Fine needle aspirate cell blocks are reliable for detection of hormone receptors and HER-2 by immunohistochemistry in breast carcinoma

Aims: To evaluate the reliability of fine needle aspirate cell blocks in the assessment of oestrogen receptor (ER), progesterone receptor (PR) and HER-2/neu proteins by immunohistochemistry in comparison with surgical specimens. Materials and methods: This is a retrospective study of 62 cases of breast carcinoma diagnosed by fine needle aspiration cytology (FNAC) and confirmed using the surgical specimen. Immunohistochemical tests were performed to assess the presence of oestrogen receptor (ER), progesterone receptor (PR) and HER-2/neu proteins in cell blocks and the corresponding surgical specimens. The cell block method used alcohol prior to formalin fixation. Cases with 10% or more stained cells were considered positive for ER and PR. Positivity for HER-2/neu was assessed on a scale of 0-3+. The criterion for positivity was a score of 3+. Results: Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of the cell blocks in the investigation of ER, PR and HER-2/neu protein (3+) were (%): ER, 92.7, 85.7, 92.7, 85.7 and 90.3; PR, 92.7, 94.7, 97.4, 87.0 and 93.5; HER-2/neu, 70.0, 100.0, 100.0, 94.5 and 95.2. Discrepancies were seen in cell blocks in the 1+ and 2+ HER-2/neu staining scores: two of 12 cases scoring 2+ and one case of 26 scoring 1+ on cell blocks scored 3+ on surgical specimens. The correlation index between cell block and corresponding surgical specimen varied from 90% to 94%. Conclusion: Cell blocks provide a useful method of assessing ER, PR and HER-2/neu, mainly for inoperable and recurrent cases, but consideration should be given to carrying out FISH analysis on 1+ as well as 2+ HER-2/neu results. © 2012 Blackwell Publishing Ltd.

Anti-inflammatory mechanisms of the annexin A1 protein and its mimetic peptide Ac2-26 in models of ocular inflammation in vivo and in vitro

Annexin A1 (AnxA1) is a protein that displays potent anti-inflammatory properties, but its expression in eye tissue and its role in ocular inflammatory diseases have not been well studied. We investigated the mechanism of action and potential uses of AnxA1 and its mimetic peptide (Ac2-26) in the endotoxin-induced uveitis (EIU) rodent model and in human ARPE-19 cells activated by LPS. In rats, analysis of untreated EIU after 24 and 48 h or EIU treated with topical applications or with a single s.c. injection of Ac2-26 revealed the anti-inflammatory actions of Ac2-26 on leukocyte infiltration and on the release of inflammatory mediators; the systemic administration of Boc2, a formylated peptide receptor (fpr) antagonist, abrogated the peptide's protective effects. Moreover, AnxA1-/- mice exhibited exacerbated EIU compared with wild-type animals. Immunohistochemical studies of ocular tissue showed a specific AnxA1 posttranslational modification in EIU and indicated that the fpr2 receptor mediated the anti-inflammatory actions of AnxA1. In vitro studies confirmed the roles of AnxA1 and fpr2 and the protective effects of Ac2-26 on the release of chemical mediators in ARPE-19 cells. Molecular analysis of NF-κB translocation and IL-6, IL-8, and cyclooxygenase-2 gene expression indicated that the protective effects of AnxA1 occur independently of the NF-κB signaling pathway and possibly in a posttranscriptional manner. Together, our data highlight the role of AnxA1 in ocular inflammation, especially uveitis, and suggest the use of AnxA1 or its mimetic peptide Ac2-26 as a therapeutic approach. Copyright © 2013 by The American Association of Immunologists, Inc.

Manipulation of the periovulatory sex steroidal milieu affects endometrial but not luteal gene expression in early diestrus Nelore cows

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Effects of catecholamines on volemic replacement with saline solution and the impact on heart rate variability in rabbits subjected to hemorrhage. A study by spectral analysis

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Increased Expression of Angiotensin II Type 2 Receptors in the Solitary-Vagal Complex Blunts Renovascular Hypertension

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Dysautonomias in parkinson's disease: cardiovascular changes and autonomic modulation in conscious rats after infusion of bilateral 6-OHDA in substantia nigra

Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES)

Interação entre as vias de sinalização de receptores serotoninérgicos e Β-adrenérgicos em artéria femoral de ratos

Fundamento: A doença coronária tem sido amplamente estudada em pesquisas cardiovasculares. No entanto, pacientes com doença arterial periférica (DAP) têm piores resultados em comparação àqueles com doença arterial coronariana. Portanto, os estudos farmacológicos com artéria femoral são altamente relevantes para a melhor compreensão das respostas clínicas e fisiopatológicas da DAP. Objetivo: Avaliar as propriedades farmacológicas dos agentes contráteis e relaxantes na artéria femoral de ratos. Métodos: As curvas de resposta de concentração à fenilefrina contrátil (FC) e à serotonina (5-HT) e os agentes relaxantes isoproterenol (ISO) e forskolina foram obtidos na artéria femoral de ratos isolada. Para as respostas ao relaxamento, os tecidos foram contraídos com FC ou 5-HT. Resultados: A potência de classificação na artéria femoral foi de 5-HT > FC para as respostas contráteis. Em tecidos contraídos com 5-HT, as respostas de relaxamento ao isoproterenol foram praticamente abolidas em comparação aos tecidos contraídos com FC. A forskolina, um estimulante da adenilil ciclase, restaurou parcialmente a resposta de relaxamento ao ISO em tecidos contraídos com 5-HT. Conclusão: Ocorre uma interação entre as vias de sinalização dos receptores β-adrenérgicos e serotoninérgicos na artéria femoral. Além disso, esta pesquisa fornece um novo modelo para estudar as vias de sinalização serotoninérgicas em condições normais e patológicas que podem ajudar a compreender os resultados clínicos na DAP.

Efeito Diabetes mellitus gestacional na modulação de genes relacionados ao metabolismo mitocondrial e a implicação na predisposiçao do recém-nascido à obesidade

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Role of alfa2-adrenoceptors in the lateral parabrachial nucleus in the control of body fluid homeostasis

Central α2-adrenoceptors and the pontine lateral parabrachial nucleus (LPBN) are involved in the control of sodium and water intake. Bilateral injections of moxonidine (α2-adrenergic/imidazoline receptor agonist) or noradrenaline into the LPBN strongly increases 0.3 M NaCl intake induced by a combined treatment of furosemide plus captopril. Injection of moxonidine into the LPBN also increases hypertonic NaCl and water intake and reduces oxytocin secretion, urinary sodium, and water excreted by cell-dehydrated rats, causing a positive sodium and water balance, which suggests that moxonidine injected into the LPBN deactivates mechanisms that restrain body fluid volume expansion. Pretreatment with specific α2-adrenoceptor antagonists injected into the LPBN abolishes the behavioral and renal effects of moxonidine or noradrenaline injected into the same area, suggesting that these effects depend on activation of LPBN α2-adrenoceptors. In fluid-depleted rats, the palatability of sodium is reduced by ingestion of hypertonic NaCl, limiting intake. However, in rats treated with moxonidine injected into the LPBN, the NaCl palatability remains high, even after ingestion of significant amounts of 0.3 M NaCl. The changes in behavioral and renal responses produced by activation of α2-adrenoceptors in the LPBN are probably a consequence of reduction of oxytocin secretion and blockade of inhibitory signals that affect sodium palatability. In this review, a model is proposed to show how activation of α2-adrenoceptors in the LPBN may affect palatability and, consequently, ingestion of sodium as well as renal sodium excretion.

Efeito da dexmedetomidina sobre a arritmia cardíaca induzida pela adrenalina em cães anestesiados pelo sevofluorano

Avaliou-se o efeito da dexmedetomidina sobre o ritmo cardíaco em 20 cães, sem raça definida, de ambos os sexos e considerados sadios, anestesiados pelo sevofluorano e submetidos a doses crescentes de adrenalina. Os animais foram, aleatoriamente, distribuídos em dois grupos (placebo e dexmedetomidina). No grupo placebo, os animais receberam, por via intravenosa, solução de NaCl a 0,9%, na dose de 0,3ml/kg. Foram considerados dois momentos, M0 e M1, imediatamente antes e após a aplicação, respectivamente. Após 10 minutos, realizou-se a indução anestésica com sevofluorano, por meio de máscara facial vedada, até a perda do reflexo laringotraqueal. em seguida, procedeu-se à intubação orotraqueal e a manutenção da anestesia foi realizada com a administração de sevofluorano na concentração de 1,5CAM, em circuito anestésico com reinalação parcial de gases. Decorridos 20 minutos da indução anestésica, iniciou-se a administração intravenosa contínua de solução de adrenalina a 2% em doses crescentes de 1, 2, 3, 4 e 5mg/kg/min, por meio de bomba de infusão, com aumento da dose em intervalos de 10 minutos. Imediatamente antes desse acréscimo eram feitas as mensurações (M2 a M6). No grupo dexmedetomidina empregou-se a mesma metodologia substituindo-se a solução de NaCl a 0,9% por hidrocloridrato de dexmedetomidina, na dose de 1µg/kg. Foram registradas as pressões arteriais, em M0 e em M2 a M6, e o traçado eletrocardiográfico, na derivação DII (M2 a M6), considerando-se para efeito estatístico o número total de bloqueios atrioventriculares (BAV) de primeiro e segundo graus e de complexos ventriculares prematuros (ESV), coincidentes com cada dose de adrenalina. Os dados foram submetidos à análise de variância seguida pelo teste de Tukey (P<0,05). Verificou-se que a dexmedetomidina interfere significativamente na condução atrioventricular levando a maior ocorrência de BAV e reduz o número de ESV nas doses infundidas de 2 e 3mg/kg/min de adrenalina. Logo após a aplicação de dexmedetomidina, observaram-se redução da freqüência cardíaca e da pressão arterial, cuja diminuição persistiu por até uma hora.

Fractal correlation of heart rate variability in obese children

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Fractal correlation property of heart rate variability in chronic obstructive pulmonary disease

Background: It was reported that autonomic nervous system function is altered in subjects with chronic obstructive pulmonary disease (COPD). We evaluated short-and long-term fractal exponents of heart rate variability (HRV) in COPD subjects.Patients and methods: We analyzed data from 30 volunteers, who were divided into two groups according to spirometric values: COPD (n = 15) and control (n = 15). For analysis of HRV indices, HRV was recorded beat by beat with the volunteers in the supine position for 30 minutes. We analyzed the linear indices in the time (SDNN [standard deviation of normal to normal] and RMSSD [root-mean square of differences]) and frequency domains (low frequency [LF], high frequency [HF], and LF/HF), and the short-and long-term fractal exponents were obtained by detrended fluctuation analysis. We considered P < 0.05 to be a significant difference.Results: COPD patients presented reduced levels of all linear exponents and decreased short-term fractal exponent (alpha-1: 0.899 +/- 0.18 versus 1.025 +/- 0.09, P = 0.026). There was no significant difference between COPD and control groups in alpha-2 and alpha-1/alpha-2 ratio.Conclusion: COPD subjects present reduced short-term fractal correlation properties of HRV, which indicates that this index can be used for risk stratification, assessment of systemic disease manifestations, and therapeutic procedures to monitor those patients.

Review of Fluconazole Properties and Analytical Methods for Its Determination

Fluconazole, alpha-(2.4-diflurofenil)-alpha-(1H-triazol-1-methyl)-1H-1,2,4-triazol-1-ethanol, is an antifungal of the triazoles class. It shows activity against species of Candida sp. and it is indicated in cases of oropharyngeal candidiasis, esophageal, vaginal, and deep infection. Fluconazole is a selective inhibitor of ergosterol, a steroid exclusive of the cell membrane of fungal cells. Fluconazole is highly absorbed by the gastrointestinal tract and spreads easily by body fluids. The main adverse reactions related to the use of fluconazole are nausea, vomiting, headache, rash, abdominal pain, diarrhea, and alopecia in patients undergoing prolonged treatment with a dose of 400 mg/day. In the form of raw material, pharmaceutical formulations, or biological material, fluconazole can be determined by methods such as titration, spectrophotometry, and thin-layer, gas, and liquid chromatography. This article discusses the pharmacological and physicochemical properties of fluconazole and also the methods of analysis applied to the determination of the drug.

A preliminary trial comparison of several anesthetic techniques in cats

The aim of this study was to investigate the effect of several drug combinations (atropine, xylazine, romifidine, methotrimeprazine, midazolam, or fentanyl) with ketamine for short term anesthesia in cats. Twelve cats were anesthetized 6 times by using a cross-over Latin square protocol: methotrimeprazine was combined with midazolam, ketamine, and fentanyi; midazolam and ketamine; romifidine and ketamine; and xylazine and ketamine. Atropine was combined with romifidine and ketamine, and xylazine and ketamine. Temperature, heart rate, and respiratory rate decreased in all groups. Apnea occurred in 1 cat treated with methotrimeprazine, romifidine, and ketamine, suggesting that ventilatory support may be necessary when this protocol is used. Emesis occurred in some cats treated with alpha(2)-adrenoceptor agonists, and this side effect should be considered when these drugs are used.

Dexmedetomidine Alters the Cardiovascular Response During Infra-Renal Aortic Cross-Clamping in Sevoflurane-Anesthetized Dogs

Some properties of the volatile anesthetics, such as vasodilatation and myocardial depression, combined with the sympathetic inhibition that alpha 2-agonists can produce may determine hemodynamic alterations during aortic, surgery. The interaction between dexmedetomidine (DEX), an alpha 2-agonist, and sevoflurane during aortic surgery is unknown. We studied the effects of DEX on hemodynamics and systemic oxygenation during aortic cross-clamping (Aox) and unclamping (UAox) in sevoflurane-anesthetized dogs Twenty dogs were. anesthetized with sevoflurane and were randomly assigned to two groups prior to Aox and UAox: control, n = 10, received saline infusion only, and DEX (1 mu g.kg(-1) load followed by 1 mu g.kg(-1).h(-1) infusion), n = 10. Hemodynamic and oxygenation variables were measured at baseline, after saline or DEX loading dose, 20 and 40 min after Aox, and 20 and 40 min after UAox. After DEX administration, heart rate, cardiac index l and systemic oxygen transport index (131021) were lower than in control group. Aox increased mean arterial pressure (MAP) and systemic vascular resistance index (SVRI) in both groups, but the effects were greater with DEX. Cl, heart rate, and DO(2)I were lower, while central venous pressure (CVP) and pulmonary artery occlusion pressure were higher in DEX compared to control. After UAox, MAP, CVP and SVRI were maintained higher in DEX in relation to control. We conclude that in sevoflurane-anesthetized dogs DEX alters the cardiovascular response during aortic surgery.