New species of Asclepias (Apocynaceae), Baphia (Leguminosae), Cochlospermum (Bixaceae) and Endostemon (Lamiaceae) from the Kalahari sands of Angola and NW Zambia, with one new combination in Vangueria (Rubiaceae)

Four new species are described from central and eastern Angola and adjacent NW Zambia. All occur in Kalahari sand savannas rich in endemic and more widely distributed geoxylic suffrutices. Despite being known from very few collections, the conservation status of one of these new species is assessed as Least Concern, as these grasslands are nutrient-poor, are in remote sparsely populated areas, and are not threatened with conversion to agriculture. The remaining three are treated as Data Deficient. In addition, one new combination is provided for Ancylanthos rubiginosus Desf. under Vangueria as V. rubiginosa (Desf.) Lantz is an illegitimate later homonym. We also make orthographic corrections to specific epithets commemorating Ilse von Nolde, a collector who made important collections from Quela in Malange in the 1930s

Overexpression of oxytocin receptors in the hypothalamic PVN increases baroreceptor reflex sensitivity and buffers BP variability in conscious rats

BACKGROUND AND PURPOSE: The paraventricular nucleus (PVN) of the hypothalamus is an important integrative site for neuroendocrine control of the circulation. We investigated the role of oxytocin receptors (OT receptors) in PVN in cardiovascular homeostasis. EXPERIMENTAL APPROACH: Experiments were performed in conscious male Wistar rats equipped with a radiotelemetric device. The PVN was unilaterally co-transfected with an adenoviral vector (Ad), engineered to overexpress OT receptors, and an enhanced green fluorescent protein (eGFP) tag. Control groups: PVN was transfected with an Ad expressing eGFP alone or untransfected, sham rats (Wt). Recordings were obtained without and with selective blockade of OT receptors (OTX), during both baseline and stressful conditions. Baroreceptor reflex sensitivity (BRS) and cardiovascular short-term variability were evaluated using the sequence method and spectral methodology respectively. KEY RESULTS: Under baseline conditions, rats overexpressing OT receptors (OTR) exhibited enhanced BRS and reduced BP variability compared to control groups. Exposure to stress increased BP, BP variability and HR in all rats. In control groups, but not in OTR rats, BRS decreased during stress. Pretreatment of OTR rats with OTX reduced BRS and enhanced BP and HR variability under baseline and stressful conditions. Pretreatment of Wt rats with OTX, reduced BRS and increased BP variability under baseline and stressful conditions, but only increased HR variability during stress. CONCLUSIONS AND IMPLICATIONS: OT receptors in PVN are involved in tonic neural control of BRS and cardiovascular short-term variability. The failure of this mechanism could critically contribute to the loss of autonomic control in cardiovascular disease

Autonomic mechanisms underpinning the stress response in borderline hypertensive rats

This study investigates blood pressure (BP) and heart rate (HR) short-term variability and spontaneous baroreflex functioning in adult borderline hypertensive rats and normotensive control animals kept on normal-salt diet. Arterial pulse pressure was recorded by radio telemetry. Systolic BP, diastolic BP and HR variabilities and baroreflex were assessed by spectral analysis and the sequence method, respectively. In all experimental conditions (baseline and stress), borderline hypertensive rats exhibited higher BP, increased baroreflex sensitivity and resetting, relative to control animals. Acute shaker stress (single exposure to 200 cycles min-1 shaking platform) increased BP in both strains, while chronic shaker stress (3-day exposure to shaking platform) increased systolic BP in borderline hypertensive rats alone. Low- and high-frequency HR variability increased only in control animals in response to acute and chronic shaker (single exposure to restrainer) stress. Acute restraint stress increased BP, HR, low- and high-frequency variability of BP and HR in both strains to a greater extent than acute shaker stress. Only normotensive rats exhibited a reduced ratio of low- to high-frequency HR variability, pointing to domination of vagal cardiac control. In borderline hypertensive rats, but not in control animals, chronic restraint stress (9-day exposure to restrainer) increased low- and high-frequency BP and HR variability and their ratio, indicating a shift towards sympathetic cardiovascular control. It is concluded that maintenance of BP in borderline hypertensive rats in basal conditions and during stress is associated with enhanced baroreflex sensitivity and resetting. Imbalance in sympathovagal control was evident only during exposure of borderline hypertensive rats to stressors

Follow-up of infants screened by auditory brainstem response in the neonatal intensive care unit

Auditory brainstem response screening at 40 and 60 dB was conducted in 100 infants in the neonatal intensive care unit to determine initial failure rate and prevalence of abnormality on follow-up. Of our NICU population, 20% failed one or both of the screening levels: 9% failed at 60 dB in both ears, and 11% failed at 40 dB in one or both ears. On follow-up, half of the 60 dB failure group were found to have sensorineural or conductive impairment and represent the 2% to 4% prevalence of serious otologic-audiologic problems generally found in an NICU population. Subsequent improvement (reversal) of the retest ABR records of the remaining infants in the 60 dB failure group was thought to be related to neural changes in the brainstem associated with recovery from hypoxic episodes. A transient or reversible conductive deficit appeared to account for the majority of failures at 40 dB. We recommend the screening protocol be expanded to include threshold and latency measures in infants who fail the initial screening. The transient nature of many ABR abnormalities makes postdischarge ABR, otologic, audiologic, and neurologic examinations mandatory before any inferences are made about hearing loss or neurodevelopmental disorders

Genetic heterogeneity and pathophysiological mechanisms in congenital myasthenic syndromes

Congenital myasthenic syndromes (CMS) are a rare heterogeneous group of inherited neuromuscular disorders associated with distinctive clinical, electrophysiological, ultrastructural and genetic abnormalities. These genetic defects either impair neuromuscular transmission directly or result in secondary impairments, which eventually compromise the safety margin of neuromuscular transmission. In this report we will explore the significant progress made in understanding the molecular pathogenesis of CMS, which is important for both patients and clinicians in terms of reaching a definite diagnosis and selecting the most appropriate treatment

Management and grading of EGFR inhibitor-induced cutaneous toxicity

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GLP1R attenuates sympathetic response to high glucose via carotid body inhibition

Aberrant sympathetic nerve activity exacerbates cardiovascular risk in hypertension and diabetes, which are common comorbidities, yet clinically sympathetic nerve activity remains poorly controlled. The hypertensive diabetic state is associated with increased reflex sensitivity and tonic drive from the peripheral chemoreceptors, the cause of which is unknown. We have previously shown hypertension to be critically dependent on the carotid body (CB) input in spontaneously hypertensive rat, a model that also exhibits a number of diabetic traits. CB overstimulation by insulin and leptin has been similarly implicated in the development of increased sympathetic nerve activity in metabolic syndrome and obesity. Thus, we hypothesized that in hypertensive diabetic state (spontaneously hypertensive rat), the CB is sensitized by altered metabolic signaling causing excessive sympathetic activity levels and dysfunctional reflex regulation. METHODS: Using a hypothesis-free RNA-seq approach, we investigated potential molecular targets implicated in energy metabolism mediating CB sensitization and its regulation of sympathetic outflow in experimental hypertension. Identified targets were characterized using molecular and functional techniques assessing peripheral chemoreflex sensitivity in situ and in vivo. RESULTS: We discovered GLP1R (glucagon-like peptide-1 receptor) expression in the CBs of rat and human and showed that its decreased expression is linked to sympathetic hyperactivity in rats with cardiometabolic disease. We demonstrate GLP1R to be localized to CB chemosensory cells, while targeted administration of GLP1R agonist to the CB lowered its basal discharge and attenuated chemoreflex-evoked blood pressure and sympathetic responses. Importantly, hyperglycemia-induced peripheral chemoreflex sensitization and associated basal sympathetic overactivity were abolished by GLP1R activation in the CB suggesting a role in a homeostatic response to high blood glucose. CONCLUSIONS: We show that GLP1 (glucagon-like peptide-1) modulates the peripheral chemoreflex acting on the CB, supporting this organ as a multimodal receptor. Our findings pinpoint CBs as potential targets for ameliorating excessive sympathetic activity using GLP1R agonists in the hypertensive-diabetic condition