Fabrication of porous particulate for the scaffold by applying solution spraying method

A simple and novel method--in the form of solution spraying--was developed to fabricate biodegradable, porous poly(L-lactic acid) (PLLA) particulates for scaffold. PLLA pellets were dissolved in an organic solvent. Then, 5 % PLLA-dioxane solution was sprayed using an air-assisted atomizer with a nozzle diameter of 2.5 mm at an air flow rate of 15 L/min. After the sprayed solution solidified in liquid nitrogen, spherical particulates with median diameter of 225microm were obtained. Morphology of sprayed products could be altered by varying the fabrication conditions. When nozzle diameter was reduced to 1.5 mm, sprayed products became fibrous. When the concentration of PLLA-dioxane solution was increased, the diameter of particulates increased too. On the other hand, when air flow rate was increased, the diameter of particulates decreased. Likewise, solidification conditions also affected the morphology of sprayed products, such that they were either thin film-like or in particulate form. Based on the results of the present study, we concluded that PLLA particulates of varying morphologies could be obtained by adjusting the fabrication conditions.     

A combination of three common inherited mitochondrial DNA polymorphisms promotes longevity in Finnish and Japanese subjects

Mitochondrial DNA (mtDNA) coding region polymorphisms, as well as the 150T polymorphism in the noncoding region, have been associated with longevity. We have studied here the association of 150T with longevity further and assessed differences in this association between various mtDNA haplogroups. We analysed a sample of 321 very old subjects and 489 middle-aged controls from Finland and Japan. 150T was more frequent among the very old than among the controls in both the Finnish and Japanese subjects. Interestingly, the association was not similar in all haplogroups, and a stratified analysis revealed that two additional common polymorphisms, 489C and 10398G, modified the association between 150T and longevity. These findings suggest that longevity is partly determined by epistatic interactions involving these three mtDNA loci.     

Diagnostic Peritoneal Lavage for Diagnosing Blunt Hollow Visceral Injury: The Accuracy of Two Different Criteria and Their Combination

Purpose To test the usefulness of diagnostic peritoneal lavage (DPL) for identifying blunt hollow visceral injury with two different sets of criteria or a combination of the two. Methods Fifty victims with physical examinations and/or computed tomography findings equivocal for blunt hollow visceral injury underwent DPL. Whether or not to perform surgery was determined based on Otomo's DPL criteria [lavage white blood cell counts (L-WBC) over lavage red blood cell counts (L-RBC) divided by 150 (L-WBC ≥ L-RBC/150) in the presence of hemoperitoneum, or L-WBC over 500/mm³ (L-WBC ≥ 500) in the absence of hemoperitoneum]. The cell count ratio, a comparison of L-WBC, L-RBC, peripheral WBC (P-WBC), and peripheral RBC (P-RBC) [(L-WBC/L-RBC)/(P-WBC/P-RBC) ≥ 1] were all calculated retrospectively. Results There were one and two false-positive cases based on Otomo's criteria and the cell count ratio, respectively, with corresponding accuracies of 97.8% and 95.7%, respectively. There were no false-positive or -negative cases according to the combined use of Otomo's criteria and cell count ratio, yielding an accuracy of 100%. Conclusion Although each criterion alone is very accurate in predicting the presence of blunt hollow visceral injury, the combined use of the two would further improve the accuracy of the diagnosis and thereby reduce the number of unnecessary celiotomies.     

Anesthetic management of tracheobronchial stent insertion in patients who underwent laser resection, balloon dilatation and tracheostomy in advance

BACKGROUND: We report successful management of tracheobronchial stent insertion under general anesthesia. METHODS: In thirty-two cases, tracheobronchial stent insertion was performed under general anesthesia. The technique for airway management was chosen depending on the type of stent or the constriction level of the airway portion. We employed tracheostomy in order to avoid repeated intubations during the insertion of Dumon or Dynamic stent. In case of severe airway stenosis, laser resection or balloon dilatation was performed before stent insertion. RESULTS: We had 32 successful cases in 36 trials. Four trials failed due to insufficient expansion in one, mismatches of stent angle in one and pneumomediastinum in one. There was no exacerbation of respiratory condition in failed cases. There was no case who needed percutaneous cardiopulmonary support system. CONCLUSIONS: We managed tracheobronchial stent insertion under general anesthesia. Both the airway expansion by laser resection or balloon dilatation before stent insertion and also the insertion of Dumon or Dynamic stent through a tracheostomy were helpful strategies. These techniques facilitated more definitive airway maintenance and stable anesthetic management.     

Hemodynamic infarction of the spinal cord: involvement of the gray matter plus the border-zone between the central and peripheral arteries

OBJECTIVE: Hemodynamic infarction of the spinal cord that affected an 81-year-old female having a dissecting aortic aneurysm is presented. During the graft replacement operation, systemic hypotension occurred and the patient was subsequently complicated with paraplegia of the lower limbs. The patient died 2 weeks after the surgery due to gastrointestinal bleeding. An autopsy, which did not include the brain, was performed and the spinal cord was sampled. The aim of this report is to describe the pathologic profile of the spinal cord of the patient, and to gain insight into the pathogenesis of the lesion. METHODS: Histochemical and immunohistochemical methods were employed to study the spinal cord ranging from the lower thoracic to sacral segments. RESULTS: The whole central areas of the spinal cord showed coagulation and/or liquefaction necroses, while the white matter on the circumference of the cord remained unaffected, thus exhibiting a 'ring-like' appearance. CONCLUSION: This case is an example of hemodynamic infarction of the spinal cord involving the gray matter that is supplied by the central artery, plus the border-zone that is supplied by both the central and peripheral arteries. The former is probably associated with selective vulnerability of the gray matter to ischemia, while the latter is probably associated with intrinsic vulnerability of the border-zone to systemic hypotension or low blood-flow states.     

Clinical effects of long-term administration of pranlukast, a leukotriene receptor antagonist, on adult patients with bronchial asthma

Eighty-one adult patients with bronchial asthma who suffered from an unstable peak expiratory flow rate (PEFR) and asthmatic attacks that developed at irregular intervals in spite of inhaling beclometasone dipropionate (CAS 5534-09-8, BDP) in excess of 400 micrograms/day were treated with pranlukast (CAS 103177-37-3, Onon) 450 mg/day for 1 to 2 years and the clinical effects of its long-term administration were studied. The patients were divided into 3 groups: Group I with drug effect seen on peak expiratory flow rate (PEFR) in a short-term; Group II showing long term PEFR improvement; and Group III with no sustained improvement in PEFR. Those in the first two groups continued oral medication for 2 years, while those of the third group withdrew from medication after one year and their clinical course was observed. The evaluation parameters were: PEFR, frequency of beta 2-stimulant inhalation, number of night time visits to health service facilities, quantity of inhalation steroids used, amount of oral steroids used at fixed intervals, peripheral eosinophil count, serum eosinophil cationic protein (ECP) concentration and FEV1.0. In Group I, the frequency of beta 2-stimulant inhalation, number of night time visits to health service facilities, quantity of inhalation steroids used, and the amount of oral steroids used at fixed intervals were reduced; and after two years, the frequency of beta 2-stimulant inhalation and quantity of inhalation steroids used were further reduced. In Group II, reductions were seen in the peripheral eosinophil count and serum ECP level. The asthmatic severity shifted from step 3 to 2 in 12 patients and from step 4 to 3 in 4 patients in Group I; and from step 3 to 2 in 3 patients in Group II. In Group III, an increase in the number of night time visits to health service facilities after the medication was interrupted and a rise in the serum ECP concentration were recognized.     

Inhibitory effects of ursodeoxycholic acid on the induction of nitric oxide synthase in vascular smooth muscle cells

The expression of inducible nitric oxide synthase (iNOS) and the resultant increased nitric oxide production are associated with endotoxemia and atherosclerotic lesions observed in transplant hearts or balloon-injured artery. Ursodeoxycholic acid has been shown to have cardiovascular protective effects, such as inhibition of the development of transplant arteriosclerosis, but its mechanism remains unclear. Here, we investigated the effects of ursodeoxycholic acid on nitric oxide production and the expression of iNOS in vascular smooth muscle cells isolated from adult rat aorta and rabbit coronary artery. Nitrite released from cells in the culture medium was measured with the Griess reaction. iNOS mRNA and protein were measured by Northern and Western blot analyses. Treatment with ursodeoxycholic acid (30-1000 microM) significantly inhibited lipopolysaccharide plus interferon-gamma-induced nitric oxide production in a concentration-dependent manner, but ursodeoxycholic acid showed only small inhibitory effects on nitric oxide production that had already been induced by lipopolysaccharide plus interferon-gamma. Ursodeoxycholic acid by itself did not affect basal nitric oxide production. Ursodeoxycholic acid also suppressed lipopolysaccharide plus interferon-gamma-induced expression of iNOS mRNA and protein. Ursodeoxycholic acid had the most potent inhibitory effect among various kinds of bile acids examined, i.e. chenodeoxycholic acid, deoxycholic acid, cholic acid and conjugated bile acids such as tauroursodeoxycholic acid. These results suggest that ursodeoxycholic acid inhibits the induction of iNOS and then nitric oxide production in aortic and coronary artery smooth muscle cells, suggesting a possible mechanism for the cardiovascular protective effect of ursodeoxycholic acid under various pathophysiological conditions such as endotoxemia and atherosclerosis.     

beta-Catenin mutation is selected during malignant transformation in colon carcinogenesis

Activating mutations in the beta-catenin gene is thought to be responsible for the excessive beta-catenin signaling involved in the majority of colon carcinomas in rodent models. Our recent study which indicated that beta-catenin mutations are present frequently in early dysplastic lesions of rat colon induced by a colon-specific carcinogen, azoxymethane led us to perform more specifically a comparative study regarding types of the beta-catenin mutation as well as K-ras mutations between such early appearing lesions and colon tumors. Male F344 rats, 6 weeks old, received s.c. injections of azoxymethane (15 mg/kg body weight) once a week for 3 weeks, and were killed at 16 and 46 weeks of age. Colons of animals killed at 16 weeks of age were processed for early altered lesions. Colon tumors from animals killed at 46 weeks of age were evaluated histopathologically. Laser capture microdissection system was used to obtain DNA of epithelial cells in both intramucosal lesions and colon tumors. After amplification of exon 3 of the beta-catenin gene and exon 1 of the K-ras gene, the products were then sequenced directly in both directions. Mutations in the exon 3 of beta-catenin gene were detected in 22 of 56 early lesions (39.3%) and 21 of 37 colon cancers (56.8%). Remarkably, all beta-catenin mutations detected in the colon tumors converged at codons encoding functionally important residues that may directly mediate beta-catenin degradation, whereas mutations in the early appearing lesions were found to be scattered in the exon 3 of the gene. K-ras mutations were also detected in 24 of 56 early lesions (42.9%) and 11 of 37 colon cancers (29.7%). All K-ras mutations converged at codon 12 and codon 13, even in the early lesions. The results of this study provide evidence for the first time that beta-catenin mutation is selected during the colon carcinogenesis. Our results also suggest that the activation of beta-catenin signaling pathway is not only an initiating event, but also plays a pivotal role in the promotion stage of colorectal carcinogenesis.     

Randomized controlled trial of the effect of bifidobacteria-fermented milk on ulcerative colitis

BACKGROUND: Alterations of intestinal flora, such as reduction in the concentration of bifidobacteria and increase in that of Bacteroides species, are apparently associated with the severity of ulcerative colitis. OBJECTIVE: We conducted a randomised clinical trial of the use of a bifidobacteria-fermented milk (BFM) supplement as a dietary adjunct in the treatment of ulcerative colitis. METHODS: The subjects were randomly divided into two groups: a group with BFM supplementation (BFM group, 11 subjects) and a control group (control group, 10 subjects). The BFM group was given 100 mL/day of BFM for one year. Colonoscopies, general blood markers and examinations of intestinal flora including the analysis of fecal organic acids were performed at the commencement of the study and after one year. RESULTS: Exacerbation of symptoms was seen in 3 out of 11 subjects in the BFM group and in 9 out of 10 in the control group. Log rank statistic analysis of the cumulative exacerbation rates showed a significant reduction in exacerbations for the BFM group (p = 0.0184). The analysis of microflora and the organic acids in the feces showed a significant reduction in the relative proportion of B. vulgatus in Bacteroidaceae and butyrate concentration, respectively, after supplementation with BFM, in comparison with before. CONCLUSION: Supplementation with the BFM product was successful in maintaining remission and had possible preventive effects on the relapse of ulcerative colitis.