Evaluation of histo-toxicity of nimesulide in Black Kites (Milvus migrans): a pharmacodynamic study.

The present experimental work was conducted to elucidate the toxicity of nimesulide at three different doses in black kites (Milvus migrans). M. migrans is one of the most common raptors near human habitations. The goal of the current investigation was to determine whether nimesulide is similarly hazardous to raptors as was diclofenac sodium and to investigate the acute oral toxicity of nimesulide in these birds. For this study, eight adult male black kites (M. migrans) were randomly divided into four groups. M. migrans in the control group (n = 02) were not treated with nimesulide. The other three groups were given nimesulide doses. The birds in the first (n = 02) were declared the control group. The second (n = 02), third (n = 02), and fourth groups were administered nimesulide at a low, medium, and high dose of 2, 4, and 6 mg/kg live body weight of bird/day, respectively, for 10 days. Nimesulide-addled birds became listless and despondent, then anorexic. The birds were standing there with their eyes closed and showing no signs of life. There was an increase in saliva production, a slowing of breathing, and dilated pupils. No clinical signs were observed in the control group. No mortality was seen in the control or treated groups. The control group did not show lesions of gout, but black kites intoxicated with nimesulide at 2, 4, and 6 mg/kg live body weight of bird/day showed inflammation, apoptosis, hemorrhage, necrosis, and leukocytic infiltration tissues of the liver, kidney, and heart of black kites (M. migrans) treated with different concentrations of nimesulide. The treated groups also showed apoptosis of myofibrils and hyperplasia. The hypertrophy, atrophy, fibrosis, necrosis of skeletal muscles and hemorrhage were prominent in the muscles of black kites (M. migrans) intoxicated with nimesulide. All observed histological alterations got worse in a dose-related way. There was no significant difference in AST, ALT, ALP, serum uric acid, but a significant difference was observed in the values of serum urea (p = 0.001) and serum creatinine (p = 0.019).

HEMATOLOGY AND PLASMA BIOCHEMISTRY REFERENCE INTERVALS FOR FREE-LIVING ADULT CHIMANGO CARACARA (MILVAGO CHIMANGO) DURING THE NONBREEDING SEASON.

Hematological and blood biochemistry values are useful in assessing the physiological, nutritional, and overall health status of captive and free-living wildlife. For the chimango caracara (Milvago chimango), the most common raptor species in Argentina, reference intervals (RIs) for hematology and blood biochemistry are lacking. For this study, 86 chimango caracaras were captured and studied in Mar del Plata and neighboring areas (Buenos Aires, Argentina) during winter (April-July) in 2018 and 2019. This is the first study to present RIs for 33 blood parameters in a large number of free-living chimango caracaras during the nonbreeding season. In addition, the variability of blood parameters according to sex and calendar year was analyzed. Overall, values for the studied parameters were similar to those described for other raptor species. There were significant differences between years for absolute monocyte counts, relative eosinophils, monocyte counts, glucose, phosphorus, and alanine aminotransferase. Only the relative count of eosinophils, aspartate aminotransferase, and calcium showed significant differences between the sexes. The values of absolute monocyte counts and the relative count of eosinophils and monocytes, glucose, phosphorus, and alanine aminotransferase were higher in 2019 than in 2018, whereas mean corpuscular hemoglobin and mean corpuscular hemoglobin concentration were higher in 2018. Relative eosinophil counts were higher for males than for females, and aspartate aminotransferase activity and calcium concentration were significantly higher for females than for males. The RIs for hematology and plasma biochemistry from this large number of chimango caracaras is of clinical relevance not only for chimango caracaras under medical care in rehabilitation centers but also in ecological studies aimed to investigate the physiological responses of this species to natural and anthropogenic changes.

The importance of in-year seasonal fluctuations for biomonitoring of apex predators: A case study of 14 essential and non-essential elements in the liver of the common buzzard (Buteobuteo) in the United Kingdom.

Trace elements are chemical contaminants spread in the environment by anthropogenic activities and threaten wildlife and human health. Many studies have investigated this contamination in apex raptors as sentinel birds. However, there is limited data for long-term biomonitoring of multiple trace elements in raptors. In the present study, we measured the concentrations of 14 essential and non-essential trace elements in the livers of the common buzzard (Buteo buteo) collected in the United Kingdom from 2001 to 2019 and investigated whether concentrations have changed during this period. In addition, we estimated the importance of selected variables for modelling element accumulations in tissues. Except for cadmium, hepatic concentrations of harmful elements in most buzzards were lower than the biological significance level of each element. Hepatic concentrations of certain elements, including lead, cadmium, and arsenic, varied markedly seasonally within years. Their peak was in late winter and trough in late summer, except copper which showed an opposite seasonal pattern. In addition, lead in the liver consistently increased over time, whereas strontium showed a decreasing trend. Hepatic concentrations of cadmium, mercury, and chromium increased with age, whereas selenium and chromium were influenced by sex. Hepatic concentrations of arsenic and chromium also differed between different regions. Overall, our samples showed a low risk of harmful effects of most elements compared to the thresholds reported in the literature. Seasonal fluctuation was an important descriptor of exposure, which might be related to the diet of the buzzard, the ecology of their prey, and human activities such as the use of lead shot for hunting. However, elucidating reasons for these observed trends needs further examination, and biomonitoring studies exploring the effects of variables such as age, sex, and seasonality are required.

Knockdown of regulatory associated protein of TOR (raptor) in hypothalamus-stimulated folliculogenesis and induced ovarian cysts.

CONTEXT: Mammalian target of rapamycin complex 1 (mTORC1) is an essential sensor that regulates fundamental biological processes like cell growth, proliferation and energy metabolism. The treatment of disease by sirolimus, a mTORC1 inhibitor, causes adverse effects, such as female fertility disorders. AIMS: The objective of the study was to decipher the reproductive consequences of a downregulation of mTORC1 in the hypothalamus. METHODS: The reduced expression of mTORC1 was induced after intracerebroventricular injection of lentivirus expressing a short hairpin RNA (shRNA) against regulatory associated protein of TOR (raptor) in adult female mice (ShRaptor mice). KEY RESULTS: The ShRaptor mice were fertile and exhibited a 15% increase in the litter size compared with control mice. The histological analysis showed an increase in antral, preovulatory follicles and ovarian cysts. In the hypothalamus, the GnRH mRNA and FSH levels in ShRaptor mice were significantly elevated. CONCLUSIONS: These results support the hypothesis that mTORC1 in the central nervous system participates in the regulation of female fertility and ovarian function by influencing the GnRH neuronal activity. IMPLICATIONS: These results suggest that a lower mTORC1 activity directly the central nervous system leads to a deregulation in the oestrous cycle and an induction of ovarian cyst development.

Method to assess the potential magnitude of terrestrial European avian population reductions from ingestion of lead ammunition.

Current estimates of terrestrial bird losses across Europe from ingestion of lead ammunition are based on uncertain or generic assumptions. A method is needed to develop defensible European-specific estimates compatible with available data that does not require long-term field studies. We propose a 2-step method using carcass data and population models. The method estimates percentage of deaths diagnosed as directly caused by lead poisoning as a lower bound and, as an upper bound, the percentage of possible deaths from sublethal lead poisoning that weakens birds, making them susceptible to death by other causes. We use these estimates to modify known population-level annual mortality. Our method also allows for potential reductions in reproduction from lead shot ingestion because reductions in survival and reproduction are entered into population models of species with life histories representative of the most groups of susceptible species. The models estimate the sustainability and potential population decreases from lead poisoning in Europe. Using the best available data, we demonstrate the method on two taxonomic groups of birds: gallinaceous birds and diurnal raptors. The direction of the population trends affects the estimate, and we incorporated such trends into the method. Our midpoint estimates of the reduction in population size of the European gallinaceous bird (< 2%) group and raptor group (2.9-7.7%) depend on the species life history, maximum growth rate, population trend, and if reproduction is assumed to be reduced. Our estimates can be refined as more information becomes available in countries with data gaps. We advocate use of this method to improve upon or supplement approaches currently being used. As we demonstrate, the method also can be applied to individual species of concern if enough data across countries are available.

Ursolic acid inhibits leucine-stimulated mTORC1 signaling by suppressing mTOR localization to lysosome.

Ursolic acid (UA), a pentacyclic triterpenoid widely found in medicinal herbs and fruits, has been reported to possess a wide range of beneficial properties including anti-hyperglycemia, anti-obesity, and anti-cancer. However, the molecular mechanisms underlying the action of UA remain largely unknown. Here we show that UA inhibits leucine-induced activation of the mechanistic target of rapamycin complex 1 (mTORC1) signaling pathway in C2C12 myotubes. The UA-mediated inhibition of mTORC1 is independent of Akt, tuberous sclerosis complex 1/2 (TSC1/2), and Ras homolog enriched in brain (Rheb), suggesting that UA negatively regulates mTORC1 signaling by targeting at a site downstream of these mTOR regulators. UA treatment had no effect on the interaction between mTOR and its activator Raptor or inhibitor Deptor, but suppressed the binding of RagB to Raptor and inhibited leucine-induced mTOR lysosomal localization. Taken together, our study identifies UA as a direct negative regulator of the mTORC1 signaling pathway and suggests a novel mechanism by which UA exerts its beneficial function.

Blood chemistry and hematologic values in free-living nestlings of Montagu's harriers (Circus pygargus) in a natural habitat.

The establishment of reference intervals for hematologic and blood chemistry values in a given species is essential for subsequent diagnosis of disease at rehabilitation facilities and in captive breeding programs. In this study, blood samples were obtained from nestlings (18 males and 22 females) of a natural-vegetation breeding population of Montagu's harrier (Circus pygargus) in eastern Spain in order to establish reference intervals for blood values. This is the first study documenting hematologic and biochemical reference intervals for free-living Montagu's harriers. The studied population may reflect typical blood values for the species, since it is a free-living population that seems not to be constrained by food availability, as it is the population of Montagu's harriers with the highest productivity within Europe. Differences related to sex, year, clutch size, brood size, and number of fledglings were analyzed. Packed cell volume and hemoglobin were significantly lower from nests with five chicks compared to values from nests with fewer chicks, indicating that the cost of rearing more than four chicks in this species may be excessive. Total protein, calcium (Ca), and phosphorus (P) were significantly lower in the year with lowest mean rainfall, which correlates with the worst breeding success rate since the population has been monitored. No gender differences were found; this is likely a result of the prepubertal age of the animals sampled.

The tail feathers of osprey nestlings (Pandion haliaetus L.) as indicators of change in mercury load in the environment of southern Sweden (1969-1998): a case study with a note on the simultaneous intake of selenium.

The tail feathers of 104 osprey nestlings (Pandion haliaetus) from Lake Asnen, southern Sweden, were analyzed for total mercury and selenium content. Concentrations of mercury in feathers from the western part of the lake fell during the period 1969-1998, when pollution from industrial mercury had decreased and a paper mill upstream of the lake was closed down in 1979. Nestlings from the eastern part of the lake had initially lower levels of mercury, predominantly from atmospheric fallout. The levels did not decrease during the period. The reason for the differences seems to be the limited water flow between the western and the eastern part of the lake. The selenium concentrations were constant over time and approximately the same in both parts of the lake. The total-Hg/Se ratio in the western part of the lake was 2.94, which is somewhat higher than the 1:1 molar ratio constant (2.54). This indicates that the bioaccumulated quantity of selenium which is thought to be protective for the organisms against the toxic effects of mercury, is somewhat insufficient to bind all body mercury.

Environmental contaminants in prey and tissues of the peregrine falcon in the Big Bend Region, Texas, USA.

Peregrine falcons (Falco peregrinus) have been recorded nesting in Big Bend National Park, Texas, USA and other areas of the Chihuahuan Desert since the early 1900s. From 1993 to 1996, peregrine falcon productivity rates were very low and coincided with periods of low rainfall. However, low productivity also was suspected to be caused by environmental contaminants. To evaluate potential impacts of contaminants on peregrine falcon populations, likely avian and bat prey species were collected during 1994 and 1997 breeding seasons in selected regions of western Texas, primarily in Big Bend National Park. Tissues of three peregrine falcons found injured or dead and feathers of one live fledgling also were analyzed. Overall, mean concentrations of DDE [1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene], a metabolite of DDT [1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane], were low in all prey species except for northern rough-winged swallows (Stelgidopteryx serripennis, mean = 5.1 microg/g ww). Concentrations of mercury and selenium were elevated in some species, up to 2.5 microg/g dw, and 15 microg/g dw, respectively, which upon consumption could seriously affect reproduction of top predators. DDE levels near 5 microg/g ww were detected in carcass of one peregrine falcon found dead but the cause of death was unknown. Mercury, selenium, and DDE to some extent, may be contributing to low reproductive rates of peregrine falcons in the Big Bend region.

Body condition effects in American kestrels fed selenomethionine.

Body composition was measured in male American kestrels (Falco sparverius) beginning after a 77-day exposure to 0, 6, or 12 ppm (dry wt.) selenium as seleno-L-methionine in their diet. Total body mass, lean body mass, and body fat were compared among groups to identify potential wasting effects of selenium, as had been reported for wild waterfowl from a selenium-contaminated site. On the last day of selenium treatment, selenium concentrations in the blood of kestrels was significantly negatively correlated with lean mass. Kestrels that had been exposed to 12 ppm selenium in the diet exhibited relatively higher lean mass (relative to total body mass) and lower normalized body fat than kestrels fed 0 or 6 ppm dietary selenium. These differences persisted throughout the 6 mo study period. The effect observed on body condition of kestrels at environmentally relevant exposure levels has implications for wild birds with respect to both overwinter survival and reproductive success.