Respiratory and cardiovascular responses to hypoxia in the Australian lungfish

Simultaneous measurements of pulmonary blood flow (qPA), coeliacomesenteric blood flow (qCoA), dorsal aortic blood pressure (PDA), heart rate (fH) and branchial ventilation frequency (fv) were made in the Australian lungfish, /Neoceratodus forsteri, /during air breathing and aquatic hypoxia. The cho­linergic and adrenergic influences on the cardiovascular system were investigated during normoxia using pharmacological agents, and the presence of catecholamines and serotonin in different tissues was investi­gated using histochemistry. Air breathing rarely occurred during normoxia but when it did, it was always associated with increased pulmonary blood flow. The pulmonary vasculature is influenced by both a cho­linergic and adrenergic tonus whereas the coeliacomesenteric vasculature is influenced by a β-adrenergic vasodilator mechanism. No adrenergic nerve fibers could be demonstrated in /Neoceratodus /but catecholamine-containing endothelial cells were found in the atrium of the heart. In addition, serotonin-­immunoreactive cells were demonstrated in the pulmonary epithelium. The most prominent response to aquatic hypoxia was an increase in gill breathing frequency followed by an increased number of air breaths together with increased pulmonary blood flow. It is clear from the present investigation that /Neoceratodus /is able to match cardiovascular performance to meet the changes in respiration during hypoxia.

Blood-respiratory and acid-base changes during extended diving in the bimodally respiring freshwater turtle Rheodytes leukops

Changes in blood-gas, acid-base, and plasma-ion status were investigated in the bimodally respiring turtle, Rheodytes leukops, during prolonged dives of up to 12 h. Given that R. leukops routinely submerges for several hours, the objective of this study was to determine whether voluntarily diving turtles remain aerobic and simultaneously avoid hypercapnic conditions over increasing dive lengths. Blood PO2, PCO2, and pH, as well as plasma concentrations of lactate, glucose, Na+, K+, Cl-, total Ca, and total Mg were determined in venous blood collected from the occipital sinus. Blood PO2 declined significantly with dive length; however, oxy-haemoglobin saturation remained greater than 30% for all R. leukops sampled. No changes were observed in blood PCO2, pH, [HCO3-], or plasma glucose, with increasing dive length. Despite repeated dives lasting more than 2 h, plasma lactate remained less than 3 mmol l(-1) for all R. leukops sampled, indicating the absence of anaerobiosis. Compensatory acid-base adjustments associated with anaerobiosis (e.g. declining [Cl-], increasing total [Ca] and [Mg]) were likewise absent, with plasma-ion concentrations remaining stable with increasing dive length. Results indicate that R. leukops utilises aquatic respiration to remain aerobic during prolonged dives, thus effectively avoiding the development of a metabolic and respiratory acidosis.

Paradoxical association between smoking and olfactory identification in psychosis versus controls

Objective: Deficits in olfactory identification have been demonstrated in patients with schizophrenia. This study examined the interaction between smoking and olfactory identification in patients with psychotic disorders versus well controls. Method: Olfactory identification was assessed in three groups of subjects using the University of Pennsylvania Smell Identification Test (UPSIT). Sixteen patients with affective psychoses, 22 patients with nonaffective psychoses, and 21 well controls were tested. Results: There was a significant interaction between diagnostic classification (patient or control) and smoking. Patients who were smokers scored higher on the UPSIT than non-smokers, while controls who were smokers scored lower than non-smokers. Conclusions: Smoking may have a 'normalising' effect on olfactory identification in some patients with psychosis. Further studies are needed to examine the relationship between psychosis, olfactory identification and the effects of nicotine.

Impaired memory and olfactory performance in NaSi-1 sulphate transporter deficient mice

In the present study, NaSi-l sulphate transporter knock-out (Nas1-/-) mice, an animal model of hyposulphataernia, were examined for spatial memory and learning in a Morris water maze, and for olfactory function in a cookie test. The Nas1-/- mice displayed significantly (P < 0.05) increased latencies to find an escape platform in the reversal teaming trials at 2 days but not 1 day after the last acquisition trial in a Morris water maze test. suggesting that Nas1-/- mice may have proactive memory interference. While the wild-type (Ncis1+/+) mice showed a significant (P < 0.02) decrease in time to locate a hidden food reward over four trials after overnight fasting, Nas1-/- mice did not change their performance, resulting in significantly (P < 0.05) higher latencies when compared to their Nas1+/+ littermates. There were no significant differences between Nas1-/- and Nas1+/+ mice in the cookie test after moderate food deprivation. In addition, both Nas1-/- and Nas1+/+ mice displayed similar escape latencies in the acquisition phase of the Morris water maze test, suggesting that learning, motivation, vision and motor skills required for the task may not be affected in Nas1-/- mice. This is the first study to demonstrate an impairment in memory and olfactory performance in the hyposulphataemic Nas1-/- mouse. (c) 2004 Elsevier B.V. All rights reserved.

Substrate-bound carbohydrates stimulate signal transduction and neurite outgrowth in an olfactory neuron cell line

SUBPOPULATIONS of olfactory receptor neurons, which are dispersed throughout the olfactory neuroepithelium, express specific cell surface carbohydrates and project to discrete regions of the olfactory bulb. Cell surface carbohydrates such as N-acetyl-lactosamine have been postulated to mediate sorting and selective fasciculation of discrete axon subpopulations during development of the olfactory pathway. Substrate-bound N-acetyl-lactosamine promotes neurite outgrowth by both clonal olfactory receptor neuron cell lines and olfactory receptor neurons in vitro, indicating that cell surface carbohydrates may be ligands for receptor-mediated stimulation of axon growth in vivo. In the present study, the role of transmembrane signaling in N-acetyl-lactosamine-stimulated neurite outgrowth was examined in the clonal olfactory neuron cell line 4.4.2. Substrate-bound N-acetyl-lactosamine stimulated neurite outgrowth which was specifically inhibited by antagonists to N- and L-type calcium channels and to tyrosine kinase phosphorylation. These results indicate that N-acetyl-lactosamine can evoke transmembrane receptor-mediated responses capable of influencing neurite outgrowth.

EphA receptors and ephrin-A ligands exhibit highly regulated spatial and temporal expression patterns in the developing olfactory system

The spatiotemporal expression patterns of the chemorepulsive EphA receptors, EphA4 and EphA7, and three ephrins-A2, A4 and A5, were examined in the developing rat primary olfactory system. Unlike the visual system that has simple and stable gradients of Ephs and ephrins, the olfactory system demonstrates complex spatiotemporal expression patterns of these molecules. Using immunohistochemistry, we demonstrate that expression of these molecules is dynamic and tightly regulated both within and between different cell types. We reveal restricted targeting of these proteins within subcellular compartments of some neurons. EphA4, ephrin-A2 and ephrin-A5 were expressed by primary olfactory axons during the embryonic formation of the olfactory nerve. There were no gradients in expression along the rostrocaudal or ventrodorsal axes in the nasal cavity and olfactory bulb. However, during the early neonatal period, axons expressing different levels of ephrin-A5 sorted out and terminated in a subpopulation of glomeruli that were mosaically dispersed throughout the bulb. The expression of EphA4 and ephrin-A2 was dramatically down-regulated on all axons during the early neonatal period of glomerular formation. The uniform co-expression of receptors and ligands before glomerular formation suggests they play a generic role in axon-axon interactions in the olfactory nerve and nerve fibre layer. In contrast, loss of EphA4 from axons during glomerular formation may facilitate the interaction of ephrin-A5 with Eph receptors on target cells in the bulb. While EphA4, EphA5 and EphA7 are not mosaically expressed by bulbar neurons, other Eph receptors may have expression patterns complementary to the ephrin-A5-positive subpopulation of glomeruli. (C) 2002 Elsevier Science B.V. All rights reserved.

Postural and respiratory activation of the trunk muscles changes with mode and speed of locomotion

Despite the importance of the deep intrinsic spinal muscles for trunk control, few studies have investigated their activity during human locomotion or how this may change with speed and mode of locomotion. Furthermore, it has not been determined whether the postural and respiratory functions, of which these muscles take part, can be coordinated when locomotor demands are increased. EMG recordings of abdominal and paraspinal muscles were made in seven healthy subjects using fine-wire and surface electrodes. Measurements were also made of respiration and gait parameters. Recordings were made for 10s as subjects walked on a treadmill at 1 and 2 ms(-1) and ran at 2, 3, 4 and 5 ms(-1). Unlike the superficial muscles, transversus abdominis was active tonically throughout the gait cycle with all tasks, except running at speeds of 3 ms(-1) and greater. All other muscles were recruited in a phasic manner. The relative duration of these bursts of activity was influenced by speed and/or mode of locomotion. Activity of all abdominal muscles, except rectus abdominis (RA), was modulated both for respiration and locomotor-related functions but this activity was affected by the speed and mode of locomotion. This study provides evidence that the deep abdominal muscles are controlled independently of the other trunk muscles. Furthermore, the pattern of recruitment of the trunk muscles and their respiratory and postural coordination is dependent on the speed and mode of locomotion. (C) 2003 Published by Elsevier B.V.

Mucosal immunisation with papillomavirus virus-like particles elicits systemic and mucosal immunity in mice

It has been shown previously that recombinant virus-like particles (VLPs) of papillomavirus can induce VLP-specific humoral and cellular immune responses following parenteral administration. To test whether mucosal administration of bovine papillomavirus type 1 (BPV1) VLPs could produce mucosal as well as systemic immune responses to VLPs, 50 mu g chimeric BPV1 VLPs containing an HPV16 E7 CTL epitope (BPVL1/E7 VLP) was administered intranasally to mice. After two immunisations, L1-specific serum IgG and IgA were observed. L1-specific IgG and IgA were also found in respiratory and vaginal secretions. Both serum and mucosal antibody inhibited papillomavirus VLP-induced agglutination of RBC, indicating that the antibody induced by mucosal immunisation may recognize conformational determinants associated with virus neutralisation. For comparison, VLPs were given intramuscularly, and systemic and mucosal immune responses were generally comparable following systemic or mucosal delivery. However, intranasal administration of VLP induced significantly higher local IgA response in lung, suggesting that mucosally delivered HPV VLP may be more effective for mediating local mucosal immune responses. Intranasal immunisation with HPV6b L1 VLP produced VLP-specific T proliferative responses in splenocytes, and immunisation with BPVL1 VLP containing an HPV16 E7 CTL epitope induced E7-specific CTL responses. We conclude that immunisation with papillomavirus VLPs via mucosal and intramuscular routes, without adjuvant, can elicit specific antibody at mucosal surfaces and also systemic VLP epitope specific T cell responses. These findings suggest that mucosally delivered VLPs may offer an alternative HPV VLP vaccine strategy for inducing protective humoral immunity to anogenital HPV infection, together with cell-mediated immune responses to eliminate any cells which become infected. (C) 1998 Academic Press.

Molecular development of the olfactory nerve pathway

There are, at least, two major questions concerning the molecular development of the olfactory nerve pathway. First, what are the molecular cues responsible for guiding axons from the nasal cavity to the olfactory bulb? Second, what is the molecular basis of axon targeting to specific glomeruli once axons reach the olfactory bulb? Studies in the primary olfactory pathway have focused on the role of the extracellular matrix and ensheathing cells in establishing an initial substrate for growth of pioneer axons between the periphery and brain. The primary axons also express a multitude of cell adhesion molecules that regulate fasciculation of axons and hence may play a role in fascicle formation in the olfactory nerve. Although the olfactory neuroepithelium principally consists of a morphologically homogeneous class of primary olfactory neurons, there are numerous subpopulations of olfactory neurons expressing chemically distinct phenotypes. In particular, numerous subpopulations have been characterized by expression of unique carbohydrate residues and olfactory receptor proteins. Some of these molecules have recently been implicated in axon guidance and targeting to specific glomeruli.

The toxins of Lyngbya majuscula and their human and ecological health effects

Lyngbya majuscula is a benthic filamentous marine cyanobacterium, which in recent years appears to have been increasing in frequency and size of blooms in Moreton Bay, Queensland. It has a worldwide distribution throughout the tropics and subtropics in water to 30m. It has been found to contain a variety of chemicals that exert a range of biological effects, including skin, eye and respiratory irritation. The toxins lyngbyatoxin A and debromoaplysiatoxin appear to give the most widely witnessed biological effects in relation to humans, and experiments involving these two toxins show the formation of acute dermal lesions. Studies into the epidemiology of the dermatitic, respiratory and eye effects of the toxins of this organism are reviewed and show that Lyngbya induced dermatitis has occurred in a number of locations. The effects of aerosolised Lyngbya in relation to health outcomes were also reported. Differential effects of bathing behaviour after Lyngbya exposure were examined in relation to the severity of health outcomes. The potential for Lyngbya to exhibit differential toxicologies due to the presence of varying proportions of a range of toxins is also examined. This paper reviews the present state of knowledge on the effects of Lyngbya majuscula on human health, ecosystems and human populations during a toxic cyanobacterial bloom. The potential exists for toxins from Lyngbya majuscula affecting ecological health and in particular marine reptiles. (C) 2001 Elsevier Science Ltd. All rights reserved.

Disorders of breathing and continence have a stronger association with back pain than obesity and physical activity

Although obesity and physical activity have been argued to predict back pain, these factors are also related to incontinence and breathing difficulties. Breathing and continence mechanisms may interfere with the physiology of spinal control, and may provide a link to back pain. The aim of this study was to establish the association between back pain and disorders of continence and respiration in women. We conducted a cross-sectional analysis of self-report, postal survey data from the Australian Longitudinal Study on Women's Health. We used multinomial logistic regression to model four levels of back pain in relation to both the traditional risk factors of body mass index and activity level, and the potential risk factors of incontinence, breathing difficulties, and allergy. A total of 38 050 women were included from three age-cohorts. When incontinence and breathing difficulties were considered, obesity and physical activity were not consistently associated with back pain. In contrast, odds ratios (OR) for often having back pain were higher for women often having incontinence compared to women without incontinence (OR were 2.5, 2.3 and 2.3 for young, mid-age! and older women, respectively). Similarly, mid-aged and older women had higher odds of having back pain often when they experienced breathing difficulties often compared to women with no breathing problems (OR of 2.0 and 1.9, respectively). Unlike obesity and physical activity, disorders of continence and respiration were strongly related to frequent back pain. This relationship may be explained by physiological limitations of co-ordination of postural, respiratory and continence functions of trunk muscles.

Simplifying the molecular mechanisms of human papillomavirus

The human papillomaviruses (HPVs) are associated with several human epithelial diseases. These diseases are confined to cutaneous and mucosal epithelia and comprise papillomas (warts) and benign or malignant neoplasms. Globally, infection by HPVs presents a considerable health problem given that at any one time approximately 10% of the population may have warts of one form or another. Of more serious concern is the prevalence of HPV-associated cervical carcinoma. It is estimated that 500,000 new cases of cervical neoplasia are diagnosed per year (primarily squamous carcinomas). Thus, HPV-associated cancer represents one of the most common cancers afflicting women and is one of the three most common causes of cancer death among women globally.(15) Although some genotypes of human papillomaviruses are clearly associated with the development of cancer (in particular, HPVs 16 and 18) these viruses share significant structural and functional similarity to the nononcogenic genotypes, and one of the puzzles of HPV biology is why essentially similar viruses vary so widely in their oncogenic potential.

Activation of the human diaphragm during a repetitive postural task

1. The co-ordination between respiratory and postural functions of the diaphragm was investigated during repetitive upper Limb movement. It was hypothesised that diaphragm activity would occur either tonically or phasically in association with the forces from each movement and that this activity would combine with phasic respiratory activity. 2. Movements of the upper limb and ribcage were measured while standing subjects performed repetitive upper limb movements 'as fast as possible'. Electromyographic (EMG) recordings of the costal diaphragm were made using intramuscular electrodes in four subjects. Surface electrodes were placed over the deltoid and erector spinae muscles. 3. In contrast to standing at rest, diaphragm activity was present throughout expiration at 78 +/- 17% (mean +/- S.D.) of its peak inspiratory magnitude during repeated upper limb movement. 4. Bursts of deltoid and erector spinae EMG activity occurred at the Limb movement frequency (similar to 2.9 Hz). Although the majority of diaphragm EMG power was at the respiratory frequency (similar to 0.4 Hz), a peak was also present at the movement frequency. This finding was corroborated by averaged EMG activity triggered from upper limb movement. In addition, diaphragm EMG activity was coherent with ribcage motion at the respiratory frequency and with upper limb movement at the movement frequency. 5. The diaphragm response was similar when movement was performed while sitting. In addition, when subjects moved with increasing frequency the peak upper limb acceleration correlated with diaphragm EMG amplitude. These findings support the argument that diaphragm contraction is related to trunk control. 6. The results indicate that activity of human phrenic motoneurones is organised such that it contributes to both posture and respiration during a task which repetitively challenges trunk posture.

Prospective survey of tick paralysis in dogs

Objective To obtain information on tick paralysis in dogs, including the nature of disease, host signalment, tick-host relationship, treatment, disease progression and recovery, and preventive measures. Design A prospective survey of 577 dogs affected by tick paralysis was conducted during 1998. Forty-two veterinary clinics along the eastern coast of Australia were instructed to complete survey forms for the first 15 dogs that presented with tick paralysis during September to November. Results Five percent of dogs died from tick paralysis. Younger dogs were more likely to survive. Long coat length was associated with a greater tick burden but not greater tick size, whereas coat thickness had no bearing on either. Dogs with mild disease recovered more quickly from tick paralysis. Respiratory and gait scores reflected disease severity and were good prognostic indicators. The size of the tick did not reflect the severity of the clinical condition it induced in the host. No method of tick removal or in situ treatment improved recovery time or reduced mortality. However, the time spent in hospital was significantly less for dogs from which the live tick was manually removed. Inspiratory strider. evident in some dogs with tick paralysis, was not related to tick attachment on the neck. The use of acepromazine maleate or dexamethasone did not reduce recovery time or mortality. Increasing the dose of tick antitoxin serum (TAS) above 0.1 mL/kg had no effect on mortality or recovery time. Dogs with severe disease that received an additional dose of TAS were significantly less likely to survive. Subcutaneous use of TAS at the site of tick attachment was of no benefit in reducing mortality or time to initial clinical improvement. A registered preventative product had not been used on the majority of dogs. Clipping the coat to search for ticks did not reduce mortality. Conclusions Therapy needs to address cardiopulmonary dysfunction that may be due directly to the effect of tick toxin and not just respiratory compromise caused by progressive respiratory muscle failure.