Gastric stimulation: influence of electrical parameters on gastric emptying in control and diabetic rats

BACKGROUND: The aim of this study was to test the effect of different pulse frequencies and amplitudes during gastric stimulation (GS) on gastric emptying in the rat. METHODS: GS was performed in 2 groups of laparotomized rats: healthy control animals, and rats with acute diabetes. The effects of four pulse frequencies (0.5, 1, 10, 20 Hz) and three pulse amplitudes (5, 20, 40 mA) were tested. The volumes emptied from the stomach after the oro-gastric instillation of a nutrient solution were compared to those obtained in animals without GS. Intragastric pH values were assessed under basal conditions and after GS. RESULTS: In both groups, GS increased emptied volumes compared to conditions without stimulation (p < 0.05) for pulse frequencies above 0.5 Hz. Increases in pulse frequencies accelerated gastric emptying (p < 0.01) with a plateau at around 10 Hz. The increase in pulse amplitudes resulted in larger emptied volumes only when the pulse frequency was 1 Hz (p < 0.04) while the opposite effect was observed at 20 Hz (p < 0.04). The most effective combinations to enhance gastric emptying compared to baseline conditions were 10 Hz with 5 or 20 mA. The overall effect of GS on gastric emptying compared to baseline conditions without stimulation, was greater in diabetic than in controls rats (p < 0.05). During stimulation, intragastric pH values were not different from basal conditions during fasting or after a meal in control and diabetic rats. CONCLUSIONS: Although both pulse frequency and amplitude should be considered during GS, frequency appears to be the most critical point. The possibility of increasing gastric emptying by electrical stimulation in diabetic rats suggests potential clinical applications for this method

Effect of muscle metaboreflex activation on spontaneous cardiac baroreflex sensitivity during exercise in humans.

NON-TECHNICAL SUMMARY: The ‘arterial baroreflex’ plays an important role in the moment-to-moment regulation of blood pressure. It does this partly by eliciting changes in heart rate, but its ability to do this (i.e. sensitivity) during exercise is reduced from rest. During exercise, chemicals accumulate in the muscles (i.e. metabolites) that stimulate sensory nerves within the muscle (i.e. muscle metaboreflex). We show for the first time in humans that the stimulation of metabolically sensitive nerves within the muscles during leg cycling exercise decreases arterial baroreflex sensitivity. This new knowledge increases our understanding of the control of the human heart during exercise. ABSTRACT: We sought to determine whether the activation of metabolically sensitive skeletal muscle afferents (muscle metaboreflex) is a potential mechanism for the decrease in spontaneous cardiac baroreflex sensitivity (cBRS) during exercise in humans. In protocol 1, 15 male subjects (22 ± 1 years) performed steady-state leg cycling at low (26 ± 4 W) and moderate workloads (105 ± 7 W), under free-flow conditions and with partial flow restriction (bilateral thigh cuff inflation at 100 mmHg) to evoke muscle metaboreflex activation during exercise. In protocol 2, rhythmic handgrip exercise at 35% maximum voluntary contraction was performed with progressive upper arm cuff inflation (0, 80, 100 and 120 mmHg) to elicit graded metaboreflex activation. Both protocols were followed by post-exercise ischaemia (PEI) to isolate the muscle metaboreflex. Leg cycling-induced increases in HR and mean BP were augmented by partial flow restriction (P < 0.05 vs. free flow), while HR and mean BP both remained elevated during PEI (P < 0.05 vs. rest). Leg cycling evoked an intensity-dependent decrease in cBRS (16 ± 2, 7 ± 1 and 2 ± 0.2 ms mmHg(−1) at rest, low and moderate workloads, respectively; P < 0.05), which was further reduced with partial flow restriction (by –2.6 ± 0.8 and –0.4 ± 0.1 ms mmHg(−1) at low and moderate workloads). cBRS remained suppressed during PEI following leg cycling with partial flow restriction (4 ± 1 ms mmHg(−1); P < 0.05 vs. rest). cBRS was unchanged during handgrip under free-flow conditions, handgrip with partial flow restriction and PEI following handgrip (P > 0.05 vs. rest). These data indicate that the activation of metabolically sensitive skeletal muscle afferents (muscle metaboreflex) decreases cardiac baroreflex responsiveness during leg cycling exercise in humans

Combined activation of MAP kinase pathway and β-catenin signaling cause deep penetrating nevi

Deep penetrating nevi (DPN) are unusual melanocytic neoplasms with unknown genetic drivers. Here the authors show that majority of DPN harbor activating mutations in the β-catenin and the MAP-kinase pathways; this characteristic can help in the classification and grading of these distinctive neoplasms

Does malaria suffer from lack of memory?

It is widely perceived that immunity to malaria is, to an extent, defective and that one component of this defective immune response is the inability to induce or maintain long-term memory responses. If true, this is likely to pose problems for development of an effective vaccine against malaria. In this article, we critically review and challenge this interpretation of the epidemiological and experimental evidence. While evasion and modulation of host immune responses clearly occurs and naturally acquired immunity is far from optimal, mechanisms to control blood-stage parasites are acquired and maintained by individuals living in endemic areas, allowing parasite density to be kept below the threshold for induction of acute disease. Furthermore, protective immunity to severe pathology is achieved relatively rapidly and is maintained in the absence of boosting by re-infection. Nevertheless, there are significant challenges to overcome. The need for multiple infections to acquire immunity means that young children remain at risk of infection for far too long. Persistent or frequent exposure to antigen seems to be required to maintain anti-parasite immunity (premunition). Lastly, pre-erythrocytic and sexual stages of the life cycle are poorly immunogenic, and there is little evidence of effective pre-erythrocytic or transmission-blocking immunity at the population level. While these problems might theoretically be due to defective immunological memory, we suggest alternative explanations. Moreover, we question the extent to which these problems are malaria-specific rather than generic (i.e. result from inherent limitations of the vertebrate immune system)