Patient-reported chronic pain after open inguinal hernia repair with lightweight or heavyweight mesh: a prospective, patient-reported outcomes study.

BACKGROUND: Chronic pain after groin hernia repair is a significant problem, and it is unclear whether or not lightweight meshes help. This national register-based study investigated whether patients who underwent open anterior mesh inguinal hernia repair with lightweight mesh had less chronic pain than those who had hernia repair with heavyweight mesh. METHODS: All patients registered in the Swedish Hernia Register between September 2012 and October 2016 were asked to complete a questionnaire assessing patient-reported outcome measures 1 year after surgery. The present study examined open anterior repair with mesh sutured in place with non-absorbable sutures in male patients only. The primary endpoint, chronic pain, was defined as pain present in the past week that could not be ignored and interfered with concentration (on chores) and daily activities. RESULTS: In total, 23 259 male patients provided data for analysis (response rate 70·6 per cent). Rates of chronic pain after repairs using regular polypropylene lightweight mesh, composite (poliglecaprone-25) polypropylene lightweight mesh and polypropylene heavyweight mesh were 15·8, 15·6 and 16·2 per cent respectively. Adjusted multiple logistic regression analysis showed no significant differences between regular (odds ratio (OR) 0·98, 95 per cent c.i. 0·90 to 1·06) or composite (OR 0·95, 0·86 to 1·04) lightweight mesh versus heavyweight mesh. The most striking risk factor for chronic pain was young age; 19·4 per cent of patients aged less than 50 years experienced pain 1 year after hernia repair (OR 1·43, 1·29 to 1·60). CONCLUSION: Patient-reported chronic pain 1 year after open mesh repair of inguinal hernia was common, particularly in young men. The risk of developing chronic pain was not influenced by the type of mesh.

ANTECEDENTES: El dolor crónico tras la reparación de la hernia inguinal es un problema significativo y no se conoce con claridad si la utilización de mallas ligeras lo disminuye o no. Este estudio basado en un registro nacional, analizó si los pacientes sometidos a reparación de una hernia inguinal con malla anterior por vía abierta (open anterior mesh, OAM) tenían menos dolor crónico con mallas ligeras que pesadas. MÉTODOS: A todos los pacientes incluidos en el Registro de Hernia sueco entre septiembre de 2012 y octubre de 2016 se les pidió que respondieran un cuestionario que evaluaba los resultados percibidos por el paciente un año después de la cirugía. Se incluyeron solamente los pacientes del sexo masculino en los que la OAM se fijó con suturas reabsorbibles. La variable principal (dolor crónico) se definió como la presencia de dolor que no podía obviarse y que interfería la concentración (en las tareas) y las actividades diarias durante la semana anterior a la de la encuesta. RESULTADOS: Respondieron a la encuesta 23.259 (tasa de respuesta 70,6%) pacientes varones tras OAM. El análisis de regresión logística múltiple con razón de oportunidades (odds ratio, OR) ajustada no demostró diferencias significativas en el dolor crónico entre las mallas ligeras de polipropileno (15,8% (OR 0,98, i.c. del 95% 0,90-1,06)) o las mallas ligeras de polipropileno compuesto (poliglecaprona-25) (15,6% (OR 0,95, i.c. del 9% 0,86-1,04)) o las mallas de polipropileno pesado (16,2%). Sorprendentemente, el factor de riesgo para el dolor crónico fue la edad temprana (< 50 años) 19,3% (OR 1,43, i.c. del 95% 1,29-1,60)). CONCLUSIÓN: El dolor crónico percibido por el paciente un año después de una reparación de una hernia inguinal abierta y con colocación de una malla fue alto, especialmente en varones jóvenes. El tipo de malla no tuvo influencia en el riesgo de aparición de dolor crónico.

Current wheeze, asthma, respiratory infections, and rhinitis among adults in relation to inspection data and indoor measurements in single-family houses in Sweden-The BETSI study.

In the Swedish Building Energy, Technical Status and Indoor environment study, a total of 1160 adults from 605 single-family houses answered a questionnaire on respiratory health. Building inspectors investigated the homes and measured temperature, air humidity, air exchange rate, and wood moisture content (in attic and crawl space). Moisture load was calculated as the difference between indoor and outdoor absolute humidity. Totally, 7.3% were smokers, 8.7% had doctor' diagnosed asthma, 11.2% current wheeze, and 9.5% current asthma symptoms. Totally, 50.3% had respiratory infections and 26.0% rhinitis. The mean air exchange rate was 0.36/h, and the mean moisture load 1.70 g/m3 . Damp foundation (OR=1.79, 95% CI 1.16-2.78) was positively associated while floor constructions with crawl space (OR=0.49, 95% CI 0.29-0.84) was negatively associated with wheeze. Concrete slabs with overlying insulation (OR=2.21, 95% CI 1.24-3.92) and brick façade (OR=1.71, 95% CI 1.07-2.73) were associated with rhinitis. Moisture load was associated with respiratory infections (OR=1.21 per 1 g/m3 , 95% CI 1.04-1.40) and rhinitis (OR=1.36 per 1 g/m3 , 95% CI 1.02-1.83). Air exchange rate was associated with current asthma symptoms (OR=0.85 per 0.1/h, 95% CI 0.73-0.99). Living in homes with damp foundation, concrete slabs with overlying insulation, brick façade, low ventilation flow, and high moisture load are risk factors for asthma, rhinitis, and respiratory infections.

Displacement Forces in Stent Grafts: Influence of Diameter Variation and Curvature Asymmetry.

OBJECTIVES: Long-term durability after endovascular aortic repair is influenced by stent graft migration causing types I and III endoleaks. Flow induced displacement forces have been shown to have the potential to cause migration. In this study, the influence of the distal diameter of iliac limb stent grafts and the shape of graft curvature on flow induced displacement forces, were investigated. METHODS: In an experimental pulsatile flow model mimicking aortic conditions in vivo, flow induced displacement forces at the proximal and distal ends of iliac limb stent grafts were studied at different angles (0-90°) and perfusion pressures (145/80, 170/90, 195/100 mmHg). Bell-bottomed, tapered, and non-tapered stent grafts and also asymmetric stent graft curvatures at 90° bend were studied. Measurements of graft movement were performed at all studied angulations and graft shapes. RESULTS: For all stent graft diameters, flow induced displacement forces increased with higher pressure and increased stent graft angulation. Forces in the bell-bottom graft were considerably higher than in tapered and non-tapered grafts, with a markedly elevated peak force at the distal end (proximal end, 2.3 ± 0.06 N and distal end, 6.9 ± 0.05 N compared with 1.7 ± 0.08 N and 1.6 ± 0.08 N in non-tapered grafts; p < .001 both). Peak forces in tapered and non-tapered grafts were not significantly different between the proximal and distal end. In asymmetric stent graft curvatures, a significant increase in displacement forces was observed in the attachment zone that was closest to the stent graft bend. Graft movement increased with greater displacement forces. CONCLUSION: Flow induced displacement forces in iliac limb stent grafts are significant and are influenced by distal stent graft diameter and the shape of the graft curvature. The displacement forces are particularly high at the large distal end of bell-bottom grafts. Wide iliac arteries treated with bell-bottom stent grafts may require more vigilant surveillance and improved stent graft fixation.

Fate of necrotic volume after microwave ablation of multiple liver metastases.

BACKGROUND/AIMS: The aim of this study was to find the rate of shrinkage of necrosis and time of peak ablation volume after multiple microwave ablations in the treatment of multiple liver metastases of colorectal cancer. These factors are not known and are important in evaluation of treatment and identification of local recurrence, as microwave treatment is becoming more used thanks to improved technology in diagnostics and interventional therapy. METHODOLOGY: A retrospective analysis of non-cirrhotic patients with multiple liver only metastases of colorectal cancer, not suited for resection for this reason. Patients were selected for palliative microwave treatment at a liver multidisciplinary team conference. 68 ablations were made in six patients. Ablation volume was analysed with repeated imaging and computer analyses. RESULTS: The ablation volume peeks after 5-7 days where after reduction of the necrosis in the liver occurs logarithmically with a 60% reduction of ablation volume after 100 days and 80% after a year. DISCUSSION: Liver regeneration after microwave ablations occurs at a constant logarithmic rate after an initial expansion of the ablation volume during the first five days. Evaluation of ablation volume in comparison to tumour volume must take this into account so that follow-up imaging is properly timed.

Displacement forces in iliac landing zones and stent graft interconnections in endovascular aortic repair: an experimental study.

OBJECTIVES: Stent graft migration influences the long-term durability of endovascular aortic repair. Flow-induced displacement forces acting on the attachment zones may contribute to migration. Proximal fixation of aortic stent grafts has been improved by using hooks, while distal fixation and stent graft interconnections depend on self-expansion forces only. We hypothesized that flow-induced displacement forces would be significant at the distal end, and would correlate with graft movements. METHODS: As part of an experimental study, an iliac limb stent graft was inserted in a pulsatile flow model similar to aortic in vivo conditions, and fixed-mounted at its proximal and distal ends to strain gauge load cells. Peak displacement forces at both ends and pulsatile graft movement were recorded at different graft angulations (0-90°), perfusion pressures (145/80, 170/90, or 195/100 mmHg), and stroke frequencies (60-100 b.p.m.). RESULTS: Flow-induced forces were of the same magnitude at the proximal and distal end of the stent graft (peak 1.8 N). Both the forces and graft movement increased with angulation and perfusion pressure, but not with stroke rate. Graft movement reached a maximum of 0.29 ± 0.01 mm per stroke despite fixed ends. There were strong correlations between proximal and distal displacement forces (r = 0.97, p < .001), and between displacement forces and graft movement (r = 0.98, p < .001). CONCLUSIONS: Pulsatile flow through a tubular untapered stent graft causes forces of similar magnitude at both ends and induces pulsatile graft movements in its unsupported mid-section. Peak forces are close to those previously reported to be required to extract a stent graft. The forces and movements increase with increasing graft angulation and perfusion pressure. Improved anchoring of the distal end of stent grafts may be considered.

The influence of paper coating content on room temperature sintering of silver nanoparticle ink.

The resistance of inkjet printed lines using a silver nanoparticle based ink can be very dependent on the substrate. A very large difference in resistivity was observed for tracks printed on paper substrates with aluminum oxide based coatings compared to silica based coatings. Silica based coatings are often cationized with polymers using chloride as a counter ion. It is suggested that the precipitation of silver salts is the cause of the high resistivity, since papers pretreated with salt solutions containing ions that precipitate silver salts gave a high resistance. Silver nitrate has a high solubility and paper pretreated with nitrate ions gave a low resistivity without sintering. The results obtained show that, by choosing the correct type of paper substrate, it is possible to manufacture printed structures, such as interconnects on paper, without the need for, or at least to reduce the need for, post-print sintering. This phenomenon is, of course, ink specific. Inks without or with a low silver ion content are not expected to behave in this manner. In some sensor applications, a high resistivity is desired and, by using the correct combination of ink and paper, these types of sensors can be facilitated.

Supercurrent and multiple Andreev reflections in an InSb nanowire Josephson junction.

Epitaxially grown, high quality semiconductor InSb nanowires are emerging material systems for the development of high performance nanoelectronics and quantum information processing and communication devices and for the studies of new physical phenomena in solid state systems. Here, we report on measurements of a superconductor-normal conductor-superconductor junction device fabricated from an InSb nanowire with aluminum-based superconducting contacts. The measurements show a proximity-induced supercurrent flowing through the InSb nanowire segment with a critical current tunable by a gate in the current bias configuration and multiple Andreev reflection characteristics in the voltage bias configuration. The temperature dependence and the magnetic field dependence of the critical current and the multiple Andreev reflection characteristics of the junction are also studied. Furthermore, we extract the excess current from the measurements and study its temperature and magnetic field dependences. The successful observation of the superconductivity in the InSb nanowire-based Josephson junction device indicates that InSb nanowires provide an excellent material system for creating and observing novel physical phenomena such as Majorana fermions in solid-state systems.

Impaired myogenic tone in isolated cerebral and coronary resistance arteries from the goto-kakizaki rat model of type 2 diabetes.

AIM: Type 2 diabetes is associated with stroke and cardiac dysfunction. We therefore investigated isolated middle cerebral arteries and coronary septal arteries from the diabetic Goto-Kakizaki (GK) rat model of nonobese type 2 diabetes. METHODS: Myogenic tone and agonist-induced responses were investigated under isobaric conditions with simultaneous recording of [Ca2+]i. Rho-kinase and NO pathways were investigated using specific pharmacological tools. RESULTS: Arteries from GK rats developed less tone at pressures from 20 to 100 mm Hg than arteries from control Wistar (CW) rats while [Ca2+]i was similar. Blocking the Rho-kinase pathway decreased the pressure-induced development of tone and after blockade no difference in myogenic tone between arteries from GK and CW rats was seen. Cerebral arteries had similar tone to a maximal concentration of U46619 (GK: 35.5±2% vs. CW: 31.6±5%), while coronary arteries from GK rats developed less tone than arteries from CW rats (12±3 vs. 26.1±3%). Endothelium-dependent vasodilation to A23187 (cerebral) and to acetylcholine (coronary) was not different between arteries from GK and CW rats. CONCLUSION: Our data suggest that in resistance arteries from the brain and the heart of GK rats the myogenic tone is decreased due to impaired calcium sensitivity likely due to a defective Rho-kinase pathway.

Observations of a Solar Energetic Particle Event From Inside and Outside the Coma of Comet 67P.

We analyze observations of a solar energetic particle (SEP) event at Rosetta's target comet 67P/Churyumov-Gerasimenko during 6-10 March 2015. The comet was 2.15 AU from the Sun, with the Rosetta spacecraft approximately 70 km from the nucleus placing it deep inside the comet's coma and allowing us to study its response. The Eastern flank of an interplanetary coronal mass ejection (ICME) also encountered Rosetta on 6 and 7 March. Rosetta Plasma Consortium data indicate increases in ionization rates, and cometary water group pickup ions exceeding 1 keV. Increased charge exchange reactions between solar wind ions and cometary neutrals also indicate increased upstream neutral populations consistent with enhanced SEP induced surface activity. In addition, the most intense parts of the event coincide with observations interpreted as an infant cometary bow shock, indicating that the SEPs may have enhanced the formation and/or intensified the observations. These solar transient events may also have pushed the cometopause closer to the nucleus. We track and discuss characteristics of the SEP event using remote observations by SOHO, WIND, and GOES at the Sun, in situ measurements at Solar Terrestrial Relations Observatory Ahead, Mars and Rosetta, and ENLIL modeling. Based on its relatively prolonged duration, gradual and anisotropic nature, and broad angular spread in the heliosphere, we determine the main particle acceleration source to be a distant ICME which emerged from the Sun on 6 March 2015 and was detected locally in the Martian ionosphere but was never encountered by 67P directly. The ICME's shock produced SEPs for several days which traveled to the in situ observation sites via magnetic field line connections.

Risk of hernia formation after radical prostatectomy: a comparison between open and robot-assisted laparoscopic radical prostatectomy within the prospectively controlled LAPPRO trial.

PURPOSE: In addition to incisional hernia, inguinal hernia is a recognized complication to radical retropubic prostatectomy. To compare the risk of developing inguinal and incisional hernias after open radical prostatectomy compared to robot-assisted laparoscopic prostatectomy. METHOD: Patients planned for prostatectomy were enrolled in the prospective, controlled LAPPRO trial between September 2008 and November 2011 at 14 hospitals in Sweden. Information regarding patient characteristics, operative techniques and occurrence of postoperative inguinal and incisional hernia were retrieved using six clinical record forms and four validated questionnaires. RESULTS: 3447 patients operated with radical prostatectomy were analyzed. Within 24 months, 262 patients developed an inguinal hernia, 189 (7.3%) after robot-assisted laparoscopic prostatectomy and 73 (8.4%) after open radical prostatectomy. The relative risk of having an inguinal hernia after robot-assisted laparoscopic prostatectomy was 18% lower compared to open radical retropubic prostatectomy, a non-significant difference. Risk factors for developing an inguinal hernia after prostatectomy were increased age, low BMI and previous hernia repair. The incidence of incisional hernia was low regardless of surgical technique. Limitations are the non-randomised setting. CONCLUSIONS: We found no difference in incidence of inguinal hernia after open retropubic and robot-assisted laparoscopic radical prostatectomy. The low incidence of incisional hernia after both procedures did not allow for statistical analysis. Risk factors for developing an inguinal hernia after prostatectomy were increased age and BMI.

Inner southern magnetosphere observation of Mercury via SERENA ion sensors in BepiColombo mission.

Mercury's southern inner magnetosphere is an unexplored region as it was not observed by earlier space missions. In October 2021, BepiColombo mission has passed through this region during its first Mercury flyby. Here, we describe the observations of SERENA ion sensors nearby and inside Mercury's magnetosphere. An intermittent high-energy signal, possibly due to an interplanetary magnetic flux rope, has been observed downstream Mercury, together with low energy solar wind. Low energy ions, possibly due to satellite outgassing, were detected outside the magnetosphere. The dayside magnetopause and bow-shock crossing were much closer to the planet than expected, signature of a highly eroded magnetosphere. Different ion populations have been observed inside the magnetosphere, like low latitude boundary layer at magnetopause inbound and partial ring current at dawn close to the planet. These observations are important for understanding the weak magnetosphere behavior so close to the Sun, revealing details never reached before.

BepiColombo mission confirms stagnation region of Venus and reveals its large extent.

The second Venus flyby of the BepiColombo mission offer a unique opportunity to make a complete tour of one of the few gas-dynamics dominated interaction regions between the supersonic solar wind and a Solar System object. The spacecraft pass through the full Venusian magnetosheath following the plasma streamlines, and cross the subsolar stagnation region during very stable solar wind conditions as observed upstream by the neighboring Solar Orbiter mission. These rare multipoint synergistic observations and stable conditions experimentally confirm what was previously predicted for the barely-explored stagnation region close to solar minimum. Here, we show that this region has a large extend, up to an altitude of 1900 km, and the estimated low energy transfer near the subsolar point confirm that the atmosphere of Venus, despite being non-magnetized and less conductive due to lower ultraviolet flux at solar minimum, is capable of withstanding the solar wind under low dynamic pressure.

Cyclophosphamide exposure assessed with the biomarker phosphoramide mustard-hemoglobin in breast cancer patients: The TailorDose I study.

Cyclophosphamide (CPA) dosing by body surface area (BSA, m2) has been questioned as a predictor for individual drug exposure. This study investigated phosphoramide mustard-hemoglobin (PAM-Hb, pmol g-1 Hb) as a biomarker of CPA exposure in 135 female breast cancer patients receiving CPA during three courses based on BSA: 500 mg/m2 (C500 group, n = 67) or 600 mg/m2 (C600 group, n = 68). The inter-individual difference was calculated for both groups by dividing the highest through the lowest PAM-Hb value of each course. The inter-occasion difference was calculated in percentage for each individual by dividing their PAM-Hb value through the group mean per course, and subsequently dividing this ratio of the latter through the previous course. A multivariable linear regression (MLR) was performed to identify factors that explained the variation of PAM-Hb. During the three courses, the inter-individual difference changed from 3.5 to 2.1 and the inter-occasion difference ranged between 13.3% and 11.9% in the C500 group. In the C600 group, the inter-individual difference changed from 2.7 to 2.9 and the inter-occasion difference ranged between 14.1% and 11.7%. The MLR including BSA, age, GFR, and albumin explained 17.1% of the variation of PAM-Hb and was significantly better then the model including only BSA. These factors should be considered when calculating the first dose of CPA for breast cancer patients.

SERENA: Particle Instrument Suite for Determining the Sun-Mercury Interaction from BepiColombo.

The ESA-JAXA BepiColombo mission to Mercury will provide simultaneous measurements from two spacecraft, offering an unprecedented opportunity to investigate magnetospheric and exospheric particle dynamics at Mercury as well as their interactions with solar wind, solar radiation, and interplanetary dust. The particle instrument suite SERENA (Search for Exospheric Refilling and Emitted Natural Abundances) is flying in space on-board the BepiColombo Mercury Planetary Orbiter (MPO) and is the only instrument for ion and neutral particle detection aboard the MPO. It comprises four independent sensors: ELENA for neutral particle flow detection, Strofio for neutral gas detection, PICAM for planetary ions observations, and MIPA, mostly for solar wind ion measurements. SERENA is managed by a System Control Unit located inside the ELENA box. In the present paper the scientific goals of this suite are described, and then the four units are detailed, as well as their major features and calibration results. Finally, the SERENA operational activities are shown during the orbital path around Mercury, with also some reference to the activities planned during the long cruise phase.

Correlation-induced conductance suppression at level degeneracy in a quantum dot.

The large, level-dependent g factors in an InSb nanowire quantum dot allow for the occurrence of a variety of level crossings in the dot. While we observe the standard conductance enhancement in the Coulomb blockade region for aligned levels with different spins due to the Kondo effect, a vanishing of the conductance is found at the alignment of levels with equal spins. This conductance suppression appears as a canyon cutting through the web of direct tunneling lines and an enclosed Coulomb blockade region. In the center of the Coulomb blockade region, we observe the predicted correlation-induced resonance. Our findings are supported by numerical and analytical calculations.

The electrical and structural properties of n-type InAs nanowires grown from metal-organic precursors.

The electrical and structural properties of 111B-oriented InAs nanowires grown using metal-organic precursors have been studied. On the basis of electrical measurements it was found that the trends in carbon incorporation are similar to those observed in the layer growth, where an increased As/In precursor ratio and growth temperature result in a decrease in carbon-related impurities. Our results also show that the effect of non-intentional carbon doping is weaker in InAs nanowires compared to bulk, which may be explained by lower carbon incorporation in the nanowire core. We determine that differences in crystal quality, here quantified as the stacking fault density, are not the primary cause for variations in resistivity of the material studied. The effects of some n-dopant precursors (S, Se, Si, Sn) on InAs nanowire morphology, crystal structure and resistivity were also investigated. All precursors result in n-doped nanowires, but high precursor flows of Si and Sn also lead to enhanced radial overgrowth. Use of the Se precursor increases the stacking fault density in wurtzite nanowires, ultimately at high flows leading to a zinc blende crystal structure with strong overgrowth and very low resistivity.

Inhibition of cytotoxicity of lymphocytes by concanavalin A in vitro.

Human lymphocytes treated with the plant protein concanavalin A are stimulated to transform into blasts, without developing cytotoxicity for chicken erythrocytes. Prior treatment of lymphocytes with concanavalin A potentiated phytohemagglutinin-induced blast transformation and DNA synthesis but completely inhibited phytohemagglutinin-induced cytotoxicity. Inhibiton was not due to suppression of the mixed lymphocyte-erythrocyte aggregation normally caused by phytohemagglutinin. Inhibition of cytotoxicity was reversible when concanavalin A was removed from the lymphocytes by treatment with methyl-alpha-D-manno-pyranoside after 1 hour but not after 20 hours. The results indicate that blast transformation and cytotoxicity are separate expressions of lymphocyte stimulation.

Short-term treatment of a resilient appliance in TMD pain patients: a randomized controlled trial.

To investigate the short-term efficacy of a resilient appliance in patients with temporomandibular disorders (TMD) suffering from pain, a randomized, controlled trial was performed in 80 recruited TMD pain patients. They were randomly allocated to one of two groups: treatment with a resilient appliance or treatment with a hard, palatal, non-occluding appliance. The primary treatment outcome measure was judged positive when patients' TMD pain at worst, according to the Visual Analog Scale (VAS), decreased by at least 30%. One additional treatment outcome was reduction of characteristic pain intensity. Number needed to treat was measured on the basis of primary treatment outcome at 10 weeks. At baseline, patient characteristics and TMD pain did not differ between the groups. There were no significant differences between groups regarding a 30% reduction in VAS-reported TMD pain at worst at 10 weeks' follow-up; 61% in the treatment group and 46% in the control group. After 6 and 10 weeks of treatment, CPI decreased in both groups. Number needed to treat was 9.1 for both the resilient and the control appliance therapy during 10 weeks. There was no statistically significant difference between the resilient appliance and the non-occluding control appliance in reducing TMD pain from a short-term perspective.

Targeting transcriptional control of soluble guanylyl cyclase via NOTCH for prevention of cardiovascular disease.

Soluble guanylyl cyclase (sGC) is an effector enzyme of nitric oxide (NO). Recent work has unravelled how levels of this enzyme are controlled, and highlighted a role in vascular disease. We provide a timely summary of available knowledge on transcriptional regulation of sGC, including influences from the NOTCH signalling pathway and genetic variants. It is speculated that hypertension-induced repression of sGC starts a vicious circle that can be initiated by periods of stress, diet or genetic factors, and a key tenet is that reduction in sGC further raises blood pressure. The idea that dysregulation of sGC contributes to syndromes caused by defective NOTCH signalling is advanced, and we discuss drug repositioning for vascular disease prevention. The advantage of targeting sGC expression rather than activity is also considered. It is argued that transcriptional inputs on sGC arise from interactions with other cells, the extracellular matrix and microRNAs (miRNAs), and concluded that the promise of sGC as a target for prevention of cardiovascular disease has increased in recent time.

Rebaudioside A directly stimulates insulin secretion from pancreatic beta cells: a glucose-dependent action via inhibition of ATP-sensitive K-channels.

Recently, we showed that rebaudioside A potently stimulates the insulin secretion from isolated mouse islets in a dose-, glucose- and Ca(2+)-dependent manner. Little is known about the mechanisms underlying the insulinotropic action of rebaudioside A. The aim of this study was to define the signalling system by which, rebaudioside A acts. Isolated mouse islets were used in the cAMP[(125)I] scintillation proximity assay to measure total cAMP level, and in a luminometric method to measure intracellular ATP and ADP concentrations. Conventional and permeabilized whole-cell configuration of the patch-clamp technique was used to verify the effect of rebaudioside A on ATP-sensitive K(+)-channels from dispersed single beta cells from isolated mouse islets. Insulin was measured by radioimmunoassay from insulinoma MIN6 cells. In the presence of 16.7 mM glucose, the addition of the maximally effective concentration of rebaudioside A (10(-9) M) increased the ATP/ADP ratio significantly, while it did not change the intracellular cAMP level. Rebaudioside A (10(-9) M) and stevioside (10(-6) M) reduced the ATP-sensitive potassium channel (K(ATP)) conductance in a glucose-dependent manner. Moreover, rebaudioside A stimulated the insulin secretion from MIN6 cells in a dose- and glucose-dependent manner. In conclusion, the insulinotropic effect of rebaudioside A is mediated via inhibition of ATP-sensitive K(+)-channels and requires the presence of high glucose. The inhibition of ATP-sensitive K(+)-channels is probably induced by changes in the ATP/ADP ratio. The results indicate that rebaudioside A may offer a distinct therapeutic advantage over sulphonylureas because of less risk of causing hypoglycaemia.