Understanding systemic lupus erythematosus physiopathology in the light of primary immunodeficiencies

Introduction Associations between systemic lupus erythematosus (SLE) and primary immunodeficiencies (PIDs) were analyzed to gain insight into the physiopathology of SLE. Some PIDs have been consistently associated with SLE or lupus-like manifestations: (a) homozygous deficiencies of the early components of the classical complement pathway in the following decreasing order: in C1q, 93% of affected patients developed SLE; in C4, 75%; in C1r/s, 57%; and in C2, up to 25%; (b) female carriers of X-linked chronic granulomatous disease allele; and (c) IgA deficiency, present in around 5% of juvenile SLE. Discussion In the first two groups, disturbances of cellular waste-disposal have been proposed as the main mechanisms of pathogenesis. On the other hand and very interestingly, there are PIDs systematically associated with several autoimmune manifestations in which SLE has not been described, such as autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED), immunedys-regulation polyendocrinopathy enteropathy X-linked (IPEX), and autoinumme lymphoproliferative syndrome (ALPS), suggesting that mechanisms considered as critical players for induction and maintenance of tolerance to autoantigens, such as (1) AME-mediated thymic negative selection of lymphocytes, (2) Foxp3+ regulatory T cell-mediated peripheral tolerance, and (3) deletion of auto-reactive lymphocytes by Fas-mediated apoptosis, could not be relevant in SLE physiopathology. The non-description of SLE and neither the most characteristic SLE clinical features among patients with agammaglobulinemia are also interesting observations, which reinforce the essential role of B lymphocytes and antibodies for SLE pathogenesis. Conclusion Therefore, monogenic PIDs represent unique and not fully explored human models for unraveling components of the conundrum represented by the physiopathology of SLE, a prototypical polygenic disease.

Leukocytoclastic vasculitis: another condition that mimics syphilis

Syphilis, a disease that in the past was associated with significant morbidity and lethality rates, has resurged in recent years principally as a consequence of changes in risk behavior. An epidemiological group that is commonly affected is the HIV-infected population. The characteristics of the disease and its progression may differ in these patients. The present report describes a case of an HIV-positive male patient, who developed florid secondary syphilis: in addition to syphilitic roseola, he also presented with bilateral panuveitis and involvement of the central nervous system. Investigation revealed the prozone phenomenon and histological examination of the skin lesions showed the presence of leukocytoclastic vasculitis. This finding is extremely rare and few cases have been documented.

Study of the discovery potential of light custodians in a clean decay channel at the LHC

Models of warped extra dimensions with custodial symmetry usually predict the existence of a light Kaluza-Klein fermion arising as a partner of the right-handed top quark, sometimes called light custodians which we will denote (b) over tilde (R). The production of these particles at the LHC can give rise to multi-W events which could be observed in same-sign dilepton channels, but its mass reconstruction is challenging. In this paper we study the possibility of finding a signal for the pair production of this new particle at the LHC focusing on a rarer, but cleaner decay mode of a light custodian into a Z boson and a b-quark. In this mode it would be possible to reconstruct the light custodian mass. In addition to the dominant standard model QCD production processes, we include the contribution of a Kaluza-Klein gluon first mode. We find that (b) over tilde (R) stands out from the background as a peak in the bZ invariant mass. However, when taking into account only the electronic and muonic decay modes of the Z boson and b-tagging efficiencies, the LHC will have access only to the very light range of masses, m((b) over tilde) = O(500) GeV.

Additional sensory information reduces body sway of individuals with anterior cruciate ligament injury

The purpose of this study was to investigate whether the additional sensory information could improve postural control in individuals with unilateral anterior cruciate ligament (ACL) injury. Twenty-eight individuals with unilateral ACL injury (mean age 23.6, 26 males, 2 females) and 28 healthy young control subjects (mean age 22.1 years, 26 males, 2 females) participated in this study. Postural control was evaluated with subjects single-leg standing on a force platform with eyes closed under two sensory conditions: normal sensory information and light touch to a stationary bar (applied force below 1 N). Three trials of 30 5 were performed in each single-leg stance and in each sensory condition. Mean sway amplitude and predominant frequency of center of pressure were calculated for both anterior-posterior and medial-lateral directions. Individuals with ACL injury showed greater mean sway amplitude than healthy control individuals even though the predominant frequency was similar for both groups. Additional sensory information improved postural control performance in individuals with ACL injury and healthy control, with a greater effect observed for the ACL group. Based on these results, we suggest that reduction in postural control performance in individuals with ACL injury would be due to the reduction of sensory information provided by the ACL, but when sensory information is enhanced, postural control performance improves. These results have implications for novel approaches to improve stability in individuals with ACL injury. (c) 2008 Elsevier Ireland Ltd. All rights reserved.

The ""single-section"" Golgi method adapted for formalin-fixed human brain and light microscopy

The Golgi method has been used for over a century to describe the general morphology of neurons in the nervous system of different species. The ""single-section"" Golgi method of Gabbott and Somogyi (1984) and the modifications made by Izzo et al. (1987) are able to produce consistent results. Here, we describe procedures to show cortical and subcortical neurons of human brains immersed in formalin for months or even years. The tissue was sliced with a vibratome, post-fixed in a combination of paraformaldehyde and picric acid in phosphate buffer, followed by osmium tetroxide and potassium dicromate, ""sandwiched"" between cover slips, and immersed in silver nitrate. The whole procedure takes between 5 and 11 days to achieve good results. The Golgi method has its characteristic pitfalls but, with this procedure, neurons and glia appear well-impregnated, allowing qualitative and quantitative studies under light microscopy. This contribution adds to the basic techniques for the study of human nervous tissue with the same advantages described for the ""single-section"" Golgi method in other species; it is easy and fast, requires minimal equipment, and provides consistent results. (C) 2010 Elsevier B.V. All rights reserved.

Plasma hormonal profiles and dendritic spine density and morphology in the hippocampal CA1 stratum radiatum, evidenced by light microscopy, of virgin and postpartum female rats

Successful reproduction requires that changes in plasma follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), oxytocin (OT), estrogen (E-2) and progesterone (P-4) occur together with the display of maternal behaviors. Ovarian steroids and environmental stimuli can affect the dendritic spines in the rat hippocampus. Here, studying Wistar rats, it is described: (a) the sequential and concomitant changes in the hormonal profile of females at postpartum days (PP) 4, 8, 12, 16, 20 and 24, comparing to estrous cycle referential values; (b) the dendritic spine density in the stratum radiatum of CA1 (CA1-SR) Golgi-impregnated neurons in virgin females across the estrous cycle and in multiparous age-matched ones; and (c) the proportion of different types of spines in the CAI-SR of virgin and postpartum females, both in diestrus. Plasma levels of gonadotrophins and ovarian hormones remained low along PP while LH increased and PRL decreased near the end of the lactating period. The lowest dendritic spine density was found in virgin females in estrus when compared to diestrus and proestrus phases or to postpartum females in diestrus (p < 0.03). Other comparisons among groups were not statistically significant (p > 0.4). There were no differences in the proportions of the different spine types in nulliparous and postpartum females (p > 0.2). Results suggest that medium layer CA1-SR spines undergo rapid modifications in Wistar females across the estrous cycle (not quite comparable to Sprague-Dawley data or to hormonal substitutive therapy following ovariectomy), but persistent effects of motherhood on dendritic spine density and morphology were not found in this area. (c) 2008 Elsevier Ireland Ltd. All rights reserved.

Dorsal cutaneous branch of the ulnar nerve: a light and electron microscopy histometric study

This study describes the normal morphology and morphometry of the dorsal cutaneous branch of the ulnar nerve (DCBU) in humans. Fourteen nerves of eight donors were prepared by conventional techniques for paraffin and epoxy resin embedding. Semiautomatic morphometric analysis was performed by means of specific computer software. Histograms of the myelinated and unmyelinated fiber population and the G-ratio distribution of fibers were plotted. Myelinated fiber density per nerve varied from 5,910 to 10,166 fibers/mm(2), with an average of 8,170 +/- 393 fibers/mm(2). The distribution was bimodal with peaks at 4.0 and 9.5 mu m. Unmyelinated fiber density per nerve varied from 50,985 to 127,108, with an average of 78,474 +/- 6, 610 fibers/mm(2), with a unimodal distribution displaying a peak at 0.8 mu m. This study thus adds information about the fascicles and myelinated and unmyelinated fibers of DCBU nerves in normal people, which may be useful in further studies concerning ulnar nerve neuropathies, mainly leprosy neuropathy.

Evaluation of erythrocyte dysmorphism by light microscopy with lowering of the condenser lens: A simple and efficient method

Aim: To demonstrate that the evaluation of erythrocyte dysmorphism by light microscopy with lowering of the condenser lens (LMLC) is useful to identify patients with a haematuria of glomerular or non-glomerular origin. Methods: A comparative double-blind study between phase contrast microscopy (PCM) and LMLC is reported to evaluate the efficacy of these techniques. Urine samples of 39 patients followed up for 9 months were analyzed, and classified as glomerular and non-glomerular haematuria. The different microscopic techniques were compared using receiver-operator curve (ROC) analysis and area under curve (AUC). Reproducibility was assessed by coefficient of variation (CV). Results: Specific cut-offs were set for each method according to their best rate of specificity and sensitivity as follows: 30% for phase contrast microscopy and 40% for standard LMLC, reaching in the first method the rate of 95% and 100% of sensitivity and specificity, respectively, and in the second method the rate of 90% and 100% of sensitivity and specificity, respectively. In ROC analysis, AUC for PCM was 0.99 and AUC for LMLC was 0.96. The CV was very similar in glomerular haematuria group for PCM (35%) and LMLC (35.3%). Conclusion: LMLC proved to be effective in contributing to the direction of investigation of haematuria, toward the nephrological or urological side. This method can substitute PCM when this equipment is not available.

The melatonin action on stromal stem cells within pericryptal area in colon cancer model under constant light

Constant light (LL) is associated with high incidence of colon cancer. MLT supplementation was related to the significant control of preneoplastic patterns. We sought to analyze preneoplastic patterns in colon tissue from animals exposed to LL environment (14 days; 300 lx), MLT-supplementation (10 mg/kg/day) and DMH-treatment (1,2 dimethylhydrazine; 125 mg/kg). Rodents were sacrificed and MLT serum levels were measured by radioimmunoassay. Our results indicated that LL induced ACF development (p < 0.001) with a great potential to increase the number of CD133(+) and CD68(+) cells (p < 0.05 and p < 0.001). LL also increased the proliferative process (PCNA-Li; p < 0.001) as well as decreased caspase-3 protein (p < 0.001), related to higher COX-2 protein expression (p < 0.001) within pericryptal colonic stroma (PCCS). However, MLT-supplementation controlled the development of dysplastic ACF (p < 0.001) diminishing preneoplastic patterns into PCCS as CD133 and CD68 (p < 0.05 and p < 0.001). These events were relative to decreased PCNA-Li index and higher expression of caspase-3 protein. Thus, MLT showed a great potential to control the preneoplastic patterns induced by LL. (C) 2011 Elsevier Inc. All rights reserved.

Effects of intrapulpal temperature change induced by visible light units on the metabolism of odontoblast-like cells

Purpose: To investigate the effects of intrapulpal temperature changes induced by a quartz tungsten halogen (QTH) and a light emitting diode (LED) curing units on the metabolism of odontoblast-like cells. Methods: Thirty-six 0.5 mm-thick dentin discs obtained from sound human teeth were randomly assigned into three groups: QTH, LED and no light (control). After placement of the dentin discs in pulp chamber devices, a thermistor was attached to the pulpal surface of each disc and the light sources were applied on the occlusal surface. After registering the temperature change, odontoblast-like cells MDPC-23 were seeded on the pulpal side of the discs and the curing lights were again applied. Cell metabolism was evaluated by the MTT assay and cell morphology was assessed by SEM. Results: In groups QTH and LED the intrapulpal temperature increased by 6.4 degrees C and 3.4 degrees C, respectively. The difference between both groups was statistically significant (Mann-Whitney; P< 0.05). QTH and LED reduced the cell metabolism by 36.4% and 33.4%, respectively. Regarding the cell metabolism, no statistically significant difference was observed between both groups (Mann-Whitney; P> 0.05). However, when compared to the control, only QTH significantly reduced the cell metabolism (Mann-Whitney; P< 0.05). It was concluded that the irradiance of 0.5 mm-thick human dentin discs with a QTH in comparison to a LED curing unit promoted a higher temperature rise, which propagates through the dentin negatively affecting the metabolism of the underlying cultured pulp cells. (Am J Dent 2009;22:151-156).

Characteristics of Filiform, Fungiform and Vallate Papillae and Surface of Interface Epithelium-Connective Tissue of the Maned Sloth Tongue Mucosa (Bradypus torquatus, Iliger, 1811): Light and Scanning Electron Microscopy Study

The study of lingual surfaces and the surface of interface epithelium-connective tissue of the tongue of Bradypus torquatus was performed by employing the light and scanning electron microscopy (SEM) techniques. The results revealed that the rostral part of the tongue presents a round apex and covered by filiform and fungiform lingual papillae and a ventral smooth surface. It was observed that the epithelial layer of the dorsal surface possesses the basal, spinosum, granular and cornified epithelial cells. The lamina propria is characterized by a dense connective tissue forming the long, short and round papillae. Numerous typical filiform papillae are located especially in the rostral part intermingled for few fungiform papillae, which were revealed in three-dimensional SEM images. Usually, the fungiform papillae are located in the border of rostral apex of the tongue exhibiting the rounded form. They are covered by keratinized epithelial cells. In the fungiform papillae, several taste pores were observed on the surface. The vallate papillae presented numerous taste buds in the wall of epithelial cells, being that the major number of taste buds is located on the superior half of vallate papilla. The taste pores are surrounded by several laminae of keratinized epithelial cells. The samples treated with NaOH solution and examined by SEM revealed, after removal of the epithelial layer, the dense connective core in original disposition, presenting different sizes and shapes. The specimens stained with Picrosirius and examined by polarized light microscopy revealed the connective tissue, indicating the collagen fibres type I and type III.

Light and scanning electron microcopy study of the tongue in Rhea americana

Morphological characteristics of the tongue were studied in adult rhea (Rhea americana). The lingual surface and the surface of epithelium-connective tissue interface of rhea tongue were examined macroscopically and by light and scanning electron microscopy. The rhea tongue revealed a triangular aspect, without adjustment of the inferior bill formation, occupying approximately of the length of the oral cavity. Lingual papilla-like structures were not observed over the lingual surface. The tongue mucosa was composed of a thick non-keratinized stratified squamous epithelium in the dorsal and ventral part, supported by a connective tissue core. The submucosa contained numerous glands with cytoplasmic granules, and luminal secretion was positive for histochemical reaction to Alcian Blue in pH 2.5 and PAS, and negative to Alcian Blue in pH 0.5. Despite the rudimentary characteristic of the tongue in rhea, our results suggest an important role of tongue secretions in food lubrication and humidification during the swallowing process, based on the enormous quantity of lingual glands in the submucosa and the histochemical characteristics of their secretions.

Redescription of Amblyomma varium Koch, 1844 (Acari : Ixodidae) based on light and scanning electron microscopy

Amblyomma varium Koch, 1844 is a Neotropical tick, known as the `sloth`s giant tick`, with records from southern Central America to Argentina. It is found almost exclusively on mammals of the families Bradypodidae and Magalonychidae (Xenarthra). Differences exist in discussions with regard to the dentition of the female hypostome being either 3/3 or 4/4. The male was also originally described as having a short spur on coxa IV, but some specimens recently collected from different Brazilian localities have this spur three times longer. These differences beg the question of whether there is more than one species included under this taxon. In order to answer this question and to clarify the taxonomic characters of this species, 258 adult specimens were examined, and a redescription of male and female based on light and scanning electron microscopy is provided. In addition, DNA was extracted from males with either a long or a short spur on coxa IV to help settle this question for future investigations on their taxonomy. The morphological study showed that the dental formula pattern for males and females is 3/3 and 4/4, respectively. When sequenced, the 12 S rDNA genes of both A. varium males with long and short spurs on coxa IV were found to be identical, indicating that the length of the spurs on coxa IV is likely to be an intraspecifically polymorphic character of this species.

Cohabitation with a sick cage mate: Effects on ascitic form of Ehrlich tumor growth and macrophage activity

The present study was designed to evaluate the effects of mice cohabitation with a sick conspecific cage mate on peritoneal macrophage activity and on resistance to Ehrlich tumor growth. Female mice housed in pairs were divided into control and experimental groups. One mouse of each control pair was inoculated with NaCl (0.1 ml/10 g) intraperitoneally and the other, called `companion of healthy partner` (CHP), was kept undisturbed. One animal of each experimental pair of mice was inoculated with 5.0 x 10(6) Ehrlich tumor cells intraperitoneally and the other, the subject of this study, was called `companion of sick partner` (CSP). Peritoneal macrophages were removed from CSP and CHP mice to analyze resident macrophage activity (experiment 1), macrophage activity after Mycobacterium bovis (experiment 2) or Ehrlich tumor cells (experiment 3) in vivo inoculations. The resistance of CSP and CHP mice to Ehrlich tumor growth was also analyzed (experiment 4). Differences between groups were not found on resident macrophage activity. However, Onco-BCG- and Ehrlich tumor-activated macrophages from CSP mice presented a decreased intensity and percentage of phagocytosis and an increased respiratory burst in the presence of Staphylococcus aureus stimulation in vitro. CSP animals at the same time displayed a decreased resistance to Ehrlich tumor growth. These data were discussed in light of a possible psychological stress effect imposed by the housing condition on mice`s peritoneal macrophage activity and, as a consequence, on their resistance to Ehrlich tumor growth. Copyright (c) 2008 S. Karger AG, Basel.