Clinical improvement in feline herpesvirus 1 infected cats by oral low dose of interleukin-12 plus interferon-gamma.

Feline herpesvirus 1 (FHV-1) is a widespread cat pathogen inducing rhinitis, conjunctivitis and corneal ulcers. To alleviate acute FHV-1-induced disease, antiviral agents are used often with antibiotics. But sometimes, these treatments, as well as conventional doses of cytokines have moderate efficacy and/or collateral effects. Herein we have investigated the effects of low dose interleukin (IL)-12 plus interferon (IFN)-gamma, prepared by Sequential Kinetic Activated (SKA), on the treatment of FHV-1 infection. Twenty-five, unvaccinated FHV-1-positive cats were recruited into a prospective, randomized, placebo-controlled, double-blinded clinical trial. Fifteen cats were treated for 6 months with oral low doses of SKA IL-12 plus IFN-gamma and 10 cats were treated with placebo. At 1, 6 and 12 months (follow-up) after the beginning of treatment, clinical assessment, PCR assay and blood count were carried out. At follow-up, in treated group, we observed significant (p<0.05) improvements in clinical signs and PCR became negative in 12/15 cats (80%). In placebo, 10/10 cats were PCR-positive, with improvements (30%) or worsening (70%) in clinical signs. Blood values were normal in both groups. Our results show that the low dose therapy, based on activated solutions of IL-12 plus IFN-gamma, represents a novel approach to treat FHV-1 infection in cats.

Chronic maternal morphine alters calbindin D-28k expression pattern in postnatal mouse brain.

The distribution pattern of calbindin (CB)-D28k-expressing neurons results to be altered in several brain regions of chronic morphine exposed adult mice. In this study, the influence of chronic maternal exposure to morphine on the distribution pattern of CB-D28k-expressing neurons in the brain of mouse offspring was investigated. Females of CD-1 mice were daily administered with saline or morphine for 7 days before mating, during the whole gestation period, and until 21 day post-partum. Their offspring were sacrificed on postnatal day 18, and the brains were examined by histology using cresyl violet and by immunohistochemistry using a rabbit polyclonal anti-CB-D28k antibody. Histology revealed no significant differences in the distribution pattern and the number of neurons between the offspring forebrain of the control group of mice and the two groups of mice treated with different doses of morphine. However, immunohistochemical analysis revealed that the number of CB-D28k-immunoreactive neurons remarkably decreased in the cingulate cortex, in the layers II-IV of the parietal cortex and in all regions of the hippocampus, while it increased in the layers V-VI of the parietal cortex and in the subicular region of the offspring brain of morphine treated mice. Overall, our findings demonstrate that maternal exposure to morphine alters the pattern of CB-D28k-expressing neuron pattern in specific regions of murine developing brain, in a layer- and dose-dependent way, thus suggesting that these alterations might represent a mechanism by which morphine modifies the functional aspects of developing brain.

Coloration and defense in the nudibranch gastropod Hypselodoris fontandraui.

The striking color patterns of chromodorid (and other) nudibranchs appear to be indicative of aposematism. In Müllerian mimicry, all the mimic species have a defense mechanism. It has been proposed that a group of blue, white, and yellow Mediterranean and northeastern Atlantic species of the genus Hypselodoris form a Müllerian mimetic circle. One of these, H. fontandraui, lacks the mantle dermal formations (repugnatorial glands) that are typically found in other members of this circle and are reservoirs of feeding deterrent compounds. It therefore seemed possible that this animal lacks chemical defense and acts like a Batesian mimic. Within this study, we found that this nudibranch contains the furanosesquiterpenoid tavacpallescensin, most probably derived from sponges of the genus Dysidea, upon which it probably feeds. The metabolite concentrations were measured from samples of the mantle rim, other external parts, and internal organs. Concentrations were about 4 times higher in the mantle rim than in the other external parts, and more than 20 times higher in the mantle rim than in the internal organs, considerably exceeding the threshold value of concentration showing the maximum dose effect as feeding deterrent against the crustacean Palaemon elegans. In conclusion, the reported data clearly demonstrate that H. fontandraui is chemically defended in much the same way as its aposematic, co-occurring, and blue-colored congeners within the Müllerian mimetic circle and is not a Batesian mimic.

Fate map of serotonin transporter-expressing cells in developing mouse heart.

Serotonin regulates cardiovascular functions during embryogenesis and adulthood. However, the source of serotonin in the cardiovascular system and the role of circulating serotonin and serotonin transporter (SERT) in the regulation of cardiovascular functions are still unclear. We used a cell fate approach to map the regions of the mouse heart expressing SERT, utilizing a Cre/loxP system driven by SERT gene expression. Cell labelling was first detected at E10.5 and was mapped until E18.5. We found labelling in the outflow tract, part of right ventricle and to a very limited extent in the left ventricle. Interestingly, the distribution pattern of SERT-fated cells was remarkably similar to that obtained with markers of the second heart field lineage. In addition, we observed staining of atrioventricular valves, consistent with valvular abnormalities observed in SERT-/-animals. Overall, our data reveal specific and regionally restricted distribution of SERT-expressing cells in the developing heart of mouse.

Expression of the serotonin transporter (SERT) in the choroid plexuses from buffalo brain.

Choroid plexuses (CPs) play pivotal roles in a wide range of processes that establish, survey, and maintain the biochemical and cellular status of the central nervous system. Mammalian CPs contain a very high density of serotonin receptors, and serotonin has been shown to affect CP functions. The serotonin transporter (SERT) regulates the entire serotonergic system, including serotonin receptors by means of modulation of serotonin concentration in the extracellular fluid. In this study, the expression of SERT in the CPs from the brain of a mammalian species, Bubalis bubalis, was established. By immunogold labeling in scanning electron microscopy, SERT immunoreactivity was found to be localized on the apical surface of the choroid epithelium. In particular, SERT positivity was detected on the apical portion of villi, and both on the membrane and in the cytoplasm of grouped cells on the surface of the choroid epithelium. Significantly, no SERT was detected in blood vessels irrigating the CPs. The expression of SERT mRNA transcripts of 440 bp in the CPs was detected by reverse-transcription polymerase chain reaction, and Western blotting analysis revealed the presence of three isoforms of the protein with molecular masses of approximately 70, 80, and 140 kDa, respectively, probably corresponding to differently glycosylated SERT. Our findings provide the first report of SERT detection in the CPs of buffalo brain and indicate that this protein is locally synthesized from the choroid epithelial cells. We suggest that SERT might have an important role in mammalian CPs, possibly regulating the serotonin flow between brain and rest of the body.