Surgical denervation of ocular sympathetic afferents decreases local transforming growth factor-beta and abolishes immune privilege.

Mounting evidence points to a role for the sympathetic nervous system in suppressing inflammation. This role might be of specific relevance for immune privilege in the eye, where, sporadically, patients with denervated sympathetic fibers develop chronic inflammation. The present study used mice to investigate whether the robust innervation of intraocular structures by the sympathetic system plays a role in maintaining ocular immune privilege.

[Primary adrenal insufficiency as the form of onset of adrenoleukodystrophy in a 4-year-old boy].

X-linked adrenoleukodystrophy is an inherited metabolic disease caused by the accumulation of saturated very long chain fatty acids (VLCFA). Given that the form of presentation can be primary adrenal insufficiency, diagnosis in affected males is important. Patient was a 4-year-old boy with attention deficit hyperactivity disorder, cutaneous-mucosal hyperpigmentation, and dehydration with hyponatremia and hyperpotassemia was diagnosed with adrenoleukodystrophy presenting as primary adrenal insufficiency.

Equilibrative nucleoside transporters in fetal endothelial dysfunction in diabetes mellitus and hyperglycaemia.

Diabetes mellitus types 1 and 2, and gestational diabetes are characterized by abnormal D-glucose metabolism and hyperglycaemia, and induce foetal endothelial dysfunction with implications in adult life increasing the risk of vascular diseases. Synthesis of nitric oxide (NO) and uptake of L-arginine (i.e.

TGF-beta1 inhibits expression and activity of hENT1 in a nitric oxide-dependent manner in human umbilical vein endothelium.

Aims: We studied whether transforming growth factor beta1 (TGF-beta1) modulates human equilibrative nucleoside transporters 1 (hENT1) expression and activity in human umbilical vein endothelial cells (HUVECs). hENT1-mediated adenosine transport and expression are reduced in gestational diabetes and hyperglycaemia, conditions associated with increased synthesis and release of nitric oxide (NO) and TGF-beta1 in this cell type. TGF-beta1 increases NO synthesis via activation of TGF-beta receptor type II (TbetaRII), and NO inhibits hENT1 expression and activity in HUVECs.

Deficiency of thrombospondin-1 reduces Th17 differentiation and attenuates experimental autoimmune encephalomyelitis.

Transforming growth factor beta (TGF-beta) plays a role both in the induction of Treg and in the differentiation of the IL-17-secreting T cells (Th17) which drive inflammation in experimental autoimmune encephalomyelitis (EAE). We investigated the role that thrombospondin-1 (TSP-1) dependent activation of TGF-beta played in the generation of an encephalitic Th17 response in EAE. Upon immunization with myelin oligodendrocyte glycoprotein peptide (MOG(35-55)), TSP-1 deficient (TSP-1(null)) mice and MOG(35-55) TCR transgenic mice that lack of TSP-1 (2D2 x TSP-1(null)) exhibited an attenuated form of EAE, and secreted lower levels of IL-17.

The Meissner and Pacinian sensory corpuscles revisited new data from the last decade.

This article reviews the biochemical, physiological, and experimental data cumulated during the last decade on the Meissner and Pacinian corpuscles. It includes information about (i) the localization of molecules recently detected in sensory corpuscles; (ii) the unsolved problem of the accessory fibers in sensory corpuscles and the occurrence of myelin within them; (iii) the development of sensory corpuscles, especially their neuronal and growth factor dependency; (iv) the composition and functional significance of the extracellular matrix as an essential part of the mechanisms involved in the genesis of the stimuli generated in sensory corpuscles; (v) the molecular basis of mechanotransduction; (vi) a miscellaneous section containing sparse new data on the protein composition of sensory corpuscles, as well as in the proteins involved in live-death cell decisions; (vii) the changes in sensory corpuscles as a consequence of aging, the central, or peripheral nervous system injury; and finally, (viii) the special interest of Meissner corpuscles and Pacinian corpuscles for pathologists for the diagnosis of some peripheral neuropathies and neurodegenerative diseases.

[Assessment of the simplified versions of the Asthma Control Questionnaire].

Background And Objective: The aim of this study was to assess the measurement properties of the Spanish version of Asthma Control Questionnaire (ACQ) when FEV1 item in the original version (ACQ-FEV1) is substituted by peak expiratory flow rate (ACQ-PEF) and when the lung function item is omitted (ACQ-wLF).

Material And Method: and 607 patients were enrolled in this study. Three study visits were carried out: at baseline, 2, and 6 weeks later.

A nasal proteosome adjuvant activates microglia and prevents amyloid deposition.

Objective: We assessed whether peripheral activation of microglia by a nasal proteosome-based adjuvant (Protollin) that has been given safely to humans can prevent amyloid deposition in young mice and affect amyloid deposition and memory function in old mice with a large amyloid load.

Methods: Amyloid precursor protein (APP) transgenic (Tg) J20 mice received nasal treatment with Protollin weekly for 8 months beginning at age 5 months. Twenty-four-month-old J20 mice were treated weekly for 6 weeks.

Cytogenetic damage induced by radiotherapy. Evaluation of protection by amifostine and analysis of chromosome aberrations persistence.

Purpose: To evaluate the cytogenetic damage induced by radiotherapy, the effect of concomitant amifostine and the persistence of translocations and dicentrics after the treatment.

Materials And Methods: Blood samples from 16 head and neck cancer patients were obtained at different times, just before treatment, at the 1st and 22nd sessions, at the end of radiotherapy, and one, four and 12 months later. Solid stain and fluorescent in situ hybridization (FISH) techniques were applied to analyse chromosome aberrations.

Obtaining the intrinsic electron spectrum of linear accelerators using the relation between the current of the bending magnet and the absorbed dose in water.

Purpose: To present a novel methodology to model the intrinsic electron spectra of a linear accelerator and its situation with respect to the energy window.

Methods: The spectra are obtained by fitting the variation of R(50) and the maximum dose rate measured in a water phantom with the bending magnet current. The obtained spectra are verified with a realistic Monte Carlo simulation of the accelerator.

Potential energy surfaces and Jahn-Teller effect on CH4...NO complexes.

The potential energy surface of the CH(4)...

Anaplastic lymphoma kinase is activated through the pleiotrophin/receptor protein-tyrosine phosphatase beta/zeta signaling pathway: an alternative mechanism of receptor tyrosine kinase activation.

Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase (RTK) first discovered as the constitutively active nucleophosmin-ALK oncoprotein in anaplastic large cell lymphomas (ALCL). Full-length ALK has a critical role in normal development and differentiation. Activated full-length ALK also is found in different malignant cancers.

Myths and misconceptions of Wernicke's encephalopathy: what every emergency physician should know.

First described in 1881, Wernicke's encephalopathy continues to be an unrecognized and often misunderstood disease. The cause of Wernicke's encephalopathy is thiamine deficiency as a result of any nutritionally deficient state, though many physicians erroneously consider this disease to be confined only to alcoholics. Unfortunately, the syndrome is most often recognized only on autopsy, especially among nonalcoholics.

Differential distribution of S100 protein and calretinin in mechanosensory and chemosensory cells of adult zebrafish (Danio rerio).

Calcium-binding proteins play a critical role in vertebrate sensory cells, and some of them have been detected in mechanosensory and chemosensory cells of bony and cartilaginous fishes. In this study immunohistochemistry and Western blot were used to investigate the occurrence and the distribution of S100 protein and calretinin in mechanosensory (neuromasts of the lateral line system; maculae and cristae ampullaris of the inner ear) as well as chemosensory (superficial and oral taste buds; olfactory epithelium) cells in adult zebrafish (Danio rerio). Specific protein bands with an estimated molecular weight of around 10 kDa and 30 kDa were detected by Western blot and were identified with S100 protein and calretinin, respectively.

Role of thrombospondin-1 in T cell response to ocular pigment epithelial cells.

Ocular pigment epithelium (PE) cells promote the generation of T regulators (PE-induced Treg cells). Moreover, T cells exposed to PE acquire the capacity to suppress the activation of bystander T cells via TGFbeta. Membrane-bound TGFbeta on iris PE cells interacts with TGFbeta receptors on T cells, leading to the conversion of T cells to CD8(+) Treg cells via a cell contact-dependent mechanism.

D-glucose stimulation of L-arginine transport and nitric oxide synthesis results from activation of mitogen-activated protein kinases p42/44 and Smad2 requiring functional type II TGF-beta receptors in human umbilical vein endothelium.

Elevated extracellular D-glucose increases transforming growth factor beta1 (TGF-beta1) release from human umbilical vein endothelium (HUVEC). TGF-beta1, via TGF-beta receptors I (TbetaRI) and TbetaRII, activates Smad2 and mitogen-activated protein kinases p44 and p42 (p42/44(mapk)). We studied whether D-glucose-stimulation of L-arginine transport and nitric oxide synthesis involves TGF-beta1 in primary cultures of HUVEC.

Subphthalocyanine-fused dimers and trimers: synthetic, electrochemical, and theoretical studies.

Subphthalocyanine (SubPc)-fused dimers and trimers bearing fluorine, iodine, and thioether peripheral substituents were synthesized and characterized. Absorption spectroscopy and electrochemical studies revealed (i) that the substituents have a strong effect on the electronic properties of the macrocycles and (ii) that there is good communication between the subphthalocyaninic moieties within the oligomeric structures. Theoretical calculations at DFT/6-31G(d,p) computational level and electron density studies support the experimental findings.

Expression of TrkB in the murine kidney.

Neurotrophins acting through Trk signal-transducing receptors play essential roles in the nervous system, and probably in some nonneuronal tissues. In the present study we used Western-blot and immunohistochemistry to investigate the occurrence and cellular localization of TrkB in the mouse kidney. Furthermore, the structure and ultrastructure of the kidney in mice carrying a mutation in the trkB gene were analyzed.

Sodium chloride regulates Extracellular Regulated Kinase 1/2 in different tumor cell lines.

Perturbations of the extracellular ionic content by different hypo- or hyperosmolar stimuli initiate stress responses to maintain cell viability that include activation of Mitogen Activated Protein Kinases (MAPK) in cell lines derived from kidney epithelium. When hyperosmolar conditions induced by different salts occurred in the extracellular environment of tumor-derived cell lines, they activated the Extracellular Regulated Kinase 1/2 by increasing its phosphorylation steady-state on Thr202/Tyr204 in a time- and dose-dependent manner. It was found that Extracellular Regulated Kinase 1/2 activation is a consequence of selective phosphorylation by mitogen-activated protein kinase/ERK kinase.

Hypertonicity activates GSK3beta in tumor cells.

Responses to perturbations in the composition of the extracellular environment are crucial to maintain cell and tissue homeostasis. In hypertonic conditions cell lines derived from kidney epithelium initiate a variety of stress responses to maintain cell viability that include activation of Mitogen Activated Protein Kinases (MAPK). We previously showed that NaCl also regulates MAPK in different tumor cell lines and we now show that when hypertonic conditions induced with NaCl and other osmolytes were used to stimulate several tumor cell lines, Glycogen Synthase Kinase 3beta (GSK3beta) was rapidly dephosphorylated at serine 9 and its kinase activity was increased.

Metabolism and disposition of a potent and selective GABA-Aalpha2/3 receptor agonist in healthy male volunteers.

[14C]7-(1,1-Dimethylethyl)-6-(2-ethyl-2H-1,2,4-triazol-3-ylmethoxy)-3-(2-fluorophenyl)-1,2,4-triazolo[4,3-b]pyridazine ([14C]-TPA023; 99 microCi/dose) was administered to five young, healthy, fasted male subjects as a single oral dose (3.0 mg) in solution (propylene glycol/water, 10:90 v/v). The parent compound was rapidly absorbed (plasma Tmax approximately 2 h), exhibited an apparent terminal half-life of 6.

Non-Markovian stochastic resonance: three-state model of ion channel gating.

Stochastic resonance in single voltage-dependent ion channels is investigated within a three-state non-Markovian modeling of the ion channel conformational dynamics. In contrast to a two-state description one assumes the presence of an additional closed state for the ion channel which mimics the manifold of voltage-independent closed subconformations (inactivated "state"). The conformational transition into the open state occurs through a domain of voltage-dependent closed subconformations (closed "state").

Accelerated ageing in mice deficient in Zmpste24 protease is linked to p53 signalling activation.

Zmpste24 (also called FACE-1) is a metalloproteinase involved in the maturation of lamin A (Lmna), an essential component of the nuclear envelope. Both Zmpste24- and Lmna-deficient mice exhibit profound nuclear architecture abnormalities and multiple histopathological defects that phenocopy an accelerated ageing process. Similarly, diverse human progeroid syndromes are caused by mutations in ZMPSTE24 or LMNA genes.

Effect of efavirenz on the pharmacokinetics of simvastatin, atorvastatin, and pravastatin: results of AIDS Clinical Trials Group 5108 Study.

Efavirenz (EFV) is associated with hyperlipidemia when used in combination with other antiretroviral drugs. EFV is a mixed inducer/inhibitor of cytochrome P450 (CYP) 3A4 isozyme and may interact with hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors that are primarily metabolized via CYP3A4. To assess the drug-drug interaction of EFV used in combination with simvastatin (SIM), atorvastatin (ATR), or pravastatin (PRA), an open-label trial was conducted in 52 healthy adult HIV-seronegative subjects across AIDS Clinical Trials Group sites in the United States.