Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 33
Filtrar
Mais filtros

Base de dados
Tipo de documento
Intervalo de ano de publicação
1.
Vox Sang ; 2024 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-39293935

RESUMO

BACKGROUND AND OBJECTIVES: The post-thaw shelf-life of cryoprecipitate is 6 h, leading to high wastage. Storage of thawed cryoprecipitate at refrigerated temperatures may be feasible to extend the shelf-life. This study aimed to evaluate the quality of thawed cryoprecipitate stored at 1-6°C for up to 14 days. MATERIALS AND METHODS: Cryoprecipitate (mini- and full-size packs derived from both apheresis and whole blood [WB] collections) was thawed, immediately sampled and then stored at 1-6°C for up to 14 days. Mini-packs were sampled at 6, 24, 48 and 72 h, day 7 and 14; full-size cryoprecipitate was sampled on day 3, 5 or 7. Coagulation factors (F) II, V, VIII, IX, X and XIII, von Willebrand factor (VWF) and fibrinogen were measured using a coagulation analyser. Thrombin generation was measured by calibrated automated thrombogram. RESULTS: FVIII decreased during post-thaw storage; this was significant after 24 h for WB (p = 0.0002) and apheresis (p < 0.0001). All apheresis and eight of 20 WB cryoprecipitate met the FVIII specification (≥ 70 IU/unit) on day 14 post-thaw. Fibrinogen remained stable for 48 h, and components met the specification on day 14 post-thaw. There were no significant differences in VWF (WB p = 0.1292; apheresis p = 0.1507) throughout storage. There were small but significant decreases in thrombin generation lag time, endogenous thrombin potential and time to peak for both WB and apheresis cryoprecipitate. CONCLUSION: Whilst coagulation factors in cryoprecipitate decreased after post-thaw storage, the thawed cryoprecipitate met the Council of Europe specifications when stored at refrigerated temperatures for 7 days.

2.
Vox Sang ; 118(11): 993-996, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37718663

RESUMO

BACKGROUND AND OBJECTIVES: In Australia, the vast distances between blood collection centres and processing facilities make it challenging to align supply with demand. Increasing the time to freezing for clinical plasma beyond 6 h would alleviate supply issues. This study aimed to determine the quality of clinical apheresis plasma frozen within 12 h of collection. MATERIALS AND METHODS: Apheresis plasma (n = 20) collected at donor centres was immediately transported to a blood processing facility, stored at 26°C and sampled aseptically at 6, 8 and 12 h post collection. Frozen samples were thawed, and coagulation factors (F) II, V, VII, VIII and XIII, von Willebrand factor (vWF) and fibrinogen were measured using a coagulation analyser. RESULTS: FVIII concentrations declined in plasma frozen at 6, 8 and 12 h post collection (1.22 ± 0.27, 1.21 ± 0.25 and 1.16 ± 0.24 IU/mL, respectively) but not significantly (p = 0.3338). Importantly, all components met the FVIII specification (>0.7 IU/mL) for clinical plasma. Fibrinogen concentrations were stable from 6 to 12 h (p = 0.3100), as were vWF concentrations (p = 0.1281). Coagulation factors II, V, VII and XIII were not significantly different (p > 0.05 for all factors). CONCLUSION: Clinical apheresis plasma can be frozen within 12 h of collection, allowing collections from donor centres further from processing centres and increasing supply.


Assuntos
Remoção de Componentes Sanguíneos , Fator de von Willebrand , Humanos , Congelamento , Preservação de Sangue , Fatores de Tempo , Fatores de Coagulação Sanguínea , Fibrinogênio , Fator VIII
3.
Vox Sang ; 117(12): 1351-1359, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36214384

RESUMO

BACKGROUND AND OBJECTIVES: Lipaemia in blood donations is thought to influence haemolysis in stored red blood cell (RBC) components. Higher lipid concentrations are believed to increase red cell fragility, exacerbating haemolysis during collection and subsequent red cell storage. This study aimed to investigate associations between lipoproteins in plasma and haemolysis of red cells stored in saline-adenine-glucose-mannitol (SAGM). MATERIALS AND METHODS: Fifty-four plasma and matched RBCs were obtained from lipaemic whole blood donations. Plasma was tested for coagulation factors, triglycerides and cholesterol. Haemolysis, glucose, lactate, extracellular potassium, lactate dehydrogenase and adenosine triphosphate (ATP) were measured in RBC on Days 7, 21 and 42 of storage. Additionally, 20 plasma and matched RBCs from non-lipaemic donations were tested as controls. RESULTS: Lipaemic plasma had significantly higher triglyceride concentrations compared with non-lipaemic plasma. However, there was no significant difference in plasma cholesterol between the two groups. There were no significant differences in glucose, extracellular potassium or ATP concentrations in RBC from either group. There was no significant difference in haemolysis at expiry in lipaemic-derived and control RBC, with a weak correlation between haemolysis and either triglycerides or cholesterol. CONCLUSION: There was no significant difference in haemolysis in RBC manufactured from lipaemic and non-lipaemic whole blood donations when stored in SAGM; however, the proportion of RBC from lipaemic donations with higher haemolysis was greater than in the controls. There was a weak correlation between red cell haemolysis and plasma triglycerides. Therefore, RBCs derived from lipaemic donations are suitable for blood bank inventories.


Assuntos
Doação de Sangue , Preservação de Sangue , Humanos , Adenina , Hemólise , Eritrócitos , Manitol , Glucose , Potássio , Trifosfato de Adenosina
4.
Proc Natl Acad Sci U S A ; 112(50): 15360-5, 2015 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-26627714

RESUMO

The lethal factor in stonefish venom is stonustoxin (SNTX), a heterodimeric cytolytic protein that induces cardiovascular collapse in humans and native predators. Here, using X-ray crystallography, we make the unexpected finding that SNTX is a pore-forming member of an ancient branch of the Membrane Attack Complex-Perforin/Cholesterol-Dependent Cytolysin (MACPF/CDC) superfamily. SNTX comprises two homologous subunits (α and ß), each of which comprises an N-terminal pore-forming MACPF/CDC domain, a central focal adhesion-targeting domain, a thioredoxin domain, and a C-terminal tripartite motif family-like PRY SPla and the RYanodine Receptor immune recognition domain. Crucially, the structure reveals that the two MACPF domains are in complex with one another and arranged into a stable early prepore-like assembly. These data provide long sought after near-atomic resolution insights into how MACPF/CDC proteins assemble into prepores on the surface of membranes. Furthermore, our analyses reveal that SNTX-like MACPF/CDCs are distributed throughout eukaryotic life and play a broader, possibly immune-related function outside venom.


Assuntos
Venenos de Peixe/química , Perforina/química , Sequência de Aminoácidos , Animais , Membrana Celular/metabolismo , Colesterol/química , Complexo de Ataque à Membrana do Sistema Complemento/química , Cristalografia por Raios X , Microscopia Eletrônica de Transmissão , Modelos Moleculares , Dados de Sequência Molecular , Filogenia , Ligação Proteica , Multimerização Proteica , Estrutura Secundária de Proteína , Estrutura Terciária de Proteína , Subunidades Proteicas/química , Solubilidade , Homologia Estrutural de Proteína
5.
Transfusion ; 55(8): 1946-54, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25823581

RESUMO

BACKGROUND: Phosphatidylserine (PS) exposure facilitates the removal of red blood cells (RBCs) from the circulation, potentially contributing to the loss of stored RBCs after transfusion, as well as senescent RBCs. Activation of the P2X7 receptor by extracellular adenosine 5'-triphosphate (ATP) can induce PS exposure on freshly isolated human RBCs, but whether this process occurs in stored RBCs or changes during RBC aging is unknown. STUDY DESIGN AND METHODS: RBCs were processed and stored according to Australian blood banking guidelines. PS exposure was determined by annexin V binding and flow cytometry. Efficacy of P2X antagonists was assessed by flow cytometric measurements of ATP-induced ethidium+ uptake in RPMI 8226 cells. Osmotic fragility was assessed by lysis in hypotonic saline. RBCs were fractionated by discontinuous density centrifugation. RESULTS: ATP (1 mmol/L) induced PS exposure on RBCs stored for less than 1 week. This process was near-completely inhibited by the P2X7 antagonists A438079 and AZ10606120 and the P2X1/P2X7 antagonist MRS2159 but not the P2X1 antagonist NF499. ATP-induced PS exposure on RBCs was not dependent on K+, Na+, or Cl- fluxes. ATP did not alter the osmotic fragility of stored RBCs. ATP-induced PS exposure was similar between RBCs of different densities. ATP-induced PS exposure was also similar between RBCs stored for less than 1 week or for 6 weeks. CONCLUSION: The propensity of RBCs to undergo P2X7-mediated PS exposure does not alter during in vivo and ex vivo aging. Thus, P2X7 activation is unlikely to be involved in the removal of senescent RBCs or stored RBCs after transfusion.


Assuntos
Preservação de Sangue , Senescência Celular , Membrana Eritrocítica/fisiologia , Lipídeos de Membrana/sangue , Fosfatidilserinas/sangue , Receptores Purinérgicos P2X7/fisiologia , Adamantano/análogos & derivados , Adamantano/farmacologia , Trifosfato de Adenosina/sangue , Trifosfato de Adenosina/farmacologia , Aminoquinolinas/farmacologia , Anexina A5/metabolismo , Compostos Azo/farmacologia , Benzenossulfonatos/farmacologia , Membrana Eritrocítica/efeitos dos fármacos , Humanos , Fragilidade Osmótica , Antagonistas do Receptor Purinérgico P2X/farmacologia , Piridinas/farmacologia , Fosfato de Piridoxal/análogos & derivados , Fosfato de Piridoxal/farmacologia , Receptores Purinérgicos P2X1/fisiologia , Tetrazóis/farmacologia
6.
Am Fam Physician ; 92(5): 358-65, 2015 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-26371569

RESUMO

The Centers for Disease Control and Prevention estimates that each year, one in six Americans will experience a foodborne illness. The most common causes in the United States are viruses, such as norovirus; bacteria, such as Salmonella, Escherichia coli, Campylobacter, and Listeria; and parasites, such as Toxoplasma gondii and Giardia. Resources are available to educate consumers on food recalls and proper handling, storage, and cooking of foods. Diagnosis and management of a foodborne illness are based on the history and physical examination. Common symptoms of foodborne illnesses include vomiting, diarrhea (with or without blood), fever, abdominal cramping, headache, dehydration, myalgia, and arthralgias. Definitive diagnosis can be made only through stool culture or more advanced laboratory testing. However, these results should not delay empiric treatment if a foodborne illness is suspected. Empiric treatment should focus on symptom management, rehydration if the patient is clinically dehydrated, and antibiotic therapy. Foodborne illnesses should be reported to local and state health agencies; reporting requirements vary among states.


Assuntos
Contaminação de Alimentos/prevenção & controle , Doenças Transmitidas por Alimentos/diagnóstico , Doenças Transmitidas por Alimentos/terapia , Vigilância da População/métodos , Anti-Infecciosos/uso terapêutico , Antidiarreicos/uso terapêutico , Antieméticos/uso terapêutico , Análise Química do Sangue , Cólica/etiologia , Diagnóstico Diferencial , Diarreia/etiologia , Surtos de Doenças/prevenção & controle , Surtos de Doenças/estatística & dados numéricos , Fezes/microbiologia , Fezes/parasitologia , Hidratação , Contaminação de Alimentos/análise , Doenças Transmitidas por Alimentos/epidemiologia , Doenças Transmitidas por Alimentos/etiologia , Humanos , Técnicas Microbiológicas , Parasitologia/métodos , Reação em Cadeia da Polimerase , Estados Unidos/epidemiologia , Vômito/etiologia
7.
Transfusion ; 54(7): 1798-807, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24617658

RESUMO

BACKGROUND: Over the past decade there has been a growth in the development of pathogen reduction technologies to protect the blood supply from emerging pathogens. This development has proven to be difficult for red blood cells (RBCs). However the S-303 system has been shown to effectively inactivate a broad spectrum of pathogens, while maintaining RBC quality. STUDY DESIGN AND METHODS: A paired three-arm study was performed to compare the in vitro quality of S-303-treated RBCs with RBCs stored at room temperature (RT) for the duration of the treatment (18-20 hr) and control RBCs stored at 2 to 6°C. Products were sampled weekly over 42 days of storage (n = 10) and tested using an array of in vitro assays to measure quality, metabolism, and functional variables. RESULTS: During S-303 treatment there was a slight loss of RBCs and hemoglobin (Hb < 5 g). Hemolysis, glucose consumption, and potassium release were similar in all groups during the 42 days of storage. S-303-treated RBCs had a significantly lower lactate concentration and pH compared to the paired controls. The S-303-treated RBCs had significantly higher adenosine triphosphate than the RT and control RBCs. There was a significant loss of 2,3-diphosphoglycerate in the S-303-treated products, which was also observed in the RT RBCs. Flow cytometry analysis demonstrated similar RBC size, morphology, expression of CD47, and glycophorin A in all groups. CONCLUSION: RBCs treated with S-303 for pathogen reduction had similar in vitro properties to the paired controls and were within transfusion guidelines.


Assuntos
Acridinas/farmacologia , Alquilantes/farmacologia , Preservação de Sangue/métodos , Patógenos Transmitidos pelo Sangue/efeitos dos fármacos , Eritrócitos/efeitos dos fármacos , Viabilidade Microbiana/efeitos dos fármacos , Compostos de Mostarda Nitrogenada/farmacologia , 2,3-Difosfoglicerato/metabolismo , Acridinas/isolamento & purificação , Trifosfato de Adenosina/metabolismo , Alquilantes/isolamento & purificação , Preservação de Sangue/normas , Segurança do Sangue/métodos , Segurança do Sangue/normas , Patógenos Transmitidos pelo Sangue/isolamento & purificação , Contagem de Eritrócitos , Eritrócitos/citologia , Eritrócitos/fisiologia , Glucose/metabolismo , Hemoglobinas/metabolismo , Hemólise , Humanos , Ácido Láctico/metabolismo , Compostos de Mostarda Nitrogenada/isolamento & purificação
8.
Am J Public Health ; 103(7): e91-9, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23678899

RESUMO

OBJECTIVES: Physician recommendation plays a crucial role in receiving endoscopic screening for colorectal cancer (CRC). This study explored factors associated with racial/ethnic differences in rates of screening recommendation. METHODS: Data on 5900 adults eligible for endoscopic screening were obtained from the National Health Interview Survey. Odds ratios of receiving an endoscopy recommendation were calculated for selected variables. Planned, sequenced logistic regressions were conducted to examine the extent to which socioeconomic and health care variables account for racial/ethnic disparities in recommendation rates. RESULTS: Differential rates were observed for CRC screening and screening recommendations among racial/ethnic groups. Compared with Whites, Hispanics were 34% less likely (P < .01) and Blacks were 26% less likely (P < .05) to receive this recommendation. The main predictors that emerged in sequenced analysis were education for Hispanics and Blacks and income for Blacks. After accounting for the effects of usual source of care, insurance coverage, and education, the disparity reduced and became statistically insignificant. CONCLUSIONS: Socioeconomic status and access to health care may explain major racial/ethnic disparities in CRC screening recommendation rates.


Assuntos
Neoplasias Colorretais/diagnóstico , Detecção Precoce de Câncer/estatística & dados numéricos , Etnicidade/estatística & dados numéricos , Disparidades em Assistência à Saúde/estatística & dados numéricos , Grupos Raciais/estatística & dados numéricos , Idoso , Neoplasias Colorretais/etnologia , Estudos Transversais , Feminino , Pesquisas sobre Atenção à Saúde , Acessibilidade aos Serviços de Saúde/estatística & dados numéricos , Disparidades em Assistência à Saúde/etnologia , Humanos , Cobertura do Seguro/estatística & dados numéricos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Médicos , Encaminhamento e Consulta/estatística & dados numéricos , Classe Social , Estados Unidos
9.
Am Surg ; 89(9): 3953-3955, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37260094

RESUMO

Constitutional mismatch repair deficiency (CMMRD) syndrome is a rare autosomal recessive genetic disorder that has little more than 200 total cases reported as of 2020. Whereas a single mutation in genes responsible for mismatch repair causes the autosomal dominant Lynch syndrome (LS), CMMRD is caused by biallelic heterozygous defects: distinct deleterious mutations on each allele for a single gene. As the disease is exceedingly rare and may present via a wide variety of signs, including neurofibromatosis type 1- and Lynch Syndrome-associated malignancies, diagnosis and subsequent surveillance are complex with suggested methods published by the International Replication Repair Deficiency Consortium. We report here the history and management of a patient whose newly diagnosed CMMRD was managed with both curative and prophylactic surgical treatment.


Assuntos
Neoplasias Encefálicas , Neoplasias Colorretais Hereditárias sem Polipose , Neoplasias Colorretais , Síndromes Neoplásicas Hereditárias , Humanos , Neoplasias Colorretais Hereditárias sem Polipose/diagnóstico , Neoplasias Colorretais Hereditárias sem Polipose/genética , Neoplasias Colorretais Hereditárias sem Polipose/terapia , Síndromes Neoplásicas Hereditárias/diagnóstico , Síndromes Neoplásicas Hereditárias/genética , Síndromes Neoplásicas Hereditárias/terapia , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/genética , Neoplasias Colorretais/terapia , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/genética , Mutação
10.
Kans J Med ; 16: 321-323, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38298387

RESUMO

Introduction: This study aimed to assess the feasibility of evaluating the short-term and long-term effectiveness of a surgery residency prep course throughout the intern year. Methods: The authors offered a surgery residency prep course to graduating medical students. We used an anonymous survey to assess the perceived confidence in medical knowledge, clinical skills and surgical skills pre-course, post-course, and at six months into residency. Participants also completed a pre- and post-course quiz. Results: Eleven students completed the course and participated in a pre-course survey, seven completed the post-course survey, and four completed the six month survey. Students felt significantly more confident for intern year following the course compared to before the course (4.0 vs. 2.7, p = 0.018). There was no significant change in perceived confidence at six months compared to post-course results (4.0 vs. 3.9, p = 0.197). Objectively, there was a significant improvement in postcourse quiz results compared to pre-course quiz results (12.9 vs. 10.6, p = 0.004). Conclusions: This study demonstrates that a surgery prep course may have long-term positive effects on resident confidence when entering a surgery residency.

11.
Am Surg ; 89(4): 961-967, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34732061

RESUMO

BACKGROUND: While Botox sphincterotomy with or without fissurectomy has been proven effective in healing anal fissures, they have not been directly compared. We evaluated cost-effectiveness and outcomes between Botox sphincterotomies with and without fissurectomy. METHODS: A 5-year retrospective review was conducted comparing all patients undergoing Botox sphincterotomy for anal fissure with or without fissurectomy. Outcomes including recurrence/persistence, additional treatments, complications, and total charges were compared between study groups. RESULTS: Patients treated without fissurectomy (n = 53) had recurrent/persistent fissure more often (56.6 vs 31.0%, P = .001), and required more Botox treatments. Those treated with fissurectomy (n = 154) had more complications (13.5 vs 0%, P = .003). Patients initially treated without fissurectomy had a median total charge of $2 973, while median total charge for those initially treated with fissurectomy was $17 925 (P < .001). CONCLUSIONS: Botox sphincterotomy in an office without fissurectomy is a viable option. It may result in longer healing times but is associated with reduced cost, lower complication rates, and no need for anesthesia or operative intervention in most cases. But the choice of treatment route must be individualized.


Assuntos
Toxinas Botulínicas Tipo A , Fissura Anal , Humanos , Toxinas Botulínicas Tipo A/uso terapêutico , Canal Anal/cirurgia , Doença Crônica , Fissura Anal/tratamento farmacológico , Fissura Anal/cirurgia , Cicatrização , Resultado do Tratamento
12.
Obes Surg ; 33(2): 469-474, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36474099

RESUMO

PURPOSE: Data regarding the associations between percent weight loss and the volume and weight of stomach resected during sleeve gastrectomy (SG) are mixed. The purpose of this study was to evaluate the effect of the size and volume of stomach removed during laparoscopic SG on percent total body weight lost (%TBWL). METHODS: An observational case series study was performed on 67 patients for 1 year after SG at a single university-affiliated, tertiary care hospital. Data were collected on demographics, medical history, and %TBWL at 3, 6, and 12 months post-operatively. Pearson's correlation matrices and multiple linear regression analyses were performed. RESULTS: Most patients (88.1%) were female with a mean age of 44 years. The mean volume of stomach resected was 1047.0 cubic centimeters, and the median weight resected was 123.0 g. Follow-up data were available for 44 patients at 1-year post-operation. There was no association between the volume and weight of stomach resected and %TBWL at 1-year post-operation; however, greater %TBWL was associated with younger patient age (r = - 0.525, p < 0.001). CONCLUSION: One year after SG, no associations between %TBWL and the volume and weight of stomach resected were observed.


Assuntos
Laparoscopia , Obesidade Mórbida , Humanos , Feminino , Adulto , Masculino , Obesidade Mórbida/cirurgia , Estômago/cirurgia , Gastrectomia , Redução de Peso , Período Pós-Operatório , Estudos Retrospectivos , Resultado do Tratamento
13.
Transfusion ; 52(3): 503-9, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21880041

RESUMO

BACKGROUND: Collecting apheresis platelets (PLTs) into additive solution has many potential benefits. The new Trima software (Version 6.0, CaridianBCT) allows automated addition of PLT additive solution (PAS) after collection, compared to Trima Version 5.1, which only collects PLTs into plasma. The aim of this study was to compare PLT quality during extended storage, after collection with the different Trima systems. STUDY DESIGN AND METHODS: Apheresis PLTs were collected using both Trima Accel apheresis systems. The test PLT units (n = 12) were collected using the new Trima Version 6.0 into PLT AS (PAS-IIIM), while the control units (n = 8) were collected into autologous plasma using Trima Version 5.1. All units were stored for 9 days, and in vitro cell quality variables were evaluated during this time. RESULTS: PLTs collected in PAS-IIIM maintained a stable pH between 7.2 and 7.4, whereas plasma-stored apheresis units exhibited significantly increased acidity during storage, due to lactate accumulation and bicarbonate exhaustion. Plasma-stored PLTs also demonstrated a more rapid consumption of glucose. However, there was little difference in PLT activation or cytokine secretion between PAS-IIIM and control PLTs. CONCLUSION: These data indicate that apheresis PLT concentrates collected in PAS-IIIM, using Trima Version 6.0 software, maintained acceptable PLT metabolic and cellular characteristics until Day 9 of storage.


Assuntos
Plaquetas/citologia , Preservação de Sangue/métodos , Plaquetoferese/instrumentação , Plaquetoferese/métodos , Acetatos/metabolismo , Bicarbonatos/metabolismo , Plaquetas/efeitos dos fármacos , Plaquetas/metabolismo , Preservação de Sangue/normas , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Citocinas/metabolismo , Glucose/farmacocinética , Humanos , Ácido Láctico/metabolismo , Ativação Plaquetária/efeitos dos fármacos , Ativação Plaquetária/fisiologia , Plaquetoferese/normas , Software , Soluções/farmacologia , Fatores de Tempo
14.
Mol Cell Proteomics ; 9(11): 2369-90, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-20631207

RESUMO

Venom has only been recently discovered to be a basal trait of the Anguimorpha lizards. Consequently, very little is known about the timings of toxin recruitment events, venom protein molecular evolution, or even the relative physical diversifications of the venom system itself. A multidisciplinary approach was used to examine the evolution across the full taxonomical range of this ∼130 million-year-old clade. Analysis of cDNA libraries revealed complex venom transcriptomes. Most notably, three new cardioactive peptide toxin types were discovered (celestoxin, cholecystokinin, and YY peptides). The latter two represent additional examples of convergent use of genes in toxic arsenals, both having previously been documented as components of frog skin defensive chemical secretions. Two other novel venom gland-overexpressed modified versions of other protein frameworks were also recovered from the libraries (epididymal secretory protein and ribonuclease). Lectin, hyaluronidase, and veficolin toxin types were sequenced for the first time from lizard venoms and shown to be homologous to the snake venom forms. In contrast, phylogenetic analyses demonstrated that the lizard natriuretic peptide toxins were recruited independently of the form in snake venoms. The de novo evolution of helokinestatin peptide toxin encoding domains within the lizard venom natriuretic gene was revealed to be exclusive to the helodermatid/anguid subclade. New isoforms were sequenced for cysteine-rich secretory protein, kallikrein, and phospholipase A(2) toxins. Venom gland morphological analysis revealed extensive evolutionary tinkering. Anguid glands are characterized by thin capsules and mixed glands, serous at the bottom of the lobule and mucous toward the apex. Twice, independently this arrangement was segregated into specialized serous protein-secreting glands with thick capsules with the mucous lobules now distinct (Heloderma and the Lanthanotus/Varanus clade). The results obtained highlight the importance of utilizing evolution-based search strategies for biodiscovery and emphasize the largely untapped drug design and development potential of lizard venoms.


Assuntos
Evolução Molecular , Lagartos , Peçonhas/química , Sequência de Aminoácidos , Animais , Biblioteca Gênica , Humanos , Lagartos/anatomia & histologia , Lagartos/classificação , Lagartos/metabolismo , Masculino , Dados de Sequência Molecular , Filogenia , Precursores de Proteínas/genética , Precursores de Proteínas/metabolismo , Ratos , Ratos Sprague-Dawley , Alinhamento de Sequência , Peçonhas/genética , Peçonhas/metabolismo
15.
Proc Natl Acad Sci U S A ; 106(22): 8969-74, 2009 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-19451641

RESUMO

The predatory ecology of Varanus komodoensis (Komodo Dragon) has been a subject of long-standing interest and considerable conjecture. Here, we investigate the roles and potential interplay between cranial mechanics, toxic bacteria, and venom. Our analyses point to the presence of a sophisticated combined-arsenal killing apparatus. We find that the lightweight skull is relatively poorly adapted to generate high bite forces but better adapted to resist high pulling loads. We reject the popular notion regarding toxic bacteria utilization. Instead, we demonstrate that the effects of deep wounds inflicted are potentiated through venom with toxic activities including anticoagulation and shock induction. Anatomical comparisons of V. komodoensis with V. (Megalania) priscus fossils suggest that the closely related extinct giant was the largest venomous animal to have ever lived.


Assuntos
Extinção Biológica , Lagartos/anatomia & histologia , Lagartos/fisiologia , Comportamento Predatório , Peçonhas , Animais , Bactérias/patogenicidade , Dentição , Lagartos/microbiologia , Crânio/anatomia & histologia , Crânio/fisiologia
16.
Mol Biol Evol ; 27(2): 395-407, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19837656

RESUMO

The origin and evolution of venom proteins in helodermatid lizards were investigated by multidisciplinary techniques. Our analyses elucidated novel toxin types resultant from three unique domain-expression processes: 1) The first full-length sequences of lethal toxin isoforms (helofensins) revealed this toxin type to be constructed by an ancestral monodomain, monoproduct gene (beta-defensin) that underwent three tandem domain duplications to encode a tetradomain, monoproduct with a possible novel protein fold; 2) an ancestral monodomain gene (encoding a natriuretic peptide) was medially extended to become a pentadomain, pentaproduct through the additional encoding of four tandemly repeated proline-rich peptides (helokinestatins), with the five discrete peptides liberated from each other by posttranslational proteolysis; and 3) an ancestral multidomain, multiproduct gene belonging to the vasoactive intestinal peptide (VIP)/glucagon family being mutated to encode for a monodomain, monoproduct (exendins) followed by duplication and diversification into two variant classes (exendins 1 and 2 and exendins 3 and 4). Bioactivity characterization of exendin and helokinestatin elucidated variable cardioactivity between isoforms within each class. These results highlight the importance of utilizing evolutionary-based search strategies for biodiscovery and the virtually unexplored potential of lizard venoms in drug design and discovery.


Assuntos
Lagartos/metabolismo , Proteínas/genética , Peçonhas/química , Sequência de Aminoácidos , Animais , Aorta Torácica/efeitos dos fármacos , Teorema de Bayes , Antagonistas de Receptor B2 da Bradicinina , DNA Complementar , Feminino , Cobaias , Íleo/efeitos dos fármacos , Técnicas In Vitro , Masculino , Dados de Sequência Molecular , Peptídeos/química , Peptídeos/classificação , Peptídeos/genética , Peptídeos/farmacologia , Filogenia , Proteínas/química , Proteínas/classificação , Proteínas/farmacologia , Ratos , Ratos Sprague-Dawley , Homologia de Sequência de Aminoácidos , Peçonhas/classificação , Peçonhas/genética , Peçonhas/farmacologia
17.
Kans J Med ; 14: 149-152, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34178245

RESUMO

INTRODUCTION: Physicians entering surgical residency often feel unprepared for tasks expected of them beginning July 1, including responding to pages, writing orders, doing procedures independently, and a multitude of other requirements. Our aim was to design a surgical boot camp to help graduating senior medical students feel more confident entering residency. METHODS: A two-week intensive surgery residency prep course was conducted in the spring of 2019 at an Accreditation Council for Graduate Medical Education-accredited General Surgery residency program. The course was designed combining aspects from existing prep courses and innovative ideas tailored to resources available at our institution. Medical students participated in the Surgery Residency Prep Course as an elective at the end of their fourth year of medical school. An anonymous survey was given pre- and post-prep course completion evaluating confidence in medical knowledge, clinical skills, and surgical skills. Data were compared using Wilcoxon Signed-Rank Test. RESULTS: Six students completed the course as a medical elective. Students felt more confident at course completion in most aspects, were significantly more confident in all areas of surgical skills taught and evaluated, and nearly all areas of medical knowledge. Subjectively, students felt as though the course was beneficial and helped them feel more prepared for starting internship. CONCLUSIONS: This course designed at our institution was successful in helping prepare and instill confidence in graduating medical students prior to starting their internship.

18.
J Urban Health ; 87(2): 244-253, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-20012702

RESUMO

Incarceration affords an opportunity to provide health care to populations with limited access to care. Women in this population are at high risk for experiencing unintended pregnancies. It is not known what proportion of these women engage in unprotected intercourse in the days prior to incarceration and therefore may benefit from being offered emergency contraception upon their arrest to decrease their risk of unintended pregnancies. We sought to describe the proportion and characteristics of newly arrested women who are eligible for and interested in taking emergency contraception by conducting a cross-sectional study in an urban county jail booking facility. A 63-item survey was administered to women ages 18-44 within 24 h of being arrested in San Francisco. Eighty-four (29%) women were eligible for emergency contraception. Of these, 48% indicated a willingness to take emergency contraception if offered. Half of the women eligible for emergency contraception expressed ambivalent attitudes about pregnancy. Women who had taken emergency contraception in the past were more likely to say they would accept it (45%) than women who had never used it (25%, p = .05). The strongest predictor of willingness to take emergency contraception was not having a misperception about its safety, efficacy, or mechanism of action (RR = 1.9, 95% CI 1.2-3.0). Seventy-one percent of all women indicated that they would accept an advance supply of emergency contraception upon release from jail. Emergency contraception counseling and provision should be offered to newly arrested women as a key reproductive and public health intervention for a traditionally marginalized, high-risk population.


Assuntos
Anticoncepção Pós-Coito/estatística & dados numéricos , Aceitação pelo Paciente de Cuidados de Saúde , Prisioneiros/psicologia , Saúde Pública , Adolescente , Adulto , Estudos Transversais , Feminino , Humanos , São Francisco , Adulto Jovem
19.
Toxicol Lett ; 187(2): 94-8, 2009 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-19429250

RESUMO

Although CSL box jellyfish antivenom (AV) remains the primary treatment for Chironex fleckeri envenoming, there has been considerable debate regarding its clinical effectiveness. Animal studies have shown that AV is largely ineffective in preventing C. fleckeri-induced cardiovascular collapse. This study examined the effectiveness of CSL box jellyfish AV (ovine IgG), raised against 'milked' venom, and polyclonal rabbit IgG antibodies (Ab) raised against nematocyst-derived venom. A venom dose of 30microg/kg, i.v., which causes an initial presser response (34+/-5mmHg; n=7) followed by cardiovascular collapse, was used in all experiments. A bolus dose of AV (3000U/kg, i.v.) or Ab (12mg; i.e. an equivalent protein 'load' to 3000U/kg AV), administered 15min prior to a bolus dose of venom, did not significantly attenuate the effects of venom. The venom response was also not significantly attenuated when AV (3000U/kg) was given as a bolus dose 10-60min prior to venom infusion. However, when the venom was incubated with either AV (3000U/kg) or Ab (12mg) for 3h prior to infusion, the effect of the venom was almost abolished. The results of this study demonstrate that antibodies raised against both 'milked' and nematocyst-derived venom are able to neutralise the cardiovascular collapse produced by the venom. However, large amounts of AV are required and must be preincubated with the venom to be protective. This indicates a very rapid action of the toxin(s) and that AV is unlikely to be clinically effective because it cannot be administered early enough.


Assuntos
Anticorpos/farmacologia , Antivenenos/farmacologia , Venenos de Cnidários/antagonistas & inibidores , Cubomedusas , Animais , Pressão Sanguínea/efeitos dos fármacos , Venenos de Cnidários/administração & dosagem , Venenos de Cnidários/imunologia , Venenos de Cnidários/toxicidade , Masculino , Ratos , Ratos Sprague-Dawley
20.
Public Health Rep ; 134(6): 592-598, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31600452

RESUMO

The 2014-2016 Ebola epidemic in West Africa influenced how public health officials considered migration and emerging infectious diseases. Responding to the public's concerns, the US government introduced enhanced entry screening and post-arrival monitoring by public health authorities to reduce the risk of importation and domestic transmission of Ebola while continuing to allow travel from West Africa. This case study describes a new initiative, the Check and Report Ebola (CARE+) program that engaged travelers arriving to the United States from countries with Ebola outbreaks. The Centers for Disease Control and Prevention employed CARE ambassadors, who quickly communicated with incoming travelers and gave them practical resources to boost their participation in monitoring for Ebola. The program aimed to increase travelers' knowledge of Ebola symptoms and how to seek medical care safely, increase travelers' awareness of monitoring requirements, reduce barriers to monitoring, and increase trust in the US public health system. This program could be adapted for use in future outbreaks that involve the potential importation of disease and require the education and active engagement of travelers to participate in post-arrival monitoring.


Assuntos
Educação em Saúde , Doença pelo Vírus Ebola/epidemiologia , Programas de Rastreamento , Vigilância da População , Saúde Pública/tendências , Viagem , África Ocidental , Centers for Disease Control and Prevention, U.S. , Epidemias/prevenção & controle , Comunicação em Saúde , Doença pelo Vírus Ebola/prevenção & controle , Humanos , Estados Unidos/epidemiologia
SELEÇÃO DE REFERÊNCIAS
Detalhe da pesquisa