Involvement of FAK, PI3-K and PKC in cell adhesion induced by microtubule disruption

We have previously shown that microtubule disruption results in an increase in cell adhesion to ECM proteins. In this work we show that this enhanced cell attachment was completely abolished by specific inhibitors of tyrosine-kinases, PI3-K and PKCs. Microtubule depolymerisation was associated with an important increased in tyrosine phosphorylation of FAK and paxilline, as well as with subcellular localisation of PKCgamma, delta and epsilon. We also observed significant alterations in actin cytoskeleton leading to reduced cell spreading. Thus, microtubule depolymerisation appears to activate various intracellular kinases that lead to actin cytoskeletal changes and to an increase of integrin-dependent adhesion. Whether this enhanced attachment is due to intracellular events resulting in changes in integrin affinity or avidity remains to be determined.     

Unlabelled iododeoxyuridine increases the rate of uptake of [125I]iododeoxyuridine in human xenografted glioblastomas

5-Iodo-2'-deoxyuridine (IdUrd), a thymidine (TdR) analogue, can be radiolabelled with iodine-125, an Auger radiation emitter, to provoke double-strand breaks once incorporated into DNA of cancer cells. We have previously shown that co-incubation of [125I]IdUrd with unlabelled IdUrd provided an additive cytotoxicity in two human glioblastoma cell lines. This observation was unexpectedly correlated with an increase in the rate of DNA incorporation of [125I]IdUrd. Here, we further evaluated the effects of unlabelled IdUrd on the uptake of [125I]IdUrd in vitro and in vivo in mice xenografted with three human glioblastoma lines. The results showed that, in these three glioblastoma lines, unlabelled IdUrd increased the rate of uptake of [125I]IdUrd in vitro by 2- to 4.4-fold and in vivo by 1.5- to 2.8-fold. The rate of uptake of [125I]IdUrd in normal rapidly dividing tissues was also increased by 1.3- to 2.8-fold. TdR completely blocked [125I]IdUrd uptake in tumours and tissues. Analogues of IdUrd, such as deoxyuridine and 5-iodo-1,3-dimethyuracil, did not reproduce the effect of IdUrd on the uptake of [125I]IdUrd, suggesting that it is not related to protection against [125I]IdUrd degradation. It is concluded that combined administration of unlabelled IdUrd may improve the use of radiolabelled IdUrd for cancer diagnosis or therapy.     

The Model State Emergency Health Powers Act: planning for and response to bioterrorism and naturally occurring infectious diseases

The Center for Law and the Public's Health at Georgetown and Johns Hopkins Universities drafted the Model State Emergency Health Powers Act (MSEHPA or Model Act) at the request of the Centers for Disease Control and Prevention. The Model Act provides state actors with the powers they need to detect and contain bioterrorism or a naturally occurring disease outbreak. Legislative bills based on the MSEHPA have been introduced in 34 states. Problems of obsolescence, inconsistency, and inadequacy may render current state laws ineffective or even counterproductive. State laws often date back to the early 20th century and have been built up in layers over the years. They frequently predate the vast changes in the public health sciences and constitutional law. The Model Act is structured to reflect 5 basic public health functions to be facilitated by law: (1) preparedness, comprehensive planning for a public health emergency; (2) surveillance, measures to detect and track public health emergencies; (3) management of property, ensuring adequate availability of vaccines, pharmaceuticals, and hospitals, as well as providing power to abate hazards to the public's health; (4) protection of persons, powers to compel vaccination, testing, treatment, isolation, and quarantine when clearly necessary; and (5) communication, providing clear and authoritative information to the public. The Model Act also contains a modernized, extensive set of principles and requirements to safeguard personal rights. Law can be a tool to improve public health preparedness. A constitutional democracy must balance the common good with respect for personal dignity, toleration of groups, and adherence to principles of justice.      

Pregnancy in adolescence: maternal-fetal prognosis

The adolescent's pregnancy is not rare. In the clinical view the maternal prognosis is better than the foetal which is reserved. In fact the rate of prematurity, intra uterin under development, genetous malformation and perinatality death is increased. In the psychosocial view, these pregnancies occurs problems specially the relationship between mother and child and real social break of these adolescents.     

Manipulation pharmacologique de l'anabolisme : l'exemple de l'hormone de croissance

Optimal enteral or parenteral nutrition is not sufficient to correct protein catabolism during major metabolic stress or to systematically improve protein anabolism in chronic malnutrition. The administration of anabolic factors is therefore logical. The availability of human recombinant growth hormone (rhGH) and Insulin-like Growth Factor-I (rhIGF-I) permits their utilization in cases of metabolic stress and muscle catabolism. Their efficiency has been globally demonstrated. On the other hand, the data regarding possible clinical benefits are practically non-existent and the risk-benefit and cost-benefit ratios require further evaluation.This review summarizes the main clinical studies of rhGH and rhIGF-I and the relationship with catabolism or protein deficit. The main pathophysiological bases are presented.     

Primary T-cell lymphoma of the pancreas in children

Involvement of the gastrointestinal tract is frequently reported among the extranodal sites of non-Hodgkin's lymphoma, but primary lymphoma of the pancreas is very rare. We report the case of a 11-year-old boy explored for epigastric pain with fever leading to the diagnosis of high-grade primary non Hodgkin's T-cell lymphoma, originating from pancreas. This pancreatic lesion is documented by sonography, CT and MRI. This patient died quickly with sever infection.     

Serum lactate dehydrogenase and its isoenzymes in nasopharyngeal carcinoma in Tunisia

Our prospective study interested 41 patients, from 13 to 70 years old, and present a nasopharyngeal carcinoma confirmed histologically, during the period going from September 1999 to March 2000, and 45 healthy controls. A blood sample was collected from each patient before any treatment, as well as controls to measure serum LDH and its isoenzymes. Two groups of patients were selected after a period varying from 12 to 37 months with a mean of 29 months: 29 with favourable evolution, 12 with non favourable evolution. The mean serum total LDH and its isoenzymes values were significantly higher in patients than those in controls with values of variable p of 0.001 to 0.05. A significant correlation was found between ganglionnary extension and serum values of total LDH, LDH3 and LDH5. No significant difference were observed between the means serum total LDH before treatment and the clinical evolution of patients. Diagnostic contribution of total LDH is limited, by its ubiquitary character, but could constitute for LDH3 a good marker of the disease progression.     

Do prothrombin time, transaminases, and platelet count predict the severity of fibrosis in viral liver diseases?

The goal of our study is to assess the performance of a score combining 3 serological parameters (PT, platelets and transminases) in predictive hepatic fibrosis. The study involved 54 patients, 29 of which resulted in distributing them according to the score of Metavir into 2 groupes: Group A with mild fibrosis (F1,F2) and group B with severe fibrosis (F3,F4). PT, platelets and transminase values in serum were assessed for all patients. The total score of the 3 biological parameters combined, was significantly more elabled in the severe fibrosis group than in the mild fibrosis group (P = 0.01) but it was not of much importance in 30% of cases as it did not allow to classify the patients with certainty in group A or in group B. This score does not seem to grant exemption from needle liver biopsy, but it can be improved by the association of other direct markers of fibrosis.     

Assessment of ascorbic acid stability in different multilayered parenteral nutrition bags: critical influence of the bag wall material

BACKGROUND: The recent development of multilayered bags has minimized ascorbic acid oxidation in parenteral nutrition (PN) admixtures. However, the gas-barrier property of multilayered bags depends on their plastic material. This study compared ascorbic acid stability in different multilayered bags under experimental conditions. METHODS: Oxygen permeability of a newly developed 6-layered bag (6-L) was compared with a highly mechanical-resistant 3-layered bag (3-L(R)) and a highly flexible 3-layered bag (3-L(F)) using gas chromatography. Ascorbic acid stability was assessed by iodine titration in bags filled with 2.5 L H(2)O and 40 g carbohydrates after setting residual O(2) content at < or =1 or > or =5 ppm. The effect of storage at 4 degrees C, 21 degrees C, and 40 degrees C on ascorbic acid stability was assessed over 48 hours in a complete PN admixture (ie, 330 g carbohydrates, 100 g lipids, 96 g amino acids and trace elements) using high-pressure liquid chromatography. RESULTS: Oxygen permeability was markedly reduced in 6-L bags (0.5 mL O(2) /m(2)/d) compared with 3-L(R) (150 mL O(2) /m(2)/d) and 3-L(R) (1500 mL O(2)/m(2)/d). Accordingly, ascorbic acid was more stable in 6-L bags (half-life [T(1/2)] = 16 days up to 40 degrees C) than in 3-L(R) (T(1/2) = 9 days at 4 degrees C, 47 hours at 21 degrees C and 29 hours at 40 degrees C) and 3-L(F) (T(1/2) = 15 hours at 4 degrees C, 10 hours at 21 degrees C, and 6 hours at 40 degrees C). During the first 6 hours after PN admixture compounding, an additive ascorbic acid loss of 4.6 +/- 0.5 mg/L/ppm O(2) occurred because of residual O(2) in the bag. CONCLUSIONS: The new combination of plastic layers and careful O(2) monitoring during the filling process allowed near to complete prevention of ascorbic acid degradation in multilayered PN bags during 48 hours, regardless of the storage temperature.