Single‐ and Multiple‐Dose Randomized Studies of Blosozumab,a Monoclonal Antibody Against Sclerostin,in Healthy Postmenopausal Women

Two clinical studies were conducted to assess the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of single and multiple doses (intravenous [iv] and subcutaneous [sc]) of blosozumab in postmenopausal women, including prior/current bisphosphonate (BP) users. In these phase 1, randomized, subject‐ and investigator‐blind, placebo‐controlled studies, subjects received escalating doses of blosozumab: single iv doses up to 750 mg, single sc doses of 150 mg, multiple iv doses up to 750 mg every 2 weeks (Q2W) for 8 weeks, multiple sc doses up to 270 mg Q2W for 8 weeks, or placebo. Six subjects were randomized to each dose in the single‐dose study (12 to placebo) and up to 12 subjects to each arm in the multiple‐dose study. Blosozumab was well tolerated with no safety concerns identified after single or multiple administrations up to 750 mg. Dose‐dependent responses were observed in sclerostin, N‐terminal propeptide of procollagen type 1, bone‐specific alkaline phosphatase, osteocalcin, C‐terminal fragment of type 1 collagen, and bone mineral density (BMD) after single and multiple (up to 5) administrations of blosozumab. There was up to a 3.41% (p = 0.002) and up to a 7.71% (p < 0.001) change from baseline in lumbar spine BMD at day 85 after single or multiple administrations of blosozumab, respectively. Prior BP use did not appear to have a clear impact on the effects of single doses of blosozumab when considering bone biomarker and BMD responses. Antibodies to blosozumab were detected by a screening assay, but no patterns with regard to dose or route of administration and no clear impact on blosozumab exposure or PD responses were identified. In summary, blosozumab was well tolerated and exhibited anabolic effects on bone. These findings support further investigation of blosozumab as a potential anabolic therapy for osteoporosis. © 2014 American Society for Bone and Mineral Research.     

Clinical hematological and biochemical parameters in Swiss,BALB/c,C57BL/6 and B6D2F1 Mus musculus

BackgroundAnimal models are widely used in scientific research in order to obtain information from a whole organism under a specific set of experimental conditions. Various lineages of mice have been used to investigate diseases and new therapeutic strategies, and, consequently, hematological and biochemical tests in these laboratory animals are essential to validate scientific studies. Our study seeks to establish reference values for hematological and biochemical parameters of four lineages of mice.MethodsWe evaluated the hematological and biochemical profiles of 20 males and 20 females from the lineages Swiss (heterogeneous), BALB/c and C57BL/6 (isogenic), and B6D2F1 (hybrid), totaling 160 mice. Analysis were standardized using the systems pocH‐100iV Diff™ for 19 hematological parameters and VITROS^® 350 for 12 biochemical parameters.ResultsResults are shown as means and standard deviation, grouped by lineage and genre. Comparing the values obtained in this study with the values from previous studies, some variations were detected, which could be explained by differences in methodologies or individual variability.ConclusionThus our study shows that knowledge and disclosure of the values of physiological parameters of laboratory animals is necessary, and emphasises the importance of considering variations influenced by gender, lineage and genotype in the choice of the best experimental model.     

Compliance with and acceptability of two fortified balanced energy protein supplements among pregnant women in rural Nepal

Some evidence suggests that balanced energy protein (BEP) supplements taken during pregnancy and lactation can have positive effects on birth outcomes such as small‐for‐gestational age and birthweight, but more evidence is needed on the long‐term use and acceptability of such supplements. We conducted a mixed‐methods formative research study to assess and compare compliance with and acceptability of two BEP supplements, a lipid‐based peanut paste and a biscuit, to identify BEP supplements for subsequent inclusion in an efficacy trial. We conducted an 8‐week feeding trial of daily supplementation among two groups of 40 pregnant women each in rural Nepal. Compliance data were collected and supplements distributed at the weekly visits. Sensory properties of the supplements were assessed using a 7‐point Likert scale. In addition, in‐depth interviews with women (n = 16), family members (n = 6) and health workers (n = 6) and focus group discussions (FGDs) (n = 4) were conducted to explore themes related to general use and intention of future use of the supplement. Overall self‐reported compliance was high: medians of 91.1% in the lipid‐based peanut paste group and 96.4% in the biscuit group. Both supplements were rated highly on overall likability (median score 6/7) and sensory properties. Qualitative findings showed that sustained use of the supplements was attributed to expected health benefits, favourable sensory attributes, and family support. The FGDs suggested providing the option to choose between more than one type/flavour of supplements to improve compliance. Sharing was mostly evident in the first week with higher sharing reported in the biscuit group.     

First report of homoanatoxin-a and associated dog neurotoxicosis in New Zealand.

In November 2005, at least five dogs died rapidly after contact with water from the Hutt River (lower North Island, New Zealand). Necropsy performed 24h later on one of the dogs (a 20-month-old Labrador) revealed few findings of interest, except for copious amounts of froth in the respiratory tract down to the bifurcation of the trachea and large quantities of algal material in the dog's stomach. Low and relatively stable flows in the Hutt River during spring had resulted in the proliferation of benthic cyanobacteria that formed large black/brown mats along the river edge. Samples from the Labrador's stomach contents and cyanobacterial mats were analysed microscopically and screened using chemical and biochemical assays for cyanotoxins: anatoxin-a, homoanatoxin-a, cylindrospermopsins, saxitoxins and microcystins. Liquid chromatography-mass spectrometry (LC-MS) confirmed the presence of the neurotoxic cyanotoxins anatoxin-a and homoanatoxin-a and their degradation products, dihydro-anatoxin-a and dihydro-homoanatoxin-a. This is the first report of homoanatoxin-a and associated degradation product in New Zealand. Based on morphology, the causative species was identified as Phormidium sp. Subsequent phylogenetic analysis of 16S rRNA gene sequences demonstrated that the causative organism was most similar to Phormidium autumnale. Further investigations led to the detection of homoanatoxin-a and anatoxin-a in cyanobacterial mats from four other rivers in the Wellington region (lower North Island, New Zealand). Access restrictions were placed on over 60% of river catchments in the western Wellington region, severely affecting recreational users.