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1.
J Zoo Wildl Med ; 54(1): 49-55, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36971628

RESUMO

Blood samples were obtained from the dorsal cervical sinus of free-ranging hawksbill sea turtles (Eretmochelys imbricata) collected at Glover's Reef Marine Reserve, 42 km east of the coast of Belize, for hematology and plasma biochemistry analysis. Unknown sex, subadult turtles (N = 32) were sampled in 2013 (n = 22) and 2017 (n = 10). To provide a more robust data set, parameters that did not have statistically significant differences were pooled and treated as a single population. Eleven hematologic parameters were evaluated; of these, five were pooled. Twenty-three plasma biochemical parameters were evaluated; of these, 15 were pooled. The PCV observed in this study (mean 33.44%) was double that observed in two studies of juvenile hawksbills in Dubai (means 17% and 16%), whereas the total WBC count was half that observed in immature and adult hawksbills sampled in the Galápagos (mean 2.91 × 103 versus 5.3 × 103/µl). Total protein and albumin were lower than regionally similar, adult female hawksbills in Brazil (means 3.36 versus 5.45 g/dl and 0.93 versus 2.11 g/dl, respectively). Globulins were higher (mean 2.43 versus 1.06 and 0.5 g/dl), driving the albumin:globulin ratio lower than that observed in two studies of juvenile hawksbills in Dubai (0.4:1 versus 1.1:1 and 1:1, respectively). These findings represent a geographically distinct population from previous reports, highlight the variability in blood parameters from disparate populations, and reaffirm the vital importance of considering a multitude of variables when interpreting reptilian blood values. The similarities in the majority of values observed in 2013 and 2017 provide confidence in the stability of these parameters in this population.


Assuntos
Hematologia , Tartarugas , Animais , Feminino , Belize , Brasil
2.
J Zoo Wildl Med ; 52(1): 206-216, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33827178

RESUMO

Sarcocystosis was diagnosed in a captive flock of thick-billed parrots (Rhynchopsitta pachyrhyncha) at the Wildlife Conservation Society's Queens Zoo. Since the index case in 2005, 45% of mortalities in birds over 30 days of age were due to sarcocystosis. Sarcocystis falcatula was repeatedly identified as the causative agent. The disease predominantly affected younger adult parrots. Administration of antiparasitic medications prior to development of respiratory signs prolonged life in infected birds, but disease was fatal until utilization of a three-drug combination (pyrimethamine, trimethoprim-sulfamethoxazole, and ponazuril). This protocol may require in excess of 6 mo of therapy to achieve clinical resolution of active disease. Plasma creatine kinase activity was found to be the most useful test in diagnosing infection and monitoring response to therapy. Polymerase chain reaction (PCR) for apicomplexan organisms on antemortem whole blood, blood smears, or dried blood spots helped confirm suspected cases, but due to the poor sensitivity was sometimes misleading when assessing response to therapy or resolution of clinical disease. Preventive measures, focusing on exclusion and removal of Virginia opossums (Didelphis virginiana) from zoo grounds failed to curtail the occurrence of sarcocystosis in the flock. Other preventative steps, such as modification of feeding stations to exclude potential arthropod paratenic hosts and prophylaxis trials with diclazuril, appeared to successfully mitigate new infections. Given the diagnostic and therapeutic challenges, prevention of exposure to S. falcatula is essential to ex-situ conservation efforts for thick-billed parrots.


Assuntos
Antiprotozoários/uso terapêutico , Doenças das Aves/parasitologia , Papagaios/parasitologia , Sarcocistose/veterinária , Animais , Animais de Zoológico , Doenças das Aves/tratamento farmacológico , Doenças das Aves/mortalidade , Sarcocistose/tratamento farmacológico , Sarcocistose/mortalidade
3.
J Zoo Wildl Med ; 52(4): 1185-1194, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34998288

RESUMO

Cefovecin is a third-generation cephalosporin antibiotic with an efficacy of 2 wk following a single injection in domestic dogs and cats. A high degree of plasma protein binding to cefovecin has been proposed as one of the mechanisms responsible for the long elimination half-life, but protein binding has not been evaluated extensively in nondomestic species. In this study, a review of the current literature was conducted, and pharmacokinetic data were compiled for species in which cefovecin has been evaluated thus far. Additionally, in vitro cefovecin protein binding was evaluated in plasma from 22 nondomestic species representing a broad range of taxa. Animals of the order Carnivora demonstrated protein-binding levels of >98%, which is supportive of the long elimination half-life seen in related species. Protein binding was highly variable in Artiodactyl and Perissodactyl species, with dolphins (Tursiops truncatus) and barasingha (Rucervus duvaucelii) displaying high protein binding (99.12% to >99%), but not gazelles (Eudorcas thomsonii) or equids (91.76-92.70%). Cefovecin was not highly bound in any reptiles or birds, corresponding to short half-lives reported for these taxa. These results suggest that a high percentage of plasma protein binding in vitro may predict in which species cefovecin may exhibit a long half-life and duration of action in vivo. These findings may aid in selecting species for cefovecin pharmacokinetic research and for empirical treatment of infections caused by susceptible bacteria.


Assuntos
Doenças do Gato , Doenças do Cão , Animais , Antibacterianos , Gatos , Cefalosporinas , Cães , Injeções Subcutâneas/veterinária , Ligação Proteica
4.
Zoo Biol ; 39(6): 405-410, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33220009

RESUMO

Mortality data for Magellanic penguins (Spheniscus magellanicus) housed in zoos and aquariums in the United States has not previously been published. Necropsy and histopathology records were examined for Magellanic penguins housed at 12 Association of Zoos and Aquariums institutions from 2008 through 2018. If birds lived through the first year, the mean longevity was found to be 18.9 years of age (standard deviation: 7.9). Prefledge chicks and geriatric penguins experienced the highest mortality rates. Aspergillosis was a major cause of death in this species. There was no significant difference in mortality between males and females. Based on these data, recommendations for the husbandry and veterinary care of captive Magellanic penguins can be made.


Assuntos
Animais de Zoológico , Aspergilose/veterinária , Doenças das Aves/mortalidade , Longevidade , Spheniscidae , Animais , Aspergilose/epidemiologia , Aspergilose/mortalidade , Doenças das Aves/microbiologia , Surtos de Doenças , Feminino , Masculino , Estudos Retrospectivos , Estados Unidos/epidemiologia
5.
HPB (Oxford) ; 21(3): 370-378, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30266497

RESUMO

BACKGROUND: This retrospective UNOS database evaluation analyzes the prevalence of preoperative portal vein thromboses (PVT), and postoperative thromboses leading to graft failure in pediatric patients undergoing liver transplantation (LT). METHODS: The evaluation was performed in three age groups: I (0-5), II (6-11), III (12-18) years old. Factors predictive of pre- and postoperative thromboses were analyzed. RESULTS: Between 2000 and 2015, 8982 pediatric LT were performed in the US. Of those, 390 patients had preoperative PVT (4.3%), and 396 (4.4%) had postoperative thromboses. The prevalence of both types of thromboses was less in Group III than in the other two groups (3.20% vs 4.65%, p = 0.007 and 1.73% vs. 5.13%, p < 0.001, respectively). The prevalence of postoperative thromboses was significantly higher in Group I than in the other two groups (5.49% vs. 2.51%, p < 0.001). Preoperative PVT was independently associated with postoperative thromboses (OR = 1.7, p = 0.02). Children less than 5 years of age were more likely to develop postoperative thromboses leading to graft failure (OR = 2.9, p < 0.001). CONCLUSION: Younger children undergoing LT are prone to pre-and postoperative thrombotic complications. Preoperative PVT at the time of transplantation was independently associated with postoperative thromboses. Perioperative antithrombotic therapy should be considered in pediatric patients undergoing LT.


Assuntos
Doença Hepática Terminal/cirurgia , Transplante de Fígado/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Trombose/epidemiologia , Fatores Etários , Criança , Pré-Escolar , Bases de Dados Factuais , Doença Hepática Terminal/mortalidade , Feminino , Humanos , Masculino , Prevalência , Estudos Retrospectivos , Fatores de Risco
6.
Paediatr Anaesth ; 23(8): 720-5, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23682965

RESUMO

INTRODUCTION: Selective Dorsal Rhizotomy (SDR) is the only surgical intervention with class I evidence supporting permanent reduction in spasticity for children with cerebral palsy (Paediatr Anaesth, 12, 2002, 296; Neurosurg Focus, 21, 2006, e2). Postoperatively, adequate analgesia can be difficult to achieve (J Neurosurg, 105, 2006, 8; Childs Nerv Syst, 17, 2001, 556; Pediatr Neurosurg, 43, 2007, 107; Anesth Analg, 79, 1994, 340; Reg Anesth Pain Med, 24, 1999, 438; Pediatr Anesth, 19, 2009, 1213). This study examines a novel regimen utilizing the combination of epidurally infused ropivacaine - hydromorphone and scheduled ketorolac. This regimen was compared to a protocol utilizing systemic fentanyl and diazepam. METHODS: Following IRB approval, 31 patients receiving epidural analgesia were compared with 41 patients who received systemic analgesia. All surgeries were performed by one surgeon with standardized anesthetic and nursing care. Studied outcomes included: pain scores; episodes of severe pain; nausea, itching; oxygen desaturation; and ICU admission. Data were analyzed using Mann-Whitney U-test, CHI square, and Fisher exact test where indicated with P < 0.05 considered significant. RESULTS: Studied groups had similar demographics, biometrics and disease burdens. Patients in the epidural group had statistically and clinically significant reductions in peak recorded pain scores for each 4-h period in the first 24 postoperative hours. Severe pain (score >5) was markedly reduced in the epidural group with 9% of epidural patients vs. 68% of systemic patients experiencing at least one episode. Fewer epidural patients experienced oxygen desaturation during the first two postoperative days (6.5% vs. 41%, 6.5% vs. 39%). CONCLUSION: Epidural analgesia resulted in substantial improvements in pain control and safety. The data supports the superiority of a multimodal analgesia approach centered on epidural analgesia. A similar protocol should be considered following simple laminectomies or procedures associated with lower-extremity muscle spasm.


Assuntos
Analgesia Epidural/métodos , Analgesia/métodos , Paralisia Cerebral/complicações , Manejo da Dor/métodos , Assistência Perioperatória/métodos , Analgesia/efeitos adversos , Analgesia Epidural/efeitos adversos , Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/efeitos adversos , Criança , Protocolos Clínicos , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Procedimentos Neurocirúrgicos , Medição da Dor , Dor Pós-Operatória/tratamento farmacológico , Segurança do Paciente , Náusea e Vômito Pós-Operatórios/epidemiologia , Náusea e Vômito Pós-Operatórios/terapia , Insuficiência Respiratória/etiologia , Insuficiência Respiratória/terapia , Estudos Retrospectivos , Rizotomia
7.
J Zoo Wildl Med ; 44(3): 596-604, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24063087

RESUMO

A crossover study was performed in 12 Himalayan tahr (Hemitragus jemlahicus) undergoing preshipment examinations to compare a partially reversible to a fully reversible intramuscular chemical immobilization protocol. The partially reversible protocol (MKA) consisted of induction with medetomidine (0.06 +/- 0.009 mg/kg) and ketamine (2.03 +/- 0.315 mg/kg) and antagonism by atipamezole (0.30 +/- 0.044 mg/kg). The fully reversible protocol (CXNA) consisted of induction with carfentanil (0.009 +/- 0.003 mg/kg) and xylazine (0.08 +/- 0.019 mg/kg) and antagonism by naltrexone (0.867 +/- 0.332 mg/kg) and atipamezole (0.105 +/- 0.023 mg/ kg). Animals were monitored for quality and length of induction and recovery, depth of immobilization, heart rate, respiratory rate, rectal temperature, indirect mean blood pressure (MBP), oxygen saturation, and end-tidal carbon dioxide concentration. Blood was collected for serum cortisol measurement. Significant (P < 0.05) differences included a higher MBP, higher serum cortisol, and longer recovery time with MKA compared to CXNA. In addition, the quality of induction and recovery were different. With MKA, animals ambulated less during induction, remained recumbent longer during recovery, and demonstrated more ataxia on rising. Despite differences between the protocols, both provided an acceptable level of immobilization for pre-shipment testing to be done and appeared to be safe in the study population. These differences should be taken into consideration when selecting the anesthetic protocol because either regimen may be more or less desirable for different medical or immobilization settings.


Assuntos
Hipnóticos e Sedativos/farmacologia , Ruminantes , Animais , Fentanila/administração & dosagem , Fentanila/análogos & derivados , Fentanila/farmacologia , Hipnóticos e Sedativos/administração & dosagem , Imidazóis/administração & dosagem , Imidazóis/farmacologia , Ketamina/administração & dosagem , Ketamina/farmacologia , Medetomidina/administração & dosagem , Medetomidina/farmacologia , Naltrexona/administração & dosagem , Naltrexona/farmacologia , Xilazina/administração & dosagem , Xilazina/farmacologia
8.
J Zoo Wildl Med ; 44(2): 395-403, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23805558

RESUMO

All anuran specimens in the Wildlife Conservation Society's collections testing positive for Batrachochytrium dendrobatidis (Bd) were treated with itraconazole and then studied after treatment to assess the long-term effects of itraconazole and the drug's effectiveness in eliminating Bd carriers. Twenty-four individuals and eight colonies of 11 different species (75 total specimens) tested positive for Bd via polymerase chain reaction (PCR) on multicollection survey. All positive individuals and colonies were treated with a 0.01% itraconazole bath solution and retested for Bd via one of two PCR methodologies within 14 days of treatment completion, and all were negative for Bd. A total of 64 animals received secondary follow-up PCR testing at the time of death, 6-8 mo, or 12-15 mo post-treatment. Fourteen animals (14/64, 21.9%) were PCR positive for Bd on second follow-up. The highest percentage positive at second recheck were green-and-black poison dart frogs (Dendrobates auratus; 5/5 specimens, 100%), followed by red-eyed tree frogs (Agalychnis callidryas; 4/11, 36.4%), grey tree frogs (Hyla versicolor; 1/3, 33.3%), and green tree frogs (Hyla cinera; 3/11, 27.3%). Re-testing by PCR performed on 26/28 individuals that died during the study indicated 11/26 (42.3%) were positive (all via DNA extracted from formalin-fixed paraffin-embedded skin sections). However, there was no histologic evidence of chytridiomycosis in any of 27/28 individuals. The small number of deceased animals and effects of postmortem autolysis limited the ability to determine statistical trends in the pathology data, but none of the necropsied specimens showed evidence of itraconazole toxicity. Problems with itraconazole may be species dependent, and this report expands the list of species that can tolerate treatment. Although itraconazole is effective for clearance of most individuals infected with Bd, results of the study suggest that repeat itraconazole treatment and follow-up diagnostics may be required to ensure that subclinical infections are eliminated in amphibian collections.


Assuntos
Anuros/microbiologia , Quitridiomicetos/isolamento & purificação , Itraconazol/uso terapêutico , Micoses/veterinária , Reação em Cadeia da Polimerase/veterinária , Animais , Antifúngicos/administração & dosagem , Antifúngicos/uso terapêutico , Itraconazol/administração & dosagem , Micoses/tratamento farmacológico , Micoses/microbiologia
9.
Front Pediatr ; 11: 1173700, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37325354

RESUMO

Background: The caudal block and transversus abdominis plane block (TAP) are commonly used in combination with general anesthesia for pediatric lower abdominal, inguinal, and genitourinary surgeries. There is limited data directly comparing the impact of these techniques on recovery. In this meta-analysis, we compare the duration of postoperative analgesia between these two techniques. Objective: This review examined the duration of analgesia in pediatric patients (age 0-18 years) undergoing surgery who received caudal or TAP block after induction of general anesthesia. The primary outcome was duration of analgesia, defined as the time to first rescue analgesic dose. Secondary outcomes included number of rescue analgesic doses, acetaminophen usage within 24 h postoperatively, 24 h pain score area under the curve, and postoperative nausea and vomiting. Evidence review: We systematically searched Pubmed, Central, EMBASE, CINAHL, Google Scholar, Web of Science citation index, the US clinical trials register, and abstracts from prominent 2020-2022 anesthesia conferences for randomized controlled trials that compared these blocks and reported analgesia duration. Findings: Twelve RCTs inclusive of 825 patients were identified. TAP block was associated with longer analgesia duration (Mean difference = 1.76 h, 95% CI: 0.70-2.81, p = 0.001) and reduced doses of rescue analgesic within 24 h (Mean difference = 0.50 doses, 95% CI: 0.02-0.98, p = 0.04). No statistically significant differences were detected in other outcomes. Conclusion: This meta-analysis suggests that TAP block provides greater duration of analgesia than caudal block after pediatric surgeries. TAP block was also associated with fewer rescue analgesic doses in the first 24 h without increased pain scores. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=380876, identifier: CRD42022380876.

10.
Reg Anesth Pain Med ; 48(1): 29-36, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36167478

RESUMO

INTRODUCTION: Regional techniques are a key component of multimodal analgesia and help decrease opioid use perioperatively, but some techniques may not be suitable for all patients, such as those with spina bifida. We hypothesized peripheral regional catheters would reduce postoperative opioid use compared with no regional analgesia without increasing pain scores in pediatric patients with spina bifida undergoing major urological surgery. METHODS: A retrospective review of a multicenter database established for the study of enhanced recovery after surgery was performed of patients from 2009 to 2021 who underwent bladder augmentation or creation of catheterizable channels. Patients without spina bifida and those receiving epidural analgesia were excluded. Opioids were converted into morphine equivalents and normalized to patient weight. RESULTS: 158 patients with pediatric spina bifida from 7 centers were included, including 87 with and 71 without regional catheters. There were no differences in baseline patient factors. Anesthesia setup increased from median 40 min (IQR 34-51) for no regional to 64 min (IQR 40-97) for regional catheters (p<0.01). The regional catheter group had lower median intraoperative opioid usage (0.24 vs 0.80 mg/kg morphine equivalents, p<0.01) as well as lower in-hospital postoperative opioid usage (0.05 vs 0.23 mg/kg/day morphine equivalents, p<0.01). Pain scores were not higher in the regional catheters group. DISCUSSION: Continuous regional analgesia following major urological surgery in children with spina bifida was associated with a 70% intraoperative and 78% postoperative reduction in opioids without higher pain scores. This approach should be considered for similar surgical interventions in this population. TRIAL REGISTRATION NUMBER: NCT03245242.


Assuntos
Analgesia Epidural , Disrafismo Espinal , Criança , Humanos , Analgésicos Opioides , Morfina , Estudos Multicêntricos como Assunto , Dor Pós-Operatória/diagnóstico , Dor Pós-Operatória/etiologia , Dor Pós-Operatória/prevenção & controle , Estudos Retrospectivos , Disrafismo Espinal/diagnóstico , Disrafismo Espinal/cirurgia , Disrafismo Espinal/complicações
11.
Oncotarget ; 13: 281-290, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35136485

RESUMO

GZ17-6.02 is undergoing clinical evaluation in solid tumors and lymphoma. The present studies were performed to define its biology in renal carcinoma cells and to determine whether it interacted with axitinib to enhance tumor cell killing. GZ17-6.02 interacted in an arithmetically greater than additive fashion with axitinib to kill kidney cancer cells. GZ17-6.02 and axitinib cooperated to inactivate ERBB2, c-MET, c-KIT, c-SRC, the AMPK, STAT3, STAT5 and eIF2α and to activate PERK, ULK1 and ATG13. The drugs interacted to increase the expression of FAS-L and to decrease the levels of MCL1, BCL-XL, and HDACs 1-3. The drugs as single agents inactivated the Hippo pathway. GZ17-6.02 and axitinib interacted to enhance autophagosome formation and autophagic flux. Knock down of Beclin1, ATG5, eIF2α, toxic BH3 domain proteins or CD95/FADD significantly reduced drug combination lethality. GZ17-6.02 and axitinib increased the expression of BAK, BIM, Beclin1 and ATG5, effects blocked by knock down of eIF2α. The drugs increased phosphorylation of ULK1 S757 and ATG13 S318 and decreased the phosphorylation of mTORC1 and mTORC2, effects blocked by knock down of AMPKα. Knock down of Beclin1 or ATG5 prevented the drug combination reducing expression of HDACs 1-3 and from enhancing the expression of MHCA. Knock down of HDACs 1-3 enhanced MHCA expression. We conclude that GZ17-6.02 and axitinib interact to kill requiring ER stress signaling, autophagy and death receptor signaling. Autophagic degradation of HDACs played a key role in enhancing MHCA expression and of a potential improved response to checkpoint inhibitory immunotherapy.


Assuntos
Antineoplásicos , Carcinoma de Células Renais , Neoplasias Renais , Proteínas Quinases Ativadas por AMP/metabolismo , Antineoplásicos/farmacologia , Autofagia , Axitinibe/farmacologia , Proteína Beclina-1/metabolismo , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/genética , Linhagem Celular Tumoral , Sinergismo Farmacológico , Fator de Iniciação 2 em Eucariotos/metabolismo , Humanos , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/genética , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Alvo Mecanístico do Complexo 2 de Rapamicina/metabolismo , Proteína de Sequência 1 de Leucemia de Células Mieloides/metabolismo , Receptores de Morte Celular/metabolismo , Fator de Transcrição STAT5/metabolismo
12.
Oncotarget ; 13: 92-104, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35035775

RESUMO

GZ17-6.02 is presently undergoing clinical evaluation in solid tumors and lymphoma. The present studies were performed to define its biology in estrogen receptor positive breast cancer cells and to determine whether it interacted with palbociclib to enhance tumor cell killing. GZ17-6.02 interacted in an additive fashion with palbociclib to kill ER+ breast cancer cells. GZ17-6.02 and palbociclib cooperated to inactivate mTOR and AKT and to activate ULK1 and PERK. The drugs interacted to increase the expression of FAS-L and BAX, and to decrease the levels of MCL1, the estrogen receptor, and HDACs 1-3. Palbociclib activated ERBB3, an effect blocked by GZ17-6.02. GZ17-6.02 and palbociclib interacted to increase the expression of multiple toxic BH3 domain proteins and to reduce MCL1 and BCL-XL expression. Knock down of FAS-L reduced the lethality of [GZ17-6.02 + palbociclib]. GZ17-6.02 and palbociclib interacted to enhance autophagosome formation and autophagic flux. Knock down of Beclin1, ATG5, BAG3, eIF2α, toxic BH3 domain proteins or CD95 significantly reduced drug combination lethality. GZ17-6.02 and palbociclib increased the expression of Beclin1 and ATG5, effects blocked by knock down of eIF2α. The drugs also increased the phosphorylation of the AMPK and ATG13, effects blocked by knock down of ATM. Knock down of ATM or the AMPK, or expression of activated mTOR significantly reduced the abilities of GZ17-6.02 and palbociclib to enhance autophagosome formation and autophagic flux.


Assuntos
Antineoplásicos , Neoplasias da Mama , Proteínas Quinases Ativadas por AMP/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Antineoplásicos/farmacologia , Proteínas Reguladoras de Apoptose , Proteína Beclina-1/metabolismo , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Linhagem Celular Tumoral , Sinergismo Farmacológico , Fator de Iniciação 2 em Eucariotos/metabolismo , Feminino , Humanos , Proteína de Sequência 1 de Leucemia de Células Mieloides/metabolismo , Piperazinas , Proteínas Proto-Oncogênicas c-akt/metabolismo , Piridinas , Receptores de Estrogênio/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Proteína X Associada a bcl-2/metabolismo
13.
Front Oncol ; 11: 711043, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34490108

RESUMO

We determined the molecular mechanisms by which the novel therapeutic GZ17-6.02 killed non-small cell lung cancer (NSCLC) cells. Erlotinib, afatinib, and osimertinib interacted with GZ17-6.02 to kill NSCLC cells expressing mutant EGFR proteins. GZ17-6.02 did not interact with any EGFR inhibitor to kill osimertinib-resistant cells. GZ17-6.02 interacted with the thymidylate synthase inhibitor pemetrexed to kill NSCLC cells expressing mutant ERBB1 proteins or mutant RAS proteins or cells that were resistant to EGFR inhibitors. The drugs interacted to activate ATM, the AMPK, and ULK1 and inactivate mTORC1, mTORC2, ERK1/2, AKT, eIF2α; and c-SRC. Knockdown of ATM or AMPKα1 prevented ULK1 activation. The drugs interacted to cause autophagosome formation followed by flux, which was significantly reduced by knockdown of ATM, AMPKα1, and eIF2α, or by expression of an activated mTOR protein. Knockdown of Beclin1, ATG5, or [BAX + BAK] partially though significantly reduced drug combination lethality as did expression of activated mTOR/AKT/MEK1 or over-expression of BCL-XL. Expression of dominant negative caspase 9 weakly reduced killing. The drug combination reduced the expression of HDAC2 and HDAC3, which correlated with lower PD-L1, IDO1, and ODC levels and increased MHCA expression. Collectively, our data support consideration of combining GZ17-6.02 and pemetrexed in osimertinib-resistant NSCLC.

14.
Reg Anesth Pain Med ; 2019 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-30992412

RESUMO

OBJECTIVE: Pediatric liver transplantation presents a number of anesthetic challenges, especially in providing adequate perioperative analgesia. In an effort to reduce opioid consumption and improve functional outcomes following pediatric liver transplantation, we have instituted a novel analgesia protocol centered on the provision of continuous regional analgesia with erector spinae plane (ESP) blockade. CASES: We describe preincisional bilateral ESP catheter placement in two pediatric patients undergoing orthotopic liver transplantation. The first case was a 12-year-old boy with maple syrup urine disease undergoing initial transplantation and the second case was an 8-year-old boy who underwent an 11 hours complex redo liver transplant in the setting of glycogen storage disease type 1A requiring initial liver transplant in 2014. The 8-year-old boy presented to the operating suite with acute Budd-Chiari syndrome with comorbid ascites and a large right pleural effusion. In both cases, ESP blockade resulted in good analgesia, markedly reduced intraoperative and postoperative opioid consumption as compared with institutional data and published rates of consumption and was associated with rapid return of bowel function. CONCLUSIONS: These early experiences suggest a role for continuous ESP blockade to improve analgesia and potentially change the paradigm of treatment in this fragile patient population. The technique should be considered in similar interventions. Further study will be undertaken to validate our observation.

15.
A A Pract ; 13(7): 267-270, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31206387

RESUMO

Although originally described to assist airway management of fetal congenital malformations with life-threatening airway obstruction, the indications for an ex utero intrapartum treatment (EXIT) have expanded to include surgical resection of lesions that are potentially incompatible with life in the absence of uteroplacental circulatory support. We describe the case of an infantile fibrosarcoma (IFS) that presented with fetal hydrops and was successfully managed with an emergency EXIT that necessitated the initiation of a massive fetal blood transfusion both with and without the support of uteroplacental circulation.


Assuntos
Fibrossarcoma/congênito , Fibrossarcoma/terapia , Neoplasias de Cabeça e Pescoço/congênito , Neoplasias de Cabeça e Pescoço/terapia , Adolescente , Transfusão de Sangue Intrauterina , Cesárea , Tratamento Farmacológico , Edema/etiologia , Tratamento de Emergência , Feminino , Doenças Fetais/terapia , Fibrossarcoma/diagnóstico por imagem , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Circulação Placentária , Gravidez
16.
Am J Primatol ; 70(7): 629-33, 2008 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-18366107

RESUMO

Hepatic hemosiderosis is one of the most common postmortem findings in captive callitrichid species. Noninvasive evaluation of hematologic iron analytes has been used to diagnose hepatic iron storage disease in humans, lemurs, and bats. This study evaluated the relationship between hematologic iron analyte values (iron, ferritin, total iron binding capacity, and percent transferrin saturation) and hepatic hemosiderosis in callitrichids at the Wildlife Conservation Society's Central Park and Bronx Zoos. Results revealed that both ferritin and percent transferrin saturation levels had strong positive correlations with hepatic iron concentration (P<0.001, r=0.77, n=20; P<0.001, r=0.85, n=10, respectively). Serum iron levels positively correlated with hepatic iron concentration (P=0.06, r=0.56, n=11), but this finding was not significant. Serum total iron binding capacity did not significantly correlate with hepatic iron concentration (P=0.47, r=0.25, n=10). Both ferritin and hepatic iron concentration positively correlated with severity of hepatic iron deposition on histology (P<0.05, r=0.49, n=21; P<0.001, r=0.67, n=21, respectively). This study suggests that ferritin, serum iron concentration, and percent transferrin saturation are convenient, noninvasive, antemortem methods for assessing severity of hemosiderosis in callitrichids.


Assuntos
Callitrichinae/sangue , Hemossiderose/veterinária , Ferro/sangue , Hepatopatias/veterinária , Doenças dos Macacos/sangue , Animais , Feminino , Hemossiderose/sangue , Hepatopatias/sangue , Masculino
17.
A A Pract ; 11(9): 250-252, 2018 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-29794802

RESUMO

The erector spinae plane block is an emerging technique for the provision of thoracolumbar analgesia with reported pediatric applications. We describe the placement of a continuous erector spinae plane catheter at the T5-T6 level in a 7-month-old infant who was undergoing thoracotomy for left upper lobectomy due to congenital pulmonary airway malformation. This technique resulted in outstanding analgesia without the need for opioid rescue analgesia. This block has a low degree of technical difficulty and is placed in area devoid of nearby critical structures and could be used in a number of potentially painful interventions.


Assuntos
Catéteres , Bloqueio Nervoso , Dor Pós-Operatória/tratamento farmacológico , Analgesia , Feminino , Humanos , Lactente , Vértebras Torácicas , Toracotomia
18.
J Zoo Wildl Med ; 37(4): 513-7, 2006 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17315436

RESUMO

Thiafentanil oxalate, previously known as A-3080, is a synthetic opioid used for chemical immobilization of a variety of nondomestic hoofstock species. This study compared the combination of thiafentanil oxalate, medetomidine, and ketamine (TMK; 0.09 +/- 0.02 mg/kg, 0.01 +/- 0.003 mg/kg, and 1.36 +/- 0.33 mg/kg, respectively) with the combination of medetomidine and ketamine (MK; 0.09 +/- 0.02 mg/kg and 3.48 +/- 0.55 mg/kg, respectively) for anesthetization of 17 captive male axis deer (Axis axis) for vasectomy. Nine deer received TMK and eight deer received MK via projectile syringe during the months of January and February, 2005. Mean induction and arousal times, vital signs, and arterial blood gas values were monitored and compared. All animals received supplemental oxygen during the surgical procedure. Animals receiving TMK were reversed with naltrexone (100 mg/mg thiafentanil) and atipamazole (5 mg/mg medetomidine). Animals receiving MK were reversed with atipamazole (5 mg/mg medetomidine). Two MK animals and three TMK animals required supplementation with ketamine i.v. immediately upon handling. Six of the nine animals immobilized with TMK required intubation for positive-pressure ventilation. Two of these six animals also required isoflurane to maintain anesthesia. Mean induction time was 3.5 +/- 2.0 min in the TMK group, and 9.8 +/- 6.7 min in the MK group. Despite shorter mean induction times, animals anesthetized with TMK experienced unpredictable inductions, apnea, muscle rigidity, limb movement, and significant respiratory and metabolic lactic acidosis. MK resulted in smoother inductions, better respiratory function, and less adverse metabolic disturbances, and thus was considered superior to TMK for anesthesia in captive axis deer at the dosages tested.


Assuntos
Anestésicos Combinados/administração & dosagem , Gasometria/veterinária , Cervos/fisiologia , Imobilização/veterinária , Anestésicos Dissociativos/administração & dosagem , Animais , Animais Selvagens , Cervos/cirurgia , Fentanila/administração & dosagem , Fentanila/análogos & derivados , Frequência Cardíaca/efeitos dos fármacos , Frequência Cardíaca/fisiologia , Hipnóticos e Sedativos/administração & dosagem , Imobilização/métodos , Ketamina/administração & dosagem , Masculino , Medetomidina/administração & dosagem , Respiração/efeitos dos fármacos , Fatores de Tempo , Vasectomia/métodos , Vasectomia/veterinária
19.
J Vet Diagn Invest ; 27(3): 392-5, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25943128

RESUMO

A captive, juvenile, female northern map turtle (Graptemys geographica) was found dead following a brief period of weakness and nasal discharge. Postmortem examination identified pneumonia with necrosis and numerous epithelial, intranuclear viral inclusion bodies, consistent with herpesviral pneumonia. Similar intranuclear inclusions were also associated with foci of hepatocellular and splenic necrosis. Polymerase chain reaction (PCR) screening of fresh, frozen liver for the herpesviral DNA-dependent DNA polymerase gene yielded an amplicon with 99.2% similarity to recently described emydid herpesvirus 1 (EmyHV-1). Molecular screening of turtles housed in enclosures that shared a common circulation system with the affected map turtle identified 4 asymptomatic, EmyHV-1 PCR-positive painted turtles (Chrysemys picta) and 1 asymptomatic northern map turtle. Herpesvirus transmission between painted and map turtles has been previously suggested, and our report provides the molecular characterization of a herpesvirus in asymptomatic painted turtles that can cause fatal herpesvirus-associated disease in northern map turtles.


Assuntos
Infecções por Herpesviridae/veterinária , Herpesviridae/isolamento & purificação , Tartarugas , Animais , Diagnóstico Diferencial , Feminino , Herpesviridae/genética , Infecções por Herpesviridae/diagnóstico , Fígado/virologia , Reação em Cadeia da Polimerase/veterinária
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