Cystic fibrosis in Afro-Brazilians: XK haplotypes analysis supports the European origin of p.F508del mutation.

Cystic fibrosis (CF) is a common autosomal recessive disorder, being the p.F508del the most frequent mutation. Also, a nearby restriction fragment length polymorphism (RFLP) named XK (KM19 and XV2C) is non-randomly associated with specific CF alleles. Our aim was to analyze the occurrence of the p.F508del mutation and XK haplotypes in Afro-Brazilians CF patients and controls, since these data is available for the other two main ethnic groups found in Brazil (Euro-Brazilians and Brazilian Amerindians), contributing for the whole comprehension of these haplotypes in the Brazilian population. A total of 103 patients and 54 controls were studied. PCR and PCR-RFLP methodologies were used to identify the presence of the p.F508del and the XK haplotype in the subjects. The combined data show that 84.2% of p.F508del mutation is associated with haplotype B and only 15.8% with haplotype A; no other haplotypes were found to be associated with this mutation. Our data suggest that the occurrence of p.F508del mutation and haplotype B in Afro-Brazilian patients occurs probably due to admixture with Euro-descendants. Therefore this mutation and haplotype could be used as a admixture marker.

Physical-chemical characterization and stability study of alpha-trypsin at pH 3.0 by differential scanning calorimetry.

alpha-Trypsin is a serine-protease with a polypeptide chain of 223 amino acid residues and six disulfide bridges. It is a globular protein with predominance of antiparallel ss-sheet secondary structure and it has two domains with similar structures. In the present work, a stability study of alpha-trypsin in the acid pH range was performed and some physical-chemical denaturation parameters were measured by using differential scanning calorimetry (DSC). The alpha-trypsin has a shelf-life (t(95%)) of about 10 months at pH 3.0 and 4 degrees C and its hydrolysis into the psi-trypsin isoform is negligible during 6 months. The observed ratio DeltaH(cal)/DeltaH(vH) is close to unity, which suggests the occurrence of a two-state transition. At pH 3.0, alpha-trypsin unfolded with T(m) = 325.9 K and DeltaH = 99.10 kcal mol(-1), and the change in heat capacity between the native and unfolded forms of the protein was estimated to be 1.96+/-0.18 kcal mol(-1)K(-1). The stability of alpha-trypsin calculated at 298 K was DeltaG(U)=6.10 kcal mol(-1) at pH 3.0. These values are in the range expected for a small globular protein. These results show that the thermodynamic parameters of unfolding of beta-trypsin do not change substantially after its conversion to alpha-trypsin.

CD43-mediated signals induce DNA binding activity of AP-1, NF-AT, and NFkappa B transcription factors in human T lymphocytes.

Although numerous reports document a role for CD43 in T cell signaling, the direct participation of this molecule in cell activation has been questioned. In this study we show that CD43 ligation on human normal peripheral T cells was sufficient to induce interleukin-2, CD69, and CD40-L gene expression, without requiring signals provided by additional receptor molecules. This response was partially inhibited by cyclosporin A and staurosporine, suggesting the participation of both the Ca(2+) and the protein kinase C pathways in CD43 signaling. Consistent with the transient CD43-dependent intracellular Ca(2+) peaks reported by others, signals generated through the CD43 molecule resulted in the induction of NF-AT DNA binding activity. CD43-dependent signals resulted also in AP-1 and NFkappaB activation, probably as a result of protein kinase C involvement. AP-1 complexes bound to the AP-1 sequence contained c-Jun, and those bound to the NF-AT-AP-1 composite site contained c-Jun and Fos. NFkappaB complexes containing p65 could be found as early as 1 h after CD43 cross-linking, suggesting that CD43 participates in early events of T cell activation. The induction of the interleukin-2, CD69, and CD-40L genes and the participation of AP-1, NF-AT, and NFkappaB in the CD43-mediated signaling cascade implicate an important role for this molecule in the regulation of gene expression and cell function.

[Massive hepatobiliary fascioliasis]. / Fasciolosis hepatobiliar masiva.

UNLABELLED: Massive hepatobiliary fascioliasis. Report of two cases. INTRODUCTION: Liver fascioliasis is the most frequent parasitic disease of the biliary tract in Mexico. Massive infestation is common in sheep and bovines and rarely occurs in humans. Only two previous cases of massive fascioliasis has been reported and we present here in two additional cases. Case reports. Both cases presented in alcohol-related liver disease patients who had eaten watercress Nasturium officinalis. Upper abdominal pain, obstructive jaundice, and choledochal dilatation were the salient manifestations. Diagnosis was made by surgical exploration and adult fluke identification. One patient died due to progressive liver failure and the other, is alive and received praziquantel treatment. CONCLUSIONS: Since 1935, approximately fifty cases of massive hepatobiliary fascioliasis have been reported in Mexico, most misdiagnosed as cholelithiasis; however, a history of watercress ingestion has been recorded in most of these cases.

Gliomatosis cerebri: findings with computed tomography and magnetic resonance imaging.

Gliomatosis cerebri (GC), is a rare neoplastic disease (less than 150 cases reported in the literature) with a diffuse, widespread proliferation of neoplastic glial cells in the brain, generally affecting both hemispheres and involving the gray and white matter [1-3]. Less commonly, the cerebellum, the brain stem and the medulla can be affected. Histologic evaluation reveals neoplastic astrocytes with varying levels of differentiation. Perineuronal and perivascular spread of tumor infiltration is observed. Demyelination can be found in the affected areas. A well-preserved underlying neuroanatomic architecture is considered characteristic [2]. Clinical signs vary and are non-specific, including changes in the mental state and headaches, followed by focal motor deficits and convulsive episodes [4]. The prognosis is poor, ranging from weeks to some years after the manifestation of the symptoms. Steroids may be useful in the short term, but chemotherapy is of little value and radiotherapy of questionable benefit. The literature was reviewed and the radiological pattern of three new cases of GC is reported. In two cases the diagnosis was achieved ante-mortem.

Hyperalgesic effect induced by barbiturates, midazolam and ethanol: pharmacological evidence for GABA-A receptor involvement

The involvement of GABA-A receptors in the control of nociception was studied using the tail-flick test in rats. Non-hypnotic doses of the barbiturates phenobarbital (5-50 mg/kg), pentobarbital (17-33 mg/kg), and thiopental (7.5-30 mg/kg), of the benzodiazepine midazolam (10 mg/kg) or of ethanol (0.4-1.6 g/kg) administered by the systemic route reduced the latency for the tail-flick response, thus inducing a 'hyperalgesic' state in the animals. In contrast, non-convulsant doses of the GABA-A antagonist picrotoxin (0.12- 1.0 mg/kg) administered systemically induced an increase in the latency for the tail-flick response, therefore characterizing an 'antinociceptive' state. Previous picrotoxin (0.12 mg/kg) treatment abolished the hyperalgesic state induced by effective doses of the barbiturates, midazolam or ethanol. Since phenobarbital, midazolam and ethanol reproduced the described hyperalgesic effect of GABA-A-specific agonists (muscimol, THIP), which is specifically antagonized by the GABA-A antagonist picrotoxin, our results suggest that GABA-A receptors are tonically involved in the modulation of nociception in the rat central nervous system.

Clonidine-induced diuresis and its relation to endogenous opioid peptides

Para estudar a diurese induzida por clonidina, esta substância foi administrada, por via intraperitoneal, em ratos. Intenso efeito diurético foi observado com doses entre 0,025 e 1,25 mg/kg, além de excreçäo aumentada de íons sódio e potássio. Esse efeito diurético foi intensamente inibido pela administraçäo prévia de ioimbina (bloqueador de receptores alfa-dois adrenérgicos) ou N-metil-nalorfina (bloqueador de receptores) opióides que penetra mal o sistema nervoso central). Por outro lado, seu efeito diurético foi aumentado, pela administraçäo prévia de naloxona, um bloqueador de receptores opióides mi. É provável que a ativaçäo de receptores alfa-dois adrenérgicos pela clonidina possa induzir a liberaçäo de substâncias endógenas opióides que causem diurese através da ativaçäo de receptores periféricos com baixa afinidade por naloxona

[Epidemic outbreak of scabies related to a patient with human immunodeficiency virus infection and Norwegian scabies]. / Brote epidémico de escabiosis en relación con un paciente con infección por el virus de la inmunodeficiencia humana y sarna noruega.

A patient with AIDS was admitted to our hospital because of pruritic and disabling erythroderma, it was treated with Lindane without improvement. Skin biopsy of a crusty lesion showed Sarcoptes scabiei hominis, and the diagnosis of Norwegian scabies was made. After a long and intensive treatment with several drugs, cure was achieved. In the following three months we detected 42 people with scabies, all in some relation with the index case. This feature of high contagiousness of Norwegian scabies in a constant, through the scanty literature we have found; and it is due to its diagnostic and therapeutic problems.

Estudos sobre os níveis sanguíneos de sulfametoxazol em caninos e ovinos: necessidade de adequaçäo do regime posológico / Sulphamethoxazol blood levels in dogs and sheep. Evidence for a differentiated dosage regimen

Os níveis sanguíenos de sulfametoxazol (SMT) foram determinados em caninos e ovinos, após administraçäo de produto comercial potencializado pela trimeoprina, em dose única de 30 mg/kg, por via intramuscular. Os níveis máximos alcançados foram: 6,52 mg/l em cäes, 4 h após a administraçäo, decaindo gradativamente até 24 h e 5,50 mg/l, em ovinos 2 h após a administraçäo, decaindo gradativamente até 12 h. A meia-vida biológica foi de 7,55 h para os caninos e 3,93 h, para os ovinos. O "clearance" total foi de 7,16 e 12,66 ml/min/kg, respectivamente no cäo e no carneiro. Cálculos adicionais mostraram que para se manter, nos ovinos, os mesmos níveis sanguíneos previstos para os caninos será necessário administrar dose 1,56 vezes maior ou diminuir o intervalo entre as administraçöes, nesta mesma proporçäo

Effect of potent antiglucocorticoids on dexamethasone induced enzymes in cultured hepatoma and rat liver cells.

The antagonism by 3 synthetic steroids of the induction of tyrosine aminotransferase and tryptophan dioxygenase by dexamethasone were compared in HTC and FAZA hepatoma cells and in isolated liver cells. It was observed: (i) the sensitivity of liver cells to glucocorticoid agonists and antagonists changed in relation to time of culture; (ii) the extent of the inhibitory effect on enzyme induction depends on the nature of the antagonist; (iii) hepatoma cells, especially HTC cells, appeared more sensitive to glucocorticoid antagonism than liver cells.

[Characterization of tyrosine aminotransferase by an immunoadsorption technic. Application to the measurement of the specific messenger RNA]. / Caractérisation de la tyrosine aminotransférase par une technique d'immunoadsorption. Application à la mesure de l'ARN messager spécifique.

A specific antiserum was used in an enzyme-linked immunoadsorbent assay (ELISA) for tyrosine amino-transferase TAT. Protein A bound on Sepharose was allowed to react with antiserum preincubated with the enzyme. Inhibition curves in the presence of protein A were parallel to those obtained in the absence of protein A. In the case of cell-free synthesized TAT, the complex bound to the solid phase contains the (35S) labelled enzyme; the sensitivity of the test was greatly increased when the bulk of protein was discarded by pretreatment of the reaction mixture at 70 degree and chromatography on DEAE cellulose. The immunoadsorbed polypeptides were analyzed by dodecylsulfate/polyacrylamide gel electrophoresis. The pattern of polypeptides neosynthesized using RNA from different origins (rat liver, hepatoma cells) and after various treatments (glucocorticoid hormones, sodium butyrate) exhibited some different in the TAT region which can be related to the level of the specific mRNA for TAT. This method is very useful for further studies on TAT gene expression and might also shed light on the mechanism of hormonal action and drug processes.