Transdermal Pharmacology of Small Molecule Cyclic C5a Antagonists

Overproduction or underregulation of the proinflammatory complement component C5a has been implicated in numerous immune and inflammatory conditions. Therefore, targeting the C5a receptor (C5aR) has become an innovative strategy for antiinflammatory drug development. The novel cyclic peptide C5aR antagonist, AcF-[OP(D-Cha)WR] (PMX53), attenuates injury in numerous animal models of inflammation following intravenous, subcutaneous, intraperitoneal, and oral administration. In the present study the transdermal pharmacology of PMX53 and three analogs designed with increased lipophilicity, hydrocinnamate-[OP(D-Cha)WCit] (PMX200), AcF-[OP(D-Cha)WCit] (PMX201) and hydrocinnamate-[OP(D-Cha)WR] (PMX205), have been examined in order to assess their transdermal permeability and inhibitory effect on C5a-mediated lipopolysaccharide (LPS)-induced systemic responses. In the rat, PMX53, PMX201, and PMX205, were bioavailable following topical dermal administration (10 mg/50 cm(2) site/rat). All analogs functionally antagonized neutropenia and hypotension induced by systemic challenge with LPS (I mg/kg i.v.). Interestingly, PMX200 attenuated LPS-induced neutropenia more effectively than other analogs, despite undetectable (< 5 ng/ml) circulating levels following topical administration. In conclusion, we have demonstrated that cyclic peptide C5aR antagonists can penetrate transdermally sufficiently to have systemic effects. However, increasing lipophilicity in these compounds did not result in increased blood levels. Nonetheless, topical application of C5aR antagonists produced circulating levels of the drugs that antagonized the LPS-induced systemic responses of neutropenia and hypotension. This suggests that these small-molecule C5aR antagonists may be developed for topical administration for the treatment of local and systemic inflammatory conditions in the human and veterinary pharmaceutical markets.

Genetic diversity among Toxoplasma gondii isolates of small ruminants from Brazil: Novel genotypes revealed

Recent studies indicated that Toxoplasma gondii isolates of many domestic animal hosts from Brazil are genetically and biologically different from those in USA and Europe. Despite of high pathogenicity of this parasite to small ruminants, the epidemiology and genetic diversity of T. gondii in these animals are not well understood in Brazil. In this study, a total of 28 T. gondii samples (16 isolates from sheep in Sao Paulo state, and 12 isolates from goats in the states of Sao Paulo and Rio Grande do Norte) were genotyped using genetic markers SAG1, SAG2, SAG3, BTUB, CRAG, c22-8, c29-2, L358, PK1, Apico and CS3. Eleven genotypes were identified from these T. gondii isolates. Eight isolates (4 from sheep and 4 from goats) were grouped into the common clonal type Brl lineage. One sheep isolate was grouped to the type BrIII lineage. Five isolates grouped to three previously identified genotypes in Brazil, and 13 isolates grouped to six novel genotypes. Mixed genotype was found in one isolate from goat in Sao Paulo. No classical clonal Type I. II or III isolates were found, confirming previous reports that these clonal lineages are rare in Brazil. The allele types at the CS3 locus are strongly linked to mouse virulence of the parasite. The results of this study indicate that even though a large number of T. gondii genotypes have been identified from a variety of animal hosts in Brazil, high percentage of new genotypes are continuously identified from different animal species, suggesting extremely high diversity of T. gondii in the population. (C) 2010 Elsevier B.V. All rights reserved.

Gender, marital status, farm size and other factors influencing the extent of cash cropping in Kenya: A case study

This article examines the effects of commercialisation of agriculture on land use and work patterns by means of a case study in the Nyeri district in Kenya. The study uses cross sectional data collected from small-scale farmers in this district. We find that good quality land is allocated to non-food cash crops, which may lead to a reduction in non-cash food crops and expose some households to greater risks of possible famine. Also the proportion of land allocated to food crops declines as the farm size increases while the proportion of land allocated to non-food cash crops rises as the size of farm increases. Cash crops are also not bringing in as much revenue commensurate with the amount of land allocated to them. With growing commercialisation, women still work more hours than men. They not only work on non-cash food crops but also on cash crops including non-food cash crops. Evidence indicates that women living with husbands work longer hours than those married but living alone, and also longer than the unmarried women. Married women seem to lose their decision-making ability with growth of commercialisation, as husbands make most decisions to do with cash crops. Furthermore husbands appropriate family cash income. Husbands are less likely to use such income for the welfare of the family compared to wives due to different expenditure patterns. Married women in Kenya also have little or no power to change the way land is allocated between food and non-food cash crops. Due to deteriorating terms of trade for non-food cash crops, men have started cultivation of food cash crops with the potential of crowding out women. It is found that both the area of non-cash crops tends to rise with farm size but also the proportion of the farm area cash cropped rises in Central Kenya.

Collection and evaluation of semen from the three-toed sloth (Bradypus tridactylus)

Sloths (Bradypus sp.) are extremely sensitive animals that suffer with the destruction and fragmentation of forests. They present a low population growth rate and need to be further studied for the preservation of the specie. Thus, the aim of this study was to establish an efficient semen collection protocol as well as characterize sperm concentration, motility and morphology in order to contribute with information about the reproductive traits of this specie, which has never been described in the literature before. For that, nine Bradypus tridactylus males were captured during the wet season and six during the dry season, in Manaus (AM), located in the north region of Brazil, semen was collected by electroejaculation with shocks given in sequences of progressive intensities (minimum 20 mA and maximum 60 mA). All animals ejaculated small volumes of semen and in some of them, the volume ejaculated was not enough for a complete spermiogram. Physical characteristics observed on the collections of the wet season were different from those seen in the specimen collected in the dry season. Motility an vigor was very low and did not show forward progression, only oscillatory movement. After Spermac stain, spermatozoa presented a wide variety of defects; however, the differences in morphology were not significant between seasons. The morphology assessed by scanning electron microscopy shows that the head in both groups could be elongated, short or could have a base narrower than the apex and the midpiece narrowed abruptly, forming a nip in its transition to the tail. Although further studies are necessary to verify our preliminary findings concerning seasonal variation in sperm quality, these results demonstrate that semen can be safely collected from sloths by electroejaculation and provide the first reports of semen characteristics in this species. (C) 2008 Elsevier Ltd. All rights reserved.

Detection of Horizontal Root Fracture with Small-volume Cone-Beam Computed Tomography in the Presence and Absence of Intracanal Metallic Post

Introduction: The aim of the present study was to test the accuracy of small-volume cone-beam computed tomography (CBCT) scanning in the detection of horizontal root fractures and to assess the influence of a metallic post. Methods: Forty teeth were divided into four groups based on the presence of metallic posts and horizontal root fracture. The teeth were examined by small-volume CBCT scanning at 0.2-mm voxel resolution. Three observers analyzed the samples for the presence of a horizontal root fracture. Sensitivity and specificity were calculated. Results: High values for accuracy (73%-88%) were obtained in the groups without a metallic post, and statistically significant differences were found when the group with a metallic post has been observed (55%-70%). Intraobserver agreement also showed statistically significant differences in the groups with a metallic post. Conclusions: Small-volume CBCT scanning showed high accuracy in detecting horizontal root fracture without a metallic post. However, the presence of a metallic post significantly reduced the specificity and sensitivity of this examination. (J Endod 2011;37:1456-1459)

Willingness of Sri Lankan farmers to pay for a scheme to conserve elephants: An empirical analysis

This paper explores the feasibility of adopting an integrated economic approach to raise farmers’ tolerance of the presence of elephants on their farming lands. Responses to this approach were sought from a sample of farmers in the areas affected by human elephant conflict in the northwestern province of Sri Lanka. Results from a contingent valuation survey of their willingness to pay for a scheme to conserve elephants are also reported. Two separate logit regression analyses were undertaken to examine the factors that influence the farmers’ responses for the payment principle question and their opinions on the integrated economic approach. Although found that the majority of the respondents expressed their willingness to pay for the proposed scheme and supported for the implementation of the integrated approach, we have insufficient data yet to determine if their support and financial contribution would be sufficient to set up this programme and also to predict its economic viability. Nevertheless, the overall finding of this study provides an improved economic assessment of the farmers’ attitudes towards the wild elephant in Sri Lanka. At the same time the study shows that, contrary to commonly held assumptions, farmers in this developing country, do support wildlife conservation.

Wildlife damage, insurance/compensation for farmers and conservation: Sri Lankan elephants as a case

The interference with agriculture has been recognised as the main cause for the current conflict between farmers and wild elephants in Sri Lanka, as elsewhere in the Asian elephant range. Thus compensating farmers for the damages caused by elephants is essential, if this endangered species is to survive in the long run. This paper explores the practicality of establishing an improved publicly funded insurance/compensation scheme to recompense farmers for the elephant damages. It does so by analysing results from two contingent valuation surveys undertaken in Sri Lanka. We find that possible public support of farmers plus urban dwellers significantly exceeds the financial requirement of the insurance scheme proposed in this study for perpetuity. The article also shows that it is often inappropriate from an economic viewpoint to analyse crop insurance as if it only involves the insurance of a private good because important positive externalities can arise from ‘crop’ damages by wildlife, e.g. elephants. The use of agricultural land by some species is essential for their long-term survival and this is often positively valued by the community as a whole.

Effect of diabetes on orthodontic tooth movement in a mouse model

Orthodontic tooth movement is achieved by the remodeling of alveolar bone in response to mechanical loading. Type 1 diabetes results in bone remodeling, suggesting that this disease might affect orthodontic tooth movement. The present study investigated the effects of the diabetic state on orthodontic tooth movement. An orthodontic appliance was placed in normoglycemic (NG), streptozotocin-induced diabetes (DB), and insulin-treated DB (IT) C57BL6/J mice. Histomorphometric analysis and quantitative PCR of periodontium were performed. The DB mice exhibited greater orthodontic tooth movement and had a higher number of tartrate-resistant acid phosphate (TRAP) -positive osteoclasts than NG mice. This was associated with increased expression of factors involved in osteoclast activity and recruitment (Rankl, Csf1, Ccl2, Ccl5, and Tnfa) in DB mice. The expression of osteoblastic markers (Runx2, Ocn, Col1, and Alp) was decreased in DB mice. Reversal of the diabetic state by insulin treatment resulted in morphological findings similar to those of NG mice. These results suggest that the diabetic state up-regulates osteoclast migration and activity and down-regulates osteoblast differentiation, resulting in greater orthodontic tooth movement.

CCR5 Down-regulates Osteoclast Function in Orthodontic Tooth Movement

During orthodontic tooth movement, there is local production of chemokines and an influx of leukocytes into the periodontium. CCL5 plays an important role in osteoclast recruitment and activation. This study aimed to investigate whether the CCR5-receptor influences these events and, consequently, orthodontic tooth movement. An orthodontic appliance was placed in wild-type mice (WT) and CCR5-deficient mice (CCR5(-/-)). The expression of mediators involved in bone remodeling was evaluated in periodontal tissues by Real-time PCR. The number of TRAP-positive osteoclasts and the expression of cathepsin K, RANKL, and MMP13 were significantly higher in CCR5(-/-). Meanwhile, the expression of two osteoblastic differentiation markers, RUNX2 and osteocalcin, and that of bone resorption regulators, IL-10 and OPG, were lower in CCR5(-/-). Analysis of the data also showed that CCR5(-/-) exhibited a greater amount of tooth movement after 7 days of mechanical loading. The results suggested that CCR5 might be a down-regulator of alveolar bone resorption during orthodontic movement.

Crocodile farms and management of saltwater crocodiles in Northern Territory: Results of a survey of NT crocodile farmers plus analysis of secondary information

After outlining some relevant background information about the NT crocodile farming industry and explaining the purpose of our survey of NT crocodile farmers conducted in the first half of 2005, this paper reports the results of the survey. The information received from the survey is supplemented by secondary data and by information from secondary sources. This report covers the location of respondents; the size of crocodile farms; farmers’ stated knowledge of and attitudes towards the NT Crocodile Management Plan; the involvement of farms in the harvesting of crocodile eggs and the costs involved; views of crocodile farmers about whether the NT Crocodile Management Plan encourages landholders to conserve crocodiles and their perceptions of the benefits to landholders; predicted production trends and trends in the number of farms operating in NT; economic characteristics of crocodile farms producing in NT including the economic advantages and disadvantages of crocodile farming in NT. Concluding comments provide, amongst other things, an overview of the structure of the crocodile farming industry in the NT gleaned from a consideration of data available from the NT Government’s Department of Business, Industry and Resource Development.