PI3K inhibition by BKM120 results in anti-proliferative effects on corticotroph tumor cells.

PURPOSE: Cushing's disease is associated with significant morbidity; thus, additional tumor-directed drugs with the potential to exert antineoplastic effects on corticotroph adenoma cells are desired. The phosphoinositide-3-kinase (PI3K)/protein kinase B (AKT) pathway, which plays regulatory role in cell survival and proliferation, is activated in pituitary adenomas. The present study evaluated the effects of BKM120 (Buparlisib), an oral PI3K inhibitor, on cell viability, apoptosis, cell cycle phase distribution, and ACTH production in mouse corticotroph tumor cells. METHODS: AtT-20/D16v-F2 mouse pituitary corticotroph tumor cells were treated with increasing concentrations of BKM120 or vehicle. Cell viability was measured using an MTS-based assay. Apoptosis was evaluated by Annexin V staining. Cell cycle analysis was performed by propidium iodide DNA staining and flow cytometry. Gene expression of cell cycle regulators (Cdkn1b, Ccnd1, Ccne1, Cdk2, Cdk4, Myc, and Rb1) was assessed by qPCR. Protein expression of p27, total and phosphorylated Akt was assessed by Western blot. ACTH levels were measured in the culture supernatants by chemiluminescent immunometric assay. RESULTS: Treatment with BKM120 decreased AtT-20/D16v-F2 cell viability, induced a G0/G1 cell cycle arrest, reduced the phosphorylation of Akt at Serine 473, and increased p27 expression. Furthermore, BKM120 treatment diminished ACTH levels in the cell culture supernatants. CONCLUSION: In vitro inhibition of PI3K/AKT pathway by BKM120 resulted in anti-proliferative effects on corticotroph tumor cells, decreasing cell viability and ACTH production. These encouraging findings shape the path for further experiments with the inhibition of PI3K/AKT pathway in Cushing's disease.

Removal of flocculated TiO2 nanoparticles by settling or dissolved air flotation.

Engineered nanoparticles of TiO2 (TiO2-NPs) are used in the industry for a great number of applications. After their usage, the particles end up in aquatic environments, contaminating supply waters and watercourses. Bench-scale studies report removal of TiO2-NPs (450 nm, the mean volumetric diameter) by flocculation followed by settling or by dissolved air flotation (4 bar saturation pressure and 30% recycling ratio). Floc formation was conducted after heterocoagulation with iron hydroxide (30-40 mg L-1 Fe3+) and gelatinized corn starch (10-20 mg L-1) as flocculant, at pH 7. Particle size distribution and zeta potential, removal efficiencies as a function of time and microphotography of flocs were analyzed. Mechanisms involve ferric hydroxide precipitation, heterocoagulation with the nanoparticles and flocculation of the loaded carrier precipitates with gelatinized starch. Best results showed removals between 95-100% of TiO2-NPs, either by settling or flotation after 5 min. Clear treated waters with low turbidity < 3 nephelometric turbidity units (NTU) and TiO2-NPs concentrations <1 mg L-1 were obtained. A practical advantage in DAF was the higher solids content (1.9% w/w) of the sludge, when compared to settling (0.7% w/w). This would facilitate the sludge dewatering and disposal, but DAF has the disadvantage of the poor efficiency at high concentration of the nanoparticles of titanium oxide (>100 mg L-1). Conversely, the removal by settling of the flocs increased at high dosages. It is believed that both processes are sustainable in terms of reagents and the removal efficiencies of TiO2 nanoparticles from water.

Repair of a perforated sinus membrane with an autogenous periosteal graft: a study in 24 patients.

We describe a technique for repairing a perforation of the sinus membrane with a periosteal graft. Of 117 patients who had augmentation of the sinus floor, the sinus membrane perforated in 24, and these were repaired with autogenous periosteal grafts. Patients were followed up daily for the first 10days and monthly for the next six months, and clinical and radiographic variables were recorded. Patients had to be free of complications such as wound dehiscence, sinus infections, exposure of the graft, local inflammation, or pain. The radiographs showed correct osseointegration of all implants. Periosteal grafts are an effective alternative for repair of a perforation of the sinus membrane.

Separation of emulsified crude oil in saline water by flotation with micro- and nanobubbles generated by a multiphase pump.

The flocculation-column flotation with hydraulic loading (HL, >10 m h-1) was studied for the treatment of oil-in-water emulsions containing 70-400 mg L-1 (turbidity = 70-226 NTU) of oil and salinity (30 and 100 g L-1). A polyacrylamide (Dismulgan, 20 mg L-1) flocculated the oil droplets, using two floc generator reactors, with rapid and slow mixing stages (head loss = 0.9 to 3.5 bar). Flotation was conducted in two cells (1.5 and 2.5 m) with microbubbles (MBs, 5-80 µm) and nanobubbles (NBs, 50-300 nm diameter, concentration of 108 NBs mL-1). Bubbles were formed using a centrifugal multiphase pump, with optimized parameters and a needle valve. The results showed higher efficiency with the taller column reducing the residual oil content to 4 mg L-1 and turbidity to 7 NTU. At high HL (27.5 m h-1), the residual oil concentrations were below the standard emission (29 mg L-1), reaching 18 mg L-1. The best results were obtained with high concentration of NBs (apart from the bigger bubbles). Mechanisms involved appear to be attachment and entrapment of the NBs onto and inside the flocs. Thus, the aggregates were readily captured, by bigger bubbles (mostly MBs) aiding shear withstanding. Advantages are the small footprint of the cells, low residence time and high processing rate.

Cardiac morphofunctional characteristics of transgenic rats with overexpression of the bradykinin B1 receptor in the endothelium.

Our aim was to evaluate whether endothelial overexpressing of the bradykinin B1 receptor could be associated with altered left ventricular and myocardial performance. Echocardiography and hemodynamic were employed to assess left ventricular morphology and function in Sprague Dawley transgenic rats overexpressing the endothelial bradykinin B1 receptor (Tie2B1 rats). The myocardial inotropism was evaluated on papillary muscles contracting in vitro. In Tie2B1 animals, an enlarged left ventricular cavity and lower fractional shortening coupled with a lower rate of pressure change values indicated depressed left ventricular performance. Papillary muscle mechanics revealed that both Tie2B1 and wild-type rat groups had the same contractile capacities under basal conditions; however, in transgenic animals, there was accentuated inotropism due to post-pause potentiation. Following treatment with the Arg(9)-BK agonist, Tie2B1 papillary muscles displayed a reduction in myocardial inotropism. Endothelial B1 receptor overexpression has expanded the LV cavity and worsened its function. There was an exacerbated response of papillary muscle in vitro to a prolonged resting pause, and the use of a B1 receptor agonist impairs myocardial inotropism.

Effectiveness of insole use in rheumatoid feet: a randomized controlled trial.

OBJECTIVES: To assess the effectiveness of foot orthoses with regard to pain, function, quality of life, and global perceived effect in patients with rheumatoid arthritis (RA). METHOD: A double-blind randomized controlled trial (RCT) was carried out. Eighty women with RA were randomly assigned to an experimental group (EG) or a control group (CG). The EG used an insole with metatarsal and medial arch supports and the CG used a flat insole for 6 months. Evaluations performed at baseline and after 45, 90, and 180 days by a blinded assessor were: foot pain while walking and at rest, function, quality of life, and global perceived effect with treatment. RESULTS: The groups were homogeneous for all parameters at baseline. A statistically significant improvement (p < 0.001) was found in the EG regarding pain while walking (mean difference: -2.2 for the right foot and -2.1 for the left foot) and at rest (mean difference: -0.3 for the right foot and -0.5 for the left foot) in comparison to CG. There were no differences in any other observed measures. The time of insole use correlated with foot pain and function in the EG. CONCLUSIONS: Foot orthoses with metatarsal and medial arch supports decreases pain during walking and at rest in both feet in patients with RA. Time of insole use correlated with improvements in pain and function.

Three unequal masses on a ring and soft triangular billiards.

The dynamics of three soft interacting particles on a ring is shown to correspond to the motion of one particle inside a soft triangular billiard. The dynamics inside the soft billiard depends only on the masses ratio between particles and softness ratio of the particles interaction. The transition from soft to hard interactions can be appropriately explored using potentials for which the corresponding equations of motion are well defined in the hard wall limit. Numerical examples are shown for the soft Toda-like interaction and the error function.

Soft wall effects on interacting particles in billiards.

The effect of physically realizable wall potentials (soft walls) on the dynamics of two interacting particles in a one-dimensional (1D) billiard is examined numerically. The 1D walls are modeled by the error function and the transition from hard to soft walls can be analyzed continuously by varying the softness parameter sigma . For sigma-->0 the 1D hard wall limit is obtained and the corresponding wall force on the particles is the delta function. In this limit the interacting particle dynamics agrees with previous results obtained for the 1D hard walls. We show that the two interacting particles in the 1D soft walls model is equivalent to one particle inside a soft right triangular billiard. Very small values of sigma substantiously change the dynamics inside the billiard and the mean finite-time Lyapunov exponent decreases significantly as the consequence of regular islands which appear due to the low-energy double collisions (simultaneous particle-particle-1D wall collisions). The rise of regular islands and sticky trajectories induced by the 1D wall softness is quantified by the number of occurrences of the most probable finite-time Lyapunov exponent. On the other hand, chaotic motion in the system appears due to the high-energy double collisions. In general we observe that the mean finite-time Lyapunov exponent decreases when sigma increases, but the number of occurrences of the most probable finite-time Lyapunov exponent increases, meaning that the phase-space dynamics tends to be more ergodiclike. Our results suggest that the transport efficiency of interacting particles and heat conduction in periodic structures modeled by billiards will strongly be affected by the smoothness of physically realizable walls.

[Polymyositis and HTLV-I infection: case report]. / Polimiosite associada a infecção por HTLV-I: relato de caso.

We report the case of a 57 years-old woman presenting polymyositis associated to HTLV-I infection without clinical signs of involvement of the central and peripheral nervous system. Pathophysiologic aspects of muscular involvement in HTLV-I infection are discussed.

[HTLV-I-associated myelopathy, tropical spastic paraparesis: report of the first cases in Sergipe, Brazil]. / Mielopatia associada ao HTLV-I/paraparesia espástica tropical. Relato dos primeiros casos em sergipe.

HTLV-I associated myelopathy/tropical spastic paraparesis (HAM/TSP) has been described in practically all regions of Brazil. The authors present eight clinically defined cases of HAM/TSP, as being the first reported in Sergipe (Northeastern Brazil). All of them were confirmed through ELISA in two examinations, although only two were confirmed by Western Blot. According to clinical/laboratorial investigation protocol, all patients presented involvement of the pyramidal tract with minimal sensory loss and sphincter alteration. The authors call the attention for the endemicity of HTLV-I in the region, whose prevalence amongst blood donors is significant (0.43%).

Peptic disease and Helicobacter pylori are highly prevalent in patients with the indeterminate form of Chagas' disease: report of 21 cases.

Given that chagasic patients in the indeterminate form of this disease, can have abnormal motility of the digestive tract and immunologic abnormalities, we decided to assess the frequency of peptic disease and Helicobacter pylori (Hp) infection in these individuals. Twenty-one individuals, 13 males and 8 females, mean age 37.6 +/- 11.1 years, were examined. Biopsies of the duodenum, antrum, lesser and greater gastric curvature and esophagus were performed. The endoscopic findings were of chronic gastritis in 20 (95.2%) patients, duodenal ulcer in 3 (14.3%), gastric and duodenal ulcer in 3 (14.3%), gastric ulcer alone in 1 (4.8%), esophagitis in 5 (23.8%), and duodenitis in 5 (23.8%). The diagnosis of infection by the Hp was done by the urease test and histologic examination. Hp infection was found in 20 (95.2%) individuals: in 20 out of them in the antrum, in 17 in the lesser curvature, and in 17 in the greater curvature. Hp was not found in the esophagus and duodenum. The only individual with no evidence of infection by Hp was also the only one with normal endoscopic and histologic examinations. The histologic examinations confirmed the diagnoses of gastric ulcer as peptic, chronic gastritis in 20 patients, duodenitis in 14, and esophagitis in 9. In this series the patients had a high frequency of peptic disease, which was closely associated with Hp infection.

[Wernicke's encephalopathy: report of a case with obstructive pyloric syndrome]. / Encefalopatia de Wernicke: a próposito de um caso com síndrome pilórica obstrutiva.

The authors present one case of Wernicke's encephalopathy in a patient with obstructive pyloric syndrome caused by gastric adenocarcinoma, without previous history of alcoholism or malnutrition. They comment on the importance of physiological aspects of thiamine as a co-enzyme of transketolase and pyruvate-decarboxilase in the metabolic pathway for ATP production and the possibility of existing an interaction between genetical and environmental factors in the onset the symptoms. They draw attention for the clinical diagnosis, which should be precocious for the therapy with thiamine to be effective, especially in patients without previous history of alcoholism or malnutrition.

[Poliomyelitis in Sergipe]. / A poliomielite em Sergipe.

A retrospective study of poliomyelitis in Sergipe, Northeast of Brazil, is presented by the authors. The study was divided in three periods, taking in consideration the notification rate of positive cases and emphasizing the period from 1979 to 1989 through the study of 159 consecutive cases. The following information was gathered for each case: sex, age, origin, former immunization status and clinical development. Also evaluated were annual incidence, relationship of incidence/vaccinal coverage and geographic distribution. Comments were made about the change in the wild poliovirus circulation (P1 to P3) and about epidemiological outbreaks occurred in 1984 and 1986, and problems related to the lack of immunity in children with complete vaccinal scheme. Poliomyelitis was considered to be controlled in the State of Sergipe but the necessity of maintenance of effective epidemiological vigilance for all cases of acute and flabby paralysis in children under 14 years is emphasized.

[Persistent primitive trigeminal artery: critical review of the clinical significance]. / Persistência da artéria trigeminal primitiva. Revisão crítica do significado clínico.

The authors report three cases of persistence of primitive trigeminal artery with no evidence of a relationship between its presence and any specific clinical syndrome. They discuss embryological aspects and establish the correlation between the presence of this malformation and other intracranial pathologies, such as "tic douloureux" and morphologic alteration of the circle of Willis. A critical review of the literature is also presented.

[Inclusion dermoid cyst of the anterior fontanel region in adults: report of a case]. / Cisto dermóide de inclusão localizado na região da fontanela anterior no adulto: apresentação de um caso.

The author describes one case of congenital inclusion dermoid cyst located over the region of the anterior fontanel in an adult patient aged 24 years. The question of racial prevalence is discussed and considerations on the incidence of these cysts in adult patients are made based on the review of cases previously reported in the literature.

Monitorização hemodinâmica no pós-operatório de crianças submetidas a correção de cardiopatia congênita / Hemodynamic monitoring in postoperative period of children subjected to correction of congenital heart diseases

Propõe-se um método de monitorização hemodinâmica que compreende a avaliação do debito cardíaco, pressões atriais, pressão arterial, frequência cardíaca, temperatura corporal e volume urinário. Esta monitorização mais ampla foi utilizada em 12 crianças com media de idade 24 meses (desvio padrão 17 meses). As principais indicações foram: idade e peso reduzidos, necessidade de drogas inotrópicas ao sair de circulação extracorpórea, complexidade da cardiopatia e da correção cirúrgica, e insuficiência cardíaca ou respiratória antes da operação. São analisados os resultados terapêuticos, através de curva de função ventricular e particularidades na evolução hemodinâmica no pós-operatório em gráficos separados. O debito cardíaco foi obtido por termodiluição e são discutidos aspectos relacionados com o método utilizado em sua determinação. O procedimento revelou-se seguro e reprodutível, fornecendo subsídios importantes para decisões terapêuticas