bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of phototherapy two times and four times a week with low doses of narrow‐band ultraviolet B in Asian patients with psoriasis
Authors: Leenutaphong Vichit , Nimkulrat Peerapat , Sudtim Srismorn
Published: March 2003

Background/Aims: The optimum narrow‐band (TL‐01) ultraviolet (UV) B weekly treatment frequency for psoriasis has yet to be defined, especially in Asian patients with TL‐01. Our purpose was to compare 2× weekly and 4× weekly therapy with narrow‐band UVB at low doses for psoriasis vulgaris.

Methods: Sixty‐nine patients with moderately severe psoriasis were recruited and allocated to the 2× weekly or 4× weekly treatment group. The patients were treated with a new protocol using low doses of narrow‐band UVB with varied exposure increments. Outcomes were evaluated by means of Psoriasis Area and Severity Index (PASI) scores, time (weeks), cumulative UVB dose and number of treatments to clearance.

Results: No significant difference was found between the two regimens in the PASI score at the end of treatment, in the proportion of patients whose skin cleared during treatment and in the time to clearance (8 weeks). Those who completed treatment achieved clearance after a median of 16 exposures with 2× weekly treatment compared with 32 exposures with 4× weekly treatment (P=0.0304), and 12.5 minimal erythema dose multiples (MEDs) compared with 39.7 MEDs (P=0.0470). Acute side effects of the treatment were similar for the two groups (P=0.8462).

Conclusion: For skin phototype III‐V populations, a greater long‐term risk is expected, connected with the higher cumulative UVB dose and number of exposures required in the 4× weekly group. Therefore, 4× weekly phototherapy will no longer be used for psoriasis.
Photoaging of human skin
Authors: Berneburg M. , Plettenberg H. , Krutmann J.
Published: March 2003

Chronic sun exposure causes photoaging of human skin, a process that is characterized by clinical, histological and biochemical changes which differ from alterations in chronologically aged but sun‐protected skin. Within recent years, substantial progress has been made in unraveling the underlying mechanisms of photoaging. Induction of matrix metalloproteinases as a consequence of activator protein (AP)‐1 and nuclear factor (NF)‐κB activation as well as mutations of mitochondrial DNA have been identified recently. This has increased our understanding of photoaging significantly and has led to new prophylactic and therapeutic strategies aimed at the prevention and repair of the detrimental effects of chronic sun‐exposure on the skin.
Pharmacokinetic behaviour of sublingually administered 8‐methoxypsoralen for PUVA therapy
Authors: Shephard Sarah E. , Langguth Peter , Panizzon Renato G.
Published: March 2003

Background: Conventional oral PUVA therapy is hampered by large inter‐ and intraindividual variations in the bioavailability of 8‐methoxypsoralen (8‐MOP), caused by its low solubility in the gastrointestinal juices and large interindividual differences in hepatic metabolism rate (hepatic first pass).

Aims: New galenic formulations of 8‐MOP based on solid dispersions, suspensions, and saturated solutions containing penetration enhancers were developed for sublingual administration, a drug delivery route which avoids the hepatic first pass metabolism.

Methods: Solubility properties of 8‐MOP were tested in 22 potential penetration enhancers and solubilizers. Following preliminary in vivo tests of 13 sublingual 8‐MOP formulations, five were administered to groups of volunteers at a nominal dose of 0.6 mg/kg body weight: two solid dispersions based on PEG 1540 (with and without Xylitol); a solution in Labrasol® (glyceryl and PEG‐8 caprylate/caprate), PEG 400, Transcutol® (ethoxydiglycol) (1:1:1); a micronized suspension in sorbitol, water, ethanol, propylene glycol (ca. 3:1:1:5 w/v); and Oxsoralen® capsules. Pharmacokinetic behaviour of 8‐MOP was examined in serum; samples were analysed by HPLC. Photosensitivity was measured in seven subjects.

Results: The peak of maximum 8‐MOP concentration in blood was sharp, rapid and reproducible: tmax of 8‐MOP in blood averaged 23±3 min, independent of the particular formulation. Cmax was higher when 8‐MOP was presented in dissolved form (solution and capsule formulations, 85±29 and 85±35 ng/ml, respectively) and lowest with the suspension (42±15 ng/ml). Photosensitivity peaked reproducibly at 45 min. post dosing.

Conclusions: Sublingual PUVA therapy is suitable for patients with skin types I and II, in particular patients who are less suitable candidates for standard PUVA therapy (due to hepatic, renal, or cardiac insufficiency) or who have experienced side effects with standard PUVA.
Beneficial effects of melatonin in a rat model of splanchnic artery occlusion and reperfusion
Authors: Cuzzocrea Salvatore , Costantino Giuseppina , Mazzon Emanuela , Micali Antonio , De Sarro Angela , Caputi Achille P.
Published: March 2003

The aim of the present study was to investigate the protective effect of the pineal secretary product melatonin in a model of splanchnic artery occlusion shock (SAO). SAO shock was induced in rats by clamping both the superior mesenteric artery and the celiac trunk for 45 min, followed thereafter by release of the clamp (reperfusion). At 60 min after reperfusion, animals were sacrificed for tissue histological examination and biochemical studies. There was a marked increase in the oxidation of dihydrorhodamine 123 to rhodamine (a marker of peroxynitrite‐induced oxidative processes) in the plasma of the SAO‐shocked rats after reperfusion, but not during ischemia alone. Immunohistochemical examination demonstrated a marked increase in the immunoreactivity to nitrotyrosine, an index of nitrogen species such as peroxynitrite, in the necrotic ileum in shocked rats. SAO‐shocked rats developed a significant increase of tissue myeloperoxidase and malondialdehyde activity, and marked histological injury to the distal ileum. SAO shock was also associated with a significant mortality (0% survival at 2 hr after reperfusion). Reperfused ileum tissue sections from SAO‐shocked rats showed positive staining for P‐selectin, which was mainly localized in the vascular endothelial cells. Ileum tissue sections obtained from SAO‐shocked rats with anti‐intercellular adhesion molecule (ICAM‐1) antibody showed a diffuse staining. Melatonin (applied at 3 mg/kg, 5 min prior to reperfusion, followed by an infusion of 3 mg/kg per hr), significantly reduced ischemia/reperfusion injury in the bowel as evaluated by histological examination. This prevented the infiltration of neutrophils into the reperfused intestine, as evidenced by reduced myeloperoxidase activity and reduced lipid peroxidation. This was evaluated by malondialdehyde activity which reduced the production of peroxynitrite during reperfusion, markedly reduced the intensity and degree of P‐selectin and ICAM‐1 in tissue section from SAO‐shocked rats and improved their survival. Taken together, our results clearly demonstrate that melatonin treatment exerts a protective effect and part of this effect may be due to inhibition of the expression of adhesion molecule and peroxynitrite‐related pathways and subsequent reduction of neutrophil‐mediated cellular injury.
Melatonin and its analogs potentiate the nifedipine‐sensitive high‐voltage‐activated calcium current in the chick embryonic heart cells
Authors: Mei Y.A. , Lee P.P.N. , Wei H. , Zhang Z.H. , Pang S.F.
Published: March 2003

Effects of melatonin and its analogs on the voltage‐activated calcium current of embryonic chick ventricular cardiomyocytes were investigated. Myocytes were dissociated from 14‐ to 16‐day‐old chicks (yellow Red Rob) embryonic hearts and cultured for 2–3 days. Calcium currents were studied by the patch‐clamp technique. Whole‐cell current recording showed nifedipine‐sensitive, high‐voltage‐activated L‐type calcium current inactivated in 70–100 ms during the voltage step period of 200 ms. There was no evidence of low‐voltage‐activated T‐type calcium channels. Melatonin (ejected solution: 50 μmol/L melatonin; concentration at the vicinity of recording cell: about 1–5 μmol/L melatonin) and its analogs, 2‐iodomelatonin and 2‐iodo‐n‐butanol‐5‐methoxytryptamine, significantly increased the amplitude of the calcium current by 42–62%. The effect of melatonin on the L‐type calcium current was not desensitised by repeated melatonin treatment. Our results suggest a specific melatonin receptor‐mediated action on the calcium channel of the embryonic chick myocyte. The melatonin‐induced increase in high‐voltage calcium current may increase myocyte contractility and enhance cardiac output. A regulatory role of melatonin on the chick cardiac function should be further considered.
Melatonin, mitochondria, and cellular bioenergetics
Authors: Acuña‐Castroviejo Darío , Martín Miguel , Macías Manuel , Escames Germaine , León Josefa , Khaldy Huda , Reiter Russel J.
Published: March 2003

Aerobic cells use oxygen for the production of 90–95% of the total amount of ATP that they use. This amounts to about 40 kg ATP/day in an adult human. The synthesis of ATP via the mitochondrial respiratory chain is the result of electron transport across the electron transport chain coupled to oxidative phosphorylation. Although ideally all the oxygen should be reduced to water by a four‐electron reduction reaction driven by the cytochrome oxidase, under normal conditions a small percentage of oxygen may be reduced by one, two, or three electrons only, yielding superoxide anion, hydrogen peroxide, and the hydroxyl radical, respectively. The main radical produced by mitochondria is superoxide anion and the intramitochondrial antioxidant systems should scavenge this radical to avoid oxidative damage, which leads to impaired ATP production. During aging and some neurodegenerative diseases, oxidatively damaged mitochondria are unable to maintain the energy demands of the cell leading to an increased production of free radicals. Both processes, i.e., defective ATP production and increased oxygen radicals, may induce mitochondrial‐dependent apoptotic cell death. Melatonin has been reported to exert neuroprotective effects in several experimental and clinical situations involving neurotoxicity and/or excitotoxicity. Additionally, in a series of pathologies in which high production of free radicals is the primary cause of the disease, melatonin is also protective. A common feature in these diseases is the existence of mitochondrial damage due to oxidative stress. The discoveries of new actions of melatonin in mitochondria support a novel mechanism, which explains some of the protective effects of the indoleamine on cell survival.
Melatonin reduces UV‐induced reactive oxygen species in a dose‐dependent manner in IL‐3‐stimulated leukocytes
Authors: Fischer Tobias W. , Scholz Georg , Knöll Brunhilde , Hipler Uta‐Christina , Elsner Peter
Published: March 2003

Reactive oxygen species (ROS) are presumed to be involved in inflammatory UV reactions of the skin. This in vitro study was performed to investigate the suppressive effect of melatonin in interleukin‐3 (IL‐3) stimulated leukocytes. Neutrophilic granulocytes were isolated from EDTA‐treated whole blood and placed in a phosphate‐buffered saline (PBS) containing IL‐3. Cell suspensions were either treated with PBS (control) or with increasing doses of melatonin (0.1, 0.5, 1, 2, 3, 5, 7.5, 10 mmol). One PBS solution was left unirradiated and the other nine solutions (PBS and melatonin) were irradiated with 750 mJ/cm2 UVB light (280–360 nm, max: 310 nm). Radical formation was measured by the chemiluminescence technique. UV‐irradiated leukocytes showed a 5‐fold higher radical formation than unirradiated leukocytes. Melatonin, in increasing doses in powers of ten, led to a maximum suppression of free radicals at 10 nmol (P=0.01) and 1 mmol melatonin (P=0.001), showing a biphasic, non‐linear, dose–response relationship. Melatonin, given in amounts of 0.1–10 mmol, led to a direct dose‐dependent suppression of ROS. Radical formation was suppressed significantly in a range from 0.5 to 10 mmol (P=0.001). Melatonin is known to function as a radical scavenger and antioxidant; some of these melatonin effects may be receptor independent, while others may be receptor dependent.
Melatonin and RZR/ROR receptor ligand CGP 52608 induce apoptosis in the murine colonic cancer
Authors: Winczyk K. , Pawlikowski M. , Karasek M.
Published: March 2003

The effects of melatonin and the thiazolinidinedione derivative CGP 52608 on apoptosis of Colon 38 cancer cells were investigated. Male mice were implanted subcutaneously with a suspension of Colon 38 cells. Ten days after induction of tumors, the animals were treated with melatonin or CGP 52608. Both substances were given in subcutaneous injections in daily doses of 10 or 100 μg in the evening for 6 days. The control group received solvent. The apoptotic cells were visualized in paraffin sections by means of the transferase‐mediated dUTPnick end‐labeling method. Both treatments increased significantly and to the same degree the number of apoptotic cells in tumors. This finding confirms our earlier observation that melatonin exerts a pro‐apoptotic effect on murine colonic cancer cells. Moreover, because CGP 52608 is a ligand of RZR/ROR receptors and the latter are considered by some investigators as nuclear binding sites for melatonin, our data suggest the involvement of these receptors in the pro‐apoptotic effect of melatonin.
Comparison of immune parameters of sheep with naturally high or low plasma concentrations of melatonin
Authors: Bernard Serge , Macedo Nuno , Malpaux Benoît , Chemineau Philippe
Published: March 2003

Studies in rodents and humans have suggested that the pineal gland and its secretory product melatonin play an important role in the modulation of the immune system. In this study, we tested the hypothesis of a difference in immune parameters between ewes with naturally high vs. low circulating melatonin. Thus, two comparable groups of 10 Ile‐de‐France sheep were selected from a large flock, for their naturally high and low plasma concentrations of melatonin. The mean plasma melatonin concentrations during daytime (09:00 hr) and nighttime (24:00 hr) were, respectively, 9 and 664 pg/mL (high group) and 5 and 169 pg/mL (low group; P<0.01). Animals from both groups were subjected to various in vitro and in vivo measurements of the characteristics of their immune system. The total number of white blood cells (lymphocytes, polymorphonuclears, and monocytes) and the assessment of the sub‐populations of blood lymphocytes (T4, T8, T19, B, and monocytes) did not show any significant differences between the two groups, sampled during day or night. The level of blood leukocytes proliferation after in vitro culture with ConA, LPS, or CWF stimulation, before or after experimental immunization, did not reveal any differences. No significant differences were registered in the production of antibodies between the two groups of animals. The results of the present experiment suggest that in natural conditions a high level of circulating melatonin does not modify the activity of the immune system in sheep.
Contribution of CYP1A2 in the hepatic metabolism of melatonin: studies with isolated microsomal preparations and liver slices
Authors: Skene Debra J. , Papagiannidou Eleni , Hashemi Elham , Snelling Jacquie , Lewis David F.V. , Fernandez Michelle , Ioannides Costas
Published: March 2003

The objective of the present studies was to define the enzyme systems catalysing the 6‐hydroxylation of melatonin, by monitoring the levels of 6‐sulphatoxymelatonin in rat hepatic postmitochondrial preparations and in precision‐cut liver slices. Melatonin 6‐hydroxylase activity was localized in microsomes and was supported by NADPH, but not NADH. Treatment of rats with β‐naphthoflavone more than tripled 6‐sulphatoxymelatonin formation from melatonin, but gave rise only to a moderate increase (25%) in the sulphate conjugation of 6‐hydroxymelatonin. Treatment of rats with phenobarbitone, acetone, dexamethasone and clofibrate did not increase 6‐sulphatoxymelatonin generation when either melatonin or 6‐hydroxymelatonin served as substrates. Of a number of cytochrome P450 inhibitors investigated, only furafylline inhibited markedly the conversion of melatonin to 6‐sulphatoxymelatonin without any concomitant effect on the sulphoconjugation of 6‐hydroxymelatonin. When liver slices were incubated with melatonin, treatment of rats with β‐naphthoflavone, and to a lesser extent phenobarbitone, elevated the levels of 6‐sulphatoxymelatonin in the culture medium. No such increase was seen when slices from β‐naphthoflavone‐treated rats were incubated with 6‐hydroxymelatonin, whereas a modest increase was seen with slices from phenobarbitone‐treated rats. Treatment of rats with acetone, dexamethasone or clofibrate failed to modulate the levels of 6‐sulphatoxymelatonin generated from either melatonin or 6‐hydroxymelatonin. Molecular modelling analysis revealed that melatonin had a high area/depth2 ratio, displayed characteristics of CYP1A2 substrates and could be readily accommodated into the human CYP1A2 active site in a position favouring 6‐hydroxylation. Collectively, all the above data provide strong experimental evidence that CYP1A2 is an important catalyst of the 6‐hydroxylation of melatonin.
Melatonin inhibits insulin secretion and decreases PKA levels without interfering with glucose metabolism in rat pancreatic islets
Authors: Picinato Maria Cecília , Haber Esther Piltcher , Cipolla‐Neto José , Curi Rui , De Oliveira Carvalho Carla Roberta , Carpinelli Angelo Rafael
Published: March 2003

Abstract: The effect of melatonin (0.1 μM) on freshly isolated islets from adult rats was investigated. Melatonin caused a marked decrease of insulin secretion by islets in response to glucose. The mechanism involved was then examined. Melatonin did not interfere with glucose metabolism as indicated by the measurement of glucose oxidation. However, the content of the protein kinase A (PKA) catalytic α‐subunit was significantly decreased in islets exposed to melatonin for 1 hr in the presence of 8.3 mM glucose, whereas that of the protein kinase C (PKC) α‐subunit remained unchanged. Melatonin also inhibited forskolin‐induced insulin secretion, a well known activator of adenylate cyclase (AC) activity. This may explain the low content of insulin found in islets incubated in the presence of melatonin for 3 hr. In fact, 3′,5′ ‐cyclic adenosine monophosphate (cAMP), a product of AC activity, stimulates insulin synthesis. These findings led us to postulate that a down‐regulation of the PKA signaling pathway may be the mechanism involved in the melatonin inhibition of the process of glucose‐induced insulin secretion.
Testicular activity is restored by melatonin replacement after suprachiasmatic nucleus lesion or superior cervical ganglionectomy in mink
Authors: Maurel Daniel L , Saad Mohamed Moncef Ben , Roch Gisèle , Siaud Philippe
Published: March 2003

Subcutaneous melatonin implants were inserted in mink subjected to natural (autumn) or experimental gonadostimulatory short‐days (4L:20D), after lesion of the suprachiasmatic nucleus (SCNx) or after superior cervical ganglionectomy (SCGx). Gonad stimulation was assessed by measuring testicular volume and plasma testosterone level. In SCNx and SCGx animals, all measurements were indicative of sexual quiescence. In contrast, both SCNx and SCGx animals with melatonin, maintained in natural or experimental gonadostimulating short‐days, showed an increase in testicular activity 2 months after melatonin implantation. Thus, melatonin (and pineal activity) is a prerequisite for the photoperiodic stimulation of reproductive activity, and the SCN is not necessarily the target site for melatonin action on the renewal of reproduction in the mink.
Suppression of hypothalamic pro‐opiomelanocortin (POMC) gene expression by daily melatonin supplementation in aging rats
Authors: Rasmussen Dennis D. , Marck Brett T. , Boldt Brian M. , Yellon Steven M. , Matsumoto Alvin M.
Published: March 2003

Abstract: Both plasma melatonin levels and hypothalamic arcuate nucleus pro‐opiomelanocortin (POMC) (biosynthetic precursor to the endogenous opioid ß‐endorphin and other opiomelanocortins) mRNA content decrease with aging. To test whether the decline in melatonin is responsible for the decline in POMC mRNA, we investigated the effects of daily melatonin treatment on hypothalamic POMC mRNA content in middle‐aged and older Sprague–Dawley rats. Daily nocturnal melatonin treatment (50 μg kg bw−1 night−1, in the night‐time drinking water) for 7 months, starting at 13 months of age, did not significantly alter female arcuate nucleus POMC mRNA content determined at the end of the light period (i.e., before nightly melatonin administration), but suppressed (24%, P < 0.05) POMC mRNA content at the end of the dark period (i.e., following melatonin administration). Likewise, nocturnal administration of 50 or 500 μg melatonin kg bw−1 night−1 to male rats for 7 months suppressed (31 or 28%, respectively; P < 0.05) POMC mRNA content at the middle of the dark period at 20 months of age. Finally, 10 wk administration of 30 μg melatonin kg bw−1 day−1 suppressed (31%, P < 0.01) POMC mRNA content in middle‐aged male rats killed at the end of the dark period. Melatonin treatments did not significantly alter estradiol or testosterone levels. Thus, moderate‐dosage nocturnal melatonin supplementation suppressed nocturnal hypothalamic POMC gene expression in both middle‐aged males and females, suggesting that melatonin supplementation during aging decreases, rather than increases, forebrain opiomelanocortinergic activity. These POMC responses were apparently not dependent on gonadal steroid responses and did not become refractory to melatonin treatment maintained until old age.
Melatonin production during childhood and adolescence: a longitudinal study on the excretion of urinary 6‐hydroxymelatonin sulfate
Authors: Griefahn Barbara , Bröde Peter , Blaszkewicz Meinolf , Remer Thomas
Published: March 2003

Abstract: Cross‐sectional data on urinary 6‐hydroxymelatonin sulfate (6‐OHMS) excretion in children suggest a constant melatonin secretion during growth. The present longitudinal study concerned, accordingly, the intra‐individual stability of melatonin production during childhood and adolescence. Urine samples collected during a longitudinal investigation of healthy white children and adolescents were analyzed. Forty‐six boys and 38 girls were chosen for the present study. They had passed 3–15 annual examinations between their 3rd and 18th yr of age. Each examination included the collection of urine over 24 hr. The daily urinary output of 6‐OHMS of the overall 621 samples was quantified by enzyme‐linked immunosorbent assay. The analyses clearly revealed for the first time that, despite huge inter‐individual differences, melatonin production remains constant in one and the same individual during childhood and adolescence. Additionally, neither a significant sex difference was observed nor was the 6‐OHMS output affected by season. The dramatic decrease of plasma melatonin levels as described in the literature is mainly related to an increase in body size rather than to decreasing pineal secretion.
Rehabilitation following acute anterior cruciate ligament injuries – a 12‐month follow‐up of a randomized clinical trial
Authors: Zätterström R. , Fridén T. , Lindstrand A. , Moritz U.
Published: March 2003

The efficacy of two non‐operative rehabilitation programs was studied in a consecutive randomized controlled clinical trial of 100 patients after 12 months subsequent to an acute anterior cruciate ligament (ACL) injury. Follow up of randomization to two training models was evaluated after 3 and 12 months: A self‐monitored training program (SM) of traditional mobility and muscle strength training of the injured leg was compared to a supervised (SV) training model exercising postural function in closed kinetic‐chains. Nearly 50% of the patients in the SM group required supervision after 6 weeks. An intention‐to‐treat analysis was performed and showed significantly better values in most of the results of the supervised group at 3 and 12 months. An alternative analysis of subgroups showed a significant difference between transferred male patients and original SV male patients at 3 months but not at 12 months, indicating the importance of initial guiding after an ACL injury. No such difference was observed in the female patients.
Avulsion fracture of the iliac crest in a football player
Authors: Valdés M. , Molins J. , Acebes O.
Published: March 2003

We describe an unusual injury of the iliac crest in an adolescent football player. The injury occurred as a result of a sudden twist of the trunk while kicking. Plain radiographs showed avulsion fracture of the anterior part of the iliac crest apophysis. Five months later the injury was partially ossificated but the patient felt minor pain and was not confident of returning to playing football.
Muscle power factors and VO2max as determinants of horizontal and uphill running performance
Authors: Paavolainen L. , Nummela A. , Rusko H.
Published: March 2003

This study was carried out to investigate the importance of maximal oxygen uptake (VO2max) and so‐called muscle power factors relating to neuromuscular and anaerobic characteristics as determinants of peak horizontal and uphill treadmill running velocity (Vmax). Muscle power factors were measured as peak velocity (VMART) and blood lactate concentration (BlaMART) in a maximal anaerobic running test and as maximal 30‐m run velocity (V30m). Seven middle‐distance runners, eight triathletes and eight cross‐country skiers performed an incremental VO2max‐test at horizontal (subscript max0) and 7° uphill (subscript max7) and the MART at 3° uphill on a treadmill and V30m‐test on a track. The MART consisted of n  ·  20‐s runs with a 100‐s recovery between the runs and the velocity was increased by 0.41 m  ·  s−1 for each consecutive run until exhaustion. At 0° Vmax was significantly higher but VO2max, ventilation and Bla were significantly lower than at 7° inclination. Vmax0 correlated with VMART (r=0.85, P<0.001), Blamax0 (r=0.49, P<0.05) and V30m (r=0.78, P<0.001) but not with VO2max0. Vmax7 correlated with VO2max7 (r=0.78, P<0.001), VMART (r=0.61, P<0.01) and V30m (r=0.53, P<0.05). VMART correlated with BlaMART (r=0.71, P<0.01) and V30m (r=0.96, P<0.001) but not with VO2max0 or VO2max7. Middle‐distance runners had a significantly (P<0.001) higher Vmax0, VMART, BlaMART and V30m than triathletes and cross‐country skiers, but no significant differences were found between the three groups in VO2max0, VO2max7 or Vmax7. We conclude that so‐called muscle power factors, e.g. VMART, V30m and BlaMART, contribute to peak treadmill running performance and especially to horizontal running performance and that VO2max contributes more to uphill than horizontal running performance.
Relation between myofibers and connective tissue during muscle injury repair
Authors: Kääriäinen M. , Järvinen T. , Järvinen M. , Rantanen J. , Kalimo H.
Published: March 2003

The connective tissue framework in skeletal muscle combines the contractile myofibers into a functional unit, in which the contraction of myofibers is transformed into movement via myotendinous junctions (MTJs) at their ends, where myofibers attach to tendons/fascia. The cytoskeletal contractile myofilament apparatus adheres through subsarcolemmal and transmembrane molecules to the surrounding extracellular matrix, with integrin and dystrophin associated chains of molecules being the two main adhesion complexes. In shearing type of muscle injury both myofibers and the connective tissue framework are ruptured and thereby the functional tendon–muscle–tendon units are disrupted. The stumps of the ruptured myofibers are separated and at the same time joined by a connective tissue scar, through which the ends of regenerating myofibers try to pierce, but as the scar becomes more compact the ends attach to the scar by new mini‐MTJs. During the early phase ruptured myofibers try to compensate for the lost MTJ attachment by reinforcing their integrin mediated lateral adhesion, which returns to normal low level after formation of the mini‐MTJs and at which time complementary increase of dystrophin and associated molecules on lateral sarcolemma takes place. The stumps appear to remain separated by and attached to the interposed scar for many months, possibly for ever, i.e. the original tendon–muscle–tendon units may have become permanently divided into two consecutive units. Remarkably, axon sprouts are able to penetrate through the interposed scar to form new neuromuscular junctions on those abjunctional stumps which were denervated by the rupture.
Reconstruction of anterior cruciate ligament deficient knees in soccer players with an iliotibial band autograft
Authors: Bak K. , Jørgensen U. , Ekstrand J. , Scavenius M.
Published: March 2003

One hundred and thirty‐two consecutive soccer players (117 males and 15 females, median age 23, range 16–39 years) underwent primary reconstruction of the anterior cruciate ligament (ACL) with an iliotibial band (ITB) autograft. All patients were followed prospectively for a minimum of 2 years. One hundred and eighteen patients (89%) attended an independent observer follow‐up after a median of 47 (24–92) months. The time before participating in soccer was a median of 7 (5–24) months. At a median of 4 years, 80 (68%) were still active soccer players, while 38 had changed activity to a lower level. Twenty‐five gave up soccer playing for reasons unrelated to the knee, and 13 (11%) gave up due to problems from the reconstructed knee. The Lysholm score improved from a median of 82 (range 42–99, mean [SD] 80.5 [±11.9]) points prior to the operation to a median of 99 (range 57–100, mean [SD] 94.6 [±8.5]) at follow‐up. The Tegner score improved from a median of 3.5 (0–7) preoperatively to 9 (1–10). Four patients (3%) sustained a rupture of the graft: three ruptures occurred among the 15 females (20%), and one was seen among the 117 males (0.8%) (P=0.01). Eight per cent had predominantly minor cosmetic complaints from the donor‐site hernia, while 51% had temporary discomfort from the staples used for graft fixation. Using the ITB autograft for ACL reconstruction, we found excellent and good results in soccer players with ACL deficiency and high demands for optimal knee function. The failure rate in general was comparable with other methods, and the majority was still active in soccer sports at a median of 4 years after surgery. An unacceptably high rerupture rate was registered in female players.
Serum creatine kinase level is a poor predictor of muscle function after injury
Authors: Fridén J. , Lieber R. L.
Published: March 2003

Serum creatine kinase and dorsflexion torque levels were measured in New Zealand White rabbits 1, 2, 7, 14, or 28 days after a single bout of eccentric exercise (n=26). No significant correlation was observed between creatine kinase activity and torque across time periods (P>0.15) and the regression relationship described only about 8% of the experimental variability. These data demonstrate that there exists a poor correlation between serum creatine kinase levels and skeletal muscle function after eccentric exercise.
Eccentric overload training for patients with chronic Achilles tendon pain – a randomised controlled study with reliability testing of the evaluation methods
Authors: Grävare Silbernagel K. , Thomeé R. , Thomeé P. , Karlsson J.
Published: March 2003

The purpose was to examine the reliability of measurement techniques and evaluate the effect of a treatment protocol including eccentric overload for patients with chronic pain from the Achilles tendon. Thirty‐two patients with proximal achillodynia (44 involved Achilles tendons) participated in tests for reliability measures. No significant differences and strong (r=0.56–0.72) or very strong (r=0.90–0.93) correlations were found between pre‐tests, except for the documentation of pain at rest (P<0.008, r=0.45). To evaluate the effect of a 12‐week treatment protocol for patients with chronic proximal achillodynia (pain longer than three months) 40 patients (57 involved Achilles tendons) with a mean age of 45 years (range 19–77) were randomised into an experiment group (n=22) and a control group (n=18). Evaluations were performed after six weeks of treatment and after three and six months. The evaluations (including the pre‐tests), performed by a physical therapist unaware of the group the patients belonged to, consisted of a questionnaire, a range of motion test, a jumping test, a toe‐raise test, a pain on palpation test and pain evaluation during jumping, toe‐raises and at rest. A follow‐up was also performed after one year. There were no significant differences between groups at any of the evaluations, except that the experiment group jumped significantly lower than the control group at the six‐week evaluation. There was, however, an overall better result for the experiment group with significant improvements in plantar flexion, and reduction in pain on palpation, number of patients having pain during walking, having periods when asymptomatic and having swollen Achilles tendon. The controls did not show such changes. Furthermore, at the one‐year follow‐up there were significantly more patients in the experiment group, compared with the control group, that were satisfied with their present physical activity level, considered themselves fully recovered, and had no pain during or after physical activity. The measurement techniques and the treatment protocol with eccentric overload used in the present study can be recommended for patients with chronic pain from the Achilles tendon.
Monitoring tissue oxygen availability with near infrared spectroscopy (NIRS) in health and disease
Authors: Boushel R. , Langberg H. , Olesen J. , Gonzales‐Alonzo J. , Bülow J. , Kjær M.
Published: March 2003

Near infrared spectroscopy (NIRS) is becoming a widely used research instrument to measure tissue oxygen (O2) status non‐invasively. Continuous‐wave spectrometers are the most commonly used devices, which provide semi‐quantitative changes in oxygenated and deoxygenated hemoglobin in small blood vessels (arterioles, capillaries and venules). Refinement of NIRS hardware and the algorithms used to deconvolute the light absorption signal have improved the resolution and validity of cytochrome oxidase measurements. NIRS has been applied to measure oxygenation in a variety of tissues including muscle, brain and connective tissue, and more recently it has been used in the clinical setting to assess circulatory and metabolic abnormalities. Quantitative measures of blood flow are also possible using NIRS and a light‐absorbing tracer, which can be applied to evaluate circulatory responses to exercise along with the assessment of tissue O2 saturation. The venular O2 saturation can be estimated with NIRS by applying venous occlusion and measuring changes in oxygenated vs. total hemoglobin. These various measurements provide the opportunity to evaluate several important metabolic and circulatory patterns in very localized regions of tissue and may be fruitful in the study of occupational syndromes and a variety of diseases.
The effect of short‐term strength training on human skeletal muscle: the importance of physiologically elevated hormone levels
Authors: Hansen S. , Kvorning T. , Kjær M. , Sjøgaard G.
Published: March 2003

The effect of strength training and endogenously elevated hormone levels (plasma testosterone, growth hormone (GH) and cortisol) was studied in 16 young untrained males, divided into an arm only training group, A, and a leg plus arm training group, LA, in order to increase circulating levels of anabolic hormones. Both groups performed the same one‐sided arm training for 9 weeks, twice a week. Group A trained only one arm (AT), the contralateral arm serving as control (AC), whereas group LA additionally trained their legs following the training of the one arm (LAT), with the contralateral arm serving as control (LAC). In spite of the attempt to match the two groups, the initial isometric arm strength was 20–25% lower for group LA compared to group A (significant for the arm to be trained). Isometric strength increased significantly in LAT and LAC by 37% and 10%, respectively, while the 9% and 2% increases in AT and AC, respectively, remained insignificant. Isokinetic strength increased at one out of three velocities tested for the trained arm relative to the untrained arm in both group A and group LA (P<0.05). Functional strength increased significantly by 20% in LAT, 18% in LAC, 19% in AT, and 17% in AC. Hormonal responses were monitored during the first and last training sessions. Resting hormone levels remained unchanged for both groups. However, during the first training session plasma testosterone as well as plasma cortisol increased significantly in group LA but not in group A. Plasma GH rose in all exercise tests, except during the last test in group LA, but was significantly higher in group LA than in group A in the first training session. In conclusion, a larger relative increase in isometric strength was found in the group having the highest hormonal response. However, due to the initial difference in isometric strength caution must be taken with the interpretation of this finding, which may only indicate a possible link between anabolic hormones and muscle strength with training.
Self‐reported hamstring injuries in student‐dancers
Authors: Askling C. , Lund H. , Saartok T. , Thorstensson A.
Published: March 2003

Dancing involves powerful movements as well as flexibility exercises, both of which may be related to specific injuries to the musculo‐tendinosus tissue, e.g., the hamstring muscle complex. In this study, the occurrence of acute and overuse injuries to the rear thigh in dancers was investigated retrospectively by means of a questionnaire. All but one (n = 98) of the student‐dancers (age 17–25 years) at the Ballet Academy in Stockholm participated. The results demonstrated that, during the past 10 years, every third dancer (34%) reported that they had acute injuries and every sixth dancer (17%) had overuse injuries to the rear thigh. Most (91%) of the acute injuries were subjectively located to an area close to tuber ischiadicum. The majority (88%) stated that the acute injury occurred during slow activities in flexibility training, e.g., splits, and only a few (12%) in powerful movements. Continuing problems were reported by 70% of the acutely injured dancers. Many of the dancers neglected their acute injury (14 did not even stop the ongoing dance activity) and they also greatly underestimated the recovery time. Only 4 dancers (12%) received acute medical assistance. Thus the results, based on the recollection of the subjects, indicated that stretching could induce severe strain injuries to the proximal hamstrings in dancers. Extrapolating these results to the practice, it can be recommended that stretching exercises be executed with caution in connection with dancing sessions and training, and that, information about the seriousness and acute treatment of such injuries be added to the student‐dancers' curriculum.
In vivo optical coherence tomography imaging of human skin: norm and pathology
Authors: Gladkova N. D. , Petrova G. A. , Nikulin N. K. , Radenska‐Lopovok S. G. , Snopova L. B. , Chumakov Yu. P. , Nasonova V. A. , Gelikonov V. M. , Gelikonov G. V. , Kuranov R. V. , Sergeev A. M. , Feldchtein F. I.
Published: March 2003

Background/aims: Since the majority of skin diseases are known to be accompanied by structural alterations, research efforts are focused on the development of various novel diagnostic techniques capable of providing in vivo information on the skin structure. An essential parameter here is spatial resolution. In this paper we demonstrate the capabilities of optical coherence tomography (OCT) in detecting in vivo specific features of thin and thick skin. A particular focus is made on the identification of OCT patterns typical of certain pathological processes in skin, by performing parallel histological and tomographical studies.

Methods: To obtain images of the skin, we used a compact fiber OCT system developed at the Institute of Applied Physics of the Russian Academy of Sciences. A low coherence source (superluminescent diode) operated at a wavelength of 1280 nm; the output power was 0.5–2 mW. This power is low enough to conform to the ANSI safety standards for light exposure. The in‐depth resolution limited by the spectral bandwidth (40–50 nm) of the probing light was ∼20 μm. The lateral resolution determined by the probe light focusing ranged from 15 to 30 μm. In this series of experiments the maximum depth of imaging did not extend beyond 1.5 mm. Obtaining images of skin regions 2–6 mm long took 2–4 s. OCT capabilities for imaging normal skin of different localization and some skin diseases were studied in 12 healthy volunteers and 24 patients.

Results: OCT imaging of the skin can detect in vivo such general pathological reactions of the human body as active inflammation and necrosis. OCT is useful for in vivo diagnosis of some specific processes in the skin, including hyperkeratosis, parakeratosis and formation of intradermal cavities. OCT imaging is noninvasive and therefore allows frequent multifocal examination of skin without any adverse effects. OCT can perform monitoring of disease progress and recovery in the course of therapy. Morphometric studies, measurements of the depth and extension of skin pathology within the human body can be easily performed by OCT.

Conclusions: OCT allows imaging of subsurface soft tissues with the spatial resolution of 15–20 μm, a resolution one order of magnitude higher than that provided by other clinically available noninvasive diagnostic techniques. An imaging depth of up to 1.5–2 mm, given by current OCT technology, is sufficient to examine the skin. Real time OCT imaging can provide information not only on the structure, but also on some specific features in the functional state, of tissues. OCT imaging is a noninvasive technique, i.e., OCT does not cause trauma and has no side effects since it utilizes radiation in the near infrared wavelength range at a power as low as 1 mW.
Skin color measurements: comparison between three instruments: the Chromameter®, the DermaSpectrometer® and the Mexameter®
Authors: Clarys P. , Alewaeters K. , Lambrecht R. , Barel A. O.
Published: March 2003

Background/aims: Two types of skin reflectance instruments are available nowadays for the determination of skin color: a tristumulus colorimeter (Chromameter from Minolta) using the CIE L*a*b* color system and the narrow‐band simple reflectance meters (DermaSpectrometer from Cortex and Mexameter from Courage‐Khazaka) using the erythema/melanin indices. The purpose of this study was to compare the capabilities of the three instruments (sensitivity, repeatability and correlation) in vitro and in vivo.

Methods: Comparative color measurements were carried out first in vitro on standardized color charts and subsequently in vivo on different skin areas in human volunteers. Skin color changes induced by various physico‐chemical treatments were also quantitatively evaluated with the three instruments.

Results: The in vitro and in vivo repeatabilty as well as the sensitivity of the three instruments are rather good. Erythema and skin blanching could be readily quantified by the increase of the a* parameter and of the erythema indices of the simple reflectance meters. Natural UV tanning and artificial chemical tanning could be measured by the decrease of L* and increase of b* and of the melanin indices.

Conclusion: The Chromameter and the two narrow‐band reflectance instruments were able to characterize skin color and to quantify small skin color changes. Moderate to high significant linear correlations could be established between the CIE L*a*b* color parameters and the erythema/melanin indices.
The efficiency of humectants as skin moisturizers in the presence of oil
Authors: Sagiv Assaf Eliezer , Dikstein Shabtay , Ingber Arieh
Published: March 2003

Background/aims: The research on the treatment of “dry skin syndrome” is hampered by the lack of a suitable animal model. Formerly, we developed a validated guinea pig in vivo model in which the dry skin syndrome persists at least for 1 week. We can, therefore, compare the pharmacological effectiveness of known and potential moisturizers for the treatment of dry skin syndrome. Our aim is to study whether the moisturizing efficiency of humectants depends on the solvents in which they are dissolved.

Methods: “Dry skin syndrome” was induced on the shaved skin on one side of guinea pigs by daily application of 2% sodium lauryl sulphate in deionized water (SLS) for 3 days. The other shaved side was used as control. After ascertaining skin dryness, that side was treated for 6 days with glycerol or 1,2‐hexanediol in different solvents: water, or medium chain triglycerides (MCT) or mixtures of MCT with isopropyl alcohol in different proportions. Measurement of the in vivo moisturizing effect was carried out by a Corneometer CM 825®; erythema was measured by a Mexameter MX 16®.

Results: Treatments with glycerol (1M) in water reversed the skin dryness shown by both instruments. When dissolving glycerol in MCT, no moisturizing effect was found, probably because glycerol does not dissolve in the oil. No moisturizing effect was found with different combinations of glycerol in the mixtures of MCT and isopropyl alcohol. No moisturizing effect was found using another polyol moisturizer: 1,2 hexanediol (1M) dissolved in MCT oil. Glycerol or 1,2‐hexanediol abolished the erythema only when they were dissolved in water alone.

Conclusion: Polyol moisturizers such as glycerol or 1,2‐hexanediol do not act in the presence of oils against the sodium lauryl sulphate‐induced dry skin in our guinea pig model. Since in an oil‐in‐water (O/W) emulsion, the water evaporates within several minutes, one has to question the ability of moisturizing emulsions to treat dry skin. In such instances, one cannot draw conclusions about the moisturizing efficiency of the preparation merely from the presence of the humectant. One has to study the effect of the finished preparation.
Corticosteroid‐induced atrophy and barrier impairment measured by non‐invasive methods in human skin
Authors: Kolbe Ludger , Kligman Albert M. , Schreiner Volker , Stoudemayer Tracy
Published: March 2003

Background/aims: Atrophy is a distressing side effect of potent corticosteroids. After open application of a high potency steroid, we monitored atrophogenicity by a variety of non‐invasive methods.

Methods: Volar forearms were treated twice daily for 3 or 4 weeks, with clobetasol propionate cream (Temovate®). The following methods were used: 1) confocal microscopy, 2) transepidermal water loss (TEWL), 3) dimethyl sulfoxide whealing, 4) sodium hydroxide erosions, 5) analysis of stratum corneum lipids, and 6) B‐scan ultrasound.

Results: Confocal microscopy revealed thinning of the epidermis, decreased microvasculature and decreased size of keratinocytes. Evaporimetry demonstrated transepidermal water loss. Whealing to dimethyl sulfoxide was enhanced. Sodium hydroxide erosions formed more quickly. The amount of ceramides, cholesterol, and free fatty acids was reduced. Ultrasound showed thinning of the dermis.

Conclusion: Non‐invasive methods are very useful for quantifying the atrophogenicity of topical corticosteroids.