Transfer pathways between the ovaries and the uterus in the cebus monkeys (Cebus apella)

The aim of this work was to study, in the Cebus apella monkey, the developmental changes in the microanatomy of the utero-ovarian ligament (UOL) and whether their vascular and neural elements might be involved in the transfer of signals between the ovaries and uterus. Sections including uterus, UOL, and ovary obtained from two foetuses, two prepubertal, and four cycling monkeys, two of them treated with a neuron-axonal tracer, diamidino yellow (DY) into the corpus luteum (CL) and the remaining two into the endometrium, were analyzed for the expression of neurofilament protein (NFP) and tracer distribution. Eight regularly cycling females were used to investigate the transfer to the CL of pulses of prostaglandin F(2alpha) (PGF(2alpha)) (n=4) or its vehicle (n=4) given intra-uterus. A convoluted artery, in conjunction with various vein channels, passed over the UOL allowing for a direct communication between uterus and ovaries. The artery acquired prominence during adulthood, in a manner well suited with the ovarian status. Immunohistochemical analysis revealed that NFP expression by the oocyte and by the endometrial epithelial cells was a highly conserved feature during development, whereas the appearance of NFP fibers in the ovaries, UOL, and uterus was a late event in the ontogenesis, likely regulated by the hormonal environment. Neurons, as an obvious source for these NFP fibers, were not recognized at any developmental stage, although some neuron-like cells were observed within the CL. The pattern displayed by the tracer DY, further suggested a reciprocal axonal transport among endometrial cells and follicular and luteal cells of both ovaries and between the ovaries themselves. The functionality of the utero-ovarian connection was assessed after injecting PGF(2alpha) intra-uterus. A short exposition to PGF(2alpha) pulses was required for lowering ovarian and peripheral progesterone concentrations causing luteolysis, indicating that transport mechanism operating between uterus and ovary must be very efficient. The results suggest that the vessels and axons contained in the UOL of the Capuchin monkeys might be two combined key pathways underlying the reciprocal transfer of signals controlling utero-ovarian homeostasis.     

Relationship between international normalized ratio values,vitamin K-dependent clotting factor levels and in vivo prothrombin activation during the early and steady phases of oral anticoagulant treatment

BACKGROUND AND OBJECTIVES: In vitro studies have shown that the rate of prothrombin activation is linearly related to the concentration of factor II (FII) in the assay system, suggesting a key role of prothrombin levels in the expression of the antithrombotic activity of oral anticoagulant treatment (OAT). We investigated the in vivo relationship between prothrombin activation and vitamin K-dependent clotting factor levels during the early and steady phases of OAT in patients and in healthy volunteers. DESIGN AND METHODS: The changes in international normalizezd ratio (INR) and in the plasma levels of FVII, FX, FII, protein C (PC) and prothrombin fragment 1.2 (F1+2) induced by OAT were monitored over 9 days in 10 patients not on heparin starting warfarin after heart valve replacement (HVR) and in 9 healthy volunteers submitted to an 8-day course of warfarin treatment. FII and F1+2 plasma levels were also measured in 100 patients on stable oral anticoagulant treatment with INRs ranging from 1.2 to 6.84. RESULTS: Because HVR patients had subnormal FVII, FX and FII levels after surgery, INR values > 2.0 were attained already 24 hours after the first warfarin dose. In healthy volunteers, INR values greater than 2.0 were first observed after 72 hours. Nadir levels of FVII, PC, FX and FII were reached between 40 and 88 hours in HVR patients and between 72 and 192 hours in healthy volunteers. The FII apparent half-disappearance time (t/2) was 99 hours in HVR patients and 115 hours in healthy volunteers (p = ns). In HVR patients there was no normalization of initially elevated F1+2 levels until day 7 with an apparent t/2 of 132 hours. In healthy volunteers, a decrease to subnormal F1+2 levels was observed by day 8 of treatment (apparent t/2 = 107 hours). In both HVR patients and healthy volunteers, FII and PC levels were independent predictors of the changes in F1+2 levels (p = 0.0001). In patients on stable OAT, only FII levels were independent predictors of the variation in F1+2 levels (p = 0.0001). INTERPRETATION AND CONCLUSIONS: During the early phase of oral anticoagulant treatment in vivo prothrombin activation is a function of the balance between FII and PC levels and is not significantly prevented until nadir levels of FII are obtained. This provides an explanation for the requirement of overlapping heparin and oral anticoagulant treatment for at least 48 hours after the achievement of therapeutic INR values in patients with thromboembolic diseases. In addition, in vivo prothrombin activation is a function of FII levels rather than INR values also in patients on stable oral anticoagulant treatment.     

Absence of brain involvement and factors related to positive serology in a prospective series of 61 cases with pulmonary hydatid disease

A prospective series of 65 patients with surgically confirmed lung cystic hydatid disease was evaluated in terms of their radiologic characteristics, serologic response, and presence of cysts in other organs. Cysts were mostly single and located in lower lung lobes. Liver compromise was found in 34% of the patients. Despite a systematic search, no patient showed brain cysts in this series. Twelve patients had previous hydatid disease: six in the liver and eight in the lung (two had involvement of both organs in the past). Serology using bovine cyst fluid in an immunoblot assay was 85% sensitive. Serologic response was not associated with number or cyst or compromise of other organs but was clearly associated to the presence of at least one complicated cyst. Cyst status in terms of complications should be described to allow appropriate assessment of serologic evaluations.     

The serotonin transporter is required for stress-evoked increases in adrenal catecholamine synthesis and angiotensin II AT(2) receptor expression

High numbers of serotonin transporter (SERT) binding sites and high serotonin (5-HT) content are expressed in the adrenal medulla of wild-type (SERT+/+) mice. Acute restraint stress increases adrenomedullary 5-HT, norepinephrine (NE) and epinephrine (E) release, adrenomedullary tyrosine hydroxylase (TH) mRNA, and angiotensin II AT(2) receptor expression. There are no alterations in adrenal catecholamine content during restraint. In littermate SERT-/- mice, which do not express SERT binding sites, the basal adrenomedullary 5-HT content is significantly reduced and does not increase after stress. The stress-induced increase in plasma E is higher in SERT-/- than in SERT+/+ animals. In SERT-/- mice, the stress-induced increase in expression of TH mRNA does not occur, and as a consequence, adrenal E content decreases, and adrenal E and NE content are lower than that of SERT+/+ mice during restraint. In addition, instead of increased expression, stress induces a profound decrease in the number of adrenomedullary AT(2) receptors in SERT-/- mice. Our results indicate that SERT is necessary for the stress-induced increase in adrenomedullary catecholamine synthesis and AT(2) receptor expression. These data further indicate a close relationship between the adrenomedullary 5-HT and angiotensin II systems, and an important role of adrenomedullary AT(2) receptors in catecholamine synthesis and release during stress.     

Eating disorders as risk factors for osteoporosis

Eating disorders (TCA per its abbreviation in Spanish) are common in young women, with an estimated prevalence of 4-5%. One of the physical complications of eating disorders, especially anorexia nervosa (AN) and eating disorder not otherwise specified (TANE) is bone mass loss, which affects both cortical and trabecular bone. The synergistic effect of malnutrition and estrogen deficiency produces significant bone mass loss, resulting from the uncoupling of bone turnover characterized by a decrease in osteoblastic bone formation and an increase in osteclastic bone resorption. The mechanisms implied in the pathogenesis of bone loss are the hypoestrogenism, hypercortisolism, serum leptin levels and insulin-like growth factor decrease. Severity of bone loss in anorexia nervosa varies depending on duration of illness, the minimal weight ever and sedentarism or strenuous exercise. Long term consequences occur, such as a fracture risk increase in patients who have suffered anorexia nervosa, compared with the general population. The first treatment line to recover bone mass is nutritional rehabilitation together with weight gain. Hormonal replacement therapy may be effective if combined with an anabolic method. Osteopenia and osteoporosis are terms adopted to define the deficiency of bone mass in adults. Authors have used these terms to define densitometric data in young subjects who have not reached their peak bone mass. We suggest the term "hypo-osteogenesia" to define the deficiency in the development of bone mass in adolescents or children.     

Carbohydrate-antigen-125 levels predict hospital stay duration and adverse events at long-term follow-up in Takotsubo cardiomyopathy

The aim of this study is to evaluate the possible role of carbohydrate-antigen(CA)-125 as prognostic marker at short- and long-term follow-up, in subjects with Takotsubo cardiomyopathy (TTC). Sixty-three consecutive subjects with TTC were enrolled in the study and followed for a median 139 days. Circulating levels of CA-125, NT-proBNP, and left ventricular ejection fraction (LVEF) were evaluated at admission. Duration of hospital stay, incidence of death, re-hospitalization and recurrence of TTC during follow-up were recorded. The mean hospital stay was 8.3 days, adverse events occurred during follow up in 17 % of cases. CA-125 levels at admission are inversely related to LVEF (r ?0.30, p < 0.05) and directly related to hospital stay (r 0.29, p < 0.05). CA-125 levels at admission are higher in subjects with adverse events at follow-up (88.9 ± 200.0 vs 20.9 ± 30.0 U/mL, p < 0.05). Rates of incidence of adverse events are proportionally increased with CA-125 tertiles (0, 6, 11 % respectively, p for trend <0.01), at survival analysis (Log Rank p < 0.05) and after correction for age, gender, LVEF and NT-proBNP levels in multivariable Cox analysis (p < 0.05). CA-125 levels <10 U/ml are predictors of adverse events at follow up with 91 % sensitivity, 52 % specificity, 29 % positive predictive power, and 96 % negative predictive power. Increased CA-125 admission levels are associated with a longer hospital stay, a lower LVEF, and a higher risk of adverse events during follow up. CA-125 might be useful for early risk stratification of subjects with TTC.     

Human respiratory syncytial virus N,P and M protein interactions in HEK-293T cells

Characterization of Human Respiratory Syncytial Virus (HRSV) protein interactions with host cell components is crucial to devise antiviral strategies. Viral nucleoprotein, phosphoprotein and matrix protein genes were optimized for human codon usage and cloned into expression vectors. HEK-293T cells were transfected with these vectors, viral proteins were immunoprecipitated, and co-immunoprecipitated cellular proteins were identified through mass spectrometry. Cell proteins identified with higher confidence scores were probed in the immunoprecipitation using specific antibodies. The results indicate that nucleoprotein interacts with arginine methyl-transferase, methylosome protein and Hsp70. Phosphoprotein interacts with Hsp70 and tropomysin, and matrix with tropomysin and nucleophosmin. Additionally, we performed immunoprecipitation of these cellular proteins in cells infected with HRSV, followed by detection of co-immunoprecipitated viral proteins. The results indicate that these interactions also occur in the context of viral infection, and their potential contribution for a HRSV replication model is discussed.     

Default network is not hypoactive in dementia with fluctuating cognition: an Alzheimer disease/dementia with Lewy bodies comparison

Default mode network resting state activity in posterior cingulate cortex is abnormally reduced in Alzheimer disease (AD) patients. Fluctuating cognition and electroencephalogram abnormalities are established core and supportive elements respectively for the diagnosis of dementia with Lewy bodies (DLB). Our aim was to assess whether patients with DLB with both of these features have different default mode network patterns during resting state functional magnetic resonance imaging compared with AD. Eighteen patients with DLB, 18 AD patients without fluctuating cognition, and 15 control subjects were selected after appropriate matching and followed for 2–5 years to confirm diagnosis. Independent component analysis with functional connectivity (FC) and Granger causality approaches were applied to isolate and characterize resting state networks. FC was reduced in AD and DLB patients compared with control subjects. Posterior cingulate cortex activity was lower in AD than in control subjects and DLB patients (p < 0.05). Right hemisphere FC was reduced in DLB patients in comparison with control subjects but not in patients with AD, and was correlated with severity of fluctuations (ρ = −0.69; p < 0.01). Causal flow analysis showed differences between patients with DLB and AD and control subjects.