bluuebunny/crossref_metadata_2025 huggingface dataset:
The Postnatal Development of Tail‐Flick Latencies to Acute and Repeated Stimulation in the Rat
Authors: Hassmannová Jarmila , Rokyta Richard
Published: February 2003

The development of the reaction to thermal nociceptive stimulation was studied in neonatal rats of two strains (albino Wistar and pigmented Long‐Evans). Using the tail‐flick method in neonates of both strains the effects of daily repeated thermal stimulation (sensitisation) were compared to those of acute stimulation applied on 1 day only. During the whole postnatal development period studied (3‐28 days) the pigmented rat pups were more sensitive to a repeated thermal nociceptive stimulation than the albinos. The latency of the response did not change linearly during the developmental time studied, but had a pronounced peak (decreased sensitivity) in the period of eye‐lid opening. In the pigmented animals the peak appeared 1 day earlier than in the albinos. At the time of the weaning period the latencies of the response were again shorter.
Influence of Ageing on the Fatigability of Isolated Mouse Skeletal Muscles from Mature and Aged Mice
Authors: de Paula Brotto Marco A. , Nosek Thomas M. , Kolbeck Ralph C.
Published: February 2003

We investigated the influence of ageing on the fatiguing characteristics of the mouse extensor digitorum longus (EDL) muscle as compared to those of the soleus muscle. Fatigue was produced by an intermittent stimulation protocol. We report for mature and aged animals the effects of fatigue on force produced during stimulation patterns that in non‐fatigued muscle gave maximum force (Tmax, high frequency stimulation) and approximately half‐maximum force (1/2Tmax, low frequency stimulation). In 15‐month‐old (mature) mice, fatiguing stimulation decreased Tmax in EDL and soleus muscle to 10.3 ± 1.0% and 33.4 ± 3.0% of control, respectively. In 30‐month‐old (aged) mice, the decrease in Tmax in EDL and soleus was statistically equal to that of the younger animals. Fatiguing stimulation decreased 1/2Tmax in EDL and soleus from 15‐month‐old animals to 22.5 ± 2.9% and 45.7 ± 0.3% of control, respectively. In 30‐month‐old animals, the 1/2Tmax in EDL and soleus muscle decreased to 18.2 ± 1.3% and 35.0 ± 3.6% of control, respectively. Under all conditions, the soleus fatigued significantly less. Contractile recovery from fatiguing stimulation was complete for the soleus in both age groups after 30 min, but incomplete for the EDL. The 1/2Tmax/Tmax ratio significantly increased in EDL and soleus muscle from 15‐month‐old animals after fatiguing stimulation. This increase was less significant in EDL, and absent in soleus muscle, from 30‐month‐old animals. These results indicate that fatiguing stimulation induces a leftward shift in the force‐frequency relationship in the young animals; this shift is either significantly less (EDL) or absent (soleus) in the older animals. We speculate that the leftward shift of the force‐frequency relationship may reflect a protective mechanism in younger animals against some of the damaging effects of fatiguing stimulation (i.e. oxidative stress).
Spermine Induces Precocious Development of the Spleen in Mice
Authors: Jolois O. , Peulen O. , Collin S. , Simons M. , Dandrifosse G. , Heinen E.
Published: February 2003

Spermine is a low molecular weight polyamine involved in the postnatal maturation of the gut. When it is administered orally to suckling rats, it induces maturation of the intestinal tract (liver, pancreas and small intestine). Here we show that this polyamine is able to induce precocious intestinal and splenic development in suckling mice. In fact, in 15‐day‐old mice which had received spermine orally twice daily for 3 days we observed an increase in the ratio of white pulp surface to total spleen surface in comparison with untreated mice. The two macrophage subsets of the marginal zone and the B‐cell population were more developed and reached the development level of 5‐ or 10‐week‐old mice. The proliferation rate of B‐cells was increased by spermine administration to pups. These observations suggest that spermine might play a role in immune system development; further investigation of its effects are intended, namely the evaluation of its capacity to enhance defence during the neonatal period.
Hypoxia and Expression of Vegf‐A Protein in Relation to Capillary Growth in Electrically Stimulated Rat and Rabbit Skeletal Muscles
Authors: Hudlicka O. , Milkiewicz M. , Cotter M. A. , Brown M. D.
Published: February 2003

To investigate the role of hypoxia as a stimulus to the early upregulation of vascular endothelial growth factor (VEGF) in fast skeletal muscles during chronic low frequency stimulation, blood flow, oxygen consumption, VEGF expression and capillary:fibre ratio were measured in chronically stimulated tibialis anterior and extensor digitorum longus (EDL) muscles in rabbits and rats. No differences were found in blood flow, oxygen consumption and extraction between rabbit muscles stimulated for 2 or 4 days (8 h on‐16 h off) and controls. Muscle PO2 polarographically measured immediately at the end of stimulation on day 2 was also no different from control under resting conditions (10.7 ± 1.6 vs. 9.5 ± 1.2 Torr, n.s.). Unlike control muscles, however, PO2 in 2 day stimulated muscles did not increase immediately after a further acute bout of contractions. This difference was not apparent after similar acute contractions in 4 day stimulated muscles. The involvement of VEGF in early angiogenesis in stimulated muscles was studied in serial cryosections of rat EDL. The proportion of capillaries positively immunostained for VEGF increased from 25 ± 1% to 40 ± 1% (P < 0.05) in muscles removed on day 2 immediately at the end of chronic stimulation; it decreased slightly after 16 h rest, and increased again after 4 days of stimulation. Capillary:fibre ratio was unchanged throughout the experiment. Capillary cell proliferation increased only after the rest period on day 2 (20‐fold increase) and day 4 (12‐fold increase), indicating angiogenesis in progress. Thus the timing of transient hypoxia and increase in capillary‐linked VEGF in stimulated muscles, albeit in different species, was similar, and increased VEGF staining and capillary cell proliferation occurred even after the hypoxia had resolved. This suggests (1) a connection between hypoxia and VEGF during the early stages of stimulation, although ensuing capillary proliferation may thereafter rapidly correct for local hypoxia, and (2) that the subsequent angiogenesis and VEGF expression are dependent on factors other than hypoxia.
Route of Administration Differentially Affects Fevers Induced by Gram‐Negative and Gram‐Positive Pyrogens in Rabbits
Authors: Cartmell T. , Mitchell D. , Lamond F. J. D. , Laburn H. P.
Published: February 2003

We have investigated the febrile responses of New Zealand White rabbits to a Gram‐negative pyrogen (bacterial lipopolysaccharide (LPS) from Salmonella typhosa), commonly associated with systemic infection, and a Gram‐positive pyrogen (Staphylococcus aureus), more frequently associated with superficial soft tissue infection, each administered via one of four different routes (intravenous, intramuscular, subcutaneous or intraperitoneal) at each of three different doses (LPS: 0.1, 1 and 10 μg kg−1; S. aureus: 1.5 × 107, 1.5 × 108 and 1.5 × 109 cell walls kg−1). Intravenous administration of LPS evoked rapid, dose‐dependent biphasic fever. Injection of LPS by the other routes also evoked dose‐dependent fever. However, these fevers were monophasic, had increased latency of onset, and were of lower amplitude. It is important to note that a dose of approximately 10 and 100 times that of the standard intravenous dose was required to produce a similar peak rise in temperature when administered subcutaneously and intraperitoneally, respectively. Intravenous injection of the highest dose of S. aureus evoked dose‐dependent biphasic fever, with short latency of onset, which was very similar to that induced by intravenous LPS. At lower doses, intravenous S. aureus induced monophasic fever. No fever occurred when the same doses of S. aureus were administered by any other route. We conclude that any of the four routes may be used for the study of LPS‐induced fever, provided that the doses are adjusted. However, studies of S. aureus‐induced fever, and detection of contamination with either pyrogen, requires intravenous injection.
Salt‐Sensitive Hypertension Resulting From Nitric Oxide Synthase Inhibition is Associated with Loss of Regulation of Angiotensin II in the Rat
Authors: Hodge G. , Ye V. Z. C. , Duggan K. A.
Published: February 2003

In the Dahl salt‐sensitive hypertensive rat, a diet containing L‐arginine, the natural substrate for nitric oxide synthase, abrogates the hypertension. We postulated that nitric oxide synthase inhibition might induce a salt‐sensitive form of hypertension and that this salt sensitivity might be linked to a loss of the regulatory effect of sodium ingestion on angiotensin II (Ang II) and angiotensinogen. Male Wistar‐Kyoto rats were randomised to a diet containing 0.008%, 2.2% or 4.4% sodium chloride and to treatment with the NO synthase inhibitor L‐NAME (10 mg kg−1 day−1) in the drinking water, or drinking water alone (Controls) for 4 weeks. Blood pressure was measured by tail cuff plethysmography twice weekly. After 4 weeks, the rats were anaesthetised and truncal blood collected for determination of angiotensinogen, renin, angiotensin I (Ang I), Ang II and aldosterone concentrations as well as angiotensin‐converting enzyme (ACE) activity. Systolic blood pressure increased with increasing dietary sodium intake in the L‐NAME‐treated rats (P < 0.05). Plasma renin and aldosterone concentrations decreased with increasing dietary sodium intake in both Control and L‐NAME‐treated rats. Ang I and ACE activity were unchanged by increasing dietary sodium intake. In contrast, the plasma concentration of Ang II and angiotensinogen increased with increasing dietary sodium (P < 0.05 and P < 0.005, respectively). Treatment with the Ang II receptor blocker, losartan, reversed the blood pressure increase. We conclude that treatment with L‐NAME induces an increase in blood pressure that is at least in part salt sensitive. Further, the salt‐sensitive component appears to be Ang II‐dependent, as it was associated with increasing plasma Ang II levels and could be reversed by treatment with an Ang II receptor antagonist.
Ammonia Inhibits Sodium and Chloride Absorption in Rat Distal Colon
Authors: Cermak R. , Minck K. , Lawnitzak C. , Scharrer E.
Published: February 2003

It was recently demonstrated that ammonia inhibits sodium absorption in the proximal colon of rats. In order to investigate the effect of luminal ammonia in the distal colon, sodium and chloride transport were measured in Ussing chambers. Under short‐circuit conditions, distal colon absorbed sodium and chloride. When luminal ammonia (30 mmol l−1) was present, sodium and chloride absorption was diminished. Inhibition of the two Na+‐H+ exchanger isoforms NHE2 and NHE3, which are known to be located in the apical membrane of the distal colon epithelium, failed to influence the effect of ammonia on transepithelial sodium and chloride fluxes. The inhibitory effect of ammonia was eliminated under the following conditions: after block of carbonic anhydrases with acetazolamide, in the presence of an unspecific blocker of Na+‐H+ exchangers, and under chloride‐free conditions. Ammonia did not alter electrogenic sodium absorption. These results demonstrate that luminal ammonia inhibits sodium and chloride absorption in rat distal colon. We suggest that ammonia inhibits NaCl absorption by interfering with a Na+‐H+ exchanger that is not NHE2 or NHE3.
A Ratiometric Method of Autofluorescence Correction Used for the Quantification of Evans Blue Dye Fluorescence in Rabbit Arterial Tissues
Authors: Murphy Christopher L. , Lever M. John
Published: February 2003

Evans blue dye (EBD) conjugates with albumin in the circulation and is frequently used to measure vascular protein leakage. The fluorescence of the dye from tissue sections can be used to measure its uptake at very specific anatomical locations, but problems arise with dye quantification because tissue components also fluoresce; so‐called autofluorescence. We have measured uptake of EBD by blood vessel walls at various points around the aorto‐renal branch of rabbits. High resolution, digitised, fluorescence images of histological sections of artery wall allowed detailed microscopic analysis of EBD accumulation; and a ratiometric method was developed to enable autofluorescence to be separated from EBD fluorescence. When EBD‐free tissue sections were illuminated with blue light, the ratio of red to green fluorescence was constant throughout the tissue (0.59 ± 0.03, mean ± S.D., n = 32). Therefore, at each individual pixel, the level of red autofluorescence could be determined by multiplying the green intensity at that pixel by the calculated red to green ratio. Since EBD fluorescence was detected only in the red region of the spectrum, intensity values of the dye alone were obtained from EBD‐exposed tissue by subtracting the red autofluorescence estimated by this ratiometric method. In such cases the red to green fluorescence ratio was measured from adjacent sites known to be free of EDB (0.59 ± 0.02, mean ± S.D., n = 56). We were therefore able to increase the sensitivity of tracer quantification by complete elimination of background autofluorescence on a pixel‐by‐pixel basis. Use of EBD standards allowed calibration of corrected fluorescence intensities and calculation of mass transfer coefficients for albumin into the artery wall. Spatial variations in the permeability of the artery wall around the renal ostium were detected with the present high resolution technique, with an average mass transfer coefficient of (6.8 ± 0.9)×10−8 cm s−1 for all sites combined (n = 56). The present ratiometric method could potentially be applied to other quantitative fluorescence‐based techniques.
Myocardial Stunning Reduces the Effects of Nitric Oxide on Coronary Capillary Perfusion in the Rabbit
Authors: Caria Christine , Katz Elizabeth , Scholz Peter M. , Lazar Michael J. , Weiss Harvey R.
Published: February 2003

This investigation tested the hypothesis that the effects of nitric oxide synthase on myocardial capillary perfusion were reduced during myocardial stunning. Anaesthetized open‐chest rabbits were assigned to either a control group or a group treated with a nitric oxide synthase inhibitor. To induce myocardial stunning, a coronary artery was occluded (for 15 min) and then reperfused (for 15 min) twice. During reperfusion, rabbits were given either saline or NG‐nitro‐L‐arginine methyl ester (L‐NAME, 30 mg kg−1) followed by I.V. injection of 150 mg kg−1 fluorescein isothiocyanate (FITC)‐labelled dextran (molecular weight, 150 000) for 14 s. Fluorescence microscopy was used to identify the perfused vessels and an alkaline phosphatase stain was used to locate the total microvasculature. The ‘closest‐individual’ method was used to estimate the geometric distribution of capillaries. No significant differences were observed in the total volume fraction (mm3 of capillaries per mm3 of tissue) between the control and stunned regions in either the saline‐ (0.045 ± 0.008 and 0.042 ± 0.009, respectively) or the L‐NAME‐treated hearts (0.060 ± 0.010 and 0.049 ± 0.005, respectively). There were no significant differences in the percentage volume fraction of perfused capillaries between the control and the stunned regions (49 ± 4% and 54 ± 4%, respectively) in saline‐treated hearts. In hearts treated with L‐NAME, the percentage of perfused capillaries was significantly reduced. The reduction was significantly greater in the control region (∼27%) than the stunned region (∼17%). Closest‐individual analysis of the perfused capillary distribution in both groups demonstrated a similar unchanged distribution. Thus, nitric oxide synthase is an important regulator of basal coronary capillary perfusion, and its effects are significantly reduced by myocardial stunning.
Retrograde Transfer of Ovarian Steroid Hormones to the Ovary in the Porcine Periovarian Vascular Complex
Authors: Stefañczyk‐Krzymowska S. , Krzymowski T. , Wasowska B. , Chłopek J.
Published: February 2003

The aim of the present study was to investigate the mechanism of the retrograde transfer of ovarian steroid hormones from the ovarian lymphatic and venous effluent to the arterial blood supplying the ovary. In the first experiment, reproductive organs were collected from gilts in the luteal (n= 10) and follicular (n= 10) phase of the oestrous cycle. The ovary with the mesovarium was isolated and perfused through the ovarian artery with warmed, oxygenated autologous blood. The concentrations of progesterone and oestradiol in ovarian arterial blood increased on passing through the ovarian artery to the ovary, in the luteal phase, from 20.3 ± 2.1 to 31.4 ± 3.9 ng ml−1 (P < 0.001) and from 6.2 ± 0.8 to 11.4 ± 1.4 pg ml−1 (P < 0.001), respectively, and in the follicular phase, from 1.2 ± 0.2 to 2.2 ± 0.4 ng ml−1 (P < 0.001) and from 8.2 ± 1.8 to 13.2 ± 2.3 pg ml−1 (P < 0.001), respectively. Approximately 17.5 ± 3.9% of the progesterone and 12.6 ± 1.7% of the oestradiol found in the ovarian venous effluent was retrogradely transferred from the ovarian venous blood to the ovary in the luteal phase. In the follicular phase, these values were 10.1 ± 2.0% and 8.6 ± 1.4%, respectively. The efficiency of retrograde transfer of oestradiol and the rate of retrograde transfer of progesterone differed between phases of the oestrous cycle (P < 0.05 and P < 0.0001, respectively). A direct relationship between the concentration of the steroids in the venous effluent and the efficiency and rate of the retrograde transfer to the ovary was not found. In the second experiment (luteal phase, n= 10; follicular phase, n= 5), the concentration of progesterone and oestradiol increased in both ovarian arterial blood (P < 0.0001) and in the venous effluent (P < 0.0001) after administration of the steroids into the lymphatic vessels of the isolated mesovarium with separated ovary. In the third experiment (follicular phase, n = 5), with the mesovarium isolated after the ovary was removed and ovarian venous blood flowing out under the force of gravity (without the blood pressure in the ovarian vein), it was demonstrated that the veno‐venous network covering the branches of the ovarian artery was supplied with the blood flowing out from the mesovarian tissue and that the filling of the veno‐venous network was dependent on the blood pressure in the ovarian artery. We conclude that the effective retrograde transfer of steroid hormones from ovarian venous and lymphatic effluent to the ovary is accomplished not only by the classical counter‐current exchange mechanism, but also as a result of complex processes that may be dependent on a specific part of the circulation of the blood and lymph in the periovarian vascular complex of the mesovarium.
Chronic Hypoxia Induces Prolonged Angiogenesis in Skeletal Muscles of Rat
Authors: Deveci D. , Marshall J. M. , Egginton S.
Published: February 2003

Skeletal muscle capillarity and fibre cross‐sectional area were investigated within and between diaphragm (Diaph), extensor digitorum longus (EDL), soleus (SOL) and tibialis anterior (TA) muscles of control and chronic hypoxic (12% O2 for 6 weeks) adult male Wistar rats (final body mass ∼355 g). Cryostat sections were stained for alkaline phosphatase activity to depict all capillaries, and for succinic dehydrogenase to demonstrate regional differences in oxidative capacity within the muscles. Hypoxia‐induced angiogenesis occurred in all muscles (P < 0.01), with capillary‐to‐fibre ratio (C:F) being higher in the more active and oxidative muscles, Diaph (27%) and SOL (26%), than phasically active and glycolytic muscles, TA (21%) and EDL (15%). Diaph, SOL and EDL maintained fibre size, and hence showed an increased capillary density (CD) and reduced intramuscular diffusion distance (DD), whereas TA showed fibre hypertrophy and maintained CD and DD compared to control muscles. The extent of angiogenesis among different regions of muscle varied so as to suggest that muscle fibre size has an additional influence on capillary growth during chronic systemic hypoxia, which is progressive over an extended period of systemic hypoxia.
Book Review
Authors: Forsling Mary L.
Published: February 2003

Cells, Gels and the Engines of Life. By Gerald H. Pollack
Renal Sympathetic Nerves do not Modulate Renal Responses to Haemorrhage in Conscious Lambs
Authors: Smith Francine G.
Published: February 2003

The present study was designed to investigate the renal responses to hypotensive haemorrhage early in life and the role of renal sympathetic nerves in modulating these renal responses. To this end, experiments were carried out in conscious, chronically instrumented lambs with either intact renal nerves (n = 7, Intact) or bilateral renal denervation performed at the time of surgery (n = 5, Denervated). Parameters of renal function were measured before and after 20% haemorrhage (experiment 1) and 0% haemorrhage (experiment 2), the latter serving as a time control. The two experiments were performed in random order at intervals of 24‐48 h. Within 20 min of hypotensive haemorrhage in intact lambs, glomerular filtration rate decreased by ∼60%; this response was not altered by renal denervation. Since renal plasma flow remained constant after haemorrhage, the filtration fraction also decreased. After 20% haemorrhage, urinary flow rate decreased in intact lambs; this response was also not altered by renal denervation. Excretion rates of Na+ and K+ as well as urinary osmolality and free water clearance were not altered by haemorrhage in either intact or denervated lambs. These data provide the first description of renal responses to haemorrhage early in life. In addition, the present findings provide new information that renal responses to haemorrhage early in life do not appear to be modulated by renal sympathetic nerves.
Constitutive Secretion of Immunoglobulin a and Other Proteins into Lumina of Unstimulated Submandibular Glands in Anaesthetised Rats
Authors: Proctor G. B. , Carpenter G. H. , Segawa A. , Garrett J. R. , Ebersole L.
Published: February 2003

Salivary fluid secretion is dependent upon reflex stimuli mediated by autonomic nerves. In order to determine if immunoglobulin A (IgA) and salivary proteins are secreted in the absence of nerve stimulation, small volumes (< 2 µl) of saliva were consecutively collected from the submandibular duct of anaesthetised rats following rest pauses in order to sample the protein contents of the ductal system. Within the first 5 µl of such saliva collected by parasympathetic nerve stimulation, IgA and other salivary proteins reached peak concentrations that were over 20‐fold greater than levels in parasympathetically stimulated saliva subsequently collected during a 5 min period of stimulation. Confocal microscopy of TRITC‐labelled IgA added to live, acutely isolated submandibular acini indicated that it did not enter the lumina by paracellular leakage. IgG is thought to enter saliva by paracellular leakage but did not accumulate in luminal saliva in the present study. Electrophoresis suggested that the major proteins secreted in the absence of stimulation were the same as those present in subsequently stimulated saliva. It can be concluded that IgA and other major submandibular proteins are secreted into glandular lumina in the absence of nerve stimulation. The functional significance of such unstimulated protein secretion is at present unclear.
Implications on design of rapid manufacturing
Authors: Hague R , Campbell I , Dickens P
Published: February 2003

During the last few decades, designers have been educated to develop designs with restricted geometry so that parts can be made easily. The revolutionary aspect of rapid manufacturing will be that geometry will no longer be a limiting factor. The introduction of rapid manufacturing will have a number of effects on design. It will be possible to have re-entrant shapes without complicating manufacturing, no draft angles, variable wall thickness, no split lines and fewer parts, leading to easier assembly and lower stock. The individual designer's method of working will change with the introduction of rapid manufacturing and also there will be changes to the overall design process.
Fluorescence spectral properties of cyanine dye labeled DNA near metallic silver particles
Authors: Malicka Joanna , Gryczynski Ignacy , Maliwal Badri P. , Fang Jiyu , Lakowicz Joseph R.
Published: February 2003

Recent studies have demonstrated that silver metallic particles can increase the quantum yield and decrease the lifetimes of nearby fluorophores. These studies are extended to double stranded DNA oligomers labeled with N,N′‐(dipropyl)‐tetramethylindocarbocyanine (Cy3) or N,N‐(dipropyl)‐tetramethylindodicarbocyanine (Cy5). The proximity to silver particles increases the apparent quantum yields and decreases the lifetimes of the double helical DNA 23‐mer labeled individually with Cy3 or Cy5. The decreased lifetimes are accompanied by apparently increased photostability of the labeled oligomers near silver particles. Because of spatial averaging across the sample these results are likely to significantly underestimate the effects of silver particles on labeled DNA localized at an optimal distance from the metallic surface. These results suggest that DNA arrays fabricated on substrates with silver particles can display increased sensitivity and photostability in the analysis of gene expression. © 2003 Wiley Periodicals, Inc. Biopolymers (Biospectroscopy) 72: 96–104, 2003
Human cutaneous melanoma expresses a significant phosphate‐dependent glutaminase activity: A comparison with the surrounding skin of the same patient
Authors: Zacharias Darwin Pinheiro Machado , Lima Manuela Maria Ramos , Souza Alcione Lescano , de Abranches Oliveira Santos Ivan Dunshee , Enokiara Milvia , Michalany Nilceo , Curi Rui
Published: February 2003

The protein content and the activity and type of phosphate‐dependent glutaminase were determined in freshly pigmented lesions obtained from human melanoma and adjacent skin. Significant phosphate‐dependent glutaminase activity was found in both the melanoma and non‐pigmented adjacent skin areas. A comparison between the pigmented and adjacent skin areas suggests the occurrence of gradual metabolic changes that result in an increased protein content in the centre of the neoplasia. The presence of a kidney‐type glutaminase (Km of 2–5 mm) indicates a high sensitivity of the melanoma to variations in glutamine plasma levels (0.6 to 1 mm). These data lead us to postulate that glutamine supply is an important factor for melanoma cell proliferation, being a source of nitrogen for DNA and RNA synthesis. The intense neovascularization observed in melanoma ensures the oxygen supply that is required for glutamine oxidation. These findings support the proposition that glutamine is an important fuel for melanoma. Copyright © 2002 John Wiley & Sons, Ltd.
The role of activation in the effect of total sleep deprivation on depressed mood
Authors: Beutler L. E. , Cano M. C. , Miró E. , Buela‐Casal G.
Published: February 2003

The present investigation analyzes if the effect of Total Sleep Deprivation (TSD) on depressive mood in normal subjects is related to participants' activation levels. Reaction time (RT), subjective sleepiness, and depressive mood were assessed among 48 normal subjects who were subjected to 60 h of TSD. Subjects were divided into groups based on his/her depressive mood changes following TSD: subjects with worse response (n = 11), subjects with better response (n = 12), and intermediate group (n = 25). We sought to determine if RT and subjective sleepiness were related systematically to depressive mood changes following TSD. TSD produces a general reduction in activation (i.e., a monotonic increase in RT and subjective sleepiness) modulated by circadian oscillations. Baseline activation (RT) was confirmed partially as a predictor of participants' response to TSD. Subjects with high levels of activation (lower RTs at the baseline) experienced a better response (greater reductions in depressive mood) following TSD. There was no relationship between pre‐treatment subjective sleepiness levels and the TSD effect on depressive mood. The results partially support the role of the activation level as a differential moderator of TSD effects on depressive mood in normal subjects. © 2003 Wiley Periodicals, Inc. J Clin Psychol 59: 369–384, 2003.
Self‐administered treatments for depression: A review
Authors: McKendree‐Smith Nancy L. , Floyd Mark , Scogin Forrest R.
Published: February 2003

Although there are numerous self‐help books for depression, relatively few have been empirically tested. However, those that have been used in clinical trials have fared well, with an average effect size roughly equivalent to the average effect size obtained in psychotherapy studies. Computer‐based treatments are being developed and appear promising as an alternative to bibliotherapy for those interested in self‐administered treatments. This article provides a summary of the depression bibliotherapy literature and discusses several remaining questions such as effectiveness versus efficacy, practice applications, ethics, and future research. © 2003 Wiley Periodicals, Inc. J Clin Psychol 59: 275–288, 2003.
Self‐administered psychosocial treatments for children and families
Authors: Elgar Frank J. , McGrath Patrick J.
Published: February 2003

Self‐administered psychosocial treatments for child health problems have the potential to circumvent barriers to traditional models of care. They are convenient and inexpensive to families and, for some types of problems, may be as effective as therapist‐based care. In a review of past research on child‐ and parent‐facilitated self‐administered treatments, it was found that a stronger evidence base exists in support of some formats (manual‐ and multimedia‐based treatments) than for others (inspirational literature and support groups). The practical, ethical, and legal issues associated with self‐administered treatments are discussed as well as avenues for future research. How psychologists and health care systems respond to the opportunities associated with self‐administered treatments for children will likely affect the face of the profession and the health of children in the future. © 2003 Wiley Periodicals, Inc. J Clin Psychol 59: 321–339, 2003.
Frequency‐volume chart: The minimum number of days required to obtain reliable results
Authors: Schick Erik , Jolivet‐Tremblay Martine , Dupont Charles , Bertrand Pierre E. , Tessier Jocelyne
Published: February 2003

Aims

There is wide variation in the number of days necessary to maintain a diary and still furnish reliable data on which to base a sound clinical assessment. Estimates range from 1 day to 2 weeks, 7 days probably being the criterion standard. The goal of this retrospective study was to evaluate how much the 7‐day period could be shortened without compromising the reliability of data.

Methods

Various lengths of frequency‐volume (FV) charts (from 1 day to 6 days) were compared with the standard 7‐day charts on 14 FV parameters.

Results

Overall results show that a 4‐day dairy is nearly identical to the 7‐day chart (most r ≥ 0.95). Results of the 1‐, 2‐, and 3‐day charts were frequently different statistically from the 7‐day chart, whereas comparison of the 4‐day chart with the 7‐day chart showed no statistically significant differences. In addition, results of 4‐day FV charts from a new control cohort showed no significant differences from the 7‐day charts of the main cohort.

Conclusions

In conclusion, our study indicates that the 4‐day chart is as reliable as the 7‐day chart. This reduction in the length of time, although easier for the patients, does not compromise the diagnostic value of the FV charts. Neurourol. Urodynam. 22:92–96, 2003. © 2003 Wiley‐Liss, Inc.
Overactive bladder symptoms: Do we need urodynamics?
Authors: Digesu G. Alessandro , Khullar Vik , Cardozo Linda , Salvatore Stefano
Published: February 2003

Aims

The aim of our study was to determine whether the urodynamic diagnosis is useful in the management of women with symptoms of an overactive bladder (OAB).

Methods

Women with lower urinary tract symptoms, attending a tertiary referral urogynaecology clinic were studied. All women were fully evaluated, with history, urinary symptoms questionnaire, frequency‐volume chart, vaginal examination, and videocystourethrography. Women with symptoms consistent with an overactive bladder (urinary frequency, urgency, and/or urge incontinence) were selected. Women with neurological disorders were excluded. Finally, urinary symptoms and urodynamic diagnosis were correlated. All terms and definitions are in accordance with the International Continence Society [Abrams et al., 1988, Scand J Urol Nephrol 114(Suppl):5–19.].

Results

A total of 4,500 women 22–73 years of age were studied. Only 843 women (18.7%) could be classified as having an OAB. Of these, 457 women (54.2%) had urodynamically proven detrusor instability, whereas 386 women (45.8%) had a stable urodynamic trace. Sixty‐eight (8.1%) of the women studied had postvoid residual greater than 100 mL. Of the 4,500 women studied, 1,641 (36.5%) had detrusor instability on laboratory urodynamics. Only 27.5% of these women (457 of 1,641) had OAB symptoms.

Conclusions

Symptomatic diagnosis of OAB does not correlate with a urodynamic diagnosis of detrusor instability. The diagnosis of overactive bladder based on urinary symptoms underdiagnoses the condition of detrusor instability in a population of women suffering from lower urinary tract symptoms. Therefore, symptomatic diagnosis of OAB alone is not recommended. Our study suggested that urodynamic evaluation is mandatory in the management of the women with symptoms of an overactive bladder. Neurourol. Urodynam. 22:105–108, 2003. © 2003 Wiley‐Liss, Inc.
Learning at the nanoscale: The impact of students' use of remote microscopy on concepts of viruses, scale, and microscopy
Authors: Jones M. Gail , Andre Thomas , Superfine Richard , Taylor Russell
Published: February 2003

The rapid pace of development is bringing advanced technologies to the World Wide Web (WWW), and, as a result, schools have access to new tools for science investigations. In this exploratory study, we investigated how an educational experience organized around students' use of a WWW‐controllable atomic force microscope (AFM) influenced students' understandings of viruses. The context for the study was a weeklong unit on viruses for two high school biology classes which incorporated student use of the WWW controllable AFM. We also investigated how the haptic (involving kinesthetics and touch) experiences afforded by this tool might influence students' knowledge of viruses, microscopy, and nanometer scale. Fifty students from two high school biology classes participated in a series of instructional activities and pre‐ and postassessments (knowledge test, opinion questionnaire, and interviews). Results showed that students' understandings of microscale, virus morphology, and dimensionality changed as a result of the experiences. Students' conceptions moved from a two‐dimensional textbook‐like image of a virus to a three‐dimensional image of an adenovirus. The results of this preliminary study suggest that the use of the technology as a tool for learning about morphology of materials too small to see may be beneficial. © 2003 Wiley Periodicals, Inc. J Res Sci Teach 40: 303–322, 2003
Are cytokine gene polymorphisms related to in vitro cytokine production profiles?
Authors: Warlé Michiel C. , Farhan Ayar , Metselaar Herold J. , Hop Wim C. J. , Perrey Chris , Zondervan Pieter E. , Kap Marcel , Kwekkeboom Jaap , Ijzermans Jan N. M. , Tilanus Hugo W. , Pravica Vera , Hutchinson Ian V. , Bouma Gerda J.
Published: February 2003

Currently, there is much interest in the genetic basis for diseases or disease manifestations and, in particular, in whether they are related to cytokine gene polymorphisms. It has become accepted to denote such single-nucleotide polymorphisms of cytokine genes by their presumed association with high or low in vitro cytokine production. In this article, we analyze the relationship between cytokine gene polymorphisms and in vitro tumor necrosis factor alpha (TNFα), interferon gamma (IFNγ), and interleukin (IL)-10 and IL-13 production, both in liver transplant recipients and in healthy volunteers. The evaluated cytokine gene polymorphisms involved TNF-A-308; TNF-d3; IFN-G+874; IL-10-1082, -819, and -592; and IL-13+2043, and -1055. For healthy volunteers, we observed a relationship between polymorphisms of TNF-d3 and IL-10-1082 with in vitro production of TNFα and IL-10, respectively, whereas no significant associations were found for the other tested cytokine gene polymorphisms. For liver transplant recipients, no significant relationship could be established between any of the cytokine gene polymorphisms and in vitro production of corresponding cytokines. Also, we reviewed the literature for the association between cytokine gene polymorphisms and in vitro cytokine production in various patient groups and healthy volunteers. We found that the cellular sources, from which the cytokines were released into the culture supernatant, were different between studies. They were either whole blood, isolated monocytes, or peripheral blood mononuclear cells (PBMC). Also, the in vitro incubation protocol varied to a great extent between studies. This applied for the used in vitro stimulant, the concentration of a particular stimulant, and the length of the incubation period. Moreover, the study populations were either healthy individuals or very diverse patient groups. Therefore, it was impossible to evaluate whether in vitro cytokine production profiles really can be deduced from a particular cytokine gene polymorphism. Given the inconclusive findings, we propose to set up a multicenter workshop in which the relationship between certain cytokine gene polymorphisms and in vitro cytokine production is analyzed, using an identical in vitro cell culture system and study population. Furthermore, we suggest that cytokine gene polymorphisms be described by their localization within the gene or gene-promoter, rather than by their presumed in vitro cytokine production profile, to properly evaluate the relationship between cytokine gene polymorphisms and disease manifestations.
Recombinant activated factor VII for coagulopathy in fulminant hepatic failure compared with conventional therapy
Authors: Shami Vanessa M. , Caldwell Stephen H. , Hespenheide Elizabeth E. , Arseneau Kristen O. , Bickston Stephen J. , Macik Gail B.
Published: February 2003

Severe coagulopathy in fulminant hepatic failure (FHF) is difficult to correct by conventional means. Recombinant activated factor VII (rFVIIa) is an antihemophilic factor that has shown promise in treating coagulopathy in liver disease. Our aim is to review our experience with rFVIIa in treating the coagulopathy of FHF and compare these results with those of conventional therapy. Fifteen patients with FHF who met King’s College criteria for orthotopic liver transplantation were studied. All were ascertained from our liver disease registry. Eight consecutive patients were administered fresh frozen plasma (FFP) alone, whereas seven consecutive patients were administered FFP and rFVIIa (40 μg/kg intravenous bolus). The two groups, with similar demographic characteristics, were compared in terms of measured parameters of coagulopathy (prothrombin time and international normalized ratio), amount of plasma infused, development of anasarca, ability to undergo intracranial pressure (ICP) transducer placement, bleeding complications, ability to undergo transplantation, and survival. All patients administered rFVIIa (after a single dose) versus none administered FFP alone had temporary (2- to 6-hour) correction of coagulopathy (P < .0002). All patients administered rFVIIa versus 38% administered FFP alone were able to have an ICP transducer placed (P = .03). The rFVIIa group had less anasarca (P = .04). An equal number of patients underwent transplantation from each group, but overall survival was slightly better in the rFVIIa group (P = .04). Five of seven patients in the rFVIIa group were administered one or more subsequent doses of rFVIIa after placement of the ICP monitor (two patients, for additional procedures; three patients, prophylactically in the first 24 hours after ICP transducer placement) at the discretion of the attending physicians. We conclude that rFVIIa is effective in transiently correcting laboratory parameters of coagulopathy in patients with FHF. It facilitates the performance of invasive procedures and is associated with less frequent anasarca compared with conventional therapy. Our preliminary experience supports the need for further studies to define the optimal dosing, safety, and efficacy of rFVIIa in patients with FHF.
Tacrolimus as a liver flush solution to ameliorate the effects of ischemia/reperfusion injury following liver transplantation
Authors: St. Peter Shawn D. , Post David J. , Rodriguez-Davalos Manuel I. , Douglas David D. , Moss Adyr A. , Mulligan David C.
Published: February 2003

The goal of this report is to evaluate in a prospective randomized fashion the effect of flushing hepatic allografts with tacrolimus before transplantation. A prospective, double-blinded, randomized trial was performed. Twenty patients receiving orthotopic liver transplants from October 2000 to October 2001 were randomized into two groups. Group 1 (active) was administered tacrolimus, 20 ng/mL, plus Plasma-lyte A (Baxter Healthcare Corp, Deerfield, IL) liver flush solution; and group 2 (placebo) was administered only Plasma-lyte A. Ischemia/reperfusion injury was assessed in both groups after transplantation by means of serum laboratory values to assess hepatocellular damage, synthetic function, and ion transport capacity. Peak values were recorded for each parameter, and their distributions were compared. There were no statistically significant differences between groups for age, sex, total ischemia time, or cause of liver disease. Global multivariate comparison of peak changes in all measures of liver function indicated liver injury was significantly lower with tacrolimus treatment than placebo (P = .01). The sample median for group 1 was less than for group 2 in all parameters measured. Individual statistical comparison showed that peak changes from baseline aspartate aminotransferase and activated partial thromboplastin time values were significantly improved (P ≤ .05) with tacrolimus treatment than placebo treatment. In this prospective, double-blinded, randomized trial, we show that flushing the liver before transplantation with Plasma-lyte A containing tacrolimus results in superior early graft function and decreased hepatocellular injury after reperfusion compared with flushing with Plasma-lyte A alone.
Cold preservation-warm reperfusion perturbs cytosolic calcium ion homeostasis in rat liver sinusoidal endothelial cells
Authors: Auger Stéphanie , Vallerand Diane , Haddad Pierre Selim
Published: February 2003

Increases in intracellular calcium ion (Ca2+) levels of sinusoidal endothelial cell (SEC) may have a crucial role in mediating the expression of adhesion molecules and thus contribute to the microcirculatory disturbances observed in primary graft dysfunction. The effect of changes in the composition and/or temperature of the reperfusion solution on cytosolic Ca2+ was studied in isolated rat SECs. Cells were preserved in cold University of Wisconsin (UW) solution for 0, 12, or 24 hours and loaded with Fura-2AM dye (Cedarlane, Eugene, OR) at 20°C in N-2-hydroxyethylpiperazine-propanesulfonic acid (HEPES)-buffered physiological solution (HEPES 20°C) or UW solution (UW 20°C). SEC Ca2+ levels were measured by cytofluorimetry. Basal steady-state Ca2+ levels were much lower when SECs were loaded in UW 20°C (37 ± 2 nmol/L) than in HEPES 20°C (114 ± 32 nmol/L). In unstored controls (0 hour), going from UW 20°C to HEPES 37°C induced a large transient increase (185 ± 31 nmol/L) in SEC Ca2+ levels, which was greatly inhibited (43 ± 13 nmol/L) in Ca2+-free HEPES 37°C. A similar large transient increase was observed going from UW 20°C to HEPES 20°C (163 ± 22 nmol/L). Changing temperature only (20°C to 37°C) in UW or HEPES solution had a much smaller effect on SEC Ca2+ levels (14 ± 2 and 60 ± 18 nmol/L, respectively). These changes were similar in cold-preserved cells. In unstored controls, solution changes greatly attenuated the intensity of subsequent Ca2+ responses to the purinergic agonist adenosine triphosphate (ATP). Cold preservation (CP) greatly attenuated both the frequency of appearance and intensity of ATP-induced Ca2+ responses. Hence, changing reperfusion solution composition has a greater impact on SEC steady-state Ca2+ levels than changing temperature. Cold preservation does not significantly affect changes in SEC steady-state Ca2+ levels, but greatly impairs the capacity of SECs to subsequently respond to Ca2+-mobilizing agonists.
Coordinate induction of both cytochrome P4503A and MDR1 by St John's wort in healthy subjects
Authors: Dresser George K. , Schwarz Ute I. , Wilkinson Grant R. , Kim Richard B.
Published: February 2003

Background

Many drugs are cosubstrates of cytochrome P450 (CYP) 3A and MDR1; furthermore, their disposition is markedly affected by pretreatment with inducing agents, including St John's wort. Such drug interactions reflect induction of both proteins through a common mechanism involving the steroid X receptor/pregnane X receptor. However, the relative contributions of enhanced metabolism and efflux transport to the overall induction process are unknown.

Methods

The effects of 12 days' pretreatment with St John's wort on the disposition of selected in vivo probe drugs were determined in 21 young healthy subjects. Midazolam after oral and intravenous administration was used to assess CYP3A activity in both the intestinal epithelium and the liver, whereas the disposition of fexofenadine after an oral dose was assumed to be a measure of MDR1 function, and the oral plasma concentration‐time profile of cyclosporine (INN, ciclosporin) was considered to reflect both CYP3A and MDR1 activities.

Results

St John's wort markedly affected the plasma concentration‐time profiles of all of the drugs, with associated increases in their clearance. With midazolam, the enhancement was considerably less after intravenous administration (approximately 1.5‐fold) than after oral administration (approximately 2.7‐fold), and estimated intestinal and hepatic extraction ratios were higher by approximately 1.2‐ to 1.4‐fold. By contrast, the oral clearances of fexofenadine and cyclosporine were equally increased by approximately 1.6‐fold and 1.9‐fold, respectively; these changes were both statistically less than for midazolam's oral clearance and greater than its estimated intestinal extraction.

Conclusions

Although the disposition of all 3 drugs was altered by St John's wort, the extent of induction measured by oral clearance was different with CYP3A activity (midazolam), apparently increasing more than MDR1 function (fexofenadine), whereas with cyclosporine the change in oral clearance appeared to be more closely associated with the increase in MDR1 rather than CYP3A, despite the fact that both proteins are importantly involved in its disposition. These discordances indicate that, although a common molecular mechanism may be involved, the quantitative aspects of induction are complex and depend on the particular drug and the relative contributions of CYP3A and MDR1 in its disposition.

Clinical Pharmacology & Therapeutics (2003) 73, 41–50; doi: 10.1067/mcp.2003.10
Drug labeling should be kept current
Authors: Rajpal Anil , Reidenberg Marcus M.
Published: February 2003

Clinical Pharmacology & Therapeutics (2003) 73, 4–6; doi: 10.1067/mcp.2003.20