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M Nakashima

Publications and source records attributed to M Nakashima.

At least 37 records · Page 2Linked to original sources
PubMed2003

A novel tumour marker RCAS1 in a case of extramammary Paget's disease.

A 66-year-old male, whose primary skin lesion in extramammary Paget's disease had been surgically resected 4 years previously, was hospitalized with liver metastases. Hepatic arterial infusion chemotherapy was carried out and the tumours clearly reduced in size. Serum levels of some common tumour markers were not elevated, even prior to therapy. We measured serum levels of a novel tumour-associated antigen, RCAS1, because its expression was detected in the tumour cells. The patient's serum RCAS1 level was elevated (22.0 U/mL) before therapy and fell during (10.5 U/mL) and after (5.0 U/mL) therapy. Therefore, serum RCAS1 levels may be valuable as a potential biomarker for monitoring therapeutic efficacy against Paget's disease.

Aged↗
PubMed2002

A novel gene, GliH1, with homology to the Gli zinc finger domain not required for mouse development.

The Sonic hedgehog (Shh)-Gli signaling pathway regulates development of many organs, including teeth. We cloned a novel gene encoding a transcription factor that contains a zinc finger domain with highest homology to the Gli family of proteins (61-64% amino acid sequence identity) from incisor pulp. Consistent with this sequence conservation, gel mobility shift assays demonstrated that this new Gli homologous protein, GliH1, could bind previously characterized Gli DNA binding sites. Furthermore, transfection assays in dental pulp cells showed that whereas Gli1 induces a nearly 50-fold increase in activity of a luciferase reporter containing Gli DNA binding sites, coexpression of Gli1 with Gli3 and/or GliH1 results in inhibition of the Gli1-stimulated luciferase activity. In situ hybridization analysis of mouse embryos demonstrated that GliH1 expression is initiated later than the three Gli genes and has a more restricted expression pattern. GliH1 is first detected diffusely in the limb buds at 10.0 days post coitus and later is expressed in the branchial arches, craniofacial interface, ventral part of the tail, whisker follicles and hair, intervertebral discs, teeth, eyes and kidney. LacZ was inserted into the GliH1 allele in embryonic stem cells to produce mice lacking GliH1 function. While this produced indicator mice for GliH1-expression, analysis of mutant mice revealed no discernible phenotype or required function for GliH1. A search of the Celera Genomics and associated databases identified possible gene sequences encoding a zinc finger domain with approximately 90% homology to that of GliH1, indicating there is a family of GliH genes and raising the possibility of overlapping functions during development.

Alleles↗
PubMed2002

Induction of dental pulp stem cell differentiation into odontoblasts by electroporation-mediated gene delivery of growth/differentiation factor 11 (Gdf11).

The long-term goal of dental treatment is to preserve teeth and prolong their function. In dental caries an efficient method is to cap the exposed dental pulp and conserve the pulp tissue with reparative dentin. We examined whether growth/differentiation factor 11 (GDF11), a morphogen could enhance the healing potential of pulp tissue to induce differentiation of pulp stem cells into odontoblasts by electroporation-mediated gene delivery. Recombinant human GDF11 induced the expression of dentin sialoprotein (Dsp), a differentiation marker for odontoblasts, in mouse dental papilla mesenchyme in organ culture. The Gdf11 cDNA plasmid which was transferred into mesenchymal cells derived from mouse dental papilla by electroporation, induced the expression of Dsp. The in vivo transfer of Gdf11 by electroporation stimulated the reparative dentin formation during pulpal wound healing in canine teeth. These results provide the scientific basis and rationale for gene therapy for endodontic treatments in oral medicine and dentistry.

Animals↗
PubMed2002

Suplatast tosilate inhibits thymus- and activation-regulated chemokine production by antigen-specific human Th2 cells.

BACKGROUND: Suplatast tosilate is an anti-allergic agent that suppresses cytokine production by human Th2 cells. OBJECTIVE: We investigated the effects of suplatast tosilate on the production of thymus- and activation-regulated chemokine (TARC) by T cells from allergic patients with asthma. METHODS: Purified protein derivative (PPD)-specific Th1 cell lines and Dermatophagoides farinae (Der f)-specific Th2 cell lines were established from nine patients with house dust mite-allergic asthma. The effects of suplatast tosilate on mRNA expression of TARC and protein production of TARC from antigen-specific Th1 or Th2 cell lines were investigated after stimulation with relevant antigens or phytohemagglutinin (PHA). In addition, the effects of IL-4, IL-10, and IFN-gamma on TARC production by Der f-specific Th2 cell lines in the presence or absence of suplatast tosilate were studied. RESULTS: Although PPD-specific Th1 cell lines did not produce TARC after stimulation with PPD antigen or PHA, stimulation of Der f-specific Th2 cell lines with Der f antigen or PHA increased production of TARC. Suplatast tosilate significantly and dose-dependently inhibited production of TARC by Der f-specific Th2 cell lines stimulated with either Der f antigen (76.5% inhibition at 100 microg/mL, P < 0.01) or PHA (81.9% inhibition at 100 microg/mL, P < 0.01). TARC production by Der f-specific Th2 cell lines was significantly increased only by activation with IL-4 but not with IL-10 or IFN-gamma; this increase in TARC production was significantly inhibited by suplatast tosilate (97.5% inhibition at 100 microg/mL, P < 0.01). CONCLUSION: Suplatast tosilate inhibits TARC production by human Th2 cells. Therefore, this agent inhibits both Th2 cytokine and Th2 chemokine and may be a useful anti-allergic agent.

Adult↗
PubMed2002

Seasonal variations in growth rate of phytoplankton in Hakata Bay, Japan.

Recently, water pollution with high concentrations of organic matter has occurred frequently in Hakata Bay. It is said that a high level of primary production provides much organic matter and affects water quality of the bay, and it is proved by the appearance of phytoplankton throughout the year. In this study, we simulated variations of phytoplankton population with a box-type model using monthly data in a long-term measurement and we analyzed the final growth rate changes of phytoplanktons that explain the conditions for its appearance. Consequently, we found that the final growth rate varies with pattern of half-year periodicity and water temperature and/or ambient nutrient controls the final growth rate to be low every January and July.

Environmental Monitoring↗
PubMed2001

Up-regulation of splenic prohormone convertases PC1 and PC2 in diabetic rats.

Organisms respond to infection in a complex manner involving bidirectional interactions between the neuroendocrine and immune systems. Many of the bioactive endocrine/immune factors are synthesized in a precursor form and are expected to be activated by prohormone convertases (PCs). Since patients with both type 1 and type 2 diabetes have an increased incidence and severity of infections, we hypothesized that in a condition of hyperglycemia, these processing enzymes would be activated in an immune tissue, the spleen. To test this hypothesis, we treated rats with intraperitoneal streptozotocin (STZ) (50 mg/kg/day) daily for 5 days and measured splenic PC1 and PC2 mRNA by ribonuclease protection assay. We found that PC1 mRNA was increased 6.0+/-0.02-fold (P<0.05) and PC2 mRNA was increased 1.80+/-0.01-fold (P<0.005) in the spleen of rats that received STZ compared to rats that received vehicle. Western blot indicated that the 75-kDa form of PC1 was the only form of PC1 present in the spleen and that this form increased with STZ treatment. Immunohistochemistry revealed that PC1 was found in both the white pulp (T-lymphocytes) and red pulp (monocytes and macrophages) and that its increase in immunoreactivity occurred primarily in the white pulp. PC2 and pro-opiomelanocortin (POMC, a possible splenic substrate for PC1/PC2) immunoreactivity was found predominantly in the red pulp. STZ induced an increase in splenic PC1 and POMC, but not PC2 protein levels. We conclude that in the STZ model of diabetes, splenic PCs are induced, which could lead to an increased activation of many immune-derived hormones. We speculate that this up-regulation of prohormone converting enzymes may be related to the increased infections seen in patients with both type 1 and type 2 diabetes.

Animals↗
PubMed2001

Controlled release and ocular absorption of tilisolol utilizing ophthalmic insert-incorporated lipophilic prodrugs.

To control ocular drug delivery, the O-butyryl ester prodrug of tilisolol (BUTL) and the O-palmitoyl ester prodrug of tilisolol (PalTL) were incorporated into an ophthalmic insert. The released TL from BUTL inserts and PalTL inserts in pH 7.4 phosphate-buffered saline until 5 h were approximately 25% and 3% of that from TL inserts, respectively. In addition, BUTL was also released from BUTL inserts. However, PalTL was not released from the PalTL insert. The release of drugs from TL inserts and BUTL inserts was little affected by the addition of bovine serum albumin (BSA) in pH 7.4 phosphate-buffered saline. In contrast, the release of drugs from PalTL inserts were enhanced by the addition of BSA. After application of TL, BUTL, and PalTL inserts to the rabbit eye, the aqueous humor concentration of TL was prolonged compared with TL instillation, and the plasma concentration of TL was much lower than that of TL instillation. The ratios of the area under the TL concentration-time curve (AUC) in the aqueous humor to AUC in the plasma (AUC(aqueous)/AUC(plasma)) after application of BUTL until 8 h were 3.1-fold and 3.8-fold higher than those of the TL insert and PalTL insert, respectively.

Absorption↗
PubMed2001

Expression of a tumor-associated antigen RCAS1 in hepatocellular carcinoma.

RCAS1 has been reported as a tumor-associated antigen in uterine and ovarian carcinomas. In vitro studies on RCAS1 indicated that it might function as an apoptosis-inducing factor since binding between RCAS1 and its receptor induced apoptosis in receptor-expressing cells. In this study, 68 surgically resected samples of hepatocellular carcinoma (HCC) were prepared and RCAS1 expression was examined immunohistochemically, because RCAS1 was also positive in all HCC cell lines tested. Clinical and pathological parameters were then compared between RCAS1-positive and -negative HCC cases. As a result, RCAS1 is expressed in 26.5% of HCC cases and vascular invasion is observed at a much higher rate in the RCAS1-positive cases (72.2%) than in RCAS1-negative cases (24.0%). RCAS1 is not an antigen specific for gynecological cancers. In HCC cases, the RCAS1-positive percentage is not high, however, RCAS1-positive HCCs exhibited a trend towards invasive character.

Animals↗
PubMed2001

Expression of tumor-associated antigen RCAS1 correlates significantly with poor prognosis in nonsmall cell lung carcinoma.

BACKGROUND: RCAS1 is a recently discovered antigen molecule expressed on the membrane of cancer cells, and it acts as a ligand for a putative receptor present on immune cells such as T, B and NK cells. It has been suggested that RCAS1 expression is related to the escape of tumors from immune surveillance. In this study, the relation between RCAS1 expression and various clinicopathologic variables, including patient prognosis, was investigated in lung carcinoma through immunohistochemical analysis. METHODS: One hundred two surgically resected nonsmall cell lung carcinoma cases were examined histopathologically by means of the monoclonal antibody 22-1-1, which is specific for RCAS1. The correlation between RCAS1 expression and the clinicopathologic features of patients was evaluated. Moreover, the correlation between RCAS1 expression and the survival of patients was analyzed by the Kaplan-Meier method log-rank test, and multivariate analysis was performed by using the Cox proportional hazard model. RESULTS: The samples of 48 of the 102 lung carcinoma patients (47.1%) were positive for RCAS1. There were significant correlations between RCAS1 expression and either pathologic staging (P = 0.0003) or tumor differentiation (P = 0.0308). The survival time for the RCAS1-positive group was significantly shorter than that for RCAS1-negative group (P < 0.0001). Moreover, multivariate analysis for overall survival revealed that RCAS1 expression was a significantly independent prognostic factor in nonsmall cell lung carcinoma patients. CONCLUSION: These results suggested that RCAS1 expression may play an important role in the immune escape mechanism and that RCAS1 expression may be a good indicator of poor prognosis in patients with nonsmall cell lung carcinoma.

Adult↗
PubMed2001

Receptor binding cancer antigen expressed on SiSo cells, a novel regulator of apoptosis of erythroid progenitor cells.

To better understand the control of apoptosis during erythropoiesis, this study investigated the role of a novel tumor-associated antigen, RCAS1 (receptor binding cancer antigen expressed on SiSo cells), with regard to the regulation of apoptosis of erythroid progenitor cells. Erythroid colony-forming cells (ECFCs) purified from human peripheral blood were used. Binding experiments of RCAS1 showed that ECFCs abundantly expressed receptors (RCAS1R) for RCAS1 and that the degree of binding of RCAS1 to the receptors diminished rapidly during erythroid maturation in vitro. When the soluble form of RCAS1 was added to the cultures, ECFCs underwent apoptosis, including collapse of the mitochondrial transmembrane potential, and activation of caspases 8 and 3. The addition of an anti-Fas blocking antibody or Fas-Fc failed to reduce the apoptosis induced by RCAS1, thereby indicating that effects of RCAS1 are independent of Fas activation. When binding of RCAS1 to normal bone marrow cells was analyzed, RCAS1R was evident on cells with an immature erythroid phenotype (transferrin receptor(+)/glycophorin A(-)) but not with a mature phenotype (transferrin receptor(-)/glycophorin A(+)). Histochemical staining revealed the expression of RCAS1 in the cytoplasm of bone marrow macrophages. These findings indicate that RCAS1, which is mainly produced by macrophages in hematopoietic tissue, may have a crucial role in controlling erythropoiesis by modulating apoptosis of erythroid progenitor cells via a Fas-independent mechanism.

Adenocarcinoma↗
PubMed2001

Expression of human tumor-associated antigen RCAS1 in Reed-Sternberg cells in association with Epstein-Barr virus infection: a potential mechanism of immune evasion.

RCAS1 (receptor-binding cancer antigen expressed on SiSo cells) is present in neoplastic cells, induces apoptosis of natural killer (NK)/T cells and plays a role in immune evasion. Fas ligand (FasL) is considered to have similar roles. The Epstein-Barr virus (EBV)-encoded latent membrane protein is expressed by malignant Hodgkin and Reed-Sternberg (H&RS) cells of EBV-associated Hodgkin's disease (HD) and considered to be a target of cytotoxic T lymphocytes (CTLs). However, CTL response is inadequate in HD. To determine whether RCAS1 and FasL are expressed in EBV-associated HD and participate in immune evasion, tissues of 20 EBV(-) and 15 EBV(+) HD cases were immunohistochemically stained for RCAS1, FasL and HLA classes I and II, whose deficiencies could explain CTL escape. Lymphocytes surrounding H&RS cells tended to be CD4(+) cells and rarely CD8(+), TIA-1(+) (cytotoxic marker) or NK cells. HLA class I and/or II were expressed in all EBV(+) HD cases, and RCAS1-expressing H&RS cells were found in 14/15 (93%) EBV(+) HD cases but only 8/20 (40%) EBV(-) HD cases (p < 0.05). FasL was detected in 9/15 (60%) and 7/20 (35%) EBV(+) and EBV(-) HD cases, respectively. ssDNA-positive (apoptotic) lymphocytes, surrounding H&RS cells, were rarely seen but were present in RCAS1(+) cases (20/22 cases, 91%) rather than negative cases (0/13 cases, 0%) (p < 0.005). Our findings suggest that EBV(+) H&RS cells might evade the host immune response by expressing RCAS1 rather than FasL.

Adolescent↗
PubMed2001

Ocular absorption behavior of palmitoyl tilisolol, an amphiphilic prodrug of tilisolol, for ocular drug delivery.

The objective of this study was to examine the ocular absorption behavior of an amphiphilic prodrug after instillation onto the cornea of rabbits. A micellar solution of O-palmitoyl tilisolol (PalTL), an amphiphilic prodrug, was prepared. After instillation of tilisolol (TL) and PalTL, the drug concentrations in the tear fluid, cornea, aqueous humor, iris-ciliary body, vitreous body, and blood were measured. In addition, in situ ocular absorption behavior was also evaluated. After instillation of TL, the concentration of TL in the tear fluid quickly decreased. After instillation of PalTL, prolonged retention and high concentrations of PalTL in tear fluid and the cornea were observed. In addition, more prolonged retention of the TL concentration after instillation of PalTL than after instillation of TL was observed in the cornea, aqueous humor, and iris-ciliary body. In situ experiments demonstrated that PalTL was mainly absorbed by the corneal route and the improvement effects of PalTL under in vivo conditions was due to an enhanced transit time of PalTL in ocular tissues. PalTL, an amphiphilic prodrug, exhibited increased retention in the precorneal area compared with the parent drug, TL, resulted in improved ocular absorption of the parent drug.

Absorption↗
PubMed2001

The sympathetic nervous system promotes carbon tetrachloride-induced liver cirrhosis in rats by suppressing apoptosis and enhancing the growth kinetics of regenerating hepatocytes.

Norepinephrine is considered to possess potent anti-apoptotic action in regenerating hepatocytes. To clarify the role of the sympathetic nervous system in apoptosis that occurs in chronic liver damage and following the promotion of liver cirrhosis, we studied a carbon tetrachloride (CCl4)-induced liver injury model, using spontaneously hypertensive rats (SHR), Wistar-Kyoto rats (WKY), and chemically sympathectomized WKY. At 24 h after CCl4 administration. acute damage, characterized by vacuolated hepatocytes in the centrilobular zone, was greater in SHR than in WKY. This vacuolated change in WKY hepatocytes was significantly reduced by chemical sympathectomy with 6-hydroxydopamine (6-OHDA). After 48 h, the acute damage was dramatically improved in each animal, without significant differences between the three groups. In chronic damage after weekly repetition of CCl4 treatment for 4 weeks, fibrosis was evident in SHR, while in the other groups there was only scant fibrosis in the centrilobular zone. After 8 weeks' repetition of CCl4, liver cirrhosis was seen only in SHR. The incidence of apoptotic cells in areas of both acute and chronic damage in WKY, detected by terminal deoxynucleotidyl transferase-dUTP nick end labeling, was significantly increased in comparison with that in SHR, and was further increased by 6-OHDA pretreatment. In contrast, there was significantly greater enhancement of the growth of hepatocytes in SHR than in WKY in both acute and chronic damage. Moreover. hepatocyte growth kinetics in WKY was significantly inhibited after sympathectomy in acute injury, as evidenced by immunohistochemistry for proliferating cell nuclear antigen (PCNA). In vitro, the amount of hepatocellular apoptosis induced by transforming growth factor-beta1 was significantly decreased by incubation with norepinephrine. These findings suggest that the anti-apoptotic effect of the sympathetic nervous system increases cell growth kinetics and promotes liver cirrhosis in this animal model.

Animals↗
PubMed2001

RCAS1 antigen is highly expressed in extramammary Paget's disease and in advanced stage squamous cell carcinoma of the skin.

Receptor-binding cancer antigen expressed on SiSo cells (RCAS1), which is a type II membrane protein expressed on cervical carcinoma cells, induces apoptosis in RCAS1 receptor expressing cells. RCAS1 is thus presumed to protect tumor cells from immune surveillance by infiltrating RCAS1 receptor-positive immunocytes (Sonoda et al. Int J Oncol 1995; 6: 1899-1904; Nakashima et al. Nature Med 1999; 5: 938-942). We performed immunohistochemical analysis of RCAS1 expression in various skin tumors. RCAS1 was not detected in normal human epidermis. One of 21 seborrheic keratosis (4.8%), one of 12 actinic keratosis (8.3%), two of 16 keratoacanthomas (12.5%), and two of 14 basal cell carcinomas (14.2%) expressed RCAS1. RCAS1 was not detected in Bowen's disease (0/17). RCAS1 was positive in 45 of 61 (73.8%) squamous cell carcinomas. Interestingly, the expression of RCAS1 was mostly correlated with clinical stages of squamous cell carcinoma. It was found that 46.1% of stage I, 61.1% of stage II, 85.7% of stage III, and 83.3% of stage IV squamous cell carcinomas were RCAS1-positive. In addition, RCAS1 was found to be highly expressed in extramammary Paget's disease. Fifty nine of 63 extramammary Paget's disease samples (93.7%) were positive for RCAS1. Fifty eight (92%) showed co-expression of RCAS1 and carcinoembryonic antigen (CEA). While two of 24 cases of melanoma (8.3%) expressed RCAS1 antigen, none of 20 cases of nevus pigmentosus showed positive staining. These results indicate that RCAS1 is a highly sensitive marker for extramammary Paget's disease. RCAS1 is also expressed in various skin tumors including squamous cell carcinoma, where positive correlation with clinical staging was documented.

Antigens, Neoplasm↗
PubMed2001

Immunohistochemical analysis of RCAS1 in human pituitary adenomas.

It has been reported that RCAS1 (receptor-binding cancer antigen expressed on SiSO cells) acts as a ligand for a receptor present on normal peripheral lymphocytes and induces apoptotic cell death. It is expressed in uterine and ovarian carcinomas, especially in invasive cancers. This immunohistochemical study is aimed to elucidate the expression of RCAS1 in human pituitary adenomas in order to clarify its role in their proliferative regulation and invasiveness. Five normal pituitary glands, 50 human pituitary adenomas, and one malignant glioma were subjected to immunohistochemical studies. In normal pituitary glands, immunostaining of RCAS1 and MIB-1 was not found. In malignant glioma, large numbers of cell nuclei were positive for MIB-1 (MIB-1 index: 28%), and RCAS1 was detected both in the cytoplasm and on the membrane of the tumor cells. Expression of RCAS1 was noted in 48% of pituitary adenomas immunohistochemically (60.0% of growth hormone-secreting adenomas, 60.0% of prolactin-secreting adenomas, 42.9% of adrenocorticotrophin-secreting adenomas, 40.0% of thyroid-stimulating hormone-secreting adenomas, 33.3% of nonfunctioning adenomas, and 44.4% of gonadotropin-subunit-positive adenomas). It showed no correlation with tumor type, size, and invasiveness. The statistically significant relationship between RCAS1 and MIB-1 positivity was identified in our study. These results suggest that expression of RCAS1 as well as MIB-1 positivity predict the growth potential of individual pituitary adenomas.

Adenoma↗
PubMed2001

Expression of RCAS1 and FasL in human trophoblasts and uterine glands during pregnancy: the possible role in immune privilege.

Pregnancy is an immunological balancing act. Trophoblasts do not express MHC class I or II, except HLA-C and G, but express Fas ligand (FasL), which confers immune privilege. RCAS1 (receptor-binding cancer antigen expressed on SiSo cells) has recently been recognized to play a role in immune evasion of the tumour cells. We therefore studied the involvement of RCAS1 and FasL in the infiltration of NK cells by examining the curettaged uterine contents of 20 cases of early stage of pregnancy. The cases were clinically divided into two groups; curettage was performed (A) due to the absence of foetal heart beats, and (B) due to spontaneous uterine bleeding and abortion. In group A, RCAS1 was expressed in the uterine glands and extravillous cytotrophoblasts, as was FasL. Infiltration of NK cells around the uterine glands was scarcely detected. In contrast, in group B, expression of both RCAS1 and FasL was strikingly decreased in both the level of expression and the numbers of RCAS1/FasL-positive cells and massive infiltration of NK cells was frequently detected around the uterine glands. These findings suggest that a reduction in RCAS1 and FasL expression seems to be closely associated with activation and infiltration of maternal NK cells and destruction of uterine glands, resulting in rejection of the foetus. Thus, expression of RCAS1 and FasL in the uterine glands and cytotrophoblasts may play a role in the downregulation of the maternal immune response, thereby maintaining pregnancy at early stage.

Abortion, Spontaneous↗
PubMed2001

Efficacy of budesonide Turbuhaler compared with that of beclomethasone dipropionate pMDI in Japanese patients with moderately persistent asthma.

OBJECTIVE: The aim of the study was to compare the efficacy and safety of budesonide Turbuhaler with that of beclomethasone dipropionate (BDP) pMDI. METHODOLOGY: Three hundred and fifty adult asthma patients (mean age 52.7 years, mean baseline morning peak expiratory flow (PEF) 294 L/min (< 80% predicted normal)), taking BDP via pressurized metered-dose inhaler (pMDI), 400 microg daily for at least 2 months, were randomized in an open 6 week study to receive daily doses of either budesonide 100 microg or 400 microg twice daily via Turbuhaler or continued treatment with BDP, 100 microg four times daily. The primary efficacy variable was the mean change in morning PEF from baseline to the end of treatment. Outcome was also assessed using symptom scores and investigators' assessments employed in Japanese clinical trials. RESULTS: At the end of the 6 week treatment period, mean morning PEF improved significantly from baseline in both budesonide groups, 16 L/min and 33 L/min in the 200 microg and 800 microg groups, respectively, but not in the BDP group, 5 L/min. There was no significant difference between 200 microg budesonide and 400 microg BDP treatment in the effect on PEF (P = 0.29), but 800 microg budesonide was significantly superior to BDP (P < 0.001). Final assessment of improvement and usefulness ratings showed that both budesonide treatments were significantly superior to BDP (P < 0.001). All treatments were well tolerated. CONCLUSION: Budesonide Turbuhaler (200 microg) was as effective as 400 microg BDP pMDI. The efficacy of budesonide was improved significantly by increasing the dosage to 800 microg daily. The study design shows the importance of including a higher dose treatment group when comparing two formulations of inhaled corticosteroids in order to determine whether the treatments to be compared are on the steep part of the dose-response curve. Without that information, comparative studies are usually inconclusive.

Anti-Inflammatory Agents↗