Balance between early life tolerance and sensitization in allergy: dependence on the timing and intensity of prenatal and postnatal allergen exposure of the mother

P>Allergens can be maternally transferred to the fetus or neonate, though it is uncertain how this initial allergen exposure may impact the development of allergy responses. To evaluate the roles of timing and level of maternal allergen exposure in the early life sensitization of progeny, female BALB/c mice were given ovalbumin (OVA) orally during pregnancy, lactation or weekly at each stage to investigate the immunoglobulin E (IgE) antibody production and cellular responsiveness of their offspring. Exposure to OVA during pregnancy was also evaluated in OVA-specific T-cell receptor (TCR) transgenic (DO11.10) mice. The effect of prenatal antigen exposure on offspring sensitization was dependent on antigen intake, with low-dose OVA inducing tolerance followed by neonatal immunization that was sustained even when pups were immunized when 3 weeks old. These offspring received high levels of transforming growth factor-beta via breastfeeding. High-dose exposure during the first week of pregnancy or perinatal period induced transient inhibition of IgE production following neonatal immunization; although for later immunization IgE production was enhanced in these offspring. Postnatal maternal antigen exposure provided OVA transference via breastfeeding, which consequently induced increased offspring susceptibility to IgE antibody production according to week post-birth. The effect of low-dose maternal exposure during pregnancy was further evaluated using OVA transgenic TCR dams as a model. These progeny presented pronounced entry of CD4(+) T cells into the S phase of the cell cycle with a skewed T helper type 2 response early in life, revealing the occurrence of allergen priming in utero. The balance between tolerance and sensitization depended on the amount and timing of maternal allergen intake during pregnancy.

Inhibition of the renin-angiotensin system prevents seizures in a rat model of epilepsy

The RAS (renin angiotensin system) is classically involved in BP (blood pressure) regulation and water electrolyte balance, and in the central nervous system it has been mostly associated with homoeostatic processes, such as thirst, hormone secretion and thermoregulation. Epilepsies are chronic neurological disorders characterized by recurrent epileptic seizures that affect 1-3% of the world`s population, and the most commonly used anticonvulsants are described to be effective in approx. 70% of the population with this neurological alteration. Using a rat model of epilepsy, we found that components of the RAS, namely ACE (angiotensin-converting enzyme) and the AT(1) receptor (angiotensin II type I receptor) are up-regulated in the brain (2.6- and 8.2-fold respectively) following repetitive seizures. Subsequently, epileptic animals were treated with clinically used doses of enalapril, an ACE inhibitor, and losartan, an AT(1) receptor blocker, leading to a significant decrease in seizure severities. These results suggest that centrally acting drugs that target the RAS deserve further investigation as possible anticonvulsant agents and may represent an additional strategy in the management of epileptic patients.

IGFR-I expression and structural analysis of the hard palatine mucosa in an ethanol-drinking rat strain (UChA and UChB)

The study analyzed the effects of chronic alcohol ingestion on the ultrastructure of the lining epithelium of the hard palatine mucosa of rats UChA and UChB (lines with voluntary alcohol consumption) in order to contribute to the understanding of the consequences of alcohol abuse for the morphology of the digestive system. Thirty female adult animals aged 120 days were divided into three experimental groups. (1) Ten UChA rats (genetically low ethanol consumer) with voluntary intake of 10% v/v (5.45 g/kg/day) ethanol solution and water. (2) Ten UChB (genetically high ethanol consumer) rats with voluntary intake of 10% v/v (7.16 g/kg/day) ethanol solution and water. (3) Ten Wistar rats with voluntary ad libitum water intake (control group). Both groups received Nuvital pellets ad libitum. The IGFR-I expression was intense in both experimental groups. The epithelial cells of the alcoholic rats UChA and UChB showed many alterations such as the presence of lipid droplets, altered nuclei, nuclei in corneum layer and disrupted mitochondria. It was concluded that ethanol intake induces ultrastructural lesions in the hard palatine mucosa. (C) 2011 Elsevier Ltd. All rights reserved.

Human leukocyte antigen (HLA) and single nucleotide polymorphisms (SNPs) tumor necrosis factor (TNF)-alpha-238 and-308 as genetic markers of susceptibility to psoriasis and severity of the disease in a long-term follow-up Brazilian study

Background The strongest genetic marker for psoriasis is Cw*06. Polymorphisms in the tumor necrosis factor (TNF)-alpha promoter region, especially replacement of guanine with adenine in positions -238 and -308 are related to higher TNF-alpha production and higher risk for psoriasis in Caucasoid populations, not found in Asians. We performed a case-control study of 69 patients with psoriasis type I and 70 controls, characterized clinical progression along 10-years of follow-up in mild or severe disease and determined HLA class I, II, and TNF single nucleotide polymorphisms (SNPs) -238 and -308 polymorphisms to demonstrate whether these polymorphisms may be genetic risk for susceptibility to psoriasis or severity of the disease in Brazilians. Methods Polymorphisms were identified using PCR/SSP. Alleles, genotypes, and haplotypes frequencies were compared using Fisher`s test. Results More severe disease was found in male patients. It may be suggested that alleles B*37, Cw*06, Cw*12, and DRB1*07 were associated with severe disease course, while B*57 with mild disease. No statistical difference was found between the patients and controls regarding polymorphisms frequencies in TNF SNPs. This study pointed to a higher TNF-238 G/G genotype frequency (OR: 3.21; CI: 1.06-9.71; P = 0.04) in the group with severe disease. Conclusions Polymorphisms in the TNF-alpha SNPs do not seem to be a more important genetic risk factor for psoriasis than the already known Cw*06 in Brazilian patients, but these markers may be related to clinical manifestations.

Safety of the etonogestrel-releasing implant during the immediate postpartum period: a pilot study

Background: The effects of etonogestrel (ETG)-releasing contraceptive implant during the immediate postpartum period on maternal safety are unknown. Study design: Forty healthy women exclusively breastfeeding were randomized to receive either ETG-releasing implant 24-48 h after delivery (n=20) or depot medroxyprogesterone acetate (DMPA group; n=20) at the sixth week postpartum. We measured blood pressure, maternal and neonatal weight, body mass index (BMI; kg/m(2)), waist circumference (WC), complete blood count, C-reactive protein, interleukin-6, tumor necrosis factor (TNF-alpha), lipid profile, fasting serum glucose and maintenance of exclusive lactation up to the 12th week postpartum. Results: Decreases in mean maternal weight, BMI (kg/m(2)) and WC were significantly greater in the ETG-releasing implant group than in the MPA group during the first 6 weeks postpartum (-4.64 +/- 2.71 kg vs. -2.6 +/- 2.45 kg mean +/- SD, p=.017; -1.77 +/- 1.06 kg/m(2) vs. -0.97 +/- 0.95 kg/m(2), p=.026; -15.3 +/- 6.72 cm vs. -9.05 +/- 5.84 cm, p=.003, respectively). In addition, total cholesterol and HDL, were lower in DMPA users, and TNF-alpha and leukocytes were higher in DMPA users compared to in the implant group, between 6 and 12 weeks after delivery. The newborns of implant users showed a trend towards gaining more weight, as compared with the infants of the DMPA mothers during the first 6 weeks of life (implant group: +1460.50 +/- 621.34 g vs. DMPA group: +1035.0 +/- 562.43 g, p=.05). The remaining variables, including the duration of exclusive breastfeeding, were similar between the groups. Conclusion: The insertion of ETG-releasing contraceptive implant during the immediate postpartum period was not associated with deleterious maternal clinical effects or with significant maternal metabolic alterations or decreased infant weight gain. (C) 2009 Elsevier Inc. All rights reserved.

Ovarian reserve evaluation: state of the art

Purpose Revise role of hormonal basal and dynamic tests, as well as ultrasonographic measures as ovarian reserve markers, in order to provide better counseling to subfertile couples. Methods Review of publications on the topic, with an emphasis on recent well designed articles. Results Currently available ovarian reserve tests do not provide sufficient evidence to be solely considered ideal, even for premature ovarian senescence patients who do not present subfertility complaints. However, these markers occupy important place in initial approach to treatment of subfertile couples, predicting unsatisfactory results that could be improved by differentiated induction schemes and reducing excessive psychological and financial burdens, and adverse effects. Conclusions In order to remedy the limitations due to the scarcity of strong evidence about this topic, future studies should try to clarify predictive value of markers in groups of specific diseases-related subfertility and pay special attention to propaedeutic multivariate models including anti-Mullerian hormone and antral follicle count.

Effects of sex hormonal levels and phases of the menstrual cycle in the processing of emotional faces

Several neuropsychiatry disorders have shown a sexual dimorphism in their incidence, symptom profile and therapeutic response. A better understanding of the impact of sex hormones in emotional processing sexual dimorphism could bring tight to this important clinical finding. Some studies have provided evidence of sex differences in the identification of emotional faces, however, results are inconsistent and such inconsistency could be related to the lack of experimental control of the sex hormone status of participants. More recently, a few studies evaluated the modulation of facial emotion recognition by the phase of the menstrual cycle and sex hormones, however, none of them directly compared these results with a group of men. We evaluated the accuracy of facial emotion recognition in 40 healthy volunteers. Eleven women were assigned to early follicular group, nine women to the ovulatory group and 10 women to luteal group, depending on the phase of menstrual cycle, and a group of 10 men were also evaluated. Estrogen, progesterone and testosterone levels were assessed. The performance of the groups in the identification of emotional faces varied depending on the emotion. Early follicular group were more accurate to perceive angry faces than all other groups. Sadness was more accurately recognized by early follicular group than by luteal group and regarding the recognition of fearful faces a trend to a better performance and a significantly higher accuracy was observed, respectively, in the early follicular group and in the ovulatory group, in comparison to men. In women, estrogen negatively correlated to the accuracy in perception of angry mate faces. Our results indicate sex hormones to be implicated in a sexual dimorphism in facial emotion recognition, and highlight the importance of estrogen specifically in the recognition of negative emotions such as sadness, anger and fear. (C) 2009 Elsevier Ltd. All rights reserved.

Benefits of the Intermittent Use of 6-Mercaptopurine and Methotrexate in Maintenance Treatment for Low-Risk Acute Lymphoblastic Leukemia in Children: Randomized Trial From the Brazilian Childhood Cooperative Group Protocol ALL-99

Purpose To describe event-free survival (EFS) and toxicities in children with low-risk acute lymphoblastic leukemia (ALL) assigned to receive either continuous 6-mercaptopurine (6-MP) and weekly methotrexate (MIX) or intermittent 6-MP with intermediate-dose MTX, as maintenance treatment. Patients and Methods Between October 1, 2000, and December 31, 2007, 635 patients with low-risk ALL were enrolled onto Brazilian Childhood Cooperative Group for ALL Treatment (GBTLI) ALL-99 protocol. Eligible children (n=544) were randomly allocated to receive either continuous 6-ME/MIX (group 1, n 272) or intermittent 6-MP (100 mg/m(2)/d for 10 days, with 11 days resting) and MIX (200 mg/m(2) every 3 weeks; group 2, n = 272). Results The 5-year overall survival (OS) and EFS were 92.5% +/- 1.5% SE and 83.6% +/- 2.1% SE, respectively. According to maintenance regimen, the OS was 91.4% +/- 2.2% SE (group 1) and 93.6% +/- 2.1% SE (group 2; P=.28) and EFS 80.9% +/- 3.2% SE (group 1) and 86.5% +/- 2.8% SE (group 2; P=.089). Remarkably, the intermittent regimen led to significantly higher EFS among boys (85.7% v 74.9% SE; P=027), while no difference was seen for girls (87.0% v 88.8% SE; P=.78). Toxic episodes were recorded in 226 and 237 children, respectively. Grade 3 to 4 toxic events for groups 1 and 2 were, respectively, 273 and 166 for hepatic dysfunction (P=.002), and 772 and 636 for hematologic episodes (P=.005). Deaths on maintenance were: seven (group 1) and one (group 2). Conclusion The intermittent use of 6-MP and MIX in maintenance is a less toxic regimen, with a trend toward better long-term EFS. Boys treated with the intermittent schedule had significantly better EFS.

Experimental infection of capybaras Hydrochoerus hydrochaeris by Rickettsia rickettsii and evaluation of the transmission of the infection to ticks Amblyomma cajennense

The present study evaluated the infection of capybaras (Hydrochoerus hydrochaeris) by Rickettsia rickettsii and their role as amplifier hosts for horizontal transmission of R. rickettsii to Amblyomma cajennense ticks. Two groups of two capybaras each were evaluated: on day 0, group 1 (G1) was infested by R. rickettsii-infected ticks, and group 2 (G2) was inoculated intraperitoneally with R. rickettsii. Two additional groups were control groups, not exposed to R. rickettsii, being CG1 group the control of G1, and CG2 group the control of G2. Capybara rectal temperature was measured daily. Blood samples were collected every 3 days during 30 days, and used to (i) inoculate guinea pigs intraperitoneally; (ii) DNA extraction followed by real-time PCR targeting the rickettsial gene gltA; (iii) hematology; (iv) detection of R. rickettsii-reactive antibodies by indirect immunofluorescence assay (IFA). Blood was also collected from G I capybaras every approximate to 10-30 days till the 146th day, to be tested by serology. Capybaras were infested by uninfected A. cajennense nymphs from the 3rd to the 18th day. Engorged nymphs were collected, allowed to molt to adults in an incubator. Thereafter, the subsequent flat ticks were tested by PCR. All G1 and G2 capybaras became infected by R. rickettsii, as demonstrated by guinea pig inoculation and seroconversion, but they showed no fever. Rickettsemia was continually detected from the 6th (G2 capybaras) or 9th (G1 capybaras) to the 18th day post inoculation or infestation with R. rickettsii-infected ticks. A total of 20-25% and 30-35% of the flat ticks previously fed on G1 and G2 capybaras, respectively, became infected by R. rickettsii. The study demonstrated that R. rickettsii was capable to infect capybaras without causing clinical illness, inducing rickettsemia capable to cause infection in guinea pigs and ticks. Our results indicate that capybaras act as amplifier host of R. rickettsii for A. cajennense ticks in Brazil. (c) 2008 Elsevier B.V. All rights reserved.

Prevalence and risk factors for anti-Toxoplasma gondii antibodies in goats of the Serido Oriental microregion, Rio Grande do Norte state, Northeast region of Brazil

The prevalence and risk factors for anti-Toxoplasma gondii antibodies were investigated in goats of the Serido Oriental microregion, Rio Grande do Norte state, Northeast region of Brazil. Three hundred and sixty-six blood samples from goats collected by jugular venopuncture were used. For the serologic diagnosis of Toxoplasma gondii infection, the indirect fluorescent-anti body test (IFAT) with cut-off value 1:64 was carried out. The prevalence of anti-T. gondii antibodies was 30.6% [95% CI = 25.9-35.6%] with titers ranging from 1:64 to 1: 16,384. The multivariate logistic regression analysis showed that the risk factors associated to anti-T. gondii antibodies were presence of cats in the herd, extensive/semi-intensive management systems and lack of mineral supplementation. (c) 2008 Elsevier B.V. All rights reserved.

Analysis in vitro of the cytotoxicity of potential implant materials. I: Zirconia-titania sintered ceramics

Zirconia (ZrO(2)) is a bioinert, strong, and tough ceramic, while titania (TiO(2)) is bioactive but has poor mechanical properties. It is expected that ZrO(2)-TiO(2) mixed ceramics incorporate the individual properties of both ceramics, so that this material would exhibit better biological properties. Thus, the objective of this study was to compare the biocompatibility properties of ZrO(2)-TiO(2) mixed ceramics. Sintered ceramics pellets, obtained from powders of TiO(2), ZrO(2), and three different ZrO(2)-TiO(2) mixed oxides were used. Roughnesses, X-ray diffraction, microstructure through SEM, hardness, and DRIFT characterizations were performed. For biocompatibility analysis cultured FMM1 fibroblasts were plated on the top of disks and counted in SEM micrographs 1 and 2 days later. Data were compared by ANOVA complemented by Tukey`s test. All samples presented high densities and similar microstructure. The H(2)O content in the mixed ceramics was more evident than in pure ceramics. The number of fibroblasts attached to the disks increased significantly independently of the experimental group. The cell growth on the top of the ZrO(2)-TiO(2) samples was similar and significantly higher than those of TiO(2) and ZrO(2) samples. Our in vitro experiments showed that the ZrO(2)-TiO(2) sintered ceramics are biocompatible allowing faster cell growth than pure oxides ceramics. The improvement of hardness is proportional to the ZrO(2) content. Thus, the ZrO(2)-TiO(2) sintered ceramics could be considered as potential implant material. (C) 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 94B: 305-311, 2010.

Inflammatory Papillary Hyperplasia of the Palate: Quantitative Analysis of Candida albicans and its Negative Correlation with Microscopic and Demographic Aspects

Inflammatory papillary hyperplasia of the palate (IPHP) is a tissue-reactive overgrowth characterized by hyperemic mucosa with nodular or papillary appearance in the palate. The exact pathogenesis is still unclear. In this study, the presence of Candida albicans in the epithelial lining was evaluated using the indirect immunofluorescence staining technique. Strongly stained C albicans was observed only in the lesions of the IPHP group. Therefore, the detection of C albicans in almost all samples from IPHP tissue enabled a suggestion as to the microbial etiology of the disease, since the use of dental prostheses was reported. Int J Prosthodont 2011;24:235-237

An in situ/ex vivo comparison of the ability of regular and light colas to induce enamel wear when erosion is combined with abrasion

Objective: To evaluate whether the type of cola drink (regular or diet) could influence the wear of enamel subjected to erosion followed by brushing abrasion, Method and !Materials: Ten volunteers wore intraoral devices that each had eight bovine enamel blocks divided into four groups; ER, erosion with regular cola; EAR, erosion with regular cola plus abrasion; EL, erosion with light cola; and EAL, erosion with light cola plus abrasion, Each day for 1 week, half of each device was immersed in regular cola for 5 minutes, Then, two blocks were brushed using a fluoridated toothpaste and electric toothbrush for 30 seconds four times daily, Immediately after, the other half of the device was subjected to the same procedure using a light cola, The pH, calcium, phosphorus, and fluoride concentrations of the colas were analyzed using standard procedures, Enamel alterations were measured by profilometry. Data were tested using two-way ANOVA and Bonferroni test (P < .05), Results: Regarding chemical characteristics, light cola presented pH 3.0, 13.7 mg Ca/L, 15.5 mg P/L, and 0.31 mg F/L, while regular cola had pH 2.6, 32.1 mg Ca/L, 1:8.1 mg P/L, and 0.26 mg F/L, The light cola promoted less enamel loss (EL, 0.36 pm; EAL, 0.39 pm) than its regular counterpart (ER, 0.72 pm; EAR, 0.95 pm) for both conditions, There was not a significant difference (P > .05) between erosion and erosion plus abrasion for light cola, However, for regular cola, erosion plus abrasion resulted in higher enamel loss than erosion alone,.nclusion: The data suggest that light cola promoted less enamel wear even when erosion was followed by brushing abrasion, (Quintessence Int 2011;42:xxx-xx)()

Evaluation of the buccal vestibule-palatal diffusion of 4% articaine hydrochloride in impacted maxillary third molar extractions

Aims: The aim of this study was to evaluate the vestibular-palatal diffusion of 4% articaine with epinephrine 1: 100,000 and 1: 200,000, in impacted maxillary third molar extractions, without palatal injection. Materials and Method: Two hundred teeth were selected from patients age 15 to 46. Patients were divided into 4 groups: 1A, were anesthetized with 4% articaine 1: 100,000 and the surgery was initiated 5 minutes following anesthesia. 1B, used 4% articaine 1: 100,000 but the surgery was started 10 minutes after anesthesia. 2A, used 4% articaine 1: 200,000 the surgery was started 5 minutes after. 2B, used 4% articaine 1: 200,000 but 10 minutes was allowed for anesthetic diffusion before the initiation of in groups (50 extractions each) only buccal vestibule anesthesia was initially administered (i.e. no palatal injections were used). Results: The rate of sufficient vestibule-palatal diffusion, as determined by the lack of necessity of supplemental palatal anesthesia, was: 1A(84%), 1B(98%), 2A(78%), 2B(82%). Chi-square (X2) and residual analyses showed that a higher vestibule-palatal diffusion was obtained using 4% articaine 1: 100,000 with a period of 10 minutes (p<0.05). Conclusions: Most of the extractions could be performed only with vestibule anesthesia. However, vasoconstrictor concentration and the time interval between administration of the anesthetic and initiation of surgery did influence buccal vestibule-palatal diffusion of 4% articaine in the extraction models used.

Propyretic role of the locus coeruleus nitric oxide pathway

Nitric oxide has been reported to modulate fever in the brain. However, the sites where NO exerts this modulation remain somewhat unclear. Locus coeruleus (LC) neurons express not only nitric oxide synthase (NOS) but also soluble guanylyl cyclase (sGC). In the present study, we evaluated in vivo and ex vivo the putative role of the LC NO-cGMP pathway in fever. To this end, deep body temperature was measured before and after pharmacological modulations of the pathway. Moreover, nitrite/nitrate (NOx) and cGMP levels in the LC were assessed. Conscious rats were microinjected within the LC with a non-selective NOS inhibitor (NG-monomethyl-l-arginine acetate), a NO donor (NOC12), a sGC inhibitor (1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one) or a cGMP analogue (8-bromo-cGMP) and injected intraperitoneally with endotoxin. Inhibition of NOS or sGC before endotoxin injection significantly increased the latency to the onset of fever. During the course of fever, inhibition of NOS or sGC attenuated the febrile response, whereas microinjection of NOC12 or 8-bromo-cGMP increased the response. These findings indicate that the LC NO-cGMP pathway plays a propyretic role. Furthermore, we observed a significant increase in NOx and cGMP levels, indicating that the febrile response to endotoxin is accompanied by stimulation of the NO-cGMP pathway in the LC.