Microscopic lesions and modulation of gene expression in cervical medulla during BoAHV-1and BoAHV-5 infection: A mini-review.

Bovine herpesvirus (BoAHV) types 1 and 5 are closely-related neurotropic alpha-herpesviruses. BoAHV-1 generally causes respiratory and genital disease but can occasionally cause encephalitis. BoAHV-5 is the causative agent of non suppurative meningoencephalitis in calves. During neuroinvasion, both viruses reach the central and peripheral nervous system. While brain alterations are well-described, the changes that occur in the medulla have not been fully detailed. In this work, we integrated and analyzed the virological findings, the microscopic lesions and the changes that occur in the expression of genes related to the innate immunity, cell cycle and apoptosis in the cervical medulla of calves experimentally-infected with BoAHV-1 and BoAHV-5. This will contribute to the understanding of the differential neuropathogenesis of these alpha-herpesviruses of cattle.

Infection by bovine alphaherpesvirus types 1 and 5 induces IFN-λ3 expression in neuronal-type cells and bovine neural tissues.

Type III interferons (IFNs) are components of the innate immunity, with IFN lambda- (λ)3 having the most potent bioactivity in humans. IFN-λ has a predominant role in epithelial cells. However, antiviral function in certain infections of the central nervous system has also been demonstrated. IFN-λ3 expression in neural tissues of cattle has not been investigated. Thus, the aim of this study was to analyze whether an antiviral IFN-λ3 response is mounted after infection with bovine alphaherpesviruses (BoHV-1 and BoHV-5) in vitro, in neuronal-type cells, and in neural tissues from experimentally-infected calves. This study demonstrated that there is a strong IFN-λ3 response early after BoHV-1infection of undifferentiated neuroblastoma cells. During acute BoHV-1 and BoHV-5 infection of calves, low levels of IFN-λ3 expression were detected in the brain, which would favor virus spread within this tissue. Striking differences in the transcriptional levels of IFN-λ3 were observed in trigeminal ganglion, particularly in BoHV-1-acutely- and latently-infected calves. During reactivation, IFN-λ3 expression was down-regulated, which may be a requirement for virus replication and spread. Overall, different patterns of IFN-λ3 expression were detected during BoHV-1 and BoHV-5 infection, particularly during latency.

Innate and humoral immune parameters at delivery in colostrum and calves from heifers experimentally infected with Neospora caninum.

Neospora caninum is a leading cause of abortion in cattle worldwide. The study of the immune response against N. caninum is critical to understand its epidemiology, pathogenesis, diagnosis and, ultimately, in preventing and controlling bovine neosporosis. Herein, we determined the gene expression of innate immune components endosomal RNA-sensing TLRs, BMAP28 cathelicidin, TNF-α and IL-10 and characterized the variation in both IgG ratio and avidity at delivery in N. caninum-infected heifers challenged at day 210 of gestation, colostrum and their calves. Increased BMAP28 expression was observed not only in colostrum but also in peripheral blood mononuclear cells (PBMC) and umbilical cord of calves from N. caninum-infected heifers in comparison with mock-infected control group. In addition, statistically significant decrease of TLR7 and IL-10 expression levels were observed in umbilical cord, suggesting an attempt to avoid an exacerbated immune response against the parasite. At delivery, serum and colostrum samples from infected group evidenced specific IgG anti-N. caninum. Infected heifers showed IgG1/IgG2 ratios <1 and high avidity specific IgG. As expected, colostrum samples of these animals exhibited a high IgG1 concentration and elevated avidity values. Three out of four calves from N. caninum-infected heifers had specific IgG with IgG1/IgG2 ratios>1 and lower avidity values before colostrum intake. Interestingly, both IgG1/IgG2 ratios and avidity values increased in seropositive calves after colostrum intake. Overall, this study provides novel information on neonatal immunity in congenitally infected calves, which is essential to understand how the immune pathways could be manipulated or immune components could be employed in order to improve protection against neosporosis.

Cathelicidin bovine myeloid antimicrobial peptide (BMAP) 28 is involved in the inflammatory response against alpha-herpesviruses in the bovine nervous system.

The role of the local innate immune response in the neuropathogenesis of bovine herpesvirus (BoHV) type 1 and 5 remains largely unknown. This study determined the gene transcriptional expression of relevant bovine cathelicidins, TNFα and IFNß in the nervous system of experimentally-infected cattle during the different stages of BoHV-1 and BoHV-5 infectious cycle. We studied the modulation of bovine myeloid antimicrobial peptide (BMAP) 27 and 28 by alpha-herpesviruses during acute infection of the central nervous system (CNS). However, BMAP28 was the main cathelicidin modulated. BoHV-5 supressed BMAP28 expression mainly in frontal cortex and cervical medulla whereas BoHV-1 slightly induced the expression of cathelicidins in the olfactory and posterior cortex. The differences in the regulation of the innate response are likely related to distinct replication rates of both alpha-herpesviruses in the CNS. During latency and reactivation, BoHV-1 and -5 decreased BMAP28 and BMAP27 expression, accompanied by high levels of TNFα and IFNß transcripts in the posterior brain region and medulla during BoHV reactivation. In terms of cytokines, a remarkably overexpression of IFNß was induced by BoHV-5 (133.8-fold). In trigeminal ganglion (TG) both alpha-herpesviruses induced cathelidicins gene expression at all stages of the infection cycle, while only acute BoHV-5 infection increased TNFα (129-fold) mRNA levels. This study suggests that the pronounced downregulation of BMAP28 in BoHV-5-acutely-infected CNS is due to a decreased immune stimulation during viral infection, favouring its establishment in the CNS with a low replication rate until latency. Thus, cathelicidins, together with IFNß and TNFα, are differentially regulated by BoHV-5 and BoHV-1 infections and this regulation is dependent on the stage of virus infection in the bovine nervous system.

Modulation of cathelicidins, IFNß and TNFα by bovine alpha-herpesviruses is dependent on the stage of the infectious cycle.

Production of antimicrobial peptides cathelicidins, interferons and cytokines is an important feature in airway epithelial host defense. The innate immune response to alpha-herpesvirus infection at the sites of primary replication has not been fully studied. Thus, the aim of this study was to determine the expression of innate immune components, cathelicidins, IFNß, TNFα and TNF receptors (TNFRI and TNFRII) during acute infection and reactivation of bovine herpesvirus type 1 (BoHV-1) and 5 (BoHV-5) in the respiratory tract and lymphoid tissue of their natural host. We found that BoHV infection modulates mainly the expression of BMAP28, a key cathelicidin in cattle. It was downregulated by both viruses in retropharyngeal lymph nodes of acutely infected-calves, and it was accompanied by a lower expression of IFNß, TNFα and TNFRI. BoHV-5 showed a pronounced role in the downregulation of BMAP28, even in nasal mucosa and lung. However, during reactivation, BoHV-5 upregulated both BMAP28 and IFNß in retropharyngeal lymph nodes. Acute replication induced also TNFα mRNA and protein synthesis, and expression of TNFRI and II was positively regulated during both acute infection and reactivation, particularly in the trachea. Moreover, BMAP27 was detected during BoHV-1 reactivation suggesting a potential role at this stage. Thus, cathelicidins are implicated in alpha-herpesvirus infections of the bovine respiratory system and the response is distinct during BoHV-1 and BoHV-5 acute infection and reactivation. This demonstrates that these viruses modulate differentially the components of innate immune response, possibly influencing their pathogenesis. This study provides an initial pilot analysis of factors that might be implicated in alpha-herpesvirus infection of the bovine respiratory system.

[Medical responsibilities concerning maternal breast-feeding]. / Los cargos sanitarios ante la lactancia materna.

OBJECTIVE: The objective of this study was to determine the knowledge of high ranking officers in Servei-Valencià-Salut (SVS) about breast-feeding (BF) and national and international regulation related to it, in addition to determining what sanitary policies were undertaken by them to promote BF. PATIENTS AND METHODS: A survey was sent by mail to all high ranking officers (HO) of SVS and all pediatric chief staff services (PC) in our community. To analyze data between both groups a Chi square test and odds ratio in the qualitative variables and variance in the quantitative. RESULTS: Of the surveys sent, 100% were answered by the PC and 44% the HO. Breast-feeding was ranked as superior to artificial feeding by 100% of PC and 73% of HO (p < 0.05). Both groups believed in the necessity of carrying out policies to promote BF in developed countries. Only two PC seemed to know the 1981 OMS's code. All PC carried out policies of BF promotion in their area of influence, while in the HO the percentages varied from 64% to 0% according to their position in the health service organization. CONCLUSIONS: It is necessary to spread the knowledge of and to apply the OMS/UNICEF normatives and to involve al HO with real decision-making power in the development of sanitary policies.

[Patterns of use, popular beliefs and proneness to accidents of a baby walker (go-cart). Bases for a health information campaign]. / Patrones de uso, creencias populares y accidentabilidad por andador infantil (tacatá). Bases para una campaña de información sanitaria.

Baby walkers are a potential cause of accidents in infants from 6 months to 1 year of age. We conducted a study to determine the patterns of walker use, the different points of view of the parents and the baby walker-related injuries in our health district. For this purpose, between November 1, 1992 and January 31, 1993, a questionnaire was given to 207 parents of infants between the ages of 3 and 24 months in order to evaluate the socioeconomic situation and to determine the patterns of walker use. We found that 42% of the infants between 4.3 and 13.4 months of age had a baby walker and 46.7% of them used it daily. There was a significant inverse relationship between the walker usage and the maternal level of education. Of the infants who used walkers, 24.9% had experienced an accident (falls 76.2%, injuries 14.3% and hospital admission 4.8%). The accidents were significantly more common in boys. The advantages reported by parents (for using walkers) were: 46.3% none, 34.2% comfort, 10.9% infant amusement, 12.9% help to walk earlier. Dangers reported by the parents included: 27.2% none, 33.5% leg deformities, 43% accidents (33.5% injuries and 12% falling down stairs). In conclusion, our results show a slightly lower number of walker users and walker related accidents when compared to other reports. Parents have mistaken notions about the use of baby walkers. Hence, the need for continued health education campaigns related to this subject remain.