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Changes in antimicrobial use during the pandemic in relation to long-term trends in utilization among different antimicrobial stewardship program models have not been fully characterized. We analyzed data from an integrated health system using joinpoint regression and found temporal fluctuations in prescribing as well as continuation of existing trends.
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OBJECTIVE: To document veterinarians' perceptions and understanding of medical futility and determine the frequency with which medical futility occurs in small animal practice. SAMPLE: 477 veterinarians in small animal general and specialty veterinary practice. PROCEDURES: A cross-sectional study was performed with a 25-question, web-based, confidential, anonymous survey distributed through various professional veterinary specialty associations. RESULTS: Nearly all respondents (469/474 [99.0%]) believed that futile care occurs in veterinary medicine, and 42.4% (201/474) felt it occurred commonly (> 6 times/y). A similar percentage (471/475 [99.2%]) reported encountering futile care within their careers, and 85.0% (402/476) reported encountering it within the past year. A majority (293/477 [61.4%]) reported witnessing futile care occurring in both inpatient and outpatient settings. Most respondents disagreed or strongly disagreed (320/463 [69.1%]) with a statement that providing futile care is always wrong, and only 38 (8.2%) agreed or strongly agreed. Over 70% (329/464 [70.9%]) of respondents agreed that there are situations in which provision of futile care is appropriate. CLINICAL RELEVANCE: The importance of reaching a consensus definition for medical futility in veterinary medicine is evident given the frequency with which such care is being provided. Most small animal specialist veterinarians will encounter futile care, and the establishment of an ethical framework to navigate questions surrounding medical futility may help reduce moral distress.
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Inutilidad Médica , Veterinarios , Animales , Humanos , Estudios Transversales , Encuestas y CuestionariosRESUMEN
OBJECTIVE: To evaluate the indications for, complications of, and surgical outcomes of dogs and cats that were treated with double limb amputations. ANIMALS: 14 dogs and 4 cats that underwent double limb amputations. PROCEDURES: Data collected retrospectively included patient-specific (species, age, weight, breed, sex, existing comorbidities) and amputation-specific (indication for amputation, full or partial limb amputation, associated complications, need for revision surgeries) variables. Owner satisfaction scores were also collected. RESULTS: The most common indication for double amputations was trauma (12/18) patients. Eleven patients had both amputations performed simultaneously. Nine patients had double partial limb amputations versus full limb amputations. Twelve patients underwent bilateral pelvic limb amputations, 4 underwent bilateral thoracic limb amputations, and 2 had 1 pelvic and 1 contralateral thoracic limb amputated. Five patients had reported complications over the course of the follow-up period, and complications for 3 patients were considered major. Revision surgery was reported for 2 animals. Owner satisfaction scores were reported as very satisfied/excellent (14/18), mildly satisfied (3/18), and strongly dissatisfied (1/18). Median time to follow-up was 450 days (range, 85 to 4,380 days). CLINICAL RELEVANCE: Double limb amputation may be a viable alternative to advanced limb-sparing procedures or humane euthanasia based on the owner satisfaction data and the relatively low rate of major complications in this study. Future studies should clarify patient selection criteria and differences in function between surgical types.
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Amputación Quirúrgica/veterinaria , Gatos/cirugía , Perros/cirugía , Amputación Quirúrgica/clasificación , Animales , Enfermedades de los Gatos/cirugía , Gatos/lesiones , Enfermedades de los Perros/cirugía , Perros/lesiones , Femenino , Masculino , Satisfacción del Paciente , Satisfacción Personal , Estudios Retrospectivos , Resultado del Tratamiento , Heridas y Lesiones/cirugía , Heridas y Lesiones/veterinariaRESUMEN
OBJECTIVE: Describe the clinical course and management of a dog that underwent hematopoietic stem cell transplantation (HSCT) for treatment of B-cell lymphoma and developed acquired circulating factor V (FV) inhibitors. CASE SUMMARY: An 8-year-old male castrated Briard dog diagnosed with lymphoma (IVb, B-cell) presented for allogeneic HSCT. Despite multiple platelet, fresh frozen plasma, and red blood cell transfusions prolonged recovery and clinical bleeding occurred. Circulating acquired FV inhibitors were identified and hemorrhage subsequently was managed by immunosuppression. The dog was discharged when clinical resolution of bleeding was achieved. NEW OR UNIQUE INFORMATION PROVIDED: This case report describes a dog undergoing curative intent treatment for lymphoma, and subsequently acquiring factor inhibition, and was successfully managed. Specific coagulation screening to assess for coagulation factor deficiencies or inhibitors is essential in the diagnosis and treatment of patients with refractory bleeding or only transient response to blood transfusion.
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Trastornos de la Coagulación Sanguínea , Enfermedades de los Perros , Trasplante de Células Madre Hematopoyéticas , Animales , Trastornos de la Coagulación Sanguínea/veterinaria , Transfusión Sanguínea/veterinaria , Enfermedades de los Perros/diagnóstico , Enfermedades de los Perros/terapia , Perros , Factor V , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trasplante de Células Madre Hematopoyéticas/veterinaria , Hemorragia/veterinaria , MasculinoRESUMEN
We present methods to quantify sample shapes and generate sample mounts as motivated by the needs of neutron scattering experiments. The 3D sample scanning was performed using photogrammetry and laser scanning, and a comparison is made between the two techniques. The aluminum alloy AlSi10Mg is shown to have favorable properties for many types of mounts used in neutron scattering. Parts were first prototyped with 3D plastic printers, and then, 3D AlSi10Mg prints were made. The final additively manufactured part holds the sample with more points of contact than is possible with traditional manufacturing. The goodness of fit between the mount and sample was measured by x-ray tomography.
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OBJECTIVE: To determine the success rate and complications associated with inducing emesis in dogs that have ingested foreign material. DESIGN: Retrospective case series, 2010-2014. SETTING: Private practice and referral center. ANIMALS: Sixty-one client-owned dogs that had emesis induced for the treatment of ingestion of foreign material. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Emesis was successfully induced in 59 of 61 (97%) dogs administered an emetic. Of those 59 dogs, 46 (78%) produced the foreign body. There were no complications reported in any of the dogs in which emesis was successfully induced. Dogs in which emesis was successfully induced were likely to produce the foreign body (P = 0.01). CONCLUSION: Based on the results of this study, emesis appears to be a safe and effective means for the removal of certain gastric foreign bodies in dogs.
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Apomorfina/farmacología , Enfermedades de los Perros/terapia , Cuerpos Extraños/veterinaria , Vómitos/veterinaria , Animales , Perros , Eméticos/uso terapéutico , Femenino , Cuerpos Extraños/terapia , Masculino , Estudios Retrospectivos , Vómitos/inducido químicamenteRESUMEN
CASE DESCRIPTION: A 6-month-old intact female Maltese dog was presented for acute onset of syncope. CLINICAL FINDINGS: The dog was presented for collapse upon excitement and exercise. It collapsed at discharge and suffered cardiopulmonary arrest. Echocardiography after resuscitation indicated severe pulmonary hypertension without evidence of intracardiac or extracardiac shunting. A presumptive diagnosis of congenital pulmonary hypertension was made. TREATMENT AND OUTCOME: Initial treatment with sildenafil was effective at relieving syncope, but the extent of pulmonary hypertension as determined by serial echocardiography was unchanged. Graded balloon atrial septostomy was performed as a palliative procedure. Follow-up echocardiography identified a patent interatrial communication with bidirectional shunting. The dog remained asymptomatic 18 months after treatment. CLINICAL RELEVANCE: To the best of our knowledge, this study is the first report in the veterinary literature of graded balloon atrial septostomy performed for therapeutic purposes. Further studies are required to determine if this palliative procedure is a beneficial treatment option for dogs with congenital or severe refractory pulmonary hypertension.
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Cateterismo/veterinaria , Enfermedades de los Perros/cirugía , Hipertensión Pulmonar/veterinaria , Cuidados Paliativos/métodos , Animales , Cateterismo/métodos , Perros , Femenino , Hipertensión Pulmonar/cirugía , Citrato de Sildenafil/uso terapéutico , Vasodilatadores/uso terapéuticoRESUMEN
OBJECTIVE: To identify factors associated with dehiscence and mortality rates following gastrointestinal surgery in dogs. ANIMALS: 170 client-owned dogs that underwent gastrointestinal surgery from 2010 to 2016. PROCEDURES: Medical records of all included dogs were reviewed to collect information on preoperative (breed, sex, age, body weight, American Society of Anesthesiologists [ASA] physical status classification, emergency status, and plasma lactate concentration), intraoperative (indication for surgery, type of surgery, and whether bacterial peritonitis was identified), and postoperative (development of dehiscence and survival status at 2 weeks after surgery) factors. Preoperative and intraoperative factors were evaluated for associations among each other and with postoperative factors. RESULTS: Univariate analyses revealed that preoperative plasma lactate concentration increased with increasing ASA status, and lactate concentrations were significantly higher for nonsurvivors (mean ± SD, 4.6 ± 3.7 mmol/L) than for survivors (2.4 ± 1.7 mmol/L). Multivariate analysis controlling for age, body weight, and plasma lactate concentration revealed that dogs with an ASA status ≥ 3 were more likely to develop dehiscence after gastrointestinal surgery than were dogs with a lower ASA status (OR, 17.77; 95% confidence interval, 2.17 to 144.06). Multivariate analysis also revealed that dogs with an ASA status ≥ 3 or high lactate concentration were less likely to survive than were other dogs. CONCLUSIONS AND CLINICAL RELEVANCE: These findings regarding ASA status and preoperative plasma lactate concentration and their associations with outcome may help clinicians to determine and provide optimal perioperative care to dogs requiring gastrointestinal surgery as well as to inform owners about prognosis.
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Procedimientos Quirúrgicos del Sistema Digestivo/veterinaria , Enfermedades de los Perros/mortalidad , Peritonitis/veterinaria , Animales , Procedimientos Quirúrgicos del Sistema Digestivo/mortalidad , Perros , Femenino , Masculino , Atención Perioperativa/veterinaria , Peritonitis/mortalidad , Pronóstico , Estudios RetrospectivosRESUMEN
An 8-year-old, spayed female Chihuahua mixed breed dog was presented for dyspnea and was subsequently mechanically ventilated. Propofol was utilized as part of the anesthetic protocol. The dog developed rhabdomyolysis, myoglobinuria, cardiac arrhythmias, liver enzyme elevation, and methemoglobinemia. Propofol was discontinued and N-acetylcysteine was administered after which the clinical signs resolved.
Syndrome s'apparentant à l'infusion de propofol chez un chien. Un chien Chihuaha mâle castré de race croisée âgé de 8 ans a été présenté pour de la dyspnée et a été subséquemment soumis à une ventilation mécanique. Le propofol a été utilisé dans le cadre du protocole anesthésique. Le chien a développé de la rhabdomyolyse, de la myoglobinurie, de l'arythmie cardiaque, une élévation des enzymes hépatiques et de la méthémoglobinémie. Le propofol a été discontinué et de la N-acétylcystéine a été administrée après la résolution des signes cliniques.(Traduit par Isabelle Vallières).
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Enfermedades de los Perros/inducido químicamente , Hipnóticos y Sedantes/efectos adversos , Propofol/efectos adversos , Acidosis/veterinaria , Lesión Renal Aguda/veterinaria , Animales , Arritmias Cardíacas/veterinaria , Perros , Femenino , SíndromeRESUMEN
OBJECTIVE To validate that dogs become hypocoagulable following rattlesnake envenomation and to determine whether thromboelastographic abnormalities are correlated with envenomation severity for dogs bitten by rattlesnakes native to southern California. ANIMALS 14 dogs with observed or suspected rattlesnake envenomation (envenomated dogs) and 10 healthy control dogs. PROCEDURES For each dog, a citrate-anticoagulated blood sample underwent kaolin-activated thromboelastography. For each envenomated dog, a snakebite severity score was assigned on the basis of clinical findings, and prothrombin time, activated partial thromboplastin time, and platelet count were determined when the attending clinician deemed it necessary and owner finances allowed. RESULTS For 12 of 14 envenomated dogs, the thromboelastographically determined clot strength was below the 25th percentile for the clot strength of control dogs, which was indicative of a hypocoagulable state. No envenomated dog had thromboelastographic results indicative of a hypercoagulable state. One envenomated dog had a prolonged prothrombin time, but the activated partial thromboplastin time and all thromboelastographic variables were within the respective reference ranges for that dog. Seven of 13 envenomated dogs were thrombocytopenic (platelet count, ≤ 170,000 platelets/µL). Snakebite severity score was negatively correlated with platelet count but was not correlated with any thromboelastographic variable. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that dogs generally become hypocoagulable following rattlesnake envenomation. Thromboelastography might provide an objective measure of the coagulation status of envenomated dogs and aid in the identification of dogs that are in a hypocoagulable state and in need of antivenin treatment prior to the onset of progressive clinical signs.
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Crotalus , Enfermedades de los Perros/tratamiento farmacológico , Mordeduras de Serpientes/veterinaria , Tromboelastografía/veterinaria , Animales , Antivenenos/uso terapéutico , Coagulación Sanguínea , California , Perros , Femenino , Humanos , Caolín , Masculino , Tiempo de Tromboplastina Parcial , Recuento de Plaquetas/veterinaria , Estudios Prospectivos , Tiempo de Protrombina/veterinaria , TrombofiliaRESUMEN
The Colorado potato beetle, Leptinotarsa decemlineata (Say), is a major agricultural pest of potatoes in the Central Sands production region of Wisconsin. Previous studies have shown that populations of L. decemlineata have become resistant to many classes of insecticides, including the neonicotinoid insecticide, imidacloprid. Furthermore, L. decemlineata has multiple mechanisms of resistance to deal with a pesticide insult, including enhanced metabolic detoxification by cytochrome p450s and glutathione S-transferases. With recent advances in the transcriptomic analysis of imidacloprid susceptible and resistant L. decemlineata populations, it is possible to investigate the role of candidate genes involved in imidacloprid resistance. A recently annotated transcriptome analysis of L. decemlineata was obtained from select populations of L. decemlineata collected in the Central Sands potato production region, which revealed a subset of mRNA transcripts constitutively up-regulated in resistant populations. We hypothesize that a portion of the up-regulated transcripts encoding for genes within the resistant populations also encode for pesticide resistance and can be suppressed to re-establish a susceptible phenotype. In this study, a discrete set of three up-regulated targets were selected for RNA interference experiments using a resistant L. decemlineata population. Following the successful suppression of transcripts encoding for a cytochrome p450, a cuticular protein, and a glutathione synthetase protein in a select L. decemlineata population, we observed reductions in measured resistance to imidacloprid that strongly suggest these genes control essential steps in imidacloprid metabolism in these field populations.
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Escarabajos/genética , Imidazoles/toxicidad , Proteínas de Insectos/genética , Resistencia a los Insecticidas/genética , Insecticidas/toxicidad , Nitrocompuestos/toxicidad , Interferencia de ARN , Animales , Escarabajos/efectos de los fármacos , Sistema Enzimático del Citocromo P-450/genética , Glutatión Sintasa/genética , Neonicotinoides , Transcripción Genética , Regulación hacia ArribaRESUMEN
Herpes zoster (HZ) in immunocompetent children is quite uncommon. Initial exposure to the varicella-zoster virus (VZV) may be from a wild-type or vaccine-related strain. Either strain may cause a latent infection and subsequent eruption of HZ. We present a case of HZ in a 15-month-old boy after receiving the varicella vaccination at 12 months of age. A review of the literature regarding the incidence, clinical characteristics, and diagnosis of HZ in children also is provided.
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Dermatosis Facial/diagnóstico , Herpes Zóster Oftálmico/diagnóstico , Aciclovir/uso terapéutico , Antivirales/uso terapéutico , Dermatosis Facial/tratamiento farmacológico , Herpes Zóster/diagnóstico , Herpes Zóster/tratamiento farmacológico , Herpes Zóster Oftálmico/tratamiento farmacológico , Humanos , Inmunocompetencia , Lactante , Masculino , Reacción en Cadena de la PolimerasaRESUMEN
The Colorado potato beetle, Leptinotarsa decemlineata (Say), is a major agricultural pest in the Central Sands region of Wisconsin. Imidacloprid, a neonicotinoid insecticide, has commonly been used for control of L. decemlineata since its registration in 1995. In the last 10 years, many field populations of L. decemlineata have begun to show increasing imidacloprid resistance. We studied resistance phenotype as a phenomenon that reduces neonicotinoid efficacy and has practical consequences for potato pest management. Although we have not observed complete field failure following the use of these products, multiple studies have demonstrated that the lethal concentration to kill 50% of the test organisms (LC50) in different field populations of L. decemlineata varies greatly which may suggest that resistance of L. decemlineata is heritable and involves genetic changes. An important challenge in understanding resistance is assessing the genetic mechanisms associated with resistance and classifying up-regulated genes that may be involved in combating an insecticide insult. In this study we uncovered trends in imidacloprid phenotypic response that have developed in the region by estimating the LC50 values among different field populations against a range of imidacloprid doses. The LC50 values collected in 2008-2011, and more recently in 2013 and 2014, show that some field locations remain susceptible to imidacloprid, while nearby fields (<100km) have developed high levels of resistance. We also sought to uncover potential mechanisms of resistance at each field location. We compiled a transcriptome for populations, characterized as phenotypically 'susceptible' and 'resistant', by isolating mRNA from adult beetles and analyzing gene expression level differences. Strong differences were observed in constituently up and down-regulated genes among different field populations. Most significantly, the up-regulation of 3 cytochrome p450s and a glutathione synthetase related protein in multiple resistant populations provide a mechanistic explanation of resistance evolution in L. decemlineata.
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Escarabajos/efectos de los fármacos , Escarabajos/genética , Imidazoles/toxicidad , Insecticidas/toxicidad , Nitrocompuestos/toxicidad , Animales , Femenino , Perfilación de la Expresión Génica , Resistencia a los Insecticidas , Dosificación Letal Mediana , Neonicotinoides , ARN Mensajero/genética , Solanum tuberosum/parasitología , Transcriptoma , WisconsinRESUMEN
OBJECTIVE: To review the relevant human and veterinary literature regarding the timing of surgical intervention for trauma patients and the impact on outcome. DATA SOURCES: Original research, clinical studies, and review articles with no date restrictions from both human and veterinary literature. HUMAN DATA SYNTHESIS: Despite extensive research into the ideal timing of surgical intervention for human trauma victims, debate is ongoing and views are still evolving. Prior to the 1970s, the standard of care consisted of delayed surgical treatment, as these patients were considered too ill to undergo surgery. Beginning in the 1970s, and continuing for nearly 2 decades, early definitive surgical treatment was recommended. The most recent evolution of human trauma management incorporates the concept of damage control surgery, which acknowledges the importance of early skeletal stabilization or laparotomy for reducing morbidity while attempting to avoid complications such as acute respiratory distress syndrome or multiple organ dysfunction syndrome. VETERINARY DATA SYNTHESIS: Despite a relatively large amount of literature available regarding veterinary trauma, no evidence exists to provide the clinician guidance as to the ideal timing of surgery for trauma patients. With the exception of diaphragmatic hernia, no studies were identified that attempted to evaluate this variable. CONCLUSIONS: Veterinary-specific studies are needed to evaluate the impact of surgical timing on outcome following trauma. The information that can be obtained from studies in this area can improve veterinary trauma care and may be used as models for human trauma care through translational applications.
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Gatos/lesiones , Perros/lesiones , Hernia Diafragmática Traumática/veterinaria , Heridas y Lesiones/veterinaria , Animales , Hernia Diafragmática Traumática/cirugía , Humanos , Complicaciones Posoperatorias , Análisis de Supervivencia , Factores de Tiempo , Medicina Veterinaria , Heridas y Lesiones/cirugíaRESUMEN
BACKGROUND: Although implicated in the pathogenesis of several chronic inflammatory disorders and hematologic malignancies, telomerase mutations have not been thoroughly characterized in human cancers. The present study was performed to examine the frequency and potential clinical relevance of telomerase mutations in esophageal carcinomas. METHODS: Sequencing techniques were used to evaluate mutational status of telomerase reverse transcriptase (TERT) and telomerase RNA component (TERC) in neoplastic and adjacent normal mucosa from 143 esophageal cancer (EsC) patients. MTS, flow cytometry, time lapse microscopy, and murine xenograft techniques were used to assess proliferation, apoptosis, chemotaxis, and tumorigenicity of EsC cells expressing either wtTERT or TERT variants. Immunoprecipitation, immunoblot, immunofluorescence, promoter-reporter and qRT-PCR techniques were used to evaluate interactions of TERT and several TERT variants with BRG-1 and ß-catenin, and to assess expression of cytoskeletal proteins, and cell signaling. Fluorescence in-situ hybridization and spectral karyotyping techniques were used to examine telomere length and chromosomal stability. RESULTS: Sequencing analysis revealed one deletion involving TERC (TERC del 341-360), and two non-synonymous TERT variants [A279T (2 homozygous, 9 heterozygous); A1062T (4 heterozygous)]. The minor allele frequency of the A279T variant was five-fold higher in EsC patients compared to healthy blood donors (p<0.01). Relative to wtTERT, A279T decreased telomere length, destabilized TERT-BRG-1-ß-catenin complex, markedly depleted ß-catenin, and down-regulated canonical Wnt signaling in cancer cells; these phenomena coincided with decreased proliferation, depletion of additional cytoskeletal proteins, impaired chemotaxis, increased chemosensitivity, and significantly decreased tumorigenicity of EsC cells. A279T expression significantly increased chromosomal aberrations in mouse embryonic fibroblasts (MEFs) following Zeocin™ exposure, as well as Li Fraumeni fibroblasts in the absence of pharmacologically-induced DNA damage. CONCLUSIONS: A279T induces telomere dysfunction and inhibits non-canonical telomerase activity in esophageal cancer cells. These findings warrant further analysis of A279T expression in esophageal cancers and premalignant esophageal lesions.
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Neoplasias Esofágicas/enzimología , Regulación Enzimológica de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Mutación Missense , Proteínas de Neoplasias/biosíntesis , Telomerasa/biosíntesis , Homeostasis del Telómero , Sustitución de Aminoácidos , Animales , Línea Celular Tumoral , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/patología , Femenino , Humanos , Masculino , Ratones , Ratones Desnudos , Proteínas de Neoplasias/genética , ARN/biosíntesis , ARN/genética , ARN Neoplásico/biosíntesis , ARN Neoplásico/genética , Telomerasa/genética , Telómero/enzimología , Telómero/genéticaRESUMEN
While oral isotretinoin is renowned for its ability to treat acne vulgaris, many of its off-label uses continue to go underappreciated. Since the last review on the unapproved indications of isotretinoin, relevant publications have surfaced with new recommendations. This article attempts to provide physicians with the latest information regarding successful and unsuccessful use of isotretinoin as an effective treatment for dermatological conditions, such as rosacea, psoriasis, pityriasis rubra pilaris, condyloma acuminatum, granuloma annulare, Darier's disease, systemic cutaneous lupus erythematosus, nonmelanoma skin cancer, and hidradenitis suppurativa. Variations in dosage regimens and isotretinoin viability as an alternative to other standard treatments are also discussed in relation to these conditions.
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OBJECTIVE: To determine whether epidural administration of opioids was associated with clinically important urinary retention in dogs undergoing elective orthopedic procedures. DESIGN: Retrospective cohort study. ANIMALS: 179 client-owned dogs undergoing elective surgery for cranial cruciate ligament rupture. PROCEDURES: Medical records of 179 dogs that underwent surgical correction for cranial cruciate rupture between January 2009 and October 2012 were reviewed; 120 received epidural administration of opioids and 59 did not. Signalment, type of procedure, administration of epidural analgesia, time to first postanesthetic urination, and number of urinations during the first 24 hours were evaluated and compared between groups. RESULTS: Administration of preservative-free morphine into the epidural space was not significantly associated with time to first urination following anesthetic recovery or the total number of urinations within the first 24 hours of anesthetic recovery. Administration of a hydromorphone bolus IV following surgery was significantly associated with urinary retention, compared with administration of either morphine boluses or fentanyl constant rate infusions following surgery. No other variables were significantly associated with urinary retention. CONCLUSIONS AND CLINICAL RELEVANCE: Administration of preservative-free morphine into the epidural space was not associated with clinically important urinary retention in dogs undergoing elective orthopedic procedures. Systemic administration of opioids may be associated with urinary retention.
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Analgesia Epidural/veterinaria , Ligamento Cruzado Anterior/cirugía , Enfermedades de los Perros/inducido químicamente , Morfina/efectos adversos , Complicaciones Posoperatorias/veterinaria , Retención Urinaria/veterinaria , Analgésicos Opioides/administración & dosificación , Analgésicos Opioides/efectos adversos , Analgésicos Opioides/uso terapéutico , Animales , Perros , Femenino , Inyecciones Epidurales , Masculino , Morfina/administración & dosificación , Morfina/uso terapéutico , Complicaciones Posoperatorias/inducido químicamente , Estudios Retrospectivos , Retención Urinaria/inducido químicamenteRESUMEN
BACKGROUND: Carbohydrate structures of surface-expressed and secreted/excreted glycoconjugates of the human blood fluke Schistosoma mansoni are key determinants that mediate host-parasite interactions in both snail and mammalian hosts. Fucose is a major constituent of these immunologically important glycans, and recent studies have sought to characterize fucosylation-associated enzymes, including the Golgi-localized fucosyltransferases that catalyze the transfer of L-fucose from a GDP-L-fucose donor to an oligosaccharide acceptor. Importantly, GDP-L-fucose is the only nucleotide-sugar donor used by fucosyltransferases and its availability represents a bottleneck in fucosyl-glycotope expression. METHODS: A homology-based genome-wide bioinformatics approach was used to identify and molecularly characterize the enzymes that contribute to GDP-L-fucose synthesis and Golgi import in S. mansoni. Putative functions were further investigated through molecular phylogenetic and immunocytochemical analyses. RESULTS: We identified homologs of GDP-D-mannose-4,6-dehydratase (GMD) and GDP-4-keto-6-deoxy-D-mannose-3,5-epimerase-4-reductase (GMER), which constitute a de novo pathway for GDP-L-fucose synthesis, in addition to a GDP-L-fucose transporter (GFT) that putatively imports cytosolic GDP-L-fucose into the Golgi. In silico primary sequence analyses identified characteristic Rossman loop and short-chain dehydrogenase/reductase motifs in GMD and GMER as well as 10 transmembrane domains in GFT. All genes are alternatively spliced, generating variants of unknown function. Observed quantitative differences in steady-state transcript levels between miracidia and primary sporocysts may contribute to differential glycotope expression in early larval development. Additionally, analyses of protein expression suggest the occurrence of cytosolic GMD and GMER in the ciliated epidermal plates and tegument of miracidia and primary sporocysts, respectively, which is consistent with previous localization of highly fucosylated glycotopes. CONCLUSIONS: This study is the first to identify and characterize three key genes that are putatively involved in the synthesis and Golgi import of GDP-L-fucose in S. mansoni and provides fundamental information regarding their genomic organization, genetic variation, molecular phylogenetics, and developmental expression in intramolluscan larval stages.
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Guanosina Difosfato Fucosa/metabolismo , Redes y Vías Metabólicas/genética , Schistosoma mansoni/enzimología , Schistosoma mansoni/genética , Animales , Clonación Molecular , Biología Computacional , Perfilación de la Expresión Génica , Inmunohistoquímica , Ligasas/genética , Ligasas/metabolismo , Proteínas de Transporte de Membrana/genética , Proteínas de Transporte de Membrana/metabolismo , Filogenia , Homología de Secuencia de AminoácidoRESUMEN
Fucosylated glycans of the parasitic flatworm Schistosoma mansoni play key roles in its development and immunobiology. In the present study we used a genome-wide homology-based bioinformatics approach to search for genes that contribute to fucosylated glycan expression in S. mansoni, specifically the α2-, α3-, and α6-fucosyltransferases (FucTs), which transfer L-fucose from a GDP-L-fucose donor to an oligosaccharide acceptor. We identified and in silico characterized several novel schistosome FucT homologs, including six α3-FucTs and six α6-FucTs, as well as two protein O-FucTs that catalyze the unrelated transfer of L-fucose to serine and threonine residues of epidermal growth factor- and thrombospondin-type repeats. No α2-FucTs were observed. Primary sequence analyses identified key conserved FucT motifs as well as characteristic transmembrane domains, consistent with their putative roles as fucosyltransferases. Most genes exhibit alternative splicing, with multiple transcript variants generated. A phylogenetic analysis demonstrated that schistosome α3- and α6-FucTs form monophyletic clades within their respective gene families, suggesting multiple gene duplications following the separation of the schistosome lineage from the main evolutionary tree. Quantitative decreases in steady-state transcript levels of some FucTs during early larval development suggest a possible mechanism for differential expression of fucosylated glycans in schistosomes. This study systematically identifies the complete repertoire of FucT homologs in S. mansoni and provides fundamental information regarding their genomic organization, genetic variation, developmental expression, and evolutionary history.
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Fucosiltransferasas/genética , Fucosiltransferasas/metabolismo , Genoma de los Helmintos/genética , Proteínas del Helminto/genética , Familia de Multigenes/genética , Schistosoma mansoni/enzimología , Schistosoma mansoni/genética , Animales , Clonación de OrganismosRESUMEN
Early recognition of failure of oxygen delivery and knowledge of how medications can alter oxygen delivery allow clinicians to institute appropriate therapies in a timely manner and can result in improved patient outcomes. Oxygen delivery can be estimated and evaluated using a variety of methods, including arterial blood gas sampling, blood lactate quantification, echocardiography, and direct cardiac output measurement. Delivery can be enhanced by manipulating the components of the oxygen delivery formula. Cardiac output, hemoglobin concentration, oxygen saturation, and oxygen tension can all be improved through therapeutic or pharmacologic intervention.