The combination of mitogenic stimulation and DNA damage induces chondrocyte senescence.

OBJECTIVE: Cellular senescence is a phenotypic state characterized by stable cell-cycle arrest, enhanced lysosomal activity, and the secretion of inflammatory molecules and matrix degrading enzymes. Senescence has been implicated in osteoarthritis (OA) pathophysiology; however, the mechanisms that drive senescence induction in cartilage and other joint tissues are unknown. While numerous physiological signals are capable of initiating senescence, one emerging theme is that damaged cells convert to senescence in response to sustained mitogenic stimulation. The goal of this study was to develop an in vitro articular cartilage explant model to investigate the mechanisms of senescence induction. DESIGN: This study utilized healthy cartilage derived from cadaveric equine stifles and human ankles. Explants were irradiated to initiate DNA damage, and mitogenic stimulation was provided through serum-containing medium and treatment with transforming growth factor ß1 and basic fibroblastic growth factor. Readouts of senescence were a quantitative flow cytometry assay to detect senescence-associated ß galactosidase activity (SA-ß-gal), immunofluorescence for p16 and γH2AX, and qPCR for the expression of inflammatory genes. RESULTS: Human cartilage explants required both irradiation and mitogenic stimulation to induce senescence as compared to baseline control conditions (7.16% vs 2.34% SA-ß-gal high, p = 0.0007). These conditions also resulted in chondrocyte clusters within explants, a persistent DNA damage response, increased p16, and gene expression changes. CONCLUSIONS: Treatment of cartilage explants with mitogenic stimuli in the context of cellular damage reliably induces high levels of SA-ß-gal activity and other senescence markers, which provides a physiologically relevant model system to investigate the mechanisms of senescence induction.

Use of CHADS2 and CHA2DS2-VASc scores to predict prognosis after stroke.

INTRODUCTION: Stroke is one of the most devastating neurological disorders. Currently, we don't have an ideal score that predicts the prognosis of stroke patients. The CHADS2 and CHA2DS2-VASc scores are well-validated tools for the estimation of stroke risk in patients with atrial fibrillation. The purpose of this study was to investigate if these scores can predict the outcomes of all the patients who suffered an ischemic stroke regardless of atrial fibrillation. METHODS: Consecutive patients that were admitted with an acute ischemic stroke were classified into subgroups according to pre-stroke CHADS2 and CHA2DS2-VASc scores and after 2 years the functional outcome, stroke recurrence, major cardiovascular events and mortality were assessed. RESULTS: Among the 973 patients that were included in analysis, the mean age was 56.7 (SD 15.7) and 46.6% were female. There were 226 (23.2%), 365 (37.5%) and 382 (39.3%) patients with low, intermediate and high CHADS2 score, respectively. For CHADS2-VASc score there were 81 (8.3%), 268 (27.6%), and 624 (64.1%) patients with low, intermediate and high, respectively. Both high-risk scores were associated with middle-term poor functional outcome, stroke recurrence, major cardiovascular events and all-cause mortality. CHADS2 and CHA2DS2-VASc scores presented a high sensitivity and a high negative predictive value. CHA2DS2-VASc was more sensitive than CHADS2 score. CONCLUSION: CHADS2 and CHA2DS2-VASc scores were both associated with stroke outcomes regardless of atrial fibrillation. These scores can be useful tools for the prognosis stratification of a patient with an ischemic stroke.

Changes in the Fatty Acid Profile and Phospholipid Molecular Species Composition of Human Erythrocyte Membranes after Hybrid Palm and Extra Virgin Olive Oil Supplementation.

This work aims to evaluate and compare, for the first time, the effects of extra virgin olive oil (EVOO) and hybrid palm oil (HPO) supplementation on the fatty acid profile and phospholipid (PL) molecular species composition of human erythrocyte membranes. Results supported the effectiveness of both HPO and EVOO supplementation (3 months, 25 mL/day) in decreasing the lipophilic index of erythrocytes with no significant differences between HPO and EVOO groups at month 3. On the other hand, the novel and rapid ultraperformance liquid chromatography-tandem mass spectrometry method used for PL analysis reveals an increase in the levels of phosphatidylcholine and phosphatidylethanolamine species esterified with polyunsaturated fatty acids. This work demonstrates the ability of both EVOO and HPO to increase the degree of unsaturation of erythrocyte membrane lipids with an improvement in membrane fluidity that could be associated with a lower risk of developing cardiovascular diseases.

Palm oil and cardiovascular disease: a randomized trial of the effects of hybrid palm oil supplementation on human plasma lipid patterns.

This study examines, for the first time, the effect of hybrid Elaeis oleifera × E. guineensis palm oil supplementation on human plasma lipids related to CVD risk factors. One hundred sixty eligible participants were randomized and assigned to one of the two treatments: 25 mL hybrid palm oil (HPO group) or 25 mL extra virgin olive oil (EVOO group) daily for 3 months. Fasting venous samples were obtained at baseline and after 1, 2 and 3 months for measurement of plasma lipids (TC, LDL-C, HDL-C and TAGs). Changes in body mass index and waist circumference were also assessed. Although there was an overall reduction in TC (7.4%, p < 0.001) and in LDL-C (15.6%, p < 0.001), no significant differences were found between the treatment groups in a repeated measures analysis of variance for TC (p = 0.0525), LDL-C (p = 0.2356), HDL-C (p = 0.8293) or TAGs (p = 0.3749). Furthermore, HPO consumption had similar effects on plasma lipids to EVOO, thus providing additional support for the concept that hybrid Elaeis oleifera × E. guineensis palm oil can be seen as a "tropical equivalent of olive oil".

Study of proteolysis in river buffalo mozzarella cheese using a proteomics approach.

The guarantee of the origin and quality of raw material is essential for the protection and valorization of Campana buffalo mozzarella cheese. The risk of utilization of semifinished products and stored milk in substitution for fresh milk is increasing, due to the continuous desire to reduce production costs. A proteomics approach and electrophoresis survey of retail mozzarella cheeses indicated different rates of proteolysis in the production of dairy industries. The use of fresh milk and correct cheesemaking protocol yielded only γ-caseins, which are derived from ß-casein by plasmin, and para-κ-casein, which is derived from κ-casein by chymosin. The detection of abnormal hydrolysis resulting in ß- and αS1-casein fragments, identified by mass spectrometry, indicates the use of stored milk or stored and pressed curd, or the reuse of unsold mozzarella cheese, to produce mozzarella. The formation of γ-caseins and other fragments during a long storage of raw materials at room or refrigeration temperature was ascribed to plasmin (endogenous milk enzyme), whereas formation of αS1-casein fragments, mainly αS1-I(6P)- and αS1-I(7P)-casein during the storage of curd was ascribed to the action of chymosin (exogenous enzyme) from rennet. Sodium dodecyl sulfate-PAGE and alkaline urea-PAGE permitted us to evaluate the freshness of the raw materials used in the manufacturing of buffalo mozzarella cheese and to reveal possible inappropriate preservation.

Obtención y criopreservación de células madre del tejido graso mediante liposucción / Collecting and criopreservation of stem cells obtained by liposuction from fat tissue

Existen diferentes técnicas para la obtención directa de células madre embrionarias a través de embriones criopreservados en nitrógeno líquido(-196 °C), blastómeros individuales, activación de ovocitos por transferencia nuclear y células madre del líquido amniótico. También es posible obtener células madre adultas hematopoyéticas y de la médula ósea, más conocidas y empleadas en la clínica desde hace tiempo, así como también de la sangre del cordón umbilical en recién nacidos y de la grasa corporal en adultos. La grasa autóloga corporal extraída mediante liposucción se reutiliza en ocasiones para injertar o infiltrar otras zonas corporales y faciales como material de relleno, pero en la mayoría de los casos es desechada. Por lo general, para obtener un resultado satisfactorio en el trasplante de grasa autóloga, son necesarios varios tiempos quirúrgicos por lo que sería muy útil contar con un banco de tejido adiposo personalizado. Existen diferentes estudios que demuestran que el tejido adiposo aspirado por liposucción convencional puede preservarse y almacenarse con éxito a baja temperatura (-85 °C) en banco de tejido para futuras aplicaciones. Las células madre mesenquimales (MSCs) poseen gran capacidad de proliferación y diferenciación con un alto valor terapéutico. El tejido graso es un reservorio importante de MSCs capaces de diferenciarse en tejido óseo, cartilaginoso, muscular, etc. Si reservamos una pequeña cantidad del tejido grasolipoaspirado, podemos obtener una cantidad suficiente de MSCs y conservarlas mediante un método óptimo de criopreservación. En 2007 realizamos un estudio de la (..) (AU)

There are different techniques to obtain embryonic stem cells directly through cryopreserved embryos in liquid nitrogen (-196ºC), individual blastomers, ovocyte activation by nuclear transfer and stem cells from amniotic fluid, among others. It is also possible to obtain hematopoietic adult stem cells and those from the bone marrow, better well-known and used in clinics for a long time; besides, from the blood of umbilical cord in newborns and body fat in adults. The autologous fat extracted from the body using liposuction, is sometimes reused to inject or infiltrate other body and facial areas as a filling material, but in most of the cases, it is thrown away. Sometimes it´s necessary to perform several surgical operations; therefore, it would be very useful to count on a bank of personalized adipose tissue. There are different studies that demonstrate that adipose tissue obtained through conventional liposuction can be preserved and stored successfully at a low temperature (-85 ºC) in a tissue bank for a future use. Mesenchymal stem cells (MSCs) are those with a high capacity of proliferation and differentiation with a high therapeutic value. Fat tissue is an important reservoir of MSCs, able to be differentiated in osseous, cartilaginous, muscular, etc. tissues. Therefore, if we reserve a small amount of fat tissue obtained through liposuction, we can get the enough amount and preserve the MSCs with the best method of cryopreservation. In 2007 we carried out a study of the fat obtained though liposuction in36 patients, in order to demonstrate and validate a method for adipose tissue acquisition, with the subsequent transfer, (..) (AU)

The burden of chronic kidney disease in long-term liver transplant recipients.

BACKGROUND: Chronic kidney disease (CKD) is an important risk factor for morbidity and mortality post-liver transplantation (OLT). This study focused on investigating the incidence and risk factors associated with the development CKD after OLT. METHODS: We performed a retrospective cohort study of recipients followed at least 5 years at our institution. CKD was diagnosed and classified according to National Kidney Foundation and the Kidney Disease Outcomes Quality Initiative guidelines. RESULTS: There were 231 patients, 64% men, 67% Caucasian, 16% African-American, and 17% others, with a mean age of 56 +/- 13 years. The mean glomerular filtration rate (GFR) of the population was 56 +/- 28 mL/min/1.73 m2. CKD was defined as GFR less than 60 mL/min; 144 patients (61%) were identified as having CKD. When these patients were compared to the non-CKD group, the former were significantly older (62 +/- 9 vs 52 +/- 12 years, P = .03), more likely to be hypertensive (59% vs 38%, P = .003), and required more antihypertensive medications (0.83 +/- 0.81 vs 0.52 +/- 0.77, P = .02); 26% of all patients had diabetes. However, the incidence of diabetes (43.3% vs 19.3%, P = .02) as well as the incidence of insulin dependency (21.6% vs 12.5%, P = .001) was significantly higher in the CKD population. Mean uric acid levels were higher in CKD patients compared to non-CKD patients (8.00 +/- 2.00 mg/dL vs 6.70 +/- 1.99 mg/dL respectively, P = .001); patients with uric acid more than 6.0 had a 1.7 risk of having CKD. CONCLUSIONS: CKD defined as GFR < 60 mL/min is highly prevalent in long-term OLT survivors. Older age, elevated systolic blood pressure, insulin-dependent diabetes mellitus, and elevated uric acid levels are independently associated with CKD.

An interesting case of a pituitary adenoma apoplexy mimicking an acute meningitis. Case report.

Apoplexy of a pituitary adenoma is a rare and under-diagnosed clinical occurrence. It results from either infarction or haemorrhage into an adenoma of the pituitary gland. Its clinical presentation more often includes rapid development of impaired consciousness, severe headache, visual disturbance and variable association of oculomotor nerve palsy. Meningeal irritation signs are considered very rare and usually not reported as presenting symptoms. A 33-year-old male suffered a pituitary macroadenoma apoplexy, clinically indistinguishable from an infectious meningitis at presentation. Three days after surgery, the patient developed a left ophthalmoplegia due to 3(rd) nerve palsy, which fully resolved within 2 months. A right pterional craniotomy was performed during which complete tumour removal was achieved. In conclusion the authors believe that, despite many reports in the literature, encouraging conservative management in pituitary apoplexy by administering intravenous steroids, surgery should be undertaken in order to avoid eventual visual field defects, relieve pituitary gland compression and prevent a possible recurrent apoplectic episode or tumor re-growth.

Anterior cervical corpectomy for cervical spondylotic myelopathy: experience and surgical results in a series of 70 consecutive patients.

Recently the debate over the management of cervical spondylotic myelopathy (CSM) has regained interest; more specifically whether treatment should be operative versus non-operative, raising the question about the real effectiveness of surgery in influencing the natural history of this pathology and about the choice of the most appropriate approach (anterior vs. posterior). The authors report a retrospective review of 70 consecutive patients who underwent elective anterior cervical corpectomy and fusion with iliac crest autograft or titanium mesh and placement of an anterior cervical plate for the treatment of CSM. The patients underwent pre-and postoperative evaluation, including history, and physical and neurological examination. Patients were also evaluated pre-and postoperatively using a modified version of the Japanese Orthopedics Association Scale (mJOA), which provides a fine semi-quantitative graded evaluation of overall function. Upon discharge home, patients were followed for an average of 42 months (range, 12-63 months). Following an anterior cervical decompression of the spinal cord, 94.2% of patients improved their functional status and 5.8% were unchanged; the mean preoperative mJOA score of all patients was 12.2, the postoperative was 15.4 and the amelioration was also documented by neurophysiological studies which showed an increase in amplitude and decrease in latency of somatosensory evoked potentials and motor evoked potential in 47 patients (67%). Older age and longer duration of preoperative symptoms both were not associated with a lower postoperative mJOA score (p < 0.47, p < 0.29, respectively). Single versus multiple level decompression was not predictive of a lower postoperative mJOA score (p < 0.18). Preoperative spinal cord low signal intensity changes on T1-weighted MRI were related to a lower postoperative mJOA score (p < 0.05), whereas spinal cord high-signal intensity changes on T2-weighted MRI were related to a higher postoperative mJOA score (p < 0.01); finally a lower preoperative mJOA score was highly predictive of a lower postoperative mJOA score (p < 0.0005). Anterior cervical corpectomy and fusion for CSM appears to be an effective procedure with a more favorable neurological improvement when compared to posterior decompressive laminectomy, minimally invasive procedures or non-surgical treatment. It is also a safe procedure even in the elderly population, with low morbidity and the potential for permanent spinal cord decompression and excellent bone stability.

The use of virtual fluoroscopy in managing acute type II odontoid fracture with anterior single-screw fixation. A safe, effective, elegant and fast form of treatment.

BACKGROUND: The management of odontoid fractures represents both a clinical and a technical challenge due to the singular anatomy and biomechanics of the region. At present there is still much controversy as far as any form of management (surgical vs. conservative) is concerned and in any case there is not sufficient evidence to support a standardized form of treatment. This study was designed to further evaluate safety and efficacy of anterior odontoid single-screw fixation and to better determine the usefulness of Image Guided Surgery Virtual Fluoroscopy in treating such cases assessing also its advantages over traditional fluoroscopy and CT-guided frameless stereotaxy in the upper cervical spine surgery. METHODS: This was a retrospective review of ten patients presented during a short period of 18 months with acute traumatic Type II odontoid fractures. Nine underwent fixation within a mean of 3 days after injury, whereas a patient had to be operated upon on the 22nd day due to poor alignment with conservative treatment and ongoing instability. All patients postoperatively were fitted in a collar and then followed-up with serial clinical and radiographic examinations. FINDINGS: Radiological signs of fusion were seen in 10 cases (100%) (mean follow-up: 16 months). No complications occurred during the surgical procedure, nor were any instrumentation failures recorded; all patients remained neurologically intact. CONCLUSIONS: We believe that anterior odontoid screw fixation using Image Guided Surgery virtual fluoroscopy is a safe, effective, less time consuming and low x-ray exposure technique and we recommend this as the preferred treatment method for acute Type II odontoid fractures. Moreover, the use of image guided technology affords more precision, confidence and safety enabling the surgeon to approach the upper cervical spine in an easier and faster way.

Temozolomide as first-line agent in treating high-grade gliomas: phase II study.

UNLABELLED: Temozolomide a recent, oral, second generation alkylating agent is a chemotherapeutic with demonstrated efficacy for the treatment of high-grade gliomas; its efficacy has been demonstrated in both pre-clinical and phase I and II studies. The goal of this study is to determine the activity and safety of temozolomide in improving overall survival (OS), progression-free survival (PFS) and health-related quality of life (HQL) in patient with malignant gliomas. Forty-two patients with newly diagnosed glioblastoma, anaplastic astrocytoma and anaplastic oligodendroglioma were studied. The mean follow-up period was 12 months. The overall response rate (only responsive patient) for all histological groups was 40%, 10 patients (24%) showed a stabilization of disease. The median PFS and OS was respectively 8.35 and 14.1 months: time to progression was 34 week ranging from 21 to 47. In all patients, treatment with temozolomide was associated with improvement of performance status including the patient showing disease progression: Karnofski score improved in all patients by a minimum of 10, with a median of 20 at 6 months. No patient stopped the treatment due to side-effects, no major adverse events were recorded. CONCLUSION: Temozolomide appears to be an ideal, first-line, single-agent, with a safe profile and demonstrated HQL benefits in patients with high-grade gliomas.

Cryopreservation of Arachis species by vitrification of in vitro-grown shoot apices and genetic stability of recovered plants.

A storage protocol at cryogenic temperature was established for shoot apices from in vitro plants of the cultivated groundnut (Arachis hypogaea) and wild Arachis species (A. retusa and A. burchellii) using a basic vitrification protocol with direct immersion in liquid nitrogen (LN). The effect of pre-treatments of donor-plants with ABA as well as of different supplements in the post-thaw culture medium was studied. After rapid warming at 40 C, the explants were cultured on MS medium devoid of growth regulators (MS0) or MS supplemented with 4.4(M benzylaminopurine (BAP) and 0.5(M naphthalene acetic acid (NAA) plus 5(M silver nitrate (AgNO3), 0.25% polyvinylpyrrolidone (PVP) or 0.2% activated charcoal. Non-frozen explants from the three species formed one shoot through meristematic amplification when cultured on MS0 medium. These explants also developed callus on MS supplemented with growth regulators (4.4(M BAP and 0.5(M NAA) alone or plus PVP or AgNO3. Callus formation was suppressed in the presence of activated charcoal. Post-thaw regeneration ocurred only through indirect organogenesis on media containing AgNO3 or PVP. Preculturing on medium supplemented with abscisic acid (ABA) improved regrowth rate in these media. Recovery failed to occur in the presence of activated charcoal. The genetic stability of shoots of A. burchellii originated from shoot apices was analyzed through Random Amplified Polymorphic DNA (RAPD) markers.

Cerebral effects of hyperbaric oxygen breathing: a CBF SPECT study on professional divers.

We investigated the effects on cerebral blood flow (CBF) of pure oxygen breathing exposure during dives in a group of professional divers, in both the normobaric (NBO) and the hyperbaric oxygen (HBO) breathing conditions. Using single photon emission computerized tomography (SPECT) and Tc-99m hexamethylpropylenamine oxime (HM-PAO), we studied 10 young divers and six normal volunteers. Divers were studied by SPECT in the NBO and HBO conditions, in two different sessions. The HBO state was obtained in a hyperbaric chamber at 2.8 ATA for 15 min. By ANOVA, we did not observe any significant difference in CBF distribution between controls and divers in both NBO and HBO conditions. By individual analysis, divers showed a decreased CBF in a total of 33 regions of interest (ROIs) during NBO and 46 ROIs during HBO with respect to control values. In particular, two divers showed a remarkable increase in the number of hypoperfused ROIs during HBO (+7 and +5 ROIs, respectively). Pure oxygen breathing exposure in young divers is associated with a patchy distribution of brain areas of hypoperfusion. This phenomenon is more pronounced in the HBO state than in the NBO state. Further studies on CBF are needed to help identify divers potentially prone to harmful oxygen effects.

Genetic characterisation of the Uruguayan Creole horse and analysis of relationships among horse breeds.

The genetic variability within the Uruguayan Creole horse and its relationship to a group of geographically or historically related breeds (Spanish Pure-bred, Barb, Quarter horse, Paso Fino, Peruvian Paso, Arabian and Thoroughbred horse), was evaluated using 25 loci (seven of blood groups, nine of protein polymorphisms and nine microsatellites) analyzed on a total of 145 Uruguayan Creole horses. In this study, blood group and protein polymorphism variants that are considered to be breed markers of Spanish Pure-bred and Barb horses were detected in the Creole breed. Conversely, some microsatellites and protein polymorphisms alleles were found uniquely in the Creole horse. American horse breeds together with Barb and Arabian horses clearly formed a separate cluster from the Spanish pure-bred and Thoroughbred breeds, as shown by an UPGMA dendrogram based on Nei's standard genetic distance. Data in this study provided evidence for considerable genetic variation within Uruguayan Creole horses and of a distinctive breed profile. Both traits were most likely inherited from the XVIth century Spanish horses, more closely related to Barb than to Spanish Pure-bred.

Cryopreservation of cultivated and wild Arachis species embryonic axes using desiccation and vitrification methods.

The effects of two methods of cryopreservation involving chemical vitrification and air desiccation) were studied on isolated embryonic axes of A. hypogaea. Vitrification with PVS2 and desiccation in a laminar flow cabinet resulted in high levels (70-90%) of whole plant recovery after cryopreservation. A desiccation protocol based on 1h exposure of explants to the air flow was successfully applied to six wild species of section Extranervosae, resulting in recovery levels of 70-90% after liquid nitrogen treatment.

Genomic polymorphism in Uruguayan Creole cattle using RAPD and microsatellite markers.

Uruguayan Creole cattle inhabit areas that cannot sustain conventional farming. They have adapted to fragile environments and are influenced only by natural selection. In this study, random amplified polymorphic DNA (RAPD) and microsatellite (MS) markers were used to analyse Creole cattle genome polymorphism. A comparative analysis using the RAPD technique was performed in pooled DNA of three cattle breeds (Holstein Friesian, Creole and Hereford) in order to evaluate their amplification patterns. A primary screening of RAPD primers allowed us to select and use those with higher percentage of GC base composition. A total of 215 loci ranging between 300 and 2500 bp were amplified. Bandsharing frequency (BSF) among breeds showed that less related fingerprints were observed between Creole and Hereford cattle (0.77), while the highest similarity frequency corresponded to Holstein Friesian compared to Hereford (0.81). Specific RAPD bands were identified in the three DNA pools and they were tested in every individual of each breed. It may be possible to isolate and sequence these bands to create breed-specific molecular markers. The identification of multiple alleles of the MSCYP 21 in Creole cattle with an heterozygosity of He = 0.846 supported the variability of this genetic resource. The use of molecular markers such as RAPD s and microsatellites is proposed to establish genetic distance among American Creole cattle and possibly related ancestral Iberian breeds.

Information dissemination and training: two key issues for consolidating and strengthening the results of health telematic projects.

The concepts expressed in this paper concerns the activities to be developed within HEALTHLINE, a European project under the Telematics Application programme. HEALTHLINE is an umbrella project which takes initiatives and provides links to other international projects on health telematics. The projects involved are NIVEMES and RISE; they represent the starting point from which a common approach will be developed. The experience gained from these projects has highlighted two emerging requirements: information dissemination and training. To fulfil the needs of information, an Internet corner will be set up; it will allow citizens and health professionals to find and exchange information as well as to discuss themes concerning health care. Due to the most advanced technologies recently introduced, the Health care sector has had to modify its traditional ways of working to aid professionals in exploiting new training techniques and Health Care provision methods. HEALTHLINE will focus on training and on the development of the use of new tools and services. Furthermore, the project will exploit the training methodologies based on multimedia technology for developing training-on-the-job modules. The entire system, in its final stage, will consist of a network for co-operating training and information dissemination; European sites in the project will share information, training material and provide education and information on tele-health, medical and health-care issues to health care providers, beneficiaries and the general public.

Neuroprotection, excitotoxicity and NMDA antagonists.

PURPOSE: To analyze the main aspects of neuroprotection and excitotoxicity. DISCUSSION: This is a significant theory on the pathophysiology of cerebral ischemia; it is based on the release of excitatory aminoacid (EAA), mainly glutamate. The sequence starts with a decrease of the blood flow and ends in neuronal death. The main stages of this reaction are herein presented and discussed. An in depth study of the effects of the excessive intracellular calcium is undertaken. Neuroprotectors (NP) are a group of drugs that reduce the excitotoxicity, opposing the excessive release of EAA and its intracellular effects. Neuroprotectors represent a rational approach to stroke treatment and offer a number of potential advantages. They prevent or limit ischemia-induced damage. CONCLUSION: There are many experimental and clinical NP trials. A minimum of 800 trials are currently under study worldwide. The most important NP subgroups are: N-methyl D-aspartate (NMDA) antagonists, gamma-amino butyric acid (GABA) agonists, amino-hydroxy-methyl-isoxalone propionic acid (AMPA) antagonists, reducers of intracellular Ca++ inhibitors of nitric oxide modulation pathway free radicals scavengers, sodium channel antagonists, glutamate release inhibitor, growth factors, hypothermia and potassium channel activators.

In vitro down regulation of ICAM-1 and E-cadherin and in vivo reduction of lung metastases of TS/A adenocarcinoma by a lysozyme derivative.

The aim of the present investigation was to examine the effects of the lysozyme derivative mPEG-lyso (hen egg-white lysozyme coupled with polyoxyethylenglycol), on TS/A adenocarcinoma cell line in vivo and in vitro. mPEG-lyso reduces the number of ICAM-1+ and E-cadherin+ cells of TS/A adenocarcinoma cell line in vitro, and causes a marked decrease of spontaneous lung metastases in vivo. In both cases, mPEG-lyso reduces the number of tumour cells in sythesis and pre-mitotic phases. In connection with the reduction of cells expressing adhesion molecules, mPEG-lyso reduces the number of infiltrating leukocytes in the primary tumour in vivo and reduces the binding capacity of splenocytes to tumour cells in vitro. These data stress, for the first time, that the in vivo control of mPEG-lyso on lung metastasis formation of solid metastasising tumours may be due to a combination of effects on tumour cells in addition to those on host's immune system.