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1.
Zygote ; 31(5): 507-516, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37492001

RESUMO

Wagyu bulls are known to have a highly exacerbated libido, as shown by the intense sexual interest of young calves. Therefore we believe that Wagyu male animals have specialized Sertoli and Leydig cells that are directly involved with the sexual precocity in this breed as mature bulls have a small scrotal circumference. This study aimed to evaluate whether there were differences in the hormone and sperm characteristics of Wagyu bulls compared with the same characteristics of subspecies Bos indicus and Bos taurus sires. Frozen-thawed semen from Wagyu, Nellore, and Angus sires were analyzed for sperm kinetics (computer-assisted sperm analysis), plasma membrane integrity, chromatin integrity, acrosome status, mitochondrial activity, lipid peroxidation and hormone [luteinizing hormone (LH) and testosterone] serum concentration. The results showed that Wagyu had lower total motility and an increased number of sperm with no motility when compared with Nellore and Angus bulls. Wagyu breed did not differ from those breeds when considering plasma and acrosome membranes integrity, mitochondrial potential, chromatin resistance, sperm lipid peroxidation or hormone (LH and testosterone) concentrations. We concluded that Wagyu sires had lower total motility when compared with Nellore and Angus bulls. Wagyu breed did not differ from these breeds when considering plasma and acrosome membranes integrity, mitochondrial potential, chromatin resistance, sperm lipid peroxidation, or hormone (LH and testosterone) concentrations.


Assuntos
Sêmen , Motilidade dos Espermatozoides , Masculino , Bovinos , Animais , Contagem de Espermatozoides/veterinária , Espermatozoides , Testosterona , Cromatina
2.
Immunohematology ; 37(2): 89-94, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34170644

RESUMO

The ABO blood group system includes phenotypes, or subgroups, that differ in the amount of A and B antigens present on the red blood cells (RBCs). These subgroups also differ in the A, B, or H substances present in secretions (for individuals who have the secretor phenotype). B subgroups are very rare and are less frequently reported than A subgroups. Usually, B subgroups are discovered during serologic testing when there is a discrepancy between RBC and serum grouping results. Subgroups of B are usually identified by a reference laboratory using molecular and adsorption-elution methods. This report details a case of a young, healthy, pregnant woman with a B subgroup detected by a small transfusion service using adsorption-elution methods. Serology and genotyping of the ABO gene was performed at a reference laboratory where the serology was consistent with a B subgroup, but no changes were identified in ABO gene sequencing. It is important to correctly identify B subgroups in donors and recipients to help resolve ABO discrepancies and potentially prevent ABO incompatibility in blood transfusion, thus minimizing transfusion reactions.The ABO blood group system includes phenotypes, or subgroups, that differ in the amount of A and B antigens present on the red blood cells (RBCs). These subgroups also differ in the A, B, or H substances present in secretions (for individuals who have the secretor phenotype). B subgroups are very rare and are less frequently reported than A subgroups. Usually, B subgroups are discovered during serologic testing when there is a discrepancy between RBC and serum grouping results. Subgroups of B are usually identified by a reference laboratory using molecular and adsorption-elution methods. This report details a case of a young, healthy, pregnant woman with a B subgroup detected by a small transfusion service using adsorption-elution methods. Serology and genotyping of the ABO gene was performed at a reference laboratory where the serology was consistent with a B subgroup, but no changes were identified in ABO gene sequencing. It is important to correctly identify B subgroups in donors and recipients to help resolve ABO discrepancies and potentially prevent ABO incompatibility in blood transfusion, thus minimizing transfusion reactions.


Assuntos
Tipagem e Reações Cruzadas Sanguíneas , Reação Transfusional , Sistema ABO de Grupos Sanguíneos , Transfusão de Sangue , Feminino , Hospitais , Humanos , Gravidez
3.
J Neurophysiol ; 122(3): 1123-1135, 2019 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-31291154

RESUMO

The nearly axiomatic idea that de novo protein synthesis is necessary for long-term memory consolidation is based heavily on behavioral studies using translational inhibitors such as anisomycin. Although inhibiting protein synthesis has been shown to disrupt the expression of memory, translational inhibitors also have been found to profoundly disrupt basic neurobiological functions, including the suppression of ongoing neural activity in vivo. In the present study, using transverse hippocampal brain slices, we monitored the passive and active membrane properties of hippocampal CA1 pyramidal neurons using intracellular whole cell recordings during a brief ~30-min exposure to fast-bath-perfused anisomycin. Anisomycin suppressed protein synthesis to 46% of control levels as measured using incorporation of radiolabeled amino acids and autoradiography. During its application, anisomycin caused a significant depolarization of the membrane potential, without any changes in apparent input resistance or membrane time constant. Anisomycin-treated neurons also showed significant decreases in firing frequencies and spike amplitudes, and showed increases in spike width across spike trains, without changes in spike threshold. Because these changes indicated a loss of cellular energetics contributing to maintenance of ionic gradients across the membrane, we confirmed that anisomycin impaired mitochondrial function by reduced staining with 2,3,5-triphenyltetrazolium chloride and also impaired cytochrome c oxidase (complex IV) activity as indicated through high-resolution respirometry. These findings emphasize that anisomycin-induced alterations in neural activity and metabolism are a likely consequence of cell-wide translational inhibition. Critical reevaluation of studies using translational inhibitors to promote the protein synthesis dependent idea of long-term memory is absolutely necessary.NEW & NOTEWORTHY Memory consolidation is thought to be dependent on the synthesis of new proteins because translational inhibitors produce amnesia when administered just after learning. However, these agents also disrupt basic neurobiological functions. We show that blocking protein synthesis disrupts basic membrane properties of hippocampal neurons that correspond to induced disruptions of mitochondrial function. It is likely that translational inhibitors cause amnesia through their disruption of neural activity as a result of dysfunction of intracellular energetics.


Assuntos
Anisomicina/farmacologia , Região CA1 Hipocampal/efeitos dos fármacos , Complexo IV da Cadeia de Transporte de Elétrons/efeitos dos fármacos , Potenciais da Membrana/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Biossíntese de Proteínas/efeitos dos fármacos , Inibidores da Síntese de Proteínas/farmacologia , Células Piramidais/efeitos dos fármacos , Potenciais de Ação/efeitos dos fármacos , Animais , Memória de Longo Prazo/efeitos dos fármacos , Ratos
4.
Knee Surg Sports Traumatol Arthrosc ; 25(1): 319-324, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25786825

RESUMO

PURPOSE: Chondrocalcinosis can be associated with an inflammatory arthritis and aggressive joint destruction. There is uncertainty as to whether chondrocalcinosis represents a contraindication to unicompartmental knee arthroplasty (UKA). This study reports the outcome of a consecutive series of patients with chondrocalcinosis and medial compartment osteoarthritis treated with UKA matched to controls. METHODS: Between 1998 and 2008, 88 patients with radiological chondrocalcinosis (R-CCK) and 67 patients with histological chondrocalcinosis (H-CCK) were treated for end-stage medial compartment arthritis with Oxford UKA. One-to-two matching was performed to controls, treated with UKA, but without evidence of chondrocalcinosis. Functional outcome and implant survival were assessed in each group. RESULTS: The mean follow-up was 10 years. The mean Oxford Knee Score (OKS) at final follow-up was 43, 41 and 41 in H-CCK, R-CCK and control groups (change from baseline OKS was 21, 18 and 15, respectively). The change was significantly higher in H-CCK than in control but was not significantly different in R-CCK. Ten-year survival was 96 % in R-CCK, 86 % in H-CCK and 98 % in controls. Although the survival in H-CCK was significantly worse than in control, only one failure was due to disease progression. CONCLUSION: The presence of R-CCK does not influence functional outcome or survival following UKA. Pre-operative radiological evidence of CCK should not be considered to be a contraindication to UKA. H-CCK is associated with significantly improved clinical outcomes but also a higher revision rate compared with controls. LEVEL OF EVIDENCE: Case control study, Level III.


Assuntos
Artroplastia do Joelho , Condrocalcinose/complicações , Osteoartrite do Joelho/cirurgia , Idoso , Estudos de Casos e Controles , Condrocalcinose/diagnóstico por imagem , Condrocalcinose/patologia , Estudos de Coortes , Progressão da Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Prótese do Joelho , Masculino , Pessoa de Meia-Idade , Osteoartrite do Joelho/complicações , Modelos de Riscos Proporcionais , Radiografia , Resultado do Tratamento
5.
Knee Surg Sports Traumatol Arthrosc ; 25(3): 694-702, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26611902

RESUMO

PURPOSE: Cementless unicompartmental knee replacement (UKR) was introduced to address some of the problems that can occur following cemented UKR. The aim of this study was to report the 5-year experience of the first 512 medial cementless Oxford UKR implanted by two surgeons for the recommended indications. METHODS: The first consecutive 512 cementless Phase 3 Oxford UKRs implanted by two surgeons for the recommended indications between June 2004 and October 2013 were prospectively identified and followed up independently. All the procedures were carried out through a minimally invasive approach without eversion or dislocation of the patella. Patients were assessed clinically pre-operatively and at 1, 2, 5, 7 and 10 years after surgery with functional outcome scores and radiographs. RESULTS: There were eight reoperations of which six were revisions giving a 5-year survival of 98 % (95 % CI 94-100 %). At a mean follow-up of 3.4 years (1.0-10.2), the mean OKS was 43 (SD 7), AKSS (objective) was 81 (SD 13), and AKSS (functional) was 86 (SD 17). The first 120 cases had a minimum follow-up of 5 years (mean 5.9; range 5-10.2). In these patients, the mean OKS was 41 (SD 8), AKSS (objective) was 81 (SD 14), and AKSS (functional) was 82 (SD 18). There were no femoral radiolucencies and no complete tibial radiolucencies. 11 % of tibial components had partial radiolucent lines; the remaining 89 % had no radiolucencies. CONCLUSION: The clinical results are as good as or better than those previously reported for cemented fixation. The radiographic results are better with secure bony attachment to the implants in every case. LEVEL OF EVIDENCE: IV.


Assuntos
Artroplastia do Joelho/métodos , Prótese do Joelho , Osteoartrite do Joelho/cirurgia , Complicações Pós-Operatórias/diagnóstico por imagem , Desenho de Prótese , Adulto , Idoso , Idoso de 80 Anos ou mais , Cimentos Ósseos , Estudos de Coortes , Feminino , Fêmur/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Patela , Estudos Prospectivos , Radiografia , Reoperação , Tíbia/diagnóstico por imagem , Resultado do Tratamento
6.
J Vet Pharmacol Ther ; 39(6): 572-577, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27086733

RESUMO

Use of compounded L-asparaginase became routine in veterinary oncology when manufacturing of Elspar® was discontinued in 2012. The objective of this study was to evaluate the safety of compounded L-asparaginase (CLASP, KRS Global Biotechnology, Boca Raton, FL, USA) in comparison with Elspar® (Lundbeck LLC, Deerfield, IL, USA). In addition, we documented the response to CLASP in combination with a corticosteroid in this population of dogs with lymphoma. Dogs were prospectively treated with 10 000 IU/m2 CLASP or Elspar® subcutaneously. Corticosteroids were administered concurrently. Adverse events (AE) were assessed according to the Veterinary Cooperative Oncology Group Common Terminology Criteria for Adverse Events v1.1 (VCOG-CTCAE). Response was recorded. Seventy-three dogs received 75 treatments (CLASP, n = 47; Elspar® , n = 28). No AE were attributed to CLASP. Grade I and II AE probably or possibly related to treatment were observed following two Elspar® treatments. The overall response rate to the combination of CLASP and a corticosteroid was 80% (24% CR and 56% PR). In combination with a steroid, the compounded L-asparaginase evaluated in this study is safe and demonstrates activity against canine lymphoma. In the face of the discontinuation of Elspar® , veterinarians should seek compounded LASP products that have been tested for activity, purity, and sterility.


Assuntos
Asparaginase/efeitos adversos , Doenças do Cão/tratamento farmacológico , Linfoma/veterinária , Animais , Asparaginase/química , Asparaginase/uso terapêutico , Estudos de Coortes , Corticosterona , Cães , Composição de Medicamentos , Linfoma/tratamento farmacológico
7.
Occup Med (Lond) ; 65(7): 598-600, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26136595

RESUMO

Hypersensitivity pneumonitis (HP) is an inflammatory lung disease mediated by an immunological response to an inhaled antigen. Outbreaks of HP have been reported in industrial settings where manufacturing workers are exposed to water-based metalworking fluids (MWFs). Water-based MWFs promote growth of microorganisms and can be easily aerosolized and are thus potential aetiological agents of HP. We present a case of HP caused by exposure to water-based MWF in a vocational high school teacher. Culture of MWF used at his school grew Pseudomonas pseudoalcaligenes. This is the first known report of MWF-induced HP outside an industrial setting. The growth of Pseudomonas spp in this case recalls the earliest reports of the microbiology of MWF-induced HP and suggests that routine bacterial culture may be useful in the diagnosis of HP in workplaces without standard cleaning and biocide regulations.


Assuntos
Alveolite Alérgica Extrínseca/etiologia , Metalurgia , Doenças Profissionais/etiologia , Exposição Ocupacional/efeitos adversos , Pseudomonas pseudoalcaligenes , Professores Escolares , Alveolite Alérgica Extrínseca/microbiologia , Desinfecção , Humanos , Masculino , Pessoa de Meia-Idade , Doenças Profissionais/microbiologia , Água , Local de Trabalho
8.
Reprod Domest Anim ; 49 Suppl 4: 11-21, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25277428

RESUMO

Melatonin is a ubiquitous molecule, present in a wide range of organisms, and involved in multiple functions. Melatonin relays the information about the photoperiod to the tissues that express melatonin-binding sites in both central and peripheral nervous systems. This hormone has a complex mechanism of action. It can cross the cell plasma membrane and exert its actions in all cells of the body. Certain melatonin actions are mediated by receptors that belong to the superfamily of G-protein-coupled receptors (GPCRs), the MT1 and MT2 membrane. Melatonin can also bind to calmodulin as well as to nuclear receptors of the retinoic acid receptor family, RORα1, RORα2 and RZRß. The purpose of this review is to report on recent developments in the physiological role of melatonin and its receptors. Specific issues concerning the biological function of melatonin in mammalian seasonal reproduction and spermatozoa are considered. The significance of the continuous presence of melatonin in seminal plasma with a fairly constant concentration is also discussed.


Assuntos
Melatonina/metabolismo , Receptores de Melatonina/metabolismo , Reprodução , Transdução de Sinais/fisiologia , Espermatozoides/metabolismo , Animais , Humanos , Masculino , Mamíferos , Melatonina/farmacologia , Camundongos , Fotoperíodo , Reprodução/efeitos dos fármacos
9.
Knee Surg Sports Traumatol Arthrosc ; 22(7): 1467-82, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24497054

RESUMO

PURPOSE: In August 2011, orthopaedic surgeons from more than 20 countries attended a summit on anatomic anterior cruciate ligament (ACL) reconstruction. The summit offered a unique opportunity to discuss current concepts, approaches, and techniques in the field of ACL reconstruction among leading surgeons in the field. METHODS: Five panels (with 36 panellists) were conducted on key issues in ACL surgery: anatomic ACL reconstruction, rehabilitation and return to activity following anatomic ACL reconstruction, failure after ACL reconstruction, revision anatomic ACL reconstruction, and partial ACL injuries and ACL augmentation. Panellists' responses were secondarily collected using an online survey. RESULTS: Thirty-six panellists (35 surgeons and 1 physical therapist) sat on at least one panel. Of the 35 surgeons surveyed, 22 reported performing "anatomic" ACL reconstructions. The preferred graft choice was hamstring tendon autograft (53.1 %) followed by bone-patellar tendon-bone autograft (22.8 %), allograft (13.5 %), and quadriceps tendon autograft (10.6 %). Patients generally returned to play after an average of 6 months, with return to full competition after an average of 8 months. ACL reconstruction "failure" was defined by 12 surgeons as instability and pathological laxity on examination, a need for revision, and/or evidence of tear on magnetic resonance imaging. The average percentage of patients meeting the criteria for "failure" was 8.2 %. CONCLUSIONS: These data summarize the results of five panels on anatomic ACL reconstruction. The most popular graft choice among surgeons for primary ACL reconstructions is hamstring tendon autograft, with allograft being used most frequently employed in revision cases. Nearly half of the surgeons surveyed performed both single- and double-bundle ACL reconstructions depending on certain criteria. Regardless of the technique regularly employed, there was unanimous support among surgeons for the use of "anatomic" reconstructions using bony and soft tissue remnant landmarks.


Assuntos
Lesões do Ligamento Cruzado Anterior , Reconstrução do Ligamento Cruzado Anterior/métodos , Adolescente , Adulto , Distribuição por Idade , Enxerto Osso-Tendão Patelar-Osso , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Recuperação de Função Fisiológica , Reoperação , Inquéritos e Questionários , Tendões/transplante , Transplante Autólogo , Transplante Homólogo , Falha de Tratamento , Resultado do Tratamento
10.
Knee Surg Sports Traumatol Arthrosc ; 22(8): 1887-94, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24917536

RESUMO

PURPOSE: Shortening of the patella tendon has been noted after total knee arthroplasty and has been associated with diminished functional outcomes. Traumatic and/or ischaemic injury peri-operatively are suggested causes. The Oxford domed lateral unicompartmental knee arthroplasty (UKA) requires a vertical incision through the patella tendon to facilitate orientation of the proximal tibial saw cut; this may induce scarring or impair vascularity of the tendon and can cause shortening. This study investigated the hypothesis that the trans-patella tendon incision increases the incidence of patella tendon shortening after domed lateral UKA when compared to flat lateral UKA performed without the trans-patella tendon incision. METHODS: The radiographs of 50 patients who underwent domed lateral UKA, using the trans-patella tendon approach, and a cohort of 30 patients who underwent flat lateral UKA, in which an incision through the patella tendon was not employed, were reviewed retrospectively. The patella tendon length (PTL) and the Insall-Salvati ratio were measured. In addition, pre-operative and post-operative clinical scores were recorded using both the OKS and AKSS. A change in PTL of greater than or equal to 10 % was considered to be significant. RESULTS: In the domed lateral UKA group, 13 patients demonstrated a >10 % change in the PTL at 1-year post-surgery (2 shortened and 11 lengthened). In the flat lateral UKA group, nine patients demonstrated a significant change in the PTL at 1-year post-surgery (2 shortened and 7 lengthened). CONCLUSION: This study demonstrated that using a trans-patella approach during lateral domed UKA surgery did not significantly increase patella tendon shortening and did not result in reduced clinical outcomes.


Assuntos
Artroplastia do Joelho/métodos , Ligamento Patelar/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ligamento Patelar/patologia , Estudos Retrospectivos , Fatores de Risco
11.
Knee ; 47: 13-20, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38171207

RESUMO

BACKGROUND: Periprosthetic joint infection (PJI) following unicompartmental knee replacement (UKR) is an uncommon, yet serious, complication. There is a paucity of evidence regarding the effectiveness of Debridement-Antibiotics-and-Implant-Retention (DAIR) in this setting. The aim of this study is to investigate the effectiveness of DAIR for acute UKR PJI. METHOD: Between 2006 and 2019, 5195 UKR were performed at our institution. Over this period, sixteen patients underwent DAIR for early, acute PJI. All patients met MSIS PJI diagnostic criteria. The median age at DAIR was 67 years (range 40-73) and 12 patients were male (75.0%). The median time to DAIR was 24 days (range 6-60). Patients were followed up for a median of 6.5 years (range1.4-10.5) following DAIR. RESULTS: 0.3% (16/5195) of UKR in our institution had a DAIR within 3 months. 15 of 16 patients (93.8%) were culture positive, with the most common organism MSSA (n = 8, 50.0%). Patients were treated with an organism-specific intravenous antibiotic regime for a median of 6 weeks, followed by oral antibiotics for a median duration of 6 months. The Kaplan-Meier survivor estimate for revision for PJI was 57% (95%CI: 28-78%) at five years, and survivor estimate for all cause revision 52% (95%CI: 25-74%).The median Oxford Knee Score for patients with a viable implant at final follow-up was 45 points (range 39-46). CONCLUSION: Early, acute PJI after UKR is rare. DAIR had a moderate success rate, with infection-free survivorship of 57% at 5 years. Those successfully treated with DAIR had excellent functional outcome and implant survival.


Assuntos
Antibacterianos , Artroplastia do Joelho , Desbridamento , Prótese do Joelho , Infecções Relacionadas à Prótese , Humanos , Infecções Relacionadas à Prótese/etiologia , Infecções Relacionadas à Prótese/tratamento farmacológico , Infecções Relacionadas à Prótese/terapia , Masculino , Artroplastia do Joelho/efeitos adversos , Feminino , Pessoa de Meia-Idade , Antibacterianos/uso terapêutico , Antibacterianos/administração & dosagem , Idoso , Adulto , Prótese do Joelho/efeitos adversos , Estudos Retrospectivos , Retenção da Prótese , Resultado do Tratamento
12.
Curr Oncol ; 27(3): e276-e282, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32669934

RESUMO

Background: The real-world impact of tyrosine kinase inhibitors (tkis) in clinical practice for gastrointestinal stromal tumour (gist) has not been extensively reported. We sought to assess how outcomes have changed over the eras and to evaluate the effect of access to imatinib and sunitinib on survival in patients with unresectable or metastatic gist in British Columbia. Methods: Patients with metastatic or unresectable gist were allocated to one of three eras: pre-2002, 2002-2007, and post-2007 based on treatment availability (pre-imatinib, post-imatinib, and post-sunitinib). Overall survival (os) and progression-free survival (pfs) were compared between eras. Univariate and multivariate analyses were performed to determine the effects of tumour, patient, and treatment characteristics on survival outcomes. Results: Of 657 patients diagnosed with gist throughout British Columbia during 1996-2016, 196 had metastatic disease: 23 in the pre-imatinib era, 67 in the post-imatinib era, and 106 in the post-sunitinib era. A significant increase in os, by 53.6 months (p = 0.0007), and pfs, by 29.1 months (p = 0.044), was observed after the introduction of imatinib. The introduction of sunitinib did not significantly affect os or pfs. Conclusions: Implementation of tkis has drastically improved survival outcomes for patients with metastatic gist by up to 4.55 years in the real-world setting. Our study demonstrates that implementation of tkis in clinical practice has outperformed their benefit predicted in clinical trials.


Assuntos
Antineoplásicos/uso terapêutico , Tumores do Estroma Gastrointestinal/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/farmacologia , Estudos de Coortes , Humanos , Pessoa de Meia-Idade , Inibidores de Proteínas Quinases/farmacologia , Adulto Jovem
13.
Dev Cell ; 2(1): 103-13, 2002 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-11782318

RESUMO

A central issue in signal transduction is the physiological contribution of different growth factor-initiated signaling pathways. We have generated knockin mice harboring mutations in the PDGFalpha receptor (PDGFalphaR) that selectively eliminate its capacity to activate PI3 kinase (alpha(PI3K)) or Src family kinases (alpha(Src)). The alpha(PI3K) mutation leads to neonatal lethality due to impaired signaling in many cell types, but the alpha(Src) mutation only affects oligodendrocyte development. A third knockin line containing mutations that eliminate multiple docking sites does not increase the severity of the alpha(PI3K) mutation. However, embryos with mutations in the PI3K binding sites of both PDGFRs (alpha and beta) recapitulate the PDGFalphaR null phenotype. Our results indicate that PI3K has a predominant role in PDGFalphaR signaling in vivo and that RTK-activated signaling pathways execute both specific and overlapping functions during mammalian development.


Assuntos
Receptor alfa de Fator de Crescimento Derivado de Plaquetas/genética , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/metabolismo , Transdução de Sinais/fisiologia , Alelos , Animais , Osso e Ossos/anormalidades , Fibroblastos/fisiologia , Genes Letais , Homozigoto , Camundongos , Camundongos Mutantes , Mutagênese/fisiologia , Oligodendroglia/fisiologia , Fenótipo , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Fosforilação , Quinases da Família src/genética , Quinases da Família src/metabolismo
14.
Am J Transplant ; 9(6): 1287-93, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19459786

RESUMO

Two concerns expressed by the American Society of Transplant Surgeons (ASTS) are that (1) the new Medicare regulations for transplant hospitals take a 'punitive' approach and that (2) the outcome requirement may thwart innovation by not including certain risk factors into the risk adjustment used to calculate expected outcomes. This article explains efforts by the Centers for Medicare & Medicaid Services (CMS) to encourage quality improvement. CMS limits outcomes-related enforcement to situations where failure rates exceed certain substantial 'tolerance limits', ensuring opportunity for quality improvement to be effective prior to enforcement. Transplantations involving a disproportionate share of risk factors not incorporated into the risk-adjustment methodology can also be raised through CMS''mitigating factors' process. Of the 22 mitigating factor requests completed through March 10, 2009, 7 raised issues of risk adjustment (none involved experimental protocols). Four of the seven requests were approved for other reasons (evidence of effective program changes and improved outcomes). CMS concluded that none of the seven made a persuasive case based on risk factors. The early data indicate that program deficiencies may outweigh risk adjustment issues. CMS agrees to consider the ASTS suggestions for future action and continues to monitor the situation in case a different pattern emerges.


Assuntos
Centers for Medicare and Medicaid Services, U.S./economia , Medicare/economia , Medicare/legislação & jurisprudência , Transplante de Órgãos/normas , Avaliação de Resultados em Cuidados de Saúde , Risco Ajustado/economia , Responsabilidade Social , Difusão de Inovações , Humanos , Liderança , Transplante de Órgãos/mortalidade , Sociedades Médicas , Estados Unidos
15.
Science ; 206(4419): 693-5, 1979 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-493974

RESUMO

Estradiol-17 beta stimulates the synthesis of numerous proteins exported into the culture medium by Xenopus tadpole liver tissue obtained after stage 50 and throughout metamorphosis to stage 66. Although estrogen-induced vitellogenin can be detected as early as stage 54, it is a minor percentage of the exported proteins until after the completion of metamorphosis. In hepatic tissue obtained after metamorphosis, the hormone evokes the synthesis of vitellogenin specifically without affecting the labeling of other secreted proteins.


Assuntos
Estrogênios/farmacologia , Lipoproteínas/biossíntese , Fígado/crescimento & desenvolvimento , Vitelogeninas/biossíntese , Animais , Estradiol/farmacologia , Larva , Peso Molecular , Biossíntese de Proteínas
16.
Science ; 224(4652): 994-6, 1984 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-6372095

RESUMO

The effectiveness of adriamycin in the treatment of ovarian cancer and other human tumors has been limited by the development of drug resistance. Verapamil, a calcium channel blocking agent, completely reversed adriamycin resistance in human ovarian cancer cells with moderate (three- to sixfold) degrees of resistance and partially reversed resistance in highly (150-fold) resistant cells. The potentiating effect of verapamil was due to inhibition of adriamycin efflux in the resistant cells. These results have led to a clinical trial of adriamycin and verapamil in refractory ovarian cancer patients.


Assuntos
Doxorrubicina/uso terapêutico , Neoplasias Ovarianas/tratamento farmacológico , Verapamil/uso terapêutico , Linhagem Celular , Ensaios Clínicos como Assunto , Relação Dose-Resposta a Droga , Resistência a Medicamentos , Feminino , Humanos
17.
Andrology ; 7(3): 373-381, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30920782

RESUMO

BACKGROUND: Sperm DNA integrity is crucial for transmission of genetic information to future generations and DNA damage can occur during chromatin packaging. Chromatin packaging involves the replacement of somatic nucleosomal histones by nuclear proteins called protamines. Protamine 1 (PRM1) is transcribed and translated in spermatids of all mammals; however, protamine 2 (PRM2) is transcribed in low levels in spermatids and it is not yet described in bull mature spermatozoa. OBJECTIVES: The aim of this study was to assess gene and protein expression of PRM2 and corroborate gene and protein expression of PRM1 in bull spermatozoa and testis. MATERIALS AND METHODS: For this purpose, absolute q-RT-PCR was performed to calculate the number of copies of PRM1 and PRM2 mRNAs in bovine epididymal spermatozoa and testicular tissue. Western blot and mass spectrometry were performed to identify PRM1 and PRM2 in samples of bovine epididymal spermatozoa. Samples of bovine testicular tissue were collected to identify PRM1 and PRM2 by immunohistochemistry. RESULTS: We evaluated that the number of PRM1 mRNA copies was about hundred times higher than PRM2 mRNA copies in sperm and testicular samples (p < 0.0001). In addition, we estimated the PRM1: PRM2 ratio based on mRNA number of copies. In spermatozoa, the ratio was 1: 0.014, and in testicle, the ratio was 1: 0.009. We also evaluated the immunolocalization for PRM1 and PRM2 in bovine testis, and both proteins were detected in spermatids. Western blot and mass spectrometry in bovine epididymal spermatozoa confirmed these results. CONCLUSION: Our work identifies, for the first time, PRM2 in bovine epididymal spermatozoa and in testis. Further studies are still needed to understand the role of PRM2 on the chromatin of the spermatozoa and to verify how possible changes in PRM2 levels may influence the bull fertility.


Assuntos
Bovinos/metabolismo , Protaminas/metabolismo , Espermatozoides/metabolismo , Testículo/metabolismo , Animais , Núcleo Celular/metabolismo , Epididimo/citologia , Expressão Gênica , Masculino , Protaminas/genética , RNA Mensageiro/metabolismo
18.
Curr Oncol ; 26(6): e773-e784, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31896948

RESUMO

The 20th annual Western Canadian Gastrointestinal Cancer Consensus Conference was held in Saskatoon, Saskatchewan, 28-29 September 2018. This interactive multidisciplinary conference is attended by health care professionals from across Western Canada (British Columbia, Alberta, Saskatchewan, and Manitoba) who are involved in the care of patients with gastrointestinal cancers. In addition, invited speakers from other provinces participate. Surgical, medical, and radiation oncologists, and allied health care professionals participated in presentations and discussion sessions for the purpose of developing the recommendations presented here. This consensus statement addresses current issues in the management of colorectal cancers.


Assuntos
Neoplasias Gastrointestinais , Guias de Prática Clínica como Assunto , Biomarcadores Tumorais , Consenso , Neoplasias Gastrointestinais/genética , Neoplasias Gastrointestinais/radioterapia , Neoplasias Gastrointestinais/cirurgia , Neoplasias Gastrointestinais/terapia , Humanos , Hipertermia Induzida , Terapia Neoadjuvante
19.
J Pediatric Infect Dis Soc ; 7(3): 253-256, 2018 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-28992111

RESUMO

Here, we report a complex case that involved a pediatric patient who experienced recalcitrant multidrug-resistant Pseudomonas aeruginosa infection complicated by bacteremia/sepsis; our antibacterial options were limited because of resistance, allergies, and suboptimal source control. A cocktail of 2 bacteriophages targeting the infectious organism introduced on 2 separate occasions sterilized the bacteremia.


Assuntos
Bacteriemia/terapia , Terapia por Fagos , Infecções por Pseudomonas/terapia , Bacteriemia/sangue , Pré-Escolar , Farmacorresistência Bacteriana Múltipla , Evolução Fatal , Humanos , Masculino , Terapia por Fagos/efeitos adversos , Terapia por Fagos/métodos , Infecções por Pseudomonas/sangue
20.
Theriogenology ; 107: 142-148, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29154161

RESUMO

In vitro fertility potential of individual bulls is still relatively uncharacterized. Classical sperm analysis does not include the evaluation of all sperm characteristics and thus, some cell compartments could be neglected. In humans, sperm DNA integrity has already proven to have major influence in embryo development and assisted reproduction techniques successfully. In bovine, some studies already correlated chromatin integrity with field fertility. However, none of those have attempted to relate DNA assessment approaches such as chromatin deficiency (CMA3), chromatin stability (SCSA; AO+) and DNA fragmentation (COMET assay) to predict in vitro bull fertility. To this purpose, we selected bulls with high and low in vitro fertility (n = 6/group), based on embryo development rate (blastocyst/cleavage rate). We then performed CMA3, SCSA test and COMET assay to verify if the difference of in vitro fertility may be related to DNA alterations evaluated by these assays. For the three tests performed, our results showed only differences in the percentage of cells with chromatin deficiency (CMA3+; high: 0.19 ± 0.03 vs low: 0.04 ± 0.04; p = 0.03). No difference for chromatin stability and any of COMET assay categories (grade I to grade IV) was observed between high and low in vitro fertility bulls. A positive correlation between AO + cells and grade IV cells was found. Despite the difference between groups in CMA3 analysis, our results suggest that protamine deficiency in bovine spermatozoa may not have a strong biological impact to explain the difference of in vitro fertility between the bulls used in this study.


Assuntos
Bovinos/fisiologia , Cromatina , Fragmentação do DNA , Fertilização in vitro/veterinária , Espermatozoides/fisiologia , Animais , Ensaio Cometa , Fertilidade , Masculino , Estudos Retrospectivos , Análise do Sêmen
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