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Metabolic and functional responses to extracellular Mg2+ concentration ([Mg2+]o) were studied in ... more Metabolic and functional responses to extracellular Mg2+ concentration ([Mg2+]o) were studied in perfused rat heart. Elevations of [Mg2+]ofrom 1.2 to 2.4, 5.0, and 8.0 mM dose dependently reduced contractile function and myocardial oxygen consumption (MV˙o 2) up to 80%. Intracellular Mg2+ concentration ([Mg2+]i) remained stable (0.45-0.50 mM) during perfusion with 1.2-5.0 mM [Mg2+]obut increased to 0.81 ± 0.14 mM with 8.0 mM [Mg2+]o. Myocardial ATP was unaffected by [Mg2+]o,phosphocreatine (PCr) increased up to 25%, and Pi declined by up to 50%. Free energy of ATP hydrolysis (Δ G ATP) increased from -60 to -64 kJ/mol. Adenosine efflux declined in parallel with changes in MV˙o 2 and [AMP]. At comparable workload and MV˙o 2, the effects of [Mg2+]oon cytosolic free energy were mimicked by reduced extracellular Ca2+ concentration ([Ca2+]o) or Ca2+ antagonism with verapamil. Moreover, functional and energetic effects of [Mg2+]owere reversed by elevated [Ca2+]o. Despite similar reductions...

Reproductive Biology Insights, 2013

Despite continuing significant research efforts and an increasing prevalence of preterm labor (PT... more Despite continuing significant research efforts and an increasing prevalence of preterm labor (PTL) worldwide, a comprehensive understanding of the mechanisms involved remains to be established; such is the complexity of the interactions involved. Closing the knowledge gaps in this field would afford an opportunity to improve mortality and morbidity rates on a global scale. Early identification of pregnancies at risk of PTL would increase the possibility of delaying birth (where appropriate) prior to initiation of labor. This requires identification of appropriate biomarkers that are readily detectable in easily obtained clinical samples. A family of arachidonic acid metabolites, called eicosanoids. Eicosanoids have shown promise as possible diagnostic biomarkers for PTL. The inherent problems of antibody cross-reactivity in immunoassay methods has, however, resulted in possible misinterpretation of past results. The following mini-review outlines the necessity of such diagnostic targets and the problem with previous research methods and also summarizes recent findings in the field.

There is significant research dedicated to fibroin and sericin, the two major proteinaceous compo... more There is significant research dedicated to fibroin and sericin, the two major proteinaceous components of the silk threads produced by the domesticated silkworm, Bombyx mori. While fibroin is accepted as an established biomaterial, sericin (BMSS) has been largely neglected in this respect on the account of a hypothetical allergenic activity. Research over the past decade, including our previous study (Prog Biomater 2:14, 2013), demonstrated the biocompatibility of sericin and feasibility of its use as a biomaterial. However, the current procedures for isolating BMSS from the raw silk cocoons can only provide degraded proteins, where the size and distribution of their molecular masses are significantly altered. Based on the plausible assumption that such effects can have a negative impact on the properties of sericin as a biomaterial, in this study we investigated comparatively four different extraction procedures in order to find the method that would cause the least hydrothermal degradation of BMSS. The products resulting from commonly used procedures (extraction in boiling water, alkaline extraction, and extraction in autoclave) were compared to those resulting from aqueous extraction in mild conditions as described a long time ago by Anderlini. The molecular mass distribution in BMSS resulting from each procedure was examined by electrophoretic analysis performed on sodium dodecyl sulphate-polyacrylamide gel (SDS-PAGE), while the conformational changes pertaining to secondary structure of BMSS were evaluated by Fourier transform infrared-attenuated total reflectance (FTIR-ATR) spectrometry. The electrophoretograms indicated that the aqueous extraction in mild conditions conducted at 50°C for durations up to 4 weeks, with/without stirring, afforded the least degraded BMSS. The infrared spectrometric analysis showed that BMSS resulting from the mild extraction method contained predominantly b-sheet conformations, while the more degradative methods (alkaline, autoclave) led to BMSS where the random-coil conformations were preferential. The long-duration aqueous extraction at 50°C (but not at 60°C) appeared as a valid option for obtaining BMSS products where the hydrothermally induced fragmentation of the polypeptidic components is minimized. Keywords Bombyx mori silk Á Silk proteins Á Sericin Á Methods of extraction Á Molecular mass distribution Á Electrophoresis Á FTIR analysis Abbreviations BMSF Bombyx mori silk fibroin BMSS Bombyx mori silk sericin FTIR-ATR Fourier transform infrared-attenuated total reflectance MMCO Molecular-mass cutoff SDS-PAGE Sodium dodecyl sulphate-polyacrylamide gel electrophoresis

European Journal of Gastroenterology & Hepatology, 1999

Nicotine may be of therapeutic value in ulcerative colitis (UC), although its mechanism of action... more Nicotine may be of therapeutic value in ulcerative colitis (UC), although its mechanism of action has not been established. To examine the effect of a solution of nicotine on sustained resting pressure (tone) and contractile activity in the human colon. Ten healthy volunteers, and seven with UC in symptomatic remission took part; all were non-smokers. All 17 subjects were given nicotine or placebo solution on two separate occasions in a randomized sequence. A water-perfused manometry catheter, with openings at 5, 10 and 15 cm from the tip, was placed by rigid sigmoidoscopy in the recto-sigmoid region. Baseline tone and activity were measured for 15 min prior to instillation of 20 ml of saline alone or with nicotine, 1.2 mg, at pH 4.5. Observations were made over the subsequent 15-20 min. Baseline spontaneous activity in all subjects showed both high- and low-frequency components; in three patients with UC, the low-frequency activity was of high amplitude. The nicotine reduced both t...

Endocannabinoids are a family of lipid signalling molecules. As with prostaglandins (PGs), endoca... more Endocannabinoids are a family of lipid signalling molecules. As with prostaglandins (PGs), endocannabinoids are derived from polyunsaturated fatty acids and affect cell function via receptor-mediated mechanisms. They also bind to PG receptors, although at a lower affinity. The endocannabinoid network is regulated in pregnancy from embryo development to labour onset. Even small changes in endocannabinoid exposure can retard embryo development and affect implantation success. There is now compelling evidence that aberrant expression of factors involved in the endocannabinoid pathway in the placenta and circulating lymphocytes results in spontaneous miscarriage and poor pregnancy outcomes. It is likely that competition between endocannabinoids, PGs and other similar lipids ultimately determines how phospholipid/fatty acid substrates are metabolised and, thus, the balance between the uterotonic and tocolytic activities. We, therefore, hypothesise that endocannabinoid profiles may be used as a biomarker to predict and/or identify spontaneous labour onset.

Metabolic and functional responses to extracellular Mg2+ concentration ([Mg2+]o) were studied in ... more Metabolic and functional responses to extracellular Mg2+ concentration ([Mg2+]o) were studied in perfused rat heart. Elevations of [Mg2+]ofrom 1.2 to 2.4, 5.0, and 8.0 mM dose dependently reduced contractile function and myocardial oxygen consumption (MV˙o 2) up to 80%. Intracellular Mg2+ concentration ([Mg2+]i) remained stable (0.45-0.50 mM) during perfusion with 1.2-5.0 mM [Mg2+]obut increased to 0.81 ± 0.14 mM with 8.0 mM [Mg2+]o. Myocardial ATP was unaffected by [Mg2+]o,phosphocreatine (PCr) increased up to 25%, and Pi declined by up to 50%. Free energy of ATP hydrolysis (Δ G ATP) increased from -60 to -64 kJ/mol. Adenosine efflux declined in parallel with changes in MV˙o 2 and [AMP]. At comparable workload and MV˙o 2, the effects of [Mg2+]oon cytosolic free energy were mimicked by reduced extracellular Ca2+ concentration ([Ca2+]o) or Ca2+ antagonism with verapamil. Moreover, functional and energetic effects of [Mg2+]owere reversed by elevated [Ca2+]o. Despite similar reductions...

Reproductive Biology Insights, 2013

Despite continuing significant research efforts and an increasing prevalence of preterm labor (PT... more Despite continuing significant research efforts and an increasing prevalence of preterm labor (PTL) worldwide, a comprehensive understanding of the mechanisms involved remains to be established; such is the complexity of the interactions involved. Closing the knowledge gaps in this field would afford an opportunity to improve mortality and morbidity rates on a global scale. Early identification of pregnancies at risk of PTL would increase the possibility of delaying birth (where appropriate) prior to initiation of labor. This requires identification of appropriate biomarkers that are readily detectable in easily obtained clinical samples. A family of arachidonic acid metabolites, called eicosanoids. Eicosanoids have shown promise as possible diagnostic biomarkers for PTL. The inherent problems of antibody cross-reactivity in immunoassay methods has, however, resulted in possible misinterpretation of past results. The following mini-review outlines the necessity of such diagnostic targets and the problem with previous research methods and also summarizes recent findings in the field.

There is significant research dedicated to fibroin and sericin, the two major proteinaceous compo... more There is significant research dedicated to fibroin and sericin, the two major proteinaceous components of the silk threads produced by the domesticated silkworm, Bombyx mori. While fibroin is accepted as an established biomaterial, sericin (BMSS) has been largely neglected in this respect on the account of a hypothetical allergenic activity. Research over the past decade, including our previous study (Prog Biomater 2:14, 2013), demonstrated the biocompatibility of sericin and feasibility of its use as a biomaterial. However, the current procedures for isolating BMSS from the raw silk cocoons can only provide degraded proteins, where the size and distribution of their molecular masses are significantly altered. Based on the plausible assumption that such effects can have a negative impact on the properties of sericin as a biomaterial, in this study we investigated comparatively four different extraction procedures in order to find the method that would cause the least hydrothermal degradation of BMSS. The products resulting from commonly used procedures (extraction in boiling water, alkaline extraction, and extraction in autoclave) were compared to those resulting from aqueous extraction in mild conditions as described a long time ago by Anderlini. The molecular mass distribution in BMSS resulting from each procedure was examined by electrophoretic analysis performed on sodium dodecyl sulphate-polyacrylamide gel (SDS-PAGE), while the conformational changes pertaining to secondary structure of BMSS were evaluated by Fourier transform infrared-attenuated total reflectance (FTIR-ATR) spectrometry. The electrophoretograms indicated that the aqueous extraction in mild conditions conducted at 50°C for durations up to 4 weeks, with/without stirring, afforded the least degraded BMSS. The infrared spectrometric analysis showed that BMSS resulting from the mild extraction method contained predominantly b-sheet conformations, while the more degradative methods (alkaline, autoclave) led to BMSS where the random-coil conformations were preferential. The long-duration aqueous extraction at 50°C (but not at 60°C) appeared as a valid option for obtaining BMSS products where the hydrothermally induced fragmentation of the polypeptidic components is minimized. Keywords Bombyx mori silk Á Silk proteins Á Sericin Á Methods of extraction Á Molecular mass distribution Á Electrophoresis Á FTIR analysis Abbreviations BMSF Bombyx mori silk fibroin BMSS Bombyx mori silk sericin FTIR-ATR Fourier transform infrared-attenuated total reflectance MMCO Molecular-mass cutoff SDS-PAGE Sodium dodecyl sulphate-polyacrylamide gel electrophoresis

European Journal of Gastroenterology & Hepatology, 1999

Nicotine may be of therapeutic value in ulcerative colitis (UC), although its mechanism of action... more Nicotine may be of therapeutic value in ulcerative colitis (UC), although its mechanism of action has not been established. To examine the effect of a solution of nicotine on sustained resting pressure (tone) and contractile activity in the human colon. Ten healthy volunteers, and seven with UC in symptomatic remission took part; all were non-smokers. All 17 subjects were given nicotine or placebo solution on two separate occasions in a randomized sequence. A water-perfused manometry catheter, with openings at 5, 10 and 15 cm from the tip, was placed by rigid sigmoidoscopy in the recto-sigmoid region. Baseline tone and activity were measured for 15 min prior to instillation of 20 ml of saline alone or with nicotine, 1.2 mg, at pH 4.5. Observations were made over the subsequent 15-20 min. Baseline spontaneous activity in all subjects showed both high- and low-frequency components; in three patients with UC, the low-frequency activity was of high amplitude. The nicotine reduced both t...

Endocannabinoids are a family of lipid signalling molecules. As with prostaglandins (PGs), endoca... more Endocannabinoids are a family of lipid signalling molecules. As with prostaglandins (PGs), endocannabinoids are derived from polyunsaturated fatty acids and affect cell function via receptor-mediated mechanisms. They also bind to PG receptors, although at a lower affinity. The endocannabinoid network is regulated in pregnancy from embryo development to labour onset. Even small changes in endocannabinoid exposure can retard embryo development and affect implantation success. There is now compelling evidence that aberrant expression of factors involved in the endocannabinoid pathway in the placenta and circulating lymphocytes results in spontaneous miscarriage and poor pregnancy outcomes. It is likely that competition between endocannabinoids, PGs and other similar lipids ultimately determines how phospholipid/fatty acid substrates are metabolised and, thus, the balance between the uterotonic and tocolytic activities. We, therefore, hypothesise that endocannabinoid profiles may be used as a biomarker to predict and/or identify spontaneous labour onset.