336 research outputs found

    Neuroinflammation, Mast Cells, and Glia: Dangerous Liaisons

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    The perspective of neuroinflammation as an epiphenomenon following neuron damage is being replaced by the awareness of glia and their importance in neural functions and disorders. Systemic inflammation generates signals that communicate with the brain and leads to changes in metabolism and behavior, with microglia assuming a pro-inflammatory phenotype. Identification of potential peripheral-to-central cellular links is thus a critical step in designing effective therapeutics. Mast cells may fulfill such a role. These resident immune cells are found close to and within peripheral nerves and in brain parenchyma/meninges, where they exercise a key role in orchestrating the inflammatory process from initiation through chronic activation. Mast cells and glia engage in crosstalk that contributes to accelerate disease progression; such interactions become exaggerated with aging and increased cell sensitivity to stress. Emerging evidence for oligodendrocytes, independent of myelin and support of axonal integrity, points to their having strong immune functions, innate immune receptor expression, and production/response to chemokines and cytokines that modulate immune responses in the central nervous system while engaging in crosstalk with microglia and astrocytes. In this review, we summarize the findings related to our understanding of the biology and cellular signaling mechanisms of neuroinflammation, with emphasis on mast cell-glia interactions

    Homeotic Evolution in the Mammalia: Diversification of Therian Axial Seriation and the Morphogenetic Basis of Human Origins

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    Despite the rising interest in homeotic genes, little has been known about the course and pattern of evolution of homeotic traits across the mammalian radiation. An array of emerging and diversifying homeotic gradients revealed by this study appear to generate new body plans and drive evolution at a large scale.This study identifies and evaluates a set of homeotic gradients across 250 extant and fossil mammalian species and their antecedents over a period of 220 million years. These traits are generally expressed as co-linear gradients along the body axis rather than as distinct segmental identities. Relative position or occurrence sequence vary independently and are subject to polarity reversal and mirroring. Five major gradient modification sets are identified: (1)--quantitative changes of primary segmental identity pattern that appeared at the origin of the tetrapods ; (2)--frame shift relation of costal and vertebral identity which diversifies from the time of amniote origins; (3)--duplication, mirroring, splitting and diversification of the neomorphic laminar process first commencing at the dawn of mammals; (4)--emergence of homologically variable lumbar lateral processes upon commencement of the radiation of therian mammals and ; (5)--inflexions and transpositions of the relative position of the horizontal septum of the body and the neuraxis at the emergence of various orders of therian mammals. Convergent functional changes under homeotic control include laminar articular engagement with septo-neural transposition and ventrally arrayed lumbar transverse process support systems.Clusters of homeotic transformations mark the emergence point of mammals in the Triassic and the radiation of therians in the Cretaceous. A cluster of homeotic changes in the Miocene hominoid Morotopithecus that are still seen in humans supports establishment of a new "hominiform" clade and suggests a homeotic origin for the human upright body plan

    Molecular and cellular mechanisms underlying the evolution of form and function in the amniote jaw.

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    The amniote jaw complex is a remarkable amalgamation of derivatives from distinct embryonic cell lineages. During development, the cells in these lineages experience concerted movements, migrations, and signaling interactions that take them from their initial origins to their final destinations and imbue their derivatives with aspects of form including their axial orientation, anatomical identity, size, and shape. Perturbations along the way can produce defects and disease, but also generate the variation necessary for jaw evolution and adaptation. We focus on molecular and cellular mechanisms that regulate form in the amniote jaw complex, and that enable structural and functional integration. Special emphasis is placed on the role of cranial neural crest mesenchyme (NCM) during the species-specific patterning of bone, cartilage, tendon, muscle, and other jaw tissues. We also address the effects of biomechanical forces during jaw development and discuss ways in which certain molecular and cellular responses add adaptive and evolutionary plasticity to jaw morphology. Overall, we highlight how variation in molecular and cellular programs can promote the phenomenal diversity and functional morphology achieved during amniote jaw evolution or lead to the range of jaw defects and disease that affect the human condition

    Excess Circulating Alternatively Activated Myeloid (M2) Cells Accelerate ALS Progression While Inhibiting Experimental Autoimmune Encephalomyelitis

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    Circulating immune cells including autoreactive T cells and monocytes have been documented as key players in maintaining, protecting and repairing the central nervous system (CNS) in health and disease. Here, we hypothesized that neurodegenerative diseases might be associated, similarly to tumors, with increased levels of circulating peripheral myeloid derived suppressor cells (MDSCs), representing a subset of suppressor cells that often expand under pathological conditions and inhibit possible recruitment of helper T cells needed for fighting off the disease.We tested this working hypothesis in amyotrophic lateral sclerosis (ALS) and its mouse model, which are characterized by a rapid progression once clinical symptoms are evident. Adaptive transfer of alternatively activated myeloid (M2) cells, which homed to the spleen and exhibited immune suppressive activity in G93A mutant superoxide dismutase-1 (mSOD1) mice at a stage before emergence of disease symptoms, resulted in earlier appearance of disease symptoms and shorter life expectancy. The same protocol mitigated the inflammation-induced disease model of multiple sclerosis, experimental autoimmune encephalomyelitis (EAE), which requires circulating T cells for disease induction. Analysis of whole peripheral blood samples obtained from 28 patients suffering from sporadic ALS (sALS), revealed a two-fold increase in the percentage of circulating MDSCs (LIN(-/Low)HLA-DR(-)CD33(+)) compared to controls.Taken together, these results emphasize the distinct requirements for fighting the inflammatory neurodegenerative disease, multiple sclerosis, and the neurodegenerative disease, ALS, though both share a local inflammatory component. Moreover, the increased levels of circulating MDSCs in ALS patients indicates the operation of systemic mechanisms that might lead to an impairment of T cell reactivity needed to overcome the disease conditions within the CNS. This high level of suppressive immune cells might represent a risk factor and a novel target for therapeutic intervention in ALS at least at the early stage

    Osteocyte deficiency in hip fractures

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    Osteocytes play a central role in the regulation of bone remodeling. The aim of this study was to explore osteocyte function, and particularly the expression of SOST, a Wnt inhibitor, in patients with hip fractures. Serum sclerostin levels were measured by ELISA. The expression of several osteocytic genes was studied by quantitative PCR in trabecular samples of the femoral head of patients with hip fractures, hip osteoarthritis and control subjects. The presence of sclerostin protein and activated caspase 3 was revealed by immunostaining. There were no significant differences in serum sclerostin between the three groups. Patients with fractures have fewer lacunae occupied by osteocytes (60 ± 5% vs. 64 ± 6% in control subjects, P = 0.014) and higher numbers of osteocytes expressing activated caspase 3, a marker of apoptosis. The proportion of sclerostin-positive lacunae was lower in patients with fractures than in control subjects (34 ± 11% vs. 69 ± 10%, P = 2 × 10(-8)). The proportion of sclerostin-positive osteocytes was also lower in patients. RNA transcripts of SOST, FGF23 and PHEX were also less abundant in fractures than in control bones (P = 0.002, 5 × 10(-6), and 0.04, respectively). On the contrary, in patients with osteoarthritis, there was a decreased expression of SOST and FGF23, without differences in PHEX transcripts or osteocyte numbers. Osteocyte activity is altered in patients with hip fractures, with increased osteocyte apoptosis and reduced osteocyte numbers, as well as decreased transcription of osteocytic genes. Therefore, these results suggest that an osteocyte deficiency may play a role in the propensity to hip fractures

    Characterization of street food consumption in palermo: possible effects on health

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    <p>Abstract</p> <p>Background</p> <p>Street Food (SF) consists of out-of-home food consumption and has old, historical roots with complex social-economic and cultural implications. Despite the emergence of modern fast food, traditional SF persists worldwide, but the relationship of SF consumption with overall health, well-being, and obesity is unknown.</p> <p>Methods</p> <p>This is an observational, cross-sectional study. The study was performed in Palermo, the largest town of Sicily, Italy. Two groups were identified: consumers of SF (n = 687) and conventional restaurant food (RES) consumers (n = 315). Study subjects answered a questionnaire concerning their health conditions, nutritional preferences, frequency of consumption of SF and a score relative to SF consumption ranging from 0 to 20 was calculated.</p> <p>Results</p> <p>Body mass index (BMI, kg/m<sup>2</sup>) was significantly and independently correlated with the score of street food consumption (r = 0,103; p < 0.002). The prevalence of different diseases, including hypertension and type 2 diabetes, and the use of medications did not differ between the two groups. Milza (a sandwich stuffed with thin slice of bovine spleen and lung) consumers had a significantly higher prevalence of hypertension (12.2% vs 6.2% in non consumers; p < 0.005) and in this subgroup the use of anti-hypertensive drugs was inversely correlated with the frequency of milza consumption (r = 0.11; P = 0.010).</p> <p>Conclusions</p> <p>This study suggests that SF consumption in Palermo is associated with a higher BMI and higher prevalence of hypertension in milza consumers. Further studies should evaluate whether frequent SF consumers have unfavourable metabolic and cardiovascular profile.</p

    Triglyceride/HDL ratio as a screening tool for predicting success at reducing anti-diabetic medications following weight loss.

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    PMC3712020BACKGROUND AND OBJECTIVES: Intentional weight loss, by reducing insulin resistance, results in both better glycemic control and decreased need for anti-diabetic medications. However, not everyone who is successful with weight loss is able to reduce anti-diabetic medication use. In this retrospective cohort study, we assessed the predictive accuracy of baseline triglyceride (TGL)/HDL ratio, a marker of insulin resistance, to screen patients for success in reducing anti-diabetic medication use with weight loss. METHODS: Case records of 121 overweight and obese attendees at two outpatient weight management centers were analyzed. The weight loss intervention consisted of a calorie-restricted diet (~1000Kcal/day deficit), a behavior modification plan, and a plan for increasing physical activity. RESULTS: Mean period of follow-up was 12.5 ± 3.5 months. By study exit, mean weight loss and mean HbA1c% reduction were 15.4 ± 5.5 kgs and 0.5 ± 0.2% respectively. 81 (67%) in the study cohort achieved at least 1 dose reduction of any anti-diabetic medication. Tests for predictive accuracy of baseline TGL/HDL ratio ≀ 3 to determine success with dose reductions of anti-diabetic medications showed a sensitivity, specificity, positive predictive value, negative predictive value, area under the curve, likelihood ratio (LR) + and LR-of 81, 83, 90, 70, 78, 4.8 and 0.2, respectively. Reproducibility of TGL/HDL ratio was acceptable. CONCLUSION: TGL/HDL ratio shows promise as an effective screening tool to determine success with dose reductions of anti-diabetic medications. The results of our study may inform the conduct of a systematic review using data from prior weight loss trials.JH Libraries Open Access Fun

    The quality of preventive health care delivered to adults: results from a cross-sectional study in Southern Italy

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    <p>Abstract</p> <p>Background</p> <p>It is assumed that providing clinical preventive services to patients can identify or detect early important causes of adult mortality. The aim of this study was to quantify access to preventive services in Southern Italy and to assess whether and how the provision of preventive care was influenced by any specific characteristics of patients.</p> <p>Methods</p> <p>In a cross-sectional study adults aged 18 years and over attending primary care physician (PCP) offices located in Southern Italy were interviewed from June through December 2007. Quality indicators of preventive health care developed from RAND's Quality Assessment Tools and Behavioral Risk Factor Surveillance System (BRFSS) were used. Multivariate analysis was performed to identify and to assess the role of patients' characteristics on delivery of clinical preventive services.</p> <p>Results</p> <p>A total of 1467 subjects participated in the study. Excepting blood pressure preventive check (delivered to 64.4% of eligible subjects) and influenza vaccination (recommended to 90.2% of elderly), the rates of delivery of clinical preventive services were low across all measures, particularly for screening and counseling on health habits. Rates for providing cancer screening tests at recommended times were 21.3% for colonoscopy, 51.5% for mammography and 52.4% for Pap smear. Statistical analysis showed clear disparities in the provision of clinical preventive services associated with age, gender, education level, perceived health status, current health conditions and primary care access measures.</p> <p>Conclusions</p> <p>There is overwhelming need to develop and implement effective interventions to improve delivery of routine clinical preventive services.</p
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