Schistosoma mansoni: reinfections and concomitant immunity in mice: importance of perfusion time after challenge infection for evaluation of immunoprotection

The concomitant immunity in the presence of repeated infections (with 15 cercariae) was studied in mice sacrificed on the 20th day after each infection. The comparison of the averages of immature worms, recovered from mice submitted to reinfection, with those of their respective controls (previously uninfected) showed a significantly lower worm recovery rate in the animals with previous infections (concomitant immunity). However, statiscally significant differences could not be detected among the various groups of animals, when the mice that accumulated worms in this mature stage were perfused. The theoretical projection based on the accumulation of young worms which developed to adult ones indicates a lower recovery rate of adult worms in the animals with concomitant immunity, but this projection was not corroborated by the experimental data. The visceral hemodynamic alterations that occurred in reinfections due to the pathogeny, favouring recirculation of the recent arriving worms to the other organs on the occasion of perfusion of the portal system. These results suggest that special care should be taken when one wants to investigate concomitant immunity in mice based on the distinction of the immature worms from challenge infection and the mature ones from primary infection.

Lipoxin A4 is a novel estrogen receptor modulator.

Inflammation is intimately linked with naturally occurring remodeling events in the endometrium. Lipoxins comprise a group of short-lived, nonclassic eicosanoids possessing potent anti-inflammatory and proresolution properties. In the present study, we investigated the role of lipoxin A(4) (LXA(4)) in the endometrium and demonstrated that 15-LOX-2, an enzyme necessary for LX biosynthesis, is expressed in this tissue. Our results establish that LXA(4) possesses robust estrogenic activity through its capacity to alter ERE transcriptional activity, as well as expression of estrogen-regulated genes, alkaline phosphatase activity, and proliferation in human endometrial epithelial cells. Interestingly, LXA(4) also demonstrated antiestrogenic potential, significantly attenuating E2-induced activity. This estrogenic activity was directly mediated through estrogen receptors (ERs). Subsequent investigations determined that the actions of LXA(4) are exclusively mediated through ERα and closely mimic those of the potent estrogen 17β-estradiol (E2). In binding assays, LXA(4) competed with E2 for ER binding, with an IC(50) of 46 nM. Furthermore, LXA(4) exhibited estrogenic activity in vivo, increasing uterine wet weight and modulating E2-regulated gene expression. These findings reveal a previously unappreciated facet of LXA(4) bioactions, implicating this lipid mediator in novel immunoendocrine crosstalk mechanisms.

Infusion of atrial natriuretic peptide to patients with congestive heart failure.

Atrial natriuretic peptides (ANP) exert vasodilating and natriuretic actions. The present study was undertaken to test the effect of low dose infusions of synthetic ANP on hemodynamic and humoral variables of patients with severe heart failure. Eight patients, aged 26 to 71 years, with severe congestive heart failure due to ischemic heart disease or idiopathic dilated cardiomyopathy were included in the study. Synthetic human (3-28) ANP was infused at doses ranging from 0.5 to 2 micrograms/min for up to 3 h. Pulmonary capillary wedge pressure fell from 24 +/- 1 to 16 +/- 2 mm Hg (mean +/- SEM) (p less than 0.01) and cardiac index tended to rise from 2 +/- 0.2 to 2.3 +/- 0.2 L/min/m2 (NS), while blood pressure and heart rate did not change. One patient experienced a marked drop in pulmonary capillary wedge and arterial blood pressure that necessitated the administration of saline. ANP infusion did not alter plasma renin activity or plasma aldosterone, norepinephrine, or vasopressin levels. It decreased plasma epinephrine levels from 0.472 +/- 0.077 to 0.267 +/- 0.024 nmol/L (p less than 0.05). Plasma ANP levels were markedly elevated in all patients before initiating the infusion. They had no predictive value for the hemodynamic response to exogenous ANP. No correlation was observed between the hemodynamic effects of ANP and those induced by the subsequently administered converting enzyme inhibitor captopril, which seemed to improve cardiac function more consistently.(ABSTRACT TRUNCATED AT 250 WORDS)

Exhaled nitric oxide in high-altitude pulmonary edema: role in the regulation of pulmonary vascular tone and evidence for a role against inflammation.

High-altitude pulmonary edema (HAPE) is a life-threatening condition occurring in predisposed subjects at altitudes above 2,500 m. It is not clear whether, in addition to hemodynamic factors and defective alveolar fluid clearance, inflammation plays a pathogenic role in HAPE. We therefore made serial measurements of exhaled pulmonary nitric oxide (NO), a marker of airway inflammation, in 28 HAPE-prone and 24 control subjects during high-altitude exposure (4,559 m). To examine the relationship between pulmonary NO synthesis and pulmonary vascular tone, we also measured systolic pulmonary artery pressure (Ppa). In the 13 subjects who developed HAPE, exhaled NO did not show any tendency to increase during the development of lung edema. Throughout the entire sojourn at high altitude, pulmonary exhaled NO was roughly 30% lower in HAPE-prone than in control subjects, and there existed an inverse relationship between Ppa and exhaled NO (r = -0.51, p < 0.001). These findings suggest that HAPE is not preceded by airway inflammation. Reduced exhaled NO may be related to altered pulmonary NO synthesis and/or transport and clearance, and the data in our study could be consistent with the novel concept that in HAPE-prone subjects, a defect in pulmonary epithelial NO synthesis may contribute to exaggerated hypoxic pulmonary vasoconstriction and in turn to pulmonary edema.

Early broncoconstriction in anesthetized sheep: a simplified experimental model of asthma

Résumé Cette étude décrit un modèle expérimental de bronchoconstriction précoce induite par aérosolisation d'un extrait d'Ascaris suum chez des moutons anesthésiés par de l'isoflurane et ventilés mécaniquement. Dix moutons adultes ont été anesthésiés et ventilés mécaniquement puis ont été exposés à un stimulus bronchoconstrictif sous forme d'un aérosol d'extrait d'Ascaris suum durant 25 minutes. Tous les moutons ont été exposés deux fois à huit semaines d'intervalle à ce même stimulus. Les échanges gazeux ainsi que les paramètres respiratoires ont été mesurés régulièrement durant la période d'aérosolisation ainsi que durant les 60 minutes suivantes. A la fin de la période d'aérosolisation, une augmentation significative (p<0.05) des pressions de crête (+114%) et de plateau (+148%), de la résistance expiratoire (+93%) et de la pression partielle artérielle de gaz carbonique PaCO2 (+25%) a été constatée, de même qu'une diminution significative (p<0.05) de la compliance respiratoire (-41 %) et de la pression partielle artérielle d'oxygène PaO2 (-49%). Ces modifications sont restées stables durant toute la période d'observation. Ce modèle expérimental animal de bronchoconstriction offre de nombreux avantages : la stabilité hémodynamique et le confort de l'animal sont améliorés et la réaction de stress est inhibée. Il permet de plus une distribution optimale de l'antigène respiratoire et finalement évite l'utilisation d'un pléthysmographe corporel. Abstract This study describes a simplified experimental model of early bronchoconstriction induced by aerosolization of Ascaris suum extract in isoflurane-anesthetized and mechanically ventilated sheep. Ten adult sheep were anesthetized, mechanically ventilated and then challenged with an aerosol of Ascaris suum extract during 25 minutes. All of them were challenged twice at eight weeks intervals. During the bronchoconstrictive challenges and the following sixty minutes, gas exchange was measured and respiratory mechanics parameters computed from a lung mechanics calculator. At the end of the challenge, a significant increase (p<0.05) was observed in peak (+114%) and plateau (+148%) pressures, expiratory resistance (+93%) and PaCO2 (+25%) along with a significant decrease (p<0.05) in respiratory compliance (-41 %) and PaO2 (-49%). These changes remained stable throughout the 60 minutes study period. This model offers several advantages: hemodynamic stability and animal welfare are improved and the stress response is blunted. It allows an optimal distribution of the antigen and finally avoids the need of a body plethysmograph.

High-field (3T) magnetic resonance defecography with functional assessment of the evacuation phase : a pictorial essay : P10

Purpose: Dynamic high-field magnetic resonance (MR) defecography including the evacuation phase is a promising tool for the assessment of functional pelvic disorders, nowadays seen with increasing frequency in elderly women in particular. Learning objectives: 1. To describe the adequate technique of dynamic high-field MRI (3T) in assessing pelvic floor disorders. 2. To provide an overview of the most common pathologies occurring during the evacuation phase, especially in comparison with results of conventional defecography. Methods and materials: After description of the ideal technical parameters of MR defecography performed in supine position after gel rectal filling with a 3 Tesla unit and including the evacuation phase we stress the importance of using a standardized evaluation system for the exact assessment of pelvic floor pathophysiology. Results: The typical pelvic floor disorders occurring before and/or during the evacuation phase, such as sphincter insufficiency, vaginal vault and/or uterine prolapse, cystourethrocele, peritoneo-/ entero-/ sigmoïdocele or rectal prolapse, are demonstrated. The difference between the terms "pelvic floor descent" and "pelvic floor relaxation" are pictorially outlined. MR results are compared with these of conventional defecography. Conclusion: Exact knowledge about the correct technique including the evacuation phase and the use of a standardized evaluation system in assessing pelvic floor disorders by dynamic high-field MRI is mandatory for accurate and reproducible diagnosis.

Nimesulide, a cyclooxygenase-2 preferential inhibitor, impairs renal function in the newborn rabbit.

Tocolysis with nonsteroidal anti-inflammatory drugs (NSAIDs) has been widely accepted for several years. Recently, the use of the cyclooxygenase-2 (COX2) preferential NSAID nimesulide has been proposed. However, data reporting neonatal acute renal failure or irreversible end-stage renal failure after maternal ingestion of nimesulide question the safety of this drug for the fetus and the neonate. Therefore, this study was designed to define the renal effects of nimesulide in newborn rabbits. Experiments were performed in 28 newborn rabbits. Renal function and hemodynamic parameters were measured using inulin and para-aminohippuric acid clearances as markers of GFR and renal blood flow, respectively. After a control period, nimesulide 2, 20, or 200 microg/kg was given as an i.v. bolus, followed by a 0.05, 0.5, or 5 microg.kg(-1).min(-1) infusion. Nimesulide administration induced a significant dose-dependent increase in renal vascular resistance (29, 37, and 92%, respectively), with a concomitant decrease in diuresis (-5, -23, and -44%), GFR (-12, -23, and -47%), and renal blood flow (-23, -23, and -48%). These results are in contrast with recent reports claiming that selective COX2 inhibition could be safer for the kidney than nonselective NSAIDs. These experiments confirm that prostaglandins, by maintaining renal vasodilation, play a key role in the delicate balance regulating neonatal GFR. We conclude that COX2-selective/preferential inhibitors thus should be prescribed with the same caution as nonselective NSAIDs during pregnancy and in the neonatal period.

Rapidly fatal poisoning with an insecticide containing rotenone.

Introduction: Rotenone is a botanical pesticide derived from extracts of Derris roots, which is traditionally used as piscicide, but also as an industrial insecticide for home gardens. Its mechanism of action is potent inhibition of mitochondrial respiratory chain by uncoupling oxidative phosphorylation by blocking electron transport at complex-I. Despite its classification as mild to moderately toxic to humans (estimated LD50, 300-500 mg/kg), there is a striking variety of acute toxicity of rotenone depending on the formulation (solvents). Human fatalities with rotenone-containing insecticides have been rarely reported, and a rapid deterioration within a few hours of the ingestion has been described previously in one case. Case report: A 49-year-old Tamil man with a history of asthma, ingested 250 mL of an insecticide containing 1.24% of rotenone (3.125 g, 52.1-62.5 mg/kg) in a suicide attempt at home. The product was not labeled as toxic. One hour later, he vomited repeatedly and emergency services were alerted. He was found unconscious with irregular respiration and was intubated. On arrival at the emergency department, he was comatose (GCS 3) with fixed and dilated pupils, and absent corneal reflexes. Physical examination revealed hemodynamic instability with hypotension (55/30 mmHg) and bradycardia (52 bpm). Significant laboratory findings were lactic acidosis (pH 6.97, lactate 17 mmol/L) and hypokalemia (2 mmol/L). Cranial computed tomography (CT) showed early cerebral edema. A single dose of activated charcoal was given. Intravenous hydration, ephedrine, repeated boli of dobutamine, and a perfusor with 90 micrograms/h norepinephine stabilized blood pressure temporarily. Atropine had a minimal effect on heart rate (58 bpm). Intravenous lipid emulsion was considered (log Pow 4.1), but there was a rapid deterioration with refractory hypotension and acute circulatory failure. The patient died 5h after ingestion of the insecticide. No autopsy was performed. Quantitative analysis of serum performed by high-resolution/accurate mass-mass spectrometry and liquid chromatography (LC-HR/AM-MS): 560 ng/mL rotenone. Other substances were excluded by gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS/MS). Conclusion: The clinical course was characterized by early severe symptoms and a rapidly fatal evolution, compatible with inhibition of mitochondrial energy supply. Although rotenone is classified as mild to moderately toxic, physicians must be aware that suicidal ingestion of emulsified concentrates may be rapidly fatal. (n=3): stridor, cyanosis, cough (one each). Local swelling after chewing or swallowing soap developed at the earliest after 20 minutes and persisted beyond 24 hours in some cases. Treatment with antihistamines and/or steroids relieved the symptoms in 9 cases. Conclusion: Bar soap ingestion by seniors carries a risk of severe local reactions. Half the patients developed symptoms, predominantly swellings of tongue and/or lips (38%). Cognitive impairment, particularly in the cases of dementia (37%), may increase the risk of unintentional ingestion. Chewing and intraoral retention of soap leads to prolonged contact with the mucosal membranes. Age-associated physiological changes of oral mucosa probably promote the irritant effects of the surfactants. Medical treatment with antihistamines and corticosteroids usually leads to rapid decline of symptoms. Without treatment, there may be a risk of airway obstruction.

Prise en charge de l'hémorragie du post-partum [Management of postpartum haemorrhage].

Today, postpartum hemorrhage remains a leading cause of maternal morbidity and mortality. Medical treatment, various surgical procedures and/or uterine artery embolisation have considerably reduced the risk of hysterectomy. It is important to identify the different risk factors of hemorrhage after delivery and to take the precautions to avoid it. A clear strategy defined by the obstetrical team is essential to decrease the delay in the management of this complication in order to increase the chances of a successful treatment.

Blunting the response to endotoxin in healthy subjects: effects of various doses of intravenous fish oil.

To test the dose response effect of infused fish oil (FO) rich in n-3 PUFAs on the inflammatory response to endotoxin (LPS) and on membrane incorporation of fatty acids in healthy subjects. Prospective, sequential investigation comparing three different FO doses. Three groups of male subjects aged 26.8 +/- 3.2 years (BMI 22.5 +/- 2.1). One of three FO doses (Omegaven10%) as a slow infusion before LPS: 0.5 g/kg 1 day before LPS, 0.2 g/kg 1 day before, or 0.2 g/kg 2 h before. Temperature, hemodynamic variables, indirect calorimetry and blood samples (TNF-alpha, stress hormones) were collected. After LPS temperature, ACTH and TNF-alpha concentrations increased in the three groups: the responses were significantly blunted (p < 0.0001) compared with the control group of the Pluess et al. trial. Cortisol was unchanged. Lowest plasma ACTH, TNF-alpha and temperature AUC values were observed after a single 0.2 g/kg dose of FO. EPA incorporation into platelet membranes was dose-dependent. Having previously shown that the response to LPS was reproducible, this study shows that three FO doses blunted it to various degrees. The 0.2 g/kg perfusion immediately before LPS was the most efficient in blunting the responses, suggesting LPS capture in addition to the systemic and membrane effects.

Sawhorse-type diruthenium tetracarbonyl complexes containing porphyrin-derived ligands as highly selective photosensitizers for female reproductive cancer cells.

Diruthenium tetracarbonyl complexes of the type [Ru2(CO)4(l2-g2-O2CR)2L2] containing a Ru-Ru backbone with four equatorial carbonyl ligands, two carboxylato bridges, and two axial two-electron ligands in a sawhorse-like geometry have been synthesized with porphyrin-derived substituents in the axial ligands [1: R is CH3, L is 5-(4-pyridyl)-10,15,20-triphenyl-21,23H-porphyrin], in the bridging carboxylato ligands [2: RCO2H is 5-(4-carboxyphenyl)-10,15,20-triphenyl-21,23H-porphyrin, L is PPh3; 3: RCO2H is 5-(4-carboxyphenyl)-10,15,20-triphenyl-21,23H-porphyrin, L is 1,3,5-triaza-7-phosphatricyclo [3.3.1.1]decane], or in both positions [4: RCO2H is 5-(4-carboxyphenyl)-10,15,20-triphenyl-21,23H-porphyrin, L is 5-(4-pyridyl)-10,15,20-triphenyl-21,23H-porphyrin]. Compounds 1-3 were assessed on different types of human cancer cells and normal cells. Their uptake by cells was quantified by fluorescence and checked by fluorescence microscopy. These compounds were taken up by human HeLa cervix and A2780 and Ovcar ovarian carcinoma cells but not by normal cells and other cancer cell lines (A549 pulmonary, Me300 melanoma, PC3 and LnCap prostate, KB head and neck, MDAMB231 and MCF7 breast, or HT29 colon cancer cells). The compounds demonstrated no cytotoxicity in the absence of laser irradiation but exhibited good phototoxicities in HeLa and A2780 cells when exposed to laser light at 652 nm, displaying an LD50 between 1.5 and 6.5 J/cm2 in these two cell lines and more than 15 J/cm2 for the others. Thus, these types of porphyric compound present specificity for cancer cell lines of the female reproductive system and not for normal cells; thus being promising new organometallic photosensitizers.

Renal responses to three types of renin-angiotensin system blockers in patients with diabetes mellitus on a high-salt diet: a need for higher doses in diabetic patients?

Objective Activation of the renal renin-angiotensin system in patients with diabetes mellitus appears to contribute to the risk of nephropathy. Recently, it has been recognized than an elevation of prorenin in plasma also provides a strong indication of risk of nephropathy. This study was designed to examine renin-angiotensin system control mechanisms in the patient with diabetes mellitus.Methods We enrolled 43 individuals with type 2 diabetes mellitus. All individuals were on a high-salt diet to minimize the contribution of the systemic renin-angiotensin system. After an acute exposure to captopril (25 mg), they were randomized to treatment with either irbesartan (300 mg) or aliskiren (300 mg) for 2 weeks.Results All agents acutely lowered blood pressure and plasma aldosterone, and increased renal plasma flow and glomerular filtration rate. Yet, only captopril and aliskiren acutely increased plasma renin and decreased plasma angiotensin II, whereas irbesartan acutely affected neither renin nor angiotensin II. Plasma renin and angiotensin II subsequently did increase upon chronic irbesartan treatment. When given on day 14, irbesartan and aliskiren again induced the above hemodynamic, renal and adrenal effects, yet without significantly changing plasma renin. Irbesartan at that time did not affect plasma angiotensin II, whereas aliskiren lowered it to almost zero.Conclusion The relative resistance of the renal renin response to acute (irbesartan) and chronic (irbesartan and aliskiren) renin-angiotensin system blockade supports the concept of an activated renal renin-angiotensin system in diabetes, particularly at the level of the juxtaglomerular cell, and implies that diabetic patients might require higher doses of renin-angiotensin system blockers to fully suppress the renal renin-angiotensin system. J Hypertens 29: 2454-2461 (C) 2011 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.

Pharmacokinetics of synthetic atrial natriuretic peptides in normal men.

The kinetics of atrial natriuretic peptides (ANP) and the kinetic profile of their effect on blood pressure and renal hemodynamic and electrolyte excretion were investigated in 20 salt-loaded healthy volunteers during and after constant rate infusion. At steady state, mean plasma concentrations of ANP were measured at 210, 430, and 2990 pg/ml and mean systemic clearance was 2.6, 2.5, and 1.7 L/min for ANP infusion rates of 0.5, 1, and 5 micrograms/min, respectively, which corresponds to the clearance rate of other vasoactive peptide hormones. The apparent volume of distribution averaged 17 L and the mean half-life was 4.5 minutes. ANP induced dose-related effects on systemic and renal hemodynamic, as well as urinary electrolyte excretion, albeit with a time lag between onset and full effect.

Extracorporeal membrane oxygenation support in acardia.

In extreme situations, such as hyperacute rejection of heart transplant or major heart trauma, heart preservation may not be possible. Our experimental team works on a project of peripheral extracorporeal membrane oxygenation (ECMO) support in acardia as a bridge to heart transplantation or artificial heart implantation. An ECMO support was established in five calves (58.6 ± 6.9 kg) by the transjugular insertion to the caval axis of a self-expanded cannula, with carotid artery return. After baseline measurements, ventricular fibrillation was induced, great arteries were clamped, heart was excised, and right and left atria remnants, containing pulmonary veins, were sutured together leaving an atrial septal defect over the caval axis cannula. Measurements of pump flow and arterial pressure were taken with the pulmonary artery clamped and anastomosed with the caval axis for a total of 6 hours. Pulmonary artery anastomosis to the caval axis provided an acceptable 6 hour hemodynamic stability, permitting a peripheral access ECMO support in extreme scenarios indicating a heart explantation.

Breast and cervical cancer screening programme implementation in 16 countries.

OBJECTIVES: There is a continuing need to monitor and evaluate the impact of organized screening programmes on cancer incidence and mortality. We report results from a programme assessment conducted within the International Cancer Screening Network (ICSN) to understand the characteristics of cervical screening programmes within countries that have established population-based breast cancer screening programmes. METHODS: In 2007-2008, we asked 26 ICSN country representatives to complete a web-based survey that included questions on breast and cervical cancer screening programmes. We summarized information from 16 countries with both types of organized programmes. RESULTS: In 63% of these countries, the organization of the cervical cancer screening programme was similar to that of the breast cancer screening programme in the same country. There were differences in programme characteristics, including year established (1962-2003 cervical; 1986-2002 breast) and ages covered (15-70+ cervical; 40-75+ breast). Adoption of new screening technologies was evident (44% liquid-based Pap tests; 13% human papillomavirus (HPV)-triage tests cervical; 56% digital mammography breast). There was wide variation in participation rates for both programme types (<4-80% cervical; 12-88% breast), and participation rates tended to be higher for cervical (70-80%) than for breast (60-70%) cancer screening programmes. Eleven ICSN member countries had approved the HPV vaccine and five more were considering its use in their organized programmes. CONCLUSION: Overall, there were similarities and differences in the organization of breast and cervical cancer screening programmes among ICSN countries. This assessment can assist established and new screening programmes in understanding the organization and structure of cancer screening programmes.