Daizo Saito

Efficacy and bleeding risk of antithrombin supplementation in septic disseminated intravascular coagulation: a prospective multicenter survey.

INTRODUCTIONnAlthough supplementation with antithrombin (AT) concentrates has been widely accepted for the treatment of disseminated intravascular coagulation (DIC) in Japan, the effects and adverse effects have not been investigated.nnnMATERIALS AND METHODSnWe conducted a nonrandomized multi-institutional survey. A total of 729 septic DIC patients with AT activity levels of 70% or lower, who had undergone AT substitution at either 1500 IU/day or 3000 IU/day for consecutive 3 days were analyzed. Of these, 650 and 79 patients had received 1500 IU/day (AT1500 group) and 3000 IU/day (AT3000 group), respectively.nnnRESULTSnBleeding events were observed in 6.52% of patients (severe bleeding, 1.71%). A significant decrease in initial AT level (below 50%) was observed in 69.6% of patients in AT3000 group and 48.2% in AT1500 group, and this difference was significant (P<0.01). A logistic-regression analysis conducted using age, gender, body weight, initial AT activity, and supplemented AT dose, revealed that higher initial AT activity (odds ratio (OR), 1.032; P<0.001), AT dose of 3000 IU/day (OR, 1.912; P=0.026), and age (OR, 0.985; P=0.023) were significant factors for improved survival.nnnCONCLUSIONnThe risk of severe bleeding is less than 2%, and concomitant administration of heparin did not increase the risk. The survival in AT1500 group was 65.2%, while that in AT3000 group was 74.7%.

Measurement of burn depths in rats using multiwavelength photoacoustic depth profiling.

We perform measurement of photoacoustic (PA) signals for burned skin in rats in the spectral range of 500 to 650 nm. The wavelength dependence of PA signal amplitude shows characteristics similar to those of the absorption spectrum of hemoglobin, suggesting that the PA signal originates from blood in the uninjured skin tissue under the injured tissue layer. High-contrast signals are obtained in the spectral range of 532 to 580 nm. At 550 nm, a PA detector is scanned on the wounds and PA tomograms are obtained. The tomograms clearly show the zones of stasis, demonstrating that a 2-D PA measurement is useful for burn depth assessment.

Relationship between the hemoglobin level at hospital arrival and post-cardiac arrest neurologic outcome

BACKGROUNDnThe hemoglobin (Hb) level is an essential determinant of oxygen delivery. The restoration of blood perfusion to vital organs and the capacity for oxygen delivery may be associated with ischemia and reperfusion injuries during cardiac arrest and after cardiac arrest. However, whether the Hb level is associated with neurologic outcome in post-cardiac arrest patients remains unclear.nnnMETHODSnEmergency medical service information and clinical demographics were compiled for witnessed out-of-hospital cardiac arrest patients with coma after the restoration of spontaneous circulation. The study end point was defined as a favorable neurologic outcome at 28 days. We evaluated the relationship between the Hb level at the time of hospital arrival and the neurologic outcome using univariate analyses and a multivariate logistic regression analysis.nnnRESULTSnThere were 137 witnessed cardiac arrest patients: 49 (35.7%) survived and 34 (24.8%) achieved a favorable neurologic outcome. Univariate analyses showed that the favorable outcome group was characterized as having a higher Hb level, a younger age, a higher percentage of male patients, and ventricular fibrillation as the initial cardiac rhythm. In a multivariate analysis adjusting for potential confounding factors, the Hb level at the time of hospital arrival (odds ratio, 1.26; 95% confidence interval, 1.00-1.58) was an independent predictor of a favorable neurologic outcome.nnnCONCLUSIONnA higher Hb level at the time of hospital arrival was associated with a favorable short-term neurologic outcome among post-cardiac arrest patients with a presumed cardiac etiology.

Photodynamic therapy using nanoparticle loaded with indocyanine green for experimental peritoneal dissemination of gastric cancer

Although there have been multiple advances in the development of novel anticancer agents and operative procedures, prognosis of patients with advanced gastric cancer remains poor, especially in patients with peritoneal metastasis. In this study, we established nanoparticles loaded with indocyanine green (ICG) derivatives: ICG loaded lactosomes (ICGm) and investigated the diagnostic and therapeutic value of photodynamic therapy (PDT) using ICGm for experimental peritoneal dissemination of gastric cancer. Experimental peritoneal disseminated xenografts of human gastric cancer were established in nude mice. Three weeks after intraperitoneal injection of the cancer cells, either ICGm (ICGm‐treated mice) or ICG solution (ICG‐treated mice) was injected through the tail vein. Forty‐eight hours after injection of the photosensitizer, in vivo and ex vivo imaging was carried out. For PDT, 48 h after injection of the photosensitizer, other mice were irradiated through the abdominal wall, and the body weight and survival rate were monitored. In vivo imaging revealed that peritoneal tumors were visualized through the abdominal wall in ICGm‐treated mice, whereas only non‐specific fluorescence was observed in ICG‐treated mice. The PDT reduced the total weight of the disseminated nodules and significantly improved weight loss and survival rate in ICGm‐treated mice. In conclusion, ICGm can be used as a novel diagnostic and therapeutic nanodevice in peritoneal dissemination of gastric cancer.

Effect of running training on uncoupling protein mRNA expression in rat brown adipose tissue.

The effect was investigated of endurance training on the expression of uncoupling protein (UCP) mRNA in brown adipose tissue (BAT) of rats. The exercised rats were trained on a rodent treadmill for 5 days per week and a total of 9 weeks. After the training programme, a marked decrease in BAT mass was found in terms of weight or weight per unit body weight; there was a corresponding decrease in DNA content and a downward trend in RNA and glycogen levels. The UCP mRNA was present at a markedly decreased level in BAT of trained animals. In consideration of the reduced levels of mRNAs for hormone-sensitive lipase and acylCoA synthetase, the brown adipose tissue investigated appeared to be in a relatively atrophied and thermogenically quiescent state.

Theranostic Photosensitive Nanoparticles for Lymph Node Metastasis of Gastric Cancer

BackgroundPreoperative and intraoperative diagnoses of lymph node (LN) metastasis in patients with gastric cancer is essential to determine the extent of LN dissection in order to establish individualized treatment strategies. We investigated the theranostic value of a newly developed drug delivery system employing nanoparticles loaded with the indocyanine green (ICG) derivative ICG-loaded lactosome (ICGm) using a murine draining LN metastasis model of gastric cancer.MethodsIn the experimental draining LN metastasis model of human gastric cancer, the right hind footpads of nude mice were injected with cancer cells. Three weeks later, either ICGm or ICG solution was injected through the tail vein. Forty-eight hours after the administration of a photosensitizer, in vivo and ex vivo imaging and photodynamic therapy (PDT) were performed, and size of the LNs was measured.ResultsIn vivo imaging revealed metastatic LNs in the ICGm-treated mice but not in the ICG-treated mice. PDT using ICGm induced apoptosis and significantly inhibited the growth of metastatic LNs.ConclusionsICGm presents a novel theranostic nanodevice for LN metastasis of gastric cancer.

Photoacoustic diagnosis of burns in rats: two-dimensional photo-acoustic imaging of burned tissue

We previously reported that for rat burn models, deep dermal burns and deep burns can be well differentiated by measuring the propagation time of the photoacoustic signals originated from the blood in the healthy skin tissue under the damaged tissue layer. However, the diagnosis was based on point measurement in the wound, and therefore site-dependent information on the injuries was not obtained; such information is very important for diagnosis of extended burns. In the present study, we scanned a photoacoustic detector on the wound and constructed two-dimensional (2-D) images of the blood-originated photoacoustic signals for superficial dermal burns (SDB), deep dermal burns (DDB), deep burns (DB), and healthy skins (control) in rats. For each burn model, site-dependent variation of the signal was observed; the variation probably reflects the distribution of blood vessels in the skin tissue. In spite of the variation, clear differentiation was obtained between SDB, DDB, and DB from the 2D images. The images were constructed as a function of post burn time. Temporal signal variation will be also presented.

Photoacoustic signal measurement for burned skins in the spectral range of 500-650 nm: experiment with rat burn models

This paper reports the burn diagnosis that is based on the measurement of photoacoustic waves from skin, where the acoustic waves originate from the absorption of light by blood. For this purpose, a transducer composed of a ring-shaped piezoelectric film and a quartz fiber was made. An optical parametric oscillator (500 - 650 nm) was used as a light source and its output pulses were coupled to the quartz fiber. To investigate the optimum light wavelength, we conducted experiments using rat burn models. We demonstrated that the superficial dermal burn (SDB), deep dermal burn (DDB), deep burn (DB), and control (healthy skin) could be clearly differentiated based on the photoacoustic signals induced by the light of 532 - 580nm.

Pulsed photodynamic inactivation of gram-negative bacteria: in vitro study using methylene blue

Pulsed photodynamic effect on Ps.aeruginosa has been investigated in vitro with the use of methylene blue (MB) as a photosensitizer. Bacterial suspensions were illuminated with 665-nm, nanosecond light pulses under the various drug and light dose conditions. Bacterial survival fraction decreased with increasing the drug and light doses, while no significant bacterial cell death was observed when the bacteria were washed after incubation with the drug. These results suggest a two-step photo-bactericidal mechanism; the photodynamic effect first induces membrane damage through which MB molecules were translocated into the bacterial cytoplasm, and then caused bacterial cell death.

Pulsed photodynamic inactivation of gram-negative bacteria: electron microscopic study

We previously demonstrated the methylene blue-mediated photodynamic inactivation of P. aeruginosa in vitro using pulsed light excitation. However, the photobactericidal mechanism has not been revealed yet. In this study, morphological changes induced by pulsed photodynamic treatment in bacteria were investigated by electron microscopy. The micrographs of bacteria showed an alteration in the membrane structure in the early period of illumination, and increase in the total light dose caused an alteration in the cytoplasmic structure. It was shown that the membrane damage may be lethal to bacteria.