Comparative histomorphological study of endometrium in mares.

Uterine acute post-breeding inflammation is a physiological tissue response to the entry of exogenous elements, with persistent endometritis being the main pathology responsible for subfertility in the mare (Equus ferus caballus; Linnaeus, 1758). Mares can be classified as susceptible or resistant to endometritis according to their ability to remove intrauterine fluid within 48 hr after experimental inoculation. Endometrial biopsy is a technique that is commonly used to establish the degree of lesions that can affect the fertility of the mare. Endometrial histomorphometry is an objective and highly precise diagnostic method. The aim of this study was to compare, during oestrus, the endometrial histomorphometry of mares previously classified as susceptible (SM) or resistant (RM) to endometritis. Endometrial biopsies from 24 mares at the oestrus phase of the cycle were obtained. For the histomorphometric analysis, samples were histologically processed and subjected to routine Haematoxylin-Eosin staining. For the evaluation, the variables were considered as follows: 1-Height of the lining and glandular epithelia (Lining SM = 15.9 µm vs. RM = 13.3 µm; Glandular SM = 15.0 µm vs. RM = 13.0 µm); 2-Perpendicular diameters of endometrial glands (SM = 51.3 µm vs. RM = 44.8 µm); 3-Number of endometrial glands per field (SM = 24.8 glands/field vs. RM = 20.5 glands/field). The results from this study suggest the existence of a relationship between the studied characteristics and the susceptibility/resistance to post-breeding endometritis in mares. Thus, increased epithelial height, greater glandular density and greater development of the glands during oestrus would be related to a higher susceptibility to endometritis.

Endothelial function and sympathetic nervous system activity in patients with Takotsubo syndrome.

BACKGROUND: Takotsubo syndrome (TTS) is an acute cardiomyopathy associated with intense physical or emotional stress. The precise mechanisms of the disease remain unclear. The aim of this study was to study alterations in endothelial function, vascular compliance and structure and muscle sympathetic activity in the stable phase of the disease. METHODS: In this prospective observational study, patients with TTS and controls matched for age, sex, cardiovascular risk factors and medications were recruited. Flow-mediated vasodilatation (FMD) as a measure of endothelial dysfunction was the primary endpoint. Secondary endpoints included measurements of arterial stiffness, carotid atherosclerosis, quality of life and laboratory parameters. In a subset of patients, muscle sympathetic activity was measured before and after stress tests. RESULTS: The study included 22 TTS patients and 21 matched controls. A significant increase in endothelial dysfunction was seen in TTS compared to controls (FMD 3.4±2.4% vs. 4.8±1.9%, p=0.016). No significant differences in arterial stiffness, intima-media thickness, quality of life and laboratory markers including endothelin-1 were noted. TTS patients showed a reduced carotid total plaque area compared to controls (TPA 17.3±15.1 vs 24.7±12.8mm2, p=0.02). A trend of increased muscle sympathetic activity at rest was observed in TTS patients vs. controls (53.5±28.4 vs. 29.4±16.5 bursts/100 heart beats, p=0.09) with no significant differences in muscle sympathetic activity in response to stress. CONCLUSIONS: Our findings underscore the importance of endothelial dysfunction in patients with TTS which may be involved in the pathophysiology of this syndrome. CLINICALTRIALS. GOV IDENTIFIER: NCT01249599.

The NADPH oxidase NOX2 as a novel biomarker for suicidality: evidence from human post mortem brain samples.

Recent evidence points towards a role of oxidative stress in suicidality. However, few studies were carried out on the sources of reactive oxygen species (ROS) in subjects with suicidal behaviour. We have previously demonstrated that the NADPH oxidase NOX2-derived oxidative stress has a major role in the development of neuropathological alterations observed in an animal model of psychosis. Here, we investigated the possible increase in NOX2 in post mortem brain samples of subjects who died by asphyctic suicide (AS) compared with controls (CTRL) and subjects who died by non-suicidal asphyxia (NSA). We found that NOX2 expression was significantly higher in the cortex of AS subjects than in the other two experimental groups. NOX2 immunostaining was mainly detected in GABAergic neurons, with a minor presence of NOX2-positive-stained cells in glutamatergic and dopaminergic neurons, as well as astrocytes and microglia. A sustained increase in the expression of 8-hydroxy-2'-deoxyguanosine, an indirect marker of oxidative stress, was also detected in the cortex of AS subjects, compared with CTRL and NSA subjects. A significant elevation in cortical interleukin-6 immunoreactivity in AS subjects suggested an involvement of cytokine-associated molecular pathways in NOX2 elevations. Our results suggest that the increase in NOX2-derived oxidative stress in the brain might be involved in the neuropathological pathways leading to suicidal behaviour. These results may open innovative insights in the identification of new pathogenetic and necroscopic biomarkers, predictive for suicidality and potentially useful for suicide prevention.

The effect of mare's age on multiple ovulation rate, embryo recovery, post-transfer pregnancy rate, and interovulatory interval in a commercial embryo transfer program in Argentina.

Advanced maternal age is an important predisposing factor on the reduction of reproductive efficiency. The aim of this study was to evaluate the effect of donor's age on several reproductive parameters in a commercial equine embryo transfer program. Donors were classified into 3 age groups: Group 1=fillies (3 and 4 years old), Group 2=middle age mares (aged 5-10) and Group 3=old mares (aged 13-25). Embryo recovery, multiple ovulation and pregnancy rates and interovulatory intervals were compared amongst age groups. Group 1 (171/244, 70.1%) and Group 2 (774/1081, 71.6%) had a higher (P<0.005) embryo recovery rate than Group 3 (385/701, 54.9%). Groups 2 and 3 were 2.5 and 3.4 times more likely to have multiple ovulations than Group 1 (P<0.05), respectively. The effect of age group on pregnancy rate was not significant (P>0.05). The interovulatory intervals length was influenced by individual mare (P<0.001), age (P<0.04), Day of flushing (P=0.009) and by month (P<0.012). The overall mean interovulatory interval of Group 1 (16.4±0.17 days) and Group 2 (16.6±0.12 days) was not different (P>0.05), but was shorter than the one of Group 3 (17.4±0.15 days; P<0.04). The embryo recovery rate of flushings from Groups 1 and 2 was influenced by the length of the previous interovulatory interval (P=0.03).

Acute administration of 3,4-methylenedioxymethamphetamine (MDMA) induces oxidative stress, lipoperoxidation and TNFα-mediated apoptosis in rat liver.

Liver toxicity is one of the consequences of ecstasy (3,4-methylenedioxymethamphetamine MDMA) abuse and hepatocellular damage is reported after MDMA consumption. Various factors probably play a role in ecstasy-induced hepatotoxicity, namely its metabolism, the increased efflux of neurotransmitters, the oxidation of biogenic amines, and hyperthermia. MDMA undergoes extensive hepatic metabolism that involves the production of reactive metabolites which form adducts with intracellular nucleophilic sites. MDMA-induced-TNF-α can promote multiple mechanisms to initiate apoptosis in hepatocytes, activation of pro-apoptotic (BID, SMAC/DIABLO) and inhibition of anti-apoptotic (NF-κB, Bcl-2) proteins. The aim of the present study was to obtain evidence for the oxidative stress mechanism and apoptosis involved in ecstasy-induced hepatotoxicity in rat liver after a single 20 mg/kg, i.p. MDMA administration. Reduced and oxidized glutathione (GSH and GSSG), ascorbic acid (AA), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR) and malondialdehyde (MDA), an indicator of lipid peroxidation, were determined in rat liver after 3 and 6h after MDMA treatment. The effect of a single MDMA treatment included decrease of GR and GPx activities (29% and 25%, respectively) and GSH/GSSG ratio (32%) with an increase of MDA (119%) after 3h from ecstasy administration compared to control rats. Liver cytosolic level of AA was increased (32%) after 6 h MDMA treatment. Our results demonstrate a strong positive reaction for TNFα (p<0.001) in hepatocytes and a diffuse apoptotic process in the liver specimens (p<0.001). There was correlation between immunohistochemical results and Western blotting which were quantitatively measured by densitometry, confirming the strong positivity for TNF-α (p<0.001) and NF-κB (p<0.001); weak and intense positivity reactions was confirmed for Bcl-2, SMAC/DIABLO (p<0.001) and BID reactions (p<0.001). The results obtained in the present study suggest that MDMA induces loss of GSH homeostasis, decreases antioxidant enzyme activities, and lipoperoxidation that causes an oxidative stress that accompaines the MDMA-induced apoptosis in liver cells.

Recurrent pneumococcal meningitis in a child with transethmoidal encephalocele: a case report and review of literature.

Bacterial meningitis is a life-threatening infection with a low recurrence rate. However, this possibility has always to be considered and avoided. This case report concerns a 5-year-old girl who was admitted in our Emergency Pediatric Unit for symptoms of bacterial meningitis and signs of disseminated intra-vascular coagulopathy. After a successful treatment the girl was discharged in good health. She was admitted to our hospital after one year with the same symptoms of meningitis. Laboratory examinations confirm the admittance suspect. An accurate research allowed to find out immunological deficiencies and showed an occult malformation, transethmoidal encephalocele, responsible for the recurrent meningitis. The present case suggests that the opportunity to perform an accurate cerebral imaging study (with special attention to the ethmoidal region and inner ear) in all cases of meningitis to detect occult anatomical alterations, thus preventing infectious recurrence, should always be taken into account.

Immunohistochemical characterisation and TNF-α expression of the granulomatous infiltration of the brainstem in a case of sudden death due to neurosarcoidosis.

Neurosarcoidosis carries a mortality of 10%, over twice that of sarcoidosis overall, although it has been rarely reported as a cause of sudden death. The current evidence suggests that sarcoidosis results from an enhanced immune reaction to a variety of antigens, non-self or self which causes CD4 (helper-inducer) T-cell accumulation with a ratio of helper-inducer T cells to suppressor-cytotoxic T cells usually high in affected organs, activation and release of inflammatory cytokines, and formation of granulomatous lesions. Numerous cytokines and other mediators are produced by both activated macrophages and T lymphocytes bearing the CD4-helper phenotype during the granuloma responses. A number of data suggest that interferon-gamma (IFN-gamma) and cytokines such as TNF-α, IL-2, and IL-18 play a critical role in the formation of granulomas. In this article, we describe the clinical and pathological characteristics of a patient who suddenly died due to acute respiratory failure. Neurosarcoidosis with massive and extensive involvement of the brainstem was established as the cause of death. Western blot analysis in the patient demonstrated the TNF-α presence as a 51-kDa protein in the brain tissue. The immunohistochemical analysis showed a poor positiveness for CD4 in all samples around the granulomas, as well as moderate positiveness for CD8, CD15, and CD20; CD45 and CD68 showed a strong positiveness in all the brain samples. Histological findings, immunohistochemical analysis, and proteomic studies addressed the diagnosis of neurosarcoidosis with involvement of the nucleus of the solitary tract in the brainstem and central hypoventilation as the cause of death.

Anabolic androgenic steroids abuse and liver toxicity.

In the athletes the wide use of Anabolic Androgenic Steroids (AAS) cause series damage in various organs, in particular, analyzing the liver, elevation on the levels of liver enzymes, cholestatic jaundice, liver tumors, both benign and malignant, and peliosis hepatis are described. A prolonged AAS administration provokes an increase in the activities of liver lysosomal hydrolases and a decrease in some components of the microsomal drug-metabolizing system and in the activity of the mitochondrial respiratory chain complexes without modifying classical serum indicators of hepatic function. Liver is a key organ actively involved in numerous metabolic and detoxifying functions. As a consequence, it is continuously exposed to high levels of endogenous and exogenous oxidants that are by-products of many biochemical pathways and, in fact, it has been demonstrated that intracellular oxidant production is more active in liver than in tissues, like the increase of inflammatory cytokines, apoptosis and the inhibitors of apoptosis NF- κB and Heat Shock Proteins.

[The short-stay observation unit: an experience of the Pediatric Department in Modena]. / Osservazione breve intensiva (OBI) in pediatria: l'esperienza del Policlinico di Modena.

The use of a short-stay observation unit (OBI) in a pediatric department has reduced the number of admissions. Significant cost savings and a better care for children and their families have been also achieved. During the year 2003 in our department 1759 children received OBI. 226 (12.8%) were then admitted. 1553 (87.2%) were discharged after a nine-hour mean stay. Descriptive statistics are used to outline the sample of patients and used treatments.