\dot{V}_{{{\text{O}}_{2} { \max }}} is not altered by self-pacing during incremental exercise

We tested the hypothesis that incremental cycling to exhaustion that is paced using clamps of the rating of perceived exertion (RPE) elicits higher $ \dot{V}_{{{\text{O}}_{2} { \max }}} $ values compared to a conventional ramp incremental protocol when test duration is matched. Seven males completed three incremental tests to exhaustion to measure $ \dot{V}_{{{\text{O}}_{2} { \max }}} $ . The incremental protocols were of similar duration and included: a ramp test at 30 W min^?1 with constant cadence (RAMP1); a ramp test at 30 W min^?1 with cadence free to fluctuate according to subject preference (RAMP2); and a self-paced incremental test in which the power output was selected by the subject according to prescribed increments in RPE (SPT). The subjects also completed a $ \dot{V}_{{{\text{O}}_{2} { \max }}} $ ‘verification’ test at a fixed high-intensity power output and a 3-min all-out test. No difference was found for $ \dot{V}_{{{\text{O}}_{2} { \max }}} $ between the incremental protocols (RAMP1 = 4.33 ± 0.60 L min^?1; RAMP2 = 4.31 ± 0.62 L min^?1; SPT = 4.36 ± 0.59 L min^?1; P > 0.05) nor between the incremental protocols and the peak $ \dot{V}_{{{\text{O}}_{2} }} $ measured during the 3-min all-out test (4.33 ± 0.68 L min^?1) or the $ \dot{V}_{{{\text{O}}_{2} { \max }}} $ measured in the verification test (4.32 ± 0.69 L min^?1). The integrated electromyogram, blood lactate concentration, heart rate and minute ventilation at exhaustion were not different (P > 0.05) between the incremental protocols. In conclusion, when test duration is matched, SPT does not elicit a higher $ \dot{V}_{{{\text{O}}_{2} { \max }}} $ compared to conventional incremental protocols. The striking similarity of $ \dot{V}_{{{\text{O}}_{2} { \max }}} $ measured across an array of exercise protocols indicates that there are physiological limits to the attainment of $ \dot{V}_{{{\text{O}}_{2} { \max }}} $ that cannot be exceeded by self-pacing.     

No colocalization of immunoreactivities for VIP and neuronal NOS, and a differential relation to cGMP-immunoreactivity in bovine penile smooth muscle

The distribution of immunoreactivity (IR) for the neuropeptide vasoactive intestinal polypeptide (VIP) and neuronal nitric oxide synthase (nNOS) in the bovine retractor penis muscle (RP) and penile artery (PA) was studied by using two different methods. The distribution of these immunoreactivities was also compared with that of the immunoreactivity for cyclic guanosine monophosphate (cGMP). In both tissues the nerve fibers and terminals immunoreactive for VIP had a distribution that was completely different from that of the nerve fibers and terminals immunoreactive for nNOS. This contrasts with the previous observations in penile smooth muscle of other species. In the RP, as well as in the PA, many of the VIP-IR fibers were also immunoreactive for neurofilaments (NF), whereas the nNOS-IR fibers were consistently devoid of NF-IR. Stimulation with sodium nitroprusside, a nitric oxide donor, considerably increased cGMP-IR in the smooth muscle cells in both RP and PA, and in several nerve fibers in PA. Many of these cGMP-IR nerve fibers exhibited nNOS-IR, whereas none of them was immunoreactive for VIP. Our results suggest that the degree of coexistence of VIP-IR and nNOS-IR in the nerve fibers and terminals innervating penile smooth muscle show wide species differences. They also suggest that the mechanisms by which VIP could be involved in neurogenic penile erection may vary between species.     

Automated classification of neonatal sleep states using EEG

Objective

To develop a method for automated neonatal sleep state classification based on EEG that can be applied over a wide range of age.

Intrinsic bursting of immature CA3 pyramidal neurons and consequent giant depolarizing potentials are driven by a persistent Na+ current and terminated by a slow Ca2+ -activated K+ current

The CA3 area of the mature hippocampus is known for its ability to generate intermittent network activity both in physiological and in pathological conditions. We have recently shown that in the early postnatal period, the intrinsic bursting of interconnected CA3 pyramidal neurons generates network events, which were originally called giant depolarizing potentials (GDPs). The voltage-dependent burst activity of individual pyramidal neurons is promoted by the well-known depolarizing action of endogenous GABA on immature neurons. In the present work, we show that a persistent Na+ current, I-Nap, accounts for the slow regenerative depolarization that triggers the intrinsic bursts in the neonatal rat CA3 pyramidal neurons (postnatal day 3-6), while a slow Ca2+ -activated K+ current, sI-K(Ca), is primarily responsible for the postburst slow afterhyperpolarization and consequent burst termination. In addition, we exploited pharmacological data obtained from intracellular recordings to study the mechanisms involved in network events recorded with field potential recordings. The data as a whole indicate that I-Nap and sI-K(Ca) are involved in the initiation and termination, respectively, of the pyramidal bursts and consequent network events underlying GDPs.     

AMPA/kainate receptor-mediated up-regulation of GABAA receptor delta subunit mRNA expression in cultured rat cerebellar granule cells is dependent on NMDA receptor activation

We have studied the effects of AMPA/kainate receptor agonists on GABA(A) receptor subunit mRNA expression in vitro in cultured rat cerebellar granule cells (CGCs). Kainate (KA) (100 microM) and high K(+) (25 mM) dramatically up-regulated delta subunit mRNA expression to 500-700% of that in control cells grown in low K(+) (5 mM). KA or high K(+) had no effect on the expression of the other major GABA(A) receptor subunits alpha1, alpha6, beta2, beta3 or gamma2. Up-regulation of delta mRNA was also detected with the AMPA receptor-selective agonist CPW-399 and to a lesser extent with the KA receptor-selective agonist ATPA. AMPA/kainate receptor-selective antagonist DNQX completely inhibited KA-, CPW-399- and ATPA-induced delta mRNA up-regulation indicating that the effects were mediated via AMPA and KA receptor activation. NMDA receptor-selective antagonist MK-801 inhibited 76% of the KA- and 57% of the CPW-399-induced delta up-regulation suggesting that KA and CPW-399 treatments may induce glutamate release resulting in NMDA receptor activation, and subsequently to delta mRNA up-regulation. In CGCs, delta subunit is a component of extrasynaptic alpha6betadelta receptors that mediate tonic inhibition. Up-regulation of delta during prolonged glutamate receptor activation or cell membrane depolarization may be a mechanism to increase tonic inhibition to counteract excessive excitation.     

Cardiac Stress Reactivity and Recovery of Novelty Seekers

Background  

Novelty seeking temperament has been associated with higher coronary heart disease risk factors, but the mechanism behind the association is open. Cardiac stress response is a potential candidate.     

Respiratory alkalosis in children with febrile seizures

Purpose: Febrile seizures (FS) are the most common type of convulsive events in children. FS are suggested to result from a combination of genetic and environmental factors. However, the pathophysiologic mechanisms underlying FS remain unclear. Using an animal model of experimental FS, it was demonstrated that hyperthermia causes respiratory alkalosis with consequent brain alkalosis and seizures. Here we examine the acid–base status of children who were admitted to the hospital for FS. Children who were admitted because of gastroenteritis (GE), a condition known to promote acidosis, were examined to investigate a possible protective effect of acidosis against FS. Methods: We enrolled 433 age‐matched children with similar levels of fever from two groups presented to the emergency department. One group was admitted for FS (n = 213) and the other for GE (n = 220). In the FS group, the etiology of fever was respiratory tract infection (74.2%), otitis media (7%), GE (7%), tonsillitis (4.2%), scarlet fever (2.3%) chickenpox (1.4%), urinary tract infection (1.4%), postvaccination reaction (0.9%), or unidentified (1.4%). In all patients, capillary pH and blood Pco₂ were measured immediately on admission to the hospital. Key Findings: Respiratory alkalosis was found in children with FS (pH 7.46 ± 0.04, [mean ± standard deviation] Pco₂ 29.5 ± 5.5 mmHg), whereas a metabolic acidosis was seen in all children admitted for GE (pH 7.31 ± 0.03, Pco₂ 37.7 ± 4.3 mmHg; p < 0.001 for both parameters). No FS were observed in the latter group. A subgroup (n = 15; 7%) of the patients with FS had GE and, notably, their blood pH was more alkaline (pH 7.44 ± 0.04) than in the GE‐admitted group. During the enrollment period, eight of the patients were admitted on separate occasions because of FS or GE. Consistent with the view that generation of FS requires a genetic susceptibility in addition to acute seizure triggering factors, each of these patients had an alkalotic blood pH when admitted because of FS, whereas they had an acidotic pH (and no FS) when admitted because of GE (pH 7.47 ± 0.05 vs. pH 7.33 ± 0.03, p < 0.005). Significance: The results show that FS are associated with a systemic respiratory alkalosis, irrespective of the severity of the underlying infection as indicated by the level of fever. The lack of FS in GE patients is attributable to low pH, which also explains the fact that children with a susceptibility to FS do not have seizures when they have GE‐induced fever that is associated with acidosis. The present demonstration of a close link between FS and respiratory alkalosis may pave the way for further clinical studies and attempts to design novel therapies for the treatment of FS by controlling the systemic acid–base status.     

Identification of PKCalpha isoform-specific effects in cardiac myocytes using antisense phosphorothioate oligonucleotides

Members of the mammalian protein kinase C (PKC) superfamily play key regulatory roles in multiple cellular processes. In the heart, PKC signaling is involved in hypertrophic agonist-induced gene expression and hypertrophic growth. To investigate the specific function of PKC signaling in regulating cardiomyocyte growth, we used antisense oligonucleotides to inhibit PKC alpha, the major isozyme present in the neonatal heart. Transfection of cultured neonatal cardiomyocytes with antisense PKCalpha oligonucleotides resulted in a marked reduction in both PKCalpha mRNA and protein levels. PKCalpha antisense treatment also reduced phenylephrine (PE)-induced PKC activity and perinuclear translocation of PKCalpha. Antisense inhibition of PKCalpha led to reduction of PE-induced increase in skeletal alpha-actin mRNA levels and atrial natriuretic peptide (ANP) secretion but had no significant effects on PE-induced beta-myosin heavy chain, ANP, or B-type natriuretic peptide (BNP) gene expression. On the other hand, antisense PKCalpha treatment attenuated endothelin-1-induced increase in ANP and BNP peptide secretion, whereas endothelin-1-induced gene expression of ANP and BNP remained unchanged. The hypertrophic agonist-induced growth of cardiomyocytes, characterized by increased [(3)H]leucine incorporation, was not affected with antisense PKCalpha treatment. Furthermore, we found that PE-induced increase in extracellular signal-regulated kinase (ERK) activity was partially inhibited by antisense PKCalpha treatment, implicating ERK as a downstream mediator for PKCalpha signaling. These results indicate that PKCalpha isozyme is involved in hypertrophic signaling in cardiomyocytes and provide novel strategies for future studies to identify other cellular targets controlled selectively by PKCalpha or other PKC isozymes.     

Bioelectrical behaviour of hypoxic human neocortical tissue under the influence of nimodipine and dimethyl sulfoxide

Nimodipine and dimethyl sulfoxide (DMSO) have been shown to affect electrophysiological responses in rodent brain tissue in an vitro model of hypoxia. In the present study, the same agents were now examined for their effects on human neocortical brain slices under repeated hypoxic conditions. DMSO (0.4%), with and without addition of nimodipine (40 micromol/l), did not increase the latency of anoxic depolarization (AD). This finding is not in line with our previous observations of DMSO effects, with and without nimodipine, on brain slices of guinea pigs. AD latency was significantly longer in human neocortical brain slices compared with hippocampal slices of rodents even without any pharmacological influence. A possible acute effect of DMSO-nimodipine may therefore be masked by an interspecies difference of hypoxia resistance.