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Analysis of methylprednisolone, methylprednisone and corticosterone for assessment of methylprednisolone disposition in the rat.

A sensitive, specific and precise high-performance liquid chromatographic assay for the simultaneous determination of methylprednisolone, methylprednisone and corticosterone using betamethasone as the internal standard is reported. Rat serum (0.5 ml) is extracted with methylene chloride, washed with sodium hydroxide, then water and the extract is injected onto a microparticulate silica gel column with ultraviolet detection at 254 nm. Calculated limits of quantitation are less than 10 ng/ml and the intra-day coefficient of variation is less than 5% for each steroid. This assay has been applied to preliminary studies of methylprednisolone disposition in the rat. The plasma concentration-time profile for each steroid was determined following intravenous administration of methylprednisolone (10 mg/kg). Peak serum methylprednisone concentrations of ca. 250 ng/ml occurred within 5 min of methylprednisolone administration and the average area under the curve ratio (methylprednisolone/methylprednisone) was 9.3. These findings demonstrate that methylprednisone is a metabolite of methylprednisolone in the rat and suggest that the metabolic back-conversion of methylprednisone to methylprednisolone may be less than in other species.

Animals↗

Experimentally-induced prostatic hyperplasia in young beagles: a model to evaluate the chemotherapeutic effects of gossypol.

This study investigated the effect of gossypol on hyperplastic canine prostates induced with long-term administration of androgen and estrogen. Twelve 16-week-old male beagle dogs were divided evenly (n = 3) into 4 treatment groups: (1) CONTROL: vehicle only; (2) Gossypol-Treated: 20 mg/kg gossypol acetic acid; (3) Steroid-Induced: 4 mg/kg testosterone and 40 micrograms/kg estradiol-17 beta; (4) Gossypol-Treated and Steroid-Induced: 4 mg/kg testosterone, 40 micrograms/kg estradiol-17 beta and 20 mg/kg gossypol. The subjects received treatments every other day for 1 month. The beagles treated with steroids developed an acute enlargement (approximately 10-fold) of the prostate as compared to control. The prostatic acini were underdeveloped and characterized by simple squamous to low cuboidal epithelium in the control subjects while acini in steroid-induced subjects were characterized by simple tall columnar epithelium. The subjects treated with gossypol had prostates histologically similar to controls with the exception of loosened periurethral connective tissue. Serum testosterone and estradiol-17 beta levels imply that gossypol can reduce steroid hormonal levels. Mean serum testosterone levels in gossypol-treated subjects were reduced approximately 50% from controls. Serum biochemistry profiles indicate that steroid and/or gossypol treatments were not toxic at the doses and duration used in this study. These observations imply that gossypol and steroid hormones can interact to alter prostate development and gossypol metabolism and/or clearance.

5-alpha Reductase Inhibitors↗

Progesterone, androstenedione, testosterone, 5 alpha-dihydrotestosterone and androsterone concentrations in specific regions of the human brain.

The concentrations of progesterone, androstenedione, testosterone, 5 alpha-dihydrotestosterone and androsterone were determined in tissue samples from the human hypothalamus, anterior pituitary, pineal, amygdala and parietal cortex, taken at autopsy from male (n = 4) and female cadavers (n = 4) of various ages. The measurements were performed using radioimmunoassays for the individual steroids after the chromatographic purification of solvent extracts of tissue samples on Lipidex-5000TM. Preliminary qualitative analyses of the chromatographic profiles of various steroids by radioimmunoassay demonstrated the presence of these steroids in various regions of the brain, but an immunoreactive peak corresponding to 17-hydroxyprogesterone was not found. The concentrations (ng/g tissue wet wt.) of all steroids measured were either very low or below the limit of detection in brain tissues taken from male and female infants. In the adult brain, there was no difference in the distribution of steroids between the various regions studied. There was no sex difference in the brain tissue steroid concentrations, with the exception of testosterone which was clearly much higher in brain tissues from men as compared to women. Although testosterone was undetectable in most samples taken from adult women. 5 alpha-dihydrotestosterone could be measured in almost all samples, which suggests that this is the most important androgen in the human brain. When brain tissue steroid levels are compared with serum concentrations, it can be postulated that a state of equilibrium exists between the fraction of serum steroids which are not bound to high-affinity binding proteins and the amount of steroids in brain tissues.

17-alpha-Hydroxyprogesterone↗

Steroid phobia and adherence--problems, solutions, impact on benefit/risk profile.

Adherence is important with all medications. It can be more difficult with inhaled steroids in light of concern about adverse effects. Although the degree of fear regarding inhaled steroids is difficult to quantify, it appears to be an important factor in adherence. These fears exist for several reasons, including misinformation obtained from such sources as the Internet. To improve adherence and decrease morbidity and mortality, it is vital that health care providers are aware of potential barriers to adherence. Measures such as simplifying and properly explaining medication regimens are helpful. Just as important is the establishment of a strong patient-provider relationship. This makes it easier to convince patients of the need for recommended medications. If the provider is able to effectively communicate and convince the patient of the benefit/risk ratio of steroids, improved patient outcomes can be achieved.

Administration, Inhalation↗

Hormone receptors and proliferation in breast carcinomas of equivalent histologic grades in pre- and postmenopausal women.

Breast cancers in younger, premenopausal women are more likely to exhibit an adverse prognostic profile (including negative steroid hormone receptors and a high rate of cellular proliferation) and poor outcome than breast cancers in postmenopausal women. It has been hypothesized that this adverse prognostic profile is a result of the higher histologic grade of breast cancers in pre- compared with post-menopausal women. To assess the association of expression of steroid hormone receptors and indicators of proliferation while controlling for histologic grade, we identified 100 infiltrating ductal carcinomas from premenopausal women 45 years of age or younger and 100 from postmenopausal women 65 years of age or older. The carcinomas were selected so that the histologic grades (low versus high) were distributed equally between the 2 groups. Estrogen receptors (ER), progesterone receptors (PR), p27(Kip1) and Ki-67 (to measure rate of proliferation) were assessed by immunohistochemistry and compared between groups. Clinical information and survival data were also analyzed. ER content was lower and proliferation was higher in carcinomas in premenopausal women (p = 0.048 and p = 0.005, respectively). By univariate analysis, p27(Kip1) and PR were not different between the groups; however, in multivariate analysis, p27(Kip1) was higher in postmenopausal women, but only in a subgroup with highly proliferative carcinomas. Overall survival was similar in the pre- and postmenopausal women. Furthermore, low p27(Kip1) and African-American ethnicity predicted a poorer overall survival in the premenopausal, but not in the postmenopausal, women in our study. After controlling for histologic grade, a lower expression of ER and a higher proliferative index were detected in breast carcinomas in premenopausal women. Therefore, some prognostic indicators, such as ER and proliferative rate, may be more closely associated with menopausal status than histologic grade. Our data also suggest that some prognostic factors are not equally effective as predictors of survival in pre- and postmenopausal women.

Age Factors↗

Relationship between urinary endogenous steroid metabolites and lower urinary tract function in postmenopausal women.

To investigate the relationship between the endogenous steroid hormones and the lower urinary tract function in postmenopausal women. Thirty postmenopausal volunteer women who did not have lower urinary tract symptoms or hormone replacement therapy were enrolled in this study. Urodynamic studies included uroflowmetry, multi-channel cystometry, and urethral pressure profilometry were conducted. Gas Chromatography- Mass Spectroscopy(GC-MS) was used to measure the urinary endogenous steroid hormone metabolites. The relationship between the urinary profile of the endogenous steroids and the urodynamic parameters of these patients were investigated. The mean ages of the patients were 60.6 +/- 5.5 years, and the Body Mass Index (BMI) averaged 24.56 +/- 2.23 (kg/m2). Of the progesterone metabolites, pregnandiol was significantly related to the residual volume in the uroflowmetry and the functional urethral length parameters (R=0.98, p=0.000; R= -0.65, p=0.04). Pregnantriol was significantly related to the maximum flow rate, the residual volume in uroflowmetry, the maximum urethral closure pressure and the functional urethral length (R=-0.64, p=0.04; R=0.82, p=0.01; R=0.04, p=0.04; R=- 0.79, p=0.01). In the androgen metabolites, androstenedione, 5-AT, 11- keto Et, 11-betahydroxy Et, THS, and THE were significantly related to the residual volume in uroflowmetry (R=0.92, p=0.001; R=0.84, p=0.008; R=0.99, p=0.000; R=0.72, p=0.03; R=0.97, p=0.000; R=0.85, p=0.00). beta-THF/alpha-THF was significantly related to the maximum flow rate, the residual volume in uroflowmetry, the maximum urethral closure pressure and the functional urethral length (R=-0.76, p=0.02; R=0.67, p=0.04; R=0.74, p=0.02; R=-0.92, p=0.000). alpha-cortol was significantly related to the residual volume in uroflowmetry, the maximum urethral closure pressure and the functional urethral length (R=0.81, p=0.01; R=0.71, p=0.03; R=-0.87, p=0.000). Of the estrogen metabolites, estrone (E1) was significantly related to the normal desire to void (R=0.68, p=0.04) and 17beta-estradiol/estrone was also significantly related to the normal and strong desire to void (R=-0.70, p=0.03 and R=-0.74, p=0.02, respectively). The urinary progesterone and androgen metabolite concentrations were positively related to the residual volume in uroflowmetry and positively or negatively related to MUCP and FUL. However, the urinary estrone concentration was positively related to the normal desire to void and 17beta-estradiol/estrone was significantly related to the normal and strong desire to void.

Aged↗

Biodegradable chitosan matrix for the controlled release of steroids.

Chitosan, a polysaccharide, having structural characteristics similar to glycosaminoglycans, seems to be nontoxic and bioabsorbable. This study highlights the use of chitosan matrix for controlled drug delivery systems. The steroid drugs, namely testosterone, progesterone and beta-oestradiol were mixed with chitosan and the films were prepared by evaporation technique. The in vitro release profile of these steroids from the film matrix was monitored, as a function of time, in phosphate buffered saline (PBS, pH 7.4) at 37 degree C using a U-V-spectrophotometer. The degradation, of these chitosan and drug loaded chitosan films, was also investigated by weight loss and tensile strength studies. The steroid release from chitosan films was compared with the release of these drugs from their microbeads. It appears, the films and the microbeads stayed intact during the dissolution study of 90 days and the possibility of using these systems in contraceptive applications and novel drug delivery systems are discussed.

Biocompatible Materials↗

A homologous radioimmunoassay for guinea pig corticosteroid-binding globulin.

A rapid, specific, and sensitive (requiring only 20 fmole of antigen equivalent to 0.007 microliter of serum) radioimmunoassay (RIA) was developed for the measurement of guinea pig corticosteroid-binding globulin (CBG). CBG was purified to homogeneity from guinea pig serum by affinity chromatography and used for immunization, as the standard and as the radiolabeled trace in the RIA. The antiserum to CBG was raised in rabbits. It was judged specific by immunoelectrophoresis and by comparison of RIA values with steroid-binding assay profiles obtained on serum separated on the basis of size and ion-exchange properties. The results of the radioimmunoassays agree with those of a steroid-binding assay run on identical samples. The sensitivity of the assay allows detection of CBG in serial serum samples, other biologic fluids such as milk, and cell culture supernatants.

Animals↗

Pharmacokinetic study in man with the non-steroidal antiinflammatory drug flunoxaprofen. Serum concentration-time profile after oral or topical preparations.

A clinical study on normal volunteers was performed in order to establish the pharmacokinetic pattern of the non-steroidal antiinflammatory drug S-(+)-2-(4-fluorophenyl-a-methyl-5-benzoxazole-acetic acid (flunoxaprofen, Priaxim, FLU) after oral administration or after transcutaneous absorption. Six subjects (3 men and 3 women) received FLU orally (a single dose of 200 mg) and 6 subjects (4 men and 2 women) were treated by cutaneous application on the shoulder of 1.5 g of a gel preparation containing FLU 5%. Blood samples were withdrawn before and at several time intervals after the treatments up to 48 h after oral administration and up to 24 h after cutaneous application. Serum FLU concentrations were determined by a HPLC method. The results show that a single oral dose of FLU 200 mg follows a kinetic pattern very similar to that obtained with a 100 mg dose as referred to in the literature, without significant differences of t1/2 beta, Vd and clearance values in comparison with those after FLU 100 mg. The dose-related parameters (Cmax and AUC) were higher after FLU 200 mg than after FLU 100 mg. The cutaneous application of a flunoxaprofen gel preparation did not cause detectable systemic absorption of the drug. In conclusion FLU shows favourable pharmacokinetic parameters after 200 mg oral dose, since serum values of the drug exclude the risk of accumulation; moreover the topical application of a FLU gel preparation is a safe transcutaneous treatment for inflammation and pain due to lacking systemic absorption of the drug.

Administration, Oral↗

S100A8 chemotactic protein is abundantly increased, but only a minor contributor to LPS-induced, steroid resistant neutrophilic lung inflammation in vivo.

Neutrophilic lung inflammation is an essential component of host defense against diverse eukaryotic and prokaryotic pathogens, but in chronic inflammatory lung diseases, such as chronic obstructive lung disease (COPD), severe asthma, cystic fibrosis, and bronchiolitis, it may damage the host. Glucocorticosteroids are widely used in these conditions and in their infectious exacerbations; however, the clinical efficacy of steroids is disputed. In this study, we used a proteomic approach to identify molecules contributing to neutrophilic inflammation induced by transnasal administration of lipopolysaccharide (LPS) that were also resistant to the potent glucocorticosteroid dexamethasone (Dex). We confirmed that Dex was biologically active at both the transcript (suppression of GM-CSF and TNFalphatranscripts) and protein levels (induction of lipocortin) and used 2D-PAGE/MALDI-TOF to generate global expression profiles, identifying six LPS-induced proteins that were Dex resistant. Of these, S100A8, a candidate neutrophil chemotactic factor, was profiled in detail. Steroid refractory S100A8 expression was highly abundant, transcriptionally regulated, secreted into lung lavage fluid and immunohistochemically localized to tissue infiltrating neutrophils. However, in marked contrast to other vascular beds, neutralizing antibodies to S100A8 had only a weak anti-neutrophil recruitment effect and antibodies against the related S100A9 were ineffective. These data highlight the need for extensive in vivo profiling of proteomically identified candidate molecules and demonstrates that S100A8, despite its abundance, resistance to steroids and known chemotactic activity, is unlikely to be an important determinant of LPS-induced neutrophilic lung inflammation in vivo.

Animals↗

Testosterone and doping control.

BACKGROUND AND OBJECTIVES: Anabolic steroids are synthetic derivatives of testosterone, modified to enhance its anabolic actions (promotion of protein synthesis and muscle growth). They have numerous side effects, and are on the International Olympic Committee's list of banned substances. Gas chromatography-mass spectrometry allows identification and characterisation of steroids and their metabolites in the urine but may not distinguish between pharmaceutical and natural testosterone. Indirect methods to detect doping include determination of the testosterone/epitestosterone glucuronide ratio with suitable cut-off values. Direct evidence may be obtained with a method based on the determination of the carbon isotope ratio of the urinary steroids. This paper aims to give an overview of the use of anabolic-androgenic steroids in sport and methods used in anti-doping laboratories for their detection in urine, with special emphasis on doping with testosterone. METHODS: Review of the recent literature of anabolic steroid testing, athletic use, and adverse effects of anabolic-androgenic steroids. RESULTS: Procedures used for detection of doping with endogenous steroids are outlined. The World Anti-Doping Agency provided a guide in August 2004 to ensure that laboratories can report, in a uniform way, the presence of abnormal profiles of urinary steroids resulting from the administration of testosterone or its precursors, androstenediol, androstenedione, dehydroepiandrosterone or a testosterone metabolite, dihydrotestosterone, or a masking agent, epitestosterone. CONCLUSIONS: Technology developed for detection of testosterone in urine samples appears suitable when the substance has been administered intramuscularly. Oral administration leads to rapid pharmacokinetics, so urine samples need to be collected in the initial hours after intake. Thus there is a need to find specific biomarkers in urine or plasma to enable detection of long term oral administration of testosterone.

Administration, Oral↗

Measurement of urinary and fecal steroid metabolites during the ovarian cycle in captive and wild Japanese macaques, Macaca fuscata.

We measured the concentration of steroid hormones from urine, feces, and blood samples of two captive Japanese macaques, Macaca fuscata, during nonconceptive ovarian cycles to compare the patterns of the excreted steroids with those of circulating steroids. Urine and feces were analyzed for estrone conjugates (E1C) and pregnanediol-3-glucronide (PdG) using enzyme immunoassays (EIAs), while plasma was analyzed for estradiol-17beta(E2), progesterone (P), and luteinizing hormone (LH) using radioimmunoassays (RIAs). Urinary and fecal E1C and PdG levels were approximately parallel to plasma E2 and P levels, respectively. The E1C profiles of daily urinary and fecal samples revealed a midcycle peak, followed by a sustained PdG increase lasting up to two weeks from the E1C peak. A fecal E1C peak was one day later than the urinary E1C peak. One of the captive females exhibited a discrete plasma LH peak, one indicator that ovulation has occurred, on the day following the urinary E1C peak, i.e., the same day of fecal E1C peak. We measured excreted steroids in nine wild females and determined the timing of ovulation by comparing fecal steroid profiles to those obtained in captive monkeys. Data from wild females indicated that eight of nine females conceived during their first ovulatory cycle of the sampling period, whereas the remaining female failed to conceive during the sampling period even though she ovulated. In the eight females that conceived, E1C increased again following the detected or estimated E1C peak, with levels comparable to the preovulatory peak levels, and sustained elevations of PdG for over 40 days. These data illustrate that the urinary and fecal profiles of ovarian steroid excretion obtained through the application of these noninvasive techniques provide an accurate approach for monitoring conceptive and nonconceptive ovarian cycle in captive and free-living Japanese macaques.

Animals↗

Coming of age: steroid hormones of wild immature baboons (Papio cynocephalus).

Large gaps exist in our knowledge about common patterns and variability in the endocrinology of immature nonhuman primates, and even normal hormonal profiles during that life stage are lacking for wild populations. In the present study we present steroid profiles for a wild population of baboons (Papio cynocephalus) from infancy through reproductive maturation, obtained by noninvasive fecal analyses. Fecal concentrations of glucocorticoid (fGC) and testosterone (fT) metabolites for males, and of fGC, estrogen (fE), and progestin (fP) metabolites for females were measured by radioimmunoassay (RIA). In males, infancy was characterized by high and declining levels of fGC and fT, whereas steroid concentrations were low during the juvenile years. During the months immediately prior to testicular enlargement, fT (but not fGC) concentration tended to increase. Males that matured early consistently had higher fT and fGC concentrations than those that matured late, but not significantly so at any age. Individual differences in fT concentrations were stable across ages, and average individual fT and fGC concentrations were positively correlated. For females, high and declining levels of fE characterized infancy, and values increased again after 3.5 years of age, as some females reached menarche by that age. Both fP and fGC were relatively low and constant throughout infancy and the juvenile period. During the months immediately prior to menarche, fGC concentration significantly decreased, while no changes were observed for fE levels. fP exhibited a complicated pattern of decrease that was subsequently followed by a more modest and nonsignificant increase as menarche approached. Early- (EM) and late-maturing (LM) females differed only in fP concentration; the higher fP concentrations in EM females reached significance at 4-4.5 years of age. Maternal rank at offspring conception did not predict concentrations of any hormone for either sex. Our results demonstrate the presence of individual endocrine variability, which could have important consequences for the timing of sexual maturation and subsequently for individual reproductive success. Further evaluation of the factors that affect hormone concentrations during the juvenile and adolescent periods should lead to a better understanding of mechanisms of life-history variability.

Aging↗

Osteoblast differentiation influences androgen and estrogen receptor-alpha and -beta expression.

Significant levels of estrogen and androgens circulate in men and women, and both play an important role in bone metabolism. While it is well established that either estrogen or androgen replacement therapy is effective at ameliorating bone loss associated with hypogonadism, recent evidence nevertheless suggests that estrogen and androgens have distinct molecular actions on the skeleton. In this study, we have employed normal rat calvarial osteoblast cultures to characterize relative expression profiles of estrogen (ERalpha and ERbeta) and androgen receptors (AR) during osteoblast differentiation. Normal osteoblast cultures can proceed through in vitro differentiation with distinct stages of proliferation, matrix maturation and mineralization in the appropriate differentiation medium containing ascorbic acid. Expression profiles of AR, ERalpha and ERbeta in primary cultures during osteoblast differentiation were characterized both by semi-quantitative relative RT-PCR and by Western analysis. In cultures induced to differentiate by growth in the presence of ascorbic acid, the expression profile for each receptor was unique during the course of differentiation. ERalpha levels were elevated during matrix maturation and then declined during mineralization. ERbeta expression was relatively constant throughout differentiation, exhibiting more constitutive expression. In contrast, AR levels were lowest during proliferation, and then increased throughout differentiation with highest levels in the most mature mineralizing cultures. Since steroid hormone action is generally mediated by specific cognate receptors, these results suggest that androgen actions may target cells during the mineralization stage of osteoblast differentiation, while estrogen action through either receptor isoform is more likely to affect osteoblasts earlier during matrix maturation. Interestingly, sex steroid receptor expression profiles did not exhibit the same patterns of regulation if osteoblast cultures were grown without ascorbic acid in medium that did not support extracellular matrix deposition. Thus, sex steroids may distinctly influence skeletal health by differential modulation of function during osteoblast differentiation.

Animals↗

Intestinal absorption of oestrone, oestrone glucuronide and oestrone sulphate in the rat in situ--I. Importance of hydrolytic enzymes on conjugate absorption.

The biliary excretion of steroid after administration of [3H]oestrone ([3H]E1), [3H]oestrone glucuronide ([3H]E1G) and [3H]oestrone sulphate ([3H]E1S) into the hepatic portal vein of anaesthetized rats was very rapid with more than 70% of E1S and greater than 80% of E1 and E1G excreted in the first 30 min. There was a lag period in the biliary excretion of E1S, this was less apparent with E1 and absent with E1G. Biliary excretion accurately reflects the amount of steroid in the portal circulation and was therefore used as an assessment of absorption from the gastrointestinal (GI) tract. Absorption (as judged by excretion in bile) was least after administration of each steroid into the stomach. The extent of absorption correlated well with the lipophilicity of the steroids as shown by their relative partition coefficients between n-octanol and pH 6.5 phosphate-buffered saline (E1 greater than or equal to E1S greater than or equal to E1G). There was no significant difference in excretion profile when the steroids were given into the caecum (at 5 h, E1, 46.3 +/- 9.1%; E1G, 42.2 +/- 14.5%; E1S, 39.9 +/- 7.1%). The similarity, despite marked differences in physicochemical properties, suggested conjugate hydrolysis to the parent steroid. In contrast, after administration into the small intestine, excretion of E1 was very rapid and was maximal at 1 h (72.5 +/- 8.0%); E1G showed a near-linear excretion rate (1 h, 14.4 +/- 3.0%; 5 h, 80.0 +/- 11.7%), whereas in comparison E1S excretion was low (1 h, 12.1 +/- 2.4%; 5 h, 36.9 +/- 2.7%). The involvement of hydrolytic enzymes in conjugate absorption was assessed. Ampicillin pretreatment (200 mg/kg/day for 2 days) reduced the absorption of E1G from both the proximal and distal small intestine (by approximately 50%) but had no effect on the absorption of E1S. There was, therefore, evidence that quantitative absorption of E1G requires prior hydrolysis (by mammalian and/or microbial enzymes) but intact absorption of E1S from this region of the tract was implicated. Ampicillin pretreatment reduced the absorption of both conjugates (greater with E1S) from the caecum; hydrolysis clearly precedes absorption from the caecum. The above findings were supported by an in vitro study which showed that ampicillin pretreatment abolished the hydrolysis of E1S by caecal contents but only partially reduced the hydrolysis of E1G. The presence of mammalian glucuronidase enzyme may account for this difference.

Ampicillin↗

Hormonal status of gastric cancer. II. Abnormal constitution of urinary steroids in gastric cancer patients.

We undertook a case-control study regarding the excretions of 14 urinary steroids in gastric cancer (GC) patients. The results are as follows: the levels of androgens, progestins, and two corticosteroids were, relative to tetrahydrocortisol, significantly depressed in GC patients of both sexes compared with the corresponding normal controls. The deviation profile of urinary steroids was not affected by radical gastrectomy. Evidence indicated that observed changes of GC urines were the steroidal expression of a decrease of endogenous testosterone combined with an increase of endogenous hydrocortisone; there was also evidence that the hormonal environment of our GC patients was endocrinologically homologous to that of rice-fed or salty rice-fed mice. Epidemiological inquiry revealed that GC patients having more access to rice-rich or salt-rich diets were taller and less obese than were rural healthy controls. In agreement with the anthropometric data of those cancer patients is the finding that the specific death rate of GC (as calculated for each of 15 prefectures of northern Japan) was positively correlated for each sex with the mean heights, but not with the mean weights, of 14-year-old youths of those areas. This paper discusses the possible relevancy of the hormonal and epidemiological aspects of GC patients to gastrocarcinogenesis in light of steroid physiology.

Adult↗

Steroid response pattern in Indian children with nephrotic syndrome.

The steroid response pattern to standard prednisolone therapy is of immense diagnostic, therapeutic and prognostic value for the treating physician in managing children with nephrotic syndrome. None of the studies from our country has analysed the clinical, biochemical and histopathological profile in different steroid response categories. To address this problem we conducted a study comprising 127 children with nephrotic syndrome referred to our institute. They were treated with oral prednisolone according to the APN protocol. Based on the subsequent response these children were classified into different steroid response categories on follow-up. Of the 116 children with follow-up of more than six months, infrequent relapsers constituted the majority (37.9%). The frequency of other steroid response categories was as follows: frequent relapsers (21.6%), steroid-dependent (18.1%), initial non-responders (17.3%) and subsequent non-responders (5.1%). The factors predicting a poor response to standard prednisolone therapy in our study were age of onset more than eight years, male sex, hypertension, microscopic haematuria and presence of non-minimal change nephrotic syndrome lesions on histopathology.

Child↗

[Pharmacological profile of mofezolac, a new non-steroidal analgesic anti-inflammatory drug].

Pharmacological activities of mofezolac were investigated in experimental animal models and compared with those of indomethacin, ibuprofen, mefenamic acid, aspirin and aminopyrine. Mofezolac showed a potent suppression of various writhing models in mice or rats; and its potency was slightly lower than that of indomethacin, but was higher than those of the other reference drugs. Thus, mofezolac was especially active against chemically induced writhing and also in the phenylquinone induced intraperitoneal dye leakage reaction in mice. Mofezolac also has a potent inhibitory activity on the algesic responses induced by the mechanical stimulus of the inflammed tissue. Mofezolac exhibited a therapeutic effect comparable to indomethacin in the urate synovitis in dogs. Considering the anti-inflammatory and antipyretic actions, mofezolac was obviously less effective than indomethacin, and its potency was similar to that of ibuprofen. The ulcerogenic effect of mofezolac on the gastric mucosa was far weaker than that of indomethacin. In in vitro studies, the prostaglandin biosynthesis and platelet aggregation were inhibited to the same extent by both mofezolac and indomethacin. Accordingly, it may be considered that the actions of mofezolac are due to the inhibition of cyclooxygenase. Our result suggest that mofezolac can be a useful drug that shows a rapid pain-relieving activity in acute inflammations.

Analgesics↗