Reversible hyperintensity in middle cerebellar peduncles. An infrequent finding in Marchiafava-Bignami disease. / Hiperintensidad reversible en los pedúnculos cerebelosos medios. Un hallazgo infrecuente en la enfermedad de Marchiafava-Bignami.

TITLE: Hiperintensidad reversible en los pedúnculos cerebelosos medios. Un hallazgo infrecuente en la enfermedad de Marchiafava-Bignami.

Ad libitum consumption of milk supplemented with omega 3, 6, and 9 oils from infancy to middle age alters behavioral and oxidative outcomes in male mice.

We tested the hypothesis that administration of omega (ω)-9, ω-3, and ω-6 to mice can prevent oxidative alterations responsible for behavioral and cognitive alterations related with aging. Twenty-eight-day-old mice received skim milk (SM group), SM enriched with omega oil mixture (EM group), or water (control group) for 10 and 14 months, equivalent to middle age. Mice were evaluated for behavioral alterations related to depression and memory and oxidative status [brain levels of thiobarbituric acid reactive substances (TBARS), reduced glutathione (GSH), and myeloperoxidase (MPO)]. The 10-month EM group increased immobility time during the forced swimming test compared with control, indicating increased stress response. The 14-month SM- and EM-treated groups increased sucrose consumption compared with control, showing an expanded motivational state. The 14-month SM group decreased the number of rearings compared with the 14-month control and EM groups. The number of entries and time spent in the central square of the open field was higher in the 10-month EM group than in the control, revealing an anxiolytic-like behavior. TBARS decreased in the hippocampus and striatum of the 10-month EM group compared with the control. A similar decrease was observed in the striatum of the 10-month SM group. GSH levels were higher in all 14-month treated groups compared with 10-month groups. MPO activity was higher in the 14-month EM group compared with the 14-month control and SM groups, revealing a possible pro-inflammatory status. In conclusion, omega oils induced conflicting alterations in middle-aged mice, contributing to enhanced behavior and anxiolytic and expanded motivational state, but also to increased stress response and pro-inflammatory alterations.

Ad libitum consumption of milk supplemented with omega 3, 6, and 9 oils from infancy to middle age alters behavioral and oxidative outcomes in male mice

We tested the hypothesis that administration of omega (ω)-9, ω-3, and ω-6 to mice can prevent oxidative alterations responsible for behavioral and cognitive alterations related with aging. Twenty-eight-day-old mice received skim milk (SM group), SM enriched with omega oil mixture (EM group), or water (control group) for 10 and 14 months, equivalent to middle age. Mice were evaluated for behavioral alterations related to depression and memory and oxidative status [brain levels of thiobarbituric acid reactive substances (TBARS), reduced glutathione (GSH), and myeloperoxidase (MPO)]. The 10-month EM group increased immobility time during the forced swimming test compared with control, indicating increased stress response. The 14-month SM- and EM-treated groups increased sucrose consumption compared with control, showing an expanded motivational state. The 14-month SM group decreased the number of rearings compared with the 14-month control and EM groups. The number of entries and time spent in the central square of the open field was higher in the 10-month EM group than in the control, revealing an anxiolytic-like behavior. TBARS decreased in the hippocampus and striatum of the 10-month EM group compared with the control. A similar decrease was observed in the striatum of the 10-month SM group. GSH levels were higher in all 14-month treated groups compared with 10-month groups. MPO activity was higher in the 14-month EM group compared with the 14-month control and SM groups, revealing a possible pro-inflammatory status. In conclusion, omega oils induced conflicting alterations in middle-aged mice, contributing to enhanced behavior and anxiolytic and expanded motivational state, but also to increased stress response and pro-inflammatory alterations.

[Assessment of preventive practices in primary care occurring in hospital]. / Évaluation des pratiques préventives d'une consultation de médecine générale hospitalière.

BACKGROUND: Preventive measures are available for most of the pathological conditions causing premature mortality in France. Moreover, there is a seven-year discrepancy in life expectancy figures between persons in the least favorable socio-occupational categories and the rest of the general population. The overall target of our study was to analyze preventive practices applied as part of routine primary care in the outpatient clinics of a general medicine hospital in Paris (Hotel-Dieu) where the majority of patients belong to unfavorable social categories. METHODS: We collected and analyzed the content of all outpatient visits conducted during a three-week period using a questionnaire designed to gather information about areas of preventive care requiring particular attention. RESULTS: Analysis of 211 outpatients visits shows that the population concerned was young (44±17-year-old) and that the visits lasted longer than commonly observed (21±8 min). Cancer screening was performed in 25 to 50% of the theoretical targeted population. Addictions were discussed during half of the visits, yet follow-up and advice on how to stop addictive behavior were insufficient. Blood pressure was measured during half of the visits. Vaccinations were checked for 60% of patients and STD status for 30%. Seventy percent of the patients stated they wanted to attend a preventive care consultation; the physician considered this type of consultation would be useful for 30% of patients; the opinions were in disagreement for half of the patients. Lack of time, heavy workload in terms of number of visits, and the current setup of charts prevented updating various precautionary measures, which would have been appropriate for each patient as a function of age, gender, past history and lifestyle. CONCLUSION: This inquiry highlights many weaknesses in our preventive practices. Delegating some medical acts, a more adapted medical file and the implementation of dedicated consultations could help improve prevention in this particularly vulnerable population. The key to success of such measures lies in physician and patient awareness.

Female reproductive biology of the bluemouth Helicolenus dactylopterus dactylopterus: spawning and fecundity.

The bluemouth Helicolenus dactylopterus dactylopterus is a zygoparous species that spawns multiple batches of embryos enclosed within a gelatinous matrix. Oocyte development is asynchronous, and the recruitment of secondary growth oocytes occurs continuously during the developing phase, but stops before the start of the first spawning (i.e. fecundity is determinate). The number of developing oocytes can be estimated as a function of the total length of the fish, its ovary mass and its gonado-somatic index. Only at the onset of spawning, when potential fecundity is determined, does condition also have a significant effect. The low levels of atresia detected during most of the spawning season show that this mechanism does not substantially affect the process. There is variability both in the spawning interval (with a mean of 2 days) and in the number of embryos comprising every single batch (up to 37,000). Expected effect of fisheries on the reproductive traits of this deep-sea species is also discussed.

[Atypical recurrent aseptic cutaneous abscesses as the presenting manifestation of Crohn's disease]. / Abcès cutanés aseptiques récidivants atypiques révélateurs d'une maladie de Crohn.

INTRODUCTION: We report here a case of chronic inflammatory bowel disease revealed by multiple large cutaneous aseptic distal necrotic ulcers. CASE REPORT: A 44-year-old male presented with high fever at 40°C associated with multiple necrotic abcesses located on the distal part of his limbs. They were treated successfully by debridment and dressings associated with antibiotics allowing complete healing after 1 month. Six months later, the patient relapsed on his left hand with a short episode of diarrhoea. A total coloscopy revealed a Crohn's disease. Systemic corticotherapy and azathioprine were administered and complete remission was obtained with a 1-year follow-up. CONCLUSION: Skin manifestations that this patient presented were atypical because of their number, size, and location, exclusively distally on the limbs. This report illustrates an unusual presentation of Crohn's disease with multiple necrotic ulcers only located on the patient extremities.

Agonistic sounds in the skunk clownfish Amphiprion akallopisos: size-related variation in acoustic features.

Fourteen individuals of the skunk clownfish Amphiprion akallopisos of different sizes and of different sexual status (non-breeder, male or female) were analysed for four acoustic features. Dominant frequency and pulse duration were highly correlated with standard length (r = 0.97), and were not related to sex. Both the dominant frequency and pulse duration were signals conveying information related to the size of the emitter, which implies that these sound characteristics could be useful in assessing size of conspecifics.

The rocker bone: a new kind of mineralised tissue?

In some Ophidiiform fishes, the anterior part of the swimbladder is thickened into a hard structure called the "rocker bone", which is thought to play a role in sound production. Although this structure has been described as cartilage or bone, its nature is still unknown. We have made a thorough analysis of the rocker bone in Ophidion barbatum and compared it with both classical bone and cartilage. The rocker bone appears to be a new example of mineralisation. It consists of (1) a ground substance mainly composed of proteoglycans (mucopolysaccharide acid) and fibres and (2) a matrix containing small mineralised spherules composed of a bioapatite and fibrils. These spherules are embedded in mineralised cement of a similar composition to the spherules themselves. The rocker bone grows via the apposition of new apatite spherules at its periphery. These spherules are first secreted by the innermost fibroblast layer of the capsule contained in the rocker bone and then grow extracellularly. Blood vessels, which represent the only means of transport for matrix and mineral material, are numerous. They enter the rocker bone via the hyle and ramify towards the capsule. We propose to call this new kind of mineralised tissue constituting the rocker bone "frigolite" (the Belgian name for styrofoam) in reference to the presence of spherules of different sizes and the peculiarity of the rocker bone in presenting a smooth surface when fractured.

Tepoxalin inhibits inflammation and microvascular dysfunction induced by abdominal irradiation in rats.

BACKGROUND: Inflammatory cells contribute to the acute and sub-acute sequelae of radiation therapy. Tepoxalin, an inhibitor of cyclooxygenase and 5-lipoxygenase that suppresses NF-kappaB activation, has potent anti-inflammatory activity. AIMS: To assess the effects of tepoxalin on radiation-induced inflammatory damage, and determine its mechanisms of action. METHODS: Leucocyte rolling, adhesion and emigration, and albumin leakage were determined by intra-vital microscopy in rat mesenteric venules. NF-kappaB activation was measured by electrophoretic mobility shift assays, and endothelial intercellular adhesion molecule-1 expression by the radiolabelled antibody technique. Groups of irradiated rats were treated with tepoxalin, N-acetyl-L-cysteine, zileuton (lipoxygenase inhibitor), or vehicle. RESULTS: Irradiated animals had a marked increase in the number of rolling, adherent and emigrated leucocytes in mesenteric venules, and in microvascular permeability. Tepoxalin prevented leucocyte adhesion and the increase in permeability after radiation. Tepoxalin did not inhibit radiation-induced NF-kappaB activation or intercellular adhesion molecule-1 up-regulation, while N-acetyl-L-cysteine, which attenuated NF-kappaB activation, had no effect on leucocyte recruitment. In contrast, tepoxalin inhibited the increase in leukotriene B4 levels after radiation, and the anti-inflammatory effects of the drug were mimicked by zileuton. CONCLUSIONS: Tepoxalin affords significant protection against radiation-induced inflammation and microvascular dysfunction in splanchnic organs through a mechanism dependent on leukotriene synthesis inhibition.

Chromium(VI)-mediated DNA damage: oxidative pathways resulting in the formation of DNA breaks and abasic sites.

Inside cells chromium(VI) is activated to its ultimate carcinogenic form by reducing agents including glutathione (GSH) and ascorbate (AsA). The precise mechanism by which DNA damaging species are formed is unclear. In earlier in vitro work with isolated DNA we have shown that chromium(VI) in combination with GSH or AsA is able to induce similar numbers of single strand breaks and apurinic/apyrimidinic sites (AP-sites). Moreover, the formation of both lesions followed a similar temporal pattern. It is conceivable that the two forms of DNA damage arise from a common precursor lesion (e.g. hydrogen abstraction at C4' of the DNA sugar moiety) with a partitioning along two pathways, one yielding an AP-site, the other a single strand break (SSB) and a base propenal. The present study is intended to test this hypothesis by analysing whether oxidation products of deoxyribose can be formed in the presence of chromium(VI) and GSH or AsA. It was found that mixtures of chromium(VI) and GSH or AsA were able to oxidise 2-deoxyribose to yield malondialdehyde, which was detected by reaction with thiobarbituric acid. The characteristic pink chromogen, which forms upon reaction with thiobarbituric acid, was also observed with calf thymus DNA as the substrate. In both experimental systems the addition of catalase prevented the formation of deoxyribose breakdown products. Hydroxyl radicals did not seem to be important for the generation of DNA damage as the characteristic modified DNA bases could not be detected by using gas chromatography-mass spectrometry. These results lead us to conclude that the formation of SSB during the reductive conversion of chromium(VI) proceeds primarily via hydrogen abstraction from C4'. The observation that Fenton chemistry is not involved in these processes is intriguing and necessitates further research into the ways in which chromium can activate molecular oxygen to form DNA damaging species.

Influence of dose-rate on inflammatory damage and adhesion molecule expression after abdominal radiation in the rat.

PURPOSE: The goal of this study was to assess the effects of two clinically relevant radiation dose-rates on endothelial adhesion molecule expression, inflammatory response, and microvascular dysfunction. METHODS AND MATERIALS: Rats were irradiated with 10 Gy at low (0.9 Gy/min) or high (3 Gy/min) dose-rates. Control animals received sham irradiation. Leukocyte rolling, adhesion, emigration, and microvascular permeability were assessed in mesenteric venules by intravital microscopy 6 hours after irradiation. P-selectin and intercellular adhesion molecule-1 (ICAM-1) expression were measured using radiolabeled monoclonal antibodies. RESULTS: Low dose-rate (LDR) abdominal irradiation increased leukocyte adhesion compared with sham-irradiated animals, whereas high dose-rate (HDR) irradiation resulted in enhanced leukocyte rolling, adhesion, and emigration, compared with the LDR or with sham-irradiated rats. Both dose-rates increased microvascular permeability, although this effect was significantly greater after radiation with the high (8-fold) than the low (5-fold) dose-rate. HDR radiation induced significantly larger increments in P-selectin expression in splanchnic organs than LDR, whereas in most organs ICAM-1 expression was only upregulated by the HDR. Blockade of ICAM-1, but not P-selectin, abrogated leukocyte adhesion at both dose-rates. CONCLUSIONS: The magnitude of upregulation of endothelial adhesion molecules, leukocyte recruitment, and endothelial barrier dysfunction elicited by radiation therapy is dependent on the dose-rate at which the radiation is delivered.

Impaired mesenteric leukocyte recruitment in experimental portal hypertension in the rat.

Increased incidence of septic complications in human and experimental portal hypertension has been documented. Because development of an inflammatory response is essential in defense against infectious agents, the aim of this study was to assess leukocyte-endothelial cell interactions in an experimental model of portal hypertension. Intravital microscopy studies showed that under baseline conditions, leukocyte rolling, adhesion, and emigration in mesenteric venules were similar in control, sham operated (SO), and partial portal vein ligated (PPVL) rats. Compared with either control or SO rats, PPVL animals exhibited a markedly reduced recruitment of rolling, adherent, and emigrated leukocytes in response to leukotriene B(4) (LTB(4)) stimulation. Similarly, platelet-activating factor (PAF) superfusion, which induced a large increment in leukocyte rolling and adherence in control and SO rats, was without any effect in PPVL animals. Endothelial P-selectin expression in control rats, as measured by the double radio-labeled monoclonal antibody (mAb) technique, was not modified by LTB(4), but significantly increased in response to PAF. PPVL rats had a significantly lower expression of P-selectin after stimulation with PAF. Neutrophils isolated from PPVL rats exhibited increased L-selectin shedding and CD11b up-regulation in response to PAF and LTB(4), compared with neutrophils isolated from SO rats. These observations indicate that portal hypertension is associated with a defective inflammatory response, which is manifested as a decreased recruitment of rolling leukocytes, and subsequently reduced adhesion/emigration. This defect appears to result from a reduced endothelial P-selectin up-regulation and increased L-selectin shedding.

Mechanisms underlying the anti-inflammatory actions of central corticotropin-releasing factor.

Immune activation of hypothalamic corticotropin-releasing factor (CRF) provides a negative feedback mechanism to modulate peripheral inflammatory responses. We investigated whether central CRF attenuates endothelial expression of intercellular adhesion molecule 1 (ICAM-1) and leukocyte recruitment during endotoxemia in rats and determined its mechanisms of action. As measured by intravital microscopy, lipopolysaccharide (LPS) induced a dose-dependent increase in leukocyte rolling, adhesion, and emigration in mesenteric venules, which was associated with upregulation of endothelial ICAM-1 expression. Intracisternal injection of CRF abrogated both the increased expression of ICAM-1 and leukocyte recruitment. Intravenous injection of the specific CRF receptor antagonist astressin did not modify leukocyte-endothelial cell interactions induced by a high dose of LPS but enhanced leukocyte adhesion induced by a low dose. Blockade of endogenous glucocorticoids but not alpha-melanocyte-stimulating hormone (alpha-MSH) receptors reversed the inhibitory action of CRF on leukocyte-endothelial cell interactions during endotoxemia. In conclusion, cerebral CRF blunts endothelial upregulation of ICAM-1 and attenuates the recruitment of leukocytes during endotoxemia. The anti-inflammatory effects of CRF are mediated by adrenocortical activation and additional mechanisms independent of alpha-MSH.

Effect of redox conditions on the DNA-binding efficiency of the retinoic acid receptor zinc-finger.

Retinoic acid and its derivatives are involved in many important biological processes. In the present study, we have shown that the DNA binding domain of the retinoic acid receptor, which contains two zinc fingers with the Zn(II) tetrahedrally coordinated by four Cys, is susceptible to intracellularly relevant oxidizing agents. In the presence of hydrogen peroxide or hypochlorite, the zinc-finger DNA binding activity was abolished in a concentration dependent manner. The loss of DNA binding activity was correlated with the release of Zn(II) from the zinc-finger motif as a consequence of Zn(II)-thiolate bond oxidation. A combination of glutathione and Zn(II) was able to restore the activity, suggesting that oxidation of the zinc-finger by hydrogen peroxide or hypochlorite resulted in the formation of disulfide bonds between the Cys present in the Zn(II)-binding motif. Our results indicate that in situations of oxidative-stress zinc-finger containing transcription factors may be particularly susceptible to oxidation, resulting in the disruption of control and regulation of gene expression.

Mechanisms responsible for enhanced inflammatory response to ischemia-reperfusion in diabetes.

The objective of the present study was to assess the role of lipid mediators and adhesion molecule expression in exacerbation of ischemia-reperfusion-induced inflammatory response in diabetes. Leukocyte-endothelial cell interactions were studied in mesenteric venules by intravital microscopy. Endothelial expression of intercellular adhesion molecule (ICAM)-1 was measured by the double-radiolabeled monoclonal antibody technique, and beta2-integrin expression was measured by flow cytometry. Ischemia-reperfusion elicited significantly larger increases in leukocyte adhesion and emigration in diabetic rats that were prevented by a platelet-activating factor (PAF)-receptor antagonist or a leukotriene synthesis inhibitor. Leukotriene B4 (LTB4) superfusion induced similar leukocyte recruitment in diabetic and control rats, whereas PAF elicited larger increases in diabetic rats. CD11a, but not CD11b, expression was higher in leukocytes from diabetic animals. Endothelial ICAM-1 in mesentery and in intestine did not differ between diabetic and control rats. These results indicate that diabetes is associated with an enhanced response to ischemia-reperfusion that depends on both PAF and leukotrienes. An increased sensitivity to PAF, along with an increased CD11a expression, may account for the exaggerated inflammatory response to ischemia-reperfusion in diabetes.

Gastric mucosal blood flow regulation in response to different stimuli.

We compared changes in gastric mucosal blood flow (GMBF) and left gastric artery blood flow (LGABF) in response to pharmacological, physiological, and pathological stimuli. GMBF and LGABF were measured by the hydrogen gas clearance and perivascular ultrasonic transit time techniques, respectively, under baseline conditions and following intravenous infusion of vasopressin or pentagastrin, isovolemic hemodilution, or gastric perfusion with HCl-taurocholate. Blood flow changes following vasopressin or hemodilution were significantly larger in the left gastric artery than in the gastric mucosa. In contrast, the increment in blood flow associated with pentagastrin-stimulated acid secretion was significantly greater in the gastric mucosa than in the extramural artery. Barrier disruption with acid-taurocholate induced similar changes in both measurement sites. The gastric hyperemia induced by either mechanism was significantly attenuated by blockade of NO synthesis. These data demonstrate that although functional changes in GMBF are primarily supported by changes in blood flow at the extramural gastric arteries, the gastric mucosal microvasculature is also under the influence of independent local control mechanisms.

Platelet activation In mice and human Helicobacter pylori infection.

Extracts of Helicobacter pylori (HP) have been shown to induce leukocyte adhesion in mesenteric venules, but the effects of HP infection on gastric microvessels are unknown. Inflammatory cell interactions in the gastric microcirculation were studied by intravital videomicroscopy in mice inoculated with either saline or fresh isolates of HP. Platelet aggregates were detected and quantified in murine portal blood, while endothelial P-selectin expression was determined using the dual radiolabeled mAb technique. Platelet activation and aggregation were studied in HP-infected patients and controls by measuring the platelet-aggregate ratio and platelet P-selectin expression. HP infection induced a marked increase in the flux of rolling leukocytes and the appearance of platelet and leukocyte- platelet aggregates in murine gastric venules. The HP-induced rolling and platelet aggregate formation was abrogated by mAbs against L- or P-, but not E- selectin. Endothelial cell expression of P-selectin was not altered, but platelet P-selectin expression was enhanced in HP-infected mice. Circulating platelet aggregates and activated platelets were also detected in HP-infected patients. These findings indicate that platelet activation and aggregation contribute to the microvascular dysfunction and inflammatory cell recruitment associated with HP infections.

Anemia worsens hyperdynamic circulation of patients with cirrhosis and portal hypertension.

This retrospective cohort study was aimed at investigating the effects of anemia on the hemodynamic disturbances associated with portal hypertension. In all, 202 consecutive nontreated portal-hypertensive patients referred for evaluation to our Hepatic Hemodynamic Laboratory were included. Compared to the nonanemic patients, anemic cirrhotic patients had an increased cardiac output (7.9 +/- 1.9 vs 7.1 +/- 2 liters/min, P < 0.01), and a decreased mean arterial blood pressure (82 +/- 11 vs 94 +/- 13 mm Hg, P < 0.0001) and systemic vascular resistance (838 +/- 235 vs 1102 +/- 356 dyn/sec/cm5, P < 0.0001). Similar results were obtained when Child A or Child B-C patients were analyzed separately. Multivariate logistic regression disclosed that hemoglobin concentration, in addition to age, sex azygos blood flow, and albumin concentration, was an independent factor influencing the degree of systemic vasodilation in cirrhotic portal-hypertensive patients. This study discloses that anemia worsens the hyperdynamic circulation associated with portal hypertension. Since hemoglobin concentration may change with time, this parameter should be taken into account when evaluating hemodynamics in portal-hypertensive patients.