Single-source dual-energy spectral multidetector CT of pancreatic adenocarcinoma: optimization of energy level viewing significantly increases lesion contrast.

AIM: To evaluate lesion contrast in pancreatic adenocarcinoma patients using spectral multidetector computed tomography (MDCT) analysis. MATERIALS AND METHODS: The present institutional review board-approved, Health Insurance Portability and Accountability Act of 1996 (HIPAA)-compliant retrospective study evaluated 64 consecutive adults with pancreatic adenocarcinoma examined using a standardized, multiphasic protocol on a single-source, dual-energy MDCT system. Pancreatic phase images (35 s) were acquired in dual-energy mode; unenhanced and portal venous phases used standard MDCT. Lesion contrast was evaluated on an independent workstation using dual-energy analysis software, comparing tumour to non-tumoural pancreas attenuation (HU) differences and tumour diameter at three energy levels: 70 keV; individual subject-optimized viewing energy level (based on the maximum contrast-to-noise ratio, CNR); and 45 keV. The image noise was measured for the same three energies. Differences in lesion contrast, diameter, and noise between the different energy levels were analysed using analysis of variance (ANOVA). Quantitative differences in contrast gain between 70 keV and CNR-optimized viewing energies, and between CNR-optimized and 45 keV were compared using the paired t-test. RESULTS: Thirty-four women and 30 men (mean age 68 years) had a mean tumour diameter of 3.6 cm. The median optimized energy level was 50 keV (range 40-77). The mean ± SD lesion contrast values (non-tumoural pancreas - tumour attenuation) were: 57 ± 29, 115 ± 70, and 146 ± 74 HU (p = 0.0005); the lengths of the tumours were: 3.6, 3.3, and 3.1 cm, respectively (p = 0.026); and the contrast to noise ratios were: 24 ± 7, 39 ± 12, and 59 ± 17 (p = 0.0005) for 70 keV, the optimized energy level, and 45 keV, respectively. For individuals, the mean ± SD contrast gain from 70 keV to the optimized energy level was 59 ± 45 HU; and the mean ± SD contrast gain from the optimized energy level to 45 keV was 31 ± 25 HU (p = 0.007). CONCLUSION: Significantly increased pancreatic lesion contrast was noted at lower viewing energies using spectral MDCT. Individual patient CNR-optimized energy level images have the potential to improve lesion conspicuity.

Clinico-radiologic profile of spinal cord multiple sclerosis in adults.

MRI is extremely useful for the assessment of initial disease burden and to identify the dissemination of the multiple sclerosis (MS) in time and space. Though MRI of the spinal cord is not used to establish the diagnosis of MS, spinal cord is frequently involved in this disease and there has been increasing emphasis of the spinal imaging in making clinical decision in the management of MS. We undertook a retrospective study of patients with diagnosed MS: 1) to identify radiologic pattern of spinal cord involvement in MS and 2) to correlate radiologic findings with clinical presentation. We reviewed radiologic records from 2004 to 2009 of patients with abnormal T2 signal intensity of the spinal cord with radiologic concern of demyelinating disease. Patients in this cohort who met the Revised McDonald MS Diagnostic Criteria were included in this study. 166 patients were included in the study. There was preference for cervical spinal cord particularly posterior aspect of the spinal cord. Enhancement of the lesions was rare (4.1%). Mean lesion length was 18.2 mm. The average number of lesions per patient was 2.04. Sensory symptoms were predominating and most of the patients had relapsing-remitting course. Patients with sensory symptoms, bladder and bowel involvement and motor symptoms had almost equally distributed lesions among anterior, posterior and central spinal cord. However, all of the patients presented with posterior column signs and gait abnormality had involvement of the posterior spinal cord. Radiologic manifestation of spinal cord MS is extremely variable and can involve the entire length of the spinal cord. Clinical symptoms may or may not be associated with radiologic presentation of the lesions.

Effect of menopause on cognitive performance in women with Down syndrome.

We compared cognitive function in nondemented pre- and postmenopausal women with Down syndrome, aged 21-57 years, with their age-matched male peers. The Woodcock-Johnson Tests of Cognitive Ability-Revised were used to assess cognitive function at baseline and 2 years later. Premenopausal women performed better than their age-matched male peers, while postmenopausal women performed more poorly than age-matched male peers (p = 0.007). Premenopausal women and young men showed no significant declines in cognition over time. Postmenopausal women, but not their age-matched male peers, showed significant declines in cognitive function. Our results support the hypothesis that cognitive declines in postmenopausal women are associated with estrogen deficiency rather than with age.

[Sexually transmitted diseases, AIDS, and use/abuse of psychoactive substances in adolescence] / Doenças sexualmente transmissíveis, AIDS e uso/abuso de substâncias psicoativas na adolescência.

OBJECTIVE: To discuss theoretical and practical aspects of sexually transmitted diseases, AIDS, and psychoactive substances in adolescence, focusing on a holistic and multiprofessional approach. METHODS: Review of national and international literature on concepts, classifications, social and cultural, clinical, therapeutic and preventive aspects of sexually transmitted diseases/AIDS, as well as the use of psychoactive substances, with the aim of pointing out problem-solving alternatives. RESULTS: Adolescents do not show resilient behavior and are vulnerable to environmental hazards. For this reason, preventive actions and intervention for the control of sexually transmitted diseases/AIDS and use or abuse of psychoactive substances among adolescents are a priority. According to the World Health Organization, one out of 20 adolescents acquires sexually transmitted disease in the world every year and, more than 7,000 are infected by HIV every day, totaling 2.6 millions a year. This scenario results from unprotected sex and from the interaction between sexually transmitted diseases and psychoactive substances, especially alcohol. CONCLUSIONS: It is crucial that health care providers consider magnitude, transcendence, vulnerability and feasibility as well as the set of interactions among substance, individual, and his/her social and cultural environment when the multifocal and holistic approach is used. This requires the formation of a support and protection network, involving the family, physicians, community, and adolescents. The major element in this network, though, are the adolescent themselves, who can overcome their conflicts, aiming at a healthy and longer life.

[Sexuality in adolescence: development, experience, and proposals for intervention] / Sexualidade na adolescência: desenvolvimento, vivência e propostas de intervenção.

OBJECTIVE: To present a literature review of some aspects concerning the development of sexuality in the period between childhood and adolescence, and to work on some proposals for prevention and intervention. METHODS: Review of literature on relevant issues related to the process of psychosocial and sexual development during childhood and adolescence, and to the importance of prevention education. RESULTS: Differently from genitality, which is only concerned with biological aspects, sexuality encompasses emotional aspects, life history and cultural values. These factors contribute to the formation of general identity and to the components of sexual identity: gender identity, gender role, and sexual orientation. Psychosocial and sexual development, emotional balance, and social relations are based on sexual experience during childhood and adolescence. During adolescence, the relationship with family and social group go through marked changes: conflicts arise, and experimentation and risk behavior are enhanced. The family, school, and health systems represent important links of identification, support, and protection for children and adolescents before they reach maturity. CONCLUSIONS: Sexuality education, either individually or in group, allows adolescents to experience sexuality and their emotional relations in a satisfactory, creative, and risk-free manner, combined with mutual respect and absence of gender discrimination.

Alternative RNA splicing generates a glycosylphosphatidylinositol-anchored form of ceruloplasmin in mammalian brain.

Ceruloplasmin is a copper-containing ferroxidase that is essential for normal iron homeostasis. Whereas ceruloplasmin in plasma is produced and secreted by hepatocytes, in the brain a glycosylphosphatidylinositol (GPI)-anchored form of ceruloplasmin is expressed on the surface of astrocytes. By using a cDNA cloning approach, we have now determined that the GPI-anchored form of ceruloplasmin is generated by alternative RNA splicing. The splicing occurs downstream of exon 18 and replaces the C-terminal 5 amino acids of the secreted form with an alternative 30 amino acids that signal GPI anchor addition. RNase protection analysis demonstrates that the GPI-anchored form is the major form in the brain, whereas the secreted form predominates in the liver. Individuals with aceruloplasminemia, a hereditary deficiency of ceruloplasmin, have severe iron deposition in a number of organs, including the brain where it results in neurodegeneration. Therefore, this novel GPI-anchored form of ceruloplasmin is likely to play an important role in iron metabolism in the central nervous system.

Multisecond oscillations in firing rate in the basal ganglia: robust modulation by dopamine receptor activation and anesthesia.

Multisecond oscillations in firing rate in the basal ganglia: robust modulation by dopamine receptor activation and anesthesia. Studies of CNS electrophysiology have suggested an important role for oscillatory neuronal activity in sensory perception, sensorimotor integration, and movement timing. In extracellular single-unit recording studies in awake, immobilized rats, we have found that many tonically active neurons in the entopeduncular nucleus (n = 15), globus pallidus (n = 31), and substantia nigra pars reticulata (n = 31) have slow oscillations in firing rate in the seconds-to-minutes range. Basal oscillation amplitude ranged up to +/-50% of the mean firing rate. Spectral analysis was performed on spike trains to determine whether these multisecond oscillations were significantly periodic. Significant activity in power spectra (in the 2- to 60-s range of periods) from basal spike trains was found for 56% of neurons in these three nuclei. Spectral peaks corresponded to oscillations with mean periods of approximately 30 s in each nucleus. Multisecond baseline oscillations were also found in 21% of substantia nigra dopaminergic neurons. The dopamine agonist apomorphine (0.32 mg/kg iv, n = 10-15) profoundly affected multisecond oscillations, increasing oscillatory frequency (means of spectral peak periods were reduced to approximately 15 s) and increasing the regularity of the oscillations. Apomorphine effects on oscillations in firing rate were more consistent from unit to unit than were its effects on mean firing rates in the entopeduncular nucleus and substantia nigra. Apomorphine modulation of multisecond periodic oscillations was reversed by either D1 or D2 antagonists and was mimicked by the combination of selective D1 (SKF 81297) and D2 (quinpirole) agonists. Seventeen percent of neurons had additional baseline periodic activity in a faster range (0.4-2.0 s) related to ventilation. Multisecond periodicities were rarely found in neurons in anesthetized rats (n = 29), suggesting that this phenomenon is sensitive to overall reductions in central activity. The data demonstrate significant structure in basal ganglia neuron spiking activity at unexpectedly long time scales, as well as a novel effect of dopamine on firing pattern in this slow temporal domain. The modulation of multisecond periodicities in firing rate by dopaminergic agonists suggests the involvement of these patterns in behaviors and cognitive processes that are affected by dopamine. Periodic firing rate oscillations in basal ganglia output nuclei should strongly affect the firing patterns of target neurons and are likely involved in coordinating neural activity responsible for motor sequences. Modulation of slow, periodic oscillations in firing rate may be an important mechanism by which dopamine influences motor and cognitive processes in normal and dysfunctional states.

A novel glycosylphosphatidylinositol-anchored form of ceruloplasmin is expressed by mammalian astrocytes.

Ceruloplasmin is a copper-binding protein, which is the major ferroxidase in plasma of hepatic origin. We now provide evidence for a novel membrane-bound form of ceruloplasmin expressed by astrocytes in the mammalian central nervous system. Using a monoclonal antibody (1A1), we show that the cell surface antigen recognized by this antibody is ceruloplasmin and that it is directly anchored to the cell surface via a glycosylphosphatidylinositol (GPI) anchor. Our peptide mapping and other immunochemical studies indicate that, except for the GPI anchor, the membrane-bound and secreted plasma forms are similar. We also show that the membrane-bound form of ceruloplasmin has oxidase activity. These studies therefore suggest that the GPI-anchored form of ceruloplasmin may play a role similar to the secreted form in oxidizing ferrous iron. The GPI-anchored form of ceruloplasmin expressed by astrocytes is likely to be the major form of this molecule in the central nervous system because serum ceruloplasmin does not cross the blood-brain barrier. Lack of this form of ceruloplasmin in the central nervous system could lead to the generation of highly toxic free radicals, which can cause neuronal degeneration as seen in aceruloplasminemia and other neurodegenerative diseases such as Parkinson's and Alzheimer's disease.

Coexistence of an unusual form of scabies and lepromatous leprosy. A case report.

A case of unusual crusted (Norwegian) scabies involving the entire skin of a 26 year old Brazilian patient with lepromatous leprosy is reported. The more prominent histopathological findings were acanthosis, hyperkeratosis and crusting with many mites of Sarcoptes scabiei. In the dermis, numerous foamy histiocytes filled with abundant acid-fast bacilli were seen.

Seroprevalence of HIV, HTLV-I/II and other perinatally-transmitted pathogens in Salvador, Bahia.

Generation of epidemiological data on perinatally-transmitted infections is a fundamental tool for the formulation of health policies. In Brazil, this information is scarce, particularly in Northeast, the poorest region of the country. In order to gain some insights of the problem we studied the seroprevalence of some perinatally-transmitted infections in 1,024 low income pregnant women in Salvador, Bahia. The prevalences were as follow: HIV-1 (0.10%), HTLV-I/II (0.88%), T.cruzi (2.34%). T.pallidum (3.91%), rubella virus (77.44%). T.gondii IgM (2.87%) and IgG (69.34%), HBs Ag (0.6%) and anti-HBs (7.62%). Rubella virus and T.gondii IgG antibodies were present in more than two thirds of pregnant women but antibodies against other pathogens were present at much lower rates. We found that the prevalence of HTLV-I/II was nine times higher than that found for HIV-1. In some cases such as T.cruzi and hepatitis B infection there was a decrease in the prevalence over the years. On the other hand, there was an increase in the seroprevalence of T.gondii infection. Our data strongly recommend mandatory screening tests for HTLV-I/II, T.gondii (IgM), T.pallidum and rubella virus in prenatal routine for pregnant women in Salvador. Screening test for T.cruzi, hepatitis and HIV-1 is recommended whenever risk factors associated with these infections are suspected. However in areas with high prevalence for these infections, the mandatory screening test in prenatal care should be considered.

Demonstration of mycobacterial antigens in skin biopsies fron suspected leprosy cases in the absence of bacilli.

Skin-biopsies from fifty-six patients suspected of early leprosy from Bahia State, Brazil, were examined histopathologically. The Fite-Faraco staining failed to demonstrate acid-fast bacilli in this material. The prominent features of the lesions were inflammation of the neurovascular bundles and sometimes inflammation of the skin appendages. The non-specific infiltrate was predominantly composed of histiocytes and lymphocytes. In 41 cases (73.2%) epidermal atrophy was also present. The avidin-biotin peroxidase technique was used with primary antibodies to detect bacillary antigens (anti-BCG serum) and nerve branches (anti-S-100 protein serum). Immunohistochemical detection of bacillary antigens using the anti-BCG serum was positive in 28 cases (50%). A positive staining for S-100 protein was observed in 40 cases (71.4%) in dendritic antigen-presenting cells of the skin. The detection of bacillary antigens, together with the clear demonstration of nerve bundles enhanced our capacity to fulfill morphologic criteria for the diagnosis of early leprosy. Our observations indicate that the use of immunohistochemical methods represent a useful tool for the early diagnosis of leprosy.

DNA strand breakage during physiological apoptosis of the embryonic chick lens: free 3' OH end single strand breaks do not accumulate even in the presence of a cation-independent deoxyribonuclease.

Epithelial cells from the lens equator differentiate into elongated fiber cells. In the final steps of differentiation, the chromatin appears quite condensed and chromatin breakdown into nucleosomes occurs. DNA breaks due to an endodeoxyribonuclease activity corresponding to at least two polypeptides of 30 and 40 kDa have been identified. To identify the nature and the developmental appearance of initial breaks, nick translation reaction was followed both biochemically and in situ in fiber and epithelial cells from chick embryonic lenses. There is no accumulation of single-strand breaks (SSB) with 3'OH ends in lens fiber cells during embryonic development. Such damage can be increased in these cells by treatment with DNAase I indicating the absence of an inhibitor of the nick translation reaction in fiber cells. However, there are indications of the presence of DNA breaks with blocked termini when the phosphatase activity of nuclease P1 is used. The presence of breaks is also indicated by the large amounts of (ADP-ribose)n found in lens fibers particularly at 11 days of embryonic development (E11) as ADP-ribosyl transferase binds to and is activated by DNA strand breaks. Incubation of lens cells in vitro, which causes nucleosomal fragmentation only in fiber cells, produces SSB with 3'OH ends in both epithelia and fibers. Incubation for short periods, observed in experiments in situ, induces SSB first in the central fiber nuclei, which are late in differentiation. This may indicate that these SSB play a physiological role. Long incubations produce larger numbers of SSB in epithelia than fibers. The SSB in the fibers may have been converted into double-strand breaks (D SB), seen as nucleosomal fragments, and therefore no longer act as substrates for nick translation. The nuclease activity responsible for SSB production is independent of divalent cations and could be implicated in lens terminal differentiation.

Production and characterization of xylanase from a Streptomyces species grown on agricultural wastes.

Alkali-treated corn stalk gave maximum xylanase production at supporting growth of Streptomyces HM-15. Xylanase was stable for 24 h over a pH range of 5.0 to 7.0, had optimal activity between 50 and 60°C and a halflife of 5 h at 60°C. Xylanase production and activity were inhibited by xylose.

Serum esterase activities and hyperlipidaemia in the streptozotocin-diabetic rat.

The levels of activity of four serum esterases were measured in control and streptozotocin-diabetic rats for a period of 6 months. Pseudocholinesterase activity was significantly elevated in the diabetic rats at all time points tested, reaching 250% of the control activity at 6 months. Levels of paraoxonase activity progressively decreased with time in the diabetic rats, being 36% lower than in controls at 6 months. No significant differences in either serum arylesterase or carboxylesterase activity between control and diabetic rats were observed.

Benzamides can stimulate as well as inhibit the activity of nuclear ADP-ribosyltransferase.

Benzamides are potent inhibitors of nuclear ADP-ribosyltransferase and have been extensively used to demonstrate the involvement of ADP-ribosylation in cellular function. When permeabilized L1210 cells are treated with 50 microM 3-acetylamidobenzamide (3-aab) the enzyme is inhibited. However, when 50 nM 3-aab is used a two-fold stimulation of enzyme activity is produced. This anomalous stimulation is obtained with benzamides and nicotinamides and is correlated with their activity as inhibitors. Strikingly the steady-state level of poly(ADP-ribose) in intact cells is increased by these low levels of inhibitors. The mechanisms of this effect and its consequences for the experimental use of benzamides are discussed.

Effects of serotonin1 and serotonin2 receptor agonists and antagonists on blood pressure, heart rate and sympathetic nerve activity.

Previous studies indicate that serotonin (5-HT) neurons provide a tonic excitatory input to central sympathetic neurons. The purpose of the present study was to utilize a number of 5-HT agonists in order to provide insights into the general function of the serotonergic system in the regulation of central sympathetic pathways. The 5-HT1A agonists 8-hydroxy-dipropylaminotetralin and p-aminophenyl-ethyl-m-trifluoromethylphenyl piperazine produced a dose-related inhibition of sympathetic nerve discharge (SND) recorded from either the postganglionic inferior cardiac nerve or the preganglionic splanchnic nerve in chloralose-anesthetized cats. The sympatholytic effects of 8-hydroxy-dipropylaminotetralin and p-aminophenyl-ethyl-m-trifluoromethylphenyl piperazine were accompanied by hypotension and bradycardia. The effects of 5-HT1A agonists were reversed by the 5-HT1A antagonist spiperone. In contrast, spiperone alone produced decreases in blood pressure, heart rate and SND. The 5-HT1B agonists 1[3(trifluoromethyl) phenyl]-piperazine, 1-(3-chlorophenyl) piperazine and 1-(2-methoxyphenyl) piperazine all produced variable effects on SND. In some experiments, SND was increased by these agents, whereas it was decreased in others. The 5-HT2 agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane produced a marked increase in SND. A second 5-HT2 agonist, MK212, produced similar effects. The role of 5-HT receptor subtypes in mediating the 5-HT excitation of sympathetic neurons is discussed. It is suggested that 5-HT1A agonists inhibit SND through a process of disfacilitation by inhibiting the firing rate of 5-HT neurons. Possible mechanisms by which 5-HT2 agonists increase SND are proposed.

Peroxisomal localization of glucose-6-phosphate dehydrogenase and pyrophosphate-stimulated dihydroxyacetone-phosphate acyltransferase in mouse kidney.

1. The subcellular localization of dihydroxyacetone-phosphate acyltransferase (DHAPAT) (assayed in the presence of pyrophosphate) and glucose-6-phosphate dehydrogenase (NADP+-dependent) activity in mouse kidney was investigated by density-gradient centrifugation. 2. DHAPAT has a predominantly peroxisomal distribution, and the activity in purified peroxisomes is stimulated by various organic and inorganic phosphate-containing compounds. The pH optimum is acid. 3. Approx. 10% of the cellular NADP+-dependent glucose-6-phosphate dehydrogenase activity is associated with peroxisomal fractions and may provide a source of NADPH for the peroxisomal reduction of acyl-dihydroxyacetone phosphate formed by DHAPAT activity.

Degradation of the pyrimidine bases uracil and thymine by Escherichia coli B.

Degradation of the pyrimidine bases uracil and thymine by Escherichia coli B was investigated. The known products of the reductive pathway of pyrimidine base catabolism were tested to determine if they could support the growth of E. coli B cells as sole sources of nitrogen or carbon. As might be expected if the reductive pathway was present, it was found that dihydrouracil, N-carbamoyl-beta-alanine, beta-alanine, dihydrothymine and beta-aminoisobutyric acid could sustain the growth of the bacterial cells as sole nitrogen sources by at least a fourteen-fold greater level than that observed if they were included as sole carbon sources. The existence of the reductive pathway of pyrimidine base degradation was confirmed in this micro-organism, since dihydrouracil, N-carbamoyl-beta-alanine and beta-alanine were detected following thin-layer chromatographic separation of the catabolic products of uracil and dihydrouracil.