Hofbauer cells morphology and density in placentas from normal and pathological gestations

PURPOSE: In placentas from uncomplicated pregnancies, Hofbauer cells either disappear or become scanty after the fourth to fifth month of gestation. Immunohistochemistry though, reveals that a high percentage of stromal cells belong to Hofbauer cells. The aim of this study was to investigate the changes in morphology and density of Hofbauer cells in placentas from normal and pathological pregnancies. METHODS: Seventy placentas were examined: 16 specimens from normal term pregnancies, 10 from first trimester's miscarriages, 26 from cases diagnosed with chromosomal abnormality of the fetus, and placental tissue specimens complicated with intrauterine growth restriction (eight) or gestational diabetes mellitus (10). A histological study of hematoxylin-eosin (HE) sections was performed and immunohistochemical study was performed using the markers: CD 68, Lysozyme, A1 Antichymotrypsine, CK-7, vimentin, and Ki-67. RESULTS: In normal term pregnancies, HE study revealed Hofbauer cells in 37.5% of cases while immunohistochemistry revealed in 87.5% of cases. In first trimester's miscarriages and in cases with prenatal diagnosis of fetal chromosomal abnormalities, both basic and immunohistochemical study were positive for Hofbauer cells. In pregnancies complicated with intrauterine growth restriction or gestational diabetes mellitus, a positive immunoreaction was observed in 100 and 70% of cases, respectively. CONCLUSIONS: Hofbauer cells are present in placental villi during pregnancy, but with progressively reducing density. The most specific marker for their detection seems to be A1 Antichymotrypsine. It is remarkable that no mitotic activity of Hofbauer cells was noticed in our study, as the marker of cellular multiplication Ki-67 was negative in all examined specimens.

Simultaneous occurrence of brain tumor and myeloradiculopathy in schistosomiasis mansoni: case report

Simultaneous occurrence of brain tumor and myeloradiculopathy in cases of Manson's schistosomiasis have only rarely been described. We report the case of a 38-year-old man who developed seizures during a trip to Puerto Rico and in whom a brain tumor was diagnosed by magnetic resonance imaging: brain biopsy revealed the diagnosis of schistosomiasis. He was transferred to a hospital in the United States and, during hospitalization, he developed sudden paraplegia. The diagnosis of myeloradiculopathy was confirmed at that time. He was administered praziquantel and steroids. The brain tumor disappeared, but the patient was left with paraplegia and fecal and urinary dysfunction. He has now been followed up in Brazil for one year, and his clinical state, imaging examinations and laboratory tests are presented here.

Aortic stenosis. Gender influence on left ventricular geometry and function in patients under 70 years of age

OBJECTIVE: To verify if adaptive left ventricle (LV) characteristics are also present in individuals under 70 years of age with severe aortic stenosis (AS). METHODS: The study comprised 40 consecutive patients under 70 years of age with AS and no associated coronary artery disease, referred for valve surgery. Out of the 40 patients, 22 were men and 18 women, and the mean age was 49.8±14.3 years. Cardiac symptoms, presence of systemic hypertension (SH), functional class according to the New York Heart Association (NYHA), and valve lesion etiology were considered. LV cavity dimensions, ejection fraction (EF), fractional shortening (FS), mass (MS), and relative diastolic thickness (RDT) were examined by Doppler echocardiography. RESULTS: Fourteen (63.6%) men and 11 (61.6%) women were classified as NYHA class III/IV (p=0.70). There was no difference in the frequency of angina, syncope or dyspnea between genders. The incidence of SH was greater in women than in men (10 versus 2, p=0.0044). Women had a smaller LV end-diastolic diameter index (32.1±6.5 x 36.5±5.3mm/m², p=0.027), LV end-systolic diameter index (19.9±5.9 x 26.5±6.4mm/m², p=0.0022) and LV mass index (MS) (211.4±71.1 x 270.9±74.9g/m², p=0.017) when compared with men. EF (66.2±13.4 x 52.0±14.6%, p=0.0032), FS (37.6±10.7 x 27.9±9.6%, p=0.0046) and RDT (0.58±0.22 x 0.44±0.09, p=0.0095) were significantly greater in women than in men. CONCLUSION: It is the patient gender rather than age that influences left ventricular adaptive response to AS.

Mechanisms of leukocyte lipid body formation and function in inflammation

An area of increasingly interest for the understanding of cell signaling are the spatio-temporal aspects of the different enzymes involved in lipid mediator generation (eicosanoid-forming enzymes, phospholipases and their regulatory kinases and phosphatases) and pools of lipid precursors. The compartmentalization of signaling components within discrete and dynamic sites in the cell is critical for specificity and efficiency of enzymatic reactions of phosphorilation, enzyme activation and function. We hypothesized that lipid bodies - inducible non-membrane bound cytoplasmic lipid domains - function as specialized intracellular sites of compartmentalization of signaling with major roles in lipid mediator formation within leukocytes engaged in inflammatory process. Over the past years substantial progresses have been made demonstrating that all enzymes involved in eicosanoid synthesis localize at lipid bodies and lipid bodies are distinct sites for eicosanoid generation. Here we will review our current knowledge on the mechanisms of formation and functions of lipid bodies pertinent to inflammation.

Correlation of meta 1 expression with culture stage, cell morphology and infectivity in Leishmania (Leishmania) amazonensis promastigotes

The parasitic protozoan Leishmania (Leishmania) amazonensis alternates between mammalian and insect hosts. In the insect host, the parasites proliferate as procyclic promastigotes andthen differentiate into metacyclic infective forms. The meta 1 gene is preferentially expressed during metacyclogenesis. Meta 1 expression profile determination along parasite growth curves revealed that the meta 1 mRNA level peaked at the early stationary phase then decreased to an intermediate level. No correlation was observed between meta 1 expression and infectivity. Conversely, infectivity correlated with the increase of apoptotic cells in the late stationary phase.

Decreased memory T-cell response and function in human immunodeficiency virus-infected patients with tegumentary leishmaniasis

The effects of human immunodeficiency virus (HIV) on the immune response in patients with cutaneous leishmaniasis have not yet been fully delineated. This study quantified and evaluated the function of memory T-cell subsets in response to soluble Leishmania antigens (SLA) from patients coinfected with HIV and Leishmania with tegumentary leishmaniasis (TL). Eight TL/HIV coinfected subjects and 10 HIV seronegative subjects with TL were evaluated. The proliferative response of CD4+and CD8+T-cells and naïve, central memory (CM) and effector memory (EM) CD4+T-cells in response to SLA were quantified using flow cytometry. The median cell division indices for CD4+and CD8+T-cells of coinfected patients in response to SLA were significantly lower than those in patients with Leishmania monoinfection (p < 0.05). The proportions of CM and EM CD4+T-cells in response to SLA were similar between the coinfected patients and patients with Leishmania monoinfection. However, the median CM and EM CD4+T-cell counts from coinfected patients were significantly lower (p < 0.05). The reduction in the lymphoproliferative response to Leishmaniaantigens coincides with the decrease in the absolute numbers of both EM and CM CD4+T-cells in response to Leishmania antigens in patients coinfected with HIV/Leishmania.

Morphology and anatomy in Heliconia angusta Vell. and H. velloziana L. Emygd. (Zingiberales: Heliconiaceae) from the Atlantic forest of southeastern Brazil

Morphological and anatomical features of roots, stems, leaves, and scapes were studied in Heliconia angusta and H. velloziana from the Atlantic forest in the southeastern of Brazil. Morphologically H. angusta and H. velloziana show differences in their sizes, blade shapes, number and shape of inflorescence bracts. On the other hand, they have common anatomical characteristics such as: roots with air-canals in the cortex; rhizomes with isolated fiber bundles, collateral vascular bundles, and uniseriate endodermis and pericycle; leaves presenting air-canals and collateral vascular bundles forming arcs, and thin-walled epidermal cells; scapes with collateral vascular and fiber bundles in the cortex. The distribution of the fiber bundles in the leaves and in the scapes was different for each species, having a taxonomical value, H. velloziana presenting continuous fiber bundles. Air-canals in roots and leaves with narrow mesophyll might be related to the moist understorey of the Atlantic forest habitats.

Serotonin regulates osteoblast proliferation and function in vitro

The monoamine serotonin (5-hydroxytryptamine, 5-HT), a well-known neurotransmitter, also has important functions outside the central nervous system. The objective of this study was to investigate the role of 5-HT in the proliferation, differentiation, and function of osteoblasts in vitro. We treated rat primary calvarial osteoblasts with various concentrations of 5-HT (1 nM to 10 µM) and assessed the rate of osteoblast proliferation, expression levels of osteoblast-specific proteins and genes, and the ability to form mineralized nodules. Next, we detected which 5-HT receptor subtypes were expressed in rat osteoblasts at different stages of osteoblast differentiation. We found that 5-HT could inhibit osteoblast proliferation, differentiation, and mineralization at low concentrations, but this inhibitory effect was mitigated at relatively high concentrations. Six of the 5-HT receptor subtypes (5-HT1A, 5-HT1B, 5-HT1D, 5-HT2A, 5-HT2B, and 5-HT2C) were found to exist in rat osteoblasts. Of these, 5-HT2A and 5-HT1Breceptors had the highest expression levels, at both early and late stages of differentiation. Our results indicated that 5-HT can regulate osteoblast proliferation and function in vitro.

Histopathological analysis of pre-implantation donor kidney biopsies: association with graft survival and function in one year post-transplantation

Introduction: Pre-implantation kidney biopsy is a decision-making tool when considering the use of grafts from deceased donors with expanded criteria, implanting one or two kidneys and comparing this to post-transplantation biopsies. The role of histopathological alterations in kidney compartments as a prognostic factor in graft survival and function has had conflicting results. Objective: This study evaluated the prevalence of chronic alterations in pre-implant biopsies of kidney grafts and the association of findings with graft function and survival in one year post-transplant. Methods: 110 biopsies were analyzed between 2006 and 2009 at Santa Casa de Porto Alegre, including live donors, ideal deceased donors and those with expanded criteria. The score was computed according to criteria suggested by Remuzzi. The glomerular filtration rate (GFR) was calculated using the abbreviated MDRD formula. Results: No statistical difference was found in the survival of donors stratified according to Remuzzi criteria. The GFR was significantly associated with the total scores in the groups with mild and moderate alterations, and in the kidney compartments alone, by univariate analysis. The multivariate model found an association with the presence of arteriosclerosis, glomerulosclerosis, acute rejection and delayed graft function. Conclusion: Pre-transplant chronic kidney alterations did not influence the post-transplantation one-year graft survival, but arteriosclerosis and glomerulosclerosis is predictive of a worse GFR. Delayed graft function and acute rejection are independent prognostic factors.

Follow-up study of morphology and cardiac function in rats undergoing induction of supravalvular aortic stenosis

OBJECTIVE: To characterize the follow-up of an experimental model of left ventricular hypertrophy (LVH) induced by supravalvular ascending aortic stenosis in young rats. METHODS: Wistar rats were submitted to thoracotomy and aortic stenosis was created by placing a clip on the ascending aorta (AoS group, n=12). Age-matched control animals underwent a sham operation (C group, n=12). Cardiac function was analysed by echocardiograms performed 6, 12, and 21 weeks after aortic banding. Myocardial morphological features and myocardial hydroxyproline concentration (HOP) were evaluated 2, 6, 12, and 21 weeks after surgery in additional animals. RESULTS: Aortic banding promoted early concentric LVH and a progressive increase in HOP. Under light microscopy, we observed myocyte hypertrophy and wall thickening of the intramural branches of the coronary arteries due to medial hypertrophy. Cardiac function was supranormal after 6 weeks (percentage of fractional shortening - EAo6: 70.3±10.8; C6: 61.3±5.4; p<0.05), and depressed in the last period. Diastolic dysfunction was detected after 12 weeks (ratio of early-to-late filling velocity - EAo12: 4.20±3.25; C12: 1.61±0.16; p<0.05). CONCLUSION: Ascending aortic stenosis promotes concentric LVH with myocardial fibrosis and minimal histological changes. According to the period of evaluation, cardiac function may be improved, normal, or depressed. The model is suitable and useful for studies on pathophysiology and treatment of the different phases of cardiac hypertrophy.

Standardization of a computerized method for calculating autonomic function test responses in healthy subjects and patients with diabetes mellitus

The objectives of the present study were 1) to compare results obtained by the traditional manual method of measuring heart rate (HR) and heart rate response (HRR) to the Valsalva maneuver, standing and deep breathing, with those obtained using a computerized data analysis system attached to a standard electrocardiograph machine; 2) to standardize the responses of healthy subjects to cardiovascular tests, and 3) to evaluate the response to these tests in a group of patients with diabetes mellitus (DM). In all subjects (97 healthy and 143 with DM) we evaluated HRR to deep breathing, HRR to standing, HRR to the Valsalva maneuver, and blood pressure response (BPR) to standing up and to a sustained handgrip. Since there was a strong positive correlation between the results obtained with the computerized method and the traditional method, we conclude that the new method can replace the traditional manual method for evaluating cardiovascular responses with the advantages of speed and objectivity. HRR and BPR of men and women did not differ. A correlation between age and HRR was observed for standing (r = -0.48, P<0.001) and deep breathing (r = -0.41, P<0.002). Abnormal BPR to standing was usually observed only in diabetic patients with definite and severe degrees of autonomic neuropathy.

Regulation and function of neurogenesis in the adult vertebrate brain

Most adult tissues retain a reservoir of self-renewing, multipotent stem cells that can generate differentiated tissue components. Until recently, the brain was thought to be an exception to this rule and for many years the pervasive dogma of neurobiology relegated neurogenesis to the embryonic and earlier postnatal stages of development. The discovery of constant neuronal replacement in the adult brain has changed the way we think about neurological diseases and about the exploration of new strategies for brain repair. In this review we will explore the potential of adult neural stem cells and we will present some of our own work on this subject. We will also discuss the possibility that adult neurogenesis and neuronal replacement may also play a role in therapies aimed at restoring impaired brain function. A better understanding of the various aspects of spontaneous neuronal replacement may also be used to increase the success of procedures with cell therapies.

Neutrophil function and metabolism in individuals with diabetes mellitus

Neutrophils act as first-line-of-defense cells and the reduction of their functional activity contributes to the high susceptibilityto and severity of infections in diabetes mellitus. Clinical investigations in diabetic patients and experimental studies in diabetic rats and mice clearly demonstrated consistent defects of neutrophil chemotactic, phagocytic and microbicidal activities. Other alterations that have been reported to occur during inflammation in diabetes mellitus include: decreased microvascular responses to inflammatory mediators such as histamine and bradykinin, reduced protein leakage and edema formation, reduced mast cell degranulation, impairment of neutrophil adhesionto the endothelium and migration to the site of inflammation, production of reactive oxygen species and reduced release of cytokines and prostaglandin by neutrophils, increased leukocyte apoptosis, and reduction in lymph node retention capacity. Since neutrophil function requires energy, metabolic changes (i.e., glycolytic and glutaminolytic pathways) may be involved in the reduction of neutrophil function observed in diabetic states. Metabolic routes by which hyperglycemia is linked to neutrophil dysfunction include the advanced protein glycosylation reaction, the polyol pathway, oxygen-free radical formation, the nitric oxide-cyclic guanosine-3'-5'monophosphate pathway, and the glycolytic and glutaminolytic pathways. Lowering of blood glucose levels by insulin treatment of diabetic patients or experimental animals has been reported to have significant correlation with improvement of neutrophil functional activity. Therefore, changes might be primarily linked to a continuing insulin deficiency or to secondary hyperglycemia occurring in the diabetic individual. Accordingly, effective control with insulin treatment is likely to be relevant during infection in diabetic patients.

Diabetes mellitus affects the biomechanical function of the callus and the expression of TGF-beta1 and BMP2 in an early stage of fracture healing

Transforming growth factor beta 1 (TGF-β1) and bone morphogenetic protein-2 (BMP-2) are important regulators of bone repair and regeneration. In this study, we examined whether TGF-β1 and BMP-2 expressions were delayed during bone healing in type 1 diabetes mellitus. Tibial fractures were created in 95 diabetic and 95 control adult male Wistar rats of 10 weeks of age. At 1, 2, 3, 4, and 5 weeks after fracture induction, five rats were sacrificed from each group. The expressions of TGF-β1 and BMP2 in the fractured tibias were measured by immunohistochemistry and quantitative reverse-transcription polymerase chain reaction, weekly for the first 5 weeks post-fracture. Mechanical parameters (bending rigidity, torsional rigidity, destruction torque) of the healing bones were also assessed at 3, 4, and 5 weeks post-fracture, after the rats were sacrificed. The bending rigidity, torsional rigidity and destruction torque of the two groups increased continuously during the healing process. The diabetes group had lower mean values for bending rigidity, torsional rigidity and destruction torque compared with the control group (P<0.05). TGF-β1 and BMP-2 expression were significantly lower (P<0.05) in the control group than in the diabetes group at postoperative weeks 1, 2, and 3. Peak levels of TGF-β1 and BMP-2 expression were delayed by 1 week in the diabetes group compared with the control group. Our results demonstrate that there was a delayed recovery in the biomechanical function of the fractured bones in diabetic rats. This delay may be associated with a delayed expression of the growth factors TGF-β1 and BMP-2.

Diagnosing dementia and normal aging: clinical relevance of brain ratios and cognitive performance in a Brazilian sample

The main objective of the present study was to evaluate the diagnostic value (clinical application) of brain measures and cognitive function. Alzheimer and multiinfarct patients (N = 30) and normal subjects over the age of 50 (N = 40) were submitted to a medical, neurological and cognitive investigation. The cognitive tests applied were Mini-Mental, word span, digit span, logical memory, spatial recognition span, Boston naming test, praxis, and calculation tests. The brain ratios calculated were the ventricle-brain, bifrontal, bicaudate, third ventricle, and suprasellar cistern measures. These data were obtained from a brain computer tomography scan, and the cutoff values from receiver operating characteristic curves. We analyzed the diagnostic parameters provided by these ratios and compared them to those obtained by cognitive evaluation. The sensitivity and specificity of cognitive tests were higher than brain measures, although dementia patients presented higher ratios, showing poorer cognitive performances than normal individuals. Normal controls over the age of 70 presented higher measures than younger groups, but similar cognitive performance. We found diffuse losses of tissue from the central nervous system related to distribution of cerebrospinal fluid in dementia patients. The likelihood of case identification by functional impairment was higher than when changes of the structure of the central nervous system were used. Cognitive evaluation still seems to be the best method to screen individuals from the community, especially for developing countries, where the cost of brain imaging precludes its use for screening and initial assessment of dementia.