Effects of methyl-beta-cyclodextrin on T lymphocytes lipid rafts with aging

Aging is associated with a decline in immune functions. Among them, T-cell activation is altered at several points of the signaling cascade following TCR engagement. Recent findings suggest that lipid rafts act as a platform in the initiation of T-cell activation. We have previously demonstrated that cholesterol content in T-cells increased with aging, especially in lipid rafts. Cholesterol, which is a major component of lipid rafts, serves to stabilize their structure. We hypothesized that restoring T-cell cholesterol content and membrane fluidity would restore, at least in part, T-cell function via lipid rafts. We measured the lipid rafts coalescence, the p56(Lck) and linker of activated T-cell (LAT) signaling molecules recruitment and activation, the cholesterol content and fluidity in T-cell membrane after different methyl-beta-cyclodextrin (MBCD) treatments. Our results show that high concentration of MBCD (10 mM) completely disorganized the lipid rafts in T-cell membranes of young and elderly donors, however, T-cells from elderly donors were less sensitive than T-cells of young donors to low concentration of MBCD (0.5 mM). p56(Lck) and LAT recruitment and activation were affected in T-cells of both aged groups. MBCD treatment did not affect the cholesterol content and fluidity of T-cell membranes of young donors, while the cholesterol content was decreased and fluidity increased in lipid rafts of elderly donors. These results suggested that cholesterol extraction by MBCD increased the fluidity and disrupted lipid rafts organization. The increase in cholesterol content in lipid rafts with aging and its decrease by biochemical extraction were able to affect early signaling molecules activation. Restoring cholesterol content and fluidity may have beneficial effects, however, MBCD disorganized the membrane and this might not completely restore the T-cell activation via lipid rafts with aging. Altogether these results suggest that defects in cholesterol cellular homeostasis may be part of T-cell immunosenescence via lipid rafts dysfunction.     

Frailty in the elderly is associated with insulin resistance of glucose metabolism in the postabsorptive state only in the presence of increased abdominal fat

Whether frail elderly subjects are more insulin resistant (IR) than non-frail is unclear. How obesity, muscle mass, inflammation, hormonal and lipid status, oxidative stress, antioxidant capacity and physical activity influences insulin sensitivity (IS) in frail elderly subjects remains uncertain. We determined (1) whether frail elderly persons are more IR than non-frail elderly and (2) the influence of abdominal fat mass (AFM), muscle mass index (MMI), inflammation (CRP), hormonal (cortisol, free IGF-1, DHEA) and lipid (FFA, triglyceride (TG)) status, oxidative stress (paraoxonase-1 (PON-1), malondialdehyde (MDA)), antioxidant capacity (vitamin C, E) and physical activity (PASE questionnaire) on IS (QUICKI) in 16 frail obese (FO), 17 frail lean (FL) and 21 healthy, non-obese (HN) elderly subjects. IS was lower in FO than FL, but there was no significant difference between HN and FO or FL. There were no significant differences among groups for CRP, cortisol, IGF-1, DHEA, FFA, TG, PON-1, MDA, vitamin C and E and PASE. Age, AFM and MMI significantly correlated with IS. Only AFM and MMI were significant predictors explaining, respectively, 18.5% and 8.5% of the variance in IS. Increased abdominal obesity is associated with IR in frail elderly. Non-obese frail persons are not more IR than their healthy counterparts.     

3-day treatment with azithromycin 1.5% eye drops versus 7-day treatment with tobramycin 0.3% for purulent bacterial conjunctivitis: multicentre, randomised and controlled trial in adults and children

AIM: To compare the efficacy and safety of Azyter, azithromycin 1.5% eye drops, for 3 days with tobramycin 0.3% for 7 days to treat purulent bacterial conjunctivitis. METHODS: This was a multicentre, randomised, investigator-masked study including 1043 children and adults with purulent bacterial conjunctivitis. Patients received either azithromycin 1.5% twice-daily for 3 days or tobramycin 0.3%, 1 drop every two hours for 2 days, then four times daily for 5 days. Clinical signs were evaluated and cultures obtained at D0, D3 and D9 (where D refers to "day"). Primary variable was the clinical cure at the Test-of-Cure (TOC)-visit (D9+/-1), for patients with D0-positive cultures. The cure was defined as: bulbar conjunctival injection and discharge scores of 0. RESULTS: Among 471 patients with D0-positivity in the per protocol set, 87.8% of the azithromycin 1.5% group and 89.4% of the tobramycin group were clinically cured at the TOC-visit. Azithromycin was non-inferior to tobramycin for clinical and bacteriological cure. Clinical cure was significantly higher with azithromycin 1.5% at D3. The safety profile of azithromycin was satisfactory with a good patient and investigator's acceptability. CONCLUSIONS: Azithromycin 1.5% for 3 days was as effective and as safe as tobramycin for 7 days. Furthermore, more azithromycin than tobramycin patients presented an early clinical cure at Day 3. Due to its twice daily dosing regimen for 3 days, azithromycin represents a step forward in the management of purulent bacterial conjunctivitis, especially in children.     

Cortical connections of the inferior parietal cortical convexity of the macaque monkey

We traced the cortical connections of the 4 cytoarchitectonic fields--Opt, PG, PFG, PF--forming the cortical convexity of the macaque inferior parietal lobule (IPL). Each of these fields displayed markedly distinct sets of connections. Although Opt and PG are both targets of dorsal visual stream and temporal visual areas, PG is also target of somatosensory and auditory areas. Primary parietal and frontal connections of Opt include area PGm and eye-related areas. In contrast, major parietal and frontal connections of PG include IPL, caudal superior parietal lobule (SPL), and agranular frontal arm-related areas. PFG is target of somatosensory areas and also of the medial superior temporal area (MST) and temporal visual areas and is connected with IPL, rostral SPL, and ventral premotor arm- and face-related areas. Finally, PF is primarily connected with somatosensory areas and with parietal and frontal face- and arm-related areas. The present data challenge the bipartite subdivision of the IPL convexity into a caudal and a rostral area (7a and 7b, respectively) and provide a new anatomical frame of reference of the macaque IPL convexity that advances our present knowledge on the functional organization of this cortical sector, giving new insight into its possible role in space perception and motor control.     

T-cell acute lymphoblastic leukemia /orbital lymphoblastic lymphoma in children

CASE: The authors report a case of an 6-year-old pediatric patient with a history of acute onset of proptosis of his right eye. He was admitted at hospital 6 months ago for proptosis concomitant with orbital trauma. Computed tomography scan demonstrated a mass involving the right orbit, right maxillary sinus, and zygoma with endocranial extension. RESULTS: Incisional biopsy of the mass revealed after of histopathologic and immuno-histochemical evaluation a T-cell lymphoblastic lymphoma. Systemic examination and bone marrow aspirate show a acute lymphoblastic leukemia. The patient was treated with LMT96 Protocol. A complete Remission was observed after 13 months of follow up. CONCLUSION: Primary T-cell lymphoblastic lymphoma of the orbit is a rare entity in any age group, but it is very rare in children. When tumors occurs in the orbit, it presents a challenging diagnosis problem, especially in pediatric patients.     

Vasorelaxant effects of harmine and harmaline extracted from Peganum harmala L. seeds in isolated rat aorta.

The present work describes the mechanisms involved in the vasorelaxant effect of harmine and harmaline. These alkaloids induce in a dose-dependent manner the relaxation in the aorta precontracted with noradrenaline or KCl. However, the removal of endothelium or pre-treatment of intact aortic ring with L-NAME (inhibitor of NOSe synthetase) or with indomethacin (non-specific inhibitor of cyclo-oxygenase), reduces significantly the vasorelaxant response of harmaline but not harmine. According to their IC50 values, prazosin (inhibitor of alpha-adrenorecepteors) reduces the vasorelaxant effect only of harmaline, whereas, pre-treatment with IBMX (non-specific inhibitor of phosphodiesterase) affects both the harmaline and harmine-responses. Inhibitions of L-type voltage-dependent Ca2+ channels (VOCs) in endothelium-intact aortic rings with diltiazem depress the relaxation evoked by harmaline as well as by harmine. Pre-treatment with harmaline or harmine (3, 10 or 30 microM) shifted the phenylephrine-induced dose response curves to the right and the maximum response was attenuated indicating that the antagonist effect of both alkaloids on alpha1-adrenorecepteors was non-competitive. These two alkaloids also exert an antioxidant activity by scavenging the free radical generated by DPPH. Therefore, the present results suggest that the vasorelaxant effect of harmaline but not harmine is related to its action on the prostacyclin pathway and on the endothelial cells to release NO. However, both alkaloids can act as blockers VOCs, as inhibitors of phosphodiesterase resulting in an increase of the second messenger (cAMP and cGMP) levels and finally reduce the levels of free radicals in tissues.     

A multiarchitectonic approach for the definition of functionally distinct areas and domains in the monkey frontal lobe

Over the last century, anatomical studies have shown that the cerebral cortex can be subdivided into structurally distinct regions, giving rise to a new branch of neuroanatomy: 'architectonics'. Since then, architectonics has been often accused of being overly subjective, and its validity for the definition of functionally different cortical fields has been seriously questioned. Since the late 1980s, however, the problem of localization has become particularly important in functional studies of the primate motor cortex, because of evidence that (1) the primate motor cortex is made up of a mosaic of functionally specialized areas and (2) the human motor cortex shares several general organizational principles with the monkey motor cortex. Studies of the macaque agranular frontal cortex that used a multimodal cyto-, myelo- and immuno-architectonic approach have shown that architectonic borders can be reliably and consistently defined across different individuals, even at a qualitative level of analysis. The validity of this approach has been confirmed by its ability to localize functionally distinct areas precisely and to predict the existence of new functional areas. After more than a century, architectonics as a discipline goes far beyond its original aim of generating cortical maps.     

Antioxidant-rich food intakes and their association with blood total antioxidant status and vitamin C and E levels in community-dwelling seniors from the Quebec longitudinal study NuAge

A cross-sectional study was designed to investigate the association between current consumption of a series of 26 common antioxidant-rich foods (ARF) with serum total antioxidant status (TAS) and plasma vitamin C and E levels in community-dwelling older adults. A convenience sample of the first 94 non-smoking Caucasian men (54%) and women (46%) enrolled in the Quebec Longitudinal Study NuAge were selected. The “Functional Foods Consumption Frequency Questionnaire” (FFCFQ) was administered at recruitment (T1) to ascertain patterns of consumption of ARF over the lifetime. The total Oxygen Radical Antioxidant Capacity (ORAC) of 25 ARF reported by subjects was estimated using published values. Serum TAS was determined based on the Trolox equivalent antioxidant capacity (TEAC) assay while plasma vitamins C and E (α- and γ-tocopherol) levels were analyzed by HPLC. The numbers of ARF eaten daily at T1, estimated from the FFCFQ and calculated from the diet recalls, were significantly correlated (r = 0.51, P < 0.0001) and each measure was associated with total ORAC content (r = 0.34, P < 0.001 and r = 0.59, P < 0.0001 for FFCFQ and recalls, respectively). No significant association was found between TAS and the total ORAC value of ARF determined from the quantitative 24-h diet recalls. However, daily ARF consumption at T1 obtained from the FFCFQ was significantly and positively correlated with TAS (r = 0.26, P < 0.05) and circulating levels of vitamin C (r = 0.25, P < 0.02) and α-tocopherol (r = 0.22, p < 0.05) and negatively correlated with plasma γ-tocopherol (r = − 0.25, P < 0.025). These results highlight associations between ARF consumption and circulating levels of antioxidants in the elderly and suggest benefits from antioxidant-rich foods during aging.