Effects of reduced rebreathing time, in spontaneously breathing patients, on respiratory effort and accuracy in cardiac output measurement when using a partial carbon dioxide rebreathing technique: a prospective observational study

INTRODUCTION: New technology using partial carbon dioxide rebreathing has been developed to measure cardiac output. Because rebreathing increases respiratory effort, we investigated whether a newly developed system with 35 s rebreathing causes a lesser increase in respiratory effort under partial ventilatory support than does the conventional system with 50 s rebreathing. We also investigated whether the shorter rebreathing period affects the accuracy of cardiac output measurement. METHOD: Once a total of 13 consecutive post-cardiac-surgery patients had recovered spontaneous breathing under pressure support ventilation, we applied a partial carbon dioxide rebreathing technique with rebreathing of 35 s and 50 s in a random order. We measured minute ventilation, and arterial and mixed venous carbon dioxide tension at the end of the normal breathing period and at the end of the rebreathing periods. We then measured cardiac output using the partial carbon dioxide rebreathing technique with the two rebreathing periods and using thermodilution. RESULTS: With both rebreathing systems, minute ventilation increased during rebreathing, as did arterial and mixed venous carbon dioxide tensions. The increases in minute ventilation and arterial carbon dioxide tension were less with 35 s rebreathing than with 50 s rebreathing. The cardiac output measures with both systems correlated acceptably with values obtained with thermodilution. CONCLUSION: When patients breathe spontaneously the partial carbon dioxide rebreathing technique increases minute ventilation and arterial carbon dioxide tension, but the effect is less with a shorter rebreathing period. The 35 s rebreathing period yielded cardiac output measurements similar in accuracy to those with 50 s rebreathing

Improvement of Bending Strength of Carbon Fiber/Thermoplastic Epoxy Composites <br/>—Effects of Molecular Weight of Epoxy on Carbon Fiber/Matrix Interfacial Strength and Connection of Cracks in Matrix

The bending strength of carbon fiber/thermoplastic epoxy composites (CF/TP-EP Compo.) had bi-linear increase with increase of weight-average molecular weight (Mw) of matrix. The transition in the bending strength appeared at around 55k of Mw (“k” means 103). SEM observation of fractured surface of CF/TP-EP Compo. showed that the fracture mode changed from interfacial failure to fiber breakage dominated failure. The smooth surface of carbon fibers appeared at lower Mw than 55k while some resin remained on the fibers indicating good adhesion between carbon fiber and matrix at higher Mw than 55k. The interfacial shear strength between carbon fiber and matrix bi-linearly increased with an increase of Mw similarly to the bending strength of the composite, measured by the micro droplet test. The dynamic loss tanδ of the matrix measured at 2 Hz also showed a bi-linear relationship with respect to Mw having a knee point at Mw = 55k. The connection probability of two cracks introduced on each side of specimens also confirmed that the interfacial strength between carbon fiber and matrix is the key for the mechanical performance of CF/TP-EP Compo. in bending

Reagent-free crosslinking of aqueous gelatin : manufacture and characteristics of gelatin gels irradiated with gamma-ray and electron beam

This is an Author's Accepted Manuscript of an article published in include the complete citation information for the final version of the artcle as published in the Journal of Biomaterials Science, Polymer Edition, 2003-11, copyright Taylor & Francis, available online at: http://www.tandfonline.com/10.1163/15685620332255343

Understanding In Vivo Fate of Nucleic Acid and Gene Medicines for the Rational Design of Drugs

Nucleic acid and genetic medicines are increasingly being developed, owing to their potential to treat a variety of intractable diseases. A comprehensive understanding of the in vivo fate of these agents is vital for the rational design, discovery, and fast and straightforward development of the drugs. In case of intravascular administration of nucleic acids and genetic medicines, interaction with blood components, especially plasma proteins, is unavoidable. However, on the flip side, such interaction can be utilized wisely to manipulate the pharmacokinetics of the agents. In other words, plasma protein binding can help in suppressing the elimination of nucleic acids from the blood stream and deliver naked oligonucleotides and gene carriers into target cells. To control the distribution of these agents in the body, the ligand conjugation method is widely applied. It is also important to understand intracellular localization. In this context, endocytosis pathway, endosomal escape, and nuclear transport should be considered and discussed. Encapsulated nucleic acids and genes must be dissociated from the carriers to exert their activity. In this review, we summarize the in vivo fate of nucleic acid and gene medicines and provide guidelines for the rational design of drugs

A at Single Nucleotide Polymorphism-358 Is Required for G at -420 to Confer the Highest Plasma Resistin in the General Japanese Population

Insulin resistance is a feature of type 2 diabetes. Resistin, secreted from adipocytes, causes insulin resistance in mice. We previously reported that the G/G genotype of single nucleotide polymorphism (SNP) at −420 (rs1862513) in the human resistin gene (RETN) increased susceptibility to type 2 diabetes by enhancing its promoter activity. Plasma resistin was highest in Japanese subjects with G/G genotype, followed by C/G, and C/C. In this study, we cross-sectionally analyzed plasma resistin and SNPs in the RETN region in 2,019 community-dwelling Japanese subjects. Plasma resistin was associated with SNP-638 (rs34861192), SNP-537 (rs34124816), SNP-420, SNP-358 (rs3219175), SNP+299 (rs3745367), and SNP+1263 (rs3745369) (P<10−13 in all cases). SNP-638, SNP -420, SNP-358, and SNP+157 were in the same linkage disequilibrium (LD) block. SNP-358 and SNP-638 were nearly in complete LD (r2 = 0.98), and were tightly correlated with SNP-420 (r2 = 0.50, and 0.51, respectively). The correlation between either SNP-358 (or SNP-638) or SNP-420 and plasma resistin appeared to be strong (risk alleles for high plasma resistin; A at SNP-358, r2 = 0.5224, P = 4.94×10−324; G at SNP-420, r2 = 0.2616, P = 1.71×10−133). In haplotypes determined by SNP-420 and SNP-358, the estimated frequencies for C-G, G-A, and G-G were 0.6700, 0.2005, and 0.1284, respectively, and C-A was rare (0.0011), suggesting that subjects with A at −358, generally had G at −420. This G-A haplotype conferred the highest plasma resistin (8.24 ng/ml difference/allele compared to C-G, P<0.0001). In THP-1 cells, the RETN promoter with the G-A haplotype showed the highest activity. Nuclear proteins specifically recognized one base difference at SNP-358, but not at SNP-638. Therefore, A at -358 is required for G at −420 to confer the highest plasma resistin in the general Japanese population. In Caucasians, the association between SNP-420 and plasma resistin is not strong, and A at −358 may not exist, suggesting that SNP-358 could explain this ethnic difference

Response to Urinary Trypsin Inhibitor Therapy in Ulcerative Colitis is Associated With a Decrease in Mast Cell Count in the Colonic Mucosa

BACKGROUND: Urinary trypsin inhibitor (UTI, ulinastatin (R)) inhibits proteinases and has been used for the treatment of ulcerative colitis (UC). We investigated the therapeutic effect of UTI in patients with UC and correlated this effect to mast cell (MC) and macrophages (M) counts in the colonic mucosal wall. DESIGN: Patients with UC resistant to corticosteroids (n=16) and normal control subjects (n=10) were included in this study. Biopsy specimens obtained from the sigmoid colon of patients before and after UTI therapy were immunostained with antibodies to tryptase (AA1, MC) and CD68 (M). The number of MC and M in the lamina propria (LP) was determined and expressed per mm2 of LP. RESULTS: Nine patients with UC responded to UTI treatment. The mean number of MC in the upper part of LP in responders(440ﾂｱ51/mm2)was higher than nonresponders (312ﾂｱ76/mm2)and normal controls(200ﾂｱ47/mm2). MC counts in the lower part of the LP were not different in responders and nonresponders, although the counts in both groups were significantly higher than control. The number of M in the lower part of LP was similar in responders and nonresponders, but were higher than control subjects. M counts in the upper part of LP were similar in both groups of patients and control. Effective treatment with UTI in responders was associated with a significant fall in the number of MC in the upper layer of LP but not in M. CONCLUSION. Our results showed that UTI is an effective therapy in steroid-resistant UC. Our results also showed effective therapy with UTI was associated with a reduction in MC counts in the colonic mucosa, suggesting that the control of these cells may mediate, at least in part, the therapeutic effects of UTI in UC

高齢で発症した重症筋無力症は重症化しやすい

Objective: The continuous increase in the number of patients presenting with late-onset myasthenia gravis (LOMG) underscores the need for a better understanding of the clinical course and the establishment of an optimal therapeutic strategy. We aimed to clarify factors associated with clinical outcomes in LOMG. Methods: We retrospectively reviewed the clinical profiles of 40 patients with early-onset MG (EOMG) (onset age: 49 years or younger), 30 patients with non-elderly LOMG (onset age: 50–64 years), and 28 patients with elderly LOMG(onset age: 65 years or older) and compared the subgroups according to onset age and thymus status. The evaluated parameters were MGFA classification before treatment, MG-ADL score, complicating diseases, antibody titer, treatment, and MGFA post-intervention status. Results: Elderly LOMG patients showed transition to generalized symptoms at a higher frequency and underwent thymectomyless frequently than EOMG and non-elderly LOMG patients (p < 0.001). The frequencies of crisis and plasmapheresis were significantly lower in thymectomized LOMG patients without thymoma than in thymectomized LOMG patients with thymoma or non-thymectomized LOMG patients (p < 0.01, P < 0.05, respectively). However, the outcome was not significantly different. All of the thymectomized LOMG patients without thymoma presenting with hyperplasia or thymic cyst had a favorable clinical course. Conclusions: Our study showed that elderly LOMG patients are more prone to severity, suggesting that they require aggressive immunomodulatory therapy