Evaluation of efficacy of heartworm preventive products at the FDA

The Center for Veterinary Medicine, U.S. Food and Drug Administration (FDA/CVM) has authority under the United States Code 21 under Section 514.80 to monitor for adverse experiences of approved animal products. Although veterinarians voluntarily report suspect drug-related events to manufacturers, firms that market FDA-approved animal products must report serious events to the FDA within 15 working days of the veterinarian or pet-owner's call to them. Under the present regulations, canine heartworm preventatives are approved for 100% efficacy after testing in laboratory and field conditions. The report of lack of efficacy against heartworm larvae is a serious adverse drug event because the resulting condition or the treatment of the condition is life threatening. Information on lack of effect that are deemed possibly, probably, or definitely drug-related available for review under generic product on the FDA/CVM website Surveillance of these reports indicates there are some failures for virtually all heartworm prevention product categories. Most failures have been reported in heartworm-endemic states. At this time, it is unclear whether these are representative of the rare occurrences of failure that have been in existence for a long time, but not reported regularly or promptly, or whether there is a true increase in complaints of ineffectiveness and real variability between products. This paper discusses methods, personnel, and procedures in place in the Division of Surveillance that will aid the FDA to better assess heartworm preventive treatment failures. It discusses scoring paradigms presently utilized by FDA/CVM to assess severity of complaints of lack of efficacy against heartworms, and welcomes audience input as to how to improve existing processes. Results suggest that more comprehensive reporting will provide FDA/CVM more accurate surveillance information regarding efficacy problems. Such practices will permit FDA/CVM to better interpret both incidence and severity of in-effect and possible patterns of emerging resistance and to convey this in any necessary updated labeling. It also indicates that as part of that process, practitioners should return to a more conservative testing schedule.     

Hematologic reference intervals for koi (Cyprinus carpio), including blood cell morphology, cytochemistry, and ultrastructure

BACKGROUND: Hematologic data are used routinely in the health care of humans and domestic mammals. Similar data for fish are largely fragmentary or have not been collected. OBJECTIVES: The primary purpose of this study was to determine hematologic reference intervals for koi, an ornamental strain of the common carp (Cyprinus carpio). Secondarily, the morphology, cytochemical reactions, and ultrastructure of koi blood cells were characterized. METHODS: A CBC was performed manually on heparin-anticoagulated blood specimens using Natt and Herrick's diluent and a Neubauer-ruled hemacytometer. Leukocyte differential counts were done on Wright-Leishman- and Diff-Quik-stained blood smears. Cytochemical reactions of koi leukocytes were determined using commercial kits. Transmission electron microscopy was performed to characterize the ultrastructural features of koi blood cells. RESULTS: Hematologic reference intervals were established for healthy koi for PCV (30-34%), hemoglobin concentration (6.3-7.6 g/dL), RBC count (1.7-1.9 X 10(6)/ microL), WBC count (19.8-28.1 X 10(3)/ microL), RBC indices, and differential leukocyte counts. Lymphocytes were the predominant leukocyte (accounting for up to 80% of all leukocytes), whereas eosinophils were rare. Basophils were positive with PAS staining. Naphthol AS-D chloroacetate esterase activity was observed only in eosinophils. alpha-Naphthyl butyrate esterase and beta-glucuronidase activities were positive in monocytes. Some lymphocytes were reactive for alpha-naphthyl butyrate esterase and acid phosphatase activity. Ultrastructurally, leukocytes, erythrocytes, and thrombocytes were identified on the basis of cytoplasmic organelles and granule appearance. CONCLUSION: Hematologic reference intervals and knowledge of the cytochemical reactions and ultrastructural characteristics of koi leukocytes will help standardize hematologic studies in this species.     

Validity and reliability of the Block98 food-frequency questionnaire in a sample of Canadian women

OBJECTIVE: To assess the validity and reliability of the most recent adaptation of Block's full-diet food-frequency questionnaire (FFQ) among a sample of Canadian women. DESIGN: Participants completed a self-administered FFQ (FFQ1), two unannounced 24-hour recalls (weekday and weekend) and a second FFQ (FFQ2) between October 2003 and February 2004. FFQs and recalls were analysed for 32 nutrients using Block Dietary Data Systems and the University of Minnesota's Nutrient Data System. Mean and median intakes were computed, along with crude and deattenuated Pearson correlation coefficients between FFQ1 and the average of two recalls (validity) and between FFQ1 and FFQ2 (reliability). SETTING: Ontario, Canada. SUBJECTS: A random population-based sample (n = 166) of women aged 25 to 74 years. RESULTS: One hundred and fifteen (69%) women completed FFQ1, 96 completed FFQ1 and both recalls, and 93 completed both FFQs, about 56 days apart. Mean intakes were similar for most nutrients. FFQ reliability was high, with Pearson correlation coefficients having a median of 0.75, ranging from 0.57 to 0.90 (macronutrients) and from 0.65 to 0.88 (micronutrients from supplements and food). FFQ validity was moderate to high, with deattenuated Pearson correlation coefficients having a median of 0.59, ranging from 0.11 to 0.73 (macronutrients) and from 0.50 to 0.76 (micronutrients from supplements and food). Our micronutrient correlations were similar to or higher than those of other studies that included supplements. Two correlations <0.40 were associated with fats. CONCLUSIONS: The validity and reliability of this full-diet version of the Block FFQ were moderate to high, supporting its use in future studies among Canadian women.     

Silk genes support the single origin of orb webs

The orb web is a spectacular evolutionary innovation that enables spiders to catch flying prey. This elegant, geometric structure is woven with silk fibers that are renowned for their superior mechanical properties. We used silk gland expression libraries to address a long-standing controversy concerning the evolution of the orb-web architecture. Contrary to the view that the orb-web design evolved multiple times, we found that the distribution and phylogeny of silk proteins support a single, ancient origin of the orb web at least 136 million years ago. Furthermore, we substantially expanded the repository of silk sequences that can be used for the synthesis of high-performance biomaterials.     

Inheritance of rol-genes from Agrobacterium rhizogenes through two generations in Kalancho?

Transformation of Kalancho? blossfeldiana ‘Molly’ using the naturally occurring bacterium Agrobacterium rhizogenes is a non-GMO strategy to breed compact plants. In the present study, crosses resembling a commercial breeding strategy were made to determine if the improved ornamental quality observed in the T1 generation was inherited to the offspring. F1 lines were produced by crossing the commercial Kalancho? cultivar ‘Sarah’ with a selected T1 line. Subsequently, F2 populations were produced by self-pollination of individual selected lines. The rol-genes were inherited to the progeny and the presence of rol-genes was confirmed in all F1 and many F2 plant lines exhibiting dwarfism. Screening of F1 and F2 plants showed that the rol-genes were inherited together. Besides decreased plant height, several F1 and F2 lines containing rol-genes exhibited changes in plant diameter, number of branches, flower diameter and time to first open flower and duration of flowering compared to the WT ‘Molly’. Furthermore, increased ethylene tolerance was observed in several lines containing rol-genes compared to the WT ‘Sarah’. Screening of three selected F2 populations derived from self-pollination of F1 lines containing rol-genes indicated a shift in distribution towards a lower mean plant height within the entire plant population compared to a control population of plants without rol-genes. Moreover, one of these F2 populations also exhibited earlier flowering compared to the control population. Compact potted plants and lines without delayed flowering and with improved ethylene tolerance were obtained and are valuable in commercial breeding programmes without using recombinant DNA technology.     

Effect of nutritional supplementation upon pregnancy rates of goats under semiarid rangelands and exposed to the male effect

The aim of this study was to evaluate possible effects of improved protein and energy diet upon reproductive outcomes of adult goats under marginal rangeland grazing conditions and exposed to the male effect during the anoestrous-dry season. Adult goats (Nubian × Criollo, nonpregnant, nonlactating, n?=?160, 22° 50' N, 100° 59' W, 1,653?m) were randomly divided in two experimental groups: Control (CG; n?=?80) and Supplemented (SG; n?=?80). Both CG and SG goats were kept together during the day for ranging a semiarid rangeland while separated accordingly at night. SG goats were individually supplemented [400?g?kg(-1)?day(-1)?; 14% CP and 2.92 Mcal DE kg(-1)] during a 30-day period. Thereafter, both the CG [35.5?±?0.94?kg LW, 1.95?±?0.06 U, body condition score (BCS)] and the SG [39.5?±?0.94?kg LW, 2.29?±?0.06 BCS] were exposed to adult males (Nubian, n?=?4, two per group) of proven libido and fertility and kept together at night (1700-0900) during a 42-day experimental breeding period. At the beginning of the breeding period, both LW (P??0.05), respectively. Results suggest that nutritional supplementation and the male effect were able to successfully invoke neurophysiological pathways to increase ovarian activity and to promote a uterine milieu prone to the establishment of pregnancy during the anoestrus season. However, the increased abortion rates observed in the study occurred irrespective of the nutritional regime offered during the premating stage. Therefore, there is a need to align the last third of gestation to the onset of the grazing season in order to increase reproductive and economic efficiency in those rangeland-based marginal goat production systems.