A HIF-1α-driven feed-forward loop augments HIF signalling in Hep3B cells by upregulation of ARNT.

Oxygen-deprived (hypoxic) areas are commonly found within neoplasms caused by excessive cell proliferation. The transcription factor Aryl hydrocarbon receptor nuclear translocator (ARNT) is part of the hypoxia-inducible factor (HIF) pathway, which mediates adaptive responses to ensure cellular survival under hypoxic conditions. HIF signalling leads to metabolic alterations, invasion/metastasis and the induction of angiogenesis in addition to radio-chemoresistance of tumour cells. Activation of the HIF pathway is based on the abundance of HIF-α subunits, which are regulated in an oxygen-dependent manner and form transcriptional active complexes with ARNT or ARNT2 (also referred as HIF-1ß and HIF-2ß, respectively). ARNT is considered to be unaffected by hypoxia but certain cell lines, including Hep3B cells, are capable to elevate this transcription factor in response to oxygen deprivation, which implies an advantage. Therefore, the aim of this study was to elucidate the mechanism of hypoxia-dependent ARNT upregulation and to determine implications on HIF signalling. Gene silencing and overexpression techniques were used to alter the expression pattern of HIF transcription factors under normoxic and hypoxic conditions. qRT-PCR and western blotting were performed to measure gene and protein expression, respectively. HIF activity was determined by reporter gene assays. The results revealed a HIF-1α-dependent mechanism leading to ARNT upregulation in hypoxia. Forced expression of ARNT increased reporter activity under normoxic and hypoxic conditions. In conclusion, these findings indicate a novel feed-forward loop and suggest that ARNT might be a limiting factor. Augmented HIF signalling in terms of elevated target gene expression might be advantageous for tumour cells.

Nanoscale imaging of InN segregation and polymorphism in single vertically aligned InGaN/GaN multi quantum well nanorods by tip-enhanced Raman scattering.

Vertically aligned GaN nanorod arrays with nonpolar InGaN/GaN multi quantum wells (MQW) were grown by MOVPE on c-plane GaN-on-sapphire templates. The chemical and structural properties of single nanorods are optically investigated with a spatial resolution beyond the diffraction limit using tip-enhanced Raman spectroscopy (TERS). This enables the local mapping of variations in the chemical composition, charge distribution, and strain in the MQW region of the nanorods. Nanoscale fluctuations of the In content in the InGaN layer of a few percent can be identified and visualized with a lateral resolution below 35 nm. We obtain evidence for the presence of indium clustering and the formation of cubic inclusions in the wurtzite matrix near the QW layers. These results are directly confirmed by high-resolution TEM images, revealing the presence of stacking faults and different polymorphs close to the surface near the MQW region. The combination of TERS and HRTEM demonstrates the potential of this nanoscale near-field imaging technique, establishing TERS as a very potent, comprehensive, and nondestructive tool for the characterization and optimization of technologically relevant semiconductor nanostructures.

Characterization of hepatic and brain metabolism in young adults with glycogen storage disease type 1: a magnetic resonance spectroscopy study.

In glycogen storage disease type 1 (GSD1), children present with severe hypoglycemia, whereas the propensity for hypoglycemia may decrease with age in these patients. It was the aim of this study to elucidate the mechanisms for milder hypoglycemia symptoms in young adult GSD1 patients. Four patients with GSD1 [body mass index (BMI) 23.2 +/- 6.3 kg/m, age 21.3 +/- 2.9 yr] and four healthy controls matched for BMI (23.1 +/- 3.0 kg/m) and age (24.0 +/- 3.1 yr) were studied. Combined (1)H/(31)P nuclear magnetic resonance spectroscopy (NMRS) was used to assess brain metabolism. Before and after administration of 1 mg glucagon, endogenous glucose production (EGP) was measured with d-[6,6-(2)H(2)]glucose and hepatic glucose metabolism was examined by (1)H/(13)C/(31)P NMRS. At baseline, GSD1 patients exhibited significantly lower rates of EGP (0.53 +/- 0.04 vs. 1.74 +/- 0.03 mg.kg(-1).min(-1); P < 0.01) but an increased intrahepatic glycogen (502 +/- 89 vs. 236 +/- 11 mmol/l; P = 0.05) and lipid content (16.3 +/- 1.1 vs. 1.4 +/- 0.4%; P < 0.001). After glucagon challenge, EGP did not change in GSD1 patients (0.53 +/- 0.04 vs. 0.59 +/- 0.24 mg.kg(-1).min(-1); P = not significant) but increased in healthy controls (1.74 +/- 0.03 vs. 3.95 +/- 1.34; P < 0.0001). In GSD1 patients, we found an exaggerated increase of intrahepatic phosphomonoesters (0.23 +/- 0.08 vs. 0.86 +/- 0.19 arbitrary units; P < 0.001), whereas inorganic phosphate decreased (0.36 +/- 0.08 vs. -0.43 +/- 0.17 arbitrary units; P < 0.01). Intracerebral ratios of glucose and lactate to creatine were higher in GSD1 patients (P < 0.05 vs. control). Therefore, hepatic defects of glucose metabolism persist in young adult GSD1 patients. Upregulation of the glucose and lactate transport at the blood-brain barrier could be responsible for the amelioration of hypoglycemic symptoms.

Purification and some properties of thiosulfate dehydrogenase from Acidithiobacillus ferrooxidans.

Thiosulfate dehydrogenase was purified from Acidithiobacillus ferrooxidans using three purification steps. The purification procedure involved ammonium sulfate fractionation, ion-exchange chromatography, and gel permeation chromatography. Specific activity of the purified enzyme (after IEC) was 3.26 nkat/mg, and yield of the enzyme was 78%. The purity of the enzyme was checked by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate. The enzyme is a tetramer composed of four probably identical subunits of relative molecular weight 45,000. The pH optimum of the enzyme reaction in the direction of substrate oxidation was found to be 3.0. The isoelectric point of the enzyme was 8.3. Enzyme activity was found to be particularly sensitive to the histidine-selective reagent diethylpyrocarbonate. Reagents selective for arginine, cysteine, and tryptophane had no effect on enzyme activity.

Spatio-temporal regulation of mitogen-activated protein kinase (MAPK) signalling by protein phosphatases.

ERK (extracellular-signal-regulated kinase) is a MAPK (mitogen-activated protein kinase), which regulates diverse physiological functions including cell proliferation, differentiation, transformation and survival. It is now clear that in addition to the duration and magnitude of signalling through this MAPK pathway, the spatial restriction of MAPK activity plays a key role in determining the physiological outcome of signalling. Recent work has led to the discovery of MAPK-binding proteins, which contain either nuclear localization signals or nuclear export signals. These include MAPK activators and specific protein phosphatases, which may act to both regulate MAPK activity and the subcellular localization of their substrate. This represents a mechanism by which signalling in response to extracellular stimuli may be modulated in terms of both magnitude/duration and spatial restriction thus allowing differential access of the activated MAPK to target proteins and the interpretation of this information by cells to determine an appropriate physiological response.

Differential glucocorticoid effects on proliferation and invasion of human trophoblast cell lines.

Several clinical situations require continuous glucocorticoid (GC) treatment during pregnancy. A well-known deleterious side effect of such treatment is the higher incidence of growth-restricted fetuses, for which a too shallow trophoblast invasion is presently hypothesised as the underlying cause. This study investigated whether the synthetic GC triamcinolone acetonide (TA) influences proliferation, invasion and endocrine activity of human trophoblast. BeWo and JEG-3 choriocarcinoma cell lines both express GC receptors (western blotting) and were used as models for human trophoblast. JAR devoid cells of GC receptor were used as negative control. The cells were cultured for 48 h without (control) or with 0.5, 5 and 50 microM TA. In the presence and absence of serum, proliferation was determined by cell counting and measuring the cell cycle regulating protein cyclin B1 (Western blotting); invasion was determined by a conventional Matrigel invasion assay and by measuring the secretion (ELISA) of matrix-metalloproteinases (MMP-2, MMP-9) into the culture medium; endocrine activity was assessed by measuring the levels of human chorionic gonadotropin (ELISA) into the culture medium. TA altered the number of viable and dead cells as well as cyclin B1 levels and, to a lesser extent, invasion of BeWo and JEG-3, with a strong influence of serum. BeWo and JEG-3 cells reacted differently and in most instances reverse. In the cell lines used as models of human trophoblast, TA alter some functions relevant to proliferation and invasion, and suggest that caution should be exercised when treating women with GCs during pregnancy.

EEG-tomographic studies with LORETA on vigilance differences between narcolepsy patients and controls and subsequent double-blind, placebo-controlled studies with modafinil.

The aim of the present study was to identify brain regions associated with vigilance in untreated and modafinil-treated narcoleptic patients by means of low-resolution brain electromagnetic tomography (LORETA). 16 drug-free narcoleptics and 16 normal controls were included in the baseline investigation. Subsequently patients participated in a double-blind, placebo-controlled crossover study receiving a three-week fixed titration of modafinil (200, 300, 400 mg) and placebo. Measurements comprised LORETA, the Multiple Sleep Latency Test (MSLT) and the Epworth Sleepiness Scale (ESS) obtained before and after three weeks' therapy. Statistical overall analysis by means of the omnibus significance test demonstrated significant inter-group differences in the resting (R-EEG), but not in the vigilance-controlled recordings (V-EEG). Subsequent univariate analysis revealed a decrease in alpha-2 and beta 1-3 power in prefrontal, temporal and parietal cortices, with the right hemisphere slightly more involved in this vigilance decrement. Modafinil 400 mg/d as compared with placebo induced changes opposite to the aforementioned baseline differences (key-lock principle) with a preponderance in the left hemisphere. This increase in vigilance resulted in an improvement in the MSLT and the ESS. LORETA provided evidence of a functional deterioration of the fronto-temporo-parietal network of the right-hemispheric vigilance system in narcolepsy and a therapeutic effect of modafinil on the left hemisphere, which is less affected by the disease.

Formation of iodinin by a strain of Acidithiobacillus ferrooxidans grown on elemental sulfur.

The presence of the pigment iodinin, an Acidithiobacillus ferrooxidans culture metabolite, was demonstrated after growth of bacteria on elemental sulfur. The structure of iodinin was confirmed by X-ray structure analysis; its physiological role is discussed.

Serum-dependent effects of IGF-I and insulin on proliferation and invasion of human first trimester trophoblast cell models.

Extravillous cytotrophoblasts are specialised epithelial cells of the placenta that proliferate or invade the maternal decidua. Little is known about the mechanisms that regulate these processes. Here the effects of several insulin and insulin-like growth factor-I (IGF-I) doses, either singly or in synergy with serum, on human chorionic gonadotropin-beta (hCG-beta) secretion (RIA), proliferation (cell counting, cyclin B(1) levels) and invasion [Matrigel invasion assay, secretion of matrix metalloproteinases (MMP) 2 and 9] were investigated. The choriocarcinoma cell lines BeWo, JAR and JEG-3 served as models for first trimester human trophoblasts. Both growth factors altered hCG-beta secretion and proliferation dependent on the cell line. Insulin stimulated proliferation in JAR cells and, to a lesser extent, in JEG-3 cells, and when cultured in serum-free medium, BeWo was not affected. Invasion was not affected although proMMP-2 levels in culture medium were altered under some conditions. A strong synergistic effect with serum was noted. In the presence of serum both growth factors reduced proliferation and invasion in a similar fashion. Since the cell models differ by their degree of differentiation, the data demonstrate that the effects of insulin and IGF-I strongly depend on serum and the degree of differentiation. It can be speculated that IGF-I can take on tasks of insulin in the regulation of trophoblast functions under conditions of insulinopenia.

Application of capillary zone electrophoresis to study the properties of rhodanese from Acidithiobacillus ferrooxidans.

A new capillary zone electrophoretic method was applied to the assay of enzymic activity of rhodanese from Acidithiobacillus ferroxidans. The enzyme activity determined by capillary zone electrophoresis was compared with that determined by discontinuous spectrophotometry, the values obtained being in good agreement. The method was also used to evaluate Michaelis constants of cyanide and thiocyanate as substrates; a new approach was developed to solve the problem with variable ionic strength of the samples. The pH and temperature optima for the enzyme were also determined.

Sleep laboratory studies in periodic limb movement disorder (PLMD) patients as compared with normals and acute effects of ropinirole.

Periodic limb movement disorder (PLMD) occurs in a variety of sleep disorders and can cause insomnia as well as hypersomnia with daytime somnolence. The aim of this study was to investigate 12 untreated PLMD patients as compared with 12 normal controls and to measure the acute effects of 0.5 mg ropinirole (Requip((R))) - a non-ergoline dopamine agonist - as compared with placebo. In three nights (adaptation, placebo, ropinirole night) objective and subjective sleep and awakening quality were evaluated. In the target variable 'periodic leg movements per hour of sleep' (PLM/(hTST)) PLMD patients showed an increased value of 42/h (normal 0-5/h) with a greater number of arousals due to periodic leg movements (PLM) in sleep. They further demonstrated an increased number of awakenings, sleep stage S1, S4, stage shifts and decreased S2, but there were no significant differences concerning total sleep time, sleep efficiency (SE), subjective sleep quality and morning measures of mood, drive and drowsiness. However, measures of attention variability, numerical memory, fine motor activity and reaction time performance were impaired. Ropinirole 0.5 mg was shown to significantly improve the index PLM/(hTST) by 64% and arousals due to PLM, increase spontaneous arousals, REM-latency, stage 2 and stage shifts and decrease SREM. In the morning attention variability was attenuated and numerical memory augmented. Thus, ropinirole improved some sleep architecture and early morning measures of performance but specifically all PLM variables, which suggests a dopaminergic pathogenesis in PLMD. Copyright 2001 John Wiley & Sons, Ltd.

Theophylline in snoring and sleep-related breathing disorders: sleep laboratory investigations on subjective and objective sleep and awakening quality.

The aim of the present investigation was to comparatively examine the effect of theophylline on various sleep-related breathing disorders of different severity. In a single-blind, placebo-controlled crossover study, 30 patients were polysomnographically diagnosed as suffering from primary snoring (n = 7), obstructive snoring (n = 12) or moderate sleep apnea (n = 11). Subsequent polysomnographic investigations included one baseline, one placebo and one theophylline (Respicur retard 400 mg, Byk Gulden, Konstanz, Germany) night. Subjective sleep and awakening quality was evaluated by means of a test battery completed in the morning. Concerning respiratory variables, theophylline was most effective in patients with moderate sleep apnea. Obstructive snorers only showed a tendency towards improvement and primary snorers remained unchanged. Sleep architecture generally remained unchanged in all three patient groups. Objective awakening quality was partly improved in primary snorers, obstructive snorers, as well as in moderate sleep apnea patients as compared with baseline, but not as compared with placebo. Regarding subjective sleep and awakening quality, only primary snorers and obstructive snorers showed an improvement, as compared with baseline while moderate sleep apnea patients remained unchanged. Based on intergroup comparison, we conclude that patients with moderate sleep apnea showed the most pronounced improvement in regard to respiratory events. Concerning sleep initiation and maintenance, sleep architecture and subjective sleep and awakening quality, no significant intergroup differences were found. Regarding objective awakening quality, attention showed a significantly greater improvement in primary than in obstructive snorers and sleep apnea patients, while motor performance was most improved in obstructive snorers.

Sleep laboratory studies in restless legs syndrome patients as compared with normals and acute effects of ropinirole. 2. Findings on periodic leg movements, arousals and respiratory variables.

The restless legs syndrome (RLS) is a common sensorimotor disorder which leads to severe sleep disturbances and showed a prevalence of 7.9% in our sleep laboratory. The aim of this study was to investigate periodic leg movements (PLM), arousal and respiratory variables in 12 untreated RLS patients and to measure the acute effects of 0.5 mg ropinirole, a nonergoline dopamine agonist, as compared with placebo. In the target variable PLM/h of total sleep time (PLM/h TST), RLS patients showed an increased value of 40/h (normal 0-5/h). Further, we found an increased number of PLM (368), PLM/h of time in bed (49/h), PLM/h of REM sleep (11), PLM/h of non-REM sleep (46) and PLM/h awake (61). The arousal index was also increased (32/h; normal 0-25/h), as were arousals due to PLM. In the confirmatory part of our descriptive data analysis, ropinirole 0.5 mg significantly improved, as compared with placebo, the index PLM/h TST by 75%. In the descriptive part, all the other PLM variables were improved as well. Arousals due to PLM decreased, while spontaneous arousals increased. Respiratory variables, which had a priori been in the normal range, showed a slight but significant improvement after the dopamine agonist. Thus, 0.5 mg ropinirole significantly improved the target variable PLM/h TST, along with objective and subjective sleep quality and morning noopsychic performance, as described in the preceding paper. Our data encourage further sleep studies including all above-mentioned variables in a larger group of RLS/PLM during sleep patients as well as long-term efficacy trials.

[Daytime tiredness correlated with nocturnal respiratory and arousal variables in patients with sleep apnea: polysomnographic and EEG mapping studies]. / Tagesmüdigkeit korreliert mit nächtlichen Atmungs- und Arousal-Variablen bei Schlafapnoepatienten: Polysomnographische und EEG-Mapping-Untersuchungen.

There is evidence that daytime tiredness is caused by apnea/hypopnea with oxygen desaturation and/or by sleep fragmentation due to arousals. The aim of this study was to investigate objective and subjective sleep and awakening quality and daytime vigilance--objectified by midmorning mapping of vigilance-controlled EEG (V-EEG)--in sleep apnea patients (N: 18), as compared with age- and sex-matched normal controls (N: 18) as well as to correlate nocturnal respiratory distress and arousals to daytime brain function. Statistical analyses demonstrated a deterioration in subjective and objective sleep and awakening quality in apnea patients. Midmorning V-EEG mapping in apnea patients exhibited less total power, more delta and theta, less alpha and beta activity, as well as a slower dominant frequency and centroid of the total activity compared to controls, which suggests a vigilance decrement. The Spearman rank correlation between 6 polysomnographically registered respiratory variables and 36 diurnal quantitative EEG measures demonstrated the following: the higher the apnea, apnea-hypopnea, snoring and desaturation indices and the lower the minimum and average low oxygen saturation, the more pronounced was diurnal tiredness. Eleven arousal measures based on ASDA criteria showed the following significant correlations: the higher the nocturnal arousal index and the more arousals due to hypopneas, the greater was daytime tiredness. On the other hand, the greater the average frequency change during arousals and the more spontaneous arousals, the better was daytime vigilance. Our findings show that, in contrast to the lengthy Multiple Sleep Latency (MSLT) and Maintenance of Wakefulness (MWT) tests which evaluate sleep pressure under resting conditions conducive to sleep, V-EEG mapping provides a brief objective measure of a sleep apnea patient's daytime tiredness under conditions of wakefulness more appropriate to reflect the patient's everyday life.

Placebo-controlled sleep laboratory studies on the acute effects of zolpidem on objective and subjective sleep and awakening quality in nonorganic insomnia related to neurotic and stress-related disorder.

UNLABELLED: Recent investigations in our sleep outpatient clinic demonstrated that 30% of patients exhibited organic and 70% nonorganic sleep disorders, with 41% showing as an additional diagnosis neurotic, stress-related, and somatoform disorders, 31% affective disorders and 15% mental and behavioral disorders due to psychoactive substance use. Thus, the aim of the study was to investigate the acute effects of the imidazopyridine zolpidem on objective and subjective sleep and awakening quality in the largest of the above-mentioned groups. In this single-blind, placebo-controlled cross-over study, 15 patients (9 females and 6 males aged 51.1 + 11. 3 years) diagnosed as having nonorganic insomnia (ICD-10: F 51.0) related to neurotic and stress-related disorders (F 1.1:12, F 41.2:2 and F 43.2:1) were included. Objective and subjective sleep and awakening quality measures were investigated in 3 subsequent nights in the sleep laboratory (adaptation, baseline/placebo and zolpidem 10 mg night), utilizing clinical, polysomnographic, psychometric and psychophysiological methods. The drug-free patients were matched according to age and sex with 15 normal healthy controls (age 51.2 + 11.8 years). Statistical analysis of polysomnographic variables demonstrated a significant lengthening of the total sleep period (TSP) and total sleep time (TST), an improvement in sleep efficiency and a shortening of sleep latencies after zolpidem as compared with placebo. These changes were opposite to the differences between patients and controls. Concerning sleep architecture, zolpidem increased the length of S4 and S3 + S4 as compared with placebo. Subjective sleep and awakening quality and the thymopsychic variables drive, mood, affectivity and wakefulness in the morning showed no significant changes, as a significant improvement had already occurred from the adaptation to the baseline/placebo night. Noopsychic variables (attention, concentration, attention variability, numerical memory, fine motor activity, reaction time measures) showed similar findings. Moreover, subjective sleep and awakening quality, thymopsychic and noopsychic measures during baseline/placebo recordings did not differ significantly from normative data (except for fine motor activity). Psychophysiological measures did not show any significant alterations either, except for a decrease in systolic blood pressure in the evening. CONCLUSION: As compared with placebo, zolpidem induced a significant improvement in objective sleep quality, mainly by increasing TSP, TST and sleep efficiency and shortening sleep latencies, thereby normalizing the disorder of initiating and maintaining sleep. Deep sleep stages S3 + S4 increased (although at baseline/placebo these stages did not differ from controls), while S1, S2 and SREM did not change significantly. Subjective sleep and awakening quality as well as thymopsychic and noopsychic performance in the morning mainly showed a placebo and 'first- night effect' phenomenon in these patients. Thus, the changes induced by zolpidem were somewhat different from those after classical benzodiazepines.

Determination of rhodanese enzyme activity by capillary zone electrophoresis.

A new sensitive method has been developed for the determination of rhodanese activity. The enzymatic reactions were carried out directly in thermostatted autosampler vials and the formation of SCN- was monitored by sequential capillary zone electrophoretic runs. The determinations were performed in a 75-micron fused-silica capillary using 0.1 M beta-alanine-HCl (pH 3.50) as a background electrolyte, a separation voltage of 18 kV (negative polarity), a capillary temperature of 25 degrees C and direct detection at 200 nm. Short-end injection or long-end injection procedures were used for sample application. The method is rapid, able to be automated and requires only small amounts of sample and substrates, which is especially important in the case of highly toxic cyanide. The developed capillary electrophoretic method also has great potential for thiocyanate determinations in other applications.

Efficiency of continuous positive airway pressure versus theophylline therapy in sleep apnea: comparative sleep laboratory studies on objective and subjective sleep and awakening quality.

Sleep apnea is the most common sleep-related breathing disorder characterized by repetitive episodes of hypoxemia. Therapies include behavioral, surgical, orthodontic, pneumological, and pharmacological interventions. The aim of the present study was to compare the efficiency of pneumological therapy by nasal continuous positive airway pressure (CPAP) versus a pharmacological approach with theophylline (Respicur retard(R) 400 mg) on respiratory variables as well as objective and subjective sleep and awakening quality in patients with moderate sleep apnea measured by polysomnography and psychometry. Under CPAP therapy all respiratory variables improved and normalized, while under theophylline only the apnea-hypopnea index and the desaturation index improved but still did not return to normal values. Regarding sleep initiation and maintenance, CPAP therapy prolonged sleep latency and reduced movement time, while patients treated with theophylline showed reduced total sleep period, total sleep time and sleep efficiency. Sleep architecture demonstrated an increase in deep sleep and REM stages under CPAP therapy, and remained unchanged under theophylline. Concerning subjective sleep and awakening quality, both treatments improved well-being in the morning. Regarding objective awakening quality, reaction time performance was improved in both groups. In conclusion, CPAP treatment is more effective than theophylline regarding respiratory variables as well as the normalization of sleep maintenance and sleep architecture in sleep apnea patients.

A comparison of triamcinolone acetonide nasal aerosol spray and fluticasone propionate aqueous solution spray in the treatment of spring allergic rhinitis.

BACKGROUND: Many nasal corticosteroids with different potencies and formulations are available, but they have all been proven safe and effective. The clinical relevance, if any, of these differences is not yet completely established. OBJECTIVE: We sought to compare the efficacy, safety, and patients' acceptance of triamcinolone acetonide aerosol spray and fluticasone propionate aqueous solution in the treatment of spring allergic rhinitis. METHODS: After a drug-free baseline evaluation, patients with rhinitis were randomized to receive either a triamcinolone aerosol spray of 110 microg in each nostril once daily (n = 117) or a fluticasone solution spray of 100 microg in each nostril once daily (n = 116) in a single-blind, parallel-group study. The Rhinitis Index Score (sum of scores of symptoms on a scale from 0 to 3) was evaluated daily, in the morning before drug administration, for 21 days. The efficacy of each treatment was assessed by the mean reduction from baseline in the Rhinitis Index Score and in individual symptom scores. Patients' acceptance of the study drugs was also monitored by a daily questionnaire. RESULTS: Reductions of the Rhinitis Index Score (mean +/- SEM) were 4.20 +/- 0.21 and 4.60 +/- 0.21 for triamcinolone and fluticasone, respectively (p = 0.23). There were no statistically significant differences between the drugs in the reduction of any of the individual symptoms. Patients expressed statistically significant differences between the drugs regarding acceptance; different properties of the aerosol and the solution were appreciated differently. CONCLUSIONS: This study shows that triamcinolone acetonide aerosol and fluticasone propionate solution sprays are both clinically equally effective, safe, and well tolerated for the treatment of spring pollen allergic rhinitis.

Comparison of once daily mometasone furoate (Nasonex) and fluticasone propionate aqueous nasal sprays for the treatment of perennial rhinitis. 194-079 Study Group.

BACKGROUND: Mometasone furoate (Nasonex), in a new once-daily aqueous nasal spray formulation, has been shown to be as effective and well-tolerated as twice-daily beclomethasone dipropionate aqueous nasal spray in treating symptoms of seasonal allergic rhinitis and perennial rhinitis. OBJECTIVE: To compare the effectiveness and tolerability of mometasone furoate to placebo and of fluticasone propionate aqueous nasal spray, all treatments administered once-daily, in patients with perennial rhinitis. METHODS: This was a 3-month, randomized, double-blind, double dummy, parallel group study in 550 patients, aged 12 to 77 years, at 25 centers in Canada, Latin America, and Europe. Patients allergic to at least one perennial allergen, with confirmed allergy history, skin test positivity, and moderate to severe symptomatology, were eligible to receive one of the following treatments, once daily in the morning: mometasone furoate 200 micrograms, fluticasone propionate 200 micrograms, or placebo. The primary efficacy variable was the change from baseline in total AM plus PM diary nasal symptom score over the first 15 days of treatment. RESULTS: Four hundred fifty-nine patients were valid for efficacy. For the primary efficacy variable, mometasone furoate was significantly (P < .01) more effective than placebo and was not statistically different from fluticasone propionate (percent reductions from baseline were 37, 39, and 22 for mometasone furoate, fluticasone propionate, and placebo, respectively). Generally, similar trends were seen for physician-evaluated total nasal symptoms, and patient-rated and physician-rated overall condition and response to therapy. Overall, mometasone furoate was at least as effective as fluticasone propionate at equivalent doses. There was no evidence of tachyphylaxis. All treatments were well tolerated. CONCLUSION: Mometasone furoate and fluticasone propionate adequately controlled symptoms of perennial rhinitis and were well tolerated.