Inadequate Folic Acid Intake Among Women Taking Antiepileptic Drugs During Pregnancy in Japan: A Cross-Sectional Study

This study aimed to assess characteristics of pregnant women taking antiepileptic drugs with inadequate folic acid intake. This cross-sectional study examined pregnant women taking antiepileptic drugs who were registered in the Japanese Drug Information Institute in Pregnancy (JDIIP) database between October 2005 and December 2016. Participants were classified into two groups according to when they started folic acid supplementation (before pregnancy: ‘adequate’, after pregnancy or never: ‘inadequate’). Logistic regression analysis was performed to investigate factors associated with inadequate folic acid intake. Of 12,794 registrants, 468 pregnant women were taking antiepileptics during the first trimester. Of these, we analysed data from 456 women who had no missing data. As a result, inadequate folic acid intake was noted among 83.3% of them, suggesting that the current level of folic acid intake is insufficient overall. Younger age, smoking, alcohol drinking, multiparity, unplanned pregnancy, and being prescribed AEDs by paediatric or psychiatric departments were independent factors associated with inadequate folic acid intake. As planned pregnancy was the strongest factor, healthcare professionals should ensure that childbearing women taking antiepileptics are informed of the importance of planned pregnancy. In addition, healthcare professionals must gain a better understanding of folic acid intake, as the prevalence of adequate intake differed according to which departments prescribed antiepileptic drugs

Analysis of the triplet-state kinetics of a photosensitizer for photoimmunotherapy by fluorescence correlation spectroscopy

Herein, we evaluated the intersystem crossing quantum yield (Phi(ISC)) of a silicon phthalocyanine derivatized from IRDye700DX (IR700) which is used as a photosensitizer for photoimmunotherapy (PIT), using fluorescence correlation spectroscopy (FCS). The calculated Phi(ISC) was 0.019 +/- 0.002. The FCS measurement was validated by experiment in the presence of potassium iodide, which can change the kinetics of the relaxation process in the excited state

Tocilizumab and pregnancy: Four cases of pregnancy in young women with rheumatoid arthritis refractory to anti-TNF biologics with exposure to tocilizumab

<p><i>Objectives</i>: To investigate the use of tocilizumab (TCZ) in pregnant patients with active rheumatoid arthritis (RA) refractory to anti-tumour necrosis factor (TNF) agents.</p> <p><i>Methods</i>: We retrospectively analysed the medical records of pregnant women with active RA treated between July 2008 and January 2015 by the Division of Maternal Medicine at our hospital. Inclusion criteria for this case series included active RA refractory to anti-TNF agents and exposure to TCZ at the time of conception.</p> <p><i>Results</i>: Our review of 28 patient hospital records identified four patients who met the inclusion criteria. All four patients had active synovitis before starting treatment with TCZ. Successful TCZ therapy allowed them to plan to become pregnant. When pregnancy was confirmed, TCZ was terminated as soon as possible in all patients. Three patients delivered full-term infants without any adverse outcomes. One patient had a partial molar pregnancy and miscarried during gestational week 11. Two patients remained in clinical remission with low-dose prednisolone (PSL) or no treatment for RA during pregnancy.</p> <p><i>Conclusions</i>: TCZ may be a good alternative therapy for RA patients with symptoms that are hard to control with TNF blockers who desire to bear children.</p

Instillation of Ophthalmic Formulation Containing Nilvadipine Nanocrystals Attenuates Lens Opacification in Shumiya Cataract Rats

We developed ophthalmic formulations based on nilvadipine (NIL) nanocrystals (NIL-NP dispersions; mean particle size: 98 nm) by using bead mill treatment and investigated whether the instillation of NIL-NP dispersions delivers NIL to the lens and prevents lens opacification in hereditary cataractous Shumiya cataract rats (SCRs). Serious corneal stimulation was not detected in either human corneal epithelial cells or rats treated with NIL-NP dispersions. The NIL was directly delivered to the lens by the instillation of NIL-NP dispersions, and NIL content in the lenses of rats instilled with NIL-NP dispersions was significantly higher than that in the ophthalmic formulations based on NIL microcrystals (NIL-MP dispersions; mean particle size: 21 &micro;m). Moreover, the supply of NIL prevented increases in Ca2+ content and calpain activity in the lenses of SCRs and delayed the onset of cataracts. In addition, the anti-cataract effect in the lens of rats instilled with NIL-NP dispersions was also significantly higher than that in NIL-MP dispersions. NIL-NPs could be used to prevent lens opacification

Development of a red-shifted photosensitizer for near-infrared photoimmunotherapy of cancer

Near-infrared photoimmunotherapy (NIR-PIT) is a recently described method for cancer treatment that utilizes an antibody-conjugated phthalocyanine photosensitizer and NIR light. In NIR-PIT, light of 690 nm wavelength is used to activate a photosensitizer, IR700, while longer-wavelength light penetrates deeper into tissues. Thus, more effective NIR-PIT would be achieved by using photosensitizers that are activated by longer-wavelength light. The absorption wavelength would be red-shifted by destabilizing the highest occupied molecular orbital (HOMO) energy level by introducing electron donating groups at the α positions of a phthalocyanine ring. In this study, we developed a red-shifted photosensitizer for NIR-PIT, KA800, whose absorption wavelength was red-shifted by the introduction of ethoxy groups to IR700. As intended, the absorption maximum of KA800 was red-shifted compared to IR700 by 84 nm. Although phototoxicity of the antibody-KA800 (Ab-KA800) conjugate was observed in cultured cancer cells, no therapeutic effect was observed in mice. This is because the cytotoxicity of Ab-KA800 was mainly due to singlet oxygen, which can be quenched by abundant antioxidants in vivo. KA800 had low reactivity with respect to axial ligand cleavage required for inducing cell death via aggregate formation, a unique cytotoxic mechanism in NIR-PIT. The axial ligand cleavage proceeds via the anion radical formation of the photosensitizer, and KA800 was found to be less likely to receive an electron than IR700. This may be due to the destabilization of the HOMO energy level of KA800. Therefore, our findings suggest that stabilizing the lowest unoccupied molecular orbital (LUMO) energy level would be better than destabilizing the HOMO energy level for developing a red-shifted photosensitizer for NIR-PIT

Theoretical and Experimental Studies on the Near-Infrared Photoreaction Mechanism of a Silicon Phthalocyanine Photoimmunotherapy Dye : Photoinduced Hydrolysis by Radical Anion Generation

Ligand release from IR700, a silicon phthalocyanine dye used in near-infrared (NIR) photoimmunotherapy, initiates cancer cell death after NIR absorption, although its photochemical mechanism has remained unclear. This theoretical study reveals that the direct Si-ligand dissociation by NIR light is difficult to activate because of the high dissociation energy even in excited states, i. e., >1.30 eV. Instead, irradiation generates the IR700 radical anion, leading to acid-base reactions with nearby water molecules (i. e., calculated pK(b) for the radical anion is 7.7) to produce hydrophobic ligand-released dyes. This suggests two possibilities: (1) water molecules participate in ligand release and (2) light is not required for Si-ligand dissociation as formation of the IR700 radical anion is sufficient. Experimental evidence confirmed possibility (1) by using O-18-labeled water as the solvent, while (2) is supported by the pH dependence of ligand exchange, providing a complete description of the Si-ligand bond dissociation mechanism

Theoretical and Experimental Studies on the Near‐Infrared Photoreaction Mechanism of a Silicon Phthalocyanine Photoimmunotherapy Dye: Photoinduced Hydrolysis by Radical Anion Generation

Ligand release from IR700, a silicon phthalocyanine dye used in near-infrared (NIR) photoimmunotherapy, initiates cancer cell death after NIR absorption, although its photochemical mechanism has remained unclear. This theoretical study reveals that the direct Si-ligand dissociation by NIR light is difficult to activate because of the high dissociation energy even in excited states, i. e., >1.30 eV. Instead, irradiation generates the IR700 radical anion, leading to acid-base reactions with nearby water molecules (i. e., calculated pK(b) for the radical anion is 7.7) to produce hydrophobic ligand-released dyes. This suggests two possibilities: (1) water molecules participate in ligand release and (2) light is not required for Si-ligand dissociation as formation of the IR700 radical anion is sufficient. Experimental evidence confirmed possibility (1) by using O-18-labeled water as the solvent, while (2) is supported by the pH dependence of ligand exchange, providing a complete description of the Si-ligand bond dissociation mechanism