bluuebunny/crossref_metadata_2025 huggingface dataset:
Pharmacokinetics of a contraceptive patch (Evra™/Ortho Evra™) containing norelgestromin and ethinyloestradiol at four application sites
Authors: Abrams Larry S. , Skee Donna M. , Natarajan Jaya , Wong Frankie A. , Anderson Gary D.
Published: March 2003

Aims  To determine the pharmacokinetic profile of norelgestromin (NGMN) and ethinyloestradiol (EE) following application of the contraceptive patch, Evra™/ Ortho Evra™, at each of four anatomic sites (abdomen, buttock, arm, and torso).

Methods  Thirty‐seven healthy, nonpregnant women aged 20–45 years participated in this open‐label, four‐period crossover study. Subjects were randomized to one of four treatment (site of application) sequences. Each patch was worn for 7 days, with a 1 month washout between treatments. Blood samples were collected before and at various times up to 240 h after application of each patch. Serum samples were assayed for NGMN and EE by validated methods.

Results  The serum concentration reference ranges for NGMN and EE are 0.6–1.2 ng ml−1 and 25–75 pg ml−1, respectively, based on studies of the mean Cave of oral norgestimate 250 µg and EE 35 µg. For all application sites, mean concentrations of NGMN and EE remained within these ranges during the 7 day wear period. Absorption of NGMN and EE during patch application on the buttock, arm, and torso was equivalent. Absorption of NGMN and EE during patch application on the abdomen was approximately 20% less than observed for the other three sites, although mean serum concentrations were still within reference ranges. A previous study demonstrated therapeutic equivalence of patches worn on the abdomen vs other sites.

Conclusions  Serum concentrations of NGMN and EE from the contraceptive patch remain within the reference ranges throughout the 7 day wear period, regardless of the site of application (abdomen, buttock, arm, or torso).
Molecular genetics of CYP2D6: Clinical relevance with focus on psychotropic drugs
Authors: Bertilsson Leif , Dahl Marja‐Liisa , Dalén Per , Al‐Shurbaji Ayman
Published: March 2003

Cytochrome P450 CYP2D6 is the most extensively characterized polymorphic drug‐metabolizing enzyme. A deficiency of the CYP2D6 enzyme is inherited as an autosomal recessive trait; these subjects (7% of Caucasians, about 1% of Orientals) are classified as poor metabolizers. Among the rest (extensive metabolizers), enzyme activity is highly variable, from extremely high in ultrarapid metabolizers, to markedly reduced in intermediate metabolizers. The CYP2D6 gene is highly polymorphic, with more than 70 allelic variants described so far. Of these, more than 15 encode an inactive or no enzyme at all. Others encode enzyme with reduced, ‘normal’ or increased enzyme activity. The CYP2D6 gene shows marked interethnic variability, with interpopulation differences in allele frequency and existence of ‘population‐specific’ allelic variants, for instance among Orientals and Black Africans. The CYP2D6 enzyme catalyses the metabolism of a large number of clinically important drugs including antidepressants, neuroleptics, some antiarrhythmics, lipophilic β‐adrenoceptor blockers and opioids. The present‐day knowledge on the influence of the genetic variability in CYP2D6 on the clinical pharmacokinetics and therapeutic effects/adverse effects of psychotropic drugs is reviewed.
The relationship between male head size and harem size in the sexually dimorphic mountain stone weta Hemideina maori
Authors: Jamieson Ian G.
Published: March 2003

Abstract 1. Tree weta are a group of large, flightless orthopterans with pronounced sexual dimorphism. Males have enlarged heads that are used in fighting for possession of cavities in trees or under rocks where females shelter during the day.

2. The fieldwork reported here examined the relationship between male head size and mating success in Hemideina maori, an alpine tree weta that shelters under rock slabs that have broken off isolated outcrops or tors.

3. The relationship between male head size and harem size in H. maori is not as clear‐cut as thought previously. First, overall body size is a better predictor of male mating success than head size per se. Second, both body size and head size explained a relatively low percentage (19.8%) of the overall variation in mating success. Third, despite the intensity of directional selection being estimated to move the frequency distribution of head size and femur size 0.49 and 0.54 standard deviations from the mean, male heads and femurs were ≈ 2 mm smaller at the main study site than at a second site 100 m higher in elevation. A similar pattern was found for adult females. Additional surveys have indicated that body size in H. maori decreases with decreasing altitude, which is correlated with increasing night‐time temperature.

4. Although there are reasons why natural selection might favour weta maturing earlier and at smaller body sizes in warmer environments, relatively large males would still have a mating advantage over smaller males under such conditions. This sexually dimorphic alpine insect might be a good example of the trade‐offs and conflicting demands that sexual selection versus natural selection can place on organisms.
Low-Dose Aspirin for Migraine Prophylaxis in Women
Authors: Benseñor IM , Cook NR , Lee I-M , Chown MJ , Hennekens CH , Buring JE
Published: March 2003

Although migraine is more common among women than men, the only two large, randomized trials of low-dose aspirin for migraine prophylaxis have been conducted in men. As part of the Women's Health Study, an ongoing randomized trial of low-dose aspirin and vitamin E among 39 876 female health professionals aged 45 and older, 1001 women with frequent migraine attacks were assigned to 100 mg of aspirin every other day ( n = 525) or aspirin placebo ( n = 476). Migraine frequency, as well as severity, duration, and degree of incapacitation, were assessed by self-report on questionnaires 12 months and 36 months after randomization, and also by monthly diaries kept before and after randomization. Women assigned to aspirin reported small and consistent decreases in migraine frequency (59.6% vs. 56.4% assigned to placebo reporting improvement at 36 months; odds ratio 1.13, 95% confidence interval, 0.86–1.48), as well as decreases in severity, duration, and migraine-related incapacitation. These reductions were not, however, statistically significant. These data are compatible with a small treatment effect of low-dose aspirin in the prophylaxis of migraine among middle-aged women.
The Migraine Disability Assessment (MIDAS) Questionnaire: Translation and Reliability of the Italian Version
Authors: D'Amico D , Mosconi P , Genco S , Usai S , Prudenzano AMP , Grazzi L , Leone M , Puca FM , Bussone G
Published: March 2003

We have developed and tested an Italian version of the Migraine Disability Assessment (MIDAS) questionnaire, an established instrument for assessing headache-related disability. A multistep process was used to translate and adapt the questionnaire into Italian, which was then tested on 109 Italian migraine without aura patients, 86 (78.9%) of whom completed the form a second time 21 days later. Overall MIDAS score had good test–retest reliability (Spearman's correlation 0.77), closely similar to that found in English-speaking migraineurs, and individual responses were also satisfactorily reliable. Internal consistency was good (Cronbach's alpha 0.7). These findings support the use of the MIDAS questionnaire as a clinical and research tool with Italian patients.
CTLA4 gene polymorphism contributes to the mode of onset of diabetes with antiglutamic acid decarboxylase antibody in Japanese patients: genetic analysis of diabetic patients with antiglutamic acid decarboxylase antibody
Authors: Abe T. , Yamaguchi Y. , Takino H. , Fujita N. , Yamauchi‐Degawa M. , Ozaki M. , Yamakawa K. , Sera Y. , Sakamaki H. , Uotani S. , Kawasaki E. , Awata T. , Yamasaki H. , Eguchi K.
Published: March 2003

Aim  The mode of onset is occasionally similar in Type 1 and Type 2 diabetes mellitus, and some patients with Type 2 diabetes are positive for antiglutamic acid decarboxylase antibody (GAD Ab). We investigated the contribution of Type 1 diabetes susceptibility genes to the progression of the insulin‐deficient state and mode of onset of Type 2 diabetes in GAD Ab‐positive (GAD‐Ab+) patients. We examined the variable number of tandem repeats in the promoter region of the insulin gene (INS‐VNTR, insulin‐dependent diabetes mellitus (IDDM) 2) and cytotoxic T lymphocyte antigen 4 (CTLA4, IDDM12) as representative of Type 1 diabetes susceptibility genes.

Methods  Patients with Type 2 diabetes who were GAD‐Ab+ (n = 51) were selected for this study. In INS‐VNTR, the class I allele was classified according to length (1S, 25–38 repeat units; 1M, 39–41 repeat units; 1L, 42–44 repeat units) and the exact class I allele length was analysed by specific polymerase chain reaction (PCR) amplifications. Analyses of classes II and III were performed by Southern blot. CTLA4 gene polymorphism (exon 1 position 49, G/A) was analysed by PCR–restriction fragment length polymorphism.

Results  The distribution of INS‐VNTR was no different between Type 1 diabetes and Type 2 diabetes with GAD Ab. The allele frequencies of CTLA4 gene polymorphism G and A in Type 2 diabetes/GAD‐Ab+ were significantly different from those of Type 1 diabetes/GAD‐Ab+ (G: 53%, A: 47% vs. G: 84%, A: 16%; P < 0.0001).

Conclusions  Our data showed that GAD‐Ab+ Japanese patients presenting with Type 2 diabetes have shifted A allele while patients with abrupt onset have shifted G allele of CTLA4 gene polymorphism. Our results suggest that immunological function and polymorphism of the CTLA4 gene may contribute to the pathogenesis and progression of Type 1 diabetes.

Diabet. Med. 18, 726–731 (2001)
Perinatal ‘programming’ of insulin resistance in childhood: critical impact of neonatal insulin and low birth weight in a risk population
Authors: Harder T. , Kohlhoff R. , Dörner G. , Rohde W. , Plagemann A.
Published: March 2003

Aim  Low birth weight may predispose to later insulin resistance and hyperinsulinaemia, but the pathophysiological mechanisms are unclear. The perinatal endocrine situation may play an important role, but has been little studied. Children of mothers with diabetes during pregnancy are an important risk population for later insulin resistance and hyperinsulinaemia. We therefore examined relationships between birth weight, insulin and insulin resistance at birth, and insulin secretion and insulin resistance in infancy in these children.

Methods  We studied 104 infants of mothers with Type 1 diabetes mellitus during pregnancy. Oral glucose tolerance tests (area under the curve of glucose, AUCG) with determination of insulin (area under the curve of insulin, AUCI) were performed at 1–5 years of age. Using correlation and regression analysis, birth data were related to insulin secretion (AUCI) and stimulated insulin/glucose ratio (AUCI/AUCG) in childhood.

Results  Children with an AUCI in the highest tertile of distribution had the lowest birth weights. Birth weight was negatively correlated to AUCI in childhood (P = 0.03). Insulin/glucose ratio at birth was raised in infants with an AUCI in the upper tertile, accompanied by a positive correlation between insulin/glucose ratio at birth and AUCI (P = 0.02). Insulin and insulin/glucose ratio at birth were both positively correlated to AUCI/AUCG (P = 0.04 and P= 0.02 respectively), while the correlation between birth weight and AUCI/AUCG was not significant (P = 0.12). In a stepwise regression analysis, insulin/glucose ratio contributed as much as birth weight to AUCI in childhood. Birth weight, however, was significantly negatively related to AUCI/AUCG only when the insulin/glucose ratio at birth was included in the regression model.

Conclusions  Insulin and insulin resistance at birth show a positive relation to insulin secretion and insulin resistance in later life, in addition to the influence of a low birth weight, but independent of it. Perinatal and neonatal insulin, known to be of critical importance for long‐term outcome, should be evaluated in future studies on the ‘small baby syndrome’.

Diabet. Med. 18, 634–639 (2001)
In vivo wear of three types of veneering materials using implant‐supported restorations: a method evaluation
Authors: Wiskott H. W. Anselm , Perriard Jean , Scherrer Susanne S. , Dieth Stephan , Belser Urs C.
Published: March 2003

In a previous study, we determined the precision and the positional duplicability of a system that used implant connectors to transfer restorations between the oral cavity and the measuring device. The objectives of the present study were to determine whether this testing procedure was suitable for clinical use, and to apply the procedure to the longitudinal assessment of the wear of three types of veneering materials. Ten patients received a total of 12 restorations. The restorations were made either of ceramic (positive control), poly(methylmethacrylate) resin (negative control) or of composite resin. The restorations were profiled at baseline and at 3, 6, 9, 12, 18 and 24 months. For profiling, the restorations were secured to the x–y table of the measuring device using the octagonal connector of the ITI implant system. Numerical analyzes were performed using a commercial array‐oriented software package. The ceramic and the composite wore at roughly 12–14 µm yr−1 (height) 10–12 µm3 µm2 yr−1 (volume). The resin wore at c. 50 µm yr−1 (height) and c. 45 µm3 µm2 yr−1 (volume). The error of the procedure was estimated at ± 13%. It was concluded that the procedure was applicable for clinical studies, and that the composite did not differ from the ceramic as to its wear rate.
Bronchial inflammation in corticosteroid‐sensitive and corticosteroid‐resistant asthma at baseline and on oral corticosteroid treatment
Authors: Chakir J. , Hamid Q. , Bossé M. , Boulet L.‐P. , Laviolette M.
Published: March 2003

Background Pathophysiology of corticosteroid (CS)‐resistant asthma remains incompletely understood.

Objective To determine if failure of asthma to clinically improve with CS is due to a defective response of airway bronchial inflammation to these drugs.

Methods Twenty‐one asthmatics having a decreased baseline FEV1 that improved ≥ 30% with inhaled β2 agonist got bronchial biopsies before and at the end of an oral CS treatment (methylprednisolone 40 mg daily for 14 days). They were arbitrarily divided into two groups according to baseline FEV1 improvement following this treatment: ≥ 23% designated as CS‐sensitive (CSS) (n = 10) and < 15% as CS‐resistant (CSR) (n = 11).

Results Before oral CS, counts of bronchial mucosa inflammatory cells identified by immunohistochemistry (CD3, MBP, tryptase, CD68, neutrophil elastase and CD25 for lymphocytes, eosinophils, mast cells, macrophages, neutrophils and IL‐2 receptors, respectively) were similar in CSS and CSR subjects. Oral CS decreased CD3+ cell counts (medians: 60–20 cells/mm2; P = 0.014) and MBP+ cell counts (medians: 19–4 cells/mm2; P = 0.03) in CSS asthmatics, but only tryptase+ cell counts in CSR asthmatics (medians: 30–18 cells/mm2; P = 0.05). Few bronchial neutrophil elastase+ cells were observed and their counts were similar in the two groups of asthmatics before and when on oral CS (all medians: = 2 cells/mm2).

Conclusions These data show that, in these subjects with moderate to severe asthma, lymphocytes and eosinophils constitute most of the inflammatory cells infiltrating the bronchial mucosa. They also demonstrated that clinical impaired response to CS is associated with a persistent bronchial mucosa cellular infiltrate despite oral CS treatment. Additional studies are required to determine the role of this CS‐resistant bronchial inflammation in the impaired asthma clinical response to these drugs.
Grass pollen sublingual immunotherapy for seasonal rhinoconjunctivitis: a randomized controlled trial
Authors: Lima M. Torres , Wilson D. , Pitkin L. , Roberts A. , Nouri‐Aria K. , Jacobson M. , Walker S. , Durham S.
Published: March 2003

Background Previous studies suggest that sublingual immunotherapy (SLIT) represents a safer alternative to injection immunotherapy but equivalent efficacy is yet to be confirmed.

Objective To evaluate the efficacy and safety of SLIT in grass pollen‐induced seasonal rhinoconjunctivitis.

Methods A randomized, placebo‐controlled trial in 56 adults over 18 months. Outcome measures included diary scores of seasonal symptoms and medication use, overall assessments, conjunctival and intradermal provocation tests and serum antibody measurements. To investigate possible mechanisms, sublingual biopsies were taken for measurement of local T cells, antigen‐presenting cells and IL‐12 mRNA expression.

Results There were no significant differences between the immunotherapy (IT) and placebo groups for diary symptom scores (P = 0.48) or rescue medication (P = 0.19). The patients' overall assessment of hayfever severity compared with previous years showed a highly significant improvement in favour of the IT group (P < 0.02). After treatment the late skin response was smaller (P = 0.003) and the ratio of serum allergen‐specific IgG4/IgE was higher (P = 0.05) in the IT group. Both of these variables correlated with the clinical response to SLIT. There were no differences between groups in either the sublingual epithelium or lamina propria for numbers of CD3+ cells (epithelium: P = 0.9, lamina propria: P = 0.2), CD1a+ cells (P = 0.3, P = 0.25), CD68+ cells (P = 0.9, P = 1.0) or IL‐12 mRNA+ cells (P = 0.6, P = 0.4). Local side‐effects were minor and there were no serious treatment‐related adverse events.

Conclusion Grass pollen sublingual immunotherapy was well tolerated. Although there was no significant change in diary scores, the improvement in overall assessments, which correlated with inhibition of the late skin response and increases in serum IgG4 : IgE ratio, indicates the need for larger, dose‐ranging studies.
Evolution of the Stress Field in the Northern Aegean Sea (Greece)
Authors: Papadimitriou Eleftheria E. , Sykes Lynn R.
Published: March 2003

The evolution of the stress field in the area of the northern Aegean Sea during the 20thcentury has been studied. The area is dominated by dextral strike-slip faulting and is characterized by frequent strong earthquakes. Coulomb stress changes (ΔCFF) we recalculated assuming that earthquakes can be modeled as static dislocations in an elastic half-space, and taking into account both the coseismic slip in large (M≥7.0) earth quakes and the slow tectonic stress build-up along the major fault segments. The stress change calculations were performed for strike-slip faults of strike, dip, and rake appropriate to the large events. We evaluate whether these stress changes brought a given large earthquake closer to, or farther from, failure. It was found that each of the large events occurred in regions of increased calculated Coulomb stress. Moreover, the majority of smaller events for which reliable fault-plane solutions are available were also located in areas of positive ΔCFF. By extending the calculations to 2020, and assuming that no additional large (M≥7.0) earthquake occurs between 1999 and 2020, possible sites of future large earthquakes are identified.
HLA‐DQ and DRB1 polymorphism and susceptibility to type 1 diabetes in Jamaica
Authors: Heward J. M. , Mijovic C. H. , Kelly M. A. , Morrison E. , Barnett A. H.
Published: March 2003

Genetic susceptibility to type 1 diabetes is determined by a combination of HLA‐DQ and DRB1 alleles. In the present study, HLA associations with type 1 diabetes were investigated in the Jamaican population. DRB1 and DQ genotyping was performed on 45 type 1 diabetic patients and 132 control subjects born and resident in Jamaica. The small number of patients available for study reflected the low prevalence of type 1 diabetes in Jamaica. The results were compared with those from other African heritage populations and white Caucasians. The highest relative risk was associated with the DRB1*03‐DQ2/DRB1*04‐DQ8 genotype. Both DRB1*0401‐DQ8 and DRB1*0408‐DQ8 were positively associated with disease. DRB1*0408‐DQ8 is uncommon amongst white Caucasians, where DRB1*0401‐DQ8 is the major predisposing haplotype. The DRB1*1503‐DQ6 haplotype was associated with protection from diabetes in the Jamaican population. This haplotype is rare amongst white Caucasians, where DRB1*1501‐DQ6 is the protective haplotype. Data from African heritage populations suggest that DRB1*1503‐DQ6 might be less protective than DRB1*1501‐DQ6. DRB1*03‐DQA1*0401‐DQB1*0402 was associated with protection from diabetes in the Jamaican population, whereas in white Caucasians DRB1*08‐DQA1*0401‐DQB1*0402 is predisposing. These data demonstrate that comparison of genetic associations with type 1 diabetes in races with population‐specific DRB1‐DQ haplotypes provides new information as to the exact determinants of disease susceptibility. Further support is provided for roles of the DQ genes and the DRB1 gene (or a gene in linkage disequilibrium with it) in determining susceptibility to type 1 diabetes.
Pain measurement: Understanding existing tools and their application in the emergency department
Authors: Lee Jacques S
Published: March 2003

See Commentary, page 271.
Age at Acquisition ofHelicobacter pyloriin a Pediatric Canadian First Nations Population
Authors: Sinha Samir K. , Martin Bruce , Sargent Michael , McConnell Jospeh P. , Bernstein Charles N.
Published: March 2003

Background.Few data exist regarding the epidem‐iology ofHelicobacter pyloriinfections in aboriginal, including the First Nations (Indian) or Inuit (Eskimo) populations of North America. We have previously found 95% of the adults in Wasagamack, a First Nations community in Northeastern Manitoba, Canada, are seropositive forH. pylori. We aimed to determine the age at acquisition ofH. pyloriamong the children of this community, and if any association existed with stool occult blood or demographic factors.

Materials and Methods.We prospectively enrolled children resident in the Wasagamack First Nation in August 1999. A demographic questionnaire was administered. Stool was collected, frozen and batch analyzed by enzyme‐linked immunosorbent assay (ELISA) forH. pyloriantigen and for the presence of occult blood. Questionnaire data were analyzed and correlated with the presence or absence ofH. pylori.

Results.163 (47%) of the estimated 350 children aged 6 weeks to 12 years, resident in the community were enrolled. Stool was positive forH. pyloriin 92 (56%). By the second year of life 67% were positive forH. pylori. The youngest to test positive was 6 weeks old. There was no correlation of a positiveH. pyloristatus with gender, presence of pets, serum Hgb, or stool occult blood. Forty‐three percent ofH. pyloripositive and 24% ofH. pylorinegative children were < 50th percentile for height (p = 0.024). PositiveH. pyloristatus was associated with the use of indoor pail toileting (86/143) compared with outhouse toileting (6/20) (p = 0.01).

Conclusions.In a community with widespreadH. pyloriinfection, overcrowded housing and primitive toileting,H. pyloriis acquired as early as 6 weeks of age, and by the second year of life 67% of children test positive forH. pylori.
Substrate oxidation and retention in pigs and poultry
Authors: CHWALIBOG André
Published: March 2003

A model combining data from gas exchange measurements with nutrient balances, demonstrating energy transfer between the pools of protein, carbohydrate and fat and their partition in the body, is described. Data from energy metabolism experiments with growing pigs and laying hens is incorporated into the model in order to illustrate methods of calculations and interpretations of the model. The experiments with pigs were carried out with growing pigs (20–100 kg) measured alternately on high (ad libitum) and low (near maintenance) feed levels on diets with low or high fat concentration. When energy intake from digested carbohydrate covered the requirements for growth, heat from oxidation of carbohydrate contributed 85–90% to the total heat production, while there was no net oxidation of fat. When the intake of digested carbohydrate was not sufficient to cover requirements, fat was mobilized from the body and oxidized. Energy from oxidation of carbohydrate was in all measurements below the energy in the carbohydrate pool, indicating transfer of energy from carbohydrate to fat metabolism in the process of de novo lipogeneis. The experiments with hens were carried out with 62 hens during the laying period from 26 to 47 weeks of age. The hens originated from two strains (A and B); they were kept in battery cages either individually or 3 hens/cage and fed ad libitum with an identical commercial diet. The partition of the protein pool between oxidation and retention was not influenced by the housing system. However, the genetic origin of hens effected protein utilization with relatively lower oxidation and higher retention in Strain B. The main part of the carbohydrate pool was oxidized (45–60%), but the hens kept individually oxidized more carbohydrate than those kept 3 hens/cage. Further, there were significant differences between the strains. Generally, about half of the fat pool originated from de novo lipogenesis from carbohydrate, indicating the importance of this process for fat retention in eggs. Fat oxidation depended on the energy supply from carbohydrate, hence with higher use of carbohydrate for oxidation in Strain B less fat was oxidized and more was used for fat synthesis. The presented results indicate that by combining results from gas exchange measurements with nitrogen and energy balances it is possible to evaluate the contribution of nutrients to the oxidative processes and the energy transfer between substrate pools.
Effects of FK506 and rapamycin on formation of the neural tube in chick embryos
Authors: OBATA Koji , KOIDE Masafumi , NAGATA Kohzo , IIO Akio , YAZAWA Shigenobu , ONO Tamao , SASAKI Shin‐ichi , YAMADA Yoshiji , TUAN Rocky S. , YOKOTA Mitsuhiro
Published: March 2003

FK506‐binding protein 12 (FKBP12) is an evolutionarily conserved immunophilin that binds the immunosuppressants FK506 and rapamycin. The physiological roles of this protein, however, remain unclear. The possible function of FKBP12 in embryonic development was investigated by examining the distribution of FKBP12 mRNA in chick embryos by whole‐mount in situ hybridization. The FKBP12 transcripts were detected at early stages of embryonic development, being especially abundant in the somites, heart tube and nervous system. Transcripts were also enriched in the neural fold, especially at the edge of this structure. Treatment of early embryos with rapamycin resulted in failure of neural tube closure, whereas treatment with FK506 had no such effect, suggesting that the FKBP12–rapamycin complex interferes with the formation of the neural tube. Given that rapamycin inhibits mitogenic signaling pathways, the FKBP12–rapamycin complex might disrupt mitosis during the formation of the neural tube. The lack of effect of FK506 on neural tube formation suggests that calcineurin signaling does not contribute to the formation of this structure during chick embryogenesis.
Stimulatory effect of cold acclimation on skeletal muscle branched‐chain α‐keto acid dehydrogenase in rats
Authors: TOYOMIZU Masaaki , AKAZAWA Tsunekazu , FUJII Hisao , NAKAI Naoya , SHIMOMURA Yoshiharu , AKIBA Yukio
Published: March 2003

The effects of cold‐acclimation (3 weeks at 4°C) on the actual activities of branched‐chain α‐keto acid dehydrogenase (BCKDH) and pyruvate dehydrogenase (PDH) complexes in the skeletal muscle and liver of normal 6‐week‐old rats were studied. The activities of BCKDH and PDH complexes were assayed using [1–14C] α‐ketoisocaproate and [1‐14C]pyruvate, respectively. Cold‐acclimation markedly stimulated the activity of BCKDH, and slightly but significantly increased the activities of PDH and citrate synthase (CS) in the skeletal muscle, but did not alter PDH, BCKDH or CS activities in the liver. The increase in muscle BCKDH activity (control rats, 1.45 ± 0.54 mU/g wet wt; cold‐acclimated rats, 2.54 ± 0.50 mU/g wet wt; 75% increase: P = 0.001) was much greater than the increases in PDH activity (84 ± 16 mU/g wet wt and 111 ± 25 mU/g wet wt; 32% increase: P = 0.020) or CS activities (27 ± 3 μmol/min per g wet wt and 31 ± 2 μmol/min per g wet wt; 14% increase: P = 0.046). These results suggest that, unlike PDH, BCKDH is not directly associated with the mitochondrial oxidative activity of the skeletal muscle of cold‐acclimated rats. This study provides the first evidence that BCKDH in skeletal muscle responds selectively to cold‐acclimation.
Response to mitogens of chicken splenocytes determined by three methods of measurement
Authors: KONDO Yasuhiro , OKIMOTO Yohko , ABE Asaki
Published: March 2003

The aim of the present study was to examine whether the 3‐[4,5‐dimethylthiazol‐2‐yl]‐2,5‐diphenyl tetrazolium bromide (MTT) colorimetric assay can be applied to measurement of mitogen‐induced chicken splenocyte activation. Activation was also measured by a 3H‐thymidine uptake assay and a viable cell count assay. Optimal concentrations of mitogens and incubation periods required for maximal responses to mitogens differed between the MTT assay and the viable cell count and thymidine uptake assays. This probably reflects differences in the activities measured by the MTT assay which detects mitochondrial enzyme activity, and the thymidine uptake and viable cell count assays which detect cellular proliferation activity. The validity of the MTT assay was supported by the observation that the mitogen‐induced increase in succinate dehydrogenase activity paralleled the level of mitogen‐induced MTT formazan production. Mitogen concentrations inducing maximal formazan formation in chicken splenocytes were higher than those for chicken peripheral blood lymphocytes reported previously. Results of the present study indicate that mitogen‐induced chicken splenocyte activation could be measured by the MTT colorimetric assay, although mitogen concentrations and incubation periods required for maximal splenocyte activation differed between the MTT assay and the other two assays used in this study.
Characteristics of Biceps femoris and Longissimus thoracis muscles of five cattle breeds grown in a feedlot system
Authors: RUSMAN  , SOEPARNO  , SETIYONO  , SUZUKI Atsushi
Published: March 2003

Our experiment was conducted to study physical quality and chemical composition of meat of Angus (A), Hereford (H), Friesian Holstein (FH), Australian Commercial Cross (ACC) and Murray Grey (MG) cattle breeds grown in a feedlot system. Significant differences were observed among five cattle breeds for cooking loss, tenderness, fatty acid composition, collagen and cholesterol content of meat. However, pH, water‐holding capacity, water, ash, fat and crude protein contents were not different. Cholesterol content of meat of A and FH was lower (P < 0.01) than that of H, ACC and MG. Acidity (pH), cooking loss, shear force, water, ash, crude protein, collagen and cholesterol content of Biceps femoris muscle were higher than those of Longissimus thoracis muscle, but water‐holding capacity and fat content were lower. Unsaturated fatty acid content of Biceps femoris muscle was higher (P < 0.01) than that of Longissimus thoracis. In conclusion, the differences among cattle breeds had a great effect on cooking loss, shear force, collagen, fatty acid composition and cholesterol of meat, but had little effect on water‐holding capacity, pH and proximate composition of meat. The meat of Hereford cattle was the best quality, because of the lowest shear force, cooking loss and collagen. Longissimus thoracis muscle was relatively better in cooking loss, tenderness and collagen content than Biceps femoris muscle.
Does conversion of forest to agricultural land change soil carbon and nitrogen? a review of the literature
Authors: Murty Danuse , Kirschbaum Miko U. F. , Mcmurtrie Ross E. , Mcgilvray Heather
Published: March 2003

Soil carbon is a large component of the global carbon cycle and its management can significantly affect the atmospheric CO2 concentration. An important management issue is the extent of soil carbon (C) release when forest is converted to agricultural land. We reviewed the literature to assess changes in soil C upon conversion of forests to agricultural land. Analyses are confounded by changes in soil bulk density upon land‐use change, with agricultural soils on average having 13% higher bulk density. Consistent with earlier reviews, we found that conversion of forest to cultivated land led to an average loss of approximately 30% of soil C. When we restricted our analysis to studies that had used appropriate corrections for changes in bulk density, soil C loss was 22%. When, from all the studies compiled, we considered only studies reporting both soil C and nitrogen (N), average losses of C and N were 24% and 15%, respectively, hence showing a decrease in the average C : N ratio. The magnitude of these changes in the C : N ratio did not correlate with either C or N changes. When considering the transition from forest to pasture, there was no significant change in either soil C or N, even though reported changes in soil C ranged from −50% to +160%. Among studies that reported changes in soil N as well as soil C, C : N ratios both increased and decreased, with trends depending on changes in system N. Systems with increasing soil N generally had decreased C : N ratios, whereas systems with decreasing soil N had increased C : N ratios. Our survey confirmed earlier findings that conversion of forest to cropland generally leads to a loss of soil carbon, although the magnitude of change might have been inflated in many studies by the confounding influence of bulk‐density changes. In contrast, conversion of forest to uncultivated grazing land did not, on average, lead to loss of soil carbon, although individual sites may lose or gain soil C, depending on specific circumstances, such as application of fertiliser or retention or removal of plant residues.
Potential impact of climate change on selected agricultural crops in north‐eastern Austria
Authors: Alexandrov Vesselin , Eitzinger Josef , Cajic Vesna , Oberforster Michael
Published: March 2003

The vulnerability and adaptation of major agricultural crops to various soils in north‐eastern Austria under a changing climate were investigated. The CERES crop model for winter wheat and the CROPGRO model for soybean were validated for the agrometeorological conditions in the selected region. The simulated winter wheat and soybean yields in most cases agreed with the measured data. Several incremental and transient global circulation model (GCM) climate change scenarios were created and used in the study. In these scenarios, annual temperatures in the selected region are expected to rise between 0.9 and 4.8 °C from the 2020s to the 2080s. The results show that warming will decrease the crop‐growing duration of the selected crops. For winter wheat, a gradual increase in air temperature resulted in a yield decrease. Incremental warming, especially in combination with an increase in precipitation, leads to higher soybean yield. A drier climate will reduce soybean yield, especially on soils with low water storage capacity. All transient GCM climate change scenarios for the 21st century, including the adjustment for only air temperature, precipitation and solar radiation, projected reductions of winter wheat yield. However, when the direct effect of increased levels of CO2 concentration was assumed, all GCM climate change scenarios projected an increase in winter wheat yield in the region. The increase in simulated soybean yield for the 21st century was primarily because of the positive impact of warming and especially of the beneficial influence of the direct CO2 effect. Changes in climate variability were found to affect winter wheat and soybean yield in various ways. Results from the adaptation assessments suggest that changes in sowing date, winter wheat and soybean cultivar selection could significantly affect crop production in the 21st century.
Use of anabolic steroids and associated health risks among gay men attending London gyms
Authors: Bolding Graham , Sherr Lorraine , Elford Jonathan
Published: March 2003

Aim To examine, by HIV status, the use of anabolic steroids among London gay men and their effect on physical and mental health.

Design Cross‐sectional survey using self‐administered questionnaire.

Setting Six gyms in central London.

Participants 772 gay men using the gyms in January–February 2000.

Measurements Proportion of gay men who reported (i) using steroids, (ii) sharing injecting equipment, (iii) experiencing side‐effects and (iv) having suicidal thoughts or feeling depressed.

Findings Of 772 gay men, 117 (15.2%) had used and 90 (11.7%) had injected steroids in the previous 12 months: HIV positive men (steroid use) 31.7% (40/126), HIV negative men 14.5% (69/477), never‐tested for HIV 4.7% (8/169) (p < 0.001). No one reported sharing needles or syringes. HIV positive men were more likely to have used steroids for medical reasons than other men (24.3% versus 5.9%, p = 0.01). Nearly all steroid users (96.4%) reported side effects including testicular atrophy (51.0%), insomnia (47.7%), depression between cycles (25.2%) and hypertension (19.0%). Steroid users were more likely to have had suicidal thoughts in the previous 6 months than non‐users (22.6% versus 11.2%, adjusted odds ratio after controlling for HIV status 1.84; 95% CI 1.10–3.12, p = 0.02) or to have felt depressed (49.1% versus 38.5%, adjusted OR 1.52, 95% CI 1.01–2.30, p = 0.047)

Conclusion One in seven gay men surveyed in central London gyms in 2000 said they had used steroids in the previous 12 months. HIV positive men were more likely to have used steroids than other men, some therapeutically. Side effects were reported widely and steroid use was associated with having had suicidal thoughts and feeling depressed, although cause and effect could not be established. Our findings suggest that steroid use among gay men may have serious consequences for both physical and mental health.
Blood flow in the peritendinous space of the human Achilles tendon during exercise
Authors: LANGBERG  , BÜLOW  , KJÆR
Published: March 2003

This study evaluated blood flow in the peritendinous space of the human Achilles tendon during rest and 40‐min dynamical contraction of m. tricgif surae. In 10 healthy volunteers 133Xe was injected in to the peritendinous space just ventrally to the Achilles tendon 2 and 5 cm proximal to the calcaneal insertion of the tendon, respectively. Blood flow 5 cm proximal to the Achilles tendon insertion was found to increase 4‐fold from rest to exercise whereas the exercise induced increase in blood flow was less pronounced, only 2.5‐fold, when measured 2 cm proximal to the Achilles tendon insertion. Lymph drainage from the area was found to be negligible both during rest and exercise. We conclude that dynamical calf muscle contractions result in increased peritendinous blood flow at the Achilles tendon in humans.
Regional differences in the effect of exercise intensity on thermoregulatory sweating and cutaneous vasodilation
Authors: KONDO  , TAKANO  , AOKI  , SHIBASAKI  , TOMINAGA  , INOUE
Published: March 2003

To investigate regional body differences in the effect of exercise intensity on the thermoregulatory sweating response, nine healthy male subjects (23.2 ± 0.4 year) cycled at 35, 50 and 65% of their maximal O2 uptake (V˙O2max) for 30 min at an ambient temperature of 28.3 ± 0.2 °C and a relative humidity of 42.6 ± 2.4%. Local sweating rate ( m˙sw) on the forehead, chest, back, forearm and thigh increased significantly with increases in the exercise intensity from 35 to 50% V˙O2max and from 50 to 65% V˙O2max (P < 0.05). The mean values for the density of activated sweat glands (ASG) at 50 and 65% V˙O2max at the five sites were significantly greater than at 35% V˙O2max. The mean value of the sweat output per gland (SGO) also increased significantly with the increase in exercise intensity (P < 0.05). The patterns of changes in ASG and SGO with an increase in exercise intensity differed from one region of the body to another. Although esophageal temperature (Tes) threshold for the onset of sweating at each site was not altered by exercise intensity, the sensitivity of the sweating response on the forehead increased significantly from 35 to 50 and 65% V˙O2max (P < 0.05). The threshold for cutaneous vasodilation tend to increase with exercise intensity, although the exercise intensity did not affect the sensitivity (the slope in the relationship Tes vs. percentage of the maximal skin blood flow) at each site. Tes threshold for cutaneous vasodilation on the forearm was significantly higher at 65% V˙O2max than at either 35 or 50% V˙O2max, but this was not observed at the other sites, such as on the forehead and chest. These results suggest that the increase in m˙sw seen with an increasing intensity of exercise depends first on ASG, and then on SGO, and the dependence of ASG and SGO on the increase in m˙sw differs for different body sites. In addition, there are regional differences in the Tes threshold for vasodilation in response to an increase in exercise intensity.
Is post‐tetanic potentiation, low frequency fatigue (LFF) and pre‐contractile depression (PCD) coexistent in intermittent isometric exercises of maximal intensity?
Authors: SKURVYDAS  , ZACHOVAJEVAS
Published: March 2003

The aim of our experiment was to test the hypothesis that the performance of maximal isometric exercise every 20 s would reduce the intermediate frequency force, i.e. the force that appears while stimulating the muscle at 15 and 20 Hz, and would produce less decrease the force at 10 and 50 Hz, while Pt would increase. Such changes in stimulated force should demonstrate the coexistence of potentiation, low frequency fatigue (LFF) and `post‐contractile depression' (PCD). The quadriceps muscle of 14 healthy men (aged 19–37 years) was studied. The results have shown, that during isometric exercise of maximal intensity there was significant (P < 0.05) decrease in P15 and P20, increase in Pt, however, MVC and P10 and P50 was unchanged (P > 0.05). LFF manifested itself most significantly which is evident from decrease in P20/P50. During recovery after work there was significant increase in LFF and decrease in P50 which is indicative of the manifestation of PCD. Besides, there was significant (P < 0.05) decrease immediately after exercise in RTP20 and RTP50, while no changes in T50 and RT. There were no significant changes (P > 0.05) however, either in RTP20 and RTP50 or in T50 and RT 20 min after exercise if compared to the initial and immediately post‐exercise values.
Interactions between membrane potential and intracellular calcium concentration in vascular smooth muscle
Authors: NILSSON
Published: March 2003

The intracellular calcium concentration is a major determinant of vascular tone. In the steady state it is regulated mainly by membrane potential. At the same time, several mechanisms regulating the calcium concentration, including the membrane potential, are influenced by the intracellular calcium concentration itself. There are thus multiple possible positive and negative feedback loops involved in calcium regulation. This review gives a brief overview of the different mechanisms involved, including calcium‐dependent ion channels, exchangers, and ATPases, and discusses their role in agonist‐mediated responses, in relation primarily to studies on the portal vein and mesenteric small arteries.
The cytoskeleton of the vertebrate smooth muscle cell
Authors: SMALL  , GIMONA
Published: March 2003

Smooth muscle cells possess a structural lattice composed of two primary parts: the ‘cytoskeleton’ that pervades the cytoplasm and the ‘membrane skeleton’ that provides anchorage for the cytoskeleton and contractile apparatus at the cell surface. The cytoskeleton contains two major components: first, a complement of actin filaments that links the cytoplasmic dense bodies at equispaced intervals in longitudinal fibrils; and second, a network of desmin intermediate filaments that co‐distributes with the cytoskeletal actin. The actin filaments of the contractile apparatus are presumed to interface with the cytoskeleton at the cytoplasmic dense bodies and with the longitudinal rib‐like arrays of dense plaques of the membrane skeleton that couple to the extracellular matrix. The present report focuses attention on the functional role of intermediate filaments and on the molecular domain structure of the protein calponin, which is found both in the cytoskeleton and the contractile apparatus. New information about the role of intermediate filaments in smooth muscle has come from studies of transgenic mice in which desmin expression has been ablated. These have shown that while desmin is dispensable for normal development and viability its absence has significant consequences for the mechanical properties of muscle tissue. Thus, the visceral smooth muscles develop only 40% of the normal contractile force and the maximal shortening velocity is reduced by 25–40%. Intermediate filaments therefore play an active role in force transmission and do not contribute solely to cell shape maintenance, as has hitherto been presumed. Recent studies on calponin have revealed a second actin binding domain at the C‐terminus of the molecule and have also pinpointed an N‐terminal domain that shares homology with a growing family of actin binding and signalling molecules. How these newly identified features of calponin relate to its function in vivo remains to be established.
Caldesmon: binding to actin and myosin and effects on elementary steps in the ATPase cycle
Authors: CHALOVICH  , SEN  , RESETAR  , LEINWEBER  , FREDRICKSEN  , LU  , CHEN
Published: March 2003

The actin binding protein caldesmon inhibits the actin‐activation of myosin ATPase activity. The steps in the cycle of ATP hydrolysis that caldesmon could inhibit include: (1) the binding of myosin to actin, (2) the transition between any two actin–myosin states and (3) the distribution between inactive and active states of actin. The analysis of these possibilities is complicated because caldesmon binds to both myosin and actin and because each caldesmon molecule binds to several actin monomers. This paper reviews procedures for analysing these interactions and summarizes current information on the stability and dynamics of the interaction of caldesmon with actin and myosin. Possible effects of caldesmon on transitions within the ATPase cycle of actomyosin are also discussed.
From pharmacomechanical coupling to G‐proteins and myosin phosphatase
Authors: SOMLYO  , SOMLYO
Published: March 2003

A brief summary of recent studies of pharmacomechanical coupling is presented, with emphasis on the role of GTP‐binding proteins and Ca2+‐independent regulation of contraction (Ca2+‐sensitization/desensitization) through regulatory myosin light chain (MLC20) phosphorylation and dephosphorylation. Pharmacomechanical regulation of cytosolic [Ca2+] is largely, though not solely, controlled by the phosphatidylinositol cascade and Ca2+‐pumps of the plasma membrane and the sarcoplasmic reticulum. The monomeric GTPase, RhoA, is a major upstream component of Ca2+‐sensitization. Its crystal structure and apparently obligatory translocation to the plasma membrane for activation of its downstream effectors are described. Inhibition of RhoA activity by a membrane‐permeant ADP‐ribosylating bacterial exoenzyme, DC3B, causes severe depression of the tonic component of agonist‐induced contraction, suggesting that this component is largely due to Ca2+‐sensitization. A relatively specific inhibitor (Y27632) of Rho‐kinase, a downstream effector of Ca2+‐sensitization (Uehata et al 1997), also inhibits oxytocin‐induced Ca2+‐sensitization of myometrium. The major mechanism of physiological, G‐protein‐coupled Ca2+‐sensitization is through inhibition of smooth muscle myosin phosphatase (SMPP‐1M), whereas conventional or novel protein kinase Cs play very little or no role in this process. Mechanisms of Ca2+‐desensitization include inhibition of myosin light chain kinase and activation of SMPP‐1M. Activation of SMPP‐1M in phasic smooth muscle can be attributed, at least in part, to the synergistic phosphatase activating activities of a cyclic nucleotide‐dependent kinase and its major substrate, telokin.