Patologie da Porcine Circovirus tipo 2 (PCV2) nel suino

The main work involved the PMWS (Post-weaning multisystemic Wasting Syndrome), caused by PCV-2 (Porcine Circovirus type 2) that involved post-weaned pigs. Merial Italy has funded a study activity in which groups of 3-5 animals were sampled for lungs, tracheo-bronchial and superficial inguinal lymph nodes, ileum and tonsils. The protocol applied can be identified as a more diagnostic potential on the individual than on the group. PNP. Another investigation has been conducted to study proliferative and necrotizing pneumonia (PNP), a form of interstitial pneumonia in weaning and post-weaning pigs characterized by hypertrophy and hyperplasia of type II pneumocytes, coagulative necrosis and granular debris within alveolar spaces. Many studies suggest porcine reproductive and respiratory syndrome virus (PRRSV) and porcine circovirus type 2 (PCV2) as the main causes of the disease, but Aujeszky disease virus (ADV) and swine influenza virus (SIV) are also considered. An immunohistochemical study was carried out to evaluate the role of these viruses in PNP lesions in Italy. PNP results primarily associated with PRRSV, even if co-infection is characterized by more severe histological features. Reproductive pathology. A major risk factor for PCV2 infection is a viraemic episode taking place in pregnant sows with low antibody titer which is transmitted by specific PCV2 products of conception. PCV2 can infect the fetus even by vehicles through infected semen or ova, or as a result of infection of the genital tract. An investigation was carried out to identify the presence and localization of PCV2 in the genital tracts of sows experimentally infected with PCV2 and in their fetuses. The results obtained suggest that: conventional sows can be infected by intrauterine exposition; low antibody titres increase the probability of infection; PCV2 infection close to insemination time reduces the pregnancy rate; placental lesions may represent an additional cause of fetal suffering.

Outcomes feto-neonatali dell'infezione non primaria da Cytomegalovirus

OBIETTIVI: Valutazione del rischio di trasmissione verticale e delle conseguenze dell’infezione congenita da cytomegalovirus (CMV) in caso di infezione non primaria versus l’outcome delle gravidanze complicate da infezione primaria. MATERIALI E METODI: Studio retrospettivo di coorte di gravide con infezione recente da CMV diagnosticata c/o il nostro centro negli anni 2000-2013. Le pazienti sono state suddivise in 2 gruppi in base al risultato delle indagini sierologiche (avidità IgG e immunoblot): il primo con profilo sierologico compatibile con infezione non primaria e l'altro compatibile con infezione primaria da CMV. Sono stati confrontati il rischio di trasmissione e di infezione congenita sintomatica nei due gruppi. RISULTATI: Il follow-up è risultato disponibile in 1122 casi di cui 182 con infezione materna non-primaria e 940 con infezione primaria materna. L’infezione congenita è stata diagnosticata in 7 (3.86%) feti/neonati nei casi di infezione non primaria e in 217 (23%) feti/neonati nei casi di infezione primaria (p<0.001). Tra gli infetti, erano sintomatici 43 (19,8%) e 3 (42,8%) rispettivamente nell’infezione primaria e non primaria. COMMENTO: La preesistente immunità materna offre una protezione contro la trasmissione intrauterina nell’infezione da CMV ma non protegge dalla malattia congenita sintomatica.

Pregnancy and reproduction in autoimmune rheumatic diseases

Despite evidence for the important role of oestrogens in the aetiology and pathophysiology of chronic immune/inflammatory diseases, the previous view of an unequivocal beneficial effect of oestrogens on RA compared with a detrimental effect on SLE has to be reconsidered. Likewise, the long-held belief that RA remits in the majority of pregnant patients has been challenged, and shows that only half of the patients experience significant improvement when objective disease activity measurements are applied. Pregnancies in patients with SLE are mostly successful when well planned and monitored interdisciplinarily, whereas a small proportion of women with APS still have adverse pregnancy outcomes in spite of the standard treatment. New prospective studies indicate better outcomes for pregnancies in women with rare diseases such as SSc and vasculitis. Fertility problems are not uncommon in patients with rheumatic disease and need to be considered in both genders. Necessary therapy, shortly before or during the pregnancy, demands taking into account the health of both mother and fetus. Long-term effects of drugs on offspring exposed in utero or during lactation is a new area under study as well as late effects of maternal rheumatic disease on children.

Heavy metal cations permeate the TRPV6 epithelial cation channel

TRPV6 belongs to the vanilloid family of the transient receptor potential channel (TRP) superfamily. This calcium-selective channel is highly expressed in the duodenum and the placenta, being responsible for calcium absorption in the body and fetus. Previous observations have suggested that TRPV6 is not only permeable to calcium but also to other divalent cations in epithelial tissues. In this study, we tested whether TRPV6 is indeed also permeable to cations such as zinc and cadmium. We found that the basal intracellular calcium concentration was higher in HEK293 cells transfected with hTRPV6 than in non-transfected cells, and that this difference almost disappeared in nominally calcium-free solution. Live cell imaging experiments with Fura-2 and NewPort Green DCF showed that overexpression of human TRPV6 increased the permeability for Ca(2+), Ba(2+), Sr(2+), Mn(2+), Zn(2+), Cd(2+), and interestingly also for La(3+) and Gd(3+). These results were confirmed using the patch clamp technique. (45)Ca uptake experiments showed that cadmium, lanthanum and gadolinium were also highly efficient inhibitors of TRPV6-mediated calcium influx at higher micromolar concentrations. Our results suggest that TRPV6 is not only involved in calcium transport but also in the transport of other divalent cations, including heavy metal ions, which may have toxicological implications.

Causes and mechanisms of intrauterine hypoxia and its impact on the fetal cardiovascular system: a review

Until today the role of oxygen in the development of the fetus remains controversially discussed. It is still believed that lack of oxygen in utero might be responsible for some of the known congenital cardiovascular malformations. Over the last two decades detailed research has given us new insights and a better understanding of embryogenesis and fetal growth. But most importantly it has repeatedly demonstrated that oxygen only plays a minor role in the early intrauterine development. After organogenesis has taken place hypoxia becomes more important during the second and third trimester of pregnancy when fetal growth occurs. This review will briefly adress causes and mechanisms leading to intrauterine hypoxia and their impact on the fetal cardiovascular system.

Pentalogy or hexalogy of Cantrell?

Pentalogy of Cantrell (PC) is a rare congenital syndrome involving the abdominal wall, sternum, diaphragm, pericardium, and heart. The embryonic period in which PC develops coincides with that of umbilical cord (UC) formation. The aim of the following study was to address the question of whether PC is associated with UC pathologies. Four cases, prenatally identified between 2002 and 2008, were enrolled in this study. Umbilical cord pathologies defined as single umbilical artery, short cord, or UC with atypical coiling pattern were retrospectively assessed on stored ultrasound images and from autopsy reports. The literature regarding PC and UC pathologies was reviewed. Three singleton pregnancies and 1 monoamniotic twin pregnancy with twin reversed arterial perfusion sequence were reviewed. All had a normal karyotype. Three showed the classical PC stigmata, with ectopia cordis. One fetus had no ectopia cordis; this case had a normal UC, whereas all others fetuses showed a short UC with atypical coiling pattern. Of 26 publications dealing with PC, the UC was described in only 8 cases, 7 of which were abnormal. There seems to be a strong correlation between the PC and UC abnormalities, in particular in cases with ectopia cordis. We speculate that the insult leading to the classical malformations of PC and UC abnormalities is the same or the sequence of malformations itself may alter the early fetoplacental blood flow and therefore the normal development of the UC angioarchitecture.

Sonographic Assessment of Fetal Cardiac Function: Indirect Measurements of Fetal Cardiac Function, Newer Techniques and Clinical Applications

Noninvasive blood flow measurements based on Doppler ultrasound studies are the main clinical tool for studying the cardiovascular status of fetuses at risk for circulatory compromise. Usually, qualitative analysis of peripheral arteries and in particular clinical situations such as severe growth restriction or volume overload also of venous vessels close to the heart or of flow patterns in the heart is being used to gauge the level of compensation in a fetus. However, quantitative assessment of the driving force of the fetal circulation, the cardiac output remains an elusive goal in fetal medicine. This article reviews the methods for direct and indirect assessment of cardiac function and explains new clinical applications. Part 1 of this review describes the concept of cardiac function and cardiac output and the techniques that have been used to quantify output. Part 2 summarizes the use of arterial and venous Doppler studies in the fetus and gives a detailed description of indirect measurements of cardiac function (like indices derived from the duration of segments of the cardiac cycle) with current examples of their application.

Pulsed-wave tissue Doppler echocardiography for the analysis of fetal cardiac arrhythmias

Rhythm analysis of the fetal heart is hampered by the inability to routinely obtain electrocardiographic recordings of the fetus. Doppler studies of fetal cardiac tissue movements, assessing cardiac movements both qualitatively and quantitatively, have recently been described. We used a conventional high-resolution ultrasound system to obtain rhythm data from pulsed-wave tissue Doppler signals of the fetal heart in normal cardiac rhythm and in a variety of fetal cardiac arrhythmias.

Sonographic Assessment of Fetal Cardiac Function: Introduction and Direct Measurement of Cardiac Function

Noninvasive blood flow measurements based on Doppler ultrasound studies are the main clinical tool for studying the cardiovascular status in fetuses at risk for circulatory compromise. Usually, qualitative analysis of peripheral arteries and, in particular clinical situations such as severe growth restriction or volume overload, also of venous vessels close to the heart or of flow patterns in the heart are being used to gauge the level of compensation in a fetus. Quantitative assessment of the driving force of the fetal circulation, the cardiac output, however, remains an elusive goal in fetal medicine. This article reviews the methods for direct and indirect assessment of cardiac function and explains new clinical applications. Part 1 of this review describes the concept of cardiac function and cardiac output and the techniques that have been used to quantify output. Part 2 summarizes the use of arterial and venous Doppler studies in the fetus and gives a detailed description of indirect measures of cardiac function (like indices derived from the duration of segments of the cardiac cycle) with current examples of their application.

Interaction of pregnancy and autoimmune rheumatic disease

During pregnancy, the fetus represents a natural allograft that is not normally rejected. While the maternal immune system retains the ability to respond to foreign antigens, tolerance mechanisms are up-regulated to protect the fetus from immunologic attacks by the mother. The profound immunologic adaptations during and after pregnancy do influence maternal autoimmune rheumatic diseases in several ways. One is triggering the onset of a rheumatic disease in the post partum period, the other influencing disease activity of established rheumatic disease. The review will discuss the mechanisms of increased susceptibility of rheumatoid arthritis (RA) in the first year post partum with a specific emphasis on the role of fetal cells or antigens persisting in the maternal circulation (so called microchimerism). Furthermore, the different influences of pregnancy on established rheumatic diseases will be highlighted. A marked beneficial effect of pregnancy is observed on RA whereas several other rheumatic diseases as ankylosing spondylitis (AS) and systemic lupus erythematosus (SLE) show either no particular effect or an aggravation of symptoms during pregnancy. Differences emerging in regard to modulation of disease symptoms during pregnancy seem related to response to hormones, the type of cytokine profile and immune response prevailing as well as further downstream interactions of molecular pathways that are important in disease pathogenesis.

Increased placental phospholipid levels in pre-eclamptic pregnancies

Physiological pregnancy is associated with an increase in lipids from the first to the third trimester. This is a highly regulated response to satisfy energy and membrane demands of the developing fetus. Pregnancy disorders, such as pre-eclampsia, are associated with a dysregulation of lipid metabolism manifesting in increased maternal plasma lipid levels. In fetal placental tissue, only scarce information on the lipid profile is available, and data for gestational diseases are lacking. In the present study, we investigated the placental lipid content in control versus pre-eclamptic samples, with the focus on tissue phospholipid levels and composition. We found an increase in total phospholipid content as well as changes in individual phospholipid classes in pre-eclamptic placental tissues compared to controls. These alterations could be a source of placental pathological changes in pre-eclampsia, such as lipid peroxide insult or dysregulation of lipid transport across the syncytiotrophoblast.

Acute Encephalopathy with Unilateral Cortical-Subcortical Lesions in Two Unrelated Kindreds Treated with Glucocorticoids Prenatally for Congenital Adrenal Hyperplasia due to 21-Hydroxylase Deficiency: Established Facts and Novel Insight

Background: Prenatal glucocorticoid (GC) treatment of the female fetus with 21-hydroxylase deficiency (21-OHD) may prevent genital virilization and androgen effects on the brain, but prenatal GC therapy is controversial because of possible adverse effects on fetal programming, the cardiovascular system and the brain. Case Reports: We report 2 patients with congenital adrenal hyperplasia (CAH) due to 21-OHD who were treated prenatally with dexamethasone, suffered from an acute encephalopathy and showed focal and multifocal cortical and subcortical diffusion restrictions in early MRI and signs of permanent alterations in the follow-up neuroimaging studies. Both patients recovered from the acute episode. Whereas the first patient recovered without neurological sequelae the second patient showed hemianopsia and spastic hemiplegia in the neurological follow-up examination. Conclusion: These are 2 children with CAH, both treated prenatally with high doses of dexamethasone to prevent virilization. The question arises whether prenatal high-dose GC treatment in patients with CAH might represent a risk factor for brain lesions in later life. Adverse effects/events should be reported systematically in patients undergoing prenatal GC treatment and long-term follow-up studies involving risk factors for cerebrovascular disease should be performed.

Air pollution during pregnancy and neonatal outcome: a review

There is increasing evidence of the adverse impact of prenatal exposure to air pollution. This is of particular interest, as exposure during pregnancy--a crucial time span of important biological development--may have long-term implications. The aims of this review are to show current epidemiological evidence of known effects of prenatal exposure to air pollution and present possible mechanisms behind this process. Harmful effects of exposure to air pollution during pregnancy have been shown for different birth outcomes: higher infant mortality, lower birth weight, impaired lung development, increased later respiratory morbidity, and early alterations in immune development. Although results on lower birth weight are somewhat controversial, evidence for higher infant mortality is consistent in studies published worldwide. Possible mechanisms include direct toxicity of particles due to particle translocation across tissue barriers or particle penetration across cellular membranes. The induction of specific processes or interaction with immune cells in either the pregnant mother or the fetus may be possible consequences. Indirect effects could be oxidative stress and inflammation with consequent hemodynamic alterations resulting in decreased placental blood flow and reduced transfer of nutrients to the fetus. The early developmental phase of pregnancy is thought to be very important in determining long-term growth and overall health. So-called "tracking" of somatic growth and lung function is believed to have a huge impact on long-term morbidity, especially from a public health perspective. This is particularly important in areas with high levels of outdoor pollution, where it is practically impossible for an individual to avoid exposure. Especially in these areas, good evidence for the association between prenatal exposure to air pollution and infant mortality exists, clearly indicating the need for more stringent measures to reduce exposure to air pollution.

Sonographic Assessment of the Umbilical Cord

The umbilical cord is not an inert structure, suspended between the fetus and placenta, but it plays an active role and it is involved in several processes afflicting the feto-placental unit. Its study has to be regarding not only its morphology and morphometry, and the impendance of blood flow by Doppler waveform analysis, but it includes also an analysis of the coiling type and the amount of the Wharton Jelly. The umbilical cord has been considered like an important and huge source of informations, useful to assess the well-being of the fetus and the outcome of pregnancy. The standardization of ultrasound techniques is the first step to speak the same language and make the study of this structure a fundamental part of well-being fetus assessment. This article is carefully focused on morphologic, morphometric and functional ultrasound examination of umbilical cord and suggests that any anomaly detected should provide an indication for an intense fetal follow-up, useful for early helpful therapy, preventing serious complication for the pregnancy.

A proteome signature for intrauterine growth restriction derived from multifactorial analysis of mass spectrometry-based cord blood serum profiling

Intrauterine growth restriction (IUGR) is defined as a condition in which the fetus does not reach its genetically given growth potential, resulting in low birth weight. IUGR is an important cause of perinatal morbidity and mortality, thus contributing substantially to medically indicated preterm birth in order to prevent fetal death. We subjected umbilical cord blood serum samples either belonging to the IUGR group (n = 15) or to the control group (n = 15) to fractionation by affinity chromatography using a bead system with hydrophobic interaction capabilities. So prepared protein mixtures were analyzed by MALDI-TOF mass spectrometric profiling. The six best differentiating ion signals at m/z 8205, m/z 8766, m/z 13 945, m/z 15 129, m/z 15 308, and m/z 16 001 were collectively assigned as IUGR proteome signature. Separation confidence of our IUGR proteome signature reached a sensitivity of 0.87 and a specificity of 0.93. Assignment of ion signals in the mass spectra to specific proteins was substantiated by SDS-PAGE in conjunction with peptide mass fingerprint analysis of cord blood serum proteins. One constituent of this proteome signature, apolipoprotein C-III(0) , a derivative lacking glycosylation, has been found more abundant in the IUGR cord blood serum samples, irrespective of gestational age. Hence, we suggest apolipoprotein C-III(0) as potential key-marker of the here proposed IUGR proteome signature, as it is a very low-density lipoprotein (VLDL) and high-density lipoprotein (HDL) member and as such involved in triglyceride metabolism that itself is discussed as being of importance in IUGR pathogenesis. Our results indicate that subtle alterations in protein glycosylation need to be considered for improving our understanding of the pathomechanisms in IUGR.