Nitric oxide determines the development of actinomycetoma by Nocardia brasiliensis in eNOS knockout C57BL/6 mice.

Mycetoma is a chronic human infectious disease that produces severe deformation frequently in the lower extremities. Etiological agents include fungi (eumycetoma) and bacteria (actinomycetoma) that produce similar clinical and microscopic changes. The clinical appearance includes swelling, abscesses, ulcers, scars and sinuses that drain purulent material with microbe microcolonies. The pathogenesis of actinomycetoma has been studied mainly in rodents. Using this approach, it was found that Nocardia brasiliensis produces proteases that may play a role in tissue damage, as well as immunosuppressive molecules, such as brasilicardin A. Nitric oxide (NO) is a molecule with biological activities depending on its local concentration. Its effect on killing intracellular bacteria such as Mycobacterium tuberculosis has been known for decades. NO plays an important role in innate and adaptive immunity. It can promote or suppress some biological activities despite its short half-ife. NO is produced by three different nitric oxide synthases (NOS). We used the genetic blockade of eNOS in C57BL/6 mice to demonstrate the role of NO in actinomycetoma development. Inflammation and actinomycetoma were prevented in genetically modified mice infected with N. brasiliensis. T cell proliferation was increased in these rodents, and antibody production, IL-6 and IL-10 expression were similar and TNF-α was lower.

Lactational transfer of PCBs and chlorinated pesticides in pups of southern elephant seals (Mirounga leonina) from Antarctica.

Seven pairs of southern elephant seals (Mirounga leonina) pups and their dams were sampled during the late weaning season among a breeding population of seals on Elephant Island in Antarctica. The blubber of the pups and the milk and blubber of their dams were analyzed for lipid-normalized concentrations of PCBs and organochlorines compounds in order to evaluate the lactational transfer of these contaminants. The lipid-normalized concentrations in these tissues were in the ppb range (i.e., ngg(-1) lipid). The levels of contaminants in southern elephant seals were low in comparison with residues that have been reported in pinnipeds from the northern hemisphere. The relative tissue concentrations of the analytes measured followed the pattern: SigmaDDT>mirex>SigmaPCB>Sigmachlordane>HCB>heptachlor epoxide>dieldrin>methoxychlor>SigmaHCH>other organochlorines. The very high DDE/SigmaDDT ratio (0.91) in the blubber of dams and pups was an indicative of long-term, extremely distant pollution. On the other hand, the relatively high levels of some other organochlorine pesticides (e.g. mirex, heptachlor epoxide, dieldrin, methoxychor) may reflect the continued use of these insecticides in developing countries located in the southern hemisphere. For most of the analytes measured, the lipid-normalized concentrations were lower in pup blubber and in the milk than in the maternal blubber. Lactational transfer rates were dependent on the logK(ow) (octanol/water partition coefficient) values of the analytes measured, less lipophilic compounds being more readily transferred to the pups by the lactational route.

Residues of persistent organochlorine contaminants in southern elephant seals (Mirounga leonina) from Elephant Island, Antarctica.

Contamination of blubber tissues by organochlorine pesticides (OC) and PCBs was assessed in female and male pups and juveniles, as well as in adult females and subdominant adult males of the Southern elephant seal, Mirounga leonina, from Elephant Island in the Antarctic Peninsula. All residues of persistent organochlorine contaminants analyzed were found in blubber samples, except for beta-HCH, endosulfan II, endrin, heptachlor, and aldrin. The relative concentrations of the analytes detected were sigmaDDT > sigmaPCB > sigmachlordane > mirex > dieldrin > HCB> sigmaendosulfan > methoxychlor > sigmaHCHs > other OC pesticides. OC and PCBs concentrations were 1 or 2 orders of magnitude lower than those found in pinnipeds from northern hemisphere. The ratio sigmaDDT/sigmaPCB was higher in southern elephant seals. The relative importance of some OC residues indicates that pesticides used either currently or in the recent past in countries in the southern hemisphere are the sources of contamination in the Antarctic region. Data showed that concentrations of contaminants generally increased from pups < juveniles < adults and suggested that pups accumulated contaminants through transfer from the mother seals via transplacental and lactational routes.

Pollution biomarkers in estuarine animals: critical review and new perspectives.

In this review, recent developments in monitoring toxicological responses in estuarine animals are analyzed, considering the biomarker responses to different classes of pollutants. The estuarine environment imposes stressful conditions to the organisms that inhabit it, and this situation can alter their sensitivity to many pollutants. The specificity of some biomarkers like metallothionein tissue concentration is discussed in virtue of its dependence on salinity, which is highly variable in estuaries. Examples of cholinesterase activity measurements are also provided and criteria to select sensitive enzymes to detect pesticides and toxins are discussed. Regarding non-specific biomarkers, toxic responses in terms of antioxidant defenses and/or oxidative damage are also considered in this review, focusing on invertebrate species. In addition, the presence of an antioxidant gradient along the body of the estuarine polychaete Laeonereis acuta (Nereididae) and its relationship to different strategies, which deal with the generation of oxidative stress, is reviewed. Also, unusual antioxidant defenses against environmental pro-oxidants are discussed, including the mucus secreted by L. acuta. Disruption of osmoregulation by pollutants is of paramount importance in several estuarine species. In some cases such as in the estuarine crab Chasmagnathus granulatus, there is a trade off between bioavailability of toxicants (e.g. metals) and their interaction with key enzymes such as Na(+)-K(+)-ATPase and carbonic anhydrase. Thus, the metal effect on osmoregulation is also discussed in the present review. Finally, field case studies with fish species like the croaker Micropogonias furnieri (Scianidae) are used to illustrate the application of DNA damage and immunosuppressive responses as potential biomarkers of complex mixture of pollutants.

Serum immunoglobulin G concentration in Southern elephant seal, Mirounga leonina (Linnaeus, 1758), from Elephant Island (Antarctica): sexual and adrenal steroid hormones effects.

Serum immunoglobulin G (IgG; indirect enzyme-linked immunosorbent assay), as well as sexual and adrenal steroid hormones' concentrations (radioimmunoassay) were determined in 63 (male and female) Southern elephant seals (Mirounga leonine) at different developmental stages (weaned pups, juveniles and adults). In females, IgG values (mean+/-S.D.) were higher (P<0.05) in adults (15.9+/-6.5mg ml(-1)) than in juveniles (7.9+/-4.0mg ml(-1)), but similar to weaned pups (12.0+/-5.0mg ml(-1)). Estrogen concentration was higher (P<0.05) in adults than in the weaned pups. In females, a significant (P<0.05) correlation (R=0.4) between serum IgG level and progesterone concentration was observed. In males, testosterone concentration was higher (P<0.05) in adults than in the juveniles and weaned pups. Aldosterone and cortisol concentrations were higher (P<0.05) in weaned pups (1056.0+/-643.1pmol 1(-1) and 272.7+/-110.0 nmol 1(-1), respectively) than in the juveniles (638.6+/-579.7pmol1(-1) and 152.9+/-97.3nmol 1(-1), respectively) and adults (386.5+/-209.1pmol (-1) and 145.7+/-67.3nmol 1(-1), respectively). These findings indicate that weaned pups are subjected to a higher natural stressful condition in the field. Despite this, humoral immunity, measured through IgG concentration, is not impaired in weaned pups.

The effects of aging on leukocyte glucocorticoid receptor concentration and response to dexamethasone in dogs.

Glucocorticoid receptor concentration (GR) was determined in mononuclear (MNS) and polymorphonuclear (PMNS) cells isolated from 8 aged and 9 young male dogs. In addition, leukocyte responses to dexamethasone (0.1 mg kg(-1) i.v.) and plasma glucose concentration were also measured. The GR in MNS and PMNS was higher (p<0.05) in young dogs (6.64 +/- 0.57 and 7.04 +/- 0.29 fmolesx10(6) cells, respectively, versus 4.40 +/- 0.24 and 5.06 +/- 0.33 fmolesx10(6) cells, respectively, in aged dogs). The maximum increase in neutrophils (DeltaNEU) was lower (p<0.05) in aged dogs 6003.38 +/- 1398.5x10(6) versus 11168.67 +/- 1863.16x10(6) cells l(-1) in young dogs. The maximum decrease in lymphocytes (DeltaLYM) was lower (p<0.05) in aged dogs 550 +/- 56.75x10(6) cells l(-1) versus 1825.89 +/- 313.1x10(6) cells l(-1) in young dogs. In young dogs, significant (p<0.05) correlations between GR in PMNS and DeltaNEU (r=0.80) and between GR in MNS and DeltaLYM (r=0.76) were observed. In aged dogs, these correlations were not significant. The lower GR value and the lack of correlation between this parameter and its respective Delta in aged dogs suggest that changes in leukocytes responsiveness to glucocorticoids is occurring during the aging process.