[Drug-induced Stevens-Johnson syndrome in a patient with AIDS]

The Stevens-Johnson syndrome is a severe potentially life-threatening form of the erythema multiforme, affecting both skin and mucous membranes. We present a case of a 49-year-old male patient with AIDS who developed a Stevens-Johnson syndrome while being treated with pyrimethamine, sulfadiazine and phenytoin for cerebral toxoplasmosis. Further diagnostic evaluation of this dangerous cutaneous affection may prove difficult for several reasons. In particular, in patients with AIDS who are more susceptible for adverse drug reactions and who are simultaneously receiving a variety of drugs with a considerable potential of cutaneous side effects, therapy cannot be withhold for lack of therapeutic alternatives. Moreover, the low lymphocyte count in this case may have made reliable testing with lymphocyte transformation studies impossible. The evaluation and the differential diagnosis of the drug-induced Stevens-Johnson syndrome are discussed. Especially long- and moderately long-acting sulfonamides belong to the most important agents that can cause a drug-induced Stevens-Johnson syndrome. The pathogenesis and the risk factors for cutaneous hypersensitivity reactions in HIV-infected patients are only poorly understood. These kind of reactions, however, seem to occur more often in patients with a more advanced immunodeficiency.

Antiretroviral penetration into the CNS and incidence of AIDS-defining neurologic conditions

OBJECTIVE The link between CNS penetration of antiretrovirals and AIDS-defining neurologic disorders remains largely unknown.METHODS: HIV-infected, antiretroviral therapy-naive individuals in the HIV-CAUSAL Collaboration who started an antiretroviral regimen were classified according to the CNS Penetration Effectiveness (CPE) score of their initial regimen into low (<8), medium (8-9), or high (>9) CPE score. We estimated "intention-to-treat" hazard ratios of 4 neuroAIDS conditions for baseline regimens with high and medium CPE scores compared with regimens with a low score. We used inverse probability weighting to adjust for potential bias due to infrequent follow-up.RESULTS: A total of 61,938 individuals were followed for a median (interquartile range) of 37 (18, 70) months. During follow-up, there were 235 cases of HIV dementia, 169 cases of toxoplasmosis, 128 cases of cryptococcal meningitis, and 141 cases of progressive multifocal leukoencephalopathy. The hazard ratio (95% confidence interval) for initiating a combined antiretroviral therapy regimen with a high vs low CPE score was 1.74 (1.15, 2.65) for HIV dementia, 0.90 (0.50, 1.62) for toxoplasmosis, 1.13 (0.61, 2.11) for cryptococcal meningitis, and 1.32 (0.71, 2.47) for progressive multifocal leukoencephalopathy. The respective hazard ratios (95% confidence intervals) for a medium vs low CPE score were 1.01 (0.73, 1.39), 0.80 (0.56, 1.15), 1.08 (0.73, 1.62), and 1.08 (0.73, 1.58).CONCLUSIONS: We estimated that initiation of a combined antiretroviral therapy regimen with a high CPE score increases the risk of HIV dementia, but not of other neuroAIDS conditions.

Toxoplasma gondii seroprevalence in ringed seals (Pusa hispida) from the Canadian Arctic

Toxoplasmosis is a significant public health threat for Inuit in the Canadian Arctic. This study aimed to investigate arctic seals as a possible food-borne source of infection. Blood samples collected from 828 seals in 7 Canadian Arctic communities from 1999 to 2006 were tested for Toxoplasma gondii antibodies using a direct agglutination test. Polymerase chain reaction (PCR) was used to detect T. gondii DNA in tissues of a subsample of seals. Associations between seal age, sex, species, diet, community and year of capture, and serological test results were investigated by logistic regression. Overall seroprevalence was 10.4% (86/828). All tissues tested were negative by PCR. In ringed seals, seroprevalence was significantly higher in juveniles than in adults (odds ratio = 2.44). Overall, seroprevalence varied amongst communities (P = 0.0119) and by capture year (P = 0.0001). Our study supports the hypothesis that consumption of raw seal meat is a significant source of infection for Inuit. This work raises many questions about the mechanism of transfer of this terrestrial parasite to the marine environment, the preponderance of infection in younger animals and the natural course of infection in seals. Further studies to address these questions are essential to fully understand the health risks for Inuit communities.

Nuclear-encoded proteins target to the plastid in Toxoplasma gondii and Plasmodium falciparum

A vestigial, nonphotosynthetic plastid has been identified recently in protozoan parasites of the phylum Apicomplexa. The apicomplexan plastid, or “apicoplast,” is indispensable, but the complete sequence of both the Plasmodium falciparum and Toxoplasma gondii apicoplast genomes has offered no clue as to what essential metabolic function(s) this organelle might perform in parasites. To investigate possible functions of the apicoplast, we sought to identify nuclear-encoded genes whose products are targeted to the apicoplast in Plasmodium and Toxoplasma. We describe here nuclear genes encoding ribosomal proteins S9 and L28 and the fatty acid biosynthetic enzymes acyl carrier protein (ACP), β-ketoacyl-ACP synthase III (FabH), and β-hydroxyacyl-ACP dehydratase (FabZ). These genes show high similarity to plastid homologues, and immunolocalization of S9 and ACP verifies that the proteins accumulate in the plastid. All the putatively apicoplast-targeted proteins bear N-terminal presequences consistent with plastid targeting, and the ACP presequence is shown to be sufficient to target a recombinant green fluorescent protein reporter to the apicoplast in transgenic T. gondii. Localization of ACP, and very probably FabH and FabZ, in the apicoplast implicates fatty acid biosynthesis as a likely function of the apicoplast. Moreover, inhibition of P. falciparum growth by thiolactomycin, an inhibitor of FabH, indicates a vital role for apicoplast fatty acid biosynthesis. Because the fatty acid biosynthesis genes identified here are of a plastid/bacterial type, and distinct from those of the equivalent pathway in animals, fatty acid biosynthesis is potentially an excellent target for therapeutics directed against malaria, toxoplasmosis, and other apicomplexan-mediated diseases.

Apicidin: A novel antiprotozoal agent that inhibits parasite histone deacetylase

A novel fungal metabolite, apicidin [cyclo(N-O-methyl-l-tryptophanyl-l-isoleucinyl-d-pipecolinyl-l-2-amino-8-oxodecanoyl)], that exhibits potent, broad spectrum antiprotozoal activity in vitro against Apicomplexan parasites has been identified. It is also orally and parenterally active in vivo against Plasmodium berghei malaria in mice. Many Apicomplexan parasites cause serious, life-threatening human and animal diseases, such as malaria, cryptosporidiosis, toxoplasmosis, and coccidiosis, and new therapeutic agents are urgently needed. Apicidin’s antiparasitic activity appears to be due to low nanomolar inhibition of Apicomplexan histone deacetylase (HDA), which induces hyperacetylation of histones in treated parasites. The acetylation–deacetylation of histones is a thought to play a central role in transcriptional control in eukaryotic cells. Other known HDA inhibitors were also evaluated and found to possess antiparasitic activity, suggesting that HDA is an attractive target for the development of novel antiparasitic agents.

Aromatase (Cyp19) expression is up-regulated by targeted disruption of Dax1

DAX-1 [dosage-sensitive sex reversal, adrenal hypoplasia congenita (AHC) critical region on the X chromosome, gene 1] is an orphan nuclear receptor that represses transcription by steroidogenic factor-1 (SF-1), a factor that regulates expression of multiple steroidogenic enzymes and other genes involved in reproduction. Mutations in the human DAX1 gene (also known as AHC) cause the X-linked syndrome AHC, a disorder that is associated with hypogonadotropic hypogonadism also. Characterization of Dax1-deficient male mice revealed primary testicular defects that included Leydig cell hyperplasia (LCH) and progressive degeneration of the germinal epithelium, leading to infertility. In this study, we investigated the effect of Dax1 disruption on the expression profile of various steroidogenic enzyme genes in Leydig cells isolated from Dax1-deficient male mice. Expression of the aromatase (Cyp19) gene, which encodes the enzyme that converts testosterone to estradiol, was increased significantly in the Leydig cells isolated from mutant mice, whereas the expression of other proteins (e.g., StAR and Cyp11a) was not altered. In in vitro transfection studies, DAX-1 repressed the SF-1-mediated transactivation of the Cyp19 promoter but did not inhibit the StAR or Cyp11a promoters. Elevated Cyp19 expression was accompanied by increased intratesticular levels of estradiol. Administration of tamoxifen, a selective estrogen-receptor modulator, restored fertility to the Dax1-deficient male mice and partially corrected LCH, suggesting that estrogen excess contributes to LCH and infertility. Based on these in vivo and in vitro analyses, aromatase seems to be a physiologic target of Dax-1 in Leydig cells, and increased Cyp19 expression may account, in part, for the infertility and LCH in Dax1-deficient mice.

Human V delta 2+ gamma delta T-cell tolerance to foreign antigens of Toxoplasma gondii.

Little is known about the mechanisms involved in human gammadelta T-cell tolerance to self or to foreign antigens. Patients with congenital toxoplasmosis offer a unique opportunity to examine Vdelta2+ gammadelta T-cell tolerance. Analysis of gammadelta T cells in patients with congenital toxoplasmosis revealed evidence for anergy of these cells with or without clonal Vdelta2+ gammadelta T-cell expansion in the acute phase of the Toxoplasma infection. T cells in general were unresponsive and did not proliferate upon exposure to mitogens or to Toxoplasma lysate antigens or in response to live Toxoplasma-infected cells when the congenitally infected infants were 1 month of age, and they exhibited selective anergy to Toxoplasma lysate antigens and live Toxoplasma-infected cells when the infants were aged 5 months. During the chronic phase of congenital toxoplasmosis in the patients who were more than I year of age, the repertoires of the gammadelta T-cell receptors were found to be within normal ranges. In addition, in the chronic phase, the gammadelta T cells proliferated and secreted gamma-interferon in response to exposure to live Toxoplasmia-infected cells. By contrast, alphabeta T cells remained anergic. Vdelta2+ gammadelta T cells have been considered to undergo extrathymic maturation and thus to be subject to development of peripheral tolerance. Our findings indicate that Vdelta2+ gammadelta T-cell tolerance was lost in these infected infants earlier than alphabeta T-cell tolerance. These findings suggest that gammadelta T cells play a role in protection against Toxoplasma gondii in the chronic phase when congenitally infected children are more than 1 year of age, especially in those in whom alphabeta T cells continue to exhibit deficits in specific immune responses to Toxoplasma antigens.

Isolation and characterization of a MAGE gene family in the Xp21.3 region.

A human gene with strong homology to the MAGE gene family located in Xq27-qter has been isolated by using exon-trapping of cosmids in the Xp21.3 region. We have mapped and sequenced cDNA and genomic clones corresponding to this gene, MAGE-Xp, and shown that the last exon contains the open reading frame and is present in a minimum of five copies in a 30-kb interval. MAGE-Xp is expressed only in testis and, unlike the Xq27-qter MAGE genes, it is not expressed in any of 12 different tumor tissues tested. However, the gene and predicted protein structure are conserved, suggesting a similar function. MAGE-Xp is located in the 160-kb critical interval defined for the locus involved in sex determination within Xp21 and is 50 kb distal to the DAX-1 gene, which is responsible for X-chromosome-linked adrenal hypoplasia congenita.

Intermediate hosts of Toxoplasma gondii and food safety:epidemiology, genetics and parasite survival in meat-producing animals in Italy

Toxoplasma gondii is a coccidian parasite with a global distribution. The definitive host is the cat (and other felids). All warm-blooded animals can act as intermediate hosts, including humans. Sexual reproduction (gametogony) takes place in the final host and oocysts are released in the environment, where they then sporulate to become infective. In intermediate hosts the cycle is extra-intestinal and results in the formation of tachyzoites and bradyzoites. Tachyzoites represent the invasive and proliferative stage and on entering a cell it multiplies asexually by endodyogeny. Bradyzoites within tissue cysts are the latent form. T. gondii is a food-borne parasite causing toxoplasmosis, which can occur in both animals and humans. Infection in humans is asymptomatic in more than 80% of cases in Europe and North-America. In the remaining cases patients present fever, cervical lymphadenopathy and other non-specific clinical signs. Nevertheless, toxoplasmosis is life threatening if it occurs in immunocompromised subjects. The main organs involved are brain (toxoplasmic encephalitis), heart (myocarditis), lungs (pulmonary toxoplasmosis), eyes, pancreas and parasite can be isolated from these tissues. Another aspect is congenital toxoplasmosis that may occur in pregnant women and the severity of the consequences depends on the stage of pregnancy when maternal infection occurs. Acute toxoplasmosis in developing foetuses may result in blindness, deformation, mental retardation or even death. The European Food Safety Authority (EFSA), in recent reports on zoonoses, highlighted that an increasing numbers of animals resulted infected with T. gondii in EU (reported by the European Member States for pigs, sheep, goats, hunted wild boar and hunted deer, in 2011 and 2012). In addition, high prevalence values have been detected in cats, cattle and dogs, as well as several other animal species, indicating the wide distribution of the parasite among different animal and wildlife species. The main route of transmission is consumption of food and water contaminated with sporulated oocysts. However, infection through the ingestion of meat contaminated with tissue cysts is frequent. Finally, although less frequent, other food products contaminated with tachyzoites such as milk, may also pose a risk. The importance of this parasite as a risk for human health was recently highlighted by EFSA’s opinion on modernization of meat inspection, where Toxoplasma gondii was identified as a relevant hazard to be addressed in revised meat inspection systems for pigs, sheep, goats, farmed wild boar and farmed deer (Call for proposals -GP/EFSA/BIOHAZ/2013/01). The risk of infection is more highly associated to animals reared outside, also in free-range or organic farms, where biohazard measure are less strict than in large scale, industrial farms. Here, animals are kept under strict biosecurity measures, including barriers, which inhibit access by cats, thus making soil contamination by oocysts nearly impossible. A growing demand by the consumer for organic products, coming from free-range livestock, in respect of animal-welfare, and the desire for the best quality of derived products, have all led to an increase in the farming of free-range animals. The risk of Toxoplasma gondii infection increases when animals have access to environment and the absence of data in Italy, together with need for in depth study of both the prevalence and genotypes of Toxoplasma gondii present in our country were the main reasons for the development of this thesis project. A total of 152 animals have been analyzed, including 21 free-range pigs (Suino Nero race), 24 transhumant Cornigliese sheep, 77 free-range chickens and 21 wild animals. Serology (on meat juice) and identification of T. gondii DNA through PCR was performed on all samples, except for wild animals (no serology). An in-vitro test was also applied with the aim to find an alternative and valid method to bioassay, actually the gold standard. Meat samples were digested and seeded onto Vero cells, checked every day and a RT-PCR protocol was used to determine an eventual increase in the amount of DNA, demonstrating the viability of the parasite. Several samples were alos genetically characterized using a PCR-RFLP protocol to define the major genotypes diffused in the geographical area studied. Within the context of a project promoted by Istituto Zooprofilattico of Pavia and Brescia (Italy), experimentally infected pigs were also analyzed. One of the aims was to verify if the production process of cured “Prosciutto di Parma” is able to kill the parasite. Our contribution included the digestion and seeding of homogenates on Vero cells and applying the Elisa test on meat juice. This thesis project has highlighted widespread diffusion of T. gondii in the geographical area taken into account. Pigs, sheep, chickens and wild animals showed high prevalence of infection. The data obtained with serology were 95.2%, 70.8%, 36.4%, respectively, indicating the spread of the parasite among numerous animal species. For wild animals, the average value of parasite infection determined through PCR was 44.8%. Meat juice serology appears to be a very useful, rapid and sensitive method for screening carcasses at slaughterhouse and for marketing “Toxo-free” meat. The results obtained on fresh pork meat (derived from experimentally infected pigs) before (on serum) and after (on meat juice) slaughter showed a good concordance. The free-range farming put in evidence a marked risk for meat-producing animals and as a consequence also for the consumer. Genotyping revealed the diffusion of Type-II and in a lower percentage of Type-III. In pigs is predominant the Type-II profile, while in wildlife is more diffused a Type-III and mixed profiles (mainly Type-II/III). The mixed genotypes (Type-II/III) could be explained by the presence of mixed infections. Free-range farming and the contact with wildlife could facilitate the spread of the parasite and the generation of new and atypical strains, with unknown consequences on human health. The curing process employed in this study appears to produce hams that do not pose a serious concern to human health and therefore could be marketed and consumed without significant health risk. Little is known about the diffusion and genotypes of T. gondii in wild animals; further studies on the way in which new and mixed genotypes may be introduced into the domestic cycle should be very interesting, also with the use of NGS techniques, more rapid and sensitive than PCR-RFLP. Furthermore wildlife can become a valuable indicator of environmental contamination with T. gondii oocysts. Other future perspectives regarding pigs include the expansion of the number of free-range animals and farms and for Cornigliese sheep the evaluation of other food products as raw milk and cheeses. It should be interesting to proceed with the validation of an ELISA test for infection in chickens, using both serum and meat juice on a larger number of animals and the same should be done also for wildlife (at the moment no ELISA tests are available and MAT is the reference method for them). Results related to Parma ham do not suggest a concerning risk for consumers. However, further studies are needed to complete the risk assessment and the analysis of other products cured using technological processes other than those investigated in the present study. For example, it could be interesting to analyze products such as salami, produced with pig meat all over the Italian country, with very different recipes, also in domestic and rural contexts, characterized by a very short period of curing (1 to 6 months). Toxoplasma gondii is one of the most diffuse food-borne parasites globally. Public health safety, improved animal production and protection of endangered livestock species are all important goals of research into reliable diagnostic tools for this infection. Future studies into the epidemiology, parasite survival and genotypes of T. gondii in meat producing animals should continue to be a research priority.

Transferência transplacentária de anticorpos em gestações gemelares

Há poucos dados na literatura sobre o transporte transplacentário de imunoglobulinas em gestações múltiplas. O objetivo deste estudo foi observar fatores que influenciam a concentração de imunoglobulina G (IgG) no cordão umbilical dos neonatos e a transferência transplacentária de IgG total e de IgG contra o Streptococcus grupo B (EGB), e lipopolissacarídeos (LPS) de Klebsiella spp. e Pseudomonas spp.. Métodos: estudo prospectivo realizado no Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo no período de 2012 a 2013. Foram coletadas amostras de sangue materno e de cordão umbilical no momento do parto. Os critérios de inclusão foram gestações gemelares com ausência de sinais de infecção por HIV, citomegalovírus, Hepatites B e C, toxoplasmose e rubéola e ausência de doenças autoimunes, malformação fetal e síndromes genéticas. A análise multivariada foi realizada para avaliar a associação entre os níveis de IgG em cordão umbilical e as taxas de transferência de anticorpos com a concentração materna de IgG, a corionicidade da gestação, a presença de insuficiência placentária, a restrição de crescimento intrauterino, a idade gestacional de nascimento, o peso de nascimento, o tabagismo, a doença materna e a via de parto. Resultados: a concentração de IgG total em cordão umbilical apresentou correlação positiva com os níveis maternos séricos de IgG total e a idade gestacional do parto. Os níveis de IgG total em cordão umbilical foram significativamente menores em gestações monocoriônicas quando comparadas às dicoriônicas. A taxa de transferência de IgG total apresentou correlação positiva com a idade gestacional do parto, mas negativa com as concentrações maternas de IgG total. As concentrações de IgG contra EGB e LPS de Klebsiella spp. e Pseudomonas spp. apresentaram associação com os níveis maternos de IgG específicos contra esses antígenos e com o diabetes. Os níveis de IgG contra LPS de Klebsiella spp. também foram associados com o peso de nascimento e com hipertensão materna. As taxas de transferência de IgG contra EGB e LPS de Pseudomonas spp. apresentaram correlação com os níveis maternos de IgG específicos contra os antígenos referidos. A taxa de transferência de IgG contra EGB também esteve associada com a idade gestacional do parto, enquanto a taxa de transferência de IgG contra LPS de Pseudomonas spp. apresentou correlação com diabetes. Não houve correlação entre a taxa de transferência de IgG contra a LPS de Klebsiella spp. com nenhum fator analisado. Conclusão: em gestações gemelares, a concentração total de IgG em cordão umbilical foi influenciada pela concentração materna de IgG total, pela idade gestacional do parto e pela corionicidade placentária. As concentrações de IgG total foram significativamente menores em gestações monocoriônicas que em dicoriônicas. As concentrações séricas de IgG contra EGB e LPS de Klebsiella spp. e Pseudomonas spp. em cordão umbilical apresentaram associação com os níveis maternos de IgG específicos contra esses antígenos e com a presença de diabetes. Todos os outros parâmetros estudados apresentaram diferentes associações com as concentrações de IgG e com as taxas de transferências de IgG específicas contra cada antígeno investigado

Infecção concomitante experimental de Rattus norvegicus por Toxocara canis e Toxoplasma gondii: estudo comportamental e histopatológico

A hipótese de \"manipulação comportamental\" supõe que um parasito pode alterar o comportamento de seu hospedeiro visando aumentar a probabilidade de completar seu ciclo evolutivo. Tais alterações aumentariam a taxa de transmissão hospedeirohospedeiro, assegurando ao parasito ou a seus propágulos o encontro de novo hospedeiro. A possibilidade de infecções parasitárias provocarem mudanças comportamentais em seus hospedeiros e a elevada frequência com que o acometimento de seres humanos por larvas de Toxocara e cistos de Toxoplasma ocorre, têm chamado à atenção de pesquisadores interessados no estudo das relações hospedeiro-parasita. Na infecção por Toxoplasma gondii e Toxocara canis, cistos e larvas estão presentes em diversos locais anatômicos incluindo musculatura, coração, pulmões, olhos e cérebro. A presença de parasitos no cérebro dá oportunidade de manipulação do comportamento do hospedeiro. Entretanto, não se sabe qual ou quais mecanismos estão envolvidos no processo de manipulação do comportamento. Os objetivos do presente estudo foram verificar alterações na ansiedade, medo, memória e aprendizagem de Rattus norvegicus experimentalmente infectados por Toxocara canis e/ou Toxoplasma gondii em dois períodos após infecção, bem como a localização das larvas e cistos e presença de placas beta amiloide ( A) na região do hipocampo no tecido cerebral desses roedores corado pela técnica de Hematoxilina e Eosina (HE), e Vermelho de Congo, respectivamente. Foram utilizadas 40 exemplares fêmeas da espécie Rattus norvegicus, com seis a oito semanas. Os animais foram divididos em quatro grupos: Toxocara - 10 ratos infectados com 300 ovos de Toxocara canis, Toxoplasma -10 ratos infectados com 10 cistos de Toxoplasma gondii, Infecção dupla - 10 ratos infectados com 300 ovos de Toxocara canis e 10 cistos de Toxoplasma gondii, e controle - 10 ratos sem infecção. Nos dias 40, 41, 70 e 71 após a infecção, os animais dos grupos infectados e controle foram submetidos à avaliação no Labirinto em Cruz Elevado e Campo aberto. Aos 120 após infecção foi feita avaliação da memória, aprendizado e aversão a urina de gato dos animais no Labirinto de Barnes. No final das análises comportamentais os animais foram levados a eutanásia para retirada do cérebro e confecção dos cortes histológicos preparados em HE e Vermelho de Congo. Os resultados mostraram efeito ansiolítico para ambas as infecções, principalmente para Toxoplasma gondii. Não houve comprometimento da memória e aprendizado no LB, porém os animais infectados por Toxocara canis ou Toxoplasma gondii apresentaram menor tempo para encontrar a toca com urina e entrar nela. A leitura dos cortes histológicos corados com HE mostraram larvas de Toxocara canis e cistos de Toxoplasma gondii em regiões do sistema nervoso central dos animais relacionadas com memória e aprendizado. As lâminas coradas com Vermelho de Congo apresentaram placas beta amiloides ( A) em metade dos animais infectados por Toxoplasma gondii. Conclui-se que a infecção por ambos os parasitos apresenta efeito ansiolítico quando ocorre infecção única. Quando a Infecção ocorre concomitantemente há modulação no comportamento. Além disso, ratas infectadas com infecção única apresentam-se menos aversivas à urina de gatos.

Heterogeneity in testing practices for infections during pregnancy: national survey across Switzerland.

QUESTION Detection and treatment of infections during pregnancy are important for both maternal and child health. The objective of this study was to describe testing practices and adherence to current national guidelines in Switzerland. METHODS We invited all registered practicing obstetricians and gynaecologists in Switzerland to complete an anonymous web-based questionnaire about strategies for testing for 14 infections during pregnancy. We conducted a descriptive analysis according to demographic characteristics. RESULTS Of 1138 invited clinicians, 537 (47.2%) responded and 520 (45.6%) were eligible as they are currently caring for pregnant women. Nearly all eligible respondents tested all pregnant women for group B streptococcus (98.0%), hepatitis B virus (HBV) (96.5%) and human immunodeficiency virus (HIV) (94.7%), in accordance with national guidelines. Although testing for toxoplasmosis is not recommended, 24.1% of respondents tested all women and 32.9% tested at the request of the patient. Hospital doctors were more likely not to test for toxoplasmosis than doctors working in private practice (odds ratio [OR] 2.52, 95% confidence interval [CI] 1.04-6.13, p = 0.04). Only 80.4% of respondents tested all women for syphilis. There were regional differences in testing for some infections. The proportion of clinicians testing all women for HIV, HBV and syphilis was lower in Eastern Switzerland and the Zurich region (69.4% and 61.2%, respectively) than in other regions (range 77.1-88.1%, p <0.001). Most respondents (74.5%) said they would appreciate national guidelines about testing for infections during pregnancy. CONCLUSIONS Testing practices for infections in pregnant women vary widely in Switzerland. More extensive national guidelines could improve consistency of testing practices.

International Union of Pharmacology. LXVI. Orphan nuclear receptors

Half of the members of the nuclear receptors superfamily are so-called orphan receptors because the identity of their ligand, if any, is unknown. Because of their important biological roles, the study of orphan receptors has attracted much attention recently and has resulted in rapid advances that have helped in the discovery of novel signaling pathways. In this review we present the main features of orphan receptors, discuss the structure of their ligand-binding domains and their biological functions. The paradoxical existence of a pharmacology of orphan receptors, a rapidly growing and innovative field, is highlighted.

Familial adrenal hypoplasia syndromes

The adrenal cortex secretes steroid hormones, including glucocorticoids and mineralocorticoids. Glucocorticoids control body homeostasis, stress, and immune responses, while mineralocorticoids regulate the water and electrolyte balance. A spectrum of genetic defects can disrupt the normal adrenal development, causing adrenal hypoplasia and various forms of adrenal insufficiency, which usually present in infancy or childhood with or without mineralocorticoid deficiency and with or without gonadal dysfunction. The genetic causes of adrenal hypoplasia can be broadly categorized into adrenal hypoplasia due to adrenocorticotropic hormone resistance syndromes (i.e., familial glucocorticoid deficiency and triple A syndrome) and adrenal hypoplasia due to primary defects in the development of the adrenal glands (i.e., X-linked adrenal hypoplasia congenita and primary adrenal hypoplasia caused by steroidogenic factor 1 mutations).

Análise do perfil de encaminhamento da atenção primária para pré-natal de alto risco: desafios para o ensino de competências em saúde materno-infantil

OBJECTIVE: to identify a profile of the main causes of inappropriate referrals from primary care to specialized services, as strategy for the curriculum development of core competencies related to maternal health. METHODS: a cross-sectional study was performed using document analysis of all referrals of pregnant women from primary care to the high-risk pregnancy service, state of Rio Grande do Norte, Brazil. All pregnant women referred from June to December 2014 (n = 771) were included. According to their causes the referrals were categorized as adequate, inadequate or inconclusive. RESULTS: a total of 188 referrals were classified as inadequate (24.4%) and 93 inconclusive (12.1%) totalizing 36.5% of inappropriate referrals. The main causes identified in these inappropriate referrals were: low-risk pregnancy (12.8%), unconfirmed hypertension (12.1%), risk of abortion (8.9%), teenage pregnancy (7.1%) , toxoplasmosis (5.3%), Rh incompatibility (4.6%) and urinary tract infection (4.3%). These data contributed to the formulation of the following products: 1) a continuing education program for health professionals working in primary care, undergraduate students and residents; and 2) development of a virtual platform to support professionals who need to refer patients to high-risk pregnancy service. CONCLUSION: the results of this study are relevant in the current context of education of health professionals, with potential for positively impact not only in the development of skills related to maternal health in undergraduate and graduate education, as well as contributing for improvement of the health care of the population.