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1.
Artículo en Inglés | MEDLINE | ID: mdl-32071597

RESUMEN

BACKGROUND: Between 40,000-70,000 people die yearly of rabies, an incurable disease. Besides post-bite vaccination, no treatment is available for it. METHODS: First, virus dilution for antiviral effects in mice was determined. Then, animals were treated as follows: control (NaCl 250 µL/animal/day); bufotenine (0.63, 1.05 and 2.1 mg in 250 µL of NaCl/animal/day); rabies (10-6,82CVS dilution); and test (10-6,82 CVS dilution and bufotenine, in the above-mentioned doses). Animals were observed daily for 21 days or until the 3rd stage of rabies infection. Twitch-tension and liposome studies were applied to understand the possible interaction of bufotenine with receptors, particularly acetylcholine. RESULTS: Bufotenine was able to increase the survival rate of intracerebrally virus-infected mice from 15 to 40%. Bufotenine did not seem to interfere with the acetylcholine response in the skeletal muscle, indicating that its mechanism of action is not blocking the virus entrance due to nAChR antagonism. By analyzing liposomes, we could observe that bufotenine did not passively penetrates cell membranes, indicating the necessity of complementary structures to cell penetration. CONCLUSIONS: Bufotenine is a promising candidate for drug development. After further chemical modification, it might be possible to dissociate minor side effects, increase efficiency, efficacy and pharmacokinetics, yielding a true anti-rabies drug.

2.
J. venom. anim. toxins incl. trop. dis ; 26: e20190050, 2020. graf
Artículo en Inglés | LILACS, VETINDEX | ID: biblio-1056678

RESUMEN

Between 40,000-70,000 people die yearly of rabies, an incurable disease. Besides post-bite vaccination, no treatment is available for it. Methods: First, virus dilution for antiviral effects in mice was determined. Then, animals were treated as follows: control (NaCl 250 µL/animal/day); bufotenine (0.63, 1.05 and 2.1 mg in 250 µL of NaCl/animal/day); rabies (10-6,82CVS dilution); and test (10-6,82 CVS dilution and bufotenine, in the above-mentioned doses). Animals were observed daily for 21 days or until the 3rd stage of rabies infection. Twitch-tension and liposome studies were applied to understand the possible interaction of bufotenine with receptors, particularly acetylcholine. Results: Bufotenine was able to increase the survival rate of intracerebrally virus-infected mice from 15 to 40%. Bufotenine did not seem to interfere with the acetylcholine response in the skeletal muscle, indicating that its mechanism of action is not blocking the virus entrance due to nAChR antagonism. By analyzing liposomes, we could observe that bufotenine did not passively penetrates cell membranes, indicating the necessity of complementary structures to cell penetration. Conclusions: Bufotenine is a promising candidate for drug development. After further chemical modification, it might be possible to dissociate minor side effects, increase efficiency, efficacy and pharmacokinetics, yielding a true anti-rabies drug.(AU)


Asunto(s)
Animales , Ratones , Rabia , Triptófano , Bufotenina , Preparaciones Farmacéuticas , Alcaloides , Ratones/virología
3.
Artículo en Inglés | Sec. Est. Saúde SP, SESSP-IBPROD, Sec. Est. Saúde SP | ID: but-ib17445

RESUMEN

Background: Between 40,000-70,000 people die yearly of rabies, an incurable disease. Besides post-bite vaccination, no treatment is available for it. Methods: First, virus dilution for antiviral effects in mice was determined. Then, animals were treated as follows: control (NaCl 250 µL/animal/day); bufotenine (0.63, 1.05 and 2.1 mg in 250 µL of NaCl/animal/day); rabies (10-6,82CVS dilution); and test (10-6,82 CVS dilution and bufotenine, in the above-mentioned doses). Animals were observed daily for 21 days or until the 3rd stage of rabies infection. Twitch-tension and liposome studies were applied to understand the possible interaction of bufotenine with receptors, particularly acetylcholine. Results: Bufotenine was able to increase the survival rate of intracerebrally virus-infected mice from 15 to 40%. Bufotenine did not seem to interfere with the acetylcholine response in the skeletal muscle, indicating that its mechanism of action is not blocking the virus entrance due to nAChR antagonism. By analyzing liposomes, we could observe that bufotenine did not passively penetrates cell membranes, indicating the necessity of complementary structures to cell penetration. Conclusions: Bufotenine is a promising candidate for drug development. After further chemical modification, it might be possible to dissociate minor side effects, increase efficiency, efficacy and pharmacokinetics, yielding a true anti-rabies drug.

4.
J Venom Anim Toxins Incl Trop Dis, v. 26, e20190050, fev. 2020
Artículo en Inglés | Sec. Est. Saúde SP, SESSP-IBPROD, Sec. Est. Saúde SP | ID: bud-2943

RESUMEN

Background: Between 40,000-70,000 people die yearly of rabies, an incurable disease. Besides post-bite vaccination, no treatment is available for it. Methods: First, virus dilution for antiviral effects in mice was determined. Then, animals were treated as follows: control (NaCl 250 µL/animal/day); bufotenine (0.63, 1.05 and 2.1 mg in 250 µL of NaCl/animal/day); rabies (10-6,82CVS dilution); and test (10-6,82 CVS dilution and bufotenine, in the above-mentioned doses). Animals were observed daily for 21 days or until the 3rd stage of rabies infection. Twitch-tension and liposome studies were applied to understand the possible interaction of bufotenine with receptors, particularly acetylcholine. Results: Bufotenine was able to increase the survival rate of intracerebrally virus-infected mice from 15 to 40%. Bufotenine did not seem to interfere with the acetylcholine response in the skeletal muscle, indicating that its mechanism of action is not blocking the virus entrance due to nAChR antagonism. By analyzing liposomes, we could observe that bufotenine did not passively penetrates cell membranes, indicating the necessity of complementary structures to cell penetration. Conclusions: Bufotenine is a promising candidate for drug development. After further chemical modification, it might be possible to dissociate minor side effects, increase efficiency, efficacy and pharmacokinetics, yielding a true anti-rabies drug.

5.
Curr Probl Cancer ; 43(5): 477-486, 2019 10.
Artículo en Inglés | MEDLINE | ID: mdl-30826126

RESUMEN

BACKGROUND: Recent studies report increasing incidence of colorectal cancer (CRC) in the young-age population, but data concerning clinical behavior, pathologic findings, and prognosis are controversial for this group. Early recognition of CRC in young patients is a challenge and diagnosis at advanced stage is clearly associated with worse outcomes. MATERIALS AND METHODS: We retrospectively reviewed medical records of 5806 patients diagnosed with CRC between January/2011 and November/2016 and identified 781 patients aged less than 50-years-old. RESULTS: We found an absolute increasing in the incidence of CRC in patients <50 years old of 1.88%-2.23% annually, with a relative increasing of 35.3% between 2011 and 2016. Median age was 42 years, 57.4% were female and 20.9% reported family history of CRC. Left-sided tumors were more frequent and the majority of patients were symptomatic. The most common stages at diagnosis were III (34.1%) and IV (37.3%). The median overall survival (OS) for stage IV was 25 months (95% CI 20.7-29.3) and was not reached for Stages I-III (P < 0.001). Family history of CRC was independently associated with better OS in stage IV(P = 0.02). For stages I-III, wild-type KRAS, family history of CRC, and absence of angiolymphatic invasion were associated with better OS (P = 0.02, P = 0.01 and P < 0.001, respectively). CONCLUSIONS: In our cohort, the incidence of early-onset CRC is increasing over the past years. Young patients were more likely to be diagnosed with metastatic disease, left-sided and/or rectum site and symptoms at presentation. These findings highlight the emerging importance of young-age onset CRC and the need to discuss strategies to early diagnosis.


Asunto(s)
Neoplasias Colorrectales/epidemiología , Detección Precoz del Cáncer , Necesidades y Demandas de Servicios de Salud , Tamizaje Masivo/organización & administración , Adolescente , Adulto , Edad de Inicio , Biopsia , Brasil/epidemiología , Instituciones Oncológicas/estadística & datos numéricos , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/patología , Bases de Datos Factuales/estadística & datos numéricos , Femenino , Humanos , Incidencia , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Recto/patología , Estudios Retrospectivos , Centros de Atención Terciaria/estadística & datos numéricos , Adulto Joven
6.
Cancer Treat Rev ; 56: 28-35, 2017 May.
Artículo en Inglés | MEDLINE | ID: mdl-28456055

RESUMEN

BACKGROUND: Poorly differentiated neuroendocrine carcinomas (NECs) are rare and aggressive tumors. Their molecular pathogenesis is still largely unknown, and consequently, the best therapeutic management also remains to be determined. We conducted a systematic review on molecular alterations found in gastroenteropancreatic NECs (GEP-NECs) and discuss potential applications of targeted therapies in setting. MATERIALS AND METHODS: Systematic review of studies about molecular features in tumor tissues of patients with GEP-NECs. The Medline, Lilacs, Embase, Cochrane, Scopus and Opengrey databases were sought, without time, study design or language restrictions. RESULTS: Of the 1.564 studies retrieved, 41 were eligible: 33 were retrospective studies and eight were case reports. The studies spanned the years 1997-2017 and involved mostly colorectal, stomach and pancreas primary tumors. Molecular alterations in the TP53 gene and the p53 protein expression were the most commonly observed, regardless of the primary site. Other consistently found molecular alterations were microsatellite instability (MSI) in approximately 10% of gastric and colorectal NEC, and altered signaling cascades of p16/Rb/cyclin D1, Hedgehog and Notch pathways, and somatic mutations in KRAS, BRAF, RB1 and Bcl2. In studies of mixed adeno-neuroendocrine carcinomas (MANECs) the molecular features of GEP-NEC largely resemble their carcinoma/adenocarcinomas tumor counterparts. CONCLUSIONS: Despite the paucity of data about the molecular drivers associated with GEP-NEC, some alterations may be potentially targeted with new cancer-directed therapies. Collaborative clinical trials for patients with advanced GEP-NEC are urgently needed.


Asunto(s)
Neoplasias Gastrointestinales/genética , Tumores Neuroendocrinos/genética , Neoplasias Pancreáticas/genética , Diferenciación Celular/fisiología , Neoplasias Gastrointestinales/metabolismo , Neoplasias Gastrointestinales/patología , Humanos , Inestabilidad de Microsatélites , Mutación , Tumores Neuroendocrinos/metabolismo , Tumores Neuroendocrinos/patología , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patología
7.
J. pediatr. (Rio J.) ; 90(4): 370-376, Jul-Aug/2014. tab, graf
Artículo en Inglés | LILACS, Sec. Est. Saúde SP | ID: lil-720885

RESUMEN

OBJECTIVE: to estimate the prevalence of infection by respiratory viruses in pediatric patients with cancer and acute respiratory infection (ARI) and/or fever. METHODS: cross-sectional study, from January 2011 to December 2012. The secretions of nasopharyngeal aspirates were analyzed in children younger than 21 years with acute respiratory infections. Patients were treated at the Grupo em Defesa da Criança Com Câncer (Grendacc) and University Hospital (HU), Jundiaí, SP. The rapid test was used for detection of influenza virus (Kit Biotrin, Inc. Ireland), and real-time multiplex polymerase chain reaction (FTD, Respiratory pathogens, multiplex Fast Trade Kit, Malta) for detection of influenza virus (H1N1, B), rhinovirus, parainfluenza virus, adenovirus, respiratory syncytial virus, human parechovirus, bocavirus, metapneumovirus, and human coronavirus. The prevalence of viral infection was estimated and association tests were used (χ2 or Fisher's exact test). RESULTS: 104 samples of nasopharyngeal aspirate and blood were analyzed. The median age was 12 ± 5.2 years, 51% males, 68% whites, 32% had repeated ARIs, 32% prior antibiotic use, 19.8% cough, and 8% contact with ARIs. A total of 94.3% were in good general status. Acute lymphocytic leukemia (42.3%) was the most prevalent neoplasia. Respiratory viruses were detected in 50 samples: rhinoviruses (23.1%), respiratory syncytial virus AB (8.7%), and coronavirus (6.8%). Co-detection occurred in 19% of cases with 2 viruses and in 3% of those with 3 viruses, and was more frequent between rhinovirus and coronavirus 43. Fever in neutropenic patients was observed in 13%, of which four (30.7) were positive for viruses. There were no deaths. CONCLUSIONS: the prevalence of respiratory viruses was relevant in the infectious episode, with no increase in morbidity and mortality. Viral co-detection was frequent in patients with cancer and ARIs. .


OBJETIVO: estimar a prevalência da infecção pelos vírus respiratórios em pacientes pediátricos com câncer e infecção respiratória aguda (IRA) e/ou febre. MÉTODOS: estudo transversal, de janeiro de 2011 a dezembro de 2012. Foram analisadas secreções de aspirado da nasofaringe de menores de 21 anos, com quadro respiratório agudo, atendidos nos hospitais Grendacc e HU, Jundiaí, SP. Foi aplicado o teste rápido para detecção dos vírus influenza (Kit Biotrin(r)) e a reação em cadeia da polimerase multiplex em tempo real (Kit multiplex/Fast Trade(r)) para detecção dos vírus: influenza (A, H1N1, B), rinovírus, parainfluenza, adenovírus respiratório, vírus respiratório sincicial, parechovírus, bocavírus, metapneumovírus humano e coronavírus humano. Foi estimada a prevalência de infecção viral e usados testes de associação (χ2 ou teste exato de Fisher). RESULTADOS: foram analisadas 104 amostras de aspirado de nasofaringe e sangue. A mediana para a idade foi 12±5,2 anos; masculino (51%); cor branca (68%); IVAS de repetição (32%); uso prévio de antibiótico (32%); tosse (19,8%); e contato com IVAS (8%). Apresentavam-se em bom estado geral 94,3% dos pacientes. A leucemia linfocítica aguda (42,3%) foi mais prevalente. Foram detectados vírus respiratórios em 50% das amostras: rinovírus (23,1%), vírus sincicial respiratório A/B (8,7%) e coronavírus (6,8%). Ocorreu codetecção em 19% entre dois vírus, e de 3% entre três vírus, sendo a mais frequente entre rinovírus e coronavírus 43. Febre em neutropênicos foi de 13%, sendo quatro (30,7%) com vírus positivo. Não houve óbitos. CONCLUSÕES: a prevalência de vírus respiratórios ...


Asunto(s)
Adolescente , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Neoplasias/complicaciones , Infecciones del Sistema Respiratorio/complicaciones , Virosis/complicaciones , Enfermedad Aguda , Estudios Transversales , Fiebre/complicaciones , Nasofaringe , Neoplasias/tratamiento farmacológico , Prevalencia , Virus Sincitiales Respiratorios/aislamiento & purificación , Infecciones del Sistema Respiratorio/diagnóstico , Rhinovirus/aislamiento & purificación , Virosis/diagnóstico , Virosis/epidemiología
8.
J Pediatr (Rio J) ; 90(4): 370-6, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24703819

RESUMEN

OBJECTIVE: to estimate the prevalence of infection by respiratory viruses in pediatric patients with cancer and acute respiratory infection (ARI) and/or fever. METHODS: cross-sectional study, from January 2011 to December 2012. The secretions of nasopharyngeal aspirates were analyzed in children younger than 21 years with acute respiratory infections. Patients were treated at the Grupo em Defesa da Criança Com Câncer (Grendacc) and University Hospital (HU), Jundiaí, SP. The rapid test was used for detection of influenza virus (Kit Biotrin, Inc. Ireland), and real-time multiplex polymerase chain reaction (FTD, Respiratory pathogens, multiplex Fast Trade Kit, Malta) for detection of influenza virus (H1N1, B), rhinovirus, parainfluenza virus, adenovirus, respiratory syncytial virus, human parechovirus, bocavirus, metapneumovirus, and human coronavirus. The prevalence of viral infection was estimated and association tests were used (χ(2) or Fisher's exact test). RESULTS: 104 samples of nasopharyngeal aspirate and blood were analyzed. The median age was 12 ± 5.2 years, 51% males, 68% whites, 32% had repeated ARIs, 32% prior antibiotic use, 19.8% cough, and 8% contact with ARIs. A total of 94.3% were in good general status. Acute lymphocytic leukemia (42.3%) was the most prevalent neoplasia. Respiratory viruses were detected in 50 samples: rhinoviruses (23.1%), respiratory syncytial virus AB (8.7%), and coronavirus (6.8%). Co-detection occurred in 19% of cases with 2 viruses and in 3% of those with 3 viruses, and was more frequent between rhinovirus and coronavirus 43. Fever in neutropenic patients was observed in 13%, of which four (30.7) were positive for viruses. There were no deaths. CONCLUSIONS: the prevalence of respiratory viruses was relevant in the infectious episode, with no increase in morbidity and mortality. Viral co-detection was frequent in patients with cancer and ARIs.


Asunto(s)
Neoplasias/complicaciones , Infecciones del Sistema Respiratorio/complicaciones , Virosis/complicaciones , Enfermedad Aguda , Adolescente , Niño , Preescolar , Estudios Transversales , Femenino , Fiebre/complicaciones , Humanos , Lactante , Masculino , Nasofaringe/metabolismo , Neoplasias/tratamiento farmacológico , Prevalencia , Virus Sincitiales Respiratorios/aislamiento & purificación , Infecciones del Sistema Respiratorio/diagnóstico , Rhinovirus/aislamiento & purificación , Virosis/diagnóstico , Virosis/epidemiología
9.
Cell Rep ; 6(5): 892-905, 2014 Mar 13.
Artículo en Inglés | MEDLINE | ID: mdl-24565511

RESUMEN

Condensin is a central regulator of mitotic genome structure with mutants showing poorly condensed chromosomes and profound segregation defects. Here, we identify NCT, a complex comprising the Nrc1 BET-family tandem bromodomain protein (SPAC631.02), casein kinase II (CKII), and several TAFs, as a regulator of condensin function. We show that NCT and condensin bind similar genomic regions but only briefly colocalize during the periods of chromosome condensation and decondensation. This pattern of NCT binding at the core centromere, the region of maximal condensin enrichment, tracks the abundance of acetylated histone H4, as regulated by the Hat1-Mis16 acetyltransferase complex and recognized by the first Nrc1 bromodomain. Strikingly, mutants in NCT or Hat1-Mis16 restore the formation of segregation-competent chromosomes in cells containing defective condensin. These results are consistent with a model where NCT targets CKII to chromatin in a cell-cycle-directed manner in order to modulate the activity of condensin during chromosome condensation and decondensation.


Asunto(s)
Adenosina Trifosfatasas/metabolismo , Quinasa de la Caseína II/metabolismo , Cromatina/metabolismo , Proteínas de Unión al ADN/metabolismo , Complejos Multiproteicos/metabolismo , Proteínas Nucleares/metabolismo , Proteínas de Unión al ARN/metabolismo , Acetilación , Centrómero/metabolismo , Histona Acetiltransferasas/metabolismo , Histonas/metabolismo , Mitosis/fisiología , Levaduras/metabolismo
10.
BMC Vet Res ; 9: 124, 2013 Jun 23.
Artículo en Inglés | MEDLINE | ID: mdl-23800301

RESUMEN

BACKGROUND: The use of ultrasound in veterinary medicine is widespread as a diagnostic supplement in the clinical routine of small animals, but there are few reports in wild animals. The objective of this study was to describe the anatomy, topography and abdominal sonographic features of coatis. RESULTS: The urinary bladder wall measured 0.11 ± 0.03 cm. The symmetrical kidneys were in the left and right cranial quadrant of the abdomen and the cortical, medullary and renal pelvis regions were recognized and in all sections. The medullary rim sign was visualized in the left kidney of two coatis. The liver had homogeneous texture and was in the cranial abdomen under the rib cage. The gallbladder, rounded and filled with anechoic content was visualized in all coatis, to the right of the midline. The spleen was identified in the left cranial abdomen following the greater curvature of the stomach. The parenchyma was homogeneous and hyperechogenic compared to the liver and kidney cortex. The stomach was in the cranial abdomen, limited cranially by the liver and caudo-laterally by the spleen. The left adrenal glands of five coatis were seen in the cranial pole of the left kidney showing hypoechogenic parenchyma without distinction of cortex and medulla. The pancreas was visualized in only two coatis. The left ovary (0.92 cm x 0.56 cm) was visualized on a single coati in the caudal pole of the kidney. The uterus, right adrenal, right ovary and intestines were not visualized. CONCLUSIONS: Ultrasound examination of the abdomen of coatis may be accomplished by following the recommendations for dogs and cats. It is possible to evaluate the anatomical and topographical relationships of the abdominal organs together with the knowledge of the peculiarities of parenchymal echogenicity and echotexture of the viscera.


Asunto(s)
Abdomen/anatomía & histología , Procyonidae/anatomía & histología , Abdomen/diagnóstico por imagen , Animales , Ultrasonografía/veterinaria
11.
J Biol Chem ; 287(3): 1709-18, 2012 Jan 13.
Artículo en Inglés | MEDLINE | ID: mdl-22128187

RESUMEN

RNA polymerase II initiates from low complexity sequences so cells must reliably distinguish "real" from "cryptic" promoters and maintain fidelity to the former. Further, this must be performed under a range of conditions, including those found within inactive and highly transcribed regions. Here, we used genome-scale screening to identify those factors that regulate the use of a specific cryptic promoter and how this is influenced by the degree of transcription over the element. We show that promoter fidelity is most reliant on histone gene transactivators (Spt10, Spt21) and H3-H4 chaperones (Asf1, HIR complex) from the replication-independent deposition pathway. Mutations of Rtt106 that abrogate its interactions with H3-H4 or dsDNA permit extensive cryptic transcription comparable with replication-independent deposition factor deletions. We propose that nucleosome shielding is the primary means to maintain promoter fidelity, and histone replacement is most efficiently mediated in yeast cells by a HIR/Asf1/H3-H4/Rtt106 pathway.


Asunto(s)
Proteínas de Ciclo Celular/metabolismo , Histonas/metabolismo , Chaperonas Moleculares/metabolismo , Proteínas Nucleares/metabolismo , Regiones Promotoras Genéticas/fisiología , Proteínas Represoras/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/metabolismo , Transcripción Genética/fisiología , Proteínas de Ciclo Celular/genética , Histonas/genética , Chaperonas Moleculares/genética , Complejos Multiproteicos/genética , Complejos Multiproteicos/metabolismo , Proteínas Nucleares/genética , Nucleosomas/genética , Nucleosomas/metabolismo , Proteínas Represoras/genética , Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/genética
12.
Cell ; 136(5): 952-63, 2009 Mar 06.
Artículo en Inglés | MEDLINE | ID: mdl-19269370

RESUMEN

Reversible protein phosphorylation is a signaling mechanism involved in all cellular processes. To create a systems view of the signaling apparatus in budding yeast, we generated an epistatic miniarray profile (E-MAP) comprised of 100,000 pairwise, quantitative genetic interactions, including virtually all protein and small-molecule kinases and phosphatases as well as key cellular regulators. Quantitative genetic interaction mapping reveals factors working in compensatory pathways (negative genetic interactions) or those operating in linear pathways (positive genetic interactions). We found an enrichment of positive genetic interactions between kinases, phosphatases, and their substrates. In addition, we assembled a higher-order map from sets of three genes that display strong interactions with one another: triplets enriched for functional connectivity. The resulting network view provides insights into signaling pathway regulation and reveals a link between the cell-cycle kinase, Cak1, the Fus3 MAP kinase, and a pathway that regulates chromatin integrity during transcription by RNA polymerase II.


Asunto(s)
Fosforilación , Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/metabolismo , Transducción de Señal , Acetilación , Histonas/metabolismo , Proteínas Quinasas/metabolismo
13.
Mol Cell Biol ; 28(13): 4342-53, 2008 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-18458063

RESUMEN

Acetylation of Saccharomyces cerevisiae histone H3 on K56 by the histone acetyltransferase (HAT) Rtt109 is important for repairing replication-associated lesions. Rtt109 purifies from yeast in complex with the histone chaperone Vps75, which stabilizes the HAT in vivo. A whole-genome screen to identify genes whose deletions have synthetic genetic interactions with rtt109Delta suggests Rtt109 has functions in addition to DNA repair. We show that in addition to its known H3-K56 acetylation activity, Rtt109 is also an H3-K9 HAT, and we show that Rtt109 and Gcn5 are the only H3-K9 HATs in vivo. Rtt109's H3-K9 acetylation activity in vitro is enhanced strongly by Vps75. Another histone chaperone, Asf1, and Vps75 are both required for acetylation of lysine 9 on H3 (H3-K9ac) in vivo by Rtt109, whereas H3-K56ac in vivo requires only Asf1. Asf1 also physically interacts with the nuclear Hat1/Hat2/Hif1 complex that acetylates H4-K5 and H4-K12. We suggest Asf1 is capable of assembling into chromatin H3-H4 dimers diacetylated on both H4-K5/12 and H3-K9/56.


Asunto(s)
Histona Acetiltransferasas/metabolismo , Histonas/metabolismo , Chaperonas Moleculares/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/enzimología , Acetilación , Proteínas de Ciclo Celular/metabolismo , Núcleo Celular/enzimología , Daño del ADN , Reparación del ADN , Estabilidad de Enzimas , Genoma Fúngico , Inestabilidad Genómica , Lisina/metabolismo , Análisis de Secuencia por Matrices de Oligonucleótidos , Unión Proteica , Fase S , Saccharomyces cerevisiae/citología , Saccharomyces cerevisiae/genética , Especificidad por Sustrato
14.
Mem. Inst. Oswaldo Cruz ; 101(supl.1): 313-316, Oct. 2006. tab, graf
Artículo en Inglés | LILACS | ID: lil-441265

RESUMEN

The emergence of strains of Schistosoma resistant to praziquantel has drawn attention to the search for new schistosomacide drugs. Imidazolidinic derivatives have performed outstandingly against adult S. mansoni worms when evaluated in vitro. The molecular modification of imidazolidine by way of bioisosteric replacement gives rise to variations in its biological response. This study verifies the potential of substituent groups in the derivatives (Z)3-benzyl-5-(2-fluoro-benzylidene)-imidazolidine-2,4-dione NE4, 3-benzyl-5-(4-chloro-arylazo)-4-thioxo-imidazolidin -2-ona PT5, 3-benzyl-5-(3-fluoro-benzylidene)-1-methyl-2-thioxo-imidazolidin-4-one JT53; 3-benzyl-1-methyl-5-(4-methyl-benzylidene)-2-thioxo-imidazolidin-4-one JT63; 3-benzyl-1-methyl-5-(4-methoxi-benzylidene)-2-thioxo -imidazolidin-4-one JT68; 3-(4-chloro-benzyl)-1-methyl-5-(4-methoxi-benzylidene)-2-thioxo-imidazolidin-4-one JT69; 3-(4-phenyl-benzyl)-1-methyl-5-(4-methoxi-benzylidene)-2-thioxo-imidazolidin-4-one JT72 by determining the viability in vitro of adult S. mansoni worms in the presence of these derivatives. The susceptibility of the worms obtained from mice and kept in culture in the presence of different concentrations was determined by way of schistosomacide kinetic, observed every 24 h over a period of eight days. The results show that the worms were more sensitive to the PT5 derivative at a concentration of 58 æM which killed 100 percent of the worms after 24 h of contact, also giving rise to alterations in the tegument surface of the worms with the formation of bubbles and peeling. These observations suggest a strong electronic contribution of the arylazo grouping in the biological response.


Asunto(s)
Animales , Femenino , Masculino , Ratones , Imidazolidinas/farmacología , Schistosoma mansoni/efectos de los fármacos , Esquistosomicidas/farmacología , Imidazolidinas/síntesis química , Pruebas de Sensibilidad Parasitaria , Esquistosomicidas/síntesis química , Factores de Tiempo
15.
Rev Bras Parasitol Vet ; 15(3): 105-9, 2006.
Artículo en Portugués | MEDLINE | ID: mdl-16978474

RESUMEN

The prevalence of antibodies anti-Neospora caninum in bovines was determined in 21 farms from Anápolis and Goiânia microregions, in Goiás, Brazil. Out of these 11 were dairy farms (Holstein and crossbred Holstein-Zebu), nine had beef cattle (Nelore) and one was for mixed exploitation (Simental). Blood samples were collected from 930 animals, and sera obtained were separated and stored at -20 degrees C. Serum samples were examined by the immunofluorescent antibody technique (IFAT), using tachyzoites of the NC-1 Neospora caninum strain as antigen. Antibodies anti-N. caninum were found in 283 (30.4%) of the 930 blood samples examined. All the farms were positive, with prevalence for N. caninum varying from 10.3% to 89.7% of the examined animals. The prevalence for beef herds was 29.6% (10.3% to 89.7%), for dairy herds 30.4% (14.5% to 83.3%), and for the mixed herd, the prevalence was 43.3%. No statistically significant differences were found among prevalence in animals from beef, dairy or mixed herds. Results confirmed that N. caninum is widespread in different types of bovine herds in the micro regions of Anápolis and Goiânia.


Asunto(s)
Anticuerpos Antiprotozoarios/sangre , Bovinos/sangre , Neospora/inmunología , Animales , Brasil , Enfermedades de los Bovinos/sangre , Enfermedades de los Bovinos/epidemiología , Coccidiosis/sangre , Coccidiosis/epidemiología , Coccidiosis/veterinaria , Industria Lechera , Estudios Seroepidemiológicos
16.
Mem Inst Oswaldo Cruz ; 101 Suppl 1: 313-6, 2006 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-17308788

RESUMEN

The emergence of strains of Schistosoma resistant to praziquantel has drawn attention to the search for new schistosomacide drugs. Imidazolidinic derivatives have performed outstandingly against adult S. mansoni worms when evaluated in vitro. The molecular modification of imidazolidine by way of bioisosteric replacement gives rise to variations in its biological response. This study verifies the potential of substituent groups in the derivatives (Z)3-benzyl-5-(2-fluoro-benzylidene)-imidazolidine-2,4-dione NE4, 3-benzyl-5-(4-chloro-arylazo)-4-thioxo-imidazolidin -2-ona PT5, 3-benzyl-5-(3-fluoro-benzylidene)-1-methyl-2-thioxo-imidazolidin-4-one JT53; 3-benzyl-1-methyl-5-(4-methyl-benzylidene)-2-thioxo-imidazolidin-4-one JT63; 3-benzyl-1-methyl-5-(4-methoxi-benzylidene)-2-thioxo -imidazolidin-4-one JT68; 3-(4-chloro-benzyl)-1-methyl-5-(4-methoxi-benzylidene)-2-thioxo-imidazolidin-4-one JT69; 3-(4-phenyl-benzyl)-1-methyl-5-(4-methoxi-benzylidene)-2-thioxo-imidazolidin-4-one JT72 by determining the viability in vitro of adult S. mansoni worms in the presence of these derivatives. The susceptibility of the worms obtained from mice and kept in culture in the presence of different concentrations was determined by way of schistosomacide kinetic, observed every 24 h over a period of eight days. The results show that the worms were more sensitive to the PT5 derivative at a concentration of 58 microM which killed 100% of the worms after 24 h of contact, also giving rise to alterations in the tegument surface of the worms with the formation of bubbles and peeling. These observations suggest a strong electronic contribution of the arylazo grouping in the biological response.


Asunto(s)
Imidazolidinas/farmacología , Schistosoma mansoni/efectos de los fármacos , Esquistosomicidas/farmacología , Animales , Femenino , Imidazolidinas/síntesis química , Masculino , Ratones , Pruebas de Sensibilidad Parasitaria , Esquistosomicidas/síntesis química , Factores de Tiempo
17.
Mem. Inst. Oswaldo Cruz ; 93(6): 741-4, Nov.-Dec. 1998. ilus, tab
Artículo en Inglés | LILACS | ID: lil-223876

RESUMEN

Eimeria minasensis n.sp. is described in the domestic goat Capra hircus from Brazil. Oocysts ellipsoidal are 35 x 24.5 (32-37.7 x 20.9-27.9) µm. Sporocysts elongate-ellipsoid are 15.2 x 9 (12.3-18.4 x 7.8-10.2) µm, with a Stieda body at the narrow end. Oocyst wall smooth and bilayered; outer layer about 1.2 (0.8-1.6) µm and colorless; inner layer about 0.5 (0.4-0.8) µm and dark-brown. Micropyle, a mound-shaped micropylar cap 1,6 x 8,9 (0,8-2 x 7-10,2) easily dislodged; one or more oocyst polar granules present. Oocyst residuum absent. Sporocyst residuum present, composed of many scattered granules. Sporozoites elongate, lying lengthwise, "head to tail" in the sporocysts; one or two refractile globules are usually visible. Sporulation time was 120 hr at 27ºC, prepatent period, 19 to 20 days and patent period 15 to 25 days. Gamonts, gametes and oocysts present in cecum and colon. Prevalence was 12.8 per cent (6/47) in goats from Minas Gerais, Brazil.


Asunto(s)
Animales , Eimeria/parasitología , Cabras/parasitología , Brasil , Coccidios/parasitología
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