bluuebunny/crossref_metadata_2025 huggingface dataset:
Possible effects of fatigue on muscle efficiency
Authors: WOLEDGE R. C.
Published: May 2003

The efficiency of energy transduction is defined as the ratio of the work done by a muscle to the free energy change of the chemical processes driving contraction. Two examples of the experimental measurement of muscle efficiency are: (1) the classical method of Hill which measures the value during a steady state of shortening, (2) measuring the overall efficiency during a complete cycle of a sinusoidal process, which comes closer to the situation during natural locomotion. The reasons why fatigue might lower efficiency are the following. (1) The reduction in PCr concentration and increase in Pi and Cr concentration which are characteristic of fatigued muscle, reduce the free energy of PCr splitting. This will reduce the efficiency of the recovery process. It is not known whether the efficiency of the initial process is increased to compensate. (2) There is a general conflict between efficiency and power output when motor units are chosen for a task or when the timing of activation is decided. During fatigue more powerful units have to be used to achieve a task which is no longer within the scope of less powerful units. (3) The slowing of relaxation that is sometimes found with fatigue may make it impossible to achieve the short periods of activity required for optimum efficiency during rapid cyclical movements. A reason why fatigue might increase efficiency is that muscles are thought to be more efficient energy converters when not fully activated than when fully active. Full activation is often not achieved in muscle which is considerably fatigued. Available observations do not allow us to find where the balance between these factors lies. The conclusion is thus that experiments of both the types discussed here should be performed.
Neural control in human muscle fatigue: changes in muscle afferents, moto neurones and moto cortical drive
Authors: GANDEVIA S. C.
Published: May 2003

To understand the neural factors which contribute to fatigue, it is not satisfactory to regard fatigue as occurring only when a task can no longer be performed. Changes in muscle afferent feedback, moto neuronal discharge, moto cortical output, and perceived effort develop well before an endurance limit in limb muscles. During sustained maximal contractions the discharge of moto neurones declines, commonly to below the level required to produce maximal force from the muscle whose contractile speed is usually slowed. Thus, some `central' fatigue develops. Recent findings using transcranial stimulation have revealed that the moto cortex is one site at which suboptimal output develops during human muscle fatigue. There is a need to study the reflex effects on moto neurones and the excitability of the moto cortex in experimental animals, as well as to apply rigorous methods to assess these processes in voluntary exercise in human subjects.
Mechanisms underlying the reduction of isometric force in skeletal muscle fatigue
Authors: WESTERBLAD H. , ALLEN D. G. , BRUTON J. D. , ANDRADE F. H. , LÄNNERGREN J.
Published: May 2003

A decline of isometric force production is one characteristic of skeletal muscle fatigue. In fatigue produced by repeated short tetani, this force decline can be divided into two components: a reduction of the cross‐bridges' ability to generate force, which comes early; and a reduction of the sarcoplasmic reticulum Ca2+ release, which develops late in fatigue. Acidification due to lactic acid accumulation has been considered as an important cause of the reduced cross‐bridge force production. However, in mammalian muscle it has been shown that acidification has little effect on isometric force production at physiological temperatures. By exclusion, in mammalian muscle fatigue, the reduction of force due to impaired cross‐bridge function would be caused by accumulation of inorganic phosphate ions, which results from phosphocreatine breakdown. The reduction of sarcoplasmic reticulum Ca2+ release in late fatigue correlates with a decline of ATP and we speculate that the reduced Ca2+ release is caused by a local increase of the ADP/ATP ratio in the triads.
Events of the excitation–contraction–relaxation (E–C–R) cycle in fast‐ and slow‐twitch mammalian muscle fibres relevant to muscle fatigue
Authors: STEPHENSON D. G. , LAMB G. D. , STEPHENSON G. M. M.
Published: May 2003

The excitation–contraction–relaxation cycle (E–C–R) in the mammalian twitch muscle comprises the following major events: (1) initiation and propagation of an action potential along the sarcolemma and transverse (T)‐tubular system; (2) detection of the T‐system depolarization signal and signal transmission from the T‐tubule to the sarcoplasmic reticulum (SR) membrane; (3) Ca2+ release from the SR; (4) transient rise of myoplasmic [Ca2+]; (5) transient activation of the Ca2+‐regulatory system and of the contractile apparatus; (6) Ca2+ reuptake by the SR Ca2+ pump and Ca2+ binding to myoplasmic sites. There are many steps in the E–C–R cycle which can be seen as potential sites for muscle fatigue and this review explores how structural and functional differences between the fast‐ and slow‐twitch fibres with respect to the E–C–R cycle events can explain to a great extent differences in their fatiguability profiles.
Muscle pH regulation: role of training
Authors: JUEL C.
Published: May 2003

In most cell types, including resting skeletal muscle fibers, internal pH (pHi) is kept constant at a relatively alkaline level. The high pHi is obtained in spite of a chronic acid load resulting from cellular metabolism and passive influx of protons driven by electrochemical forces. Regulation of pHi depends on continuous activity of membrane transport systems that mediate an outflux of H+ (or bicarbonate influx), whereby the acid load is counterbalanced. The transporters involved in muscle pH regulation at rest are the Na+/H+ exchange system as well as the Na+‐dependent and Na+‐independent Cl–bicarbonate transport systems. The Na+/H+ exchanger seems to be active at resting pHi levels in skeletal muscle. Therefore, pH homeostasis in skeletal muscle most likely involves an equilibrium between counter‐directed H+ fluxes.

A minor fraction of H+ release during intense exercise is mediated by the Na+/H+ exchanger. The capacity of this system is increased with training and hypoxia in rat skeletal muscle. The dominant acid extruding system associated with intense exercise is the lactate/H+ co‐transporter. It has been demonstrated that the capacity of the lactate/H+ co‐transporter of rat skeletal muscle is upregulated with training and chronic electrical stimulation, and that it is reduced upon denervation and hindlimb unweighting. Moreover, athletes can have an elevated lactate/H+ co‐transport capacity, whereas the thigh muscle of spinal cord‐injured individuals has a lower transport capacity than the one of healthy untrained subjects. Thus, it appears that the capacity of the lactate/H+ transporter is affected by the level of muscle activity in both rats and humans. In addition, the rate of H+ release from muscle may also be influenced by capillarization and local blood flow. Finally the resulting pH displacement during acid accumulation is determined by the cellular buffer capacity, which may also undergo adaptive changes.
Determination of muscle contractile properties: the importance of the nerve
Authors: GUNDERSEN K.
Published: May 2003

Contractile phenotype of muscle fibres is strongly influenced by hormones, stretch and influences from the motor neurones, although cell lineage probably also plays a role. Motor neurones can affect muscle fibres by releasing neurotrophic substances and by evoking electrical activity in the muscle. For regulating contractile properties such as speed, strength and endurance it has been demonstrated that electrical activity is crucial, while the role of putative neurotrophic substances remains unclear. The signal to change is coded in the pattern of electrical activity. Thus, high amounts of activity lead to slow shortening velocity and myosin heavy chains, while low amounts of activity lead to a fast phenotype. For regulation of twitch duration frequency also plays a role, and for preventing atrophy in denervated muscles high frequency seems to be beneficial, particularly in fast muscles. Little is known about the excitation–adaptation pathway linking action potentials to expression of genes that are relevant for contractile properties. Muscle specific transcription factors of the helix–loop–helix family such as myoD and myogenin could be important for regulating genes related to metabolic profile and fibre size/strength, while their role in determining myosin heavy chain expression and classical fibre type is more uncertain.
Relationship of physical exercise and ageing to growth hormone production
Authors: Hurel S. J. , Koppiker N. , Newkirk J. , Close P. R. , Miller M. , Mardell R. , Wood P. J. , Kendall‐Taylor P.
Published: May 2003

OBJECTIVE

The normal decline in physiological function with ageing is associated with a decrease in bioavailable growth hormone. Growth hormone has been shown to alter body composition and increase fat‐free mass in older men. Increased physical fitness is accompanied by an increase in 24‐h growth hormone release. The purpose of this study was to examine the effect of exercise on declining growth hormone concentrations with increasing age.

DESIGN AND PATIENTS

The growth hormone production of 10 male subjects running over 40 miles per week was compared to 10 healthy age‐matched sedentary males (controls 57.7 ± 2.8 vs. runners 60.5 ± 3.4 years). All subjects underwent a basal assessment including a two‐hour serum growth hormone profile followed by estimation of maximal exercise capacity on a cycle ergometer with growth hormone estimations at peak exercise activity and every five minutes whilst cycling at 40% of maximal exercise capacity.

RESULTS

Maximal exercise capacity confirmed the lifestyles of the two groups (VO2 max controls 22.36 ±6.05 vs. runners 34.91 ± 13.13 l/min/kg, P = 0.01). The runners had lower body‐mass indices than controls (BMI 22.3 ± 1.5 vs. 25.5 ± 2.0 kg/m2, P = 0.002). Peak growth hormone level during a two‐hour resting profile was higher in the runners (median (range) controls 2.10 (0.20–12.20) vs. runners 5.25 (0.80–21.00) mU/l, P = 0.03) as was the average growth hormone level during the two hour profile (mean growth hormone per 2 h median (range): controls 0.54 (0.03–4.88) vs. runners 2.17 (0.25–7.45) mU/l, P = 0.04). Growth hormone production at maximal exercise capacity was similar. Sex hormone binding globulin and testosterone were significantly higher in the runners.

CONCLUSIONS

The results suggest that regular intensive exercise in older male subjects is associated with higher growth hormone and testosterone levels and that exercise may have a role in counteracting the normal decline in growth hormone with ageing.
Repeated intramuscular injections of testosterone undecanoate for substitution therapy in hypogonadal men
Authors: Nieschlag Eberhard , Büchter Dorothee , Von Eckardstein Sigrid , Abshagen Katrin , Simoni Manuela , Behre Hermann M.
Published: May 2003

OBJECTIVE

To investigate the suitability of intramuscular testosterone undecanoate (TU) injections for substitution therapy in hypogonadal men.

STUDY DESIGN

Clinical, open‐label, non‐randomized trial of 13 hypogonadal men receiving 4 intramuscular injections of 1000 mg TU in 4‐ml castor oil at 6‐week intervals. General wellbeing, sexual parameters, clinical chemistry, hormone levels, prostate size and prostate‐specific antigen (PSA) were evaluated over 24 weeks and compared with baseline values.

RESULTS

Testosterone serum levels were never found below the lower limit of normal and only briefly after the 3rd and 4th injection above the upper limit of normal, while peak and trough values increased over the 24‐week observation period. Oestradiol and dihydrotestosterone followed this pattern, not exceeding the normal limits. No serious side‐effects were noted. Slight increases in body weight, haemoglobin, haematocrit, prostate volume and PSA, suppression of gonadotrophins as well as increased ejaculation frequency occurred as signs of adequate testosterone substitution.

CONCLUSION

Testosterone undecanoate is well tolerated by the patients. The injection intervals can be extended even beyond the 6‐week periods chosen in the present study. Altogether, intramuscular testosterone undecanoate appears to be well suited for long‐term substitution therapy in hypogonadism and hormonal male contraception.
Oestrogens prevent the increase of human serum soluble interleukin‐6 receptor induced by ovariectomy in vivo and decrease its release in human osteoblastic cells in vitro
Authors: Girasole Giuseppe , Giuliani Nicola , Modena Alberto Bacchi , Passeri Giovanni , Pedrazzoni Mario
Published: May 2003

OBJECTIVE

Interleukin‐6 (IL‐6) seems to be a key mediator of the increased bone loss that follows loss of ovarian function. Based on this and on evidence that oestrogen deficiency may also increase cell sensitivity to IL‐6, we studied the effects of ovariectomy and of oestrogen replacement therapy on the serum levels of IL‐6 and of soluble IL‐6 receptor (sIL‐6R) in vivo.

DESIGN AND PATIENTS

Thirty‐seven fertile women undergoing surgery for benign uterine diseases were divided into 3 groups and monitored for 12 months: hysterectomized women (n = 9), ovariectomized untreated women (n = 12) and ovariectomized women starting treatment with transdermal estradiol (E2, 50 μg/d) 1 month after surgery (n = 16).

RESULTS

Hysterectomy alone caused no significant changes of sIL6R whereas serum levels of sIL‐6R rose progressively after ovariectomy (mean ± SEM: 31 ± 9% and 38 ± 7% over baseline, at 6 and 12 months, respectively; P < 0.01). Oestrogen replacement therapy prevented the increase of sIL6R over a 1‐year period. A similar pattern was also found for serum IL‐6 but the changes did not reach statistical significance. In ovariectomized (OVX) women there were significant correlations between serum sIL‐6R levels and FSH (r = 0.59; P < 0.01), oestradiol (r = − 0.43; P < 0.01), testosterone (r = − 0.41; P < 0.05), osteocalcin (r = 0.42; P < 0.05) and bone alkaline phosphatase (r = 0.44; P < 0.05). To examine whether oestrogen directly regulates sIL‐6R secretion by bone cells, we studied in vitro the basal and phorbol ester (PMA) stimulated release of sIL‐6R in a human osteoblastic cell‐line (MG‐63) and in a tumour‐derived osteoclastic cell line (GCT‐51). Osteoblastic (but not osteoclastic) cells spontaneously produced considerable amounts of sIL‐6R and the protein kinase‐C activator PMA (10−8 M) increased the release of sIL‐6R by osteoblasts more than 3‐fold. More strikingly, 17β E2 (but not 17α) significantly inhibited both the spontaneous‐ and PMA‐induced release of sIL‐6R by osteoblastic cells (P < 0.05).

CONCLUSIONS

These results indicate that oestrogen loss causes alterations of the IL‐6 system, and that sIL‐6R is under the direct inhibitory control of oestrogens both in vivo and in vitro.
Effect of Whole Blood Storage on Factor VIII Recovery in Fresh Frozen Plasma and Cryoprecipitate
Authors: Allersma D.P. , Imambaks R.M.R. , Meerhof L.J.
Published: May 2003

Depending on logistics, whole blood has to be stored for several hours after collection. If storage time exceeds 8 h, storage has to be at 1–6 °C to comply with FDA regulations. In the Netherlands, however, whole blood is also stored for 12–15 h at 20–24 °C using butane‐1,4‐diol cooling devices. We compared these two storage methods for factor VIII recovery in plasma and cryoprecipitate. At laboratory scale a significantly higher factor VIII recovery was found in plasma prepared from whole blood stored at ambient temperature; in cryoprecipitate this was confirmed but differences were not significant. However, as a result of inefficient cooling in routine procedure, no significantly different factor VIII recoveries were found in plasma prepared from whole blood stored at either of the two temperatures. From our study we conclude that overnight storage of whole blood at ambient temperature using butane‐1,4‐diol cooling devices has to be favoured.
Production and Characterization ofa Reconstituted High Density Lipoprotein for Therapeutic Applications
Authors: Lerch Peter G. , Förtsch Vreni , Hodler Gerhard , Bolli Reinhard
Published: May 2003

A method is described for the large scale preparation of reconstituted high density lipoproteins (rHDL) suitable for therapeutic use. Apolipoprotein A‐I (apoA‐I) was isolated from precipitates obtained by cold ethanol fractionation of human plasma. This process includes several steps for virus removal and virus inactivation, among them pasteurization. Reconstitution of lipoprotein particles was performed by cholate dialysis using soybean phosphatidylcholine as the lipid source. An apoA‐I:lipid ratio of 1:150 (mol:mol) was obtained. Redissolved rHDLs were disc‐shaped particles resembling nascent HDL, as assessed by electron microscopy. The method was optimized for low content of free apoA‐I protein as well as the low concentration of free lipid. The product was stabilized by lyophilization in the presence of sucrose. In vitro studies show potential effects in the prevention of gram‐negative septic shock and in the inhibition of atherosclerosis.
Dr. Anthony F. H. Britten
Authors: Ala Fareydoun , Contreras Marcela
Published: May 2003

Dr Anthony Britten was the head of the blood programme of the League of Red Cross and Red Crescent Societies from 1985 to 1989 and vice chairman of the World Federation of Haemophilia. He was actively involved with Vox Sanguinis as Section Editor from 1986 to 1994 and as a very good friend of members of the Editorial Board and Foundation Vox Sanguinis. He worked ceaselessly to promote medical services for people with haemophilia, especially in developing countries where safe blood programmes did not exist. He was uniquely able to understand the medical, emotional and social needs of this population as he was born in South Africa with severe haemophilia A, at a time when almost all boys born with bleeding disorders died before they reached maturity. (Two of his uncles died in childhood.) Apart from some happy years spent at a sympathetic prep school, The Ridge, he was educated by family and tutors, for no senior school would accept the risk that such a life‐threatening condition posed.
Growth Factors and Their Impact on Transfusion Medicine
Authors: Miller Yvette M. , Klein Harvey G.
Published: May 2003

Hematopoietic growth factors, glycoproteins that stimulate self‐renewal, differentiation, and proliferation of responsive hematopoietic cells, promise to revolutionize transfusion medicine. Recombinant DNA technology has made several of these cytokines available at pharmacologic doses, and new candidate agents for clinical application appear regularly. Growth factors prescribed for patients have already reduced the requirement for red blood cell and granulocyte transfusions in selected clinical circumstances. A lineage‐specific thrombopoietin will likely limit the need for platelet transfusions. Hematopoietic cytokine injections have also been used to increase the number of red blood cells, granulocytes and circulating primitive progenitor cells in blood donors. Cytokine‐stimulated peripheral blood progenitor cell infusions have complemented and, in some instances, replaced bone marrow for adjunctive cancer chemotherapy and for bone marrow transplantation. Finally, synergistic combinations of cytokines can effect ex vivo expansion of lymphocytes and of progenitor cells to provide novel blood components. Hematopoietic growth factors are still expensive and their long‐term effects remain to be determined. However, as the biologic activities of cytokines and the physiology of hematopoietic progenitor cells become better understood, the clinical application of novel cellular components may redefine the concept of blood transfusion.
Sexual Transmission of Two Different HCV Types Causing Acute Hepatitis C
Authors: Sánchez‐Beiza Lidia , Bravo Rosa , Toribio Rafael , Navarro Silvia , Soriano Vicente
Published: May 2003

In Western countries, heterosexual transmission of hepatitis C virus (HCV) globally seems to occur in about 5% of partners of HCV‐seropositive individuals [1]. The risk increases with duration of sexual relationships [2], and male‐to‐female transmission is more efficient than vice versa [3]. Currently, little is known about the transmissibility of different HCV genotypes, although a report from Japan [4] has noted that high levels of HVC‐RNA commonly associated with HCV type 1b infection might correlate with a greater risk of transmission for this HCV subtype. Herein, we describe a case of acute hepatitis C in a young woman following transmission of HCV types 2 and 4 after having sexual contact for 1 year with a partner carrying both types.
Rh Haplotypes That Make e But Not hrB Usually Make VS
Authors: Reid Marion E. , Storry Jill R. , Issitt Peter D. , Combs Martha Rae , Beal Connie L. , Mallory Delores A. , Blancher Antoine
Published: May 2003

Background and objectives: The Rh phenotypes hrB– and VS+ are both rare in Whites but more common in Blacks. The high‐incidence antigen hrB is present on most red cells that are e+. The presence of VS on red cells is associated with an aberrant expression of e, often called eS. Materials and methods: Using conventional serologic methods, including a monoclonal anti‐hrB‐like antibody, we studied 65 e+ samples that were apparently hrB–. Results: Of the 65, we found that 59 (91%) were VS+. Recent findings have indicated that in VS+ persons a change from leucine to valine occurs at amino acid 245 of the RHCE‐encoded polypeptide. While this residue is predicted to lie within the red cell membrane bilayer, the change presumably affects alanine 226 (that is present when e is expressed) in such a way that eS is seen. Conclusions: Our findings suggest that the change from e to eS may result in nonexpression or marked depression of expression of hrB that is, perhaps, an epitope of e. While the molecular basis of the hrB– phenotype is not known, it is unlikely that the leucine‐to‐valine change at residue 245, resulting in the aberrant form of e, explains all hrB– samples. First, hrB– VS+ and hrB– VS– samples must differ. Second, some hrB– VS+ samples are C+, some are C–. Presumably diverse molecular bases are involved in hrB– phenotypes.
Gross Anatomic Organization of the Capybara's (Hydrochaeris hydrochaeris) Brachial Plexus
Authors: Fioretto E. T. , de Souza Castro M. F. , Guidi W. L. , Mainardi R. , de Souza R. R. , Ribeiro A. A. C. M.
Published: May 2003

The innervation of the capybara thoracic limb was characterized. The following nerves were observed constituting the right and left brachial plexus: n. dorsalis scapulae (C4 and C5; C4, C5 and C6) which innervates the m. serratus ventralis cervicis and m. rhomboideus; n. suprascapularis (C4, C5 and C6; C5, C6 and C7) supplying the m. supraspinatus and the m. infraspinatus; cranial and caudal nn. subscapulares (C5 and C6; C5, C6 and C7) innervating the m. subscapularis; n. axillaris (C5 and C6; C6, C7 and C8) which supplies the m. triceps brachii (caput mediale); n. radialis (C6, C7, C8 and T1; C6, C7 and C8) which innervates the m. triceps brachii (caput longum and caput mediale) and the m. extensor carpi radialis, m. extensor digitorum communis, m. extensor digitorum lateralis; n. medianus joined to the n. musculocutaneus (C6, C7, C8 and T1; C6, C7 and C8) supplying the m. biceps brachii, m. flexor carpi radialis and m. coracobrachialis; n. ulnaris (C6, C7, C8 and T1; C6, C7 and C8) leading to the m. flexor carpi radialis, the m. flexor carpi ulnaris and the m. flexor digitorum superficialis; n. thoracodorsalis (C6, C7, C8 and T1; C6, C7 and C8) supplying the m. latissimus dorsi; n. thoracicus lateralis (C8, T1; C7, C8, T1) which innervates m. pectoralis profundus (caudal portion); n. thoracicus longus (C6, C7; C7, C8) which is distributed to the m. serratus ventralis thoracis. A communication between the n. radialis and n. ulnaris was observed at the left brachial plexus.
The Origin and Course of the Greater, Lesser and Least Thoracic Splanchnic Nerves in New Zealand Rabbits
Authors: Duzler A. , Dursun N. , Cengelci A. , Cevik A.
Published: May 2003

In this study, the origin and course of the greater, lesser and least splanchnic nerves was investigated in 12 adult New Zealand rabbits with regard to sex and the side of the body. There were no significant differences between the female and male rabbits. The greater and lesser splanchnic nerves were present in all the cadavers examined. However, the least splanchnic nerve was found on the right side in 50% of the cadavers (nos. 2, 4, 6, 7, 11 and 12), and on the left side in 75% (1, 2, 4, 6, 7, 8, 9, 11 and 12). With regard to the origin and pattern of the greater, lesser and least splanchnic nerves, there were significant differences between the right and left sides of the body even in the same rabbit. No significant difference was observed between sexes.
A Study on the Morphological Structure of Syrinx in Ostriches (Struthio camelus)
Authors: Yildiz H. , Bahadir A. , Akkoç A.
Published: May 2003

The aim of this study was to investigate the topographical, anatomical and histological characteristics of syrinx in five ostriches. It was observed that the syrinx in the ostrich was tracheobronchial type and was composed of three different cartilage groups, namely tympanum, cartilagines (cartt.) tracheosyringeales and cartt. bronchosyringeales. Tympanum and cartt. tracheosyringeales were formed from three and four cartilage rings, respectively, while cartt. bronchosyringeales was formed from three C‐shaped cartilage rings. The pessulus did not contain any ossified or cartilaginous tissues and was made up of a double folded mucous membrane extending dorsoventrally from median walls of bronchus primarius into the cavum syringis.
Production and clearance of plasma triacylglycerols in ponies fed diets containing either medium‐chain triacylglycerols or soya bean oil
Authors: Hallebeek J. M. , Beynen A. C.
Published: May 2003

The hypothesis was tested that feeding ponies a diet containing medium‐chain triacylglcyerols (MCT) instead of soya bean oil causes an increase in the production of plasma triacylglycerols, which, under steady‐state conditions, is associated with an increased clearance of triacylglycerols. Six ponies were fed rations containing either MCT or an isoenergetic amount of soya bean oil according to a cross‐over design. The concentration of MCT in the total dietary dry matter was about 13%. When the ponies were fed the diets for 3 weeks, plasma triacylglycerol concentrations were 0.42 ± 0.09 and 0.17 ± 0.03 mmol/l (mean ± SE,n = 6; p < 0.05) for the MCT and soya bean‐oil treatment, respectively. Plasma triacylglycerol production was assessed using the Triton method and clearance with the use of Intralipid®infusion. Plasma triacylglycerol production was 2.91 ±  0.88 and 0.50 ± 0.14 μmol/l·min (means ± SE,n = 4; p < 0.05) for the diets containing MCT and soya bean oil, respectively. It is suggested that the calculated rates of triacylglycerol production are underestimated, the deviation being greatest when the ponies were fed the ration of soya bean oil. Triacylglycerol clearance rates were calculated on the basis of group mean values for both the fractional clearance rate and the baseline levels of plasma triacylglycerols; the values were 4.28 and 3.52 μmol/l·min for MCT and soya bean oil feeding, respectively. The mean, absolute clearance rates as based on those found in individual ponies did not show an increase when the diet with MCT was fed. Nevertheless, it is concluded that the data obtained support our hypothesis.
Amino acid, mineral and vitamin levels in hydrous faeces obtained from coprophagy‐prevented rats
Authors: Sukemori S. , Ikeda S. , Kurihara Y. , Ito S.
Published: May 2003

Amino acid, mineral and vitamin levels in hydrous faeces obtained from coprophagy‐prevented rats were examined. Two experiments were conducted with rats of different age, 4 weeks and 10 weeks. Six rats each were fed under coprophagy‐prevented and coprophagy‐allowed (conventional feeding) conditions, respectively. In the first experiment using 4‐week‐old rats, amino acid values were determined for hydrous faeces and usual faeces obtained in the above‐mentioned conditions. In the second experiment using 10‐week‐old rats, mineral values were determined for both types of faeces. Vitamin values were determined in both experiments. In a comparison of amino acid values and their patterns, specific kinds of amino acids in hydrous faeces were not recognized as growth factors. Sodium and potassium levels in hydrous faeces were significantly higher than those for usual faeces, but those levels were 1/(18–20) of those derived from feed. Although cyanocobalamin and folic acid levels in hydrous faeces were two to three times higher than those for usual faeces, folic acid supplements from coprophagy were 1/8 of those derived from feed. Cyanocobalamin supplements from hydrous faeces were five times larger than those from feed. Therefore, it appears that cyanocobalamin was supplied by the ingestion of hydrous faeces and that this cyanocobalamin supports conventional growth in rats.
A unified approach for high and low cycle fatigue based on shakedown concepts
Authors: CONSTANTINESCU A. , DANG VAN K. , MAITOURNAM M. H.
Published: May 2003

ABSTRACT The purpose of this paper is to present a unified analysis to both high and low cycle fatigue based on shakedown theories and dissipated energy. The discussion starts with a presentation of the fatigue phenomena at different scales (microscopic, mesoscopic and macroscopic) and of the main shakedown theorems. A review of the Dang Van high cycle fatigue criterion shows that this criterion is essentially based on the hypothesis of elastic shakedown and can therefore be expressed as a bounded cumulated dissipated energy. In the low cycle fatigue regime, recent results by Skelton and Charkaluk et al. show that we can speak of a plastic shakedown at both mesoscopic and macroscopic scale and of a cumulated energy bounded by the failure energy. The ideas are also justified by infrared thermography tests permitting a direct determination of the fatigue limit.
Recidivans cutaneous leishmaniasis unresponsive to liposomal amphotericin B (AmBisome®)
Authors: Gündüz Kamer , Afsar Sule , Ayhan Semin , Kandiloglu Ali Riza , Türel Aylin , Ebru Filiz Elif , Zeki Ok Ülgen
Published: May 2003

A 60‐year‐old woman with thick crusted erythematous plaques on her glabella, apex nasi and left infraorbital region was diagnosed as recidivans cutaneous leishmaniasis. The lesions were resistant to antimonial drugs. Although some response was observed on the infraorbital region, lesions on the glabella and nose continued to infiltrate despite therapy with liposomal amphotericin B.
Double‐blind clinical study reveals synergistic action between alpha‐hydroxy acid and betamethasone lotions towards topical treatment of scalp psoriasis
Authors: Kostarelos K , Teknetzis A , Lefaki I , Ioannides D , Minas A
Published: May 2003

Objective A double‐blind, single‐site, split‐face clinical study was organized and carried out in order to evaluate the efficacy, tolerability, and safety of a glycolic acid containing scalp lotion in conjunction with a betamethasone (as the 17‐valerate) scalp application against conditions of psoriasis.

Backgroundα‐hydroxy acids (AHA) have been proposed as therapeutic modalities against skin exfoliative conditions such as ichthyosis, xeroderma, and psoriasis. AHAs are hereby clinically investigated as therapeutic modalities adjuvant to corticosteroids in order to diminish systemic and topical adverse side‐effects most frequently associated with use of the latter.

Methods Twenty patients suffering from scalp psoriasis and other psoriatic conditions were included in a double‐blind, split‐face clinical study, using combinations of a 10% (w/w) glycolic acid scalp lotion, placebo lotion (excipients only), and a 0.1% (w/w) betamethasone scalp application, applied twice daily without any bandage for a period of 8 weeks. Clinical assessments were carried out by highly experienced physician evaluations based on a four‐grade scale, prior to treatment and after 2, 4, 6 and 8 weeks.

Results Improvement was observed in all cases included in the study following treatment with the 10% glycolic acid lotion. However, when equal parts of the 0.1% betamethasone lotion were combined, most of the treated sites were healed. Moreover, the duration of treatment required for healing was in this case reduced to approximately half of that needed when the glycolic acid or the betamethasone lotions were used separately for treatment.

Conclusions The present clinical study demonstrates for the first time that the effective and well tolerated therapeutic efficacy of glycolic acid scalp lotions is enhanced when used in conjunction with a 0.1% betamethasone scalp application against scalp psoriasis. This potential offers the practising dermatologist with novel treatment modes against severe skin conditions by combining topical corticosteroid with exfoliative agent therapy.
Optimized UVB treatment of psoriasis: a controlled, left‐right comparison trial
Authors: Selvaag Edgar , Caspersen Lene , Bech‐Thomsen Niels , Olivarius Frederik de Fine , Wulf Hans Christian
Published: May 2003

In a randomized, controlled, left‐right comparison study, 20 patients with chronic plaque psoriasis were treated with UVB. One side of the body received UVB in a conventional regimen with fixed dose increments, the other side was given UVB doses according to measurements of skin pigmentation. Skin pigmentation was quantified by the skin reflectance technique. The relationship between skin pigmentation and sensitivity to UV radiation was used to optimize and individualize the initial UVB exposure dose. Clinical outcome, initial, final and cumulative UVB doses, time to 50% reduction in PASI score, and side‐effects were compared. The consequence of the optimization of the UVB doses with a skin reflectance meter was that the initial UVB dose was significantly higher than in the conventional UVB regimen. PASI scoring demonstrated a more rapid improvement during the first 2 weeks of treatment on the half body receiving the optimized treatment compared to the other side (P < 0.05). This new technique offers the same therapeutical advantages and security as a dose regimen guided by minimal erythema dose testing. However, measurement of skin pigmentation by skin reflectance is a quick method which can be operated easily by nurses.
Parents' needs to talk about their experiences of childbirth
Authors: Olin Rose‐May , Faxelid Elisabeth
Published: May 2003

The purpose was to describe parents' experiences of childbirth and their views about having a postpartum talk. Questionnaires were distributed to parents (350 mothers and 343 fathers) in maternity wards in one hospital in Stockholm during a 4‐week period in 1999. Questionnaires from 251 mothers and 235 fathers were analysed. Preparation for childbirth, care received during delivery, and experiences of labour and delivery are described and analysed against whether a postpartum talk, was wanted or not. Comparisons between first‐time mothers/fathers and multiple‐time mothers/fathers were made. The results show that 66% of first‐time mothers, 74% of multiple‐time mothers, 58% of first‐time fathers, and 30% of multiple‐time fathers wanted to talk about the delivery. The issues, which the parents considered should be included in such a postpartum talk were the birth process, normal/complicated delivery, feelings of failure, pain and pain relief. Parents mainly wanted to talk to the midwife who delivered the woman and the best time for the postpartum talk seems to be at the maternity ward before discharge.
Severe postpartum distress in Icelandic mothers with difficult infants: a follow‐up study on their health care
Authors: Thome Marga
Published: May 2003

This article describes help seeking and health care of mothers with a difficult infant who suffered long‐term depressive symptoms and a high degree of parenting stress. A subsample of severely distressed mothers (n = 37) was recruited from a cross‐sectional national survey and followed up 2 months later by a semi‐structured telephone interview. The survey included all Icelandic women who gave birth during a quarter of a year and had a live baby 2 months later (n = 1053). All distressed mothers with a difficult infant were selected from sample respondents on preset scores of two self‐report distress measures. The study sample emerged during the selection process for an intervention study from which it was excluded on grounds of very high distress scores. Results showed that 5% of the surveyed population were postpartum severely distressed. Findings from this follow‐up study revealed that only one woman of four received health care for severe distress by various professionals. One woman of six received help from others. Very few women utilized the services available at Health Care Centers. About half of the women held attitudes that hindered them in seeking help and health care. It is concluded that postpartum severely distressed women receive little primary health care for mental health problems and the majority of them show little initiative to seek out for help. More active outreach by health professionals is recommended.
Cloning, expression and in vitro evaluation of recombinant canine Tum5, an angiostatic domain of mammalian type IV collagen
Authors: Mauldin G. N. , Foster T. P. , Waddell C. W. , Egan M. E.
Published: May 2003

The process of new blood vessel formation within and around neoplastic tissue, termed angiogenesis, is a significant factor in the development, progression and metastasis of malignant tumours in all species. A major cause of death in cancer patients is the development of treatment‐resistant metastatic disease, which may be avoided by therapies that target the genetically stable population of vascular endothelial cells within tumours. Tumstatin is a small protein formed by the cleavage of the alpha‐3 subunit of the non‐collagenous domain of mammalian type IV collagen. Recombinant human Tumstatin has been shown to have potent angiostatic properties in vitro and in vivo. Tumstatin is a potent initiator of apoptosis and inhibits the proliferation and migration of vascular endothelial cells in cell culture. Recently, a fragment of Tumstatin, termed Tum5, has been shown to have biologic activity similar to the parent compound. The systemic administration of angiostatic proteins like Tum5 may result in the remission of established tumours, while preventing or delaying the onset of clinically detectable metastasis.

Recombinant canine Tum5 (cTum5) was cloned and its protein expression induced in a prokaryotic vector. The resulting cTum5 protein caused dose‐dependent inhibition of vascular endothelial cells in vitro, which appears to be mediated through apoptosis.
Acetylcholine enhancement in the nucleus accumbens prevents addictive behaviors of cocaine and morphine
Authors: Hikida Takatoshi , Kitabatake Yasuji , Pastan Ira , Nakanishi Shigetada
Published: May 2003

Drug addiction poses serious social, medical, and economic problems, but effective treatments for drug addiction are still limited. Cocaine and morphine elevate dopamine levels in the nucleus accumbens (NAc), and the overwhelming actions of dopamine are implicated in reinforcement and addiction of abusive drugs. In our previous studies, we reported the regulatory role of acetylcholine (ACh) in the NAc function by selectively ablating the NAc cholinergic neurons with use of immunotoxin-mediated cell targeting. These studies indicated that ACh and dopamine acted convergently but oppositely on the NAc circuit and that cholinergic cell ablation enhanced long-lasting behavioral changes of cocaine addiction. In this investigation, we showed that immunotoxin-mediated ablation of the NAc cholinergic neurons enhanced not only the sensitivity to morphine in conditioned place preference but also negative reinforcement of morphine withdrawal in conditioned place aversion. Remarkably, acetylcholinesterase (AChE) inhibitors that act on the brain AChE suppressed both cocaine- and morphine-induced conditioned place preference and blocked the induction and persistence of cocaine-evoked hyperlocomotion. Importantly, this inhibition was abolished by ablation of the NAc cholinergic neurons. These results demonstrate that centrally active AChE inhibitors prevent long-lasting behavioral abnormalities associated with cocaine and morphine addictions by potentiating the actions of ACh released from the NAc cholinergic neurons. Centrally active AChE inhibitors could thus be approached as novel and potential therapeutic agents for drug addiction.
Binding and recognition in the assembly of an active BRCA1/BARD1 ubiquitin-ligase complex
Authors: Brzovic Peter S. , Keeffe Jennifer R. , Nishikawa Hiroyuki , Miyamoto Keiko , Fox David , Fukuda Mamoru , Ohta Tomohiko , Klevit Rachel
Published: May 2003

BRCA1 is a breast and ovarian cancer tumor suppressor protein that associates with BARD1 to form a RING/RING heterodimer. The BRCA1/BARD1 RING complex functions as an ubiquitin (Ub) ligase with activity substantially greater than individual BRCA1 or BARD1 subunits. By using NMR spectroscopy and site-directed mutagenesis, we have mapped the binding site on the BRCA1/BARD1 heterodimer for the Ub-conjugating enzyme UbcH5c. The results demonstrate that UbcH5c binds only to the BRCA1 RING domain and not the BARD1 RING. The binding interface is formed by the first and second Zn
2+
-loops and central α-helix of the BRCA1 RING domain, a region disrupted by cancer-predisposing mutations. Unexpectedly, a second Ub-conjugating enzyme, UbcH7, also interacts with the BRCA1/BARD1 complex with similar affinity, although it is not active in Ub-ligase activity assays. Thus, binding alone is not sufficient for BRCA1-dependent Ub-ligase activity.
Sexual selection affects local extinction and turnover in bird communities
Authors: Doherty Paul F. , Sorci Gabriele , Royle J. Andrew , Hines James E. , Nichols James D. , Boulinier Thierry
Published: May 2003

Predicting extinction risks has become a central goal for conservation and evolutionary biologists interested in population and community dynamics. Several factors have been put forward to explain risks of extinction, including ecological and life history characteristics of individuals. For instance, factors that affect the balance between natality and mortality can have profound effects on population persistence. Sexual selection has been identified as one such factor. Populations under strong sexual selection experience a number of costs ranging from increased predation and parasitism to enhanced sensitivity to environmental and demographic stochasticity. These findings have led to the prediction that local extinction rates should be higher for species/populations with intense sexual selection. We tested this prediction by analyzing the dynamics of natural bird communities at a continental scale over a period of 21 years (1975–1996), using relevant statistical tools. In agreement with the theoretical prediction, we found that sexual selection increased risks of local extinction (dichromatic birds had on average a 23% higher local extinction rate than monochromatic species). However, despite higher local extinction probabilities, the number of dichromatic species did not decrease over the period considered in this study. This pattern was caused by higher local turnover rates of dichromatic species, resulting in relatively stable communities for both groups of species. Our results suggest that these communities function as metacommunities, with frequent local extinctions followed by colonization. Anthropogenic factors impeding dispersal might therefore have a significant impact on the global persistence of sexually selected species.
Hydrogen-exchange stability analysis of
Bergerac
-Src homology 3 variants allows the characterization of a folding intermediate in equilibrium
Authors: Viguera Ana-Rosa , Serrano Luis
Published: May 2003

Amide hydrogen/deuterium exchange rates have been determined for two mutants of α-spectrin Src homology 3 domain (WT), containing an elongated stable (SHH) and unstable (SHA) distal loop. SHA, similarly to WT, follows a two-state transition, whereas SHH apparently folds via a three-state mechanism. Native-state amide hydrogen exchange is effective in ascribing energetic readjustments observed in kinetic experiments to species stabilized within the denatured base and distinguishing those from high-energy barrier crossings. Comparison of Δ
G
ex
and
m
ex
parameters for amide protons of these mutants demonstrates the existence of an intermediate and allows the identification of protons protected in this state. The consolidation of a form containing a prefolded long β-hairpin induces the switch to a three-state mechanism in an otherwise two-state folder. It can be inferred that the unbalanced high stability of individual elements of secondary structure in a polypeptide could ultimately complicate its folding mechanism.
Characterization of a family of endogenous neuropeptide ligands for the G protein-coupled receptors GPR7 and GPR8
Authors: Tanaka Hirokazu , Yoshida Tetsuo , Miyamoto Norimasa , Motoike Toshiyuki , Kurosu Hiroshi , Shibata Kenji , Yamanaka Akihiro , Williams S. Clay , Richardson James A. , Tsujino Natsuko , Garry Mary G. , Lerner Michael R. , King David S. , O'Dowd Brian F. , Sakurai Takeshi , Yanagisawa Masashi
Published: May 2003

GPR7 and GPR8 are orphan G protein-coupled receptors that are highly similar to each other. These receptors are expressed predominantly in brain, suggesting roles in central nervous system function. We have purified an endogenous peptide ligand for GPR7 from bovine hypothalamus extracts. This peptide, termed neuropeptide B (NPB), has a C-6-brominated tryptophan residue at the N terminus. It binds and activates human GPR7 or GPR8 with median effective concentrations (EC
50
) of 0.23 nM and 15.8 nM, respectively.
In situ
hybridization shows distinct localizations of the prepro-NPB mRNA in mouse brain, i.e., in paraventricular hypothalamic nucleus, hippocampus, and several nuclei in midbrain and brainstem. Intracerebroventricular (i.c.v.) injection of NPB in mice induces hyperphagia during the first 2 h, followed by hypophagia. Intracerebroventricular injection of NPB produces analgesia to s.c. formalin injection in rats. Through EST database searches, we identified a putative paralogous peptide. This peptide, termed neuropeptide W (NPW), also has an N-terminal tryptophan residue. Synthetic human NPW binds and activates human GPR7 or GPR8 with EC
50
values of 0.56 nM and 0.51 nM, respectively. The expression of NPW mRNA in mouse brain is confined to specific nuclei in midbrain and brainstem. These findings suggest diverse physiological functions of NPB and NPW in the central nervous system, acting as endogenous ligands on GPR7 and/or GPR8.
Adeno-associated viral transfer of opioid receptor gene to primary sensory neurons: A strategy to increase opioid antinociception
Authors: Xu Y. , Gu Y. , Xu G.-Y. , Wu P. , Li G.-W. , Huang L.-Y. M.
Published: May 2003

To develop a genetic approach for the treatment of pain, we introduced a recombinant adeno-associated viral (rAAV) vector containing the cDNA for the μ-opioid receptor (μOR) into primary afferent neurons in dorsal root ganglia (DRGs) of rats, which resulted in a long-lasting (>6 months) increase in μOR expression in DRG neurons. The increase greatly potentiated the antinociceptive effects of morphine in rAAV-μOR-infected rats with and without inflammation. Perforated patch recordings indicated that the efficacy and potency of opioid inhibition of voltage-dependent Ca
2+
channels were enhanced in infected neurons, which may underlie the increase in opiate efficacy. These data suggest that transfer of opioid receptor genes into DRG cells with rAAV vectors may offer a new therapeutic strategy for pain management.