Effects of emphysema on diaphragm blood flow during exercise

Chronichyperinflation of the lung in emphysema displaces the diaphragmcaudally, thereby placing it in a mechanically disadvantageous positionand contributing to the increased work of breathing. We tested thehypothesis that total and regional diaphragm blood flows are increasedin emphysema, presumably reflecting an increased diaphragm energeticdemand. Male Syrian Golden hamsters were randomly divided intoemphysema (E; intratracheal elastase 25 units/100 g body wt) andcontrol (C; saline) groups, and experiments were performed 16-20wk later. The regional distribution of blood flow withinthe diaphragm was determined by using radiolabeled microspheres inhamsters at rest and during treadmill exercise (walking at 20 feet/min,20% grade). Consistent with pronounced emphysema, lung volume per unitbody weight was greater in E hamsters (C, 59.3 ± 1.8; E, 84.5 ± 5.0 ml/kg; P < 0.001) and arterialPO₂ was lower both at rest (C, 74 ± 3; E, 59 ± 2 Torr; P < 0.001) and during exercise (C, 93 ± 3; E, 69 ± 4 Torr; P < 0.001). At rest, total diaphragm blood flow was not different between C and Ehamsters (C, 47 ± 4; E, 38 ± 4 ml · min¹ · 100 g¹;P = 0.18). In both C and E hamsters,blood flow at rest was lower in the ventral costal region of thediaphragm than in the dorsal and medial costal regions and the cruraldiaphragm. During exercise in both C and E hamsters, blood flowsincreased more in the dorsal and medial costal regions and in thecrural diaphragm than in the ventral costal region. Total diaphragmblood flow was greater in E hamsters during exercise (C, 58 ± 7; E,90 ± 14 ml · min¹ · 100 g¹;P = 0.03), as a consequence ofsignificantly higher blood flows in the medial and ventral costalregions and crural diaphragm. In addition, exercise-induced increasesin intercostal (P < 0.005) andabdominal (P < 0.05) muscle bloodflows were greater in E hamsters. The finding that diaphragm blood flowwas greater in E hamsters during exercise supports the contention thatemphysema increases the energetic requirements of the diaphragm.

     

Adolescent Intermittent Alcohol Exposure: Deficits in Object Recognition Memory and Forebrain Cholinergic Markers

The long-term effects of intermittent ethanol exposure during adolescence (AIE) are of intensive interest and investigation. The effects of AIE on learning and memory and the neural functions that drive them are of particular interest as clinical findings suggest enduring deficits in those cognitive domains in humans after ethanol abuse during adolescence. Although studies of such deficits after AIE hold much promise for identifying mechanisms and therapeutic interventions, the findings are sparse and inconclusive. The present results identify a specific deficit in memory function after AIE and establish a possible neural mechanism of that deficit that may be of translational significance. Male rats (starting at PND-30) received exposure to AIE (5g/kg, i.g.) or vehicle and were allowed to mature into adulthood. At PND-71, one group of animals was assessed using the spatial-temporal object recognition (stOR) test to evaluate memory function. A separate group of animals was used to assess the density of cholinergic neurons in forebrain areas Ch1-4 using immunohistochemistry. AIE exposed animals manifested deficits in the temporal component of the stOR task relative to controls, and a significant decrease in the number of ChAT labeled neurons in forebrain areas Ch1-4. These findings add to the growing literature indicating long-lasting neural and behavioral effects of AIE that persist into adulthood and indicate that memory-related deficits after AIE depend upon the tasks employed, and possibly their degree of complexity. Finally, the parallel finding of diminished cholinergic neuron density suggests a possible mechanism underlying the effects of AIE on memory and hippocampal function as well as possible therapeutic or preventive strategies for AIE.     

Olfactory Bulbectomy Leads to the Development of Epilepsy in Mice

There is a clear link between epilepsy and depression. Clinical data demonstrate a 30–35% lifetime prevalence of depression in patients with epilepsy, and patients diagnosed with depression have a three to sevenfold higher risk of developing epilepsy. Traditional epilepsy models partially replicate the clinical observations, with the demonstration of depressive traits in epileptic animals. Studies assessing pro-epileptogenic changes in models of depression, however, are more limited. Here, we examined whether a traditional rodent depression model—bilateral olfactory bulbectomy—predisposes the animals towards the development of epilepsy. Past studies have demonstrated increased neuronal excitability after bulbectomy, but continuous seizure monitoring had not been conducted. For the present study, we monitored control and bulbectomized animals by video-EEG 24/7 for approximately two weeks following the surgery to determine whether they develop spontaneous seizures. All seven bulbectomized mice exhibited seizures during the monitoring period. Seizures began about one week after surgery, and occurred in clusters with severity increasing over the monitoring period. These results suggest that olfactory bulbectomy could be a useful model of TBI-induced epilepsy, with advantages of relatively rapid seizure onset and a high number of individuals developing the disease. The model may also be useful for investigating the mechanisms underlying the bidirectional relationship between epilepsy and depression.     

Sulforaphane Protects the Liver against CdSe Quantum Dot-Induced Cytotoxicity

The potential cytotoxicity of cadmium selenide (CdSe) quantum dots (QDs) presents a barrier to their use in biomedical imaging or as diagnostic and therapeutic agents. Sulforaphane (SFN) is a chemoprotective compound derived from cruciferous vegetables which can up-regulate antioxidant enzymes and induce apoptosis and autophagy. This study reports the effects of SFN on CdSe QD-induced cytotoxicity in immortalised human hepatocytes and in the livers of mice. CdSe QDs induced dose-dependent cell death in hepatocytes with an IC₅₀ = 20.4 μM. Pre-treatment with SFN (5 μM) increased cell viability in response to CdSe QDs (20 μM) from 49.5 to 89.3%. SFN induced a pro-oxidant effect characterized by depletion of intracellular reduced glutathione during short term exposure (3–6 h), followed by up-regulation of antioxidant enzymes and glutathione levels at 24 h. SFN also caused Nrf2 translocation into the nucleus, up-regulation of antioxidant enzymes and autophagy. siRNA knockdown of Nrf2 suggests that the Nrf2 pathway plays a role in the protection against CdSe QD-induced cell death. Wortmannin inhibition of SFN-induced autophagy significantly suppressed the protective effect of SFN on CdSe QD-induced cell death. Moreover, the role of autophagy in SFN protection against CdSe QD-induced cell death was confirmed using mouse embryonic fibroblasts lacking ATG5. CdSe QDs caused significant liver damage in mice, and this was decreased by SFN treatment. In conclusion, SFN attenuated the cytotoxicity of CdSe QDs in both human hepatocytes and in the mouse liver, and this protection was associated with the induction of Nrf2 pathway and autophagy.     

G-Protein Coupled Receptor Kinase 2 Minimally Regulates Melanopsin Activity in Intrinsically Photosensitive Retinal Ganglion Cells

Phosphorylation is a primary modulator of mammalian G-protein coupled receptor (GPCR) activity. The GPCR melanopsin is the photopigment of intrinsically photosensitive retinal ganglion cells (ipRGCs) in the mammalian retina. Recent evidence from in vitro experiments suggests that the G-protein coupled receptor kinase 2 (GRK2) phosphorylates melanopsin and reduces its activity following light exposure. Using an ipRGC-specific GRK2 loss-of-function mouse, we show that GRK2 loss alters melanopsin response dynamics and termination time in postnatal day 8 (P8) ipRGCs but not in older animals. However, the alterations are small in comparison to the changes reported for other opsins with loss of their cognate GRK. These results suggest GRK2 contributes to melanopsin deactivation, but that other mechanisms account for most of modulation of melanopsin activity in ipRGCs.     

Healing in the Sámi North

There is a special emphasis today on integrating traditional healing within health services. However, most areas in which there is a system of traditional healing have undergone colonization and a number of pressures suppressing tradition for hundreds of years. The question arises as to how one can understand today’s tradition in light of earlier traditions. This article is based on material collected in Sámi areas of Finnmark and Nord-Troms Norway; it compares local healing traditions with what is known of earlier shamanic traditions in the area. The study is based on 27 interviews among healers and their patients. The findings suggest that although local healing traditions among the Sámi in northern Norway have undergone major transformations during the last several hundred years, they may be considered an extension of a long-standing tradition with deep roots in the region. Of special interest are also the new forms tradition may take in today’s changing global society.     

Cytochemical localization of peroxidase activity in root cells

Summary The distribution of peroxidase in the apical 3 mm of pea roots has been investigated using the histochemical method employing 3,3-diaminobenzidine as a substrate. At the tissue level the enzyme is localized predominately in the root cap, epidermis, inner cortical cells, endodermis, phloem and maturing xylem. At the subcellular level peroxidase is found mainly in the intercellular regions of the cortex cell walls and in the cytoplasm and vacuoles of the steler cells. Root microbodies, unlike those of leaves, do not appear to be able to oxidize this substrate. The significance of these observations is discussed in relation to the validity of the technique and the proposed roles of the enzyme in cellular metabolism.