Kinetics of insulin-mediated and non-insulin-mediated glucose uptake in humans

The kinetics of insulin-mediated glucose uptake (IMGU) and non-insulin-mediated glucose uptake (NIMGU) in humans have not been well defined. We used the glucose-clamp technique to measure rates of whole-body and leg muscle glucose uptake in six healthy lean men during hyperinsulinemia (approximately 460 pM) to study IMGU and during somatostatin-induced insulinopenia to study NIMGU at four glucose levels (4.5, 9, 12, and 21 mM). To measure leg glucose uptake, the femoral artery and vein were catheterized, and blood flow was measured by thermodilution (leg glucose uptake = arteriovenous glucose difference [A-VG] x blood flow). With this approach, we found that, during hyperinsulinemia, both whole-body and leg glucose uptake increased in a curvilinear fashion at every glucose level, the highest glucose uptake values obtained being 139 +/- 17 mumol.kg-1.min-1 and 3656 +/- 931 mumol.min-1.leg-1, respectively. Leg blood flow increased twofold from 6.0 +/- 1.7 to 11.7 +/- 3.1 dl/min (P less than 0.01) over the range of glucose and was correlated with whole-body glucose uptake (r = 0.55, P less than 0.005). Leg muscle glucose extraction, independent of changes in blood flow, which is reflected by the A-VG, saturated over the range of glucose (1.28 +/- 0.12, 2.22 +/- 0.30, 2.92 +/- 0.42, 3.02 +/- 0.41 mM, NS between last 2 values) with a half-maximal effective glucose concentration (EG50) of 5.3 +/- 0.4 mM.(ABSTRACT TRUNCATED AT 250 WORDS)     

Newborns discriminate novel from harmonic sounds: a study using magnetoencephalography.

OBJECTIVE: We investigated whether newborns respond differently to novel and deviant sounds during quiet sleep. METHODS: Twelve healthy neonates were presented with a three-stimulus oddball paradigm, consisting of frequent standard (76%), infrequent deviant (12%), and infrequent novel stimuli (12%). The standards and deviants were counterbalanced between the newborns and consisted of 500 and 750 Hz tones with two upper harmonics. The novel stimuli contained animal, human, and mechanical sounds. All stimuli had a duration of 300 ms and the stimulus onset asynchrony was 1s. Evoked magnetic responses during quiet sleep were recorded and averaged offline. RESULTS: Two deflections peaking at 345 and 615 ms after stimulus onset were observed in the evoked responses of most of the newborns. The first deflection was larger to novel and deviant stimuli than to the standard and, furthermore, larger to novel than to deviant stimuli. The second deflection was larger to novel and deviant stimuli than to standards, but did not differ between the novels and deviants. CONCLUSIONS: The two deflections found in the present study reflect different mechanisms of auditory change detection and discriminative processes. SIGNIFICANCE: The early brain indicators of novelty detection may be crucial in assessing the normal and abnormal cortical function in newborns. Further, studying evoked magnetic fields to complex auditory stimulation in healthy newborns is needed for studying the newborns at-risk for cognitive or language problems.     

Knee-chest vs horizontal side position during induction of spinal anaesthesia in patients undergoing lumbar disc surgery

In the prone knee-chest position the spread of plain 0.5% bupivacaine in the cerebrospinal fluid and associated haemodynamic changes may be different compared with the horizontal position. A randomized comparison was performed in 40 ASA I-II patients, aged 24-61 yr, undergoing lumbar disc surgery. Subarachnoid injection (27-gauge needle) at the L2-3 interspace with 3 ml of 0.5% bupivacaine was performed with the patient in the operative knee-chest position (prone knee-chest group, n = 20) or in the horizontal side position (supine side horizontal group, n = 20). Patients in the supine side horizontal group were turned into the horizontal supine position for 20 min, and subsequently they were placed in the operative knee-chest position. In three patients in the prone knee-chest group, the spinal needle was replaced by a larger needle (25-gauge). The final cephalad extension of sensory analgesia on skin tested by pinprick was T5 (median) in the prone knee-chest group and T6 in the supine side horizontal group. Recovery was also similar, on average 210 min from injection in both groups. The mean decrease in systolic arterial pressure was somewhat greater in the prone knee-chest group (30 mm Hg) than in the supine side horizontal group (13 mm Hg). The need for ephedrine occurred earlier in the supine side horizontal group (three patients, all within 10 min from local anaesthetic injection) than in the prone knee-chest group (six patients, all after 15 min). Four of the latter patients also required administration of an anticholinergic for bradycardia compared with two patients in the supine side horizontal group. Light sedation was given to five patients in the prone knee-chest group and to four in the supine side horizontal group because of numbness and aching in the shoulders. We conclude that spinal block was similar in the two groups but there was a tendency to more frequent episodes of haemodynamic deterioration in the knee-chest position.      

Chromium supplementation in impaired glucose tolerance of elderly: effects on blood glucose, plasma insulin, C-peptide and lipid levels.

Altogether twenty-six elderly subjects (aged 65-74 years) with persistent impaired glucose tolerance (World Health Organization (1985) criteria) identified in a population-based study, were randomly treated either with chromium-rich yeast (160 micrograms Cr/d) or with placebo for 6 months. The 24 h urinary Cr increased from 0.13 (SE 0.03) to 0.40 (SE 0.06) micrograms/d in the Cr group (n 13) but no change was found in the placebo group (n 11) (0.13 (SE 0.02) v. 0.11 (SE 0.02) micrograms/d). No significant change was observed in the oral glucose tolerance test (glucose dose 75 g; 0, 1 and 2 h blood glucose respectively): 5.3 (SE 0.1), 9.3 (SE 0.3), 8.2 (SE 0.3) mmol/l v. 5.0 (SE 0.1), 8.5 (SE 0.4), 7.3(SE 0.5) mmol/l in the Cr group; 4.9 (SE 0.2), 9.2 (SE 0.6), 8.1 (SE 0.3) mmol/l v. 4.8 (SE 0.2), 8.5 (SE 0.5), 7.0 (SE 0.6) mmol/l in the placebo group (baseline v. 6 months). Glycosylated haemoglobin, plasma insulin, C-peptide and apolipoprotein A1 and B levels remained unchanged, and no improvement was seen in serum total cholesterol (6.2 (SE 0.3) v. 6.4 (SE 0.3) mmol/l for the Cr group, 6.2 (SE 0.4) v. 6.5 (SE 0.3) mmol/l for the placebo group), high-density-lipoprotein-cholesterol (1.1 (SE 0.1) v. 1.2 (SE 0.1) mmol/l for the Cr group, 1.0 (SE 0.1) v. 1.1 (SE 0.1) mmol/l for the placebo group) or triacylglycerols (2.5 (SE 0.4) v. 2.0 (SE 0.4) mmol/l for the Cr group, 2.4 (SE 0.2) v. 2.5 (SE 0.2) mmol/l for the placebo group). The present results indicate that Cr supplementation does not improve glucose tolerance or serum lipid levels in elderly subjects with stable impaired glucose tolerance.     

In vitro growth inhibition of human small cell lung cancer by physalaemin

Production and secretion of neuroendocrine peptides by small cell lung cancer (SCLC) has been detected in the past years. Most recently the role of bombesin as an autocrine/paracrine growth modifier has been demonstrated. We used the soft agarose clonogenic assay to evaluate the influence of other neuroendocrine peptides on the in vitro proliferation of SCLC cell lines. Neuroendocrine peptides tested were adrenocorticotropic hormone, arginine vasopressin, calcitonin, glucagon, kassinin, neurotensin, physalaemin, somatostatin, and substance P. Experiments were carried out in serum-free and serum-supplemented media with and without serum-free incubation periods. Our results indicated that the amphibian undecapeptide physalaemin inhibits the clonal and mass culture growth of SCLC cell lines at picomolar concentrations. All other neuroendocrine peptides failed to influence SCLC growth in the test systems used. These results suggest a growth regulating effect of physalaemin and a potential new form of neuroendocrine peptide therapy for SCLC.     

Cost-effectiveness analysis of guidelines for antihypertensive care in Finland

Background  

Hypertension is one of the major causes of disease burden affecting the Finnish population. Over the last decade, evidence-based care has emerged to complement other approaches to antihypertensive care, often without health economic assessment of its costs and effects. This study looks at the extent to which changes proposed by the 2002 Finnish evidence-based Current Care Guidelines concerning the prevention, diagnosis, and treatment of hypertension (the ACCG scenario) can be considered cost-effective when compared to modelled prior clinical practice (the PCP scenario).     

Increased GABAergic transmission aggravates nucleus basalis magnocellularis lesion-induced behavioral deficits

Quisqualic acid NBM lesions had no effect on water maze performance, but slightly impaired passive avoidance acquisition. GammavinylGABA treatment alone had no effect on the passive avoidance and water maze performance, but aggravated acquisition deficit in rats subjected to NBM lesioning. However, gammavinylGABA-treated NBM-lesioned rats reached control level of performance.     

Twenty-four-hour patterns of pineal melatonin and pituitary and plasma prolactin in male rats under 'natural' and artificial lighting conditions

Natural lighting differs from usual artificial lighting mainly as follows: it has larger spectral composition, fluctuations of intensity during the day, higher intensity levels during the night (moonlight, starlight), and gradual changes of illuminance at dawn and dusk. The present experiment was performed in order to study whether these features of lighting affect the 24-hour patterns of melatonin and prolactin in male rats. The rats were kept 7 days in 'natural' lighting (sunlight through windows) or in artificial lighting (cool white fluorescent lamps) of similar periodicities (13/11 h light/dark). The samples were collected at 3-hour intervals during a 24-hour period. Pineal melatonin contents, pituitary prolactin contents, and plasma prolactin concentrations were measured radioimmunologically. The nocturnal pineal melatonin contents were higher and the daytime contents lower in natural than in artificial lighting conditions. A corresponding 'strengthening of rhythm' of prolactin was found in natural lighting. A reason for the higher amplitude variation of melatonin in the natural lighting conditions may be the gradual changes of illuminance at dawn and dusk. The different pituitary and plasma prolactin patterns of the rats kept in the two lighting conditions might partly be explained by a stimulatory effect of melatonin on the production and secretion of prolactin, but other regulatory factors had to be involved, too.     

DSP-4, a noradrenergic neurotoxin, produces more severe biochemical and functional deficits in aged than young rats

The present study examines the effects of noradrenergic lesions (either DSP-4 i.p. or 6-hydroxydopamine (6-OHDA) into the dorsal noradrenergic bundle on biochemical (noradrenaline (NA), dopamine (DA), serotonin (5-HT) and choline acetyltransferase (ChAT) activity) and cortical EEG (quantitative EEG (qEEG) and high-voltage spindle (HVS) activity in young and aged rats. Near complete 6-OHDA NA lesions, but not partial DSP-4 NA lesions, increased HVS activity in young rats. DSP-4 and 6-OHDA lesions produced no significant changes in the 5-HT or DA levels or in the ChAT activity in young rats. In some of the aged rats, DSP-4 produced similar biochemical and HVS effects, as it induced in young rats. In the remainder of the aged rats, NA levels were greatly and 5-HT levels slightly decreased. DA levels and ChAT activity were unaltered in either set of aged rats. HVS activity was increased only in that group of aged rats with the greatly lowered NA content. These results suggest that: (1) some of the aged rats are more sensitive to DSP-4 treatment than young adult rats; and (2) NA depletions have to be complete to produce an increase in HVS activity in young and aged rats.