MICROENCAPSULATION OF EMULSIFIED HYDROPHOBIC FLAVORS BY SPRAY DRYING

The retention of emulsified flavor during spray drying was investigated under various compositions of feed liquid. Drying of the emulsion solution was carried out in a spray dryer, equipped with a centrifugal atomizer. The retention of d-limonene during spray dying was nearly hundred percent independent of the composition of the feed liquid, whereas the retention of ethyl butyrate emulsified by gum arabic (GA) was much lower (0-20%). The retention of ethyl butyrate was markedly dependent on the concentration of maltodextrin and the type of emulsifier, indicating that the stability of emulsion is a controlling factor for flavor retention. The use of mixing emulsifiers, adjusting of density of ethyl butyrate, and the addition of 1% gelatin were quite effective procedures to improve the retention of ethyl butyrate, particularly when emulsified by GA.     

Microencapsulation by Spray Drying: Influence of Emulsion Size on the Retention of Volatile Compounds

ABSTRACT: The influence of the mean emulsion droplet size on flavor retention during spray drying was studied. d- Limonene, ethyl butyrate, and ethyl propionate were used as the model flavors. Gum arabic, soybean water-soluble polysaccharides, or modified starch blended with maltodextrin, were used as the wall materials. The increasing emulsion droplet decreased the retention of flavors. The distribution curve containing larger emulsion droplets shifted toward a smaller size after atomization, indicating that the larger emulsion droplets would be changed in size during atomization and result in decreasing flavor retention. For ethyl butyrate and ethyl propionate, the retention had a maximum at the mean emulsion diameter of 1.5 to 2 and 2.5 to 3.5 μm, respectively.     

Encapsulation of Proteins by Spray Drying and Crystal Transformation Method

Spray drying is commonly used as a dehydration technique in the pharmaceutical industry for making powdery products directly from liquid. It is also an attractive alternative for obtaining solid pharmaceutical molecules that are traditionally produced by freeze drying. Spray drying is often regarded as a harsh drying method, due to the high temperature of the drying gas. Therefore, some excipients were added to improve the stability in manufacturing process and storage. Emphasis was placed on the encapsulation of proteins by spray drying and crystal transformation method.     

Cis-urocanic acid down-regulates histamine-mediated activation of adenylate cyclase in the pig epidermis

OBJECTIVE: To study the efficacy of closed suction drainage in clean nonemergent surgical fracture fixation or bone grafting on the extremities or pelvis. DESIGN: A prospective randomized trial. SETTING: The orthopaedic trauma service of a Level I trauma hospital. PATIENTS: Patients were older than age eighteen years and undergoing clean nonemergent surgical fracture fixation or bone grafting procedures on the extremities (excluding hands and feet) or pelvis. INTERVENTION: The application of a surgical drain. MAIN OUTCOME MEASUREMENTS: Wound drainage, edema, hematoma and erythema, dehiscence, infection, and need for surgery or readmission were followed for six weeks. A univariate analysis with Student's t test for continuous variables and chi-squared analysis for all categorical data were used, with a p value of < or = 0.05 considered statistically significant. RESULTS: A total of 202 patients were randomized to 102 patients with no drain and 100 patients with a drain. There was no significant difference between the groups with regard to injury severity, systemic disease, age, body weight, physical status, or estimated blood loss. There was no significant difference between the drain and no-drain groups in any of the parameters evaluated. CONCLUSION: There is no significant difference between drained and nondrained wounds in clean, nonurgent orthopaedic trauma surgery. It appears that drainage systems can be safely eliminated in this group.     

Involvement of TNF alpha, IL-1 beta and IL-1 receptor antagonist in LPS-induced rabbit uveitis

The objective of the study was to investigate involvement of TNF alpha, IL-1 beta and IL-1 receptor antagonist (IL-1Ra) in lipopolysaccharide (LPS)-induced uveitis. Intravitreal injection of LPS (100 ng) to rabbits induced a massive leukocyte infiltration and protein leakage into the aqueous humor. Aqueous leukocyte counts and protein levels reached a peak 24 hr after this injection. The peak concentrations of aqueous TNF alpha (230 +/- 37 pg ml-1, at 9 hr) and IL-1 beta (185 +/- 80 pg ml-1, at 18 hr) preceded peak levels of aqueous leukocyte counts and protein levels. In contrast, the levels of aqueous IL-1Ra peaked at 48 hr (12,239 +/- 1964 pg ml-1) and a fairly high concentration of IL-1Ra remained when the inflammatory reactions subsided. Immunohistochemistry and leukocyte-depletion studies showed that infiltrating leukocytes were the major cellular sources of aqueous TNF alpha, IL-1 beta and IL-1Ra. Intravitreal injection of homologous TNF alpha (0.1-1.5 micrograms) or IL-1 beta (0.5-5 ng) reproduced a rapid leukocyte infiltration and protein leakage. Administration of anti-TNF alpha mAb (10 micrograms) suppressed the number of LPS-induced infiltrating neutrophils by 50%, mononuclear cells by 58%, and protein leakage by 42%. Administration of rabbit IL-1Ra (10 micrograms) also suppressed neutrophil influx by 78%, however, neither mononuclear cell influx nor protein leakage was inhibited by rabbit IL-1Ra. Co-administration of the two inhibitors enhanced inhibition of neutrophil infiltration to 88%, and protein leakage to 64%. We conclude that TNF alpha and IL-1 beta are the principal mediators of LPS-induced uveitis. Our observations also suggest that endogenous IL-1Ra may down-regulate inflammatory reactions.     

HLA class I and II alleles and susceptibility to generalized pustular psoriasis: significant associations with HLA-Cw1 and HLA-DQB1*0303

HLA alleles in generalized pustular psoriasis (GPP) were investigated to clarify the etiology and/or pathogenesis of this disease. Not only serological typing of HLA class I and II antigens but also genotyping of HLA class II alleles were carried out in twenty-six unrelated Japanese patients with GPP. These patients were classified according to their history of psoriasis vulgaris (PV). Serological typing revealed a significantly high incidence of HLA-Cw1 (Pc = 0.04) in the patients as compared with Japanese healthy controls. The frequency of HLA-B46 was particularly high in the patients with GPP and a previous history of PV. Genotyping of HLA class II alleles showed a highly significant increase in HLA-DQB1*0303 (Pc = 0.01) in the patients vs. the healthy controls. In particular, HLA-DQB1*0303 was significantly more frequent in the patients with no prior history of PV than in those with a history of PV. Analysis on linkage disequilibrium showed remarkably different patterns for HLA class II haplotypes between the patients and the healthy controls. Based on the comparative analysis among the amino acid sequences of the beta 1-domain of the HLA-DQB1*03 alleles, proline at residue 55 was suggested to be important as a common amino acid for determination of the susceptibility to GPP. These results revealed not only an association between the etiology and/or pathogenesis of GPP and HLA, but also different mechanisms of the immune response between the patients with GPP and PV.     

Development of a neutralizing monoclonal antibody against rabbit IL-1 receptor antagonist and utilization for ELISA and measurement of masked IL-1 activity in biological materials

To investigate the antibiotic activity of cefteram (CFTM), the minimum inhibitory concentrations (MICs) of CFTM and of the control drugs were determined against clinically isolated strains received from November 1991 to April 1993 from 19 dental facilities throughout the country, as well as against clinically isolated strains from samples obtained at this center from patients with dental infectious diseases, and the following results were obtained. 1. 430 strains were detected in 198 cases but identified strains amounted to 425. They are comprised of 204 strains of oral streptococci (48.0%), 81 strains of Peptostreptococcus spp. (19.1%), 10 strains of Bacteroides spp. (2.4%), 23 strains of Prevotella spp. (5.4%), and 9 strains of Porphyromonas spp. (2.1%). The ratios of Gram-positive bacteria v.s. Gram-negative bacteria were 78.4% and 21.6%, respectively, and the Gram-positive bacteria were isolated at higher frequency than Gram-negative bacteria. 2. The MIC90's of CFTM against oral streptococci and Peptostreptococcus spp. were 0.10 microgram/ml and 0.05 microgram/ml, and year to year increases of incidences of resistance against CFTM were not observed. Some strains, however, appeared to have obtained resistance to CFTM. 3. Among Bacteroides spp., Prevotella spp., Porphyromonas spp. which used to belong to genus Bacteroides, there were some strains resistant to CFTM. As a whole, however, no year to year increases in the incidence of CFTM resistance among these strains also. 4. Two strains of 6 Staphylococcus aureus subsp. aureus were methicillin-resistant. 5. The above observations indicate that CFTM still shows strong antimicrobial activity against clinically isolated strains that may be involved in dental infections.     

Possible Repositioning of an Oral Anti-Osteoporotic Drug,Ipriflavone, for Treatment of Inflammatory Arthritis via Inhibitory Activity of KIAA1199, a Novel Potent Hyaluronidase

KIAA1199 has a strong hyaluronidase activity in inflammatory arthritis. This study aimed to identify a drug that could reduce KIAA1199 activity and clarify its effects on inflammatory arthritis. Rat chondrosarcoma (RCS) cells were strongly stained with Alcian blue (AB). Its stainability was reduced in RCS cells, which were over-expressed with the KIAA1199 gene (RCS-KIAA). We screened the drugs that restore the AB stainability in RCS-KIAA. The effects of the drug were evaluated by particle exclusion assay, HA ELISA, RT-PCR, and Western blotting. We further evaluated the HA accumulation and the MMP1 and three expressions in fibroblast-like synoviocytes (FLS). In vivo, the effects of the drug on symptoms and serum concentration of HA in a collagen-induced arthritis mouse were evaluated. Ipriflavone was identified to restore AB stainability at 23%. Extracellular matrix formation was significantly increased in a dose-dependent manner (p = 0.006). Ipriflavone increased the HA accumulation and suppressed the MMP1 and MMP3 expression on TNF-α stimulated FLS. In vivo, Ipriflavone significantly improved the symptoms and reduced the serum concentrations of HA. Conclusions: We identified Ipriflavone, which has inhibitory effects on KIAA1199 activity. Ipriflavone may be a therapeutic candidate based on its reduction of KIAA1199 activity in inflammatory arthritis.     

Secreted Signaling Molecules at the Neuromuscular Junction in Physiology and Pathology

Signal transduction at the neuromuscular junction (NMJ) is affected in many human diseases, including congenital myasthenic syndromes (CMS), myasthenia gravis, Lambert–Eaton myasthenic syndrome, Isaacs’ syndrome, Schwartz–Jampel syndrome, Fukuyama-type congenital muscular dystrophy, amyotrophic lateral sclerosis, and sarcopenia. The NMJ is a prototypic cholinergic synapse between the motor neuron and the skeletal muscle. Synaptogenesis of the NMJ has been extensively studied, which has also been extrapolated to further understand synapse formation in the central nervous system. Studies of genetically engineered mice have disclosed crucial roles of secreted molecules in the development and maintenance of the NMJ. In this review, we focus on the secreted signaling molecules which regulate the clustering of acetylcholine receptors (AChRs) at the NMJ. We first discuss the signaling pathway comprised of neural agrin and its receptors, low-density lipoprotein receptor-related protein 4 (Lrp4) and muscle-specific receptor tyrosine kinase (MuSK). This pathway drives the clustering of acetylcholine receptors (AChRs) to ensure efficient signal transduction at the NMJ. We also discuss three secreted molecules (Rspo2, Fgf18, and connective tissue growth factor (Ctgf)) that we recently identified in the Wnt/β-catenin and fibroblast growth factors (FGF) signaling pathways. The three secreted molecules facilitate the clustering of AChRs by enhancing the agrin-Lrp4-MuSK signaling pathway.