Clusters of high-risk, low-risk, and temporal trends of breast and cervical cancer-related mortality in São Paulo, Brazil, during 2000-2016.

PURPOSE: Studying breast and cervical cancers in space and time and verifying divergences of different territorially established socioeconomic profiles. METHODS: Ecological study using spatial scanning (with socioeconomic characterization), space-time, and spatial variation of temporal trends, in order to identify significant clusters of high- and low-risk or temporal trends, of deaths from breast cancer and cervical cancer, in the city of São Paulo, Brazil, during 2000-2016. RESULTS: High-risk spatial clusters were identified in the central areas, and low-risk clusters were identified in the peripheral areas, which were associated with better and worse socioeconomic conditions, respectively. As for cervical cancer, the pattern was the opposite. High-risk space-time clusters occurred in the early years of the study, whereas low-risk clusters occurred in the most recent years. For breast cancer, the central areas showed a temporal trend of decreasing mortality and the peripheral areas showed an increasing trend. While for cervical cancer, in general, the temporal trend was for the identified clusters to fall. CONCLUSIONS: It is expected that this study will provide insights for the formulation of public policies to implement prevention and control measures, in order to reduce mortality and inequalities related to breast and cervical cancers.

Effect of gamma-oryzanol on the bioaccessibility and synthesis of cholesterol.

BACKGROUND AND OBJECTIVES: Gamma-oryzanol (gamma-OR) is a unique mixture of triterpene alcohol and sterol ferulates present in rice bran oil. Hypocholesterolemic activity of gamma-OR has been reported in various animal and human studies. However, the mechanisms for this hypocholesterolemic activity of gamma-OR remain unclear. Therefore, the aim of this in vitro study was to examine the effect of gamma-OR on the bioaccessibility and synthesis of cholesterol. METHODS: The effects of gamma-OR on the efficiency of incorporation of cholesterol into mixed micelles during digestion and apical uptake of cholesterol by Caco-2 human intestinal cells were determined using the coupled in vitro simulated digestion/Caco-2 human intestinal cell model. The impact of gamma-OR on the HMG-CoA reductase activity was also investigated. RESULTS: Although incorporation of cholesterol into synthetic micelles was significantly inhibited by 15-fold molar excess of gamma-OR, efficiency of micellarization of cholesterol during simulated digestion of the rice meal was not significantly altered by the presence of as high as 20-fold molar excess of gamma-OR. Nevertheless, 20-fold molar excess of gamma-OR significantly decreased apical uptake of cholesterol into Caco-2 intestinal cells. In addition, gamma-OR inhibited 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase activity. CONCLUSIONS: These findings suggest that the hypocholesterolemic activity of gamma-OR is due in part to impaired apical uptake of cholesterol into enterocytes and perhaps a decrease in HMG-CoA reductase activity.

Idiopathic pulmonary fibrosis: a disease with similarities and links to cancer biology.

Several clinical trials have recently targeted specific pathways implicated in the pathogenesis of idiopathic pulmonary fibrosis (IPF). However, IPF remains plagued by a median survival of 3 yrs and emphasises the need for further research with new insights and perspectives. The prevailing pathogenic hypotheses assume that either an inflammatory process or an independent epithelial/fibroblastic disorder may propagate the disease process. Based on knowledge developed with considerable scientific evidence, we provide our perspectives with an alternative point of view that IPF be considered as a neoproliferative disorder of the lung. Genetic alterations, response to growth and inhibitory signals, resistance to apoptosis, myofibroblast origin and behaviour, altered cellular communications, and intracellular signalling pathways are all fundamental pathogenic hallmarks of both IPF and cancer. The concept of IPF as a lethal malignant disorder of the lung might extend beyond the pathogenic link between these two diseases and disclose new pathogenic mechanisms leading to novel therapeutic options, adopted from cancer biology. Moreover, this vision might dawn the awareness of the public, political and scientific community of this devastating disease from an angle different from the current perception and provoke new ideas and studies to get a better understanding to control the otherwise relentless progressive disease.

[Thrombocytopenia associated with brucellosis: a case report]. / Trombocitopenia in corso di brucellosi: descrizione di un caso.

Brucellosis, a common disease in some areas of the world, beside its typical signs and symptoms, as fever, arthropathy, hepatomegaly and splenomegaly, sometimes can complicate into thrombocytopenia, even in severe forms. The pathogenesis of thrombocytopenia in course of brucellosis is variable, and a main role is played by immunological reactions. Authors describe a case report of an eight years child who presented a severe thrombocytopenia in course of acute brucellosis. The patient responded efficaciously to the antibiotic therapy combined with immunoglobulin intravenous therapy.

Trichinellosis surveillance in wildlife in northeastern argentine patagonia.

Trichinellosis is a food-borne parasitic disease produced by different nematodes of the genus Trichinella. In Argentina, it is an endemic zoonosis and an important public health problem. The infection has been detected in domestic and wild animals. Trichinella spp. muscle larvae have anaerobic metabolism, which allows their survival in decaying tissues. The aim of this study was to evaluate the presence of Trichinella spp. in carnivorous and/or scavenger wild vertebrates - birds, mammals and reptiles - in northeastern Argentine Patagonia. Skeletal muscle samples from 141 animals, which were found killed on northeastern Argentine Patagonia roads, were analyzed by the artificial digestion method. None of the 141 samples were positive for larvae of Trichinella. These results suggest that Trichinella does not use these species to complete its cycle in this region of the continent and the absence of a significant alteration in the study area makes it difficult to transmit parasitic diseases. However, due to the limited number of samples assessed for some species, this could not be confirmed. The relevance of this study resides in the fact that it is the first systematic study in South America that considers birds, reptiles and mammals as potential hosts for Trichinella.

Terahertz spectroscopy of anisotropic materials using beams with rotatable polarization.

We introduce a polarization-resolved terahertz time-domain spectrometer with a broadband (0.3-2.5 THz), rotatable THz polarization state, and which exhibits minimal change in the electric field amplitude and polarization state upon rotation. This was achieved by rotating an interdigitated photoconductive emitter, and by detecting the orthogonal components of the generated THz pulse via electro-optic sampling. The high precision (<0.1°) and accuracy (<1.0°) of this approach is beneficial for the study of anisotropic materials without rotating the sample, which can be impractical, for instance for samples held in a cryostat. The versatility of this method was demonstrated by studying the anisotropic THz optical properties of uniaxial and biaxial oxide crystals. For uniaxial ZnO and LaAlO3, which have minimal THz absorption across the measurement bandwidth, the orientations of the eigenmodes of propagation were conveniently identified as the orientation angles that produced a transmitted THz pulse with zero ellipticity, and the birefringence was quantified. In CuO, a multiferroic with improper ferroelectricity, the anisotropic THz absorption created by an electromagnon was investigated, mapping its selection rule precisely. For this biaxial crystal, which has phonon and electromagnon absorption, the polarization eigenvectors exhibited chromatic dispersion, as a result of the monoclinic crystal structure and the frequency-dependent complex refractive index.

Acute effect of high-fat meal on endothelial function in moderately dyslipidemic subjects.

OBJECTIVE: Hypercholesterolemia markedly impairs endothelial function. Whether this is the case for hypertriglyceridemia is less clear, however, and limited evidence exists on the effect of an acute increase in triglyceridemia caused by a high-fat meal. METHODS AND RESULTS: In 16 normotensive subjects with an untreated mild hypertriglyceridemia and dyslipidemia and in 7 normal controls, we measured radial artery diameter and blood flow by an echo-tracking device (NIUS02). Data were obtained at baseline, at the release of a 4-minute ischemia of the hand, which causes an increase in arterial diameter dependent on nitric oxide (NO) secretion, and at the release of a 12-minute exclusion of the arm by an arm cuff to obtain a larger increase in arterial diameter mainly of nonendothelial nature. Measurements were performed before and 6 hours after a high-fat meal (680 kcal/m(2) body surface; 82% lipids). In mild dyslipidemic hypertriglyceridemic subjects, the high-fat meal did not alter baseline blood pressure (beat-to-beat finger measurement), heart rate, radial artery diameter, and blood flow. It also did not alter the increase in blood flow induced by the 4-minute ischemia (+42.7+/-10.4 and +43.7+/-10.4 mL/min), whereas it markedly attenuated the concomitant increase in arterial diameter (+0.31+/-0.06 versus 0.13+/-0.06 mm; P<0.05). The alteration of the diameter response did not correlate with changes in total cholesterol, but it showed a significant correlation with the increase in serum triglycerides induced by high-fat meal (r=0.49, P<0.05). This attenuation was not seen in control subjects and in subjects in whom measurements were repeated after a 6-hour observation period. It was also not paralleled by an alteration of the endothelially independent response to a 12-minute ischemia whose larger effects on arterial diameter and blood flow were similar before and after the high-fat meal. CONCLUSIONS: Endothelial function is markedly impaired by a high-fat meal that causes an acute hypertriglyceridemia. This impairment is evident in dyslipidemic patients with baseline hypertriglyceridemia but not in normotriglyceridemic controls. An oral fat load was administered to 55 HIV-positive and 10 HIV-negative individuals. Postprandial clearance of triglyceride-rich lipoproteins was delayed in HIV-positive individuals. Compared with HIV-positive subjects not on PIs, those taking PIs do not have increased postprandial triglyceride-rich lipoproteins but do have increased postprandial intermediate-density and low-density lipoproteins. Hypercholesterolemia impairs endothelial function, whereas the effect of hypertriglyceridemia is less clear. In normotensive subjects with an untreated hypertriglyceridemia and hypercholesterolemia, we measured endothelial function before and 6 hours after a high-fat meal. The results demonstrate that in moderately dyslipidemic patients, endothelial function is impaired by acute hypertriglyceridemia.

Zinc suppression of initiation of sarcoma 180 growth.

Subcutaneous administration of 80 mug zinc daily to mice that had received an intraperitoneal inoculation of 1 times 10-6 sarcoma 180 cells within the preceding 2 days resulted in protection of up to 60% of the hosts. In animals in which tumors grew, daily injections of zinc did not alter the rate of tumor cell growth. We hypothesized that the metal suppressed initiation of tumor cell reproduction, possibly by stimulation of host defense cell mechanisms.

Zinc uptake by isolated rat liver parenchymal cells.

Primary cultures of rat liver parenchymal cells maintained as a monolayer in serum-free culture medium were used to investigate the characteristics of zinc accumulation in vitro. Liver parenchymal cells accumulated zinc by a temperature-dependent, saturable process that was inhibited by cyanide, azide, oligomycin, N-ethylmaleimide and iodoacetamide. Cadmium reversibly inhibited zinc accumulation in both serum-free and serum-containing media. Gel filtration chromatographic studies showed that recently accumulated intracellular zinc was present as a low molecular weight complex smaller than metallothionein, the zinc storage protein, but larger than individual amino acids. The quantity of zinc accumulated was affected by preincubation of the cells with various hor?ONES. Dexamethasone, prednisone and prednisolone each increased zinc uptake by 40--50% when either insulin or glucagon was also present. Hydrocortisone, cortisone and sex steroids did not influence zinc accumulation. Removal of the polypeptide hormones from the medium abolished the stimulatory effect of the synthetic glucocorticoid steroid hormones on zinc accumulation.

Zinc accumulation and metabolism in primary cultures of adult rat liver cells. Regulation by glucocorticoids.

Adult rat liver parenchymal cells were isolated by the collagenase perfusion technique and cultured as a monolayer for up to 20 h. The quantity of zinc accumulated from the extracellular environment was significantly increased by adding physiological concentrations of certain glucocorticosteroids to the medium. The degree of stimulation was directly related to glucocorticoid potency. Sex steroids, certain peptide hormones and prostaglandins E2 and F2alpha did not influence zinc accumulation. Control cells exhibited a decline of zinc accumulation after 4 h in culture although uptake processes were still operative. When dexamethasone, the most potent glucocorticoid used, was present in the medium the cells accumulated zinc at a linear rate greater than that seen in control cells, for at least 20 h. The dexamethasone-induced stimulation of zinc accumulation was relatively specific since 45Ca, 14C-labelled amino acids and [35S]cystine accumulation was not influenced by the hormone. A lag of 4 h was observed before an effect of dexamethasone on zinc accumulation could be detected. Moreover, the hormone-stimulated phase of accumulation was blocked when the cells were simultaneously incubated with either actinomycin D or cycloheximide. The additional complement of zinc accumulated by the dexamethasone-treated cells was localized in the cytosol fraction. Gel filtration and ion-exchange chromatography confirmed that this additional cytosol zinc was bound to metallothionein. [35S]Cystine was incorporated into metallothionein in hormone-treated cells indicating that the protein was synthesized de novo during periods of enhanced zinc accumulation.

Expression of ceruloplasmin gene in human and rat lymphocytes.

The acute phase plasma protein ceruloplasmin (Cp) appears to play some role in host defense. The possibility that production of Cp in extrahepatic sites may also be essential for the activation, effector functions and cytoprotection of immune cells in localized environments has received minimal attention. Here, we have surveyed various types of human and rat immune cells for the presence of Cp mRNA using RT-PCR with primers that span exons 17-19 as an initial step in addressing this possibility. Validated Cp RT-PCR bands were obtained from RNA samples isolated from resting and activated human lymphocytes, CD4 and CD8 T-cells and B-cells. Semiquantitative RT-PCR indicated that Cp mRNA in immune cells is present at about 0.2% the level of Cp mRNA in HepG-2 human liver cell line. Various human cell lines derived from the immune system, rat splenic MNC and purified rat T-lymphocytes also constitutively express Cp gene.

Degradation of rat liver metallothioneins in vitro.

The degradation of zinc and cadmium-induced hepatic metallothionineins was investigated in vitro. Both zinc-thionein and cadmium-thionein were labeled in vivo with [35S]cystine. The labeled proteins were isolated and purified by gel filtration and DEAE-ion exchange chromatography. Purified zinc[35S]thionein and cadmium-[35S]thionein were incubated with trypsin, chymotrypsin and pronase for varying times up to 24 h. The rate of degradation of zinc-thionein was twice that of cadmium-thionein when the proteins were incubated with trypsin. Virtually no digestion occurred when the proteins were incubated with chymotrypsin, whereas the rates of degradation were about equal when they were incubated with pronase. In contrast, degradation of zinc-thionein was twice that observed with cadmium-thionein when the proteins were incubated at pH 5.0 with a purified lysosomal extract. Degradation of these proteins by the lysosomal proteases was 77 and 46% within 3 h for zinc-thionein and cadmium-thionein, respectively. Thionein, the metal-free form of metallothionein, was degraded extremely rapidly by both neutral and lysosomal proteases. Chromatography of the digestion products on Sephadex G-25 demonstrated that all three forms of metallothionein were degraded to species of approximately 100-300 daltons. These data indicate that metals stabilize thionein polypeptides and suggest that the degradation of metallothionein in vivo is regulated in part by the species of metal bound.

Cadmium accumulation and metabolism by rat liver parenchymal cells in primary monolayer culture.

Primary cultures of adult rat liver parenchymal cells, isolated by the collagenase perfusion technique and maintained as a monolayer, were used to investigate the characteristics of hepatic cadmium accumulation and metabolism. Cadmium accumulation was found to be a temperature- and concentration-dependent process that required sulfhydryl groups and was significantly stimulated by the addition of dexamethasone to the medium. Once taken up, cadmium was less available for exit-exchange processes than its biologically required congener, zinc. Moreover, cadmium influx enhanced zinc efflux. While most of the intracellular cadmium was located in the cytosol, its distribution within this fraction was altered with time. Initially the metal was bound to both high molecular weight species (less than 50 000) and metallothionein. As the incubation period increased, the cytosol concentration of cadmium and the percentage of this metal associated with metallothionein was likewise increased. [3H]Amino acid incorporation studies indicated that the accumulation of cadmium resulted in de novo synthesis of the 1 and 2 forms of metallothionein.

Effects of prolonged immobilization of the limb on radial artery mechanical properties.

Physical training is associated with an increase in arterial distensibility. Whether the effect of training on this variable is evident also for ordinary levels of exercise or no exercise is unknown, however. We have addressed this issue by investigating the effect on radial artery distensibility of prolonged monolateral immobilization of the ipsilateral limb versus the following resumption of normal mobility. We studied 7 normotensive subjects (age, 25.4+/-3.0 years; systolic/diastolic blood pressure, 119+/-9/68+/-6 mm Hg, mean+/-SE) in whom 1 limb had been immobilized for 30 days in plaster because of a fracture of the elbow. At both the day after plaster removal and after 45 days of rehabilitation, radial artery distensibility was evaluated by an echo-tracking device (NIUS-02), which allows arterial diameter to be measured noninvasively and continuously over all pressures from diastole to systole (finger monitoring), with the distensibility values being continuously derived from the Langewouters formula. In both instances, the contralateral arm was used as control. Immediately after removal of the plaster, radial artery distensibility was markedly less in the previously immobilized and fractured limb compared with the contralateral limb (0.4+/-0.1 versus 0.8+/-0.1, 1/mm Hg 10(-3), P<0.05). After rehabilitation, the distensibility of the radial artery was markedly increased in the previously fractured limb (0.65+/-0.1 1/mm Hg 10(-3), P<0.05), whereas no change was seen in the contralateral limb. Thus, complete interruption of physical activity is associated with a marked reduction of arterial distensibility, indicating that even an ordinary level of activity plays a major role in modulation of arterial mechanical properties.

Radial artery compliance in young, obese, normotensive subjects.

Obesity is characterized by a number of cardiovascular alterations, and whether these alterations involve arterial compliance is unknown. In 12 young, obese, normotensive subjects (age, 23.9 +/- 1.3 years; mean +/- SEM) and 12 age- and sex-matched lean control subjects we measured blood pressure, radial artery diameter, and radial artery compliance continuously over the systodiastolic pressure range with a Finapres device and recently developed echo-tracking device. Measurements were obtained at baseline and after prolonged ischemia, that is, when diameter and compliance are increased. Blood pressure values were normal in both groups (obese subjects: 109.2 +/- 4.9/68.2 +/- 2.7 mm Hg; lean control subjects: 108.2 +/- 4.1/60.7 +/- 3.8 mm Hg), but in addition to a marked increase in body mass index (38.5 +/- 0.8 versus 23.1 +/- 0.9 kg/m2, P < .01), obese subjects showed a slight and nonsignificant increase in heart rate (71.1 +/- 3.2 versus 66.7 +/- 3.3 beats per minute, P = NS), increases in left ventricular wall thickness and left ventricular mass index (121.5 +/- 4.8 versus 103.4 +/- 3.3 kg/m2, P < .01), no changes in plasma renin activity and plasma norepinephrine (compared with normal values), and a marked reduction in total body glucose uptake (glucose clamp technique). Obese subjects showed radial artery diameter and compliance values that were greater than those seen in control subjects throughout the systodiastolic pressure range. The differences were 13% (P < .05) and 96% (P < .01), respectively, and both diameter and compliance remained higher in obese than lean subjects after forearm ischemia. In obese and lean subjects baseline radial artery diameter values correlated highly with body weight, body surface area, and body mass index.(ABSTRACT TRUNCATED AT 250 WORDS)

Sympathetic modulation of radial artery compliance in congestive heart failure.

Animal studies have suggested that arterial compliance can be modulated by adrenergic influences. Whether this adrenergic modulation also occurs in humans is still a matter of debate. In the present article we address this issue by examining the relationships between sympathetic tone and arterial compliance in a variety of physiological and pathophysiological conditions. We have found that cigarette smoking, ie, an action that produces a marked sympathetic activation, causes a significant reduction in radial artery compliance, as measured by an echotracking device capable of providing continuous beat-to-beat evaluation of this hemodynamic variable. When expressed as compliance index, ie, as the ratio between the area under the compliance-pressure curve and pulse pressure, the reduction amounted to 35.7 +/- 4.8% (mean +/- SEM) and was independent of the smoking-related blood pressure increase. Furthermore, pharmacological stimulation of adrenergic receptors located in the arterial wall was also shown to affect arterial compliance because the radial artery compliance index was markedly reduced (- 29.5 +/- 3.9%) during phenylephrine infusion in the brachial artery at doses devoid of any systemic blood pressure effect. Evidence was also obtained that the relationship between sympathetic activation and arterial compliance has pathophysiological relevance, because in 17 patients with congestive heart failure (New York Heart Association classes II through IV) there was a significant inverse correlation (r = .62, P < .01) between muscle sympathetic nerve activity (directly measured by microneurography in the peroneal nerve) and radial artery compliance.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin-converting enzyme inhibition and radial artery compliance in patients with congestive heart failure.

Congestive heart failure is characterized by a clear-cut impairment of arterial compliance of medium-sized arteries, but whether this alteration is irreversible or can be favorably affected by cardiovascular drugs currently used in congestive heart failure treatment is unknown. We studied 9 congestive heart failure patients (New York Heart Association class II; age, [mean +/- SEM] 60.7 +/- 3.3 years) receiving diuretic and digitalis treatment in whom arterial compliance was assessed at the level of the radial artery by an echotracking device capable of measuring the arterial diameter along the entire cardiac cycle. Beat-to-beat arterial blood pressure was concomitantly measured by a Finapres device that allowed diameter-pressure curves and compliance-pressure curves (Langewouters' formula) to be calculated for the entire systolic-diastolic blood pressure range. Arterial compliance was expressed as the area under the compliance-pressure curve normalized for pulse pressure (compliance index). Data were collected before and after 4 and 8 weeks of oral administration of benazepril (10 mg/day). Ten healthy subjects were studied before and after an observational period of 4 weeks (5 subjects) or 8 weeks (5 subjects), and 9 age-matched mildly essential hypertensive subjects studied before and after 4 to 12 weeks of benazepril administration served as control subjects. In congestive heart failure patients, baseline compliance index was significantly less than in normotensive and hypertensive subjects. However, the compliance index showed a marked increase after 4 weeks of benazepril administration (+95.7 +/- 24.9%, P < .05); the increase was also marked after 8 weeks of angiotensin-converting enzyme inhibitor treatment (+77.7 +/- 4.2%, P < .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Combined effects of hypertension and hypercholesterolemia on radial artery function.

Compliance and distensibility of middle-sized conduit arteries are increased in hypertension and reduced in hypercholesterolemia. Despite their frequent association in the same individual, the combined effect of these two conditions on arterial mechanical properties is unknown. We studied four groups of age- and sex-matched subjects: 10 normotensive normocholesterolemic subjects, 10 mild hypertensive normocholesterolemic subjects, 10 mild hypercholesterolemic normotensive subjects, and 10 mild hypertensive and mild hypercholesterolemic subjects. We measured radial artery diameter by an echotracking device and beat-to-beat blood pressure from an ipsilateral finger. Compliance-pressure and distensibility-pressure curves were derived by Langewouters' formula. Between-group comparisons were made by calculating for both compliance and distensibility the integral of the area under the portion of the curve common to the four groups ("isobaric" compliance and distensibility). Blood pressure was similarly elevated in the two hypertensive groups, and serum cholesterol was similarly elevated in the two hypercholesterolemic groups. Compared with values in normotensive normocholesterolemic subjects, isobaric compliance and distensibility were greater in hypertensive normocholesteroclemic (+38% and 47%, respectively) and smaller in normotensive hypercholesterolemic (-6% and -23%) subjects. However, when both hypertension and hypercholesterolemia were present, isobaric compliance and isobaric distensibility were significantly reduced (-26% and -18%, P < .05). Therefore, hypercholesterolemia reverses the effect of hypertension on arterial compliance and causes arterial stiffening, as when present alone.

Consequences of severe copper deficiency are independent of dietary carbohydrate in young pigs.

The ability of carbohydrates (CHO), such as fructose and sucrose, to aggravate copper deficiency in rats and the recent dietary trends of Western human populations led to the suggestion that the Cu X CHO interaction may be pertinent to public health. This hypothesis was tested with pigs because their cardiovascular and gastrointestinal systems closely resemble those of humans. Weanling pigs were fed a diet containing either 59% sucrose or cornstarch with either deficient (0.8 mg/kg diet) or adequate (6.4 mg/kg) copper for 10 wk. Plasma and tissue copper, the activities of plasma ceruloplasmin ferroxidase and erythrocyte Cu,Zn-superoxide dismutase, hematocrits, and serum cholesterol and triglyceride were all decreased (p less than 0.05) and relative cardiac mass was increased (p less than 0.05) by severe dietary copper deficiency. The type of dietary CHO did not differentially influence the values of these variables. Thus, these data fail to support the hypothesis that the Cu X CHO interaction observed in rats represents a health risk for humans.