Widespread tissue distribution and diverse functions of corticotropin-releasing factor and related peptides

Peptides of the corticotropin-releasing factor (CRF) family are expressed throughout the central nervous system (CNS) and in peripheral tissues where they play diverse roles in physiology, behavior, and development. Current data supports the existence of four paralogous genes in vertebrates that encode CRF, urocortin/urotensin 1, urocortin 2 or urocortin 3. Corticotropin-releasing factor is the major hypophysiotropin for adrenocorticotropin, and also functions as a thyrotropin-releasing factor in non-mammalian species. In the CNS, CRF peptides function as neurotransmitters/neuromodulators. Recent work shows that CRF peptides are also expressed at diverse sites outside of the CNS in mammals, and we found widespread expression of CRF and urocortins, CRF receptors and CRF binding protein (CRF-BP) genes in the frog Xenopus laevis. The functions of CRF peptides expressed in the periphery in non-mammalian species are largely unexplored. We recently found that CRF acts as a cytoprotective agent in the X. laevis tadpole tail, and that the CRF-BP can block CRF action and hasten tail muscle cell death. The expression of the CRF-BP is strongly upregulated in the tadpole tail at metamorphic climax where it may neutralize CRF bioactivity, thus promoting tail resorption. Corticotropin-releasing factor and urocortins are also known to be cytoprotective in mammalian cells. Thus, CRF peptides may play diverse roles in physiology and development, and these functions likely arose early in vertebrate evolution.     

Molecular cloning of bullfrog corticotropin-releasing factor (CRF): effect of homologous CRF on the release of TSH from pituitary cells in vitro

Corticotropin-releasing factor (CRF) plays multiple roles in vertebrate species. In non-mammalian vertebrates, CRF has been considered to be the major thyrotropin (TSH)-releasing factor. This notion, however, was derived from experimental data on CRF of mammalian origin. Moreover, in the case of amphibians it has never been directly proved that CRF stimulates the release of TSH from the pituitary. The presently described experiment was conducted to provide direct evidence that homologous CRF enhances the release of TSH from the bullfrog (Rana catesbeiana) pituitary. First, cloning of cDNA encoding bullfrog CRF (fCRF) was accomplished. The cDNA encoding fCRF precursor was isolated from a cDNA library of the bullfrog hypothalamus. The amino acid sequence of fCRF predicted from the amplified cDNA sequence showed 83 and 95% identities with the sequences of ovine and human CRFs, respectively. An antiserum against the fCRF synthesized on the basis of the amino acid sequence was raised and used for immunohistochemical staining of the hypothalamus-hypophyseal region of the bullfrog brain. It stained some of the cell bodies situated mainly in the preoptic area, the nucleus infundibularis dorsalis and nucleus hypothalamicus ventralis and the axons that terminate in the median eminence and neural lobe. The synthetic fCRF was tested for its TSH-releasing activity toward anterior pituitary cells of adult bullfrogs in an in vitro system. As a result, the fCRF caused the release of TSH from the dispersed pituitary cells into the culture medium concentration-dependently, as measured by a specific radioimmunoassay for bullfrog TSH. The potency of the fCRF was almost equivalent to that of ovine CRF. Human urocortin III (hUCN III), a CRF receptor type 2 (CRF-R2) specific agonist enhanced the release of TSH from the pituitary cells in culture, suggesting the involvement of CRF-R2 in the CRF-induced TSH release in the bullfrogs. Culture of pituitary cells in the presence of the hypothalamic extract (HE) and alpha-helical CRF(9-41), a CRF-R antagonist, revealed that the antagonist suppressed the TSH-releasing activity of the HE by approximately 50%, suggesting that endogenous CRF contributes as a TSH-releasing factor.     

Increased Hb A2 Values in an HIV-1-Infected Patient Receiving Antiretroviral Drugs: A Pitfall for Thalassemia Antenatal Diagnosis

We report a human immunodeficiency virus-1 (HIV-1)-infected couple, where the woman in the 11th week of gestation, carried a Hb E trait. She and her spouse were referred to the hemoglobinopathy counselors. Her spouse's blood was subsequently tested and showed an increased Hb A₂ value. However, his red cell indices and osmotic fragility test were different from those found in β-thalassemia (β-thal) carriers. The β-thal genes were investigated further and no mutations were observed. Therefore, it is unlikely that he is a β-thal carrier and the increased Hb A₂ value is a result of receiving antiretroviral drugs. As antenatal thalassemia screening becomes more widespread, measuring the Hb A₂ values should be taken in all HIV-1-infected couples before the initiation of antiretroviral drugs to rule out misdiagnosis of β-thal. However, if these tests are not available, the results of the red cell indices and osmotic fragility test should be considered as they may provide great value for β-thal investigations.     

The Uses and Differences of R2 and R2* in the Determination of Iron Overload in Iron Loaded Thalassemia Patients

Early attempts to use magnetic resonance imaging (MRI) for assessing iron overload in β-thalassemia (thal) patients began more than 20 years ago. With advances in MRI, more quantitative efforts focused on measuring transverse relaxation time rates (R₂ and R₂*) of the liver and/or myocardium. Recently, calibration curves of R₂ and R₂* were reported that allowed one to determine the absolute concentrations of iron in the liver, provided that R₂ and R₂* were determined with the same technique. The difficulty of obtaining sufficient myocardium biopsy samples has prevented similar calibration curves being reported for the myocardium. Preliminary data indicate that liver and myocardium R₂* vs. R₂ plots are similar over a large range of R₂* and R₂ values. Obviously, myocardium biopsy samples are needed to confirm whether myocardium R₂* and R₂ plots vs. iron concentration are similar to those published for the liver. The various methods for determining R₂ and R₂* are discussed. It is suggested to use both R₂* and R₂ for assessing iron overload in the liver and myocardium.     

Detection of Hb A2 and Hb Constant Spring (HBA2: c.427T>C) by Capillary Electrophoresis in a Patient with Hb H-Hb CS Disease

Abstract

Hb A₂ (α2δ2) is one of the key components looked for in hemoglobinopathies screening programs. Therefore, quantitative and accurate method for Hb A₂ value determination is essential for routine screening. Here, we report a case of Hb A₂ and Hb Constant Spring (Hb CS, HBA2: c.427T>C) with Hb H-Hb CS disease that was not detected by high performance liquid chromatography (HPLC), while Hb A₂ and Hb CS were clearly quantified by capillary electrophoresis (CE).     

Size and Shape’s Effects on the High-Pressure Behavior of WS2 Nanomaterials

Exploring the behavior of nanocrystals with varying shapes and sizes under high pressure is crucial to understanding the relationship between the morphology and properties of nanomaterials. In this study, we investigated the compression behaviors of WS₂ nanotubes (NT-WS₂) and fullerene-like nanoparticles (IF-WS₂) by in situ high-pressure X-ray diffraction (XRD) and Raman spectroscopy. It was found that the bulk modulus of NT-WS₂ is 81.7 GPa, which is approximately twice as large as that of IF-WS₂ (46.3 GPa). This might be attributed to the fact that IF-WS₂ with larger d-spacing along the c-axis and higher defect density are more compressible under isotropic pressure than NT-WS₂. Thus, the slender NT-WS₂ possess a more stable crystal structure than the IF-WS₂. Our findings reveal that the effects of morphology and size play crucial roles in determining the high-pressure properties of WS₂ nanoparticles, and provide significant insight into the relationship between structure and properties.     

Analysis of the Genotypes in a Chinese Population with Increased Hb A2 and Low Hematological Indices

Abstract

Increased Hb A₂ is considered the most reliable hematological finding for the identification of β-thalassemia (β-thal) carriers. The aim of this study was to determine the underlying genetic factors associated with a high Hb A₂ level in a Chinese population. Subjects were recruited from couples preparing for pregnancy who participated in the thalassemia screening program during a 2-year period. DNA analyses were used for diagnosis of β-thal and other genetic factors. A total of 5985 adults who screened positive for β-thal were recruited. Of these, 5933 (99.1%) were detected to have a β-thal mutation. In the remaining 52 (0.9%) individuals without mutations involving the β-globin gene cluster, 16 were found to have Krüppel-like factor 1 (KLF1) gene variants, and two had an α-globin gene triplication. There were still 34 individuals with unknown genetic factors for their raised Hb A₂ values. The results of this study indicate that genetic factors other than β-thal can rarely contribute to the elevation of Hb A₂. These subjects usually have borderline microcytic red cell indices and Hb A₂ values.     

Changes in the distribution of corticotropin-releasing factor (CRF)-like immunoreactivity in the larval bullfrog brain and the involvement of CRF in the cessation of food intake during metamorphosis

In submammalian vertebrates, corticotropin-releasing factor (CRF) acts as an anorexigenic neuropeptide as well as a potent stimulator of corticotropin and thyrotropin release from the pituitary. As a step for demonstrating the involvement of CRF in the feeding regulation of anuran larvae, which are known to stop feeding toward the metamorphic climax, we studied firstly the changes in the distribution of CRF-like immunoreactivity (CRF-LI) in the brain of metamorphosing bullfrog larvae. Neuronal cell bodies showing CRF-LI were invariably present in the thalamic regions throughout larval development. Cells with CRF-LI were also found in the hypothalamus. The number of cells with CRF-LI in the hypothalamus, but not in the thalamus, showed a significant increase as metamorphosis progressed. Immunoreactive nerve fibers were observed mainly in the median eminence, and became abundant as metamorphosis proceeded. The number of cells showing CRF-LI in the hypothalamus as well as the density of immunoreactive fibers in the median eminence decreased at the end of metamorphosis. Secondly, we examined the effect of intracerebroventricular (ICV) injection of CRF on the food intake in the premetamorphic larvae. ICV injection of CRF at 10 pmol/g body weight (BW) induced a significant decrease of food intake during 15 min. The CRF-induced anorexigenic action was blocked by the treatment with a CRF receptor antagonist [α-helical CRF_(9-41)] at 100 pmol/g BW. The results suggest the involvement of CRF in the accomplishment of metamorphosis through the pituitary and in the feeding restriction that occurs during the later stages of metamorphosis through the central nervous system.     

PKC activation and PIP2 depletion underlie biphasic regulation of IKs by Gq-coupled receptors

KCNQ1 is co-assembled with KCNE1 subunits in the heart to form the cardiac delayed rectifier K⁺ current (IKs), which is one of the main currents responsible for myocyte repolarization. The most commonly inherited form of cardiac arrhythmias, long-QT syndrome type 1 (LQT1), is due to mutations on KCNQ1. Gq-coupled receptors (GqPCRs) are known to mediate positive inotropism in human ventricular myocardium. The mechanism of IKs current modulation by GqPCRs remains incompletely understood. Here we studied the molecular mechanisms underlying Gq regulation of the IKs channel. Heterologously expressed IKs (human KCNQ1/KCNE1 subunits) was measured in Xenopus oocytes, expressed together with GqPCRs. Our data from several GqPCRs shows that IKs is regulated in a biphasic manner, showing both an activation and an inhibition phase. Receptor-mediated inhibition phase was irreversible when recycling of agonist-sensitive pools of phosphatidylinositol-4,5-bisphosphate (PIP2) was blocked by the lipid kinase inhibitor wortmannin. In addition, stimulation of PIP₂ production, by overexpression of phosphatidylinositol-4-phosphate-5-kinase (PIP5-kinase), decreased receptor-mediated inhibition. The receptor-mediated activation phase was inhibited by the PKC inhibitor calphostin C and by a mutation in a putative PKC phosphorylation site in the KCNE1 subunit. Our results indicate that the depletion of membrane PIP₂ underlies receptor-mediated inhibition of IKs and that phosphorylation by PKC of the KCNE1 subunit underlies the GqPCR-mediated channel activation.     

Resolution of Corticosteroid-Induced Diabetes in Allergic Bronchopulmonary Aspergillosis with Omalizumab Therapy: A Novel Approach

There are substantial numbers of reports showing that leukotrienes (LTs) play important roles in adult asthma. No definite evidence has been demonstrated that LTs are involved in asthma attacks in children, although it is highly expected. In this report, we demonstrated that the levels of LTB₄ and LTC₄ but not thromboxane B₂ (TXB₂), a stable metabolite of TXA₂, were significantly elevated in the bronchoalveolar lavage fluid, which was obtained from intubated and mechanically ventilated children with severe asthma attacks. This is direct evidence that LTB₄ and LTC₄ predominantly participate in asthma attacks in pediatric patients.     

Polymorphism of the ADRB2 Gene and Response to Inhaled Beta- agonists in Children with Asthma: A Meta-analysis

Background. About 9% of children have asthma, corresponding to almost 6.8 million children in the USA and 1.1 million in the UK. Asthma exacerbations are the leading cause of pediatric emergency room visits and impose a large burden on the individual, family, and society. There is mounting evidence that therapeutic failure of inhaled beta-agonists is associated with polymorphisms of the β₂-adrenergic receptor gene (ADRB2); specifically, mutations leading to amino acid changes at positions 16 and 27, which alter down-regulation of the β₂-adrenergic receptor (β₂AR), induce resistance to the smooth-muscle relaxing effect of β₂-adrenergic agonists. Methods. We conducted a meta-analysis to examine the association between ADRB2 polymorphisms and the response to inhaled β₂-adrenergic agonists in children with asthma. We included all published studies until November 2008, in which asthmatic children underwent testing for acute bronchodilator response, defined as ≥ 15% improvement in forced expiratory volume in 1 second (FEV₁) and single nucleotide polymorphism (SNP) genotyping for positions 16 and/or 27 of the β₂AR. Individual and summary odds ratios were calculated using a random effects model. Results. We identified three case-control or family-based studies involving 960 asthmatic children (692 children with negative β₂-bronchodilator response, defined as < 15% improvement in FEV₁ and 268 children with positive bronchodilator response). We found a significant association between favorable therapeutic response to inhaled β₂-adrenergic agonists in asthmatic children and the Arg/Arg phenotype at position 16 of the β₂AR [OR = 1.77; 95% CI (1.01; 3.1); p = 0.029], compared with the Arg/Gly or Gly/Gly phenotypes. The beneficial effect of Arg at position 16 of the β₂AR was most pronounced in African-American asthmatic children [OR = 3.54; 95% CI (1.37, 9.13)]. There was no association between clinical response to β₂-agonists and polymorphism at amino acid position 27 of the β₂AR (OR = 1.04; 95% CI [0.76,1.42]). Conclusions. Failure of bronchodilator response to inhaled beta-agonists in asthmatic children is associated with the Gly allele (Arg/Gly and Gly/Gly genotypes) at position 16 of the β₂-adrenergic receptor. Genetic typing for β₂AR polymorphism may help identify children with drug-resistant asthma.     

Prospects of Synthesized Magnetic TiO2-Based Membranes for Wastewater Treatment: A Review

Global accessibility to clean water has stressed the need to develop advanced technologies for the removal of toxic organic and inorganic pollutants and pathogens from wastewater to meet stringent discharge water quality limits. Conventionally, the high separation efficiencies, relative low costs, small footprint, and ease of operation associated with integrated photocatalytic-membrane (IPM) technologies are gaining an all-inclusive attention. Conversely, photocatalysis and membrane technologies face some degree of setbacks, which limit their worldwide application in wastewater settings for the treatment of emerging contaminants. Therefore, this review elucidated titanium dioxide (TiO₂), based on its unique properties (low cost, non-toxicity, biocompatibility, and high chemical stability), to have great potential in engineering photocatalytic-based membranes for reclamation of wastewater for re-use. The environmental pathway of TiO₂ nanoparticles, membranes and configuration types, modification process, characteristics, and applications of IPMs in water settings are discussed. Future research and prospects of magnetized TiO₂-based membrane technology is highlighted as a viable water purification technology to mitigate fouling in the membrane process and photocatalyst recoverability. In addition, exploring life cycle assessment research would also aid in utilizing the concept and pressing for large-scale application of this technology.     

Photocatalytic Reduction of Carbon Dioxide on TiO2 Heterojunction Photocatalysts—A Review

The photocatalytic reduction of carbon dioxide to renewable fuel or other valuable chemicals using solar energy is attracting the interest of researchers because of its great potential to offer a clean fuel alternative and solve global warming problems. Unfortunately, the efficiency of CO₂ photocatalytic reduction remains not very high due to the fast recombination of photogenerated electron–hole and small light utilization. Consequently, tremendous efforts have been made to solve these problems, and one possible solution is the use of heterojunction photocatalysts. This review begins with the fundamental aspects of CO₂ photocatalytic reduction and the fundamental principles of various heterojunction photocatalysts. In the following part, we discuss using TiO₂ heterojunction photocatalysts with other semiconductors, such as C₃N₄, CeO₂, CuO, CdS, MoS₂, GaP, CaTiO₃ and FeTiO₃. Finally, a concise summary and presentation of perspectives in the field of heterojunction photocatalysts are provided. The review covers references in the years 2011–2021.     

Reduced levels of the adenomatous polyposis coli (APC) protein are associated with ceramide-induced apoptosis of colon cancer cells

Purpose Mutations of the adenomatous polyposis coli (APC) and p53 genes are commonly found in colorectal cancers. We therefore analyzed the relative roles of APC and p53 in the induction of apoptosis of colon cancer cells by comparing the effects of the natural chemopreventive agent, C₂-ceramide, on different human colon cancer cell lines with and without wild-type p53 and APC genes.Methods We studied the effect of C₂-ceramide and C₂-dihydroceramide on proliferation and/or apoptosis of colon cancer cell lines in vitro and determined the role of p53 and APC proteins in these processes. The protein and mRNA levels in colon cancer cell lines with and without treatments were determined by Western and Northern blot analysis, respectively. The cell cycle and apoptosis profiles were determined by FACS analysis and PARP-1 cleavage.Results Our findings indicate that C₂-ceramide can induce apoptosis independently of the p53/p21(Waf-1/Cip-1) pathway. In addition, the C₂-ceramide induction of apoptosis showed a correlation with a reduction in the levels of the APC protein and mRNA. Moreover, the C₂-ceramide-induced apoptosis was blocked by pre-treatment with ZnCl₂, which stabilizes APC protein levels.Conclusions These results suggest that C₂-ceramide treatment reduces the levels of APC protein and that the reduction in the levels of this protein plays a key role in the ability of C₂-ceramide to induce apoptosis of colon cancer cells.     

A Novel Synthesized 1D Nanobelt-like Cobalt Phosphate Electrode Material for Excellent Supercapacitor Applications

In the present report, we synthesized highly porous 1D nanobelt-like cobalt phosphate (Co₂P₂O₇) materials using a hydrothermal method for supercapacitor (SC) applications. The physicochemical and electrochemical properties of the synthesized 1D nanobelt-like Co₂P₂O₇ were investigated using X-ray diffraction (XRD), X-ray photoelectron (XPS) spectroscopy, and scanning electron microscopy (SEM). The surface morphology results indicated that the deposition temperatures affected the growth of the 1D nanobelts. The SEM revealed a significant change in morphological results of Co₂P₂O₇ material prepared at 150 °C deposition temperature. The 1D Co₂P₂O₇ nanobelt-like nanostructures provided higher electrochemical properties, because the resulting empty space promotes faster ion transfer and improves cycling stability. Moreover, the electrochemical performance indicates that the 1D nanobelt-like Co₂P₂O₇ electrode deposited at 150 °C deposition temperature shows the maximum specific capacitance (Cs). The Co₂P₂O₇ electrode prepared at a deposition temperature 150 °C provided maximum Cs of 1766 F g⁻¹ at a lower scan rate of 5 mV s⁻¹ in a 1 M KOH electrolyte. In addition, an asymmetric hybrid Co₂P₂O₇//AC supercapacitor device exhibited the highest Cs of 266 F g⁻¹, with an excellent energy density of 83.16 Wh kg⁻¹, and a power density of 9.35 kW kg⁻¹. Additionally, cycling stability results indicate that the 1D nanobelt-like Co₂P₂O₇ material is a better option for the electrochemical energy storage application.     

Metastable Materials Accessed under Moderate Pressure Conditions (P ≤ 3.5 GPa) in a Piston-Cylinder Press

In this review, we describe different families of metastable materials, some of them with relevant technological applications, which can be stabilized at moderate pressures 2–3.5 GPa in a piston-cylinder press. The synthesis of some of these systems had been previously reported under higher hydrostatic pressures (6–10 GPa), but can be accessed under milder conditions in combination with reactive precursors prepared by soft-chemistry techniques. These systems include perovskites with transition metals in unusual oxidation states (e.g., RNiO₃ with Ni³⁺, R = rare earths); double perovskites such as RCu₃Mn₄O₁₂ with Jahn–Teller Cu²⁺ ions at A sites, pyrochlores derived from Tl₂Mn₂O₇ with colossal magnetoresistance, pnictide skutterudites M_xCo₄Sb₁₂ (M = La, Yb, Ce, Sr, K) with thermoelectric properties, or metal hydrides Mg₂MH_x (M = Fe, Co, Ni) and AMgH₃ (A: alkali metals) with applications in hydrogen storage. The availability of substantial amounts of sample (0.5–1.5 g) allows a complete characterization of the properties of interest, including magnetic, transport, thermoelectric properties and so on, and the structural characterization by neutron or synchrotron X-ray diffraction techniques.     

Synthesis of Nano-Oxide Precipitates by Implantation of Ti,Y and O Ions in Fe-10%Cr: Towards an Understanding of Precipitation in Oxide Dispersion-Strengthened (ODS) Steels

The properties of oxide dispersion-strengthened steels are highly dependent on the nature and size distribution of their constituting nano-oxide precipitates. A fine control of the processes of synthesis would enable the optimization of pertinent properties for use in various energy systems. This control, however, requires knowledge of the precise mechanisms of nucleation and growth of the nanoprecipitates, which are still a matter of debate. In the present study, nano-oxide precipitates were produced via the implantation of Y, Ti, and O ions in two different sequential orders in an Fe-10%Cr matrix that was subsequently thermally annealed. The results show that the oxides that precipitate are not necessarily favoured thermodynamically, but rather result from complex kinetics aspects related to the interaction between the implanted elements and induced defects. When Y is implanted first, the formation of nanoprecipitates with characteristics similar to those in conventionally produced ODS steels, especially with a core/shell structure, is evidenced. In contrast, when implantation starts with Ti, the precipitation of yttria during subsequent high-temperature annealing is totally suppressed, and corundum Cr₂O₃ precipitates instead. Moreover, the systematic involvement of {110} matrix planes in orientation relationships with the precipitates, independently of the precipitate nature, suggests matrix restriction effects on the early stages of precipitation.     

Photo(electro)catalyst of Flower-Like Cobalt Oxide Co-Doped g-C3N4: Degradation of Methylene Blue under Visible Light Illumination

This work reported on the solid state synthesis of the flower-like Co(OH)₂/g-C₃N₄ nanocomposite, using a modified hydrothermal method, for the degradation of MB, an organic pollutant. These nanomaterials were characterized for structure, surface morphology and composition using XRD, SEM and XPS, respectively. The photocatalytic activities of the as-prepared materials loaded on FTO glass substrates were evaluated for their degradation of methylene blue (MB) under visible irradiation and constant voltage. The promoting effect of Fw-Co(OH)₂ on g-C₃N₄ was investigated under the influence of introduced various Co(OH)₂ amounts. The fabricated composite catalyst showed significantly improved catalytic performance compared to pristine g-C₃N₄. Degradation by 25% Fw-Co(OH)₂/g-C₃N₄ can achieve about a 100% ratio within 180 min under visible light in a three-electrode system. Moreover, Fw-Co(OH)₂/g-C₃N₄ was easily regenerated and reused, and still possessed good degradation ability. These results suggest that Fw-Co(OH)₂/g-C₃N₄ could be promising for application as a low-cost and high-efficiency catalyst for wastewater treatment and organic pollutant degradation.     

Intrinsic Properties of Multi-Layer TiO2/V2O5/TiO2 Coatings Prepared via E-Beam Evaporation

Nanocomposite multi-layer TiO₂/V₂O₅/TiO₂ thin films were prepared via electron-beam evaporation using high-purity targets (TiO₂ and V₂O₅ purity > 99.9%) at substrate temperatures of 270 °C (TiO₂) and 25 °C (V₂O₅) under a partial pressure of oxygen of 2 × 10⁻⁴ mbar to maintain the stoichiometry. Rutherford backscattering spectrometry was used to confirm the layer structure and the optimal stoichiometry of the thin films, with a particle size of 20 to 40 nm. The thin films showed an optical transmittance of ~78% in the visible region and a reflectance of ~90% in the infrared. A decrease in transmittance was observed due to the greater cumulative thickness of the three layers and multiple reflections at the interface of the layers. The optical bandgap of the TiO₂ mono-layer was ~3.49 eV, whereas that of the multi-layer TiO₂/V₂O₅/TiO₂ reached ~3.51 eV. The increase in the optical bandgap was due to the inter-diffusion of the layers at an elevated substrate temperature during the deposition. The intrinsic, structural, and morphological features of the TiO₂/V₂O₅/TiO₂ thin films suggest their efficient use as a solar water heater system.     

Inspecting Insulin Products Using Water Proton NMR. I. Noninvasive vs Invasive Inspection

Background:There is a clear need to transition from batch-level to vial/syringe/pen-level quality control of biologic drugs, such as insulin. This could be achieved only by noninvasive and quantitative inspection technologies that maintain the integrity of the drug product.Methods:Four insulin products for patient self-injection presented as prefilled pens have been noninvasively and quantitatively inspected using the water proton NMR technology. The inspection output is the water proton relaxation rate R₂(¹H₂O), a continuous numerical variable rather than binary pass/fail.Results:Ten pens of each product were inspected. R₂(¹H₂O) displays insignificant variation among the 10 pens of each product, suggesting good insulin content uniformity in the inspected pens. It is also shown that transferring the insulin solution out of and then back into the insulin pen caused significant change in R₂(¹H₂O), presumably due to exposure to O₂ in air.Conclusions:Water proton NMR can noninvasively and quantitatively inspect insulin pens. wNMR can confirm product content uniformity, but not absolute content. Its sensitivity to sample transferring provides a way to detect drug product tampering. This opens the possibility of inspecting every pen/vial/syringe by manufacturers and end-users.