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Physiological Regulation (physiological + regulation)
Selected AbstractsA Longitudinal Examination of Physiological Regulation in Cocaine-Exposed Infants Across the First 7 Months of LifeINFANCY, Issue 1 2009Pamela Schuetze This study examined the association between prenatal exposure to cocaine and physiological regulation across the first 7 months of age. Measures of respiratory sinus arrhythmia (RSA) were obtained from 169 (82 cocaine-exposed and 87 nonexposed) infants during baseline periods at 1 month and 7 months of age and during tasks designed to elicit positive and negative affect at 7 months of age. After controlling for maternal age, gestational age, and obstetrical risk, structural equation modeling indicated that the association between prenatal exposure to cocaine and baseline RSA at 7 months of age was direct even in the presence of an indirect effect through baseline RSA at 1 month of age. There were no indirect effects through maternal affect during mother-infant interactions assessed at 1 month of age. Analyses also indicated a direct association between prenatal exposure to cocaine and RSA regulation to negative affect at 7 months of age. [source] Physiological regulation linked with physical activity and healthTHE JOURNAL OF PHYSIOLOGY, Issue 23 2009M.J. Joyner No abstract is available for this article. [source] Exposure to Interparental Conflict and Children's Adjustment and Physical Health: The Moderating Role of Vagal ToneCHILD DEVELOPMENT, Issue 6 2001Mona El-Sheikh Physiological regulation, as indexed by baseline vagal tone and delta vagal tone (the change in vagal tone during an attention-demanding or challenging task), was examined as a moderator in the relations between exposure to verbal and physical parental marital conflict and children's adjustment and physical health. Higher vagal tone was posited to serve a protective function (i.e., buffer) for children exposed to higher levels of marital conflict. Seventy-five 8- to 12-year-olds and their mothers completed measures of parental conflict, and children's adjustment and physical health. Children's vagal tone was assessed during baseline conditions and during exposure to an audiotaped interadult argument. Results indicate that higher vagal tone buffered children against increased externalizing, internalizing, and health problems related to exposure to more frequent marital conflict, especially verbal conflict. Further, higher levels of delta vagal tone protected boys against externalizing problems associated with verbal conflict, and health problems associated with physical conflict. [source] Abnormalities in cardiac and respiratory function observed during seizures in childhoodDEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 1 2005Mary E O'Regan MRCP MRCPCH The aim of this study was to observe any changes in cardiac and respiratory function that occur during seizures. Thirty-seven children (20 males, 17 females; median age 7y 6mo, range 1y 6mo to 15y 6mo) were studied. We recorded electroencephalograms, respiratory rate, heart rate, electrocardiograms, blood pressure, oxygen saturation, heart rate variability (time domain analysis), and cardiac vagal tone. A respiratory pause was defined as an interruption in respiration lasting more than 3s but less than 15s. Apnoea was defined as absence of respiration for more than 15s. Tachypnoea was defined as a 10% increase in respiratory rate from the pre-ictal baseline. Bradypnoea was defined as a 10% decrease in respiratory rate from the pre-ictal baseline. Significant hypoxia was defined as a saturation of less than 85%. A significant change in heart rate was taken as a 10% increase or decrease below the baseline rate. Data were obtained from 101 seizures: 40 focal seizures, 21 generalized seizures, and 40 absences. Focal seizures were frequently associated with significant respiratory abnormalities, tachypnoea in 56%, apnoea in 30%, frequent respiratory pauses in 70%, and significant hypoxaemia in 40%. The changes seen in respiratory rate were statistically significant. Changes in cardiac parameters, an increase or decrease in heart rate, were observed in only 26% of focal seizures and 48% of generalized seizures. We conclude that seizure activity can disrupt normal physiological regulation and control of respiratory and cardiac activity. [source] Hedgehog and Fgf signaling pathways regulate the development of tphR -expressing serotonergic raphe neurons in zebrafish embryosDEVELOPMENTAL NEUROBIOLOGY, Issue 3 2004H. Teraoka Abstract Serotonin (5HT) plays major roles in the physiological regulation of many behavioral processes, including sleep, feeding, and mood, but the genetic mechanisms by which serotonergic neurons arise during development are poorly understood. In the present study, we have investigated the development of serotonergic neurons in the zebrafish. Neurons exhibiting 5HT-immunoreactivity (5HT-IR) are detected from 45 h postfertilization (hpf) in the ventral hindbrain raphe, the hypothalamus, pineal organ, and pretectal area. Tryptophan hydroxylases encode rate-limiting enzymes that function in the synthesis of 5HT. As part of this study, we cloned and analyzed a novel zebrafish tph gene named tphR. Unlike two other zebrafish tph genes (tphD1 and tphD2), tphR is expressed in serotonergic raphe neurons, similar to tph genes in mammalian species. tphR is also expressed in the pineal organ where it is likely to be involved in the pathway leading to synthesis of melatonin. To better understand the signaling pathways involved in the induction of the serotonergic phenotype, we analyzed tphR expression and 5HT-IR in embryos in which either Hh or Fgf signals are abrogated. Hindbrain 5HT neurons are severely reduced in mutants lacking activity of either Ace/Fgf8 or the transcription factor Noi/Pax2.1, which regulates expression of ace/fgf8, and probably other genes encoding signaling proteins. Similarly, serotonergic raphe neurons are absent in embryos lacking Hh activity confirming a conserved role for Hh signals in the induction of these cells. Conversely, over-activation of the Hh pathway increases the number of serotonergic neurons. As in mammals, our results are consistent with the transcription factors Nk2.2 and Gata3 acting downstream of Hh activity in the development of serotonergic raphe neurons. Our results show that the pathways involved in induction of hindbrain serotonergic neurons are likely to be conserved in all vertebrates and help establish the zebrafish as a model system to study this important neuronal class. © 2004 Wiley Periodicals, Inc. J Neurobiol 60: 275,288, 2004 [source] Trace metals, stable isotope ratios, and trophic relations in seabirds from the North Pacific OceanENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 12 2005John E. Elliott Abstract Trace elements including mercury, cadmium, selenium, and stable nitrogen isotope ratios (,15N) were measured in tissues of Pacific seabirds. Two species of albatross (Diomedea immutabilis, Diomedea nigripes), four species of shearwaters (Puffinus bulleri, Puffinus carneipes, Puffinus griseus, Puffinus tenuirostris), northern fulmar (Fulmarus glacialis), and horned puffin (Fratercula corniculata) were collected opportunistically by an experimental fishery in the North Pacific Ocean. Two species each of petrels (Oceanodroma leucorhoa, Oceanodroma furcata) and auklets (Ptychoramphus aleuticus, Cerorhinca monocerata) were collected at breeding colonies on the north coast of British Columbia, Canada. Concentrations of toxic trace metals varied considerably among the pelagic nonbreeders; highest concentrations consistently were in D. nigripes (e.g., Hg), 70-fold greater than F. corniculata (e.g., Cd), eightfold greater than P. tenuirostris (e.g., Se), and fourfold greater than F. corniculata. Most essential trace elements varied little among species, consistent with physiological regulation. Values for ,15N correlated positively with hepatic Se (r = 0.771, p = 0.025) and negatively with Co (r = 0.817, p = 0.013). Among the four breeding species, there were significant positive associations for ,15N in muscle and hepatic Se (r = 0.822, p = 0.002), Hg (r = 0.744, p = 0.0001), and Cd (r = 0.589, p = 0.003). Differences in time scales integrated by ,15N versus trace metals in tissues probably reduced the apparent associations between trace-metal exposure and diet. [source] A Longitudinal Examination of Physiological Regulation in Cocaine-Exposed Infants Across the First 7 Months of LifeINFANCY, Issue 1 2009Pamela Schuetze This study examined the association between prenatal exposure to cocaine and physiological regulation across the first 7 months of age. Measures of respiratory sinus arrhythmia (RSA) were obtained from 169 (82 cocaine-exposed and 87 nonexposed) infants during baseline periods at 1 month and 7 months of age and during tasks designed to elicit positive and negative affect at 7 months of age. After controlling for maternal age, gestational age, and obstetrical risk, structural equation modeling indicated that the association between prenatal exposure to cocaine and baseline RSA at 7 months of age was direct even in the presence of an indirect effect through baseline RSA at 1 month of age. There were no indirect effects through maternal affect during mother-infant interactions assessed at 1 month of age. Analyses also indicated a direct association between prenatal exposure to cocaine and RSA regulation to negative affect at 7 months of age. [source] Lymphatics at the crossroads of angiogenesis and lymphangiogenesisJOURNAL OF ANATOMY, Issue 6 2004Claudio Scavelli Abstract The lymphatic system is implicated in interstitial fluid balance regulation, immune cell trafficking, oedema and cancer metastasis. However, the sequence of events that initiate and coordinate lymphatic vessel development (lymphangiogenesis) remains obscure. In effect, the understanding of physiological regulation of lymphatic vasculature has been overshadowed by the greater emphasis focused on angiogenesis, and delayed by a lack of specific markers, thereby limiting this field to no more than a descriptive characterization. Recently, new insights into lymphangiogenesis research have been due to the discovery of lymphatic-specific markers and growth factors of vascular endothelial growth factor (VEGF) family, such as VEGF-C and VEGF-D. Studies using transgenic mice overexpressing VEGF-C and VEGF-D have demonstrated a crucial role for these factors in tumour lymphangiogenesis. Knowledge of lymphatic development has now been redefined at the molecular level, providing an interesting target for innovative therapies. This review highlights the recent insights and advances into the field of lymphatic vascular research, outlining the most important aspects of the embryo development, structure, specific markers and methods applied for studying lymphangiogenesis. Finally, molecular mechanisms involved in the regulation of lymphangiogenesis are described. [source] Interspecific variations of otolith chemistry in estuarine fish nurseriesJOURNAL OF FISH BIOLOGY, Issue 10 2008P. Reis-Santos Otolith chemical composition differed between juveniles of five fish species (Solea solea, Solea senegalensis, Platichthys flesus, Diplodus vulgaris and Dicentrarchus labrax) in nursery areas of six estuaries along the Portuguese coast (Douro, Ria de Aveiro, Mondego, Tejo, Sado and Mira). Spatially consistent patterns in the concentration of some elements were responsible for differences between species. Discrimination of estuaries using data from all species simultaneously averaged 44·7% of correctly classified cases, whilst discrimination of species averaged 76·2%. Moreover, species-related patterns in otolith fingerprints were highlighted when comparing species for each estuarine nursery area, with intra estuarine species discrimination averages ranging from 86·2 to 100·0%. Similarities in the otolith elemental fingerprints were larger between species with close phylogeny and ecology, particularly between flatfish and perciform species. In addition to the differences in physiological regulation of species, specific microhabitat use in a common environment was suggested as a relevant factor for the differentiation of otolith chemistry among species occurring in the same locations. Despite positive results in specific estuaries, variation in otolith composition limited the use of species as proxies to classify others to their system of origin. [source] Tissue- and agonist-specific regulation of human and murine plasminogen activator inhibitor-1 promoters in transgenic miceJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 11 2003M. Eren Summary., Numerous studies have described regulatory factors and sequences that control transcriptional responses in vitro. However, there is a paucity of information on the qualitative and quantitative regulation of heterologous promoters using transgenic strategies. In order to investigate the physiological regulation of human plasminogen activator inhibitor type-1 (hPAI-1) expression in vivo compared to murine PAI-1 (mPAI-1) and to test the physiological relevance of regulatory mechanisms described in vitro, we generated transgenic mice expressing enhanced green fluorescent protein (EGFP) driven by the proximal ,2.9 kb of the hPAI-1 promoter. Transgenic animals were treated with Ang II, TGF-,1 and lipopolysaccharide (LPS) to compare the relative activation of the human and murine PAI-1 promoters. Ang II increased EGFP expression most effectively in brain, kidney and spleen, while mPAI-1 expression was quantitatively enhanced most prominently in heart and spleen. TGF-,1 failed to induce activation of the hPAI-1 promoter but potently stimulated mPAI-1 in kidney and spleen. LPS administration triggered robust expression of mPAI-1 in liver, kidney, pancreas, spleen and lung, while EGFP was induced only modestly in heart and kidney. These results indicate that the transcriptional response of the endogenous mPAI-1 promoter varies widely in terms of location and magnitude of response to specific stimuli. Moreover, the physiological regulation of PAI-1 expression likely involves a complex interaction of transcription factors and DNA sequences that are not adequately replicated by in vitro functional studies focused on the proximal ,2.9 kb promoter. [source] Competitive AMPA receptor antagonistsMEDICINAL RESEARCH REVIEWS, Issue 2 2007Daniela Catarzi Abstract Glutamic acid (Glu) is the major excitatory neurotransmitter in the mammalian central nervous system (CNS) where it is involved in the physiological regulation of different processes. It has been well established that excessive endogenous Glu is associated with many acute and chronic neurodegenerative disorders such as cerebral ischaemia, epilepsy, amiotrophic lateral sclerosis, Parkinson's, and Alzheimer's disease. These data have consequently added great impetus to the research in this field. In fact, many Glu receptor antagonists acting at the N -methyl- D -aspartic acid (NMDA), 2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propionic acid (AMPA), and/or kainic acid (KA) receptors have been developed as research tools and potential therapeutic agents. Ligands showing competitive antagonistic action at the AMPA type of Glu receptors were first reported in 1988, and the systemically active 2,3-dihydroxy-6-nitro-7-sulphamoyl-benzo[f]quinoxaline (NBQX) was first shown to have useful therapeutic effects in animal models of neurological disease in 1990. Since then, the quinoxaline template has represented the backbone of various competitive AMPA receptor antagonists belonging to different classes which had been developed in order to increase potency, selectivity and water solubility, but also to prolong the "in vivo" action. Compounds that present better pharmacokinetic properties and less serious adverse effects with respect to the others previously developed are undergoing clinical evaluation. In the near future, the most important clinical application for the AMPA receptor antagonists will probably be as neuroprotectant in neurodegenerative diseases, such as epilepsy, for the treatment of patients not responding to current therapies. The present review reports the history of competitive AMPA receptor antagonists from 1988 up to today, providing a systematic coverage of both the open and patent literature. © 2006 Wiley Periodicals, Inc. [source] Orchid mycorrhiza: implications of a mycophagous life styleOIKOS, Issue 3 2009Hanne N. Rasmussen Orchid mycorrhiza probably affects about 25,000 plant species and thus roughly one tenth of all higher plants. Histologically, this symbiosis resembles other kinds of endomycorrhiza, the fungal hyphae growing within living plant cells. Considerable evidence, however, suggests that it is not a two-way exchange relationship and thus not potentially mutualistic, such as the wide-spread endomycorrhiza between plants and Glomalean fungi, known as arbuscular mycorrhiza. During the achlorophyllous seedling stage orchids are obligately dependent on the fungi; some species remain so through life, while others establish photosynthesis but to varying degrees remain facultatively dependent of /responsive to fungal infection as adults. None of the fungi involved are so far known to depend on the symbiosis with orchids. Transfer of organic carbon compounds from hyphae to the orchid has been demonstrated repeatedly, but it is not clear to what extent this takes place during a biotrophic phase while the intracellular hyphae remain intact, or during the subsequent extensive degradation of the hyphal coils. The advantage of viewing orchid mycorrhiza basically as a unilateral mycophagous relationship, in spite of hypothetical beneficial spin-offs to the mycobiont, is that it provides a conceptual framework similar to that of other parasitic or fungivore relationships; mechanisms known in such relationships could be searched for in future studies of the orchid,fungus symbiosis. These could include mechanisms for recognition, attraction and selection of fungi, physiological regulation of internal hyphal growth, breakdown, and material transfer, nutritional consequences of the plant's preference(s) and trophic changes, fungal avoidance mechanisms, and consequences at population and ecosystem levels. A whole range of possible life strategies becomes apparent that could support divergent evolution and lead to the proliferation of species that has indeed occurred in the orchid family. We outline some of the possible physiological mechanisms and ecological implications of this approach. [source] Distribution of corticotropin-releasing hormone in the developing zebrafish brainTHE JOURNAL OF COMPARATIVE NEUROLOGY, Issue 4 2007Gayathri Chandrasekar Abstract Corticotropin-releasing hormone (CRH) plays a central role in the physiological regulation of the hypothalamus-pituitary-adrenal/interrenal axis mediating endocrine, behavioral, autonomic, and immune responses to stress. Despite the wealth of knowledge about the physiological roles of CRH, the genetic mechanisms by which CRH neurons arise during development are poorly understood. As a first step toward analyzing the molecular and genetic pathways involved in CRH lineage specification, we describe the developmental distribution of CRH neurons in the embryonic zebrafish, a model organism for functional genomics and developmental biology. We searched available zebrafish expressed sequence tag (EST) databases for CRH-like sequences and identified one EST that contained the complete zebrafish CRH open reading frame (ORF). The CRH precursor sequence contained a signal peptide, the CRH peptide, and a cryptic peptide with a conserved sequence motif. RT-PCR analysis showed crh expression in a wide range of adult tissues as well as during embryonic and larval stages. By whole-mount in situ hybridization histochemistry, discrete crh -expressing cell clusters were found in different parts of the embryonic zebrafish brain, including telencephalon, preoptic region, hypothalamus, posterior tuberculum, thalamus, epiphysis, midbrain tegmentum, and rostral hindbrain and in the neural retina. The localization of crh mRNA within the preoptic region is consistent with the central role of CRH in the teleost stress response through activation of the hypothalamic-pituitary-interrenal axis. The widespread distribution of CRH-synthesizing cells outside the preoptic region suggests additional functions of CRH in the embryonic zebrafish brain. J. Comp. Neurol. 505:337,351, 2007. © 2007 Wiley-Liss, Inc. [source] Effect of P2X7 receptor knockout on exocrine secretion of pancreas, salivary glands and lacrimal glandsTHE JOURNAL OF PHYSIOLOGY, Issue 18 2010Ivana Novak The purinergic P2X7 receptors are expressed in different cell types where they have varied functions, including regulation of cell survival. The P2X7 receptors are also expressed in exocrine glands, but their integrated role in secretion is unclear. The aim of our study was to determine whether the P2X7 receptors affect fluid secretion in pancreas, salivary glands and tear glands. We monitored gland secretions in in vivo preparations of wild-type and P2X7,/, (Pfizer) mice stimulated with pilocarpine. In cell preparations from pancreas, parotid and lacrimal glands we measured ATP release and intracellular Ca2+ activity using Fura-2. The data showed that pancreatic secretion and salivary secretions were reduced in P2X7,/, mice, and in contrast, tear secretion was increased in P2X7,/, mice. The secretory phenotype was also dependent on the sex of the animal, such that males were more dependent on the P2X7 receptor expression. ATP release in all cell preparations could be elicited by carbachol and other agonists, and this was independent of the P2X7 receptor expression. ATP and carbachol increased intracellular Ca2+ activity, but responses depended on the gland type, presence of the P2X7 receptor and the sex of the animal. Together, these results demonstrate that cholinergic stimulation leads to release of ATP that can via P2X7 receptors up-regulate pancreatic and salivary secretion but down-regulate tear secretion. Our data also indicate that there is an interaction between purinergic and cholinergic receptor signalling and that function of the P2X7 receptor is suppressed in females. We conclude that the P2X7 receptors are important in short-term physiological regulation of exocrine gland secretion. [source] Effect of corazonin and crustacean cardioactive peptide on heartbeat in the adult American cockroach (Periplaneta americana)ARCHIVES OF INSECT BIOCHEMISTRY AND PHYSIOLOGY (ELECTRONIC), Issue 2 2006Karel Sláma Abstract Changes in the frequency of cardiac pulsations have been monitored in the decapitated body of adult P. americana before and 5 h after the injections of [Arg7]-corazonin and CCAP, using newly invented touch-free, noninvasive optocardiographic methods. Relatively large dosages of these peptides (10,6 M concentrations in the body) had no effect on the rate of the heartbeat beyond the Ringer control limits. It has been concluded, therefore, that Corazonin and CCAP, which are currently cited in the literature as "the most potent cardiostimulating peptides" in insects, have no effect on the physiological regulation of cardiac functions in the living body. Arch Insect Biochem Physiol 62:91,103, 2006. © 2006 Wiley-Liss, Inc. [source] Phosphodiesterase-linked inhibition of nonmicturition activity in the isolated bladderBJU INTERNATIONAL, Issue 9 2004J.I. Gillespie Over the past few months Gillespie has published several papers in the BJU International investigating the overactive bladder and BOO, using novel models and theories. This next paper continues these concepts and shows that the mechanisms influencing the frequency of agonist-induced phasic activity in the isolated bladder model is slowed by cAMP. These findings will have important implications in future pharmacological strategies in the overactive bladder. OBJECTIVE To explore the influence of intracellular cAMP on phasic activity in the isolated bladder (phasic rises in intravesical pressure associated with waves of contraction and local stretches that can be activated by muscarinic or nicotinic agonists), as it has been argued that this activity underlies nonmicturition contractions, and that it contributes to the generation and modulation of afferent nerve activity. MATERIALS AND METHODS Isolated whole bladders from female guinea pigs (270,300 g) were cannulated via the urethra and suspended in a chamber containing oxygenated Tyrode solution at 33,35 °C. Bladder pressure was recorded and pharmacological agents added to the solution bathing the abluminal surface of the bladder. RESULTS Forskolin (1,3 µmol/L), an activator of adenyl cyclase, reduced the frequency and amplitude of the phasic activity induced by the muscarinic agonist arecaidine (300 nmol/L). There were similar changes in frequency and amplitude in bladders exposed to the nonspecific phosphodiesterase (PDE) inhibitor iso-butyl-methyl-xanthene (IBMX). The actions of specific PDE inhibitors were explored to assess which isoenzymes might be responsible for regulating phasic activity. ENHA (PDE-2), zaprinast (PDE-5, -6, -8, -9 and -11) and siguazodan (PDE-3) had no effect. Zardavarine (PDE-3, -4) and Ro 20-1724 (PDE-4) reduced both the frequency and amplitude of the phasic activity. Nerve-mediated rises in intravesical pressure were also inhibited by Ro 20-1724, and the inhibition was more pronounced at 6.5 Hz than at 30 Hz stimulation. Ro 20-1724 inhibited nerve-mediated fluctuations induced by prolonged (200 s) stimulation at 6.5 Hz. CONCLUSION The mechanisms influencing the frequency of agonist-induced phasic activity in the isolated bladder are slowed by cAMP. Degradation of intracellular cAMP in the cells responsible for phasic activity appears to involve primarily PDE-4. The importance of these observations in relation to the overall physiological regulation of the bladder are discussed, and the possible importance of these findings in the development of pharmacological strategies to modulated bladder activity reviewed. [source] Inhibition of calcium-calmodulin kinase restores nitric oxide production and signaling in submandibular glands of a mouse model of salivary dysfunctionBRITISH JOURNAL OF PHARMACOLOGY, Issue 8 2004Florencia Rosignoli Nitric oxide is an intracellular and diffusible messenger of neurotransmitters involved in salivary secretion, as well as an inflammatory mediator in salivary gland diseases. It is synthesized by three different isoforms of nitric oxide synthase (NOS), each subject to a fine transcriptional, post-transcriptional and/or post-translational regulation. Our purpose was to study the possible mechanisms leading to NOS downregulation in submandibular glands of normal mice and in the nonobese diabetic (NOD) mouse model of salivary dysfunction with lower NOS activity. NOS activity and cGMP accumulation were determined by radioassays in submandibular glands of both mice in the presence of the protein kinase inhibitors KN-93 and bisindolylmaleimide. NOS I mRNA and protein expression and localization were assessed by RT,PCR, Western blot and immunohistochemistry. A downregulatory effect of calcium,calmodulin kinase II (CaMK II) on NOS activity in submandibular glands of both NOD and BALB/c mice was observed. Our results are consistent with a physiological regulation of NOS activity by this kinase but not by PKC in normal BALB/c mice. They are also supportive of a role for CaMK II in the lack of detectable NOS activity in submandibular glands of NOD mice. KN-93 also restored cGMP accumulation in NOD submandibular glands. The downregulation of NOS in NOD mice seems to be mainly mediated by this kinase rather than the result of a lower expression or different cellular localization of the enzyme. It was not related to different substrate or cofactors availability either. British Journal of Pharmacology (2004) 143, 1058,1065. doi:10.1038/sj.bjp.0705952 [source] Effects of moisturization on epidermal homeostasis and differentiationCLINICAL & EXPERIMENTAL DERMATOLOGY, Issue 1 2007R. W. Short Summary Moisturizers are commonly used for routine skin care. This study assessed the effects of a moisturizer on barrier function, epidermal architecture, keratinocyte proliferation, and physiological regulation of the epidermis in photoaged but otherwise normal skin. Fifteen women with moderately photoaged forearms were treated twice a day for 4 weeks with a moisturizer containing dimethicone and glycerine. Baseline and post-treatment transepidermal water loss (TEWL) and ipsilateral forearm biopsies were obtained. Epidermal thickness, melanin levels, keratinocyte proliferation, and expression of keratins were evaluated. Induction of keratins 6 and 16, commonly associated with keratinocyte proliferation and wound healing, was observed. Epidermal thickness increased by 0.019 mm (P = 0.005), barrier function improved (TEWL decreased by 13%) and melanin intensity decreased (P = 0.004). Even nonxerotic, photoaged skin may appear younger, benefiting structurally and functionally from routine use of moisturizers containing dimethicone and glycerine. [source] Functional Roles Of KATP Channels In Vascular Smooth MuscleCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 4 2002Joseph E Brayden SUMMARY 1. ATP-sensitive potassium channels (KATP) are present in vascular smooth muscle cells and play important roles in the vascular responses to a variety of pharmacological and endogenous vasodilators. 2. The KATP channels are composed of four inwardly rectifying K+ channel subunits and four regulatory sulphonylurea receptors. The KATP channels are inhibited by intracellular ATP and by sulphonylurea agents. 3. Pharmacological vasodilators such as cromakalim, pinacidil and diazoxide directly activate KATP channels. The associated membrane hyperpolarization closes voltage-dependent Ca2+ channels, which leads to a reduction in intracellular Ca2+ and vasodilation. 4. Endogenous vasodilators such as calcitonin gene-related peptide, vasoactive intestinal polypeptide, prostacylin and adenosine activate KATP by stimulating the formation of cAMP and increasing the activity of protein kinase A. Part of the mechanism of contraction of endogenous vasoconstrictors is due to inhibition of KATP channels. 5. The KATP channels appear to be tonically active in some vascular beds and contribute to the physiological regulation of vascular tone and blood flow. These channels also are activated under pathophysiological conditions, such as hypoxia, ischaemia, acidosis and septic shock, and, in these disease states, may play an important role in the regulation of tissue perfusion. [source] Effects of TNF-alpha antagonism on E-selectin in obese subjects with metabolic dysregulationCLINICAL ENDOCRINOLOGY, Issue 1 2010Markella V. Zanni Summary Objective, Endothelial adhesion molecules like E-selectin play an important role in leukocyte recruitment and development of atherosclerotic plaque. E-selectin is increased in obesity, yet little is known regarding the specific factors contributing to elevated E-selectin in obesity and whether tumour necrosis factor alpha (TNF-alpha) increases E-selectin in vivo in this population. The objectives of this study were to: (1) determine the body composition, metabolic and inflammatory factors associated with increased E-selectin and (2) determine the role of TNF-alpha in the physiological regulation of E-selectin by antagonism of TNF-alpha with etanercept among obese subjects. Methods, E-selectin levels, body composition, metabolic parameters and inflammatory cytokines were assessed in 51 obese subjects and 37 non-obese healthy controls. Obese subjects were randomized to etanercept 50 mg weekly or placebo for 4 weeks. Changes in E-selectin were compared between treatment groups. Results, Obese subjects had higher E-selectin than non-obese controls (47·4 [32·7,58·8] vs. 27·2 [20·3,42·1] ng/ml, obese vs. non-obese, P < 0·0001). E-selectin was significantly associated with multiple body composition measures and metabolic parameters, along with specific measures of TNF-alpha activation, including soluble tumour necrosis factor receptors 1 (P = 0·03) and 2 (P = 0·02). In multivariate modelling, visceral adipose tissue, but not other measures of body composition, remained significantly associated with E-selectin. Among obese subjects, treatment with etanercept significantly decreased E-selectin (,5·7 ± 8·7 vs. 0·5 ± 6·0 ng/ml, etanercept vs. placebo, P = 0·005). Conclusions, E-selectin is increased in obesity, in relationship to increased visceral adiposity and markers of TNF-alpha activation. TNF-alpha antagonism with etanercept reduces E-selectin in obese subjects, providing evidence that the systemic circulatory release of E-selectin is regulated at least in part by TNF-alpha in obesity. [source] Hormonal control of somatic cell oocyte interactions during ovarian follicle development,MOLECULAR REPRODUCTION & DEVELOPMENT, Issue 3 2004Catherine M.H. Combelles Abstract In the mammalian ovarian follicle, paracrine signaling between the oocyte and somatic granulosa cells is bidirectional but the structural basis and physiological regulations of communication between gametic and somatic compartments remain unknown. The present experiments were designed to test the hypothesis that follicle stimulating hormone (FSH) regulates the ability of granulosa cells to make connections with the oocyte. We show that in prepubertal unprimed mice and mice carrying a targeted deletion of the FSH, subunit gene, granulosa cells exhibit orientation towards the oocyte manifest by the elaboration of transzonal projections (TZPs) and "apical" centrosome positioning at sites of granulosa-zona contact. In vivo FSH treatment results in a retraction of TZPs. Coincident with TZP retraction induced by FSH are changes in oocyte transcriptional activity and meiotic competence, which suggests one means by which the oocyte-granulosa cell dialogue may be modulated during development of ovarian follicles. Mol. Reprod. Dev. 69: 347,355, 2004. © 2004 Wiley-Liss, Inc. [source] | |||||||||||||||||||