Expression and function of the stromal cell-derived factor-1 (SDF-1) and CXC chemokine receptor 4 (CXCR4) in the swine ovarian follicle.

The most characterized stromal cell-derived factor-1 (SDF-1) variants are the isoform α, which is the predominant one but undergoes rapid proteolysis, and the ß isoform, which is more resistant. Through the interaction with a specific chemokine receptor called CXCR4, SDF-1 is able to regulate different physiological processes. The aim of this study was to verify the expression and potential functional role of SDF-1 and CXCR4 in the porcine ovary. Firstly, the expression of SDF-1 and its receptor in different ovarian districts was verified for the first time. Thereafter, the effect of SDF-1 ß isoform (51-72) fragment on functional parameters, such as proliferation, metabolic activity, redox status, nitric oxide production, and steroidogenic activity, was assessed on granulosa cells collected from follicles. In addition, the potential effect of this protein in vascular events was verified through investigations on porcine aortic (AOC) endothelial cells, such as the production of nitric oxide and viability tests. The proliferation and metabolic activity were not affected by treatment with the cytokine. As regard to steroidogenesis, the peptide stimulated both estrogen (P = 0.049) and progesterone production (P = 0.039). Redox status was affected by the examined substance since superoxide anion was inhibited (P = 0.001), while antioxidant power (P = 0.034), as well as nitric oxide generation, were stimulated (P = 0.034). Tests performed on AOCs showed significant stimulation of nitric oxide production (P = 0.004) by the examined peptide, while cell viability was unaffected. Therefore, the potential role of cytokine in the mechanisms involved in the regulation of follicular function can be hypothesized.

Inhibition of Eph/ephrin interaction with the small molecule UniPR500 improves glucose tolerance in healthy and insulin-resistant mice.

Eph/ephrin interactions and their bidirectional signaling are integral part of the complex communication system between ß-cells, essential for glucose homeostasis. Indeed, Eph/ephrin system was shown to be directly involved in the glucose-stimulated insulin secretion (GSIS) process occurring in the pancreatic islets. Here we tested the Eph antagonist UniPR500 as GSIS enhancer. UniPR500 was validated as EphA5-ephrin-A5 inhibitor in vitro and its efficacy as GSIS enhancer was assessed on EndoC-ßH1 cells. The selectivity of UniPR500 was evaluated by testing this compound on a panel of well-known molecular targets responsible for the regulation of glucose homeostasis. Plasmatic levels of UniPR500 were measured by HPLC/MS approach after oral administration. Finally, UniPR500 was tested as hypoglycemic agent in healthy mice, in a non-genetic mouse model of insulin resistance (IR) and in a non-genetic mouse model of type 1 diabetes (T1D). The compound is an orally bioavailable and selective Eph antagonist, able to increase GSIS from EndoC-ßH1 cells. When tested in vivo UniPR500 showed to improve glucose tolerance in healthy and IR mice. As expected by a GSIS enhancer acting on healthy ß-cells, UniPR500 was ineffective when tested on a non-genetic mouse model of type 1 diabetes, where pancreatic function was severely compromised. In conclusion our findings suggest that Eph targeting is a new and valuable pharmacological strategy in the search of new hypoglycemic agents.

Orexin A in swine corpus luteum.

Orexin A (OXA) is a hypothalamic neuropeptide which acts on 2 known G-protein-coupled receptors. It has been demonstrated that OXA is a central molecular link between food intake and reproduction. More recently, its peripheral role has been investigated, and we demonstrated its involvement in regulating ovarian follicle function. The present study was undertaken to explore a potential physiological role of orexin system in swine corpus luteum, a transient ovarian endocrine organ. Our aim was, first, to analyze the localization and eventual colocalization of OXA and its 2 receptors within the different cell types composing the corpus luteum structure. Second, we wanted to explore the effects of OXA on isolated luteal cells, and finally to verify a potential involvement of OXA in angiogenesis, a crucial event in corpus luteum development. Our data demonstrate the local expression of OXA and its receptors in swine corpus luteum. Luteal cell functions were affected by treatment with OXA. In particular, progesterone production was inhibited (P < 0.05) and nonenzymatic scavenging activity was increased (P < 0.05). Moreover, OXA inhibited (P < 0.05) new vessel growth. Our results suggest that OXA could act locally to play a role in corpus luteum demise.

Orexin system in swine ovarian follicles.

Successful reproduction is strictly linked to metabolic cues. The orexins are a family of hypothalamic neurohormones, well known for their key role in the control of food intake and the involvement in several aspects of the reproductive process. The biological actions of both orexins are carried out through binding to the related Orexin 1 (OX1R) and Orexin 2 (OX2R) G-protein-coupled receptors. The purpose of this study was to investigate the presence of orexin system components in the porcine ovaries, to contribute to expand the knowledge about their pleiotropic role. First, we investigated the localization of orexin A (OXA) and its receptors by immunochemistry in different ovarian districts. Thereafter, we evaluated the expression of the prepro-orexin (PPO) gene and OXA effects on granulosa cell functions. Immunohistochemical study revealed the presence of orexinergic system components in porcine ovarian follicles. Moreover, our data show the expression of PPO messenger RNA in swine ovarian follicles >5 mm. In addition, OXA influences proliferation (P < 0.05), steroidogenic activity (P < 0.05), and redox status of granulosa cells (P < 0.05). Therefore, we hypothesize that OXA could exert a local physiological role in swine ovarian follicles even if further studies are required to deeply define the function of this pleiotropic system.

Complete uterine prolapse without uterine mucosal eversion in a queen.

A five-year-old female cat weighing 3 kg was presented by the owner after noticing a large pink, bilobed mass protruding through the vulva during labour. The cat was in good condition, with appropriate lactation, and the newborn kittens were nursing normally. The uterus was not reverted or invaginated at examination, and there was rupture of the mesovarium, mesometrium and uterine-vaginal connection around the cervix. Manual reduction of the prolapsed uterus was not possible because of torn ligaments. A coeliotomy was performed to remove the ovaries, and the apex of the uterine horns was passed by the vaginal route. The remaining part of the mesometrium was disconnected, and the prolapsed uterus was removed. The queen and kittens were discharged from the hospital on the second day after surgery. An unusual feature of this case is that the prolapse was complete, without eversion of any part of the uterus through a vaginal tear.

Effects of intraarticular treatment with stanozolol on synovial membrane and cartilage in an ovine model of osteoarthritis.

Aim of the study was to verify the clinical and morphological effects of intra-articular stanozolol or placebo treatment, lasting 3 and 9 months, in sheep in which a femoro-tibial osteo-arthritis (OA) were surgically induced (medial bilateral meniscectomy). Twenty healthy sheep divided into four groups and two control animals group, after surgical medial bilateral meniscectomy, were weekly injected in femoral-tibial joint (FTJ) with stanozolol or placebo. Lameness evaluation was performed and synovial fluid was collected from all sheep at each treatment time. Necropsies were performed after 3 or 9 month as described in experimental design. Gross pathologies were described and specimen tissues collected from femoro-tibial articular joints were processed for routine histological examination. The gross anatomy of the FTJ was well-preserved in stanozolol-treated sheep; this also applied to the histological features of articular cartilage. Joint aseptic inflammation and fibrosis were observed in placebo-treated sheep, associated with a different degree of severity of condylar and tibial plate cartilage degeneration. Stanozolol intra-articular treatment reduces osteophytes formation and subchondral bone reaction and promotes articular cartilage regeneration.

D-dimer deposits in lungs and kidneys suggest its use as a marker in the clinical workup of dogs with heartworm (Dirofilaria immitis) disease.

It has been reported that dogs with heartworm disease (Dirofilaria immitis) show increased plasma levels of D-dimer, a fibrin degradation product present in the blood after a blood clot is degraded by fibrinolysis. In the present study the authors show that, in dogs with both experimental and natural infections with D. immitis, D-dimer deposits in lungs and kidneys are associated with pulmonary thromboembolism and microfilariemic status, as well as there was a clear association between increased plasma values of D-dimer and positive staining in immunohistochemistry. Results suggest that the monitoring of D-dimer levels in infected dogs could be useful in evaluating the presence of pulmonary thromboembolism in the lungs and that microfilariae may induce microthrombosis in kidneys, thus contributing to renal pathology.

Myocardial damage in dogs affected by heartworm disease (Dirofilaria immitis): immunohistochemical study of cardiac myoglobin and troponin I in naturally infected dogs.

It has recently been reported that dogs affected by canine heartworm disease (Dirofilaria immitis) can show an increase in plasma levels of myoglobin and cardiac troponin I, two markers of muscle/myocardial injury. In order to determine if this increase is due to myocardial damage, the right ventricle of 24 naturally infected dogs was examined by routine histology and immunohistochemistry with anti-myoglobin and anti-cardiac troponin I antibodies. Microscopic lesions included necrosis and myocyte vacuolization, and were associated with loss of staining for one or both proteins. Results confirm that increased levels of myoglobin and cardiac troponin I are indicative of myocardial damage in dogs affected by heartworm disease.

Canine bladderworm (Capillaria plica) infection associated with glomerular amyloidosis.

Capillaria plica (Trichuroidea: Capillariidae), commonly known as bladderworm, is a nematode rarely associated with clinical disease that resides in the lower urinary tract of wild and domestic canids. In the present paper a case of canine urinary capillariosis associated with glomerular amyloidosis is described. The dog, an 8-year-old, male, hunting Jagd terrier had a history of weight loss and diarrhoea and was referred to the University of Parma Teaching Veterinary Hospital (UPTVH). Clinical and laboratory tests shown here suggest that C. plica may be a contributing factor to glomerular amyloidosis.

Is alexithymia a personality trait increasing the risk of depression? A prospective study evaluating alexithymia before, during and after a depressive episode.

BACKGROUND: Whether alexithymia is a personality trait that increases the risk of major depression (MD) is still debated. In this prospective study, alexithymic levels were evaluated before, during and after a depressive episode. METHOD: The alexithymic levels, the presence of MD and the severity of anxious-depressive symptoms were evaluated at intervals of about 1 month in pregnant women attending the Centers for Prenatal Care, using the Toronto Alexithymia Scale (TAS), the Primary Care Evaluation of Mental Disorders (PRIME-MD) and the Hospital Anxiety and Depression Scale (HADS). RESULTS: Sixteen women affected by MD, 21 affected by subthreshold depression and 112 non-depressed women were included in the study. Women who developed depression, compared to non-depressed women, showed similar TAS and HADS scores during the pre-morbid phase, a significant increase in the scores during depression and a significant decrease after remission, whereas no change was observed in non-depressed women. CONCLUSIONS: Our data suggest that in pregnant women alexithymia does not represent a personality trait that increases the risk of developing a depressive episode, and they support the hypothesis that alexithymia is a state-dependent phenomenon in depressed pregnant women.

The effect of temperament and character on response to selective serotonin reuptake inhibitors in panic disorder.

OBJECTIVE: In this prospective study, temperament and character were evaluated in patients with panic disorder (PD), before 1 year of medication therapy, to verify whether these factors influenced the outcome of treatment. METHOD: Seventy-one PD patients were evaluated with the SCID-IV, the Temperament and Character Inventory (TCI), the SCL-90, the Ham-A and the Ham-D. Patients were treated with pharmacotherapy and were evaluated monthly over 1 year. RESULTS: Before treatment, non-remitted patients showed higher levels of harm avoidance (HA) and lower levels of persistence (P), self-directedness (SD) and cooperativeness (C), whereas remitted patients showed only higher levels of HA. After controlling the effect of the confounding variables, the likelihood to achieve remission was positively related to SD score (OR = 1.12; P = 0.002), particularly 'self-acceptance' SD dimension (OR = 1.30; P = 0.02). CONCLUSIONS: Our data suggest that in PD: i) the evaluation of personality, using the Cloninger's model, confirms the presence of personality pathology as one predictor of non-response to treatment; ii) in patients with low SD a combination of medication and cognitive-behaviour therapy should be the most effective treatment.

Predictors of symptom resolution in panic disorder after one year of pharmacological treatment: a naturalistic study.

OBJECTIVE: In this naturalistic and prospective study, patients with panic disorder (PD) were treated for one year 1) to verify the rate of patients achieving the resolution of full-symptom attacks, limited-symptom attacks, anticipatory anxiety, phobic avoidance and depression; and 2) to identify the predictors of symptom resolution for each domain. METHOD: One hundred patients with PD, according to DSM-IV criteria, participated in the study. In all patients, a baseline and a follow-up with monthly evaluations of SCL-90, Ham-A, Ham-D and panic diaries were carried out over a one-year period. All patients were treated with paroxetine or citalopram. RESULTS: Seventy-one patients completed the study, whereas the remaining 29 dropped out. Among completers, remission of full- and limited-symptom panic attacks was observed in 76 % of patients, whereas complete remission (resolution of panic attacks, anticipatory anxiety, phobic anxiety, and depression) was achieved by only 46 % of patients. Predictors of absence of symptom remissions were obsessive-compulsive disorder (OCD) and recurrent major depression (MD) comorbidity (for panic attacks), pre-treatment severity of anxious symptoms (for anticipatory anxiety), phobic anxiety (for phobic avoidance), and depressive symptoms (for depression). CONCLUSION: This naturalistic study shows that the high comorbidity of OCD and MD and the greater pre-treatment severity of anxious, phobic and depressive symptoms reduced the likelihood of achieving complete remission of symptoms in PD patients who completed the protocol, even though they were adequately treated with SSRI medication.

Unusual hyperparathyroidism in a cat.

A 5 month-old, male, domestic short hair cat was presented with inappetence and vomiting. it was depressed and reluctant to move. The cat had difficulties in keeping the standing position and grossly deformed thighs. Lytic changes and disruption of normal architecture of the bone were observed, involving mainly the femoral diaphyses. An inverse Ca/P ratio and kidney failure were diagnosed. The possibility of whether the bone changes could have been related to primary or secondary renal hyperparathyroidism is discussed.

A model for phase noise generation in amplifiers.

In this paper, a model is presented for predicting the phase modulation (PM) and amplitude modulation (AM) noise in bipolar junction transistor (BJT) amplifiers. The model correctly predicts the dependence of phase noise on the signal frequency (at a particular carrier offset frequency), explains the noise shaping of the phase noise about the signal frequency, and shows the functional dependence on the transistor parameters and the circuit parameters. Experimental studies on common emitter (CE) amplifiers have been used to validate the PM noise model at carrier frequencies between 10 and 100 MHz.

The response of pigs inoculated with a thymidine kinase-negative (TK-) pseudorabies virus to challenge infection with virulent virus.

12 Large-White-Landrace piglets were subdivided in four groups of 3 and housed in separate units. The piglets of three groups were inoculated with the 86/27V 6C2 thymidine kinase negative (TK-) mutant of pseudorabies virus (PRV), by different routes. A second inoculation with the same mutant was given to the pigs 21 days later. The animals of a fourth group were left as uninoculated controls. 21 days following the second inoculation with the TK- mutant all pigs were challenge infected with the virulent PRV. On post challenge day (PCD) 30 all pigs were killed and samples for virus detection and histology were taken from several organs. The inoculated TK- mutant of PRV did not induce any ill effects in the pigs except a transient febrile reaction in some animals. Virus was recovered from nasal swabbings from one pig 2 days after the first inoculation of the mutant. After challenge exposure with virulent PRV, the TK- mutant-inoculated pigs were apparently protected, whereas the control pigs all were severely affected and recovered very slowly over 3 weeks. Virus was isolated from the nasal swabbings from the TK- mutant-inoculated pigs on PCDs 2 and 4, whereas the nasal swabbings from the control piglets were all positive for virus from PCD 2 through PCD 10. DNA analysis of the virus recovered showed a pattern identical to that of the virulent PRV. Histologic lesions were found in the respiratory and the central nervous systems, however, the lesions in the TK- mutant-inoculated pigs were much milder compared to those registered for the control pigs. Virus was not isolated from any of the tissue samples that were tested, but viral DNA with sequences typical of PRV genome was detected by PCR in all samples of trigeminal ganglia from either the TK- mutant-inoculated pigs or from the controls.

[Clinical and cytogenetic variability in 12 Mexican families with Fanconi's anemia and its relationship with the complement gruoup to which they belong]. / Variabilidad clínica y citogenética en doce familias mexicanas con anemia de fanconi y su relación con el grupo de complementación al que pertenecen.

OBJECTIVE: To describe the clinical and cytogenetic features of Mexican patients with Fanconi anemia, while assessing whether the phenotypic variation is related to the complementation group. MATERIAL AND METHODS: The cytogenetic diagnosis was done using mitomycin C and diepoxybutane on peripheral blood lymphocytes. The severity of the anemia and each patient's clinical manifestations were classified using Alter's and Auerbach's clinical scores, respectively. Lymphoblastoid cell lines were established for eight patients and complementation group determined following cell fusion procedures in four propositi. RESULTS: Twenty-five Fanconi anemia patients from 12 families were studied. All patients had high, spontaneous and induced chromosomal breakages, no relationship was found between the clinical severity of the disease and the anemic state. Twelve patients were considered severely ill, while the remaining 13 were considered mild cases. Three individuals were anemia-free, while in 13 the anemia was mild, moderate in 7, and severe in 1. The mortality rate was 32% (8/25). No relationship was found between the clinical picture and degree of the anemia or mortality rate. Eleven patients were assigned to complementation group A with mild clinical findings and anemia. Their cytogenetic results showed variability. One patient assigned to group C was considered as a severe case with transfusion-dependent anemia and high sensitivity to mutagens. Thirteen patients were not classified. A lymphoblastoid cell line resistant to mitomycin C was obtained suggesting somatic mosaicism. CONCLUSIONS: The establishment of a complementation group does not necessarily explain variability. There are other important factors, such as somatic mosaicism, that modify the cellular phenotype.

[Peripartum dilatative cardiomyopathy. Case report with literature review]. / La cardiomiopatia dilatativa peripartum. Messa a punto e descrizione di un caso clinico.

Peripartum cardiomyopathy (PPCM) is a rare form of heart failure affecting women in the last month of pregnancy or the first six months post-partum. The etiology of PPCM remains poorly understood although some risk factors were described. Diagnosis is often difficult and is always necessary to exclude other prior heart disease and other cause of left ventricular dysfunction in pregnancy. Medical therapy for PPCM is similar to that for other forms of congestive heart failure; prognosis is better than in idiopathic cardiomyopathy but many authors observed that women who have had one episode of PPCM are likely to have recurrences in subsequent pregnancies. The present report describes the case of a woman presenting with severe cardiac failure immediately after cesarean section for twin pregnancy. The patient is a 35-year-old nulliparous white woman, with history of anorexia, subsequent amenorrhea, sterility and pregnancy induced with Gn-Rh. The diagnosis of PPCM was difficult for the presence of preeclampsia and acute pulmonary edema occurred four hours after delivery. The successful outcome was possible with an intensive treatment (mechanical ventilation, Swan-Ganz catheter). The whole resolution of the heart failure, six months post-partum, was demonstrated by ultrasonography.