bluuebunny/crossref_metadata_2025 huggingface dataset:
Ethnic Variation in Tyrosinase and TYRP1 Expression in Photoexposed and Photoprotected Human Skin
Authors: Alaluf Simon , Barrett Karen , Blount Margaret , Carter Nik
Published: March 2003

The relative expression of a number of key mediators of human pigmentation including tyrosinase, tyrosinase related protein‐1 (TYRP1), endothelin‐1 and adrenocorticotrophic hormone (ACTH) proteins were analysed and quantified in immunohistochemically stained skin sections using semiquantitative computer assisted image analysis. Comparisons were made between a range of different ethnic skin types including European, Chinese, Mexican, Indian and African at both chronically photoexposed and photoprotected sites. Melanocyte number varied little with ethnicity except in the European group which had 60–80% more melanocytes than other skin types (P < 0.01, n = 10; Student Neuman–Keuls). However, melanocyte number was increased ∼twofold in chronically photoexposed skin of all ethnic groups (P < 0.001, n = 48; paired t‐test). Tyrosinase protein expression in melanocytes did not vary with ethnicity, but TYRP1 protein was significantly elevated (∼2.6‐fold) in darkly pigmented African and Indian skin types compared with lightly pigmented Mexican, Chinese and European skin types. In melanocytes from chronically photoexposed skin, there was a modest but significant increase in the expression of tyrosinase protein (∼1.2‐fold, P < 0.001, n = 48; paired t‐test), together with a significant and slightly larger increase in the expression of TYRP1 protein (∼1.6‐fold, P < 0.005, n = 48; paired t‐test). In contrast, the expression of endothelin‐1 and ACTH showed no significant variation with either ethnicity or photoexposure. These data are consistent with the view that maintenance of a chronically hyperpigmented phenotype in chronically photoexposed human skin is largely the result of a stable increase in the number of tyrosinase positive melanocytes at these sites. Moreover, the observed ethnic variation in TYRP1 protein expression suggests that TYRP1 may play a significant role in mediating ethnic differences in melanogenesis and constitutive skin pigmentation in vivo.
Phenotypical and functional analysis of T cells in periodontitis
Authors: Petit M. D. A. , Hovenkamp E. , Hamann D. , Roos M. T. L. , Van Der Velden U. , Miedema F. , Loos B. G.
Published: March 2003

To explore aspects of cellular immune responses in the pathogenesis of periodontitis we analyzed phenotype and function of peripheral T cells. Two groups of subjects participated: one group consisted of 10 highly susceptible patients with severe periodontitis (mean age 29 years) and a control group consisted of 10 age, gender and race matched subjects with gingivitis. From all subjects peripheral blood was collected. The results showed that the numbers of CD3+, CD4+ and CD8+ T cells as well as the CD4/CD8 ratio, and the proliferative capacity of T cells, were not different between the two groups of subjects. Also, proportions of naive and memory T cells for both the CD4+ and CD8+ subpopulations were not different. Functional heterogeneity within the CD4+ and CD8+ T cell compartments was determined by intracellular analysis of interferon‐γ(IFN‐γ) and interleukin‐4 (IL‐4) production. On the basis of these latter analyses among CD4+ and CD8+ cells, T helper (Th) 1 or Th2 function and T cytotoxic (Tc) 1 or Tc2 function, respectively, could be deduced. No significant differences in proportions of CD4+ and CD8+ T cells positive for intracellular IFN‐γ or IL‐4 were observed between periodontitis patients and gingivitis controls; however a higher level of intracellular IL‐4 in CD8+ T cells was seen in periodontitis patients. This might indicate that there is a shift towards a Tc2 function within the CD8+ T cell subpopulation. The current explorative study suggests that further research into the role of CD8+T cells in the pathogenesis of periodontitis is warranted.
Hepatocyte growth factor secreted by periodontal ligament and gingival fibroblasts is a major chemoattractant for gingival epithelial cells
Authors: Ohshima Mitsuhiro , Noguchi Yoshihiro , Ito Mitsuyasu , Maeno Masao , Otsuka Kichibee
Published: March 2003

To ascertain whether periodontal fibroblasts could be involved in the pathogenesis of periodontal pocket formation, the chemotactic activity of periodontal ligament fibroblast‐conditioned medium (PLF‐CM) and gingival fibroblast‐conditioned medium (GF‐CM) for gingival epithelial cells was examined using a modified Boyden chamber assay. Both PLF‐CM and GF‐CM possessed significant chemotactic activity, which was decreased markedly by treatment with anti‐human hepatocyte growth factor (HGF) neutralizing antibody. Furthermore, the chemotactic activity of PLF‐CM and GF‐CM was well correlated with HGF content. These results show that PLF and GF secrete an HGF‐like factor, and suggest that such a factor derived from periodontal fibroblasts might play a role in epithelial apical migration in periodontitis.
Differential gene expression in neutrophils from patients with generalized aggressive periodontitis
Authors: Kubota Takehiko , Morozumi Toshiya , Shimizu Kunihiko , Sugita Noriko , Kobayashi Tetsuo , Yoshie Hiromasa
Published: March 2003

Differential gene expression was investigated in neutrophils stimulated with N‐formyl‐methionyl‐leucyl‐phenylalanine using RNA fingerprinting by arbitrarily primed polymerase chain reaction (RAP‐PCR). The cells were isolated from 3 groups of subjects: patients with generalized aggressive periodontitis (Aggressive‐P, n=6), generalized chronic periodontitis (Chronic‐P, n=6) and healthy controls (H, n=8). Our results show that 37 genes were upregulated, while 27 genes were down‐regulated in all Aggressive‐P neutrophils by using RAP‐PCR with 45 primer pairs. Reverse transcription‐PCR analyses revealed that mRNA levels were significantly different (p<0.05) for heat shock transcription factor 4b (HSF4b) gene, Kruppel‐like zinc finger transcription factor 9 (Zf9) and muskelin genes. HSF4b was greater in neutrophils from Aggressive‐P compared to groups H and Chronic‐P. Zf9 and muskelin genes were lower in Aggressive‐P compared to the H groups, but no significant difference was noted compared to the Chronic‐P group. The control genes, IL‐1β and VEGF genes, were expressed at a significantly higher level in Aggressive‐P and Chronic‐P than H (p<0.01, p<0.05). In conclusion, the RAP‐PCR technique used in this study enabled us to identify 3 Aggressive‐P related genes, which had not been reported previously. Neutrophil functions in Aggressive‐P patients are suggested to be altered by regulatory factors of the immune system including HSF4b (transcription factor), Zf9 (activator of TGF‐β) and muskelin (cellular adhesion).
Expression of integrins by human periodontal ligament and gingival fibroblasts and their involvement in fibroblast adhesion to enamel matrix‐derived proteins
Authors: Van Der Pauw M. T. M. , Everts V. , Beertsen W.
Published: March 2003

We showed recently that human periodontal ligament (PDL) and gingival fibroblasts adhere and spread on enamel matrix protein (EMP) coatings (1). In the present study, we investigated whether this interaction can be attributed to integrin expression. Human PDL and gingival fibroblasts were cultured for periods up to 24 h on EMP coatings, in the presence of synthetic RGD‐containing peptide or an antibody against the β1 integrin subunit. The cells were first cultured for 24 h under serum‐free conditions and then cultured on EMP coatings for 48 h. Integrin expression levels were assessed by flow cytometry analysis. It was found that attachment and spreading on EMP was inhibited by the synthetic RGD‐containing peptide, but not by a synthetic RGE‐peptide. Both PDL and gingival fibroblasts showed expression of the integrin subunits, α2, α5, β1, and the integrin, αvβ3. Incubation with an antibody against the β1 subunit significantly inhibited the attachment and spreading of PDL and gingival fibroblasts on EMP coatings. We conclude that integrins are involved in the interaction of PDL and gingival fibroblasts with EMP.
The role of LFA‐1 in osteoclast development induced by co‐cultures of mouse bone marrow cells and MC3T3‐G2/PA6 cells
Authors: Tani‐Ishii N. , Penninger J. M. , Matsumoto G. , Teranaka T. , Umemoto T.
Published: March 2003

Interactions between leukocyte function‐associated antigen‐1 (LFA‐1) and intercellular adhesion molecule‐1 (ICAM−1) influence the development of osteoclasts. However, little is known about how these adhesion molecules are involved in the process of osteoclast development. This study evaluated the role of LFA‐1 and its ligands in osteoclast development and bone resorption. Co‐cultures of bone marrow cells from LFA‐1‐deficient mice and MC3T3‐G2/PA6 (PA6) cells were cultured in the presence of 1α,25(OH)2D3 and dexamethasone for 7 days. The number of TRAP‐positive cells that were generated by bone marrow cells from LFA‐1‐deficient mice was smaller than that generated by bone marrow cells from wild‐type mice. In addition, the bone‐resorbing activity of osteoclast‐like cells that were generated from LFA‐1‐deficient mice was lower than that generated by osteoclast‐like cells from wild‐type mice. Immunofluorescence flow cytometry showed that osteoclast stromal PA6 cells expressed the cell adhesion molecules, ICAM‐1 and VCAM‐1. When monoclonal antibodies to mice VCAM‐1, CD11b or CD18 were added separately to the co‐culture system, the number of TRAP‐positive cells that were generated from LFA‐1‐deficient mice was 20–30% smaller than that generated from wild‐type mice. The formation of TRAP‐positive cells from both LFA‐1 deficient and wild‐type mice was especially inhibited by anti‐CD18 antibody, in comparison to the addition of normal IgG serum. These results suggest that LFA‐1 adhesion molecules play a role in osteoclast development by affecting adhesion between stromal cells and osteoclast progenitors before the occurrence of ODF‐ODF receptor signaling. CD18 appears to be a key adhesion molecule in cell‐to‐cell contacts during the early stage of osteoclast development.
Inactivation of Creatine Kinase Induced by Stilbene Derivatives
Authors: Miura Toshiaki , Muraoka Sanae , Fujimoto Yukio
Published: March 2003

Abstract: Compounds acting as antioxidants to lipids often have a prooxidant effect on DNA or protein. In this study, inactivation of creatine kinase was examined as an indicator of protein damage induced by antioxidative stilbene derivatives, including diethylstilboestrol, resveratrol and tamoxifen, with horseradish peroxidase and hydrogen peroxide (horseradish peroxidase‐H2O2). Diethylstilboestrol and resveratrol, but not tamoxifen, rapidly inactivated creatine kinase. Also, creatine kinase in heart homogenate was inactivated by diethylstilboestrol and resveratrol. Tamoxifen, which has no phenolic hydroxyl groups in its structure, was about 10 times less active in protecting lipids and creatine kinase than diethylstilboestrol and resveratrol, suggesting that phenolic hydroxyl groups in diethylstilboestrol and resveratrol of stilbene derivatives are anti‐ and pro‐oxidative. Absorption spectra of these stilbene derivatives rapidly changed during the reaction with horseradish peroxidase‐H2O2. Diethylstilboestrol and resveratrol free radicals emitted electron spin resonance signals and creatine kinase effectively diminished the electron spin resonance signals. These results suggest that free radicals of diethylstilboestrol and resveratrol formed through reaction with horseradish peroxidase‐H2O2 inactivated creatine kinase. Presumably, oxidation of essential cysteine and tryptophan residues lead to inactivation of creatine kinase. Other enzymes, including alcohol dehydrogenase and cholinesterase, were also sharply inhibited by diethylstilboestrol and resveratrol with horseradish peroxidase‐H2O2. Free radicals of diethylstilboestrol and resveratrol seem to mediate between anti‐ and prooxidative actions.
Molecular Basis of Agonist Binding to the Type A Cholecystokinin Receptor
Authors: Miller Laurence J. , Lybrand Terry P.
Published: March 2003

Abstract: The receptors for cholecystokinin (CCK) peptides are guanine nucleotide‐binding protein‐coupled receptors in the rhodopsin/β‐adrenergic receptor family. The molecular basis of natural ligand binding to the type A CCK receptor has been studied using ligand structure‐activity series, receptor mutagenesis, and photoaffinity labeling studies. These have focused attention on the extracellular loop and tail domains, with the most direct insights coming from intrinsic photoaffinity labeling studies. A model of the binding of CCK to this receptor is consistent with all these studies. This model places the carboxyl terminus of CCK adjacent to the amino‐terminal tail outside of transmembrane segment 1, the mid‐region of the peptide adjacent to the third extracellular loop outside of transmembrane segment 7, and includes a charge‐charge interaction between peptide residue tyrosine‐sulfate 27 and the arginine residue in the second extracellular loop of the receptor in position 197.
The Cellular Localization of the Cholecystokinin 2 (Gastrin) Receptor in the Stomach
Authors: Waldum Helge L. , Kleveland Per M. , Sandvik Arne K. , Brenna Eiliv , Syversen Unni , Bakke Ingunn , Tømmerås Karin
Published: March 2003

Abstract: The role of the gastric acid secretagogues acetylcholine, gastrin and histamine has been debated for decades. Initially, the mast cell was considered the source of acid stimulatory histamine. Later, Håkanson & Owman (1969) showed that the entero‐chromaffinlike (ECL) cell produces and stores histamine in several species, including rat and man. Kahlson et al. (1964) showed that food and gastrin stimulated oxyntic mucosal histamine synthesis and release, Berglindh et al. (1976) that histamine and cholinergics but not gastrin induced acid secretion in isolated oxyntic glands and parietal cells, and Rangachari (1995) that acetylcholine or gastrin released histamine in isolated mucosa. These findings suggested that gastrin stimulates acid secretion through release of ECL cell histamine. Studying simultaneous histamine release and acid secretion in isolated oxyntic mucosal cells, we found that gastrin stimulated acid secretion only in preparations releasing histamine. Moreover, in the isolated rat stomach, gastrin stimulated both histamine release and acid secretion. Maximal acid output was higher with histamine than with gastrin, and augmented by acetylcholine but not by gastrin. These findings strongly suggested that gastrin acts by releasing histamine. Finally, a fluorescein‐labelled gastrin analogue bound to the ECL cell, not to the parietal or stem cell regions. This is interesting, recalling that gastrin has a potent and specific trophic effect on the ECL cell and only a general effect on all other oxyntic cell types. In conclusion, physiological observations are best explained by localising the CCK2 receptor only to the ECL cell, the other effects of gastrin on the gastric mucosa being secondary to the release of mediators from the ECL cell.
Cholecystokinin Modulation of Mesolimbic Dopamine Function: Regulation of Motivated Behaviour
Authors: Rotzinger Susan , Bush David E. A. , Vaccarino Franco J.
Published: March 2003

Abstract: This article reviews evidence and presents a hypothesis regarding the effects of stress on motivated behaviour, and in particular the observation that stress can have both motivationally inhibitory and motivationally facilitatory effects. This issue will be addressed with regard to psychostimulant self‐administration, and the role that the neurobiological mechanisms underlying motivated behaviour are thought to be involved in the evolution of addictions. Evidence from animal studies shows that stress and stress‐related hormones such as corticosterone can facilitate mesolimbic dopamine function and the behavioural effects of psychostimulants, particularly at lower levels of stress. Conversely, higher levels of stress can inhibit motivated behaviour, and evidence is presented that this may occur in part through the effects of the neuropeptide cholecystokinin (CCK), acting through CCK‐B receptors in the nucleus accumbens. Individual differences in endogenous CCK and dopamine systems are hypothesized to be important modulators of individual differences in motivated behaviour.
The Chemical UV‐Filter 3‐Benzylidene Camphor Causes an Oestrogenic Effect in an in vivo Fish Assay
Authors: Holbech Henrik , Nørum Ulrik , Korsgaard Bodil , Bjerregaard Poul
Published: March 2003

Abstract: Chemical UV‐filters are used in sun protection products and various kinds of cosmetics. The lipophilic chemical UV‐filter 3‐benzylidene camphor was investigated for its capability to cause vitellogenin induction, possibly via oestrogen receptor binding, in a well‐established in vivo fish assay (juvenile rainbow trout, Oncorhynchus mykiss, vitellogenin ELISA). A clear relationship was demonstrated between the dose of injected 3‐benzylidene camphor and the concentration of plasma vitellogenin with a 105‐times induction from 68 mg 3‐benzylidene camphor /kg/injection and above compared to the control vitellogenin level. The relationship between the injected dose of 3‐benzylidene camphor and the percent of responding fish (vitellogenin) was evaluated by logistic regression analysis and effective dose‐values (ED‐values) were determined. ED10, ED50 and ED90 of 3‐benzylidene camphor after 6 days (2 injections) were 6.4, 16 and 26 mg/kg/injection, respectively. These ED‐values place 3‐benzylidene camphor among the more potent xenooestrogens discovered to date and necessitates investigations on the distribution, concentration, persistence and bioaccumulation of 3‐benzylidene camphor and other UV‐filters in nature.
Effect of childhood and adolescent ultraviolet exposures on cumulative exposure in South East Queensland schools
Authors: Parisi A. V. , Meldrum L. R. , Wong J. C. F. , Aitken J. , Fleming R. A.
Published: March 2003

Quantitative estimates of the childhood and adolescent erythemal ultraviolet (UV) exposure received in South East Queensland schools are provided in this paper for age groups 0 to 6, 7 to 12 and 13 to 19 years. For the neck, hand and lower arm, sites of high UV exposure that are generally not covered by clothing, 13 to 19 year olds received the highest exposure of the three age groups, followed by 7 to 12 year olds. Exposure for 13 to 19 year olds contributed up to 44% of cumulative exposure to 20 years of age, and exposures for the 7 to 12 year olds contributed up to 31%. If the annual UV exposure for these two age groups were reduced to the average of all the age groups, cumulative erythemal UV exposure from 0 to 20 years would be reduced by up to 16%. On the other hand, if mothers can protect their babies by reducing the level of annual exposure to 30% of the annual UV exposure of the 7 to 12 year olds for the first four years then cumulative exposure to UV to age 20 would be reduced by up to 19%. These data confirm the importance of targeting young age groups in public campaigns for sun protection.
A device for minimizing the risk of overexposure of patients undergoing phototherapy
Authors: Allan W. , Diffey B. L.
Published: March 2003

Phototherapy irradiation cabinets normally rely on one timer or dose meter in order to control the ultraviolet (UV) exposure of patients. Faults may occur in the electronic control, or the operator may set the prescribed dose incorrectly. If this happens, a patient will receive an exposure different from that intended, which in the case of overexposure may result in severe burning resulting in hospitalization. Some phototherapy equipment has secondary devices (e.g. mechanical timer) for controlling the dose in case the primary system fails. We have designed and built a secondary dose meter that sounds an alarm if an overdose is about to occur. The unique feature of our device is that it measures the irradiance level within the cabinet and uses this value in combination with the dose set by the operator, to calculate the alarm time. Using the measured irradiance value in this manner ensures that the calculated exposure time compensates for variations in UV output as the lamps age.
Testing high SPF sunscreens: a demonstration of the accuracy and reproducibility of the results of testing high SPF formulations by two methods and at different testing sites
Authors: Agin Patricia Poh , Edmonds Susan H.
Published: March 2003

Background/Purpose: The goals of this study were (i) to demonstrate that existing and widely used sun protection factor (SPF) test methodologies can produce accurate and reproducible results for high SPF formulations and (ii) to provide data on the number of test‐subjects needed, the variability of the data, and the appropriate exposure increments needed for testing high SPF formulations.

Methods: Three high SPF formulations were tested, according to the Food and Drug Administration's (FDA) 1993 tentative final monograph (TFM) ‘very water resistant’ test method and/or the 1978 proposed monograph ‘waterproof’ test method, within one laboratory. A fourth high SPF formulation was tested at four independent SPF testing laboratories, using the 1978 waterproof SPF test method. All laboratories utilized xenon arc solar simulators.

Results: The data illustrate that the testing conducted within one laboratory, following either the 1978 proposed or the 1993 TFM SPF test method, was able to reproducibly determine the SPFs of the formulations tested, using either the statistical analysis method in the proposed monograph or the statistical method described in the TFM. When one formulation was tested at four different laboratories, the anticipated variation in the data owing to the equipment and other operational differences was minimized through the use of the statistical method described in the 1993 monograph.

Conclusions: The data illustrate that either the 1978 proposed monograph SPF test method or the 1993 TFM SPF test method can provide accurate and reproducible results for high SPF formulations. Further, these results can be achieved with panels of 20–25 subjects with an acceptable level of variability. Utilization of the statistical controls from the 1993 sunscreen monograph can help to minimize lab‐to‐lab variability for well‐formulated products.
021 UVB emitting fiber optic hair brush for the treatment of scalp psoriasis
Authors: Taneja A. , Trehan M. , Gupta S. , Racette A. , Regan S. , Gourgouliatos Z. , Taylor C.R.
Published: March 2003

This work‐in‐progress evaluates the efficacy of a unique UVB fiber optic comb device for treating scalp psoriasis. Informed consent was obtained on 11 enrolled patients. One scalp psoriasis plaque was left as a control, while another was selected for treatment. An MED was performed on the lower back or gluteal skin to determine the subject's baseline sensitivity to the comb device. On the selected sit, mineral oil was first applied with a soaked gauze to enhance UV delivery and the first treatment was at 1 MED. Subsequent treatments were thrice weekly at 72 h intervals with maximum increments of 20% per treatment. Treatments ended after 12 weeks or when clearing occurred, whichever came first. Clinical evaluation and standardized photographs were taken at baseline and every 2 weeks thereafter.

Results  On average, patients have received 24 treatments (range: 2–36). At baseline, PASI scores for the treated and control sides did not differ significantly (mean difference: 0.4, P= 0.1106). Improvement scores, calculated by subtracting the most recent PASI score from the baseline value, were higher for the treated sides (3.9 vs. 0.3, P = 0.0002).

Three patients showed worsening in the control area. Ten of the 11 patients showed improvement in the treated area; none experienced worsening of symptoms.

Conclusions  The fiber optic brush offers an exciting potential for treating scalp psoriasis.
007 308 nm excimer laser for the treatment of scalp psoriasis
Authors: Gupta S. , Taneia A. , Racette A. , Trehan M. , Taylor C.R.
Published: March 2003

Our intent was to determine the effectiveness of the 308 rim excimer laser for the treatment of scalp psoriasis through a non‐blinded, randomized, controlled study. Institutional approval for this study was achieved. Twenty consecutive volunteers with stable large plaques of scalp psoriasis were enrolled. Mineral oil was applied before each treatment. A modified psoriasis area severity index (PASI) score was determined before each treatment. Excimer laser generated 308‐rim (Photomedex, San Diego, CA, Model #AL 7000) UV‐13 radiation was administered evenly to each large plaque of scalp psoriasis twice weekly for up to 30 treatments. Untreated areas of adjacent scalp psoriasis served as controls. Each plaque received a set dose of radiation based on a predetermined minimal erythema dose. The dose of radiation was increased incrementally at each visit, as tolerated. There was a clear improvement as assessed by the mean PASI scores for treated vs. untreated plaques of scalp psoriasis. Adverse effects were minimal. The 308 nm excimer laser is a safe, novel and effective method of treating scalp psoriasis.
Melatonin, a pineal secretory product with antioxidant properties, protects against cisplatin‐induced nephrotoxicity in rats
Authors: Hara Masayuki , Yoshida Minoru , Nishijima Hironori , Yokosuka Makoto , Iigo Masayuki , Ohtani‐Kaneko Ritsuko , Shimada Akinori , Hasegawa Tatsuya , Akama Yoshifumi , Hirata Kazuaki
Published: March 2003

In an attempt to define the role of the pineal secretory melatonin and an analogue, 6‐hydroxymelatonin (6‐OHM), in limiting oxidative stress, the present study investigated the cisplatin (CP)‐induced alteration in the renal antioxidant system and nephroprotection with the two indolamines. Melatonin (5 mg/kg), 6‐OHM (5 mg/kg), or an equal volume of saline were administered intraperitoneally (i.p.) to male Sprague–Dawley rats 30 min prior to an i.p. injection of CP (7 mg/kg). After CP treatment, the animals each received indolamine or saline every day and were sacrificed 3 or 5 days later and plasma as well as kidney were collected. Both plasma creatinine and blood urea nitrogen increased significantly following CP administration alone; these values decreased significantly with melatonin co‐treatment of CP‐treated rats. In the kidney, CP decreased the levels of GSH (reduced glutathione)/GSSG (oxidized glutathione) ratio, an index directly related to oxidative stress. When animals were treated with melatonin, the reduction in the GSH/GSSG ratio was prevented. Treatment of CP‐enhanced lipid peroxidation in the kidney was again prevented in animals treated with melatonin. The activity of the antioxidant enzyme, glutathione peroxidase (GSH‐Px), decreased as a result of CP administration, which was restored to control levels with melatonin co‐treatment. Upon histological analysis, damage to the proximal tubular cells was seen in the kidneys of CP‐treated rats; these changes were prevented by melatonin treatment. 6‐OHM has been shown to have some antioxidative capacity, however, the protective effects of 6‐OHM against CP‐induced nephrotoxicity were less than those of melatonin. The residual platinum concentration in the kidney of melatonin co‐treated rats was significantly lower than that of rats treated with CP alone. It is concluded that administration of CP imposes a severe oxidative stress to renal tissue and melatonin confers protection against the oxidative damage associated with CP. This mechanism may be reasonably attributed to its radical scavenging activity, to its GSH‐Px activating property, and/or to its regulatory activity for renal function.
Chimeric Gαq subunits can distinguish the long form of the Xenopus Mel1c melatonin receptor from the mammalian mt1 and MT2 melatonin receptors
Authors: Lai Frank P.L. , Mody Sejal M. , Yung Lisa Y. , Pang Celia S. , Pang Shiu F. , Wong Yung H.
Published: March 2003

The family of melatonin receptors is composed of the mt1, MT2, and Mel1c subtypes. The Mel1c is further divided into one long and two short isoforms. A recent study has shown that, unlike mt1 and MT2, the long form of Mel1c is incapable of activating the pertussis toxin‐insensitive G16. Here we used three well‐characterized Gαq chimeras to explore the coupling specificity of the melatonin receptors. The qi5, qo5, and qz5 chimeras can link numerous Gi‐coupled receptors to the stimulation of phosphoinositide‐specific phospholipase C. Both mt1 and MT2 receptors interacted productively with the Gαq chimeras, while the long form of Mel1c was totally ineffective. Among the Gαq chimeras, qo5 was less efficiently coupled to the melatonin receptors. Such differential coupling is best explained by structural differences between the melatonin receptors as well as among the Gαq chimeras. Since the long form of Mel1c receptor possesses an exceptionally large C‐terminal tail, we tested the ability of four melatonin receptor C‐terminal tail chimeras (Chi 1–4) to interact with the Gαq chimeras. The presence of the large C‐terminal tail of Mel1c in Chi 1 and Chi 3 markedly hindered their coupling to the Gαq chimeras. On the other hand, the attachment of either the mt1 or MT2 C‐terminal tail to a Mel1c backbone produced chimeras (Chi 2 and Chi 4) that were capable of activating the Gαq chimeras. These findings suggest the involvement of C‐terminal regions of melatonin receptors in the recognition of G proteins.
Incorporation, distribution, and metabolism of polyunsaturated fatty acids in the pineal gland of rainbow trout (Oncorhynchus mykiss) in vitro
Authors: Falcón Jack , Henderson R. James
Published: March 2003

The in vitro incorporation of 3H‐radio‐labeled arachidonic (20:4n‐6) and docosahexaenoic (22:6n‐3) acids by the photosensitive trout pineal gland was visualized using photon and electron microscopy. After 6 hr of incubation, 3H‐20:4n‐6 appeared distributed in photoreceptors, as well as in glial cells, whereas 3H‐22:6n‐3 was preferentially taken up by photoreceptors, mainly in the apical part (including the photoreceptive outer segment). Radioactivity was mainly seen over membranes of glia when the incorporation of 3H‐20:4n‐6 was followed by 12–18 hr of chase. We also report differences in the incorporation of 14C‐radio‐labeled linoleic (18:2n‐6), linolenic (18:3n‐3), eicosapentenoic (20:5n‐3), 20:4n‐6, and 22:6n‐3 acids into the lipids in glands cultured under different lighting regimes. Phosphatidylcholine and triacylglycerols contained most of the radio‐labeled polyunsaturated fatty acids (PUFA) incorporated. The proportion of incorporated 20:4n‐6 recovered in phosphatidylinositol was always significantly higher than that found with the other PUFA. At least 10% of radioactivity from each incorporated substrate, except 22:6n‐3, was recovered in elongation products. It is concluded that the pineal gland of the trout can assimilate exogenous PUFA into cellular lipids in vitro, in a manner consistent with our previous in vivo findings. In terms of lipid composition, the trout pineal gland resembles more the vertebrate retina than the rat pineal gland. This might be related to the loss of direct photosensitivity of the mammalian pineal. Together, the differences reported herein between 22:6n‐3 and 20:4n‐6 suggest the former plays an important role in the phototransduction process, whereas the latter might be more specifically involved in the production of phosphoinositide‐derived second messengers.
Melatonin protects against ischemia/reperfusion‐induced oxidative damage to mitochondria in fetal rat brain
Authors: Wakatsuki A. , Okatani Y. , Shinohara K. , Ikenoue N. , Fukaya T.
Published: March 2003

We investigated the effects of melatonin on ischemia/reperfusion‐induced oxidative damage to mitochondria in fetal rat brain. The utero‐ovarian arteries were occluded bilaterally for 20 min in female Wistar rats on day 19 of pregnancy to induce fetal ischemia. Reperfusion was achieved by releasing the occlusion and restoring circulation for 30 min. A sham operation was performed in control rats. Melatonin (10 mg/kg) or vehicle was injected intraperitoneally 60 min prior to occlusion. We measured the respiratory control index (RCI) and the adenosine 5‐diphosphate (ADP)/oxygen ratio as indicators of mitochondrial respiratory activity, as well as the concentration of thiobarbituric acid‐reactive substances (TBARS) in the mitochondria of fetal brain. Ischemia/reperfusion significantly elevated the concentration of TBARS and significantly reduced the RCI as well as the ADP/oxygen ratio. Melatonin treatment reversed the ischemia/reperfusion‐induced reductions in the RCI (2.29±0.06–2.64±0.09, P<0.05) and in the ADP/oxygen ratio (1.48±0.03–1.57±0.02, P<0.05), and also reduced the elevation in concentration of TBARS (11.00±0.34–7.57±0.74 nM/mg protein, P<0.01), resulting in values similar to those in untreated, sham‐ischemic animals. The results indicate that administration of melatonin to pregnant rats may prevent ischemia/reperfusion‐induced oxidative mitochondrial damage in fetal rat brain.
Melatonin protects against gastric ulceration and increases the efficacy of ranitidine and omeprazole in reducing gastric damage
Authors: Bandyopadhyay Debashis , Bandyopadhyay Arun , Das Pratap K. , Reiter Russel J.
Published: March 2003

The antiulcer effect of melatonin on gastric lesions caused by restraint‐cold stress was studied with the intent of determining the mechanism of action of this agent. Melatonin dose‐dependently prevented restraint‐cold stress‐induced gastric damage with around 90% inhibition at a dose of 60 mg/kg BW. When compared with already marketed antiulcer drugs such as ranitidine and omeprazole, melatonin was found to be more effective than ranitidine but less effective than omeprazole in preventing stress ulcer. As stress‐induced gastric lesions are mainly caused by oxidative damage because of hydroxyl radicals (·OH), the effect of melatonin in scavenging the ·OH generated during stress conditions in vivo as well as in an in vitro model system were studied. The results indicate that melatonin caused an 88% reduction of endogenous b˙OH during stress in vivo, an observation confirmed in an established in vitro system. Furthermore, a decrease in the activity of gastric peroxidase (GPO) and an increase in the gastric mitochondrial superoxide dismutase (Mn‐SOD) activity because of restraint‐cold stress was attenuated by melatonin pretreatment indicating that the indole possibly exerts its gastroprotective effects through its direct as well as indirect antioxidant activities. Moreover, in separate experiments, cotreatment of rats with melatonin and ranitidine or omeprazole was found to protect against stress ulceration in doses at which either of these alone could not protect the stomach. The findings raise the possibility of melatonin being considered as an effective gastroprotective agent individually or as a cotreatment with either ranitidine and omeprazole.
Variations of mt1 melatonin receptor density in the rat uterus during decidualization, the estrous cycle and in response to exogenous steroid treatment
Authors: Zhao H. , Pang S. F. , Poon A. M. S.
Published: March 2003

Abstract: The expression of mt1 receptor protein in the rat uterus was investigated using an anti‐mt1 polyclonal antibody against the rat mt1 receptor. A melatonin receptor protein of 37 kDa was detectable by Western blotting in the rat uterine membrane preparations. Autoradiography with the melatonin ligand, 2‐[125I]iodomelatonin, was used to localize melatonin receptors in the uterus of the estrous rats and to study the changes of melatonin receptors in pregnancy. Melatonin receptors were found to be localized in the estrous rat uterine antimesometrial stroma. As decidualization of the uterine stroma progressed during pregnancy, the melatonin binding sites were progressively reduced and became confined to the antimesometrial non‐decidualized outer stroma. 2‐[125I]Iodomelatonin binding sites were not seen in the mesometrial stromal cells during pregnancy. The role of ovarian hormones in the regulation of uterine melatonin receptors was examined by studying the binding at various phases of the estrous cycle, after ovariectomy with and without follow‐on treatment of estradiol (E2), progesterone (P4) or both. 2‐[125I]Iodomelatonin binding in the rat uterus fluctuated during the estrous cycle, being lowest during metestrus. Ovariectomy caused an almost 70% reduction of 2‐[125I]iodomelatonin binding compared with the control. Injections of ovariectomized (OVX) rats with E2 or P4 alone or in combination for 11 days induced a partial restoration of 2‐[125I]iodomelatonin binding in the OVX rats. The results show that mt1 melatonin receptors in the rat antimesometrial stroma are regulated by ovarian hormones.
Melatonin suppresses osteoclastic and osteoblastic activities in the scales of goldfish
Authors: Suzuki Nobuo , Hattori Atsuhiko
Published: March 2003

Abstract: The effects of melatonin on osteoclastic and osteoblastic cells were examined using a culture system of the goldfish scale. Tartrate‐resistant acid phosphatase (TRACP) and alkaline phosphatase (ALP) were used as markers of osteoclastic and osteoblastic cells, respectively. In Earle's minimum essential medium containing melatonin (10−9 to 10−5 m), activities of both enzymes in scales were significantly suppressed at 6 hr after incubation (TRACP: 10−8, 10−6, 10−5 m; ALP: 10−7 to 10−5 m), but at 18 hr only ALP activity was significantly lowered (10−8, 10−7 m). Estradiol‐17ß (E2) enhanced both activities, which were significantly inhibited and brought down to the level of the controls when co‐incubated with E2 and melatonin (TRACP at 6 hr: 10−9 to 10−5 m; ALP at 6 hr: 10−7 m; ALP at 18 hr: 10−8 m). Moreover, using reverse‐transcription polymerase chain reaction, the mRNA expression of the estrogen receptor (ER) and insulin‐like growth factor (IGF)‐1, which are related to osteoblastic growth and differentiation, was decreased in the melatonin‐treated scales. These results suggest that melatonin acts directly on the scale osteoclastic and osteoblastic cells where it suppresses the ALP activity via down‐regulation of ER and IGF‐1 mRNAs expression. This is the first report on the function of melatonin in osteoclasts and on the suppressive effect of melatonin in osteoblasts among vertebrates.
Changes in hemoglobin values in elite cross‐country skiers from 1987 to 1999
Authors: Videman T. , Lereim I. , Hemmingsson P. , Turner M. S. , Rousseau‐Bianchi M.‐P. , Jenoure P. , Raas E. , Schönhuber H. , Rusko H. , Stray‐Gundersen J.
Published: March 2003

Hemoglobin data have been available from ski teams beginning from 1987, and from 1989 to 1999 we have followed hemoglobin values in elite cross‐country skiers in international competitions. The mean values at the 1989 World Nordic Ski Championships were lower than population reference values, as would be expected from plasma volume expansion associated with endurance training. However, an increase, particularly in the maximal values, became obvious in 1994 and rose further in 1996. These extreme values provide both a health risk to the individual athlete and unfair competition. After a rule limiting hemoglobin values was introduced, the drop of the highest values was remarkable: among men 15 g/l (0.23 mmol/l) and among women 42 g/l (0.65 mmol/l). It would appear that the rule had achieved its goal of limiting extreme hemoglobin values. Yet the mean hemoglobin concentrations in men and women have continued to rise, suggesting the continued use of artificial methods to increase total hemoglobin mass.
Is a knee brace advantageous after anterior cruciate ligament surgery?
Authors: Brandsson S. , Faxén E. , Kartus J. , Eriksson B. I. , Karlsson J.
Published: March 2003

The aim of this study was to evaluate the use of a knee brace after arthroscopic anterior cruciate ligament reconstruction using central third patellar tendon autografts. Fifty patients were randomly allocated to two groups. The patients in Group A wore a brace for three weeks post‐operatively, while the patients in Group B were rehabilitated without the use of a brace. Pre‐operatively, the groups were comparable in terms of age, sex, activity level, knee laxity and muscle strength. The follow‐up examination was performed by one independent observer. All the patients were followed up for a minimum of two years. At the follow‐up, there were no significant differences between the study groups in terms of the Tegner activity level, Lysholm score, IKDC evaluation system, one‐leg‐hop quotient, KT‐1000 measurements and isokinetic torque. Using the visual analogue scale, the patients in Group A evaluated their pain during the first two post‐operative weeks as 1.0 (0–7), compared with 2.3 (0–9) in Group B (P=0.04). Furthermore, the patients in Group A had a tendency towards fewer problems with swelling, haemathrosis and wound leakage during the early post‐operative period (P=0.08). We conclude that the patients who were rehabilitated with the use of a brace had less pain and a tendency towards fewer complications during the early post‐operative period than the patients who were rehabilitated without the use of a brace. However, there were no differences in terms of function or knee laxity at the two‐year follow‐up.
Effects of remobilization on rat femur are dose‐dependent
Authors: Järvinen T. L. N. , Kannus P. , Sievänen H. , Józsa L. , Heinonen O. J. , Vieno T. , Järvinen M.
Published: March 2003

Seventy 9 to 11‐week‐old Sprague‐Dawley male rats were divided into seven groups [baseline, 3‐week, 11‐week control groups; a group with a left limb immobilization for 3 weeks; and three groups with a similar immobilization and subsequent 8‐week free (FR), low‐intensity running (LR) or high‐intensity running (HR) remobilization] to determine the site‐specific effects of decreased mechanical loading and subsequent increased activity on rat femur. Bone mineral content of the proximal femur (PBMC), femoral midshaft (SBMC) and distal femur (DBMC) and the histomorphometry of the distal femur were used as outcome variables. The 3‐week immobilization period resulted in significant bone loss in the proximal and distal ends of the immobilized left limb, the deficit being −5.9% in PBMC and −14.7% in DBMC. Immobilization also led to marked microarchitectural changes in the distal femur, the left‐side deficit in trabecular bone volume (BV/TV) being −23.9%. After remobilization, there was a clear indication for dose‐dependent response; i.e., immobilization‐induced left‐to‐right side differences in BV/TV persisted in the FR animals (−23.8%), while these left limb deficits were significantly reduced in the LR group (−15.0%) and virtually absent in the HR group (−3.1%). The left limb deficit in PBMC was still significant in all groups after the 8‐week period of remobilization [−9.6% in the FR group; −13.4% in the LR group; and −7.2% in the HR group]. The left‐limb deficit in SBMC was significant in the HR11 group only (−7.2%), and, contrary to histomorphometric data, virtually absent in DBMC in all remobilization groups. As compared with the age‐matched control data, the weight‐adjusted BMCs of both limbs of the LR and HR groups were comparable or even higher (right limbs) than those of the controls. In conclusion, this study indicates that remobilization‐induced bone recovery depends on the intensity of the remobilization so that during the 8‐week period of remobilization, high‐intensity running results in better recovery than low‐intensity running, both of which are more efficient than free‐cage activity only. Immobilization‐induced changes in rat femur are also restored in a site‐specific fashion, the most trabecular distal region of the femur showing more complete recovery than the more cortical proximal and midshaft regions.
Specific pulmonary responses during the cycle‐run succession in triathletes
Authors: Hue O. , Le Gallais D. , Préfaut C.
Published: March 2003

The aim of the present study was to investigate the relationship between alterations in pulmonary function (i.e., diffusing capacity for carbon monoxide and pulmonary volumes) and the ventilatory response elicited during the cycle‐run succession in triathletes. Ten well‐trained triathletes performed three exercises: 1) 30 min cycling plus 20 min of running, termed the cycle‐run succession; 2) 30 min cycling; and 3) 20 min running. Before and 10 min after each trial, the triathletes underwent pulmonary function testing, including spirometry and diffusing capacity for carbon monoxide. During all trials, ventilatory data were collected every minute using an automated breath‐by‐breath system. The ventilatory response was significantly higher in the run subsequent to cycling as compared with the run performed independently (P<0.001). There was no change in pulmonary volumes before and after exercises; however, the diffusing capacity for carbon monoxide and the transfer coefficient were similarly decreased (P<0.05) after cycling and the cycle‐run succession, but not decreased after running. The increase in minute ventilation in the run segment of the cycle‐run succession versus in running alone was significantly correlated with the decrease in diffusing capacity for carbon monoxide measured after versus before the cycle‐run succession (P<0.01). This same increase in ventilation was also correlated with the decrease in diffusing capacity measured after the cycle‐run succession versus after cycling alone (P<0.03). These results suggest the possibility that the DLCO decrease contributes in part to the ventilatory increase noted in the run after cycling during the cycle‐run succession of the triathlon.
Musculoskeletal injuries in the Norwegian National Ballet: a prospective cohort study
Authors: Byhring S. , Bø K.
Published: March 2003

The purpose of the present study was to determine the incidence of musculoskeletal injuries among professional ballet dancers in the Norwegian National Ballet.

A 19 weeks prospective study with registration and clinical assessment of dancers with injuries was conducted. Medical staff working for the National Ballet registered incidence of injuries. In addition the dancers filled out a questionnaire about previous injuries, their work situation, and factors they believed increased the risk of injuries.

Of the 41 dancers (80% response rate), 31 dancers experienced one injury or more. The majority of injuries involved foot and ankle. Twenty‐two per cent of the injuries were acute injuries. Seventy‐five per cent of the injuries were soft tissue injuries. Most injuries were of mild to moderate severity. Sixteen per cent of the injuries resulted in absence from work. Factors, the dancers believed were associated with risk of injuries were related to training, organizational factors and environmental factors. Seventy‐eight per cent of the dancers experienced “negative” stress at work. Sixty‐four per cent experienced that they had little influence on their work conditions. This study showed, however, no significant association between these psychological factors and musculoskeletal injuries. It is concluded that there is a high incidence of musculoskeletal injuries in the Norwegian National Ballet.