Triterpenoid saponins, new metalloprotease snake venom inhibitors isolated from Pentaclethra macroloba.

We report here the antiproteolytic and antihemorrhagic properties of triterpenoid saponin inhibitors, named macrolobin-A and B, from Pentaclethra macroloba, against Bothrops snake venoms. The inhibitors were able to neutralize the hemorrhagic, fibrin(ogen)olytic, and proteolytic activities of class P-I and P-III metalloproteases isolated from B. neuwiedi and B. jararacussu venoms. Clotting and fibrinogenolytic activities induced by snake venoms and isolated thrombin-like enzymes were partially inhibited. Furthermore, the potential use of these inhibitors to complement antivenom therapy as an alternative treatment and/or used as molecular models for development of new therapeutical agents in the treatment of snake bite envenomations needs to be evaluated in future studies.     

Preoperative Chemotherapy Alone and Combined with Preoperative Radiotherapy in Small-Size Breast Cancer

Abstract: Breast conservation surgery is an effective and safe treatment for many breast carcinomas. It may be possible to further limit the extent of resection (or expand the indication for breast conservation) by the application of preoperative chemotherapy and radiotherapy. We explored the feasibility of this in a pilot study.
Seventy-three patients (mean age 48, 63% premenopausal) with confirmed breast cancer, less than 2.5 cm, received chemotherapy (Group A) or chemotherapy plus radiotherapy (Group B) prior to limited resection (tumorectomy). Axillary dissection was always performed. Results: In 6/31 (19%) Group A and 17/42 (40%) Group B patients the tumor was not palpable after preoperative treatment, with complete pathological remission in 1 and 3 cases respectively. Histologic grading, mitosis, cellular alteration, and cellularity evaluations indicated a consistently greater therapeutic effect with chemoradiotherapy than with chemotherapy alone.
In conclusion, radiotherapy appears useful in the preoperative treatment of breast cancer and its use in association with various drug combinations should be further explored.     

Phase II trial of piroxantrone in metastatic breast cancer

Summary Thirty-two eligible patients with advanced metastatic breast cancer who had received no more than 1 prior chemotherapy regimen for metastatic disease (16 had received prior doxorubicin) were treated with piroxantrone at a dose of 120 mg/m² intravenously every 21 days. In the twenty-seven patients evaluable for response, two partial responses were seen. Toxicities observed were primarily hematologic with grade 3 or greater granulocytopenia occurring in 34% of the patients. One patient developed symptomatic congestive heart failure at a total cumulative dose of 960 mg/m². We conclude that piroxantrone given at this dose and schedule has minimal activity in patients with metastatic breast cancer.     

What really matters in the social network–mortality association? A multivariate examination among older Jewish-Israelis

The aim of the inquiry was to examine the social network–mortality association within a wider multivariate context that accounts for the effects of background framing forces and psychobiological pathways. The inquiry was based upon the Berkman et al. (2000) conceptual model of the determinants of health. Its main purpose was to identify the salient network correlates of 7-year all cause mortality among Jewish men and women, aged 70 and over, in Israel (n = 1,811). The investigation utilized baseline data from a national household survey of older adults from 1997 that was linked to records from the National Death Registry, updated through 2004. At the time of the study, 38% of the sample had died. Multivariate Cox hazard regressions identified two main network-related components as predictors of survival: contact with friends, a social network interaction variable, and attendance at a synagogue, a social engagement variable. Friendship ties are seen to uniquely reduce mortality risk because they are based on choice in nature, and reflect a sense of personal control. Synagogue attendance is seen to promote survival mainly through its function as a source of communal attachment and, perhaps, as a reflection of spirituality as well. Other possibly network-related correlates of mortality were also noted in the current analysis—the receipt of instrumental support and the state of childlessness. The study on which this article is based was made possible by grants from the Israel Ministry of Science and Technology to the Israel Gerontological Data Center.     

Laparoscopic cryosurgery for hepatic tumors

Background: Hepatic cryosurgery has been shown to be a safe technique that may be well suited to a laparoscopic approach. Methods: The technical feasibility and safety of laparoscopic cryosurgery was explored first in a pig model. Thereafter we performed the first successful case of laparoscopic hepatic cryosurgery at our institution. Results: In the animal model, we found that it is possible to safely identify, target, and cryoablate specific lesions in the liver. Temperature in the peritoneal cavity remained above 35°C, and pathologic examination of the abdominal wall around the cryoprobe site revealed no damage. We also successfully treated a 62-year-old man with a metastatic colorectal carcinoma deep in the right lobe of the liver with laparoscopic cryosurgery using a transpleural approach. Conclusion: We conclude that laparoscopic cryosurgery is feasible for lesions anywhere in the liver. For lesions high on the dome of the liver, a transpleural approach may provide better access.     

Expression of a 1,25-dihydroxyvitamin D3 membrane-associated rapid-response steroid binding protein during human tooth and bone development and biomineralization.

The calciotropic hormone 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] has been established to control skeletal tissue formation and biomineralization via the regulation of gene expression. This action involves the well-characterized nuclear 1,25(OH)2D3 receptor. However, it has been recognized that several cellular responses to 1,25(OH)2D3 may not to be related to the exclusive nuclear receptor. Indeed, this secosteroid is able to generate rapid responses that have been proposed to be mediated by interactions of the ligand, which is a putative cell membrane-associated rapid-response steroid (MARRS) binding protein for 1,25(OH)2D3 [1,25D3-MARRS]. The nongenomic pathway of 1,25(OH)2D3 was studied here in detail by immunolocalization of the 1,25D3-MARRS during the specific context of human prenatal development. Western blotting with proteins extracted from 4 week- to 27-week-old embryos was performed, evidencing a 65-kDa molecular species recognized by antibody Ab 099 generated against synthetic peptides corresponding to the N terminus of the 1,25D3-MARRS from chick intestinal basolateral membranes. Based on this biochemical conservation of protein in the human species, the temporospatial expression patterns were established in the craniofacial skeleton at the same ages. Comparative analysis was performed in teeth and bones from early morphogenesis to terminal cell differentiation and extracellular biomineralization. The data show the potential implication of 1,25D3-MARRS in the heterogeneous cell population including ameloblasts, odontoblasts, osteoblasts, and osteoclasts. The epithelial-mesenchymal cascade related to odontogenesis was coincident with a sequence of up- and down-regulation of immunoreactive 1,25D3-MARRS. Biomineralization was associated with a striking up-regulation in the adjoining secretory cells in all tissues. Finally, osteoclasts appeared also to express the 1,25D3-MARRS during these early phases of bone modeling. Previously obtained data of the nuclear vitamin D receptor (VDR) expression and this study on 1,25D3-MARRS suggest the existence of cross-talk between the genomic and nongenomic pathways during human development.     

Automated assessment of cervical dystonia.

We developed an automated and objective method to measure posture and voluntary movements in patients with cervical dystonia using Fastrack, an electromagnetic system consisting of a stationary transmitter station and four sensors. The junction lines between the sensors attached to the head produced geometrical figures on which the corresponding aspects of the head were superimposed. The head position in the space was reconstructed and observed from axial, sagittal, and coronal planes. Four patients with cervical dystonia and 6 healthy subjects were studied. Each patient was representative of one of the typical patterns of cervical dystonia. The study allowed the authors to collect quantitative data on posture and range of motion of the head. This pilot study demonstrates the efficacy of the Fastrack system to objectively measure the head position in cervical dystonia patients.     

Blood vessels in epiphyseal cartilage of human fetal femoral bone: a scanning electron microscopic study of corrosion casts

Formation of intrachondral vessels (cartilage canals) in the proximal femoral epiphysis was studied in 13- to 22-week-old human fetuses using a corrosion casting technique and scanning electron microscopy. Several successive morphological stages of angiogenesis occurring inside the hyaline cartilage were distinguished. The process of cartilage vascularization starts with the formation of hairpin loops sent off from the perichondrial vascular network into the adjacent cartilage. A capillary glomerulus is then formed at the leading end, and the entire vascular unit grows in length, assuming a mushroom-like shape. Its further elongation is accompanied by a backward expansion of the capillary network which surrounds a pair of main vessels (arteriole and venule) like a manchette. The subsequent branching of such primary vascular units proceeds according to the same morphological patterns. The resulting tree-like vascular formations become interconnected via their lateral branches. This study clearly supports the invasion theory of cartilage canal formation.     

Sub-acute intoxication by Senna occidentalis seeds in rats.

Senna occidentalis (So) is a weed that grows in pastures along fences and in fields cultivated with cereals such as corn and soybean, and many reports have been showing intoxication with this plant in different animal species. It is also used in many medicinal purposes. The objective of the present study was to better evaluate the toxic effects of prolonged administration of So seeds to rats. Forty male Wistar rats were divided into four groups of 10 animals each, three of them respectively fed rations containing 1%, 2% and 4% So seeds, and the last one (control) fed commercial ration for a period of 2 weeks. Fourteen rats were also used in a pair-feeding (PF) experiment. The rats of the experimental groups showed lethargy, weakness, recumbency, depression and emaciation. Two rats of the 4% group and two of the PF group died during the experiment. Histopathological study showed fiber degenerations in the skeletal (Tibial, pectoral and diaphragm) and cardiac muscles. In the liver parenchyma, was observed vacuolar degeneration and, in the kidney, mild nefrosis in the proximal convoluted tubules. All of these alterations occurred in a dose-dependent fashion. Moderate to severe degeneration and spongiosis in the central nervous system, especially in cerebellum. Electron microscopy revealed mitochondrial lesions in all analyzed tissues.