Investigation of the direct effects of salmon calcitonin on human osteoarthritic chondrocytes

<p>Abstract</p> <p>Background</p> <p>Calcitonin has been demonstrated to have chondroprotective effects under pre-clinical settings. It is debated whether this effect is mediated through subchondral-bone, directly on cartilage or both in combination. We investigated possible direct effects of salmon calcitonin on proteoglycans and collagen-type-II synthesis in osteoarthritic (OA) cartilage.</p> <p>Methods</p> <p>Human OA cartilage explants were cultured with salmon calcitonin [100 pM-100 nM]. Direct effects of calcitonin on articular cartilage were evaluated by 1) measurement of proteoglycan synthesis by incorporation of radioactive labeled ³⁵SO₄[5 μCi] 2) quantification of collagen-type-II formation by pro-peptides of collagen type II (PIINP) ELISA, 3) QPCR expression of the calcitonin receptor in OA chondrocytes using four individual primer pairs, 4) activation of the cAMP signaling pathway by EIA and, 5) investigations of metabolic activity by AlamarBlue.</p> <p>Results</p> <p>QPCR analysis and subsequent sequencing confirmed expression of the calcitonin receptor in human chondrocytes. All doses of salmon calcitonin significantly elevated cAMP levels (P < 0.01 and P < 0.001). Calcitonin significantly and concentration-dependently [100 pM-100 nM] induced proteoglycan synthesis measured by radioactive ³⁵SO₄incorporation, with a 96% maximal induction at 10 nM (P < 0.001) corresponding to an 80% induction of 100 ng/ml IGF, (P < 0.05). In alignment with calcitonin treatments [100 pM-100 nM] resulted in 35% (P < 0.01) increased PIINP levels.</p> <p>Conclusion</p> <p>Calcitonin treatment increased proteoglycan and collagen synthesis in human OA cartilage. In addition to its well-established effect on subchondral bone, calcitonin may prove beneficial to the management of joint diseases through direct effects on chondrocytes.</p

Emerging Technologies for the Detection of Rabies Virus: Challenges and Hopes in the 21st Century

The diagnosis of rabies is routinely based on clinical and epidemiological information, especially when exposures are reported in rabies-endemic countries. Diagnostic tests using conventional assays that appear to be negative, even when undertaken late in the disease and despite the clinical diagnosis, have a tendency, at times, to be unreliable. These tests are rarely optimal and entirely dependent on the nature and quality of the sample supplied. In the course of the past three decades, the application of molecular biology has aided in the development of tests that result in a more rapid detection of rabies virus. These tests enable viral strain identification from clinical specimens. Currently, there are a number of molecular tests that can be used to complement conventional tests in rabies diagnosis. Indeed the challenges in the 21st century for the development of rabies diagnostics are not of a technical nature; these tests are available now. The challenges in the 21st century for diagnostic test developers are two-fold: firstly, to achieve internationally accepted validation of a test that will then lead to its acceptance by organisations globally. Secondly, the areas of the world where such tests are needed are mainly in developing regions where financial and logistical barriers prevent their implementation. Although developing countries with a poor healthcare infrastructure recognise that molecular-based diagnostic assays will be unaffordable for routine use, the cost/benefit ratio should still be measured. Adoption of rapid and affordable rabies diagnostic tests for use in developing countries highlights the importance of sharing and transferring technology through laboratory twinning between the developed and the developing countries. Importantly for developing countries, the benefit of molecular methods as tools is the capability for a differential diagnosis of human diseases that present with similar clinical symptoms. Antemortem testing for human rabies is now possible using molecular techniques. These barriers are not insurmountable and it is our expectation that if such tests are accepted and implemented where they are most needed, they will provide substantial improvements for rabies diagnosis and surveillance. The advent of molecular biology and new technological initiatives that combine advances in biology with other disciplines will support the development of techniques capable of high throughput testing with a low turnaround time for rabies diagnosis

The mammals of Angola

Scientific investigations on the mammals of Angola started over 150 years ago, but information remains scarce and scattered, with only one recent published account. Here we provide a synthesis of the mammals of Angola based on a thorough survey of primary and grey literature, as well as recent unpublished records. We present a short history of mammal research, and provide brief information on each species known to occur in the country. Particular attention is given to endemic and near endemic species. We also provide a zoogeographic outline and information on the conservation of Angolan mammals. We found confirmed records for 291 native species, most of which from the orders Rodentia (85), Chiroptera (73), Carnivora (39), and Cetartiodactyla (33). There is a large number of endemic and near endemic species, most of which are rodents or bats. The large diversity of species is favoured by the wide range of habitats with contrasting environmental conditions, while endemism tends to be associated with unique physiographic settings such as the Angolan Escarpment. The mammal fauna of Angola includes 2 Critically Endangered, 2 Endangered, 11 Vulnerable, and 14 Near-Threatened species at the global scale. There are also 12 data deficient species, most of which are endemics or near endemics to the countryinfo:eu-repo/semantics/publishedVersio

Predictors of diastolic dysfunction in ethnic groups : observations from the Hypertensive Cohort of The Ethnic-Echocardiographic Heart of England Screening Study (E-ECHOES)

The study aimed to establish a relationship of ethnicity to diastolic dysfunction in subjects of African-Caribbean and South Asian origins and the impact of diastolic dysfunction and ethnicity on all-cause and cardiovascular mortality. Hypertensive subjects with ejection fraction ≥55% and no history of ischaemic heart disease/valve pathology (n  =  1546, 830 South Asians and 716 African-Caribbeans) were identified from the Ethnic-Echocardiographic Heart of England Screening Study (E-ECHOES). Diastolic function and cardiac remodelling were measured by echocardiography. African-Caribbean ethnicity was associated with lower prevalence of having diastolic dysfunction (odds ratio 0.67, 95% confidence interval 0.51–0.87, p  =  0.003) and increased left ventricular filling pressure (odds ratio 0.48, 95% confidence interval 0.34–0.69, p <  0.001) as well as lower left atrial index (p  <  0.001). This was the case despite the fact that African-Caribbean ethnicity was independently associated with higher left ventricular mass index (p   < 0.001). Ninety-two deaths (6%) occurred during 68  ±  21 months follow-up. On Cox regression analysis, South Asian ethnicity (p  =  0.024) was predictive of all-cause death before adjustment for parameters of diastolic dysfunction, but it was no longer predictive of death after accounting for these variables. South Asian ethnicity is independently associated with worse parameters of diastolic function in hypertension, despite African-Caribbeans having more prominent hypertrophy