[Assessment of two frailty scales for the preoperative period]. / Fragilidad: en busca de herramientas de evaluación preoperatoria.

BACKGROUND: In the perioperative context, a frailty evaluation scale must consider certain characteristics such as validation, execution speed, simplicity, the capacity to measure multiple dimensions and not being dependent on a cognitive or physical test that could not be performed prior to surgery. The test should select patients that could benefit from interventions aimed to improve their postoperative outcomes. AIM: To validate two frailty evaluation scales for the perioperative period. MATERIAL AND METHODS: The Risk Analysis Index with local modifications (RAI-M) were applied to 201 patients aged 73 ± 7 years (49% women) and the Edmonton frailty scale were applied in 151 patients aged 73 ± 7 years (49% women) in the preoperative period. Their results were compared with the Rockwood frailty index. RESULTS: The Edmonton frail scale showed adequate psychometric properties and assessed multiple dimensions through 8 of the 11 original questions, achieving a discrimination power over 80% compared to the Rockwood Index. The RAI- M, demonstrated solid psychometric properties with a tool that examines 4 dimensions of frailty through 15 questions and reviewing the presence of 11 medical comorbidities. This scale had a discrimination power greater than 85% and it was significantly associated with prolongation of the planned hospital stay and mortality. CONCLUSIONS: RAI-M is a short and easily administered scale, useful to detect frailty in the preoperative period.

Intramolecular and Metal-to-Molecule Charge Transfer Electronic Resonances in the Surface-Enhanced Raman Scattering of 1,4-Bis((E)-2-(pyridin-4-yl)vinyl)naphthalene.

Electrochemical surface-enhanced Raman scattering (SERS) of the cruciform system 1,4-bis((E)-2-(pyridin-4-yl)vinyl)naphthalene (bpyvn) was recorded on nanostructured silver surfaces at different electrode potentials by using excitation laser lines of 785 and 514.5 nm. SERS relative intensities were analyzed on the basis of the resonance Raman vibronic theory with the help of DFT calculations. The comparison between the experimental and the computed resonance Raman spectra calculated for the first five electronic states of the Ag2-bpyvn surface complex model points out that the selective enhancement of the SERS band recorded at about 1600 cm-1, under 785 nm excitation, is due to a resonant Raman process involving a photoexcited metal-to-molecule charge transfer state of the complex, while the enhancement of the 1570 cm-1 band using 514.5 nm excitation is due to an intramolecular π→π* electronic transition localized in the naphthalenyl framework, resulting in a case of surface-enhanced resonance Raman spectrum (SERRS). Thus, the enhancement of the SERS bands of bpyvn is controlled by a general chemical enhancement mechanism in which different resonance processes of the overall electronic structure of the metal-molecule system are involved.

BMP type I receptor ALK2 is required for angiotensin II-induced cardiac hypertrophy.

Bone morphogenetic protein (BMP) signaling contributes to the development of cardiac hypertrophy. However, the identity of the BMP type I receptor involved in cardiac hypertrophy and the underlying molecular mechanisms are poorly understood. By using quantitative PCR and immunoblotting, we demonstrated that BMP signaling increased during phenylephrine-induced hypertrophy in cultured neonatal rat cardiomyocytes (NRCs), as evidenced by increased phosphorylation of Smads 1 and 5 and induction of Id1 gene expression. Inhibition of BMP signaling with LDN193189 or noggin, and silencing of Smad 1 or 4 using small interfering RNA diminished the ability of phenylephrine to induce hypertrophy in NRCs. Conversely, activation of BMP signaling with BMP2 or BMP4 induced hypertrophy in NRCs. Luciferase reporter assay further showed that BMP2 or BMP4 treatment of NRCs repressed atrogin-1 gene expression concomitant with an increase in calcineurin protein levels and enhanced activity of nuclear factor of activated T cells, providing a mechanism by which BMP signaling contributes to cardiac hypertrophy. In a model of cardiac hypertrophy, C57BL/6 mice treated with angiotensin II (A2) had increased BMP signaling in the left ventricle. Treatment with LDN193189 attenuated A2-induced cardiac hypertrophy and collagen deposition in left ventricles. Cardiomyocyte-specific deletion of BMP type I receptor ALK2 (activin-like kinase 2), but not ALK1 or ALK3, inhibited BMP signaling and mitigated A2-induced cardiac hypertrophy and left ventricular fibrosis in mice. The results suggest that BMP signaling upregulates the calcineurin/nuclear factor of activated T cell pathway via BMP type I receptor ALK2, contributing to cardiac hypertrophy and fibrosis.

BMP type II receptors have redundant roles in the regulation of hepatic hepcidin gene expression and iron metabolism.

Expression of hepcidin, the hepatic hormone controlling iron homeostasis, is regulated by bone morphogenetic protein (BMP) signaling. We sought to identify which BMP type II receptor expressed in hepatocytes, ActR2a or BMPR2, is responsible for regulating hepcidin gene expression. We studied Bmpr2 heterozygous mice (Bmpr2(+/-)), mice with hepatocyte-specific deficiency of BMPR2, mice with global deficiency of ActR2a, and mice in which hepatocytes lacked both BMPR2 and ActR2a. Hepatic hepcidin messenger RNA (mRNA) levels, serum hepcidin and iron levels, and tissue iron levels did not differ in wild-type mice, Bmpr2(+/-) mice, and mice in which either BMPR2 or ActR2a was deficient. Deficiency of both BMP type II receptors markedly reduced hepatic hepcidin gene expression and serum hepcidin levels leading to severe iron overload. Iron injection increased hepatic hepcidin mRNA levels in mice deficient in either BMPR2 or ActR2a, but not in mice deficient in both BMP type II receptors. In addition, in mouse and human primary hepatocytes, deficiency of both BMPR2 and ActR2a profoundly decreased basal and BMP6-induced hepcidin gene expression. These results suggest that BMP type II receptors, BMPR2 and ActR2a, have redundant roles in the regulation of hepatic hepcidin gene expression and iron metabolism.

The type I BMP receptor Alk3 is required for the induction of hepatic hepcidin gene expression by interleukin-6.

Increased IL-6 production induces, via STAT3 phosphorylation, hepatic transcription of the gene encoding the iron-regulatory hormone, hepcidin, leading to development of anemia of chronic disease (ACD). Inhibition of bone morphogenetic protein (BMP) signaling prevents the induction of hepcidin gene expression by IL-6 and ameliorates ACD. Using mice with hepatocyte-specific deficiency of Alk2 or Alk3, we sought to identify the BMP type I receptor that participates in IL-6-mediated induction of hepcidin gene expression. Mice were injected with adenovirus specifying IL-6 (Ad.IL-6) or control adenovirus. Seventy-two hours later, serum iron concentrations and hepatic levels of STAT3 phosphorylation and hepcidin messenger RNA were measured. Additional mice were injected with recombinant murine IL-6 (mIL-6) or vehicle, and hepatic hepcidin gene expression was measured 4 hours later. Deficiency of Alk2 or Alk3 did not alter the ability of Ad.IL-6 injection to induce hepatic STAT3 phosphorylation. Ad.IL-6 increased hepatic hepcidin messenger RNA levels and decreased serum iron concentrations in Alk2- but not Alk3-deficient mice. Similarly, administration of mIL-6 induced hepatic hepcidin gene expression in Alk2- but not Alk3-deficient mice. These results demonstrate that the ability of IL-6 to induce hepatic hepcidin gene expression and reduce serum iron concentrations is dependent on the BMP type I receptor Alk3.

Pulmonary hypertension after prolonged hypoxic exposure in mice with a congenital deficiency of Cyp2j.

Cytochrome P450 epoxygenase-derived epoxyeicosatrienoic acids contribute to the regulation of pulmonary vascular tone and hypoxic pulmonary vasoconstriction. We investigated whether the attenuated acute vasoconstrictor response to hypoxic exposure of Cyp2j(-/-) mice would protect these mice against the pulmonary vascular remodeling and hypertension associated with prolonged exposure to hypoxia. Cyp2j(-/-) and Cyp2j(+/+) male and female mice continuously breathed an inspired oxygen fraction of 0.21 (normoxia) or 0.10 (hypoxia) in a normobaric chamber for 6 weeks. We assessed hemoglobin (Hb) concentrations, right ventricular (RV) systolic pressure (RVSP), and transthoracic echocardiographic parameters (pulmonary acceleration time [PAT] and RV wall thickness). Pulmonary Cyp2c29, Cyp2c38, and sEH mRNA levels were measured in Cyp2j(-/-) and Cyp2j(+/+) male mice. At baseline, Cyp2j(-/-) and Cyp2j(+/+) mice had similar Hb levels and RVSP while breathing air. After 6 weeks of hypoxia, circulating Hb concentrations increased but did not differ between Cyp2j(-/-) and Cyp2j(+/+) mice. Chronic hypoxia increased RVSP in Cyp2j(-/-) and Cyp2j(+/+) mice of either gender. Exposure to chronic hypoxia decreased PAT and increased RV wall thickness in both genotypes and genders to a similar extent. Prolonged exposure to hypoxia produced similar levels of RV hypertrophy in both genotypes of either gender. Pulmonary Cyp2c29, Cyp2c38, and sEH mRNA levels did not differ between Cyp2j(-/-) and Cyp2j(+/+) male mice after breathing at normoxia or hypoxia for 6 weeks. These results suggest that murine Cyp2j deficiency does not attenuate the development of murine pulmonary vascular remodeling and hypertension associated with prolonged exposure to hypoxia in mice of both genders.

Perturbation of hepcidin expression by BMP type I receptor deletion induces iron overload in mice.

Bone morphogenetic protein (BMP) signaling induces hepatic expression of the peptide hormone hepcidin. Hepcidin reduces serum iron levels by promoting degradation of the iron exporter ferroportin. A relative deficiency of hepcidin underlies the pathophysiology of many of the genetically distinct iron overload disorders, collectively termed hereditary hemochromatosis. Conversely, chronic inflammatory conditions and neoplastic diseases can induce high hepcidin levels, leading to impaired mobilization of iron stores and the anemia of chronic disease. Two BMP type I receptors, Alk2 (Acvr1) and Alk3 (Bmpr1a), are expressed in murine hepatocytes. We report that liver-specific deletion of either Alk2 or Alk3 causes iron overload in mice. The iron overload phenotype was more marked in Alk3- than in Alk2-deficient mice, and Alk3 deficiency was associated with a nearly complete ablation of basal BMP signaling and hepcidin expression. Both Alk2 and Alk3 were required for induction of hepcidin gene expression by BMP2 in cultured hepatocytes or by iron challenge in vivo. These observations demonstrate that one type I BMP receptor, Alk3, is critically responsible for basal hepcidin expression, whereas 2 type I BMP receptors, Alk2 and Alk3, are required for regulation of hepcidin gene expression in response to iron and BMP signaling.

Plasmon Chemistry on Ag Nanostars: Experimental and Theoretical Raman/SERS Study of the Pesticide Thiacloprid Bond Cleavage by the Plasmon Deactivation Effect.

Silver nanoparticles (AgNPs) were synthetized and employed in surface-enhanced Raman scattering measurements to study the chemical behavior when thiacloprid (Thia) interacts with the surface of Ag nanospheres (AgNSp) and Ag nanostars (AgNSt) upon excitation of the system with a 785 nm laser. Experimental results show that the deactivation of the localized surface plasmon resonance induces structural changes in Thia. When AgNSp are used, it is possible to observe a mesomeric effect in the cyanamide moiety. On the other hand, when AgNSt are employed, it promotes the cleavage of the methylene (-CH2-) bridge in Thia to produce two molecular fragments. To support these results, theoretical calculations based on topological parameters described by the atoms in molecules theory, Laplacian of the electron density at the bond critical point (∇2ρ BCP), Laplacian bond order, and bond dissociation energies were made, confirming that the bond cleavage is centered at the -CH2- bridge in Thia.

A photochemical route in the synthesis and characterization of La2Ti2O7 and La2Ti2O7/AgO films and its evaluation in Congo red degradation and as antibacterial control to Staphylococcus aureus.

In this article, we propose a simple photochemical method to synthesize pure La2Ti2O7 films and La2Ti2O7 films doped with silver at 1.0, 3.0, and 5.0 mol%. After annealing the photo-deposited films at 900 °C, XRD, SEM, and XPS analyses showed the formation of a monoclinic La2Ti2O7 phase and the presence of Ag and AgO in doped samples. Photocatalytic tests for Congo red degradation demonstrated that pure La2Ti2O7 achieved 25.4% degradation, while doped samples reached a maximum of 92.7% degradation. Moreover, increasing silver doping on La2Ti2O7 films significantly reduced the growth of Staphylococcus aureus, indicating potential antibacterial properties. The enhanced photoactivity was attributed to the formation of a type I heterojunction between La2Ti2O7 and AgO, and a degradation mechanism was proposed based on Congo red degradation.

Resveratrol-Schiff Base Hybrid Compounds with Selective Antibacterial Activity: Synthesis, Biological Activity, and Computational Study.

Nowadays, antimicrobial resistance is a serious concern associated with the reduced efficacy of traditional antibiotics and an increased health burden worldwide. In response to this challenge, the scientific community is developing a new generation of antibacterial molecules. Contributing to this effort, and inspired by the resveratrol structure, five new resveratrol-dimers (9a−9e) and one resveratrol-monomer (10a) were synthetized using 2,5-dibromo-1,4-diaminobenzene (8) as the core compound for Schiff base bridge conformation. These compounds were evaluated in vitro against pathogenic clinical isolates of Pseudomonas aeruginosa, Staphylococcus aureus, Bacillus sp., and Listeria monocytogenes. Antibacterial activity measurements of resveratrol-Schiff base derivatives (9a−9e) and their precursors (4−8) showed high selectivity against Listeria monocytogenes, being 2.5 and 13.7 times more potent than chloramphenicol, while resveratrol showed an EC50 > 320 µg/mL on the same model. Moreover, a prospective mechanism of action for these compounds against L. monocytogenes strains was proposed using molecular docking analysis, finding a plausible inhibition of internalin C (InlC), a surface protein relevant in bacteria−host interaction. These results would allow for the future development of new molecules for listeriosis treatment based on compound 8.

SERS study on the aggregation mechanisms resulting from the orientation of dipyridinic derivatives on gold nanoparticles.

In this work, was studied the adsorption and orientation of three dipyridinic derivatives 9,10-bis-((E)-2-(pyridin-4-yl)vinyl)anthracene (DPAC), 1,4-bis-((E)-2-(pyridin-4-yl)vinyl)naphthalene (DPNA-T) and 2,6-bis-((E)-2-(pyridin-4-yl)vinyl)naphthalene (DPNA-L) on gold nanoparticles, using Surface Enhanced Raman Scattering (SERS). Systematic modification in the shapes of the bifunctional systems (Cross-shape, T-shape and Linear-shape) shows changes significant in the preferential orientation of these analytes on the nanostructured gold surface. Additional data from UV-vis measurements and TEM images are in agreement with the Reaction Limited Colloid Aggregation (RLCA) mechanisms for DPAC and DPNA-T and Diffusion Limited Colloid Aggregation (DLCA) mechanisms for DPNA-L, showing that for the same analyte concentration, the aggregation mechanism depends on the molecular shape. These results allow us to rationalize the fundamental aspects involved in the development of devices based on plasmonic resonance with potential applications in the field of molecular electronics.

Adiponectin decreases pulmonary arterial remodeling in murine models of pulmonary hypertension.

Remodeling of the pulmonary arteries is a common feature among the heterogeneous disorders that cause pulmonary hypertension. In these disorders, the remodeled pulmonary arteries often demonstrate inflammation and an accumulation of pulmonary artery smooth muscle cells (PASMCs) within the vessels. Adipose tissue secretes multiple bioactive mediators (adipokines) that can influence both inflammation and remodeling, suggesting that adipokines may contribute to the development of pulmonary hypertension. We recently reported on a model of pulmonary hypertension induced by vascular inflammation, in which a deficiency of the adipokine adiponectin (APN) was associated with the extensive proliferation of PASMCs and increased pulmonary artery pressures. Based on these data, we hypothesize that APN can suppress pulmonary hypertension by directly inhibiting the proliferation of PASMCs. Here, we tested the effects of APN overexpression on pulmonary arterial remodeling by using APN-overexpressing mice in a model of pulmonary hypertension induced by inflammation. Consistent with our hypothesis, mice that overexpressed APN manfiested reduced pulmonary hypertension and remodeling compared with wild-type mice, despite developing similar levels of pulmonary vascular inflammation in the model. The overexpression of APN was also protective in a hypoxic model of pulmonary hypertension. Furthermore, APN suppressed the proliferation of PASMCs, and reduced the activity of the serum response factor-serum response element pathway, which is a critical signaling pathway for smooth muscle cell proliferation. Overall, these data suggest that APN can regulate pulmonary hypertension and pulmonary arterial remodeling through its direct effects on PASMCs. Hence, the activation of APN-like activity in the pulmonary vasculature may be beneficial in pulmonary hypertension.

Adiponectin deficiency increases allergic airway inflammation and pulmonary vascular remodeling.

Obesity is associated with an increased incidence and severity of asthma, as well as other lung disorders, such as pulmonary hypertension. Adiponectin (APN), an antiinflammatory adipocytokine, circulates at lower levels in the obese, which is thought to contribute to obesity-related inflammatory diseases. We sought to determine the effects of APN deficiency in a murine model of chronic asthma. Allergic airway inflammation was induced in APN-deficient mice (APN(-/-)) using sensitization without adjuvant followed by airway challenge with ovalbumin. The mice were then analyzed for changes in inflammation and lung remodeling. APN(-/-) mice in this model develop increased allergic airway inflammation compared with wild-type mice, with greater accumulation of eosinophils and monocytes in the airways associated with elevated lung chemokine levels. Surprisingly, APN(-/-) mice developed severe pulmonary arterial muscularization and pulmonary arterial hypertension in this model, whereas wild-type mice had only mild vascular remodeling and comparatively less pulmonary arterial hypertension. Our findings demonstrate that APN modulates allergic inflammation and pulmonary vascular remodeling in a model of chronic asthma. These data provide a possible mechanism for the association between obesity and asthma, and suggest a potential novel link between obesity, inflammatory lung disease, and pulmonary hypertension.

Application of surface-enhanced resonance Raman scattering (SERS) to the study of organic functional materials: electronic structure and charge transfer properties of 9,10-bis((E)-2-(pyridin-4-yl)vinyl)anthracene.

The electron donor-acceptor properties of 9,10-bis((E)-2-(pyridin-4-yl)vinyl) anthracene (BP4VA) are studied by means of surface-enhanced Raman scattering (SERS) spectroscopy and vibronic theory of resonance Raman spectroscopy. The SERS spectra recorded in an electrochemical cell with a silver working electrode have been interpreted on the basis of resonance Raman vibronic theory assisted by DFT calculations. It is demonstrated that the adsorbate-metal interaction occurs through the nitrogen atom of the pyridyl moiety. Concerning the electron donor-acceptor properties of the adsorbate, it is shown that the charge transfer excited states of BP4VA are not optically active, in contrast, an internal transition to an excited state of BP4VA, which is localized in the anthracene framework, is strongly allowed. The charge transfer states will be populated by an ultrafast non-radiative process, that is, internal conversion. Thus, irradiation of BP4VA interacting with an appropriate surface creates an effective charge separation.

Augmented noncanonical BMP type II receptor signaling mediates the synaptic abnormality of fragile X syndrome.

Epigenetic silencing of fragile X mental retardation 1 (FMR1) causes fragile X syndrome (FXS), a common inherited form of intellectual disability and autism. FXS correlates with abnormal synapse and dendritic spine development, but the molecular link between the absence of the FMR1 product FMRP, an RNA binding protein, and the neuropathology is unclear. We found that the messenger RNA encoding bone morphogenetic protein type II receptor (BMPR2) is a target of FMRP. Depletion of FMRP increased BMPR2 abundance, especially that of the full-length isoform that bound and activated LIM domain kinase 1 (LIMK1), a component of the noncanonical BMP signal transduction pathway that stimulates actin reorganization to promote neurite outgrowth and synapse formation. Heterozygosity for BMPR2 rescued the morphological abnormalities in neurons both in Drosophila and in mouse models of FXS, as did the postnatal pharmacological inhibition of LIMK1 activity. Compared with postmortem prefrontal cortex tissue from healthy subjects, the amount of full-length BMPR2 and of a marker of LIMK1 activity was increased in this brain region from FXS patients. These findings suggest that increased BMPR2 signal transduction is linked to FXS and that the BMPR2-LIMK1 pathway is a putative therapeutic target in patients with FXS and possibly other forms of autism.

FT-IR, FT-Raman, UV-visible, and NMR spectroscopy and vibrational properties of the labdane-type diterpene 13-epi-sclareol.

In this work, FT-IR, FT-Raman, UV-Visible and NMR spectroscopies and density functional theory (DFT) calculations were employed to study the structural and vibrational properties of the labdane-type diterpene 13-epi-sclareol using the hybrid B3LYP method together with the 6-31G(∗) basis set. Three stable structures with minimum energy found on the potential energy curves (PES) were optimized, and the corresponding molecular electrostatic potentials, atomic charges, bond orders, stabilization energies and topological properties were computed at the same approximation level. The complete assignment of the bands observed in the vibrational spectrum of 13-epi-sclareol was performed taking into account the internal symmetry coordinates for the three structures using the scaled quantum mechanical force field (SQMFF) methodology at the same level of theory. In addition, the force constants were calculated and compared with those reported in the literature for similar compounds. The predicted vibrational spectrum and the calculated (1)H NMR and (13)C NMR chemical shifts are in good agreement with the corresponding experimental results. The theoretical UV-Vis spectra for the most stable structure of 13-epi-sclareol demonstrate a better correlation with the corresponding experimental spectrum. The study of the three conformers by means of the theory of atoms in molecules (AIM) revealed different H bond interactions and a strong dependence of the interactions on the distance between the involved atoms. Furthermore, the natural bond orbital (NBO) calculations showed the characteristics of the electronic delocalization for the two six-membered rings with chair conformations.

Vibrational and structural study of onopordopicrin based on the FTIR spectrum and DFT calculations.

In the present work, the structural and vibrational properties of the sesquiterpene lactone onopordopicrin (OP) were studied by using infrared spectroscopy and density functional theory (DFT) calculations together with the 6-31G(∗) basis set. The harmonic vibrational wavenumbers for the optimized geometry were calculated at the same level of theory. The complete assignment of the observed bands in the infrared spectrum was performed by combining the DFT calculations with Pulay's scaled quantum mechanical force field (SQMFF) methodology. The comparison between the theoretical and experimental infrared spectrum demonstrated good agreement. Then, the results were used to predict the Raman spectrum. Additionally, the structural properties of OP, such as atomic charges, bond orders, molecular electrostatic potentials, characteristics of electronic delocalization and topological properties of the electronic charge density were evaluated by natural bond orbital (NBO), atoms in molecules (AIM) and frontier orbitals studies. The calculated energy band gap and the chemical potential (µ), electronegativity (χ), global hardness (η), global softness (S) and global electrophilicity index (ω) descriptors predicted for OP low reactivity, higher stability and lower electrophilicity index as compared with the sesquiterpene lactone cnicin containing similar rings.

Fragilidad: en busca de herramientas de evaluación preoperatoria / Assessment of two frailty scales for the preoperative period

Background: In the perioperative context, a frailty evaluation scale must consider certain characteristics such as validation, execution speed, simplicity, the capacity to measure multiple dimensions and not being dependent on a cognitive or physical test that could not be performed prior to surgery. The test should select patients that could benefit from interventions aimed to improve their postoperative outcomes. Aim: To validate two frailty evaluation scales for the perioperative period. Material and Methods: The Risk Analysis Index with local modifications (RAI-M) were applied to 201 patients aged 73 ± 7 years (49% women) and the Edmonton frailty scale were applied in 151 patients aged 73 ± 7 years (49% women) in the preoperative period. Their results were compared with the Rockwood frailty index. Results: The Edmonton frail scale showed adequate psychometric properties and assessed multiple dimensions through 8 of the 11 original questions, achieving a discrimination power over 80% compared to the Rockwood Index. The RAI- M, demonstrated solid psychometric properties with a tool that examines 4 dimensions of frailty through 15 questions and reviewing the presence of 11 medical comorbidities. This scale had a discrimination power greater than 85% and it was significantly associated with prolongation of the planned hospital stay and mortality. Conclusions: RAI-M is a short and easily administered scale, useful to detect frailty in the preoperative period.

Determination of attapulgite and nifuroxazide in pharmaceutical formulations by sequential digital derivative spectrophotometry.

A new method for the sequential determination of attapulgite and nifuroxazide in pharmaceutical formulations by first- and second-derivative spectrophotometry, respectively, has been developed. In order to obtain the optimal conditions for nifuroxazide stability, studies of solvent, light, and temperature effects were performed. The results show that a previous hydrolysis of 2 h in 1.0 x 10(-1)M NaOH solution is necessary in order to obtain stable compounds for analytical purposes. Subsequently, the first- and second-derivative spectra were evaluated directly in the same samples. The sequential determination of the drugs can be performed using the zero-crossing method; the attapulgite determination was carried out using the first derivative at 278.0 nm and the nifuroxazide determination, using the second derivative at 282.0 nm. The determination ranges were 5.7 x 10(-6)-1.0 x 10(-4) and 3.7 x 10(-8) -1.2 x 10(-4)M for attapulgite and nifuroxazide, respectively. Repeatability (relative standard deviation) values of 1.2 and 3.0% were observed for attapulgite and nifuroxazide, respectively. The ingredients commonly found in commercial pharmaceutical formulations do not interfere. The proposed method was applied to the determination of these drugs in tablets. Further, infrared spectroscopy and cyclic voltammetry studies were carried out in order to obtain knowledge of the decomposition products of nifuroxazide.

Deletion of the sequence encoding the tail domain of the bone morphogenetic protein type 2 receptor reveals a bone morphogenetic protein 7-specific gain of function.

The bone morphogenetic protein (BMP) type II receptor (BMPR2) has a long cytoplasmic tail domain whose function is incompletely elucidated. Mutations in the tail domain of BMPR2 are found in familial cases of pulmonary arterial hypertension. To investigate the role of the tail domain of BMPR2 in BMP signaling, we generated a mouse carrying a Bmpr2 allele encoding a non-sense mediated decay-resistant mutant receptor lacking the tail domain of Bmpr2. We found that homozygous mutant mice died during gastrulation, whereas heterozygous mice grew normally without developing pulmonary arterial hypertension. Using pulmonary artery smooth muscle cells (PaSMC) from heterozygous mice, we determined that the mutant receptor was expressed and retained its ability to transduce BMP signaling. Heterozygous PaSMCs exhibited a BMP7­specific gain of function, which was transduced via the mutant receptor. Using siRNA knockdown and cells from conditional knockout mice to selectively deplete BMP receptors, we observed that the tail domain of Bmpr2 inhibits Alk2­mediated BMP7 signaling. These findings suggest that the tail domain of Bmpr2 is essential for normal embryogenesis and inhibits Alk2­mediated BMP7 signaling in PaSMCs.