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1.
Vet Clin North Am Equine Pract ; 39(3): 475-487, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37625917

RESUMO

Mesenchymal stem cells (MSCs) are used as a regenerative therapy in horses for musculoskeletal injury since the late 1990s and in some regions are standard of care for certain injuries. Yet, there is no Food and Drug Administration-approved MSC therapeutic in the United States for horses. In humans, lack of regulatory approval in the United States has been caused by failure of late-phase clinical trials to demonstrate consistent efficacy, perhaps because of nonuniformity of MSC preparation and application techniques. This article discusses clinical evidence for musculoskeletal applications of MSCs in the horse and current challenges to marketing approval.


Assuntos
Doenças dos Cavalos , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Doenças Musculoesqueléticas , Humanos , Cavalos , Animais , Transplante de Células-Tronco Mesenquimais/veterinária , Transplante de Células-Tronco Mesenquimais/métodos , Doenças dos Cavalos/terapia , Doenças Musculoesqueléticas/terapia , Doenças Musculoesqueléticas/veterinária
2.
Vet Surg ; 51(2): 259-269, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34970755

RESUMO

OBJECTIVE: To determine the short-term effect of plantar fasciotomy and neurectomy (PFN) of the deep branch of the lateral plantar nerve on the proximal suspensory ligament (PSL) cross-sectional area (CSA) in horses with hindlimb proximal suspensory desmopathy (PSD). STUDY DESIGN: Analytical, observational, cohort study. SAMPLE POPULATION: Twenty-one horses. METHODS: Records of horses with chronic PSD treated by PFN were included if a preoperative ultrasonographic examination was available and at least one postoperative ultrasonographic examination. One masked observer measured the ultrasonographic cross-sectional area (CSA) of the PSL. Intraobserver reliability was determined by repeatedly measuring a subset of ultrasonographic images (n = 127). Two masked observers measured the cross-sectional area of the proximal suspensory ligament (PSL-CSA) on preoperative proton density (PD)-weighted transverse high field magnetic resonance images (n = 19 horses) . Agreements for PSL-CSA between preoperative ultrasonographic and MRI measures and between the two magnetic resonance imaging (MRI) observers were assessed. Follow up considered the horses' ability to return to exercise and their owners' satisfaction. RESULTS: The reliability of the ultrasonographic measurement of the PSL-CSA was excellent. Agreement between ultrasonographic assessment and MRI assessment of PSL-CSA was good. No difference was detected between preoperative (median, interquartile range; oblique-incidence, 2.07, 1.72-2.55; on-incidence, 2.23, 1.98-2.65) and postoperative (oblique-incidence, 2.08, 1.80-2.74; on-incidence, 2.28, 2.01-2.74) PSL-CSAs. At a median of 12 months (4-33 months), 16/20 (80%) owners reported the horse was "better" and 15/20 (75%) functioned at or above preoperative levels. CONCLUSION: Ultrasonographic measurement of the PSL-CSA was reproducible and in good agreement with MRI measurement. The PSL-CSA was not influenced by PFN. CLINICAL SIGNIFICANCE: The PSL-CSA cannot be used to guide return to function.


Assuntos
Doenças dos Cavalos , Animais , Estudos de Coortes , Denervação/veterinária , Fasciotomia/veterinária , Doenças dos Cavalos/diagnóstico por imagem , Doenças dos Cavalos/cirurgia , Cavalos , Ligamentos/diagnóstico por imagem , Ligamentos/cirurgia , Reprodutibilidade dos Testes
3.
BMC Vet Res ; 15(1): 211, 2019 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-31234844

RESUMO

BACKGROUND: Bisphosphonates (BPs) are a family of molecules characterized by two key properties: their ability to bind strongly to bone mineral and their inhibitory effects on mature osteoclasts and thus bone resorption. Chemically two groups of BPs are recognized, non-nitrogen-containing and nitrogen-containing BPs. Non-nitrogen-containing BPs incorporate into the energy pathways of the osteoclast, resulting in disrupted cellular energy metabolism leading to cytotoxic effects and osteoclast apoptosis. Nitrogen-containing BPs primarily inhibit cholesterol biosynthesis resulting in the disruption of intracellular signaling, and other cellular processes in the osteoclast. BODY: BPs also exert a wide range of physiologic activities beyond merely the inhibition of bone resorption. Indeed, the breadth of reported activities include inhibition of cancer cell metastases, proliferation and apoptosis in vitro. In addition, the inhibition of angiogenesis, matrix metalloproteinase activity, altered cytokine and growth factor expression, and reductions in pain have been reported. In humans, clinical BP use has transformed the treatment of both post-menopausal osteoporosis and metastatic breast and prostate cancer. However, BP use has also resulted in significant adverse events including acute-phase reactions, esophagitis, gastritis, and an association with very infrequent atypical femoral fractures (AFF) and osteonecrosis of the jaw (ONJ). CONCLUSION: Despite the well-characterized health benefits of BP use in humans, little is known regarding the effects of BPs in the horse. In the equine setting, only non-nitrogen-containing BPs are FDA-approved primarily for the treatment of navicular syndrome. The focus here is to discuss the current understanding of the strengths and weaknesses of BPs in equine veterinary medicine and highlight the future utility of these potentially highly beneficial drugs.


Assuntos
Doenças Ósseas/veterinária , Difosfonatos/uso terapêutico , Doenças dos Cavalos/tratamento farmacológico , Animais , Doenças Ósseas/tratamento farmacológico , Osso e Ossos/efeitos dos fármacos , Previsões , Cavalos , Humanos , Coxeadura Animal/tratamento farmacológico , Osteocondrose/tratamento farmacológico , Osteocondrose/veterinária , Osteoclastos/efeitos dos fármacos
4.
J Assist Reprod Genet ; 36(3): 543-556, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30470961

RESUMO

PURPOSE: This study aims to determine if intra-ovarian injection of bone marrow-derived mesenchymal stem cells (MSCs) improves or restores ovarian function in aged females. METHODS: Prospective randomized study of eight aged mares and six young mares receiving intra-ovarian injection of MSCs or vehicle. Main outcome measures were antral follicle count and serum anti-Müllerian hormone (AMH) (aged and young mares), and for aged mares, oocyte meiotic and developmental competence; gross and histological ovarian assessment; evaluation of presence of chimerism in recovered granulosa cells and in ovarian tissue samples; and gene expression in ovarian tissue as assessed by RNA sequencing. RESULTS: Injection of MSCs was not associated with significant changes in follicle number, oocyte recovery rate on follicle aspiration, oocyte maturation rate, or blastocyst rate after ICSI in aged mares, or in changes in follicle number in young mares. There were no significant changes in peripheral AMH concentrations, indicating a lack of effect on growing follicles. MSC donor DNA was not recovered in granulosa cells or in ovarian tissue, indicating lack of persistence of injected MSC. RNA sequencing revealed significant differences in gene expression between MSC- and vehicle-injected ovaries. CONCLUSIONS: Intra-ovarian injection of bone marrow-derived MSCs altered gene expression but did not improve ovarian function in aged mares.


Assuntos
Células da Granulosa/transplante , Transplante de Células-Tronco Mesenquimais , Folículo Ovariano/crescimento & desenvolvimento , Ovário/crescimento & desenvolvimento , Animais , Estradiol/metabolismo , Feminino , Cavalos , Células-Tronco Mesenquimais/citologia , Recuperação de Oócitos , Oócitos/crescimento & desenvolvimento , Estudos Prospectivos , Análise de Sequência de RNA
5.
Mol Ther ; 25(10): 2415-2426, 2017 10 04.
Artigo em Inglês | MEDLINE | ID: mdl-28822690

RESUMO

Tendon injuries (tendinopathies) are common in human and equine athletes and characterized by dysregulated collagen matrix, resulting in tendon damage. We have previously demonstrated a functional role for microRNA29a (miR29a) as a post-transcriptional regulator of collagen 3 expression in murine and human tendon injury. Given the translational potential, we designed a randomized, blinded trial to evaluate the potential of a miR29a replacement therapy as a therapeutic option to treat tendinopathy in an equine model that closely mimics human disease. Tendon injury was induced in the superficial digital flexor tendon (SDFT) of 17 horses. Tendon lesions were treated 1 week later with an intralesional injection of miR29a or placebo. miR29a treatment reduced collagen 3 transcript levels at week 2, with no significant changes in collagen 1. The relative lesion cross-sectional area was significantly lower in miR29a tendons compared to control tendons. Histology scores were significantly better for miR29a-treated tendons compared to control tendons. These data support the mechanism of microRNA-mediated modulation of early pathophysiologic events that facilitate tissue remodeling in the tendon after injury and provides a strong proof of principle that a locally delivered miR29a therapy improves early tendon healing.


Assuntos
Colágeno/metabolismo , MicroRNAs/genética , Traumatismos dos Tendões/metabolismo , Traumatismos dos Tendões/terapia , Tendões/metabolismo , Tendões/patologia , Animais , Colágeno/genética , Feminino , Cavalos , Masculino , MicroRNAs/metabolismo , Traumatismos dos Tendões/genética
6.
Vet Surg ; 47(5): 715-721, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29774961

RESUMO

OBJECTIVE: To determine the influence of epidural detomidine and morphine on serum corticosteroid concentrations and pain-related behavioral responses in mares during and after ovariectomy via colpotomy. STUDY DESIGN: Blinded prospective study. ANIMALS: Nine university-owned mares. METHODS: Five of 9 horses received caudal epidural detomidine hydrochloride (0.01 mg/kg) and morphine sulfate (0.1 mg/kg) prior to surgery. All horses received local anesthetic around the ovarian pedicle, 0.02 mg/kg butorphanol IV at the start of the procedure and after first ovary removal, were sedated as required throughout the procedure, and were monitored for leg lifting, grunting, and abdominal tensing. Horses were monitored hourly for pain postoperatively. Heart rate was recorded every 4 hours, and photographs were taken to assess pain according to the horse grimace scale (HGS). Control group horses (n = 4) were treated with butorphanol (0.02 mg/kg IV) every 4 hours for 24 hours postoperatively. All horses received oral phenylbutazone 18 hours postoperatively. Serum cortisol was measured prior to the procedure, after first and second ovary removal, and 8 and 24 hours postoperatively. RESULTS: No differences were detected between horses receiving caudal epidural detomidine and morphine and those that received systemic opioids. A decrease in HGS score occurred after phenylbutazone administration. CONCLUSION: Administration of caudal epidural detomidine and morphine resulted in similar pain-related behavior and corticosteroid concentrations as did administration of systemic butorphanol every 4 hours for 24 hours postoperatively. CLINICAL SIGNIFICANCE: Caudal epidural detomidine and morphine may mitigate the requirement for frequent systemic opioid administration after a potentially painful procedure.


Assuntos
Analgesia Epidural/veterinária , Analgésicos/farmacologia , Cavalos/fisiologia , Hidrocortisona/metabolismo , Imidazóis/farmacologia , Ovariectomia/veterinária , Dor Pós-Operatória/veterinária , Analgésicos/administração & dosagem , Analgésicos/uso terapêutico , Animais , Colpotomia/veterinária , Método Duplo-Cego , Feminino , Cavalos/cirurgia , Hidrocortisona/sangue , Imidazóis/administração & dosagem , Imidazóis/uso terapêutico , Medição da Dor/efeitos dos fármacos , Medição da Dor/veterinária , Dor Pós-Operatória/prevenção & controle , Estudos Prospectivos
7.
Vet Clin North Am Equine Pract ; 33(2): 299-314, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28687092

RESUMO

Despite differences in etiology and diagnostics, the mainstay of therapy in the foal is similar to the adult: local lavage and/or debridement and local antimicrobial therapy. When musculoskeletal infection is concurrent with neonatal sepsis, the prognosis for survival is fair. When musculoskeletal infection is the primary problem, the prognosis is fair to good for survival of synovial, bony, and physeal infections with appropriate and aggressive local therapy. Recent literature may indicate that prognosis for survival and potential athleticism in foals that are treated expediently with local therapies and are without comorbidities may be more favorable than has been previously indicated.


Assuntos
Artrite Infecciosa/veterinária , Doenças dos Cavalos/diagnóstico , Doenças dos Cavalos/terapia , Osteíte/veterinária , Osteomielite/veterinária , Animais , Animais Recém-Nascidos , Artrite Infecciosa/diagnóstico , Artrite Infecciosa/terapia , Feminino , Cavalos , Masculino , Osteíte/diagnóstico , Osteíte/terapia , Osteomielite/diagnóstico , Osteomielite/terapia , Prognóstico , Estudos Retrospectivos
8.
Vet Clin North Am Equine Pract ; 33(2): 431-438, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28687099

RESUMO

Many long bone fractures that are not considered repairable in the adult horse are repairable in the foal. This is largely because of reduced patient size and more rapid healing in the foal. When there is no articular communication, the long-term prognosis for athletic function can be very good. Emergency care and transport of the foal with a long bone fracture is different than the adult.


Assuntos
Animais Recém-Nascidos/lesões , Fraturas Ósseas/veterinária , Cavalos/lesões , Fatores Etários , Animais , Serviços Médicos de Emergência , Fraturas do Fêmur/diagnóstico , Fraturas do Fêmur/terapia , Fraturas do Fêmur/veterinária , Consolidação da Fratura , Fraturas Ósseas/diagnóstico , Fraturas Ósseas/terapia , Fraturas do Úmero/diagnóstico , Fraturas do Úmero/terapia , Fraturas do Úmero/veterinária , Prognóstico , Fraturas do Rádio/diagnóstico , Fraturas do Rádio/terapia , Fraturas do Rádio/veterinária , Escápula/lesões , Fraturas da Tíbia/diagnóstico , Fraturas da Tíbia/terapia , Fraturas da Tíbia/veterinária , Fraturas da Ulna/diagnóstico , Fraturas da Ulna/terapia , Fraturas da Ulna/veterinária
9.
Vet Surg ; 43(3): 282-8, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24467593

RESUMO

OBJECTIVES: To determine the effect of regional limb perfusion (RLP) with amikacin sulfate alone and in combination with ticarcillin/clavulanate on synovial fluid concentration and antimicrobial activity of amikacin. SAMPLE POPULATION: Experimental study. METHODS: RLP with amikacin alone (A; 2.5 g) or amikacin and ticarcillin/clavulanate (AT; 2.5 g amikacin, 7 g ticarcillin/clavulanate) was performed with a tourniquet placed at mid-antebrachium in standing, sedated horses. Perfusate blood was collected immediately after injection and again before tourniquet release. Blood from the jugular vein was collected before tourniquet release. Synovial fluid from the middle carpal joint was collected 0, 30, and 60 minutes after tourniquet release. Amikacin concentration and antimicrobial activity of synovial fluid against Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, and Pseudomonas aeruginosa were determined. RESULTS: There was significantly lower amikacin concentration in the middle carpal joint synovial fluid of group AT compared with group A at 30 minutes (AT = median 4.4 µg/mL, IQR 3.0-11.2 µg/mL; A = 17.5 µg/mL, 6.6-80.1 µg/mL) and 60 minutes (AT = median 4.6 µg/mL, IQR 3.1-8.1 µg/mL; A = 15.0 µg/mL, 6.7-61.7 µg/mL) after tourniquet release. Zones of inhibition for ticarcillin-resistant Klebsiella pneumoniae from group AT were significantly smaller than group A from synovial fluid at 30 and 60 minutes after tourniquet release and in the perfusate serum before tourniquet release. CONCLUSIONS: The combination of amikacin with ticarcillin/clavulanate during RLP resulted in significantly lower amikacin synovial concentration and antimicrobial activity on amikacin susceptible and ticarcillin resistant cultures compared with amikacin alone.


Assuntos
Amicacina/farmacocinética , Antibacterianos/farmacocinética , Cavalos/metabolismo , Líquido Sinovial/química , Amicacina/administração & dosagem , Amicacina/metabolismo , Animais , Antibacterianos/administração & dosagem , Antibacterianos/metabolismo , Ácidos Clavulânicos/administração & dosagem , Ácidos Clavulânicos/farmacocinética , Interações Medicamentosas , Quimioterapia Combinada , Feminino , Membro Anterior , Masculino , Líquido Sinovial/metabolismo , Ticarcilina/administração & dosagem , Ticarcilina/farmacocinética , Distribuição Tecidual
10.
J Shoulder Elbow Surg ; 21(2): 278-94, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22244071

RESUMO

Repair of rotator cuff tears in experimental models has been significantly improved by the use of enhanced biologic approaches, including platelet-rich plasma, bone marrow aspirate, growth factor supplements, and cell- and gene-modified cell therapy. Despite added complexity, cell-based therapies form an important part of enhanced repair, and combinations of carrier vehicles, growth factors, and implanted cells provide the best opportunity for robust repair. Bone marrow-derived mesenchymal stem cells provide a stimulus for repair in flexor tendons, but application in rotator cuff repair has not shown universally positive results. The use of scaffolds such as platelet-rich plasma, fibrin, and synthetic vehicles and the use of gene priming for stem cell differentiation and local anabolic and anti-inflammatory impact have both provided essential components for enhanced tendon and tendon-to-bone repair in rotator cuff disruption. Application of these research techniques in human rotator cuff injury has generally been limited to autologous platelet-rich plasma, bone marrow concentrate, or bone marrow aspirates combined with scaffold materials. Cultured mesenchymal progenitor therapy and gene-enhanced function have not yet reached clinical trials in humans. Research in several animal species indicates that the concept of gene-primed stem cells, particularly embryonic stem cells, combined with effective culture conditions, transduction with long-term integrating vectors carrying anabolic growth factors, and development of cells conditioned by use of RNA interference gene therapy to resist matrix metalloproteinase degradation, may constitute potential advances in rotator cuff repair. This review summarizes cell- and gene-enhanced cell research for tendon repair and provides future directions for rotator cuff repair using biologic composites.


Assuntos
Terapia Genética/métodos , Transplante de Células-Tronco Mesenquimais/métodos , Regeneração/fisiologia , Traumatismos dos Tendões/terapia , Animais , Previsões , Terapia Genética/tendências , Humanos , Transplante de Células-Tronco Mesenquimais/tendências , Recuperação de Função Fisiológica , Lesões do Manguito Rotador , Tendões/fisiologia , Resistência à Tração , Resultado do Tratamento , Cicatrização/fisiologia
11.
Vet Clin North Am Equine Pract ; 33(2): xi-xii, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28687100
12.
J Am Vet Med Assoc ; 238(8): 1032-9, 2011 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-21492047

RESUMO

OBJECTIVE: To investigate the efficacy and safety of a low-volume, single-catheter, continuous peripheral neural blockade (CPNB) technique to locally deliver bupivacaine to alleviate signs of severe forelimb pain resulting from experimentally induced tendonitis in horses. DESIGN: Randomized controlled experimental trial. SAMPLE: 14 horses and 5 forelimbs from equine cadavers. PROCEDURES: Horses underwent collagenase-induced superficial digital flexor tendonitis in the midmetacarpal region of 1 forelimb. To deliver analgesia, a closed-tip catheter was placed from lateral to medial, approximately 12 cm distal to the accessory carpal bone, between the suspensory ligament and accessory ligament of the deep digital flexor tendon. Success of catheter placement and anesthetic delivery was documented ex vivo in 5 forelimbs from equine cadavers. Effective analgesia in affected forelimbs of horses from continuous (n = 7) versus intermittent (7) local anesthetic delivery (intermittent peripheral neural blockade; IPNB) was compared over a 3-day period. RESULTS: Horses that received CPNB in the affected forelimb were less lame than horses that received IPNB. A lower proportion of CPNB-treated horses had behavioral and physiologic signs of pain, compared with IPNB-treated horses. Neither technique completely blocked the sensation of pain or resulted in swelling in the distal portion of the forelimb, vasodilation, or an increase in lameness. After removal, Staphylococcus aureus was cultured from 1 catheter tip. CONCLUSIONS AND CLINICAL RELEVANCE: For short-term treatment, CPNB was more effective than IPNB for reduction in signs of severe pain in the distal aspect of the forelimb of horses.


Assuntos
Bupivacaína/farmacologia , Doenças dos Cavalos/tratamento farmacológico , Bloqueio Nervoso/veterinária , Dor/veterinária , Tendinopatia/veterinária , Anestésicos Locais/administração & dosagem , Anestésicos Locais/farmacologia , Animais , Bupivacaína/administração & dosagem , Colagenases , Cavalos , Bloqueio Nervoso/métodos , Tendinopatia/induzido quimicamente , Tendinopatia/tratamento farmacológico
13.
Vet Surg ; 40(5): 563-70, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21545461

RESUMO

OBJECTIVE: To determine in vitro elution characteristics of amikacin and ticarcillin from fiber reinforced calcium phosphate beads (FRCP). SAMPLE POPULATION: Experimental. METHODS: FRCP beads with water (A), amikacin (B), ticarcillin/clavulanate (C), or both amikacin and ticarcillin/clavulanate (D) were bathed in mL phosphate-buffered saline (PBS) at 37°C, 5% CO(2) and 95% room air. PBS was sampled (eluent) and beads were placed in fresh PBS at time points 1 and 8 hours and 1, 2, 3, 4, 5, 6, 7, 10, 12, 14, 18, 21, 25, 28, 35, 42, 49, and 56 days. Antibiotic concentration and antimicrobial activity of eluent against Escherichia coli, Staphylococcus aureus, and Klebsiella pneumoniae were determined. RESULTS: Both antibiotics eluted in a bimodal pattern. Beads with a single antibiotic eluted 20.8 ± 2.5% of amikacin and 29.5 ± 0.8% of ticarcillin over 56 days. Coelution of the antibiotics resulted in a lower proportion (AUC(0-∞) ) of antibiotics eluted for both amikacin (9.5 ± 0.2%) and ticarcillin (21.7 ± 0.09%). Bioassay of antimicrobial activity of the eluent (t = 1, 8, and 24 hours) established reduced antimicrobial activity of amikacin from combination beads (D). CONCLUSIONS: FRCP beads with amikacin or ticarcillin/clavulanate, but not the combination, are suitable carriers for wound implantation. CLINICAL RELEVANCE: Duration before complete resorption of FRCP beads in vivo should be determined before clinical use as a resorbable depot. The results of this study underscore the importance of testing drug combinations, despite success of the combination systemically, before their use in local applications.


Assuntos
Implantes Absorvíveis , Amicacina/farmacocinética , Antibacterianos/farmacocinética , Cimentos Ósseos , Fosfatos de Cálcio , Ticarcilina/farmacocinética , Amicacina/administração & dosagem , Amicacina/farmacologia , Antibacterianos/administração & dosagem , Antibacterianos/farmacologia , Testes de Sensibilidade a Antimicrobianos por Disco-Difusão , Portadores de Fármacos , Combinação de Medicamentos , Escherichia coli/efeitos dos fármacos , Técnicas In Vitro , Klebsiella pneumoniae/efeitos dos fármacos , Poliglactina 910 , Staphylococcus aureus/efeitos dos fármacos , Ticarcilina/administração & dosagem , Ticarcilina/farmacologia
14.
Front Vet Sci ; 8: 724041, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34595230

RESUMO

Fetal bovine serum (FBS) is used for MSC preparation in pre-clinical animal models and veterinary applications, recently in US clinical trials, and for MSC products with current foreign market authorizations. The effect of anti-bovine titers, which are common in animals and humans, has not been investigated. In the equine model, where anti-bovine titers are universally high due to routine vaccination, we evaluated the recipient immune response to autologous MSCs prepared with and without FBS. Preparation of MSCs with FBS resulted in post injection inflammation and antibody mediated cytotoxicity of MSCs when compared to MSCs prepared without FBS. Importantly, synovial MSC concentrations were reduced and LPS induced pain was higher, when FBS was used to prepare MSCs, demonstrating reduced efficacy of FBS prepared MSCs. Fetal bovine serum should no longer be utilized for MSC preparation in pre-clinical study, clinical study, or veterinary applications. The use of FBS in previously reported studies, and in MSC therapeutics with current foreign market authorization, should be considered when interpreting results.

15.
Bone ; 142: 115711, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33141069

RESUMO

Bisphosphonates (BPs) are characterized by their ability to bind strongly to bone mineral and inhibit bone resorption. However, BPs exert a wide range of pharmacological activities beyond the inhibition of bone resorption, including the inhibition of cancer cell metastases and angiogenesis and the inhibition of proliferation and apoptosis in vitro. Additionally, the inhibition of matrix metalloproteinase activity, altered cytokine and growth factor expression, as well as reductions in parameters of pain have also been reported. In humans, clinical BP use has transformed the treatment of post-menopausal osteoporosis, rare bone diseases such as osteogenesis imperfecta, as well as multiple myeloma and metastatic breast and prostate cancer, albeit not without infrequent but significant adverse events. Despite the well-characterized health benefits of BP use in humans, the evidence-base for the therapeutic efficacy of BPs in veterinary medicine is, by comparison, limited. Notwithstanding, BPs are used widely in small animal veterinary practice for the medical management of hyperparathyroidism, idiopathic hypercalcemia in cats, as well as for the palliative care of bone tumors which are common in dogs, and in particular, primary bone tumors such as osteosarcoma. Palliative BP treatment has also recently increased in veterinary oncology to alleviate tumor-associated bone pain. In equine veterinary practice, non-nitrogen-containing BPs are FDA-approved to control clinical signs associated with navicular syndrome in adult horses. However, there are growing concerns regarding the off-label use of BPs in juvenile horses. Here we discuss the current understanding of the strengths, weaknesses and current controversies surrounding BP use in veterinary medicine to highlight the future utility of these potentially beneficial drugs.


Assuntos
Neoplasias Ósseas , Reabsorção Óssea , Mieloma Múltiplo , Animais , Osso e Ossos , Gatos , Difosfonatos/uso terapêutico , Cães , Cavalos , Humanos , Masculino
16.
Stem Cells Transl Med ; 10(5): 694-710, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33369287

RESUMO

Allogeneic mesenchymal stromal cells (MSCs) have been used clinically for decades, without cross-matching, on the assumption that they are immune-privileged. In the equine model, we demonstrate innate and adaptive immune responses after repeated intra-articular injection with major histocompatibility complex (MHC) mismatched allogeneic MSCs, but not MHC matched allogeneic or autologous MSCs. We document increased peri-articular edema and synovial effusion, increased synovial cytokine and chemokine concentrations, and development of donor-specific antibodies in mismatched recipients compared with recipients receiving matched allogeneic or autologous MSCs. Importantly, in matched allogeneic and autologous recipients, but not mismatched allogeneic recipients, there was increased stromal derived factor-1 along with increased MSC concentrations in synovial fluid. Until immune recognition of MSCs can be avoided, repeated clinical use of MSCs should be limited to autologous or cross-matched allogeneic MSCs. When non-cross-matched allogeneic MSCs are used in single MSC dose applications, presensitization against donor MHC should be assessed.


Assuntos
Imunidade Adaptativa , Imunidade Inata , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Aloenxertos , Animais , Quimiocina CXCL12 , Teste de Histocompatibilidade/veterinária , Cavalos , Complexo Principal de Histocompatibilidade , Líquido Sinovial/imunologia , Transplante Autólogo
17.
J Am Vet Med Assoc ; 258(2): 165-169, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33405987

RESUMO

OBJECTIVE: To determine the effectiveness of a digital interactive multimedia tutorial (DIMT) for preparing veterinary students to perform ultrasonography in horses. SAMPLE: 42 third-year veterinary students. PROCEDURES: Students were randomly assigned to 3 instructional methods: independent study (ie, 45 minutes to read a highlighted textbook chapter), lecture (ie, 45-minute lecture by a faculty member), or digital interactive multimedia tutorial (DIMT; ie, 45-minute narrated, interactive module). Written and practical tests were administered after each instruction session. For the practical test, each student was required to obtain a series of ultrasound images of a live horse, and images were later scored for quality by an individual unaware of the instructional method used. RESULTS: Higher-quality ultrasound images were obtained by veterinary students who had reviewed the DIMT rather than the analogous information in textbook chapters. No difference in scores was identified between students in the lecture group and those in the DIMT group. Students' perceptions suggested that practical instruction facilitated by clinicians was a key component of learning how to perform ultrasonography in horses. CONCLUSIONS AND CLINICAL RELEVANCE: Results supported the use of DIMTs in preparing veterinary students to perform ultrasonography in horses.


Assuntos
Instrução por Computador , Multimídia , Animais , Humanos , Avaliação Educacional , Cavalos , Estudantes , Ultrassonografia/veterinária
18.
Vet Surg ; 39(2): 244-53, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20210975

RESUMO

OBJECTIVE: To report a technique for laser-facilitated, minimally invasive proximal interphalangeal joint (PIJ) arthrodesis in horses. STUDY DESIGN: Case series. ANIMALS: Horses (n=6); 5 thoracic and 2 pelvic limb PIJ. METHODS: PIJ osteoarthritis (OA) diagnosis was confirmed by radiography. A diode laser was used to apply 2000 J of energy to the joint followed by insertion of 3 parallel 5.5 mm screws in lag fashion through stab incisions to achieve PIJ arthrodesis. After anesthetic recovery, limbs were maintained in bandages (n=2) or bandage casts (5) for 3 weeks. Horses were allowed exercise or turnout by 3 months. RESULTS: Three horses (4 limbs) were sound throughout follow-up (6-18 months). One horse remained lame the 1st month, another had mild lameness at pasture at 6 weeks, and another had persistent low-grade lameness and delayed joint fusion (1 year). Within 6 months, 5 horses were sound, 4 had radiographic evidence of successful joint fusion, and 5 had returned to intended use. CONCLUSION: Diode laser-facilitated, 3 parallel screw arthrodesis for PIJ OA costs less and is associated with less pain compared with standard, open PIJ arthrodesis using 3 parallel screws inserted in lag fashion. CLINICAL RELEVANCE: In horses with advanced PIJ OA, this technique appears to be a viable alternative for PIJ arthrodesis. Further study including characterization of the effects of the laser, ideal case selection indications, and optimal laser dose is indicated before this technique is recommended for routine PIJ arthrodesis.


Assuntos
Artrodese/veterinária , Parafusos Ósseos/veterinária , Osteoartrite/veterinária , Animais , Artrodese/métodos , Feminino , Cavalos/cirurgia , Coxeadura Animal/cirurgia , Terapia a Laser/métodos , Terapia a Laser/veterinária , Masculino , Osteoartrite/cirurgia , Resultado do Tratamento
19.
J Tissue Eng Regen Med ; 13(2): 191-202, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30536848

RESUMO

Mesenchymal stem cells (MSCs) improve the osteoarthritis condition, but the fate of MSCs after intra-articular injection is unclear. We used fluorescent nanoparticles (quantum dots [QDs]) to track equine MSCs (QD-labelled MSCs [QD-MSCs]) in vivo after intra-articular injection into normal and osteoarthritic joints. One week after injection of QD-MSCs, unlabelled MSCs, or vehicle, we determined the presence of QD-MSCs in synovium and articular cartilage histologically. In vitro, we evaluated the persistence of QDs in MSCs and whether QDs affected proliferation, immunophenotype, or differentiation. In joints injected with QD-MSCs, labelled cells were identified on the synovial membrane and significantly less often on articular cartilage, without differences between normal and osteoarthritic joints. Joints injected with QD-MSCs and MSCs had increased synovial total nucleated cell count and protein compared with vehicle-injected joints. In vitro, QDs persisted in nonproliferating cells for up to 8 weeks (length of the study), but QD fluorescence was essentially absent from proliferating cells within two passages (approximately 3 to 5 days). QD labelling did not affect MSC differentiation into chondrocytes, adipocytes, and osteocytes. QD-MSCs had slightly different immunophenotype from control cells, but whether this was due to an effect of the QDs or to drift during culture is unknown. QD-MSCs can be visualized in histological sections 1 week after intra-articular injection and are more frequently found in the synovial membrane versus cartilage in both normal and osteoarthritic joints. QDs do not alter MSC viability and differentiation potential in vitro. However, QDs are not optimal markers for long-term tracking of MSCs, especially under proliferative conditions.


Assuntos
Células da Medula Óssea/metabolismo , Doenças dos Cavalos , Articulações , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/metabolismo , Osteoartrite , Pontos Quânticos/química , Aloenxertos , Animais , Células da Medula Óssea/patologia , Doenças dos Cavalos/metabolismo , Doenças dos Cavalos/patologia , Doenças dos Cavalos/terapia , Cavalos , Articulações/metabolismo , Articulações/patologia , Células-Tronco Mesenquimais/patologia , Osteoartrite/metabolismo , Osteoartrite/patologia , Osteoartrite/terapia
20.
Vet Surg ; 37(2): 161-5, 2008 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-18251810

RESUMO

OBJECTIVE: To report a technique for open reduction and internal fixation of scapulohumeral joint luxation in large animals, and outcome. STUDY DESIGN: Clinical case reports. ANIMALS: Mature alpacas (n=3) and immature miniature steer (1). METHODS: Shoulder joint luxation was diagnosed by physical examination and confirmed by radiography. Open reduction was performed with internal fixation using lateral tension band sutures. RESULTS: Animals maintained shoulder joint reduction and were sound with radiographically normal shoulder joints (n=2) and normal range of motion without appreciable gait abnormalities (4) at follow-up 8-36 months later. CONCLUSIONS: In contrast to previous reports of open reduction with internal fixation of shoulder joint luxation in large animals, open reduction and use of lateral scapulohumeral tension sutures resulted in functionally normal shoulder joints. CLINICAL RELEVANCE: Stabilization of the shoulder joint with lateral scapulohumeral tension sutures after open reduction is effective, technically simple, and should be considered in large animal species weighing <100 kg.


Assuntos
Camelídeos Americanos , Bovinos , Fixação Interna de Fraturas/veterinária , Instabilidade Articular/veterinária , Articulação do Ombro , Técnicas de Sutura/veterinária , Animais , Doenças dos Bovinos/cirurgia , Instabilidade Articular/diagnóstico por imagem , Instabilidade Articular/cirurgia , Coxeadura Animal , Masculino , Radiografia , Amplitude de Movimento Articular , Resultado do Tratamento
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