M. Piccinno

Oxidative Stress During Pregnancy In The Sheep

During physiological pregnancy, all tissues and, mostly, placenta and foetus require high amounts of oxygen. Reactive oxygen species (ROS), generated both by mother and foetus, are implicated in foetal growth because they promote replication, differentiation and maturation of cells and organs. Nevertheless, ROS excess, if not properly counterbalanced, may lead to an alteration in cell constituents, with harmful effects both on mother and foetus.ROS exert a biphasic effect because adequate ROS concentration is essential for embryo development, implant, foetal defence against uterine infections, steroidogenesis, pregnancy maintainance and partum. On the other hand, an uncontrolled ROS generation, beyond physiological antioxidant defences, may lead to embryo resorption, placental degeneration with subsequent alteration in maternal-foetal exchanges, delay in foetal growth, pregnancy interruption, stillbirths. This review investigates the mechanisms underlying ROS generation and effects, throughout physiological and pathological pregnancy in sheep, with a look to antioxidants and their importance in such a critical phase of the reproductive cycle of the sheep.

Oxidative Stress in Neonatology. A Review

Free radicals are highly reactive oxidizing agents containing one or more unpaired electrons. Both in human and veterinary neonathology, it is generally accepted that oxidative stress functions as an important catalysator of neonatal disease. Soon after birth, many sudden physiological and environmental conditions make the newborn vulnerable for the negative effects of oxidative stress, which potentially can impair neonatal vitality. As a clinician, it is important to have in depth knowledge about factors affecting maternal/neonatal oxidative status and the cascades of events that enrol when the neonate is subjected to oxidative stress. This report aims at providing clinicians with an up-to-date review about oxidative stress in neonates across animal species. It will be emphasized which handlings and treatments that are applied during neonatal care or resuscitation can actually impose oxidative stress upon the neonate. Views and opinions about maternal and/or neonatal antioxydative therapy will be shared.

Tyrosine kinase inhibitors (TKIs) in human and pet tumours with special reference to breast cancer: A comparative review

Tyrosine kinase receptors (TKRs) play a key role in tumour cell proliferation and survival since they are involved in endothelial cell activation leading to tumour neoangiogenesis. In particular, vascular endothelial growth factor receptors (VEGFRs), platelet-derived growth factor receptor (PDGFR), stem cell factor receptor (c-KitR), and colony-stimulating factor 1 (CSF-1) are overexpressed or constitutively activated in human and pet malignancies. A variety of small molecule inhibitors targeting specific tyrosine kinases (known as tyrosine kinase inhibitors or TKIs) have recently been approved, or are under investigation, for the treatment of human cancer. TKI application in animal cancer is however relatively recent. This review aims to illustrate the major aspects of tyrosine kinase dysfunctions, with special regard to human and animal cancer of the mammary gland, providing an update on the background of the anti-angiogenic and anti-neoplastic properties of TKIs in human and veterinary cancer.

Modulatory effect of three antibiotics on uterus bovine contractility in vitro and likely therapeutic approaches in reproduction

This in vitro study investigates the modulatory effect of three antibiotics (amoxicillin, enrofloxacin, and rifaximin) on contractility of the bovine uterine tissue in follicular and luteal phases. The effects of these antibiotics at three single doses (10(-6), 10(-5), and 10(-4) M) on their basal contractility were evaluated in isolated organ bath. The functionality of the strip throughout the experiment was evaluated by a dose of carbachol (10(-5) M); the obtained effect had to be repeatable (difference of ≤20%) that is comparable to that induced by the previous administration of the same substance. The results demonstrate the different modulatory activities of these antibiotics on uterine contractility in follicular and luteal phases. The effects induced by amoxicillin and enrofloxacin are opposite: the first relaxes and the second increases the uterine contractility in both cycle phases. Instead, the activity of rifaximin varies depending on the phase of estrous cycle: it increases in the follicular phase and relaxes in the luteal phase. The obtained data provide the hypothesis of possible implications of these drugs in the pharmacologic modulation of uterine contractions. Their action at this level, associated with their specific antimicrobial effects, could suggest using these antibiotics for the treatment of diseases related to postpartum or infections that may occur in pregnant cattle, by virtue of their effects on myometrial contractility too.

In vivo model for mastocytosis: A comparative review.

Human mastocytosis are heterogeneous group of neoplastic diseases characterized by a different degree of uncontrolled mast cell (MC) proliferation and activation. Interestingly, human mastocytosis share several biological and clinical features with canine mast cell disorders, so called canine mast cell tumors (CMCTs). These CMCTs are the most common spontaneous cutaneous tumors found in dogs representing a valid model to study neoplastic mast cell disorders. It has been discovered that the pathological activation of c-Kit receptor (c-KitR), expressed by MCs, has been involved in the pathogenesis of neoplastic MC disorders. In this review we have focused on human mastocytosis in terms of: (i) epidemiology and classification; (ii) pathogenesis at molecular levels; (iii) clinical presentation. In addition, we have summarized animal models useful to study neoplastic MC disorders including CMCTs and murine transgenic models. Finally, we have revised therapeutic approaches mostly common in human and canine MCTs and novel tyrosine kinase inhibitors approved for CMCTs and recently translated in human clinical trials.

Evaluation of serum concentrations of interleukin (IL)-4, IL-10, and IL-12 during pregnancy in bitches

Complex cytokine networks play an important role in a wide range of pregnancy-related processes. During physiological pregnancy, the balance of T helper lymphocytes Th1 and Th2 is strongly shifted toward Th2, which has a protective role in the feto-maternal interaction. The aim of the present study is to establish the serum concentrations, ranges, and trends of anti-inflammatory interleukin (IL)-4 and IL-10, and inflammatory IL-12A, during three phases of gestation in the bitch (20-30, 31-40, and 41-57 days of gestation). Our results indicate that, in early gestation, IL-4 and -10 serum concentrations are elevated and might depend on progesterone that could act as a potent inhibitor of Th1 responses inducing, conversely, the production of Th2-type cytokines (i.e., IL-10 and IL-4). On the other hand, between 30 and 40 days of gestation, the concentrations of the anti-inflammatory ILs decrease probably because of high concentrations of prolactin, which is endowed with immunostimulatory properties on different immune cell types. In the third phase of gestation (41-57 days), an increase in IL-10 occurs, which might depend on high levels of 17β-estradiol that, during pregnancy, interfere with the ability of dendritic cells to stimulate T lymphocytes, acting as an anti-inflammatory factor. Conversely, the low and persistent concentrations of inflammatory IL-12A, throughout pregnancy, compared with anti-inflammatory ILs, might depend on the characteristic cytokine products of Thl and Th2 cells that are known to be mutually inhibitory. The monitoring of immunological status via the levels of cytokines during pregnancy in the bitch, could represent a diagnostic tool to predict and/or prevent pregnancy abnormality, as demonstrated in women.

Dynamics of the progesterone and cholesterol concentrations within the bovine corpus luteum cavity

The aim of this study was to examine the concentrations of progesterone (P4) and cholesterol (CHOL) in fluid of cavitary corpus luteum (CL) and in serum of dairy cattle. Cavitary corpora lutea, collected from cows at a local abattoir, were divided in four stages of development, based on days of the estrous cycle (stage I: 1-4days; stage II: 5-10days; stage III: 11-17days; stage IV: 18-20). Fluid of the their cavity was aspirated and P4 and CHOL concentrations were evaluated. The concentrations of P4 in CL cavity fluids were very high (1640-4666.67ng/mL) and showed a peak at the stage III. CHOL values were similar to those of serum and the highest levels were found in the stage I.

Immunological aspects of metritis in dairy cows: a review.

This paper reviews puerperal metritis in the cow, particularly the complex and multi-factorial pathogenesis characterized by an altered cross-talk among infectious agents, endocrine and immune systems. Uterine infections impair fertility and is one of the main causes of economic losses in dairy production. The early postpartum is a period characterized by an increased exposition to infectious agents and the disruption of the metabolic homeostasis, leading to endocrine and immunologic disorders. Dysregulation of uterine defence mechanisms results in the development of metritis. Because there is a complex interaction between infectious, endocrine and immune factors during metritis, there is need to use safer and cheaper drugs which are able to strengthen the anti-infective actions of the routine therapies.

Lidocaine decreases the xylazine-evoked contractility in pregnant cows.

The objective of this in vitro study was to evaluate and compare the effects of xylazine on basal uterine contractility of bovine pregnant uterine strips and that of lidocaine on xylazine-sensitized bovine pregnant uterine strips, at different stages of pregnancy. Basal contractility was evaluated in an isolated organ bath and the functionality of the strips throughout the experiment was evaluated using a dose of carbachol (10(-5)M). Uterine motility, expressed with amplitude, frequency of contractions as well as the area under the curve, was recorded in different stages of pregnancy and data were collected at 15-min intervals (5-min before and 5-min after xylazine administration and 5-min after lidocaine addition on the plateau contraction induced by xylazine). Uterine motility increased in all the stages of pregnancy after xylazine addition and gradually decreased after treatment with lidocaine. These data suggest that lidocaine might decrease the tonic effect induced by xylazine on bovine pregnant uteri.

Application of an innovative technique for unilateral ovariectomy in dairy cows

This report describes an innovative unilateral ovariectomy technique for the surgical treatment of follicular cysts in dairy cows. Five cows, with a diagnosis of follicular cysts, were submitted to unilateral ovariectomy via a paralumbar fossa approach, in standing position. The linear cutter proved useful for clamping the ovary, stapling the vessels and cutting in one stroke, thus reducing surgery times. After unilateral ovariectomy, all cows underwent heat 7–30 days after surgery, and three cows became pregnant. All cows showed increased milk production. The results of this case report showed that flank ovariectomy, performed in this way, is an efficient, low-risk technique for surgical treatment of follicular cysts in dairy cows.