Avian Influenza-Killed Vaccine on Tissue Distribution and Shedding of Avian Influenza Virus H9N2 in Ducklings.

Ducks play an important role in the transmission of avian influenza to poultry farms. Because of the importance of vaccination in reducing virus shedding, this study evaluated avian influenza-killed vaccine H9N2 on tissue distribution and shedding of avian influenza virus H9N2 in ducklings. One hundred-day-old ducklings were purchased and, after bleeding from 20 birds, were kept in four separate rooms under standard conditions. Groups 1 and 2 were vaccinated at 9 days, and groups 2 and 3 were challenged with 0.1 ml of allantoic fluid containing 105 EID50 (A/chicken/Iran/Aid/2013(H9)) virus intranasally at 30 days. Group 4 chicks were kept as the control group. Chicks were observed two times daily. On days 1, 3, 5, and 8 after inoculation, 3 chicks were randomly selected from each group and cloaca and trachea swabs samples were collected from each bird. Then the ducklings were euthanized and trachea, lung, spleen, intestine, liver, and brain tissue samples were collected for molecular detection. The virus was detected in the tissues and tracheal and cloacal swabs by polymerase chain reaction (PCR), and anti-AIV titres were measured by HI test. The results showed no clinical signs in the challenged groups. In the vaccinated challenged group, virus was detected only in cloacal swabs, but in the unvaccinated challenged group, virus was detected more in tracheal swabs than in cloacal swabs. In challenged-unvaccinated chicks, virus was detected in the trachea and lungs, and in challenged-vaccinated birds, virus was detected in the intestines. In conclusion, vaccinating ducks against the AI H9N2 virus reduced shedding and tissue distribution of AI viruses in challenged ducks.

Comparison of Knee Stability, Strength Deficits, and Functional Score in Primary and Revision Anterior Cruciate Ligament Reconstructed Knees.

Comparing to primary surgery, revision ACL reconstruction is more technically demanding and has a higher failure rate. Theoretically, rehabilitation can improve knee function after ACL reconstruction surgery. This study aimed to compare knee stability, strength, and function between primary and revision ACL reconstructed knees. 40 primary and 40 revision ACL reconstruction surgeries were included between April 2013 and May 2016. Patients with revision surgery had a higher anteroposterior translation comparing those with primary reconstruction (median laxity, 2.0 mm vs. 3.0 mm, p = 0.0022). No differences were noted in knee extensor at 60°/sec or 180°/sec (p = 0.308, p = 0.931, respectively) or in flexor muscle strength at 60°/sec or 180°/sec between primary and revision ACL reconstruction knees (p = 0.091, p = 0.343, respectively). There were also no significant differences between functional scores including IKDC score and Lysholm score in primary versus revision surgeries at 12th months after index operation (p = 0.154, p = 0.324, respectively). In conclusion, despite having higher anteroposterior instability, patients with revision ACL reconstruction can have non-inferior outcomes in isokinetic knee strength and function compared to those with primary ACL reconstruction after proper rehabilitation.

PHYSICAL AND CHEMICAL STABILITY ANALYSIS OF COSMETIC MULTI- PLE EMULSIONS LOADED WITH ASCORBYL PALMITATE AND SODIUM ASCORBYL PHOSPHATE SALTS.

Stability of hydrophilic and lipophilic vitamin C derivatives for quenching synergistic antioxidant activities and to treat oxidative related diseases is a major issue. This study was aimed to encapsulate hydrophilic and lipophilic vitamin C derivatives (ascorbyl palmitate and sodium ascorbyl phosphate) as functional ingredients in a newly formulated multiple emulsion of the W//W type to attain the synergistic antioxidant effects and the resultant system's long term physical and chemical stability. Several multiple emulsions using the same concentration of emulsifiers but different concentrations of ascorbyl palmitate and sodium ascorbyl phosphate were developed. Three finally selected multiple emulsions (ME1, ME2 and ME3) were evaluated for physical stability in terms of rheology, microscopy, conductivity, pH, and organoleptic characteristics under different storage conditions for 3 months. Chemical stability was determined by HPLC on Sykam GmbH HPLC system (Germany), equipped with a variable UV detector. Results showed that at accelerated storage conditions all the three multiple emulsions had shear thinning behavior of varying shear stress with no influence of location of functional ingredients in a carrier system. Conductivity values increased and pH values remained within the skin pH range for 3 months. Microscopic analysis showed an increase in globule size with the passage of time, especially at higher temperatures while decreased at low temperatures. Centrifugation test did not cause phase separation till the 45th day, but little effects after 2 months. Chemical stability analysis by HPLC at the end of 3 months showed that ascorbyl palmitate and sodium ascorbyl phosphate were almost stable in all multiple emulsions with no influence of their location in a carrier system. Multiple emulsions were found a stable carrier for hydrophilic and lipophilic vitamin C derivatives to enhance their desired effects. Considering that many topical formulations contain simple vitamin C it is suggested that present study may contribute to the development of more stable formulations with a combination of vitamin C derivatives to enhance their cosmetic benefits.

Fabrication, physicochemical characterization and preliminary efficacy evaluation of a W/O/W multiple emulsion loaded with 5% green tea extract

Complex multiple emulsions have an excellent ability to fill large volumes of functional cosmetic agents. This study was aimed to encapsulate large volume of green tea in classical multiple emulsion and to compare its stability with a multiple emulsion without green tea extract. Multiple emulsions were developed using Cetyl dimethicone copolyol as lipophilic emulsifier and classic polysorbate-80 as hydrophilic emulsifier. Multiple emulsions were evaluated for various physicochemical aspects like conductivity, pH, microscopic analysis, rheology and these characteristics were followed for a period of 30 days in different storage conditions. In vitro and in vivo skin protection tests were also performed for both kinds of multiple emulsions i.e. with active (MeA) and without active (MeB). Both formulations showed comparable characteristics regarding various physicochemical characteristics in different storage conditions. Rheological analysis showed that formulations showed pseudo plastic behavior upon continuous shear stress. Results of in vitro and in vivo skin protection data have revealed that the active formulation has comparable skin protection effects to that of control formulation. It was presumed that stable multiple emulsions could be a promising choice for topical application of green tea but multiple emulsions presented in this study need improvement in the formula, concluded on the basis of pH, conductivity and apparent viscosity data.

Emulsões múltiplas complexas possuem excelente habilidade de agregar grandes quantidades de agentes cosméticos funcionais. Este estudo teve por objetivo encapsular grandes volumes de chá verde em uma emulsão múltipla clássica e comparar sua estabilidade com a emulsão múltipla sem o extrato do chá verde. Emulsões múltiplas são desenvolvidas usando cetil dimeticona copoliol como emulsificante lipofílico e o clássico polissorbato-80 como emulsificante hidrofílico. As emulsões múltiplas foram avaliadas por meio de vários aspectos fisico-químicos como condutividade, pH, análise microscópica e reologia. Estas características foram observadas por um período de 30 dias sob diferentes condições de armazenamento. Testes de proteção da pele in vivo e in vitro foram realizados para ambos os tipos de emulsões testadas, i.e. com o ativo em estudo (MeA) e sem ativo (MeB). Ambas as formulações apresentaram características comparáveis no que diz respeito aos diferentes fatores físico-químicos avaliados sob diferentes condições de armazenamento. A análise reológica mostrou que as formulações apresentaram comportamento pseudo-plástico sob contínuo estresse de cisalhamento. Os resultados dos testes in vivo e in vitro sobre a proteção da pele revelaram que a formulação ativa promoveu efeitos comparáveis à formulação controle. Nossos dados mostraram que emulsões múltiplas estáveis poderiam ser escolhas promissoras para a aplicação tópica do chá verde. Entretanto, a fórmula das emulsões múltiplas apresentadas neste estudo precisam ser melhoradas no que diz respeito ao pH, condutividade e viscosidade aparente.

Eudragit FS based colonic microparticls of metoprolol tartrate.

Metoprolol, a cardioselective ß-blocker, is well absorbed in colon after oral administration with mean elimination half life of 3 h with bioavailability 50% due to extensive first pass effect, thus it was aimed to develop its modified release dosage form to reduce dosing frequency. Metoprolol tartrate loaded Eudragit FS microparticles were formulated using solvent evaporation technique by varying polymer contents and then compressing into tablets. The dissolution test was performed in simulated gastrointestinal fluid. All tabletted microparticles were tested for stability after storage in accelerated conditions. As a result of various analytical tests like FTIR, XRD and DSC analyses, drug was found stable in the microparticles. Metoprolol tartrate loaded Eudragit FS tabletted microparticles were stable in accelerated storage conditions. The release behavior of pH-dependent formulations was affected by the dissolution medium pH and the concentration of polymer used. There was a decrease in drug release rate with the increase in polymer concentration. In vitro drug release data (except test formulation F3) were best fitted to zero order model, which indicated the controlled release nature of formulation, while the Korsmeyer-Peppas model explored that drug release occurred according to case II relaxation transport mechanism (n > 0.89). Based on the results, it can be concluded that Eudragit FS is a suitable polymer to design pH dependent microparticles using solvent evaporation technique for the release of drug in colon and T2 can be considered as an optimum formulation on the basis of model independent (f2 test) kinetic interpretation of dissolution results (f2 < 50 for T2 versus reference).

Formulation and characterization of a cream containing terminalia chebula extract.

BACKGROUND: This study aimed to formulate a water-in-oil emulsion (formulation) of Terminalia chebula versus its vehicle (base) as control, and investigate its effects on skin melanin, skin erythema, skin moisture content, and transepidermal water loss (TEWL). MATERIAL AND METHODS: Base containing no active material, and formulation containing 5% concentrated extract of T. chebula, were developed. Different stability parameters were monitored at 8, 25, and 40 °C, as well as 40 °C + 75% relative humidity, for a period of 4 weeks. It was concluded that the creams remained stable at all storage conditions. Both base and formulation were applied to the cheeks of human volunteers for a period of 8 weeks. Different skin parameters were monitored every week to measure any effect produced by these creams. RESULTS: Changes in TEWL produced by base and formulation were insignificant (p > 0.05) with respect to time while significant (p ≤ 0.05) with respect to base and formulation. The skin moisture content increased after the application of formulation throughout the study period; this effect was insignificant (p > 0.05) with respect to time while significant (p ≤ 0.05) with respect to base and formulation. Both base and formulation showed insignificant (p > 0.05) effects on skin melanin content with respect to time. Skin erythema was reduced by the formulation. Both base and formulation produced statistically insignificant (p > 0.05) effects on skin sebum. CONCLUSION: Both creams were aesthetic with respect to sensory evaluation. T. chebula topical cream showed a positive rejuvenating effect on human skin. Hopefully, this study will encourage more attention towards the research and utilization of herbal medicines.

Pharmaceutical and biopharmaceutical evaluation of extracts from different plant parts of indigenous origin for their hypoglycemic responses in rabbits.

This study was designed to evaluate the hypoglycemic effects of different plant extracts in single and in combined formulation, in experimentally induced "diabetic rabbits". The extracts were obtained from seeds of Syzygium jambolana, fruits of Momordica charantia and leaves of Azadirachta indica. Treatment of diabetes with plant extracts was started at 8 days after alloxan injection. Rabbits were randomly divided into four groups, each group consisting of six rabbits. Each group of rabbits was given a dose of granules containing 200 mg/kg b.w. concentrated ethanolic extract of a plant while the fourth group was given a dose of granules consisting of combined extract of all three folk plants. Blood samples were drawn at 0, 2, 4, 8, 12, 24, 36, 48, 72 and 96 h. Serum glucose estimation was done by glucose oxidase kit method. Anti-diabetic effect was produced after 72 h in groups 1, 2 and 3 that were administered with a dose of granules of ethanolic extract of single plant but in group 4, treated with 200 mg/kg body weight of combined extract of all three plants, hypoglycemic effect was produced after 96 h. Hypoglycemic effects may be induced in rabbits by administration of extracts of various plant parts. The hypoglycemic effect produced by granules of single plant extract was more pronounced than antidiabetic effect produced by combining three extracts in a single formulation.

A rare case of diplopodia and syndactyly: anatomical and surgical considerations.

Diplopodia is a rare congenital disorder that has not been extensively discussed in textbooks, and case reports appear to be the main source of information. Although the exact cause of diplopodia remains unknown, the presence of extra digits as well as metatarsals and tarsals allows it to be differentiated from pedal polydactyly. Syndactyly refers to the congenital fusion of the digits. Concomitant bilateral syndactyly and diplopodia is extremely unusual, and in this report we describe a case of right diplopodia and left polydactyly combined with bilateral manual syndactyly in a 15-year-old girl who was ultimately treated with through-the-knee amputation. Radiological examination of the right leg revealed tibial hypoplasia and the right foot displayed 8 digits with corresponding metatarsals and tarsals, whereas the left leg revealed 2 extra digits on the medial aspect of the foot with corresponding metatarsal and tarsal bones. Anatomical dissection of the right foot revealed that it was divided into halves consisting of 8 toes with corresponding metatarsals and tarsals, as well as tibial hypoplasia and absence of the great toe. Diplopodia associated with tibial hypoplasia and syndactyly can be treated surgically, and the present case report details the clinical, radiological, and anatomical elements of this rare deformity.

Changes in skin mechanical properties after long-term application of cream containing green tea extract.

BACKGROUND AND AIMS: We studied longterm application of cream containing green tea extract, to obtain knowledge of its effects on epidermal mechanics by 2-mm diameter Cutometer probe. METHODS: Using this non-invasive device, we assessed the effects of green tea extract cream on skin mechanical properties. Healthy male volunteers (n=10) were included in this study, which lasted 60 days. The biomechanical properties of the skin were examined by a non-invasive suction device (Cutometer) and the cheeks were defined as the test area. RESULTS: Statistically significant (p<0.05) results were notable for the R6 (Uv/Ue) parameter with respect to time (ANOVA); R0, R2 (Ua/Uf) and R7 (Ur/Uf) parameters were found statistically not significant by ANOVA. This study demonstrates that green tea formulation has a certain effect on R6 (Uv/Ue) parameter when applied regularly for a certain period of time. CONCLUSIONS: These results indicate that the formulation has no pronounced overall effects on skin elastic or biological properties, but significant R6 (Uv/Ue) values indicate that it does have definite effects on the viscoelastic properties of the skin.

Outcomes of 3% green tea emulsion on skin sebum production in male volunteers.

This study was aimed to depict potential effects of stable formulation (water in oil emulsion), containing 3% green tea (Camellia sinensis L) extract on skin sebum production in healthy human volunteers. For this purpose formulation was designed using 3% ethanolic green tea extract and Abil®EM90 was used as an emulsifier. Formulation was applied to the cheeks of healthy human volunteers (n=10) for a period of 8 weeks. Measurements for skin sebum production were considered using Sebumeter MPA 5. Results were compiled and any effect produced by the formulation was justified statistically. It was observable that statistically significant (p < 0.5%) results were found for skin sebum production after long term application of the formulation. 3% formulation of green tea extract was ideal in all aspects and can be experienced in skin disorders like acne to further investigate its effects in unhealthy volunteers.

The prevalence of oilseed rape hypersensitivity in a mixed cereal farming population.

BACKGROUND: Oilseed rape production is widespread in cereal growing areas. Many patients attending our clinics for seasonal allergy claim that they are allergic to it. AIM: To determine the prevalence of oilseed rape allergy in our population. POPULATION: General population within a mixed cereal farming area attending a rhinology and allergy clinic in a district general hospital, UK. METHODS & MATERIALS: Retrospective chart analysis. The results of 1475 consecutive patients who underwent skin prick allergy testing over a 2-year period (January 2003-December 2005) and of 640 consecutive patients over a 1-year period (September 2008-September 2009) were analysed and compared. RESULTS: Allergy to house dust mite was found to be most common (n = 526, 25%) followed by grass pollen (n = 519, 24%) and cereals (n = 429, 20%). Oilseed rape hypersensitivity was relatively uncommon, comprising only 2% of the population tested (n = 28). CONCLUSION: Oilseed rape does not cause significant allergy, even in areas of high production. It is likely that those patients exhibiting oilseed rape allergy may in fact be symptomatic due to the effect of other allergens, acting either synergistically with the oilseed rape allergen, or more likely, in spite of it.

The effect of binders on the bioavailability of ofloxacin tablets in animal model.

Present study was undertaken to evaluate the effect of binders on the bioavailability of the drug. Two formulations of ofloxacin were manufactured with two different binders, i.e. gelatin and starch, which were analyzed by different in vitro tests such as dissolution test using USP apparatus II (paddle method) by using 0.1 M HCl solution. For in vivo studies, blood samples were collected through the heparinized syringe at zero time (before dosing) and at 0.5, 1.0, 2.0, 4.0, 6.0, 8.0, 10.0, 12.0, 24.0 hours after the dosing of ofloxacin tablets to 24 rabbits and analyzed by high performance liquid chromatography. Mobile phase consisted of distilled water, acetonitrile and triethylamine (700 : 300 : 1.4, v/v/v). The pH of the mobile phase was adjusted at 2.4 with orthophosphoric acid. The maximum plasma concentration attained after the administration of formulation 1 (containing gelatin) was 7.56 +/- 0.835 microg/mL (the mean +/- SEM) and of formulation 2 (containing starch) was 3.4417 +/- 1.16 microg/mL (the mean +/- SEM). There is also statistically significant difference between the volume of distribution and total body clearance of both formulations. Therefore, formulation 1 is more bioavailable than formulation 2. Thus it can be concluded that binder can affect the bioavailability and pharmacokinetics of a drug.

Formulation and characterization of a cream containing extract of fenugreek seeds.

Fenugreek seeds possess antioxidant effects and contain a mucilage which has emollient properties. It can also produce skin healing, whitening, moisturizing, skin soothening and antiwrinkle effects. The purpose of study was to formulate a stable W/O emulsion containing fenugreek seeds extract using liquid paraffin oil. Fenugreek seeds extract, which was obtained by concentrating methanolic extract of fenugreek seeds, was entrapped in the inner aqueous phase of W/O emulsion. A base containing no active material and a formulation containing concentrated extract of fenugreek (in a concentration of 4%) in the internal aqueous phase (W/O emulsion) were prepared and stored at different accelerated conditions for a period of four weeks to predict the stability of these creams. It was found that both, the base and the formulation, were stable at all the accelerated conditions regarding color, liquifaction and phase separation. However, insignificant changes in the pH of base and significant changes in the pH of the formulation were observed with the passage of time. Both the base and the formulation were applied to the cheeks of human volunteers for six weeks and various parameters of the skin were evaluated every week to measure any effect produced by these creams. All the effects of base were statistically significant except the sebum contents and pH, which changed but insignificantly. A significant decrease on skin melanin and erythma was produced by the formulation. An insignificant decrease in TEWL was observed for the formulation.

Establishment and characterization of a steroidogenic human granulosa-like tumor cell line, KGN, that expresses functional follicle-stimulating hormone receptor.

We established a steroidogenic human ovarian granulosa-like tumor cell line, designated KGN, from a patient with invasive ovarian granulosa cell carcinoma. KGN had a relatively long population doubling time of about 46.4 h and had an abnormal karyotype of 45,XX, 7q-, -22. A steroid analysis of the cultured medium by RIA performed 5 yr after the initiation of culture showed that KGN was able to secrete pregnenolone and progesterone, and both dramatically increased after stimulation with (Bu)(2)cAMP. However, little or no secretion of 17alpha-hydroxylated steroids, dehydroepiandrosterone, androstenedione, or estradiol was observed. The aromatase activity of KGN was relatively high and was further stimulated by (Bu)(2)cAMP or FSH. These findings showed a pattern similar to that of steroidogenesis in human granulosa cells, thus allowing analysis of naturally occurring steroidogenesis in human granulosa cells. Fas-mediated apoptosis of KGN was also observed, which mimicked the physiological regulation of apoptosis in normal human granulosa cells. Based on these findings, this cell line is considered to be a very useful model for understanding the regulation of steroidogenesis, cell growth, and apoptosis in human granulosa cells.

Inhibin-like immunoreactivity produced by the adrenal gland is circulating in vivo.

To clarify the contribution of the inhibin-like immunoreactivity (inhibin-LI) produced by adrenal glands to the total circulating levels of inhibin-LI, we measured serum inhibin-LI in normal and hypogonadal subjects under ACTH-loading or dexamethasone-loading condition. The mean basal concentration of inhibin-LI in the peripheral serum of the hypogonadal cases was 3.6 +/- 1.3 IU/ml (mean +/- SD, n = 5), which corresponded to 19.5 +/- 5.8% of that of normal controls matched for age and sex. The low levels of inhibin-LI in hypogonadal subjects (n = 7) rose significantly (3.6 +/- 1.1 vs 8.1 +/- 1.7 IU/ml, p < 0.001) after the administration of synthetic 1-24ACTH (40 units/day intramuscular injection) for 2 days, while the levels of serum inhibin-LI were not increased in two cases of Addison's disease with hypogonadism after the administration of ACTH. After the oral administration of a low dose of dexamethasone (1 mg) the serum inhibin-LI level in normal subjects (eight males and eight females) decreased significantly (male, 16.2 +/- 3.3 vs 14.5 +/- 4.1 IU/ml; female, 12.9 +/- 6.3 vs 10.8 +/- 5.6 IU/ml; p < 0.01 each) without significant change in the levels of serum gonadotropin (LH and FSH) and those of gonadal steroid (testosterone or estradiol). These results indicate that a small; but significant amount of inhibin-LI is secreted from the adrenal gland and circulating in vivo, and that the proportion of adrenal-derived inhibin-LI is much higher in patients with hypogonadism.

[Insulin secretin and resistance accompany immobilization of the aged patient].

Physical activity is known to increase glucose tolerance and insulin sensitivity. To examine the influence of physical inactivity on insulin sensitivity in aged people, insulin sensitivity and secretion was measured by using a two-step euglycemic glucose clamp, a glucagon tolerance test (GTT), an oral glucose tolerance test (OGGT) and urinary CPR excretion in 11 aged patients immobilized in bed for more than 12 weeks. The results were compared with those of nine healthy mobile aged controls. The muscle volume of the immobilized patients decreased by 20-25% compared with that of the controls, and insulin sensitivity decreased 50% in each step. These results mean that the immobilized patients had decreased insulin sensitivity and responsiveness, even when there was muscle atrophy. The glucose and insulin responses in both the GTT and OGTT showed that there was a slight decrease in the initial response of insulin in the immobilized patients and was in the controls compared with adolescent controls. There was no difference in the initial response of insulin between the immobilized patients and the aged controls. The ratio of impaired glucose tolerance in the OGTT was 4/11 of the immobilized patients and 3/9 of the controls. Total insulin secretion was increased and insulin sensitivity and responsiveness was decreased in the immobilized patients. This suggests that the decreased insulin sensitivity was compensated for increased by insulin secretion in the immobilized patients.

Androgen insensitivity syndrome due to new mutations in the DNA-binding domain of the androgen receptor.

Androgen insensitivity syndrome (AIS) is associated with a wide range of quantitative or qualitative defects in the androgen receptor (AR). In some patients with AIS, however, no defects are detectable in the ligand-binding properties of the AR. We have analyzed the ARs of two unrelated patients with this category (termed 'receptor-positive type') of AIS. Sequence analysis of these patients' AR gene revealed single amino acid substitutions (579Cys(TGC)-->Phe(TTC) and 582Phe(TTC)-->Tyr(TAC)) in exon B encoding the first zinc finger of the DNA-binding domain of the AR. These mutations have not been previously reported. Moreover, cotransfection assays and mobility shift assays revealed that these patients' mutant ARs had defective transcriptional activity of the target gene because of impaired DNA-binding ability to the androgen-responsive element. These findings strongly indicate that these mutations are responsible for the pathogenesis of AIS in these patients.

1,25-Dihydroxyvitamin D3 enhances the enzymatic activity and expression of the messenger ribonucleic acid for aromatase cytochrome P450 synergistically with dexamethasone depending on the vitamin D receptor level in cultured human osteoblasts.

Not every postmenopausal woman with a low level of estrogen suffers from osteoporosis, and no correlation of bone density with serum estrogen level, but a significant correlation with adrenal androgens is often noted. Vitamin D3 has been reported to be osteoclastic in vitro, whereas the effectiveness of vitamin D3 for the treatment of osteoporosis is clinically relevant. To study the roles of these factors in the development of osteoporosis, we characterized aromatase activity converting androgens to estrogens in human osteoblasts, because postmenopausal women maintain considerable levels of adrenal androgens. Glucocorticoids at 10(-9)-10(-7) M transiently induced the expression and enzymatic activity of aromatase cytochrome P450 (P450AROM) in primary cultured osteoblasts, and the Km value for androstenedione (4.7 +/- 2.9 nM) was lower than that in adipose tissue and skin. Human osteoblasts showed a promoter specificity different from that found in other tissues. 1,25-Dihydroxyvitamin D3 [1,25-(OH)2D3] alone did not induce aromatase activity, but enhanced and maintained glucocorticoid-induced P450AROM gene expression. This synergistic effect was not observed by other sex steroids or retinoic acids. The enhancement of P450AROM activity by 1,25-(OH)2D3 varied from 0.94-fold (no enhancement) to 2.40-fold (maximal enhancement) among the individual human osteoblasts examined, but the magnitude of the enhancement was significantly correlated with the level of vitamin D receptor messenger RNA (P < 0.05). Cycloheximide did not abolish the synergistic effect of 1,25-(OH)2D3, suggesting that de novo protein synthesis is not required for the synergism with 1,25-(OH)2D3. These results suggest that bone tissue can synthesize estrogen from adrenal androgens by a unique aromatase activity depending on the level of vitamin D receptor expressed.

Serum dehydroepiandrosterone (DHEA) and DHEA-sulfate (DHEA-S) in Alzheimer's disease and in cerebrovascular dementia.

A decreased concentration of dehydroepiandrosterone sulfate (DHEA-S) in patients with Alzheimer's disease (AD) has been reported but is still controversial. In the present study, serum concentrations of DHEA and DHEA-S were determined in 19 patients with AD, 21 patients with cerebrovascular dementia (CVD) and 45 age- and gender matched elderly control individuals from the Japanese community at large. Serum concentration of DHEA among controls, patients with AD and patients with CVD did not significantly differ from one another. However, patients with AD and patients with CVD were found to have lower concentration of serum DHEA-S and a lower DHEA-S/DHEA ration compared to normal control individuals. No significant difference was observed in the concentration of serum DHEA-S or the DHEA-S/DHEA ratio between patients with AD and those with CVD. These results suggest that reduced concentrations of serum DHEA-S may not be unique to AD, but instead reflect a common phenomenon in dementing diseases. However, since serum concentration of DHEA in these patients remained unchanged, the significance of DHEA in dementia remains unclear.