International Recommendations for Training Future Toxicologic Pathologists Participating in Regulatory-Type, Nonclinical Toxicity Studies

The International Federation of Societies of Toxicologic Pathologists (IFSTP) proposes a common global framework for training future toxicologic pathologists who will support regulatory-type nonclinical toxicology studies. Trainees optimally should undertake a scientific curriculum of at least 5 years at an accredited institution leading to a clinical degree (veterinary medicine or medicine). Trainees should then obtain 4 or more years of intensive pathology practice during a residency and/or on-the-job "apprenticeship," at least 2 years of which must be focused on regulatory-type toxicologic pathology topics. Possession of a recognized pathology qualification (i.e., certification) is highly recommended. A non-clinical pathway (e.g., a graduate degree in medical biology or pathology) may be possible if medically trained pathologists are scarce, but this option is not optimal. Regular, lifelong continuing education (peer review of nonclinical studies, professional meetings, reading, short courses) will be necessary to maintain and enhance one's understanding of current toxicologic pathology knowledge, skills, and tools. This framework should provide a rigorous yet flexible way to reliably train future toxicologic pathologists to generate, interpret, integrate, and communicate data in regulatory-type, nonclinical toxicology studies. (J Toxicol Pathol 2010; 23: 171-181)

International recommendations for training future toxicologic pathologists participating in regulatory-type, nonclinical toxicity studies

The International Federation of Societies of Toxicologic Pathologists (IFSTP) proposes a common global framework for training future toxicologic pathologists who will support regulatory-type - nonclinical toxicology studies. Trainees optimally should undertake a scientific curriculum of at least 5 years at an accredited institution leading to a clinical degree (veterinary medicine or medicine). Trainees should then obtain 4 or more years of intensive pathology practice during a residency and/or on-the-job "apprenticeship," at least 2 years of which must be focused on regulatory-type toxicologic pathology topics. Possession of a recognized pathology qualification (i.e., certification) is highly recommended. A nonclinical pathway (e.g., a graduate degree in medical biology or pathology) may be possible if medically trained pathologists are scarce, but this option is not optimal. Regular, lifelong continuing education (peer review of nonclinical studies, professional meetings, reading, short courses) will be necessary to maintain and enhance one's understanding of current toxicologic pathology knowledge, skills, and tools. This framework should provide a rigorous yet flexible way to reliably train future toxicologic pathologists to generate, interpret, integrate, and communicate data in regulatory-type, nonclinical toxicology studies. (C) 2010 Reprinted by Permission of SAGE Publications Inc. Published by Elsevier GmbH. All rights reserved.

Culture of osteogenic cells from human alveolar bone: A useful source of alkaline phosphatase

The aim of this study was to obtain membrane-bound alkaline phosphatase from osteoblastic-like cells of human alveolar bone. Cells were obtained by enzymatic digestion and maintained in primary culture in osteogenic medium until subconfluence. First passage cells were cultured in the same medium and at 7, 14, and 21 days, total protein content, collagen content, and alkaline phosphatase activity were evaluated. Bone-like nodule formation was evaluated at 21 days. Cells in primary culture at day 14 were washed with Tris-HCl buffer, and used to extract the membrane-bound alkaline phosphatase. Cells expressed osteoblastic phenotype. The apparent optimum pH for PNPP hydrolysis by the enzyme was pH 10.0. This enzyme also hydrolyzes ATP, ADP, fructose-1-phosphate, fructose-6-phosphate, pyrophosphate and beta-glycerophosphate. PNPPase activity was reduced by typical inhibitors of alkaline phosphatase. SDS-PAGE of membrane fraction showed a single band with activity of similar to 120 kDa that could be solubilized by phospholipase C or Polidocanol. (c) 2007 International Federation for Cell Biology. Published by Elsevier Ltd. All rights reserved.

Influence of visual information on optimal obstacle crossing

Human motion seems to be guided by some optimal principles. In general, it is assumed that human walking is generated with minimal energy consumption. However, in the presence of disturbances during gait, there is a trade-off between stability (avoiding a fall) and energy-consumption. This work analyses the obstacle-crossing with the leading foot. It was hypothesized that energy-saving mechanisms during obstacle-crossing are modulated by the requirement to avoid a fall using the available sensory information, particularly, by vision. A total of fourteen subjects, seven with no visual impairment and seven blind, walked along a 5 meter flat pathway with an obstacle of 0.26 m height located at 3 m from the starting point. The seven subjects with normal vision crossed the obstacle successfully 30 times in two conditions: blindfolded and with normal vision. The seven blind subjects did the same 30 times. The motion of the leading limb was recorded by video at 60 Hz. There were markers placed on the subject's hip, knee, ankle, rear foot, and forefoot. The motion data were filtered with a fourth order Butterworth filter with a cut-off frequency of 4 Hz. The following variables were calculated: horizontal distance between the leading foot and the obstacle at toe-off prior to (DHPO) and after (DHOP) crossing, minimal vertical height from the foot to the obstacle (DVPO), average step velocity (VELOm). The segmental energies were also calculated and the work consumed by the leading limb during the crossing obstacle was computed for each trial. A statistical analysis repeated-measures ANOVA was conducted on these dependent variables revealing significant differences between the vision and non-vision conditions in healthy subjects. In addition, there were no significant differences between the blind and people with vision blindfolded. These results indicate that vision is crucial to determine the optimal trade-off between energy consumption and avoiding a trip during obstacle crossing.

Uma proposta de framework como infra-estrutura de implementação de sistemas informacionais baseados na visão dos FRBR orientado a objetos

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Cervical Lactobacillus and leukocyte infiltration in preterm premature rupture of membranes

Objectives: To evaluate the possible association between microorganisms present in the cervical secretions and amniotic fluid of pregnant women with preterm premature rupture of membranes (PPROM), and histologic chorioamnionitis. Methods: Thirty-seven pregnant women with PPROM and 21 healthy pregnant women were studied. Secretions from the cervical canal and amniotic fluid were collected to isolate microorganisms present in the genital tract. Cervical smears were Gram stained and evaluated microscopically. At delivery, chorioamniotic membranes were collected for histopathologic analysis. Results: Microscopic examination of the cervical secretion smears obtained from the PPROM group showed a low rate of Lactobacillus species, large numbers of leukocytes, and a wide diversity of microorganisms compared with the control group. The PPROM group presented an 80% rate of chorioamnionitis. Staphylococcus aureus isolation in cervical secretion was associated with intense inflammatory infiltrate in the membranes and might play a role in the pathogenesis of PPROM. Conclusions: the low colonization of cervical flora by Lactobacillus species associated with an intense leukocyte infiltrate detected in Gram-stained cervical smears can be considered a rapid method of detecting chorioamnionitis in pregnant women with PPROM. (C) 2003 International Federation of Gynecology and Obstetrics. Published by Elsevier B.V. Ireland Ltd. All rights reserved.

Repercussions of castration and vasectomy on the ductal system of the rat ventral prostate

Diseases. such as cancer and benign prostatic hyperplasia, are related to disruption of the mechanism regulating the balance between cell proliferation and apoptosis in prostatic cells. Since castration and vasectomy might alter that balance, this study evaluates the cell proliferation, apoptosis and height of the secretory epithelium of the ventral-prostate ductal system post-castration and vasectomy. Immunohistochemical (PCNA and Ki67), cytochemical (Fuelgen reaction) and morphometric investigation have been carried out. Cell proliferation indices decreased significantly in both regions of the ventral-prostate ductal system after castration compared to the sham-operated group. The apoptotic index increased significantly after 48 h, declining 7 days post-castration. The cell proliferation indices did not differ after 48 h significantly; however, they increased 7 days post-vasectomy in both regions. The apoptotic index did not differ significantly in either time post-vasectomy. Castration caused an imbalance in favor of apoptosis, whereas vasectomy caused an imbalance in favor of cell proliferation. (c) 2005 International Federation for Cell Biology. Published by Elsevier Ltd. All rights reserved.

Markers of tumors susceptibility in head and neck cancer

Genetic polymorphisms are associated with a number of enzymes involved in the induction of head and neck carcinomas. It has been suggested that such polymorphisms may be linked to cancer susceptibility. Using a control-case study molecular genetic approach, we have investigated the association between polymorphisms genes (CYPs, GSTs and NAT2 genes) and susceptibility in head and neck cancer.

Differential proliferative response of the ventral prostate and seminal vesicle to testosterone replacement

We have investigated epithelial cell proliferation and the rate of glandular recovery of the ventral prostate (VP) and seminal vesicle (SV) promoted by testosterone replacement (TR) in castration-induced regressed glands. Adult male Wistar rats were castrated and, after 21 days, they were treated with testosterone propionate (4 mg/kg/day). Intact (CT) and castrated rats without TR (CS) were also analysed. VP and SV were processed for histochemistry, morphometric-stereological analysis and immunocytochemistry to determine the PCNA index (PI). After 10 days of TR, the VP weight reached similar to 72% of the CT values, while the SV weight exceeded similar to 17% of the CT values. By the third day of TR, VP and SV presented a mean P1 of 34% and 94% for distal region and 14% and 22% for proximal region, respectively. SV also had more luminal cells PCNA-positive than VP, mainly in the distal region. The PI values fell on days 5, 7 and 10, but were still higher than CT. These findings indicate that epithelial cells from involuted SV are more responsive to TR than those from VP when Stimulated to proliferate and replace the luminal cell population, suggesting a different mechanism regulating cell proliferation in response to androgenic stimuli. (c) 2006 International Federation for Cell Biology. Published by Elsevier Ltd. All rights reserved.

Chemical detection of the proteins and lipids in the fat body cells from workers of Attini ants (Hymenoptera: Formicidae)

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Influence of blood viscosity to cerebral blood flow in older humans compared to young subjects

Objective: Since blood viscosity (BV) is one of the most important factors determining blood flow, this study aimed to investigate the possible correlation between increased blood viscosity and reduction of regional cerebral blood flow (rCBF) in healthy ageing.Methods: Male subjects were distributed in two groups: "young", aged 20-30 (27 volunteers), or "elderly", aged 60-70 (50 volunteers). Whole blood viscosity was obtained with a Wells-Brookfield Cone/Plate Viscometer. Cerebral blood flow was analysed by means of single photon emission computed tomography (SPECT).Results: The mean BV values were 3.28 +/- 0.43 mPa in the group of young volunteers and 4.33 +/- 0.73 mPa in the group of elderly volunteers (t = -6.9, p < 0.0001). The elderly had a lower blood flow than the young in the following regions: bilateral parietal; temporal-parietal and temporal of the left hemisphere. Pearson's correlation between BV and rCBF showed a good inverse correlation when the BV was above 3.95 +/- 0.83 mPa.Conclusions: Our results point to a close relationship between the two parameters analysed, BV and rCBF. The impairment in rCBF observed in the elderly volunteers might be due to an increase in BV, among other factors.Significance: These findings suggest interesting possibilities for the treatment/prevention of brain ageing. (C) 2011 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

Modulation of smooth muscle cell function: Morphological evidence for a contractile to synthetic transition in the rat ventral prostate after castration

In this study, we evaluated the involvement of rat ventral prostate smooth muscle cells (SMC) in secretory activity and whether this function is modulated after castration. Cell morphology was examined at both light and electron microscopy levels and the organelles involved in secretory function were labeled by the zinc-iodide-osmium (ZIO) method at the ultrastructural level and their volume density was determined by stereology. Castration resulted in marked changes of the SMC, which adopted a spinous aspect and abandoned the layered arrangement observed in the prostates of non-castrated rats. The volume density of ZIO reactive organelles increased progressively after castration, reaching significantly higher levels 21 days after castration, Since previous studies have demonstrated that SMC express SMC markers (even 21 days after castration) and are able to respond to adrenergic stimulation, we concluded that differentiated SMC are able to shift from a predominantly contractile to a more synthetic phenotype without changing their differentiation status. (c) 2005 International Federation for Cell Biology. Published by Elsevier Ltd. All rights reserved.

Acid phosphatase activity in gerbil prostate: comparative study in male and female during postnatal development

The prostate is present in both male and female mammals. It is composed of secretory epithelium, connective stroma, smooth muscle and neuroendocrine cells, which are under hormonal regulation. Acid phosphatases catalyze the hydrolysis of orthophosphate monoesters. We have compared the expression of acid phosphatases in gerbil (Meriones unguiculatus) prostate glands in both sexes using young, adult and old animals. Eighteen prostates were isolated, frozen, sectioned, fixed, incubated with sodium beta-glycerophosphate sodium, washed with acetate buffer solution, treated with ammonium sulfide and counterstained with Methyl-Green aqueous solution. Ultracytochemical analyses were also conducted. This substrate revealed total acid phosphatase activity. The expression of the enzyme was heterogeneous, occurring in all ages during postnatal development. The data. revealed that the female prostate matured before the male prostate. In addition, acid phosphatase activity in both sexes was regulated by androgen variation concomitant with development. (C) 2004 International Federation for Cell Biology. Published by Elsevier Ltd. All rights reserved.

Cellular and extracellular behavior in the gerbil (Meriones unguiculatus) ventral prostate following different types of castration and the consequences of testosterone replacement

Mongolian gerbils (Meriones unguiculatus) were grouped into two experimental groups: GEx.01 suffered orchiectomy and after 30 days received doses of testosterone cipionate (T), while GEx.02 received weekly and alternated doses of the anti-androgens cyproterone acetate and flutamide for 30 days, and the animals were then euthanized. Structural evaluation reveals a more intense reduction in epithelial height in GEx.02. Smooth muscle cells (SMC) presented a star-shaped aspect after 30 days of hormonal ablation and basal membrane was shown to be more intensely grooved in GEx.01. In both groups, after hormonal replacement, recovery in epithelial height could be noted and the SMC presented its phenotypes, but an increase in RER was seen, characterizing a modulation from its contractile to secreting phenotype. In conclusion, the prostate presented involution capacity after androgen ablation and the ability to reorganize after hormonal replacement, but events resulting from orchiectomy and subsequent T replacement were shown to be more aggressive to the prostate. (c) 2006 International Federation for Cell Biology. Published by Elsevier Ltd. All rights reserved.

Interaction of human neutrophils with endothelial cells regulates the expression of endogenous proteins annexin 1, galectin-1 and galectin-3

Annexin 1 (ANXA1), galectin-1 (Gal-1) and galectin-3 (Gal-3) proteins have been identified as important mediators that promote or inhibit leukocyte migration. The expression of these proteins was studied in human neutrophils and endothelial cells (ECs) during a transmigration process induced by IL-8. Upon neutrophil adhesion to EC, a significant increase in the cleaved ANXA1 (LCS3, raised against all ANXA1 isoforms) expression was detected in the plasma membrane of adhered neutrophils and ECs compared to intact ANXA1 isoform (LCPS1, against N-terminus of protein). Adherent neutrophils had elevated Gal-3 levels in the nucleus and cytoplasm, and ECs in their plasma membranes. In contrast, a decrease in the total amounts of Gal-1 was detected in migrated compared to non-migrated neutrophils. Therefore, ANXA1 and Gal-3 changed in their content and localization when neutrophils adhere to endothelia, suggesting a process of sensitive-balance between two endogenous anti- and pro-inflammatory mediators. (c) 2006 International Federation for Cell Biology. Published by Elsevier Ltd. All rights reserved.