ALZHEIMER'S DISEASE - ESTROGENS AND SELECTIVE ESTROGEN RECEPTOR MODULATORS, FRIENDS OR FOES?

Alzheimer's disease(AD) is the leading cause of dementia and is characterized by the presence of extensive plaque deposition and neurofibrillary pathology. The aim of the present study was to make an update regarding the influence of estrogens and SERMs on inflammation and on the resolution of inflammation, respectively, focusing on these most important features implicated in the pathophysiology of AD. Several hypothesised mechanisms of action of estrogens and SERM are exposed and also some relevant clinical studies on this subject are analysed. The analyzed studies have a high heterogeneity of preparations used, of administration routes, of the female population included and of the periods of time from the appearance/induction of menopause to the therapeutic intervention and also of follow-up periods of patients and of the means of evaluating their cognitive decline. One can say that all the ways of pharmacological influence on the membrane or intracellular signalling system associated to estrogens that may have clinical importance in the prevention and possibly in the treatment of AD have not been exhausted. Estrogens with selective ERα or G protein-coupled estrogen receptors (GPER1 or GqMER) effects could be used to influence the resolution of inflammation process, with positive effects on AD evolution.

To dance or not to dance? A comparison of balance, physical fitness and quality of life in older Irish set dancers and age-matched controls.

OBJECTIVE: The objective of this study is to determine if older adults regularly participating in Irish set dancing have superior balance, physical fitness and quality of life compared to age-matched controls. STUDY DESIGN: This study used a community-based, observational cross-sectional design. METHODS: Regular set dancers (n = 39) and age-matched controls (n = 33) were recruited. Participants were assessed using the physical activity scale for the elderly (physical activity levels), mini-BESTest (balance) and senior fitness test (battery of functional fitness tests). Quality of life was also assessed using the EuroQol EQ visual analogue scale. RESULTS: When controlling for between-group differences in levels of physical activity (ANCOVA analysis), the dancers had significantly better balance, functional capacity and quality of life (all P < 0.05) compared to controls. No differences between the groups were observed in other measures of functional fitness. CONCLUSION: The findings of this study suggest regular participation in set dancing is associated with health benefits for older adults. These results may inform future studies prospectively examining the role of set dancing for falls prevention, emotional well-being and cognitive function in community-dwelling older adults.

Probing the high momentum component of the deuteron at high Q2.

The (2)H(e,e'p)n cross section at a momentum transfer of 3.5 (GeV/c)(2) was measured over a kinematical range that made it possible to study this reaction for a set of fixed missing momenta as a function of the neutron recoil angle θ(nq) and to extract missing momentum distributions for fixed values of θ(nq) up to 0.55 GeV/c. In the region of 35°≤θ(nq)≤45° recent calculations, which predict that final-state interactions are small, agree reasonably well with the experimental data. Therefore, these experimental reduced cross sections provide direct access to the high momentum component of the deuteron momentum distribution in exclusive deuteron electrodisintegration.

[Radiofrequency ablation for liver metastases--mini invasive therapeutic option for patients with unresecable tumors]. / Distructia prin radiofrecventa a metastazelor hepatice--optiune terapeutica miniinvazia optimala la pacientii non-rezecabili chirurgical.

UNLABELLED: Radiofrequency ablations (RFA), a new therapeutic option for liver metastases, proceeded by open surgery or laparoscopic approach, provide an acceptable control of local tumor process, involved lower risks than resection surgery. OBJECTIVES: We analyzed this procedure, for classic indication in hepatic metastatic tumors, based on four years experience, focused on perioperative complications, recurrence rate and long distant evolution. METHOD: Between December 2006 and December 2010, 61 patients with liver metastases underwent RFA; 46 cases had metastatic lesions from colo-rectal cancer, 9 cases from breast cancer, 4 cases from gastric cancer and 2 cases from ovarian cancer. RFA was performed in 55 patients via open surgery and laparoscopic approach in 6 patients. Postoperative course was followed with CT scan at 1 month, and then at 3 month interval, in correlation with tumor markers level. RESULTS: Perioperative complications occurred in 8 cases, consist of prolonged fever, severe hepatic cytolysis, without other complications such, biliary tract injury, hemorrhage, and peritonitis; no mortality caused by RFA procedure. 10 cases had local recurrence, at 6 and 25 month after post RFA procedure. CONCLUSIONS: Initial experience shows that RFA is a safe procedure for treatment of liver metastases, with low rate of morbidity and local recurrence, indicated for patients with unresecable lesions or high risks for surgical resection.

Measurements of the electric form factor of the neutron up to Q2=3.4 GeV2 using the reaction 3He(e,e'n)pp.

The electric form factor of the neutron was determined from studies of the reaction 3He(e,e'n)pp in quasielastic kinematics in Hall A at Jefferson Lab. Longitudinally polarized electrons were scattered off a polarized target in which the nuclear polarization was oriented perpendicular to the momentum transfer. The scattered electrons were detected in a magnetic spectrometer in coincidence with neutrons that were registered in a large-solid-angle detector. More than doubling the Q2 range over which it is known, we find G(E)(n)=0.0236±0.0017(stat)±0.0026(syst), 0.0208±0.0024±0.0019, and 0.0147±0.0020±0.0014 for Q(2)=1.72, 2.48, and 3.41 GeV2, respectively.

Probing quark-gluon interactions with transverse polarized scattering.

We have extracted QCD matrix elements from our data on doubly polarized inelastic scattering of electrons on nuclei. We find the higher twist matrix element d˜2, which arises strictly from quark-gluon interactions, to be unambiguously nonzero. The data also reveal an isospin dependence of higher twist effects if we assume that the Burkhardt-Cottingham sum rule is valid. The fundamental Bjorken sum rule obtained from the a0 matrix element is satisfied at our low momentum transfer.

The gastric mucosa in portal hypertension: structural and ultrastructural observations.

The gastric mucosal lesions represent a frequent cause of hemorrhage in the portal hypertension (PHG) and in the hepatic cirrhosis. This study was undertaken to assess the structural and ultra structural modifications in the intimal lamina of the stomach in this pathology. The cells of mucosa show graded alterative transformations. In the gastric mucosa, some of the chief (enzymatic) cells present a quasi-normal histological organization; others increased alterations such as irregular and heterochromatic nuclei, fewer cytoplasm organelles, numerous clear vesicles and heterogeneous lysosomes. The parietal (oxyntic) cells show in their apical cytoplasm wide dilatations of the intracellular canalicles, vesicles, a reduced number of organelles and irregular nuclei. The enteroendocrine cells (APUD) present an increased number of granules and organelles in the cytoplasm. The connective inter-glandular tissue contains active fibroblasts, micro inflammatory zones, blood vessels with hypertrophied endothelium, irregular and dilated lumen. Subsequent to these alterations in the structures of the gastric mucosa in portal hypertension, the function of synthesis/excretion of the pepsinogen, lipase, hydrochloric acid, intrinsic factor, serotonin, etc. are affected.

VEGF-induced corneal neovascularisation in a rabbit experimental model.

INTRODUCTION AND PURPOSE: Various conditions may cause vascularization of the normally avascular cornea. The aim of the present study was to create a reproducible experimental model that could enable the investigation of the phenomena leading to corneal vascularization. This involved creating a software to record the experimental data, enabling a subsequent digital analysis based on the growth models. The VEGF-induced pattern of neovascularization was also investigated. MATERIAL AND METHODS: Twenty-seven rabbits divided in groups were used for the purposes of the present study. Some of them underwent intracorneal implants with or without vascular endothelial growth factor (VEGF) pellets, using an original microsurgical technique. Central and peripheral corneal burns were induced to other groups of animals in order to mimic the neovascularization process induced by inflammation. Finally, Dexamethasone (Maxidex) was given intraocularly, on days 1 and 3 after the onset of neovascularisation, in rabbit groups with both corneal burns and VEGF-implants. Video recording and data analysis of the corneal vascularization were made with an advanced biomicroscope, a computerized imaging system and a special software. A histochemical study of the animals' eyes was also carried out. RESULTS AND DISCUSSION: The recorded data showed the simplicity and reproducibility of the present experimental model. The results showed the importance of VEGF as an initiator and promoter of corneal vascularization through a non-inflammatory mechanism, quite different from the inflammation illustrated by the corneal burn. At the same time, Dexamethasone therapy proved its effectiveness in corneal angiogenesis induced by thermal burn, but not by VEGF-implant.

High-resolution spectroscopy of Lambda16N by electroproduction.

An experimental study of the (16)O(e,e'K(+))(Lambda)(16)N reaction has been performed at Jefferson Lab. A thin film of falling water was used as a target. This permitted a simultaneous measurement of the p(e,e'K(+))Lambda, Sigma(0) exclusive reactions and a precise calibration of the energy scale. A ground-state binding energy of 13.76+/-0.16 MeV was obtained for (Lambda)(16)N with better precision than previous measurements on the mirror hypernucleus (Lambda)(16)O. Precise energies have been determined for peaks arising from a Lambda in s and p orbits coupled to the p(1/2) and p(3/2) hole states of the (15)N core nucleus.

Beta 3 adrenergic receptors: molecular, histological, functional and pharmacological approaches.

Different classes of receptors mediate norepinephrine and epinephrine effects, one of the most recently discovered being the beta 3 adrenergic ones. The paper has proposed itself to present the history of the discovery of beta 3 adrenergic receptors, different techniques for their identification, their structure, localization, genetic data and also the mechanism of regulation of their functions. It also contains an exhaustive approach regarding the histological localization and functions of beta 3 adrenergic receptors in different apparatus and systems, making evident their effect on glucidic, lipidic and energetic metabolism. The substances that influence beta 3 adrenergic receptors activities, especially the agonists, have been studied regarding their practical applications in the treatment of diabetes mellitus and of the disturbances of lipid metabolism.

High resolution spectroscopy of (lambda)(12)B by electroproduction.

An experiment measuring electroproduction of hypernuclei has been performed in hall A at Jefferson Lab on a 12C target. In order to increase counting rates and provide unambiguous kaon identification two superconducting septum magnets and a ring imaging Cherenkov detector were added to the hall A standard equipment. An unprecedented energy resolution of less than 700 keV FWHM has been achieved. Thus, the observed (Lambda)(12)B spectrum shows for the first time identifiable strength in the core-excited region between the ground-state s-wave Lambda peak and the 11 MeV p-wave Lambda peak.

[Effects of serotonin on reactivity of ocular vasculature]. / Efectele serotoninei asupra reactivitatii vasculare oculare.

INTRODUCTION: Serotonin presents specific receptors of many types and subtypes. The aim of this study was to analyze the differences in reactivity between the vessels (arteries and veins) of the iris and conjunctiva. The vascular diameter was measured using a noninvasive technique after intraocular administration of different doses of serotonin. MATERIAL AND METHODS: The tests were performed on rats, divided in control and study groups. The modifications of studied vessels' diameters before and after topical administration of the solutions were evaluated by measuring these diameters at fixed time intervals of 30 seconds, for 6 minutes. Differentiation between arteries and veins was made using topical administration of felodipine after the testing 6 minutes interval The statistical significance of differences between the values obtained in each interval of 30 seconds and the control values at the initial moment was evaluated using t-test, the "paired" variant. RESULTS: There were obtained differences in reactivity between iris and conjunctival vessels and between iris arteries and veins for the different concentrations of tested serotonin solutions. CONCLUSIONS: Iris and conjunctival vessels contain serotonin receptors with different types and densities, whose activation produced vasoconstriction in both territories, but with different evolution and intensity. Differences in reactivity were found between iris arteries and veins, probably due to a different density of receptors between those two territories. The different vascular response might be a protective mechanism against dissemination of conjunctival infections.

Reelin and its receptors, VLDLR and ApoER2, in melanocytic nevi.

Reelin is an extracellular signaling protein synthesized by Cajal-Retius cells in utero and early after birth, its presence being signaled in adult life too. Reelin acts on its receptors, VLDLR and ApoER2, acting on cytoskeleton, controlling migration and subsequently positioning and stabilizing the cortical neurons. We investigated the reelin presence and its receptors, VLDLR and ApoER2, in melanocytic nevi considering the neural crest origin of the nevus cells and their migration into skin during embrionary period. Melanocytic nevi present a strict cellular architecture and an increased malignant transforming capacity. We investigated reelin presence in 32 melanocytic nevi (5 junctional, 27 compound or 14 dysplastic nevi and 18 non dysplastic nevi). The assessment of reelin presence was performed by histological semiquantitative criteria. Results showed the presence of reelin in 29 cases (29/ 32). The presence of reelin was elevated in junctional areas as in dysplastic nevi. VLDLR presented positive values in 16 cases (16/ 32) and ApoER2 was weak positive in 7 cases. Reelin or its receptors was peritumorally absent. Our study showed the presence of reelin in nevus cells from cutaneous melanocytic nevi and, in these cells, only the VLDLR receptor was present in half of the cases. The significance of the reelin presence in cutaneous nevus cells may be hypothetically considered correlated with the position maintenance of the nevus cells or migration of these cells in malignant transforming situation. Abbreviations: ApoER2 = apolipoprotein receptor 2, VLDLR = very low density lipoprotein receptor, DAB-1 = DIABLO protein, HMB45 = gene HMB45.

Axillary basal cell carcinoma--a rare form of a frequent kind of carcinoma.

Basal cell carcinoma (BCC) is the most common cutaneous cancer. It seems that the most important prognostic factor is exposure to ultraviolet radiation (solar and artificial), correlated with other factors as well. In this article, we aimed to review basal cell carcinoma located in the axilla, referring to cases from our hospital. Axillary location of BCC is rare, with a very low number of cases quoted in the literature, compared to the high prevalence of basal cell carcinoma in the general population. During a period of two years, we detected only four cases of axillary basal cell carcinoma out of a total number of 921 cases diagnosed as BCC. We were interested in identifying certain factors involved in causing BCC, post-excision clinical evolution, histological type and aggressiveness of axillary basal cell carcinoma. Therefore, we quantified objectively the tumor and stromal expression of some immunological markers like: metalloproteinases MMP1, 3, 11, Ber-EP4 and Ki67. Histological types of tumors investigated here belong to the category of non-aggressive BCC, namely as nodular and superficial, although Ki67 index is greater than the average reported in the literature for this type of tumor. MMPs exhibited increased expression in tumors and stromal compartments, especially at the tumor invasion front, and was not associated with tumor ulceration or surrounding tissue remodeling-related changes. Our results confirm the literature data concerning the involvement of MMPs in BCC progression, whatever the tumor location is.

Cannabinoid system and cyclooxygenases inhibitors.

RATIONALE: The cannabinoid system consists of a complex array of receptors, substances with agonist/antagonist properties for those receptors, biosynthetic machineries and mechanisms for cellular uptake and degradation for endocannabinoids. This system is in interrelation with other systems that comprise lipid mediators like prostaglandins/leukotrienes systems. A clear antagonist, additive or synergic effect of nonsteroidal anti-inflammatory drugs (NSAIDs)-cannabinoid associations was not yet demonstrated. Aim. The present study tried to summarize the existent data on NSAIDS-cannabinoid system interactions. METHODS AND RESULTS: A bibliographic research in Medline, Scirus, Embase was made using as keywords cannabinoid, nonsteroidal anti-inflammatory drugs, aspirin, ibuprofen, flurbiprofen, diclofenac, indomethacin, acetaminophen, coxibs, antinociceptive, antinociception, analgesia DISCUSSIONS: A systematization of the results focusing on the NSAIDs drugs interaction with the cannabinoid system was presented. Out of all the substances analyzed in the present review, acetaminophen was studied the most regarding its interferences with the cannabinoid system, mainly due to contradictory results. CONCLUSIONS: Some NSAIDs have additional influences on the cannabinoid system either by inhibiting fatty acid amide hydrolase (FAAH) or by inhibiting a possible intracellular transporter of endocannabinoids. All the NSAIDs that inhibit COX2 can influence the cannabinoid system because a possible important degradative pathway for anandamide and 2-arachidonoyl glycerol might involve COX 2. One of the causes for the variety of experimental results presented might be due to pharmacokinetic mechanisms, depending on the route of administration and the dose

Serum total gangliosides level: clinical prognostic implication.

PURPOSE: The gangliosides overexpression contributes to the development of skin melanoma. The purpose of this study was to determine if the total gangliosides serum levels might predict the tumor growth in patients with melanoma or if the transfer of shed cell gangliosides reflects the implication in the clinical prognostic of these patients. PATIENTS AND METHODS: Total gangliosides serum levels were measured in the cryopreserved serum by estimating lipid-associated sialic acid in 761 patients before surgical resection of melanoma, in 406 patients with precancerous pigmentary lesions, and in 410 healthy individuals. This study was performed at the Dermatovenereological Research Center, Bucharest, Romania, during 1991-2010. All sera obtained after surgical resection of melanocytic tumors were analyzed to see if adjuvant therapy (chemo-, immuno-, immunochemo-therapy) induced gangliosides changes in melanoma patients and if the responses were correlated with survival. RESULTS: Total gangliosides serum levels were higher in melanoma patients than in precancerous melanocytic lesions patients or in healthy individuals. Larger tumors in Breslow index and more advanced stage of disease were correlated with higher total gangliosides serum values. Augmented total gangliosides serum levels after melanoma adjuvant treatment were predictive for decreased overall survival, whereas decreased total gangliosides serum levels were predictable for improved overall survival. CONCLUSIONS: A marker for early melanoma complications and survival may be the total gangliosides serum level.

Measurements of the proton elastic-form-factor ratio mu pG p E/G p M at low momentum transfer.

High-precision measurements of the proton elastic form-factor ratio, mu pG p E/G p M, have been made at four-momentum transfer, Q2, values between 0.2 and 0.5 GeV2. The new data, while consistent with previous results, clearly show a ratio less than unity and significant differences from the central values of several recent phenomenological fits. By combining the new form-factor ratio data with an existing cross-section measurement, one finds that in this Q2 range the deviation from unity is primarily due to G p E being smaller than expected.

Proton spin structure in the resonance region.

We have examined the spin structure of the proton in the region of the nucleon resonances (1.085 GeV

Measurement of the electric form factor of the neutron at Q2=0.5 and 1.0 GeV2/c2.

The electric form factor of the neutron was determined from measurements of the d-->(e-->,e'n)p reaction for quasielastic kinematics. Polarized electrons were scattered off a polarized deuterated ammonia (15ND3) target in which the deuteron polarization was perpendicular to the momentum transfer. The scattered electrons were detected in a magnetic spectrometer in coincidence with neutrons in a large solid angle detector. We find G(n)(E)=0.0526+/-0.0033(stat)+/-0.0026(sys) and 0.0454+/-0.0054+/-0.0037 at Q(2)=0.5 and 1.0 (GeV/c)(2), respectively.