos/anatomia & histologia , Masculino , Caracteres Sexuais
4.
Commun Biol ; 5(1): 283, 2022 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-35422092

RESUMO

The taxonomically diverse terrestrial tetrapod fauna from the late Mississippian East Kirkton Limestone includes the earliest known members of stem Amphibia and stem Amniota. Here we name and describe a new East Kirkton tetrapod with an unusual hindlimb morphology reminiscent of that of several stem- and primitive crown amniotes. It displays a unique ilium with two slender and elongate processes and a 5-digit pes with a long, stout metatarsal IV and a greatly elongate digit IV. The new taxon broadens our knowledge of East Kirkton tetrapods, adding to the remarkable diversity of their hindlimb constructions, functional specializations, locomotory modes, and adaptations to a wide variety of substrates. An unweighted character parsimony analysis places the new taxon in a polytomy alongside some other Carboniferous groups. Conversely, weighted parsimony and Bayesian analyses retrieve it among the earliest diverging stem amniotes, either as the basalmost anthracosaur or within a clade that includes also Eldeceeon and Silvanerpeton, crownward of an array of chroniosaurs plus anthracosaurs.


Assuntos
Evolução Biológica , Fósseis , Animais , Teorema de Bayes , Membro Posterior , Filogenia
5.
J Physiol Sci ; 72(1): 6, 2022 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-35264097

RESUMO

We investigated the protective effect of losartan, an angiotensin II type 1 receptor blocker, on soleus muscle atrophy. Age-matched male and female Wistar rats were subjected to hindlimb unloading, and the soleus muscle was removed on days 1 and 7 for analysis. Females showed greater reductions in relative weight and myofiber cross-sectional area of the soleus muscle than males on day 7 post-hindlimb unloading. Losartan partially protected females against muscle atrophy. Activation of the canonical TGF-ß signaling pathway, assessed via Smad2/3 phosphorylation, was lower in females following losartan treatment and associated with lower levels of protein ubiquitination after 1 (myofibril) and 7 (cytosol) days of unloading. However, no effect was observed in non-canonical TGF-ß signaling (p44/p42 and p38 MAPK phosphorylation) in males or females during unloading. Our results suggest that losartan provides partial protection against hindlimb unloading-induced soleus muscle atrophy in female rats, possibly associated with decreased canonical TGF-ß signaling.


Assuntos
Elevação dos Membros Posteriores , Losartan , Animais , Feminino , Membro Posterior , Elevação dos Membros Posteriores/fisiologia , Losartan/metabolismo , Losartan/farmacologia , Masculino , Músculo Esquelético/metabolismo , Atrofia Muscular/metabolismo , Ratos , Ratos Wistar , Transdução de Sinais/fisiologia , Fator de Crescimento Transformador beta/metabolismo , Fator de Crescimento Transformador beta/farmacologia
6.
Artigo em Chinês | MEDLINE | ID: mdl-35255556

RESUMO

Objective: To study the effects of vibration on the expression of mitochondrial fusion and fission genes and ultrastructure of skeletal muscle in rabbits. Methods: Thirty-two 3.5-month-old New Zealand rabbits were randomly divided into low-intensity group, medium-intensity group, high-intensity group and control group, with 8 rabbits in each group. The rabbits in the experimental group were subjected to hind limb vibration load test for 45 days. The vibration intensity of the high intensity group was 12.26 m/s(2), the medium intensity group was 6.13 m/s(2), and the low intensity group was 3.02 m/s(2) according to the effective value of weighted acceleration[a(hw (4))] for 4 hours of equal energy frequency. The control group was exposed to noise only in the same experimental environment as the medium-intensity group. The noise levels of each group were measured during the vibration load experiment. After the test, the mRNA expression of mitochondrial fusion gene (Mfn1/Mfn2) and fission gene (Fis1, Drp1) by RT-PCR in the skeletal muscles were measured and the ultrastructure of the skeletal muscles were observed in high intensity group. Results: The mRNA expression of mitochondrial in the skeletal muscle tissues of control group, low intensity group, medium intensity group and high intensity group were Mfn1: 3.25±1.36, 3.85±1.90, 4.53±2.31 and 11.63±7.68; Mfn2: 0.68±0.25, 1.02±0.40, 0.94±0.33 and 1.40±0.45; Fis1: 1.05±0.62, 1.15±0.59, 1.53±1.06 and 2.46±1.51 and Drp1: 3.72±1.76, 2.91±1.63, 3.27±2.01 and 4.21±2.46, respectively. Compared with the control group, the expressions of Mfn1 mRNA, Mfn2 mRNA and Fis1 mRNA in the high-intensity group increased significantly (P<0.05) , and the expressions of Mfn2 mRNA in the medium-intensity group and the low-intensity group increased significantly (P<0.05) . Compared with the control group, the ultrastructure of skeletal muscle of high intensity group showed mitochondrial focal accumulation, cristae membrane damage, vacuole-like changes; Z-line irregularity of muscle fibers, and deficiency of sarcomere. Conclusion: Vibration must be lead to the abnormal mitochondrial morphology and structure and the disorder of energy metabolism due to the expression imbalance of mitochondrial fusion and fission genes in skeletal muscles of rabbits, which may be an important target of vibration-induced skeletal muscle injury.


Assuntos
Dinâmica Mitocondrial , Vibração , Animais , Membro Posterior/metabolismo , Mitocôndrias/metabolismo , Proteínas Mitocondriais/genética , Proteínas Mitocondriais/metabolismo , Proteínas Mitocondriais/farmacologia , Músculo Esquelético , Coelhos , Vibração/efeitos adversos
7.
Front Neural Circuits ; 16: 839521, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35310548

RESUMO

Spinal interneurons play a critical role in motor output. A given interneuron may receive convergent input from several different sensory modalities and descending centers and relay this information to just as many targets. Therefore, there is a critical need to quantify populations of spinal interneurons simultaneously. Here, we quantify the functional connectivity of spinal neurons through the concurrent recording of populations of lumbar interneurons and hindlimb motor units in the in vivo cat model during activation of either the ipsilateral sural nerve or contralateral tibial nerve. Two microelectrode arrays were placed into lamina VII, one at L3 and a second at L6/7, while an electrode array was placed on the surface of the exposed muscle. Stimulation of tibial and sural nerves elicited similar changes in the discharge rate of both interneurons and motor units. However, these same neurons showed highly significant differences in prevalence and magnitude of correlated activity underlying these two forms of afferent drive. Activation of the ipsilateral sural nerve resulted in highly correlated activity, particularly at the caudal array. In contrast, the contralateral tibial nerve resulted in less, but more widespread correlated activity at both arrays. These data suggest that the ipsilateral sural nerve has dense projections onto caudal lumbar spinal neurons, while contralateral tibial nerve has a sparse pattern of projections.


Assuntos
Interneurônios , Medula Espinal , Animais , Membro Posterior/fisiologia , Interneurônios/fisiologia , Neurônios Aferentes , Medula Espinal/fisiologia
8.
J Nanobiotechnology ; 20(1): 145, 2022 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-35305670

RESUMO

Peripheral vascular disease (PVD) is a common clinical manifestation of atherosclerosis. Vascular endothelial growth factor (VEGF) gene therapy is a promising approach for PVD treatment. However, due to single-gene therapy limitations and high H2O2 pathological microenvironment, VEGF gene therapy are not as expectations and its clinical application are limited. Synergistic effects of Nerve factors and vascular factors in angiogenesis have attracted attention in recent years. In this study, VEGF and nerve growth factor (NGF) genes co-delivery nanoparticles (VEGF/NGF-NPs) were prepared by using H2O2 responsive 6s-PLGA-Po-PEG as a carrier. 6s-PLGA-Po-PEG could react with H2O2 specifically due to the internal peroxalate bond. Angiogenic effects of VEGF/NGF-NPs has been evaluated in cells and hindlimb ischemia mice model. Results showed that VEGF/NGF-NPs promoted VEGF and NGF co-expression simultaneously, eliminated excessive H2O2, strengthened reactions between SH-SY5Ys and HUVECs, and finally enhanced migration, tube formation, proliferation and H2O2 damage resistance of HUVECs. VEGF/NGF-NPs also recovered blood perfusion, promoted the expression of VEGF, NGF, eNOS and NO, and enhanced vascular coverage of pericytes. Treatment effects of VEGF/NGF-NPs may related to VEGF/eNOS/NO pathway. Altogether, VEGF/NGF-NPs eliminated excessive H2O2 while achieving gene co-delivery, and promoted stable angiogenesis. It's a promising way for PVD treatment by using VEGF/NGF-NPs.


Assuntos
Fator de Crescimento Neural , Fator A de Crescimento do Endotélio Vascular , Animais , Membro Posterior/irrigação sanguínea , Membro Posterior/metabolismo , Membro Posterior/patologia , Peróxido de Hidrogênio , Isquemia/tratamento farmacológico , Isquemia/patologia , Camundongos , Fator de Crescimento Neural/genética , Fator de Crescimento Neural/metabolismo , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo
9.
Behav Brain Res ; 425: 113816, 2022 05 03.
Artigo em Inglês | MEDLINE | ID: mdl-35231498

RESUMO

It is known that primates including human regain some locomotor function after a partial spinal cord injury, but the locomotor pattern is different from before the injury. Although these observations have many implications for improving rehabilitative strategies, these mechanisms are not well understood. In this study, we used a common marmoset hemisection SCI model to examine temporal changes in locomotor pattern, in particular, intersegmental coordination of left hindlimb. Marmoset showed loss of detectable function in the left forelimb and hindlimb after left unilateral hemisection of cervical spinal cord. At two weeks after injury, weight-bearing of the left forelimb during locomotion was limited, but the left hindlimb was able to plantar step. Then marmosets showed gradual recovery in walking ability, but kinematics analysis showed differences in the endpoint trajectory and joint angle movement. Furthermore, intersegmental coordination in left hindlimb represented by planar covariation was preserved over time after the injury. Previous studies have reported that planar covariance is disrupted in patients with stroke or SCI, and that improvement in planarity correlates with recovery in walking ability after rehabilitation. In this study, quadrupedal marmosets were able to walk without loss of balance even after SCI; the different balance needs of bipedal and quadrupedal walkers may lead to differences in planar covariation. Our results show that planar covariation was preserved at all time points after the cervical unilateral hemisection.


Assuntos
Medula Cervical , Traumatismos da Medula Espinal , Animais , Callithrix , Membro Posterior , Humanos , Locomoção , Recuperação de Função Fisiológica , Medula Espinal
10.
J Ethnopharmacol ; 292: 115206, 2022 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-35301099

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Oridonin (Ori), extracted from Isodon rubescens (Hemsl.) H.Hara, is a well-known traditional Chinese herbal medicinal product that possesses antioxidant and anti-inflammatory activities. Oxidative stress and inflammation are the main pathophysiological mechanisms in hindlimb IR injury. However, whether Ori has a protective effect on hind limb IR injury is unknown. AIM OF THE STUDY: The present study was designed to determine the effect of Ori on hindlimb IR injury and its relationship with oxidative stress and inflammation. MATERIALS AND METHODS: The hind limb IR injury model in mice was used to evaluate the protective effect and related mechanisms of Ori. Forty-eight C57BL/6 mice (n = 12 per group) were randomly divided into four groups: Sham group; IR group; IR + Ori (10 mg/kg) group and IR + Ori (20 mg/kg) group. Mice in the IR and IR + Ori groups were subjected to hindlimb IR injury, while mice in the Sham group were subjected to no hindlimb IR injury. HE staining, Masson's staining, TTC staining, DHE staining, TUNEL staining, western blotting analysis and quantitative real-time PCR were employed to explore the mechanisms by which Ori exerts a protective effect on a classical hindlimb IR model in mice. RESULTS: We found that Ori pretreatment prevented muscle damage and decreased cell apoptosis levels compared with the vehicle control. Moreover, the SOD2, CAT, MDA and ROS levels in muscle showed that Ori could significantly reduce oxidative stress in hindlimb IR mice, while the IL-1ß and TNF-α levels in muscle showed that Ori could significantly attenuate IR-induced inflammation. We also found that Ori could increase the expression of Nrf2 and its downstream protein HO-1 and inhibit the expression levels of NLRP3-related proteins (NLRP3, ASC and Caspase-1) in vivo. CONCLUSIONS: Our study suggested that Ori has a protective effect on hindlimb IR injury, which may be related to Nrf2-mediated oxidative stress and NLRP3-mediated inflammasome activation.


Assuntos
Fator 2 Relacionado a NF-E2 , Traumatismo por Reperfusão , Animais , Diterpenos do Tipo Caurano , Membro Posterior , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Fator 2 Relacionado a NF-E2/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Estresse Oxidativo , Traumatismo por Reperfusão/metabolismo
11.
Sci Rep ; 12(1): 4788, 2022 03 21.
Artigo em Inglês | MEDLINE | ID: mdl-35314731

RESUMO

This study aims to develop a 4-limb canine gait analysis system using wireless inertial measurement units (IMUs). 3D printed sensor holders were designed to ensure quick and consistent sensor mounting. Signal analysis algorithms were developed to automatically determine the timing of swing start and end in a stride. To evaluate the accuracy of the new system, a synchronized study was conducted in which stride parameters in four dogs were measured simultaneously using the 4-limb IMU system and a pressure-sensor based walkway gait system. The results showed that stride parameters measured in both systems were highly correlated. Bland-Altman analyses revealed a nominal mean measurement bias between the two systems in both forelimbs and hindlimbs. Overall, the disagreement between the two systems was less than 10% of the mean value in over 92% of the data points acquired from forelimbs. The same performance was observed in hindlimbs except for one parameter due to small mean values. We demonstrated that this 4-limb system could successfully visualize the overall gait types and identify rapid gait changes in dogs. This method provides an effective, low-cost tool for gait studies in veterinary applications or in translational studies using dog models of neuromuscular diseases.


Assuntos
Membro Anterior , Marcha , Algoritmos , Animais , Cães , Extremidades , Membro Posterior
12.
J Physiol ; 600(9): 2105-2125, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35343594

RESUMO

Mechanical and metabolic signals associated with skeletal muscle contraction stimulate the sensory endings of thin fibre muscle afferents, which, in turn, generates reflex increases in sympathetic nerve activity (SNA) and blood pressure (the exercise pressor reflex; EPR). EPR activation in patients and animals with heart failure with reduced ejection fraction (HF-rEF) results in exaggerated increases in SNA and promotes exercise intolerance. In the healthy decerebrate rat, a subtype of acid sensing ion channel (ASIC) on the sensory endings of thin fibre muscle afferents, namely ASIC1a, has been shown to contribute to the metabolically sensitive portion of the EPR (i.e. metaboreflex), but not the mechanically sensitive portion of the EPR (i.e. the mechanoreflex). However, the role played by ASIC1a in evoking the EPR in HF-rEF is unknown. We hypothesized that, in decerebrate, unanaesthetized HF-rEF rats, injection of the ASIC1a antagonist psalmotoxin-1 (PcTx-1; 100 ng) into the hindlimb arterial supply would reduce the reflex increase in renal SNA (RSNA) evoked via 30 s of electrically induced static hindlimb muscle contraction, but not static hindlimb muscle stretch (model of mechanoreflex activation isolated from contraction-induced metabolite-production). We found that PcTx-1 reduced the reflex increase in RSNA evoked in response to muscle contraction (n = 8; mean (SD) ∫ΔRSNA pre: 1343 (588) a.u.; post: 816 (573) a.u.; P = 0.026) and muscle stretch (n = 6; ∫ΔRSNA pre: 688 (583) a.u.; post: 304 (370) a.u.; P = 0.025). Our data suggest that, in HF-rEF rats, ASIC1a contributes to activation of the exercise pressor reflex and that contribution includes a novel role for ASIC1a in mechanosensation that is not present in healthy rats. KEY POINTS: Skeletal muscle contraction results in exaggerated reflex increases in sympathetic nerve activity in heart failure patients compared to healthy counterparts, which likely contributes to increased cardiovascular risk and impaired tolerance for even mild exercise (i.e. activities of daily living) for patients suffering with this condition. Activation of acid sensing ion channel subtype 1a (ASIC1a) on the sensory endings of thin fibre muscle afferents during skeletal muscle contraction contributes to reflex increases in sympathetic nerve activity and blood pressure, at least in healthy subjects. In this study, we demonstrate that ASIC1a on the sensory endings of thin fibre muscle afferents plays a role in both the mechanical and metabolic components of the exercise pressor reflex in male rats with heart failure. The present data identify a novel role for ASIC1a in evoking the exercise pressor reflex in heart failure and may have important clinical implications for heart failure patients.


Assuntos
Canais Iônicos Sensíveis a Ácido , Insuficiência Cardíaca , Canais Iônicos Sensíveis a Ácido/metabolismo , Animais , Pressão Sanguínea/fisiologia , Insuficiência Cardíaca/metabolismo , Membro Posterior , Masculino , Contração Muscular/fisiologia , Músculo Esquelético/fisiologia , Ratos , Ratos Sprague-Dawley , Reflexo/fisiologia
13.
J Exp Biol ; 225(Suppl_1)2022 03 08.
Artigo em Inglês | MEDLINE | ID: mdl-35258618

RESUMO

A considerable biomechanical challenge faces larger terrestrial animals as the demands of body support scale with body mass (Mb), while muscle force capacity is proportional to muscle cross-sectional area, which scales with Mb2/3. How muscles adjust to this challenge might be best understood by examining varanids, which vary by five orders of magnitude in size without substantial changes in posture or body proportions. Muscle mass, fascicle length and physiological cross-sectional area all scale with positive allometry, but it remains unclear, however, how muscles become larger in this clade. Do larger varanids have more muscle fibres, or does individual fibre cross-sectional area (fCSA) increase? It is also unknown if larger animals compensate by increasing the proportion of fast-twitch (higher glycogen concentration) fibres, which can produce higher force per unit area than slow-twitch fibres. We investigated muscle fibre area and glycogen concentration in hindlimb muscles from varanids ranging from 105 g to 40,000 g. We found that fCSA increased with modest positive scaling against body mass (Mb0.197) among all our samples, and ∝Mb0.278 among a subset of our data consisting of never-frozen samples only. The proportion of low-glycogen fibres decreased significantly in some muscles but not others. We compared our results with the scaling of fCSA in different groups. Considering species means, fCSA scaled more steeply in invertebrates (∝Mb0.575), fish (∝Mb0.347) and other reptiles (∝Mb0.308) compared with varanids (∝Mb0.267), which had a slightly higher scaling exponent than birds (∝Mb0.134) and mammals (∝Mb0.122). This suggests that, while fCSA generally increases with body size, the extent of this scaling is taxon specific, and may relate to broad differences in locomotor function, metabolism and habitat between different clades.


Assuntos
Glicogênio , Lagartos , Animais , Tamanho Corporal , Membro Posterior , Mamíferos , Fibras Musculares Esqueléticas , Músculo Esquelético/fisiologia
14.
Ultrasound Med Biol ; 48(6): 1058-1069, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35287996

RESUMO

Mouse models are critical in developing new therapeutic approaches to treat peripheral arterial disease (PAD). Despite decades of research and numerous clinical trials, the efficacy of available therapies is limited. This may suggest shortcomings in our current animal models and/or methods of assessment. We evaluated perfusion measurement methods in a mouse model of PAD by comparing laser Doppler perfusion imaging (LDPI, the most common technique), contrast-enhanced ultrasound (CEUS, an emerging technique) and fluorescent microspheres (conventional standard). Mice undergoing a femoral artery ligation were assessed by LDPI and CEUS at baseline and 1, 4, 7, 14, 28, 60, 90 and 150 d post-surgery to evaluate perfusion recovery in the ischemic hindlimb. Fourteen days after surgery, additional mice were measured with fluorescent microspheres, LDPI, and CEUS. LDPI and CEUS resulted in broadly similar trends of perfusion recovery until 7 d post-surgery. However, by day 14, LDPI indicated full recovery of perfusion, whereas CEUS indicated ∼50% recovery, which failed to improve even after 5 mo. In agreement with the CEUS results, fluorescent microspheres at day 14 post-surgery confirmed that perfusion recovery was incomplete. Histopathology and photoacoustic microscopy provided further evidence of sustained vascular abnormalities.


Assuntos
Arteriopatias Oclusivas , Doença Arterial Periférica , Animais , Modelos Animais de Doenças , Membro Posterior/irrigação sanguínea , Membro Posterior/diagnóstico por imagem , Isquemia/diagnóstico por imagem , Isquemia/patologia , Lasers , Camundongos , Perfusão , Imagem de Perfusão/métodos , Doença Arterial Periférica/diagnóstico por imagem
15.
J Ethnopharmacol ; 292: 115166, 2022 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-35248678

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Shuxuetong (SXT) injection is formulated by leech and earthworm, has been widely used in the treatment of thrombotic cardiovascular and cerebrovascular diseases with remarkable clinical efficacy. AIM OF THE STUDY: The purpose of this study is to investigate the protective mechanism of SXT injection on the mice model of hindlimb ischemia, and to evaluate the angiogenic effects of SXT injection and its main active substances. MATERIALS AND METHODS: Hindlimb ischemia was induced by left femoral artery ligation. After operation, the mice were injected with saline, 10 mg/kg/d cilostazol, 37.5 mg/kg/d SXT injection, 75 mg/kg/d SXT injection and 150 mg/kg/d SXT injection via tail vein for 4 weeks. Ischemia severity was assessed using laser Doppler perfusion imaging system. Tissue recovery and capillary density were evaluated by histological and immunofluorescent staining. Vascular endothelial growth factor-A (VEGF-A) and platelet-derived growth factor (PDGF-BB) expression were measured by reverse transcription polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) analyses. Human umbilical vein endothelial cells (HUVECs) proliferation was measured using a BrdU kit and the viability of HUVECs was performed by MTT assay. Migration of HUVECs was performed by the wound healing method and a modified transwell assay. Capillary tube formation by HUVECs was examined by using Matrigel assay. Western blotting was used to detect the expressions of p-Cofilin, p-MYPT1, and p-LIMK1. RESULTS: SXT injection treatment significantly restored the blood flow and reduced tissue injury in mouse gastrocnemius muscle. SXT injection treatment increased capillary density and promoted angiogenesis in hindlimb ischemia. Moreover, SXT injection enhanced the expression of VEGF-A and PDGF-BB at both mRNA and protein levels in ischemic tissue of mice. SXT injection and its main active peptides dramatically increased the migration and capillary tube formation of HUVECs. SXT injection and its peptides enhanced protein expressions of the phosphorylation of MYPT1, Cofilin, and LIMK1. DSYVGDEAQSKR, YNELRVAPEEHP, and IQFLPEGSPVTM may act as the active components of SXT injection. CONCLUSION: SXT injection promoted angiogenesis and improved function recovery in hindlimb ischemia mice by regulation of VEGF-A/PDGF-BB. Moreover, SXT injection and its active peptides induced cell migration and tube formation in HUVECs through activating the MYPT1/LIMK1/Cofilin pathway. This study provided experimental basis for SXT injection in the treatment of ischemic diseases and revealed the effective substance of SXT injection in regulating angiogenesis, providing better evidence for the clinical application of SXT injection.


Assuntos
Neovascularização Fisiológica , Fator A de Crescimento do Endotélio Vascular , Fatores de Despolimerização de Actina/metabolismo , Fatores de Despolimerização de Actina/farmacologia , Animais , Becaplermina , Medicamentos de Ervas Chinesas , Membro Posterior/irrigação sanguínea , Células Endoteliais da Veia Umbilical Humana , Humanos , Isquemia/tratamento farmacológico , Isquemia/metabolismo , Camundongos , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo
16.
Nat Ecol Evol ; 6(5): 614-621, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35347258

RESUMO

Among living tetrapods, many lineages have converged on a snake-like body plan, where extreme axial elongation is accompanied by reduction or loss of paired limbs. However, when and how this adaptive body plan first evolved in amniotes remains poorly understood. Here, we provide insights into this question by reporting on a new taxon of molgophid recumbirostran, Nagini mazonense gen. et sp. nov., from the Francis Creek Shale (309-307 million years ago) of Illinois, United States, that exhibits extreme axial elongation and corresponding limb reduction. The molgophid lacks entirely the forelimb and pectoral girdle, thus representing the earliest occurrence of complete loss of a limb in a taxon recovered phylogenetically within amniotes. This forelimb-first limb reduction is consistent with the pattern of limb reduction that is seen in modern snakes and contrasts with the hindlimb-first reduction process found in many other tetrapod groups. Our findings suggest that a snake-like limb-reduction mechanism may be operating more broadly across the amniote tree.


Assuntos
Evolução Biológica , Membro Anterior , Animais , Membro Posterior , Filogenia
17.
Physiol Rep ; 10(3): e15181, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35146957

RESUMO

The mechanisms by which lower limb ischemia/reperfusion induces acute kidney injury (AKI) remain largely uncharacterized. We hypothesized that tourniquet-induced lower limb ischemia/reperfusion (TILLIR) would inhibit mitochondrial function in the renal cortex. We used a murine model to show that TILLIR of the high thigh regions inflicted time-dependent AKI as determined by renal function and histology. This effect was associated with decreased activities of mitochondrial complexes I, II, V and citrate synthase in the kidney cortex. Moreover, TILLIR reduced mRNA levels of a master regulator of mitochondrial biogenesis PGC-1α, and its downstream genes NDUFS1 and ATP5o in the renal cortex. TILLIR also increased serum corticosterone concentrations. TILLIR did not significantly affect protein levels of the critical regulators of mitophagy PINK1 and PARK2, mitochondrial transport proteins Tom20 and Tom70, or heat-shock protein 27. TILLIR had no significant effect on mitochondrial oxidative stress as determined by mitochondrial ability to generate reactive oxygen species, protein carbonylation, or protein levels of MnSOD and peroxiredoxin1. However, TILLIR inhibited classic autophagic flux by increasing p62 protein abundance and preventing the conversion of LC3-I to LC3-II. TILLIR increased phosphorylation of cytosolic and mitochondrial ERK1/2 and mitochondrial AKT1, as well as mitochondrial SGK1 activity. In conclusion, lower limb ischemia/reperfusion induces distal AKI by inhibiting mitochondrial function through reducing mitochondrial biogenesis. This AKI occurs without significantly affecting PINK1-PARK2-mediated mitophagy or mitochondrial oxidative stress in the kidney cortex.


Assuntos
Injúria Renal Aguda/terapia , Membro Posterior/irrigação sanguínea , Isquemia/metabolismo , Precondicionamento Isquêmico/métodos , Mitofagia , Biogênese de Organelas , Injúria Renal Aguda/metabolismo , Animais , Proteínas de Choque Térmico HSP27/metabolismo , Precondicionamento Isquêmico/instrumentação , Masculino , Camundongos , Mitocôndrias Musculares/metabolismo , Estresse Oxidativo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Proteínas Quinases/metabolismo , Ubiquitina-Proteína Ligases/metabolismo
18.
Int J Mol Sci ; 23(3)2022 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-35163147

RESUMO

Thyroid hormone (T3) receptors (TRs) mediate T3 effects on vertebrate development. We have studied Xenopus tropicalis metamorphosis as a model for postembryonic human development and demonstrated that TRα knockout induces precocious hind limb development. To reveal the molecular pathways regulated by TRα during limb development, we performed chromatin immunoprecipitation- and RNA-sequencing on the hind limb of premetamorphic wild type and TRα knockout tadpoles, and identified over 700 TR-bound genes upregulated by T3 treatment in wild type but not TRα knockout tadpoles. Interestingly, most of these genes were expressed at higher levels in the hind limb of premetamorphic TRα knockout tadpoles than stage-matched wild-type tadpoles, suggesting their derepression upon TRα knockout. Bioinformatic analyses revealed that these genes were highly enriched with cell cycle and Wingless/Integrated (Wnt) signaling-related genes. Furthermore, cell cycle and Wnt signaling pathways were also highly enriched among genes bound by TR in wild type but not TRα knockout hind limb. These findings suggest that direct binding of TRα to target genes related to cell cycle and Wnt pathways is important for limb development: first preventing precocious hind limb formation by repressing these pathways as unliganded TR before metamorphosis and later promoting hind limb development during metamorphosis by mediating T3 activation of these pathways.


Assuntos
Proliferação de Células , Regulação da Expressão Gênica no Desenvolvimento , Membro Posterior/embriologia , Metamorfose Biológica , Organogênese , Receptores alfa dos Hormônios Tireóideos/metabolismo , Via de Sinalização Wnt , Animais , Feminino , Masculino , Receptores alfa dos Hormônios Tireóideos/genética , Xenopus laevis
19.
Adv Mater ; 34(14): e2110352, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35107869

RESUMO

Restoration of sufficient blood supply for the treatment of ischemia remains a significant scientific and clinical challenge. Here, a cell-like nanoparticle delivery technology is introduced that is capable of recapitulating multiple cell functions for the spatiotemporal triggering of vascular regeneration. Specifically, a copper-containing protein is successfully prepared using a recombinant protein scaffold based on a de novo design strategy, which facilitates the timely release of nitric oxide and improved accumulation of particles within ischemic tissues. Through closely mimicking physiological cues, the authors demonstrate the benefits of bioactive factors secreted from hypoxic stem cells on promoting angiogenesis. Following this cell-mimicking manner, artificial hybrid nanosized cells (Hynocell) are constructed by integrating the hypoxic stem cell secretome into nanoparticles with surface coatings of cell membranes fused with copper-containing protein. The Hynocell, hybridized with different cell-derived components, provides synergistic effects on targeting ischemic tissues and promoting vascular regeneration in acute hindlimb ischemia and acute myocardial infarction models. This study offers new insights into the utilization of nanotechnology to potentiate the development of cell-free therapeutics.


Assuntos
Biomimética , Neovascularização Fisiológica , Animais , Cobre , Membro Posterior/irrigação sanguínea , Isquemia/terapia
20.
Vet Surg ; 51(3): 509-519, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35170065

RESUMO

OBJECTIVE: To evaluate the effectiveness of a novel crescent-shaped tibial plateau-leveling osteotomy (TPLO) saw guide (crescent guide) to assist with saw control in novice participants. STUDY DESIGN: Ex vivo study. SAMPLE POPULATION: Synthetic bones (n = 54) and medium sized dog pelvic limbs (n = 36). METHODS: The 6 participants (interns and residents) without any prior experience performing a TPLO each performed 9 osteotomies on synthetic tibia models, and 6 osteotomies in cadaveric limbs of medium-sized dogs. Osteotomies made with the crescent guide were compared with those made with a standard jig and a radial saw guide with a jig. Osteotomy angulation, distance of eccentricity (DOE), and medial tibial cortical damage (synthetic bone models only) were measured from calibrated photographs. Participants rated their experiences with each technique. RESULTS: There was no difference in the DOE, coronal or axial osteotomy angulation between the 3 alignment devices for synthetic bone models or cadavers. Average medial cortical damage with the crescent guide (3.8 ± 7.3 mm2 ) was lower than with the radial guide (35.7 ± 27 mm2 ) and standard jig (51.2 ± 63.2 mm2 ) guides (P = <.01). Five of 6 participants preferred the crescent guide over the standard jig and radial guide. CONCLUSION: There was no difference in accuracy of osteotomy positioning but using the crescent guide resulted in lower cortical damage and more favorable participant perceptions. CLINICAL RELEVANCE: The crescent guide may improve control of the radial saw during TPLO in novice surgeons but does not appear to aid accurate osteotomy positioning.


Assuntos
Lesões do Ligamento Cruzado Anterior , Doenças do Cão , Osteotomia , Animais , Lesões do Ligamento Cruzado Anterior/veterinária , Cadáver , Doenças do Cão/cirurgia , Cães , Extremidades , Membro Posterior , Humanos , Osteotomia/métodos , Osteotomia/veterinária , Joelho de Quadrúpedes/cirurgia , Tíbia/cirurgia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA