Characterization of Trypanosoma cruzi Sirtuins as Possible Drug Targets for Chagas Disease

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Differences in transcriptional activity of human papillomavirus type 6 molecular variants in recurrent respiratory papillomatosis

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Anestesia peridural com lidocaína em um potro: relato de caso

Um equino macho, raça Manga Larga, de 20 dias de idade, pesando 55 kg foi atendido no Hospital Veterinário “Luiz Quintiliano de Oliveira” com histórico de queda no dia anterior, apresentando impotência funcional e desvio do eixo ósseo do membro pélvico esquerdo (MPE). Ao exame radiográfico, constatou-se uma fratura classificada como Salter- Harris tipo II, na região distal da tíbia esquerda, com indicação para osteossíntese. Ao exame físico geral, observou-se frequência cardíaca (FC) de 82 batimentos.min-1, frequência respiratória (f) de 60 movimentos.min-1, mucosas róseas, tempo de preenchimento capilar de dois segundos, temperatura retal (ToC) de 38,5oC e hidratação adequada. Como medicação pré-anestésica, administrou-se xilazina (0,5 mg.kg-1) IV. A indução foi realizada por meio da administração de midazolam (0,1mg.kg-1) e cetamina (2mg.kg-1) IV. Seguiu-se a intubação orotraqueal com sonda n o 12 conectando-se a um circuito anestésico com reinalação parcial de gases, e a manutenção foi realizada com isofluorano em fluxo diluente de oxigênio a 100%, sob ventilação espontânea. Realizou-se a técnica de anestesia peridural com o paciente em decúbito lateral direito, introduzindo uma agulha 30x8 percutaneamente até atingir o espaço peridural entre as vértebras L6 e S1, onde se administrou lidocaína a 2% (2,2mg.kg-1) com vasoconstritor, perfazendo um volume de 6 mLs. Adicionalmente foi realizado o bloqueio perineural dos nervos tibial e fibular do membro acometido, com administração de 5 mLs de lidocaína a 2% com vasoconstritor em cada ponto. A administração de anestésicos locais pela via peridural na região L6 – S1 não é rotineiramente usada em equinos, uma vez que provoca ataxia ou perda do tônus muscular, aumentando os riscos relacionados à intervenção anestésica. No entanto, a recuperação do potro nesse relato de caso foi rápida e isenta de complicações, provalvelmente proporcionando anestesia multimodal e consequentemente menor depressão cardiovascular. A associação da anestesia peridural e bloqueio dos nervos tibial e fibular à anestesia geral, pode ser uma alternativa para intervenções cirúrgicas em membros pélvicos de potros, uma vez que demonstrou ser efetiva e de fácil execução.

Anatomo-histopatologia de fígados bovinos: relação entre as lesões e os sistemas de produção

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Piperacillin/tazobactam-induced neurotoxicity in a hemodialysis patient: a case report

Antibiotics are potentially a cause of neurotoxicity in dialysis patients, the most common are thebeta-lactams as ceftazidime and cefepime, and few cases have been reported after piperacillin/tazobactam use. This report presents a case of a hypertensive and diabetic 67-year-old woman inregular hemodialysis, which previously had a stroke. She was hospitalized presenting pneumonia,which was initially treated with cefepime. Two days after treatment, she presented dysarthria, lefthemiparesis, ataxia, and IX and X cranial nerves paresis. Computed tomography showed no acutelesions and cefepime neurotoxicity was hypothesized, and the antibiotic was replaced bypiperacillin/tazobactam. The neurologic signs disappeared; however, 4 days after with piperacillin/tazobactam treatment, the neurological manifestations returned. A new computed tomographyshowed no new lesions, and the second antibiotic regimen withdrawn. After two hemodialysissessions, the patient completely recovered from neurological manifestations. The patient presentedsequentially neurotoxicity caused by two beta-lactams antibiotics. This report meant to alertclinicians that these antibiotics have dangerous neurological effects in chronic kidney diseasepatients.

Papiloma de plexo coroide em um cão

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Biopsias luteais em vacas Nelore

The present study describes a technique to obtain consecutive luteal samples by colpotomy. The animals received an epidural anesthesia and local anesthesia (vaginal vault) and after ten minutes the vaginal vault was incised with a scalpel blade and tissue was dissected to provide access to the pelvic cavity and to retract the ovary into the vagina. Then, a luteal biopsy was performed with a Yomann biopsy nipper. Signs indicative of pain and stress during the vaginal vault incision, traction of ovary or luteal biopsy were observed only in two collections. However, these signs were observed in ten collections during dissection of the vaginal wall and peritoneum. The occurrence of ataxia was observed in 26 collections and it was usually related to a longer duration of the procedure. Ataxia could be divided in light (15/26), moderate (6/26) and severe (5/26). The occurrence of ovarian adhesions ipsilateral to the incision was evaluated only in the initial four collections. Adhesions were present in 16 collections. The protocol described above provided a safe and efficient method to acquire luteal samples. The low incidence of adhesions allows the consecutive use of females without any interference in subsequent ovulations and collections.

Estudo clínico randomizado e duplo cego comparando dois métodos de escleroterapia para veias reticulares e telangiectasias em membros inferiores

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Acetaminophen as an Oral Toxicant for Nile Monitor Lizards (Varanus niloticus) and Burmese Pythons (Python molurus bivittatus)

Context. Invasive species are a growing global problem. Biological invasions can result in numerous harmful impacts on local ecologies, and non-native herpetofauna are frequently ignored. Nile monitor lizards (Varanus niloticus) and Burmese pythons (Python molurus bivittatus, recently reassessed as Python bivittatus bivittatus), have become established in southern Florida. Both are large, semi-aquatic predators that pose serious threats to a variety of threatened and endangered species, as well as to the unique ecology of the area. Aims. Acetaminophen (CAS#103-90-2), a lethal oral toxicant for the invasive brown treesnake (Boiga irregularis) on Guam, was investigated as a possible toxicant in juvenile Burmese pythons and Nile monitors. Methods. Dead neonatal mouse (DNM) baits containing 0, 10, 20, or 40 mg acetaminophen were force-fed to Nile monitors, whereas DNM containing doses of 0, 20, 40, or 80 mg were freely consumed by Burmese pythons. Subjects were frequently observed post-treatment for general condition and position, with special attention paid to activity (if any), behaviour, respiration, bleeding, emesis, ataxia, and mortality. Key results. In Nile monitors, acetaminophen doses of 10, 20, or 40 mg resulted in 0, 50 and 100% mortality, respectively. In Burmese pythons, doses of 20, 40, or 80 mg resulted in 14.3, 85.7 and 100% mortality, respectively. No mortality was observed in control individuals of either species. A negative correlation between dosage (mg kg–1) and time-to-death was observed in both species. Dosages ranging from 522 to 2438 mg kg–1 and 263 to 703 mg kg–1 were uniformly lethal to monitors and pythons, respectively. Neither species exhibited signs of pain or discomfort following acetaminophen treatment. Conclusions. Acetaminophen is an effective toxicant in juvenile Nile monitors and Burmese pythons. Further investigation into acetaminophen toxicity in adults of these species is merited. Implications. Although further investigation into adult lethal dosages and strategies to optimize bait deployment while minimizing secondary hazards is required, acetaminophen may have a role to play in the control of these invasive species in Florida.

Thyroid hormone action is required for normal cone opsin expression during mouse retinal development

PURPOSE. The expression of S- and M-opsins in the murine retina is altered in different transgenic mouse models with mutations in the thyroid hormone receptor (TR)-beta gene, demonstrating an important role of thyroid hormone (TH) in retinal development. METHODS. The spatial expression of S- and M-opsin was compared in congenital hypothyroidism and in two different TR mutant mouse models. One mouse model contains a ligand-binding mutation that abolishes TH binding and results in constitutive binding to nuclear corepressors. The second model contains a mutation that blocks binding of coactivators to the AF-2 domain without affecting TH binding. RESULTS. Hypothyroid newborn mice showed an increase in S- opsin expression that was completely independent of the genotype. Concerning M-opsin expression, hypothyroidism caused a significant decrease (P < 0.01) only in wild-type animals. When TR beta 1 and -beta 2 were T3-binding defective, the pattern of opsin expression was similar to TR beta ablation, showing increased S- opsin expression in the dorsal retina and no expression of M-opsin in the entire retina. In an unexpected finding, immunostaining for both opsins was detected when both subtypes of TR beta were mutated in the helix 12 AF-2 domain. CONCLUSIONS. The results show, for the first time, that the expression of S- and M-opsin is dependent on normal thyroid hormone levels during development.

Comparison of Laser Versus Sclerotherapy in the Treatment of Lower Extremity Telangiectases: A Prospective Study

BACKGROUND Lower extremity telangiectasia affects approximately 40% of women. The demand for aesthetic treatment of these veins continues to grow. Few studies have compared laser and sclerotherapy to treat leg telangiectasias. OBJECTIVE To compare the efficacy of conventional sclerotherapy and neodymium-doped yttrium aluminum garnet (Nd:YAG) laser in the treatment of leg telangiectasias. METHODS AND MATERIALS Thirty women were enrolled in the study. One leg was randomly assigned laser treatment and the other sclerotherapy with 75% glucose solution. All patients were photographed before and after treatment. The applying physician and two independent observers rated photographic improvement of the treated areas. Complications and adverse effects were noted during follow-up. Patients answered a questionnaire that addressed pain, clearing of the vessels, and satisfaction with the results. RESULTS There was a significant difference between the modes of treatment regarding pain. Twelve patients using laser and 16 using sclerotherapy considered the clearing of the vessels to be good to excellent after three sessions of both laser and scleratherapy. Mean scores after photographic assessment were 7.9 for laser and 7.0 for sclerotherapy. CONCLUSION Lower extremity telangiectases may be treated equally well using Nd:YAG 1064-nm laser or conventional sclerotherapy.

Late Adverse Effects of the Coadministration of Valproate and Lamotrigine

Individuals treated with combined valproate-lamotrigine rarely present late adverse effects (unrelated to introduction and titration). We describe four patients in whom such effects occurred after continuous, long-term use of valproate-lamotrigine (at 9 months to 2 years after final antiepileptic drug adjustment). The patients presented heterogeneous disturbances, including ataxia, vertigo, and headache, and rare movement disorders, such as tics and abnormal eye movements. Although these effects are heterogeneous in their occurrence and timing, they can alert physicians to the possibility of late neurologic disturbances, and must be considered in order to avoid unnecessary ancillary tests. Treatment discontinuation is unnecessary, given that a small decrease in dose led to remission of these adverse effects. (c) 2012 Elsevier Inc. All rights reserved.

LTR point mutations in the Tax-responsive elements of HTLV-1 isolates from HIV/HTLV-1-coinfected patients

Background: In Virology Journal 2011, 8: 535, Neto et al. described point mutations into Tax-responsive elements (TRE) of the LTR region of HTLV-1 isolates from asymptomatic carriers from Sao Paulo, Brazil, and hypothesized that the presence of the G232A mutation in the TRE-1 increase viral proliferation and consequently the proviral load (PvL), while the A184G mutation in the TRE-2 do not have such effect. Findings: We performed the real-time PCR assay (pol) and sequenced LTR region of HTLV-1 isolates from 24 HIV/HTLV-1-coinfected patients without HTLV-1-associated diseases from the same geographic area. These sequences were classified as belonging to the transcontinental subgroup A of the Cosmopolitan subtype a. The frequency of G232A mutation (16/24, 66.7%) was high as much as 61.8% reported by Neto's in HTLV-1 asymptomatic carriers with high PvL. High frequency (13/24, 54.2%) of double mutations G232A and A184G was also detected in HIV/HTLV-1-coinfected patients. We did not quantify PvL, but comparative analyses of the cycle threshold (Ct) median values of the group of isolates presenting the mutated-types sequences (Ct 33.5, n = 16) versus the group of isolates with the wild-type sequences (Ct 32, n = 8) showed no statistical difference (p = 0.4220). Conclusion: The frequencies of mutated-type sequences in the TRE-1 and TRE-2 motifs were high in HIV/HTLV-1-coinfected patients from Sao Paulo, Brazil. If these LTR point mutations have predictive value for the development of HTLV-1-associated diseases or they correspond to the subtype of virus that circulate in this geographic area has to be determined.

Dasatinib Overrides Imatinib Resistance Mediated by the F359I Residue Mutation in Two Patients with Chronic Myeloid Leukemia

Despite the beneficial effects of imatinib mesylate, some patients may either not respond or respond suboptimally. Here, we report two chronic myelogenous leukemia patients; one had a suboptimal response according to European LeukemiaNet criteria (a major molecular response was not achieved after 18 months of standard-dose imatinib therapy) and the other had failure with a standard dose of imatinib. At the time of the suboptimal response in patient 1 and the failure in patient 2, we were able to detect the F359I mutation in the BCR-ABL tyrosine kinase domain using DNA sequencing in both patients. Therefore, it was decided to change the therapeutic regimen to dasatinib at a dose of 100 mg once daily in both patients. This change resulted in the achievement of complete cytogenetic remission in patient 1 after 4 months and a major molecular response within 2 and 3 months in both patients. Detection of the F359I mutation in our two cases likely explains the suboptimal response to imatinib in case 1 and the failure in case 2. This implies that in such cases dasatinib should be considered to effectively suppress the mutated clones. Copyright (C) 2011 S. Karger AG, Basel

Aberrant transcript produced by a splice donor site deletion in the TECTA gene is associated with autosomal dominant deafness in a Brazilian family

We ascertained a Brazilian family with nine individuals affected by autosomal dominant nonsyndromic sensorineural hearing loss. The bilateral hearing loss affected mainly mid-high frequencies, was apparently stable with an early onset. Microsatellites close to the DFNA8/DFNA12 locus, which harbors the TECTA gene, showed significant multipoint lod scores (32) close to marker D11S4107. Sequencing of the exons and exon-intron boundaries of the TECTA gene in one affected subject revealed the deletion c.5383 + 5delGTGA in the 5' end of intron 16, that includes the last two bases of the donor splice site consensus sequence. This mutation segregates with deafness within the family. To date, 33 different TECTA mutations associated with autossomal dominant hearing loss have been described. Among them is the mutation reported herein, first described by Hildebrand et al. (2011) in a UK family. The audioprofiles from the UK and Brazilian families were similar. In order to investigate the transcripts produced by the mutated allele, we performed cDNA analysis of a lymphoblastoid cell line from an affected heterozygote with the c.5383 + 5delGTGA and a noncarrier from the same family. The analysis allowed us to identify an aberrant transcript with skipping of exon 16, without affecting the reading frame. One of the dominant TECTA mutations already described, a synonymous substitution in exon 16 (c.5331 G<A), was also shown to affect splicing resulting in an aberrant transcript lacking exon 16. Despite the difference in the DNA level, both the synonymous substitution in exon 16 (c.5331 G<A) and the mutation described herein affect splicing of exon 16, leading to its skipping. At the protein level they would have the same effect, an in-frame deletion of 37 amino-acids (p.S1758Y/G1759_N1795del) probably leading to an impaired function of the ZP domain. Thus, like the TECTA missense mutations associated with dominant hearing loss, the c5383 + 5delGTGA mutation does not have an inactivating effect on the protein. (C) 2012 Elsevier B.V. All rights reserved.