bluuebunny/crossref_metadata_2025 huggingface dataset:
Levormeloxifene: safety, pharmacodynamics and pharmacokinetics in healthy postmenopausal women following single and multiple doses of a new selective oestrogen receptor modulator
Authors: Skrumsager Birte K. , Kiehr Benedicte , Pedersen Poul Christian , Gerrits Mireille , Watson Norma , Bjarnason Ketil
Published: March 2003

Aims  The safety, pharmacodynamics and pharmacokinetics of levormeloxifene, a selective oestrogen receptor modulator (SERM), were investigated in postmenopausal women following single doses and multiple dosing once daily up to 56 days.

Methods  The two randomized, double‐blind, placebo controlled studies of six single ascending doses and at four multiple dose levels, respectively, included a total of 104 healthy postmenopausal women. Safety assessments comprised vital signs, ECG, haematology, clinical chemistry and reporting of adverse events. The pharmacodynamic properties were investigated after multiple dosing by assessment of the short‐term effects on bone and lipid metabolism and on the hypothalamic‐pituitary axis. Blood samples for pharmacokinetic analysis were collected at intervals until 648 h (27 days) after single and multiple dosing.

Results Levormeloxifene was tolerated well after single doses in the range of 2.5–320 mg and multiple once daily dosing in the range of 20–160 mg. Adverse events reported were generally mild or moderate. The most frequent adverse events after multiple dosing were headache, abdominal pain and leukorrhea with the highest frequency reported after the highest daily dose of 160 mg levormeloxifene. Five weeks of treatment with 20–160 mg levormeloxifene and 8 weeks of treatment with 40 or 80 mg levormeloxifene reduced the biochemical marker of bone turnover, the collagen I C‐terminal telopeptide (CrossLapsTM) by 44.4% [95% CI: 11.3, 65.1] and 35.5% [95% CI: 14.0, 51.6], respectively, without any dose‐dependent decrease in the studied dose range. The total cholesterol and LDL‐cholesterol concentrations were significantly reduced by 19–25% and 28–35%, respectively, when compared with placebo. HDL‐cholesterol and triglyceride concentrations were not affected. An oestrogen‐like effect on the hypothalamic‐pituitary axis was observed with approximately 50% reductions of FSH and LH after 8 weeks of treatment. No clinically significant changes of other safety variables were observed. The pharmacokinetic analysis demonstrated a rapid absorption (mean tmax: 2–3 h), a slow elimination (mean t½: 4.8–8.4 days) and dose linearity of Cmax and AUC for doses up to 160 mg. As expected for a drug with slow elimination given frequently, the relative fluctuation around the steady state plasma concentration was small and the drug accumulation considerable (RA: 3–5).

Conclusions Short‐term administration of levormeloxifene in postmenopausal women was well‐tolerated at doses that elicited a favourable pharmacodynamic response suggesting oestrogen‐like bone preserving and antiatherogenic effects. Little variation of peak‐trough plasma concentrations was observed during daily administration due to a plasma half‐life of approximately 1 week.
A double masked placebo controlled study on the effect of nifedipine on optic nerve blood flow and visual field function in patients with open angle glaucoma
Authors: Rainer Georg , Kiss Barbara , Dallinger Susanne , Findl Oliver , Georgopoulos Michael , Vass Clemens , Menapace Rupert , Polak Kaija , Eichler Hans‐Georg , Wolzt Michael , Schmetterer Leopold
Published: March 2003

Aims  To investigate whether nifedipine affects ocular perfusion or visual fields in open angle glaucoma patients.

Methods  In a parallel group study nifedipine or placebo was administered for 3 months (n = 30). Ocular fundus pulsation amplitude (FPA), cup blood flow (Flowcup) and visual field mean deviation (MD) were measured.

Results  Five patients receiving nifedipine discontinued due to adverse events. Nifedipine did not affect FPA [difference: 0.3 µm (95% CI −0.3,0.9); P = 0.70], Flowcup: [difference: −9 rel.units (95% CI −133,114); P = 0.99], or MD [difference: 0.2dB (95% CI −2.2,2.7); P = 0.51]vs placebo.

Conclusions  Systemic nifedipine is not well tolerated in glaucoma patients and exerts no effect on visual fields or ocular perfusion.
Use of lipid‐lowering drugs during 1991–98 in Northern Jutland, Denmark
Authors: Riahi Sam , Fonager Kirsten , Toft Egon , Hvilsted‐Rasmussen Lars , Bendsen Jørgen , Paaske Johnsen Søren , Toft Sørensen Henrik
Published: March 2003

Aims  To examine a) the use of lipid‐lowering drugs in North Jutland County in Denmark from 1991 to 1998 and b) the pattern of usage according to sex and age.

Methods and results We used the Pharmaco‐Epidemiological Prescription Database in the county to identify all reimbursed prescriptions for lipid‐lowering therapy from 1991 to 1998. One‐year incidence rates (IR) and prevalence (P) of the use of lipid‐lowering drugs were calculated. Both IR and P of patients in lipid‐lowering therapy were stable until 1994, with the IR below 100 per 100 000 for both sexes. The IR then increased from 59.9 to 236.5 per 100 000 person‐years in 1998 for women, and from 88.6 to 322.8 per 100 000 person‐years for men. The utilization patterns were identical between the sexes. Thus, in both women and men the highest prevalence and incidence rates of lipid‐lowering drug therapy were seen in the 60–69‐year‐olds. Furthermore, the marked increase in both prevalence and incidence of persons on lipid‐lowering drug therapy between 1994 and 1998 was the result of an increased number of prescriptions in the 50–59, 60–69 and 70 + years olds, in both women and men. There was a remarkable 4–5 fold increase in the numbers of new patients who received statins during the same period.

Conclusions  The overall use of lipid‐lowering drugs has increased markedly over the last few years in Northern Jutland, Denmark. The increase began following publication of the first major trial documenting the benefit of therapy with statins.
Effect of alosetron on theophylline pharmacokinetics
Authors: Koch K. M. , Ricci B. M. , Hedayetullah N. S. , Jewell D. , Kersey K. E.
Published: March 2003

Aims  To examine the potential for alosetron to alter the pharmacokinetics of theophylline by inhibiting its metabolism, as suggested by in vitro and in vivo effects on CYP1A2 activity.

Methods  Ten healthy female volunteers received theophylline 200 mg twice daily alone for 8 days and with alosetron 1 mg twice daily for 15 days in this randomized, placebo‐controlled, two‐way‐crossover study.

Results  Alosetron had no significant effect on theophylline plasma concentrations (Cmax≈9 µg ml−1, AUC≈90 µg ml−1 h) or oral formation clearance of three major metabolites produced via CYP1A2: 3‐methylxanthine, 1‐methylurate and 1,3‐dimethylurate (5, 7 and 16 ml min−1, respectively). Concomitant administration of alosetron and theophylline was well tolerated.

Conclusions  The absence of a clinical drug interaction involving inhibition of theophylline metabolism by alosetron was not predicted by in vitro and in vivo metabolic probe data.
Pharmacokinetics of finrozole (MPV‐2213ad), a novel selective aromatase inhibitor, in healthy men
Authors: Ahokoski Outi , Irjala Kerttu , Taalikka Mikko , Manninen Pekka , Halonen Kaija , Kangas Lauri , Salminen Eeva , Huupponen Risto , Scheinin Harry
Published: March 2003

Aims  To investigate the pharmacokinetics of finrozole (MPV‐2213ad), a novel competitive aromatase enzyme inhibitor, in healthy male volunteers.

Methods  The study was an open, partly randomized cross‐over study including 23 volunteers receiving single doses of 3, 9 mg or 30 mg of finrozole as tablets or solution with 14 days between the administrations. The highest dose was given as tablets only. Serum concentrations of finrozole were determined using high performance liquid chromatography combined with mass spectrometry.

Results  The mean time to peak serum concentration ranged from 2.5 to 3.1, and 0.6–0.7 h after tablets and solution, respectively. The Cmax values increased as the dose increased. The calculated apparent mean elimination half‐life (t1/2,z) was approximately 3 h after the solution, and approximately 8 h after the tablet. The AUC(0,∞) after finrozole tablets increased proportionally from 3 mg to 9 mg and from 3 to 30 mg. The calculated relative mean bioavailabilities (AUC(0,∞)−ratio) for the 3 mg and 9 mg doses of finrozole as tablets were 89% and 78%, respectively.

Conclusions  The absorption of finrozole from the tablet formulation was relatively rapid, and the apparent elimination half‐life was longer after the tablet than after the solution, probably reflecting overlap of the absorption with the elimination phase.
Statins and the risk of idiopathic venous thromboembolism
Authors: Yang Chen‐Chang , Jick Susan S. , Jick Hershel
Published: March 2003

Aims  To evaluate the association between current statin use and the risk of idiopathic venous thromboembolism (VTE).

Methods  A population‐based retrospective follow‐up with a nested case‐control analysis using the General Practice Research Database.

Results  There were 72 cases of idiopathic VTE. Using normolipidaemic nonuse as the reference group, the adjusted relative risks for idiopathic VTE for current/recent statin use, past statin use, past other lipid‐lowering drug use, and hyperlipidaemic nonuse were 0.8 (0.3, 2.7), 2.4 (0.6, 10.0), 1.8 (0.4, 7.4), and 0.9 (0.4, 2.0) in the follow‐up analysis, and were 1.1 (0.3, 4.3), 3.7 (0.6, 24.1), 2.0 (0.3, 11.6), and 0.4 (0.2, 1.2) in the case‐control analysis.

Conclusions  Current statin use was not associated with a reduced risk of idiopathic VTE.
Patient reporting of potential adverse drug reactions: a methodological study
Authors: Jarernsiripornkul N. , Krska J. , Capps P. A. G. , Richards R. M. E. , Lee A.
Published: March 2003

Aims  To develop a systematic generic method of enabling patients to report symptoms which they believe to be due to a particular prescribed drug.

Methods  A piloted body system‐based questionnaire was distributed to patients registered with 79 medical practices in Grampian prescribed one of nine recently marketed ‘black triangle’ drugs. These comprised four antidepressants, three antiepileptics and two analgesics. This requested respondents to identify any symptoms experienced over the previous year which they thought could be due to the ‘black triangle’ drug they had used. A sample of medical records was examined to compare symptoms recorded with those reported by patients. A classification system was developed for the study to enable the assessment of symptoms reported for their potential relationship to patients' drug therapy. All symptoms reported were classified, taking into account information provided by patients on their concomitant drugs and diseases. A specialist pharmacist independently re‐classified a sample of the symptoms to validate the process.

Results  A 36.3% response rate was obtained (837/2307) with 742 respondents (88.6%) reporting at least one symptom. The median per patient was 6.0 (range 0–71), with almost half (406, 48.5%) reporting fewer than five symptoms. Most symptoms (71.0%) were classified as being probably or possibly related to the drugs studied. Agreement between researcher and specialist on the classification of 75.3% of 716 symptoms was obtained (Kappa=0.563). Responses from patients prescribed antidepressant drugs were more likely to include symptoms potentially caused by these drugs (74.5% of all symptoms reported) than those from patients prescribed analgesics (67.4%) or antiepileptics (65.1%, χ2 = 23.858, d.f. = 2, P < 0.001). Patients reporting large numbers of symptoms were more likely to report some which were classed as unlikely to be an ADR or unattributable (χ2 = 80.587, d.f. = 3, P < 0.001). Of the 742 reporting symptoms in questionnaires, 402 (54.2%) claimed to have reported some or all of these to their doctor. Only 162 (22.6%) of 716 patient‐reported symptoms were documented in the primary care medical records of 103 patients prescribed tramadol or venlafaxine.

Conclusions  Respondents were clearly willing to report symptoms, the majority of which were classed as possibly/probably related to the drugs studied. The results suggest that patients do not report all symptoms they suspect to be ADRs to their GP and that GPs do not record all symptoms which may be reported to them. The method could help to identify problems which patients perceive as being related to their drug therapy and contribute to increased ADR reporting.
Pharmacokinetics of moxifloxacin, a novel 8‐methoxy‐quinolone, in patients with renal dysfunction
Authors: Stass H. , Kubitza D. , Halabi A. , Delesen H.
Published: March 2003

Aims  To evaluate the influence of impaired renal function on the plasma and urinary pharmacokinetics of moxifloxacin, a novel 8‐methoxy‐quinolone antibacterial drug.

Methods  Twenty male and 12 female subjects (8 healthy subjects, 24 patients with impaired renal function), 18–75 years of age were investigated in parallel fashion with four groups stratified according to creatinine clearance (CLCR; n=8 for each group). The pharmacokinetics of moxifloxacin and the metabolites M1 (sulphonate metabolite) and M2 (glucuronide) in plasma and urine were determined repeatedly up to 96 h after single oral doses of 400 mg. Patients were monitored intensively with regard to clinical and laboratory safety and tolerability.

Results  Single doses of 400 mg moxifloxacin were safe and well tolerated. The urinary excretion of moxifloxacin (Aeur, P: 0.0002) and renal clearance (CLR, P<0.0001) were reduced with decreasing CLCR, mean Cmax was slightly reduced (Cmax‐ratio 85.0%, 90% CI 67.9, 106.4% severe renal impairment vs healthy subjects) but the AUC was unchanged even in severe renal impairment (AUC‐ratio 101.3%, 90% CI 79.7, 128.6%). The mean AUC of the N‐sulphonate M1 was slightly increased (by about 53% for the most severe disease) by impaired renal function, but there was no significant correlation between individual AUC and CLCR, whilst Aeur and CLR were significantly correlated with CLCR. In contrast, for the acylglucuronide M2, Aeur (P: 0.0026), CLR (P<0.0001) and AUC (P: 0.0011) were directly correlated with CLCR.

Conclusions  Renal dysfunction had little effect on the plasma pharmacokinetics of either moxifloxacin or metabolite M1, although their renal clearance and urinary excretion were reduced. In contrast renal dysfunction did result in changes in the plasma pharmacokinetics of metabolite M2, causing greater and longer exposure. However the extent of these changes is unlikely to be of clinical relevance.
Efficacy of calcium channel blockers as maintenance therapy for asthma
Authors: Ann Twiss Mary , Harman Eloise , Chesrown Sarah , Hendeles Leslie
Published: March 2003

Aims  Previous bronchoprovocation studies indicate that nifedipine attenuates airway responsiveness to several stimuli whereas diltiazem has no effect. The aim of this study was to determine whether such studies predict the efficacy of calcium channel blockers as maintenance therapy for persistent asthma.

Methods  Twenty‐one otherwise healthy adults with persistent asthma, mean age 25 years, completed treatment with maximum tolerated doses of placebo (P), nifedipine (N), and diltiazem (D) in a double‐blind, randomized, three‐treatment, three‐period, crossover manner, each for 4 weeks. Frequency and severity of asthmatic symptoms were recorded twice daily, as well as peak expiratory flow and frequency of ‘prn’ use of inhaled terbutaline. Blood pressure, heart rate, P‐R interval of the ECG and spirometry were measured biweekly. At the end of each treatment, airway responsiveness to exercise was measured.

Results  The mean (s.e. mean)% of days with wheeze was 69±7% during P, 75±6% during N and 72±6% during D (P=0.7). FEV1 was 79±2% of predicted during P, 81±2% during N and 79±2% during D (P=0.6). The decrease in FEV1 after exercise was 32±4% during P, 32±5% during N and 27±4% during D (P=0.5). Heart rate was elevated during N (P=0.0002) whereas P‐R interval was prolonged during D (P=0.0001).

Conclusions  Maintenance therapy with calcium channel blockers, at doses that produce cardiovascular effects, do not suppress the signs and symptoms of persistent asthma. Previous bronchoprovocation studies did not predict these results.
Comparative human pharmacokinetics and metabolism of single‐dose oral and intravenous sildenafil
Authors: Muirhead Gary J. , Rance David J. , Walker Donald K. , Wastall Philip
Published: March 2003

Aims  To characterize the absorption, metabolism and excretion of an oral and intravenous (IV) dose of radiolabelled [14C]‐sildenafil citrate in healthy male subjects. Specific objectives were to measure the cumulative amount of drug‐related radiolabelled material excreted in the urine and faeces to characterize urinary and faecal radioactivity as unchanged sildenafil or its metabolites, and to quantify blood and plasma total radioactivity and unchanged drug concentrations.

Methods  Six healthy male subjects between the ages of 45 and 58 years were enrolled in an open‐label, parallel‐group study; three subjects received the oral dose and three received the IV dose. Oral drug was administered as a single dose of 50‐mg [14C]‐sildenafil, and IV drug was administered as a single dose of 25‐mg [14C]‐sildenafil infused over 25 min. Each dosage form contained 50 µCi of radioactivity. For radioactivity assays, whole blood, plasma, urine and faeces samples were taken predose and at specified intervals up to 5 days postdose. Plasma samples were assayed for sildenafil and the metabolites UK‐103,320 and UK‐150,564. Metabolite profiling was also performed in plasma, faeces and urine.

Results  Absorption of sildenafil after oral administration was rapid and approximately 92% whilst the absolute bioavailability was limited to 38%, due to first‐pass metabolism. Mean AUCt values showed that sildenafil accounted for about 60% of the total circulating radioactivity in the plasma after IV administration and for 32% after oral administration. Concentrations of radioactivity in whole blood were lower than in plasma, indicating limited penetration of sildenafil into blood cells. No unchanged sildenafil was detected in either urine or faeces, demonstrating that metabolism was the major mechanism of drug clearance. The principal routes of metabolism were N‐demethylation, oxidation and aliphatic dehydroxylation. Sildenafil was well tolerated, with treatment‐related adverse events reported by three subjects. Two of these were mild, and there was one case of moderate leg pain.

Conclusions  The pharmacokinetics of radiolabelled [14C]‐sildenafil were consistent with rapid absorption, first‐pass metabolism and primarily faecal elimination of N‐demethylated metabolites.
Daytime liver glycogen accumulation, measured by 13C magnetic resonance spectroscopy, in young children with Type 1 diabetes mellitus
Authors: Matyka K. , Dixon R. M. , Mohn A. , Rajagopalan B. , Shmueli E. , Styles P. , Dunger D. B.
Published: March 2003

Aim  To examine daytime liver glycogen accumulation in prepubertal children with Type 1 diabetes mellitus (Type 1 DM) compared with non‐diabetic controls.

Methods  Liver glycogen content was ascertained in the fasting (morning) and fed (afternoon) state using 13C magnetic resonance (MR) spectroscopy. Data were analysed from six children with Type 1 DM (median (range) age 8.7 (6.3–12.2) years), who were all on conventional insulin regimens, and six healthy controls (age 8.9 (7–10.2) years).

Results  Children with diabetes tended to have lower fasting glycogen values than controls but this did not reach statistical significance (median (range) 154 (70–177) vs. 178 (120–203) mM glycosyl units, Type 1 DM vs. controls respectively; P = 0.06). Glycogen increased in all children with diabetes during the day and concentrations were similar to those in controls by the afternoon (175 (157–299) vs. 172 (136–238) mM glycosyl units; P = 0.7).

Conclusions  The ability of young children with Type 1 DM to replace liver glycogen depleted after an overnight fast was at least as good as that in control subjects, suggesting that impaired glycogen storage is not a contributory factor in nocturnal hypoglycaemia.

Diabet. Med. 18, 659–662 (2001)
The influence of the polymorphism in apolipoprotein B codon 2488 on insulin and lipid levels in a Danish twin population
Authors: Bentzen J. , Poulsen P. , Vaag A. , Beck‐Nielsen H. , Fenger M.
Published: March 2003

Aims The apolipoprotein B codon 2488 polymorphism has been associated with the metabolism of lipoproteins in subjects with Type 2 diabetes. However, no data are available on the influence of the polymorphism on insulin or glucose metabolism. This study examines the impact of the polymorphism on parameters associated with the insulin resistance syndrome in Danish twins.

Methods The effect of the polymorphism on lipid, glucose and insulin measures was studied in 548 same sex twins aged 55–74 years.

Results The codon 2488 polymorphism influenced fasting triglyceride levels, as well as insulin, as measured at 120 min in an oral glucose tolerance test. Subjects with the genotype T2488T had 14% higher triglyceride levels (P = 0.02) and 31% higher insulin levels (P = 0.004) than subjects with genotype C2488C. In twins discordant for genotype, the T‐allele was associated with higher levels of triglyceride (P = 0.04) and insulin (P = 0.02) and lower levels of HDL‐cholesterol (P = 0.04).

Conclusion The T‐allele of the codon 2488 polymorphism influenced parameters related to the insulin resistance syndrome, i.e. increased levels of insulin, increased levels of triglyceride and decreased levels of HDL. As the polymorphism is silent, these effects must be mediated through linkage to other polymorphisms in apolipoprotein B or other genes on chromosome 2.
Tectonostratigraphic model for the North Croatian and North Bosnian sector of the Miocene Pannonian Basin System
Authors: Pavelić D.
Published: March 2003

ABSTRACT The formation of the North Croatian Basin, which represents the south‐western marginal part of the Pannonian Basin System and the Central Paratethys Bioprovince, began during Ottnangian time (early Miocene) by continental rifting. The syn‐rift phase lasted until the middle Badenian (middle Miocene), and resulted in the formation of elongated half‐grabens characterized by large sediment thicknesses strongly influenced by tectonics and gradually increasing volcanism. Towards the end of the syn‐rift phase sinistral strike‐slip faulting took place, transverse to oblique to the master faults, which disintegrated the longitudinal structures contemporaneously with volcanic activity. The depositional environments gradually changed from alluvial and lacustrine to marine. The syn‐ to post‐rift boundary was characterized by significant erosion of the uplift fault block footwalls. The post‐rift phase extended from the middle Badenian to the end of the Pontian (latest Miocene). Tectonic influence drastically decreased, volcanism ceased, and subsidence of the basin was controlled predominantly by cooling of the lithosphere. Marine connections gradually decreased, resulting in a transition from marine to brackish, ‘caspi‐brackish’ and finally fluvial‐marsh environments. By the end of the Miocene the basin was finally infilled. The basin evolution was also complicated by an alternation of phases of extension and compression.
Sound lateralization during passive whole‐body rotation
Authors: Lewald Jörg , Karnath Hans‐Otto
Published: March 2003

The effect of passive whole‐body rotation about the earth‐vertical axis on the lateralization of dichotic sound was investigated in human subjects. Pure‐tone pulses (1 kHz; 0.1 s duration) with various interaural time differences were presented via headphones during brief, low‐amplitude rotation (angular acceleration 400°/s2; maximum velocity 90°/s; maximum displacement 194°). Subjects made two‐alternative forced‐choice (left/right) judgements on the acoustic stimuli. The auditory median plane of the head was shifted opposite to the direction of rotation, indicating a shift of the intracranial auditory percept in the direction of rotation. The mean magnitude of the shift was 10.7 µs. This result demonstrates a slight, but significant, influence of rotation on sound lateralization, suggesting that vestibular information is taken into account by the brain for accurate localization of stationary sound sources during natural head and body motion.
The African Enigma: Low Prevalence of Gastric Atrophy, High Prevalence of Chronic Inflammation in West African Adults and Children
Authors: Campbell David I. , Warren Bryan F. , Thomas Julian E. , Figura Natalia , Telford John L. , Sullivan Peter B.
Published: March 2003

Background.

Helicobacter pylori infection is very common in Africa, yet peptic ulcer disease and gastric malignancy are rare.

Aim.

The aim of this study was to quantify mucosal responses to H. pylori in Gambian adults and children and to estimate the prevalence of antibodies to bacterial virulence factors (cagA and vacA) in a symptomatic population.

Patients and methods.

Adults (mean 36 SD 12 years) with dyspepsia and children (mean 1.4 years SD 0.4 years) with malnutrition underwent gastroscopy with biopsy. Blood was simultaneously drawn for cagA and vacA antibody status. Histopathological scoring used the modified Sydney classification.

Results.

Both adults (n = 45) and children (n = 37) mainly demonstrated chronic mild antral inflammation. Only 2/83 cases of focal atrophy (GA) and 4/83 cases of intestinal metaplasia (IM) were observed. Adults tended to demonstrate more frequent acute (AI) and chronic inflammation (CI) (38% compared with 18% and 85% compared with 72%, respectively). Sixty‐seven percent of children were cagA IgG+ and 21%vacA IgG+ and 93% of adults were IgG cagA+ and 86%vacA+. There were no differences in mucosal responses between those who were cagA or vacA positive compared with those who were negative.

Conclusion.

Gambian adults and children mount a CI response to H. pylori but GA, IM and AI are uncommon. cagA and vacA are commonly expressed in Gambian strains of H. pylori. Further studies are needed in order to confirm that GA and IM are not late findings in old age.
Anatomical and physiological characteristics of ostrich (Struthio camelus var. domesticus) meat determine its nutritional importance for man
Authors: COOPER Ross Gordon , HORBAÑCZUK Jaroslaw Olav
Published: March 2003

The ostrich is increasingly gaining interest as a livestock animal because of its potential to produce healthy red meat with a low fat content. This article describes the characteristics of ostrich meat that allow it to be marketed as a healthy alternative to beef. The muscles utilized for human consumption include the dorsal Muscularis obturatorius medialis and the hindquarters. The trade names of ostrich muscles are currently not standardized and classification is based on location and scientific nomenclature. Meat cuts of a high commercial value reach as much as 80–90% in the ostrich compared with approximately 45% in other species. Described here are key product characteristics important in its marketing, including fat content, cholesterol, fatty acids, sodium, iron, color, flavor and odor, tenderness, pH and water‐holding capacity.
Regulation of fermentation in a ruminal bacterium, Streptococcus bovis, with special reference to rumen acidosis
Authors: ASANUMA Narito , HINO Tsuneo
Published: March 2003

When high‐starch diets are fed to ruminants, Streptococcus bovis often predominates in the rumen and produces lactate as the major fermentation product. Lactate production by S. bovis is regulated by the activity ratio of lactate dehydrogenase (LDH) to pyruvate formate‐lyase (PFL) in response to an energy supply or the intracellular pH. The activities of LDH and PFL are affected not only by the amounts of enzyme proteins, but also by the concentrations of allosteric effectors, such as fructose‐1, 6‐bisphosphate (FBP) and triose phosphates. Synthesis of LDH and PFL is regulated at the transcriptional level in opposing directions. The inverse relationship between LDH and PFL synthesis amplifies a change in the proportion of lactate in the total fermentation products. A high capacity to regulate lactate production in response to low pH allows S. bovis to grow at low pH and as one of the most acid‐tolerant bacteria among the prevailing ruminal bacteria, S. bovis also has a high capacity to extrude intracellular H+ by an F1F0 H+‐ATPase, which is important for acid tolerance. In addition, S. bovis is able to augment H+‐ATPase synthesis at the transcriptional level in response to low pH. The activities of H+‐ATPase and pyruvate kinase are enhanced by FBP and strongly inhibited by inorganic phosphate (Pi). Intracellular FBP and Pi concentrations affect sugar metabolism in S. bovis through regulation of the expression of catabolic genes and controlling the activity of sugar transport systems. Synthesis of the enzymes involved in sugar transport and fermentation appears to be regulated by the catabolite control protein A (CcpA) –phosphotransferase system (PTS) system.
Net grassland carbon flux over a subambient to superambient CO2 gradient
Authors: Mielnick P. C. , Dugas W. A. , Johnson H. B. , Polley H. W. , Sanabria J.
Published: March 2003

Increasing atmospheric CO2 concentrations may have a profound effect on the structure and function of plant communities. A previously grazed, central Texas grassland was exposed to a 200‐µmol mol−1 to 550 µmol mol−1 CO2 gradient from March to mid‐December in 1998 and 1999 using two, 60‐m long, polyethylene‐ covered chambers built directly onto the site. One chamber was operated at subambient CO2 concentrations (200–360 µmol mol−1 daytime) and the other was regulated at superambient concentrations (360–550 µmol mol−1). Continuous CO2 gradients were maintained in each chamber by photosynthesis during the day and respiration at night. Net ecosystem CO2 flux and end‐of‐year biomass were measured in each of 10, 5‐m long sections in each chamber. Net CO2 fluxes were maximal in late May (c. day 150) in 1998 and in late August in 1999 (c. day 240). In both years, fluxes were near zero and similar in both chambers at the beginning and end of the growing season. Average daily CO2 flux in 1998 was 13 g CO2 m−2 day−1 in the subambient chamber and 20 g CO2 m−2 day−1 in the superambient chamber; comparable averages were 15 and 26 g CO2 m−2 day−1 in 1999. Flux was positively and linearly correlated with end‐of‐year above‐ground biomass but flux was not linearly correlated with CO2 concentration; a finding likely to be explained by inherent differences in vegetation. Because C3 plants were the dominant functional group, we adjusted average daily flux in each section by dividing the flux by the average percentage C3 cover. Adjusted fluxes were better correlated with CO2 concentration, although scatter remained. Our results indicate that after accounting for vegetation differences, CO2 flux increased linearly with CO2 concentration. This trend was more evident at subambient than superambient CO2 concentrations.
Isoform of Na+, K+‐ATPase from rumen epithelium identified and quantified by immunochemical methods
Authors: HANSEN
Published: March 2003

Using biopsies of rumen epithelium papillae a net influx of [86Rb+] was measured corresponding to a high concentration of Na+, K+‐pumps found in [3H]ouabain‐binding studies (
Kristensen et al. 1995
). In the present study the Na+, K+‐ATPase in papillae homogenates is compared with purified (Na+, K+)‐ATPase from different sources, immunochemically characterized with respect to the isoform of the hydrolytic α subunit and the concentration of pumps substantiated by a novel immunochemical method. Na+, K+‐ATPase purified from bovine kidney was shown to contain one homogeneous high‐affinity population of [3H]ouabain‐binding sites (Kd 1.37 n
M). The ouabain‐binding capacity was 0.82 nmol (mg protein)−1. Site‐directed polyclonal antibodies raised to isoform‐specific sequences of the three known α‐subunit isoforms and monoclonal α1‐specific antibodies were used for isoform characterization on western blots of peptides separated by SDS‐polyacrylamide gel electrophoresis. All three isoforms were present in Na+, K+‐ATPase prepared from bovine brain. The α isoform of bovine kidney Na+, K+‐ATPase and of rumen epithelium homogenate appeared to be α1 whereas α2 and α3 were undetectable. Using an α1‐specific antibody and 125I‐labelled antimouse IgG the content of (Na+, K+)‐ATPase in rumen epithelium was determined by comparison of the signal from known amount of bovine kidney Na+, K+‐ATPase on western blots. By this method rumen epithelium was found to contain 2.6 nmol Na+, K+‐ATPase (g wet wt)−1, i.e. a similarly high or even higher concentration than previously seen in ouabain‐binding studies on biopsies.
Preconditioning does not attenuate cardiac dysfunction after global ischaemia in the guinea‐pig
Authors: VALEN G.
Published: March 2003

Ischaemic preconditioning reduces infarct size, but the effects on cardiac function after global ischaemia are more controversial. Additionally, species differences may exist. The present study investigates the effects of preconditioning on cardiac performance in the globally ischaemic, Langendorff‐perfused guinea‐pig heart. Hearts were stabilized for 25 min, and divided into the following groups: (1) (n = 8) control perfusion for 16 min before 30‐min global ischaemia and 30‐min reperfusion, (2) (n = 7) two episodes of 3‐min ischaemia and 5‐min reperfusion before global ischaemia, (3) (n = 7) 5‐min ischaemia and 10‐min reperfusion before ischaemia, (4) (n = 8) control perfusion before 40‐min ischaemia and 30‐min reperfusion, (5) (n = 8) Preconditioning as group 2 before ischaemia as group 4, (6) (n = 9) Control perfusion before 50‐min ischaemia and 30‐min reperfusion, (7) (n = 10) Preconditioning as group 2 before ischaemia as group 6. A dose‐dependent reduction of left ventricular systolic pressure, and increase of end‐diastolic pressure was observed during reperfusion after 30‐, 40‐ and 50‐min ischaemia. Preconditioning did not influence these changes, nor did it attenuate the incidence of severe reperfusion arrhythmias or reduction of coronary flow. In conclusion, ischaemic preconditioning does not improve cardiac function during reperfusion of the globally ischaemic, isolated guinea‐pig heart.
Appearance of contractile endothelin‐B receptors in rat mesenteric arterial segments following organ culture
Authors: ADNER  , GEARY  , EDVINSSON
Published: March 2003

The aim of this study was to examine how different procedures for organ culture affect the expression of contractile endothelin(ET)‐B receptors in a branch of the rat mesenteric artery. In fresh segments, ET‐1 and ET‐3 induced similar strong contractions, ET‐1 being 20‐fold more potent, whereas neither of the selective ETB receptor agonists, sarafotoxin 6c (S6c) nor IRL 1620, induced significant contractions. In segments cultured for 1 day, ET‐3 was only 3‐fold less potent as ET‐1, and S6c and IRL 1620 induced concentration‐dependent contractions which were about 60% of the ET‐1 induced contraction. The maximum contractile response to S6c was not altered in segments cultured with foetal calf serum or in buffer solution, but was reduced to about 20% of the control value when cultured in glucose‐free buffer solution. The contraction to S6c was abolished in segments placed in cold (4 °C) buffer solution. Removal of the endothelium had no effect on the S6c‐induced contractions. Arteries cultured at isometric tension (at 2 mN) for 1day achieved the same contractile response for ETB agonists as resting segments. Pressurized arteries (60 mmHg) did not constrict to S6c when mounted as a fresh segment but demonstrated a strong contraction after 1 day at this transmural pressure. This study suggests that the appearance of ETB receptor mediated contraction following organ culture is not dependent on specific nutrients, endothelial factors or absence of intrinsic tension, but is a metabolically active process.
Left ventricular function in endurance runners during exercise
Authors: JENSEN‐URSTAD  , BOUVIER  , NEJAT  , SALTIN  , BRODIN
Published: March 2003

Left ventricular function in elite runners and controls was compared by means of nuclear angiocardiography. Fifteen middle‐ or long‐distance runners and a control group of 10 sedentary to moderately physically active subjects were studied at rest and during semi‐sitting incremental exercise. Ejection fraction was higher in the runners than the controls both at rest and during exercise. At the transition from rest to exercise left ventricular end‐diastolic volume initially increased similarly in runners and controls by an average of 14 and 12%, respectively, with an increase in stroke volume by ≈25 and 23%. The parallel increase in stroke volume and left ventricular end‐diastolic volume could a least partly be because of the Frank–Starling mechanism. With increasing workloads, left ventricular end‐diastolic volume and ejection fraction remained fairly constant, resulting in an unchanged stroke volume from the lowest to the highest exercise intensity. This was in the runners␣accomplished by a 41% increase in peak filling rate and a 38% increase in peak emptying rate with similar changes observed in the controls. This has to be due to increased myocardial contractility paralleling the systolic shortening with increasing heart rate. We conclude that endurance‐trained athletes have a better systolic function expressed as higher ejection fraction both at rest and during exercise than untrained subjects reflecting an enhanced myocardial contractility contributing to the maintenance of a large stroke volume during exercise. The regulatory mechanisms however, appear to be similar for athletes and healthy controls.
Autonomic nervous influence of the female guinea‐pig urinary bladder during the oestrus cycle
Authors: LIU  , ANDERSSON  , HAMMARSTRÖM  , LARSON
Published: March 2003

The mammalian urinary bladder receives dual innervation. The excitatory innervation is considered to be partly cholinergic and partly mediated via NANC‐receptors. Several (co‐)transmitters have been suggested. The adrenergic inhibitory innervation is mediated via α‐ and β‐receptors. Female sex hormones could change autonomic influence of urogenital organs. It was considered to be of interest to characterize the spontaneous and nerve stimulation‐induced muscular activity in the urinary bladder of the female guinea‐pig during the oestrus cycle. Both the spontaneous activity and nerve‐induced activity varied according to the hormonal status of the animal. An α‐adrenergic inhibitory influence was identified. It was further confirmed that the excitatory innervation could not be blocked by the cholinergic antagonist scopolamine, while α‐β‐methylene ATP partly inhibited nerve stimulation‐induced smooth muscle response, most prominent at cycle day 6. Indomethacin did not impair spontaneous activity or nerve stimulation‐induced activity. Nitric oxide reduced nerve stimulation‐induced responses on cycle day 12. Imperative urinary bladder contractions are reported to diminish after oestrogen use and in the female a hormonal effect of the nervous influence on the urinary bladder smooth muscle is suggested.
Exercise‐induced decreases in sarcoplasmic reticulum Ca2+–ATPase activity attenuated by high‐resistance training
Authors: GREEN  , GRANGE  , CHIN  , GOREHAM  , RANNEY
Published: March 2003

Muscle biopsies were performed on the vastus lateralis muscle prior to and during a high‐resistance training (HRT) programme in order to examine the effects of hypertrophy on sarcoplasmic reticulum Ca2+ ATPase activity at rest and during exercise. In six male untrained volunteers (peak aerobic power, V˙O2 peak = 3.39 ± 0.13 L min−1, mean ± SE), the resting Ca2+ ATPase activity (μmol min−1 g wet wt−1) at 0 (4.89 ± 0.20), 4 (5.62 ± 0.56), 7 (5.15 ± 0.41) and 12 (4.82 ± 0.11) weeks was unchanged by HRT. During cycle ergometer exercise, prior to training, Ca2+‐ATPase was reduced (P < 0.05) by 14% during the initial 30 min at 58% VO2 peak and (P < 0.05) a further 19% during 30 min at 72% VO2 peak. Following 7 and 12 weeks of training, the decreases in SR Ca2+‐ATPase were less pronounced (P < 0.05). These results indicate that muscle hypertrophy, although incapable of altering Ca2+‐ATPase pump activity at rest, can attenuate the decrease observed in exercise by mechanism(s) as yet unknown.
Effects of creatine monohydrate ingestion in sedentary and weight‐trained older adults
Authors: BERMON  , VENEMBRE  , SACHET  , VALOUR  , DOLISI
Published: March 2003

To investigate the effects of an oral creatine supplementation in older adults, 32 elderly subjects (67–80 years; 16 females, 16 males) were randomly assigned to four equivalent subgroups (control‐creatine; control‐placebo; trained‐creatine; trained‐placebo) based on whether or not they took part in an 8‐week strength training programme and an 8‐week oral creatine monohydrate creatine supplementation programme. The strength training programme consisted of three sets of eight repetitions at 80% of one‐repetition maximum, for leg press, leg extension and chest press, 3 days a week. The 52‐day supplementation programme consisted of 20 g of creatine monohydrate (or glucose) and 8 g of glucose per day for the initial 5 days followed by 3 g of creatine monohydrate (or glucose), and 2 g of glucose per day. Prior to and after the training and supplementation periods, body mass, body fat, lower limb muscular volume, 1‐, 12‐repetitions maxima and isometric intermittent endurance tests for leg press, leg extension and chest press were determined. In all groups, no significant changes in anthropometric parameters were observed. For all movements, the increases in 1‐ and 12‐repetitions maxima were greater (P < 0.02) in trained than control subjects. No significant interactions (supplementation/training/time) were observed for the 1‐, 12‐repetitions maxima, and the isometric intermittent endurance, whatever the movement considered. We conclude that oral creatine supplementation does not provide additional benefits for body composition, maximal dynamical strength, and dynamical and isometric endurances of healthy elderly subjects, whether or not it is associated with an effective strength training.
Contribution of pH, diprotonated phosphate and potassium for the reflex increase in blood pressure during handgrip
Authors: BOUSHEL  , MADSEN  , NIELSEN  , QUISTORFF  , SECHER
Published: March 2003

The relative importance of pH, diprotonated phosphate (H2PO4−) and potassium (K+) for the reflex increase in mean arterial pressure (MAP) during exercise was evaluated in seven subjects during rhythmic handgrip at 15 and 30% maximal voluntary contraction (MVC), followed by post‐exercise muscle ischaemia (PEMI). During 15% MVC, MAP rose from 92 ± 1 to 103 ± 2 mmHg, [K+] from 4.1 ± 0.1 to 5.1 ± 0.1 mmol L−1, while the intracellular (7.00 ± 0.01 to 6.80 ± 0.06) and venous pH fell (7.39 ± 0.01 to 7.30 ± 0.01) (P < 0.05). The intracellular [H2PO4−] increased 8.4 ± 2 mmol kg−1 and the venous [H2PO4−] from 0.14 ± 0.01 to 0.16 ± 0.01 mmol L−1 (P < 0.05). During PEMI, MAP remained elevated along with the intracellular [H2PO4−] as well as a low intracellular and venous pH. However, venous [K+] and [H2PO4−] returned to the level at rest. During 30% MVC handgrip, MAP rose to 130 ± 3 mmHg, [K+] to 5.8 ± 0.2 mmol L−1, the intracellular and extracellular [H2PO4−] by 20 ± 5 mmol kg−1 and to 0.20 ± 0.02 mmol L−1, respectively, while the intracellular (6.33 ± 0.06) and venous pH fell (7.23 ± 0.02) (P < 0.05). During post‐exercise muscle ischaemia all variables remained close to the exercise levels. Analysis of each variable as a predictor of blood pressure indicated that only the intracellular pH and diprotonated phosphate were linked to the reflex elevation of blood pressure during handgrip.
Control of cross‐bridge cycling by myosin light chain phosphorylation in mammalian smooth muscle
Authors: BUTLER  , SIEGMAN
Published: March 2003

This review focuses on experiments in which the single turnover of myosin‐bound ADP is used to characterize the regulation of the cross‐bridge cycle by myosin light chain phosphorylation in mammalian smooth muscle. Under isometric conditions, at rest, when the myosin light chain is not phosphorylated, myosin cycles very slowly (about 0.004 s−1), while phosphorylation of the light chain results in a 50‐fold increase in cycling rate to 0.2 s−1. Experiments consistently show that some myosin does not increase its cycling rate although its light chain is phosphorylated. Studies at low levels of myosin light chain phosphorylation show that phosphorylation also induces an increase in the cycling rate of unphosphorylated myosin. The fast cycling phosphorylated myosin is the main determinant of suprabasal myosin ATPase activity, while the cycling rate of cooperatively activated unphosphorylated myosin is slow and appears to depend on the extent of phosphorylation of the entire thick filament. Single turnover experiments measuring the rate of phosphorylation and dephosphorylation of myosin light chain show that the turnover of light chain phosphate can be very rapid (0.3–0.4 s−1) at suprabasal calcium concentrations. The expected effect of such a rapid turnover of light chain phosphorylation on the turnover of myosin‐bound ADP is not observed. The effects of low levels of myosin light chain phosphorylation on the single turnover of myosin suggest that the same small pool of myosin remains phosphorylated for relatively long periods of time rather than the entire pool of myosin spending a small fraction of its cycle time in the phosphorylated state.
Effects of selenium deficiency on diaphragmatic function after resistive loading
Authors: ANDRADE  , ANZUETO  , NAPIER  , LEVINE  , LAWRENCE  , JENKINSON  , MAXWELL
Published: March 2003

Diaphragmatic fatigue has been associated with increased production of reactive oxygen species. Among the defences against reactive oxygen species is the glutathione redox system. The selenium‐dependent enzyme glutathione peroxidase is an important component of this system. Thus, we hypothesized that selenium deficiency would lower glutathione peroxidase activity and render the diaphragm more susceptible to a mild exertional protocol. Sprague–Dawley rats were fed a selenium‐deficient or control diet for 12 weeks then divided into four experimental groups: (1) unloaded, basic diet with selenium supplementation (control); (2) unloaded, selenium‐deficient diet; (3) loaded, basic diet with selenium supplementation; and (4) loaded, selenium‐deficient diet. Diaphragmatic in vitro contractile properties, glutathione peroxidase activity and glutathione content were measured. During inspiratory resistive loading, the animals breathed against an inspiratory resistor at 70% of maximal airway pressure until the target pressure was not achieved for five consecutive breaths. Selenium deficiency resulted in a significant decrease in diaphragmatic glutathione peroxidase activity, without changes in total glutathione content. Neither selenium deficiency nor inspiratory resistive loading alone impaired diaphragmatic contractility. Selenium deficiency in conjunction with inspiratory resistive loading resulted in a significant decrease in diaphragmatic twitch and tetanic force, with a downward shift in the force/frequency curve. These data suggest that selenium deficiency lowers diaphragmatic glutathione peroxidase activity, and when these animals are subjected to the oxidative stress of resistive loading, there is an impairment in muscle function. We conclude that a functional glutathione peroxidase is necessary to protect the diaphragm against the effects of resistive loading.