bluuebunny/crossref_metadata_2025 huggingface dataset:
Donitriptan, but not sumatriptan, inhibits capsaicin‐induced canine external carotid vasodilatation via 5‐HT1Brather than 5‐HT1Dreceptors
Authors: Muñoz‐Islas E , Gupta S , Jiménez‐Mena L R , Lozano‐Cuenca J , Sánchez‐López A , Centurión D , Mehrotra S , MaassenVanDenBrink A , Villalón C M
Published: August 2006

Background and purpose:

It has been suggested that during a migraine attack capsaicin‐sensitive trigeminal sensory nerves release calcitonin gene‐related peptide (CGRP), resulting in cranial vasodilatation and central nociception; hence, trigeminal inhibition may prevent this vasodilatation and abort migraine headache. This study investigated the effects of the agonists sumatriptan (5‐HT1B/1Dwater‐soluble), donitriptan (5‐HT1B/1Dlipid‐soluble), PNU‐142633 (5‐HT1Dwater‐soluble) and PNU‐109291 (5‐HT1Dlipid‐soluble) on vasodilator responses to capsaicin,α‐CGRP and acetylcholine in dog external carotid artery.

Experimental approach:

59 vagosympathectomized dogs were anaesthetized with sodium pentobarbitone. Blood pressure and heart rate were recorded with a pressure transducer, connected to a cannula inserted into a femoral artery. A precalibrated flow probe was placed around the common carotid artery, with ligation of the internal carotid and occipital branches, and connected to an ultrasonic flowmeter. The thyroid artery was cannulated for infusion of agonists.

Key results:

Intracarotid infusions of capsaicin,α‐CGRP and acetylcholine dose‐dependently increased blood flow through the carotid artery. These responses remained unaffected after intravenous (i.v.) infusions of sumatriptan, PNU‐142633, PNU‐109291 or physiological saline; in contrast, donitriptan significantly attenuated the vasodilator responses to capsaicin, but not those toα‐CGRP or acetylcholine. Only sumatriptan and donitriptan dose‐dependently decreased the carotid blood flow. Interestingly, i.v. administration of the antagonist, SB224289 (5‐HT1B), but not of BRL15572 (5‐HT1D), abolished the inhibition by donitriptan.

Conclusions and implications:

Our results suggest that the inhibition produced by donitriptan of capsaicin‐induced external carotid vasodilatation is mainly mediated by 5‐HT1B, rather than 5‐HT1D, receptors, probably by a central mechanism.

British Journal of Pharmacology(2006)149, 82–91. doi:10.1038/sj.bjp.0706839
Systemically administered trefoil factors are secreted into the gastric lumen and increase the viscosity of gastric contents
Authors: Kjellev S , Nexø E , Thim L , Poulsen S S
Published: August 2006

Background and purpose:

Trefoil factors (TFFs) secreted by mucus‐producing cells are essential for the defence of the gastrointestinal mucosa. TFFs probably influence the viscoelastic properties of mucus, but this has not been demonstrated in vivo. We therefore studied the gastric secretion of systemically administered TFF2 and TFF3, and their influence on the viscosity of the secretions.

Experimental approach:

Mice and rats under general anaesthesia were injected intravenously with human (h) TFF2, hTFF3 (5 mg kg−1 to mice and 25 mg kg−1 to rats), murine (m) 125I‐TFF3, or 125I‐hTFF3 (300 000 cpm, mice only). The appearance of TFFs in the gastric mucosa and luminal secretions was analysed by autoradiography, gamma‐counting, and ELISA, and the viscosity by rheometry.

Key results:

125I‐mTFF3 and 125I‐hTFF3 were taken up by secretory cells of the gastrointestinal tract and detected at the gastric mucosal surface 15 min after injection. Stressing the stomach by carbachol (3.5 μg kg−1) and pyloric ligation significantly increased the uptake. Injected hTFF2, hTFF3, and mTFF3 were retrieved from the gastric contents after 4 h. In rats, an approximately seven‐fold increase in the viscosity was detected after injection of TFF2 compared to the controls, whereas TFF3 did not increase the viscosity. In mice, TFF2 increased the viscosity approximately 4‐fold.

Conclusions:

These data indicate that systemically administered TFFs are transferred to the gastric lumen in a biologically active form.

British Journal of Pharmacology (2006) 149, 92–99. doi:10.1038/sj.bjp.0706840
Protection from experimental colitis by theaflavin‐3,3′‐digallate correlates with inhibition of IKK and NF‐κB activation
Authors: Ukil A , Maity S , Das P K
Published: August 2006

Background and purpose:

Inflammatory bowel disease (IBD) is associated with activation of nuclear factor κ B (NF‐κB) involved in regulating the expression of inducible nitric oxide synthase (iNOS) and proinflammatory cytokine genes. As theaflavin‐3,3′‐digallate (TFDG), the most potent anti‐oxidant polyphenol of black tea, down‐regulates NF‐κB activation, we investigated if TFDG is beneficial in colonic inflammation by suppressing iNOS and proinflammatory cytokines.

Experimental approach:

Thein vivoefficacy of TFDG was assessed in mice with trinitrobenzene sulfonic acid (TNBS)‐induced colitis. Both mRNA and protein levels of proinflammatory cytokines and iNOS were analyzed in colon tissue treated with or without TFDG. NF‐κB activation was determined by electrophoretic mobility shift assay and levels of NF‐κB inhibitory protein (IκBα) were analyzed by Western blotting.

Key results:

Oral administration of TFDG (5 mg kg−1daily i.g.) significantly improved TNBS‐induced colitis associated with decreased mRNA and protein levels of TNF‐α, IL‐12, IFN‐γand iNOS in colonic mucosa. DNA binding and Western blotting revealed increase in NF‐κB activation and IκBαdepletion in TNBS‐treated mice from Day 2 through Day 8 with a maximum at Day 4, which resulted from increased phosphorylation of IκBαand higher activity of IκB kinase (IKK). Pretreatment with TFDG markedly inhibited TNBS‐induced increases in nuclear localization of NF‐κB, cytosolic IKK activity and preserved IκBαin colon tissue.

Conclusions and Implications:

TFDG exerts protective effects in experimental colitis and inhibits production of inflammatory mediators through a mechanism that, at least in part, involves inhibition of NF‐κB activation.

British Journal of Pharmacology(2006)149, 121–131. doi:10.1038/sj.bjp.0706847
Characterization of COMMD protein–protein interactions in NF-κB signalling
Authors: de Bie Prim , van de Sluis Bart , Burstein Ezra , Duran Karen J. , Berger Ruud , Duckett Colin S. , Wijmenga Cisca , Klomp Leo W. J.
Published: August 2006

COMMD [copper metabolism gene MURR1 (mouse U2af1-rs1 region 1) domain] proteins constitute a recently identified family of NF-κB (nuclear factor κB)-inhibiting proteins, characterized by the presence of the COMM domain. In the present paper, we report detailed investigation of the role of this protein family, and specifically the role of the COMM domain, in NF-κB signalling through characterization of protein–protein interactions involving COMMD proteins. The small ubiquitously expressed COMMD6 consists primarily of the COMM domain. Therefore COMMD1 and COMMD6 were analysed further as prototype members of the COMMD protein family. Using specific antisera, interaction between endogenous COMMD1 and COMMD6 is described. This interaction was verified by independent techniques, appeared to be direct and could be detected throughout the whole cell, including the nucleus. Both proteins inhibit TNF (tumour necrosis factor)-induced NF-κB activation in a non-synergistic manner. Mutation of the amino acid residues Trp24 and Pro41 in the COMM domain of COMMD6 completely abolished the inhibitory effect of COMMD6 on TNF-induced NF-κB activation, but this was not accompanied by loss of interaction with COMMD1, COMMD6 or the NF-κB subunit RelA. In contrast with COMMD1, COMMD6 does not bind to IκBα (inhibitory κBα), indicating that both proteins inhibit NF-κB in an overlapping, but not completely similar, manner. Taken together, these data support the significance of COMMD protein–protein interactions and provide new mechanistic insight into the function of this protein family in NF-κB signalling.
Integrin signalling regulates the nuclear localization and function of the lysophosphatidic acid receptor-1 (LPA1) in mammalian cells
Authors: Waters Catherine M. , Saatian Bahman , Moughal Noreen A. , Zhao Yutong , Tigyi Gabor , Natarajan Viswanathan , Pyne Susan , Pyne Nigel J.
Published: August 2006

We show that LPA1 (lysophosphatidic acid receptor-1) is constitutively localized in the nucleus of mammalian cells. LPA1 also traffics from cell membranes to the nucleus in response to LPA (lysophosphatidic acid). Several lines of evidence suggest an important role for cell-matrix interaction in regulating the constitutive nuclear localization of LPA1. First, the RGDS peptide, which blocks cell matrix-induced integrin clustering and cytoskeletal rearrangement, reduced the number of cells containing LPA1 in the nucleus. Secondly, a higher proportion of cells contained nuclear LPA1 when adhesion on fibronectin-coated glass was compared with adherence to polylysine-coated glass. Thirdly, pre-treatment of cells with the Rho kinase inhibitor (Y27632) or the myosin light chain kinase inhibitor (ML9) reduced the number of cells containing nuclear LPA1. The addition of LPA and/or Ki16425 (which binds to LPA1) to isolated nuclei containing LPA1 induced the phosphorylation of several proteins with molecular masses of 34, 32, 14 and 11 kDa. These findings demonstrate that trafficking of LPA1 to the nucleus is influenced by cell-matrix interactions and that nuclear LPA1 may be involved in regulating intranuclear protein phosphorylation and signalling.
MT1-MMP hemopexin domain exchange with MT4-MMP blocks enzyme maturation and trafficking to the plasma membrane in MCF7 cells
Authors: Atkinson Susan J. , Roghi Christian , Murphy Gillian
Published: August 2006

The hemopexin-like domain of membrane-type matrix metalloproteinase-1 (MT1-MMP) enables MT1-MMP to form oligomers that facilitate the activation of pro-matrix metalloproteinase-2 (pro-MMP-2) at the cell surface. To investigate the role of the MT1-MMP hemopexin domain in the trafficking of MT1-MMP to the cell surface we have examined the activity of two MT1–MT4-MMP chimaeras in which the hemopexin domain of MT1-MMP has been replaced with that of human or mouse MT4-MMP. We show that MT1-MMP bearing the hemopexin domain of MT4-MMP was incapable of activating pro-MMP-2 or degrading gelatin in cell based assays. Furthermore, cell surface biotinylation and indirect immunofluorescence show that transiently expressed MT1–MT4-MMP chimaeras failed to reach the plasma membrane and were retained in the endoplasmic reticulum. Functional activity could be restored by replacing the MT4-MMP hemopexin domain with the wild-type MT1-MMP hemopexin domain. Subsequent analysis with an antibody specifically recognising the propeptide of MT1-MMP revealed that the propeptides of the MT1–MT4-MMP chimaeras failed to undergo proper processing. It has previously been suggested that the hemopexin domain of MT4-MMP could exert a regulatory mechanism that prevents MT4-MMP from activating pro-MMP-2. In this report, we demonstrate unambiguously that MT1–MT4-MMP chimaeras do not undergo normal trafficking and are not correctly processed to their fully active forms and, as a consequence, they are unable to activate pro-MMP-2 at the cell surface.
A common genetic system for functional studies of pitrilysin and related M16A proteases
Authors: Alper Benjamin J. , Nienow Tatyana E. , Schmidt Walter K.
Published: August 2006

Pitrilysin is a bacterial protease that is similar to the mammalian insulin-degrading enzyme, which is hypothesized to protect against the onset of Alzheimer's disease, and the yeast enzymes Axl1p and Ste23p, which are responsible for production of the a-factor mating pheromone in Saccharomyces cerevisiae. The lack of a phenotype associated with pitrilysin deficiency has hindered studies of this enzyme. Herein, we report that pitrilysin can be heterologously expressed in yeast such that it functionally substitutes for the shared roles of Axl1p and Ste23p in pheromone production, resulting in a readily observable phenotype. We have exploited this phenotype to conduct structure–function analyses of pitrilysin and report that residues within four sequence motifs that are highly conserved among M16A enzymes are essential for its activity. These motifs include the extended metalloprotease motif, a second motif that has been hypothesized to be important for the function of M16A enzymes, and two others not previously recognized as being important for pitrilysin function. We have also established that the two self-folding domains of pitrilysin are both required for its proteolytic activity. However, pitrilysin does not possess all the enzymatic properties of the yeast enzymes since it cannot substitute for the role of Axl1p in the repression of haploid invasive growth. These observations further support the utility of the yeast system for structure–function and comparative studies of M16A enzymes.
Differential role played by the MEK/ERK/EGR-1 pathway in orthopoxviruses vaccinia and cowpox biology
Authors: Silva Patrícia N. G. , Soares Jamária A. P. , Brasil Bruno S. A. F. , Nogueira Sarah V. , Andrade Anderson A. , de Magalhães José C. , Bonjardim Marisa B. , Ferreira Paulo C. P. , Kroon Erna G. , Bruna-Romero Oscar , Bonjardim Cláudio A.
Published: August 2006

Appropriation of signalling pathways facilitates poxvirus replication. Poxviruses, as do most viruses, try to modify the host cell environment to achieve favourable replication conditions. In the present study, we show that the early growth response 1 gene (egr-1) is one of the host cell factors intensely modulated by the orthopoxviruses VV (vaccinia virus) and CPV (cowpox virus). These viruses stimulated the generation of both egr-1 mRNA and its gene product, throughout their entire replication cycles, via the requirement of MEK [mitogen-activated protein kinase/ERK (extracellular-signal-regulated kinase) kinase]/ERK pathway. We showed that, upon VV infection, EGR-1 translocates into the nucleus where it binds to the EBS (egr-1-binding site) positioned at the 5′ region of EGR-1-regulated genes. In spite of both viruses belonging to the same genus, several lines of evidence, however, revealed a remarkable contrast between them as far as the roles played by the MEK/ERK/EGR-1 pathway in their biological cycles are concerned. Hence (i) the knocking-down of egr-1 by siRNA (small interfering RNA) proved that this transcription factor is of critical relevance for VV biology, since a decrease of about one log cycle in virus yield was verified, along with a small virus plaque phenotype, whereas the gene silencing did not have a detrimental effect on either CPV multiplication or viral plaque size; (ii) while both pharmacological and genetic inhibition of MEK/ERK resulted in a significant decrease in VV yield, both approaches had no impact on CPV multiplication; and (iii) CPV DNA replication was unaffected by pharmacological inhibition of MEK/ERK, but phosphorylation of MEK/ERK was dependent on CPV DNA replication, contrasting with a significant VV DNA inhibition and VV DNA replication-independence to maintain ERK1/2 phosphorylation, observed under the same conditions.
Home use of margarine is an important determinant of plasma trans fatty acid status: a biomarker study
Authors: Murray Skeaff C. , Gowans Sonya
Published: August 2006

The contribution of the home use of margarines, made with partially hydrogenated vegetables oils, to total trans fatty acid intake is difficult to determine using dietary assessment because food composition databases are incomplete for trans fatty acids; moreover, hidden fats in manufactured foods may be the predominant sources of trans fatty acids. The objective of our study was to determine, using plasma phospholipid trans fatty acid composition as a surrogate measure of exposure, whether the home use of margarine or butter is an important determinant of trans fatty acid status. We conducted a community-based (Dunedin, New Zealand), cross-sectional survey of people who consumed either margarine (n 65) or butter (n 64) but not both for home use. The levels of the 18:1 trans isomers commonly found in partially hydrogenated vegetable oils were all significantly higher in the plasma phospholipids of margarine compared with butter consumers, with the exception of 18:1n-7t, which did not differ. Among margarine consumers, the percentage of total fat from margarine was significantly correlated with levels of phospholipid 18:1n−6t, 18:1n-8t and 18:1n-1/t isomers (r 0·57–0·63, P<0·001) but only weakly with 18:1n-7t (r 0·30, P=0·016). The intake of fat from fast foods, bakery products or meat and meat products was not associated with plasma phospholipid trans isomeric composition. The home use of margarine, made with partially hydrogenated vegetable oils, is an important determinant of trans fatty acid exposure in New Zealand.
Effects of daily ingestion of chilli on serum lipoprotein oxidation in adult men and women
Authors: Ahuja Kiran D. K. , Ball Madeleine J.
Published: August 2006

Laboratory studies have shown that the resistance of isolated LDL-cholesterol or linoleic acid to oxidation is increased in incubations with chilli extracts or capsaicin – the active ingredient of chilli. It is unknown if these in vitro antioxidative effects also occur in the serum of individuals eating chilli regularly. The present study investigated the effects of regular consumption of chilli on in vitro serum lipoprotein oxidation and total antioxidant status (TAS) in healthy adult men and women. In a randomised cross-over study, twenty-seven participants (thirteen men and fourteen women) ate ‘freshly chopped chilli’ blend (30g/d; 55% cayenne chilli) and no chilli (bland) diets, for 4 weeks each. Use of other spices, such as cinnamon, ginger, garlic and mustard, was restricted to minimum amounts. At the end of each dietary period serum samples were analysed for lipids, lipoproteins, TAS and Cu-induced lipoprotein oxidation. Lag time (before initiation of oxidation) and rate of oxidation (slope of propagation phase) were calculated. There was no difference in the serum lipid, lipoproteins and TAS at the end of the two dietary periods. In the whole group, the rate of oxidation was significantly lower (mean difference −0·23 absorbance ×10−3/min; P=0·04) after the chilli diet, compared with the bland diet. In women, lag time was higher (mean difference 9·61min; P<0·001) after the chilli diet, compared with the bland diet. In conclusion, regular consumption of chilli for 4 weeks increases the resistance of serum lipoproteins to oxidation.
Appetite during consumption of enteral formula as a sole source of nutrition: the effect of supplementing pea-fibre and fructo-oligosaccharides
Authors: Whelan Kevin , Efthymiou Loukia , Judd Patricia A. , Preedy Victor R. , Taylor Moira A.
Published: August 2006

Liquid enteral formulas are commonly used as a sole source of nutritional support of patients in hospital and community settings. Their effect on appetite has important consequences for dietary management of such patients and is likely to be affected by the formula composition. The aim of the present study was to compare appetite within healthy subjects consuming both a standard formula and one supplemented with pea-fibre (10g/l) and fructo-oligosaccharide (FOS; 5g/l) as a sole source of nutrition. Eleven healthy subjects consumed a standard formula or a pea-fibre/FOS formula as a sole source of nutrition for 14d in a double-blind, cross-over trial. Appetite was recorded using standard 100mm lines anchored at each end by a phrase denoting the most extreme appetite sensation. Consumption of the pea-fibre/FOS formula resulted in higher mean fullness (46 v.37mm, P=0·035), minimum fullness (13 v. 9mm, P=0·024) and minimum satiety (12 v. 8mm, P=0·012) compared to the standard formula. As there were no differences in macronutrient intake between formulas, these differences are likely to be due to supplementation with pea-fibre and FOS. The effect on appetite of the composition of an enteral formula, both with respect to nutrient content and functional components such as pea-fibre and FOS, may be an important aspect to consider in the dietary management of patients consuming enteral formula as a sole source of nutrition.
Butyrylated starch is less susceptible to enzymic hydrolysis and increases large-bowel butyrate more than high-amylose maize starch in the rat
Authors: Bajka Balázs H. , Topping David L. , Cobiac Lynne , Clarke Julie M.
Published: August 2006

Large-bowel fermentation of resistant starch produces SCFA that are believed to be important in maintaining visceral function. High-amylose maize starch (HAMS) and acylated starches are sources of resistant starch and are an effective means of increasing colonic SCFA. Cooking increases digestibility of starches but its effects on the capacity of these starches to raise large-bowel SCFA are unknown. We have examined the effects of cooking of HAMS and butyrylated HAMS (HAMSB) on amylolysis in vitro and their capacity to raise caeco-colonic SCFA in rats. The starches were boiled in excess water and microwaved, followed by drying at 100°C. Cooking increased in vitro glucose release for both starches but significantly less from HAMSB. Rat growth rates were unaffected when fed cooked resistant starch. Digesta pH was increased in the caecum and proximal colon of rats fed cooked HAMS. Distal colonic pH was highest in rats fed cooked HAMSB. Factorial analyses (2×2) of caecal SCFA pools showed significant differences between HAMS and HAMSB, and that cooking significantly lowered caecal butyrate pools. Portal venous butyrate concentrations were higher in both HAMSB groups than those fed HAMS. The data suggest that HAMSB is less susceptible to in vitro amylolysis than HAMS following cooking and delivers more butyrate to rat caecum than HAMS. This attribute may be useful in food applications for specific delivery of SCFA to the colon. Preparation of carbohydrates to simulate human food in animal experiments may be important to assess nutritional and physiological effects accurately.
Favourable impact of low-calorie cranberry juice consumption on plasma HDL-cholesterol concentrations in men
Authors: Ruel Guillaume , Pomerleau Sonia , Couture Patrick , Lemieux Simone , Lamarche Benoît , Couillard Charles
Published: August 2006

A low HDL-cholesterol concentration is an independent risk factor for CVD. Studies have suggested that flavonoid consumption may be cardioprotective, and a favourable impact on circulating HDL-cholesterol concentrations has been suggested to partially explain this association. The aim of the present study was to determine the effect of consuming increasing daily doses of low-calorie cranberry juice cocktail (CJC) on the plasma lipid profile of abdominally obese men. For that purpose, thirty men (mean age 51 (SD 10) years) consumed increasing doses of CJC during three successive periods of 4 weeks (125ml/d, 250ml/d, 500ml/d). Before the study and after each phase, we measured changes in physical and metabolic variables. We noted a significant increase in plasma HDL-cholesterol concentration after the consumption of 250ml CJC/d (+8·6±14·0%v.0ml CJC/d;P<0·01), an effect that plateaued during the last phase of the study (500ml CJC/d: +8·1±10·0%v.0ml CJC/d;P<0·0001). Multivariate analyses revealed that changes in plasma apo A-I (IR2=48%,P<0·0001) and triacylglycerol (R2=16%,P<0·005) concentrations were the only variables significantly contributing to the variation in plasma HDL-cholesterol concentration noted in response to the intervention. No variation was observed in total as well as in LDL and VLDL cholesterol. The present results show that daily CJC consumption is associated with an increase in plasma HDL-cholesterol concentrations in abdominally obese men. We hypothesise that polyphenolic compounds from cranberries may be responsible for this effect, supporting the notion that the consumption of flavonoid-rich foods can be cardioprotective.
Mediterranean dietary pattern and mortality among young women: a cohort study in Sweden
Authors: Lagiou Pagona , Trichopoulos Dimitrios , Sandin Sven , Lagiou Areti , Mucci Lorelei , Wolk Alicja , Elisabete Elisabete , Adami Hans-Olov
Published: August 2006

Studies of diet and health focus increasingly on dietary patterns. Although the traditional Mediterranean diet is perceived as being healthy, there is little information on its possible benefit to young people. We studied whether closer adherence to the traditional Mediterranean dietary pattern was associated with overall and cancer mortality in a cohort of 42237 young women, aged 30–49 years at enrolment, who were recruited in 1991–2 from the general population in the Uppsala Health Care Region, Sweden, and followed up, almost completely, for about 12 years. Adherence to the Mediterranean diet was assessed by a 10-point score incorporating the characteristics of this diet. Among women less than 40 years old at enrolment – whose causes of death are mainly cancer with probable genetic influences, injuries or suicide – there was no association of the Mediterranean diet score with total or cancer mortality. Among women 40–49 years old at enrolment, a 2-point increase in the score was associated with considerable reductions in overall mortality (13%; 95% CI 1%, 23%;P∼0·05) and cancer mortality (16%; 95% CI −1%, 29%;P∼0·06). Few cardiovascular deaths occurred in this cohort of young women. The findings of the present study in a northern European population of young women indicate that closer adherence to a Mediterranean dietary pattern reduces mortality even among young persons.
Glutathione S-transferase polymorphisms may be associated with risk of oedematous severe childhood malnutrition
Authors: Marshall Kwesi G , Howell Sharon , Reid Marvin , Badaloo Asha , Farrall Martin , Forrester Terrence , McKenzie Colin A.
Published: August 2006

It has been estimated that more than 50% of deaths before the age of 5 years have undernutrition as an underlying cause. Severe childhood malnutrition, an extreme form of undernutrition, occurs as oedematous and non-oedematous syndromes. The reasons why only some children develop oedematous severe childhood malnutrition (OSCM) have remained elusive, but the heterogeneity of clinical appearances among children from relatively homogeneous backgrounds suggests that interindividual variation in susceptibility to OSCM may exist. We investigated variants of four glutathione S-transferase (GST) genes in a retrospective study among subjects (n136) previously admitted to the Tropical Metabolism Research Unit, Jamaica, for the treatment of either OSCM (cases) or non-oedematous severe childhood malnutrition (controls). We found that GSTP1 Val105homozygotes were significantly more common among the cases (odds ratio (OR) 3·5; 95% CI 1·1, 10·8). We also found an association of borderline significance between non-deletion GSTT1 genotypes (i.e. +/+ or +/0) and OSCM (OR 2·4; 95% CI 1·0, 5·9). There was no significant association between OSCM and any of the other GST variants. These preliminary findings suggest that genetic variation within the GST superfamily may contribute to the risk of OSCM. Additional, larger data sets and studies of variants in other candidate genes are required in order to properly assess the true contribution, if any, of genetic variation to risk of OSCM. Such studies may improve our understanding of the causes of clinical heterogeneity in malnutrition.
Nutrient intake among Chinese women living in Shanghai, China
Authors: Chen Zhi , Shu Xiao Ou , Yang Gong , Li Honglan , Li Qi , Gao Yu-Tang , Zheng Wei
Published: August 2006

It has been increasingly recognized that dietary factors play a major role in the development of chronic diseases, including cancers and CVD. The identification of patterns of nutrient intake in populations with different disease incidence will be helpful in understanding the diet and disease association. The present report describes nutrient intake in 74810 Chinese women, aged between 40 and 70 years, who participated in a population-based cohort study in Shanghai from 1997 to 2000. A food frequency questionnaire was used to derive estimates of nutrient intakes. The average daily energy intake was 7027·8kJ in the study population, with protein, fat and carbohydrates contributing 15·9%, 15·6% and 68·5%, respectively. Factors, including younger age, higher income, attainment of education at the college level or above, being married or holding a professional job, were related to higher intake levels of most nutrients. The present results highlight the need for continuing to promote public health strategies aimed at improving the diets of women from both older and lower socio-demographic backgrounds, and in the meantime, continuing to help address the current dearth of data on nutrient intakes for middle-aged and elderly urban Chinese women.
Metformin-like effect of Salvia officinalis (common sage): is it useful in diabetes prevention?
Authors: Lima Cristovao F. , Azevedo Marisa F. , Araujo Rita , Fernandes-Ferreira Manuel , Pereira-Wilson Cristina
Published: August 2006

Common sage (Salvia officinalis L.) is among the plants that are claimed to be beneficial to diabetic patients, and previous studies have suggested that some of its extracts have hypoglycaemic effects in normal and diabetic animals. In the present study, we aimed to verify the antidiabetic effects of an infusion (tea) of common sage, which is the most common form of this plant consumed. Replacing water with sage tea for 14d lowered the fasting plasma glucose level in normal mice but had no effect on glucose clearance in response to an intraperitoneal glucose tolerance test. This indicated effects on gluconeogenesis at the level of the liver. Primary cultures of hepatocytes from healthy, sage-tea-drinking rats showed, after stimulation, a high glucose uptake capacity and decreased gluconeogenesis in response to glucagon. Essential oil from sage further increased hepatocyte sensitivity to insulin and inhibited gluconeogenesis. Overall, these effects resemble those of the pharmaceutical drug metformin, a known inhibitor of gluconeogenesis used in the treatment and prevention of type 2 diabetes mellitus. In primary cultures of rat hepatocytes isolated from streptozotocin (STZ)-induced diabetic rats, none of these activities was observed. The present results seem to indicate that sage tea does not possess antidiabetic effects at this level. However, its effects on fasting glucose levels in normal animals and its metformin-like effects on rat hepatocytes suggest that sage may be useful as a food supplement in the prevention of type 2 diabetes mellitus by lowering the plasma glucose of individuals at risk.
Effect of insulin on transcription of lipogenic and lipolytic-related genes and lipid metabolism in primary porcine adipocytes
Authors: Jian-Xiong Lu , Fen-Fen Chen , Gong-She Yang
Published: August 2006

Primary adipocytes from subcutaneous adipose tissue samples obtained from 7-day-old Yorkshire×Landrace crossbreed piglets were exposed to 0–400 nmol/l of insulin for 48 h. The accumulated triglyceride was measured through Oil Red O staining and the cumulative glycerol released was determined to assess lipolytic activity in adipocytes. Transcription levels of sterol regulatory element binding protein (SREBP)-1c, carbohydrate response element binding protein (ChREBP), acetyl-CoA carboxylase 1 (ACC1), fatty acid synthase (FAS), and hormone-sensitive lipase (HSL) were assessed using reverse transcriptase-polymerase chain reaction (RT-PCR). The results showed that ChREBP and ACC1 mRNA levels were not influenced by insulin alone under low glucose (5 nmol/l). FAS mRNA level was markedly stimulated by all doses of insulin except 200 nmol/l, and SREBP-1c mRNA level increased with 100–300 nmol/l insulin. High insulin doses (300 and 400 nmol/l) increased the HSL mRNA level as well as lipolytic activity.
Isolation and analysis of sox9 gene derived from yellow catfish Pelteobagrus fulvidraco
Authors: Ju-Hua Yu , Jian-Lin Li , Li-Ping Cao , Ting-Ting Wu , Hong Yang
Published: August 2006

Sox9 is one of the important genes related to sex differentiation and determination. Two partial cDNAs encoding sox9 were derived from brain, testis and ovary of yellow catfish Pelteobagrus fulvidraco using reverse transcriptase-polymerase chain reaction (RT-PCR). Sequence analysis revealed that the ovarian sox9a2 was different from sox9a1 derived from brain and testis. The identity rate of cDNA was 77%, that of amino acids was 84%, and the different nucleotides were distributed in different sites all over the cDNA. This finding confirmed that there were transcripts from two genes. Based on the homology of the amino-acid sequences for sox9 of other animals, the similarity for sox9a1 from yellow catfish and sox9 of other animals averaged 86%. The similarity for sox9a2 reached a mean of 83%. The phylogenetic analysis revealed yellow catfish sox9a1 and sox9a2 were clustered into the fish branch. And yellow catfish sox9a2 was different from the other fish sox9. There was no significant branch including all sox9 derived from testis and brain or including all ovarian sox9. The genetic distance was the same with the results of the traditional taxonomy. RT-PCR analysis indicated that sox9a1 was expressed in male and female yellow catfish forebrain as well as in gonads, whereas sox9a2 was only expressed in ovaries. The function of sox9a2 in female sex formation and ovary development needs to be studied in depth.
Genetic analysis of isozyme inPteria penguinR. and offspring from inbreeding and hybridized stocks ofPinctada martensiiD.
Authors: Mei-Fang Wang , Xiang-Yong Yu , Yong Liu , Yong Mao , Fei-Long Liang
Published: August 2006

The genetic variation of isozymes [esterase (EST), superoxide dismutase (SOD), malate dehydrogenase (MDH), malic enzyme (ME) and glucose-6-phosphate dehydrogenase (G6PD)] extracted from two different adult tissues (adductor muscle and gill) ofPteria penguinR. and offspring from two stocks ofPinctada martensiiD. were analysed by vertical polyacrylamide gel electrophoresis. The result showed an obvious and stable variation in the isozyme phenotypes in two different pearl oyster species. The SOD and EST isozymes from gill and MDH, ME and G6PDH from adductor muscle were species-specific. The electrophoretograms of these isozymes could be used as markers to differentiate the two pearl oysters. Between inbreeding and hybridized stocks ofP. martensii, the electrophoresis patterns of isozymes were alike, but the similarities of electrophoretograms in the inbreeding progenies were higher than in the hybridized ones. The characteristic electrophoretograms of isozymes could be applied as molecular markers in the breeding of pearl oysters.
Approaches to improve heterogeneous gene expression in transgenic plants
Authors: Tao Yin , Shang-long Zhang , Jing-mei Liu , De-ming Chen
Published: August 2006

With the development of plant genetic engineering, many transformation methods can be used to transfer heterogeneous genes into plants to develop genetic crops. However, a lot of research results have shown that transgene expression remains largely unpredictable and there is great variation of expression level in different transgenic plant lines. Plant genetic engineering research is reviewed in the present paper. We analysed the reasons why low efficiency of heterogeneous gene expression has happened in transgenic plants in terms of DNA modification, localization of proteins and methods of transformation used. Some strategies for improving heterogeneous gene expression in transgenic plants are also discussed.
Isolation, cultivation and identification of pancreatic stem/progenitor cells in rabbit
Authors: Hui-Ru Zhang , Ruo-Peng Feng , Xia Liu , Yu-Xiao Liu , Quan-Hai Pang , Zhong-Ying Dou
Published: August 2006

Pancreases obtained from 1–9-day-old rabbits were digested with 1 mg/ml ?? collagenase and cultivated with low-glucose Dulbecco's modified Eagle's medium (DMEM). The cells were subcultured almost until confluence. They were identified as pancreatic stem/progenitor cells using two methods: an immunohistochemical staining technique and the response of glucose-stimulated insulin secretion after β-cell induction. Results showed that the cells of rabbits acquired strong proliferation ability, and expressed the markers of pancreatic stem/progenitor cells: PDX-1, CK19 and nestin. After β-cell induction for 2 days, 20% of cells were dithizone (DTZ) positive, rapidly increasing to 80% after 6 days. Insulin secretion was stimulated by a high glucose concentration (26 mmol/l). These powerful tests demonstrated that isolated and cultivated cells in rabbits were pancreatic stem/progenitor cells. This result has not yet been reported elsewhere.
Gawky is a component of cytoplasmic mRNA processing bodies required for early Drosophila development
Authors: Schneider Mary D. , Najand Nima , Chaker Sana , Pare Justin M. , Haskins Julie , Hughes Sarah C. , Hobman Tom C. , Locke John , Simmonds Andrew J.
Published: August 2006

In mammalian cells, the GW182 protein localizes to cytoplasmic bodies implicated in the regulation of messenger RNA (mRNA) stability, translation, and the RNA interference pathway. Many of these functions have also been assigned to analogous yeast cytoplasmic mRNA processing bodies. We have characterized the single Drosophila melanogaster homologue of the human GW182 protein family, which we have named Gawky (GW). Drosophila GW localizes to punctate, cytoplasmic foci in an RNA-dependent manner. Drosophila GW bodies (GWBs) appear to function analogously to human GWBs, as human GW182 colocalizes with GW when expressed in Drosophila cells. The RNA-induced silencing complex component Argonaute2 and orthologues of LSm4 and Xrn1 (Pacman) associated with 5′–3′ mRNA degradation localize to some GWBs. Reducing GW activity by mutation or antibody injection during syncytial embryo development leads to abnormal nuclear divisions, demonstrating an early requirement for GWB-mediated cytoplasmic mRNA regulation. This suggests that gw represents a previously unknown member of a small group of genes that need to be expressed zygotically during early embryo development.
Role of TIF1α as a modulator of embryonic transcription in the mouse zygote
Authors: Torres-Padilla Maria Elena , Zernicka-Goetz Magdalena
Published: August 2006

The first events of the development of any embryo are under maternal control until the zygotic genome becomes activated. In the mouse embryo, the major wave of transcription activation occurs at the 2-cell stage, but transcription starts already at the zygote (1-cell) stage. Very little is known about the molecules involved in this process. We show that the transcription intermediary factor 1 α (TIF1α) is involved in modulating gene expression during the first wave of transcription activation. At the onset of genome activation, TIF1α translocates from the cytoplasm into the pronuclei to sites of active transcription. These sites are enriched with the chromatin remodelers BRG-1 and SNF2H. When we ablate TIF1α through either RNA interference (RNAi) or microinjection of specific antibodies into zygotes, most of the embryos arrest their development at the 2–4-cell stage transition. The ablation of TIF1α leads to mislocalization of RNA polymerase II and the chromatin remodelers SNF2H and BRG-1. Using a chromatin immunoprecipitation cloning approach, we identify genes that are regulated by TIF1α in the zygote and find that transcription of these genes is misregulated upon TIF1α ablation. We further show that the expression of some of these genes is dependent on SNF2H and that RNAi for SNF2H compromises development, suggesting that TIF1α mediates activation of gene expression in the zygote via SNF2H. These studies indicate that TIF1α is a factor that modulates the expression of a set of genes during the first wave of genome activation in the mouse embryo.
Interactions between heparan sulfate and proteins: the concept of specificity
Authors: Kreuger Johan , Spillmann Dorothe , Li Jin-ping , Lindahl Ulf
Published: August 2006

Proteoglycan (PG) coreceptors carry heparan sulfate (HS) chains that mediate interactions with growth factors, morphogens, and receptors. Thus, PGs modulate fundamental processes such as cell survival, division, adhesion, migration, and differentiation. This review summarizes recent biochemical and genetic information that sheds new light on the nature of HS–protein binding. Unexpectedly, many interactions appear to depend more on the overall organization of HS domains than on their fine structure.
Fast Adaptation in Mouse Olfactory Sensory Neurons Does Not Require the Activity of Phosphodiesterase
Authors: Boccaccio Anna , Lagostena Laura , Hagen Volker , Menini Anna
Published: August 2006

Vertebrate olfactory sensory neurons rapidly adapt to repetitive odorant stimuli. Previous studies have shown that the principal molecular mechanisms for odorant adaptation take place after the odorant-induced production of cAMP, and that one important mechanism is the negative feedback modulation by Ca2+-calmodulin (Ca2+-CaM) of the cyclic nucleotide-gated (CNG) channel. However, the physiological role of the Ca2+-dependent activity of phosphodiesterase (PDE) in adaptation has not been investigated yet. We used the whole-cell voltage-clamp technique to record currents in mouse olfactory sensory neurons elicited by photorelease of 8-Br-cAMP, an analogue of cAMP commonly used as a hydrolysis-resistant compound and known to be a potent agonist of the olfactory CNG channel. We measured currents in response to repetitive photoreleases of cAMP or of 8-Br-cAMP and we observed similar adaptation in response to the second stimulus. Control experiments were conducted in the presence of the PDE inhibitor IBMX, confirming that an increase in PDE activity was not involved in the response decrease. Since the total current activated by 8-Br-cAMP, as well as that physiologically induced by odorants, is composed not only of current carried by Na+ and Ca2+ through CNG channels, but also by a Ca2+-activated Cl− current, we performed control experiments in which the reversal potential of Cl− was set, by ion substitution, at the same value of the holding potential, −50 mV. Adaptation was measured also in these conditions of diminished Ca2+-activated Cl− current. Furthermore, by producing repetitive increases of ciliary's Ca2+ with flash photolysis of caged Ca2+, we showed that Ca2+-activated Cl− channels do not adapt and that there is no Cl− depletion in the cilia. All together, these results indicate that the activity of ciliary PDE is not required for fast adaptation to repetitive stimuli in mouse olfactory sensory neurons.
Infectious Diseases Physicians' Preferences for Continuing Medical Education on Antimicrobial Resistance and Other General Topics
Authors: Blakely Jennifer Tuboku-Metzger , Sinkowitz-Cochran Ronda L. , Jarvis William R.
Published: August 2006

A 19-item survey instrument was designed and mailed by the Infectious Diseases Society of America to its membership to determine the media preferred by infectious diseases physicians for continuing medical education on general topics and on antimicrobial resistance. The objective of the survey was to offer the developers of educational programs knowledge on which to base more-effective ways to deliver educational materials to physicians in this specialty.
Highly Sensitive and Efficient Computer–Assisted System for Routine Surveillance for Surgical Site Infection
Authors: Chalfine Annie , Cauet Daniel , Lin Wei Chi , Gonot Jacqueline , Calvo-Verjat Nadine , Dazza François-Emile , Billuart Olivier , Kitzis Marie Dominique , Blériot Jean Pierre , Pibarot Marie Laure , Carlet Jean
Published: August 2006

Objectives.

Surveillance of surgical site infections (SSIs) is effective in reducing the rates of these complications, but it is extremely time-consuming and, consequently, underused. We determined the sensitivity and specificity of a computer-assisted surveillance system, compared with a conventional method involving review of medical records, and the time saved with the computer-assisted system.

Method.

A prospective study was conducted from January 1 to December 31, 2001. With the computer-assisted method, screening for SSIs relied on identification in the laboratory database of positive results of microbiological tests of surgical-site specimens; confirmation was obtained via computer-generated questionnaires completed by the surgeon in charge of the patient. In the conventional method, SSIs were identified by exhaustive chart review. The time spent on surveillance was recorded for both methods.

Setting.

A 25-bed gastrointestinal surgery unit in a tertiary care hospital.

Patients.

A total of 766 consecutive patients who underwent gastrointestinal surgery.

Results.

The sensitivity of the computer-assisted method was 84.3% (95% confidence interval, 0.66-0.94); the specificity was 99.9%. For the 807 surgical procedures in the study, 197 had an SSI identified by culture of a surgical-site specimen. After elimination of 63 duplicate cultures with positive results, 134 questionnaires were sent to the surgeons, who confirmed 27 SSIs. The conventional method identified 32 SSIs. The computer-assisted method required 60% less time than the conventional method (90 hours vs 223 hours).

Conclusion.

Surveillance for SSIs using computer-assisted, laboratory-based screening and case confirmation by surgeons is as efficient as and far less time-consuming than the conventional method of chart review. This method permits routine surveillance for SSIs with reliable accuracy.
Admission-Specific Chronic Disease Scores as Alternative Predictors of Surgical Site Infection for Patients Undergoing Coronary Artery Bypass Graft Surgery
Authors: Batista Ruth , Kaye Keith , Yokoe Deborah S.
Published: August 2006

Objective.

To evaluate the admission chronic disease score (ACDS) and a variant of the ACDS as predictors of surgical site infection (SSI) for study participants who underwent coronary artery bypass graft (CABG) surgery.

Design.

Retrospective case-control study.

Setting.

A 750-bed academic medical center.

Participants.

All participants with an SSI that was identified through hospital-based surveillance (defined as case patients) and a random sample of participants without SSI following CABG surgery (defined as control subjects) between July 1, 1999, and June 30, 2001.

Results.

An ACDS based on medications ordered on the day of hospital admission was determined for 264 study participants admitted prior to the day of the surgical procedure. A preadmission chronic disease score (PACDS) based on outpatient medications was calculated for 281 participants, using the record of preadmission medications in the patient's discharge summary. The ACDS and PACDS were significantly higher for case patients, compared with control subjects (P = .03 and P = .05, respectively). American Society of Anesthesiologists (ASA) score and the standard National Nosocomial Infection Surveillance system (NNIS) risk index were not significant predictors of SSI. In logistic regression models, only the ACDS (odds ratio, 1.02 per 100 ACDS points), the PACDS (odds ratio, 1.02 per 100 PACDS points), the highest PACDS quintile (odds ratio, 2.89 [compared with lowest quintile]), and a modified NNIS-PACDS score of 2 (odds ratio, 3.5 [compared with a score of 0]) were significant predictors of SSI.

Conclusions.

Because preoperative medications are likely to reflect comorbidities that influence the risk of SSI, medication-based scoring systems such as the ACDS and PACDS may allow for better risk stratification than the standard NNIS risk index, particularly for patient populations with relatively homogenous wound classification and ASA score distributions.