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Biomedical subjects

J Boucher

Publications and source records attributed to J Boucher.

At least 19 recordsLinked to original sources

[Female condom or male condom: offer a choice!].

OBJECTIVES: As in the entire Ile-de-France, the Val-de-Marne is facing an increase in female contamination by HIV, a clear increase in STI and furthermore the number of legal abortions is still high. Various recent studies have emphasized the decrease in condom use since 1998. Can the possibility of proposing another condom, more specifically controlled by women, boost condom use? PATIENTS AND METHODS: The conseil général (local government authority) thus initiated a study in the general population, from January 1st 2001 to December 31st 2001, in order to study the criteria of acceptability of the female condom (FC). RESULTS: Although the women coming to consultation had no specific requests a quarter finally tested the female condom during sexual intercourse. Among them 4 out of 10 are ready to use it again. Curiosity was the primary motivation of those who accepted to test the female condom (77 %). Women who were more at ease with their sexuality were twice more likely to test the female condom. Three main advantages were put forward by the women who tested the FC: the strength of the FC, the fact that insertion was possible prior to the sexual act and the possibility of postponing removal, the latter being considered a supplementary advantage. The disadvantages most frequently cited before use were its appearance and difficult insertion process. The frequency of utilisation of the FC was multiplied by three when women practised putting the condom in place in a non-sexual context. However, even when they recognized one or several disadvantages women accepted to test it. In addition, whenever a woman finds at least one advantage before use she is twice more likely to test it. This is where counselling by professionals in charge of presenting the FC becomes a deciding factor. DISCUSSION AND CONCLUSIONS: The chance of using at least one sort of condom is increased when a choice of condoms is available. When both male and female condoms are available, the responsibility for prevention is better balanced within the couple: each partner can then be in charge of his or her own health. However the adoption of a barrier method such as the condom, means that the individual is conscious of such a need and finds that there are benefits mainly staying in good health. However the insufficient number of prevention and health promotion campaigns in France does not favour such an awareness. The availability of inexpensive female condoms in pharmacies, supermarkets as well as free distribution by certain institutions remains an unresolved question.

Acquired Immunodeficiency Syndrome↗

Potential involvement of adipocyte insulin resistance in obesity-associated up-regulation of adipocyte lysophospholipase D/autotaxin expression.

AIMS/HYPOTHESIS: Autotaxin is a lysophospholipase D that is secreted by adipocytes and whose expression is substantially up-regulated in obese, diabetic db/db mice. The aim of the present study was to depict the physiopathological and cellular mechanisms involved in regulation of adipocyte autotaxin expression. METHODS: Autotaxin mRNAs were quantified in adipose tissue from db/db mice (obese and highly diabetic type 2), gold-thioglucose-treated (GTG) mice (highly obese and moderately diabetic type 2), high-fat diet-fed (HFD) mice (obese and moderately diabetic type 2), streptozotocin-treated mice (thin and diabetic type 1), and massively obese humans with glucose intolerance. RESULTS: When compared to non-obese controls, autotaxin expression in db/db mice was significantly increased, but not in GTG, HFD, or streptozotocin-treated mice. During db/db mice development, up-regulation of autotaxin occurred only 3 weeks after the emergence of hyperinsulinaemia, and simultaneously with the emergence of hyperglycaaemia. Adipocytes from db/db mice exhibited a stronger impairment of insulin-stimulated glucose uptake than non-obese and HFD-induced obese mice. Autotaxin expression was up-regulated by treatment with TNFalpha (insulin resistance-promoting cytokine), and down-regulated by rosiglitazone treatment (insulin-sensitising compound) in 3T3F442A adipocytes. Finally, adipose tissue autotaxin expression was significantly up-regulated in patients exhibiting both insulin resistance and impaired glucose tolerance. CONCLUSIONS/INTERPRETATION: The present work demonstrates the existence of a db/db-specific up-regulation of adipocyte autotaxin expression, which could be related to the severe type 2 diabetes phenotype and adipocyte insulin resistance, rather than excess adiposity in itself. It also showed that type 2 diabetes in humans is also associated with up-regulation of adipocyte autotaxin expression.

Adipocytes↗

Influence of high-fat diet on amine oxidase activity in white adipose tissue of mice prone or resistant to diet-induced obesity.

Decreased monoamine oxidase (MAO) activity has been observed in adipose tissue of obese patients. Since substrates of MAO and semicarbazide-sensitive amine oxidase (SSAO) can modify adipocyte metabolism, this work investigates whether changes in amine oxidase activity may occur during white adipose tissue (WAT) development. We evaluated MAO and SSAO activities in WAT of high-fat diet (HFD) and low-fat diet fed mice. To distinguish the effect of HFD on its own from the effect of fat mass enlargement, obesity-prone transgenic line of the FVBn strain lacking beta3-adrenergic receptors (AR) but expressing human beta3-AR and alpha2-AR (mbeta3-/-, hbeta3+/+, halpha2+/-) was compared to its obesity-resistant control (mbeta3-/-, hbeta3+/+). As already reported, the former mice became obese while the latter resisted to HFD. No significant change in SSAO or MAO activity was found in WAT of both strains after HFD when expressing oxidase activity per milligram of protein. However, when considering the overall capacity of the fat depots to oxidize tyramine or benzylamine, there was an increase in MAO and SSAO activity only in the enlarged WAT of HFD-induced obese mice. Therefore, the comparison of these models allowed to demonstrate that the higher amine oxidase capacity hold in enlarged fat stores of obese mice is more likely the consequence of increased fat cell number rather than the result of an increased expression of MAO or SSAO in the adipocyte.

Adipose Tissue↗

Adipokine expression profile in adipocytes of different mouse models of obesity.

Adipose tissue produces and secretes multiple adipokines. Most studies on adipokine production/expression have been performed on whole adipose tissue. In addition, data concerning an overall of adipokine expression are scarce and can be heterogeneous depending on the obesity model studied. Our first aim was to compare the expression of adipokines involved in the interplay between obesity and insulin resistance in isolated adipocytes from different mouse models of obesity displaying different levels of weight gain and insulin sensitivity. The second aim was to determine perigonadal/subcutaneous ratio of each adipokine. Only resistin expression was decreased in obese mice without modifications in glucose and insulin blood levels. In addition to decreased levels of resistin, obesity models associated with hyperglycemia and hyperinsulinemia presented an increased expression of leptin and tumor necrosis factor-alpha (TNFalpha). Obese and diabetic mice were the only animals to exhibit high expression of plasminogen activator inhibitor type-1 and interleukin-6. All adipokines except TNFalpha were more heavily expressed in perigonadal than in subcutaneous adipocytes. Interestingly, fat-enriched diet and overweight on their own did not modify the distribution of adipokines between the two fat depots. However, severe obesity modified the distribution of proinflammatory adipokines. In conclusion, the level and number of adipokines with altered expression increased with obesity and hyperinsulinemia in mice. The physiopathological impact of depot-specific differences of adipokine expression in adipocytes remains to be clarified.

Adipocytes↗

Effect of non-digestible gluco-oligosaccharides on glucose sensitivity in high fat diet fed mice.

Non digestible dietary carbohydrates have been reported to modify lipaemia and post-prandial glycaemia and insulinaemia. The aim of this study was to investigate the effect of a non-digestible gluco-oligosaccharides (GOS) diet on glucose, insulin, triglycerides and free fatty acid blood levels and glucose sensitivity in high fat diet fed mice (a high fat diet composed of 45% fat, 35% carbohydrate and 20% protein). Female C57B16/J mice were divided into two groups fed a high fat diet (HF) for 20 weeks supplemented or not with 1.5 g/kg/day of GOS (HF-GOS). The GOS supplementation did not change body weight nor fat pad mass, nor any of the blood parameters measured (glucose, insulin, leptin, triglycerides, and free fatty acids). However, mice which received the GOS supplemented diet showed an increased glucose utilization after a 1 g/kg load of glucose compared with the mice fed the high fat diet alone. Our results suggest a role for non-digestible GOS in the regulation of carbohydrate metabolism.

Adipose Tissue↗

[Development of nutritional obesity in transgenic mice with an adrenergic receptivity in adipose tissue comparable with that of humans].

Obesity is characterized by an excessive development of fat mass which is a consequence of increased fat cell size and/or fat cell number. Several hormones and neurotransmitters are regulators of adipose tissue development and metabolism. Among them, catecholamines play a major role by acting through alpha 2- and beta-adrenergic receptors. Stimulation of alpha 2-adrenergic receptors induce inhibition of lipolysis in mature adipocytes as well as preadipocyte proliferation. The antilipolytic effect mediated by alpha 2-adrenergic receptors is in part responsible for the weak lipid mobilization of some fat deposits in humans (subcutaneous fat in particular). Changes in beta- and alpha 2-adrenergic receptors ratio and function have been proposed to explain the lipolytic disturbances described in some obese subjects. Human and rodent adipocytes differ considerably with respect to the balance between beta- and alpha 2-adrenergic receptors. Human adipocytes express mainly alpha 2- but very few beta 3-adrenergic receptors while the reverse is true for rodent adipocytes. Since no suitable animal model was available to study the contribution of alpha 2/beta-adrenergic balance in adipocytes in vivo, we combined gene targeting and transgenic approaches to create a mice with increased alpha 2/beta-adrenergic ratio in adipose tissue. Specifically, we have generated transgenic mice strains on a beta 3-adrenergic receptor knock-out background which express human alpha 2-adrenergic receptors. No particular phenotype was observed in mice maintained in normal diet whereas when fed a high fat diet, transgenic mice increased significantly body weight and fat mass. These results underline the physiologic relevance of the interaction of the presence of alpha 2-adrenergic receptors with a high fat diet in the control of adipose tissue development.

Animals↗

Human alpha 2A-adrenergic receptor gene expressed in transgenic mouse adipose tissue under the control of its regulatory elements.

Catecholamines regulate white adipose tissue function and development by acting through beta- and alpha2-adrenergic receptors (ARs). Human adipocytes express mainly alpha 2A- but few or no beta 3-ARs while the reverse is true for rodent adipocytes. Our aim was to generate a mouse model with a human-like alpha2/beta-adrenergic balance in adipose tissue by creating transgenic mice harbouring the human alpha 2A-AR gene under the control of its own regulatory elements in a combined mouse beta 3-AR-/- and human beta 3-AR+/+ background. Transgenic mice exhibit functional human alpha 2A-ARs only in white fat cells. Interestingly, as in humans, subcutaneous adipocytes expressed higher levels of alpha2-AR than perigonadal fat cells, which are associated with a better antilipolytic response to epinephrine. High-fat-diet-induced obesity was observed in transgenic mice in the absence of fat cell size modifications. In addition, analysis of gene expression related to lipid metabolism in isolated adipocytes suggested reduced lipid mobilization and no changes in lipid storage capacity of transgenic mice fed a high-fat diet. Finally, the development of adipose tissue in these mice was not associated with significant modifications of glucose and insulin blood levels. Thus, these transgenic mice constitute an original model of diet-induced obesity for in vivo physiological and pharmacological studies with respect to the alpha2/beta-AR balance in adipose tissue.

Adipocytes↗

Decreased resistin expression in mice with different sensitivities to a high-fat diet.

The regulation of resistin, a new adipose-derived circulating factor, is the subject of controversy. In particular, the question of its modulation in obesity led to opposite results reported by two different groups. In the current study, we assayed adipocyte resistin mRNA using fluorescent real-time RT-PCR. We studied the expression of resistin in mice which are differently sensitive to diet-induced obesity: the FVB/n strain, which poorly responds to high-fat diet and transgenic mice that express human alpha 2A-AR in adipose tissue in the absence of beta 3-adrenergic receptor (AR) under the FVB genetic background which are highly sensitive to high-fat diet and develop hyperplastic obesity. We observed that FVB mice, which have no significant increased body weight after an 8-week high-fat diet period, exhibited no alteration of resistin expression. In contrast, the transgenic mice developing high-fat diet-induced obesity exhibited markedly downregulated adipocyte resistin mRNA. We also showed that obesity induced by gold thioglucose injection in FVB/n mice reduces the expression of resistin in isolated adipocytes. This argues for decreased expression of resistin as a hallmark of obesity. Moreover, our data show that feeding a high-fat diet is not a primary determinant of resistin regulation.

Adipose Tissue↗

Amine oxidase substrates mimic several of the insulin effects on adipocyte differentiation in 3T3 F442A cells.

We have previously reported that substrates of monoamine oxidase (MAO) and semicarbazide-sensitive amine oxidase (SSAO) exert short-term insulin-like effects in rat adipocytes, such as stimulation of glucose transport. In the present work, we studied whether these substrates could also mimic long-term actions of insulin. Adipose differentiation of 3T3 F442A cells, which is highly insulin-dependent, served as a model to test the effects of sustained administration of amine oxidase substrates. Daily treatment of confluent cells with 0.75 mM tyramine (a substrate of MAO and SSAO) or benzylamine (a substrate of SSAO) over 1 week caused the acquisition of typical adipocyte morphology. The stimulation of protein synthesis and triacylglycerol accumulation caused by tyramine or benzylamine reached one half of that promoted by insulin. This effect was insensitive to pargyline (an MAO inhibitor), but was inhibited by semicarbazide (an SSAO inhibitor) and by N-acetylcysteine (an antioxidant agent), suggesting the involvement of the H(2)O(2) generated during SSAO-dependent amine oxidation. Chronic administration of amine oxidase substrates also induced the emergence of adipose conversion markers, such as aP2, glycerol-3-phosphate dehydrogenase, the glucose transporter GLUT4, and SSAO itself. Moreover, cells treated with amines acquired the same insulin sensitivity regarding glucose transport as adipocytes classically differentiated with insulin. In all, most of the adipogenic effects of amines were additive to insulin. Our data reveal that amine oxidase substrates partially mimic the adipogenic effect of insulin in cultured preadipocytes. Furthermore, they suggest that SSAO not only represents a novel late marker of adipogenesis, but could also be directly involved in the triggering of terminal adipocyte differentiation.

3T3 Cells↗

The new credential: advanced diabetes management.

A new multidisciplinary credential, the advanced diabetes manager, has been developed by the American Association of Diabetes Educators (AADE) and the American Nurses Credentialing Center (ANCC), in collaboration with the American Dietetic Association, the American Diabetes Association, and the American Pharmaceutical Association (APhA). The credential, designated as BC-ADM, is conferred upon successful completion of an exam to registered dietitians, registered nurses and registered pharmacists who hold advanced degrees and meet experience requirements. The exam is based on the scope and standards of practice approved by the governing agencies of the sponsoring organizations and defines advanced diabetes management knowledge and skills associated with improved outcomes. Information related to the test content outline, application process, suggested exam preparation, test sites, etc., is available from www.aadenet.org or www.nursingworld.org/ancc.

Accreditation↗

'Here's the weavery looming up': verbal humour in a woman with high-functioning autism.

A case study of Grace, a 29-year-old woman with high-functioning autism, is presented. Grace is unusual for a person with autism in that she produces a great deal of humorous and creative word play. She is also unusual in that she writes and then audio-records 'letters' to her family, and produces copious cartoon-like drawings which she annotates, with the result that multiple examples of her humour are available in permanent form. We present examples of Grace's use of puns, jokes, neologisms, 'portmanteau' words, irreverent humour, irony, sarcasm and word play based on her obsessional interests. The examples are used to illustrate the forms and content of Grace's humour, and are discussed in relation to current theories of autism and of normal humour.

Adult↗

Using tests of false belief with children with autism: how valid and reliable are they?

Twenty-two children with autism were given four tests of false belief understanding: the Sally-Anne task, two variants of the deceptive box task, and the three boxes task. The overall consistency of the children's performance was high, 77 percent of the participants either passing or failing all of the tasks. The convergent validity (across-task consistency) of the deceptive box and the three boxes paradigms was high, and the convergent validity of the three boxes and Sally-Anne tasks was also acceptable. However, a weaker level of convergent validity was found for the deceptive box and Sally-Anne tasks, suggesting that these paradigms test slightly different aspects of cognition. The reliability (within-child consistency) of the children's performances across two versions of the deceptive box task was high. These findings are discussed in terms of their practical implications for practitioners and researchers.

Adolescent↗

Dual action of octopamine on glucose transport into adipocytes: inhibition via beta3-adrenoceptor activation and stimulation via oxidation by amine oxidases.

Octopamine, which is closely related to norepinephrine, acts as a neurotransmitter in invertebrates and is a trace amine with undefined properties in vertebrates. The octopaminergic receptors identified in insects are targets of various pesticides but are absent in vertebrates. We have established that octopamine stimulates fat cell lipolysis in mammals via activation of beta3-adrenoceptors (ARs), whereas this amine has been described elsewhere as an alpha2-AR agonist and as a substrate for monoamine oxidase (MAO) or semicarbazide-sensitive amine oxidase (SSAO). Because we have recently reported that amine oxidase substrates promote glucose transport in rat and human adipocytes, the in vitro octopamine effects on lipolysis and glucose uptake were reassessed by using adipocytes from beta3-AR-deficient mice. The lipolytic effect and the counter-regulation of insulin action on glucose transport provoked by 0.1 to 1 mM octopamine or by 1 microM beta3-AR agonists found in control animals disappeared in adipocytes from beta3-AR-deficient mice. This revealed an insulin-like effect of octopamine on glucose uptake, which was dependent on its oxidation by MAO or SSAO, as was the case for tyramine and benzylamine, devoid of beta3-adrenergic agonism. Similarly, octopamine promoted glucose transport in human adipocytes and exhibited a weaker lipolytic stimulation than in rodent adipocytes. These findings indicate that, besides its lipolytic activity, octopamine exerts, at millimolar dose, dual effect on glucose transport in adipocytes: counteracting insulin action via beta3-AR activation and stimulating basal transport via its oxidation by MAO or SSAO.

Adipocytes↗

Convergent neuroanatomical and behavioural evidence of an amygdala hypothesis of autism.

In this study we report a convergence of behavioural and neuroanatomical evidence in support of an amygdala hypothesis of autism. We find that people with high-functioning autism (HFA) show neuropsychological profiles characteristic of the effects of amygdala damage, in particular selective impairment in the recognition of facial expressions of fear, perception of eye-gaze direction, and recognition memory for faces. Using quantitative magnetic resonance (MR) image analysis techniques, we find that the same individuals also show abnormalities of medial temporal lobe (MTL) brain structure, notably bilaterally enlarged amygdala volumes. These results combine to suggest that developmental malformation of the amygdala may underlie the social-cognitive impairments characteristic of HFA. This malformation may reflect incomplete neuronal pruning in early development.

Adolescent↗

Nucleotide-binding domain 1 of cystic fibrosis transmembrane conductance regulator production of a suitable protein for structural studies.

Cystic fibrosis is caused by mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR). This protein belongs to the large ATP-binding cassette (ABC) family of transporters. Most patients with cystic fibrosis bear a mutation in the nucleotide-binding domain 1 (NBD1) of CFTR, which plays a key role in the activation of the channel function of CFTR. Determination of the three dimensional structure of NBD1 is essential to better understand its structure-function relationship, and relate it to the biological features of CFTR. In this paper, we report the first preparation of recombinant His-tagged NBD1, as a soluble, stable and isolated domain. The method avoids the use of renaturing processes or fusion constructs. ATPase activity assays show that the recombinant domain is functional. Using tryptophan intrinsic fluorescence, we point out that the local conformation, in the region of the most frequent mutation DeltaF508, could differ from that of the nucleotide-binding subunit of histidine permease, the only available ABC structure. We have undertaken three dimensional structure determination of NBD1, and the first two dimensional 15N-1H NMR spectra demonstrate that the domain is folded. The method should be applicable to the structural studies of NBD2 or of other NBDs from different ABC proteins of major biological interest, such as multidrug resistance protein 1 or multidrug resistance associated protein 1.

Adenosine Triphosphatases↗