Vascular endothelial growth factor A (VEGFA) modulates bovine placenta steroidogenesis in vitro

Our objectives were to investigate the possible role of VEGFA in bovine placenta steroid synthesis and to determine whether cloned derived placental cells present similar responses as non-cloned ones. Placental cells from cloned (term) and non-cloned (days 90, 150, 210 and term) pregnancies were isolated and treated with VEGFA (50 ng/ml) for 24, 48 or 96 h. Progesterone (P-4) and estrone sulfate (E1S) were assessed by RIA, while aromatase P450-positive cells were quantified using the point counting test. The percentages of steroidogenic and non-steroidogenic populations were determined by flow cytometry. VEGFA augmented or decreased P-4 and E1S concentrations as well as aromatase P450-positive cell density, depending on gestational age and time in culture. The percentage of steroidogenic cells was lower than that of non-steroidogenic ones for each culture time (P < 0.05). VEGFA treatment did not change the proportion of steroidogenic and non-steroidogenic cells. Placental cells derived from cloned pregnancies presented higher concentrations of E1S and P4 than the non-cloned group. However, aromatase P450-positive cells were similar between groups (P > 0.05). VEGFA treatment altered P-4 and E1S levels in placental cells depending on type of gestation. These results suggest that VEGFA acts locally in the bovine placenta to modulate steroidogenesis during gestation, but in a different pattern between cloned and non-cloned derived placental cells at term. Therefore, this factor can be considered an important regulator of placental development and function. (C) 2012 Elsevier Ltd. All rights reserved.

Motor function measure scale, steroid therapy and patients with Duchenne muscular dystrophy

Objective: To assess the evolution of motor function in patients with Duchenne muscular dystrophy (DMD) treated with steroids (prednisolone or deflazacort) through the Motor Function Measure (MFM), which evaluates three dimensions of motor performance (D1, D2, D3). Methods: Thirty-three patients with DMD (22 ambulant, 6 non-ambulant and 5 who lost the capacity to walk during the period of the study) were assessed using the MFM scale six times over a period of 18 months. Results: All the motor functions remained stable for 14 months in all patients, except D1 for those who lost their walking ability. In ambulant patients, D2 (axial and proximal motor capacities) motor functions improved during six months; an improvement in D3 (distal motor capacity) was noted during the total follow-up. D1 (standing posture and transfers) and total score were useful to predict the loss of the ability to walk. Conclusions: The use of the MFM in DMD patients confirms the benefits of the steroid treatment for slowing the progression of the disease.

Melatonin reduces LH, 17 beta-estradiol and induces differential regulation of sex steroid receptors in reproductive tissues during rat ovulation

Abstract Background Melatonin is associated with direct or indirect actions upon female reproductive function. However, its effects on sex hormones and steroid receptors during ovulation are not clearly defined. This study aimed to verify whether exposure to long-term melatonin is able to cause reproductive hormonal disturbances as well as their role on sex steroid receptors in the rat ovary, oviduct and uterus during ovulation. Methods Twenty-four adult Wistar rats, 60 days old (+/- 250 g) were randomly divided into two groups. Control group (Co): received 0.9% NaCl 0.3 mL + 95% ethanol 0.04 mL as vehicle; Melatonin-treated group (MEL): received vehicle + melatonin [100 μg/100 g BW/day] both intraperitoneally during 60 days. All animals were euthanized by decapitation during the morning estrus at 4 a.m. Results Melatonin significantly reduced the plasma levels of LH and 17 beta-estradiol, while urinary 6-sulfatoximelatonin (STM) was increased at the morning estrus. In addition, melatonin promoted differential regulation of the estrogen receptor (ER), progesterone receptor (PR), androgen receptor (AR) and melatonin receptor (MTR) along the reproductive tissues. In ovary, melatonin induced a down-regulation of ER-alpha and PRB levels. Conversely, it was observed that PRA and MT1R were up-regulated. In oviduct, AR and ER-alpha levels were down-regulated, in contrast to high expression of both PRA and PRB. Finally, the ER-beta and PRB levels were down-regulated in uterus tissue and only MT1R was up-regulated. Conclusions We suggest that melatonin partially suppress the hypothalamus-pituitary-ovarian axis, in addition, it induces differential regulation of sex steroid receptors in the ovary, oviduct and uterus during ovulation.

Lung function monitoring in patients with duchenne muscular dystrophy on steroid therapy

Background Duchenne muscular dystrophy (DMD) is a sex-linked inherited muscle disease characterized by a progressive loss in muscle strength and respiratory muscle involvement. After 12 years of age, lung function declines at a rate of 6 % to 10.7 % per year in patients with DMD. Steroid therapy has been proposed to delay the loss of motor function and also the respiratory involvement. Method In 21 patients with DMD aged between seven and 16 years, the forced vital capacity (FVC) and the forced expiratory volume in one second (FEV1) were evaluated at three different times during a period of two years. Results We observed in this period of evaluation the maintenance of the FVC and the FEV1 in this group of patients independently of chronological age, age at onset of steroid therapy, and walking capacity. Conclusion The steroid therapy has the potential to stabilize or delay the loss of lung function in DMD patients even if they are non-ambulant or older than 10 years, and in those in whom the medication was started after 7 years of age.

Proteinuria predicts relapse in adolescent and adult minimal change disease

OBJECTIVE: This study sought to outline the clinical and laboratory characteristics of minimal change disease in adolescents and adults and establish the clinical and laboratory characteristics of relapsing and non-relapsing patients. METHODS: We retrospectively evaluated patients with confirmed diagnoses of minimal change disease by renal biopsy from 1979 to 2009; the patients were aged >13 years and had minimum 1-year follow-ups. RESULTS: Sixty-three patients with a median age (at diagnosis) of 34 (23-49) years were studied, including 23 males and 40 females. At diagnosis, eight (12.7%) patients presented with microscopic hematuria, 17 (27%) with hypertension and 17 (27%) with acute kidney injury. After the initial treatment, 55 (87.3%) patients showed complete remission, six (9.5%) showed partial remission and two (3.1%) were nonresponders. Disease relapse was observed in 34 (54%) patients who were initial responders (n = 61). In a comparison between the relapsing patients (n = 34) and the non-relapsing patients (n = 27), only proteinuria at diagnosis showed any significant difference (8.8 (7.1-12.0) vs. 6.0 (3.6-7.3) g/day, respectively, p = 0.001). Proteinuria greater than 7 g/day at the initial screening was associated with relapsing disease. CONCLUSIONS: In conclusion, minimal change disease in adults may sometimes present concurrently with hematuria, hypertension, and acute kidney injury. The relapsing pattern in our patients was associated with basal proteinuria over 7 g/day.

Coordinated expression of oestrogen and androgen receptors in HER2-positive breast carcinomas: impact on proliferative activity

Aims Human epidermal growth factor receptor 2 (HER2)-positive breast cancers are aggressive neoplasms associated with a variable response to systemic therapies. Therefore, the identification of biomarkers to better characterise this heterogeneity would improve treatment efficacy. The aim of this study was to evaluate the influence of androgen receptor (AR) and oestrogen receptor (ER) on clinicopathological features in a series of HER2-positive breast carcinomas. Methods A total of 104 carcinomas were selected and reviewed. Immunohistochemical studies for ER, progesterone receptor and Ki-67 were analysed on tumour whole histological sections. AR expression was analysed on samples represented on tissue microarrays. According to steroid receptor expression, cases were classified into three groups: AR positive/ER positive (48 cases), AR positive/ER negative (41 cases) and AR negative/ER negative (13 cases). Results AR-positive tumours corresponded to 89 (85.6%) of 104 carcinomas. AR-positive carcinomas were associated with a higher frequency of ER and progesterone receptor co-expression and lower proliferative activity determined by the expression of Ki-67. AR-negative carcinomas were more often high grade. The group of AR-positive/ER-negative carcinomas was associated with the highest frequency of apocrine morphological features. The group of AR-negative/ER-negative carcinomas was associated with the highest proliferative activity and the highest frequency of high histological and nuclear grade. The lowest frequency of high-grade tumours and the lowest proliferative activity were seen among tumours with expression of both receptors. Conclusions These results suggest that co-expression of AR and ER can provide a protective effect based on phenotypical presentation of HER2-positive carcinomas. Furthermore, lack of both steroid hormone receptors characterises the most aggressive phenotype.

The first cardiac transplant experience in a patient with mucopolysaccharidosis

Hunter syndrome (MPSII) is a rare X-linked lysosomal storage disorder that can affect multiple systems but primarily affects the heart. We report the case of a previously asymptomatic 23-year-old patient who had an attenuated form of MPSII and presented with refractory heart failure that required a heart transplant. The diagnosis was confirmed by detection of an increase in urinary excretion of glycosaminoglycans, a deficiency in enzymatic activity, and molecular analysis. A myocardial biopsy revealed hypertrophic cardiomyocytes, mild fibrosis, and lysosomal storage in interstitial cells. Molecular analysis identified a novel mutation in the iduronate-2-sulfatase gene. Although the clinical outcome was not favorable, we believe that this approach may be valid in end-stage heart failure. (C) 2012 Elsevier Inc. All rights reserved.

Action of ANP on the nongenomic dose-dependent biphasic effect of aldosterone on NHE1 in proximal S3 segment

The rapid (2 min) nongenomic effects of aldosterone (ALDO) and/or spironolactone (MR antagonist), RU 486 (GR antagonist), atrial natriuretic peptide (ANP) and dimethyl-BAPTA (BAPTA) on the intracellular pH recovery rate (pHirr) via NHE1 (basolateral Na+/H+ exchanger isoform), after the acid load induced by NH4Cl, and on the cytosolic free calcium concentration ([Ca2+](i)) were investigated in the proximal S3 segment isolated from rats, by the probes BCECF-AM and FLUO-4-AM, respectively. The basal pHi was 7.15+/-0.008 and the basal pHirr was 0.195+/-0.012 pH units/min (number of tubules/number of tubular areas = 16/96). Our results confirmed the rapid biphasic effect of ALDO on NHE1: ALDO (10(-12) M) increases the pHirr to approximately 59% of control value, and ALDO (10(-6)M) decreases it to approximately 49%. Spironolactone did not change these effects, but RU 486 inhibited the stimulatory effect and maintained the inhibitory effect. ANP (10(-6) M) or BAPTA (5 x 10(-5) M) alone had no significant effect on NHE1 but prevented both effects of ALDO on this exchanger. The basal [Ca2+](i) was 104+/-3 nM (15), and ALDO (10(-12) or 10(-6) M) increased the basal [Ca2+](i) to approximately 50% or 124%, respectively. RU 486, ANP and BAPTA decreased the [Ca2+](i) and inhibited the stimulatory effect of both doses of ALDO. The results suggest the involvement of GR on the nongenomic effects of ALDO and indicate a pHirr-regulating role for [Ca2+](i) that is mediated by NHE1, stimulated/impaired by ALDO, and affected by ANP or BAPTA with ALDO. The observed nongenomic hormonal interaction in the S3 segment may represent a rapid and physiologically relevant regulatory mechanism in the intact animal under conditions of volume alterations. (C) 2011 Elsevier Ltd. All rights reserved.

The Impact of Tacrolimus as Rescue Therapy in Children Using a Double Immunosuppressive Regimen After Heart Transplantation

Background. Organ transplant recipients with refractory rejection or intolerance to the prescribed immunosuppressant may respond to rescue therapy with tacrolimus. We sought to evaluate the clinical outcomes of children undergoing heart transplantation who required conversion from a cyclosporine-based, steroid-free therapy to a tacrolimus-based regimen. Methods. We performed a prospective, observational, cohort study of 28 children who underwent conversion from cyclosporine-based, steroid-free therapy to a tacrolimus-based therapy for refractory or late rejection or intolerance to cyclosporine. Results. There was complete resolution of refractory rejection episodes and adverse side effects in all patients. The incidence rate (X100) of rejection episodes before and after conversion was 7.98 and 2.11, respectively (P <= .0001). There was a 25% mortality rate in patients using tacrolimus after a mean period of 60 months after conversion. Conclusion. Tacrolimus is effective as rescue therapy for refractory rejection and is a therapeutic option for pediatric patients.

Proactive management of extreme prematurity: disagreement between obstetricians and neonatologists

Objective: To verify, in extremely preterm infants, if disagreement between obstetricians and neonatologists regarding proactive management is associated with early death. Study Design: Prospective cohort of 484 infants with 23(0/7) to 26(6/7) weeks, without malformations, born from January 2006 to December 2009 in eight Brazilian hospitals. Pro-active management was defined as indication of >= 1 dose of antenatal steroid or cesarean section (obstetrician) and resuscitation at birth according to the international guidelines (neonatologist). Main outcome was neonatal death in the first 24 h of life. Result: Obstetricians and neonatologists disagreed in 115 (24%) patients: only neonatologists were proactive in 107 of them. Disagreement between professionals increased 2.39 times the chance of death in the first day (95% confidence interval 1.40 to 4.09), adjusted for center and maternal/neonatal clinical conditions. Conclusion: In infants with 23 to 26 weeks of gestation, disagreement between obstetricians and neonatologists, translated as lack of antenatal steroids and/or vaginal delivery, despite resuscitation procedures, increases the odds of death in the first day. Journal of Perinatology (2012) 32, 913-919; doi:10.1038/jp.2012.28; published online 29 March 2012

Treatment of central giant cell lesions using bisphosphonates with intralesional corticosteroid injections

Central giant cell lesions are benign intraosseous proliferative lesions that have considerable local aggressiveness. Nonsurgical treatment methods, such as intralesional corticosteroid injections, systemic calcitonin and interferon have been reported. Recently, bisphosphonates have been used to treat central giant cell lesions. A case of a 36-year-old male with a central giant cell lesion crossing the mandibular midline was treated with intralesional corticosteroids combined with alendronate sodium for the control of systemic bone resorption. The steroid injections and the use of bisphosphonates were stopped after seven months when further needle penetration into the lesion was not possible due to new bone formation. After two years, the bony architecture was near normal, and only minimal radiolucency was present around the root apices of the involved teeth. The patient was followed up for four years, and panoramic radiography showed areas of new bone formation. Thus far, neither recurrence nor side effects of the medication have been detected.

An integrated approach to evaluate emerging contaminants in drinking water

The chemical stock of emerging contaminants in Brazilian drinking water is of great interest due to the poor water quality at surface water intakes. In addition, little is known about the effect of some contaminants, such as endocrine disrupting chemicals (EDCs), which may be present in both raw and treated water. The aim of this work was to evaluate selected emerging contaminants in Brazilian waters using both chemical and biological analyses. Sampling sites were established in different municipalities based upon raw water quality data. Estrone, 17 beta-estradiol, estriol, 17 alpha-ethinylestradiol, bisphenol A, 4-n-octylphenol and 4-n-nonylphenol were determined in the samples by liquid chromatography-tandem mass spectrometry. A yeast assay using a Saccharomyces cerevisiae bioluminescent bioreporter was used to evaluate the estrogenic activity of the water samples. The first integrated results revealed similarities between the two individual approaches, since higher values for the bioassay were accompanied by significant concentrations of some selected compounds in surface water samples. No estrogenicity was observed for drinking water samples. Our results also indicate that the usual paradigm of evaluating water quality by measuring selected EDCs in a given water sample via chemical analysis, needs to be reviewed since the observed estrogenicity of a water sample is now a better guiding parameter to the selection of samples and substances to be chemically investigated in further analysis. So far, the data bank produced in this work, i.e., the comparison between chemical burden and observed estrogenicity, is not yet sufficiently robust to fully guide this decision. (C) 2011 Elsevier B.V. All rights reserved.

Tunnel excavation triggering pulmonary sarcoidosis

Context A definite cause of sarcoidosis has not been identified, however past research suggests that environmental factors may be triggers of the granulomatous response in genetically susceptible individuals. Case Presentation A 22-year-old male non-smoker, presented with progressive exertional dyspnea and cough of 3 months duration. One year before, when he started working in tunnel excavation, he had a normal chest radiograph. Chest imaging revealed bilateral nodules and masses of peribronchovascular distribution plus mediastinal lymphadenomegaly. Histologic lymph node analysis revealed non-caseating confluent granulomas. Sarcoidosis was diagnosed. The patient was treated with corticosteroids and advised to change jobs. Complete remission of the disease was achieved and persisted for at least one year without steroid treatment. Discussion Sarcoidosis is believed to have environmental triggers. The timing of the onset of sarcoidosis in this patient following intensive exposure to tunnel dust suggests an environmental contribution. The recognition that sarcoidosis may have occupational triggers have medical, employment, and legal implications. Am. J. Ind. Med. 55: 390-394, 2012. (C) 2011 Wiley Periodicals, Inc.

Fhos encodes a Drosophila Formin-Like Protein participating in autophagic programmed cell death

Larval tissues undergo programmed cell death (PCD) during Drosophila metamorphosis. PCD is triggered in a stage and tissue-specific fashion in response to ecdysone pulses. The understanding of how ecdysone induces the stage and tissue-specificity of cell death remains obscure. Several steroid-regulated primary response genes have been shown to act as key regulators of cellular responses to ecdysone by inducing a cascade of transcriptional regulation of late responsive genes. In this article, the authors identify Fhos as a gene that is required for Drosophila larval salivary gland destruction. Animals with a P-element mutation in Fhos possess persistent larval salivary glands, and precise excisions of this P-element insertion resulted in reversion of this salivary gland mutant phenotype. Fhos encodes the Drosophila homolog of mammalian Formin Fhos. Fhos is differentially transcribed during development and responds to ecdysone in a method that is similar to other cell death genes. Similarly to what has been shown for its mammalian counterpart, FHOS protein is translocated to the nucleus at later stages of cell death. Fhos mutants posses disrupted actin cytoskeleton dynamics in persistent salivary glands. Together, our data indicate that Fhos is a new ecdysone-regulated gene that is crucial for changes in the actin cytoskeleton during salivary gland elimination in Drosophila. genesis 50:672684, 2012. (c) 2012 Wiley Periodicals, Inc.