A study was undertaken in man to investigate whether during moderate cold stress, the proportion of carbohydrate (CHO) oxidized is increased, and whether prior prolonged exhaustive exercise compromises thermoregulation. Eight euglycaemic men were cooled by a liquid-conditioned suit (1) after an overnight fast (Con) and (2) [similar]2 h after an exercise protocol in which CHO availability was substantially lowered (Post-Ex). The cooling stimulus lasted 90 min (Cooling) and was preceded by a 30 min thermo-neutral baseline phase (Base). In Con, aural temperature (Taural) and the rate of CHO oxidized (CHOox) were not altered from the values at Base during Cooling, whereas the following were increased: the rate of heat production (Hprod, [similar]1·9-fold), thigh electromyographical activity (EMG, [similar]2·5-fold), and the rate of fat oxidized (FATox, [similar]1·7-fold). In Post-Ex, Taural did not decrease from the value at Base during Cooling, and compared with Con, EMG, CHOox and the rate of heat loss were not different, whereas Hprod (P [less than or equal to] 0·01), FATox (P [less than or equal to] 0·01) and mean skin temperature (P [less than or equal to] 0·01) were higher, and Taural was lower (P [less than or equal to] 0·05). It is concluded that during moderate cold stress, shivering thermogenesis is supported by an increase in the oxidation of fat, and despite an alteration in the initial thermoregulatory responses to Cooling [similar]2 h after exhaustive exercise, thermoregulation was not impaired.

The properties are discussed of system y+L, a broad scope amino acid transporter which was first identified in human erythrocytes. System y+L exhibits two distinctive properties: (a) it can bind and translocate cationic and neutral amino acids, and (b) its specificity varies depending on the ionic composition of the medium. In Na+ medium, the half-saturation constant for L-lysine influx was 9·5 ± 0·67 µM and the inhibition constant (Ki) for L-leucine was 10·7 ± 0·72 µM. L-Leucine is the neutral amino acid that binds more powerfully, whereas smaller analogues, such as L-alanine and L-serine interact less strongly (the corresponding inhibition constants were Ki,Ala, 0·62 ± 0·11 mM; Ki,Ser, 0·49 ± 0·08 mM). In the presence of K+, the carrier functions as a cationic amino acid specific carrier, but Li+ is able to substitute for Na+ facilitating neutral amino acid binding. The effect of the inorganic cations is restricted to the recognition of neutral amino acids; translocation occurs at similar rates in the presence of Na+, K+ and Li+. The only structural feature that appears to impair translocation is bulkiness and substrates with half-saturation constants differing by more than 100-fold translocate at the same rate. This suggests that translocation is largely independent of the forces of interaction between the substrate and the carrier site. System y+L activity has been observed in Xenopuslaevis oocytes injected with the cRNA for the heavy chain of the 4F2 human surface antigen. 4F2hc is an integral membrane protein with a single putative membrane-spanning domain and it remains to be clarified whether it is part of the transporter or an activator protein.

The autonomic control of submandibular secretion has been investigated in fully weaned, anaesthetized calves 7 weeks after birth. Stimulation of the parasympathetic (chorda-lingual) innervation invariably produced a flow of saliva, the rate of which was frequency dependent over the range 2-8 Hz continuously. Neither the rate of flow nor the output of protein was enhanced by stimulating in bursts at relatively high frequencies. Stimulation of the sympathetic innervation (20 Hz for 1 s at 10 s intervals) alone produced a much slower flow of saliva but with a considerably higher protein content. Stimulation of both together produced no greater flow of saliva than occurred with either alone at the lower frequencies (2 and 4 Hz) but there was a pronounced synergy in respect of the secretion of protein. Following pre-treatment with propranolol (1·0 mg kg-1 I.V.), during on-going chorda-lingual stimulation at 4 Hz, intra-arterial injections of 1 nmol of either vasoactive intestinal peptide (VIP) or pituitary adenylate cyclase activating peptide (PACAP) elicited an increase in the flow and protein output of about the same order of magnitude. Calcitonin gene-related peptide (CGRP) also produced these same effects with roughly half the efficacy of VIP and PACAP but substance P had no detectable effect. It is concluded that VIP, PACAP and possibly CGRP are candidates for neurotransmitters with a role in the control of secretion in this gland.

The present study was planned to investigate the effect of left ventricular pressure and inotropic state on coronary arterial inflow in systole in the anaesthetized dog. A wide range of left ventricular systolic pressures, including the physiological range, were studied. Experiments were done under conditions of maximal vasodilatation and low perfusion pressure in order to avoid vascular autoregulative interference and to keep the microvascular pressure within the normal range. In five anaesthetized dogs, perfused with extracorporeal circulation system, ventricular volume was changed from 20 to 50 ml in steps of 10 ml by filling an intraventricular latex balloon, and the related changes in left ventricular pressure and coronary flow were measured. The volume was then extended to 70 ml to obtain an overstretch which induced a transient decrease in cardiac contractility. During the period of low cardiac contractility the volume was brought back to 20 ml in steps of 10 ml. Systolic ventricular pressure changed with volume but was lower during the period of low contractility. For systolic pressures below 100 mmHg there was no significant relationship between pressure and coronary systolic flow, but the relationship shifted to higher flows during low contractility. For systolic pressures above 100 mmHg systolic coronary flow decreased significantly when systolic pressure increased. In this case the slopes of the relationships were not significantly different before and after the reduction in contractility. These findings suggest that for systolic pressures less than 100 mmHg (i.e. below the physiological range) the shielding effect of the contracting ventricle prevents the ventricular pressure from being transmitted in the myocardial wall. When systolic pressure exceeds 100 mmHg the shielding effect is overcome and the amplitude of the systolic flow reduction varies with ventricular pressure.

Electromanometric recordings of caecal pressures were made in chronically cannulated ponies. Endoscopy allowed direct observation of the caecal base and cupola while recording intracaecal pressures and enabled a functional interpretation of caecal pressure profiles. Using gas-tight seals, the caecal gas cap baseline pressure (tone) was usually below atmosphere, becoming less negative postprandially. Diurnal variations were observed in the amplitude and frequency of caecal pressure profiles and the direction of caecal movements, during which intra-caecal gas cap pressures briefly became positive. A paraprandial (psychic) phase of enhanced caecal motility was observed. Manipulation of the caecal gas cap volume, by insufflation of nitrogen gas, demonstrated the capacity of the caecal base to regulate gas pressures and to eliminate fermenting gases.

Most cancer deaths result from the cancer either being intrinsically resistant to chemotherapeutic drugs, or becoming resistant after being initially sensitive (Leyland-Jones, Dalton, Fisher & Sikic, 1993). Often, in cells grown in cell culture, drug resistance correlates with the presence of one or more of the so-called P-glycoproteins or multidrug resistance (MDR) proteins, products of the mdr family of genes (Endicott & Ling, 1989). The mdr genes (with two forms in humans (MDR1 and MDR2), and three (mdr1, mdr2 and mdr3) in mice and hamsters) have been cloned, sequenced (Gros, Croop & Housman, 1986) and shown to be members of the 'ABC' (ATP binding cassette) or 'traffic ATPase' superfamily (Doige & Ames, 1993). All members of this superfamily (which includes the CFTR chloride ion channel, the product of the STE6 gene in yeast that transports the [alpha]-mating factor polypeptide, bacterial protein translocator HlyB that exports haemolysin, and many bacterial permeases) have a membrane transport function and share homologous sequences that often bind ATP (Kane, Pastan, Gottesman, 1990; Gros & Buschman, 1993) and can hydrolyse it. Human MDR1 and mouse mdr1 and mdr3 (Tang-Wai, Kajiji, Dicapua, de Graaf, Roninson & Gros, 1995) confer multidrug resistance, while human MDR2 and mouse mdr2 transport phosphatidylcholine and function as lipid translocases (Smit et al. 1993). The genes have tandem repeated structures, each coding for polypeptide sequences which putatively straddle the membrane six times, and each containing an ATP-binding region. The MDR genes code for glycoproteins of molecular weight 150000-180000. In drug-resistant cells, the genes are generally present as multiple repeats on episomes. Some clinical studies show that expression of the MDR1 gene is enhanced in drug-resistant tumours in patients and that this expression is a good predictor of resistance (Chan et al. 1991).Expression of the mdr genes is associated with a greatly increased resistance to the killing action of many cytotoxic drugs (Biedler & Riehm, 1970; Johnson, Chitnis, Embrey & Gregory, 1978). It brings about a marked (up to fiftyfold) reduction in the cellular steady-state level of its numerous 'substrates' (Dano, 1973; Inaba, Kobayashi, Sakurai & Johnson, 1979; Fojo, Akiyama, Gottesman & Pastan, 1985) which are fairly hydrophobic compounds but possess also some hydrophilicity. Many of these substrates are weak bases. Some bear permanent positive charges (Lampidis et al. 1989), but zwitterions seem not to be substrates. The MDR protein transports such drugs actively out of the cells in which the mdr gene is expressed (Lankelma, Spoelstra, Dekker & Broxterman, 1990; Dordal, Winter & Atkinson, 1992), that is, it is a drug pump. The protein can be present in as many as 8 × 105 (Sehested, Simpson, Skovsgaard & Jesnsen, 1989; Demant, Sehested & Jensen, 1990) or even 3 × 106 (Shapiro & Ling, 1994) copies per cell. Resistance is reversed by numerous compounds, termed 'reversers', 'modulators', or 'chemo-sensitizers' (e.g. verapamil; Tsuruo, Iida, Yamashiro, Tsukagoshi & Sakurai, 1982) and also by other MDR substrates (Horio, Lovelace, Pastan & Gottesman, 1991). P-glycoprotein has been isolated from cell membranes and demonstrated to be an ATPase, with a turnover number of some 25 s-1 at 37¡C (Ambudkar, Lelong, Zhang, Cardarelli, Gottesman & Pastan, 1992; Urbatsch, Al-Shawi & Senior, 1994; Sharom, Yu, Chu & Doige, 1995). P-glycoprotein is often present in tissues and at tissue surfaces that transport water and nutrients (kidney, gut, the blood-brain barrier; Thiebaut, Tsuruo, Hamada, Gottesman, Pastan & Willingham, 1987; Lum & Gosland, 1995), but is also present in the pancreas.What might be the physiological role of the P-glycoproteins? It was early suggested that they may be concerned in the protection of the organism from toxic, perhaps mutagenic, xenobiotic substances (Gottesman & Pastan, 1988). Their appearance in cytotoxin-resistant tumours would be an example of the ectopic expression of genes that is so often encountered in tumours. P-glycoprotein thus acts as a double-edged sword, protecting its wielder in most situations, at the expense of aiding in his or her destruction when tumours have already developed (Gottesman & Pastan, 1988). Studies using animals in which one or other mdr gene has been knocked out have thrown light on the matter. Thus, Schinkel et al. (1994), in an elegant study using mice with a knock-out mutation in the mdr1A gene, have shown that the P-glycoprotein is a major component of the blood-brain barrier, ensuring that lipid-soluble toxins (ivermectin, for example) are pumped out of the brain tissues across that barrier, protecting the organism against brain damage. P-glycoprotein acts also to keep intracellular drug concentrations low in a number of other body tissues. Blocking P-glycoprotein using knock-out mice (Schinkel et al. 1994) or by the addition of reversers of P-glycoprotein (Lyubimov, Lan, Pashinsky, Ayesh & Stein, 1995) leads to a significant rise in the tissue content of vinblastine. The tissues in which P-glycoprotein brings about a reduced concentration of cytotoxin are, in many cases, just those that are intrinsically resistant to chemotherapy by cytotoxins (Lum & Gosland, 1995).There is no fully accepted model for the mechanism of action of this important molecule. There is much evidence that P-glycoprotein behaves quite differently from conventional membrane pumps. The 'vacuum cleaner' model (Raviv, Pollard, Bruggemann, Pastan & Gottesman, 1990), in which P-glycoprotein is a machine that cleans its substrates out of the plasma membrane, and delivers them to the exterior aqueous phase, provides an intriguing general framework for discussion of the pump's action and is the basic standpoint of this paper.

Chewing and acid on the tongue evoked a flow of saliva from the duct-cannulated parotid gland of the conscious rat despite pretreatment with atropine and adrenoceptor antagonists. This non-adrenergic, non-cholinergic (NANC) response depended on an intact parasympathetic innervation and was abolished by a tachykinin antagonist. The present findings are consistent with a physiological role for the secretory NANC mechanisms of the salivary glands.

For moderate work rates (i.e. below the lactate threshold, [theta]L), oxygen uptake ([Vdot]O2) approaches the steady state mono-exponentially. At higher work rates, the [Vdot]O2 kinetics are more complex, reflecting the delayed superimposition of an additional, slow component. The mechanisms of this ‘slow’ component are poorly understood. It has been demonstrated, however, that while a prior bout of supra-[theta]L cycling (with a 6 min recovery) does not significantly affect the [Vdot]O2 time course for a subsequent sub-[theta]L bout, it significantly speeds the [Vdot]O2 response to a subsequent supra-[theta]L bout (Gausche, Harmon, Lamarra & Whipp, 1989; Gerbino, Ward & Whipp, 1996). These investigators proposed that this speeding was a result of improved muscle perfusion during the exercise transient, possibly related to the residual metabolic acidaemia still present at the start of the subsequent exercise bout. To determine whether speeding of the [Vdot]O2 kinetics could also be induced by a bout of prior high-intensity exercise performed at a remote site (e.g. the arms), subjects each performed two 6 min bouts of high-intensity cycling (leg exercise: LE) at a work rate equivalent to 50 % of ‘[Delta]LE’ (the difference between maximum [Vdot]O2,LE and [theta]L,LE). On one occasion this was preceded by a 6 min period of cycling at 50 % [Delta]LE and, on another, by a similar period of arm-crank exercise (arm exercise: AE) at 50 % [Delta]AE; in each case, the work bouts were separated by 6 min of unloaded pedalling. Pulmonary gas exchange variables were derived breath-by-breath. During unloaded pedalling and at minute 6 of each work bout, arterialized venous blood samples were drawn from the dorsum of the heated hand or at the wrist for analysis of pH, lactate, pyruvate, noradrenaline (NAdr), adrenaline (Adr), and potassium (K+). The difference in [Vdot]O2 between minute 6 and 3 of each work bout ([Delta][Vdot]O2,[6-3]) and the 'partial' O2 deficit (O2 Def) provided indices of the slow phase of [Vdot]O2 kinetics. The initial AE and LE bouts resulted in similar degrees of metabolic (lactic) acidaemia; the residual acidaemia at the end of the subsequent 6 min recovery phase was also similar for the two protocols, as were [K+], [Adr] and [NAdr]. The subsequent LE bouts were associated with reductions in both [Delta][Vdot]O2,[6-3] and O2 Def, relative to control, with the effect being more marked when the work was preceded by a prior LE bout than a prior AE bout: [Delta][Vdot]O2,[6-3] averaging 32 and 56 % of control, respectively, and O2 Def 71 and 81 %. Consequently, the increase in [lactate] and decrease in pH induced in this second LE bout were smaller when preceded by prior leg exercise than prior arm exercise. It is therefore concluded that while metabolic acidaemia induced at a site remote from the legs is associated with a less prominent slow phase of the [Vdot]O2 kinetics for high-intensity leg exercise, a component specific to the involved contractile units appears to exert the dominant effect. The mechanisms underlying this response are, however, presently uncertain.

The mechanism by which pulmonary blood flow increases and pulmonary vascular resistance decreases after birth is not fully understood. The aim of this study was to simulate the decrease in lung volume caused by the onset of air-breathing at birth and determine whether it can duplicate the changes in pulmonary blood flow and vascular resistance that occur at this time. In chronically catheterized fetal sheep near term (145 days of gestation), fetal pulmonary arterial blood flow was measured, using coloured microspheres, before and after fetal lung liquid volumes were reduced from 52·2 ± 2·7 to 21·2 ± 1·6 ml kg-1. During the 30 min period following the reduction in lung liquid volume, the pulmonary-to-systemic arterial pressure difference decreased from 6·8 ± 1·2 mmHg (pulmonary > systemic) to 1·6 ± 0·5 mmHg. Reducing the volume of fetal lung liquid increased pulmonary blood flow from 59·1 ± 10·5 to 204·2 ± 40·4 ml min-1 (100 g tissue)-1 and reduced pulmonary vascular resistance from 0·53 ± 0·20 to 0·14 ± 0·04 mmHg min ml-1 (100 g tissue)-1. We conclude that a reduction in fetal lung liquid volume, which simulates the reduction in lung volume that occurs at birth, causes a 3- to 4-fold increase in pulmonary blood flow and a reduction in pulmonary vascular resistance of a similar magnitude. Thus, the reduction in lung volume associated with the lung changing from a liquid- to an air-filled organ, may partly account for the increase in pulmonary blood flow and decrease in pulmonary vascular resistance at birth.

The neurohypophysial hormone vasopressin contributes to control of urine output and, while urine flow shows a clear daily rhythm, there has been debate as to whether this is true of neurohypophysial hormones. A study was performed on fifteen adult males, with a mean age of 25 years, over a 24 h period, nine blood samples being taken at regular intervals for the determination of neurohypophysial hormones and indices of fluid balance. Samples were taken via an indwelling cannula so that sleep was undisturbed. A daily variation in the plasma concentrations of oxytocin and vasopressin was demonstrated with concentrations reaching a nadir in the late afternoon. Concentrations of both hormones peaked at 02.00 h. Vasopressin concentrations were inversely correlated with packed cell volume, indicating that the altered hormone release was affecting fluid retention. Consistent with this was the observation that the relationship of plasma osmolality to vasopressin depended on the time of day. To determine the effect of ageing, a similar study was performed on nine healthy elderly subjects with a mean age of 70 years. The nocturnal peak of vasopressin was markedly attenuated, while oxytocin release was similar to that in the younger group. These observations confirm the existence of a daily rhythm in the plasma concentrations of neurohypophysial hormones and indicate that the amplitude of the vasopressin change decreases with age.

The effect of anaesthetics on the relation between local cerebral blood flow (rCBF) and extracellular glucose was studied in rat striatum. Cerebral blood flow was measured using the hydrogen clearance method and extracellular glucose using an implanted glucose oxidase-based biosensor. Rats were given an intraperitoneal (I.P.) injection of either sodium pentobarbitone (60 mg kg-1) or chloral hydrate (350 mg kg-1). The effect of the I.P. injection, as demonstrated by an I.P. saline injection, was a brief increase in rCBF accompanied by a decrease in glucose. Sodium pentobarbitone produced a decrease in both rCBF and glucose, whereas chloral hydrate caused a decrease in glucose but an increase in rCBF. These findings show a dissociation between rCBF and extracellular glucose and suggest that glucose in the extracellular compartment is not derived directly from the blood vascular compartment.

A stress protocol - 6 h of daily immobilization - was applied throughout male rat sexual development. Immobilization caused a small reduction in food intake and body weight gain whereas pair-fed animals had a marginal decrease only in body weight gain. Stress, confirmed by increased plasma adrenocorticotrophic hormone (ACTH) and corticosterone, caused a decrease in plasma luteinizing hormone (LH) after 15 and 60 days of immobilization and in plasma testosterone after 60 days, but produced an opposite androgenic response in pubertal animals (15 days of immobilization). A presumed sympathetic over-stimulation is suggested to account for increased testosterone levels in pubertal stressed rats.

I am still puzzling over such questions as to what is the largest object caught in a spider's web and what are the limitations to building larger webs? Or, what might be the selective forces that have operated on the evolution of aglomerular kidneys that has occurred in a few marine teleost species? These are just a couple of the thought-provoking questions that are posed liberally throughout the latest (4th) edition of Eckert's Animal Physiology that has been revised by Randall, Burggren and French. For those students and teachers who found the earlier editions of this book instructional and a valuable resource, its extensive revision and expansion will be received with enthusiasm. The authors have produced an excellent textbook of animal physiology. The animal kingdom is so diverse, one wonders how such a book can be confined to 700 pages. The aim of the authors has been to carefully elucidate the general physiological principles and physico-chemical laws which govern all forms of animal life and then to illustrate these laws with examples of adaptations drawn from a wide range of organisms. This aim has been largely fulfilled and the authors are to be congratulated on their revision.

During prolonged exercise in a cold environment, fatigue is generally associated with a depletion of endogenous glycogen stores. This has lead many authors to hypothesize that the carbohydrate (CHO) content of fluids ingested in cool environments should be high, yet this hypothesis has not been specifically examined. In the present study, six healthy males cycled to exhaustion at approximately 80 % of their maximum oxygen consumption ([Vdot]O2,max) with either no drink (ND), a 15 % CHO-electrolyte drink (15 % CHO) or a 2 % CHO-electrolyte drink (2 % CHO). Dietary intake and exercise were replicated 2 days prior to each trial. Mean (S.D.) ambient temperature was 10·0 (0·3)°C with a relative humidity of 72 (2) % and an air velocity of approximately 0·7 m s-1 on all trials. Weighted mean skin temperature was calculated, and rectal temperature and heart rate were recorded at rest, during exercise and at exhaustion. Venous samples were drawn before and during exercise and at exhaustion for determination of haemoglobin, haematocrit, blood metabolites and serum electrolytes and osmolality. Expired air was collected for calculation of [Vdot]O2 and respiratory exchange ratio which were used to estimate rates of fuel oxidation. Ratings of perceived exertion (RPE) were also obtained. Exercise capacity was not different (P = 0·49) between trials, with median (range) times to exhaustion of 90·6 (66·8-106·0), 97·7 (60·9-112·0) and 102·0 (77·1-170·7) min for the ND, 15 % CHO and 2 % CHO trials, respectively. The 15 % CHO drink significantly (P < 0·05) elevated blood glucose concentration and total CHO oxidation compared with the ND trial. The 2 % CHO drink significantly (P < 0·05) reduced the estimated change in plasma volume and resulted in a lower serum osmolality than the other two trials. No differences were observed in any thermoregulatory or cardiorespiratory responses between trials. These data suggest that maintenance of blood-borne substrate and/or plasma volume does not influence exercise capacity in the cold, as is commonly reported during this type and intensity of exercise in warmer environments.

The present study examined the hypothesis that the antagonistic ankle dorsiflexor coactivation level during maximum isometric voluntary plantarflexion (MVC) is a function of ankle angle. Six male subjects generated plantarflexion and dorsiflexion MVC trials at ankle angles of -15 deg (dorsiflexed direction), 0 deg (neutral position), +15 deg (plantarflexed direction) and +30 deg having the knee flexed at an angle of 90 deg. In all contractions surface EMG measurements were taken from tibialis anterior and soleus which were considered representative muscles of all dorsiflexors and plantarflexors, respectively. Antagonistic dorsiflexor coactivation was expressed as normalized EMG and moment. Calculations of the antagonistic dorsiflexor moment were based on the tibialis anterior EMG-dorsiflexor moment relationship from contractions at 50, 40, 30, 20 and 10 % of the dorsiflexion MVC moment. In both legs dorsiflexor coactivation level followed an open U-shaped pattern as a function of ankle angle. Differences of 9 and 14 % (P < 0·05) were found in the measured net plantarflexion MVC moment between legs at ankle angles of -15 and +30 deg, respectively. No difference (P > 0·05) was found in the calf circumference between legs. Differences were found in the antagonistic dorsiflexor coactivation between legs at ankle angles of -15 and +30 deg. In the weaker leg the antagonistic EMG measurements were higher by 100 and 45 % (P < 0·01) and the estimated antagonistic moments were higher by 70 and 43 % (P < 0·01) compared with the weaker leg at -15 and +30 deg, respectively. This finding was associated with a decreased range of motion (ROM) in the weaker leg (14 %, P < 0·01), such that no difference (P > 0·05) was found in dorsiflexor antagonistic coactivation between legs at end-range ankle angles. The findings of the study (i) have to be taken into consideration when estimating musculoskeletal loads in the lower extremity, (ii) imply that stretching training can result in a stronger plantarflexion at end-range ankle angles through inhibition of the dorsiflexors, and (iii) imply a neural drive inadequacy during a plantarflexion MVC at end-range angles.

The control of self-initiated falls from different heights was studied. The objective of the study was to investigate in a quantitative manner the modulation of EMG timing (i.e. onset from take-off and duration from onset to touch-down) and amplitude (before and after foot contact) as a function of fall height. The muscles studied were m. soleus and m. tibialis anterior. Kinematic (ankle joint angle) and kinetic (ground reaction force) variables were also measured. Six subjects took part in the experiments that consisted of ten landings from each of five heights (0·2, 0·4, 0·6, 0·8 and 1 m) onto a force platform. We found a consistent pattern of co-contraction before and after touch-down across the fall heights studied. In both muscles, the onset of pre-landing EMG activity occurred at a longer latency following take-off when landing from greater heights. The absolute EMG duration was affected to a lesser extent by increasing fall height. These findings suggest that the onset of muscle activity of the muscles studied prior to foot contact is timed relative to the expected time of foot contact. Pre- and post-landing EMG amplitude tended to increase with height. Despite a doubling in the magnitude of ground reaction force, the amplitude of ankle joint rotation caused by the impact remained constant across heights. These findings suggest that the observed pattern of co-contraction is responsible for increasing ankle joint stiffness as fall height is increased. The attainment of an appropriate level of EMG amplitude seems to be controlled by (a) timing muscle activation at a latency timed from the expected instant of foot contact and (b) varying the rate at which EMG builds up.

This is the fourth in a series of texts on fetal physiology and the changes occurring during the transitional period from intra- to extra-uterine life, a most critical and dangerous period in human life. The volumes in the series are each devoted to a particular system, the previous three volumes being devoted to the crucial areas of circulation, respiration and growth. The fourth volume follows the established format, considering first fetal development and perinatal changes, then pathophysiology and finally applying the information to clinical conditions. There is emphasis on the importance of basic research and animal models to clinical practice. The text therefore will appeal to a wide audience from undergraduate students of the basic sciences to clinicians working in the field of neonatal medicine. It is well presented and, in general, well illustrated.There are major differences in fluid balance between the fetus and adult. Apart from the fact that the fetus develops in a fluid environment, the tissues have a higher water content and overall the fluid shifts are greater. The text opens with a summary of the developmental stages of the kidney and the development of functional characteristics, in particular the endocrine function of the kidney and renally active hormones. Areas of current interest are highlighted including the ontogeny and regulation of water channels. Dynamics of fluid balance and the importance of the lymphatic system, fetal swallowing and exchange with amniotic fluid are considered in the next three chapters. More might have been said of transplacental flow and the altered fluid status of the mother. The section on basic physiology closes with a useful review of the changes in renal function observed at birth.The next section, that on pathophysiology, considers abnormalities in renal development whether as a result of congenital abnormalities, renal agenesis and obstructive uropathies or as a result of fetal growth retardation. The final chapter of this section is devoted to hydrops fetalis, a pathological increase of interstitial and total fetal body water. The many possible causes are reviewed.The final, clinical section centres on a detailed consideration of the management and correction of obstructive uropathies, fetal oedema, oligohydramnios and polyhydramnios. The relative advantages and disadvantages of available diagnostic and therapeutic interventions are comprehensively covered. The final chapter on management of postnatal disorders brings together many of the themes developed in earlier sections.This multiauthored book employs a wide range of expertise and presents critical consideration not found in standard texts. This fact, together with the focus on both basic science and practical aspects of fetal and neonatal medicine, makes the text a valuable source of reference. The production of a series of separate volumes rather than a single comprehensive text has resulted in relatively rapid publication with references up to 1996 being cited.

Using microdialysis, we measured nitric oxide (NO) levels in healthy human skin, in vivo, before and during the local inflammatory response to histamine. Basal dialysate NO concentration, assayed using an amperometric technique, was 0·49 ± 0·06 µM (mean ± S.E.M., 21 probes, 14 subjects). Histamine injection produced transient increases in NO concentration within both the weal and flare which was blocked by the NO synthase inhibitor, NG-nitro-L-arginine-methyl ester (L-NAME). Dialysate NO concentration also increased following transdermal delivery of the nitrosovasodilator, glyceryl trinitrate. Thus, using microdialysis, it is possible to quantify NO production in human skin in vivo and study its modulation during the acute inflammatory response.

It has been suggested that the glucose transport system of human erythrocytes contains an arginine shield to prevent the leak of potassium through the transporter. To investigate this suggestion we treated human erythrocytes with the specific arginine reagent 1,2-cyclohexanedione. Under conditions which produce a covalent reaction between arginine and the reagent, a steady leak of potassium occurs. If glucose, maltose or the inhibitor phloretin are present during the reaction the extent of the leak is reduced. These findings support the view that arginines have a role in preventing potassium loss through the glucose transporter.

This is a long awaited update of a much loved text, first produced in 1976. Bentley has retained a very successful format considering structures, actions and physiological roles of hormones across the vertebrate series. The evolution and origins of hormones and their receptors is discussed in the context of their contribution to major body systems and the ecology and evolutionary development of key vertebrate groups. In this way the integrative functions of hormones are examined in major body systems including nutrition, reproduction, osmoregulation, calcium homeostasis and in relation to animal colouration, moulting and development. Species considered range from representatives of lower chordates through the major fish groups to tetrapods including mammals.