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PURPOSE: Myrrh, the oleo-gum resin of Commiphora molmol, is well known for its anti-inflammatory properties. In different animal models, it protected against DSS-, TNBS- and oxazolone-induced colitis. To date, no information concerning the effect of myrrh on barrier properties are available. Thus, this study investigates the effect of myrrh on paracellular barrier function in the absence or presence of the pro-inflammatory cytokine TNFα. METHODS: Monolayers of human colon cell lines HT-29/B6 and Caco-2 were incubated with myrrh under control conditions or after challenge with the pro-inflammatory cytokine TNFα. Barrier function was analysed by electrophysiological and permeability measurements, Western blotting, immunostaining in combination with confocal microscopy, and freeze-fracture electron microscopy. RESULTS: In Caco-2 cells, myrrh induced an increase in transepithelial resistance (TER) which was associated with downregulation of the channel-forming tight junction (TJ) protein claudin-2 via inhibition of the PI3 kinase signalling pathway. In HT-29/B6 cells, myrrh had no effect on barrier properties under basic conditions, but protected against barrier damage induced by TNFα, as indicated by a decrease in TER and an increase in fluorescein permeability. The TNFα effect was associated with a redistribution of the sealing TJ protein claudin-1, an increase in the expression of claudin-2 and a change in TJ ultrastructure. Most importantly, all TNFα effects were inhibited by myrrh. The effect of myrrh on claudin-2 expression in this cell line was mediated via inhibition of the STAT6 pathway. CONCLUSIONS: This study shows for the first time that myrrh exerts barrier-stabilising and TNFα-antagonising effects in human intestinal epithelial cell models via inhibition of PI3K and STAT6 signalling. This suggests therapeutic application of myrrh in intestinal diseases associated with barrier defects and inflammation.
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Enterocitos/citología , Sustancias Protectoras/farmacología , Resinas de Plantas/farmacología , Células CACO-2 , Manzanilla/química , Carbón Orgánico/farmacología , Café/química , Commiphora , Enterocitos/efectos de los fármacos , Enterocitos/metabolismo , Células HT29 , Humanos , Modelos Biológicos , Transporte de Proteínas/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Proteínas de Uniones Estrechas/metabolismo , Uniones Estrechas/efectos de los fármacos , Uniones Estrechas/metabolismo , Uniones Estrechas/ultraestructura , Factor de Necrosis Tumoral alfa/farmacologíaRESUMEN
AIMS: To verify the efficacy, safety and tolerability of intravesical administration of 0.1% oxybutynin hydrochloride compared to its oral administration for treatment of neurogenic detrusor overactivity (NDO) in a randomized, prospective, controlled, open-label, multi-center trial in 35 adult patients. METHODS: NDO was confirmed within the previous 24 months by urodynamic studies (UDS). Group 1 (n = 18) received 10 ml 0.1% oxybutynin hydrochloride intravesically three times per day and group 2 (n = 17) 5 mg oxybutynin hydrochloride orally three times per day for a period of 28 days. Primary efficacy criterion was the change in the maximum bladder capacity between the beginning of the study and after 4 weeks as assessed by UDS. Adverse drug reactions (ADR) were collected and an evaluation of anticholinergic effects was conducted. RESULTS: The increase in maximum bladder capacity was 117 ml with intravesical application (P = 0.0002) versus 18 ml with the oral application (P = 0.51). The difference was statistically significant (P = 0.0086). ADR were reported by 10 (55.6%) of patients with intravesical administration, and by 14 (82.4%) of patients with oral administration. Significant differences in favor of the intravesical application were observed in ADR affecting vision (1/10 vs. 9/14), gastrointestinal tract (8/10 vs. 14/14), nervous system (2/10 vs. 8/14), and skin and subcutis (1/10 vs. 6/14). No serious adverse drug reactions were reported. CONCLUSIONS: This study demonstrates the efficacy and safety of intravesical 0.1% oxybutynin hydrochloride in the treatment of NDO with respect to the increase in maximum bladder capacity. Neurourol. Urodynam. 35:582-588, 2016. © 2015 Wiley Periodicals, Inc.
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Ácidos Mandélicos/administración & dosificación , Vejiga Urinaria Hiperactiva/tratamiento farmacológico , Agentes Urológicos/administración & dosificación , Administración Intravesical , Administración Oral , Adulto , Femenino , Humanos , Masculino , Estudios Prospectivos , Soluciones , Resultado del Tratamiento , Vejiga Urinaria Neurogénica/tratamiento farmacológicoRESUMEN
PURPOSE: We investigated the pharmacokinetics of intravesical oxybutynin and discuss the clinical implications of the results. MATERIALS AND METHODS: We performed an open label, randomized, 3-period crossover clinical study in 20 healthy adults. In periods 1 and 2 subjects received a single dose of 10 mg oxybutynin HCl solution intravesically or a 5 mg tablet orally. Period 3 comprised repeat intravesical applications (7 doses) of 10 mg oxybutynin HCl. Enantioselective concentrations of oxybutynin and N-desethyloxybutynin were quantified by liquid chromatography-mass spectrometry. Pharmacokinetic parameters were calculated by noncompartmental methods, analyzed by descriptive statistics and compared using the average bioequivalence approach. RESULTS: Systemic exposure to racemic oxybutynin after intravesical administration was significantly greater, yielding 294% (90% CI 211-408) of that after oral intake of immediate release preparations, as measured by the dose normalized area under the plasma concentration time curve. In contrast, systemic exposure to racemic N-desethyloxybutynin reached only 21% (90% CI 15-29). The area under the plasma concentration time curve ratio of N-desethyloxybutynin to oxybutynin was 14-fold decreased for intravesical administration. After intravesical multidose administration, the cumulation of oxybutynin (1.3-fold) and N-desethyloxybutynin (1.6-fold) was weak, absorption was prolonged and apparent elimination half-lives were longer. The study medication was well tolerated with a third of participants reporting anticholinergic adverse effects. CONCLUSIONS: Our study provides evidence of significantly higher bioavailability of intravesical vs oral administration of oxybutynin due to circumvention of the intestinal first pass metabolism. Given the high efficacy and decreased rate of adverse effects, intravesical oxybutynin should be considered in patients with neurogenic lower urinary tract dysfunction who do not tolerate oral administration or in whom oral preparations fail to improve detrusor overactivity.
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Ácidos Mandélicos/administración & dosificación , Ácidos Mandélicos/farmacocinética , Agentes Urológicos/administración & dosificación , Agentes Urológicos/farmacocinética , Administración Intravesical , Administración Oral , Adolescente , Adulto , Estudios Cruzados , Humanos , Ácidos Mandélicos/efectos adversos , Persona de Mediana Edad , Estudios Prospectivos , Agentes Urológicos/efectos adversos , Adulto JovenRESUMEN
BACKGROUND: Tropaeolum majus herb (nasturtium) and Armoracia rusticana root (horseradish) produce three different isothiocyanates as secondary metabolites, which exert antibacterial, anti-inflammatory, and immune-modulatory functions in humans. PURPOSE: Combined in the medicinal product ANGOCIN® Anti-Infekt N, the two natural components demonstrated promising effects against acute bronchitis. STUDY DESIGN: A randomized, two-armed, placebo-controlled, double-blind, phase IV study revealed the healing fostering effect of the two herbal plant components METHODS: This study included 384 patients, with 195 in the treatment and 189 in the placebo group. The 'bronchitis severity score' (BSS) was utilized as primary endpoint. This score sums the ratings for five significant bronchitis symptoms, which are established at the patient's visits to the clinic. RESULTS: Compared to placebo intake, the group of patients treated with the phytomedicine showed statistically significant accelerated healing of bronchitis symptoms after three days of treatment, with reductions in coughing, mucous production, and chest pain. This beneficial effect persisted for the entire duration of treatment until day ten. CONCLUSION: In conclusion, a combination of Tropaeolum majus herb and Armoracia rusticana root promotes an elevated improvement of bronchitis symptomatology.
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Bronquitis , Tropaeolum , Humanos , Armoracia , Bronquitis/tratamiento farmacológico , Bronquitis/inducido químicamente , Extractos Vegetales/efectos adversos , Fitoterapia , Enfermedad AgudaRESUMEN
Oxybutynin is a racemic anticholinergic drug used for the symptomatic treatment of detrusor overactivity. The formation of active metabolites related to tolerability problems depends on the route of administration. The objective of this evaluation was to develop a pharmacokinetic model for oral/intravesical administration as the basis for simulations with different dosages. Data from a published changeover clinical study with 18 healthy adults receiving a single oral dose of 5 mg immediate-release oxybutynin and single and multiple intravesical doses of 10 mg oxybutynin solution was evaluated. Enantioselective plasma concentrations of oxybutynin and N-desethyloxybutynin (NDO) were used to establish a population pharmacokinetic model using nonlinear mixed-effects modeling with NONMEM 7.4.1. For both enantiomers, the data were described well by a 2-compartment model for oxybutynin with an additional compartment for NDO. Oxybutynin absorption was modeled by transit compartments for oral and first-order absorption for intravesical application. Bioavailability of the more active (R)-enantiomer was 7% for oral and 10%-22% for intravesical administration. In simulations, intravesical doses of 5 to 15 mg (R)-oxybutynin administered 2 to 3 times daily decreased peak-trough fluctuations of NDO to 8% compared with 24% after oral administration. The NDO/oxybutynin ratio was reduced from 17 after oral administration to unity. Chronic intravesical versus oral administration of (R)-oxybutynin generates distinctly lower and less variable concentrations of (R)-NDO. Pharmacokinetic simulations suggest that exposure for 12.5 mg (R)-oxybutynin administered twice daily might not compromise efficacy and tolerability compared with exposure for standard thrice-daily administrations. This assumption needs to be assessed in clinical studies.
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Antagonistas Colinérgicos/química , Antagonistas Colinérgicos/farmacocinética , Ácidos Mandélicos/química , Ácidos Mandélicos/farmacocinética , Administración Intravesical , Administración Oral , Área Bajo la Curva , Antagonistas Colinérgicos/administración & dosificación , Relación Dosis-Respuesta a Droga , Voluntarios Sanos , Humanos , Ácidos Mandélicos/administración & dosificación , Ácidos Mandélicos/metabolismo , Tasa de Depuración Metabólica , Modelos BiológicosRESUMEN
2-Alkenylchroman-4-ones, 2-alkenylthiochroman-4-ones, and 2-alkenylquinol-4-ones were prepared with very good regioselectivity by Me3SiOTf-mediated conjugate addition of alkenylmagnesium bromides and alkenyllithium compounds to chromones thiochromones, and quinol-4-ones. A number of products exhibit a considerable antimicrobial activity. The best activity, with respect to the spectrum of antimicrobial activity, was observed for 2-vinylchroman-4-ones containing an unsubstituted vinyl group and a chloride group located at the chromanone moiety.
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Antibacterianos/síntesis química , Antibacterianos/farmacología , Cromonas/síntesis química , Cromonas/farmacología , Antibacterianos/química , Bacillus subtilis/efectos de los fármacos , Cromonas/química , Escherichia coli/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Staphylococcus aureus/efectos de los fármacos , Levaduras/efectos de los fármacosRESUMEN
BACKGROUND: The rate of infections occurring during hospitalization is increasing. Urinary tract infections (UTIs) comprise the majority of cases (40%), many of which are catheter-associated. Antibiotic resistance due to antibiotic misuse and overuse exacerbates this situation. Alternative therapies are consequently becoming more important in daily clinical practice. One of the few approved alternatives for the treatment of UTIs is Angocin®, a herbal medicinal product containing nasturtium and horseradish powder. OBJECTIVES: Evaluate the efficacy and safety of Angocin® in adult patients with catheter-associated UTIs. MATERIALS AND METHODS: Ninety-six inpatients with catheter-associated UTI successfully completed a 3-arm, 5-week observational study. Three patient groups were assessed: 1) monotherapy with Angocin® (Repha GmbH, Langenhagen, Germany) (42%), 2) Angocin® as an add-on to antibiotic therapy (29%), and 3) antibiotic therapy alone (29%). Outcome measures included: pathogen number and resistance spectrum in the urine, inflammation markers in the blood, antibiotic use, adverse events (AE), adverse drug reaction (ADR), efficacy, and tolerability. RESULTS: One-hundred percent of initial UTIs were healed with add-on therapy and pure antibiotic therapy after an average of 10.5 and 9 days, respectively. The Angocin® monotherapy led to a successful treatment rate of 46% after an average of 28 days. Dosages of Angocin® with 3â¯× 4 or 3â¯× 3 tablets per day were markedly below the recommended upper dosage level. The recurrence rate of UTI was markedly reduced with Angocin® mono- and add-on therapies (both 50%) in contrast to pure antibiotic therapy (79.3%). The incidence of AEs and ADRs in the Angocin® monotherapy group (23.8%) was also lower than that reported in the add-on therapy group (44.8%) and pure antibiotic group (34.5%). CONCLUSION: Mono- and add-on therapies using the herbal medicinal product Angocin® substantially reduced the recurrence of catheter-associated UTIs in comparison to antibiotic therapy alone. This results in a potential prophylactic efficacy by Angocin® which may represent a promising alternative for the treatment and prevention of recurrent catheter-associated UTIs, reducing antibiotic use. Further clinical trials are warranted to confirm these findings.
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Nasturtium , Infecciones Urinarias , Armoracia , Alemania , Humanos , FitoterapiaRESUMEN
OBJECTIVES: To demonstrate non-inferiority of an herbal combination (horseradish root and nasturtium herb) to an antibiotic (co-trimoxazole) in acute uncomplicated cystitis. DESIGN: Randomized, prospective, double-blind, double-dummy, multicenter, phase III clinical study, using block randomization of 4 blocks (size 2). SETTING: Twenty-six centers in Germany, from May 2011 to June 2013. PARTICIPANTS: Adult patients (median age, 38.5 years; 90% female) with acute uncomplicated cystitis confirmed via urinalysis and bacterial counts. INTERVENTIONS: Patients received the herbal combination (five tablets, four times per day) or the antibiotic (two tablets daily) for a period of 7 or 3 days, respectively, followed by a 21-days without drug treatment. Placebos ensured blinding. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary endpoint was the percentage of responders, expressed as reduction of germ count from >105 to <103 CFU/mL of pathogens between visit 1 (day 0) and 3 (day 15). Secondary endpoints included change of symptom scores, duration of symptoms, efficacy assessments, relapse frequency, and safety. A sample size of 178 patients per group was estimated. RESULTS: Of the 96 randomized patients (intent-to-treat; 45 in the phytotherapy group, 51 in the antibiotic group), 51 were considered per-protocol patients (22 in the phytotherapy group, 29 in the antibiotic group). Responder rates were 10/22 (45.5%) for the phytotherapy group and 15/29 (51.1%) for the antibiotic group (group difference: -6.27% [95% CI: -33.90%-21.3%]). The study was terminated prematurely due to slow recruitment rates. Non-inferiority could not be assumed by predefined criteria. During the follow-up period, one relapse occurred in each group. Both treatments were well tolerated. CONCLUSION: This clinical trial indicates comparable efficacy of the herbal combination and antibiotic, although non-inferiority was not proved. However, the results and lessons learned are important for the planning of future trials. Issues that led to the premature trial discontinuation were considered.
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BACKGROUND: Centuries ago cupping was one of the most used medical therapies worldwide but it is now regarded as an antiquated and unsafe treatment. Nevertheless it is widely used especially in Germany and China. OBJECTIVE: To investigate the effectiveness of "wet cupping" of a defined connective tissue area (over the Musculus trapezius) in patients suffering from brachialgia paresthetica nocturna. DESIGN: Monocenter, randomised, controlled, sequential clinical trial. SETTING: Section of pain management at the District Hospital of Rüdersdorf, Germany. PATIENTS: Brachialgia-patients of both sexes without age restictions were eligible if they suffered from chronical tonsillar irritations and showed pathologic indurations of the connective tissue area. INTERVENTIONS: The active group was "wet cupped" once, i.e. the skin first was scarified and then blood was drawn by applying vacuum cupping glasses. The control group was left untreated. MAIN OUTCOME MEASURE: Pre- to post-treatment change of brachialgia severeness, calculated from 1-week averages of the means of three subscales (pain, tingling and numbness), each assessed on a 0-10 numeric analogue scale. RESULTS: N=20 patients were randomised (13 women, median age 47 years). Treatment effects can be found in the active (-2.3+/-1.9 score points) but not in the control group (+0.5+/-1.0 points; p=0.002; triangle test). The results are supported by secondary outcome criteria. Adverse events were not documented in any patient. CONCLUSIONS: This study suggests short-term effects of a single wet cupping therapy, which remain at least for 1 week. As the trial lacks of an adequate and blinded placebo therapy the findings are potentially biased.
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Neuropatías del Plexo Braquial/terapia , Terapias Complementarias/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proyectos PilotoRESUMEN
OBJECTIVE: This prospective observational postmarketing multicentre study was performed to collect data on the clinical efficacy, safety and tolerability of a licensed herbal combination of myrrh, coffee charcoal and chamomile extracts in patients with symptoms of acute diarrhoea. MATERIAL AND METHODS: Patients aged 12â years and above with symptoms of acute diarrhoea due to acute inflammatory disorders (AID) of the gastrointestinal tract, inflammatory bowel diseases (IBD) or irritable bowel syndrome (IBS) were treated with the herbal preparation either as monotherapy, add-on therapy or with other therapies. The primary outcome parameter was the pre-post change of total mean symptom score. Secondary outcome parameters were changes of score of single symptoms, physician's assessment of the clinical course and efficacy, and patient's satisfaction. RESULTS: 1062 patients (mean age 43.2±17.8â years, range 12-89, 42.3% men) were included. A decrease of the overall mean total symptom score was observed in all treatment groups (monotreatment: 1.33±0.51 to 0.15±0.34, add-on treatment: 1.39±0.41 to 0.30±0.37, other therapy: 1.31±0.43 to 0.24±0.33). No significant differences between three treatment options were observed within AID and IBD groups. However, in the IBS group, monotreatment with the herbal preparation resulted in a significantly better outcome when compared to either add-on treatment (mean difference 0.140; 95% CI 0.036 to 0.245; p=0.009) or other therapy (mean difference 0.217; 95% CI 0.085 to 0.349; p=0.001). Secondary efficacy criteria showed comparable results between different treatment options in the respective disorder groups. Patient satisfaction was generally higher with monotreatment in the AID and IBS groups, while add-on treatment was preferred in the IBD group. CONCLUSIONS: The combination of myrrh, coffee charcoal and chamomile flower extract is effective, well tolerated and safe for use in patients with symptoms of acute diarrhoea. The effects are comparable to conventional therapies used in routine care.
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OBJECTIVE: The aim of this ICH-GCP study was to investigate the efficacy and safety of a prophylactic administration of a combination herbal medicinal product (CHMP) in two dosages compared to placebo with respect to the incidence of new occurring infections of the respiratory tract (RTI). Clinical experience of prophylactic treatment of respiratory tract infections with the marketed CHMP containing horseradish root (Armoraciae rusticanae radix) and nasturtium (Tropaeoli majoris herba) has existed for decades. METHODS: The study was performed as a phase III, multicentre, randomised, double-blind, double-dummy, placebo-controlled, parallel-group trial. All groups received two film coated tablets three times a day. Group 1 received the CHMP tablets 3 × 2 per day, group 2 the CHMP tablets 2 × 2 and placebo tablets 2 × 1 per day and group 3 received placebo tablets 3 × 2 per day. Maximum duration of treatment was 84 days. The primary efficacy criterion was the comparison of the incidences of new occurring RTIs between the treatment groups during the prophylactic treatment. In addition the character of occurring infections, number of sick days and severity of infections were compared. Further criteria were subjects' well being, the satisfaction of subjects with the respective treatments and severity and incidence of the observed adverse events (AE) and serious adverse events (SAE) during the study period. TRIAL REGISTRATION: EudraCT No. 2010-023227-26. RESULTS: From 371 subjects screened, a total of 351 subjects of both sexes from 18 to 75 years were randomly allocated to one of the three groups. In order to achieve scientifically and medically impeccable results it was necessary to address acute infections of the respiratory tract occurring during the normal incubation period. Early infections (≤day 7) were excluded from the data set in a sensitivity analysis. In the intention to treat (ITT) population excluding early infections ≤day 7 (n = 344) the infection rates were 13.3% for CHMP 3 × 2 (n = 113), 18.4% for CHMP 2 × 2 (n = 114) and 25.6% for placebo (n = 117). The statistical trend test showed significant results (p = 0.0171). For the per protocol (PP) population - also excluding infections ≤day 7 (n = 334) - infection rates were: CHMP 3 × 2 (n = 110) 12.7%, CHMP 2 × 2 (n = 113) 18.6% and placebo (n = 111) 24.3% (p = 0.0266). Secondary parameters of infections (infection diagnosis, intensity, duration) showed no relevant differences between the treatment groups. The study medication was well tolerated. LIMITATIONS: This was the first clinical ICH-GCP study with the CHMP conducted in this indication and with a sufficient number of subjects. The study population comprised subjects from 18 to 75 years and covered different diagnoses of RTIs. The results show a benefit when using 3 × 2 film tablets of CHMP for prophylaxis of RTIs. However, no data are available on use of the CHMP in this indication in children, adolescents and the elderly (over 75 years). CONCLUSION: This trial demonstrates the efficacy and safety of the combination herbal medicinal product as the treatment of first choice in the prophylactic treatment of episodes of respiratory tract infections. Clinical experience was confirmed in an ICH-GCP study.
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Brassicaceae , Medicina de Hierbas , Infecciones del Sistema Respiratorio/tratamiento farmacológico , Adulto , Método Doble Ciego , Femenino , Humanos , Masculino , Placebos , Estudios ProspectivosRESUMEN
To infect host cells, most enveloped viruses must insert a hydrophobic fusion peptide into the host cell membrane. Thus, fusion peptides may be valuable targets for developing drugs that block virus entry. We have shown previously that a natural 20-residue fragment of α(1)-antitrypsin, designated VIRus-Inhibitory Peptide (VIRIP), that binds to the gp41 fusion peptide of HIV-1 prevents the virus from entering target cells in vitro. Here, we examine the efficacy of 10-day monotherapy with the optimized VIR-576 derivative of VIRIP in treatment-naïve, HIV-1-infected individuals with viral RNA loads of ≥10,000 copies per ml. We report that at the highest dose (5.0 grams per day), intravenous infusion of VIR-576 reduced the mean plasma viral load by 1.23 log(10) copies per ml without causing severe adverse effects. Our results are proof of concept that fusion peptide inhibitors suppress viral replication in human patients, and offer prospects for the development of a new class of drugs that prevent virus particles from anchoring to and infecting host cells.
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Fármacos Anti-VIH/uso terapéutico , Proteína gp41 de Envoltorio del VIH/antagonistas & inhibidores , Infecciones por VIH/tratamiento farmacológico , Internalización del Virus/efectos de los fármacos , Fármacos Anti-VIH/efectos adversos , Fármacos Anti-VIH/química , Línea Celular Tumoral , Proteína gp41 de Envoltorio del VIH/genética , Humanos , Fragmentos de Péptidos/efectos adversos , Fragmentos de Péptidos/química , Fragmentos de Péptidos/uso terapéutico , alfa 1-Antitripsina/efectos adversos , alfa 1-Antitripsina/química , alfa 1-Antitripsina/uso terapéuticoRESUMEN
PATIENTS AND METHODS: In this study which was carried out in the period between 1st May until 4th October 2006 in 65 study sites as a prospective cohort study in 858 children, adolescents and juveniles in the age between 4 and 18 years who consulted the physician due to an acute sinusitis, acute bronchitis or acute urinary tract infection (UTI). Data of in total 858 patients were recorded. The patients were treated either with the herbal drug preparation Angocin Anti-Infekt N (test group, n = 523, 61%) or with a standard antibiotic (control group, n = 335, 39%) according to the decision of the physician. The duration of treatment as well as the dosage was determined by the physician. 297 patients suffering from acute sinusitis (197 test group 66%, 100 control patients 34%), 290 patients suffering from acute bronchitis (178 test group 61%, 112 control patients 39%) and 271 patients with acute urinary tract infection (148 test group 55%, 123 control patients 45 %) were included. The patients recorded in a diary the utilization of the medication, concomitant procedures and adverse events (AEs). The physician recorded at study start and at the end of the study the compliance in a standardised form. Single symptoms were recorded according to their intensity with a score ranging from 0 = no symptom to 3 = severe symptoms. At the end of the study (disease free or after 7-14 days) the physicians finally judged on the course of the treatment as well on the efficacy as observed. The patients recorded their satisfaction with the treatment. Primary efficacy criterion was the change of the complaints quantified by the change of the relative symptom score average over all symptoms between result at study start and study end related to the baseline value. RESULTS: The two therapy groups differ in their basis data with regard to the mean age (test group 12.2 years, control group 13.5 years; p > 0.001) and the frequency of concomitant diseases (test group 6.3%, control group 2.4%; p = 0.008). At start of treatment the complaints in the test group were significantly less severe (mean of the complaint score 1.67) compared to the control group (mean 2.00; p > 0.001). At the end of treatment there were no significant differences in the mean complaint score between the groups (test group 0.41, control group 0.49; p = 0.722). The mean reduction of the complaint score expressed in percentages was for the indication acute sinusitis in the test group 84.8% and in the control group 85.5%, for the indication acute bronchitis in the test group 82.1% and in the control group 77.7% and for the indication acute urinary tract infection in the test group 89.9% and in the control group 93.1%. In total the mean reduction of the complaint score for the test group was 85.3% and in the test group 85.7% (p = 0.828). The 95% confidence interval for difference of the expected reductions between test group and control group ranged from -3.87% up to 3.10%. With a border of +/- 10% the mean reduction for both groups is equivalent, and more importantly non-inferior for the test group compared with the control group. Adverse events were recorded for 3 patients (0.6%) of the test group and for 14 patients (3.9%) of the control group (p = 0.001). In conclusion it was demonstrated that therapy with the herbal drug preparation in the indications acute sinusitis, acute bronchitis and acute urinary tract infection is--with regard to efficacy--comparable to a treatment with standard antibiotics. The test preparation displayed in all indications a significantly lower potential for adverse events compared to a treatment with standard antibiotics and, therefore, a better safety profile could be concluded.
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Antibacterianos/uso terapéutico , Bronquitis/tratamiento farmacológico , Extractos Vegetales/efectos adversos , Extractos Vegetales/uso terapéutico , Sinusitis/tratamiento farmacológico , Infecciones Urinarias/tratamiento farmacológico , Enfermedad Aguda , Adolescente , Niño , Preescolar , Estudios de Cohortes , Femenino , Humanos , Masculino , Satisfacción del Paciente , Estudios ProspectivosRESUMEN
OBJECTIVES: The aim of this study was to verify the efficacy and safety of a herbal medicinal product containing Tropaeoli majoris herba and Armoraciae rusticanae radix in the prophylactic treatment of chronically recurrent urinary tract infections (UTIs), and to test whether the medicinal product decreases the incidence of relapses over the study period. METHODS: A total of 219 adults aged between 18 and 75 years were screened and 174 patients enrolled. Of these 174 patients, a group of 45 patients were screening failures. Patients were randomised to receive either the study drug or placebo twice daily for 90 days. A UTI is confirmed by defined symptoms together with a laboratory result. The diagnosis of a new episode of a recurrent UTI included urine analysis from a central laboratory. The primary efficacy criterion - the number of recurrent UTIs over the study period - was tested between the treatment groups. RESULTS: For the per-protocol population, the mean number of recurrent UTIs in the study period was 0.43 versus 0.77 for the placebo group. This result is statistically significant (p = 0.035). A total of 36 patients in the test group and 37 patients in the placebo group reported adverse events. Two serious adverse events were reported in the placebo group and one serious adverse event in the treatment group (not associated with the study medication). CONCLUSION: This randomised, double-blind, placebo-controlled trial demonstrates the efficacy and safety of the herbal medicinal product Angocin Anti-Infekt N* in the prophylactic treatment of chronically recurrent UTIs.
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Armoracia/química , Medicina de Hierbas , Nasturtium/química , Infecciones Urinarias/prevención & control , Adolescente , Adulto , Anciano , Enfermedad Crónica , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Satisfacción del Paciente , Placebos , Recurrencia , Resultado del TratamientoRESUMEN
PATIENTS AND METHODS: In a prospective cohort study from 251 centers in Germany patients with age of 4 years or above who were treated due to acute sinusitis, bronchitis or urinary tract infections (UTI) in the period from 1st March 2004 - 30th July 2005, were elected. They were included in the study analysis, if they had no exclusion criteria (severe diseases, need for antibiotic therapy, participation in another trial) and came to the final investigation. The patients were treated either with the nasturtium herb and horseradish root containing herbal drug Angocin Anti-Infekt N (test group, n = 1223) or with standard antibiotic therapy (control group, n = 426). Treatment, dosage and treatment duration were determined by the physician in accordance with the patient. 536 subjects (408 test, 128 control patients) suffered from acute sinusitis, 634 subjects (469 test, 165 control patients) from acute bronchitis and 479 subjects (346 test, 133 control patients) from UTI. At study start and end the severity of the symptoms were judged by the investigator and quantified with 4 scores (0 = no symptom, 3 severe symptom). During the treatment information on use of medication, concomitant procedures and adverse events (AEs) in a patient diary. At the end of the study (disease free or after 7-14 days) the patient returned to the investigator, who recorded the vital parameters, finally judged the treatment efficacy and potential persisting symptoms on the basis of score values. Primary efficacy criterion was the change of the complaints quantified by the change of the relative symptom score averaged over all symptoms and related to the baseline value. RESULTS: In patients with acute sinusitis the mean relative reduction of the averaged symptom score was 81.3% for the test group and 84.6% for the control group, in patients with acute bronchitis the mean reduction was 78.3% for the test group and 80.3% for the control group, in patients with UTI 81.2% for the test group and 87.9% for the control group. The 95% confidence interval for the difference of the expected reductions between test and control group was -8.5% to 1.8% for acute sinusitis, 7.6% to 3.6% for acute bronchitis and -13.1% to -0.1% for UTI. Non-inferiority of the test treatment, i.e. if the lower limit of the 95% confidence interval is greater than 10%, could be stated for acute sinusitis and bronchitis. In UTI the non-inferiority level was exceeded only by 3%. Complementary procedures were less in the test group than in the control group. For 1.5 % of test patients and 6.8% of control patients AEs were observed CONCLUSION: Therapy with the herbal drug in the indications acute sinusitis, acute bronchitis und acute urinary tract infection is - with regard to its efficacy comparable to the treatment with standard antibiotics. The application of supportive procedures and the administration of concurrent medication were less expressed in the group treated with the herbal drug. In the above mentioned indications the group treated with the herbal drug displayed a clear advantageous safety profile compared to the group treated with standard antibiotics.
Asunto(s)
Armoracia/química , Bronquitis/tratamiento farmacológico , Nasturtium/química , Fitoterapia , Sinusitis/tratamiento farmacológico , Infecciones Urinarias/tratamiento farmacológico , Adulto , Antibacterianos/uso terapéutico , Armoracia/efectos adversos , Estudios de Cohortes , Femenino , Humanos , Masculino , Nasturtium/efectos adversos , Fitoterapia/efectos adversos , Extractos Vegetales , Raíces de Plantas/efectos adversos , Raíces de Plantas/química , Estudios Prospectivos , Resultado del TratamientoRESUMEN
UNLABELLED: Projective and reflex zones of inner organs to the body's surface are well described but there are only few clinical studies about abnormal zones. OBJECTIVE: The aim of our study was to investigate associations between chronic irritation of tonsils, abnormalities of the connective tissue areas over the musculus trapezius and the severity of brachialgia paresthetica nocturna. METHODS: Cross sectional study in 100 adult pain patients from an outpatient pain department. Patients with tonsillectomy were excluded. Examinations of tonsils and the connective tissue area were done separately by two mutually blinded physicians. Both were also blinded to the patients' evaluation of his/her brachialgia. RESULTS: Regardless of the lateralization, the severity of the tonsil irritations was correlated with the abnormalities of the connective tissue areas (Spearman's rho = 0.82; 95% confidence interval (CI): 0.74-0.87; p < 0.001) and the severity of the brachialgia (rho = 0.64, CI: 0.50-0.74; p < 0.001), furthermore indurations of connective tissue areas correlated with the severity of brachialgia homolaterally (rho = 0.57; CI: 0.42-0.69; p < 0.001). These correlations are considerably higher than those of other connective tissue areas. CONCLUSIONS: The results support the existence of easy to diagnose reflex zones, at least in a highly selected population of pain patients. They can give plausible hints for naturopathic treatments of brachialgia paresthetica nocturna, i.e. treatment of the relevant connective tissue zone above the M. trapezius.
Asunto(s)
Neuritis del Plexo Braquial/patología , Plexo Braquial/patología , Tejido Conectivo/patología , Naturopatía/métodos , Tonsila Palatina/patología , Parestesia/patología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Neuritis del Plexo Braquial/diagnóstico , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Parestesia/diagnósticoRESUMEN
The one-pot cyclization of dilithiated oximes with epibromohydrin provided a convenient and regioselective approach to 6-hydroxymethyl-5,6-dihydro-4H-1,2-oxazines. The reaction of the latter with phosphorus tribromide resulted in a Beckmann rearrangement and formation of 5-bromomethyl-2-iminotetrahydrofurans. The reaction of dilithiated hydrazones with epibromohydrin afforded oxazolo[3,4-b]pyridazin-7-ones, which were formed by a novel domino cyclization.
RESUMEN
A series of novel 2-vinylchroman-4-ones, analogues of the natural products Aposphaerin A and B, were identified as potent antibiotics. Derivatives exhibit a significant activity against multiresistant strains of S. aureus, such as MRSA (methicillin resistant S. aureus). The 2-vinylchroman-4-ones were efficiently prepared by Lewis acid mediated conjugate addition of vinylmagnesium bromide to chromones.
Asunto(s)
Antraquinonas/química , Antraquinonas/farmacología , Antibacterianos/química , Antibacterianos/farmacología , Cromonas , Espectroscopía de Resonancia Magnética , Espectrometría de Masas , Resistencia a la Meticilina , Pruebas de Sensibilidad Microbiana , Espectrofotometría Infrarroja , Staphylococcus aureus/efectos de los fármacos , Relación Estructura-ActividadRESUMEN
2-Alkylidenethiazolidine-4,5-diones were prepared by novel one-pot cyclizations of arylacetonitriles with isothiocyanates and ethyl 2-chloro-2-oxoacetate. The products show antibiotic activity against the Gram-positive bacteria Bacillus subtilis and Staphylococcus aureus.