bluuebunny/crossref_metadata_2025 huggingface dataset:
Dermal Nevus Cells from Congenital Nevi Cannot Penetrate the Dermis in Skin Reconstructs
Authors: Gontier Etienne , Cario‐André Muriel , Lepreux Sébastien , Vergnes Pierre , Bizik Jozef , Surlève‐Bazeille Jean‐Etienne , Taïeb Alain
Published: March 2003

Congenital nevi are composed of pigment cells bearing common features with melanocytes but showing altered differentiation which leads to nesting and dermal involvement. Using a dead de‐epidermized dermis seeded with a combination of keratinocytes and various sources of pigment cells (normal melanocytes, dermal nevus cells from congenital nevi, Bowes melanoma cells), we have studied the formation of nests and the dermal migration of pigment cells together with their secretion profiles of matrix metalloproteinases (MMP). Dermal fibroblasts were also used as control cells in epidermal reconstructs. Besides their morphologic features, the absence of pigment donation to keratinocytes was the major characteristic of dermal nevus cells. A positive correlation was established between the increasing percentage of seeded nevus cells and the patchy pigmentation of reconstructs, as well as the clustering of cells in junctional nests. However, the presence of nevus cells in the dermis of reconstructs was never detected, whereas melanoma cells and dermal fibroblasts could invade the dermis during the time span of the experiments. MMP9 was never expressed in congenital dermal nevus cells but pro‐MMP2 was constitutively expressed by all strains of congenital nevus cells and dermal fibroblasts. Melanocytes produced comparable amounts of both pro‐MMP2 and pro‐MMP9, and Bowes melanoma cells secreted a marginal level of pro‐MMP2. In view of their three‐dimensional behaviour and secretion of MMPs, we propose that dermal congenital nevus cells correspond to an intermediate status of differentiation between normal melanocytes and melanoma cells. Activation of MMPs by a cofactor or the activation of another signalling pathway seems necessary to induce the dermal passage of nevus cells.
Keratinocytes Control the Pheo/Eumelanin Ratio in Cultured Normal Human Melanocytes
Authors: Duval Christine , Smit Nico P. M. , Kolb Adriana M. , Régnier Marcelle , Pavel Stan , Schmidt Rainer
Published: March 2003

The pheo/eumelanin ratio of cultured normal human melanocytes is distinct from the ratio observed for the same cells in vivo where they are in close contact with keratinocytes. To study the possible involvement of keratinocytes in the control of melanogenesis, we compared quantitatively and qualitatively the melanin production in melanocyte mono‐cultures, in melanocyte–keratinocyte co‐cultures and in pigmented reconstructed epidermis. Pheomelanin and eumelanin contents were assessed by high‐performance liquid chromatography with electrochemical and fluorometric detection of their specific degradation products and revealed striking differences in the presence of keratinocytes. In the absence of keratinocytes (melanocyte mono‐cultures), we observed a very limited eumelanin production and a very high pheomelanin synthesis. The pheo/eumelanin ratio in mono‐cultures could be slightly influenced by changing the composition of the culture medium, however, the very strong imbalance in favor of pheomelanin remained unchanged. An induction of eumelanin synthesis accompanied by an important reduction of pheomelanin formation was only observed in the presence of keratinocytes. The pheo/eumelanin ratio in melanocyte mono‐culture dropped from 1043 down to about 25 in the presence of keratinocytes (co‐cultures). The same observations were made when the melanocytes were integrated into a reconstructed human epidermis. Interestingly, under co‐culture conditions resulting in only a partial contact between melanocytes and keratinocytes, the reduction of the pheo/eumelanin ratio were less pronounced. From these results we conclude that keratinocytes play an important role in the melanin production, affecting the melanogenic pathways.
Bone resorption and local interleukin‐1α and interleukin‐1β synthesis induced by Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis lipopolysaccharide
Authors: Nishida Eiji , Hara Yoshitaka , Kaneko Takashi , Ikeda Yasuo , Ukai Takashi , Kato Ihachi
Published: March 2003

Different types of periodontopathic bacterial lipopolysaccharide (LPS) exert various biological activities in vitro. However, whether or not these activities also occur in vivo remains unclear. Thus the present study investigates bone resorption, as well as local IL‐1α and IL‐1β synthesis induced by Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis LPS in the periodontal tissue of mice. Both types of LPS were injected into mouse gingiva every 48 h and the animals were sacrificed 6 h after the 1st, 4th, 7th, 10th, 13th, 16th, 20th, or 24th injection. Bone resorption in the injected gingiva was histopathologically and histomorphometrically investigated and local concentrations of IL‐1α and IL‐1β were detected using an enzyme‐linked immunosorbent assay. The active resorption ratio was significantly higher in the group given the 10th injection of LPS from A. actinomycetemcomitans than in the group given P. gingivalis LPS. Furthermore, A. actinomycetemcomitans LPS stimulated significantly more synthesis of IL‐1α than P. gingivalis LPS after the 4th and 10th injections, and of IL‐1β after the 4th, 7th, 10th, 13th, 16th and 20th injections. These results suggest that A. actinomycetemcomitans LPS is a more potent inducer of bone resorption and synthesis of IL‐1α and IL‐1β in the short term than P. gingivalis LPS.
Localization of the chemokine interleukin‐8 and interleukin‐8 receptors in human gingiva and cultured gingival keratinocytes
Authors: Sfakianakis Andreas , Barr Charles E. , Kreutzer Don L.
Published: March 2003

Interleukin‐8 (IL‐8) has been implicated in a wide variety of diseases. Previous studies have demonstrated the expression of IL‐8 in periodontal tissues, yet little is known about the exact source(s), mechanisms and factors involved in gingival expression of IL‐8. Additionally, nothing is known about the presence and distribution of IL‐8 receptors (IL‐8R) in gingival cells. Therefore it was hypothesized that, in vivo, periodontal pathogens induce IL‐8 expression from gingival keratinocytes (GK) which enhances leukocyte, microvascular endothelial cell (MVEC) and GK migration via specific IL‐8 receptors present on these cells. The objective of the present study was to determine the distribution of IL‐8 and IL‐8R in gingival tissues and cultured human GK in vitro. Standard immunohistochemical and immunocytochemical techniques were utilized in order to localize IL‐8 and its receptors CXCR‐1 and CXCR‐2 in archival gingival specimens (eight periodontitis and four non‐inflamed controls) and in cultured gingival keratinocytes. It was demonstrated that, in vivo, IL‐8 and IL‐8R were present in gingival epithelium, MVEC and leukocytes. In vitro studies verified the above results, by showing expression of IL‐8 and IL‐8R in cultured gingival keratinocytes. It is concluded that IL‐8 and IL‐8 receptors are expressed in gingival epithelium both in vivo and in vitro. This new evidence indicates that epithelium plays a critical role in the host defense against invading pathogens and that keratinocytes can actively respond to IL‐8 and other host cytokines, via specific receptors.
Treponema denticola may stimulate both epithelial proliferation and apoptosis through MAP kinase signal pathways
Authors: Leung W. Keung , Wu Qiang , Hannam Pauline M. , McBride Barry C. , Uitto Veli‐Jukka
Published: March 2003

Mitogen‐activated protein kinases (MAP kinases) play a key role in the regulation of cell survival and death. Effects of Treponema denticola ATCC 35405 on ERK, p38 and JNK MAP kinases, and cell behavior was studied using non‐keratinizing periodontal ligament epithelial cells (PLE) in vitro. Compared to Chinese hamster ovary cells, human cervix adenocarcinoma cells, human osteosacroma cells and human gingival fibroblasts, PLE cells were much more resistant to T. denticola‐induced reduction in cell viability, assayed by tetrazolium and crystal violet assays. A low dose of 5 × 107T. denticola cells/ml increased DNA synthesis ([3H]thymidine uptake) in PLE cells but at higher concentrations DNA synthesis was decreased. TUNEL staining analysis showed that about 50% of epithelial cells in onolayers died through apoptosis when exposed to a high dose of 1011T. denticola/ml for 24 h. Morphological light and electron microscopic analysis supported the idea that both apoptotic and necrotic cell death took place. Rounding, membrane damage, fragmentation and detachment were observed in selective cells of both mono‐ and multilayered PLE cultures challenged with T. denticola. Western blot analysis using MAP kinase phosphospecific antibodies showed that T. denticola strongly but transiently activated ERK1 and ERK2, signals mediating cell proliferation, and JNK and p38, kinases mediating apoptosis. While a specific inhibitor of the ERK MAP kinase pathway prevented the T. denticola stimulation of cell proliferation, inhibitor of p38 increased the cell numbers in T. denticola‐treated cultures. The results suggest that T. denticola activates epithelial cell MAP kinase signal pathways controlling cell proliferation and cell survival. In addition, T. denticola exerts cytotoxic effects that appear to predominate at higher bacterial concentrations.
Antibiotic treatment of incipient drug‐induced gingival overgrowth in adult renal transplant patients
Authors: Mesa F. L. , Osuna A. , Aneiros J. , Gonzalez‐Jaranay M. , Bravo J. , Junco P. , Del Moral R. G. , O'Valle F.
Published: March 2003

Background: Drug‐induced gingival overgrowth (GO) remains a challenge in periodontics. Partial and total regressions of this GO have been reported after a short course of antibiotics.

Methods: We conducted a double‐blinded controlled randomised study to determine the effect of metronidazole (MNZ) or azithromycin (AZM) on the regression of incipient cyclosporin A‐induced GO in 40 adult renal transplanted patients. The quantitation of the GO was performed with Image Digital Analysis.

Results:None of the patients with GO showed complete remission after 30 days. The pretreatment GO index was 0.895 ± 0.16 in the metronidazole treatment group (MNZ group,n = 13), 0.932 ± 0.11 in the azithromycin treatment group (AZM group,n = 14), and 1.073 ± 0.32 in the controls (placebo group,n=13). At the end of the study (30 days), the GO index score was lower in 54.4% and 62.3% of the MNZ and AZM groups, respectively, and the mean score differences were statistically significant between the groups (0.897 ± 0.28, MNZ group vs. 0.909 ± 0.15, AZM group vs. 1.130 ± 0.3, placebo group,P < 0.05 ANOVA).

Conclusions:A 7‐day course of MNZ or AZM does not induce remission of CsA‐induced GO, although it acts on concomitant bacterial over‐infection and gingival inflammation.
Microdialysis Sampling of Carbamazepine, Phenytoin and Phenobarbital in Subcutaneous Extracellular Fluid and Subdural Cerebrospinal Fluid in Humans: An in vitro and in vivo Study of Adsorption to the Sampling Device
Authors: Lindberger Martin , Tomson Torbjörn , Ståhle Lars
Published: March 2003

Abstract: The purpose of the study was to determine if binding of the drugs to the sampling equipment during microdialysis would influence the results for carbamazepine, phenytoin and phenobarbital. In vitro experiments with microdialysis catheters and separate parts of catheters were performed to estimate the degree of drug binding to the dialysis equipment. A mathematical model to calculate drug binding and recovery is proposed. In vivo protein unbound carbamazepine concentrations in subcutaneous extracellular fluid at different flow rates (6 patients), unbound carbamazepine (1 patient) and unbound phenobarbital (1 patient) in subdural cerebrospinal fluid and subcutaneous extracellular fluid were estimated and the in vivo data were compared to the in vitro results and data generated by the mathematical model. Binding to the soft outlet polyurethane tubing was extensive and variable for phenytoin, which precluded in vivo testing, but limited and more predictable for carbamazepine and phenobarbital. None of the three compounds bound to the hard internal tubing. Phenytoin and phenobarbital did not bind to the dialysis membrane, while a small degree of binding may be present for carbamazepine. In vivo estimates of carbamazepine protein unbound subcutaneous extracellular concentrations by microdialysis, adjusted for binding to the plastic tubing, were 81% of protein unbound plasma concentrations. In single case studies, subdural cerebrospinal fluid and subcutaneous extracellular levels of carbamazepine and phenobarbital were similar and when corrected for binding to the plastic tubings they were also close to protein unbound plasma concentrations. Microdialysis can be used for reliable estimations of protein unbound carbamazepine and possibly phenobarbital concentrations when drug binding to the plastic tubing is considered. Reliable estimation of unbound phenytoin is not possible at present.
Gastric Functions in Gastrin Gene Knock‐Out Mice
Authors: Friis‐Hansen Lennart
Published: March 2003

Abstract: The gastric hormone gastrin was the 2nd hormone to be identified and was initially recognized for its ability to induce acid secretion. Following the purification and subsequent development of specific radioimmunoassays for gastrin, it was also shown to be a regulator of oxyntic mucosal growth. To explore the importance of gastrin or its receptors for gastric development and gastric physiology both have been knocked out. The knock‐out mice are viable, develop with any gross abnormalities, and are fertile. Even though gastrin acts as a growth factor during hypergastrinaemia there was no general atrophy of the gastrin mucosa in the knock‐out mice. But the maturation of both parietal and ECL cells were disturbed and the number of parietal cells reduced. Furthermore, lack of gastrin impaired basal acid secretion and rendered the parietal cells unresponsive to histamine and acetylcholine, the other two major stimulators of gastric acid secretion. Despite the major changes in gastric physiology, the number of genes down‐regulated in the gastrin knock‐out mice is modest. The achlorhydria due to lack of gastrin also leads to bacterial overgrowth of the stomachs of the gastrin knock‐out mice, which could facilitate the development of gastric ulcer disease and cancer.
Melatonin prevents endotoxin‐induced circulatory failure in rats
Authors: Wu Chin‐Chen , Chiao Chin‐Wei , Hsiao George , Chen Ann , Yen Mao‐Hsiung
Published: March 2003

The pineal secretory product melatonin was found to exert protective effects in septic shock. In a host infected by bacterial lipopolysaccharide (LPS), the expression and release of proinflammatory tumor necrosis factor‐α (TNF‐α) is rapidly increased, suggesting that TNF‐α is associated with the etiology of endotoxic shock. Recent reports show that the expression of NO synthase (NOS) II and the production of superoxide anion ( in aortae. In addition, the infiltration of polymorphonuclear neutrophils into the liver from the surviving LPS mice treated with melatonin was reduced. Thus, our results support the clinical use of melatonin in endotoxemia.
Melatonin in plant organs
Authors: Van Tassel David L. , Roberts Nicholas , Lewy Alfred , O'Neill Sharman D.
Published: March 2003

The indoleamine melatonin, a well‐known animal chemical, has been identified in extracts from several plant species. The function of melatonin in plants is unknown. Two major functions of melatonin in animals are dark signaling and antioxidant protection. Fruit ripening was used as a model physiological process that involves changes in the oxidative status of an organ. Tomato fruits at various stages of ripeness were sampled. Morning glory (Pharbitis nil Choisy, cv. Violet) and tomato (Lycopersicon esculentum Mill., cv. T5 and Castlemart) organs were collected throughout a light/dark cycle to determine whether melatonin levels increased during the night. No consistent evidence was found that melatonin increased significantly in organs of these plants during the night, as it does in many animals. The melatonin content of the fruits generally increased during ripening up to the mature ripe stage and thereafter as the fruit became over ripe.
Aging‐dependent changes in the effect of daily melatonin supplementation on rat metabolic and behavioral responses
Authors: Rasmussen Dennis D. , Mitton Dennis R. , Larsen Shana A. , Yellon Steven M.
Published: March 2003

Pineal melatonin secretion has been reported to commonly decrease with aging, whereas intra‐abdominal adiposity, plasma insulin and plasma leptin levels tend to increase. We recently demonstrated that daily melatonin administration starting at middle age suppressed male rat intra‐abdominal fat, plasma leptin and plasma insulin to youthful levels, suggesting that aging‐related changes in pineal melatonin secretion and in energy regulation may be functionally related. Accordingly, we have now investigated the effects of daily melatonin treatment on energy regulation in young versus middle‐aged male Sprague–Dawley rats. Addition of melatonin to the drinking water (0.2 μg/mL) produced nocturnal and diurnal plasma melatonin concentrations in middle‐aged rats (12 months) equivalent to those of young adult (5 months) rats. Administration of this melatonin dosage every day for 10 wk starting at 10 months of age suppressed (P<0.01) relative intra‐abdominal fat, non‐fasted plasma insulin and plasma leptin by 27, 39, and 51%, respectively (vs. vehicle‐treated controls). In contrast, administration of melatonin for 10 wk starting at 3 months of age did not significantly alter (P>0.10) any of these parameters. The melatonin administration stimulated (102%, P<0.001) behavioral responsiveness of the middle‐aged rats in a test of response to novelty, restoring youthful levels, but did not significantly alter behavioral responsiveness of the young rats. These results suggest that suppression of intra‐abdominal adiposity and plasma leptin and insulin levels and stimulation of behavioral responsiveness in response to daily exogenous melatonin begins at middle age, coincident with and likely dependent upon the aging‐associated decline in endogenous pineal melatonin secretion. These results further suggest that appropriate melatonin supplementation may potentially provide therapy or prophylaxis not only for the insulin resistance, increased intra‐abdominal fat and resulting pathologies that occur with aging, but also for some aging‐associated behavioral changes.
Preventive effect of melatonin against DNA damage induced by cyanide, kainate, glutathione/Fe3+/O2, or H2O2/Fe2+
Authors: Yamamoto Hiro‐aki , Mohanan Parayanthala V.
Published: March 2003

We have investigated hydroxyl free radical (⋅OH)‐mediated damage to calf thymus DNA produced by potassium cyanide, kainate, H2O2/Fe2+, or glutathione/Fe3+ by in vitro method. When calf thymus DNA was exposed to potassium cyanide (0.5, 0.75, 1.0, 1.5, or 2.0 mM) or kainate (0.25, 0.5, or 1.0 mM) for 90 min at 37°C in homogenate or the 9000g supernatant of mice brain, the quantity of DNA damage was observed to be concentration‐dependent. Similarly, glutathione (1.0, 2.0, 4.0, 5.0, or 6.0 mM) inflicted damage on calf thymus DNA in the presence of Fe3+ (3.0 μM). In addition, hydrogen peroxide (0.15, 0.30, 0.75, 1.50, or 3.0 mM) also caused damage to calf thymus DNA in the presence of Fe2+ (3.0 μM) in the same manner. Furthermore, it was observed that the DNA damage induced by potassium cyanide (2.0 mM), kainate (0.5 mM), glutathione (4.0 mM)/Fe3+, and H2O2 (1.5 mM)/Fe2+ was prevented by the treatment with melatonin (1.0 or 1.5 mM), a potent ⋅OH scavenger. These results suggest that cyanide, kainate, glutathione/Fe3+, and H2O2/Fe2+‐mediated ⋅OH may play a cardinal role for DNA damage induced by these chemicals. Hence the conclusion of the present study is that melatonin protects against DNA damage induced by the ⋅OH produced by these chemicals.
Melatonin modulates allergic lung inflammation
Authors: Martins Eivor , Ligeiro de Oliveira Ana Paula , Fialho de Araujo Ana Maria , Tavares de Lima Wothan , Cipolla‐Neto José , Costa Rosa Luis Fernando B. P.
Published: March 2003

Asthma is an inflammatory lung disease characterized by cell migration, bronchoconstriction and hyperresponsiveness, and can be induced, as an experimental model, by ovalbumin sensitization followed by a challenge. In addition to the well‐known immunostimulatory effects of melatonin, research has identified some of its anti‐inflammatory properties. In this study, we evaluated the influence of pinealectomy and melatonin administration on cell migration in an experimental model of allergic airway inflammation. We evaluated, in pinealectomized rats treated or not with melatonin, cell migration into the bronchoalveolar fluid, the number of cells and their proliferative activity in the bone marrow, and plasma corticosterone levels. Pinealectomy reduces, 24 hr after the challenge, the total cell number count in the lung and bone marrow cell proliferation, without changing the number of cells in the bone marrow or in the peripheral blood. This fact suggests that melatonin is important in the control of cell recruitment from the bone marrow and the migration of those cells to the lung. Melatonin administration to pinealectomized rats seems to restore the ability of cells to migrate from the bone marrow to the bronchoalveolar fluid. So, the development of specific inhibitors of melatonin would benefit patients with asthma.
Effect of melatonin and nifedipine on some antioxidant enzymes and different energy fuels in the blood and brain of global ischemic rats
Authors: El‐Abhar Hanan S. , Shaalan Mona , Barakat Maged , El‐Denshary Ezzedin S.
Published: March 2003

Abstract: The brain normally derives most of its energy from the aerobic oxidation of glucose and therefore it must be nourished with a rich supply of both glucose and oxygen. Interference with the blood supply, such as in ischemia, could shift the brain to search for another source of energy and to spare its own glucose. Ischemia results not only in energy fuel disturbance, but also in free radical formation and Ca2+ homeostasis disruption. Therefore, our investigations studied the influence of ischemia on energy fuels, on some natural free radical scavengers, and the relationship between the changes of these parameters in brain and blood. Each of these was also studied under the influence of melatonin, a well‐known free radicalscavenger, and nifedipine, a Ca2+‐channel blocker and antioxidant, during ischemia followed by reperfusion (I/R). Adult male Wistar rats were subjected to global ischemia by occlusion of the two carotid arteries for 1 hr (group I), followed by reperfusion for another hour in group II. Drugs were injected after ischemia (group I), and before or after reperfusion onset in the second group. Two series of animals were used. In the first series the effect of the two drugs on the activity of superoxide dismutase (SOD), glutathione reductase (GR), and lactate dehydrogenase (LDH) was investigated in thecytosolic fraction of four brain areas, viz., cortex (CC), thalamus/hypothalamus (T/TH), midbrain (MB) and medulla, pons and cerebellum (MPC). Moreover, the level of both SOD and GR in the erythocytes of these rats was also estimated. In the second series, we studied the effect of each drug on the content of glucose and β‐hydroxybutyrate (β‐HB) in whole brain, in addition to the plasma levels of glucose, β‐HB and lactate. The results showed that (i), ischemia elevated the brain levels of LDH and β‐HB, as well as the plasma level of glucose, β‐HB, lactate and erythocytic GR. Conversely, it lowered glucose, SOD and GR levels in the brain; (ii), reperfusion reversed the ischemic effect on all the previously altered parameters except for plasma levels of lactate and glucose; (iii), melatonin (10 mg/kg, i.p) and nifedipine (1.5 mg/kg, i.p), restored the energy fuel levels in the brain of ischemic and I/R rats, as well as the ischemic effect on the erythocyte activities of SOD and GR. Furthermore, both drugs reversed I/R effect on the cytosolic activities of the antioxidant enzymes. We conclude that melatonin and nifedipine are both neuroprotective with improvement in the antioxidant system and energy fuels.
Spontaneous central melatonin secretion and resorption kinetics of exogenous melatonin: a ventricular CSF study
Authors: Debus Otfried M. , Lerchl Alexander , Bothe Hans W. , Bremer Janbernd , Fiedler Barbara , Franssen Meike , Koehring Jessica , Steils Michaela , Kurlemann Gerhard
Published: March 2003

Abstract: Pineal secretion of melatonin, a potential sleep‐inducing agent, is stimulated by nighttime darkness. To gain better insight into the control of melatonin physiology in man, we studied melatonin concentrations in ventricular cerebrospinal fluid (v‐CSF). In four patients aged 1–4 yr with therapeutic v‐CSF drainage, including one with lumbar CSF (l‐CSF) drainage, CSF samples were collected sequentially over 24‐hr periods. One further patient with severe sleep disturbance had one collection period under chloral hydrate and another after oral melatonin administration. Reduction of light intensity or night periods, respectively, led to increased melatonin levels. At the moment of falling asleep, additional melatonin peaks were observed in v‐CSF but not in l‐CSF. Oral melatonin, but not chloral hydrate, caused a rapid increase in CSF melatonin between 10 and 80 min after intake, raising levels far beyond physiological concentrations. The commencement of sleep is associated with an additional melatonin peak v‐CSF which is independent of baseline secretion during the day–night cycle. The possibility is discussed that the induction of sleep might depend on a critical level or increased melatonin concentrations, which can be achieved with orally administered melatonin.
Melatonin increases oestradiol‐induced bone formation in ovariectomized rats
Authors: Ladizesky Marta G. , Boggio Verónica , Albornoz Liliana E. , Castrillón Patricia O. , Mautalen Carlos , Cardinali Daniel P.
Published: March 2003

Abstract: To assess the effect of melatonin on bone metabolism in ovariectomized rats, receiving oestradiol therapy or not, melatonin was administered in the drinking water (25 μg/mL water) and oestradiol (10 μg/kg body weight) or vehicle was given subcutaneously 5 days/week for up to 60 days after surgery. Urinary deoxypyridinoline (a marker of bone resorption) and circulating levels of bone alkaline phosphatase activity (a marker of bone formation), as well as serum calcium and phosphorus levels, were measured every 15 days. Bone area (BA), bone mineral content (BMC), bone mineral density (BMD) and total body fat (expressed as 100 g body weight) were measured by dual‐energy X‐ray absorptiometry at the end of the experiment. Body weight and total body fat were augmented after ovariectomy, and decreased after melatonin or oestradiol treatment. The effect of melatonin on body weight was seen in sham‐operated rats only. Ovariectomy augmented, and melatonin or oestradiol lowered, urinary deoxypyridinoline excretion. This effect of melatonin and oestradiol was seen mainly in ovariectomized rats. The efficacy of oestradiol to counteract ovariectomy‐induced bone resorption was increased by melatonin. Melatonin or oestradiol lowered serum bone alkaline phosphatase activity. Melatonin inhibition was seen mainly on the increase of bone alkaline phosphatase activity that followed ovariectomy. Serum phosphorus levels decreased after melatonin administration and were augmented after oestradiol injection; overall, melatonin impaired the increase of serum phosphorus caused by oestradiol. Ovariectomy decreased, and oestradiol increased, serum calcium levels while melatonin augmented serum calcium in sham‐operated rats only. On day 60 after surgery, BMD and content decreased after ovariectomy and were increased after oestradiol injection. Melatonin augmented BA of spine and BMC of whole of the skeleton and tibia. The highest values observed were those of rats treated concurrently with oestradiol and melatonin. The present results indicate that: (i) melatonin treatment restrained bone remodelling after ovariectomy; (ii) the effect of melatonin required adequate concentrations of oestradiol; (iii) melatonin augmented oestradiol effects on bone in ovariectomized rats; (iv) a counter‐regulation by melatonin of the increase in body fat caused by ovariectomy was uncovered. The melatonin doses employed were pharmacological in terms of circulating melatonin levels but not necessarily for some other fluids or tissues.
A 7‐year study on risks and costs of knee injuries in male and female youth participants in 12 sports
Authors: Loës M. , Dahlstedt L. J. , Thomée R.
Published: March 2003

Knee injuries are common and account in various sports for 15–50% of all sports injuries. The cost of knee injuries is therefore a large part of the cost for medical care of sports injuries. Furthermore, the risk of acquiring a knee injury during sports is considered higher for females than for males. The nationwide organization “Youth and Sports” represents the major source of organized sports and recreation for Swiss youth and engages annually around 370  000 participants in the age group of 14 to 20 years. The purpose of this study was to combine data on knee injuries from two sources, the first being data on the exposure to risk found in the activity registration in “Youth and Sports” and the second injuries with their associated costs resulting from the activities and filed at the Swiss Military Insurance. This allowed calculation of knee injury incidences, to compare risks between males and females and to estimate the costs of medical treatment. The study comprises 3864 knee injuries from 12 sports during 7 years. Females were significantly more at risk in six sports: alpinism, downhill skiing, gymnastics, volleyball, basketball and team handball. The incidences of knee injuries and of cruciate ligament injuries in particular, together with the costs per hour of participation, all displayed the same sports as the top five for both females and males: icehockey, team handball, soccer, downhill skiing and basketball. Female alpinism and gymnastics had also high rankings. Knee injuries comprised 10% of all injuries in males and 13% in females, but their proportional contribution to the costs per hour of participation was 27% and 33%, respectively. From this study it can be concluded that females were significantly more at risk for knee injuries than males in six sports and that knee injuries accounted for a high proportion of the costs of medical treatment.
Aiming routines and their electrocortical concomitants among competitive rifle shooters
Authors: Konttinen N. , Landers D. M. , Lyytinen H.
Published: March 2003

The present study focused on an examination of competitive shooters’ aiming process during a rifle shooting task. The barrel movements of the rifle, as detected by a laser system during the last 1000‐ms time period preceding the triggering, were recorded from six elite and six pre‐elite shooters. Electrocortical slow potentials (SPs) from frontal (Fz), centro‐lateral (C3, C4), and occipital (Oz) brain areas were recorded to get an additional insight into the underlying covert processing. The results suggested that the elite shooters did not pull the trigger until they reached a sustained rifle position. In the pre‐elite shooters the rifle appeared to be in a less stable position, and their strategy was to take advantage of the first appropriate moment of steadiness without a sustained rifle position so they could pull the trigger. The observed pre‐trigger readiness potential (RP) shifts at Fz and Oz were more positive among the elite shooters relative to the pre‐elite shooters, reflecting their more pronounced covert effort, rather than increasing preparedness for the trigger pull. The present study lends support for the view that a successful aiming strategy is mainly based on sustained rifle balancing. With regards to the brain slow potentials, it can be concluded that the RP shift does not specifically reflect the preparation for the trigger pull.
The effect of heart rate controlled low resistance circuit weight training and endurance training on maximal aerobic power in sedentary adults
Authors: Kaikkonen H. , Yrjämä M. , Siljander E. , Byman P. , Laukkanen R.
Published: March 2003

The effects of a 12‐week low resistance circuit weight training (CWT) on cardiovascular and muscular fitness were studied in 90 healthy sedentary adults. The subjects were randomized into three equally fit groups: CWT, Endurance (END) and Control (CON) according to their maximal aerobic power (VO2max). Both training groups exercised for 12 weeks, 3 days a week in sessions of 40 min, with a heart rate (HR) level of 70–80% HRmax. The CWT group trained with air resistance machines. Heart rate was controlled by setting the speed of movement. The END group walked, jogged, cross‐country skied or cycled. The net differences (between pre‐ and posttraining changes) between the CWT and CON groups was statistically significant for VO2max (2.45 ml  ·  min−1  ·  kg−1, 95% CI 1.1; 3.8), for abdominal muscles (3.7 reps, CI 0.3; 7.1), for push‐ups (1.1 reps, CI 0.2; 2.1), and for kneeling (2.25 reps, CI 0.01; 4.5). The net difference (between pre‐ and posttraining changes) in the END and CON groups was statistically significant for VO2max (2.75 ml  ·  min−1  ·  kg−1, 95% CI 0.9; 4.6), and kneeling (3.0 reps, CI 0.7; 5.3). Low resistance CWT with moderately hard HR level has effects comparable to an equal amount of endurance training on the cardiovascular fitness of sedentary adults. The CWT model was benefical also on muscular fitness. Based on the results, this type of exercise can be recommended for beginners because of its multilevel effects.
Biochemical composition of muscle extracellular matrix: the effect of loading
Authors: Takala T. E. , Virtanen P.
Published: March 2003

Collagen plays an important role in skeletal muscle both during muscle differentiation and normal muscle growth, and also serves a role as a supportive structure. It is the most abundant protein of the extracellular matrix and of the 19 distinct collagen types, types I, III, IV and V are the dominating ones in skeletal muscle. Both collagen synthesis as well as degradation is influenced by either physical loading or immobilization in skeletal muscle, and recent methods have allowed for greater understanding of the posttranslational processing of collagen.
Traumatic arthritis in sport
Authors: Fredberg U. , Bolvig L.
Published: March 2003

After the introduction of ultrasonography in sports medicine, traumatic arthritis is recognized relatively frequently among athletes. In this case study, the ultrasonographic findings and the prompt effect of ultrasonographically guided intra‐articular injection of long‐acting steroid are demonstrated in two patients.
Injuries in adolescent female players in European football: a prospective study over one outdoor soccer season
Authors: Söderman K. , Adolphson J. , Lorentzon R. , Alfredson H.
Published: March 2003

In this prospective study, injuries in 153 adolescent female soccer players were recorded during one outdoor season (April–October). The overall injury incidence rate was 6.8 per 1000 h soccer (games and practice) and the incidence rate of traumatic injury 9.1 and 1.5 per 1000 player‐hours in games and practice, respectively. Sixty‐three players (41%) sustained 79 injuries. Sixty‐six percent of the injuries were traumatic and 34% were overuse injuries. Most of the traumatic injuries occurred during games. Eighty‐nine percent of the injuries were located in the lower extremities and 42% occurred in the knee or ankle. The most frequent type of injury was ankle sprain (22.8%). Forty‐one percent of the traumatic injuries and 56% of the ankle sprains were re‐injuries. Most of the injuries were of moderate severity (52%), while 34% were minor and 14% were major. Most of the major injuries were traumatic such as knee ligament injuries and ankle sprains.
Fracture‐dislocation of the tarsal navicular in a soccer player
Authors: Lüthje P. , Nurmi I.
Published: March 2003

We describe an unusual injury of the mid‐tarsal region in a soccer goalkeeper. The injury occurred in a training game as a result of an abduction‐plantar‐flexion. Radiographs showed a fracture‐dislocation of the tarsal navicular. The patient was treated by closed reduction with percutaneous fixation using two Kirschner wires. The end‐result was satisfactory but the patient felt pain in the mid‐foot during and after sports activities and was unable to continue playing as a goalkeeper.
Delayed‐onset muscle soreness does not reflect the magnitude of eccentric exercise‐induced muscle damage
Authors: Nosaka Kazunori , Newton Mike , Sacco Paul
Published: March 2003

This study investigated the relationship between delayed‐onset muscle soreness and other indicators of muscle damage following eccentric exercise. Male students (n = 110) performed 12 (12ECC), 24 (24ECC), or 60 maximal eccentric actions of the elbow flexors (60ECC). Maximal isometric force, relaxed and flexed elbow joint angles, upper arm circumference, and plasma creatine kinase activity were assessed immediately before and after, and for 4 days after exercise. Muscle soreness (SOR) was evaluated by a visual analog scale (a 50‐mm line, 0: no pain, 50: extremely painful) when the elbow flexors were palpated (SOR–Pal), flexed (SOR–Flx) and stretched (SOR–Ext). Although 24ECC and 60ECC resulted in significantly (P <; 0.05) larger changes in all indicators and slower recovery compared to 12ECC, no significant differences were evident for SOR–Pal and SOR–Flx between 12ECC and 24ECC, or 12ECC and 60ECC. In contrast, SOR–Ext was significantly (P <; 0.05) lower for 12ECC compared to 24ECC and 60ECC. A Pearson product‐moment correlation showed SOR–Pal did not correlate significantly with any indicators, however, SOR–Ext and SOR–Flx showed weak (r <; 0.32) but significant (P <; 0.05) correlations with other indicators. Because of generally poor correlations between DOMS and other indicators, we conclude that use of DOMS is a poor reflector of eccentric exercise‐induced muscle damage and inflammation, and changes in indirect markers of muscle damage and inflammation are not necessarily accompanied with DOMS.
Measurement of viscoelastic properties of tendon structures in vivo
Authors: Kubo K. , Kawakami Y. , Kanehisa H. , Fukunaga T.
Published: March 2003

The purpose of this study was to investigate the viscoelastic properties of tendon structures in humans. Elongation of the tendon and aponeurosis of medial gastrocnemius muscle (MG) was directly measured by ultrasonography, while subjects (n=19) performed ramp isometric plantar flexion up to the voluntary maximum, followed by a ramp relaxation. The relationship between tendon elongation (L) and estimated muscle force (Fm) was fitted to a linear regression, the slope of which was defined as compliance of the tendon structures. The hysteresis was calculated as the ratio of the area within the L‐Fm loop (elastic energy dissipated) to the area beneath the load portion of the curve (elastic energy input). The resulting L‐Fm relationship was non‐linear in form, as previously reported on animal and human tendons in vitro. The mean compliance was 4.5±1.1  ·  10−2 mm/N. However, there was a considerable inter‐subject variability (2.9 to 7.2  ·  10−2 mm/N). The Young's modulus, i.e., the slope of the stress–strain curve, was 280 MPa, which tended to be lower than the previously reported values for human tendons. It was also found that the strain of the tendon structures was homogeneously distributed along their length. The mean hysteresis (energy dissipation) was 22.2±8.8%. However, again there was a considerable inter‐subject variability (9.7 to 37.2%). The present results indicated that the tendon structures of human MG were considerably compliant and their hysteresis was in accordance with previously reported values.
Automated melanoma diagnosis: where are we at?
Authors: Day Greg R. , Barbour Robert H.
Published: March 2003

Background:

It has been over a decade since the first mention was made of the computer as a tool for assisting clinicians in diagnosing skin lesions. This review tabulates and summarises the major research papers, and comments on the state of the field after a decade of research.

Conclusions: We conclude that epiluminescent microscopy has become the image‐capture technique of choice in this field. However, the reporting of research to date has been less than exemplary, making “reinvention of the wheel” likely. It also appears that although the goal of a clinically useful diagnostic system is closer, the complexity and variation displayed by skin lesions, coupled with the ad hoc direction and reporting of research, may hinder the achievement of this goal for some time to come.
Transepidermal water loss, temperature and sebum levels on women's facial skin follow characteristic patterns
Authors: Lopez Sabine , Le Fur Isabelle , Morizot Frédérique , Heuvin Guylaine , Guinot Christiane , Tschachler Erwin
Published: March 2003

Background/aims: The aim of this study was to compare the biophysical properties of different facial zones.

Methods: We investigated transepidermal water loss (TEWL), skin temperature and sebum casual level (CL) on 90 adjacent test sites distributed on the forehead, cheeks and chin of five women.

Results: All three parameters showed a symmetrical distribution around the facial median line. Only minor variations of individual values were found within the forehead and the chin areas. In contrast, the cheeks exhibited a distinct gradient with highest values in the paranasal zones and lowest on the cheek bones for all of the three parameters. The mean values on both cheeks of a given individual were nearly identical, and the patterns within the two cheeks were superimposable. Both CL and skin temperature distributions pointed out a “T‐zone” with highest values on the forehead, on the chin and on the median part of the cheek.

Conclusions: Our data demonstrate that biophysical skin properties differ considerably between different facial areas but that they follow a characteristic distribution.
Fluorescein dermofluorometry for the assessment of diabetic microvascular disease
Authors: Oh Deborah K. , Jones Richard N. , Marshall William , Magin Richard L.
Published: March 2003

Background/aims: Fluorescein dermofluorometry can be used to relate the uptake of fluorescein in the skin to blood flow. We have characterized the uptake of the dye by a wash‐in time constant that is inversely proportional to the local blood flow. The purpose of this study was to explore the use of dermofluorometry in the assessment of patients with diabetic microvascular disease.

Methods: Fluorescein dermofluorometry was performed in four groups of patients: non‐diabetic control patients, diabetic control patients, diabetic patients with chronic foot ulcers, and diabetic patients with acute foot ulcers. The outcomes of the patients with foot ulcers were documented 4–14 months after participation. Following an intravenous injection of sodium fluorescein, the change in the fluorescein signal with time was continuously measured at the plantar surface of the foot. Both the initial slope of the signal and the wash‐in time constant were calculated in each subject.

Results: Significant differences in the wash‐in time constant were found between diabetic and non‐diabetic subjects and between diabetic subjects with and without foot ulcers. Of the eight patients with foot ulcers, two of them did not display an early wash‐out in the dermofluorometer signal and later both required amputations.

Conclusion: The fluorescein wash‐in time constant demonstrated better correlation with the presence of diabetic microvascular disease than did the initial slope of the signal. Differences in the wash‐in time constants of non‐diabetic and diabetic subjects support the hemodynamic hypothesis for the development of microvascular disease. The indication of early wash‐out of the fluorescein signal may also be useful in the prediction of ulcer healing.
Development and validation of a semiautomatic image analysis system for measuring skin desquamation with D‐Squames®
Authors: Wilhelm K.‐P. , Kaspar K. , Schumann F. , Articus K.
Published: March 2003

Background D‐Squames®, have gained wide acceptance for assessing skin desquamation. The amount of corneocytes adhering to D‐Squames® can be assessed visually by trained observers or by computerized image analysis. Different image analysis algorythms for the evaluation of D‐Squames® have been published but have not been compared with each other. It was our aim to develop an image analysis system that does not require an expensive image analysis programming tool but should be optimized for routine tasks of analysing large numbers of samples. A second objective of this study was to compare two published image analysis algorythms and visual grading.

Material and Methods The hardware components of the system are a CCD camera connected to a frame grabber card and a light box equipped with fluorescent tubes on two sides that provide a relatively cool, diffuse and even illumination of the sample. The following features were included into the software: generation and identification of bar codes for sample identification; semiautomatic recognition of ROI (region of interest), integration of study design into the analysing process, rapid calculation of desquamation index (DI: integration of the per cent area covered by scales and their thickness distribution) and/or scaling index (SI: distribution of grey values), data storage and export for further analysis.

In a first step the system was validated by examining D‐Squames covering a wide range of desquamation, by examining different ROI shapes (circle and square), by performing repeat measurements with different positions of the samples and by repeat measurements after re‐callibrating the system. In a second step the effect of treatment with different moisturizers was evaluated by the two image analysis parameters DI and SI and compared with hydration measurements (Corneometer®).

Results The shape of the ROI showed no influence on the results (variability < 5%). Reproducibility of measurements was satisfactory (COV CDI): 1.7%, COV (SI): 2.6%).There was a good correlation between image analysis results and visual evaluation (means of 3 technicians) (r = 0.986) as well as between the two different image analysis parameters DI and SI (r = 0.971). In the clinical study moisturizer treatment resulted in variable reduction of desquamation that was closely correlated with increase in stratum corneum hydration (r = 0.97).

Conclusion Analysing D‐Squames® with the image analysis system proved to be reproducible, independent of the shape of ROI, cost effective and fast and easy to operate. It has shown to be a suitable and reliable method for the objective determination of desquamation levels.