Cannabis use before age 15 and subsequent executive functioning

Background Many studies have suggested that adolescence is a period of particular vulnerability to neurocognitive effects associated with substance misuse. However, few large studies have measured differences in cognitive performance between chronic cannabis users who started in early adolescence (before age 15) with those who started later. Aims To examine the executive functioning of individuals who started chronic cannabis use before age 15 compared with those who started chronic cannabis use after 15 and controls. Method We evaluated the performance of 104 chronic cannabis users (49 early-onset users and 55 late-onset users) and 44 controls who undertook neuropsychological tasks, with a focus on executive functioning. Comparisons involving neuropsychological measures were performed using generalised linear model analysis of variance (ANOVA). Results The early-onset group showed significantly poorer performance compared with the controls and the late-onset group on tasks assessing sustained attention, impulse control and executive functioning. Conclusions Early-onset chronic cannabis users exhibited poorer cognitive performance than controls and late-onset users in executive functioning. Chronic cannabis use, when started before age 15, may have more deleterious effects on neurocognitive functioning.

The involvement of CD4(+)CD25(+) T cells in the acute phase of Trypanosoma cruzi infection

The infection with Trypanosoma cruzi leads to a vigorous and apparently uncontrolled inflammatory response in the heart. Although the parasites trigger specific immune response, the infection is not completely cleared out, a phenomenon that in other parasitic infections has been attributed to CD4(+)CD25(+) T cells (Tregs). Then, we examined the role of natural Tregs and its signaling through CD25 and GITR in the resistance against infection with T. cruzi. Mice were treated with mAb against CD25 and GITR and the parasitemia, mortality and heart pathology analyzed. First, we demonstrated that CD4(+)CD25(+)GITR(+)Foxp3(+) T cells migrate to the heart of infected mice. The treatment with anti-CD25 or anti-GITR resulted in increased mortality of these infected animals. Moreover, the treatment with anti-GITR enhanced the myocarditis, with increased migration of CD4(+), CD8(+), and CCR5(+) leukocytes, TNF-alpha production, and tissue parasitism, although it did not change the systemic nitric oxide synthesis. These data showed a limited role for CD25 signaling in controlling the inflammatory response during this protozoan infection. Also, the data suggested that signaling through GITR is determinant to control of the heart inflammation, parasite replication, and host resistance against the infection. (C) 2008 Elsevier Masson SAS. All rights reserved.

Multiplex semi-nested RT-PCR with exogenous internal control for simultaneous detection of bovine coronavirus and group A rotavirus

Neonatal calf diarrhea is a multi-etiology syndrome of cattle and direct detection of the two major agents of the syndrome, group A rotavirus and Bovine coronavirus (BCoV) is hampered by their fastidious growth in cell culture. This study aimed at developing a multiplex semi-nested RT-PCR for simultaneous detection of BCoV (N gene) and group A rotavirus (VP1 gene) with the addition of an internal control (mRNA ND5). The assay was tested in 75 bovine feces samples tested previously for rotavirus using PAGE and for BCoV using nested RT-PCR targeted to RdRp gene. Agreement with reference tests was optimal for BCoV (kappa = 0.833) and substantial for rotavirus detection (kappa = 0.648). the internal control, ND5 mRNA, was detected successfully in all reactions. Results demonstrated that this multiplex semi-nested RT-PCR was effective in the detection of BCoV and rotavirus, with high sensitivity and specificity for simultaneous detection of both viruses at a lower cost, providing an important tool for studies on the etiology of diarrhea in cattle. (C) 2010 Elsevier B.V. All rights reserved.

Reproductive toxic effects of Tityus serrulatus scorpion venom in rats

Tityus serrulatus is the most venomous scorpion in Brazil. Little is known about the effect of maternal exposure to the venom on fetal development. We investigated the effect of low to moderate doses of the venom (0.3 or 1.0 mg/kg s.c. on either day 5 or day 10 of gestation) on pregnant rats and on their offspring. For dams, we observed their body weight gain and reproductive parameters. For the offspring, we observed their body weight and weight of internal organs and the number of live and dead fetuses, and we investigated whether the venom caused external, visceral, skeletal or histopathological alterations in the offspring. The offspring were examined on gestational day 21. Injection of the venom on gestational day 5 did not change the reproductive parameters of the dams, their weight or fetuses` weight. Rats that received the high dose of the venom (1.0 mg/kg) on gestational day 10 had heavier placentas and heavier fetuses with heavier lungs. Injections on day 10 of gestation did not alter the reproductive parameters of the dams nor their weight gain at either dose. The venom did not cause malformations of the fetal skeleton or viscera and did not delay fetal development with either dose. In conclusion, subcutaneous administration of 0.3 or 1.0 mg/kg T. serrulatus venom to pregnant Wistar rats at either day 5 or day 10 of gestation did not cause maternal or clear fetal toxicity. Subtle increases in placental weight and fetal body and lung weights observed following treatment with 1.0 mg/kg on day 10 of gestation were not associated with histopathological findings. Whether these observations represent a reaction to treatment and, if so, the underlying mechanisms and their toxicological impact remain to be examined further in future studies. (C) 2008 Elsevier Inc. All rights reserved.

Histopathology of the Hematopoietic Bone Marrow in the Temporomandibular Joint of Rats Subjected to Undernutrition and to Mandibular Condyle Fracture

Undernutrition can cause important functional and morphological alterations in the hematopoietic bone marrow (HBM). Degeneration of the HBM in malnourished individuals has been observed in the long bones, but none has been described in the cranial bones. Mandibular condyle fracture can lead to determine nutritional effects due to the high catabolism needed for the bone healing added to the difficulties of mastication. The aim of this study is to describe the histological aspect of HBM in the fractured mandibular condyle and in the temporal bone of malnourished rats. Thirty adult rats suffered unilateral mandibular condyle fracture and were divided into well-nourished (FG) and malnourished (MG) groups. In the MG the animals received a hypoproteic diet during the experiment. Histological sections of the temporomandibular joint were stained to visualize and quantify the HBM in this region at 24h, and 7, 15, 30, and 90 days post-fracture. At 24 hours, FG and MG showed hypocellularity and ischemic degeneration in the mandibular condyle and in the temporal bone. At 7 days, FG exhibited high cellularity in comparison with MG in the condyle; the temporal bone of both groups presented hypocellularity and degeneration. At 30 and 90 days, FG exhibited similar characteristics to those of the control; MG maintained the degeneration level mainly in the temporal bone. Malnutrition prejudices the regeneration of the HBM during a fracture healing in the temporomandibular joint. This fact contributes to a complete modification of the bone structure as well as to an impairment of the healing process.

Effect of laser phototherapy on recurring herpes labialis prevention: an in vivo study

Alternative treatment for recurrent labial infection by herpes simplex virus (HSV) have been considered. The aim of this study was to evaluate the effectiveness of laser phototherapy in prevention and reduction of severity of labial manifestations of herpes labialis virus. Seventy-one patients, divided into experimental (n = 41) and control (n = 30) groups were followed up for 16 months. Patients in the control group were treated topically with aciclovir and patients in the experimental group were subjected to laser phototherapy (one session per week, 10 weeks): 780 nm, 60 mW, 3.0 J/cm(2) or 4.5 J/cm(2) on healthy (no HSV-1 infection) and affected (with HSV-1 infection) tissues. Patients in the experimental group presented a significant decrease in dimension of herpes labialis lesions (P = 0.013) and inflammatory edema (P = 0.031). The reduction in pain level (P = 0.051) and monthly recurrences (P = 0.076) did not reach statistical significance. This study represents an in vivo indication that this treatment should be further considered as an effective alternative to therapeutic regimens for herpes labialis lesions.

Use of laser phototherapy on a delayed wound healing of oral mucosa previously submitted to radiotherapy: case report

Radiotherapy produces both acute and delayed effects on mucosal tissues, disturbing their healing. This report shows a successful treatment with laser phototherapy (LPT) on a delayed wound healing in oral mucosa previously submitted to radiotherapy with a follow up of 3 years. A 47-year-old patient treated 6 months earlier for tongue squamous cell carcinoma by surgery and radiotherapy presented with a mass in the operated area. Biopsy showed chronic inflammatory infiltrate around a residual polyglactin suture. After 2 months there was a painful mucosal dehiscence on the biopsy site. LPT was performed using a semiconductor laser with 660-nm wavelength (InGaAlP) and spot size of 0.04 cm(2). The parameters applied were 40 mW, 4 Jcm(2)/point, 0.16 J/point, 2.4 J/session. The irradiation was performed punctually, through contact mode in 15 points (4 seconds/point), on top of and around the lesion, during ten sessions. The wound healed completely after ten sessions. This treatment proved to be conservative and effective, inducing healing of a chronic wound in a tissue previously submitted to radiotherapy.

Comparison of dentin root canal permeability and morphology after irradiation with Nd:YAG, Er:YAG, and diode lasers

The aim of this study was to compare the effects of Nd:YAG, Er:YAG, and diode lasers on the morphology and permeability of root canal walls. The three laser wavelengths mentioned interact differently with dentin and therefore it is possible that the permeability changes caused will determine different indications during endodontic treatment. Twenty-eight human single-rooted teeth were instrumented up to ISO 40 and divided into four groups: group C, control (GC), non-laser irradiated; group N (GN), irradiated with Nd:YAG laser; group E (GE), with Er:YAG laser and group D (GD) with diode laser. After that, the roots were filled with a 2% methylene blue dye, divided into two halves and then photographed. The images were analyzed using Image J software and the percentage of dye penetration in the cervical, middle, and apical root thirds were calculated. Additional scanning electron microscopy (SEM) analyses were also performed. The analysis of variance (ANOVA) showed significant permeability differences between all groups in the middle and cervical thirds (p < 0.05). The Tukey test showed that in the cervical third, GN presented means of dye penetration statistically significantly lower than all of the other groups. In the middle third, GE and GD showed statistically higher dye penetration means than GC and GN. SEM analysis showed melted surfaces for GN, clean wall surfaces with open dentinal tubules for GE, and mostly obliterated dentinal tubules for GD. Er:YAG (2,094 nm) laser and diode laser (808 nm) root canal irradiation increase dentinal permeability and Nd:YAG (1,064 nm) laser decreases dentin permeability, within the studied parameters.

Effect of the microstructure on the lifetime of dental ceramics

Objectives. To evaluate the effect of the microstructure on the Weibull and slow crack growth (SCG) parameters and on the lifetime of three ceramics used as framework materials for fixed partial dentures (FPDs) (YZ - Vita In-Ceram YZ; IZ - Vita In-Ceram Zirconia; AL - Vita In-Ceram AL) and of two veneering porcelains (VM7 and VM9). Methods. Bar-shaped specimens were fabricated according to the manufacturer`s instructions. Specimens were tested in three-point flexure in 37 degrees C artificial saliva. Weibull analysis (n = 30) and a constant stress-rate test (n = 10) were used to determine the Weibull modulus (m) and SCG coefficient (n), respectively. Microstructural and fractographic analyzes were performed using SEM. ANOVA and Tukey`s test (alpha = 0.05) were used to statistically analyze data obtained with both microstructural and fractographic analyzes. Results. YZ and AL presented high crystalline content and low porosity (0.1-0.2%). YZ had the highest characteristic strength (sigma(0)) value (911 MPa) followed by AL (488 MPa) and IZ (423 MPa). Lower sigma(0) values were observed for the porcelains (68-75 MPa). Except for IZ and VM7, m values were similar among the ceramic materials. Higher n values were found for YZ (76) and AL (72), followed by IZ (54) and the veneering materials (36-44). Lifetime predictions showed that YZ was the material with the best mechanical performance. The size of the critical flaw was similar among the framework materials (34-48 mu m) and among the porcelains (75-86 mu m). Significance. The microstructure influenced the mechanical and SCG behavior of the studied materials and, consequently, the lifetime predictions. (C) 2011 Academy of Dental Materials. Published by Elsevier Ltd. 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.

Enhanced programmed death 1 (PD-1) and PD-1 ligand (PD-L1) expression in patients with actinic cheilitis and oral squamous cell carcinoma

PD-1 and PD-L1 can be involved in tumor escape, and little is known about the role of these molecules in oral tumors or pre-malignant lesions. In the present study, we investigated the expression of PD-1 and PD-L1 in the blood and lesion samples of patients with actinic cheilitis (AC) and oral squamous cell carcinoma (OSCC). Our results showed that lymphocytes from peripheral blood and tissue samples exhibited high expression of PD-1 in both groups analyzed. Patients with AC presented higher percentage as well as the absolute numbers of CD4(+)PD-1(+) and CD8(+)PD-1(+) lymphocytes in peripheral blood mononuclear cells (PBMC) than healthy individuals, while patients with OSCC presented an increased frequency of CD8(+)PD1(+) in PBMC when compared with controls. On the other hand, increased frequency of CD4(+) and CD8(+) T cells expressing PD-1(+) accumulate in samples from OSCC, and the expression of PD-L1 was intense in OSCC and moderate in AC lesion sites. Lower levels of IFN-gamma and higher levels of TGF-beta were detected in OSCC samples. Our data demonstrate that PD-1 and PD-L1 molecules are present in blood and samples of AC and OSCC patients. Further studies are required to understand the significance of PD-1 and PD-L1 in oral tumors microenvironment.

CCR5-dependent regulatory T cell migration mediates fungal survival and severe immunosuppression

Paracoccidioidomycosis, a debilitating pulmonary mycosis, is caused by the dimorphic fungus Paracoccidioides brasiliensis. The infection results in the formation of granulomas containing viable yeast cells that are the fungal sources for disease reactivation. Because CD4(+)CD25(+) regulatory T cells (Tregs) are in the lesions of patients with paracoccidioidomycosis, the migration of Treg cells is dependent on the axis chemokine-chemokine receptors, and CCR5 ligands are produced in P. brasiliensis-induced lesions, we investigated the role of CCR5 in the control of the infection. The results showed that CCR5(-/-) mice are more efficient in controlling fungal growth and dissemination and exhibited smaller granulomas than wild-type (WT) mice. In the absence of CCR5, the percentage of CD4(+)CD25(+) T cells expressing Foxp3, glucocorticoid-induced TNFR (GITR), CD103, CD45(low), and CTLA-4 in the granulomas was significantly decreased. Interestingly, P. brasiliensis infection resulted in an absence of T cell proliferation in response to Con A in WT but not CCR5(-/-) mice that was abrogated by anti-CTLA-4 mAb and anti-GITR mAb. Moreover, the adoptive transfer of CD4(+)CD25(+) but not CD4(+)CD25(-) T cells from infected WT to infected CCR5(-/-) mice resulted in a significant increase in fungal load. Overall, CCR5 is a key receptor for the migration of Treg cells to the site of P. brasiliensis infections leading to down-modulation of effector immune response and the long-term presence of the fungus in the granulomas. Thus, a tight control of Treg cell migration to the granulomatous lesions could be an important mechanism for avoiding exacerbation and reactivation of the disease.

Dental caries status and salivary properties of asthmatic children and adolescents

Aims. This study aimed to investigate the dental caries status and salivary properties in 3- to 15-year-old children/adolescents. Methods. The sample was split in two groups: asthma group (AG), composed of 65 patients who attended Public Health Service; asthma-free group (AFG), composed of 65 nonasthmatic children/adolescents recruited in two public schools. Stimulated salivary samples were collected for 3 min. Buffering capacity and pH were ascertained in each salivary sample. A single trained and calibrated examiner (kappa = 0.98) performed the dental caries examination according to WHO criteria. Results. The AFG showed salivary flow rate (1.10 +/- 0.63 mL/min) higher (P = 0.002) than AG (0.80 +/- 0.50 mL/min). An inverse relationship was observed between asthma severity and salivary flow rate (Phi coefficient, r phi: 0.79, P = 0.0001). Children with moderate or severe asthma showed an increased risk for reduced salivary flow rate (OR: 17.15, P < 0.001). No association was observed between drug use frequency (P > 0.05) and drug type (P > 0.05) with salivary flow rate. Buffering capacity was similar in both groups. No significant differences were encountered in dental caries experience between AFG and AG groups. Conclusions. Although asthma can cause reduction in flow rate, the illness did not seem to influence dental caries experience in children with access to proper dental care.

Effects of a mixture of growth factors and proteins on the development of the osteogenic phenotype in human alveolar bone cell cultures

Strategies to promote bone repair have included exposure of cells to growth factor (GF) preparations from blood that generally include proteins as part of a complex mixture. This study aimed to evaluate the effects of such a mixture on different parameters of the development of the osteogenic phenotype in vitro. Osteoblastic cells were obtained by enzymatic digestion of human alveolar bone and cultured under standard osteogenic conditions until subconfluence. They were subcultured on Thermanox coverslips up to 14 days. Treated cultures were exposed during the first 7 days to osteogenic medium supplemented with a GFs + proteins mixture containing the major components found in platelet extracts [plate I et-derived growth factor-BB, transforming growth factor (TGF)-beta 1, TGF-beta 2, albumin, fibronectin, and thrombospondin] and to osteogenic medium alone thereafter. Control cultures were exposed only to the osteogenic medium. Treated cultures exhibited a significantly higher number of adherent cells from day 4 onward and of cycling cells at days 1 and 4, weak alkaline phosphatase (ALP) labeling, and significantly decreased levels of ALP activity and mRNA expression. At day 14, no Alizarin red-stained nodular areas were detected in cultures treated with GFs + proteins. Results were confirmed in the rat calvaria-derived osteogenic cell culture model. The addition of bone morphogenetic protein 7 or growth and differentiation factor 5 to treated cultures upregulated Runx2 and ALP mRNA expression, but surprisingly, ALP activity was not restored. These results showed that a mixture of GFs + proteins affects the development of the osteogenic phenotype both in human and rat cultures, leading to an increase in the number of cells, but expressed a less differentiated state.

Chronic Diseases: Chronic Diseases and Development 2 Health, agricultural, and economic effects of adoption of healthy diet recommendations

Transition to diets that are high in saturated fat and sugar has caused a global public health concern as the pattern of food consumption is a mayor modifiable risk factor for chronic non-communicable diseases Although agri food systems are intimately associated with this transition, agriculture and health sectors are largely disconnected in their priorities policy, and analysis with neither side considering the complex inter relation between agri trade patterns of food consumption health, and development We show the importance of connection of these perspectives through estimation of the effect of adopting a healthy diet on population health, agricultural production trade the economy and livelihoods, with a computable general equilibrium approach On the basis of case studies from the UK and Brazil we suggest that benefits of a healthy diet policy will vary substantially between different populations, not only because of population dietary intake but also because of agricultural production trade and other economic factors