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Biophysical and pharmacological diversity of high-voltage-activated calcium currents in layer II neurones of guinea-pig piriform cortex.

1. High-voltage-activated calcium currents were studied with the whole-cell, patch-clamp technique in acutely dissociated pyramidal neurones from guinea-pig piriform cortex layer II. Barium ions were used as charge carriers. 2. Barium currents (IBa) displayed a remarkable kinetic diversity in different neurones. The ratio between the current amplitude at the end of the test pulses and the peak amplitude (Re/p) showed two frequency-distribution peaks at approximately 0.4 and 0.8. The index of current activation speed (rise time 10-90 %) directly correlated with the index of current persistence, Re/p. 3. The half-activation potential (V ) of total IBas positively correlated with the Re/p of the corresponding currents. This implied that the high-decay IBas also had a more negative voltage range of activation than the more persistent ones. 4. The L- and N-type channel blockers nifedipine (10 microM) and omega-conotoxin GVIA (omega-CTx GVIA, 0.5-1 microM) additively blocked 20 and 25 % of the total IBa, respectively. The P/Q-type calcium channel blockers omega-agatoxin IVA (100 nM), omega-conotoxin MVIIC (1 microM) and 3.3 funnel toxin (1 microM), had little effect on IBa. 5. The nifedipine- and omega-CTx GVIA-sensitive current had a Re/p > 0.55 and their voltage dependence of activation was of the high-voltage-activated type (V approximately 0 mV). 6. High-, intermediate- and low-decay blocker-resistant currents were observed in different neurones. Their Re/p values highly correlated with those of the corresponding total IBas and with the voltage dependence of activation of the underlying conductances. Exponential fittings of the inactivation phase of blocker-resistant currents returned very fast time constants (lower than 30 ms) for high-decay currents (Re/p < 0.25). The intermediate-decay currents (Re/p approximately 0.55) could not derive from variable combinations of high- and low-decay current components. 7. Our data demonstrate a remarkable variety in voltage-activated calcium currents expressed by piriform cortex neurones, that include currents resistant to high-voltage-activated calcium-channel blockers.

Algorithms↗

Surveillance for antimicrobial susceptibility among clinical isolates of Pseudomonas aeruginosa and Acinetobacter baumannii from hospitalized patients in the United States, 1998 to 2001.

Pseudomonas aeruginosa and Acinetobacter baumannii are the most prevalent nonfermentative bacterial species isolated from clinical specimens of hospitalized patients. A surveillance study of 65 laboratories in the United States from 1998 to 2001 found >90% of isolates of P. aeruginosa from hospitalized patients to be susceptible to amikacin and piperacillin-tazobactam; 80 to 90% of isolates to be susceptible to cefepime, ceftazidime, imipenem, and meropenem; and 70 to 80% of isolates to be susceptible to ciprofloxacin, gentamicin, levofloxacin, and ticarcillin-clavulanate. From 1998 to 2001, decreases in antimicrobial susceptibility (percents) among non-intensive-care-unit (non-ICU) inpatients and ICU patients, respectively, were greatest for ciprofloxacin (6.1 and 6.5), levofloxacin (6.6 and 3.5), and ceftazidime (4.8 and 3.3). Combined 1998 to 2001 results for A. baumannii isolated from non-ICU inpatients and ICU patients, respectively, demonstrated that >90% of isolates tested were susceptible to imipenem (96.5 and 96.6%) and meropenem (91.6 and 91.7%); fewer isolates from both non-ICU inpatients and ICU patients were susceptible to amikacin and ticarcillin-clavulanate (70 to 80% susceptible); and <60% of isolates were susceptible to ceftazidime, ciprofloxacin, gentamicin, or levofloxacin. From 1998 to 2001, rates of multidrug resistance (resistance to at least three of the drugs ceftazidime, ciprofloxacin, gentamicin, and imipenem) showed small increases among P. aeruginosa strains isolated from non-ICU inpatients (5.5 to 7.0%) and ICU patients (7.4 to 9.1%). From 1998 to 2001, rates of multidrug resistance among A. baumannii strains isolated from non-ICU inpatients (27.6 to 32.5%) and ICU patients (11.6 to 24.2%) were higher and more variable than those observed for P. aeruginosa. Isolates concurrently susceptible, intermediate, or resistant to both imipenem and meropenem accounted for 89.8 and 91.2% of P. aeruginosa and A. baumannii isolates, respectively, studied from 1998 to 2001. In conclusion, for aminoglycosides and most beta-lactams susceptibility rates for P. aeruginosa and A. baumannii were constant or decreased only marginally (</=3%) from 1998 to 2001. Greater decreases in susceptibility rates were, however, observed for fluoroquinolones and ceftazidime among P. aeruginosa isolates.

Acinetobacter baumannii↗

Glucosylation of lipopolysaccharide in Salmonella: mutants negative for O antigen factor 1221.

In salmonella O group B, the O antigen factor 12(2) is created by glucosylation at C4 of the galactose units of the O side chains; phage-determined glucosylation at C6 of these galactose units yields factor 1. 12(2)-negative mutants were isolated from 12(2) (+) (stable) parents (genetically oafR(+st)). All 20 mutants studied were stable in respect of their 12(2) character. In eight of them, lysogenization by phage P22 resulted in the appearance of the 12(2) factor-these were interpreted to be defective in the enzyme(s) needed to synthesize the glucose-lipid intermediate that participates in both 12(2)- and 1-specific glucosylation; the corresponding cistron was termed oafE. This "complementation" assay also demonstrated that the P22 genome can determine the synthesis of this glucose-lipid intermediate. The 12(2) character in the oafE(-) mutants became variable after P22 lysogenization, corresponding to factor 1 variation normally determined by this phage. In the remaining 12 mutants, P22 caused the appearance of a variable factor 1, but not of 12(2). The lesion in all the 12(2) mutants was mapped close to the gene purE at min 19 of the Salmonella map. This is the same area where the locus oafR that controls the variation (stable or variable, + or -) of 12(2) had been previously mapped. The results suggest the presence of a 12(2) glucosylation operon in this region.

Animals↗

Modulation of electrical heterogeneity by compensated hypertrophy in rat left ventricle.

Modulation of the regional distribution of the action potential by left ventricular hypertrophy and the role of the L-type Ca2+ current (I(Ca)) and transient outward current (I(to)) in the action potential duration (APD) were investigated in normal and hypertrophied rat ventricular myocytes from the apex (A), septum (S) and left ventricular free wall (FW) by using whole cell current- and voltage-clamp techniques. Hypertrophy was induced by abdominal aortic constriction. In control cells, the APD measured at 20% repolarization (APD20) assumed the shortest values in the A and the longest in the S, whereas FW cells showed intermediate values. Hypertrophy significantly prolonged the APD20 and increased APD variability within the A and FW regions but did not modify the APD in S cells. Analysis of the APD, I(Ca), and I(to) at the instant of 20% repolarization in the same cell showed that in control cells the shortest APD20 was associated with a prominent I(to) in the A and FW, whereas the long APD20 was identified with a lower I(to) in S myocytes. Hypertrophy-induced prolongation ofAPD20 was associated with a reduction in the I(to) in the A and FW. Significant correlations could be established between the APD20 and the "net current," defined as the algebraic addition of I(to) and I(Ca) in the A and FW control groups but not in the control S or hypertrophied cells whatever their origin. Our results indicate that interregional APD heterogeneity is lost while intraregional APD variability is increased in the A and FW during the hypertrophic process. These effects are largely due to a change in the balance between the I(Ca) and I(to), which is a major contributing factor to the heterogeneity of the initial phase of repolarization in the normal rat ventricle.

Action Potentials↗

Peroxynitrite is a contractile agonist of cerebral artery smooth muscle cells.

On reperfusion of ischemic tissue, a prolonged phase of vasoconstriction occurs, the mechanism of which is poorly understood. However, it is known that peroxynitrite (ONOO-) is formed during reperfusion. In this study the contractile properties of ONOO- were investigated in Wistar rat middle cerebral arteries. The effects of ONOO- on vessel diameter were dose dependent. Low-dose ONOO- (10 microM) caused vessels to constrict by 15%. At an intermediate concentration of 25 microM, the effect of ONOO- was variable, whereas at the highest concentration (100 microM), vessels underwent persistent dilation and became insensitive to the endogenous vasoconstrictor 5-hydroxytryptamine. At the single cell level, ONOO- caused cerebral artery smooth muscle cells to contract. Reduced, but not oxidized, glutathione completely inhibited the contractile action of ONOO- on single cells. Vehicle and decomposed ONOO- each had minimal effect on cell length. These data show that ONOO- is a contractile agonist of middle cerebral arteries, at the single cell and whole vessel levels, suggesting that formation of ONOO- may contribute mechanistically to ischemic brain injury during stroke. Moreover, relatively high concentrations of ONOO- result in vascular paralysis.

Animals↗

Occurrence of B chromosomes in lizards: a review.

Although B chromosomes have been reported in many species of plants and animals, few studies have revealed the presence of these extra chromosomes in lizards. B chromosomes of lizards show different morphologies and sizes, from microchromosomes to macrochromosomes, or elements of intermediate size between smaller and larger A chromosomes, and number variability at intra- and inter-individual levels. In most cases, they are late-replicating and show either heterochromatic or no distinctive patterns after C-banding. The great majority of the publications about supernumerary chromosomes in this group have been based on conventional staining analyses, and there is no study designed to address questions related to their composition and structure or origin and evolution.

Animals↗

A new scoring system to stratify risk in unstable angina.

BACKGROUND: We performed this study to develop a new scoring system to stratify different levels of risk in patients admitted to hospital with a diagnosis of unstable angina (UA), which is a complex syndrome that encompasses different outcomes. Many prognostic variables have been described but few efforts have been made to group them in order to enhance their individual predictive power. METHODS: In a first phase, 473 patients were prospectively analyzed to determine which factors were significantly associated with the in-hospital occurrence of refractory ischemia, acute myocardial infarction (AMI) or death. A risk score ranging from 0 to 10 points was developed using a multivariate analysis. In a second phase, such score was validated in a new sample of 242 patients and it was finally applied to the entire population (n = 715). RESULTS: ST-segment deviation on the electrocardiogram, age > or = 70 years, previous bypass surgery and troponin T > or = 0.1 ng/mL were found as independent prognostic variables. A clear distinction was shown among categories of low, intermediate and high risk, defined according to the risk score. The incidence of the triple end-point was 6 %, 19.2 % and 44.7 % respectively, and the figures for AMI or death were 2 %, 11.4 % and 27.6 % respectively (p < 0.001). CONCLUSIONS: This new scoring system is simple and easy to achieve. It allows a very good stratification of risk in patients having a clinical diagnosis of UA. They may be divided in three categories, which could be of help in the decision-making process.

Age Factors↗

Prognostic factors in multiple myeloma: definition of risk groups in 410 previously untreated patients: a Grupo Argentino de Tratamiento de la Leucemia Aguda study.

Four hundred ten previously untreated multiple myeloma patients entered onto two consecutive Grupo Argentino de Tratamiento de la Leucemia Aguda (GATLA) protocols were analyzed to identify significant prognostic factors influencing survival. The univariate analysis selected the following variables: performance status, renal function, percentage of bone marrow plasma cells at diagnosis, hemoglobin, and age. A multivariate analysis showed that performance status, renal function, percentage of bone marrow plasma cells, hemoglobin, and age were the best predictive variables for survival. A score was assigned to each patient according to these variables, which led to their classification in three groups: good, intermediate, and poor risk, with a probability of survival of 26% and 10% at 96 months, and 5% at 56 months, and median survival of 60, 37, and 14 months, respectively (P = .0000). In our patient population, this model proved to be superior to the Durie-Salmon staging system in defining prognostic risk groups, and separating patients with significantly different risks within each Durie-Salmon stage.

Adult↗

Sources of scattering in cervical tissue: determination of the scattering coefficient by confocal microscopy.

Most models of light propagation through tissue assume that the scattering properties of various tissue layers are the same. We present evidence that the scattering coefficient of cervical epithelium varies by a factor of 3 within the epithelium owing to variations in nuclear density and to the presence of keratin. We estimated the scattering coefficient from regions of normal and precancerous cervical epithelium by fitting reflectance measurements from confocal images to an exponential function of depth based on Beer's law of attenuation. The results suggest that the normal cervix is characterized by highly variable scattering in the superficial epithelium, low scattering in the intermediate epithelium, and high scattering in the basal and stromal regions. In high-grade dysplasia, high scattering from high-density nuclei is observed throughout the entire epithelium.

Algorithms↗

Variants of alpha 1-antitrypsin in Puerto Rican children with asthma.

A survey of 393 Puerto Rican and 354 non-Hispanic pediatric patients at Beth Israel Hospital, New York, revealed a significantly larger percentage of asthmatic subjects among Puerto Ricans, confirming findings of a study of Puerto Rican adults in New York. Assays of alpha 1-antitrypsin (AAT) concentration and phenotypes in 61 Puerto Rican asthmatic children revealed a significantly larger number with an S or Z variant in AAT phenotype. The AAT concentration was not a significant variable in this relationship, since four of five subjects with intermediate deficient AAT concentrations and a PiM phenotype were among control nonasthmatic Puerto Rican subjects. A family history of asthma was more common among asthmatic than control subjects and was most common for variant AAT phenotypes in either asthmatic or control subjects. We speculate that the S or Z variant of AAT affects the inflammatory response in such a way as to predispose to asthma.

Adolescent↗

Bispectral Index (BIS) monitoring in morbidly obese patients undergoing gastric bypass surgery: experience in 23 patients.

BACKGROUND: Early and uneventful postoperative recovery of morbidly obese patients remains a challenge for anesthesiologists. BIS monitoring is useful in providing fast recovery. METHODS: We describe the anesthetic management of 23 morbidly obese patients who underwent elective open Roux-en-Y gastric bypass (RYGBP) for morbid obesity. Thoracic epidural analgesia combined with light general anesthesia with propofol and nitrous oxide adjusted to keep the bispectral index (BIS) around 60 was performed. Intraoperative hemodynamic stability, early and intermediate recovery and patient satisfaction were assessed. RESULTS: The cardiovascular variables were fairly stable during surgery. Times to spontaneous respiration, response to orders, tube removal and orientation were 4 +/- 3, 6 +/- 2, 8 +/-3, and 13 +/- 7 respectively. Times until the patients were able to sit unassisted, stand unassisted and walk freely without assistance were 319 +/- 25, 803 +/- 78, 1070 +/- 75 respectively (values expressed as min, mean +/- se). CONCLUSION: Propofol-nitrous oxide anesthesia adjusted to keep BIS around 60, combined with thoracic epidural analgesia, seems to be effective in providing predictable and uneventful recovery to patients submitted to elective RYGBP.

Anastomosis, Roux-en-Y↗

Insulin analogues and other developments in insulin therapy for diabetes.

Diabetes mellitus is a common chronic disorder, which is increasing in prevalence on a global scale. Insulin replacement therapy is required for all people with Type 1 diabetes and for many with Type 2 diabetes, to correct the metabolic abnormalities of these disorders. However, the pharmacokinetics and glucodynamics of available insulins have numerous limitations. Problems include delayed absorption from subcutaneous absorption sites (soluble [regular] insulin), and wide variability of absorption characteristics (insulin isophane suspension [NPH] and insulin lente) that is influenced by the adequacy of resuspension, and by a variable and insufficient duration of action, which usually requires intermediate-acting insulins to be administered twice-daily. All insulin preparations are associated with the common side effect of hypoglycaemia, and encourage weight gain.

Absorption↗

Virulence profile of ten Paracoccidioides brasiliensis isolates: association with morphologic and genetic patterns.

Ten isolates of Paracoccidioides brasiliensis were examined for differences in virulence in outbred mice intravenously inoculated with the fungus, associated with mycelial morphology, and genetic patterns measured by random amplified polymorphic DNA (RAPD). Virulence was evaluated by viable yeast cell recovery from lungs and demonstration of histopathologic lesions in different organs. The results showed that the isolates presented four virulence degrees: high virulence, intermediate, low and non-virulence. RAPD clustered the isolates studied in two main groups with 56% of genetic similarity. Strains with low virulence, Pb265 or the non-virulent, Pb192, showed glabrous/cerebriform morphology and high genetic similarity (98.7%) when compared to the other isolates studied. The same was observed with Bt79 and Bt83 that shared 96% genetic similarity, cottony colonies and high virulence. The RAPD technique could only discriminate P. brasiliensis isolates according to glabrous/cerebriform or cottony colonies, and also high from low virulence strains. Isolates with intermediate virulence such as Pb18, Pb18B6, Bt32 and Bt56 showed variability in their similarity coefficient suggesting that RAPD was able to detect genetic variability in this fungal species. Virulence profile of P. brasiliensis demonstrated that both mycelial morphologic extreme phenotypes may be associated with fungal virulence and their in vitro subculture time. Thus, RAPD technique analysis employed in association with virulence, morphologic and immunologic aspects might prove adequate to detect differences between P. brasiliensis isolates.

Animals↗

Longitudinal changes in blood lead level in children and their relationship to season, age, and exposure to paint or plaster.

Children screened for lead poisoning in the Brownsville district of New York City in either summer or winter were followed with blood lead tests for approximately six months to one year from screening to measure longitudinal changes in blood lead level and to identify some determinants of the changes. Only minimal evidence was found of the hypothesized summer rise in blood lead level, while the predominant trend seemed to be for blood lead levels to display statistical regression to the mean. In children found to have low to intermediate blood lead levels (less than 55 microgram/100ml) at screening, variables which were found to predict a rise in blood lead level of 10 microgram/100ml or greater from winter to summer were under age three and/or exposure to paint or plaster.

Age Factors↗

Time of daily supplementation for steers grazing dormant intermediate wheatgrass pasture.

To compare the effects of time of daily protein supplementation on grazing behavior, forage intake, digesta kinetics, ruminal fermentation, and serum hormones and metabolites, 12 ruminally cannulated Holstein steers (449 and 378 kg average initial and final BW, respectively) were allotted to three groups. Treatments consisted of CON = no supplement, AM = cottonseed meal (.25% of BW) at 0600, and PM = cottonseed meal (.25% of BW) at 1200. Steers grazed a dormant (1.1% N) intermediate wheatgrass (Thinopyrum intermedium Host) pasture. Sampling trials occurred in December, January, and February. Supplementation altered (P = .01) time spent grazing; CON steers grazed approximately 1.5 h longer than supplemented steers. Supplemented steers lost less (P = .02) BW (-40 kg) than CON steers (-75 kg) did. Supplementation did not alter (P greater than .15) forage OM intake; however, total OM intake was greater (P = .01) for supplemented steers (22.3 g/kg of BW) than for CON (18.4 g/kg of BW) steers. Supplementation did not affect (P greater than .15) digesta kinetics. Extent of in situ NDF (96 h) and rate (%/h) of disappearance for supplemented steers was greater (P = .01) than for CON steers. Across all periods, ruminal NH3 N and total VFA concentrations were lower (P = .01) for CON steers than for supplemented steers. Serum insulin (ng/mL) concentration was lower (P = .03) and concentration of serum growth hormone (ng/mL) was higher (P = .02) for CON steers than for supplemented steers. Cottonseed meal supplementation enhanced utilization of intermediate wheatgrass; however, supplementation time had minimal effects on the variables measured.

Animal Feed↗

First genomic insights into the introgression of almond PPV-Marcus resistance into peach.

AIM: Sharka, caused by Plum pox virus (PPV), is one of the most damaging viral diseases of stone fruit crops, with peach among the most susceptible cultivated Prunus species. Almond is a promising source of resistance, but its genetic architecture and expression in a peach genetic background remain largely unknown. This study aimed to construct parental genetic linkage maps and identify genomic regions associated with PPV response in almond &#xd7; peach interspecific populations. METHODS: Progenies derived from the almond cultivars 'Del Cid', 'Garrigues', and 'Mono' were evaluated by RT-PCR after graft inoculation with the PPV-Marcus (PPV-M) strain over consecutive infection cycles. Phenotypic data were summarized for each genotype using best linear unbiased estimates (BLUEs). High-density SNP almond and peach arrays were used to construct parental maps for 'Garrigues' and 'Mono' and perform quantitative trait locus (QTL) analysis. RESULTS: Phenotypic variation was observed among and within families. 'Del Cid'-derived progenies showed the greatest resistance, 'Garrigues'-derived progenies displayed intermediate responses, and 'Mono'-derived progenies showed greater susceptibility and variability. The parental maps covered 546.69 cM in 'Mono' and 521.72 cM in 'Garrigues', with average intervals of 0.61 and 1.26 cM per unique marker position, respectively, and showed strong collinearity with the reference genome. QTL associated with PPV-M response were detected on linkage groups (LG) 1 and 6 in 'Garrigues' and LG2 in 'Mono'. The main QTL in 'Garrigues' peaked near 22.39 Mb on LG1, whereas the 'Mono' QTL was located at 22.27-22.62 Mb on LG2; a weaker QTL was detected near 25.38 Mb on LG6 in 'Garrigues'. The results support a quantitative and genetic-background-dependent architecture of PPV resistance. CONCLUSION: This study provides the first evidence of genomic regions associated with PPV-Marcus response in almond &#xd7; peach populations. The detected QTLs provide an initial basis to support the introgression of almond-derived resistance into peach breeding material.

Prunus↗

Adaptation to time-compressed speech: phonological determinants.

Perceptual adaptation to time-compressed speech was analyzed in two experiments. Previous research has suggested that this adaptation phenomenon is language specific and takes place at the phonological level. Moreover, it has been proposed that adaptation should only be observed for languages that are rhythmically similar. This assumption was explored by studying adaptation to different time-compressed languages in Spanish speakers. In Experiment 1, the performances of Spanish-speaking subjects who adapted to Spanish, Italian, French, English, and Japanese were compared. In Experiment 2, subjects from the same population were tested with Greek sentences compressed to two different rates. The results showed adaptation for Spanish, Italian, and Greek and no adaptation for English and Japanese, with French being an intermediate case. To account for the data, we propose that variables other than just the rhythmic properties of the languages, such as the vowel system and/or the lexical stress pattern, must be considered. The Greek data also support the view that phonological, rather than lexical, information is a determining factor in adaptation to compressed speech.

Adaptation, Psychological↗

[Risk behavior among Brazilian Military conscripts, 1998: an study of HIV infections following socioeconomic differences].

A study of HIV-related risk behavior was carried out in 1998 among Brazilian military conscripts aged 17-20 years. A sample of 30,318 subjects was selected in three strata, pertaining to counties from: 1) the North and Central-West (N/CW); 2) South (S); and the states of Rio de Janeiro and São Paulo. HIV prevalence rates were estimated in all strata. The objective of this paper was to analyze the results according to differences in socioeconomic status (SES). The statistical analysis used an index of sexual risk behavior and logistic regression models. The N/CW stratum showed the worst indicators for SES, sexual risk behavior, and sexually transmitted infections (STIs), as well as the highest HIV seroprevalence rate. The best indicators for all variables were found in the RJ/SP stratum. The South showed intermediate results. Level of schooling also played a relevant role. In all three strata the conscripts with an incomplete high school education displayed the worst sexual risk behavior index, shown to be a relevant predictor of STI-related problems, including HIV infection.

Adolescent↗