Low-dose radioiodine therapy for patients with intermediate- to high-risk differentiated thyroid cancer

Annals of Nuclear Medicine - The efficacy of low-dose radioiodine therapy (RIT) for intermediate-risk or high-risk differentiated thyroid cancer (DTC) patients is controversial. Because of the...     

Pharmacokinetics and tissue distribution of 3,4‐diaminopyridine in rats

Lambert‐Eaton myasthenic syndrome (LEMS) is characterized by muscle weakness, amyotrophy, easy fatigability, and depressed tendon reflexes. 3,4‐Diaminopyridine (3,4‐DAP) is the recommended therapy for the treatment of LEMS. However, estimations of 3,4‐DAP pharmacokinetics in human and animals, such as rats, are rarely reported because 3,4‐DAP is an orphan drug for the treatment of a very rare disease (LEMS). In particular, little is known about its tissue distribution. Therefore, the pharmacokinetics of 3,4‐DAP were studied, with particular focus on tissue distribution, in rats. After intravenous administration of 3,4‐DAP to rats, the half‐life of 3,4‐DAP was 15.9 ± 3.9 min and the volume of distribution at steady‐state was 2.8 ± 0.7 L/kg. The tissue‐to‐plasma partition coefficient (Kp) was high in the kidney, heart, and muscle. In addition, with increased steady state plasma concentration (Css), a tendency toward increased Kp was found in most tissues. In the muscle, a likely target region of 3,4‐DAP in LEMS patients, the Kp was higher than in the plasma. Furthermore, more than 68% of 3,4‐DAP was distributed to the muscle as determined by the ratio of 3,4‐DAP distribution calculated from the apparent volumes of distribution. Hence, 3,4‐DAP may provide for more effective and long‐lasting effects.     

Systematic Study of Effective Hydrothermal Synthesis to Fabricate Nb-Incorporated TiO2 for Oxygen Reduction Reaction

Fuel cells are expected to serve as next-generation energy conversion devices owing to their high energy density, high power, and long life performance. The oxygen reduction reaction (ORR) is important for determining the performance of fuel cells; therefore, using catalysts to promote the ORR is essential for realizing the practical applications of fuel cells. Herein, we propose Nb-incorporated TiO₂ as a suitable alternative to conventional Pt-based catalysts, because Nb doping has been reported to improve the conductivity and electron transfer number of TiO₂. In addition, Nb-incorporated TiO₂ can induce the electrocatalytic activity for the ORR. In this paper, we report the synthesis method for Nb-incorporated TiO₂ through a hydrothermal process with and without additional load pressures. The electrocatalytic activity of the synthesized samples for the ORR was also demonstrated. In this process, the samples obtained under various load pressures exceeding the saturated vapor pressure featured a high content of Nb and crystalline TiNb₂O₇, resulting in an ellipsoidal morphology. X-ray diffraction results also revealed that, on increasing the Nb doping amounts, the diffraction peak of the anatase TiO₂ shifted to a lower angle and the full width at half maximum decreased. This implies that the Ti atom is exchanged with the Nb atom during this process, resulting in a decrease in TiO₂ crystallinity. At a doping level of 10%, Nb-incorporated TiO₂ exhibited the best electrocatalytic activity in terms of the oxygen reduction current (i_ORR) and onset potential for the ORR (E_ORR); this suggests that 10% Nb-doped samples have the potential for enhancing electrocatalytic activity.     

Two forms of diffuse alveolar damage in the lungs of patients with acute respiratory distress syndrome

Acute respiratory distress syndrome is a severe disease, the treatment and pathophysiology of which are not completely established. The pathology of acute respiratory distress syndrome involves diffuse alveolar damage, which comprises severe alveolar epithelial cell damage, hyaline membrane formation, and festinate myofibroblast proliferation and fibrosis in the intra-alveolar spaces. We performed a clinicopathologic investigation of 26 autopsy cases of diffuse alveolar damage. Three cases of them were diagnosed as acute interstitial pneumonia that is idiopathic illness and resembles pathologically organizing diffuse alveolar damage. Immunohistochemical staining for types I and IV collagen, α-smooth muscle actin, and Ki-67 was carried out, and the sites of myofibroblast proliferation and type I collagen production were examined. All diffuse alveolar damage cases in the proliferative phase showed intra-alveolar myofibroblast proliferation. When diffuse alveolar damage was diagnosed pathologically as being due to severe infection, all 7 patients showed multiple organ dysfunction syndrome, whereas only 2 of 7 patients showed interstitial myofibroblast proliferation. When diffuse alveolar damage was attributed to tumor treatment with chemotherapy or to drug toxicity, 3 of 16 patients showed multiple organ dysfunction syndrome; 15 of 16 showed interstitial myofibroblast proliferation, 3 of 3 acute interstitial pneumonia patients did not show multiple organ dysfunction syndrome; and 3 of 3 acute interstitial pneumonia showed marked interstitial myofibroblast proliferation. These results suggest that the pathophysiologic mechanism of diffuse alveolar damage caused by severe infection is one of systemic circulation disturbance, although the mechanism underlying diffuse alveolar damage due to tumor with chemotherapy or drug toxicity appears to involve interstitial pneumonia-like lesions that are similar to acute interstitial pneumonia.     

Utility of high-resolution computed tomography for predicting risk of sputum smear-negative pulmonary tuberculosis

Background

To diagnose sputum smear-negative pulmonary tuberculosis (PTB) is difficult and the ability of high-resolution computed tomography (HRCT) for diagnosing PTB has remained unclear in the sputum smear-negative setting. We retrospectively investigated whether or not this imaging modality can predict risk for sputum smear-negative PTB.

Methods

We used HRCT to examine the findings of 116 patients with suspected PTB despite negative sputum smears for acid-fast bacilli (AFB). We investigated their clinical features and HRCT-findings to predict the risk for PTB by multivariate analysis and a combination of HRCT findings by stepwise regression analysis. We then designed provisional HRCT diagnostic criteria based on these results to rank the risk of PTB and blinded observers assessed the validity and reliability of these criteria.

Results

A positive tuberculin skin test alone among clinical laboratory findings was significantly associated with an increase of risk of PTB. Multivariate regression analysis showed that large nodules, tree-in-bud appearance, lobular consolidation and the main lesion being located in S1, S2, and S6 were significantly associated with an increased risk of PTB. Stepwise regression analysis showed that coexistence of the above 4 factors was most significantly associated with an increase in the risk for PTB. Ranking of the results using our HRCT diagnostic criteria by blinded observers revealed good utility and agreement for predicting PTB risk.

Conclusions

Even in the sputum smear-negative setting, HRCT can predict the risk of PTB with good reproducibility and can select patients having a high probability of PTB.     

Leukotoxin, 9,10-Epoxy-12-Octadecenoate, Causes Pulmonary Vasodilation by Stimulation of Vascular eNOS and iNOS

We have previously reported that leukotoxin, 9,10-epoxy-12-octadecenoate (Lx) dilates rat pulmonary arteries by means of nitric oxide synthase (NOS) activation. In this study, we investigated if Lx stimulates constitutive and/or inducible NOS. We studied the effect of the NOS inhibitors, N^G-monomethyl-l-arginine and aminoguanidine, as well as endothelium denudation on Lx-induced rat pulmonary arterial dilation and that of aminoguanidine on Lx-induced endothelium denuded lipopolysaccharide (LPS)-treated rat pulmonary arterial dilation and tissue cGMP content. Furthermore, we assessed the effect of aminoguanidine, an inducible NOS (iNOS) inhibitor, on the cGMP content increase induced by Lx in LPS-treated human pulmonary artery smooth muscle cells (HPASMC). The NOS inhibitors and endothelium denudation significantly attenuated Lx-induced vasodilation. Aminoguanidine also significantly attenuated Lx-induced vasodilation in LPS-treated rat denuded pulmonary arteries, and attenuated Lx-induced cGMP content increase in denuded pulmonary arterial rings from LPS-treated rats and in LPS-treated HPASMC. These results suggest that Lx causes pulmonary vasodilation by stimulation of vascular endothelial NOS (eNOS) and iNOS. Accepted for publication: 1 March 2000