Antiproliferative and toxicological properties of methanolic extract obtained from <Emphasis Type="Italic">Solanum capsicoides</Emphasis> All. seeds and carpesterol

Natural products are considered important sources of potential chemotherapeutic agents. Here, we evaluated the antiproliferative activity and the toxicological effects of the methanolic extract and a pure compound obtained from Solanum capsicoides seeds. The phytochemical profile was analyzed by chromatographic and spectroscopy methods. The acute toxicity was assessed in mice orally treated with the extract (2000 mg/kg), in vitro hemolytic activity and micronucleus test. The mutagenicity, developmental toxicity, and lethal dose (LD50) of carpesterol were estimated by the Toxicity Estimation Software Tool (TEST) software. A sulforhodamine B assay was employed to evaluate the antiproliferative activity. The toxicological assays did not observe signs of toxicity, either during the behavioral observations or in the autopsies, as well as no mutagenicity and hemolytic activity. The carpesterol did not present mutagenic effect and hemolytic activity but presents developmental toxicology and LD50 of 410 mg/kg in toxicity estimations by the TEST software. The S. capsicoides extract exhibited antiproliferative activity mainly in leukemia (K562) cell lineage. However, carpesterol presented antiproliferative activity in glioma (U251), breast (MCF-7), kidney (786-0), ovary (OVCAR-03), and K562 cell lineages. The data obtained show that S. capsicoides extract presents antiproliferative and does not present toxicological effects. In addition, it was shown for the first time the antiproliferative and toxicological parameters of carpesterol.     

Characterization of VHL promoter variants in patients suspected of Von Hippel-Lindau disease

Von Hippel-Lindau (VHL) disease is a hereditary tumor syndrome in which carriers are at an increased risk of developing a variety of tumors in multiple organ systems. A clinical diagnosis of VHL is determined by the presence of specific clinical manifestations while a molecular genetic diagnosis results from a pathogenic variant in the VHL gene. The majority of mutations occur in VHL coding exons and DNA analysis of these regions has a reported sensitivity of nearly 100%. However, rare variants in the VHL gene promoter may be detected in some cases of suspected VHL disease. We report two cases where VHL promoter variants were detected and describe the role of multi-step mRNA and protein analysis in the diagnostic evaluation of these cases.     

A biomarker for tegumentary and visceral leishmaniasis based on a recombinant Leishmania hypothetical protein

The measures for leishmaniasis control include the precise diagnosis of disease. However, although several recombinant antigens have been tested with this biotechnological purpose, no effective product exists, which could detects patients with the active disease, as well as differentiates them from cured and treated patients. In this study, a conserved Leishmania hypothetical protein, which was identified in Leishmania infantum parasites, but evaluated to presents high homology in the amino acid sequences between distinct parasite species, was evaluated for the diagnosis of tegumentary and visceral leishmaniasis. In addition, PBMCs collected from treated and untreated mucosal leishmaniasis (ML) and visceral leishmaniasis (VL) patients, as well as in healthy subjects living in endemic region of disease, were in vitro stimulated, when IFN-γ, IL-4 and IL-10 levels were evaluated in the cell supernatant. Regarding the serological analyses, ELISA experiments using the recombinant protein (rLiHyL) and a human serological panel revealed high sensitivity and specificity values to detect both diseases, while control antigens showed worst results. Regarding the cellular response, results showed that rLiHyL-stimulated cells produced higher IFN-γ and lower IL-4 and IL-10 levels in the supernatants. Also, the anti-protein antibody production was evaluated in these patients, and data showed higher IgG2 and lower IgG1 levels found in the treated patients and healthy controls, demonstrating the stimulation of a Th1-type response induced by the rLiHyL protein. In conclusion, this hypothetical protein can be considered as antigenic in TL and VL, as well as a vaccine candidate to be tested in future studies to protect against disease.     

Case of recurrent paracoccidioidomycosis in female. 10 years after initial treatment

This report describes a case of recurrence of chronic paracoccidioidomycosis 10 years following the initial diagnosis. A 56-year-old female was admitted to the Dental Clinic of the Pontifical Catholic University of Paraná complaining of oral soreness. Mulberry-like ulcerations were observed on the gingiva, right labial comissura, and vermillion of the lip. The patient reported persistent chronic cough, weight loss, appetite loss and fever. The anamnesis revealed that the patient had developed and been treated for paracoccidioidomycosis 10 years earlier. A biopsy was performed and microscopic examination revealed microabscesses, collections of macrophages organized into granulomas, multinucleated giant cells and Paracoccidioides brasiliensis. The patient was treated with Itraconazole and, the oral lesions disappeared within 3 months. Persistent follow-up examination in patients with a history of paracoccidioidomycosis is essential in the management of this disease.     

Monitoring alendronate therapy for osteoporosis.

Alendronate is an antiresorptive therapy for osteoporosis and results in a decrease in bone turnover. To choose the optimal measurement for monitoring this therapy, the size of the change needs to be compared with the variability of the measurement. We studied 26 women with postmenopausal osteoporosis (bone mineral density [BMD] T score < -2.5), who were randomized in a 2:1 ratio to receive alendronate (10 mg/day) and calcium carbonate (500 mg/day) or calcium carbonate alone for 6 months. We measured serum markers of bone formation (osteocalcin [OC], bone isoform of alkaline phosphatase [BAP], and collagen type I C-terminal propeptide [CICP]) and urinary markers of bone resorption (cross-linked N-telopeptide [NTx], free deoxypyridinoline [iFDpd], and free pyridinolines). All subjects had two measurements 1 week apart at baseline to calculate the short-term variability. Biochemical measurements were then made at 4, 8, 12, 24, and 25 weeks. Measurements of bone mass were made by dual-energy X-ray absorptiometry (DXA) at the lumbar spine and proximal femur twice at baseline and then at 24 and 25 weeks. The mean difference in change in BMD and markers between both groups at the end of the study that were significant were (short-term variability in brackets): DXA total hip 4.3% (2.5%), NTX 49% (10%), iFDpd 22% (12%), OC 28% (13%), BAP 31% (13%), and CICP 31% (11%). Five of the six markers showed significant responses to alendronate therapy, but they differed in the relationship between size of response and variability. These biochemical markers performed better than DXA for monitoring alendronate therapy over 6 months.     

Surgical treatment of the substernal goitre.

This report describes the surgical experience gained from 32 patients with substernal goitre, operated on during January 1995 to December 1997. The material corresponds to 15.7% of the total thyroidectomies performed. The diagnosis was clinical. In spite of 65.6% of the patients being asymptomatic, breathing problems, dysphagia and hyperthyroidism were observed. The patients underwent tests of thyroid function, simple chest radiograph and computerized tomography of mediastinum. All patients underwent surgical treatment through a transverse cervical incision. Two patients (6.25%) needed median sternotomy. Vocal cord palsy (3.12%), transient hypocalcemia (6.25%) and one death due to cardiac causes (3.12%) were the complications that occurred.     

Rectal adenocarcinoma: assessment of tumour involvement of the lateral resection margin by MRI of resected specimen.

The aim of the present study was to investigate whether MRI could predict tumour involvement of the lateral resection margin on resected rectal cancer specimens. 26 specimens obtained after total mesorectal excision were examined in the sagittal and axial plane on a clinical 1.5 T MR system using phased-array surface coils. The shortest distance between the deepest point of tumour penetration and the lateral resection margin was measured. This distance is referred to as LRM. The results were correlated to measurements on digital images of giant histopathological sections. The total number of lymph nodes and lymph node metastases was also counted. LRM was less than or equal to 1 mm (a distance considered for non-radically excised tumours) in eight of the histopathological specimens. On MR images of the resected specimen, LRM was less than or equal to 1 mm in seven of these specimens. LRM was shorter in MR examinations than in histopathological giant sections in 11 specimens. The sensitivity, specificity, positive and negative predictive values for prediction of tumour involvement of the lateral resection margin (LRM < or = 1 mm) by MR of the resected specimen were 88%, 78%, 64% and 93%, respectively. Presence of lymph node metastases could not accurately be predicted by MR. However, it is concluded that the presence of a tumour free lateral resection margin can be predicted by MRI of resected rectal specimens when this exceeds 1 mm.     

Screening for inborn errors of metabolism in high-risk children from Rio de Janeiro, Brazil

From 1988 to 1995, our laboratory at the Institute of Chemistry of the Federal University of Rio de Janeiro, in Rio de Janeiro, screened 2650 samples from 2000 high-risk patients (mostly children) for Inborn Errors of Metabolism (IEM). Chemical tests, various chromatographic techniques and enzyme assays were performed on urine, plasma and in some cases, cerebrospinal fluid (CSF). A total of 145 cases of IEM (7.2%) was identified. These were related to: the metabolism of amino acids (41) and carbohydrates (17), organic acids (7), lysosomal enzymes (61), membrane transport system (16), metals (2), intestinal disaccharidases (1) and porphyrin metabolism (3). Furthermore, a relevant number of patients with abnormal findings is still under investigation. Biochemical results and clinical symptoms are presented and the importance of reference laboratories for the detection of IEM is stressed.     

Multivariate Analysis of Clinical Factors in Restenosis after Coronary Stenting

Ojbective To find the independent predictors for restenosis after coronary stenting. Methods Quantitative angiography was performed on 60 cases (67 successfully dilated lesions) after angio-plasty over 6-months follow-up, and both univariate and multivariate logistic regression analysis were done to i-dentify the correlations of restenosis with clinical factors. Results The total restenosis rate was 31. 3% (21 of 67 lesions), and according to univariate analysis the patients who underwent coronary stenting≥ 3. 5mm had a lower rate of restenosis ( P < 0. 01). Collateral circulation to the obstruction site, high maximal inflation pressure, smoking and the less minimal lumen diameter after PTCA made the rate of restenosis higherower ( P < 0. 05) . Multivariate logistic regression analysis showed that coronary stenting ≥3. 5mm had a low rate of restenosis, but high maximal inflation pressure and smoking made the restenosis rate higher. Conclusion Coronary stent size, maximal inflation pressure and. smokin