Nettle extract (Urtica dioica) affects key receptors and enzymes associated with allergic rhinitis

A nettle (Urtica dioica) extract shows in vitro inhibition of several key inflammatory events that cause the symptoms of seasonal allergies. These include the antagonist and negative agonist activity against the Histamine‐1 (H₁) receptor and the inhibition of mast cell tryptase preventing degranulation and release of a host of pro‐inflammatory mediators that cause the symptoms of hay fevers. The nettle extract also inhibits prostaglandin formation through inhibition of Cyclooxygenase‐1 (COX‐1), Cyclooxygenase‐2 (COX‐2), and Hematopoietic Prostaglandin D₂ synthase (HPGDS), central enzymes in pro‐inflammatory pathways. The IC₅₀ value for histamine receptor antagonist activity was 251 (±13) µg mL^?1 and for the histamine receptor negative agonist activity was 193 (±71) µg mL^?1. The IC₅₀ values for inhibition of mast cell tryptase was 172 (±28) µg mL^?1, for COX‐1 was 160 (±47) µg mL^?1, for COX‐2 was 275 (±9) µg mL^?1, and for HPGDS was 295 (±51) µg mL^?1. Through the use of DART TOF‐MS, which yields exact masses and relative abundances of compounds present in complex mixtures, bioactives have been identified in nettle that contribute to the inhibition of pro‐inflammatory pathways related to allergic rhinitis. These results provide for the first time, a mechanistic understanding of the role of nettle extracts in reducing allergic and other inflammatory responses in vitro. Copyright © 2009 John Wiley & Sons, Ltd.     

Supplementary pharmacist prescribers' views about communication skills teaching and learning,and applying these new skills in practice

Objective To explore supplementary pharmacist prescribers' (SPPs') views of communication skills teaching and learning, and its impact on their practice. Method Semi‐structured in‐depth telephone interviews. Key findings A total of 66/143 (46%) pharmacists consented to take part. Of these 66, nine SPPs were purposively selected to represent three different sectors of pharmacy: primary care, hospital and community. Questions for a semi‐structured interview schedule were derived from themes identified from SPP self‐reflective essays submitted earlier in the course. Framework analysis was used to interpret the data. SPPs' views of communication skills teaching and learning were positive. Topics raised as particularly useful were how to structure the consultation, eliciting a patient‐centred history, including the patient's perspective on their situation and/or illness, and working in partnership with the patient. However, interviewees highlighted some practical difficulties with putting these new skills into practice. Conclusions The results indicate that SPPs view communication skills training as changing aspects of their consultation practice. The communication skills identified for further development tended to be those not usually required in traditional pharmacy consultations. The results emphasise the importance of providing communication skills training for extended roles.     

Worksite Interventions: A Methodological Exploration and Pilot Study Promoting Behavior Change

This paper explores the methodological implications of using multiple methods in conducting preventive interventions, employing the stages of change model as a conceptual framework. We discuss the issues involved in using three empirically supported interventions (expert systems, group support, and self-help manuals) in the context of promoting smoking cessation. Although these methods have been assessed in different contexts, they have not been combined using the worksite as the location of intervention. Worksite interventions have the potential to reach large numbers of people and facilitate changes in social and environmental norms, yet there is a need to further examine how various methods can be combined to facilitate behavior change. Implementation of two pilot studies in the worksite provides initial evidence of the feasibility of a theoretically-based multi-method approach to intervention.     

Extramedullary infiltrates of AML are associated with CD56 expression, 11q23 abnormalities and inferior clinical outcome

We evaluated the frequency and prognostic significance of extramedullary infiltrates (EMI) at presentation of acute myeloid leukemia (AML) in adult patients. Of 331 cases with de novo AML, 101(30.5%) had extramedullary infiltrates at diagnosis. The extramedullary manifestations included: lymphadenopathy, splenomegaly, hepatomegaly, gingival hypertrophy, skin infiltrates and involvement of central nervous system (CNS). Patients with EMI had a high initial WBC count and a high proportion of M4/M5 morphological variants. The complete remission rate (CR) with induction chemotherapy was lower in patients with EMI (P=0.0077) and their overall survival was also inferior (P=0.0017). Flow cytometric evaluation of the surface antigens expressed by the leukemic blasts for CD34, TdT, HLADR, CD7, CD19 and CD56 found that only CD56 expression was associated with EMI. The association of CD56 expression with lymphadenopathy was statistically significant (P=0.035). Abnormal karyotypes were found in 50.6% of patients with EMI and 49.7% of patients without EMI. Only 11q23 abnormalities were associated with specific sites of EMI; lymphadenopathy (P=0.0111) and gingival hypertrophy (P=0.0016). Our study of adult AML patients demonstrates that EMI at diagnosis is associated with CD56 expression by leukemic blasts, 11q23 karyotypic abnormalities, low complete remission rate and poor overall survival.     

A slow release formulation of insulin as a treatment for osteoarthritis

OBJECTIVE: To examine the potential of insulin, in a sustained delivery system, as a treatment for arthritis. DESIGN: The effect of insulin on matrix synthesis, matrix breakdown, and nitric oxide production in primary cartilage explants was examined. The activity of insulin on diseased cartilage from Dunkin Hartley guinea pigs, diabetic mice, and osteoarthritic patients was measured. The specificity of insulin stimulation was compared to that of IGF-I using osteoblasts and fibroblasts. Finally, the stability of insulin in a biologically relevant system was tested, and a slow-release formulation of insulin was developed and characterized. RESULTS: In articular cartilage explants, insulin stimulated proteoglycan (PG) synthesis, inhibited PG release and nitric oxide production, and overcame the detrimental effects of interleukin 1 (IL-1). The mechanism whereby insulin decreased matrix breakdown was through inhibition of aggrecanase activity. Insulin was active on cartilage at concentrations at which insulin does not cross-react with insulin-like growth factor I (IGF-I) receptors nor stimulate proliferation of other cells types. The response of cartilage to insulin did not diminish with age or disease. Insulin stimulated matrix synthesis in osteoarthritic cartilage and local treatment with insulin overcame endogenous suppression of matrix synthesis in diabetic cartilage. Poly-lactic-coglycolic acid (PLGA) was found to be an effective carrier for delivery of insulin, and PLGA-Insulin was active on articular cartilage in vitro and in vivo. CONCLUSIONS: As the incidence of arthritis increases with the aging population, an effective therapy to induce repair of cartilage is needed. Based on its biological activities, insulin appears to be an attractive protein therapeutic candidate. Maximum insulin effectiveness may require a sustained delivery system.     

Short-Term Clinical Outcomes After Anterior Cruciate Ligament Reconstruction In Adolescents During The COVID-19 Pandemic

Background/PurposeThe COVID-19 pandemic has impacted adolescents across multiple areas of health. While many factors influence outcomes following anterior cruciate ligament reconstruction (ACLR), the impact of the COVID-19 pandemic on early patient outcomes after ACLR is currently unknown in an adolescent population. The purpose of this study was to determine if short-term clinical outcomes were different in adolescents after ACLR for those who underwent surgery pre-COVID versus during the COVID-19 pandemic timeframe.DesignRetrospective cohortMethodsA retrospective review of records occurred for patients who underwent ACLR with a quadriceps tendon autograft. Two separate review timeframes were defined according to date of surgery (control: September 2017 - October 2019; COVID: March 2020 - May 2021). Patients were classified into pre-COVID (control) and COVID groups by surgical date and were then age- and sex-matched. Three-month postoperative outcomes were included for analysis, including normalized isometric quadriceps and hamstring peak torque, Anterior Cruciate Ligament – Return to Sport after Injury (ACL-RSI), and the Pedi International Knee Documentation Committee Form (Pedi-IKDC) scores.ResultsSixty patients met the inclusion criteria (34 females, 56.7%). Follow-up testing occurred at 3.2 months (98.13 ± 14.91 days) postoperative. A significant difference was found between groups for normalized quadriceps peak torque on the uninvolved limb, with the control group (2.03 ± 0.47 Nm/kg) demonstrating decreased peak torque compared to the COVID group (2.49 ± 0.61 Nm/kg) (p =0.002, effect size (d) = 0.84). For the involved limb, no difference in normalized quadriceps peak torque was observed between the control group (1.25 ± 0.33 Nm/kg) and those who underwent surgery during the COVID-19 pandemic (1.49 ± 0.70 Nm/kg) (p = 0.09). No differences were identified between groups for any of the other strength outcomes (p = 0.31 – 0.87). Similarly, no differences in patient reported outcomes were found for Pedi-IKDC or ACL-RSI between groups (p = 0.12 – 0.43).ConclusionAt roughly three months after ACLR, normalized quadriceps peak torque on the uninvolved limb was reduced by 18.5% for adolescents who underwent surgery pre-COVID versus during the COVID-19 pandemic timeframe. No group differences were observed for other isometric strength outcomes, Pedi-IKDC, or ACL-RSI scores.     

The International Collaboration on Air Pollution and Pregnancy Outcomes: initial results

Background: The findings of prior studies of air pollution effects on adverse birth outcomes are difficult to synthesize because of differences in study design.Objectives: The International Collaboration on Air Pollution and Pregnancy Outcomes was formed to understand how differences in research methods contribute to variations in findings. We initiated a feasibility study to a) assess the ability of geographically diverse research groups to analyze their data sets using a common protocol and b) perform location-specific analyses of air pollution effects on birth weight using a standardized statistical approach.Methods: Fourteen research groups from nine countries participated. We developed a protocol to estimate odds ratios (ORs) for the association between particulate matter ≤ 10 μm in aerodynamic diameter (PM₁₀) and low birth weight (LBW) among term births, adjusted first for socioeconomic status (SES) and second for additional location-specific variables.Results: Among locations with data for the PM₁₀ analysis, ORs estimating the relative risk of term LBW associated with a 10-μg/m³ increase in average PM₁₀ concentration during pregnancy, adjusted for SES, ranged from 0.63 [95% confidence interval (CI), 0.30–1.35] for the Netherlands to 1.15 (95% CI, 0.61–2.18) for Vancouver, with six research groups reporting statistically significant adverse associations. We found evidence of statistically significant heterogeneity in estimated effects among locations.Conclusions: Variability in PM₁₀–LBW relationships among study locations remained despite use of a common statistical approach. A more detailed meta-analysis and use of more complex protocols for future analysis may uncover reasons for heterogeneity across locations. However, our findings confirm the potential for a diverse group of researchers to analyze their data in a standardized way to improve understanding of air pollution effects on birth outcomes.