Cell size-proliferation relationship in rat glioma cells

The homeostasis of the central nervous system is highly controlled by glial cells and is dramatically altered in the case of glioma. In this respect, the complex connection between cell size and division is of particular importance and needs clarifying. In order to investigate this connection, cell number and volume were measured in C6 rat glioma cells under different experimental conditions, including continuous cell culture, Cl- channel blockade, and anisotonicity, and in the presence of an inhibitory conditioned medium collected from cell cultures or in a medium containing a low level of fetal calf serum. The rate of cell proliferation changed with cell volume in a bell-shaped manner, so that it is optimal within a cell volume window and appears to be controlled by low and high cell size checkpoints. The cell size-proliferation relationship can be defined by Boltzmann-like equations, which may reflect the effects of macromolecular crowding on proteins controlling the cell cycle progression. Altogether, these observations indicate that glioma cell proliferation is controlled predominantly but not exclusively by cell size-dependent mechanisms.     

Distinct patterns of tau-dependent process formation in mammalian cell lines

Tau is a microtubule-associated protein involved in axonal elongation and central to the pathogenesis of a number of neurodegenerative conditions. To better establish the contribution of the cellular context to tau-dependent microtubule organization, we compared the phenotypes resulting from heterologous tau expression in different mammalian cell lines after disruption of the actin cytoskeleton. After cytochalasin D treatment, tau-expressing CHO cells display one or two long neurite-like extensions whereas cells transfected with MAP2c developed multiple shorter processes. By contrast, under the same conditions, tau-transfected PtK2 cells elaborate microtubule bundles forming numerous processes. These results suggest that cell-specific factors are involved in tau-dependent microtubule organization, a notion that could facilitate functional assessment of tau abnormalities associated with neurodegenerative disease.     

Vascular cognitive disorder: a new diagnostic category updating vascular cognitive impairment and vascular dementia

Vascular cognitive impairment (VCI) was proposed as an umbrella term to include subjects affected with any degree of cognitive impairment resulting from cerebrovascular disease (CVD), ranging from mild cognitive impairment (MCI) to vascular dementia. VCI may or may not exclude the host of "focal" circumscribed impairments of specialized functions such as language (aphasia), intentional gesture (apraxia), or categorical recognition (agnosia), among others, that may result from a stroke. Therefore, there are no universally accepted diagnostic criteria for VCI. We conclude that this concept could be more useful if it were to be limited to cases of vascular MCI without dementia, by analogy with the concept of amnestic MCI, currently considered the earliest clinically diagnosable stage of Alzheimer disease (AD). In agreement with our view,the Canadian Study on Health and Aging successfully implemented a restricted definition of VCI, excluding cases of dementia (i.e., vascular cognitive impairment no dementia, VCI-ND). The Canadian definition and diagnostic criteria could be utilized for future studies of VCI. This definition excludes isolated impairments of specialized cognitive functions.Vascular dementia (VaD): The main problem of this diagnostic category stems from the currently accepted definition of dementia that requires memory loss as the sine qua non for the diagnosis. This may result in over-sampling of patients with AD worsened by stroke (AD+CVD). This problem was minimized in controlled clinical trials of VaD by excluding patients with a prior diagnosis of AD, those with pre-existing memory loss before the index stroke, and those with amnestic MCI. We propose a definition of dementia in VaD based on presence of abnormal executive control function, severe enough to interfere with social or occupational functioning. Vascular cognitive disorder (VCD): This term, proposed by Sachdev [P. Sachdev, Vascular cognitive disorder. Int J Geriat Psychiatry 14 (1999)402-403.] would become the global diagnostic category for cognitive impairment of vascular origin, ranging from VCI to VaD. It would include specific disease entities such as post-stroke VCI, post-stroke VaD, CADASIL, Binswanger disease, and AD plus CVD. This category explicitly excludes isolated cognitive dysfunctions such as those mentioned above.     

Antiplatelet drug discontinuation is a risk factor for ischemic stroke

Antiplatelet drugs (APD) are widely used in the prevention of ischemic cardio- and cerebrovascular diseases. The authors studied the frequency of stroke occurring after APD discontinuation, the cause of discontinuation, and the delay between APD disruption and stroke. Only 4.49% of strokes were related to a recent APD discontinuation, but all cases occurred between 6 and 10 days after drug discontinuation (p < 0.0001). This temporal pattern has biologic plausibility because the inhibited platelets circulate in the blood for about 10 days.     

Nutritional effects of carnitine supplementation in hemodialysis patients

AIMS: Carnitine is involved in fatty acid metabolism and it is cleared by dialysis. As it plays a role in energy utilization and because malnutrition is a frequent complication of HD treatment, we studied the effects of carnitine supplementation on several nutritional parameters in HD patients. MATERIAL AND METHODS: The main selection criterion was a body mass index (BMI; body weight/(height)2) < 22 kg/m2. Fifty-three patients were enrolled to participate in this open and randomized study. For 6 months, 28 patients received 15 mg/kg of intravenous L-carnitine at the end of each hemodialysis (HD) treatment (Group A), the remaining 25 patients were controls (Group B). The measured parameters were the post-dialysis body weight, serum albumin concentration (nephelemetry), food intake assessed by a 3-day food questionnaire, nPNA (normalized protein equivalent of nitrogen appearance), creatinine generation, and anthropometry. RESULTS: Forty-five patients completed the study (Group A: 14 F/9 M, 66.7 years old; Group B: 11 F/11 M, 65.2 years old). At the beginning of the study, there were no differences between the groups for age, gender, HD duration, BMI, diabetes prevalence, plasma carnitine levels and measured nutritional parameters. 65.2% and 77.3% in each group were carnitine-deficient (plasma total carnitine level < 35 micromol/l). After 6 months of L-carnitine supplementation, none of the nutritional parameters had changed in either group, except that serum albumin concentration decreased in both groups. Dividing each group according to their respective median serum albumin concentrations, daily energy and protein intakes, creatinine generation or triceps skinfold thickness did not show any difference in the various nutritional parameters with or without carnitine supplementation. CONCLUSION: Carnitine supplementation, despite normalization of plasma carnitine levels, has no effect on the nutritional status of HD patients.     

The dental care pathway of welfare recipients in Quebec

IN Quebec (Canada), the utilization of dental care services varies greatly from one social class to another: whereas the well-to-do visit the dentist often for check-ups, those most in need demonstrate a "wait-and-see" attitude. The objective of our research was to describe the dental care pathway of the underprivileged when confronted with symptoms, and to understand how this pathway might be interrupted and possibly lead to tooth extractions. We arranged 16 one-on-one interviews with adult Montrealers who had experienced a dental problem during the 12 months preceding the interview. These participants, 9 women and 7 men aged between 30 and 48, lived in great poverty: all were welfare recipients, and as such, enjoyed the benefits of a government programme that entitled them to free basic dental care. During the interviews, the interviewers asked the participants to describe their latest dental problem and their subsequent behaviour.The dental care pathway of our participants was characterized by a strategy of adapting to the symptoms. This process of adapting, which can last several months, is essentially an individual process in which the individuals often resort to self-medication to soothe their pain. They decide to visit a dentist when the pain is too great and self-medication is no longer effective. Once this decision is made, their dental care pathway may nevertheless be interrupted in two ways: first, in the failure to find a dentist, and second, later, in the failure to complete treatments that are not covered by the welfare program, such as endodontic treatment. The fragmented character of these dental care pathways refers us to two features of accessibility: financial accessibility and acceptability. With regard to financial accessibility, our study shows that the public coverage intended for welfare recipients presents major gaps. As for acceptability, our participants are strongly critical of the dental profession, and develop a culture of rejection of it.     

Antioxidant effects of zinc supplementation in Tunisians with type 2 diabetes mellitus

OBJECTIVE: To determine the effects of zinc (Zn) supplementation on oxidative stress in persons with type 2 diabetes mellitus (type 2 DM). DESIGN: Tunisian adult subjects with HbA1c >7.5% were supplemented for six months with 30 mg/day of Zn as Zn gluconate or placebo. The effects of supplementation on plasma zinc (Zn), copper (Cu), urinary Zn, plasma thiobarbituric acid reactive substances (TBARS), Cu-Zn superoxide dismutase (SOD) and glutathione peroxidase activities (GPX) in red blood cells, blood lipids and lipoproteins, HbA1c and fasting glucose were measured at the beginning of the study and after three and six months. RESULTS: At the beginning of the study, more than 30% of the subjects exhibited plasma Zn values less than the normal minimum of 10.7 micro mol/L, whereas levels of plasma Cu and antioxidant RBC Cu-Zn SOD and GPx enzyme activities were in the normal ranges. Oxidative stress, monitored by plasma TBARS, was increased in individuals with diabetes compared with healthy Tunisian subjects (3.32 +/- 0.05 micro mol/L vs. 2.08 +/- 0.04 micro mol/L) and an inverse correlation was found between Zn plasma levels and plasma TBARS. After three and six months of Zn supplementation, all of the subjects exhibited plasma Zn values greater than 10.7 micro mol/L. There was a decrease of plasma TBARS in Zn supplemented group after six months (15%) with no significant changes in the placebo group. Supplementation did not alter significantly HbA1c nor glucose homeostasis. No adverse effects of Zn supplementation were observed on Cu status or HDL cholesterol. CONCLUSIONS: These data suggest the potential beneficial antioxidant effects of Zn supplementation in persons with type 2 DM. These results are particularly important in light of the deleterious consequences of oxidative stress in persons with diabetes.     

GABAA receptor-expressing astrocytes in the supraoptic nucleus lack glutamate uptake and receptor currents

An important function of astrocytes is the clearance of excess extracellular glutamate via specific carriers whose expression has become an astrocytic marker. In the present study, we found that a large population of astrocytes in the supraoptic nucleus (SON) of the rat hypothalamus lacks glutamate uptake currents and receptor responses but expresses GABAA receptors. Patch clamp recordings in acute hypothalamic slices that included the SON showed typical astrocytic membrane currents and demonstrated that GABA, via GABAA receptor activation, triggered a conductance increase with the reversal potential close to the Cl- equilibrium potential and a decrease in resting K+ conductance. Intracellular labeling with Lucifer Yellow revealed that these cells had a radial glia-like morphology, with cell bodies lined up along the base of the brain and long processes traversing the nucleus; they were not dye-coupled. Parallel immunocytochemical labelings showed that they expressed strong GABAA receptor and glial fibrillary acidic protein (GFAP) immunoreactivities. In addition, our electrophysiological and morphological analyses revealed another population of astrocytes in this nucleus, located next to the subarachnoid space. They were less numerous than the radial type, had a round morphology and few processes, and were dye-coupled. Unlike the radial astrocytes, they showed little immunoreactivity for GABAA receptor or GFAP. Moreover, they did not respond to GABA but to glutamate, a response that was partially mimicked by aspartate, indicating glutamate transporter expression. Taken together, our observations add to growing evidence illustrating heterogeneity of astrocytes in the adult brain, a heterogeneity that reflects striking differences in form and function of astrocytic populations in regions as discrete as the SON of the hypothalamus.