Dermal Delivery of Korean Red Ginseng Extract: Impact on Storage Stability of Different Carrier Systems and Evaluation of Rg1 and Rb1 Skin Permeation Ex Vivo.

The root extract of Panax ginseng C.A. Meyer (Korean red ginseng/KRG extract) is a traditional Asian remedy introduced to dermal products for its antioxidative potential. However, little is known about technological aspects or skin penetration of main ginsenosides. Thus, stable oil-in-water nanoemulsions (NEs) and hydrogels for dermal delivery of KRG extract were developed and characterised using light scattering methods, analysis of flow properties and pH measurements. In addition, Rg1 and Rb1 contents were monitored by UHPLC/MS. Different surfactants (phosphatidylcholine, monoacylphosphatidylcholine and polysorbate 80) and polymers (polyacrylic acid and hydroxyethylcellulose) were tested and compared for their compatibility with KRG extract. The results showed that incorporation of KRG extract led to a significantly reduced formulation pH in hydroxyethylcellulose gels (-22%), NEs (-15%) and carbomer gels (-4-5%). The dynamic viscosity was in the range of 24-28 Pas at 10 s-1 for carbomer gels. The highest storage stability and skin permeation were observed for a hydroalcoholic gel with carbomer 50,000 and TRIS buffer (each of 1% w/w), containing ethanol (20% w/w) and KRG extract (2% w/w). Ex vivo diffusion cell studies confirmed skin permeation of the moderately lipophilic Rg1, but not the more hydrophilic Rb1 with a larger molecular weight.

[Community-Based Nutrition Health Promotion Interventions - Evaluation of the Project "Gesunde Südstadt" in Nuremberg]. / Maßnahmen der kommunalen Gesundheitsförderung im Handlungsfeld Ernährung ­ Evaluation des Projekts "Gesunde Südstadt" der Stadt Nürnberg.

HINTERGRUND: Das Projekt "Gesunde Südstadt" hat den Schwerpunkt Gesundheitsförderung in der Lebenswelt Kommune. Es wurde im Rahmen des "Präventionsgesetzes" (SGB V §20a) initiiert und zielt ab auf die Verringerung der gesundheitlichen Ungleichheit in der Stadt Nürnberg. Die Maßnahmen der kommunalen Gesundheitsförderung im Handlungsfeld Ernährung wurden durch eine externe multiperspektivische, multimethodische Prozess- und Ergebnisevaluation begleitend untersucht. METHODEN: 55 Maßnahmenberichte, 8 Interviews mit Teilnehmenden sowie 3 Interviews mit Maßnahmendurchführenden wurden mit qualitativer Inhaltsanalyse ausgewertet. Eine Teilnehmendenbefragung (n=35) mittels Fragebögen wurde quantitativ-statistisch ausgewertet. ERGEBNISSE: Die Ergebnisse zeigen, dass die Gesundheitsförderungsmaßnahmen durch die Teilnehmenden eine hohe Akzeptanz erfuhren und ein ausgeprägtes Maß an Partizipation ermöglicht wurde. Weiterhin zeigen die Ergebnisse, dass die Maßnahmen die interaktive sowie die funktionale Gesundheitskompetenz förderten. Ein empirisches Pfadmodell für kommunale Gesundheitsförderungsprojekte wurde abgeleitet. SCHLUSSFOLGERUNG: Die Ergebnisse belegen gesundheitsförderliche Effekte eines verhältnis- und verhaltensbasierten, kommunalen Ansatzes zur Gesundheitsförderung bei Teilnehmenden an Maßnahmen im Handlungsfeld Ernährung. Das Projekt "Gesunde Südstadt" stellt einen systematischen, lebensweltrelevanten und niedrigschwelligen Ansatz der soziallagenbezogenen Gesundheitsförderung im kommunalen Setting dar. Methodische Einschränkungen, wie das Querschnittsdesign der Studie, werden diskutiert. BACKGROUND AND OBJECTIVES: The Project "Gesunde Südstadt" is focused on community-based health promotion interventions. It was initiated as part of the "Prevention Act" (SGB V §20a) and aims to reduce health inequalities in the city of Nuremberg. The community-based health promotion interventions focussing on nutrition were evaluated with an external multi-perspective, multi-method evaluation approach with a focus both on process and outcome results. METHODS: 55 reports on activities, 8 interviews with participants and 3 interviews with trainers were coded using qualitative content analysis. Statistical analyses were conducted on a participant survey (n=35). RESULTS: Results showed that the community-based health promotion interventions were not only widely accepted by the participants but also enabled them to participate in health-related activities. Additionally, health promotion interventions in the community were found to promote interactive and functional health competences. An empirically derived path model for community-based health promotion interventions was statistically tested. CONCLUSIONS: Results show health promotion effects of community-based nutrition-related health promotion interventions on participants. The project "Gesunde Südstadt" thus represents a systematic, relevant and low-threshold approach to health promotion in a communal setting. Methodological limitations such as the cross-sectional design are discussed.

Effects of interleukin-1ß inhibition with canakinumab on hemoglobin A1c, lipids, C-reactive protein, interleukin-6, and fibrinogen: a phase IIb randomized, placebo-controlled trial.

BACKGROUND: To test formally the inflammatory hypothesis of atherothrombosis, an agent is needed that reduces inflammatory biomarkers such as C-reactive protein, interleukin-6, and fibrinogen but that does not have major effects on lipid pathways associated with disease progression. METHODS AND RESULTS: We conducted a double-blind, multinational phase IIb trial of 556 men and women with well-controlled diabetes mellitus and high cardiovascular risk who were randomly allocated to subcutaneous placebo or to subcutaneous canakinumab at doses of 5, 15, 50, or 150 mg monthly and followed over 4 months. Compared with placebo, canakinumab had modest but nonsignificant effects on the change in hemoglobin A1c, glucose, and insulin levels. No effects were seen for low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, or non-high-density lipoprotein cholesterol, although triglyceride levels increased ≈10% in the 50-mg (P=0.02) and 150-mg (P=0.03) groups. By contrast, the median reductions in C-reactive protein at 4 months were 36.4%, 53.0%, 64.6%, and 58.7% for the 5-, 15-, 50-, and 150-mg canakinumab doses, respectively, compared with 4.7% for placebo (all P values ≤0.02). Similarly, the median reductions in interleukin-6 at 4 months across the canakinumab dose range tested were 23.9%, 32.5%, 47.9%, and 44.5%, respectively, compared with 2.9% for placebo (all P≤0.008), and the median reductions in fibrinogen at 4 months were 4.9%, 11.7%, 18.5%, and 14.8%, respectively, compared with 0.4% for placebo (all P values ≤0.0001). Effects were observed in women and men. Clinical adverse events were similar in the canakinumab and placebo groups. CONCLUSIONS: Canakinumab, a human monoclonal antibody that neutralizes interleukin-1ß, significantly reduces inflammation without major effect on low-density lipoprotein cholesterol or high-density lipoprotein cholesterol. These phase II trial data support the use of canakinumab as a potential therapeutic method to test directly the inflammatory hypothesis of atherosclerosis.

Randomized, prospective, three-arm study to confirm the auditory safety and efficacy of artemether-lumefantrine in Colombian patients with uncomplicated Plasmodium falciparum malaria.

The safety of artemether-lumefantrine in patients with acute, uncomplicated Plasmodium falciparum malaria was investigated prospectively using the auditory brainstem response (ABR) and pure-tone thresholds. Secondary outcomes included polymerase chain reaction-corrected cure rates. Patients were randomly assigned in a 3:1:1 ratio to either artemether-lumefantrine (N = 159), atovaquone-proguanil (N = 53), or artesunate-mefloquine (N = 53). The null hypothesis (primary outcome), claiming that the percentage of patients with a baseline to Day-7 ABR Wave III latency increase of > 0.30 msec is ≥ 15% after administration of artemether-lumefantrine, was rejected; 2.6% of patients (95% confidence interval: 0.7-6.6) exceeded 0.30 msec, i.e., significantly below 15% (P < 0.0001). A model-based analysis found no apparent relationship between drug exposure and ABR change. In all three groups, average improvements (2-4 dB) in pure-tone thresholds were observed, and polymerase chain reaction-corrected cure rates were > 95% to Day 42. The results support the continued safe and efficacious use of artemether-lumefantrine in uncomplicated falciparum malaria.

Similar efficacy and safety of artemether-lumefantrine (Coartem®) in African infants and children with uncomplicated falciparum malaria across different body weight ranges.

BACKGROUND: Artemisinin-based combination therapy, including artemether-lumefantrine (AL), is currently recommended for the treatment of uncomplicated Plasmodium falciparum malaria. The objectives of the current analysis were to compare the efficacy and safety of AL across different body weight ranges in African children, and to examine the age and body weight relationship in this population. METHODS: Efficacy, safety and pharmacokinetic data from a randomized, investigator-blinded, multicentre trial of AL for treatment of acute uncomplicated P. falciparum malaria in infants and children in Africa were analysed according to body weight group. RESULTS: The trial included 899 patients (intent-to-treat population 886). The modified intent-to-treat (ITT) population (n = 812) comprised 143 children 5 to < 10 kg, 334 children 10 to < 15 kg, 277 children 15 to < 25 kg, and 58 children 25 to < 35 kg. The 28-day PCR cure rate, the primary endpoint, was comparable across all four body weight groups (97.2%, 98.9%, 97.8% and 98.3%, respectively). There were no clinically relevant differences in safety or tolerability between body weight groups. In the three AL body weight dosing groups (5 to < 15 kg, 15 to < 25 kg and 25 to < 35 kg), 80% of patients were aged 10-50 months, 46-100 months and 90-147 months, respectively. CONCLUSION: Efficacy of AL in uncomplicated falciparum malaria is similar across body weight dosing groups as currently recommended in the label with no clinically relevant differences in safety or tolerability. AL dosing based on body weight remains advisable.

Efficacy and safety of artemether-lumefantrine in the treatment of acute, uncomplicated Plasmodium falciparum malaria: a pooled analysis.

Randomized trials have confirmed the efficacy and safety of artemether-lumefantrine (AL) for treatment of uncomplicated Plasmodium falciparum malaria. Data from seven studies supported by Novartis (1996-2007), including 647 adults (> 16 years of age, 83.3% completed the study) and 1,332 children (≤ 16 years of age, 89.3% completed the study) with microscopically confirmed uncomplicated P. falciparum malaria and treated with the recommended regimen of AL, were pooled. The 28-day polymerase chain reaction-corrected parasitologic cure rate (primary efficacy endpoint) was 97.1% (495 of 510) in adults and 97.3% (792 of 814) in children (evaluable population). Gametocytemia prevalence after day was 4.2% (23 of 554) in adults and 0.9% (8 of 846) in children. No noteworthy safety signals were observed. Serious adverse events occurred in 1.4% of the adults and 1.3% of the children. This study is the largest data set to date assessing AL therapy for treatment of acute uncomplicated P. falciparum malaria. Artemether-lumefantrine showed high cure rates and rapid resolution of parasitemia, fever, and gametocytemia in adults and children, and showed an excellent safety and tolerability profile.

Safety of artemether-lumefantrine in pregnant women with malaria: results of a prospective cohort study in Zambia.

BACKGROUND: Safety data regarding exposure to artemisinin-based combination therapy in pregnancy are limited. This prospective cohort study conducted in Zambia evaluated the safety of artemether-lumefantrine (AL) in pregnant women with malaria. METHODS: Pregnant women attending antenatal clinics were assigned to groups based on the drug used to treat their most recent malaria episode (AL vs. sulphadoxine-pyrimethamine, SP). Safety was assessed using standard and pregnancy-specific parameters. Post-delivery follow-up was six weeks for mothers and 12 months for live births. Primary outcome was perinatal mortality (stillbirth or neonatal death within seven days after birth). RESULTS: Data from 1,001 pregnant women (AL n = 495; SP n = 506) and 933 newborns (AL n = 466; SP n = 467) showed: perinatal mortality (AL 4.2%; SP 5.0%), comprised of early neonatal mortality (each group 2.3%), stillbirths (AL 1.9%; SP 2.7%); preterm deliveries (AL 14.1%; SP 17.4% of foetuses); and gestational age-adjusted low birth weight (AL 9.0%; SP 7.7%). Infant birth defect incidence was 1.8% AL and 1.6% SP, excluding umbilical hernia. Abortions prior to antenatal care could not be determined: abortion occurred in 4.5% of women treated with AL during their first trimester; none were reported in the 133 women exposed to SP and/or quinine during their first trimester. Overall development (including neurological assessment) was similar in both groups. CONCLUSIONS: These data suggest that exposure to AL in pregnancy, including first trimester, is not associated with particular safety risks in terms of perinatal mortality, malformations, or developmental impairment. However, more data are required on AL use during the first trimester.

A randomized, double-blind, placebo-controlled trial assessing the efficacy and safety of tegaserod in patients from China with chronic constipation.

AIM: To evaluate the efficacy and safety of tegaserod, 6 mg twice daily (b.i.d.), in men and women with chronic constipation (CC) from China. METHODS: This was a multicenter, double-blind, placebo-controlled study. Following a 2-wk treatment-free baseline period, patients were randomized to receive either tegaserod (6 mg b.i.d.) or placebo (b.i.d.) for 4 wk. An analysis of covariance with repeated measures was used to determine the overall effect of treatment for the primary efficacy variable; the change from baseline in the number of complete spontaneous bowel movements (CSBMs) during the 4-wk treatment period. Secondary efficacy endpoints included other measures of response in terms of CSBMs, and patients' daily and weekly assessment of bowel habits. Safety was also assessed, based on the incidence and severity of adverse events (AEs). RESULTS: A total of 607 patients were randomized to receive either tegaserod (n = 304) or placebo (n = 303). Tegaserod treatment resulted in a rapid and significant increase from baseline in the adjusted mean number of CSBMs per week over wk 1-4 compared with placebo (1.39 vs 0.91, P = 0.0002). A statistically significant difference in favor of tegaserod was also observed for a mean increase > or = 1 CSBM/wk over wk 1-4 (47.7% vs 35.0%, tegaserod vs placebo, respectively, P = 0.0018) and for the absolute number of > or = 3 CSBMs/wk over wk 1-4 (25.0% vs 14.5%, tegaserod vs placebo, respectively, P = 0.0021). Improvements in other symptoms of CC were also seen in the tegaserod group, including improved stool form and reduced straining. In addition, more patients in the tegaserod group reported satisfactory relief from their constipation symptoms. The frequency and severity of AEs was comparable between tegaserod and placebo groups, with the exception of a greater incidence of diarrhea in patients receiving tegaserod (3.6%) compared with placebo (1.7%). CONCLUSION: Tegaserod treatment improved multiple symptoms of CC and was associated with a favorable safety profile.