The zoapatle III — Biological and uterotonic properties of aqueous plant extract

Differences in uterotonic activity were observed between zoapatle $\text{Montanoa}$(Cerv.), plants growing in their natural habitat and plants growing in an experimental agricultural plot. Details of an $\text{in vitro}$analogic model for assaying uterotonic potency in guinea pig strips is described. Important species differences on the uterine response to zoapatle aqueous crude extract were noticed in rats, hamsters, guinea pigs, cats and Rhesus monkeys. The need for proper biological evaluation of chemical substances already isolated from zoapatle specimens, is mentioned, and the advantages of working with zoapatle specimens grown under controlled ecological conditions are pointed out.     

The International Classification of Functioning (ICF) to evaluate deep brain stimulation neuromodulation in childhood dystonia-hyperkinesia informs future clinical & research priorities in a multidisciplinary model of care

The multidisciplinary team (MDT) approach illustrates how motor classification systems, assessments and outcome measures currently available have been applied to a national cohort of children and young people with dystonia and other hyperkinetic movement disorders (HMD) particularly with a focus on dyskinetic cerebral palsy (CP). The paper is divided in 3 sections. Firstly, we describe the service model adopted by the Complex Motor Disorders Service (CMDS) at Evelina London Children's Hospital and King's College Hospital (ELCH-KCH) for deep brain stimulation. We describe lessons learnt from available dystonia studies and discuss/propose ways to measure DBS and other dystonia-related intervention outcomes. We aim to report on current available functional outcome measures as well as some impairment-based assessments that can encourage and generate discussion among movement disorders specialists of different backgrounds regarding choice of the most important areas to be measured after DBS and other interventions for dystonia management. Finally, some recommendations for multi-centre collaboration in regards to functional clinical outcomes and research methodologies for dystonia-related interventions are proposed.     

Metabolic Syndrome and Mammographic Density in Premenopausal Chilean Women

Background: Metabolic syndrome (MetS) has been previously associated with an increased risk of breast cancer in postmenopausal women. Mammographic density (MD) is a marker of breast cancer risk. There is little evidence of an association between MetS and MD in premenopausal women. Methods: Through a cross-sectional study, we evaluated 364 premenopausal Chilean women in which we measured anthropometric, blood pressure, and metabolic markers. MetS and its components were defined according to the National Cholesterol Education Program Adult Treatment Plan III criteria. We estimated MD by absolute dense volume (ADV, cm³), nondense volume (NDV, cm³), and percentage of dense volume (PDV, %). The relationship between MetS and MD was assessed by linear regression models. Results: After adjusting for sociodemographic and gyneco-obstetrics variables, nonsignificant association was found between MetS and ADV (log β = 0.10; 95%CI: ?0.01, 0.21). However, abdominal obesity, high triglycerides, and number of components of MetS were directly related to higher ADV (P < 0.05). Conclusion: Our results showed no association between MetS and ADV; nevertheless, abdominal obesity and triglycerides were related to higher ADV. If MD could be modifiable through nutritional factors, it would open new perspectives for the prevention of breast cancer through obesity prevention strategies at population level.     

Resolution of brainstem edema after treatment of a dural tentorial arteriovenous fistula

We report a patient with a petrosal arterio-venous dural fistula draining into the ponto-mesencephalic and medullary venous systems presenting with edema of the brain stem and complete reversal of magnetic resonance imaging (MRI) abnormalities after combined endovascular and surgical treatments. The venous anatomy of the posterior fossa and the significance of the venous involvement as the cause of clinical symptoms and imaging abnormalities in cerebro-medullary vascular lesions are discussed.     

Natural Antibody Contributes to Host Defense against an Attenuated Brucella abortus virB Mutant

Brucella abortus is an intracellular pathogen that persists within phagocytic cells of the reticuloendothelial system. To identify in vivo interactions between B. abortus and the host that lead to persistent infection, we studied the persistence of B. abortus and an isogenic virB mutant deficient in the VirB type IV secretion system (T4SS) in knockout mice. In contrast to control mice, mice lacking B cells (Igh6^−/−) were permissive for infection with the attenuated virB mutant. To determine the basis for this phenotype, we characterized immune functions of Igh6^−/− mice in the context of B. abortus infection. Igh6^−/− mice had greater numbers of extracellular bacteria in the spleen and increased early expression of proinflammatory cytokines during B. abortus infection. Further, a virB mutant, despite its wild-type level of survival, failed to elicit microgranuloma formation in the spleens of Igh6^−/− mice, suggesting a requirement for the T4SS to elicit this pathological change. Passive transfer of immunoglobulin G from naïve mice restored the ability of Igh6^−/− mice to control the persistence of the virB mutant by a complement-independent mechanism. Further, adoptive transfer of CD11b⁺ cells from C57BL/6 mice to Igh6^−/− mice restored the ability of the knockout mice to limit the replication of the virB mutant in the spleen, suggesting that the Igh6^−/− mutation affects phagocyte function and that phagocyte function can be restored by natural antibody.Human brucellosis is a febrile disease resulting from the transmission of Brucella abortus, B. suis, B. melitensis, or B. canis from its respective zoonotic reservoir in cattle, swine, goats and sheep, or dogs (47). These pathogens are endemic in many areas of the world, including Central and South America, the Mediterranean, and Central Asia, and are responsible for an estimated 500,000 new brucellosis cases each year (1). In human brucellosis, as well as in the zoonotic reservoir species, bacteria may persist for long periods of time in the reticuloendothelial system (7). This aspect of infection can be modeled in the mouse, which has been used to identify and characterize the virulence factors involved in the systemic persistence of Brucella spp. (2, 22).One essential virulence factor of the human pathogenic Brucella species is the type IV secretion system (T4SS) encoded by the virB locus on chromosome II (18, 29, 40). The T4SS of Brucella spp., similar to those of other bacterial pathogens, mediates the translocation of proteins into host cells; however, the functions of two newly identified B. abortus T4SS substrates, VceA and VceC, is not yet known (12, 25, 39, 45, 46). In cultured macrophages and dendritic cells (DC), the T4SS is essential for the intracellular replication and persistence of B. abortus (13, 36, 40). The T4SS mediates exclusion of late endosomal/lysosomal markers from the Brucella-containing vacuole and targeting of B. abortus to exit sites of the endoplasmic reticulum, where replication occurs (5, 6, 12, 41), suggesting that T4SS effectors are involved in this function. After intraperitoneal (i.p.) inoculation of mice, the T4SS is required not for the initial systemic dissemination of B. abortus but rather for persistence in the reticuloendothelial system (31, 34). In order to better understand the interactions between the host and B. abortus that lead to the persistence of wild-type (WT) strains and the eventual clearance of virB mutants, we examined the immune mechanisms required for clearance of the virB mutant. Unexpectedly, mice lacking B cells (Igh6^−/−) were permissive for the splenic persistence of the virB mutant, while the persistence of WT B. abortus was not increased. When cultured ex vivo, macrophages from Igh6^−/− mice behaved identically to macrophages from control mice in their ability to control the intracellular replication of the virB mutant while permitting the replication of WT B. abortus (34).In this study, we attempted to pinpoint the defect in Igh6^−/− mice that renders them permissive for persistent infection by the virB mutant. Our results show that nonspecific antibody can reverse the defect of these mice in controlling virB mutant replication without affecting WT B. abortus. These results suggest that the T4SS mediates the evasion of a natural antibody-dependent immune clearance function by B. abortus during persistence in vivo.     

Comparative and Prospective Study of Different Immune Parameters in Healthy Subjects at Risk for Tuberculosis and in Tuberculosis Patients

It has not been fully elucidated which of the components of the immune response against Mycobacterium tuberculosis is indicative of resistance or susceptibility. The aim of this study was to identify an immune parameter that could be indicative of either resistance or susceptibility to M. tuberculosis infection. We prospectively studied (three determinations, at months 0, 8, and 12) 15 patients with chronic pulmonary tuberculosis and 42 healthy individuals with a recent and frequent contact with tuberculosis patients. Peripheral blood mononuclear cells were stimulated with a whole-protein extract or the 30-kDa antigen of M. tuberculosis for 6 days, and several immune parameters were determined. No consistent differences between tuberculosis patients and healthy controls were detected in most immune parameters studied, including the expression of different activation antigens, cytokine secretion, lymphocyte proliferation, and nitric oxide production. However, the synthesis of tumor necrosis factor alpha, the intracellular detection of gamma interferon, and the apoptosis of monocytes under certain culture conditions tended to show clear-cut differences in cells from patients and controls (P < 0.05 in all cases for most determinations). Nevertheless, when results were analyzed on an individual basis, it was evident that a significant degree of overlapping of values from patients and controls occurred for all parameters studied. We conclude that although the immune parameters tested do not allow the identification of individuals susceptible to M. tuberculosis, the specificity and sensitivity of some of them could be improved through future studies.