C-C motif chemokine receptor 2 as a novel intermediate in the ovulatory cascade.

Expression of immune function genes within follicle cells has been reported in ovaries from many species. Recent work from our laboratory showed a direct effect of the monocyte chemoattractant protein 1/C-C motif chemokine receptor 2 system within the feline cumulus oocyte complex, by increasing the mRNA levels of key genes involved in the ovulatory cascade in vitro. Studies were designed to evaluate if C-C motif chemokine receptor 2 acts as a novel mediator of the ovulatory cascade in vitro. Therefore, feline cumulus oocyte complexes were cultured in the presence or absence of a highly selective C-C motif chemokine receptor 2 antagonist together with known inducers of cumulus-oocyte expansion and/or oocyte maturation to assess mRNA expression of key genes related to periovulatory events in other species as well as oocyte maturation. Also, the effects of recombinant monocyte chemoattractant protein 1 on spontaneous or gonadotrophin-induced oocyte maturation were assessed. This is an in vitro system using isolated cumulus oocyte complexes from feline ovaries. The present study reveals the modulation of several key ovulatory genes by a highly selective C-C motif chemokine receptor 2 antagonist. However, this antagonist was not enough to block the oocyte maturation induced by gonadotropins or amphiregulin. Nonetheless, recombinant monocyte chemoattractant protein 1 had a significant effect on spontaneous oocyte maturation, increasing the percentage of metaphase II stage oocytes in comparison to the control. This is the first study in any species to establish C-C motif chemokine receptor 2 as a mediator of some actions of the mid-cycle gonadotrophin surge.

A prostaglandin E2 receptor antagonist prevents pregnancies during a preclinical contraceptive trial with female macaques.

STUDY QUESTION: Can administration of a prostaglandin (PG) E2 receptor 2 (PTGER2) antagonist prevent pregnancy in adult female monkeys by blocking periovulatory events in the follicle without altering menstrual cyclicity or general health? SUMMARY ANSWER: This is the first study to demonstrate that a PTGER2 antagonist can serve as an effective non-hormonal contraceptive in primates. WHAT IS KNOWN ALREADY: The requirement for PGE2 in ovulation and the release of an oocyte surrounded by expanded cumulus cells (cumulus-oocyte expansion; C-OE) was established through the generation of PTGS2 and PTGER2 null-mutant mice. A critical role for PGE2 in primate ovulation is supported by evidence that intrafollicular injection of indomethacin in rhesus monkeys suppressed follicle rupture, whereas co-injection of PGE2 with indomethacin resulted in ovulation. STUDY DESIGN, SIZE, DURATION: First, controlled ovulation protocols were performed in adult, female rhesus monkeys to analyze the mRNA levels for genes encoding PGE2 synthesis and signaling components in the naturally selected pre-ovulatory follicle at different times after the ovulatory hCG stimulus (0, 12, 24, 36 h pre-ovulation; 36 h post-ovulation, n = 3-4/time point). Second, controlled ovarian stimulation cycles were utilized to obtain multiple cumulus-oocyte complexes (COCs) from rhesus monkeys to evaluate the role of PGE2 in C-OE in vitro (n = 3-4 animals/treatment; ≥3 COCs/animal/treatment). Third, adult cycling female cynomolgus macaques were randomly assigned (n = 10/group) to vehicle (control) or PTGER2 antagonist (BAY06) groups to perform a contraceptive trial. After the first treatment cycle, a male of proven fertility was introduced into each group and they remained housed together for the duration of the 5-month contraceptive trial that was followed by a post-treatment reversibility trial. PARTICIPANTS/MATERIALS, SETTING, METHODS: Quantitative real-time PCR, COC culture and expansion, immunofluorescence/confocal microscopy, enzyme immunoassay, contraceptive trial, ultrasonography, complete blood counts, serum biochemistry tests and blood lipid profiles. MAIN RESULTS AND THE ROLE OF CHANCE: Several mRNAs encoding proteins involved in PGE2 synthesis, metabolism and signaling increase (P < 0.05) in the periovulatory follicle after administration of an ovulatory hCG bolus. PGE2 signaling through PTGER2 induces cumulus cell expansion and production of hyaluronic acid, which are critical events for fertilization. Moreover, chronic administration of a selective PTGER2 antagonist resulted in a significant (P < 0.05 versus vehicle-treated controls) contraceptive effect without altering steroid hormone patterns or menstrual cyclicity during a 5-months contraceptive trial. Fertility recovered as early as 1 month after ending treatment. LIMITATIONS, REASONS FOR CAUTION: This is a proof-of-concept study in a non-human primate model. Further investigations are warranted to elucidate the mechanism(s) of PTGER2 antagonist action in the primate ovary. Although PTGER2 antagonist treatment did not produce any obvious undesirable effects, improvements in the mode of administration, as well as the efficacy of these compounds, are necessary to consider such a contraceptive for women. WIDER IMPLICATIONS OF THE FINDINGS: Monitoring as well as improving the efficacy and safety of female contraceptives is an important public health activity. Even though hormonal contraceptives are effective for women, concerns remain regarding their side-effects and long-term use because of the widespread actions of such steroidal products in many tissues. Moreover, some women cannot take hormones for medical reasons. Thus, development of non-hormonal contraceptives for women is warranted. STUDY FUNDING/COMPETING INTEREST(S): Supported by Bayer HealthCare Pharmaceuticals, The Eunice Kennedy Shriver NICHD Contraceptive Development and Research Center (U54 HD055744), NIH Office of the Director (Oregon National Primate Research Center P51 OD011092), and a Lalor Foundation Postdoctoral Basic Research Fellowship (MCP). The use of the Leica confocal was supported by grant number S10RR024585. Some of the authors (N.B., A.R., K.-H.F., U.F., B.B. and B.L.) are employees of Bayer Healthcare Pharma.

Interaction between epidermal growth factor receptor and C-C motif chemokine receptor 2 in the ovulatory cascade.

The epidermal growth factor receptor (EGFR) signaling pathway is one of the main pathways responsible for propagating the luteinizing hormone (LH) signal throughout the cumulus cells and the oocyte. Recently, we have proposed the C-C motif chemokine receptor 2 (CCR2) and its main ligand (monocyte chemoattractant protein-1, MCP1) as novel mediators of the ovulatory cascade. Our previous results demonstrate that the gonadotropins (GNT), amphiregulin (AREG), and prostaglandin E2 (PGE2) stimulation of periovulatory gene mRNA levels occurs, at least in part, through the CCR2/MCP1 pathway, proposing the CCR2 receptor as a novel mediator of the ovulatory cascade in a feline model. For that purpose, feline cumulus-oocyte complexes (COCs) were cultured in the presence or absence of an EGFR inhibitor, recombinant chemokine MCP1, and gonadotropins [as an inducer of cumulus-oocyte expansion (C-OE), and oocyte maturation] to further assess the mRNA expression of periovulatory key genes, C-OE, oocyte nuclear maturation, and steroid hormone production. We observed that MCP1 was able to revert the inhibition of AREG mRNA expression by an EGFR inhibitor within the feline COC. In accordance, the confocal analysis showed that the GNT-stimulated hyaluronic acid (HA) synthesis, blocked by the EGFR inhibitor, was recovered by the addition of recombinant MCP1 in the C-OE culture media. Also, MCP1 was able to revert the inhibition of progesterone (P4) production by EGFR inhibitor in the C-OE culture media. Regarding oocyte nuclear maturation, recombinant MCP1 could also revert the inhibition triggered by the EGFR inhibitor, leading to a recovery in the percentage of metaphase II (MII)-stage oocytes. In conclusion, our results confirm the chemokine receptor CCR2 as a novel intermediate in the ovulatory cascade and demonstrate that the EGFR/AREG and the CCR2/MCP1 signaling pathways play critical roles in regulating feline C-OE and oocyte nuclear maturation, with CCR2/MCP1 signaling pathway being downstream EGFR/AREG pathway within the ovulatory cascade.

[Impact of methicillin resistance on mortality and surveillance of vancomycin susceptibility in bacteremias caused by Staphylococcus aureus]. / Impacto de la resistencia a la meticilina sobre la mortalidad y vigilancia de la sensibilidad a la vancomicina en bacteriemias causadas por Staphylococcus aureus.

Staphylococcus aureus is a major nosocomial pathogen that causes severe morbidity and mortality in many hospitals worldwide. Besides, the incidence of S. aureus bacteremia has significantly increased over the past decades. The aims of this study were to detect the risk factors for methicillin resistance and mortality and to evaluate vancomycin susceptibility in methicillin-resistant isolates. Thus, 39 S. aureus isolates from blood cultures of hospitalized patients with bacteremia were studied in Nueva Clínica Chacabuco Tandil, Buenos Aires, Argentina during 01/2006-12/2008. The overall mortality was 51.3%, which was significantly associated with methicillin resistance (OR: 4.20, IC95%: 1.08-16.32, p: 0.05), even though it was not an independent mortality predictor as it was the mechanical ventilation (OR: 15.99, IC95%: 3.24 - 78.86). Previous surgery (OR: 17.23, IC95%: 1.80-164.60) and hospitalization in intensive care units (OR: 21.12, IC95%: 2.33-191.30) were independent predictors of meticillin-resistance. No isolates were found with reduced vancomycin susceptibility. All the studied isolates were in vitro susceptible to vancomycin with a MIC50 and MIC90 of 0.5 µg/ml.

Use of different kinds of persulfate activation with iron for the remediation of a PAH-contaminated soil.

Contamination of soils by persistent pollutants is considered an important matter of increasing concern. In this work, activated persulfate (PS) was applied for the remediation of a soil contaminated with polycyclic aromatic hydrocarbons (PAHs), such as anthracene (ANT), phenanthrene (PHE), pyrene (PYR) and benzo[a]pyrene (BaP). PS activation was performed by different ways; where ferric, ferrous sulfate salts (1-5mmol·L(-1)) and nanoparticles of zerovalent iron (nZVI) were used as activators. Moreover, in order to improve the oxidation rate of contaminants in the aqueous phase, the addition of sodium dodecyl sulfate (SDS), as anionic surfactant, was tested. On the other hand, it was also studied the role of humic acids (HA), as reducing agent or surfactant, on PAHs conversion. Removal efficiencies near 100% were achieved for ANT and BaP in all the runs carried out. Nevertheless, remarkable differences on removal efficiencies were observed for the different techniques applied in case of PHE and PYR. In this sense, the highest conversions of PHE (80%) and PYR (near 100%) were achieved when nZVI was used as activator. Similar results were obtained when activation was carried out either with Fe(2+) or Fe(3+). This can be explained by the presence of quinone type compounds, as 9,10-anthraquinone (ATQ), that can promote the reduction of Fe(3+) into Fe(2+), permitting PS radicals to be generated. On the other hand, the addition of HA did not produce an improvement of the process while surfactant addition slightly increases the PAHs removal. Furthermore, a kinetic model was developed, describing the behavior of persulfate consumption, and contaminants removal under first order kinetics.

[Compromise of work capacity and quality of life of epileptic subjects]. / Compromissione della capacità lavorativa e qualità della vita nei soggetti epilettici.

The authors test epileptic subjects as far as their professional ability is concerned. An enquiry into patients admitted to the Epilepsy Centre of San martino Hospital in Genova has been performed through a questionnaire about professional performance and quality of life. As far as work related problems are concerned 44.6 per cent of the subjects show the presence of difficulties, while the quality of life is primarily repressed in men relatively to work and in women relatively to social relationship.

Impacto de la resistencia a la meticilina sobre la mortalidad y vigilancia de la sensibilidad a la vancomicina en bacteriemias causadas por Staphylococcus aureus / Impact of methicillin resistance on mortality and surveillance of vancomycin susceptibility in bacteremias caused by Staphylococcus aureus

Staphylococcus aureus es uno de los principales patógenos nosocomiales y produce una alta morbimortalidad en numerosos hospitales del mundo. Además, la incidencia de bacteriemias por este microorganismo ha aumentado significativamente en las últimas décadas. Los objetivos del presente trabajo fueron identificar los factores de riesgo que favorecen la aparición de resistencia a la meticilina en aislamientos de S. aureus y los factores que afectan la mortalidad por bacteriemias asociadas a este patógeno, así como evaluar la sensibilidad a la vancomicina de las cepas resistentes a la meticilina. Se estudiaron 39 aislamientos de S. aureus provenientes de hemocultivos de pacientes internados con bacteriemia en la Nueva Clínica Chacabuco de Tandil (Pcia. de Buenos Aires, Argentina) en el período 01/2006-12/2008. La mortalidad global fue del 51,3% y estuvo significativamente asociada con la resistencia a la meticilina (OR: 4,20; IC95%: 1,08-16,32; p: 0,05); aunque dicho factor no fue un predictor independiente de mortalidad. La cirugía previa (OR: 17,23; IC95%: 1,80-164,60) y la estancia previa en la unidad de cuidados intensivos (OR: 21,12; IC95%: 2,33-191,30) fueron predictores independientes de la resistencia a la meticilina y la asistencia respiratoria mecánica (OR: 15,99; IC: 3,24-78,86) fue un predictor independiente de la mortalidad. No se detectaron cepas con sensibilidad disminuida a la vancomicina. Todos los aislamientos estudiados fueron sensibles in vitro a la vancomicina, con una CIM50 y una CIM90 de 0,5 μg/ml.

Staphylococcus aureus is a major nosocomial pathogen that causes severe morbidity and mortality in many hospitals worldwide. Besides, the incidence of S. aureus bacteremia has significantly increased over the past decades. The aims of this study were to detect the risk factors for methicillin resistance and mortality and to evaluate vancomycin susceptibility in methicillin-resistant isolates. Thus, 39 S. aureus isolates from blood cultures of hospitalized patients with bacteremia were studied in Nueva Clínica Chacabuco Tandil, Buenos Aires, Argentina during 01/2006-12/2008. The overall mortality was 51.3%, which was significantly associated with methicillin resistance (OR: 4.20, IC95%: 1.08-16.32, p: 0.05), even though it was not an independent mortality predictor as it was the mechanical ventilation (OR: 15.99, IC95%: 3.24 - 78.86). Previous surgery (OR: 17.23, IC95%: 1.80-164.60) and hospitalization in intensive care units (OR: 21.12, IC95%: 2.33-191.30) were independent predictors of meticillin-resistance. No isolates were found with reduced vancomycin susceptibility. All the studied isolates were in vitro susceptible to vancomycin with a MIC50 and MIC90 of 0.5 μg/ml.

[Acute intrathoracic respiratory infections in hospitalized children. Uruguay 1984-1986]. / Infecciones respiratorias agudas intratorácicas en niños hospitalizados. Uruguay 1984-1986.

Between may 1984 and november 1986, a study, which included 475 children under five years of age hospitalized due to acute intrathoracic respiratory infections, was carried out in order to obtain clinical, radiological and etiological characteristics which may aid in establishing norms to diagnose and treat these patients. Nasopharyngeal aspirations were performed on each child, while viral diagnosis was done through viral isolation techniques and indirect immunofluorescence. The presence of a virus was detected in 34.4% of the cases and in 28.8% of a subsample. A precoded questionnaire was used to obtain the clinical information needed and all X-rays were reviewed by the same radiologist using simple pre-established criteria. A comparison was made on the similarities found between both the clinical and radiological diagnosis, as well as the sensitivity and specificity of some of the clinical signs which characterize bronchiolitis and the pneumoniae.

Counterimmunoelectrophoresis with influenza antigens. I. Use of avian plague virus to detect type-specific antibodies to influenza A in human sera.

Avian plague virus was used as antigen in a counterimmunoelectrophoresis technique. This virus was selected because it detects only type-specific influenza A antibodies in human sera, avoiding the possible interference of other antigens with anodic migration. The results with reference sera, as well as the correlation of positive sera found by counterimmunoelectrophoresis and complement fixation with the proposed antigen, in the absence of other types of antibodies to fowl plague virus antigen, support the conclusion that the counterimmunoelectrophoresis technique reveals type-specific antibodies. The test is more sensitive than immunodiffusion but less sensitive than complement fixation. Its sensitivity, simplicity, and rapidity make it suitable for serologic surveys of human influenza A.

A possible new trend in the management of the carcinoma of the cervix uteri.

Thirty-three patients with locally advanced carcinoma of the cervix were treated with chemotherapy as first line treatment. Great emphasis was applied to document, in the most objective manner, the tumor size response. The first 8 patients received a conventional scheme composed of vincristine, bleomycin and cis-platinum (VBP) at 21-day intervals. The results were not as satisfactory as expected. In the other 25 patients a more aggressive VBP scheme was used, at 10-day intervals. Surprisingly satisfactory results and tolerance were observed. In many instances verified tumor reduction allowed surgical radical treatment in prechemotherapy inoperable cases.

Citopunción ecoguiada de lesiones mamarias no palpables. Ventajes y limitaciones / Cytopuncture guided of nonpalpable breast lessions. Advantes and limitations

La nueva imagenología mamaria ha descubierto un grupo de lesiones no palpables que puede alcanzar hasta el treinta por ciento de los casos examinados