bluuebunny/crossref_metadata_2025 huggingface dataset:
Instar‐specific sensitivity of specialist Manduca sexta larvae to induced defences in their host plant Nicotiana attenuata
Authors: Van Dam Nicole M. , Hermenau Uta , Baldwin Ian T.
Published: March 2003

1. The time delay associated with the activation of induced defences is thought to be a liability for this type of defence because it allows herbivores to remove biomass before the defence is fully induced. When defences are costly and plants grow with competitors, however, it may be more advantageous not to induce defences too fast and motivate the herbivore to move to the neighbour when it is most voracious.

2. Such a strategy can only work when the costs for the herbivore of moving to a neighbouring plant are smaller than the costs of staying on a fully induced plant. For lepidopteran herbivores, both the sensitivity to induced defences and the costs of moving may vary considerably between instars and this variation may constrain the plant's defensive opportunities.

3. This study was designed to examine whether the cost of moving, mimicked by a starvation period of 8 h, was larger than the cost of staying on a fully induced plant for each larval instar of the specialist Manduca sexta feeding on induced and control tissues of Nicotiana attenuata.

4. For first‐ and second‐instar larvae, the costs of moving were larger than the costs of staying on a fully induced plant. In contrast, feeding on induced plant material retarded development in third‐instar larvae more than did starvation, indicating that in this instar the costs of leaving are smaller than the costs of staying on an induced plant. More than 98% of the lifetime leaf mass consumed by a M. sexta larva is consumed during the fourth and fifth instars, and during these instars larval development was not affected by either induced defences or starvation. Thus the third instar, the stage just before larvae cause the majority of damage, represents a window of sensitivity to induced defences during which larvae can be motivated to change plants.

5. These results suggest that N. attenuata plants, which commonly compete with conspecifics in nature, have the opportunity to manipulate the behaviour of the specialist herbivore M. sexta to minimise the fitness effects of inducing defences when these defences are most costly, i.e. when plants grow under intraspecific competition.
Task‐partitioned nectar transfer in stingless bees: work organisation in a phylogenetic context
Authors: Hart Adam G. , Ratnieks Francis L. W.
Published: March 2003

Abstract 1. The eusocial corbiculate bee tribes comprise the Apini (honey bees), Bombini (bumble bees), and Meliponini (stingless bees). Honey bee foragers (Apis) transfer nectar to receiver bees within the nest. This is an example of task partitioning, in which a task is split into sub‐tasks connected by material transfer. Nectar transfer does not occur in Bombini. Although it is reported in some species of Meliponini, it has not been subject to detailed study.

2. Nectar transfer was investigated in five genera of Meliponini from Yucatan, Mexico (Melipona, Trigona, Scaptotrigona, Nannotrigona, and Plebeia). Nectar transfer occurred in all species and for > 99% of foragers. Multiple transfer, in which a forager unloads nectar to more than one receiver, occurred but at a lower level than in Apis. In M. beecheii, multiple transfer was associated strongly with putative recruitment dances.

3. The data provide some support for the hypothesis that task partitioning is favoured by large colony size, in that the Meliponini never have small colonies because colonies are swarm founded. This ensures that colonies are always large enough to prevent delays in finding a transfer partner imposing high costs. Further tests of this hypothesis are suggested.

4. Viewed in a phylogenetic context, the most parsimonious interpretation is that nectar transfer evolved once in the clade (Apini + Meliponini).
Cornicle length in Macrosiphini aphids: a comparison of ecological traits
Authors: Mondor Edward B. , Roitberg Bernard D. , Stadler Bernhard
Published: March 2003

Abstract 1. Aphids often emit cornicle droplets when attacked by predators. While the function of cornicle droplets has long been debated (i.e. mechanical protection vs. chemical signalling), it is not understood why aphid species have cornicles of different lengths.

2. It was hypothesised that aphids living in more scattered colonies have longer cornicles to scent‐mark predators with cornicle droplets containing alarm pheromone, so that clone‐mates are provided with advanced warning of a threat, even if not at the predation site. To test this hypothesis, multiple regression analyses were used, due to a lack of phylogenetic information on these taxa, to address which ecological traits (amount of wax on an aphid, degree of colony aggregation, feeding shelter, ant attendance) are correlated with cornicle length.

3. Aphids living in dense colonies tended to have shorter cornicles than aphids living in more scattered colonies. Also, aphids with more protection (i.e. wax) on their bodies had shorter cornicles. Aphids also tended to have shorter cornicles when tended by ants. The presence of a feeding shelter was not a good predictor of cornicle length.

4. It is suggested that longer cornicles function to scent‐mark predators with alarm pheromone to increase the inclusive fitness of a clone; however the negative correlation between the amount of individual protection, and also ant attendance, and cornicle length argues for a trade‐off between different forms of defence.
A review of competition in north temperate dung beetle communities
Authors: Finn John A. , Gittings Tom
Published: March 2003

Abstract.1. Studies of north temperate dung beetle communities frequently invoke competition as an influential ecological process. In this review, the evidence for competition in north temperate dung beetle communities is evaluated and the role of competition as a factor affecting community structure is assessed.

2. Resource limitation and the evidence for interspecific competition are assessed by collating the available experimental and observational evidence for both the adult and larval stages of the dung beetle life cycle. The role of competition as a structuring force in dung beetle communities is discussed under the following headings: niche dynamics, migration to and from individual pats, the aggregation model of co‐existence, and metapopulations.

3. Some of the main conclusions are that competition for space is much more likely to occur than competition for food; the effects of competition on community structure are poorly understood; several of the influential studies of competition in north temperate dung beetle communities need to be evaluated carefully. The differences in ecology between tropical and temperate dung beetle communities are clarified.

4. As priorities for future research, resource utilisation and competition should be researched experimentally: density‐dependent relationships should be investigated, particularly for the larval stages, as should competitive interactions with other dung fauna. If such experimental approaches establish convincingly the occurrence of competition, then the extent of competition in the field and under real world conditions needs to be established. A functional group classification of dung beetles and other dung fauna is described, which may improve the generality of interpretation from individual, site‐specific results.
Mate discrimination by females in the burying beetle Nicrophorus orbicollis: the influence of male size on attractiveness to females
Authors: Beeler Andria E. , Rauter Claudia M. , Moore Allen J.
Published: March 2003

1. Female burying beetles behave differently towards males of different sizes, avoiding mating with large males that are not defending resources but mating with small males regardless of the presence of resources. Females of the burying beetle Nicrophorus orbicollis were therefore examined to determine whether they discriminate among males using only pheromonal signals. The influence of female size on its own mate choice was also examined.

2. Females do use male pheromonal signals to discriminate among males and these signals do appear to convey information about male body size to females. Overall, females were more likely to be attracted to larger males than to smaller males.

3. Female choice of a male was influenced by both the female's own body size and the size of the female relative to the size of the two males available to it.

4. While there is an overall mating advantage for larger males, resulting from female preferences based on odour cues, smaller males are also attractive to some females under some circumstances.

5. It is argued that there are different costs and benefits of mating with different sized males, leading to the evolution of context‐dependent mate choice for females and the need to be able to discriminate males of different sizes from a distance.
Current situation of Tomato yellow leaf curl virus in Portugal
Authors: Louro D. , Fernandes J. E. , Quinot A.
Published: March 2003

The name Tomato yellow leaf curl virus (TYLCV) has been applied to a group of virus species of the genus Begomovirus in the family Geminiviridae that cause a similar tomato disease worldwide. In 1995, TYLCV was first reported in Algarve (southern Portugal) as responsible for an epidemic outbreak of a severe tomato disease. Molecular data have shown that this Portuguese TYLCV isolate was distinct from those previously reported in Europe, as it belonged to the TYLCV‐Israel species1. Since then, TYLCV epidemics have occurred annually, being a limiting factor mainly for autumn/winter glasshouse tomato crops. In 1998, TYLCV was also found associated with the emergence of a novel disease of Phaseolus vulgaris in Algarve. The affected bean plants were severely stunted and gave no marketable yield. However, the disease occurs only sporadically, even in conditions of high TYLCV infection pressure. Recently, Tomato chlorosis virus (ToCV), a whitefly‐transmitted bipartite closterovirus (genus Crinivirus, family Closteroviridae), was found associated with an unusual tomato yellow leaf syndrome, in single or mixed infection with TYLCV. The impact of this new pathosystem on tomato production has yet to be determined. Surveys are in progress in mixed cropping systems infested with whiteflies. So far, TYLCV and ToCV diseases are limited to the Algarve region.
Serological detection of plant viruses in their aphid vectors and host plants in Tunisia
Authors: Raboudi F. , Ben Moussa A. , Makni H. , Marrakchi M. , Makni M.
Published: March 2003

DAS‐ELISA was used to study the presence of viruses in four aphid species (Aphis gossypii, Aphis craccivora, Myzus persicae and Macrosiphum euphorbiae) and in their host plants potato, capsicum and tomato. Samples were collected in different regions in Tunisia: north, Cap Bon, Sahel, centre and south. A. gossypii and M. persicae carried all the viruses detected: Cucumber mosaic cucumovirus, Tomato aspermy cucumovirus, Tobacco etch potyvirus, Potato Y potyvirus, Alfalfa mosaic alfamovirus and Potato leafroll polerovirus. These two aphids were also those that occurred most frequently on the crops concerned.
Autoantibodies directed against phospholipids or human β2‐glycoprotein 1 in HIV‐seropositive patients: relationship with endothelial activation and antimalonic dialdehyde antibodies
Authors: Constans  , Guérin  , Couchouron  , Seigneur  , Ryman  , Blann  , Amiral  , Amara  , Peuchant  , Moreau  , Pellegrin  , Pellegrin  , Fleury  , Leng  , Conri
Published: March 2003

Background

We investigated the possible role of antiphospholipid (APA) and anti‐human β2‐glycoprotein I (β2‐GPI) antibodies (Ab) in thrombosis and atherosclerosis in human immunodeficiency (HIV)‐positive patients, in whom they seem to be more frequent.

Methods

We measured APA and anti‐β2‐GPI Ab in 58 HIV‐positive patients together with markers of disease progression, circulating β2‐GPI, plasma lipids, biological markers of endothelial activation and integrity (plasma thrombomodulin, von Willebrand factor, vascular cell adhesion molecule 1) and with antimalonic dialdehyde antibodies (anti‐MDA Ab).

Results

We found a 41% frequency of IgG APA in the HIV‐positive patients. APA IgMs were rarely positive (7%), and anti‐β2‐GPI IgGs were positive in 3.4% patients. There was no correlation between APA or anti‐β2‐GPI Ab and the presence of opportunistic infections. Although plasma thrombomodulin, von Willebrand factor and vascular cell adhesion molecule 1 were significantly increased in the HIV‐positive patients, APA was correlated only with vascular cell adhesion molecule 1, suggesting that APAs are correlated with endothelial activation but not with vascular endothelial lesions. A correlation between APA and anti‐MDA IgG was demonstrated using multivariate analysis (r = 0.542,  P < 0.0001), suggesting a relationship between the targets of these antibodies. Finally, IgG APAs are frequent in HIV infection but are not correlated with biological markers of endothelial injury.

Conclusion

Our results do not support a role for APA or anti‐β2‐GPI in HIV‐associated silent vascular endothelial damage. However, the role of these autoantibodies in clinically relevant thrombotic events should be investigated in HIV‐positive patients.
Apo E isoforms, insulin output and plasma lipid levels in essential hypertension
Authors: Dembińska‐Kieć  , Kawecka‐Jaszcz  , Kwaśniak  , Guevara  , Pankiewicz  , Malczewska‐Malec  , Iwanejko  , Hartwich  , Zdzienicka  , Stochmal  , Leszczyńska‐Goľˇląbek
Published: March 2003

Background

The association between apo E isoforms and insulin output during the oral glucose test (OGTT) in 60 non‐diabetic, non‐obese patients with essential hypertension and in control subjects (non‐obese, non‐diabetic normotensive subjects) was estimated.

Methods

According to low or high insulin output during OGTT, the subjects were divided into the following groups: normotensive subjects with low (NLI) and high (NHI) and hypertensive subjects with low (HLI) and high (HHI) insulin output.

Results

The apo E 4/2 phenotype was detected in 32% of hypertensive subjects but not in control subjects. The frequency of apo E 3/2 phenotype in hypertensive subjects was 5% and in normotensive subjects 15%. An increased frequency of phenotype apo E 4/3 was noticed both in HHI (46%) and in NHI (50%) compared with HLI (22%) and NLI (17%) groups.

Conclusion

The results suggest that the determination of phenotypes apo E and insulin output may contribute to an early detection of individuals at high risk of hypertension development.
The effects of IGF‐I and IGF‐II on proliferation and differentiation of human osteoblasts and interactions with growth hormone
Authors: Langdahl  , Kassem  , Møller  , Eriksen
Published: March 2003

Background

We have previously shown that growth hormone (GH) consistently stimulates proliferation of human osteoblasts in vitro. In rat osteoblasts, GH augments the effects of insulin‐like growth factor (IGF) I on cell proliferation and differentiation. We therefore investigated the effects of IGF‐I and ‐II alone and in combination with GH on human osteoblasts in vitro.

Methods

Human osteoblast‐like cells (HOB) were established from trabecular explants (n = 18) and human marrow stromal cells (HMS) from marrow aspiration (n= 21). The cell cultures were stimulated with IGF‐I or IGF‐II (1, 10 or 100 ng mL−1) alone, in combination with hGH (100 ng mL−1) or after prestimulation with hGH.

Results

IGF‐I alone, in combination with hGH and after pretreatment with hGH, increased proliferation of HOB and HMS by 49–190% (P < 0.05–0.01). IGF‐II alone, in combination with hGH and after pretreatment with hGH increased proliferation of HOB by 57–158% (P < 0.01). In HMS only IGF‐II in combination with hGH and after prestimulation with hGH increased proliferation. IGF‐I alone and in combination with hGH decreased alkaline phosphatase (AP) in both cell types. IGF‐II did not affect AP in HOB, but increased AP in HMS, this effect was abolished by hGH. In HOB, collagen production (PICP) was increased by IGF‐II but unaffected by IGF‐I. In HMS, PICP was decreased by IGF‐I and ‐II but increased by hGH. Co‐stimulation further increased PICP.

Conclusion

IGF‐I and ‐II exerted proliferative effects on both HOB and HMS. Co‐stimulation with GH exhibited synergism in enhancing the proliferative response. In HMS prestimulation improved the proliferative response significantly. The effects of the IGFs on differentiation are more complex and dependent on cell maturation and of the IGF used.
Hypotheses on the role of cytokines in peptic ulcer disease
Authors: Lehmann  , Stalder
Published: March 2003

Helicobacter pylori is the cause of chronic type B gastritis and occurs in almost all patients with duodenal ulcers. Infection with H. pylori is characterized by an increased production of several inflammatory cytokines. Increasing evidence suggests a central role of these cytokines in the pathogenesis of H. pylori‐associated gastritis and peptic ulcer disease. Cytokines may be crucial in the recruitment and activation of inflammatory cells and in stimulation of gastrin release. In addition to their proinflammatory properties, cytokines may also inhibit the ulcer occurrence by stimulation of prostaglandins and somatostatin release and by direct impairment of acid secretion. The balance of these factors may determine the clinical outcome of H. pylori infection.
Decreased urinary apolipoprotein (a) excretion in patients with impaired renal function
Authors: Kostner  , Clodi  , Bodlaj  , Watschinger  , Hörl  , Derfler  , Huber
Published: March 2003

Background

Plasma lipoprotein (a) [Lp(a)] levels are elevated in patients with kidney disease and are strongly associated with premature cardiovascular disease and stroke.

Methods

As the kidney is suggested to play an important role in apolipoprotein (a) [apo(a)] catabolism and as apo(a) fragments appear in urine, we determined plasma Lp(a) levels and urinary apo(a) excretion in relation to kidney function in a large cohort of renal patients. A total of 368 renal patients with normal or different degrees of impaired renal function and 163 healthy control subjects matched for age and sex were investigated. Plasma Lp(a) and urinary apo(a) were analysed immunochemically.

Results

Renal patients were found to have significantly elevated total cholesterol and low‐density lipoprotein (LDL)‐C values but lower high‐density lipoprotein (HDL)‐C values than control subjects. Plasma Lp(a) values were significantly higher only in patients with creatinine clearance < 70 mL min−1. There was a significant correlation between urinary apo(a) and plasma Lp(a) in patients and control subjects. Urinary apo(a) excretion was significantly lower in patients than in control subjects and showed no correlation with urinary protein excretion.

Conclusion

Although it is unlikely that impaired renal excretion of apo(a) fragments largely contributes to increased plasma Lp(a) levels in patients suffering from impaired kidney function, these data suggest that urinary apo(a) excretion is significantly decreased in renal patients and that this might contribute to increased plasma Lp(a) levels in this patient group.
Gelatinases in drug‐induced toxic epidermal necrolysis
Authors: Paquet  , Nusgens  , Piérard  , Lapière
Published: March 2003

Background

The matrix metalloproteinases (MMPs) MMP2 and MMP9 play a significant role in epidermal detachment, inflammation and re‐epithelialization. We have evaluated their activity in toxic epidermal necrolysis (TEN).

Design

The level and pattern of activity of MMP2 and MMP9 were investigated by measuring the degradation of 3H‐labelled gelatin and by zymography in blister fluid from six TEN patients and compared the results with three other blistering conditions: bullous pemphigoid (n = 6), second‐degree burn (n = 13) or suction blister (n = 3).

Results

A higher amount of MMP2 was found in TEN blister fluid with the constant presence of a significantly larger proportion of the activated forms of MMP2, a particular feature of TEN, than the other blistering diseases studied.

Conclusion

This study emphasizes the potential role of MMP2 in the specific inflammatory reaction and reparation process in TEN skin.
Adenine nucleotides modulate epithelial wound healing in vitro
Authors: Dignass  , Becker  , Spiegler  , Goebell
Published: March 2003

Background

Adenine nucleotides have been demonstrated to enhance structural and functional regeneration in experimental renal injury in rats. The mechanisms of adenine nucleotide action have not been elucidated. The aim of this study was to characterize the effects of adenine nucleotides on intestinal epithelial wound healing in vitro.

Methods

The effects of adenine nucleotides on cell migration, cell proliferation and cell adhesion were studied in the non‐transformed small intestinal epithelial cell line IEC‐6 using an in vitro wounding model, a colorimetric BrdU assay and a hexosaminidase adhesion assay.

Results

The adenine nucleotides ADP and ATP were found to significantly stimulate epithelial cell restitution (migration) in vitro. Stimulation of epithelial restitution averaged 42% for ADP and 57% for ATP. In addition, adenine nucleotides inhibited the proliferation of rat small intestinal epithelial cells, averaging 56% for ADP and 74% for ATP. Enhancement of intestinal epithelial restitution and inhibition of epithelial cell proliferation by adenine nucleotides were mediated through transforming growth factor (TGF)‐β‐independent pathways.

Conclusion

These findings suggest that adenine nucleotides exert functional effects on intestinal epithelial cell populations and may play a role in the morphogenesis of the gastrointestinal tract and its remodeling after injury.
Direct evidence for an increase in thrombopoiesis after liver transplantation
Authors: Stiegler  , Stohlawetz  , Peck‐Radosavljevic  , Jilma  , Pidlich  , Wichlas  , Höcker  , Panzer
Published: March 2003

Background

In advanced liver cirrhosis, thrombocytopenia results from ‘hypersplenism’ due to increased platelet sequestration and platelet ‘pooling’ in the enlarged spleen and/or from reduced platelet production in the bone marrow. We sought to differentiate between these two mechanisms by studying thrombopoiesis before and after orthotopic liver transplantation by the determination of reticulated platelets, direct indicators for the thrombopoietic activity in the bone marrow.

Methods

Reticulated platelets, peripheral platelet counts, mean platelet volumes and platelet‐reactive antibodies were determined in 15 patients suffering from advanced liver cirrhosis before and during an observation period of 14 days after orthotopic liver transplantation (OLT). Thrombopoietin levels of ten patients were determined before transplantation and consecutively for 14 days after surgery.

Results

All patients except one were thrombocytopenic before transplantation (median count 94 × 109 L−1, range 69–114 × 109 L−1). Although levels of reticulated platelets rose 2 days after surgery from baseline values of 1.0% (range 0.2–1.6%) to peak values of 4.6% (range 1.7–17.9%, P < 0.05) on day 6, platelet counts declined during the first 5 days after transplantation. When peripheral platelet counts increased to the normal range (median day 11, range day 8–33), reticulated platelets were again at pretransplant levels. Thrombopoietin levels before OLT were within the normal range (< 85 pg mL−1). On day 5 post surgery, a maximum increase of 5.8‐fold (range 2.2‐ to 28‐fold) over baseline values was observed. Mean platelet volume did not show any significant deviation from the baseline values and platelet antibodies could not be detected during the observation period.

Conclusion

Our findings provide direct evidence for an increase in de novo platelet production after orthotopic liver transplantation. As the elevation of reticulated platelets precedes platelet recovery, it could serve as an early indicator to predict thrombopoiesis as a result of reconstituted liver function.
Coexistent thyroiditis is associated with lower tumour stage in thyroid carcinoma
Authors: Schäffler  , Palitzsch  , Seiffarth  , Höhne  , Riedhammer  , Hofstädter  , Schölmerich  , Rüschoff
Published: March 2003

Background

Microsatellite instability (MSI) is a new mechanism described in carcinogenesis of several tumours and seems to predispose for cancer in some chronic inflammatory diseases. As thyroiditis is thought to be both the cause and the consequence of thyroid carcinoma, it was the aim of this retrospective study to investigate the epidemiology and the influence of a coexistent thyroiditis on prognosis and clinicopathological parameters in an iodine‐deficient area.

Methods

The grade of lymphocytic infiltration (LI) of 153 thyroid carcinomas was determined in paraffin‐embedded tissues: G0 = no LI, G1 = peritumoral LI, G2 = peritumoral LI with follicle, G3 = diffuse LI. A non‐radioactive PCR‐based screening method was used for detection of MSI.

Results

Twenty‐seven (17.7%) out of 153 carcinomas were accompanied by thyroiditis (G1, 16; G2, 5; G3, 6). Ten cases fulfilled the criteria necessary for diagnosing Hashimoto's thyroiditis. Nine out of 10 (90%) Hashimoto's cases and 16 out of 17 (94%) other thyroiditis cases were associated with a significantly (χ2 < 0.01) lower pT stage (pT1, pT2) than cases without thyroiditis. No statistical association was found by comparing multifocality or sclerosing variants with the grade of lymphocytic infiltration. MSI was detected neither in patients with severe inflammation nor in the absence of thyroiditis.

Conclusions

MSI does not seem to play a role in the pathogenesis of thyroid carcinoma. Coexistent thyroiditis is associated with a lower pT stage and thus could be an indicator of a better prognosis.
Influence of residual insulin secretion and duration of diabetes mellitus on the control of luteinizing hormone secretion in women
Authors: Volpi  , Chiodera  , Gramellini  , Capretti  , Caffarri  , Speroni  , Vescovi  , Coiro
Published: March 2003

Background

The aim of the present study was to establish whether the persistence of residual beta‐cell activity after long‐term diabetes mellitus (DM) exerts a protective role on luteinizing hormone (LH) secretion.

Methods

The LH responses to stimulation with gonadotropin‐releasing hormone (Gn‐RH) (100 μg in an i.v. bolus) or naloxone (4 mg injected in an i.v. bolus, followed by the constant infusion of 8 mg in 2 h) were measured in C‐peptide‐positive (CpP) and C‐peptide‐negative (CpN) normally menstruating women with short‐term (group 1 < 3 years, CpP n = 11, CpN n = 11) or long‐term (group 2 > 10 years, CpP n = 11, CpN n = 11) DM and in age‐matched normal control subjects (n = 11).

Results

Gn‐RH induced significant increments in LH secretion in all groups. Significant LH responses to naloxone were observed in all groups, except in group 2 CpN patients. However, the LH response to either Gn‐RH or naloxone was significantly lower in group 1 CpN, group 2 CpP and group 2 CpN patients than in the normal control subjects. Furthermore, the LH response was significantly lower in group 2 CpP than in group 1 CpP patients and in group 2 CpN than in group 1 CpN subjects.

Conclusions

These results indicate a role for both deficiency in residual endogenous insulin secretion and duration of diabetes in the derangement of LH secretory control. The data suggest that the protective role exerted by residual beta‐cell activity on LH secretion during the early years of DM diminishes with time elapsed after the onset of diabetes mellitus.
Derangement of mucosal barrier function by bacteria colonizing the rat colonic mucosa
Authors: García‐Lafuente  , Antolín  , Guarner  , Crespo  , Salas  , Forcada  , Malagelada
Published: March 2003

Background

Interaction between gut flora and the intestinal barrier may involve changes in permeability.

Methods

Rats with a colonic segment excluded from faecal transit were surgically prepared. Matched groups were either kept on luminal antibiotics to prevent colonization of the segment or recolonized with mixed rat flora. Permeability to low‐dose trinitrobenzenesulphonic acid (TNBS) or trinitrophenol (TNP), and mucosal injury by the compounds at a high dose were tested in antibiotic and recolonized rats (the compounds differ in water solubility but share a common antigenic domain).

Results

Lumen to blood clearance of the hydrophilic probe (TNBS) was faster in recolonized than in antibiotic rats. The hydrophobic compound TNP was absorbed at faster rates than TNBS, but there was no difference between antibiotic and recolonized rats. Instillation of TNBS at a high dose induced mucosal release of inflammatory mediators and tissue myeloperoxidase accumulation in recolonized rats but not in antibiotic rats. Large necrotic lesions with submucosal involvement after TNBS were only observed in recolonized rats. In contrast, TNP induced mucosal inflammation and large lesions with submucosal necrosis both in recolonized and in antibiotic rats.

Conclusion

Colonizing bacteria may increase intestinal permeability to hydrophilic compounds and render the mucosa susceptible to injury.
Diet, exercise and behavioural intervention: the nonpharmacological approach
Authors: Brownell
Published: March 2003

Behaviour is an important factor in both the aetiology and treatment of obesity. Successful long‐term weight management ultimately depends on the ability of patients to change their behaviour patterns, particularly with regard to diet and exercise. Many patients find such changes extremely difficult to initiate and maintain. The failure to properly address behavioural modification is part of the reason why so many weight loss programmes cannot produce long‐term weight loss, even though initial weight loss is often achieved with relative ease. Four examples of lifestyle changes are discussed in this paper: exercise; relapse prevention; the concept of a reasonable weight; and attribution theory. Behavioural therapy should be an integral part of a multifaceted approach for managing obesity and associated conditions, such as type II (non‐insulin‐dependent) diabetes.
Management of renal cell carcinoma in von Hippel–Lindau disease
Authors: Hes  , Slootweg  , Van Vroonhoven  , Hené  , Feldberg  , Zewald  , Ploos van Amstel  , Höppener  , Pearson  , Lips
Published: March 2003

Background

An evaluation of nephron‐sparing surgery (NSS) or radical nephrectomy (RN) for treating renal cell carcinoma (RCC) in patients with von Hippel–Lindau disease (VHL) was carried out.

Methods

Between 1976 and 1997, 10 patients with RCC from four VHL families, of whom seven were from one family, were studied by clinical and histopathological examination. Before 1991, three patients were treated using RN, and thereafter five patients were treated using NSS. Two patients were not operated on.

Results

RCCs in our patients showed a slow growth rate (on average 0.3 cm year−1), and asymptomatic patients presented with tumours of low‐grade malignancy. In all patients, tumours were surrounded by a fibrous pseudocapsule. In 5 out of 17 tumours, pseudocapsular invasion was observed, and three of these five tumours broke through the pseudocapsule. To date, these patients have not shown a less favourable outcome than those without pseudocapsular involvement by tumour growth. Multicentricity of RCC was relatively low (4.6 lesions per kidney). In two of the three RN patients, only a single satellite lesion, in the direct vicinity of a RCC, was found in one kidney. Six tumours (1.8–5.5 cm) were enucleated by NSS. During a mean follow‐up of 30 months, renal function in these patients was well preserved.

Conclusions

In our patients, RCCs grew slowly, were of low grade, had a dense fibrous pseudocapsule and were thus good candidates for NSS.
The sensitivity of the lactulose/rhamnose gut permeability test
Authors: Van Nieuwenhoven M. A. , Geerling B. J. , Deutz N. E. P. , Brouns F. , Brummer R.‐J. M.
Published: March 2003

Background

The lactulose/rhamnose (L/R) intestinal permeability test is widely used. However, different quantities and proportions of lactulose and rhamnose are used. The aim of this study was to determine whether a low dosage of lactulose is able to discriminate between normal and increased permeability.

Materials and methods

Two groups of 10 healthy subjects were studied. In group 1, three different iso‐osmolar test solutions were administered on 3 days. The solutions consisted of 10 g of L with 1 g of R, 5 g of L with 0.5 g of R and 1 g of L with 0.1 g of R in 65 mL of water. Group 2 ingested these solutions 1 h after ingestion of 750 mg of chenodeoxycholeic acid (CDCA), which is known to increase permeability. The urinary L/R ratio was determined using high‐performance liquid chromatography. Data are presented as medians (range).

Results

In group 1, no differences were observed between the three solutions. In Group 2, there was a significant difference (P = 0.045) between the three solutions. The L/R ratios were 0.0079 (0.0024–0.0152) (1L to 0.1R), 0.0138 (0.0066–0.0192) (5L to 0.5R) and 0.0144 (0.0074–0.0374) (10L to 1R). The L/R ratio differed significantly between Groups 1 and 2 (P < 0.001) using the 5L to 0.5R and 10L to 1R solutions respectively.

Conclusion

If the permeability is increased, the urinary L/R ratio depends on the quantity of lactulose and rhamnose administered in equal proportion. 5L to 0.5R is sufficient to discriminate between a normal and a moderately increased permeability.
In vivo kinetics of human apolipoprotein A‐I variants in rabbits
Authors: Saku  , Von Eckardstein  , Zhang  , Liu  , Jimi  , Ou  , Ohta  , Assmann  , Arakawa
Published: March 2003

Background

Genetic variants of human apolipoprotein (apo) A‐I, the major protein component of high‐density lipoprotein (HDL), with a single amino acid substitution have been reported, and some of these result in very low plasma HDL‐cholesterol (C) levels. Examining the kinetics of radiolabelled apolipoprotein is a straightforward technique for determining its metabolism in vivo. In this study, we investigated the in vivo kinetics of several human apo A‐I variants, which we had identified previously, in rabbits.

Materials and methods

Apo A‐I variants from heterozygous carriers of Lys‐107→0, Lys‐107→Met, Pro‐3→Arg, Pro‐4→Arg, Pro‐165→Arg and Glu‐198→Lys and the corresponding normal apo A‐I were purified and then radioiodinated with 131I and 125I. A kinetic study of apo A‐I variants was performed in normolipidaemic rabbits after simultaneous injection of the two isotopes that had been incorporated into HDL. The fractional catabolic rate (FCR) was calculated from the radioactive decay curve.

Results

Acidic mature (negatively charged) apo A‐I variants caused by a single amino acid substitution (Lys‐107→0, and Lys‐107→Met) were catabolized faster (FCR, 1.931 ± 0.539 per day vs. 1.636 ± 0.460 per day, P ≤ 0.01 using the Wilcoxon signed‐rank test) and basic mature (positively charged) apo A‐I variants (Pro‐3→Arg, Pro‐4→Arg, Pro‐165→Arg and Glu‐198→Lys) were catabolized more slowly (FCR 1.470 ± 0.380 per day vs. 1.654 ± 0.430 per day, P ≤ 0.01) than the corresponding normal mature apo A‐I in vivo in rabbits. In addition, an inverse linear relationship was observed between the deviation in the FCR of variant human apo A‐I from that of normal human apo A‐I and the number of electric charges that the apo A‐I variant carried (r = –0.90, k = –0.188, P = 0.0003), as assessed by a linear regression analysis, suggesting that the electric charge of apo A‐I variants may determine, at least in part, its in vivo kinetics in rabbits.

Conclusions

Genetic variants of apo A‐I with a single amino acid substitution show abnormal kinetics, and the electric charge of a apo A‐I variant could contribute to determining its kinetics in vivo in this xenologous model.
The role of melatonin in pathogenesis of aspirin‐sensitive asthma
Authors: Evsyukova H. V.
Published: March 2003

Background

Platelets are involved in the pathogenesis of bronchial asthma, including aspirin‐sensitive asthma (ASA). The pineal hormone melatonin (MT) has been described as inhibiting several physiological processes in platelets. The MT metabolite −N‐acetyl‐5‐methoxy‐kynurenamine − has a chemical structure similar to that of acetylsalicylic acid. Because ASA patients usually suffer from an active disease, despite the avoidance of aspirin and cross‐reactive drugs, it has been suggested that the MT synthesis may be lower and sensitivity of platelet reception to MT may be higher in aspirin‐sensitive asthmatic subjects than in aspirin‐tolerant ones. The objective of this study was to investigate this hypothesis.

Materials and methods

We studied the urinary excretion of 6‐sulphatoxymelatonin, the major metabolite of melatonin, and the effect of different MT doses on ADP‐induced platelet aggregation in vitro in 17 ASA patients, 17 patients with aspirin‐tolerant asthma (ATA) and 16 healthy subjects.

Results

The results of the study have revealed a lower level of daytime aMT6s excretion in ASA patients (12.7 ± 2.7 ng mL−1) than in ATA patients (32.7 ± 9.9 ng mL−1, P < 0.05) and control subjects (19.9 ± 5.8 ng mL−1, P < 0.05). The preincubation of platelet‐rich plasma with the MT in a dose of 0.01 pg mL−1 plasma results in an increase in the intensity and the rate of the first platelet aggregation phase only in the ASA patients compared with the ATA patients and control subjects.

Conclusion

We conclude that the reduction in MT production in ASA patients defines the character of ADP‐induced platelet aggregation and the change in its first phase after the further addition of MT in vitro. The latter is associated with the opening of some receptor‐operated channels for Ca2+ or/and its mobilization from the intracellular stores. The higher sensitivity of platelet reception and a distorted reaction not only to MT but also to its metabolite may be prerequisites for aspirin intolerance in ASA patients.
Acute‐phase response patterns in isolated hepatic perfusion with tumour necrosis factor α (TNF‐α) and melphalan in patients with colorectal liver metastases
Authors: De Vries M. R. , Borel Rinkes I. H. M. , Swaak A. J. G. , Hack C. E. , Van de Velde C. J. H. , Wiggers T. , Tollenaar R. A. E. M. , Kuppen P. J. K. , Eggermont A. M. M.
Published: March 2003

Background

In this study, we have evaluated hepatotoxicity, secondary cytokine production and hepatic acute‐phase response (APR) in patients who underwent isolated hepatic perfusion (IHP) with tumour necrosis factor (TNF) α and melphalan for irresectable colorectal liver metastases.

Design

An extracorporeal veno‐venous bypass was used to shunt blood from the lower body and intestines to the heart. Inflow catheters were placed in the hepatic artery and portal vein, and an outflow catheter in the inferior caval vein. The liver was perfused for 60 min with 0.4 mg of TNF‐α plus 1 mg kg−1 melphalan (IHPTM group, n = 6) or 1 mg kg−1 melphalan (IHPM group, n = 3). The liver was washed with macrodex before restoring vascular continuity.

Results

After the washout procedure, a TNF‐α peak (169 ± 38 pg mL−1) was demonstrated in the IHPTM group only. Both groups demonstrated peak levels of interleukin 6 (IL‐6) in the perfusate as well as systemically. These were significantly higher in the IHPTM group. Acute‐phase protein (APP) levels followed a similar pattern as has been demonstrated after major surgery, with no significant differences between both groups. The addition of TNF‐α to the perfusate did not lead to a significant difference in APP levels and the time course between groups.

Conclusions

IHP with TNF and melphalan is followed by a transient systemic peak of TNF directly after liver washout. Secondary IL‐6 induction was seen in the present study after IHP with and without TNF, which was highest when TNF was added. This phenomenon cannot be extrapolated to APP induction, which appeared unaffected by the addition of TNF, presumably because the surgical procedure itself already causes maximal stimulation of APP production.
Occurrence of sialic acids in healthy humans and different disorders
Authors: Sillanaukee  , Pönniö  , Jääskeläinen
Published: March 2003

Sialic acid (SA), N‐acetylated derivatives of neuraminic acid, play a central role in the biomedical functioning of humans. The normal range of total sialic acid (TSA) level in serum/plasma is 1.58–2.22 mmol L−1, the free form of SA only constituting 0.5–3 μmol L−1 and the lipid‐associated (LSA) forms 10–50 μmol L−1. Notably, considerably higher amounts of free SA are found in urine than in serum/plasma (approximately 50% of the total SA).

In inherited SA storage diseases such as Salla's disease, SA levels are elevated many times over, and their determination during clinical investigation is well established. Furthermore, a number of reports describe elevated SA levels in various other diseases, tentatively suggesting broader clinical utility for SA markers. Increased SA concentrations have been reported during inflammatory processes, probably resulting from increased levels of richly sialylated acute‐phase glycoproteins. A connection between increased SA levels and elevated stroke and cardiovascular mortality risk has also been reported. In addition, SA levels are slightly increased in cancer, positively correlating with the degree of metastasis, as well as in alcohol abuse, diabetes, chronic renal failure and chronic glomerulonephritis. Several different mechanisms are assumed to underlie the elevated SA concentrations in these disorders.

The apparent non‐specificity of SA to a given disease limits the potential clinical usefulness of SA determination. In addition, some non‐pathological factors, such as aging, pregnancy and smoking, may cause changes in SA concentrations. The absolute increases in SA levels are also rather small (save those in inherited SA storage disorders); this further limits the clinical potential of SA as a marker.

Tentatively, SA markers might serve as adjuncts, when combined with other markers, in disease screening, disease progression follow‐up, and in the monitoring of treatment response. To become clinically useful, however, the existing SA determination assays need to be considerably refined to reduce interferences, to be specific for certain SA forms, and to be more easy to use.
Advancing age and insulin resistance: new facts about an ancient history
Authors: Paolisso  , Tagliamonte  , Rizzo  , Giugliano
Published: March 2003

The relationship between advancing age and insulin resistance is widely known, but the cause(s) of such association are less well understood. Age‐related changes in anthropometric characteristics and environmental factors (changes in diet habits and decline in physical activity) have been hypothesized as being among the main causes. More recently, the role of plasma insulin‐like growth factor I (IGF‐I), dehydroepiandrosterone sulphate (DHEAS) and tumour necrosis factor α (TNF‐α) concentrations as well as the degree of oxidative stress have also been evaluated. As far as the anthropometric changes are concerned, a decline in fat‐free mass and a relative or absolute increase in fat mass are common findings in aged subjects. Such changes are combined with a decline in plasma DHEAS and IGF‐I concentration and a rise in plasma TNF‐α concentrations and oxidative stress, which, in turn, may interact with the anthropometric changes determining the worsening in insulin‐mediated glucose uptake. Finally, age‐related environmental factors (changes in diet quality and decline in the degree of physical activity) might be a common factor allowing anthropometric factors and age‐related remodelling to accelerate their negative impact on insulin action.
Inhaled nitric oxide does not influence bleeding time or platelet function in healthy volunteers
Authors: Albert  , Norman  , Wallén  , Frostell  , Hjemdahl
Published: March 2003

Background

Bleeding time has been reported to increase during gaseous nitric oxide (NO) inhalation in healthy volunteers and patients, and it has been speculated that inhaled NO inhibits platelet function. However, results have not been unanimous, and we have been unable to document any effects of inhaled NO on circulating platelets.

Materials and methods

We performed a double‐blind, placebo controlled cross‐over study in which healthy volunteers (n = 15) inhaled NO (30 ppm, 30 min) or control gas. Aspirin (640 mg × 1 orally) was used as positive control on the third occasion (n = 14). Bleeding time was measured, and platelet function was determined flow cytometrically by measuring the expression of P‐selectin on circulating platelets and locally activated platelets in wound blood. Skin perfusion close to the site for bleeding time incisions was assessed by laser Doppler flowmetry.

Results

Bleeding time was unaffected by NO, as there were slight increases during both NO and control inhalation (+20% and +14% respectively, P = 0.9). Similarly, NO inhalation had no effect on platelet P‐selectin expression in either systemic or wound blood, or on skin perfusion. Aspirin pretreatment, on the other hand, prolonged bleeding time (P < 0.001) and decreased P‐selectin expression of platelets in wound blood (P = 0.03).

Conclusions

This first placebo‐controlled study indicates that inhaled NO does not influence either bleeding time, platelet activity or skin perfusion. Thus, it is unlikely that treatment of critically ill patients with inhaled NO will aggravate haemostatic disturbances, which has previously been feared, by influencing platelet function.
A metabolic syndrome of hypertension, hyperinsulinaemia and hypercholesterolaemia in the New Zealand obese mouse
Authors: Ortlepp  , Kluge  , Giesen  , Plum  , Radke  , Hanrath  , Joost
Published: March 2003

Background

New Zealand obese (NZO) mice exhibit a polygenic obesity associated with hyperinsulinaemia and hyperglycaemia. Here we show that the strain presents additional features of a metabolic syndrome, i.e. elevated blood pressure, serum cholesterol and serum triglyceride levels.

Materials and methods

A back‐cross model of NZO mice with the lean Swiss Jackson Laboratory (SJL) strain was established in order to investigate further the correlation between hypertension, obesity, serum insulin and hyperglycaemia.

Results

Systolic blood pressure was significantly elevated at 6 weeks of age and appeared to parallel the weight gain of the animals. Serum insulin levels, presumably reflecting insulin resistance, and systolic blood pressure values were significantly correlated with the body mass index (r2 = 0.707 and 0.486, respectively) in the back‐cross mice. In contrast, blood pressure was only weakly correlated with serum insulin (r2 = 0.288) in non‐diabetic mice, and was independent of serum insulin levels in diabetic animals.

Conclusion

The data are consistent with the concept that hypertension and insulin resistance are a characteristic consequence of the genetic constellation leading to obesity in the NZO strain, and that these traits reflect related mechanisms. It appears unlikely, however, that hypertension is a direct consequence of hyperinsulinaemia.