The role of interleukin-6, endothelins, and apoptotic genes in small bowel transplantation, in a swine model of ischemia and reperfusion injury

IRI is closely related to sepsis in ITx setting. Complete understanding of the mechanisms involved in IRI development may improve outcomes. Ortothopic ITx without immunosuppression was performed in order to characterize IRI-associated mucosal damage. Twenty pigs underwent ITx. Two groups were assigned to different CI times: G1: 90 min and, G2: 180 min. Euro-Collins was used as preservation solution. Jejunal fragments were collected at donor laparotomy, 30 min, and 3 days after reperfusion. IRI assessment involved: histopathologic analysis, quantification of MPO-positive cells through immunohistochemical studies, quantification of epithelial apoptotic cells using TUNEL staining, and quantification of IL-6, ET-1, Bak, and Bcl-XL genes expression by RT-PCR. Neutrophilic infiltration increased in a similar fashion in both groups, but lasted longer in G2. Apoptosis detected by TUNEL staining increased and anti-apoptotic gene Bcl-XL expression decreased significantly in G1, 3 days after surgery. Endothelin-1 and IL-6 genes expression increased 30 min after the procedure and returned to baseline 3 days after surgery. In conclusion, IL-6 and ET-1 are involved precociously in the development of intestinal IRI. Apoptosis was more frequently detected in G1 grafts by TUNEL-staining and by RT-PCR.

A Dynamic Model of Hand-and-Foot Syndrome in Patients Receiving Capecitabine

For the purpose of developing a longitudinal model to predict hand-and-foot syndrome (HFS) dynamics in patients receiving capecitabine, data from two large phase III studies were used. Of 595 patients in the capecitabine arms, 400 patients were randomly selected to build the model, and the other 195 were assigned for model validation. A score for risk of developing HFS was modeled using the proportional odds model, a sigmoidal maximum effect model driven by capecitabine accumulation as estimated through a kinetic-pharmacodynamic model and a Markov process. The lower the calculated creatinine clearance value at inclusion, the higher was the risk of HFS. Model validation was performed by visual and statistical predictive checks. The predictive dynamic model of HFS in patients receiving capecitabine allows the prediction of toxicity risk based on cumulative capecitabine dose and previous HFS grade. This dose-toxicity model will be useful in developing Bayesian individual treatment adaptations and may be of use in the clinic.

Complete Clinical Response After Neoadjuvant Chemoradiation Therapy for Distal Rectal Cancer: Characterization of Clinical and Endoscopic Findings for Standardization

BACKGROUND: Complete tumor regression may develop after neoadjuvant chemoradiation therapy for distal rectal cancer. Studies have suggested that selected patients with complete clinical response may avoid radical surgery and close surveillance may provide good outcomes with no oncologic compromise. However, definition of complete clinical response is often imprecise and may vary between different studies. The aim of this study is to provide a clear definition for a complete clinical response after neoadjuvant chemoradiation therapy in patients with distal rectal cancer in addition to actual endoscopic videos from patients managed nonoperatively. METHODS: Patients with nonmetastatic distal rectal cancer treated by neoadjuvant chemoradiation therapy, including 50.4 Gy and concomitant 5-fluorouracil and leucovorin, were assessed for tumor response at least 8 weeks after chemoradiation therapy completion. Complete and incomplete clinical responses were defined based on clinical and endoscopic findings. Patients with complete clinical response were not immediately operated on and were closely followed. Early and late endoscopic findings were recorded. RESULTS: Definition of a complete clinical response should be based on very strict clinical and endoscopic criteria. The finding of any residual superficial ulceration, irregularity, or nodule should prompt surgical attention, including transanal full-thickness excision or even a radical resection with total mesorectal excision. Standard or incisional biopsies should be avoided in this setting. Complete clinical responders should harbor no more than whitening of the mucosa, teleangiectasia with mucosal integrity to be considered for a nonoperative approach. In the presence of these findings, regularly scheduled reassessments may provide a safe alternative to these patients with early detection of recurrent disease. CONCLUSION: Strict definition of the clinical and endoscopic findings of patients experiencing complete clinical response after neoadjuvant chemoradiation therapy may provide a useful tool for the understanding of outcomes of patients managed with no immediate surgery allowing standardization of classifications and comparison between the experiences of different institutions.

Leptospirosis pulmonary haemorrhage syndrome is associated with linear deposition of immunoglobulin and complement on the alveolar surface

Leptospirosis is a zoonotic infection associated with severe diseases such as leptospirosis pulmonary haemorrhage syndrome (LPHS). The cause of pulmonary haemorrhage is unclear. Understanding which mechanisms and processes are involved in LPHS will be important in treatment regimens under development for this life-threatening syndrome. In the present study, we evaluated 30 lung specimens from LPHS patients and seven controls using histology and immunohistochemistry (detection of IgM, IgG, IgA and C3) in order to describe the pathological features associated with this syndrome. Immunoglobulin deposits were detected on the alveolar surface in 18/30 LPHS patients. Three staining patterns were observed for the immunoglobulins and C3 in the lung tissues of LPHS patients: AS, delicate linear staining adjacent to the alveolar surface, which was indicative of a membrane covering the luminal surface of type I and II pneumocyte cells; S, heterogeneous staining which was sporadically distributed along the alveolar septum; and IA, weak, focal intra-alveolar granular staining. Human LPHS is associated with individual and unique histological patterns that differ from those of other causes of pulmonary haemorrhage. In the present study, it was found that the linear deposition of immunoglobulins (IgA, IgG and IgM) and complement on the alveolar surface may play a role in the pathogenesis of pulmonary haemorrhage in human leptospirosis.

Transvaginal ultrasonography with bowel preparation is able to predict the number of lesions and rectosigmoid layers affected in cases of deep endometriosis, defining surgical strategy

Successful surgical treatment of deep bowel endometriosis depends on obtaining detailed information about the lesions, prior to the procedure. The objective of this study was to determine the capability of transvaginal ultrasonography with bowel preparation (TVUS-BP) to predict the presence of one or more rectosigmoid nodules and the deepest bowel layer affected by the disease. A prospective study of 194 patients with clinical and TVUS-BP suspected deep endometriosis submitted to videolaparoscopy. Image data were compared with surgical and histological results. With respect to bowel nodule detection and presence of at least two rectosigmoid lesions, TVUS-BP had a sensitivity of 97 and 81%, specificity 100 and 99%, positive predictive value (PPV) 100 and 93% and negative predictive value (NPV) 98 and 96%, respectively. Regarding diagnosis of infiltration of the submucosal/mucosal layer, TVUS-BP had a sensitivity of 83%, specificity 94%, PPV 77%, NPV 96%. These findings show that TVUS-BP is an adequate exam for evaluating the presence of one or more rectosigmoid nodules and the deepest layer affected in deep infiltrating bowel endometriosis, confirming the importance of this technique for defining the most appropriate surgical strategy to be implemented.

CpG-Induced Th1-Type Response in the Downmodulation of Early Development of Allergy and Inhibition of B7 Expression on T Cells of Newborn Mice

Several differences have been described between neonatal and adult immune responses. The predisposition in early life to Th2-type response or tolerance makes it a susceptible period for infections and allergic sensitization. The aim of this work was to evaluate the effects of CpG-containing oligodeoxynucleotides on neonatal and adult immunization with ovalbumin and Blomia tropicalis extract and compare the CpG effects on B and T cells of neonatal and adult mice. Mice that received CpG showed reduced immunoglobulin E (IgE) antibody production in both neonatal and adult periods, in parallel to increased IgG2a antibody levels. We observed that spleen cells of mice that received CpG in early life produced increased amounts of interferon-gamma upon anti-CD3 stimulation. Negative regulation of IgE response was more pronounced in adult than neonate mice; further, CpG decreased anaphylactic antiovalbumin IgG1 only in adults. Also, an upregulation of toll-like receptor 9 expression was detected in adult B cells, but not in neonatal, upon CpG stimuli. Neonatal B cells showed enhanced interleukin (IL)-10 expression and decreased IL-6 levels than adult B cells in response to CpG. When we analyzed in vitro activation of CD4+ T cells, an increased expression of B7 molecules on T cells in neonates was suppressed by CpG. Altogether, we verified qualitative and quantitative evidences regarding CpG effect on neonatal and adult allergens immunizations, which points to the importance of understanding neonatal immune system to establish immunomodulatory strategies for prevention of allergic diseases.

Acute Cardiovascular and Inflammatory Toxicity Induced by Inhalation of Diesel and Biodiesel Exhaust Particles

Analysis of fuel emissions is crucial for understanding the pathogenesis of mortality because of air pollution. The objective of this study is to assess cardiovascular and inflammatory toxicity of diesel and biodiesel particles. Mice were exposed to fuels for 1 h. Heart rate (HR), heart rate variability, and blood pressure were obtained before exposure, as well as 30 and 60 min after exposure. After 24 h, bronchoalveolar lavage, blood, and bone marrow were collected to evaluate inflammation. B100 decreased the following emission parameters: mass, black carbon, metals, CO, polycyclic aromatic hydrocarbons, and volatile organic compounds compared with B50 and diesel; root mean square of successive differences in the heart beat interval increased with diesel (p < 0.05) compared with control; low frequency increased with diesel (p < 0.01) and B100 (p < 0.05) compared with control; HR increased with B100 (p < 0.05) compared with control; mean corpuscular volume increased with B100 compared with diesel (p < 0.01), B50, and control (p < 0.001); mean corpuscular hemoglobin concentration decreased with B100 compared with B50 (p < 0.001) and control (p < 0.05); leucocytes increased with B50 compared with diesel (p < 0.05); platelets increased with B100 compared with diesel and control (p < 0.05); reticulocytes increased with B50 compared with diesel, control (p < 0.01), and B100 (p < 0.05); metamyelocytes increased with B50 and B100 compared with diesel (p < 0.05); neutrophils increased with diesel and B50 compared with control (p < 0.05); and macrophages increased with diesel (p < 0.01), B50, and B100 (p < 0.05) compared with control. Biodiesel was more toxic than diesel because it promoted cardiovascular alterations as well as pulmonary and systemic inflammation.

Comparative study of pressure- and volume-controlled ventilation on pulse pressure variation in a model of hypovolaemia in rabbits

Background and objective: Dynamic indices represented by systolic pressure variation and pulse pressure variation have been demonstrated to be more accurate than filling pressures in predicting fluid responsiveness. However, the literature is scarce concerning the impact of different ventilatory modes on these indices. We hypothesized that systolic pressure variation or pulse pressure variation could be affected differently by volume-controlled ventilation and pressure-controlled ventilation in an experimental model, during normovolaemia and hypovolaemia. Method: Thirty-two anaesthetized rabbits were randomly allocated into four groups according to ventilatory modality and volaemic status where G1-ConPCV was the pressure-controlled ventilation control group, G2-HemPCV was associated with haemorrhage, G3-ConVCV was the volume-controlled ventilation control group and G4-HemVCV was associated with haemorrhage. In the haemorrhage groups, blood was removed in two stages: 15% of the estimated blood volume withdrawal at M1, and, 30 min later, an additional 15% at M2. Data were submitted to analysis of variance for repeated measures; a value of P < 0.05 was considered to be statistically significant. Results: At MO (baseline), no significant differences were observed among groups. At M1, dynamic parameters differed significantly among the control and hypovolaemic groups (P < 0.05) but not between ventilation modes. However, when 30% of the estimated blood volume was removed (M2), dynamic parameters became significantly higher in animals under volume-controlled ventilation when compared with those under pressure-controlled ventilation. Conclusions: Under normovolaemia and moderate haemorrhage, dynamic parameters were not influenced by either ventilatory modalities. However, in the second stage of haemorrhage (30%), animals in volume-controlled ventilation presented higher values of systolic pressure variation and pulse pressure variation when compared with those submitted to pressure-controlled ventilation.

Carios mimon (Acari: Argasidae): description of adults and redescription of larva

Carios mimon is an argasid tick common on Chiroptera, originally described from larvae collected on bats Mimon crenulatum from Bolivia and Eptesicus brasiliensis from Uruguay. Later it was also registered from Argentina and recently included among the Brazilian tick fauna. In Brazil, this species is very aggressive to man, resulting in intense inflammatory response and pain. It is known only by the larval description and its morphology resembles that from other species currently included into the genus Carios, formerly classified into the subgenus Alectorobius, genus Ornithodoros. Here we describe adults and redescribe the larva of C. mimon, based on light and scanning electron microscopy. Remarks about its morphological similarity with other species of this genus are also discussed. Molecular analysis inferred from a portion of the 16S rRNA mitochondrial gene placed C. mimon in a cluster supported by maximal bootstrap value (100%) with other argasid species (mostly bat parasites in the New World), which have been classified into either the genus Ornithodoros or Carios, depending on the Argasidae classification adopted by different authors.

A Comparison of the Home Range Sizes of Mainland and Island Populations of Black-Faced Lion Tamarins (Leontopithecus caissara) Using Different Spatial Analysis

The critically endangered black-faced lion tamarin, Leontopithecus caissara, has a restricted geographical distribution consisting of small mainland and island populations, each with distinct habitats in coastal southeastern Brazil. Necessary conservation management actions require an assessment of whether differences in habitats are reflected in use of space by the species. We studied two tamarin groups on the mainland at Sao Paulo state between August 2005 and March 2007, and compared the results with data from Superagui Island. Three home range estimators were used: minimum convex polygon (MCP), Kernel, and the new technique presented dissolved monthly polygons (DMP). These resulted, respectively, in home ranges of 345, 297, and 282 ha for the 12-month duration of the study. Spatial overlap of mainland groups was extensive, whereas temporal overlap was not, a pattern that indicates resource partitioning is an important strategy to avoid intraspecific competition. L. caissara large home ranges seem to be dynamic, with constant incorporation of new areas and abandonment of others through time. The main difference between mainland and island groups is the amount and variety of sleeping sites. A better understanding of the home range sizes, day range lengths, and territorial behavior of this species will aid in developing better management strategies for its protection. Additionally, the presented DMP protocol is a useful improvement over the MCP method as it results in more realistic home range sizes for wildlife species. Am. J. Primatol. 73: 1114-1126, 2011. (C) 2011 Wiley Periodicals, Inc.

Development and validation of nested-PCR for the diagnosis of clinical and subclinical infectious laryngotracheitis

A standardised nested-PCR method that amplifies a region of the glycoprotein E gene of avian infectious laryngotracheitis virus (ILTV) has been developed for the diagnosis of infection by Gallid herpesvirus 1. The two sets of primers employed produced the expected ampIification products of 524bp(externa I primers) and 219bp (internal primers) in the presence of ILTV DNA, whereas no Such amplicons were obtained with other avian respiratory pathogens or with DNA extracted from the cells of uninfected chickens. The identity of the 219bp amplified product was con firmed by DNA sequencing. The standardised nested-PCR method detected ILTV DNA from trachea, lung, conjunctiva and trigeminal ganglia samples from flocks of birds with and without clinical signs. and showed hi.-h sensitivity (95.4%) and specificity (93.1%) when compared with the reference test involving virus isolation in specific-pathogen-free chicken embryos. The standardised nested-PCR method described may be used to detect clinical and latent ILTV infections, and will be of significant value for both diagnostic and epidemiological Studies. (c) 2008 Elsevier B.V. All rights reserved.

Evaluation of pH and Calcium Ion Release of Root-end Filling Materials Containing Calcium Hydroxide or Mineral Trioxide Aggregate

Introduction: To evaluate calcium ion release and pH of Sealer 26 (S26) (Dentsply, Rio de Janeiro, RJ, Brazil), white mineral trioxide aggregate (MTA), Endo CPM Sealer (CPM1) (EGEO SRL Bajo licencia MTM Argentina SA, Buenos Aires, Argentina), Endo CPM Sealer in a thicker consistency (CPM 2), and zinc oxide and eugenol cement (ZOE). Methods: Material samples (n = 10) were placed in polyethylene tubes and immersed in 10 mL of distilled water. After 3, 6,12,24, and 48 hours and 7,14, and 28 days, the water pH was determined with a pH meter, and calcium release was assessed by atomic absorption spectrophotometry. An empty tube was used as the control group. Results: The control group presented a pH value of 6.9 at all studied periods and did not show the presence of calcium ion. S26 presented greater hydroxyl ion release up to 12 hours (p < 0.05). From 24 hours until 28 days, S26, MTA, CPM1, and CPM2 had similar results. in ail periods, ZOE presented the lowest hydroxyl ion release. CPM1, followed by CPM2, released the most calcium ions until 24 hours (p < 0.05). Between 48 hours and 7 days, CPM1 and CPM2 had the highest release. A greater calcium ion release was observed for CPM2, followed by CPM1 at 14 days and for S26, CPM1, and CPM2 at 28 days. ZOE released the least calcium ions in all periods. Conclusion: Sealer 26, MTA, and Endo CPM sealer at normal or thicker consistency release hydroxyl and calcium ions. Endo CPM sealer may be an alternative as root-end filling material. (J Endod 2009;35:1418-1421)

Bleaching Agents with Varying Concentrations of Carbamide and/or Hydrogen Peroxides: Effect on Dental Microhardness and Roughness

To evaluate the effect of low and highly concentrated bleaching agents on microhardness and surface roughness of bovine enamel and root dentin. According to a randomized complete block design, 100 specimens of each substrate were assigned into five groups to be treated with bleaching agents containing carbamide peroxide (CP) at 10% (CP10); hydrogen peroxide (HP) at 7.5% (HP7.5) or 38% (HP38), or the combination of 18% of HP and 22% of CP (HP18/CP22), for 3 weeks. The control group was left untreated. Specimens were immersed in artificial saliva between bleaching treatments. Knoop surface microhardness (SMH) and average surface roughness (Ra) were measured at baseline and post-bleaching conditions. For enamel, there were differences between bleaching treatments for both SMH and Ra measurements (p = 0.4009 and p = 0.7650, respectively). SMH significantly increased (p < 0.0001), whereas Ra decreased (p = 0.0207) from baseline to post-bleaching condition. For root dentin, the group treated with CP10 exhibited the significantly highest SMH value differing from those groups bleached with HP18/CP22, HP7.5, which did not differ from each other. Application of HP38 resulted in intermediate SMH values. No significant differences were found for Ra (p = 0.5975). Comparing the baseline and post-bleaching conditions, a decrease was observed in SMH (p < 0.0001) and an increase in Ra (p = 0.0063). Bleaching agents with varying concentrations of CP and/or HP are capable of causing mineral loss in root dentin. Enamel does not perform in such bleaching agent-dependent fashion when one considers either hardness or surface roughness evaluations. Bleaching did not alter the enamel microhardness and surface roughness, but in root dentin, microhardness seems to be dependent on the bleaching agent used.