The ability of phosphodiesterase-5 inhibitors sildenafil and ordonafil to reverse L-NAME induced cardiac hypertrophy in the rabbit: possible role of calcineurin and p38

Phosphodiesterase 5 inhibitors (PDE-5Is) can suppress and (or) reverse pressure overload induced myocardial hypertrophy. This study investigated the suppressive effect of 2 PDE-5Is (sildenafil and ordonafil) on N-nitro-l-arginine methyl ester (L-NAME)-induced cardiac hypertrophy in rabbit heart, and examined their possible mechanism of action. L-NAME increased left ventricular thickness to 6.1± 0.18?mm from 4.6?± 0.13?mm (p?< 0.05), which regressed after treatment with either sildenafil or ordonafil to 5.1?± 0.1?mm and 4.8?± 0.2?mm, respectively (p?< 0.05). Phenylephrine increased neonatal rat ventricular myocyte cell surface area to 131%?± 3% of the control value, which was associated with significant increment in ERK1/2 to 143%?± 5% of the control value (p?< 0.05). Ordonafil and sildenafil decreased cell surface area to 95%?± 3% and 90%?± 1% of the control value, respectively. Both drugs decreased ERK1/2 to 88%?± 4% of the control value. Calcineurin activity was significantly decreased after 1?h of treatment with 0.1?mg·L(-1) ordonafil (1.15?± 0.05, p?< 0.05). For sildenafil (0.1?mg·L(-1)), calcineurin activity significantly decreased only after 24?h of incubation (22%). Also p38 activation was attenuated by ordonafil and sildenafil (0.1?mg·L(-1)). It is suggested that both drugs have the ability to reverse L-NAME-induced cardiac hypertrophy and suppress phenylphrine-induced myocyte hypertrophy, and that these effects may be mediated through the attenuation of calcineurin and its downstream signaling pathways (p38) in neonatal rat ventricular myocytes.     

Interaction of spin-labeled tryptophan with sickle hemoglobin: probing the microenvironment of the contact sites by spin-probe--spin-label techniques

The spin-labeled tryptophan was used as a structural probe of hemoglobin contact sites. The ESR spectral data indicated that the probe exhibits weak binding to hemoglobin with a dissociation constant of 3.2.10(-5) and 4.0 mol bound per hemoglobin tetramer. The spectrum suggested that the bound tryptophan was 'partially immobilized' with a correlation time reflecting the environment of the tryptophan binding site of 8.2 ns. The topology of the contact sites was investigated by using dual spin-label methodology in which spin-labeled tryptophan and (2H,15N) substituted and deuterated maleimide spin label [2H-15N]MSL covalently-bound to Cys-beta 93 residue were used. The ESR spectral data suggested that the tryptophan binding sites were located within 8-10 A of the nitroxide free radical of spin-labeled hemoglobin. The environment of the contact sites is discussed.     

Stable coexistence of two <Emphasis Type="Italic">Caldicellulosiruptor</Emphasis> species in a <Emphasis Type="Italic">de novo</Emphasis> constructed hydrogen-producing co-culture

Background  

Mixed culture enrichments have been used frequently for biohydrogen production from different feedstock. In spite of the several advantages offered by those cultures, they suffer poor H₂ yield. Constructing defined co-cultures of known H₂ producers may offer a better performance than mixed-population enrichments, while overcoming some of the limitations of pure cultures based on synergies among the microorganisms involved.     

ROS Dynamics Delineate Functional States of Hippocampal Neural Stem Cells and Link to Their Activity-Dependent Exit from Quiescence

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Acute effects of capacitive and resistive electric transfer (CRet) on the Achilles tendon

This study aimed to investigate the acute effects of capacitive and resistive electric transfer (CRet) on Achilles tendon elongation during muscle contraction, as well as the circulation in the peritendinous region. Sixteen healthy men participated in this study. All 16 participants underwent 2 interventions: (1) CRet trial and (2) CRet without power (sham trial). Tendon elongation was measured four times. Using near-infrared spectroscopy, the blood circulation (volume of total-hemoglobin (Hb), oxygenated hemoglobin (oxy-Hb), and deoxygenated hemoglobin (deoxy-Hb)) was measured for 5 min before the intervention and for 30 min after the intervention. The differences between the measurements obtained before and after intervention were compared between the two interventions. The changes in tendon elongation and deoxy-Hb were not significantly different between the interventions. Total- and oxy-Hb were significantly increased in the CRet trial compared with the sham trial. In addition, the increases in total-Hb and oxy-Hb lasted for 30 min after the CRet intervention (CRet vs. sham: oxy-Hb: F = 8.063, p = 0.001, total-Hb: F = 4.564, p = 0.011). In conclusion, CRet significantly improved blood circulation in the peritendinous region.     

Comparative Analysis of Human Growth Hormone in Serum Using SPRi,Nano-SPRi and ELISA Assays

Sensitive and selective methods for the detection of human growth hormone (hGH) over a wide range of concentrations (high levels of 50-100 ng ml⁻¹ and minimum levels of 0.03 ng ml⁻¹) in circulating blood are essential as variable levels may indicate altered physiology. For example, growth disorders occurring in childhood can be diagnosed by measuring levels of hGH in blood. Also, the misuse of recombinant hGH in sports not only poses an ethical issue it also presents serious health threats to the abuser. One popular strategy for measuring hGH misuse, relies on the detection of the ratio of 22 kDa hGH to total hGH, as non-22 kDa endogenous levels drop after exogenous recombinant hGH (rhGH) administration.Surface plasmon resonance imaging (SPRi) is an analytical tool that allows direct (label-free) monitoring and visualization of biomolecular interactions by recording changes of the refractive index adjacent to the sensor surface in real time. In contrast, the most frequently used colorimetric method, enzyme-linked immunosorbent assay (ELISA) uses enzyme labeled detection antibodies to indirectly measure analyte concentration after the addition of a substrate that induces a color change. To increase detection sensitivity, amplified SPRi uses a sandwich assay format and near infrared quantum dots (QDs) to increase signal strength. After direct SPRi detection of recombinant rhGH in spiked human serum, the SPRi signal is amplified by the sequential injection of detection antibody coated with near-infrared QDs (Nano-SPRi). In this study, the diagnostic potential of direct and amplified SPRi was assessed for measuring rhGH spiked in human serum and compared directly with the capabilities of a commercially available ELISA kit.     

Glycolysis regulates Hedgehog signalling via the plasma membrane potential

The authors regret omitting the citation of a bioRxiv preprint study by preprint: Emmons‐Bell et al (2020), who independently discovered the role of ion channel‐dependent membrane depolarization for Smo membrane accumulation in the fly wing disc. This study used a different methodological approach and did not describe the mechanism of how membrane potential affects hedgehog signaling. The reference is herewith added.