Topical anti-inflammatory activity of dianemycin isolated fromStreptomyces sp. MT 2705-4

In order to develop new anti-inflammatory agents having different action mechanisms compared with nonsteroidal and steroidal anti-inflammatory drugs, the culture broths of various actinomycetes isolated from soil were screened using anin vivo mouse ear edma assay and one strain (Streptomyces sp. MT 2705-4: KCTC 8651P) was selected. Activity-guided purification led to the isolation of a polyether compound, dianemycin. Topically, dianemycin showed a potent anti-inflammatory activity in mouse ear edema induced by croton-oil or arachidonic acid. ED(50) value of dianemycin was found to be 0.8 mg/ear compared to 0.4 mg/ear of prednisolone in croton-oil ear edema. However, dianemycin did not show the inhibitory activity in UV-erythema and delayed hypersensitivity reaction. These results indicate that dianemycin is a potential topical anti-inflammatory agent.     

Clonazepam release from core-shell type nanoparticlesin vitro

AB-type amphiphilic copolymers (abbreviated as LE) composed of poly (L-leucine) (PLL) as the A component and poly (ethylene oxide) (PEO) as the B component were synthesized by the ring-opening polymerization of L-leucine N-carboxy-anhydride initiated by methoxy polyoxyethylene amine (Me-PEO-NH₂) and characterized. Core-shell type nanoparticles were prepared by the diafiltration method. Particle size distribution obtained by dynamic light scattering was dependent on PLL composition and the size for LE-1, LE-2 and LE-3 was 369.6±267, 523.4±410 and 561.2±364 nm, respectively. Shapes of the nanoparticles observed by transmission electron microscope (TEM) were almostly spherical. The critical micelle concentration (CMC) of the nanoparticles determined by a fluorescence probe technique was dependent on the composition of hydrophobic PLL, and the CMC for LE-1, LE-2 and LE-3 was 2. 0×10⁻⁶, 1.7×10⁻⁶ and 1.5×10⁻⁶ (mol/l), respectively. Clonazepam release from core-shell type nanoparticles in vitro was dependent on PLL composition and drug loading content.     

Ginsenoside Rs3, a genuine dammarane-glycoside from Korean red ginseng

A genuine dammarane-glycoside, named as ginsenoside Rs₃, was isolated from the MeOH extracts of Korean red ginseng (Panax ginseng C.A. Meyer) through repeated silica gel column chromatographies and its chemical structure was determined as (20S)-protopanaxadiol 3-O-[6″-O-acetyl-β-D-glucopyranosyl (1→2)-β-D-glucopyranoside on the basis of several spectral and physical evidences including HMBC and FAB-MS.     

I269S Mutation in horse liver alcohol dehydrogenase S isoenzyme and its reactivity for steroids and retinoids

Ile-269 in horse liver alcohol dehydrogenase isoenzyme S(HLADH-S) was mutated to serine by phosphorothioate-based site-directed mutagenesis in order to study the role of the residue in coenzyme binding. The specific activity of the mutant(I269S) enzyme to ethanol was increased 49-fold. All turnover numbers of I269S enzyme toward 9 primary alcohols were increased. The mutant enzyme showed 3.6, 4.6, 11.6-fold higher catalytic efficiency for 5β-androstane-3,17-dione, 5β-cholanic acid-3-one and retinal than wild-type, respectively. The reaction mechanism of I269S enzyme was ordered bi bi as wild-type's. These results indicate that the hydrophobic interaction of Ile-269 residue with coenzyme plays an important role in dissociation of coenzyme from enzyme-coenzyme complex, which has been known as the rate limiting step of ADH reaction.     

Ages at different reproductive events, numbers of menstrual cycles in between and breast cancer risk

One hundred and seventy-five pathologically confirmed new cases of female breast cancer in National Taiwan University Hospital were selected as the case group. Four hundred and fifty-seven inpatient controls were individually matched for each case by age and date of admission. Information of reproductive factors and potential confounders were collected from questionnaire interview and medical records. Menstrual cycles before and after first fuIl-term pregnancy were estimated from the questionnaire. Conditional logistic regression was used to estimate the effects of reproductive risk factors and numbers of menstrual cycles before and after first full-term pregnancy. After adjusting for educational level, body mass index, family history of breast cancer and oral contraceptive use, age at menarche and menopause only showed borderline significance. Age at first full-term birth predicted breast cancer risk better. Parity was the most important protective factor. Number of menstrual cycles before first full-term pregnancy was also positively associated with breast cancer risk with linear trends.     

Proteoglycan depletion alone is not sufficient to stimulate proteoglycan synthesis in cultured bovine cartilage explants

Articular cartilage comprises a small number of cells embedded within a matrix primarily composed of collagen and proteoglycan (PG). The functional integrity of the tissue is highly dependent on the maintenance of matrix structure, which, in turn, is controlled by the chondrocytes. In normal tissue there is a slow but steady turnover of matrix components such that their levels remain constant. In certain diseased states the equilibrium is upset, resulting in a net loss of matrix components. The object of the present study was to artificially upset the synthetic/loss equilibrium by enzymic depletion and assess the ability of chondrocytes to respond by increasing PG synthesis. Cultured bovine articular cartilage explants were depleted using enzymes as follows; 10 U/ml Streptomyces hyaluronidase (induced a 30% loss of PG), 2000 U/ml testicular hyaluronidase (70% loss of PG) and 100 U/ml collagenase (35% loss of PG) and control (6% loss of PG). Collagenase also induced a 50% loss of collagen. Collagenase treatment induced a 50% stimulation of PG synthesis above control levels. Elevated synthesis levels were maintained for 9 days. Testicular hyaluronidase induced a brief elevation in PG synthesis on day 3 of culture. Streptomyces hyaluronidase treatment did not cause an alteration in the rate of PG synthesis above control levels. Histological examination indicated that collagenase-treated explants formed outgrowths consisting of rounded chondrocytes within a fine fibrous matrix which stained intensely with safranin-O, indicating a high concentration of PG. The production of repair-like outgrowths may explain the elevated PG synthesis rates measured. It appears, therefore, that collagen and matrix organization is more important than PG levels in the control of PG synthesis in articular cartilage explant cultures.     

Improving vaccination coverage in urban areas through a health communication campaign: the 1990 Philippine experience.

From March to September 1990 the Philippine Department of Health, with the assistance of the HEALTHCOM Project, carried out a national mass-media communication campaign to support routine vaccination services. The essential elements of the campaign strategy were as follows: focusing on measles as a way to get mothers to bring their children to the health centre; emphasizing logistic knowledge in the mass-media messages, in particular popularizing a single day of the week as "vaccination day" and giving clear information about the age for measles vaccination; and focusing on urban areas, which had lower vaccination rates than rural areas. Evaluation of the effects of the campaign indicates an increase in vaccination coverage and a substantial increase in the timeliness of vaccination that can be attributed to improvement in carers'' knowledge about vaccination. Furthermore, most of the observed increase in knowledge was related to exposure to the mass-media campaign. There was no evidence of any programmatic change that could account for the increase in vaccination or evidence that increased health education efforts at health centres could account for the change in knowledge. These results indicate that when countries meet certain conditions--a high level of access to the media, sufficient expertise and funds available to develop and produce high-quality radio and television advertisements, and a routine system that is able to serve the increased demand--a mass communication campaign can significantly improve vaccination coverage.     

An audit of occupational medicine consultation records

There is a need to develop and test methods of audit of theconsultation process in occupational medicine and to draw conclusionsfrom the findings. An external audit was carried out on 313randomly selected consultation records from the occupationalhealth services of three health boards over a 26-month period.Additionally, nine months after the date of the first externallyaudited sample, a prospective internal audit was commenced withinone board. In 58 of the consultations selected (19 per cent),audit was not possible mainly because records could not be found.In an appreciable proportion of the rest, there were shortcomingsin the referral record or in the consultation record. The consultationrecords of ‘career’ occupational physicians werebetter than those of ‘non-career’ physicians, especiallyin recording specific diagnoses (91 per cent vs. 67 per cent;P<0.0001) and in conclusions regarding occupational implications(86 per cent vs. 74 per cent; P<0.0001). Multivariate regressionsshowed a highly significant improvement associated with prospectiveinternal audit in one item, namely the record of occupationalimplications. However, the magnitude of this difference beforeand after audit was smaller than the independent differencearising from the career status of the physicians. The valueof medical audit in improving quality of care and educationin occupational medicine is discussed.