Lactose drives Enterococcus expansion to promote graft-versus-host disease.

Disruption of intestinal microbial communities appears to underlie many human illnesses, but the mechanisms that promote this dysbiosis and its adverse consequences are poorly understood. In patients who received allogeneic hematopoietic cell transplantation (allo-HCT), we describe a high incidence of enterococcal expansion, which was associated with graft-versus-host disease (GVHD) and mortality. We found that Enterococcus also expands in the mouse gastrointestinal tract after allo-HCT and exacerbates disease severity in gnotobiotic models. Enterococcus growth is dependent on the disaccharide lactose, and dietary lactose depletion attenuates Enterococcus outgrowth and reduces the severity of GVHD in mice. Allo-HCT patients carrying lactose-nonabsorber genotypes showed compromised clearance of postantibiotic Enterococcus domination. We report lactose as a common nutrient that drives expansion of a commensal bacterium that exacerbates an intestinal and systemic inflammatory disease.

Use of a GnRH synthetic analog (buserelin) for estrous induction in female dogs / Utilização de análogo sintético de GnRH (buserelina) na indução do estro em cadelas

The aim of this study was to evaluate the effectiveness of a GnRH synthetic analog, as an estrous inducer in female dogs when administered during the anestrous phase, and to evaluate the pregnancy rate achieved through natural copulation. For this purpose, ten female dogs of different breeds were used. The subjects received buserelin by intramuscular injections at a dose of 2,1mcg when female dogs weighed up to 10kg (Group 1) and of 4,2mcg when the dogs weighed above 10kg (Group 2). Of the ten subjects, only three presented estrus after a single injection of buserelin: two dogs from Group 1 and one dog from Group 2 on average 7±1.29 days. The remaining seven dogs were given a second dose of buserelin, equal to the first administration. Of these, three belonged to Group 1 and four to Group 2. Four of these dogs exhibited clinical signs of estrus within, on average 9±7.3 days from the second injection. The seven female dogs that did enter estrus were fertilized successfully through natural copulation. The administration of buserelin was effective in inducing estrus in female dogs during the anestrous phase, with a maximum of two administrations.(AU)

Objetivou-se avaliar a eficácia de um análogo sintético ao GnRH como indutor de estro em cadelas em anestro e a taxa de prenhez por meio de cópula natural. Para isso, foram utilizadas 10 fêmeas caninas de diferentes raças. Cadelas de até 10kg de peso (grupo 1) foram submetidas à administração de buserelina por via intramuscular, na dose de 2,1mcg, e cadelas acima de 10kg (grupo 2) foram submetidas à mesma medicação, porém na dose de 4,2mcg. Das fêmeas em anestro, apenas três apresentaram estro com apenas uma aplicação, sendo duas do grupo 1 e uma do grupo 2, em 7±1,29 dias, em média. Em sete cadelas foi administrada mais uma dose de buserelina; destas, quatro eram pertencentes ao grupo 2 e três eram do grupo 1. Os sinais de estro ocorreram, em média, após 9±2,73 dias da segunda aplicação. As sete cadelas que manifestaram estro foram fertilizadas por meio de cópula natural. A administração de buserelina é eficiente para a indução de estro, em cadelas em anestro, em, no máximo, duas aplicações.(AU)

Efeitos de detomidina e xilazina intravenosa sobre as variáveis basais e respostas comportamentais em bovinos / Effects of intravenous detomidine and xilazine on basal parameters and behavioral responses in bovine

Avaliaram-se, durante 60 minutos, 10 bovinos após administração intravenosa de 0,1mg.kg-1 de xilazina ou 10μg.kg-1 de detomidina, quanto às frequências cardíaca e respiratória, movimentos ruminais, pressão arterial média, temperatura retal e respostas comportamentais como ataxia ou decúbito, ptose palpebral, estado de alerta ou sedação e redução da altura da cabeça em relação ao solo, além da presença de salivação, micção e concentração sanguínea de glicose. Observou-se que a xilazina, via intravenosa, em bovinos, ao mesmo tempo que promove sedação mais intensa e prolongada que a detomidina, induz a uma maior quantidade de efeitos indesejáveis, como salivação e decúbito, e redução das frequências cardíaca e respiratória, da pressão arterial média, da motilidade ruminal e da temperatura, sendo estas alterações mais prolongadas. Conclui-se que a detomidina pode ser utilizada com segurança em bovinos na dose de 10μg.kg-1, promovendo sedação e permanência do animal em posição quadrupedal.

Ten bovine were evaluated after intravenous injection of 0,1mg.kg-1 of xylazine or 10μg.kg-1 of detomidine during 60 minutes for heart and respiratory rate, ruminal motility, mean arterial pressure, rectal temperature and behavioral responses like ataxia or recumbency, palpebral ptoses, state of sedation or alert and head drop, besides the measurement of salivation, urination and blood glucose concentration. It was observed that intravenous xylazine in bovine promotes more intense and prolonged sedation than detomidine, and at the same time induces a larger and more prolonged quantity of unwanted side effects such as salivation, recumbency, decrease of cardiac and respiratory rate, mean arterial pressure, ruminal motility and temperature. We concluded that detomidine can be used safely in bovines at 10μg.kg-1 dose, promoting sedation with standing position.

Purinergic modulation in the development of the rat uncrossed retinotectal pathway.

Adenosine is a neuromodulator implicated in nervous system development and plasticity and its effects are mediated by inhibitory (A(1), A(3)) and excitatory (A(2a), A(2b)) receptors. The role of adenosine in the synaptic activity depends mainly on a balanced activation of A(1) and A(2a) receptors which are activated by various ranges of adenosine concentrations. Herein, we investigated the expression of A(1) and A(2a) receptors and also the accumulation of cAMP in the superior colliculus at different stages of development. Furthermore, we examined the effects of an acute in vivo blockade of adenosine deaminase during the critical period when the elimination of misplaced axons/terminals takes place with a simultaneous fine tuning of terminal arbors into appropriate terminal zones. Lister Hooded rats ranging from postnatal days (PND) 0-70 were used for ontogeny studies. Our results indicate that A(1) expression in the visual layers of the superior colliculus is higher until PND 28, while A(2a) expression increases after PND 28 in a complementary developmental pattern. Accordingly, the incubation of collicular slices with 5'-N-ethylcarboxamido-adenosine, a non-specific adenosine receptor agonist, showed a significant reduction in cAMP accumulation at PND 14 and an increase in adults. For the anatomical studies, the uncrossed retinotectal projections were traced after the intraocular injection of horseradish peroxidase. One group received daily injections of an adenosine deaminase inhibitor (erythro-9(2-hydroxy-3-nonyl adenine), 10 mg/kg i.p.) between PND 10 and 13, while control groups were treated with vehicle injections (NaCl 0.9%, i.p.). We found that a short-term blockade of adenosine deaminase during the second postnatal week induced an expansion of retinotectal terminal fields in the rostrocaudal axis of the tectum. Taken together, the results suggest that a balance of purinergic A(1) and A(2a) receptors through cAMP signaling plays a pivotal role during the development of topographic order in the retinotectal pathway.

Molecular alterations of KIT and PDGFRA in GISTs: evaluation of a Portuguese series.

AIM: To assess KIT and PDGFRA mutations frequencies in a Portuguese series of gastrointestinal stromal tumours (GISTs). METHODS: 78 GISTs were evaluated for CD117 expression and screened for mutations in KIT (exons 9, 11, 13, 14 and 17) and PDGFRA (exons 12, 14 and 18) genes. RESULTS: KIT activating mutations were identified in 44 (56%) of the 78 GISTs. Forty cases (91%) presented a mutation in KIT exon 11, and 4 (9%) in exon 9. One case showed a 4 bp deletion in intron 14. PDGFRA mutations were observed in 5 cases (6%): 2 (3%) in exon 12 and 3 (4%) in exon 18. Survival analysis was performed in 63 of the 78 GISTs. The presence of mutated KIT was significantly correlated with shorter survival of patients (p = 0.0460), and inversely associated with epithelioid histological type of GISTs (p = 0.0064). CONCLUSIONS: Overall, the incidence of both KIT and PDGFRA mutations in these Portuguese series was 63%, being in agreement with other studies, mainly of Iberian populations. The great majority of mutations were located in KIT exon 11, statistically associated with worse prognosis and indicative of favourable response to imatinib-based therapy in this Portuguese series of GISTs.

Mutations in gastrointestinal stromal tumors diagnosed by endoscopic ultrasound-guided fine needle aspiration.

Gastrointestinal stromal tumors (GISTs) are characterized by overexpression and mutations of c-Kit. Approximately 80% of c-Kit mutations occur in exon 11, being a response factor to imatinib (Gleevec) therapy. We aimed to assess whether c-Kit and PDGFRA mutation analysis of GISTs obtained by endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) could be routinely performed. Mutation analysis of c-Kit hotspot exons (9, 11, 13 and 17) and PDGFRA hotspot exons (12 and 18) was performed in aspirates 51 mesenchymal tumors. We identified c-Kit mutations in 61% of GIST cases, in accordance with previously published ranges (30-90%). Nearly 95% (19/20) of c-kit-mutant tumors carried exon 11 mutations. Mutation analysis is possible in FNA cell blocks and can assist in the diagnosis and therapeutic decisions in GIST cases.

Non-progressive leukoencephalopathy with bilateral temporal cysts.

We report two cases of a peculiar leukoencephalopathy with temporal cysts. Both patients have a non-progressive neurological disorder with mental retardation, microcephaly and sensorineural deafness although clinical differences between them may reflect a different aetiology. The metabolic disorders with white matter involvement and the recently described leukoencephalopathies (Van Der Knaap disease, 'vanishing white matter disease') were excluded based on clinical, biologic and imaging findings. Cytomegalovirus infection is a likely possibility in the first case although the magnetic resonance imaging picture is only partially similar to previously reported cases. Our patients are strikingly similar to the patients reported by Deonna et al. and Olivier et al. We discuss the clinical and imaging findings in our patients and the differential diagnosis considering the known disorders of the white matter in childhood.

Risk factors for breast cancer among pre- or post-menopausal women in Belo Horizonte, Brazil.

BACKGROUND: Much controversy has been generated about pre- and post-menopausal breast cancer patients and investigators have sought to identify whether risk factors differ between these two groups. In Brazil, breast cancer is an important cause of death among women and there are few analytical studies concerning pre- or post-menopausal comparisons. METHODS: A case-control study was carried out at the Federal University Hospital, Belo Horizonte, Brazil, to determine if selected socio-economic and reproductive risk factors for breast cancer differed between pre-menopausal and post-menopausal women. Cases were 300 women with breast carcinoma and controls were 600 women with other benign diseases matched for age and date of diagnosis, admitted to the same hospital during the same period (1978-1987). Univariate and multivariate conditional logistic regression analyses were performed. RESULTS: Multivariate analysis showed no differences in breast cancer risk in pre- and post-menopausal women (risk factors were similar in direction and magnitude). Occupation, irregular menstrual cycles, parity, history of breast cancer in at least one first-degree female relative, and oral contraceptive use had similar associations in both groups. CONCLUSIONS: The present study indicates that breast cancer diagnosed before and after menopause has a similar risk profile.

A case-control study of risk factors for breast cancer in Brazil, 1978-1987.

BACKGROUND: There are still controversies regarding the role of many risk factors assessed for breast cancer worldwide. In Brazil, it represents a major cause of death among women but yet few analytical studies have been published to date. METHODS: The association of selected factors with breast cancer was assessed in a case-control study of 300 women, aged 25-75 years, treated at the Federal University Hospital, Belo Horizonte, Brazil, from 1978 to 1987. In all, 300 cases with diagnosed breast carcinoma were compared with 600 controls matched on age and date of diagnosis. Socio-economic, demographic and reproductive factors were analysed. RESULTS: Multiple logistic regression analysis showed the following factors to be independently associated with increased risk of breast cancer: a) monthly family income (odds ratio [OR] = 1.69, 95% confidence interval [CI]: 1.18-2.42); b) being a housewife (OR = 2.86, 95% CI: 1.83-4.47; c) parity of less than six deliveries and nulliparous women (OR = 5.06, 95% CI: 3.01-8.52 and OR = 2.42, CI: 1.64-3.59, respectively); d) history of breast cancer among first degree female relatives (OR = 9.35, 95% CI: 3.22-27.14); and e) oral contraceptive use (OR = 1.81, 95% CI: 1.15-2.85). Irregular menstrual cycle (OR = 0.44, 95% CI: 0.25-0.75) was associated with breast cancer as a protective effect. CONCLUSIONS: The study has confirmed most risk/protective factors previously demonstrated elsewhere in the world and provides clear documentation of breast cancer epidemiology in Brazil.