Evaluation of piper cubeba extract, (-)-cubebin and its semi-synthetic derivatives against oral pathogens.

The activities of the crude ethanol extract from Piper cubeba seeds, (-)-cubebin and its semi-synthetic derivatives were evaluated against oral pathogens. The crude ethanol extract was more active against Streptococcus salivarius (MIC value of 80 microg/mL). (-)-Cubebin displayed MIC values ranging from 0.20 mm for Streptococcus mitis to 0.35 mm for Enterococcus faecalis. The natural product (-)-cubebin and its semi-synthetic derivative (-)-hinokinin displayed bacteriostatic activity at all evaluated concentrations, as well as fungicidal activity against Candida albicans at 0.28 mm. The O-benzyl cubebin derivative showed fungistatic and fungicidal effects against C. albicans at 0.28 mm and 0.35 mm, respectively. Also, the other dibenzylbutyrolactone derivatives [(-)-6,6'-dinitrohinokinin and (-)-O-(N,N-dimethylaminoethyl)-cubebin] displayed bacteriostatic and fungistatic effects at the evaluated concentrations. Moreover, the semi-synthetic derivative (-)-6,6'-dinitrohinokinin was the most active compound against all the evaluated microorganisms. Therefore, it may be suggested that the presence of the carbonyl group at C-9 plus the introduction of polar groups in the aromatic rings improve the antimicrobial activity of dibenzylbutyrolactone compounds.

Analgesic and anti-inflammatory activities of (-)-o benzyl cubebin, a (-)-cubebin derivative, obtained by partial synthesis.

The anti-inflammatory and antinociceptive effects of the benzylated cubebin derivative, obtained by reaction of (-)-cubebin with benzyl bromide, were investigated using different animal models. The (-)-o-benzyl cubebin showed a low anti-inflammatory effect (16.2%) in relation to cubebin (57%) and indomethacin (77%) in the carrageenin-induced paw edema in rats, but on the other hand it was more effective (80%) than (-)-cubebin (41%) in inhibiting acetic acid-induced writhing in mice, producing dose-response correlation with doses of 10, 20 and 40 mg/kg, respectively. Moreover, this derivative compound did not show activity in both the hot plate and the cell migration test in rats. Overall, the results showed that the benzylation of cubebin were efficient in enhancing only its analgesic activity.

Equine monocytic Ehrlichiosis (Potomac horse fever) in horses in Uruguay and southern Brazil.

A disease named locally as churrío or churrido equino (i.e., equine scours) has occurred for at least 100 years in Uruguay and southern Brazil in farms along both shores of the Merín lake. This report describes cases of churrido equino and provides serologic, pathologic, and DNA-based evidence indicating that the disease is in fact equine monocytic ehrlichiosis (Potomac horse fever). Results of an epidemiological investigation conducted on an endemic farm are also presented. Clinical signs in 12 horses were fever, depression, diarrhea, dehydration, and sometimes colic and distal hind limb edema. Postmortem findings of 3 horses were of acute enterocolitis. Inclusion bodies containing ehrlichial organisms were found in the cytoplasm of macrophages of the large colon of 1 horse. Eleven of the 12 horses were serologically positive to Ehrlichia risticii (indirect fluorescent antibody assay) and, of 3 paired samples, 2 showed seroconversion. Ehrlichia risticii DNA was identified by a nested polymerase chain reaction in peripheral blood of an affected horse. A healthy horse inoculated with peripheral blood from an affected horse developed the disease and antibodies to E. risticii. The disease had a peak incidence in March (summer) and was statistically associated with a marshy ecosystem near the Merín lake, where large numbers of Pomacea spp. (Ampullariidae) snails were found. Incidence density was almost 8 times higher in nonnative horses than in native horses. It was concluded that the previous diarrheic disease of horses known in Uruguay and southern Brazil as churrido equino is equine monocytic ehrlichiosis.

[Primary immunodeficiency secondary to ZAP-70 deficiency]. / Imunodeficiência primária por défice de ZAP-70.

The authors present the case of a child with recurrent infections since the age of 4 months, including bilateral pneumonia by Pneumocystis carinii and protracted varicella. Serum immunoglobulin values (when 10 months old), and B cell values were normal. There was persistent lymphocytic leucocytosis, near absence of CD8+ cells, and an increased CD4/CD8 ratio. The percentage of activated T cells and the expression of HLA class I were normal. Proliferation, activation and IL-2 synthesis studies in T cells showed a TCR/CD3-associated signal transduction deficit. ZAP-70 cDNA sequencing showed a mutation, and no ZAP-70 protein was detected in T cells. ZAP-70 deficiency is associated with a rare immune deficiency with absence of CD8+ T cells as well as a functional deficiency in T cells. Seven months after bone marrow transplantation the child is clinically well and immunologically recovered.

[HCV genotypes. Liver histopathology and immunologic profile in four groups of patients]. / Genótipos do VHC. Histopatologia hepática e perfil imunológico em quatro grupos de doentes.

AIM: Study on the prevalence of MCV genotypes, and correlation with liver pathology and immunological parameters. PATIENTS AND METHODS: 77 chronic hepatitis C patients (52 males, 25 females), mean age 44 +/- 14 years, belonging to four groups: (1) 23 (11 males) without other aetiology, (II) 19 (18 males) excessive drinkers, (III) 18 (12 males) haemodialysed, (IV) 17 (11 males) renal transplantation patients Genotyping was done by PCR (primers of the core, and hybridisation with specific probes). Serum Igs A, G, and M (by nephelometry), and peripheral blood lymphocyte (PBL) subsets (by flow cytometry) were determined. RESULTS: One genotype was found in 62 patients (1b 69.2%, 1a 21.5%, 2a 3.1%, 2b 3.1%, 3a 9.2%), and two genotypes in 4 patients (1b + 3a in 1 of group 1, 1b + 2a in 2 and 1a + 3a in 1 of group 111). Twelve cases (15.6%) were not identified (NI). Relative prevalence was not different in the four groups, but in 7 drug addicts 1 b was not found (Ia in 71.4%, 3 a 28.6%) The relationship between genotypes and age was significant (p < 0.05): in the 34 patients with less than 40 years, 1b was found in 38.2%, in the others in 41.2%, and NI in 20.6%; in those with 40-60 years, 1b was found in 68.8%, in the others in 15.6%, M in 15.6%; in those above 60 years, 1b was found in 90.9%, in the others in 9.1%. Of those identified, only genotype 1 (1a and 1b) was associated to moderate or severe activity, and infected 11/13 cases of cirrhosis or severe fibrosis. IgM (g/dL) was lower in 1b than in the others: 1.58 + 1.23 vs. 2.53 + 1.93 (p < 0.01). PBL (per mm3) were lesser in 1b than in the others, with significance for the CD8+: 540t239 vs. 739 + 420 (p < 0.01). CONCLUSIONS: Genotype 1b was the most prevalent in Portuguese patients, more significantly in the elderly, and was absent in drug addicts. The prevalence of genotypes is similar in general patients, in chronic haemodialysed, in renal transplantation recipients and in alcoholics. More severe liver pathology was associated with 1b and 1a genotypes. IgM and CD8+ had lower mean values in 1b infected patients. Other genotypes are certainly important in Portugal.

[Thoracic endometriosis]. / Endometriose torácica.

Endometriosis was first described by Russel more than one-hundred years ago and still remains a clinical entity of difficult comprehension, with totally aberrant symptomatology, particularly in extra-genital situations. The present article describes a clinical case of recurring right-sided catamenial pneumothorax in a 45 year-old caucasian woman. In her last episode of right chest pain the X-ray film showed, besides the presence of a pneumothorax, a nodular image, later identified by CT scan as being a transdiaphragmatic hernia with hepatic content. The patient was then submitted to diagnostic and therapeutic thoracotomy and the diaphragmatic endometriosis was confirmed. Finally, a total hysterectomy with bilateral salpingo-ophorectomy was performed and the patient's condition remained uneventful with combined hormone therapy. The clinical presentation, pathogenesis, and therapeutic resolution of this nosological entity are briefly discussed.

[Hysterosalpingography in the diagnosis of pelvic endometriosis]. / A histerossalpingografia no diagnóstico da endometriose pélvica.

Endometriosis is a common cause of chronic pelvic pain. Laparoscopy is considered the gold standard for definitive diagnosis. This work aims to evaluate whether hysterosalpingography (14SG), a cheaper and more accessible examination, is worth while as a diagnostic tool in this pathology. Thirty patients submitted to laparoscopy for chronic pelvic pain where retrospectively studied. Three different observers evaluated their hysterosalpingographies. The imaging diagnoses were classified as suggestive or not suggestive of external pelvic endometriosis. With laparoscopy, 18 patients had endometriosis, 11 with mild lesions by Acosta classification. Compared to laparoscopy, HSG diagnosis, when made by at least two observers, revealed a sensitivity of 55.5%, a specificity of 75%, a positive predictive value of 77%, and a negative predictive value of 53%. In the presence of clinical pathologic uterosacral--US ligaments and/or sterility, the specificity of HSG may be 100%, but the sensitivity falls below the 40%. We concluded that in a population with chronic pelvic pain, HSG is not a first choice diagnostic tool. This examination only permits the identification of 1/3 of the patients with external endometriosis, being unable to exclude its presence. However, it may be useful in patients with infiltrative endometriosis of the US ligaments.

Functional aspects of cord blood lymphocytes response to polyclonal and allogeneic activation.

With the purpose of contributing to a better knowledge of the phenotypic characteristics and functional activity of umbilical cord blood (UCB) lymphocytes, we have carried out extensive immunophenotyping of these cells, evaluated their immune response to polyclonal and allogeneic activation and then compared these results with those obtained with peripheral blood lymphocytes of healthy donors (PBHD). Our results showed, in CD4+ UCB lymphocytes, an increase of CD38 and CD45RA and a decrease of CD11a (S6F1), CD54 and HLA-DR double positive cells. An increase of CD38, CD45RA and CD56, and a decrease of CD28, CD57 and HLA-DR were observed in CD8+ UCB lymphocytes. Most natural killer UCB cells are CD16+, CD56+, CD57-, and among the UCB cells there is a lower number of CD8+ and TCRgammadelta+ (either CD8- or CD8+), and higher number of CD4+ lymphocytes. After allogeneic stimulus the majority of these phenotypic differences disappeared, which seems to be in agreement with the normal allogeneic response (assessed through MLR, frequency of CTL and helper T lymphocytes precursors) presented by UCB lymphocytes. Regarding the response to polyclonal activation, among the mitogens used, only PHA induced a different result: a lower IFNgamma production by UCB cells.

Relatedness among Basques, Portuguese, Spaniards, and Algerians studied by HLA allelic frequencies and haplotypes.

HLA-A, -B, -DRB1, -DQA1, and DQB1 alleles were studied in Iberian and Algerian populations by serology and DNA sequence methodologies. The genetic and cultural relatedness among Basques, Spaniards, and paleo-North Africans (Berbers or Tamazights) was established. Portuguese people have also maintained a certain degree of cultural and ethnic-specific characteristics since ancient times. The results of the present HLA study in Portuguese populations show that they have features in common with Basques and Spaniards from Madrid: a high frequency of the HLA-haplotypes A29-B44-DR7 (ancient western Europeans), A2-B7-DR15 (ancient Europeans and paleo-North Africans), and A1-B8-DR3 (Europeans) are found as common characteristics. Portuguese and Basques do not show the Mediterranean A33-B14-DR1 haplotype, suggesting a lower admixture with Mediterraneans; Spaniards and Algerians do have this haplotype in a relatively high frequency, indicating a more extensive Mediterranean genetic influence. The paleo-North African haplotype A30-B18-DR3 present in Basques, Algerians, and Spaniards is not found in Portuguese either. The Portuguese have a characteristic unique among world populations: a high frequency of HLA-A25-B18-DR15 and A26-B38-DR13, which may reflect a still detectable founder effect coming from ancient Portuguese, i.e., oestrimnios and conios; Basques and Algerians also show specific haplotypes, A11-B27-DR1 and A2-B35-DR11, respectively, probably showing a relatively lower degree of admixture. A neighbor-joining dendrogram place Basques, Portuguese, Spaniards, and Algerians closer to each other and more separated from other populations. Genetic, cultural, geological, and linguistic evidence also supports the hypothesis that people coming from a fertile Saharan area emigrated towards the north (southern Europe, Mesopotamia, the Mediterranean Islands, and the North African coast) when the climate changed drastically to hotter and drier ca 10 000 years B.C.