Frequency of thrombophilia determinant factors in patients with livedoid vasculopathy and treatment with anticoagulant drugs - a prospective study

Background Livedoid vasculopathy (LV) is a chronic idiopathic disease characterized by painful purpuric macules on lower extremities. Its exact aetiology remains uncertain, but thrombotic and microcirculatory phenomena have been implicated as possible pathogenic factors. Objectives To assess prospectively the frequency of thrombophilia and to verify the effectiveness of anticoagulant therapy among LV patients. Methods Thirty-four LV patients were tested for prothrombin time, activated partial thromboplastin time, antithrombin activity, protein C and S activity, anticardiolipin antibodies, lupus anticoagulant, prothrombin gene mutation, factor V Leiden mutation, methylenetetrahydrofolate reductase mutation, plasma homocysteine and fibrinogen. Thirteen of these patients were treated with anticoagulant drugs (either warfarin or heparin). Results Of 34 patients, 18 (52%) presented laboratory abnormalities of procoagulant conditions. Positive treatment response to anticoagulant therapy was observed in 11 patients. Improvement of pain was obtained in 1-3 weeks, an average of 1.8 week. Complete healing of the lesions was observed in about 2.3 months. Remission was sustained even after treatment interruption and lasted an average 7.8 months. No severe adverse effects were noticed. Conclusion The authors suggest all patients with diagnosis of LV to be investigated for thrombophilic status. Anticoagulant drugs were well tolerated and seemed to be effective in treating not only LV symptoms but also its ulcerations.

Allergic rhinitis in the child and associated comorbidities

Allergic rhinitis (AR) typically presents after the second year of life, but the exact prevalence in early life is unknown. AR affects 10-30% of the population, with the greatest frequency found in children and adolescents. It appears that the prevalence has increased in the pediatric population. As the childs` immune system develops between the 1st and 4th yr of life, those with an atopic predisposition begin to express allergic disease with a clear Th(2) response to allergen exposure, resulting in symptoms. In pediatric AR, two or more seasons of pollen exposure are generally needed for sensitization, so allergy testing to seasonal allergens (trees, grasses, and weeds) should be conducted after the age of 2 or 3 years. Sensitization to perennial allergens (animals, dust mites, and cockroaches) may manifest several months after exposure. Classification of AR includes measurement of frequency and duration of symptoms. Intermittent AR is defined as symptoms for < 4 days/wk or < 4 consecutive weeks. Persistent AR is defined as occurring for more than 4 days/wk and more than 4 consecutive weeks. AR is associated with impairments in quality of life, sleep disorders, emotional problems, and impairment in activities such as work and school productivity and social functioning. AR can also be graded in severity - either mild or moderate/severe. There are comorbidities associated with AR. The chronic effects of the inflammatory process affect lungs, ears, growth, and others. AR can induce medical complications, learning problems and sleep-related complaints, such as obstructive sleep apnea syndrome and chronic and acute sinusitis, acute otitis media, serous otitis media, and aggravation of adenoidal hypertrophy and asthma.

In vivo electrochemical characterization and inflammatory response of multiwalled carbon nanotube-based electrodes in rat hippocampus

Stimulating neural electrodes are required to deliver charge to an environment that presents itself as hostile. The electrodes need to maintain their electrical characteristics (charge and impedance) in vivo for a proper functioning of neural prostheses. Here we design implantable multi-walled carbon nanotubes coating for stainless steel substrate electrodes, targeted at wide frequency stimulation of deep brain structures. In well-controlled, low-frequency stimulation acute experiments, we show that multi-walled carbon nanotube electrodes maintain their charge storage capacity (CSC) and impedance in vivo. The difference in average CSCs (n = 4) between the in vivo (1.111 mC cm(-2)) and in vitro (1.008 mC cm(-2)) model was statistically insignificant (p > 0.05 or P-value = 0.715, two tailed). We also report on the transcription levels of the pro-inflammatory cytokine IL-1 beta and TLR2 receptor as an immediate response to low-frequency stimulation using RT-PCR. We show here that the IL-1 beta is part of the inflammatory response to low-frequency stimulation, but TLR2 is not significantly increased in stimulated tissue when compared to controls. The early stages of neuroinflammation due to mechanical and electrical trauma induced by implants can be better understood by detection of pro-inflammatory molecules rather than by histological studies. Tracking of such quantitative response profits from better analysis methods over several temporal and spatial scales. Our results concerning the evaluation of such inflammatory molecules revealed that transcripts for the cytokine IL-1 beta are upregulated in response to low-frequency stimulation, whereas no modulation was observed for TLR2. This result indicates that the early response of the brain to mechanical trauma and low-frequency stimulation activates the IL-1 beta signaling cascade but not that of TLR2.

Host genetic background affects regulatory T-cell activity that influences the magnitude of cellular immune response against Mycobacterium tuberculosis

Using two mouse strains with different abilities to generate interferon (IFN)-gamma production after Mycobacterium tuberculosis infection, we tested the hypothesis that the frequency and activity of regulatory T (Treg) cells are influenced by genetic background. Our results demonstrated that the suppressive activity of spleen Treg cells from infected or uninfected BALB/c mice was enhanced, inhibiting IFN-gamma and interleukin (IL)-2 production. Infected C57BL/6 mice exhibited a decrease in the frequency of lung Treg cells and an increased ratio CD4(+):CD4(+)Foxp3(+) cells compared with infected BALB/c mice and uninfected C57BL/6 mice. Moreover, infected C57BL/6 mice also had a decrease in the immunosuppressive capacity of spleen Treg cells, higher lung IFN-gamma and IL-17 production, and restricted the infection better than BALB/c mice. Adoptive transfer of BALB/c Treg cells into BALB/c mice induced an increase in bacterial colony-forming unit (CFU) counts. Furthermore, BALB/c mice treated with anti-CD25 antibody exhibited lung CFU counts significantly lower than mice treated with irrelevant antibody. Our results show that in BALB/c mice, the Treg cells have a stronger influence than that in C57BL/6 mice. These data suggest that BALB/c and C57BL/6 mice may use some different mechanisms to control M. tuberculosis infection. Therefore, the role of Treg cells should be explored during the development of immune modulators, both from the perspective of the pathogen and the host. Immunology and Cell Biology (2011) 89, 526-534; doi:10.1038/icb.2010.116; published online 19 October 2010

Prelimbic but not infralimbic cortex is involved in the pressor response to chemoreflex activation in awake rats

The ventral portion of the medial prefrontal cortex comprises the prelimbic cortex (PL) and the infralimbic cortex (IL). Several studies have indicated that both the PL and the IL play an important role in cardiovascular control. Chemoreflex activation by systemic administration of potassium cyanide (KCN) evokes pressor and bradycardiac responses in conscious rats, in addition to an increase in respiratory frequency. We report here a comparison between the effects of pharmacological inhibition of PL and IL neurotransmission on blood pressure and heart rate responses evoked by chemoreflex activation using KCN (i.v.) in conscious rats. Bilateral microinjection of 200 nl of the unspecific synaptic blocker CoCl(2) (1 mm) into the PL evoked a significant attenuation of the pressor response, without affecting the chemoreflex-induced heart rate decrease. However, IL local synapse inhibition evoked no changes in cardiovascular responses induced by chemoreflex activation. Thus, our results suggest that the pressor but not the bradycardiac response to chemoreflex activation is, at least in part, mediated by local neurotransmission present in the PL cortex, without influence of the IL cortex.

Validation of a food frequency questionnaire for assessing dietary nutrients in Brazilian children 5 to 10 years of age

Objective: This study aimed to assess the relative validity of a food frequency questionnaire.(FFQ), previously validated to measure usual intakes in adults, for measuring dietary intakes in children 5 to 10 y of age. Methods: Dietary intakes were measured using an FFQ and a 3-d dietary record. Healthy children, 5 to 10 y old (n = 151), were recruited from public schools and asked to answer the questions in the FFQ and to provide non-consecutive 3-d dietary records based on reported estimated portion sizes. Paired sample t tests and Pearson`s correlation coefficients were conducted to determine whether the two instruments reported similar values for energy and nutrients. The agreement of quartile categorization between the two instruments was also examined. Results: Estimated energy and nutrient intakes derived from the FFQ were significantly higher than those derived from 3-d dietary records. As expected, Pearson`s correlations increased after adjusting for residual measurement error, presumably due to exclusion of the high within-person variability in intake of these nutrients. Moderate to high (r > 0.50) correlation coefficients were verified for some nutrients such as calcium, folate, vitamin 132, vitamin A, and vitamin C. Conclusion: This FFQ, originally developed for use in adults, appears to overestimate usual energy and nutrient intakes in children 5 to 10 y of age. Further work is necessary to conduct a calibration study to establish adequate portion sizes before instrument adoption in this population. (c) 2008 Elsevier Inc. All rights reserved.

Focal CO2 dialysis in raphe obscurus does not stimulate ventilation but enhances the response to focal CO2 dialysis in the retrotrapezoid nucleus

Simultaneous inhibition of the retrotrapezoid nucleus (RTN) and raphe obscurus (ROb) decreased the systemic CO2 response by 51%, an effect greater than inhibition of RTN (- 24%) or ROb (0%) alone, suggesting that ROb modulates chemoreception by interaction with the RTN (19). We investigated this interaction further by simultaneous dialysis of artificial cerebrospinal fluid equilibrated with 25% CO2 in two probes located in or adjacent to the RTN and ROb in conscious adult male rats. Ventilation was measured in a whole body plethysmograph at 30 C. There were four groups (n = 5): 1) probes correctly placed in both RTN and ROb (RTN-ROb); 2) one probe correctly placed in RTN and one incorrectly placed in areas adjacent to ROb (RTN-peri-ROb); 3) one probe correctly placed in ROb and one probe incorrectly placed in areas adjacent to RTN (peri-RTN-ROb); and 4) neither probe correctly placed (peri-RTN-peri-ROb). Focal simultaneous acidification of RTN-ROb significantly increased ventilation ((V) over dot E) up to 22% compared with baseline, with significant increases in both breathing frequency and tidal volume. Focal acidification of RTN-peri-ROb increased (V) over dot E significantly by up to 15% compared with baseline. Focal acidification of ROb and peri-RTN had no significant effect. The simultaneous acidification of regions just outside the RTN and ROb actually decreased (V) over dot E by up to 11%. These results support a modulatory role for the ROb with respect to central chemoreception at the RTN.

Oleic acid modulation of the immune response in wound healing: A new approach for skin repair

Injury triggers inflammatory responses and tissue repair. Several treatments are currently in use to accelerate healing: however, more efficient formulations are still needed for specific injuries. Since unsaturated fatty acids modulate immune responses, we aimed to evaluate their therapeutic effects on wound healing. Skin wounds were induced in BALB/c mice and treated for 5 days with n-3, n-9 fatty acids or vehicle (control). n-9 treated mice presented smaller wounds than control and n-3 at 120 h post-surgery (p.s.). Collagen III mRNA,TIMP1 and MMP9 were significantly elevated in n-9 group compared to n-3 or vehicle at 120 h p.s. Among the inflammatory mediators studied we found that IL-10, TNF-alpha and IL-17 were also higher in n-9 treated group compared to n-3 or vehicle at 120 h p.s. Interestingly, COX2 had decreased expression on wound tissue treated with n-9. Inflammatory infiltrate analysis revealed diminished frequency of CD4(+), CD8(+) and CD11b(+) cells in n-9 wounds at 24 and 120 h p.s., which was not related to cell death, since in vitro apoptosis experiments did not show any cell damage after fatty acids administration. These results suggested that unsaturated fatty acids, specifically n-9, modulate the inflammation in the wound and enhance reparative response in vivo. n-9 may be a useful tool in the treatment of cutaneous wounds. (C) 2010 Elsevier GmbH. All rights reserved.

Differences in thermoregulatory ability between slick-haired and wild-type lactating Holstein cows in response to acute heat stress

Animals inheriting the slick hair gene have a short, sleek, and sometimes glossy coat. The objective of the present study was to determine whether slick-haired Holstein cows regulate body temperature more effectively than wild-type Holstein cows when exposed to an acute increase in heat stress. Lactating slick cows (n = 10) and wild-type cows (n = 10) were placed for 10 h in an indoor environment with a solid roof, fans, and evaporative cooling or in an outdoor environment with shade cloth and no fans or evaporative cooling. Cows were exposed to both environments in a single reversal design. Vaginal temperature, respiration rate, surface temperature, and sweating rate were measured at 1200, 1500, 1800, and 2100 h (replicate 1) or 1200 and 1500 h (replicate 2), and blood samples were collected for plasma cortisol concentration. Cows in the outdoor environment had higher vaginal and surface temperatures, respiration rates, and sweating rates than cows in the indoor environment. In both environments, slick-haired cows had lower vaginal temperatures (indoor: 39.0 vs. 39.4 degrees C; outdoor 39.6 vs. 40.2 degrees C; SEM = 0.07) and respiration rate (indoor: 67 vs. 79 breaths/min; outdoor 97 vs. 107 breaths/min; SEM = 5.5) than wild-type cows and greater sweating rates in unclipped areas of skin (indoor: 57 vs. 43 g.h(-1)/m(2); outdoor 82 vs. 61 g.h(-1)/m(2); SEM = 8). Clipping the hair at the site of sweating measurement eliminated the difference between slick-haired and wild-type cows. Results indicate that slick-haired Holstein cows can regulate body temperature more effectively than wild-type cows during heat stress. One reason slick-haired animals are better able to regulate body temperature is increased sweating rate.

Chemokines and chemokine receptors coordinate the inflammatory immune response in human cutaneous leishmaniasis

Cutaneous leishmaniasis (CL) includes different clinical manifestations displaying diverse intensities of dermal Inflammatory infiltrate Diffuse CL (DCL) cases are hyporesponsive and lesions show very few lymphocytes and a predominance of macrophages In contrast localized CL (LCL) cases are responsive to leishmanial antigen and lesions exhibit granulocytes and mononuclear cell infiltration in the early phases changing to a pattern with numerous lymphocytes and macrophages later in the lesion Therefore different chemokines may affect the predominance of cell infiltration in distinct clinical manifestations In lesions from LCL patients we examined by flow cytometry the presence of different chemokines and their receptors in T cells and we verified a higher expression of CXCR3 in the early stages of LCL (less than 30 days of infection) and a higher expression of CCR4 in the late stages of disease (more than 60 days of infection) We also observed a higher frequency of T cells producing IL-10 in the late stage of LCL Using immunohistochemistry we observed a higher expression of CCL7 CCL17 in lesions from late LCL as well as CCR4 suggesting a preferential recruitment of regulatory T cells in the late LCL Comparing lesions from LCL and DCL patients we observed a higher frequency of CCL7 in DCL lesions These results point out the Importance of the chemokines defining the different types of cells recruited to the site of the infection which could be related to the outcome of infection as well as the clinical form observed (C) 2010 American Society for Histocompatibility and Immunogenetics Published by Elsevier Inc All rights reserved

Patients with oral squamous cell carcinoma are characterized by increased frequency of suppressive regulatory T cells in the blood and tumor microenvironment

Oral squamous cell carcinoma (OSCC) is a cancerous lesion with high incidence worldwide. The immunoregulatory events leading to OSCC persistence remain to be elucidated. Our hypothesis is that regulatory T cells (Tregs) are important to obstruct antitumor immune responses in patients with OSCC. In the present study, we investigated the frequency, phenotype, and activity of Tregs from blood and lesions of patients with OSCC. Our data showed that > 80% of CD4(+)CD25(+) T cells isolated from PBMC and tumor sites express FoxP3. Also, these cells express surface Treg markers, such as GITR, CD45RO, CD69, LAP, CTLA-4, CCR4, and IL-10. Purified CD4(+)CD25(+) T cells exhibited stronger suppressive activity inhibiting allogeneic T-cell proliferation and IFN-gamma production when compared with CD4(+)CD25(+) T cells isolated from healthy individuals. Interestingly, approximately 25% of CD4(+)CD25(-) T cells of PBMC from patients also expressed FoxP3 and, although these cells weakly suppress allogeneic T cells proliferative response, they inhibited IFN-gamma and induced IL-10 and TGF-beta secretion in these co-cultures. Thus, our data show that Treg cells are present in OSCC lesions and PBMC, and these cells appear to suppress immune responses both systemically and in the tumor microenvironment.

Auditory steady state response in pediatric audiology

The main issue regarding pediatric audiology diagnosis is determining procedures to configure reliable results which can be used to predict frequency-specific hearing thresholds. Aim: To investigate the correlation between auditory steady-state response (ASSR) with other tests in children with sensorineural hearing loss. Methods: Prospective cross-sectional contemporary cohort study. Twenty-three children (ages 1 to 7; mean, 3 years old) were submitted to ASSR, behavioral audiometry, click audiometry brain stem response (ABR), tone burst ABR, and predicting hearing level from the acoustic reflex. Results: the correlation between behavioral thresholds and ASSR was (0.70- 0.93), for the ABR tone burst it was (0.73 -0.93), for the ABR click it was (0.83-0.89) only at 2k and 4 kHz. The match between the ASSR and the hearing threshold prediction rule was considered moderate. Conclusion: there was a significant correlation between the ASSR and audiometry, as well as between ABR click (2k and 4 kHz) and for the ABR tone burst. The acoustic reflex can be used to add information to diagnosis in children.

Remote probe microphone measurement to verify hearing aid performance

We assessed the feasibility of obtaining probe microphone measurements of hearing aids at a distance. Face-to-face and remote probe microphone measurements were carried out in 60 hearing aid users (mean age 67 yrs) with uni- or bilateral hearing losses (105 ears tested). The participant and a facilitator were located in a room equipped with a probe microphone system interfaced to a PC. Desktop videoconferencing and application sharing was used to allow an audiologist in another room to instruct the facilitator and control the equipment via the LAN. There were significant correlations between face-to-face and remote real ear unaided response (REUR), aided response (REAR) and insertion gain (REIG) at seven discrete frequencies from 250 to 6000 Hz. Differences between face-to-face and remote responses were within the reported variability for probe microphone measurements themselves. The results show that remote probe microphone measurements are feasible and might improve the quality of public hearing aid services and professional training in Brazil.

Functional development of the inferior colliculus (IQ and its relationship with the auditory brainstem response (ABR) in the tammar wallaby (Macropus eugenii)

To discover the developmental relationship between the auditory brainstem response (ABR) and the focal inferior colliculus (IC) response, 32 young tammar wallabies were used, by the application of simultaneous ABR and focal brainstem recordings, in response to acoustic clicks and tone bursts of seven frequencies. The ic or the tammar wallaby undergoes a rapid functional development from postnatal day (PND) 114 to 160. The earliest (PND 114) auditory evoked response was recorded from the rostral IC. With development, more caudal parts of the IC became functional until age about PND 127, when all parts of the IC were responsive to sound. Along a dorsoventral direction, the duration of the IC response decreased, the peak latency shortened, while the amplitude increased, reaching a maximum value at the central IC, then decreased. After PND 160, the best frequency (BF) of the ventral IC was the highest, with values between 12.5 and 16 kHz, the BF of the dorsal IC was the lowest, varying between 3.2 and 6.4 kHz, while the BF of the central IC was between 6.4 and 12.5 kHz. Between PND 114 and 125, the IC response did not have temporal correlation with the ABR. Between PND 140 and 160, only the early components of the responses from the ventral and central IC correlated with the P4 waves of the ABR. After PND 160, responses recorded from different depths of the IC had a temporal correlation with the ABR. (C) 2001 Published by Elsevier Science B.V.

Assessment of body composition by bioelectrical impedance analysis without the need for measurement of height

Conventional whole-body single frequency bioelectrical impedance analysis (BIA) of body composition typically uses height as a surrogate measure of conductor length. A new method of BIA analysis for the prediction of body cell mass (BCM) and extracellular water (ECW, as % body weight) not using height has been introduced-the Soft Tissue Analyser (STA(TM), Akern Sri, Florence, Italy)-making it ideal for use in subjects where measurement of height is difficult or impossible. The performance of the new analytical method in predicting BCM and ECW in 139 normal control subjects was assessed by comparison with reference data obtained from a four-component (4-C) model of body composition and with predictions obtained from conventional BIA analysis. Both predicted BCM and ECW were strongly (r = 0.82, SEE = 6.3 kg and 0.89, SEE = 1.3 kg respectively) correlated with the corresponding 4-C model measurements although differing significantly from the lines of identity (P < 0.0001). Fat-free mass, calculated from STA estimates of BCM and ECW, was better predicted (r = 0.91, SEE = 5.6 kg). The significant differences in STA-group mean values for BCM and ECW and wide limits of agreement compared with the reference data indicate that the method cannot be used with confidence for prediction of these body compartments despite the obvious advantage of not requiring an accurate measurement of height. (C) 2001 Harcourt Publishers Ltd.