bluuebunny/crossref_metadata_2025 huggingface dataset:
Photopheresis affects the course of experimental allergic encephalomyelitis in Lewis rat
Authors: Chabannes D. , Besnier D. P. , Esnault V. L. M.
Published: March 2003

Background/Purpose: The mechanism responsible for the beneficial effects of extracorporeal photochemotherapy (ECP) remains unknown. In the rat model of experimental allergic encephalomyelitis (EAE), the transfer of encephalitogenic cells (EAE cells) induces transient passive EAE, followed by resistance to subsequent disease induction through immunization with central nervous system antigens (active EAE).

Methods: We tested whether ECP exerts its therapeutic effect by inducing an immune response targeted on circulating pathogenic T‐lymphocytes, which results from their increased immunogenicity. We compared the potential of untreated versus ECP‐treated encephalitogenic cells to transfer passive EAE and protect against active induction of the disease. The UVA irradiation conditions were derived from intensive ECP protocols used in human clinical studies.

Results: Animals receiving untreated cells showed clinical symptoms following cell transfer but not after subsequent immunisation, whereas those receiving ECP‐treated cells remained healthy following cell transfer but experienced clinical symptoms after subsequent immunisation. However, these symptoms were less marked than in control naive rats.

Conclusion: Under these ECP protocol conditions, ECP‐treated cells have no greater active stimulatory potential for the recipient immune system than untreated cells, since they are less effective at triggering the response that causes the resistant state to active EAE. We suggest that intensive ECP protocol may have deleterious effects with a risk of relapses after treatment discontinuation. The search for the irradiation threshold that would inhibit the T‐cell pathogenic properties, but retain their ability to educate the immune system, remains a major research challenge.
Phototoxicity to diuretics and antidiabetics in the cultured keratinocyte cell line HaCaT: evaluation by clonogenic assay and single cell gel electrophoresis Comet assay)
Authors: Selvaag Edgar , Petersen Anita B. , Gniadecki Robert , Thorn Tine , Wulf Hans Christian
Published: March 2003

Background: Potential phototoxicity has been described for a number of drugs and chemical substances. Psoralens, chlorpromazines and fluoroquinolones have been described as inducing photomutagenicity and photocarcinogenicity in vitro and in vivo. We wanted to investigate oral antidiabetics and diuretics for potential phototoxicity and possible DNA damage in the HaCaT cell line.

Methods: The oral antidiabetics tolbutamide, glibenclamide and glipizide, and the diuretics bendroflumethiazide, butizide, furosemide, hydrochlorothiazide and trichlormethiazide were dissolved in DMSO to final concentrations of 1 mM, 0.1 mM, and 0.01 mM, incubated together with the cells, and exposed to UVA1 (23 or 48 J/cm2). Cell survival was evaluated in a clonogenic assay and phototoxic DNA damage was investigated by single cell gel electrophoresis (comet assay). To investigate possible inhibiting effects of antioxidants, L‐ascorbic acid and α‐tocopherol were added at a final concentration of 1 mM 24 h before treatment with the drugs.

Results: Bendroflumethiazide, furosemide, hydrochlorothiazide, trichlormethiazide and tolbutamide induced dose‐dependent phototoxicity in the clonogenic assay. Cells incubated with bendroflumethiazide, tolbutamide and glibenclamide and irradiated with UVA1 demonstrated increased oxidative DNA damage, revealed as alkali‐labile sites in the comet assay. Pretreatment with L‐ascorbic acid or α‐tocopherol suppressed the UVA‐induced DNA damage in cells incubated with 1 mM bendroflumethiazide, furosemide, glibenclamide, glipizide, tolbutamide or trichloromethiazide.

Conclusion:  Several oral antidiabetics and diuretics show phototoxic effects in the HaCaT cell line. Inhibiting effects of antioxidants point towards involvement of reactive oxygen species in phototoxic DNA damage, suggesting a link between the phototoxic and photocancerogenic potential of the sulfonamide‐derived oral antidiabetic and diuretic drugs. Excessive exposure to UV light may be deleterious for patients treated with oral antidiabetic and diuretic drugs.
004 Validation of in vivo and in vitro methods to measure UVA protectiveness of sunscreen
Authors: Cole C. , Natter F. , Ruvolo E. , Issachar N.
Published: March 2003

Standard methods for measuring the sunburning protection of sunscreens (SPF) are globally established. In vivo methods of determining UVA protectiveness of sunscreens have been reduced to either a Persistent Pigment Darkening (PPD) or Protection Factor A (PFA‐either persistent pigment darkening or erythema endpoints) test protocols. Both of these techniques require human exposure to UVA radiation that can be time consuming and do not benefit the human subject. Validated methodologies that would minimize the UVA exposure, or could be performed in vitro would simplify the determination of UVA protectiveness and assist product optimization. Diffuse reflectance spectroscopy of sunscreens on human skin was utilized to evaluate a series of seven model sunscreen systems that were previously evaluated in vivo by both PPD and PFA testing. Correlation of the values found with this technique correlated highly with the in vivo test results, with 1:1 correspondence of protection values. Separately, an in vitro test model was assessed on these same model sunscreens. Sunscreen was applied to roughened surface quartz plates, and the absorbance of the sunscreens was measured before and after UV exposure. The absorbance was mathematically forced to fit the in vivo SPF value and the UVA protectiveness was calculated using both erythema and pigment darkening action spectra. The in vitro predictions of UVA was highly correlated with the in vivo PPD and PFA values. It was determined that preirradiation of the sunscreen samples is needed to accurately predict the protection provided by sunscreens that are not photostable. Both of these techniques provide new ways to accurately predict sunscreen UVA protectiveness.
Positive effect of using calcipotriol ointment with narrow‐band ultraviolet B phototherapy in psoriatic patients
Authors: Rim Jong‐Hyun , Choe Yong‐Beom , Youn Jai‐Il
Published: March 2003

Background/purpose: The successful use of narrow‐band ultraviolet B (UVB) phototherapy for the management of psoriasis has prompted the examination of various combination treatments with narrow‐band UVB. However, there have been contradictory reports on the effect of the calcipotriol–narrow‐band UVB combination. This study was performed to compare the clinical efficacy of the calcipotriol–narrow‐band UVB combination with narrow‐band UVB alone.

Methods: Of the 28 psoriasis patients, 10 were treated with the calcipotriol–narrow‐band UVB and 18 with narrow‐band UVB alone. Phototherapy was done once daily three times a week and the dose was gradually increased in a stepwise fashion by 0.05 J/cm2. At the end of therapy, overall efficacy was classified according to the chosen grading system.

Results: On assessing the therapeutic results using the criteria selected, 90.0% patients (n = 9) in the calcipotriol–narrow‐band UVB group and 61.1% patients (n = 11) in the narrow‐band UVB group showed grade IV at the end of therapy. The calcipotriol–narrow‐band UVB group showed more rapid improvement at the early stage. The final and total UVB dose were slightly lower in the calcipotriol–narrow‐band UVB group but no significant difference was observed with respect to the total number of irradiations, duration of treatment, final UVB dose or total cumulative UVB dose required to reach grade IV in both groups (P > 0.05). The pattern of adverse effects was similar in both groups with a slightly higher frequency in the calcipotriol–narrow‐band UVB group.

Conclusion: Our results demonstrated that the total cumulative UVB dose required to reach grade IV was not significantly different in both groups, although it was slightly lower in the calcipotriol–narrow‐band UVB group. However, a higher percentage of patients attained grade IV at the end of therapy in the combination group and this therapy was more effective in reducing the Psoriasis Area and Severity Index early in treatment. More studies are warranted to confirm these results.
Multi‐night exposure to 60 Hz magnetic fields: Effects on melatonin and its enzymatic metabolite
Authors: Graham Charles , Cook Mary R. , Sastre Antonio , Riffle Donald W. , Gerkovich Mary M.
Published: March 2003

Magnetic field‐induced suppression of nocturnal melatonin in humans has been reported in occupational and residential studies, but not in laboratory‐based exposure studies. The present study examined whether this contrasting pattern of results might be related to associated differences in exposure duration or to field‐induced measurement instability over time. Thirty healthy young men were evaluated using a randomized, double‐blind test protocol. Statistical analysis indicated that 4 consecutive nights of exposure to power‐frequency magnetic fields at occupational intensity (resultant flux density=28.3 microtesla, μT, [283 milligauss, mG]) had no differential effect on concentrations of melatonin or its major enzymatic metabolite (6‐hydroxymelatonin sulfate, 6‐OHMS) in daily morning urine samples, compared to equivalent no‐exposure sham control conditions. The consistency of intra‐individual urinary measurements over the 4 test nights also was quite high (P<0.01) in the sham control condition. In contrast, repeated
nightly exposure to the magnetic field was associated with reduced
consistency. Morning urinary measures obtained after exposure on night 4
differed (P<0.01) from similar measures obtained after the second and third exposure night. Thus, while the overall results of this study do not support the melatonin hypothesis, there is some suggestion of a possible cumulative effect of magnetic field exposure on the stability of individual melatonin measurements over time. Additional research with longer periods of controlled exposure may be warranted.
Ototoxicity caused by aminoglycosides is ameliorated by melatonin without interfering with the antibiotic capacity of the drugs
Authors: Lopez‐Gonzalez Miguel A. , Guerrero Juan M. , Torronteras Rafael , Osuna Carmen , Delgado Francisco
Published: March 2003

The production of free radicals seems to be involved in the mechanisms of ototoxicity. Aminoglycosides produce ototoxicity, which can be determined through distortion product otoacoustic emissions (OAEs) that measure the activity of the outer hair cells of the organ of Corti. An ototoxic chart was obtained in rats using gentamicin or tobramycin. Together with this treatment, the animals ingested melatonin in the drinking water, or melatonin was injected subcutaneously or intramuscularly. The distortion product OAEs were determined over a prolonged period of time for each of the groups. The effect of melatonin on the antibiotic capacity of the aminoglycosides used was also studied. Antibiograms inoculated with Escherichia coli or Pseudomonas
aeruginosa and treated with gentamicin or tobramycin in the presence or absence of melatonin at quantities from pharmacological to physiological doses were performed. The ototoxicity produced by gentamicin and tobramycin was maximal from days 3 to 5 post‐treatment, returning to normal values in 2 wk. When melatonin was present, the recovery was at day 5 post‐treatment, independently of the means of administration of the pineal product. The antibiograms showed that melatonin had no effect on the antibiotic capacity. It is concluded that the ototoxicity caused by gentamicin and tobramycin is ameliorated by melatonin and that the pineal hormone does not interfere with the antibiotic capacity of these antibiotics.
Roles of nocturnal melatonin and the pineal gland in modulation of water‐immersion restraint stress‐induced gastric mucosal lesions in rats
Authors: Otsuka Migusa , Kato Kimitoshi , Murai Ichiro , Asai Satoshi , Iwasaki Ariyoshi , Arakawa Yasuyuki
Published: March 2003

The roles of melatonin and the pineal gland in the circadian variation of water‐immersion restraint stress‐induced gastric mucosal lesions in rats were investigated. Fasted rats were subjected to water‐immersion restraint stress during both the diurnal and nocturnal phases of a light:dark cycle. Pinealectomized and sham‐operated rats were also subjected to water‐immersion restraint stress at night. The lesion area after 4 hr of stress during the dark phase was significantly lower than in light‐phase controls. Pinealectomy increased the lesion area in the dark phase, compared to the sham operation, but this effect was counteracted by intracisternal melatonin preadministration at a dose of 100 ng/rat. Melatonin concentrations in control rats during the light phase were significantly increased 4 hr after water‐immersion restraint stress. In contrast, melatonin concentrations 4 hr after water‐immersion restraint stress in the dark phase were significantly depressed compared with the control levels at the corresponding time. Melatonin levels after stress exposure were markedly decreased in pinealectomized rats as compared with sham‐operated rats. These results suggest that circadian rhythm has an important role in the formation of stress‐induced gastric mucosal lesions in rats and that melatonin responses to water‐immersion restraint stress differ between day and night. The pineal gland modulates the stress response and melatonin contributes to gastric protection via a mechanism involving the central nervous system.
Melatonin counteracts potentiation by lysophosphatidylcholine of serotonin‐induced vasoconstriction in human umbilical artery: relation to calcium influx
Authors: Okatani Yuji , Wakatsuki Akihiko , Watanabe Kazushi , Taniguchi Katsunori , Fukaya Takao
Published: March 2003

We evaluated mechanisms underlying the antioxidant property of melatonin as related to vasospastic effects in the human umbilical artery from lysophosphatidylcholine (LPC), a component of oxidized lipoprotein. Helical sections of umbilical artery without endothelium were obtained at elective cesarean delivery between 37 and 39 wk of gestation. Changes in 5‐hydroxytryptamine (5‐HT)‐induced vasoconstriction were measured. Arterial sections were treated with LPC (15 or 30 μM) alone or pretreated with a hydroxyl radical (·OH) scavenger, mannitol (20 mM), an H2O2 scavenger, catalase (1200 U/mL), or melatonin (0.1 or 1.0 μM). The effect of LPC on the response of arterial sections to external calcium in the presence of KCl (20 mM) was determined. LPC potentiated 5‐HT‐induced vasoconstriction in a concentration‐dependent manner; pretreatment with mannitol or catalase significantly reduced this vasospastic effect. LPC (30 μM) significantly augmented the contractile response to external calcium. Melatonin (1.0 μM) pretreatment significantly suppressed the contractile response to external calcium. The results suggest that LPC potentiates 5‐HT‐induced umbilical artery vasoconstriction, in part by increasing the calcium influx into smooth muscle cells via activation of voltage‐dependent calcium channels. Given a previous finding, the vasospastic effect of LPC on the umbilical artery also appears to involve the suppression of endothelial nitric oxide production. Melatonin significantly suppresses the vasospastic effect of LPC, probably by scavenging ·OH arising from LPC.
Acute modulation of somatostatin receptor function by melatonin in the rat frontoparietal cortex
Authors: Izquierdo‐Claros Rosa María , Del Carmen Boyano‐Adánez María , Torrecillas Guadalupe , Rodríguez‐Puyol Manuel , Arilla‐Ferreiro Eduardo
Published: March 2003

Since melatonin (N‐acetyl‐5‐methoxytryptamine) decreases locomotor activity and rearing and increases grooming behavior in a similar manner as somatostatin (SRIF), we examined if melatonin could induce these changes through somatostatinergic neurotransmission in the rat frontoparietal cortex. Male Wistar rats (200–250 g) received a single injection of melatonin (25 μg/kg per day) subcutaneously (s.c.) and were sacrificed 5 hr later. Melatonin treatment increased the number of 125I‐Tyr11‐SRIF receptors in frontoparietal cortical membranes without any changes in the dissociation constant (Kd). The capacity of SRIF to inhibit basal and forskolin (FK)‐stimulated adenylyl cyclase (AC) activity was increased in melatonin‐treated rats as compared to the control animals. Melatonin administration also induced a lower AC activity, both under basal conditions and after stimulation of the enzyme via stimulatory guanine nucleotide‐binding proteins (Gs), or directly with FK. Functional inhibitory guanine nucleotide‐binding protein (Gi) activity was increased in frontoparietal cortical membranes from melatonin‐treated rats when compared to controls. Western blot analyzes showed that melatonin administration did not alter the amount of the Giα1 or Giα3 subunits, but reduced Giα2 levels in frontoparietal cortical membranes. No significant changes in SRIF‐like immunoreactivity content and SRIF mRNA levels were detected in this brain area after melatonin treatment. Administration of the melatonin receptor antagonist luzindole (10 mg/kg, s.c.) 30 min before melatonin injection did not change the melatonin‐induced effects on the SRIF receptor–effector system. In conclusion, the present results show that acute melatonin administration increases the activity of the SRIF receptor–effector system and decreases Giα2 levels in the rat frontoparietal cortex. In addition, the coupling of Gs to AC is disturbed by melatonin.
Phototransduction for human melatonin suppression
Authors: Rea Mark S. , Bullough John D. , Figueiro Mariana G.
Published: March 2003

Human adult males were exposed to combinations of two illuminances and two broadband spectral power distributions over the course of four night‐time sessions. Results showed that melatonin suppression is dominated by short visible wavelengths (420–520 nm), consistent with recently published studies. Although the authors of these recent studies suggest that a novel opsin underlies melatonin suppression, the present paper offers a more conservative interpretation of the data based on what is known about existing photoreceptors and associated neuroanatomy and neurophysiology.
Hepatic mitochondrial dysfunction in senescence‐accelerated mice: correction by long‐term, orally administered physiological levels of melatonin
Authors: Okatani Yuji , Wakatsuki Akihiko , Reiter Russel J. , Miyahara Yasuyo
Published: March 2003

Abstract: Mitochondrial oxidative damage from free radicals may be a factor underlying aging. We investigated whether long‐term administration of physiological levels of melatonin, a direct free radical scavenger and indirect antioxidant, influences mitochondrial respiratory activity in liver of senescence‐accelerated mice (SAM). Liver was obtained in the middle of dark period of the daily light:dark cycle from SAMP8, a strain of mice prone to accelerated senescence, and from SAMR1, a senescence‐resistant strain, at 6 and 12 months of age. Respiratory control index (RCI), adenosine‐5‐diphosphate (ADP)/O ratio, State 3 respiration and dinitophenol (DNP)‐dependent uncoupled respiration exhibited significant age‐associated decreases in SAMP8. SAMP8 also showed significant age‐associated reductions in respiratory chain complex I and IV activities. No age‐related effects were found in these parameters in SAMR1. Daily oral melatonin administration (2 μg/mL of drinking fluid) beginning at 7 months of age significantly increased RCI, State 3 respiration, DNP‐dependent uncoupled respiration, and complex I and IV activities in both mouse strains when they were 12 months old. These results reveal age‐related reductions in mitochondrial function in SAM mice which are modified by melatonin; the most likely explanation for the corrective actions of melatonin relate to its antioxidative actions in mitochondria and other portions of the cell. The implication of the findings is that melatonin may be beneficial during aging as it reduces the deteriorative oxidative changes in mitochondria and other portions of the cell associated with advanced age.
Receptor (MT1) mediated influence of melatonin on cAMP concentration and insulin secretion of rat insulinoma cells INS‐1
Authors: Peschke Elmar , Mühlbauer Eckhard , Mußhoff Ulrich , Csernus Valer J. , Chankiewitz Erik , Peschke Dorothee
Published: March 2003

Abstract: Recent functional, autoradiographic, and molecular investigations have shown that the pineal secretory product melatonin reduces the forskolin‐stimulated insulin secretion from isolated pancreatic islets of neonate rats. Autoradiographic and binding studies as well as reverse transcriptase‐polymerase chain reaction (RT‐PCR) experiments proved that these effects are mediated through specific, high‐affinity pertussis‐toxin‐sensitive Gi‐protein‐coupled MT1 receptors and subsequent inhibition of the adenylyl cyclase/cyclic adenosine monophosphate (cAMP) system. This hypothesis was proved by blocking the intracellular signal transduction pathway using the non‐hydrolyzable guanosine triphosphate analog guanosine 5′‐O‐(3‐thiotriphosphate) (GTPγS) or the competitive melatonin receptor antagonist luzindole. Both GTPγS and luzindole diminished the melatonin effect. We have published these prior results elsewhere. So far, however, no information is available on both whether the MT1 receptors are located on the β‐cells and whether the consecutive functional reactions are based on a direct influence of melatonin on the insulin producing β‐cells. In order to examine this question, we used a glucose responsive insulin producing insulinoma cell line INS‐1 isolated from rats. Comparable with the results of islets the competitive receptor antagonist luzindole diminished the insulin‐decreasing effect of melatonin. In addition, our RT‐PCR experiments, using specific primers for the rat melatonin receptor MT1 showed that this melatonin receptor mRNA is also expressed in the INS‐1 cells. Furthermore we radioimmunologically analyzed the forskolin‐stimulated cAMP concentration in the superfusate. Similar to insulin secretion, the cAMP concentration was significantly reduced by melatonin. Following the hypothesis that cAMP is actively secreted from INS‐1 cells by an energy‐dependent mechanism based on either a OAT1/ROAT1 like anion exchanger or MDR‐like transport systems, we used probenecid (p‐[dipropylsulfamoyl] benzoic acid), a known inhibitor of cAMP extrusion. Probenecid blocks the export of cAMP by acting on transport mechanisms which are as yet not completely understood. Consistently, insulin secretion was increased and cAMP concentration diminished. The application of the phosphodiesterase inhibitor IBMX (3‐isobutyl‐1‐methylxanthine) caused a marked rise of insulin secretion as well as cAMP concentration in the perifusate. From these data we conclude that the MT1 receptor is located on the INS‐1 cell and therefore in general on pancreatic β‐cells.
Melatonin reduces nitric oxide level during ischemia but not blood–brain barrier breakdown during reperfusion in a rat middle cerebral artery occlusion stroke model
Authors: Pei Z. , Fung P. C. W. , Cheung R. T. F.
Published: March 2003

Abstract: Melatonin is a potent antioxidant and free radical scavenger. Previously, we showed that a single injection of melatonin before ischemia significantly reduced the infarct volume in both permanent and 3‐hr middle cerebral artery occlusion (MCAO) rat stroke models. Nitric oxide (NO) and other free radicals play an important role in the pathogenesis of cerebral ischemia, and they have been postulated to mediate the breakdown of the blood–brain barrier (BBB) during ischemia. In this study, we evaluated the influence of melatonin, given at 30 min before MCAO, on brain NO concentration and BBB breakdown. Brain NO concentration was measured at 15 min of MCAO using electron paramagnetic resonance spectroscopy. BBB breakdown at 3 hr of reperfusion following 3 hr of MCAO was assessed using Evans blue extravasation. The relative brain NO concentration was increased to 141.69 ± 9.71% (mean ± S.E.M.; n = 9) at 15 min of MCAO. Treatment with melatonin at 1.5, 5, or 50 mg/kg significantly reduced the brain NO concentration to 104.20 ± 11.20% (n = 8), 55.67 ± 5.58% (n = 11), and 104.86 ± 12.56% (n = 9), respectively. Melatonin at 5 mg/kg did not affect Evans blue extravasation. Our results suggest that a single injection of melatonin protects against focal cerebral ischemia partly via inhibition of ischemia‐induced NO production and that this regimen does not prevent BBB breakdown following ischemia–reperfusion.
Melatonin treatment protects against ischemia/reperfusion‐induced functional and biochemical changes in rat urinary bladder
Authors: Şener Göksel , Şehirli Ahmet Özer , Paskaloğlu Kübra , Dülger Gül Ayanoğlu , Alican İnci
Published: March 2003

Abstract: Reactive oxygen metabolites play important roles in ischemia/reperfusion (I/R) injury in several systems. The aim of this study was to investigate the role of melatonin against I/R injury of the rat urinary bladder. The abdominal aorta was clamped to induce ischemia for 30 min, then the animals were subjected to 60 min of reperfusion. Melatonin (10 mg/kg, i.p.) or the vehicle (control 1% alcohol i.p.) was administered before I/R. After decapitation, the bladder was removed and the tissue was either used for functional studies or stored for measurement of products of lipid peroxidation (LP), glutathione (GSH) levels and myeloperoxidase activity (MPO). Bladder strips were suspended in oxygenated Tyrode's buffer at 37°C and isometric contractions to carbachol (CCh; 10−8–10−4 m) were recorded.

In the I/R group, the contractile responses of the bladder strips were lower than those of the control group (P < 0.01–0.001) and were reversed by treatment with melatonin (P < 0.05–0.001). LP which was higher in I/R group compared with control (27.68 ± 1.69 and 10.59 ± 1.27 nmol/g, respectively; P < 0.001) was partially reversed by melatonin (19.01 ± 1.85 nmol/g; P < 0.01). Similarly, GSH showed a decrease in the I/R group compared with controls (0.27 ± 0.03 and 0.43 ± 0.04 μmol/g, respectively; P < 0.05) and melatonin prevented this effect completely (0.45 ± 0.04 μ mol/g; P < 0.05). MPO activity in the I/R group (4.19 ± 0.08 U/g) was significantly higher than that of the control group (1.41 ± 0.08 U/g; P < 0.001) and melatonin treatment reduced MPO levels compared with I/R alone (3.16 ± 0.07; P < 0.001). Melatonin almost completely reversed the low contractile responses of rat urinary bladder strips to CCh and prevented oxidative tissue damage following I/R.
Inhibitory effects of melatonin on neural lipid peroxidation induced by intracerebroventricularly administered homocysteine
Authors: Baydas Giyasettin , Kutlu Selim , Naziroglu Mustafa , Canpolat Sinan , Sandal Suleyman , Ozcan Mete , Kelestimur Haluk
Published: March 2003

Abstract: Melatonin, the main secretory product of the pineal gland, has been shown to be potentially effective in prevention of numerous types of neurodegenerative disorders in which free radical processes are involved. Homocysteine (Hcy), an independent risk factor for atherosclerosis, undergoes auto‐oxidation and generates reactive oxygen species. The purpose of this study was to test whether intracerebroventricular (ICV) injection of Hcy leads to neural lipid peroxidation and also to investigate the protective effects of melatonin on the brain tissue from oxidative stress of Hcy. Adult male Wistar rats under anaesthesia were injected ICV with Hcy at a dose of 143 μg/kg. Melatonin was administered intraperitoneally to a group of rats for three consecutive days before Hcy injection. The rats were decapitated and brain tissues were removed and hippocampus, cortex and cerebellum were dissected. There was a significant development of oxidative stress as indicated by an increase in malondialdehyde in hippocampus, cortex and cerebellum of rats injected with Hcy, whereas melatonin prevented the elevation of lipid peroxidation. Furthermore, melatonin significantly increased glutathione levels and glutathione peroxidase activity in all brain regions. The present study demonstrates that Hcy, in high levels, may be a causal factor in generation of free radicals in the brain and it may be one of the mechanisms which cause neurodegeneration in elderly people. It also shows that melatonin could potentially be beneficial in prevention of neurodegeneration caused by hyperhomocysteinemia.
Effects of continuous light exposure on antioxidant enzymes, porphyric enzymes and cellular damage in the Harderian gland of the Syrian hamster
Authors: Tomás‐Zapico Cristina , Coto‐Montes Ana , Martínez‐Fraga Jorge , Rodríguez‐Colunga María Josefa , Tolivia Delio
Published: March 2003

Abstract: The Syrian hamster Harderian gland (HG), an organ present in the male two secretory cell types (type‐I and type‐II cells), is physiologically exposed to high oxidative stress because of high concentrations of porphyrins and their precursor, 5‐aminolevulinic acid. Because of its juxtaorbital location, the HG is accessible to light, and subject to phototoxic effects of these substances. After having previously demonstrated circadian rhythms in antioxidant enzymes, porphyric enzymes and oxidative damage of proteins and lipids, as well as influences of melatonin on these parameters, we have now studied the effects of continuous light (LL), which suppresses melatonin secretion by the pineal gland. Measurements were performed in two different circadian phases, in order to detect the presence or absence of day/night differences. In LL, no differences between circadian phases of subjective day and subjective night were demonstrable for 5‐aminolevulinate synthase, 5‐aminolevulinate dehydratase, porphobilinogen deaminase, or superoxide dismutase; temporal differences in glutathione reductase and catalase were markedly diminished, whereas all these parameters showed marked day/night differences in the rats exposed to a light/dark cycle of 14:10. In LL, oxidative damage to lipids was minimally effected, while protein damage was enhanced. LL also caused a reduction in the percentage of type‐II cells. Therefore, cell differentiation in the HG does not seem to be controlled only by the androgen, but, unexpectedly, also by melatonin.
Biological treatment of joint cartilage damage
Authors: Tyyni A. , Karlsson J.
Published: March 2003

The structure and composition of articular cartilage provides unique mechanical properties which effectively dampen and distribute loads during weightbearing. Acute traumatic damage to the articular cartilage destroys the original structure and composition of the articular cartilage and impairs its function. Lesions in articular cartilage can cause patients severe disabling symptoms from the affected joint. These symptoms also run the risk of developing into degenerative osteoarthrosis with time. Unfortunately, articular cartilage does not have any real ability to heal itself after injury. Different treatment methods have been developed in an attempt to restore the function of the injured joint and to prevent further deterioration in the articular cartilage. Some of these methods have produced promising results in clinical studies, but further research is necessary to establish their efficacy and indications for treatment. Today, no controlled studies that compare these different methods are available.
Post‐exercise muscle soreness after eccentric exercise: psychophysical effects and implications on mean arterial pressure
Authors: Bajaj P. , Graven‐Nielsen T. , Arendt‐Nielsen L.
Published: March 2003

The aim of the study was to examine the time course of changes in pressure pain threshold (PPT), visual analogue scale (VAS) pain and tenderness scores, McGill Pain Questionnaire (MPQ) descriptors, pain areas, skin temperature and mean arterial pressure (MAP) following intensive eccentric exercise. In 11 healthy male subjects, eccentric exercise of the first dorsal interosseous muscle (FDI) of the right hand with 114% maximum voluntary contraction weight (MVC) was used to induce post‐exercise muscle soreness (PEMS) in the right hand, while the left hand served as a control. At 24 h to 48 h all the pain profiles indicated the presence of PEMS in the right hand when compared to before exercise (P<0.05). MPQ and pain area assessments also indicated PEMS immediately after the exercise, while the pain assessment by PPT and tenderness VAS showed insignificant pain immediately after the exercise. Skin temperature measured in the first web space of the hand did not change at any time. MAP was significantly reduced at 48 h. It is concluded that eccentric exercise of a small hand muscle is followed by PEMS and a reduced MAP after 48 h that may suggest a role of central mechanisms in the PEMS, thereby giving further insight into clinical aspects of muscle pain.
Reliability of isokinetic supine bench press in healthy women using the Ariel Computerized Exercise System
Authors: Grooten W. J. A. , Puttemans V. , Larsson R. J. M.
Published: March 2003

The aim of this study was to assess reliability of the Ariel Computerized Exercise System (ACES) ‘multifunction exerciser’. Twenty‐three healthy women completed three sets, three repetitions each, of maximal isokinetic supine bench press at two different velocities, slow (10/s) and moderate (25/s). The following performance parameters were studied: peak and average force, peak and average power, and total work. The experiment was repeated for two days. Intraclass correlation coefficients (ICC[2,1]) varied between 0.947 and 0.755 at 10 °/s and between 0.861 and 0.654 at 25 °/s. The standard error of the measurement (SEM), the smallest detectable difference (SDD), and the coefficient of variation (CV) indicated that it is possible to achieve reliable and clinically relevant measurements with the ACES.
Clinical decision making in the acutely injured knee based on repeat clinical examination and MRI
Authors: Odgaard F. , Tuxoe J. , Joergensen U. , Lange B. , Lausten G. , Brettlau T. , Thomsen H. S.
Published: March 2003

To determine the correlation between Magnetic Resonance Imaging (MRI) and clinical examination of the knee after an acute injury, and to see to what extent MRI affected the planned treatment, we examined 90 consecutive patients in a prospective study, clinically and with an extremity Magnetic Resonance (MR) scanner. The number of meniscal lesions, bone bruises and osteochondral lesions found on MRI was significantly higher than the clinical examinations indicated. Despite this, the treatment was only changed in 6 cases. In no case did MRI prevent a planned arthroscopy. MRI may reveal many clinically silent changes in the knee, also after minor injuries. The significance of these MRI findings must await long‐term follow‐up.
Eating disorder behavior in physically active Norwegian women
Authors: Augestad L. B. , Flanders W. D.
Published: March 2003

Competitive female athletes may have higher risk of eating disorders (ED) than recreational athletes, in part because low body fat may be advantageous in sports. However, women who participate in sports or physical activities might also do this for weight reduction, altering body shape, and for other food related reasons. This study was conducted to evaluate the association between hours of leisure time physical activity (PA) and prevalence of ED, and whether the association between the Eating Disorders Inventory (EDI) scales and ED, as classified by the Survey of Eating Disorders (SED), was the same among women with high vs. low physical activity levels. The community‐based study sample consisted of 898 female students aged 18–50 years. Subjects filled out the EDI, the SED, and a questionnaire concerning physical activity and demographic data. Physical activity was not associated with increased risk of having a SED‐defined diagnosis of an ED or of having an EDI score greater than 40, which is sometimes used to define women at risk for having an eating disorder. Women with a SED‐defined ED had higher scores on all subscales of the EDI, but did not differ with respect to age, BMI or hours of weekly activity. The strongest predictors of having a SED‐defined ED were body mass index (BMI), two EDI scales, drive of thinness and Bulimia Nervosa, with no differences between the two PA groups. Among women with a SED‐defined ED, those with more than 5 h weekly PA did not differ from others with respect to scoring on the EDI or BMI. Results suggest that hours of physical activity may not increase risk of developing ED. Effective interventions are needed to help the growing numbers of persons with body‐image and eating difficulties. For some, moderate physical training might be helpful.
Physiological predictors of performance in cross‐country skiing from treadmill tests in male and female subjects
Authors: Larsson P. , Olofsson P. , Jakobsson E. , Burlin L. , Henriksson‐Larsén K.
Published: March 2003

In order to study which parameter that best corresponds to performance during cross‐country skiing, seven male and nine female cross‐country skiers were tested with treadmill tests. Parameters measured or computed by metabolic gas measurements were the anaerobic threshold (AT), threshold of decompensated metabolic acidosis (TDMA), the exercise intensity where the Respiratory exchange ratio reaches 1.0 (R = 1) and peak oxygen (O2) uptake (VO2peak). Onset of blood lactate accumulation (OBLA, 4 mmol·l−1 blood lactate) was also measured. The various parameters were measured in percentage of maximal heart rate, percentage of peak O2 uptake, VO2 ml·kg−1·min−1, VO2 ml·min−1·kg−2/3 and VO2 l·min−1. Results from four large competitions were also collected to rank the subjects. With correlation analysis, it was revealed that in male subjects a high OBLA was associated with good ranking results (r = (−0.829) − (−0.964); P < 0.05–0.001). In female subjects, the best association with competition results was found for R = 1 (r = (−0.715) − (−0.810); P < 0.05). Concerning VO2 measurements, for male subjects the unit l·min−1 is suggested to be used and for female subjects either the units l·min−1, ml·min−1·kg−2/3, or ml·kg−1·min−1 could be used when predicting performance in cross‐country skiing. In conclusion, treadmill tests can be used for the prediction of performance in cross‐country skiing. Further, various parameters from treadmill tests in men and women are best used as predictors of performance in cross‐country skiing.
A high exercise load is linked to pathological weight control behavior and eating disorders in female fitness instructors
Authors: Höglund K. , Normén L.
Published: March 2003

Demographic data, exercise habits, weight control behavior, attitudes towards body shape, eating disorder (ED) experience, and menstrual regularity among female fitness instructors were descriptively assessed. A 60‐item questionnaire was sent to 295 female fitness instructors at eight fitness centers. Responders (57%) reported a mean weekly exercise load of 5.5 h week‐‐1 (SD 2.6), which indicates frequent training, however, less than that of athletes. Overall, 35% reported ED experience (DSM‐IV criteria), with an onset at 15–17 years of age. The problems had lasted 5–7 years, and 20% of the entire group reported recovery, however, 11% still had EDs. For the entire group, it was found that a high weekly exercise load was linked to a pathological weight control behavior. Fitness instructors with an active ED exercised more than instructors who never had an ED or who had a past ED. Menstrual irregularity was more common among instructors who did not use contraceptives (14%), compared to those who did (5%).

As ED experience and pathological weight control behavior were common in the studied group, the importance of guidelines regarding communication from female fitness instructors about healthy training habits to regular exercisers is discussed in the article.
Elite athletes' experiences of the motivational climate: The coach matters
Authors: Pensgaard A. M. , Roberts G. C.
Published: March 2003

Recent research investigating the effect of the motivational climate has found that even elite athletes benefit from a mastery climate. The purpose of the present study was to obtain a deeper understanding of the importance of the climate surrounding an athlete and the role of the coach for elite athletes by conducting in‐depth interviews with a group of athletes (n=7). The athletes also completed the Perception of Success Questionnaire (POSQ) and Perception of Motivational Climate Questionnaire (PMCQ) to measure motivational indices. All the athletes were very high on task orientation and moderate to high on ego orientation. Most of the athletes perceived a high mastery climate and a low performance climate. The athletes emphasized the importance of the coach as the creator of the climate, as well as their preference for a supportive and caring climate. This speaks for an emphasis on a mastery climate for elite athletes.
Degreasing method for the seborrheic areas with respect to regaining sebum excretion rate to casual level
Authors: Rode Birgitte , Ivens Ulla , Serup Jørgen
Published: March 2003

Background/aims: Sebum excreted from the seborrheic glands keeps the skin surface subtle and moist. Before determining the activity of seborrheic glands, the skin surface must be degreased to remove contamination but without provoking sebum excretion. The purpose of this study was to set up a standardised degreasing procedure for various seborrheic areas in different skin types. The method will take day‐to‐day variations into account with respect to the kinetics of refatting.

Methods: The Sebumeter® from Courage+Khazaka is used to quantify the sebum excretion. Day‐to‐day variations were measured on the forehead in groups of 12 volunteers on 2 consecutive days. The degreasing procedure was investigated by individual cleaning with alcohol compared to washing with a mild detergent followed by wipes with alcohol on the forehead. The degree of refatting was monitored until 3 h after defatting on seborrheic areas: the forehead, cheek, nose, chin and upper back.

Results: There was no statistical significant difference in the variation from day to day (P<0.05), although a change in the individual skin types was observed. An individual difference in the number of alcoholic wipes needed to degrease the forehead was seen. Washing followed by several repetitions of alcoholic wipes was not sufficient for the forehead, chin and nose (P>0.05). For the cheek and upper back, it was sufficient to wash with soap (P<0.05). The time from degreasing the skin until the sebum output reached the casual level was 2 h (P>0.05). The area under the curve (AUC) indicates that individual skin types return to casual level after defatting.

Conclusion: There was no statistically significant day‐to‐day variation using the Sebumeter®. We ended up with different degreasing procedures in different seborrheic areas. Washing gently with a detergent solution and then performing three wipes with alcohol was optimal for degreasing the forehead, nose and chin. For the cheek and upper back, it was sufficient to use a mild soap. Casual level was reached after 2 h in all seborrheic areas, irrespective of level of oiliness.
Surfactant irritation: in vitro corneosurfametry and in vivo bioengineering
Authors: Gabard Bernard , Chatelain Eric , Bieli Elsbeth , Haas Stephan
Published: March 2003

Background/aims: Irritant reactions to surfactants, cleansing products, soaps and detergents are common in clinical and occupational dermatology. Mildness has become a major benefit claimed, and testing for mildness now ranks among the first concerns of the manufacturing industry. A wealth of publications deals with this problem, trying to improve the methodology, reduce the costs of testing and facilitate decision‐making. Differences in vivo can be measured clinically and/or instrumentally. This is difficult, as commercially available products are generally safe to use and none are harsh in the absolute sense.

Methods: Nineteen different products (syndets, shampoos, personal cleansers), all claiming to be mild, were tested in vitro by a newly introduced method, corneosurfametry. For evaluating the aggressiveness of the products, the calculation of an index of irritation (IOI) was proposed. A concentration‐effect curve of sodium lauryl sulfate (SLS) as standard and model surfactant was obtained. Some of the products were further tested in vivo with a flex wash test and with a soap chamber test and compared to SLS. Bioengineering methods (transepidermal water loss TEWL, skin color) were used to evaluate the results.

Results and Conclusions:

The results of the corneosurfametry allowed us to classify the products in three categories, with increasing aggressiveness towards the stratum corneum, according to their IOIs. The in vivo tests were not able to discriminate between the products, but ranks from the results of the bioengineering measurements showed a good correlation between TEWL changes, but not between colour changes, and IOIs from corneosurfametry. Corneosurfametry emerged as a simple, low‐cost and fast method for ranking commercial products according to their mildness. However, the skin bioengineering techniques showed that some products could lead to skin reactions, such as erythema, that could not be detected by the in vitro technique.
Development of a new test for mechanical irritation:behind the knee as a test site
Authors: Farage Miranda A. , Gilpin Debbie A. , Enane Ninah A. , Baldwin Sue
Published: March 2003

Background/aims: Certain consumer products, such as feminine hygiene products, and baby and adult diapers, are worn for prolonged periods of time in close proximity to the skin. A sensitive test method was needed to evaluate these products and their components for the potential to cause mechanical irritation during use.

Methods: We investigated several test sites on the body where normal, daily activities provided the opportunity for movement and, therefore, friction. These test sites were: the back of the knee, the axilla, and the wrist. Three exposure regimens were tested: 6‐h daily for 4 days, 24‐h daily for 3 days, and 24‐h daily for 4 days. Controls consisted of satin fabric (a non‐irritating material) or burlap (an irritating material). Test materials were secured to the test sites using an Ace® elastic bandage (on the back of the knee), a snug fitting garment (on the axilla), or an athletic band (on the wrist). Test sites were scored for irritation on a visual scale prior to the initial application and 30–60 min after removal each day. Data were evaluated for the ability to reliably detect irritating materials, and for the ability to consistently differentiate between irritating and non‐irritating materials. Quantitative measures of these abilities were used to rank the overall effectiveness of various test protocols as a model for mechanical irritation.

Results/Conclusion: The results of these studies indicated that a protocol using the back of the knee as a test site with an exposure regimen of 6‐h daily for 4 days, best met the success criteria for an effective test system for evaluating mechanical irritation.