Supply and demand in cerebral energy metabolism: the role of nutrient transporters.

Glucose is the obligate energetic fuel for the mammalian brain, and most studies of cerebral energy metabolism assume that the majority of cerebral glucose utilization fuels neuronal activity via oxidative metabolism, both in the basal and activated state. Glucose transporter (GLUT) proteins deliver glucose from the circulation to the brain: GLUT1 in the microvascular endothelial cells of the blood-brain barrier (BBB) and glia; GLUT3 in neurons. Lactate, the glycolytic product of glucose metabolism, is transported into and out of neural cells by the monocarboxylate transporters (MCT): MCT1 in the BBB and astrocytes and MCT2 in neurons. The proposal of the astrocyte-neuron lactate shuttle hypothesis suggested that astrocytes play the primary role in cerebral glucose utilization and generate lactate for neuronal energetics, especially during activation. Since the identification of the GLUTs and MCTs in brain, much has been learned about their transport properties, that is capacity and affinity for substrate, which must be considered in any model of cerebral glucose uptake and utilization. Using concentrations and kinetic parameters of GLUT1 and -3 in BBB endothelial cells, astrocytes, and neurons, along with the corresponding kinetic properties of the MCTs, we have successfully modeled brain glucose and lactate levels as well as lactate transients in response to neuronal stimulation. Simulations based on these parameters suggest that glucose readily diffuses through the basal lamina and interstitium to neurons, which are primarily responsible for glucose uptake, metabolism, and the generation of the lactate transients observed on neuronal activation.     

Cognitive rehabilitation in the elderly: overview and future directions.

This study provides an overview of the papers emanating from the experimental trial that evaluated a new cognitive rehabilitation program in older adults who were experiencing normal cognitive decline. The main features of the design are summarized, along with evidence that the training produced long-lasting improvement in memory performance, goal management, and psychosocial status. The benefits were attributed to several factors, including the program's emphasis on techniques that promoted efficient strategic processing. Limitations of the program and directions for future research are discussed.     

Fetal heart rate changes during diabetic ketosis

A case of diabetic ketosis during pregnancy is presented in which the fetal heart rate tracing demonstrated tachycardia complicated by late and severe variable decelerations. Intravenous administration of insulin resulted in prompt abolition of the deceleration patterns. The implications of these findings are discussed.     

Antagonism of central and peripheral anorectic effects of caerulein by L-364,718

The reduction in food intake induced by i.p. injections of the cholecystokinin (CCK) analogue caerulein was antagonised by a low dose (0.25 mumol/kg s.c.) of the selective CCK antagonist L-364,718. To block the anorectic effect of centrally administered caerulein a dose of 25 mumol/kg of L-364,718 was required, demonstrating that central CCK receptors can be blocked effectively in the rat by choosing appropriate doses of L-364,718.     

Signs of ocular disease: A prevalence study in optometric practice

Data on the prevalence of all ocular conditions seen in 1500 consecutive optometric patients were obtained during an investigation into the effectiveness of routine visual field screening. In many instances, these are the first prevalence figures for optometric patient populations. Some of the estimates of prevalence are compared with other optometric and general population surveys. Many disorders were observed, the most frequent being slight to moderate increases in retinal arterial reflex and attenuation, optic cup/disc ratio of 0.4, shallow anterior chambers and family history of glaucoma. The occurrence of some conditions was sporadic, resulting from the relatively small sample. However, this survey may serve as an audit of ocular disease detection for other practitioners.     

The glaucoma suspect: Differentiation of the future glaucoma eye from the non-glaucomatous suspect eye

Visual-field areas to a I_2e stimulus were measured planimetrically using an X-Y digitizer and a computer program. Sampling of normal subjects and patients suspected of having glaucoma was done at two points in time. Calculations of eye-wall stress were done using ultrasonic data and intra-ocular pressure (IOP) measurements from patient records. For those suspected of having glaucoma who developed chronic open-angle glaucoma (COAG), the time of transition was the second point in time. The visual field area was regressed against patient age at the two points in time. No difference in the regression slopes was found for the normal subjects and unchanged patients. The patients who did develop glaucoma were significantly different. The mean annual rate of visual-field change (rate of decay) was calculated and found to be 28.5 mm²/year for the normals, 153.5 mm²/year for the suspects, and 376.4 mm²/year for those patients who developed glaucoma. The rate of visual-field decay only correlated with patient age (P = 0.03) and eye-wall stress (P < 0.01) in the patients who developed glaucoma.     

Effect of meptazinol on evoked responses in rat vas deferens

Responses of rat isolated vas deferens to electrical stimulation through field electrodes (400 mA, 1 ms duration, single shocks at 5 min intervals) were potentiated by meptazinol (10 to 300 microM) in whole tissues and also in the separated prostatic and epididymal portions. The effect was fast in onset, reproducible and easily reversed by washing. Prazosin (0.1 microM) practically abolished the response of the epididymal portion to electrical stimulation while the response of the prostatic portion was only slightly reduced (less than 20%). In the presence of prazosin, meptazinol still produced potentiation of the response of the prostatic portion. Nifedipine (2 microM) practically abolished the response of the prostatic portion to electrical stimulation while the response of the epididymal portion was only slightly reduced (less than 20%). In the presence of nifedipine, meptazinol no longer produced potentiation of the response of the epididymal portion. Exogenous ATP (5 microM to 1 mM) and phenylephrine (1 to 50 microM) produced a contractile response which was potentiated in the presence of meptazinol (100 microM) but in the presence of meptazinol (100 microM) and nifedipine (5 mM) together, potentiation of phenylephrine no longer occurred. It is suggested that potentiation by meptazinol of electrically induced responses in this tissue is due to a direct action on the smooth muscle.