A putative OTU domain-containing protein 1 deubiquitinating enzyme is differentially expressed in thyroid cancer and identifies less-aggressive tumours.

BACKGROUND: This study aimed to identify novel biomarkers for thyroid carcinoma diagnosis and prognosis. METHODS: We have constructed a human single-chain variable fragment (scFv) antibody library that was selected against tumour thyroid cells using the BRASIL method (biopanning and rapid analysis of selective interactive ligands) and phage display technology. RESULTS: One highly reactive clone, scFv-C1, with specific binding to papillary thyroid tumour proteins was confirmed by ELISA, which was further tested against a tissue microarray that comprised of 229 thyroid tissues, including: 110 carcinomas (38 papillary thyroid carcinomas (PTCs), 42 follicular carcinomas, 30 follicular variants of PTC), 18 normal thyroid tissues, 49 nodular goitres (NG) and 52 follicular adenomas. The scFv-C1 was able to distinguish carcinomas from benign lesions (P=0.0001) and reacted preferentially against T1 and T2 tumour stages (P=0.0108). We have further identified an OTU domain-containing protein 1, DUBA-7 deubiquitinating enzyme as the scFv-binding antigen using two-dimensional polyacrylamide gel electrophoresis and mass spectrometry. CONCLUSIONS: The strategy of screening and identifying a cell-surface-binding antibody against thyroid tissues was highly effective and resulted in a useful biomarker that recognises malignancy among thyroid nodules and may help identify lower-risk cases that can benefit from less-aggressive management.

Stress in neonatal rats with different maternal care backgrounds: monoaminergic and hormonal responses.

The first 2 weeks of life in rats are known as the stress hyporesponsive period because stress responses in pups are diminished as compared to adult animals. However, it is considered a critical period in development in which infant rats are susceptible to environmental events, such as stressful stimuli and quality of maternal care received. These early life events have long-lasting effects, shaping a variety of outcomes, such as stress responsivity. This study investigated the effects of maternal care and sex differences on the response to an aversive stimulus in rat pups from high (HL) and low licking (LL) mothers. Plasma corticosterone, oxytocin (OT), and central monoaminergic activity in 13-day-old rats submitted to cold stress were analyzed. Stress increased plasma corticosterone and marginally decreased hypothalamic dihydroxyphenylacetic acid/dopamine ratio. HL pups showed higher levels of plasma OT than LL pups. The maternal effect was also detected in the hippocampus, in which 5-hydroxyindole-3-acetic acid/serotonin ratio was increased in HL pups, independently of the sex and stress. Investigating the early life events is useful not only into understand the neurobiological and hormonal mechanisms underlying maternal and stressful influences on infant development into a healthy or psychopathological adult phenotype, but also to unveil the immediate outcomes on infancy.

Stress in Neonatal Rats with Different Maternal Care Backgrounds: Monoaminergic and Hormonal Responses.

The first 2 weeks of life in rats are known as the stress hyporesponsive period because stress responses in pups are diminished as compared to adult animals. However, it is considered a critical period in development in which infant rats are susceptible to environmental events, such as stressful stimuli and quality of maternal care received. These early life events have long-lasting effects, shaping a variety of outcomes, such as stress responsivity. This study investigated the effects of maternal care and sex differences on the response to an aversive stimulus in rat pups from high (HL) and low licking (LL) mothers. Plasma corticosterone, oxytocin, and central monoaminergic activity in 13-day-old rats submitted to cold stress were analyzed. Stress increased plasma corticosterone and marginally decreased hypothalamic dihydroxyphenylacetic acid/dopamine (DOPAC/DA) ratio. HL pups showed higher levels of plasma oxytocin than LL pups. The maternal effect was also detected in the hippocampus, in which 5-hydroxyindole-3-acetic acid/serotonin (5-HIAA/5-HT) ratio was increased in HL pups, independently of the sex and stress. Investigating the early life events is useful not only into understand the neurobiological and hormonal mechanisms underlying maternal and stressful influences on infant development into a healthy or psychopathological adult phenotype, but also to unveil the immediate outcomes on infancy.

Decrease in anti-Leishmania IgG3 and IgG1 after cutaneous leishmaniasis lesion healing is correlated with the time of clinical cure.

For better efficiency in the establishment of American tegumentary leishmaniasis clinical cure, the World Health Organization suggests that the clinical criteria are supported by serologic data. The present study aims to investigate the dynamics of IgG subclass production in clinical evolution post-treatment of cutaneous leishmaniasis (CL). Paired sera from 23 subjects with CL resulting from Leishmania braziliensis infection were studied during the active lesion phase (aCL) and after clinical cure post-therapy (hCL), which included an alternative protocol with a low dose of antimony. Anti-Leishmania IgG and its subclasses were measured using ELISA, and the immunoglobulin levels were correlated with patients' clinical data. All of the subjects were clinically healed and did not present relapse during follow-up. Serum levels of anti-Leishmania IgG (r = -0·79; P < 0·0001), IgG1 (r = -0·64, P < 0·001) and IgG3 (r = -0·42, P < 0·045) in hCL were negatively correlated with the duration of clinical cure. After 24 months of clinical cure, 73% of samples were negative for IgG1 and 78% were negative for IgG3. In conclusion, the detection of serum anti-Leishmania IgG1 and IgG3 is an improved laboratory strategy to aid in the decision of interruption of the ambulatory follow-up of CL patients.

Neonatal handling and the maternal odor preference in rat pups: involvement of monoamines and cyclic AMP response element-binding protein pathway in the olfactory bulb.

Early-life environmental events, such as the handling procedure, can induce long-lasting alterations upon several behavioral and neuroendocrine systems. However, the changes within the pups that could be causally related to the effects in adulthood are still poorly understood. In the present study, we analyzed the effects of neonatal handling on behavioral (maternal odor preference) and biochemical (cyclic AMP response element-binding protein (CREB) phosphorylation, noradrenaline (NA), and serotonin (5-HT) levels in the olfactory bulb (OB)) parameters in 7-day-old male and female rat pups. Repeated handling (RH) abolished preference for the maternal odor in female pups compared with nonhandled (NH) and the single-handled (SH) ones, while in RH males the preference was not different than NH and SH groups. In both male and female pups, RH decreased NA activity in the OB, but 5-HT activity increased only in males. Since preference for the maternal odor involves the synergic action of NA and 5-HT in the OB, the maintenance of the behavior in RH males could be related to the increased 5-HT activity, in spite of reduction in the NA activity in the OB. RH did not alter CREB phosphorylation in the OB of both male and females compared with NH pups. The repeated handling procedure can affect the behavior of rat pups in response to the maternal odor and biochemical parameters related to the olfactory learning mechanism. Sex differences were already detected in 7-day-old pups. Although the responsiveness of the hypothalamic-pituitary-adrenal axis to stressors is reduced in the neonatal period, environmental interventions may impact behavioral and biochemical mechanisms relevant to the animal at that early age.

Down-modulation of nitric oxide production in murine macrophages treated with crude plant extracts from the Brazilian Cerrado.

Several plant species from the Cerrado biome in Brazil are popularly used as herbal medicines for its reputed analgesic, anti-acid, anti-microbial, anti-inflammatory and anti-tumoral properties, among others. It has been reported that some plant extracts interfere in the production of nitric oxide (NO), an important inflammatory mediator. In the present study, we investigated the effect of hexanic and ethanolic extracts from three plant species on NO production by LPS/IFN-gamma-activated J774 macrophages based on traditional use. The cytotoxic effect of the crude extracts was determined by the thiazolyl blue test (MTT) to measure cell viability. Serjania lethalis stem extracts and Cupania vernalis leaf extracts significantly inhibited NO production, while extracts from Casearia sylvestris var. lingua were inactive or showed low activity on NO production, or were very cytotoxic. The ethanolic stem bark and leaf extracts of Serjania lethalis and Cupania vernalis, respectively, almost completely inhibited the production of NO by J774 macrophages. It can be concluded that the selected extracts are potential sources of active compounds that might be used as anti-inflammatory agents.

Patterns of antibiotic use among children in an urban Brazilian slum.

Antibiotics are utilized excessively in many areas of the world. To better define how often and why these drugs are used, we prospectively studied antibiotic use among a cohort of 105 children less than five years of age in a poor area of the northeastern Brazilian city of Fortaleza. During a 16-week period, 65 children took 137 courses of antibiotics. Physicians recommended 54% of these, mothers or their associates 39%, and pharmacy workers 7%. Mothers and pharmacy workers recommended drugs for shorter courses than physicians, and were more likely to recommend drugs inappropriate for children. Duration of illness was not a risk factor for antibiotic use, but both poor nutritional status and poor socioeconomic status were. Health care seeking behaviour was further studied in 58 diarrhoea episodes. The type of care sought was related to the duration of illness. Overall, antibiotic use was very common and often inappropriate among children in this poor urban area. More controlled use might decrease the use of potentially dangerous drugs and the use of these drugs when no benefit is likely.

Malnutrition is associated with increased diarrhoea incidence and duration among children in an urban Brazilian slum.

This study was undertaken to further define the relationship between malnutrition and subsequent diarrhoeal illness among children. A cohort of 61 children under five years of age was followed for two years in an urban Brazilian slum. Nutritional status was determined at two-month intervals and was used to predict the subsequent occurrence of diarrhoea. A significant, graded association between worsened nutritional status, as measured by length- or weight-for-age, and diarrhoea incidence was found. This relationship was present for both two-month and one-year periods following nutritional assessment. The average duration of diarrhoea was also significantly longer during the two-month periods which were preceded by the worst nutritional status. Overall, the most malnourished children had nearly twice the total number of days of diarrhoea that better nourished children had. These results provide additional evidence that a significant association between malnutrition and both increased diarrhoea incidence and duration exists.

Diarrhea as a cause and an effect of malnutrition: diarrhea prevents catch-up growth and malnutrition increases diarrhea frequency and duration.

Diarrhea and malnutrition, alone or together, constitute major causes of morbidity and mortality among children throughout the tropical world. Data from northeast Brazil, taken with numerous other studies, clearly show that diarrhea is both a cause and an effect of malnutrition. Diarrheal illnesses impair weight as well as height gains, with the greatest effects being seen with recurrent illnesses, which reduce the critical catch-up growth that otherwise occurs after diarrheal illnesses or severe malnutrition. Malnutrition (whether assessed by impaired weight or height for age) leads to increased frequencies and durations of diarrheal illnesses, with a 37% increase in frequency and a 73% increase in duration accounting for a doubling of the diarrhea burden (days of diarrhea) in malnourished children. A multi-pronged approach focusing on those with prolonged diarrhea and severe malnutrition is suggested.

Evaluation of the dentogingival area during early plaque formation.

BACKGROUND: The aims of this investigation were to evaluate the pattern of supragingival plaque formation in the dentogingival area within 96 hours after abstinence from mechanical plaque control and to clinically analyze the gingival inflammatory response observed. METHODS: Six male volunteers, 20 to 23 years of age, had their upper incisors and cuspids polished. Four independent periods of no mechanical plaque control--24, 48, 72, and 96 hours--were instituted. In each period, plaque was disclosed and standardized individual photographs were taken. Impressions were taken and replicas were analyzed by scanning electron microscopy. Gingival crevicular fluid (GCF) was collected at baseline and 96 hours. The height of the gingival papilla was measured at baseline, 24, and 96 hours. RESULTS: Results showed the presence of a plaque-free zone (PFZ) along the gingival margin up to 72 hours. After 96 hours, there was a significant reduction in the presence of PFZ in the proximal thirds of the buccal surface when compared to the other experimental periods. At the end of the study, there was a significant increase in the GCF flow as well as edema of the interdental papilla, when compared to baseline values. CONCLUSIONS: The PFZ observed during the initial phase was less apparent at the 96-hour period. At this time, there was an increase in the gingival inflammatory response, represented clinically by increased GCF flow and edema.

Diagnosis of approximal caries in primary teeth: radiographic versus clinical examination using tooth separation.

PURPOSE: To compare the accuracy of clinical examination performed with bitewing radiographs or clinical examination using tooth separation to identify carious lesion activity. MATERIALS AND METHODS: 320 surfaces from 40 bitewing radiographs were examined for approximal caries on the maxillary and mandibular primary molars of 20 patients 3-10 years old. The patients were divided into three groups: (1) Absence of the permanent first molar; (2) Partial eruption of the permanent first molar; and (3) Full eruption of the permanent first molar. Two examiners evaluated the radiographs using a megascope, a magnifying glass (x2), and an amplifying image screen. Approximal radiolucencies were identified on 72 surfaces. Following the radiographic examinations, the two examiners performed conventional clinical inspection using a No. 4 dental mirror, a No. 5 dental explorer, and an air-water syringe, with artificial light and relative isolation. The separation method was performed with elastic bands, which were removed after 24 hours, and the clinical examination conducted as in the non-separation group. RESULTS: The correlation between the extension of interproximal radiolucent lesions in primary dentition and their clinical diagnoses following separation of the teeth, was similar to findings on literature evaluating the permanent dentition. On radiographic findings for enamel lesions, white spots predominated both in the inner (100%) and in the outer (94%) half of enamel upon clinical examination with separation of teeth. For radiolucent lesions in dentin, on the other hand, cavities predominated over white spot lesions (84%). In Groups 1 and 2 (young primary), white spots occurred in cases where the radiolucent lesions reached the dentin (15% and 25%), similar to findings for young permanent teeth. Clinical diagnosis performed with the mechanical separation of teeth cannot be considered conclusive for the primary dentition.

Selection of natural treatment processes for algae removal from stabilisation ponds effluents in Brasilia, using multicriterion methods.

A multicriterion methodology is used in the evaluation and selection of the most appropriate alternative(s) for removing algae from stabilisation ponds effluents in a case study in Brasilia. For this purpose, five different natural treatment processes are tested at pilot scale: rock filter, sand filter, floating aquatic plants, constructed wetlands, and overland flow. These pilot units were constructed in Brasilia and set in parallel, each one receiving a portion of the effluent that comes from an existing wastewater treatment plant composed of preliminary treatment, UASB reactors, and high-rate stabilisation ponds. Several evaluation criteria are used in order to relate the capabilities of the post-treatment processes to the multiple objectives in this case. Two multicriterion decision-aid methods--compromise programming and ELECTRE-III--are used to select the most satisfying processes. The top ranking alternatives are indicated for subsequent studies, considering the possible implementation of these technologies to existing plants.

Umbanda healers as effective AIDS educators: case-control study in Brazilian urban slums (favelas).

During a 12-month period (November 1994-October 1995), Afro-Brazilian Umbanda healers (Pais-de-Santo) taught 126 fellow healers from 51 Umbanda centres (terreiros) located in seven overcrowded slums (favelas) (population 104-343) in Brazil's northeast, the biomedical prevention of AIDS, including safe sex practices, avoidance of ritual blood behaviours and sterilization of cutting instruments. A face-to-face educational intervention by healers, marginalized in society yet respected by devotees, which blended traditional healing-its language, codes, symbols and images- and scientific medicine and addressed social injustices and discrimination was utilized in this project supported by the Brazilian Ministry of Health, National Program in STDs/AIDS. Significant increases (P < 0.001) in AIDS awareness, knowledge about risky HIV behaviour, information about correct condom use, and acceptance of lower-risk, alternative ritual blood practices and decreases (P < 0.001) in prejudicial attitudes related to HIV transmission were found among mobilized healers as compared to 100 untrained controls. Respected Afro-Brazilian Pais-de-Santo can be creative and effective partners in national HIV prevention programmes when they are equipped with biomedical information about AIDS.

Frequency of Trichomonas vaginalis, Candida sp and Gardnerella vaginalis in cervical-vaginal smears in four different decades.

CONTEXT: Vaginitis is one of the principal motives that lead women to seek out an obstetrician or gynecologist. Bacterial vaginosis, candidiasis and trichomoniasis are responsible for 90% of the cases of infectious vaginitis. OBJECTIVE: To verify the frequency of the three main causative agents of vaginitis, Trichomonas vaginalis, Candida sp and Gardnerella vaginalis, in four different decades (1960's, 1970's, 1980's and 1990's). DESIGN: Retrospective. PLACE: A tertiary referral center. PARTICIPANTS: Patients attended to as gynecology and obstetrics outpatients at the Faculdade de Medicina do Triângulo Mineiro during the years 1968, 1978, 1988, 1998, taken as samples of each decade. MAIN MEASUREMENTS: Diagnoses of infection by Trichomonas vaginalis, Candida sp and Gardnerella vaginalis were gathered from 20,356 cervical-vaginal cytology tests on patients attended to as gynecology outpatients at Faculdade de Medicina do Triângulo Mineiro during the years 1968, 1978, 1988, 1998, representing the four decades. The results were grouped according to the age group of the patients: under 20, between 20 and 29, between 30 and 39, between 40 and 49, and 50 or over. Statistical analysis was done via the chi-squared (Mantel-Haentzel) test with a significance level of 5%. RESULTS: In 1968 infections by Trichomonas vaginalis and Candida sp were diagnosed in 10% and 0.5% of the cytology tests and in 1978, 5.1% and 17.3%, respectively (P < 0.0001). Infection by Gardnerella vaginalis could only be evaluated in the latter two decades. In 1988, 19.8% of the women had positive tests for Gardnerella vaginalis, which was the most frequent agent in that year, diminishing in the subsequent decade to 15.9% (P < 0.0001). Candidiasis was the most frequent infection in 1998, detected in 22.5% of the tests (P < 0.0001). In a general manner, all the infections were most frequent among younger patients, especially those aged under 20, in all decades, whereas infections were least frequent among patients aged 50 or over (P < 0.05). CONCLUSION: There was a reduction in the frequency of cervical-vaginal infection by Trichomonas vaginalis and an increase in the frequency of Candida sp over the four decades studied. All the infections were most frequent in patients aged under 20 years.

[Multiple neoplasms after a well succeeded treatment of Hodgkin's disease]. / Neoplasias múltiplas após tratamento bem sucedido de doença de Hodgkin.

The authors refer to a 21-year-old Caucasian (white) woman, who in 1977 presented fever and cervical and axillary adenopathy, whose biopsy showed nodular sclerosis Hodgkin's Disease, stage IIIB. The patient received six chemotherapy cycles associated with immunotherapy and supplemented with radiation therapy with good response. RESULTS--In 1985, after routine gynaecological examination and a hysterectomy, cervical intraepithelial neoplasia grade 3 (CIN 3) and atypic leiomyoma of the uterine body were diagnosed. Five years later, biopsies diagnosed invasive duct carcinoma in the right breast and homolateral axillary and cervical nodes. The patient was submitted to chemo and radiation therapy and died nine months later. CONCLUSION--The possibility of later occurrence of a second or multiple new malignancies in patients successfully treated for Hodgkin's Disease points out the need for a more complete long-term follow-up, including periodic mammography.

Neonatal handling alters the structure of maternal behavior and affects mother-pup bonding.

During early life, a mother and her pups establish a very close relationship, and the olfactory learning of the nest odor is very important for the bond formation. The olfactory bulb (OB) is a structure that plays a fundamental role in the olfactory learning (OL) mechanism that also involves maternal behavior (licking and contact). We hypothesized that handling the pups would alter the structure of the maternal behavior, affect OL, and alter mother-pup relationships. Moreover, changes in the cyclic AMP-response element binding protein phosphorylation (CREB) and neurotrophic factors could be a part of the mechanism of these changes. This study aimed to analyze the effects of neonatal handling, 1 min per day from postpartum day 1 to 10 (PPD 1 to PPD 10), on the maternal behavior and pups' preference for the nest odor in a Y maze (PPD 11). We also tested CREB's phosphorylation and BDNF signaling in the OB of the pups (PPD 7) by Western blot analysis. The results showed that handling alters mother-pups interaction by decreasing mother-pups contact and changing the temporal pattern of all components of the maternal behavior especially the daily licking and nest-building. We found sex-dependent changes in the nest odor preference, CREB and BDNF levels in pups OB. Male pups were more affected by alterations in the licking pattern, and female pups were more affected by changes in the mother-pup contact (the time spent outside the nest and nursing).

Case report: Clinical, histological and ultrastructural characterization of type II dentinogenesis imperfecta.

BACKGROUND: Type II dentinogenesis imperfecta (DGIII) is an autosomal dominant dental development anomaly that affects both the primary and permanent dentition. CASE REPORT: This case report describes the clinical, radiographic and morphological characteristics of the teeth of a seven-year-old child with DGI-II determined by optical microscopy and scanning electron microscopy. TREATMENT: This consisted of extraction of the primary teeth with periapical lesions due to the advanced state of tooth resorption. Aesthetic restorations were performed on the mandibular anterior teeth and occlusal fissure sealants were applied to erupting teeth. A removable partial upper denture was made in order to return anterior aesthetic function and to aid mastication and speech. FOLLOW UP: The child was examined at 3 month intervals. Over the following 3 years the prosthesis was replaced due to facial growth and fluoride was applied at each follow-up visit to all teeth. The patient remains in follow up and management. CONCLUSION: Individuals with DGI-II must not neglect their dental health. Early diagnosis, professional advice and treatment with periodic follow-up can help improve the quality of life of such patients.