Tumor fibroso solitario del paladar blando

The solid fibrous solitary tumour of the oral cavity is an extremely rare entity. It is also of complicated diagnosis because of its extensive morphologic diversity (especially when there is a small amount of biopsied tissue) and because of its similarity to many mesenchymal injuries, mostly with hemangiopericytoma. The prognosis is reserved because of the few cases reported, mainly depending on tumour location and size.     

Safety and feasibility of carotid revascularization in patients with cerebral embolic strokes associated with carotid webs and histopathology revisited

IntroductionCarotid web is increasingly recognized as the cause of ischemic embolic strokes in younger patients. The best way to treat carotid web is debatable and carotid artery stenting (CAS) has been reported as a treatment for the carotid web in only a few case series. In this study we evaluate the safety and feasibility of CAS in symptomatic carotid webs and examined the histopathology of a carotid web.Materials and methodsAt our institution between 2017 and 2019, 10 consecutive patients with symptomatic carotid webs were treated. We retrospectively analyzed the data for patient demographics, clinical presentation, imaging, treatment methodology and follow up.ResultsAll the patients had presented with ipsilateral embolic stroke. The mean age at presentation was 50 years (range 37–71) with seven female and three male patients. All patients underwent CAS except one patient who underwent carotid endarterectomy (CEA). In one stented patient, there was significant hypotension in the post-procedural period lasting a week. The patients were followed for a mean of 5.5 months (range one day-12 months). No recurrent stroke or transient ischemic attack (TIA) occurred. Surgical pathological studies confirmed fibromuscular dysplasia in one specimen.ConclusionIn our experience CAS for carotid web is feasible and safe in patients presenting with ischemic embolic strokes.     

Choroidal tubercles with tuberculous meningitis

We found choroidal tubercles in two children with meningitis. This finding supposed an important clue in establishing a tuberculous etiology. Following, we discuss the evolution and fluorescein angiographie findings of choroidal tubercles. As many authors have remarked, a thorough fundus examination is of great value in cases of fever of undetermined origin and meningitis. Choroidal tubercles can also be the first sign of a common pulmonary or extrapulmonary tuberculosis.     

Zac1 is up-regulated in neural cells of the limbic system of mouse brain following seizures that provoke strong cell activation

Zac1, a new zinc-finger protein that regulates both apoptosis and cell cycle arrest, is abundantly expressed in many proliferative/differentiation areas during brain development. In the present work, we studied Zac1 gene expression and protein in experimental seizure models following i.p. injection of pentylenetetrazole (PTZ) or kainic acid (KA). Following KA treatment, an early and intense up-regulation of Zac1 is detected in the limbic areas, such as the hippocampus, cortex and amygdaloid and hypothalamic nuclei. Pre-treatment with MK-801, an antagonist of the NMDA receptors, fully blocks the effect of KA in the hippocampus, whereas it only attenuates KA-induced Zac1 up-regulation in the other areas of the limbic system. A reduced induction is obtained with PTZ-treated animals, specifically in the entorhinal and piriform cortices as well as in amygdaloid and hypothalamic nuclei. Thus, Zac1 is highly induced in the seizure models that generate strong neuronal stimulation and/or extensive cell damage (cell death), reinforcing its putative role in the control of the cell cycle and/or apoptosis. Moreover, strong induction is observed in the granular cells of the dentate gyrus (which are resistant to neurodegeneration) and in some glial cells of the dentate gyrus and subventricular zone, suggesting that Zac1 may be implicated in the mechanisms of neural plasticity following injury.     

The outer membranes of Brucella spp. are resistant to bactericidal cationic peptides.

The actions of polymyxin B, rabbit polymorphonuclear lysosome extracts, 14 polycationic peptides (including defensin NP-2, cecropin P1, lactoferricin B, and active peptides from cationic protein 18 and bactenecin), EDTA, and Tris on Brucella spp. were studied, with other gram-negative bacteria as controls. Brucella spp. were comparatively resistant to all of the agents listed above and bound less polymyxin B, and their outer membranes (OMs) were neither morphologically altered nor permeabilized to lysozyme by polymyxin B concentrations, although both effects were observed for controls. EDTA and peptides increased or accelerated the partition of the hydrophobic probe N-phenyl-naphthylamine into Escherichia coli and Haemophilus influenzae OMs but had no effect on Brucella OMs. Since Brucella and H. influenzae OMs are permeable to hydrophobic compounds (G. Martínez de Tejada and I. Moriyón, J. Bacteriol. 175:5273-5275, 1993), the results show that such unusual permeability is not necessarily related to resistance to polycations. Although rough (R) B. abortus and B. ovis were more resistant than the controls were, there were qualitative and quantitative differences with smooth (S) brucellae; this may explain known host range and virulence differences. Brucella S-lipopolysaccharides (LPSs) had reduced affinities for polycations, and insertion of Brucella and Salmonella montevideo S-LPSs into the OM of a Brucella R-LPS mutant increased and decreased, respectively, its resistance to cationic peptides. The results show that the core lipid A of Brucella LPS plays a major role in polycation resistance and that O-chain density also contributes significantly. It is proposed that the features described above contribute to Brucella resistance to the oxygen-independent systems of phagocytes.     

Sigma-1 receptor inhibition reverses acute inflammatory hyperalgesia in mice: role of peripheral sigma-1 receptors

Rationale

Sigma-1 (σ₁) receptor inhibition ameliorates neuropathic pain by inhibiting central sensitization. However, it is unknown whether σ₁ receptor inhibition also decreases inflammatory hyperalgesia, or whether peripheral σ₁ receptors are involved in this process.

Objective

The purpose of this study was to determine the role of σ₁ receptors in carrageenan-induced inflammatory hyperalgesia, particularly at the inflammation site.

Results

The subcutaneous (s.c.) administration of the selective σ₁ antagonists BD-1063 and S1RA to wild-type mice dose-dependently and fully reversed inflammatory mechanical (paw pressure) and thermal (radiant heat) hyperalgesia. These antihyperalgesic effects were abolished by the s.c. administration of the σ₁ agonist PRE-084 and also by the intraplantar (i.pl.) administration of this compound in the inflamed paw, suggesting that blockade of peripheral σ₁ receptors in the inflamed site is involved in the antihyperalgesic effects induced by σ₁ antagonists. In fact, the i.pl. administration of σ₁ antagonists in the inflamed paw (but not in the contralateral paw) was sufficient to completely reverse inflammatory hyperalgesia. σ₁ knockout (σ₁-KO) mice did not develop mechanical hyperalgesia but developed thermal hypersensitivity; however, the s.c. administration of BD-1063 or S1RA had no effect on thermal hyperalgesia in σ₁-KO mice, supporting on-target mechanisms for the effects of both drugs. The antiedematous effects of σ₁ inhibition do not account for the decreased hyperalgesia, since carrageenan-induced edema was unaffected by σ₁ knockout or systemic σ₁ pharmacological antagonism.

Conclusions

σ₁ receptors play a major role in inflammatory hyperalgesia. Targeting σ₁ receptors in the inflamed tissue may be useful for the treatment of inflammatory pain.     

Inhibition of human leukemia in an animal model with human antibodies directed against vascular endothelial growth factor receptor 2. Correlation between antibody affinity and biological activity.

Vascular endothelial growth factor (VEGF) and its receptors (VEGFR) have been implicated in promoting solid tumor growth and metastasis via stimulating tumor-associated angiogenesis. We recently showed that certain 'liquid' tumors such as leukemia not only produce VEGF, but also express functional VEGFR, resulting in an autocrine loop for tumor growth and propagation. A chimeric anti-VEGFR2 (or kinase insert domain-containing receptor, KDR) antibody, IMC-1C11, was shown to be able to inhibit VEGF-induced proliferation of human leukemia cells in vitro, and to prolong survival of nonobese diabetic-severe combined immune deficient (NOD-SCID) mice inoculated with human leukemia cells. Here we produced two fully human anti-KDR antibodies (IgG1), IMC-2C6 and IMC-1121, from Fab fragments originally isolated from a large antibody phage display library. These antibodies bind specifically to KDR with high affinities: 50 and 200 pM for IMC-1121 and IMC-2C6, respectively, as compared to 270 pM for IMC-1C11. Like IMC-1C11, both human antibodies block VEGF/KDR interaction with an IC(50) of approximately 1 nM, but IMC-1121 is a more potent inhibitor to VEGF-stimulated proliferation of human endothelial cells. These anti-KDR antibodies strongly inhibited VEGF-induced migration of human leukemia cells in vitro, and when administered in vivo, significantly prolonged survival of NOD-SCID mice inoculated with human leukemia cells. It is noteworthy that the mice treated with antibody of the highest affinity, IMC-1121, survived the longest period of time, followed by mice treated with IMC-2C6 and IMC-1C11. Taken together, our data suggest that anti-KDR antibodies may have broad applications in the treatment of both solid tumors and leukemia. It further underscores the efforts to identify antibodies of high affinity for enhanced antiangiogenic and antitumor activities.     

The average cumulative risks of breast and ovarian cancer for carriers of mutations in BRCA1 and BRCA2 attending genetic counseling units in Spain.

PURPOSE: It is not clear that the published estimates of the breast and ovarian cancer penetrances of mutations in BRCA1 and BRCA2 can be used in genetic counseling in countries such as Spain, where the incidence of breast cancer in the general population is considerably lower, the prevalence of BRCA2 mutations seems to be higher, and a distinct spectrum of recurrent mutations exists for both genes. We aimed to estimate these penetrances for women attending genetic counseling units in Spain. EXPERIMENTAL DESIGN: We collected phenotype and genotype data on 155 BRCA1 and 164 BRCA2 mutation carrier families from 12 centers across the country. Average age-specific cumulative risks of breast cancer and ovarian cancer were estimated using a modified segregation analysis method. RESULTS: The estimated average cumulative risk of breast cancer to age 70 years was estimated to be 52% [95% confidence interval (95% CI), 26-69%] for BRCA1 mutation carriers and 47% (95% CI, 29-60%) for BRCA2 mutation carriers. The corresponding estimates for ovarian cancer were 22% (95% CI, 0-40%) and 18% (95% CI, 0-35%), respectively. There was some evidence (two-sided P = 0.09) that 330A>G (R71G) in BRCA1 may have lower breast cancer penetrance. CONCLUSIONS: These results are consistent with those from a recent meta-analysis of practically all previous penetrance studies, suggesting that women with BRCA1 and BRCA2 mutations attending genetic counseling services in Spain have similar risks of breast and ovarian cancer to those published for other Caucasian populations. Carriers should be fully informed of their mutation- and age-specific risks to make appropriate decisions regarding prophylactic interventions such as oophorectomy.