bluuebunny/crossref_metadata_2025_split huggingface dataset:
The neuropeptide PACAP contributes to the glucagon response to insulin‐induced hypoglycaemia in mice
Authors: PERSSON K. , AHRÉN B. 
Published: March 2003

ABSTRACTThe neuropeptide pituitary adenylate cyclase‐activating polypeptide (PACAP) is a neuropeptide in the autonomic nerves innervating the pancreatic islets and previous studies have shown that it stimulates insulin and glucagon secretion. It is known that autonomic nerve activation contributes to the glucagon response to hypoglycaemia. In the present study, we evaluated whether PACAP is involved in this glucagon response by examining the glucagon response to insulin‐induced hypoglycaemia in mice genetically deleted of the specific PACAP receptor, the PAC1 receptor. We found that insulin (1 U kg–1 ip) reduced circulating glucose to a hypoglycaemic level of ≈2.5 mmol L–1 in PAC1R–/– mice and their wild‐type counterparts with no difference between the groups. However, the glucagon response to this hypoglycaemia was markedly impaired in the PAC1R–/– mice. Thus, after 120 min, plasma glucagon was 437 ± 79 ng L–1 in wild‐type mice vs. only 140 ± 36 ng L–1 in PAC1R–/– mice (P=0.004). In contrast, the glucagon response to intravenously administered arginine (0.25 g kg–1) was the same in the two groups of mice. We conclude that PACAP through activation of PAC1 receptors contribute to the glucagon response to insulin‐induced hypoglycaemia. Therefore, the glucagon response to hypoglycaemia is dependent not only on the classical neurotransmitters but also on the neuropeptide PACAP.
Effect of exercise on the rat mammary gland: implications for carcinogenesis
Authors: WESTERLIND K. C. , MCCARTY H. L. , GIBSON K. J. , STRANGE R. 
Published: March 2003

ABSTRACTPhysical activity has been associated with decreased risk for developing breast cancer yet to date, the mechanism remains unknown. The purpose of this investigation was to evaluate the effects of moderate exercise training on the normal mammary gland in an attempt to identify alterations or differences that might be associated with tumour inhibition. A total of 170 female Sprague–Dawley rats were randomized to baseline (n=10), exercise (EX; n=80), or sham‐exercise groups (SHAM; n=80). Treadmill training (20–25 m min–1, 15% grade, 30 min day–1, 5 days week–1) was started at 28 days of age (DOA). Animals were killed at 28, 42, 56, 70 and 84 DOA. Mammary glands were evaluated by histology and immunohistochemistry. Terminal end buds (TEB), structures susceptible to carcinogenesis, were counted. Sexual maturation, estradiol and progesterone, and organ and muscle weights were also evaluated. No differences in growth, sexual maturation, or steroid hormones were observed in response to training. No difference in the number of TEBs was observed at any timepoint between EX and SHAM. Proliferation was significantly increased at 56 DOA and tended to be increased at 42 and 70 DOA in the EX animals whereas cell death was significantly increased at 70 DOA and tended to be increased at 84 DOA in the EX animals. These data suggest no difference in the number of carcinogen‐susceptible structures as a result of moderate exercise. The changes in cell proliferation and apoptosis with exercise training suggest altered cell turnover that will necessitate future study particularly with relevance to carcinogenesis.
Are early clinical effects of cholesterol lowering mediated through effects on inflammation?
Authors: Olsson A. G. , Schwartz G. G. , Jonasson L. , Linderfalk C. 
Published: March 2003

ABSTRACTIn a randomized, double‐blind trial in 3086 patients with unstable angina pectoris or non‐Q wave myocardial infarction we investigated if 80 mg of atorvastatin daily could improve outcome of cardiovascular events during a short period of time (16 weeks) compared with placebo. Baseline LDL cholesterol was 3.2 mmol L−1 (124 mg dL−1) and decreased by 40% to 1.9 mmol L−1 (72 mg dL−1) during atorvastatin treatment. The primary endpoint, which was a composite of death, non‐fatal acute myocardial infarction, cardiac arrest with resuscitation or recurrent symptomatic myocardial ischaemia with objective evidence and requiring emergency rehospitalization occurred in 228 patients (14.8%) in the atorvastatin group and 269 patients (17.4%) in the placebo group. The relative risk was0.84 and 95% confidence interval was 0.70–1.00 (P = 0.048). Thus for patients with acute coronary syndromes, lipid‐lowering therapy with high dose atorvastatin reduces recurrent ischaemic events in the short‐term. A possible mechanism behind this rapid clinical effect induced by statin treatment is on inflammatory processes. Recent studies strongly suggest that acute T‐cell activation is involved in the pathogenesis of unstable angina. In another study we investigated whether circulating T cells showed signs of activation in patients with stable angina pectoris (SA). Systemic venous blood samples were taken from 38 men with SA and 42 healthy controls. The T‐cell receptor expression was assessed by three‐colour flow cytometry using monoclonal antibodies against CD3,CD4, CD8, CD25 and human leucocyte antigen (HLA)‐DR. Soluble interleukin‐2 receptor (sIL‐2R) was measured as the circulating form in serum. Levels of circulating CD3+ and CD4+ T cells tended to be higher in patients compared with controls. Patients were also shown to have a significant increase in CD4+ T cells expressing the activation markers CD25 (P < 0.05) and HLA‐DR (P < 0.01). Furthermore, serum levels of sIL‐2R were significantly higher (P < 0.001) in patients than in controls. We also observed that the T‐cell response was more pronounced in patients without simvastatin treatment (n = 18) compared with simvastatin‐treated patients (n = 20). In conclusion, our findings indicate that a continuous immune system activation takes place in patients with chronic angina pectoris, predominantly involving proliferation of CD4+ T cells. Statin treatment seems to be able to decrease this inflammatory response.
Lipophilic oestrogen derivatives contained in lipoprotein particles
Authors: Tikkanen M. J. , Vihma V. , Höckerstedt A. , Jauhiainen M. , Helisten H. , Kaamanen M. 
Published: March 2003

ABSTRACTSteroid fatty acid esters constitute a unique family of lipophilic hormones carried exclusively in circulating lipoproteins. Our studies have focused on the formation of 17β fatty acid esters of labelled oestradiol in in vitro incubations with human ovarian follicular fluid and plasma and demonstrated the accumulation of these labelled derivatives in lipoprotein particles. The oestradiol esters are formed in a reaction catalysed by lecithin : cholesterol acyltransferase in association with high‐density lipoprotein particles and they can be transferred to low‐density lipoprotein particles in a process mediated by cholesteryl ester transfer protein. Using a novel quantitative method for the determination of oestradiol esters their endogenous concentrations in follicular fluid and in early and late pregnancy plasma have been determined. In addition, using labelled genistein and its chemically synthesized fatty acid esters, we also demonstrated that phytoestrogen derivatives could be incorporated in lipoprotein particles. Both oestradiol and genistein contain aromatic hydroxyl groups which cause them to exert powerful antioxidant activity in lipid‐aqueous systems in vitro. The physiological role of the steroidal fatty acid esters remains to be elucidated. In theory, the hormonal esters might form a reservoir constituted by esterified hormones stored in lipoprotein particles and perhaps in fat tissue, or they might use lipoproteins as vehicles for endocrine transport, or they could act as antioxidant protection of the lipoprotein particles. Enzyme systems necessary for the formation of lipophilic oestrogen and phytoestrogen derivatives as well as for their incorporation in lipoprotein particles are present in human body fluids. Because of their water‐insolubility, steroid fatty acid esters are carried exclusively by circulating lipoproteins. These esters can provide antioxidant protection for lipoprotein particles.
Substrate utilization in sea level residents during exercise in acute hypoxia and after 4 weeks of acclimatization to 4100 m
Authors: Lundby C. , Van Hall G. 
Published: March 2003

ABSTRACTTo investigate the effect of acclimatization to hypoxia on substrate utilization, eight sea level residents were studied during exercise at the same relative (rel) and absolute (abs) work rate as at sea level (SL), under acute (AH), and after 4 weeks exposure to 4100 m altitude (CH). Carbohydrate (CHO) and fat oxidation during exercise at SL were 2.0 ± 0.2 and 0.3 ± 0.0 g min−1, respectively. At AHabs and CHabs CHO oxidation increased (P < 0.05) to 2.5 ± 0.2 and 2.3 ± 0.1 for CHO, and fat oxidation decreased (P < 0.05) to 0.2 ± 0.01 and 0.2 ± 0.01 g min−1, respectively. Exercise in AHrel and CHrel did not cause a change in the relative CHO and fat oxidation compared with SL, the absolute rate of CHO oxidized being 1.7 ± 0.1 and 1.7 ± 0.02 g min−1, respectively, and fat oxidation was 0.2 ± 0.02 g min−1 in ACrel and 0.3 ± 0.02 g min−1 in CHrel. In conclusion, substrate utilization is unaffected by AH and CH, when the work rate is matched to the same relative intensity as at SL.
Nandrolone decanoate pre‐treatment attenuates unweighting‐induced functional changes in rat soleus muscle
Authors: Joumaa W. H. , Bouhlel A. , Bigard X. , Léoty C. 
Published: March 2003

ABSTRACTThe effect of nandrolone decanoate pre‐treatment (15 mg kg−1 week−1, for 6 weeks) was tested on the changes in mass and contractile properties of soleus muscle associated with 3 weeks of hindlimb suspension. Male rats were assigned to four groups (eight animals/group): control, nandrolone decanoate hindlimb‐loaded, hindlimb‐unweighted and nandrolone decanoate hindlimb‐unweighted. Compared with age‐matched control values, suspension induced a reduction in relative muscle mass and a shift in tension characteristics from slow‐towards fast‐twitch type. Nandrolone decanoate pre‐treatment of suspended animals (nandrolone decanoate hindlimb‐unweighted vs. nandrolone decanoate hindlimb‐loaded) partially spared the relative soleus mass. Furthermore, (1) the relative twitch tension (nandrolone decanoate hindlimb‐loaded: 5.4 ± 0.7%; nandrolone decanoate hindlimb‐unweighted: 5.1 ± 0.5%), (2) the time to peak tension (nandrolone decanoate hindlimb‐loaded: 152 ± 9 ms; nandrolone decanoate hindlimb‐unweighted: 167 ± 15 ms), (3) the time constant of relaxation (nandrolone decanoate hindlimb‐loaded: 274 ± 12 ms; nandrolone decanoate hindlimb‐unweighted: 245 ± 20 ms), (4) the relative K+ contracture tension (nandrolone decanoate hindlimb‐loaded: 81.7 ± 3.8%; nandrolone decanoate hindlimb‐unweighted: 86.9 ± 4.2%) and (5) the relative caffeine contracture tension (0.5 mm) (nandrolone decanoate hindlimb‐loaded: 5.2 ± 0.8%; nandrolone decanoate hindlimb‐unweighted: 5.9 ± 1.1%) were not significantly modified. The present results demonstrate that exogenously provided nandrolone decanoate pre‐treatment attenuates functional changes occurring in soleus muscle subject to unweighting.
The paraventricular nucleus: an important component of the central neurocircuitry regulating sympathetic nerve outflow
Authors: Kenney M. J. , Weiss M. L. , Haywood J. R. 
Published: March 2003

AbstractAim: The sympathetic nervous system plays an important role in the regulation of physiological homeostasis under basal conditions and in response to acute and chronic stressors. It is known that multiple levels of the neuroaxis, including the paraventricular nucleus (PVN) of the hypothalamus, are involved in regulation of efferent sympathetic nerve discharge (SND). This review focuses on the role of the PVN in regulation of functional characteristics of efferent SND.Results: The available experimental evidence indicates that the level of efferent sympathetic nerve activity is altered after microinjection of numerous substances into the PVN, including excitatory amino acids,γ‐aminobutyric acid (GABAA) receptor agonists and antagonists, and PVN nitric oxide synthase inhibitors. In addition, antagonism of PVN GABAAreceptors changes the pattern of synchronized discharge bursts in efferent sympathetic nerves and enhances the frequency‐domain coupling between low‐frequency bursts in sympathetic nerve pairs. Finally, PVN microinjections of excitatory amino acids (l‐glutamate,d,l‐homocysteic acid) have been shown to produce non‐uniform changes in the level of efferent sympathetic nerve activity.Conclusion: These findings support the concept that the PVN is an important component of the central neurocircuitry regulating functional characteristics (basal level of activity, bursting pattern, and relationships between discharges in nerves innervating different targets) of efferent sympathetic nerve outflow.
Transmission of signals through sympathetic ganglia – modulation, integration or simply distribution?
Authors: McLachlan E. M. 
Published: March 2003

AbstractAim: On structural grounds, synaptic transmission in sympathetic ganglia is potentially complex with extensive divergence and convergence between preganglionic and postganglionic neurones. In this review, the focus is on what constitutes a functional synapse in sympathetic ganglia and how intracellular recordings have enabled us to identify how the transmission process operates in vivo.Results: Only one or two suprathreshold or ‘strong’ inputs are involved in activating each postganglionic neurone. The functional significance of the subthreshold or ‘weak’ inputs remains obscure. The strong inputs, and sometimes the weak ones as well, respond in the same way during reflexes. The expansion of ineffective weak connections enables the rapid restoration of functional control after lesions that damage preganglionic neurones. These novel connections may generate erroneous reflex responses after spinal injury. Postganglionic discharge in vivo consists of the summed firing of the strong preganglionic inputs limited, at high preganglionic discharge rates, by the properties of the afterhyperpolarization.Conclusion: Preganglionic signals are distributed widely through paravertebral ganglia with little modification.
Vestibular activation of sympathetic nerve activity
Authors: Ray C. A. , Carter J. R. 
Published: March 2003

AbstractAim: The vestibulosympathetic reflex refers to sympathetic nerve activation by the vestibular system. Animal studies indicate that the vestibular system assists in blood pressure regulation during orthostasis. Although human studies clearly demonstrate activation of muscle sympathetic nerve activity (MSNA) during engagement of the otolith organs, the role of the vestibulosympathetic reflex in maintaining blood pressure during orthostasis is not well‐established. Examination of the vestibulosympathetic reflex with other cardiovascular reflexes indicates that it is a powerful and independent reflex. Ageing, which is associated with an increased risk for orthostatic hypotension, attenuates the vestibulosympathetic reflex. The attenuated reflex is associated with a reduction in arterial pressure.Conclusion: These findings suggest that the vestibulosympathetic reflex assists in blood pressure regulation in humans, but future studies examining this reflex in other orthostatically intolerant populations are necessary to address this hypothesis.
Sympathetic activation in human heart failure: diverse mechanisms, therapeutic opportunities
Authors: Floras J. S. 
Published: March 2003

AbstractPlasma noradrenaline (NA) concentrations relate both to the severity of heart failure, and to its impact on survival, but have shortcomings that limit their usefulness as measures of sympathetic discharge. Neural recordings and the isotopic dilution method for determining organ‐specific rates of NA spillover into plasma have enhanced our understanding of mechanisms responsible for sympathetic activation. Because the arterial baroreceptor reflex control of heart rate is impaired in heart failure, a parallel reduction in the reflex inhibition of sympathetic outflow has been assumed. However, human heart failure is characterized by rapidly responsive arterial baroreflex regulation of muscle sympathetic nerve activity (MSNA), attenuated cardiopulmonary reflex modulation of MSNA, and activation of a cardiac‐specific sympatho‐excitatory reflex related to increased cardiopulmonary filling pressures. Together, these baroreceptor mediated mechanisms account only, in part, for the time course and magnitude of adrenergic activation in heart failure. Non‐baroreflex sympatho‐excitatory mechanisms include: a metaboreflex arising from exercising skeletal muscle, mediated, in part, by adenosine, co‐existing sleep apnoea, and pre‐junctional facilitation of NA release. Thus, sympathetic activation in the setting of impaired systolic function reflects the net balance and interaction between augmented excitatory and diminished inhibitory influences. Variation, between patients, in the dynamics, magnitude and progression of sympathetic activation mandates an individualized approach to investigation and therapy. Excessive sympathetic outflow to the heart and periphery can be addressed by several complimentary strategies: attenuating these sympatho‐excitatory stimuli, modulating the neural regulation of NA release, and blocking the actions of catecholamines at post‐junctional receptors.
Sympathetic nerve activity and neurotransmitter release in humans: translation from pathophysiology into clinical practice
Authors: Esler M. , Lambert G. , Brunner‐La Rocca H. P. , Vaddadi G. , Kaye D. 
Published: March 2003

AbstractAim:  There has been a revolution in cardiovascular neuroscience in recent years with, in some cases, translation into clinical practice of the knowledge of pathophysiology gained through application of sympathetic nerve recording and catecholamine isotope dilution methodology.Obesity‐related hypertension:  An earlier hypothesis, based on findings in most models, was that weight gain in obesity is due in part to sympathetic nervous underactivity reducing thermogenesis. Microneurography and regional noradrenaline spillover measurements in human obesity have disproven this hypothesis, weakening the case for the use of β3‐adrenergic agonists to stimulate thermogenesis. Sympathetic nerve firing rates in post‐ganglionic fibres directed to the skeletal muscle vasculature are increased, as is renal sympathetic tone, with a doubling of the spillover rate of noradrenaline from the kidneys. Given these findings, antiadrenergic antihypertensive drugs may be the preferred agents for obesity‐related hypertension, but this has not been adequately tested.Essential hypertension:  Whether stress causes high blood pressure, previously hotly debated, has been under recent review by an Australian Government body, the Specialist Medical Review Council. Despite medicolegal implications, the ruling was that stress is one proven cause of hypertension. The judgment was reached after consideration of the epidemiological evidence, but in particular the described neural pathophysiology of essential hypertension: (a) persistent sympathetic nervous stimulation is commonly present, (b) suprabulbar projections of noradrenergic brainstem neurones are activated and (c) adrenaline is released as a cotransmitter in sympathetic nerves. These were taken to be biological markers of stress.Cardiac failure:  At one time, the failing heart was thought to be sympathetically denervated. Longterm administration of inotropic adrenergic agonists, to provide the cardiac catecholamine stimulation thought to be lacking, increased mortality. Noradrenaline isotope dilution methodology subsequently demonstrated that the sympathetic outflow to the heart was preferentially activated, cardiac noradrenaline spillover being increased as much as 50‐fold. The level of stimulation of the cardiac sympathetic nerves was the most powerful predictor of death. These observations provide the theoretical foundation for the very successful introduction of β‐adrenergic blockers for treatment of heart failure.
Changes in termite (Isoptera) communities due to the clearance and cultivation of tropical forest in Uganda
Authors: Okwakol Mary J. N. 
Published: March 2003

Changes in termite communities following clearance and cultivation of part of Mabira Forest Reserve were studied. The study sites included natural forest, a cleared but not cultivated site and six sites cultivated for different periods, ranging from 1 to 20 years.A total of 25 species, includingOdontotermes amanicus(Sjostedt) andMicrotermes luteus(Harris), both not previously identified in Uganda, was recorded in the natural forest. Forest clearance resulted in drastic reduction of the number of species to about 40% of what existed in the natural forest, while cultivation led to further elimination, leaving only four and two species, respectively, in the 1‐ and 20‐year‐old banana groves.The study showed that termite species diversity declines when the natural forest is cleared and cultivated. It is suggested that reduction in termite diversity alters ecological processes and may result in diminishing productivity with time.
Habitat constraints limit the distribution and population density of redwing francolin, Francolinus levaillantii, in the highland grasslands of Mpumalanga province, South Africa
Authors: Jansen R. , Robinson E. R. , Little R. M. , Crowe T. M. 
Published: March 2003

AbstractWe investigated a variety of habitat characteristics along a land‐use gradient in an attempt to determine which factors may have influenced the population decline of redwing francolin, Francolinus levaillantii, in commercial pasture farms in the highland grasslands of Mpumalanga province, South Africa. Within three microhabitats (wetlands, rocky outcrops and grassland), number and diversity of food plants, height of the sward and percentage cover were significantly lower in habitat exposed to commercial grazing with sheep. Increased cover and height of the sward were positively correlated with higher diversity and availability of francolin food plants. Crop analyses revealed a lower intake in the number of food plant species, but higher incidence of invertebrates, ingested by birds collected in heavily grazed and frequently burned grasslands. Intestinal caecae were significantly (P < 0.001) longer in birds collected from grazed/burned grasslands – possibly associated with a low quality, more fibrous diet. Both the quantity and quality of habitat in terms of food abundance, diversity and cover are important factors influencing the distribution of redwing francolin in these grasslands.
Butterfly populations in two forest fragments at the Kenya coast
Authors: Rogo Lucie , Odulaja Adedapo 
Published: March 2003

AbstractSpecies richness, diversity and composition of butterflies in two Kenya coastal forest remnants, Muhaka and Mrima hill, were investigated. Sixty‐three species were recorded from each forest remnant from a total of 1329 individuals. Species accumulation curves for both forests did not reach an asymptote. High species similarity was recorded between the forest interior and the surrounding matrix, primarily due to invasion of the forest interior clearings by the savanna species. Despite their small sizes, these forest remnants were found to maintain viable populations of true forest butterflies. However, the number of species was less than half that recorded from the larger forest reserve of Arabuko‐Sokoke, located in the same geographical area. Records from Muhaka forest show species unique to it, not found in the larger forest reserves, underscoring the importance of small remnants in the preservation of forest biodiversity. The high species similarity between the forest remnants implied that if habitat corridors were created, gene flow between these remnants and other larger forest reserves would be possible. This would reduce the isolation of true forest butterfly populations within the remnants and potential local extinction.