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At least 127 records · Page 7Linked to original sources

Fetal maturity cascade: a rapid and cost-effective method for fetal lung maturity testing.

One hundred ninety-three amniotic fluid samples were tested for fetal lung maturity using a maturity cascade scheme involving the sequential use of, in order, the shake test, fluorescence polarimetry, and lecithin: sphingomyelin (L:S) ratio. If any of these tests indicated maturity, the sequence was terminated and no further test was performed, and the fetus was considered mature. Seventy percent of the tests yielded mature values and of these, 85 (63%) required a shake test only, 37 (27%) had a shake test and a fluorescence polarimetry, and only 14 (10%) required all three tests. From these 193 amniocenteses, 111 patients delivered within 72 hours of the procedure. One of 94 infants had respiratory distress syndrome after a mature test (1% false maturity) and ten of 17 had respiratory distress syndrome after an immature cascade (41% falsely immature). This approach saves time and cost and by confirming immaturity with multiple tests only when necessary and may improve predictability of neonatal respiratory distress syndrome.

Amniocentesis↗

Screening for coronary artery disease in assymptomatic adults is not recommended, so why is it still done?

The rationale behind screening for asymptomatic coronary artery disease is that it may diagnose advanced disease that, while frequently without symptoms, may present for the first time as sudden death. Identifying significant coronary artery disease would enable intervention against risk factors and, if necessary, preventive revascularization. The most recent evidence shows that screening for coronary artery disease with resting electrocardiogram, exercise tolerance testing or electron-beam computerized tomography in low-risk patients does more harm than good, and should not be performed. This negative recommendation is based on the fact that the use of the aforementioned tests has a negative benefit-harm ratio, because the false-positive rate cancels out any benefit from the occasional detection of real disease, inducing a cascade of further testing (sometimes with angiography) and overdiagnosis of a disease that is not in fact present, with negative psychological and financial consequences, such as increased insurance premiums. We feel that the Portuguese Society of Cardiology should intervene with the institutions performing screening of coronary heart disease in asymptomatic patients, and recommend abandoning a practice that is of little use and, overall, harmful.

Adult↗

Methylprednisolone in high doses gives different effects on the early and the late part of complement.

The effects of methylprednisolone (MP) on endotoxin-induced activation of complement were studied in citrated pool plasma. Complement activation was tested in two immunoassays: one evaluating C3 activation fragments (C3act) and the other the terminal complement complex (TCC). These components are indicators of initial and terminal complement activation, respectively. Plasma samples were obtained at 1, 2, 4 and 6 h of incubation. Plasma containing endotoxin (2.10(9) ng/l) without MP revealed a marked increase of both C3act and TCC after 1 h. MP in high doses (10 mg/ml) gave an additive effect on activation of the initial part of the complement cascade compared to test plasma containing only endotoxin. In contrast, endotoxin-induced activation of the terminal part of the complement cascade was inhibited by the same dose of MP. The influence of lower doses of MP (0.1 and 1 mg/ml) on endotoxin-induced activation of complement was insignificant. Interestingly, MP without endotoxin induced activation of the initial part of complement. In test plasmas containing 5 and 10 mg/ml of MP (without endotoxin) marked increases of C3act values were seen. Despite this obvious activation of the early part of complement, only insignificant changes were found in TCC values. Test plasmas containing 0.1 and 1 mg/ml of MP revealed only minor changes in both C3act and TCC. In conclusion, the present study shows that high doses of MP activate the initial part of complement and that the endotoxin-induced activation of this cascade system was facilitated by MP. The terminal part of complement was, on the other hand, inhibited by high doses of MP.

Complement Activation↗

Is fluorescence polarization reliable and cost efficient in a fetal lung maturity cascade?

OBJECTIVE: The objective of the study was to compare the accuracy of the TDxFLM test (Abbott Laboratories) with the fetal lung maturity cascade (shake, foam stability index, lecithin/sphingomyelin tests) and to determine whether the TDxFLM test could increase the efficiency and reduce the cost without decreasing the reliability of a cascade. STUDY DESIGN: A prospective, single-blinded study was conducted. Uncontaminated amniotic fluid obtained by transabdominal amniocentesis for fetal lung maturity assessment was evaluated with use of the fetal lung maturity cascade and the TDxFLM test. At study completion the results of the TDxFLM test were compared with those of the maturity cascade with regard to hyaline membrane disease, which was defined by strict clinical and radiographic parameters. A power analysis was performed requiring a sample size of 100 infants delivered within 72 hours of amniocentesis with use of the 95% confidence interval. RESULTS: A total of 115 cases had a full maturity cascade performed, of which 40 (35%) had a positive shake or foam stability index and 75 cases required progression to a lecithin/sphingomyelin ratio because of negative results. The TDxFLM test result was > or = 70 mg/gm in 42 (37%) of these 115. One hundred eight newborns were delivered within 72 hours of the amniocentesis; 65% (71) of these were between 30 and 37 weeks of estimated gestational age. There were 7 cases of hyaline membrane disease in the 108 newborns. Of these 108, 87 had a mature original cascade versus 85 mature tests with use of a proposed TDxFLM test-lecithin/sphingomyelin ratio cascade with one case of respiratory distress syndrome and hyaline membrane disease. The sensitivity, specificity, and positive and negative predictive values for the original cascade were 86%, 84%, 27%, and 99%, respectively; for the proposed TDxFLM test-lecithin/sphingomyelin ratio cascade the values were 86%, 83%, 26%, and 99%, respectively. The TDxFLM test-lecithin/sphingomyelin ratio cascade would have resulted in a cost reduction of 24% with no significant delay in turnaround time. CONCLUSION: The TDxFLM test appears to be a reliable and accurate assessment of fetal lung maturity. Furthermore, by replacing the shake and foam stability index portion of the cascade with the TDxFLM test, a cost savings of 24% would occur without a decrease in safety. These results also reveal that it could enhance patient care and be cost efficient for institutions not currently doing fetal pulmonary maturity testing to undertake use of the TDxFLM test and to only send out specimens for a lecithin/sphingomyelin ratio that have an initial immature TDxFLM test result (< 70 mg/gm). Likewise, institutions currently only performing a lecithin/sphingomyelin ratio may consider a TDxFLM test-lecithin sphingomyelin ratio cascade. Although direct costs would increase, they would be counterbalanced by a significant reduction in laboratory technician time.

Amniocentesis↗

Thromboelastography in abruptio placentae.

The purpose of this study was to document thromboelastographic (TEG) changes in abruptio placentae and to compare these results with that of conventional tests used to monitor coagulation. This was a prospective study of 30 patients with abruptio placentae. All coagulation investigations including the TEG were performed on admission, immediately following delivery, and after periods of 4 hours and 24 hours. Results showed that standard coagulation tests detected coagulation abnormalities except the platelet count returned to normal limits within 24 hours of delivery. There was strong correlation between fibrinogen levels and the TEG parameters, ma and k time (r=0.8). There was moderate correlation between platelet count and ma (r=0.6). In conclusion, minor abnormalities in the clotting profile are clinically unimportant. The TEG does not detect such minor abnormalities because of its inherent ability to test the coagulation cascade as a whole. Major abnormalities are clinically relevant and the TEG detect 75% of them. Further, the TEG establishes the diagnosis of hypercoagulability an early sign of disseminated intravascular coagulation. Although standard laboratory tests are still necessary to detect coagulation abnormalities on admission, the TEG is a useful test in large obstetric units where laboratory results are not immediately available for the purposes of monitoring and treating ongoing coagulation defects.

Journal Article↗

Neural interactions between cone photoreceptors and horizontal cells in the turtle (Mauremys caspica) retina.

Horizontal cells and cone photoreceptors in the vertebrate retina are interconnected by a complex network of synapses leading to the generation of color-coded responses in chromaticity horizontal cells. A simple cascade model of excitatory feedforward and inhibitory feedback synapses had been suggested to underlie these observations. In this study, the photoresponses of cones and horizontal cells were recorded intracellularly from the turtle eyecup. Three different approaches were adopted in order to test quantitatively the cascade model. Comparing linearity functions between these neurons indicated multiple excitatory inputs to each type of horizontal cells. The depolarizing photoresponses of R/G C-type horizontal cells were considerably faster than those of L-type horizontal cells but slower than those recorded from L-cones. This observation disagrees with the basic assumption of the cascade model that assign the depolarizing photoresponses of R/G C-type horizontal cells to a negative feedback pathway from L-type horizontal cells onto M-cones. Finally, the action spectra of each of the three types of horizontal cells could not be solely accounted for by input from one spectral type of cones. Only by assuming excitatory and inhibitory inputs from all spectral types of cones, the action spectra of all types of horizontal cells could be reconstructed. These findings suggest that the negative feedback pathways from horizontal cells onto cones in the turtle retina cannot solely account for the chromatic properties of the horizontal cells and support a direct inhibitory inputs from cones to turtle horizontal cells.

Animals↗

Amyloid-induced neurofibrillary tangle formation in Alzheimer's disease: insight from transgenic mouse and tissue-culture models.

Of all forms of dementia, Alzheimer's disease is the most prevalent. It is histopathologically characterized by beta-amyloid-containing plaques, tau-containing neurofibrillary tangles, reduced synaptic density and neuronal loss in selected brain areas. For the rare familial forms of Alzheimer's disease, pathogenic mutations have been identified in both the gene encoding the precursor of the Abeta peptide, APP, itself and in the presenilin genes which encode part of the APP-protease complex. For the more frequent sporadic forms of Alzheimer's disease, the pathogenic trigger has not been unambiguously identified. Whether Abeta is again the main cause remains to be heavily discussed. In a related disorder termed frontotemporal dementia, which is characterized by tangles in the absence of beta-amyloid deposition, mutations have been identified in tau which also lead to neurodegeneration and dementia. For Alzheimer's disease the existence of familial forms lead to the proposition of the amyloid cascade hypothesis, which claims that beta-amyloid causes or enhances the tangle pathology. In this review, we describe tau transgenic mouse models in which aspects of the tau-associated pathology, including tangle formation, has been achieved. Moreover, tau transgenic mouse and tissue-culture models were used to test the amyloid cascade hypothesis. In addition, we discuss alternative hypotheses to explain the sporadic forms. The animal and tissue-culture models will provide insight into the underlying biochemical mechanisms of tau aggregation and nerve cell degeneration. These mechanisms may be partially shared between sporadic Alzheimer's disease, the familial forms and frontotemporal dementia. Eventually, Alzheimer's disease may be redefined based on biochemical events rather than phenotype.

Alzheimer Disease↗

Rethinking the coagulation cascade.

The concept of coagulation as a "cascade" of proteolytic reactions was a conceptual breakthrough in understanding how the coagulation process acts as a biologic amplifier. The model that it evolved into, with "extrinsic" and "intrinsic" pathways meeting in a common pathway, delineates the interactions between the coagulation proteins and provides a framework for interpreting the common screening coagulation tests. The coagulation "cascade" has significant limitations as a model of how hemostasis occurs in vivo, however. This article describes how the modern view of hemostasis has evolved to emphasize the role of cells in controlling and directing the coagulation reactions. It also highlights how host factors that are not part of the coagulation process per se can influence the effectiveness of coagulation.

Blood Coagulation↗

Ex-vivo in-vitro inhibition of lipopolysaccharide stimulated tumor necrosis factor-alpha and interleukin-1 beta secretion in human whole blood by extractum urticae dioicae foliorum.

An extract of Urtica dioica folium (IDS 23, Rheuma-Hek), monographed positively for adjuvant therapy of rheumatic diseases and with known effects in partial inhibition of prostaglandin and leukotriene synthesis in vitro, was investigated with respect to effects of the extract on the lipopolysaccharide (LPS) stimulated secretion of proinflammatory cytokines in human whole blood of healthy volunteers. In the assay system used, LPS stimulated human whole blood showed a straight increase of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) secretion reaching maximum concentrations within 24 h following a plateau and slight decrease up to 65 h, respectively. The concentrations of these cytokines was strongly positively correlated with the number of monocytes/macrophages of each volunteer. TNF-alpha and IL-1 beta concentration after LPS stimulation was significantly reduced by simultaneously given IDS 23 in a strictly dose dependent manner. At time 24 h these cytokine concentrations were reduced by 50.8% and 99.7%, respectively, using the highest test IDS 23 assay concentration of 5 mg/ml (p < 0.001). After 65 h the corresponding inhibition was 38.9% and 99.9%, respectively (p < 0.001). On the other hand IDS 23 showed no inhibition but stimulated IL-6 secretion in absence of LPS alone. Simultaneously given LPS and IDS 23 resulted in no further increase. In contrast to described effects on arachidonic acid cascade in vitro, tested Urtica dioica phenol carbon acid derivates and flavonoides such as caffeic malic acid, caffeic acid, chlorogenic acid, quercetin and rutin did not influence LPS stimulated TNF-alpha, IL-1 beta and IL-6 secretion in tested concentrations up to 5 x 10(-5) mol/l. These further findings on the pharmacological mechanism of action of Urticae dioica folia may explain the positive effects of this extract in the treatment of rheumatic diseases.

Adult↗

Next generation pharmaceutical impactor (a new impactor for pharmaceutical inhaler testing). Part I: Design.

A new cascade impactor has been designed specifically for pharmaceutical inhaler testing. This impactor, called the Next Generation Pharmaceutical Impactor (NGI), has seven stages and is intended to operate at any inlet flow rate between 30 and 100 L/min. It spans a cut size (D50) range from 0.54-microm to 11.7-microm aerodynamic diameter at 30 L/min and 0.24 microm to 6.12 microm at 100 L/min. The aerodynamics of the impactor follow established scientific principles, giving confident particle size fractionation behavior over the design flow range. The NGI has several features to enhance its utility for inhaler testing. One such feature is that particles are deposited on collection cups that are held in a tray. This tray is removed from the impactor as a single unit, facilitating quick sample turn-around times if multiple trays are used. For accomplishing drug recovery, the user can add up to approximately 40 mL of an appropriate solvent directly to the cups. Another unique feature is a micro-orifice collector (MOC) that captures in a collection cup extremely small particles normally collected on the final filter in other impactors. The particles captured in the MOC cup can be analyzed in the same manner as the particles collected in the other impactor stage cups. The user-friendly features and the aerodynamic design principles together provide an impactor well suited to the needs of the inhaler testing community.

Administration, Inhalation↗

A branch in the ToxR regulatory cascade of Vibrio cholerae revealed by characterization of toxT mutant strains.

Co-ordinate expression of genes associated with pathogenicity in Vibrio cholerae requires two transcription activators, ToxR and ToxT. Work carried out to date suggests that ToxR activates transcription of the toxT gene and that ToxT directly activates transcription of several genes whose products play a role in colonization or CT production by V. cholerae. Previous work also suggests that ToxR can directly activate transcription of the CT operon (ctxAB) independently of ToxT, thereby implying a degree of complexity in control of the cixAB operon not found with other genes of the ToxR regulon. We tested the regulatory cascade model of virulence gene expression by constructing strains of classical and El Tor V. cholerae deleted for the coding sequence for the putative DNA-binding domain of toxT. Phenotypic analysis of these strains suggests that V. cholerae has ToxT-dependent and ToxT-independent branches of its virulence regulon. The results also raise questions about the precise role for ToxR in activation of ctxAB transcription.

Adhesins, Bacterial↗

Personal air samplers for measuring occupational exposures to biological hazards.

Microbiological air samplers, designed to be worn as personal samplers, were evaluated for studying occupational exposures to aerosols of infectious and allergenic materials. Gelatin filter media, an impinger sampler, and spiral and cascade impactors were tested for collection efficiency for small (less than or equal to 2 microns) latex spheres and for recovery of bacterial aerosols. Only 20% of an aerosol of 0.8 micron latex particles passed through the impinger uncollected, while recovery of bacteria equalled or exceeded collection in an all-glass impinger. Gelatin filters matched the collection efficiency of membrane filters, but were unsatisfactory for the isolation of bacteria sensitive to dehydration. The spiral sampler and the cascade impactor provide information on the size distribution of collected particles, although, at present, collection efficiencies for very small particles are too low for rigorously quantitative studies. Methods of collection, and sampling strategies for biological aerosols are similar to those used for measuring exposures of workers to chemical and mineral aerosols; however, preparation of samples and identification of isolates may have to be referred to experts in the fields of bacteriology, virology, and mycology.

Aerosols↗

Inhibition by thiamine tetrahydrofurfuryl disulfide (TTFD) of the arachidonic acid cascade-line activation as evidenced in the heart-lung preparation of the dog.

The effects of thiamine tetrahydrofurfuryl disulfide (TTFD) on the gradual increase in the coronary blood flow (CBF) inherent in the canine heart-lung preparation were studied. TTFD is a disulfide-type derivative of thiamine reported to have an antiinflammatory effect in experimental animals. Since it was found that the substance could reverse the gradual increase in CBF, the possibility that the reversal was brought about through an inhibition of activation of the arachidonic acid cascade-line was tested, examining the effects of this substance on the CBF increase produced by arachidonic acid (AA) and prostacyclin (PGI2). The vasodilator response to AA, which was barely detectable at the start of the experiment at which CBF was at a physiological low level, became potentiated as the gradual increase in CBF occurred, returning to the initial magnitude after TTFD, while the vasodilator response to PGI2 remained essentially unchanged during the entire course of the experiment. It was concluded that TTFD reversed the gradual increase in CBF in the HLP through the inhibition of the arachidonic acid cascade-line activation.

Animals↗

Induction of the primary dorsalizing center in Xenopus by the Wnt/GSK/beta-catenin signaling pathway, but not by Vg1, Activin or Noggin.

The molecular nature of the primary dorsalizing inducing event in Xenopus is controversial and several secreted factors have been proposed as potential candidates: Wnts, Vg1, Activin and Noggin. Recent studies, however, have provided new insight into the activity of the dorsalizing region, called the Nieuwkoop Center. (1) The activity of this dorsalizing center involves an entire signal transduction pathway that requires maternal beta-catenin (Heasman, J., Crawford, A., Goldstone, K., Garner-Hamrick, P., Gumbiner, B., McCrea, P., Kintner, C., Noro, C. Y. and Wylie, C. (1994) Cell 79, 791-803). (2) A transcription factor with potent dorsalizing activity, Siamois, is expressed within the Nieuwkoop Center (Lemaire, P., Garrett, N. and Gurdon, J. B. (1995) Cell 81, 85-94). We have used these two properties of the Nieuwkoop Center to evaluate the dorsalizing activity of the four secreted factors Wnt8, Vg1, Activin and Noggin. The requirement for beta-catenin was tested by coexpressing a cadherin, which sequesters beta-catenin at the cell membrane and specifically blocks its intracellular signaling activity (Fagotto, F., Funayama, N., Gluck, U. and Gumbiner, B. M. (1996) J. Cell Biol. 132, 1105-1114). Induction of Siamois expression was detected by RT-PCR. Of the four growth factors, only Wnt was sensitive to inhibition of beta-catenin activity and only Wnt could induce Siamois expression. Therefore, Wnt is able to induce a bonafide Nieuwkoop Center, while Vg1, Activin and Noggin probably induce dorsal structures by a different mechanism. To order the steps in the Nieuwkoop Center signaling cascade, we have tested the relationship between beta-catenin and GSK, a serine-threonine kinase that has been implicated in axis formation in a step downstream of Wnt. We found that GSK acts upstream of beta-catenin, similar to the order of these components in the Wingless pathway in Drosophila. We have also examined the relationship between the Wnt/beta-catenin pathway and Siamois. We show that beta-catenin induces expression of Siamois and that the free signaling pool of beta-catenin is required for normal expression of endogenous Siamois. We conclude that the sequence of steps in the signaling pathway is Wnt-->GSK-->beta-catenin-->Siamois.

Activins↗

[Cognitive impairment and cardiovascular disease risk factors. Project CASCADE Kraków. III. Assessment of cognitive function in elderly women and men (65-78 years old)].

There are commonly used simple tests for cognitive function that allow for rather superficial assessment in population based study. The goal of the paper was to present the results of cognitive function assessment in elderly men and women recruited from Polish rural population obtained using the battery of tests designed for the CASCADE Project and to assess the relations between the results of tests included in the battery. Studied group were 182 persons at the age of 65-78 years. The battery of tests included: MMSE, Stroop Test, Test Purdue Pegboard (TPP), letter-digit substitution test, word recall test (3 word lists including one with distraction), word fluency test and prospective memory test. The battery allowed for the assessment of short, semantic and prospective memory, attention, speed of perception and processing, word fluency and motoric function. The results of all tests were strongly correlated and indicated for a decreased cognitive function in men and women at the age of 65-78 years with low level of education. Decreased level of cognitive function could be related both to physiological ageing of the brain and to the presence of pathological process.

Aged↗

Selenazoles (selenium compounds) facilitate survival of cultured rat pheochromocytoma PC12 cells after serum-deprivation and stimulate their neuronal differentiation via activation of Akt and mitogen-activated protein kinase, respectively.

The activation of extracellular receptor kinase (ERK) is one of the checkpoints to assess the activation of the classical Ras/mitogen-activated protein kinase (MAPK) cascade. Therefore, we tested more than 100 selenium-containing compounds for their ability to activate the MAPK signal pathway. Among them, we found that three selenazoles, 5-chloroacetyl-2-piperidino-1,3-selenazole (CS1), 5-chloroacetyl-2-morpholino-1,3-selenazole (CS2), and 5-chloroacetyl-2-dimethylamino-1,3-selenazole (CS3), induced the phosphorylation of ERK. These compounds also enhanced the phosphorylation of Akt, a signal transducing protein kinase for cell survival; and this phosphorylation was followed by suppression of cell death, thus suggesting that they had anti-apoptotic effects. Moreover, CSs 1-3 induced neurite outgrowth and facilitated the expression of neurofilament-M of PC12 cells, demonstrating that they induced neuronal differentiation of these cells. On the other hand, the CS-induced phosphorylation of MAPK was enhanced by buthionine sulfoximine (BSO), an activator of protein tyrosine phosphatases (PTPs), but inhibited by N-acetyl-l-cysteine (NAC), an inhibitor of receptor tyrosine kinase. These results imply that activation of some receptor tyrosine kinase(s) is involved in the mechanism of action of CSs 1-3. The activation of MAPK by CSs 1-3 was suppressed by U0126, a MEK inhibitor, but not by K252a, an inhibitor of TrkA; AG1478, an antagonist of epidermal growth factor receptor (EGFR); or by pertussis toxin. These results demonstrate that the CS-induced phosphorylation of Akt and MAP kinase (receptor tyrosine kinase(s)-MEK1/2-ERK1/2) cascades was responsible for suppression of apoptosis and facilitation of neuronal differentiation of PC12 cells, respectively. Our results suggest that CSs 1-3 are promising candidates as neuroprotective and/or neurotrophic agents for the treatment of various neurodegenerative neurological disorders.

Animals↗

The 14CO2 breath test: facilities and limitations of a rapid and noninvasive method for in vivo evaluation of modified hepatic cytochrome P-450--a critique.

By means of the breath test technique the cascade from O-demethylations to CO2 was investigated after pretreatment of mice with warfarin, phenobarbital, cobaltous chloride, sodium vanadate and metyrapone. It was the intention to examine the validity of the technique with respect to cytochrome P-450 activity. Therefore three different radioactive labeled substrates, i.e., hydrogen carbonate, formate and xenobiotics, were applied at three different levels of the one-carbon pathway and were utilized to demonstrate possible interference of the modifiers with the sequence from O-demethylation to CO2. Real in vivo information about a modified cytochrome P-450 system can be obtained using model substrates carefully selected with regard to the type of expected modification of the monooxygenase system. In addition, a parallel monitoring of the consecutive reaction sequence by measuring the conversion of formate to CO2 is necessary in order to guarantee the validity of the in vivo technique in visualizing the activity of the hepatic monooxygenase system.

Animals↗

Inhibition of Fas-induced apoptotic cell death by osmotic cell shrinkage.

Apoptosis is an active physiological mechanism permitting the elimination of cells by triggering an intracellular signalling cascade. Here, we tested whether osmotic alterations of cell volume interfere with apoptotic cell death in Jurkat T-lymphocytes. Apoptotic cell death of Jurkat cells was elicited by activation of the Fas receptor which results in sphingomyelinase stimulation, release of ceramide, activation of Ras, Rac-proteins and formation of O2. Osmotic cell shrinkage inhibited apoptotic cell death induced by the Fas receptor in Jurkat T-lymphocytes. Osmotic cell shrinkage did not interfere with Fas induced activation of the acidic sphingomyelinase or activation of Ras but impaired the formation of O2 suggesting an important function of cell volume in the synthesis of reactive oxygen intermediates upon Fas receptor ligation.

Apoptosis↗