Labeling index in pituitary adenomas evaluated by means of MIB-1: is there a prognostic role? A critical review

Objective: The present article presents an overview of the literature, and analyses the methods and the primary questions related to assessment of proliferation index using the Ki-67/MIB-1 labeling index in pituitary adenomas. Although atypical adenomas are characterized by their atypical morphological features by an elevated mitotic index, a Ki-67 (MIB-1) labeling index greater than 3% and extensive nuclear staining for p53, use of the proliferation index (LI) of pituitary adenomas in assessing the degree of tumor aggressiveness is a controversial topic in the literature, and there are disparate results involving many studies.Methods: A review of literature was carried out to correlate the role of Ki-67 LI and its correlation with clinical findings, tumor size, invasiveness, recurrence, adenoma subtype, adenoma doubling time, and pituitary carcinomas is addressed. Results: The prognosis cannot be predicted on the basis of the Ki-67 LI alone. Although there is no direct relation between Ki-67 LI and some of these variables and controversial data were found regarding some topics, our review justify the use of Ki-67 in the analysis of pituitary adenomas as an additional information for clinical decision.Conclusion: Although assessment of proliferative may be helpful in predicting subsequent tumor recurrence or invasiveness, there are many other important and as yet unidentified factors pituitary tumors. It is clear that further research is needed to clarify these molecular mechanisms to predict those with a potentially poor clinical outcome.

Interaction between the lateral preoptic area and the subfornical organ in the control of water ingestion caused by cellular dehydration, hypotension, hypovolemia, and deprivation

Water intake was studied in albino rats with lesions in the lateral preoptic area, in the subfornical organ, and in both the lateral preoptic area and the subfornical organ. Drinking was induced by cellular dehydration, hypovolemia, hypotension (isoproterenol or caval ligation), and water deprivation. The animals with lesions in both areas showed a significant reduction in their water intake in response to cellular dehydration. Drinking due to extracellular dehydration was reduced in the animals that received only subfornical organ lesions, and was reduced even further in the animals with both areas ablated. The lesions in the subfornical organ were sufficient to reduce the thirst induced by caval ligation. The lesions in both areas inhibit water intake induced by caval ligation. Water intake induced by deprivation was reduced when both areas were destroyed. These findings demonstrate that both the lateral preoptic area and the subfornical organ are necessary for normal drinking in response to cellular dehydration, hypovolemia, and hypotension. There is further evidence that the lateral preoptic area and subfornical organ interact in the control of water intake induced by a variety of thirst challenges.

Cara inchada and cellular immunity in cattle

Attempts were made to study possible effects of the periodontal disease cara inchada (CI) on the cellular immunity of cattle, using adherence-, chemotaxis- and ph-agocytosis-determinations. Adherence of Bacteroides melaninogenicus to bovine granulocytes was significantly decreased in animals with CI. Phagacytosis of B. melaninogenicus by polymorphonuclear granulocytes (PMN) was also decreased in CI-diseased animals. Chemotaxis of the granulocytes appeared to be slightly increased in animals with CI and animals without CI coming from CI-affected herds.

Endocytic activity in the thrombocytes of the turtle Phrynopys hilarii (freshwater South American species)

The phagocytic process in cells depends on lysosomal enzymes, high-energy metabolism and cellular recognition. In this paper, we investigated the presence of energy and recognition factors in thrombocytes of turtle Phrynopys hilarii (a freshwater South American species). Turtle thrombocytes (P. hilarii) present glycogen - possibly β particles - dispersed in their cytoplasm and glycoproteins in the cell surface, as well as a large number of enzymes involved in the endocytic process (Pellizzon, 1996). The activity of these enzymes depends on high-energy metabolism and on cellular recognition provided by specific glycoconjugates (Alberts et al., 1994). This metabolic characterization is demonstrated by the large amount of glycogen particles observed in the cytoplasm by Thiéry's method. Glycogen labeling was also observed when concanavalin A-peroxidase was used as a marker for thrombocytes and for endocyted charcoal particles. Our results show that these cells have phagocytic ability, suggesting that their function in blood circulation is not limited to aggregation but may also involve a great potential for phagocytosis.

Electrode poling of cellular polypropylene films with short high-voltage pulses

Recently, piezoelectric cellular polypropylene (PP) was proposed as a new type of quasi-ferroelectric. The observed hysteresis of the charge density as a function of the electric field could be explained as field-dependent charging inside the gas-filled voids. Interestingly enough, the measurable poling behavior of the macroscopic dipoles formed by charges that are trapped at the internal void surfaces is phenomenologically completely identical to the cooperative poling behavior of microscopic molecular dipoles in ferroelectric polymers. Therefore, it can be assumed that charge separation (or charge redistribution) and subsequent trapping in cellular PP is a rather fast switching process. In order to examine the poling dynamics, we developed an experimental setup for pulsed poling. High-voltage pulses with a duration of 45 μs (FWHM) were applied in direct contact to two-side metallized cellular PP films. The pulsed poling yields piezoelectricity in the cellular PP. We study and discuss the dependence of the resulting piezoelectricity on the poling field. We also characterize the charge separation during application of higher electric poling fields of up to -10 kV in direct contact to the two-side metallized films for longer times.

Mushroom-derived preparations in the prevention of H2O2-induced oxidative damage to cellular DNA

Aqueous extracts of the sporophores of eight mushroom species were assessed for their ability to prevent H2O2-induced oxidative damage to cellular DNA using the single-cell gel electrophoresis (Comet) assay. The highest genoprotective effects were obtained with cold (20°C) and hot (100°C) water extracts of Agaricus bisporus and Ganoderma lucidum fruit bodies, respectively. No protective effects were observed with Mushroom Derived Preparations (MDPs) from Flammulina velutipes, Auricularia auricula, Hypsizygus marmoreus, Lentinula edodes, Pleurotus sajor-caju, and Volvariella volvacea. These findings indicate that some edible mushrooms represent a valuable source of biologically active compounds with potential for protecting cellular DNA from oxidative damage. © 2002 Wiley-Liss, Inc.

IL-12 and neutralization of endogenous IL-10 revert the in vitro antigen-specific cellular immunosuppression of paracoccidioidomycosis patients

Treatment of patients with paracoccidioidomycosis is still a challenge. Patients present defective lymphoproliferation and IFN-γ responses to the main Paracoccidioides brasiliensis antigen (gp43), which correlates with disease severity. Here, we demonstrated that the patients show also a defective synthesis of interleukin (IL)-12. Therefore, we attempted to revert this immune disfunction by adding IL-12 and neutralizing anti-IL-10 antibody to gp-43-stimulated peripheral blood mononuclear cell cultures. Both treatments increased IFN-γ secretion to levels observed with healthy sensitized individuals, but affected proliferation only modestly. When combined, the treatments further increased IFN-γ synthesis and cell proliferation. The addition of suboptimal concentrations of IL-2 also further increased the IL-12-mediated secretion of IFN-γ. Interestingly, the immune modulation was mostly antigen-specific, since the responses to Candida albicans' antigen were not affected. These results suggest that appropriate immune intervention with cytokines and/or anti-cytokines may help in the treatment of PCM. © 2002 Elsevier Science Ltd. All rights reserved.

Physiological and cellular responses in two populations of the mussel Perna perna collected at different sites from the Coast of São Paulo, Brazil

The physiological conditions of mussels from Ubatuba and Santos and also of organisms transplanted from Ubatuba to Santos were studied by using different techniques. Assays for lysosomal stability were conducted on the haemolymph. Heart rate activity was monitored for 6h. The embryonic development of larvae obtained from the collected mussels was analysed. For all the compared groups of mussels, no significant differences were observed for the cardiac activity monitoring and the embryonic bioassays. The mean Neutral Red (NR) retention time was similar for the animals from Santos and Ubatuba, whereas the organisms transplanted to Santos showed a reduction in the retention time of the dye, indicating damage in the lysosomal membranes. These differences were possibly due to environmental factors, but further investigations are required to confirm this hypothesis.

Evolutionary modeling of larval dispersal in blowflies using non-uniform cellular automata

When the food supply flnishes, or when the larvae of blowflies complete their development and migrate prior to the total removal of the larval substrate, they disperse to find adequate places for pupation, a process known as post-feeding larval dispersal. Based on experimental data of the Initial and final configuration of the dispersion, the reproduction of such spatio-temporal behavior is achieved here by means of the evolutionary search for cellular automata with a distinct transition rule associated with each cell, also known as a nonuniform cellular automata, and with two states per cell in the lattice. Two-dimensional regular lattices and multivalued states will be considered and a practical question is the necessity of discovering a proper set of transition rules. Given that the number of rules is related to the number of cells in the lattice, the search space is very large and an evolution strategy is then considered to optimize the parameters of the transition rules, with two transition rules per cell. As the parameters to be optimized admit a physical interpretation, the obtained computational model can be analyzed to raise some hypothetical explanation of the observed spatiotemporal behavior. © 2006 IEEE.

Cellular and molecular mechanisms of apoptosis in skeletal muscle atrophy

Apoptosis is necessary for maintaining the integrity of proliferative tissues, such as epithelial cells of the gastrointestinal and integumentary systems. The role of apoptosis in post-mitotic tissues, such as skeletal muscle, is less well defined, but several lines of evidence suggest that it occurs in both myofiber and other interstitial muscle cell types. Apoptosis of myonuclei likely contributes to the loss of muscle mass, but the mechanisms underlying this process are largely unknown. Caspase-dependent as well as caspase-independent pathways have been implicated, and the mode by which atrophy is induced likely determines the apoptotic mechanisms that are utilized. It remains to be determined whether a decrease in apoptosis will alleviate atrophy and distinct research strategies may be required to clarify the different causes of skeletal muscle mass loss. In this review, it was also speculated that apoptosis is a normal regulatory process that the myofiber can use to reduce the number of nuclear domains, thus ensuring optimal cell functions according to the mechanical load imposed on the muscle. ©FUNPEC-RP.

Effects of atrazine on female Wistar rats: Morphological alterations in ovarian follicles and immunocytochemical labeling of 90 kDa heat shock protein

Fertility in female mammals may be affected by a variety of endocrine disrupters present in the environment. Herbicide atrazine is an example of endocrine disrupter employed in agriculture, which disrupts estrous cyclicity in rats. Aiming to characterize morphologically the effect of low and sublethal doses of atrazine on the ovaries of Wistar rats, in an effort to determine the possible intrafollicular target site through which this herbicide acts adult females were submitted to both subacute and subchronic treatments. Additionally, immunocytochemical labeling of 90 kDa heat shock protein (HSP90) was performed in order to evaluate the role played by this protein in the ovary, under stressed conditions induced by herbicide exposure. The results indicated that atrazine induced impaired folliculogenesis, increased follicular atresia and HSP90 depletion in female rats submitted to subacute treatment, while the subchronic treatment with low dose of atrazine could compromise the reproductive capacity reflected by the presence of multioocytic follicle and stress-inducible HSP90. © 2007 Elsevier Ltd. All rights reserved.

Problem of assignment cells to switches in a cellular mobile network via beam search method

The problem of assigning cells to switches in a cellular mobile network is an NP-hard optimization problem. So, real size mobile networks could not be solved by using exact methods. The alternative is the use of the heuristic methods, because they allow us to find a good quality solution in a quite satisfactory computational time. This paper proposes a Beam Search method to solve the problem of assignment cell in cellular mobile networks. Some modifications in this algorithm are also presented, which allows its parallel application. Computational results obtained from several tests confirm the effectiveness of this approach to provide good solutions for medium- and large-sized cellular mobile network.

Cellular localization of androgen synthesis in equine granulosa-theca cell tumors: Immunohistochemical expression of 17α-hydroxylase/17,20-lyase cytochrome P450

Elevated blood testosterone concentrations, often accompanied by male-typical behaviors, is a common signalment of mares with granulosa-theca cell tumors (GCTCs), but no definitive information exists regarding the cellular differentiation of tumors associated with androgen secretion. This study was conducted to localize and thereby define the cellular expression of 17α-hydroxylase/17,20-lyase cytochrome P450 (P450c17), the enzyme most directly responsible for androgen synthesis, in 30 GTCTs and control tissues (gonads and adrenal glands) using immuno-histochemistry (IHC). Immuno-reactivity for P450c17 was evident in approximately half of 30 specimens examined, was most consistent in the interstitial cells surrounding existing or developing cysts, and was less intense in cells within cysts in the smaller proportion of specimens where this was observed. In control tissues, the expression of P450c17 was localized primarily in theca interna of normal ovarian follicles, in theca-lutein cells of some corpora lutea, but not in granulosa-lutein cells. Testicular interstitial cells and islands of adreno-cortical cells located in the adrenal medulla of the adrenal cortex further established the specificity of the antisera used. These data provided the first substantive evidence that polyhedral cells identified previously in GTCTs by histopathology have the potential to synthesize and secrete androgens, similar to theca interna and theca lutein cells in normal equine ovaries. © 2010 Elsevier Inc.