Biomedical subjects

E Papa

Publications and source records attributed to E Papa.

15 recordsLinked to original sources

PubMed2006

Linear QSAR regression models for the prediction of bioconcentration factors by physicochemical properties and structural theoretical molecular descriptors.

The development of QSAR models useful for the prediction of fish bioconcentration factor (BCF) for a wide range of different chemical classes is crucial for the assessment and prioritisation of potentially persistent bioaccumulative and toxic substances. In this study we present QSAR models for BCF developed on a wide range of chemical structural classes of environmental and toxicological interest (such as dyes and various chlorinated and brominated compounds). The aim is to provide valid QSAR models, statistically validated for predictivity, for the prediction of BCF in general, but also for problematical chemical classes such as highly hydrophobic chemicals. Several descriptors, calculated by different commercially available software packages, have been employed in order to take into account relevant information provided by physicochemical properties (octanol/water partition coefficient and water solubility) and molecular features (structural and quantum-chemical molecular descriptors). The best descriptor subsets for the models were selected using the Genetic Algorithm-Variable Subset Selection strategy (GA-VSS) and calculations were performed by ordinary least squares regression. Starting from a data set of 640 compounds (logK(ow) range from -2.34 to 12.66), we developed linear QSARs, firstly for a data set of 620 compounds (logK(ow) range from -2.34 to 10.35) and secondly specifically for 87 highly hydrophobic chemicals (logK(ow) range from 6.00 to 10.35). All these models have been statistically validated (both internally by cross-validation and bootstrap and externally, by "a priori" splitting of available data by Kohonen Map-ANN in training and prediction sets) and their structural chemical domain has been verified by the leverage approach.

Animals↗

PubMed2002

Ranking of volatile organic compounds for tropospheric degradability by oxidants: a QSPR approach.

The limited availability and variability of data related to atmospheric degradation reaction is a very relevant issue in studies related to environmental fate and behavior of chemicals. For screening purposes, the experimental data of the oxidation rate constants for the reactions with the radicals OH, NO3 and with ozone of 65 heterogeneous organic compounds were explored by Principal Component Analysis: a ranking of volatile organic chemicals (VOC) according to their relative overall atmospheric degradability and an atmospheric persistence index (ATPIN) is proposed. This index has been modeled by theoretical molecular descriptors to obtain MLR models with high predictive power, both internally and externally validated, and the definition of chemical domain applicability. This procedure allows a fast ranking of VOCs according to their tendency to be degraded by atmospheric oxidants, starting only from the knowledge of their molecular structure.

Air Pollutants↗

PubMed2000

Sit-to-stand motor strategies investigated in able-bodied young and elderly subjects.

For the execution of a certain motor task, a motor strategy is chosen by each individual among those that are consistent with the structural and functional constraints of his/her locomotor system, and that tends to maximise the effectiveness of the motor act. The identification of this strategy allows for the assessment of the individual's functional status. This study aimed at identifying the motor strategies adopted for the execution of the sit-to-stand motor task, at different speeds and initial postures, in a sample of 35 community-dwelling elders and in a sample of 16 young able-bodied individuals. This was done using a method, least perceivable to the test subject and "economical" for the experimenter, which entailed the recording of external forces only. A musculo-skeletal system model, based on a telescopic inverted-pendulum (TIP) moved by a linear and two rotational muscle-equivalent actuators, was then used. Parameters describing the kinematics and dynamics of these actuators were extracted and submitted to statistical analysis. Different motor strategies were identified in the two age groups, as well as associated with both a different initial posture (ankle dorsiflexion angle) and speed of execution of the motor task. In particular, the elder group, as compared with the young group, prior to seat-off tended to flex the trunk more, thus bringing the CM closer to the base of support, and at a higher velocity, thus gaining a higher momentum. After seat-off, elders rotated the body forward and, only after having brought their CM over the base of support, effectively started elevation. Both global muscular effort and coordination effort associated with the achievement of balance and raising were lower. However, maximal speed was also lower. The above results indicated that the elders could count on a lower functional reserve than the young individuals and, from the methodological viewpoint, that the TIP approach is a good candidate for subject-specific functional evaluation in a clinical context.

Adult↗

PubMed2000

Gastrin inhibits cholangiocyte growth in bile duct-ligated rats by interaction with cholecystokinin-B/Gastrin receptors via D-myo-inositol 1,4,5-triphosphate-, Ca(2+)-, and protein kinase C alpha-dependent mechanisms.

We studied the role of gastrin in regulating cholangiocyte proliferation induced by bile duct ligation (BDL). In purified cholangiocytes, we evaluated (1) for the presence of cholecystokinin-B (CCK-B)/gastrin receptors, (2) the effect of gastrin on D-myo-Inositol 1,4,5-triphosphate (IP(3)) levels, and (3) the effect of gastrin on DNA synthesis and adenosine 3', 5'-monophosphate (cAMP) levels in the absence or presence of CCK-A (L-364,718) and CCK-B/gastrin (L-365,260) receptor inhibitors, 1, 2-bis(2-aminophenoxy)-ethane-N,N,N',N'-tetraacetic acid tetrakis(acetxymethyl ester) (BAPTA/AM; an intracellular Ca(2+) chelator), and 2 protein kinase C (PKC) inhibitors, 1-(5-Isoquinolinylsulfonyl)-2-methylpiperazine (H7) and staurosporin. To evaluate if gastrin effects on cholangiocyte proliferation are mediated by the isoform PKCalpha, we evaluated (1) for the presence of PKCalpha in cholangiocytes and (2) the effect of gastrin on the PKCalpha protein expression in a triton-soluble (containing cytoplasm + membrane) and a triton-insoluble (containing cytoskeleton) fraction. To evaluate the effects of gastrin in vivo, immediately following BDL, gastrin or bovine serum albumin (BSA) was infused by minipumps for 7 days to rats and we measured cholangiocyte growth and cAMP levels. We found CCK-B/gastrin receptors on cholangiocytes. Gastrin increased IP(3) levels. Gastrin inhibited DNA synthesis and cAMP synthesis in cholangiocytes. Gastrin effects on cholangiocyte functions were blocked by L-365,260, BAPTA/AM, H7, and staurosporin but not by L-364,718. Gastrin induced translocation of PKCalpha from cholangiocyte cytoskeleton to membrane. In vivo, gastrin decreased cholangiocyte growth and cAMP synthesis compared with controls. We concluded that gastrin inhibits cholangiocyte growth in BDL rats by interacting with CCK-B/gastrin receptors through a signal transduction pathway involving IP(3), Ca(2+), and PKCalpha.

Animals↗

PubMed1999

A telescopic inverted-pendulum model of the musculo-skeletal system and its use for the analysis of the sit-to-stand motor task.

For field applicability of biomechanical methodologies aiming at assessing motor ability in disabled, or at risk of disablement (e.g. elderly), subjects, measurements must be carried out using a least perceivable to the subject and essential experimental apparatus. Since data thus obtained do not necessarily lend themselves to straightforward interpretation, they should be fed to a model of the portion of the musculo-skeletal system involved that already embodies the invariant aspects of both the modelled system and the motor task. Through such a minimum measured-input model, richer, physiology-related, and thus easier to interpret, information may be expected. In this framework, the present study investigated the sit-to-stand motor task using information obtained only from a force plate located under seat and subject's feet, a seat uniaxial load-cell and basic anthropometric parameters. Data were collected in a sample of 12 able-bodied subjects while executing the motor task at different speeds. The musculo-skeletal system was modelled as a telescopic inverted pendulum (TIP) that could vary its length (shortening or elongation) by effect of a force actuator and its orientation in space by effect of two couple actuators that were looked upon as muscle equivalent effectors. The TIP model output consisted in the kinematics and dynamics of these actuators. It allowed the identification of four functional phases in which the seat-to-stand motor task could be divided, and a detailed description of the relevant mechanics in terms of balance control and centre of mass elevation. Motor strategy modifications associated with speed variation could also be identified. For a global evaluation of the motor act it showed to be no less informative than more demanding multi-segment models. Although it is true that specific musculo-articular functions can only be inferred, the more compact information yielded by the TIP model is expected to facilitate subject and/or disability classification.

Adult↗

PubMed1999

Inter- and intra-individual variability of ground reaction forces during sit-to-stand with principal component analysis.

Variable reduction is an important issue in biomechanics, because the definition of a non-redundant set of variables necessary for a complete description of a given motor act provides information about the motor strategy. A systematic tool for dealing with variable reduction problems is Principal Component Analysis. In this paper, as an example of an application of this technique, the set of Ground Reaction Forces (GRFs) provided by a six-component force plate, gained during standing up in a heterogeneous population of 82 normal individuals, was reduced to a set of fewer variables. Each subject was required to stand up from a chair five times at different, randomly self selected, speeds, obtaining a data set of 410 trials. Principal Components (PCs) of GRFs were computed for each trial. On average, over the ensemble of trials, first and second PCs (PC1 and PC2) explained together 90% of PCs. Inter- and intra-individual repeatability of the first two PCs was investigated by examining the correlation coefficient between PC waveforms obtained from the whole set of trials and within the set of trials performed by the same subject, respectively. While the PC1 exhibited repeatable patterns, the second one, although repeatable within the group of trials performed by the same subject, displayed marked inter-individual variability. Therefore, PC1 was related to intrinsic aspects of the motor task and PC2 to inter-subject features.

Adult↗

PubMed1999

Effect of pharmacological modulation of liver P-glycoproteins on cyclosporin A biliary excretion and cholestasis: a study in isolated perfused rat liver.

In different cell types P-glycoproteins (P-gp) are involved in the transport of cyclosporin A (CyA). The aim of this study was to evaluate the effect of the pharmacological modulation of the hepatic P-gp on biliary secretion of CyA and on cholestasis induced by acute administration of CyA in the isolated perfused rat liver (IPRL). Verapamil was used as a P-gp specific inhibitor and acetylaminofluorene (AAF) as a P-gp inducer. CyA biliary excretion was determined by administering in the IPRL a tracer dose of [3H]CyA with or without verapamil or AAF. The effect on bile flow was evaluated by administering increasing doses of CyA (2.8, 8, and 20 mg/kg body wt) in the IPRL. Morphological evidence of damage was evaluated by optical and electron microscopy in the liver as well as in primary culture of rat hepatocytes exposed to CyA +/- verapamil. Verapamil significantly inhibited the biliary excretion of a tracer dose of [3H]CyA (0.15+/-0.04 vs 0.33+/-0.07%; P < 0.05). In contrast, pretreatment with AAF significantly increased the biliary excretion of [3H]CyA, (0.61+/-0.10 vs 0.33+/-0.07%; P < 0.05). CyA induced a dose-dependent inhibition of bile flow with a maximal effect at 20 mg/kg CyA (-49.3+/-4.5% decrease of basal bile flow). CyA cholestasis was significantly worsened by the P-gp inhibitor, verapamil (-75.5+/-7.5%; P < 0.05), but it was unaffected by induction of P-gp via AAF pretreatment (-44.9+/-1.7%). During CyA cholestasis, the cumulative biliary excretion of [3H]CyA was lower than in the absence of cholestasis (0.22+/-0.05 vs 0.33+/-0.07%; P < 0.05), was inhibited by verapamil (0.08+/-0.01%; P < 0.05), but was unaffected by AAF (0.23+/-0.05%). No morphological evidence of damage was observed in the liver, and no evidence of cytoskeleton derangement was seen in primary cultures of rat hepatocytes exposed to CyA +/- verapamil. We demonstrated that pharmacological modulation of P-gp may influence the biliary excretion of CyA. The acute cholestatic effect of CyA is worsened by P-gp inhibitors, while it is unaffected by P-gp inducers. This indicates CyA should not be given with other P-gp substrates or inhibitors.

2-Acetylaminofluorene↗

PubMed1999

Acute carbon tetrachloride feeding induces damage of large but not small cholangiocytes from BDL rat liver.

Bile duct damage and/or loss is limited to a range of duct sizes in cholangiopathies. We tested the hypothesis that CCl4 damages only large ducts. CCl4 or mineral oil was given to bile duct-ligated (BDL) rats, and 1, 2, and 7 days later small and large cholangiocytes were purified and evaluated for apoptosis, proliferation, and secretion. In situ, we measured apoptosis by morphometric and TUNEL analysis and the number of small and large ducts by morphometry. Two days after CCl4 administration, we found an increased number of small ducts and reduced number of large ducts. In vitro apoptosis was observed only in large cholangiocytes, and this was accompanied by loss of proliferation and secretion in large cholangiocytes and loss of choleretic effect of secretin. Small cholangiocytes de novo express the secretin receptor gene and secretin-induced cAMP response. Consistent with damage of large ducts, we detected cytochrome P-4502E1 (which CCl4 converts to its radicals) only in large cholangiocytes. CCl4 induces selective apoptosis of large ducts associated with loss of large cholangiocyte proliferation and secretion.

Animals↗

PubMed1998

Endothelin-1 inhibits secretin-stimulated ductal secretion by interacting with ETA receptors on large cholangiocytes.

We studied the expression of endothelin-1 (ET-1) receptors (ETA and ETB) and the effects of ET-1 on cholangiocyte secretion. The effects of ET-1 on cholangiocyte secretion were assessed in normal and bile duct-ligated (BDL) rats by measuring 1) basal and secretin-induced choleresis in vivo, 2) secretin receptor gene expression and cAMP levels in small and large cholangiocytes, and 3) luminal expansion in response to secretin in intrahepatic bile duct units (IBDU). ETA and ETB receptors were expressed by small and large cholangiocytes. ET-1 had no effect on basal bile flow or bicarbonate secretion in normal or BDL rats but decreased secretin-induced bicarbonate-rich choleresis in BDL rats. ET-1 decreased secretin receptor gene expression and secretin-stimulated cAMP synthesis in large cholangiocytes and secretin-induced luminal expansion in IBDU from normal or BDL rats. The inhibitory effects of ET-1 on secretin-induced cAMP synthesis and luminal duct expansion were blocked by specific inhibitors of the ETA (BQ-610) receptor. ET-1 inhibits secretin-induced ductal secretion by decreasing secretin receptor and cAMP synthesis, two important determinants of ductal secretion.

Animals↗

PubMed1991

Failure of routine susceptibility tests to detect imipenem resistance among strains of methicillin-resistant Staphylococcus aureus.

We tested 75 methicillin-resistant Staphylococcus aureus strains for susceptibility to imipenem by using disk diffusion tests and broth microdilution tests with standard and heavy inocula. Population analysis was performed on isolates that appeared to be susceptible by these methods. All of the strains contained subpopulations of cells that are phenotypically resistant to imipenem.

Drug Resistance, Microbial↗

PubMed1989

[Experimental peritonitis: sequential bacteriologic study of the lymph and blood].

In 7 dogs with fecal peritonitis, induced by incision of the cecum, and in the same number of control animals the thoracic duct was cannulized at the neck level together with a femoral vein for the purpose of sequential study of the routes of bacterial dissemination. The findings show: a) rapid appearance of germs in lymph and then in blood in animals with peritonitis, b) a progressive increase in the number of species isolated in each sample, and c) that the lymphatic flow and drainage of bacterias lasted throughout the 12 hours that the experiment lasted. The microbes isolated in lymph and blood were related to the flora of the intestinal segment where the infection originated, with development of a large number of anaerobic species.

Animals↗

PubMed1986

Novel plasmid-mediated beta-lactamase in members of the family Enterobacteriaceae from Ohio.

Epidemiologic studies of plasmid-mediated resistance at the Cleveland Veterans Administration Medical Center revealed that related plasmids had disseminated among members of the family Enterobacteriaceae. We studied the beta-lactamases encoded by these plasmids in Escherichia coli C600 transformants or transconjugants. Substrate and inhibition profiles of the enzymes determined by two of these plasmids suggested an activity resembling TEM-1; however, isoelectric focusing revealed a pI of 7.0. These two plasmids were originally found in a Serratia marcescens (pDS076) and an Enterobacter cloacae (pDS075) strain isolated from the same sink in the medical intensive care unit and later, in an Enterobacter cloacae (pDS142 identical to pDS076) isolate colonizing a patient in the same unit. The plasmids also carried the aminoglycoside resistance determinant, 2"-aminoglycoside nucleotidyl transferase. A 2-kilobase AvaI restriction endonuclease digestion fragment of pSD075 known to carry the beta-lactamase determinant was used as a molecular probe. This probe did not recognize sequences of any plasmid-mediated beta-lactamase tested including the recently described determinants ROB-1, TLE-1, and OXA-4-7. A TEM-1 probe derived from the 0.7-kilobase PstI-EcoRI fragment of pBR322 failed to recognize the new beta-lactamase gene. Four additional Enterobacter cloacae and two Enterobacter aerogenes strains isolated in Columbus, Ohio, have been shown to produce a pI 7.0 beta-lactamase and to carry plasmids recognized by the 2-kilobase probe. These data suggest dissemination of a novel plasmid-mediated beta-lactamase among members of the family Enterobacteriaceae in Ohio and demonstrate the development and utility of a molecular probe for the new determinant. We suggest that the novel beta-lactamase be named OHIO-1.

DNA, Bacterial↗

PubMed1985

Gram-negative bacilli resistant to third-generation cephalosporins: beta-lactamase characterization and susceptibility to Sch 34343.

We studied 192 recent clinical isolates, comprising six species of Gram-negative bacilli resistant either to cefotaxime or latamoxef (Moxalactam), from several hospitals. All isolates were resistant to several other third-generation cephalosporins or a monobactam. Two to five types of chromosomal beta-lactamases, as defined by isoelectric focusing, were readily identified in each species. Isolates of Citrobacter, Enterobacter and Serratia produced higher levels of chromosomal beta-lactamase than corresponding cefotaxime-susceptible strains. In addition, 20 of 57 produced one or two plasmid-determined beta-lactamases, TEM-1, OXA-2, or a novel enzyme, OHIO-1. The penem and carbapenem antibiotics, Sch 34343 and imipenem, were more active than cefotaxime, ceftazidime, ceftriaxone, latamoxef and aztreonam against isolates of Acinetobacter, Citrobacter, Ent. aerogenes, Ent. cloacae and Morganella, whereas imipenem, ceftazidime, and aztreonam were more active against Serratia isolates. The addition of plasmid-determined beta-lactamase increased resistance to piperacillin, cefoperazone and cefamandole but not to cefotaxime, ceftazidime, ceftriaxone, latamoxef, aztreonam, Sch 34343, or imipenem. Of 24 strains susceptible to aminoglycosides, none produced a plasmid-determined beta-lactamase, whereas 20 were found among the 33 strains resistant to aminoglycosides. Resistance of clinical isolates to newer beta-lactams appears to be due primarily to a high level of chromosomal cephalosporinase present without inducing agents. The plasmid-determined beta-lactamases, TEM-1 and OHIO-1, contributed little to resistance to most of the newer beta-lactams but were strongly associated with aminoglycoside resistance in these selected isolates. The greater in-vitro efficacy of the penem and carbapenem antibiotics, Sch 34343 and imipenem, against most of these isolates makes them promising candidates as first line agents against these pathogens.

Acinetobacter↗

PubMed1974

[Not Available].

Explore the source record for details and available documents.

Disease↗

PubMedDate not supplied

Hormonal regulation of bicarbonate secretion in the biliary epithelium.

Bicarbonate excretion in bile is a major function of the biliary epithelium. It is driven by the apically located Cl-/HCO3- exchanger which is functionally coupled with a cAMP-dependent Cl- channel (CFTR). A number of hormones and/or neuropeptides with different mechanisms and at different intracellular levels regulate, in concert, the processes underlying bicarbonate excretion in the biliary epithelium. Secretin induces a bicarbonate rich choleresis by stimulating the activity of the Cl-/HCO3- exchanger by cAMP and protein kinase A mediated phosphorylation of CFTR regulatory domain. Protein phosphatase 1/2A are involved in the run-down of secretory stimulus after secretin removal. Acetylcholine potentiates secretin-choleresis by inducing a Ca(++)-calcineurin mediated "sensitization" of adenyl cyclase to secretin. Bombesin and vasoactive intestinal peptide also enhance the Cl-/HCO3- exchanger activity, but the intracellular signal transduction pathway has not yet been defined. Somatostatin and gastrin inhibit basal and/or secretin-stimulated bicarbonate excretion by down-regulating the secretin receptor and decreasing cAMP intracellular levels induced by secretin.

Adenylyl Cyclases↗