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PubMed1995

Alterations in diaphragm EMG activity during opiate-induced respiratory depression.

While opiate-induced increases in thoracic muscle tone may contribute to impaired ventilation during opiate anesthesia, the effects of high-dose opiates on diaphragm muscle activity have not been elucidated. The effects of the opiate agonist alfentanil (ALF, 500 micrograms/kg subcutaneously) on diaphragm (DIA) and intercostal (IC) electromyographic (EMG) activity in spontaneously ventilating adult rats were studied. EMG segments corresponding to inspiration and expiration were selected using an impedance plethysmographic respiratory waveform. Total EMG activity over a respiratory cycle was significantly greater in the DIA than in the IC. ALF produced a decrease in inspiratory and an increase in expiratory DIA EMG activity. These changes in diaphragm function following ALF were accompanied by significant respiratory depression. The effects of the alpha-2 agonist dexmedetomidine on ALF-induced changes in diaphragm and intercostal EMG activity were also examined. While dexmedetomidine alone had minimal effects on DIA activity, it significantly attenuated the ALF-induced increase in expiratory DIA EMG. The potential etiology and implications of these opiate-induced changes in diaphragm muscle function are discussed.

Alfentanil↗
PubMed1984

Chemical modification of cytoskeletal proteins of human blood platelets by diamide.

Incubation of human blood platelets with diamide (azo-dicarboxylic acid-bis-dimethylamide, DIA) influences the aggregation behaviour considerably. Depending on concentration and incubation time DIA induces a reversible aggregation or brings about complete inhibition. The effect is reversible and may be due to the regeneration of reduced glutathione (GSH) which will be oxidized to GSSG by DIA. DIA causes disulfide-linked polymer formation of certain cytoskeletal proteins. At least three polymer families (Pa, Pb, Pc) with different molecular weights are formed depending on dosage and incubation time of DIA. The appearance of a double band in Pa correlates with reversible aggregation, the formation of Pc is always accompanied by a complete inhibition of aggregation. A disturbance of cytoskeleton-membrane interaction by polymer formation can be assumed. GSH serves as a reductant of disulfide-linked polymers whereby a direct link between the maintenance of SH/SS status of platelets and GSH can be established.

Azo Compounds↗
PubMed1983

Size distribution and stability of the trans-membrane channels formed by complement complex C5b-9.

We have performed double marker sieving experiments with molecules ranging from ca. 0.5-3 nm dia. in order to evaluate the size distribution of the channels formed by complement in resealed sheep erythrocyte ghosts. Evidence is presented that marker release through the channels reached equilibrium between the ghosts and the extracellular fluid in a period of 3 hr and that the channels are stable at 37 degrees C for this period of time. Under these experimental conditions we have observed a differential in the endpoint release of inositol and sucrose, which indicates that some of the ghosts carried channels measuring between 0.7 and 0.9 nm dia. No differential was observed between release of sucrose and raffinose (0.9 and 1.1 nm mol. dia., respectively). Comparisons between sucrose and inulin (0.9 and 3 nm mol. dia, respectively) showed a difference in marker release. Also, there was substantial release of inulin, indicating the presence of channels above 3 nm in dia. Hence, the present data indicate formation of channels in three size ranges, namely, 0.7-0.9 nm, 0.9-3 nm and greater than 3 nm.

Animals↗
PubMed1995

Baroreflex function in streptozotocin (STZ) induced diabetic rats.

To determine whether the renal sympatho-inhibition and bradycardia in responses to acute increases in arterial pressure are altered in the diabetic state, the renal nerve discharge and heart rate were measured in streptozotocin (STZ) induced diabetic (DIA) rats. Integrated renal sympathetic nerve activity and heart rate were measured before and during an acute increase in blood pressure in anesthetized (Inactin 0.1 g/kg, i.p.) control (vehicle) and DIA rats (Sprague Dawley rats injected with STZ 65 mg/kg i.p.). Blood glucose levels were significantly elevated in the DIA group compared with the control group. Baroreflex changes in renal nerve activity and heart rate were not significantly different in the DIA rats compared with control rats at a time when the renal sympatho-inhibition in response to acute volume expansion was blunted in the diabetic rats. In addition, blocking the effect of elevated angiotensin II in diabetic rats with the converting enzyme inhibitor enalapril did not change the baroreflex function in DIA rats compared with control rats. However, administration of vasopressin failed to potentiate the baroreflex in diabetic rats as it did in normal control rats. This study demonstrates that (1) the baroreflex function is normal in STZ induced diabetic rats unlike the volume reflex during the early phase of the disease, (2) blockade of the AII system does not alter baroreflex function in diabetic rats and (3) vasopressin fails to potentiate the baroreflex in diabetic rats as it does in the euglycemic normal rats.

Analysis of Variance↗
PubMed1994

A multiple antigen detection dipstick colloidal dye immunoassay for the field diagnosis of trypanosome infections in cattle.

Monoclonal antibodies (McAbs) were developed against aspartate aminotransferase purified from Trypanosoma brucei rhodesiense bloodstream form (bf) soluble extracts using a combination of anion-exchange and hydrophobic interaction chromatography. McAb 1A1 was Trypanozoon and Nannomonas specific while 2F1 was Trypanozoon bloodstream form specific. A dipstick colloidal dye immunoassay (DIA) was employed as a field diagnostic test for African trypanosome infections and designed using affinity purified polyclonal antibodies (PcAbs) raised against T. b. rhodesiense bf and the two McAbs, 1A1 and 2F1. PcAbs were adsorbed onto Palanil Red dye particles and used as dye reagents. Dipsticks were dotted with the three different antibodies, which captured trypanosomal antigens in samples tested, while the dye reagent bound to the captured antigens; the presence of coloured dots on the dipstick identified trypanosome infections. A field trial of the DIA was carried out in southeastern Uganda. A total of 1686 cattle from seven areas were bled and tested by DIA and haematocrit centrifuge technique (HCT). A total of 798 cattle (47.3%) were found to be trypanosomal antigen positive by DIA while only 162 (9.6%) were revealed to harbour trypanosomes by HCT, of which 151 (93%) were also positive by DIA.

Animals↗
PubMed1990

Dot immunobinding assay in comparison with enzyme-linked immunosorbent assay for the detection of bluetongue virus antibodies in sheep.

A total of 384 sheep serum samples collected from two organised sheep farms was tested by dot immunobinding assay (DIA) and indirect enzyme-linked immunosorbent assay (I-ELISA) for the presence of bluetongue virus (BTV) antibodies. The results of both these assays were compared to find a sensitive, specific, rapid, easily performed and economical test for the diagnosis of bluetongue disease. DIA detected BTV antibodies in 210 samples (54.94%) and I-ELISA detected 157 positive samples (40.88%). Competitive ELISA (C-ELISA) was performed to check the discrepancies in I-ELISA and DIA. On the basis of these tests the overall agreement, relative specificity and sensitivity between ELISA and DIA were 75%, 87.6% and 100%, respectively. DIA was found to be a rapid, sensitive, easily performed and economical test as compared to ELISA.

Animals↗
PubMed2003

Adsorption and desorption of atrazine, desethylatrazine, deisopropylatrazine, and hydroxyatrazine in vegetated filter strip and cultivated soil.

Adsorption and desorption of atrazine and its metabolites in vegetated filter strip soil (VFS) has not been evaluated, yet these data are needed to predict the transport of these compounds through the VFS. Adsorption and desorption parameters for atrazine, desethylatrazine (DEA), deisopropylatrazine (DIA), and hydroxyatrazine (HA) were compared between a cultivated Houston Black clay (CS) and an adjacent 12-year-old VFS established in a mixed stand of bermudagrass [Cynodon dactylon (L.) Pers.] and buffalograss [Buchloe dactyloides (Nutt. Engelm)]. Adsorption and desorption isotherms were determined by batch equilibrium. The evaluated chemical and physical properties of the VFS and CS were similar with the exception of a 1.7-fold increase in the organic carbon content of the VFS. Adsorption and desorption coefficients for atrazine were at least 59% higher in VFS than in CS. The adsorption coefficient for HA was 48% higher in VFS compared with CS, but desorption was not statistically different between soils. Adsorption and desorption coefficients for DEA and DIA were not statistically different between soils. The predicted order of mobility in CS is HA < atrazine = DIA = DEA. In VFS, the predicted order of mobility is HA < atrazine = DIA < DEA. These data indicate that the higher organic carbon in VFS will likely retard the transport of atrazine and HA to surface and ground waters; however, the transport rates of DEA and DIA will be similar between soils.

Adsorption↗
PubMed2004

Influence of humic acid on adsorption and desorption of atrazine, hydroxyatrazine, deethylatrazine, and deisopropylatrazine onto a clay-rich soil sample.

Adsorption and desorption properties of atrazine and some of its metabolites, hydroxyatrazine (AT-OH), deethylatrazine (DEA), and deisopropylatrazine (DIA), were studied with a clay-rich soil sample (clay content of 53%). A part of this soil was treated with humic acid (Soil-HA) to assess the influence of this important component of natural organic matter on adsorption and desorption processes. This study was performed using the batch approach with 1.0 g of soil, or Soil-HA, in 5.0 mL of 0.010 mol L(-)(1) CaCl(2) solution containing the herbicide and the metabolites in a concentration range between 0.010 and 5.0 mg L(-)(1). After 24 h of contact time, the suspensions were centrifuged and the four compounds were quantified in the supernatant phases by high-performance liquid chromatography. The adsorption and desorption data of both Soil and Soil-HA were properly fitted by the linearized Freundlich equation. For the untreated soil, the adsorption affinity order evaluated as a function of the K(f) values was AT-OH > AT > DIA > DEA, while desorption followed the order DEA > DIA approximately AT > AT-OH. The presence of humic acid increased significantly the adsorption of all compounds, following the same affinity order observed for the untreated soil. Increase in adsorption was especially high for AT-OH and AT. On the other hand, the dealkylated metabolites, DEA and DIA, were more easily desorbed from the Soil-HA sample, suggesting that natural organic matter facilitates the leaching of these compounds. Desorption order in the presence of humic acid was DEA > DIA > AT > AT-OH.

Adsorption↗
PubMed1989

Change in specificity of glycosidase inhibition by N-alkylation of amino sugars.

The synthetic amino sugar 1,4-dideoxy-1,4-imino-L-allitol (DIA) is a moderately good inhibitor of human liver alpha-D-mannosidases and a weak inhibitor of alpha-L-fucosidase, N-acetyl-beta-D-hexosaminidase and beta-D-mannosidase. Methylation of the ring nitrogen of DIA markedly decreases the inhibition of all the glycosidases except N-acetyl-beta-D-hexosaminidase. N-Benzylation of DIA essentially abolishes all inhibitory activity, except towards alpha-L-fucosidase, which is more strongly inhibited than by either DIA or N-methyl-DIA. This is the first report of a change of specificity of inhibition of a glycosidase inhibitor by substitution of the ring nitrogen.

Benzyl Compounds↗
PubMed2002

Nonchemotherapy drug-induced agranulocytosis: experience of the Strasbourg teaching hospital (1985-2000) and review of the literature.

Agranulocytosis is a life-threatening disorder that frequently occurs as an adverse reaction to drugs. The overall incidence of nonchemotherapy drug-induced agranulocytosis (DIA) ranges from 2.6 to 10 cases per million patients exposed to drugs per year. Although patients experiencing DIA may initially be asymptomatic, the severity of the neutropenia usually leads to severe sepsis, requiring intravenous broad-spectrum antibiotic therapy. In this setting, old age, septicaemia, shock, and the metabolic complications of infection, such as renal failure, are poor prognostic variables. The severity of neutropenia (< 0.1 x 10(9))/l) and its duration (> 10 days) may also impact negatively on the outcome. With appropriate management using pre-established procedures, the mortality rate is now around 5%. Haematopoietic growth factors have been shown to shorten the duration of neutropenia in DIA. However, it has yet to be determined whether their use translates into a better outcome in DIA patients experiencing sepsis. DIA still remains a rare event. However, given the increased life expectancy and subsequent longer exposure to drugs, as well as the development of new agents, physicians should be aware of this complication and its management.

Aged↗
PubMed2006

Advanced cytologic techniques for the detection of malignant pancreatobiliary strictures.

BACKGROUND & AIMS: Two advanced cytologic techniques for detecting aneuploidy-digital image analysis (DIA) and fluorescence in situ hybridization (FISH)-have recently been developed to help identify malignant pancreatobiliary strictures. The aim of this study was to assess the clinical utility of cytology, DIA, and FISH for the identification of malignant pancreatobiliary strictures. METHODS: Brush cytologic specimens from 233 consecutive patients undergoing endoscopic retrograde cholangiopancreatography for pancreatobiliary strictures were examined by all 3 (cytology, DIA, and FISH) techniques. Strictures were stratified as proximal (n = 33) or distal (n = 114) based on whether they occurred above or below the cystic duct, respectively. Strictures in patients with primary sclerosing cholangitis (n = 86) were analyzed separately. RESULTS: Despite the stratification, the performances of the tests were similar. Conventional cytology has a low sensitivity (4%-20%) but 100% specificity. Because of the high specificity for cytology, we assessed the performance of the other tests when conventional cytology was negative. In this clinical context, FISH had an increased sensitivity (35%-60%) when assessing for chromosomal gains (polysomy) while preserving the specificity of cytology. The sensitivity and specificity of DIA was intermediate as compared with routine cytology and FISH but was additive to FISH values demonstrating only trisomy of chromosome 7 or chromosome 3. CONCLUSIONS: These findings suggest that FISH and DIA increase the sensitivity for the diagnosis of malignant pancreatobiliary tract strictures over that obtained by conventional cytology while maintaining an acceptable specificity.

Adolescent↗
PubMed2001

Calibration of the calcium dissociation constant of Rhod(2)in the perfused mouse heart using manganese quenching.

Both theoretical and experimental results are presented for in vivo calibration of the dissociation constant K(Ca)(d)of the calcium-sensitive fluorescent dye Rhod(2)in the perfused mouse heart, using manganese quenching of fluorescence transients. An analytical model is derived, based on the biochemical equilibrium of manganese competition with calcium for Rhod(2)binding. Expressing the differential of the changes between systole and diastole in fluorescence transient (delta Delta F(sys-dia)). delta DeltaF(sys-dia)in a beating heart as a function of the perfusate manganese concentration [Mn(2+)](p)allows correlation of the measured differential transient changes delta Delta F(sys-dia)with the calcium dissociation constant K(Ca)(d)of Rhod(2)and the calcium concentration in the heart. Numerical modeling indicates that the K(Ca)(d)predominantly affects the asymptotic slope of the delta Delta F(sys-dia)versus [Mn(2+)](p)curve at certain manganese concentrations, which suggests that the K(Ca)(d)can be inversely calculated by partially fitting the delta Delta F(sys-dia)distribution as a function of the perfusate manganese concentration. The feasibility of this approach is confirmed by quenching of calcium transients by manganese infusion into isolated perfused beating mouse hearts. The resulting calculated dissociation constant K(Ca)(d)of Rhod(2)is 720nM. Using the same approach, we are able to also estimate intracellular calcium concentrations of 700nM at peak systole and 300nM in diastole. This is in good agreement with values obtained by calibration of fluorescence values with a calcium saturation tetanization procedure in the same perfused mouse heart model.

Animals↗
PubMed2001

Diaphragm movement before and after cholecystectomy: a sonographic study.

UNLABELLED: Respiratory disorders after abdominal surgery are commonly explained by changes in diaphragmatic movement that are difficult to demonstrate and quantify. Our aim was thus to quantify these changes using a noninvasive method. We used M-mode sonography for the prospective study to measure diaphragmatic amplitude in 14 patients before and after cholecystectomy. During quiet breathing, the diaphragm inspiratory amplitude (DIA) was significantly decreased after surgery from 1.4 +/- 0.2 cm to 1 +/- 0.1 cm and from 1.6 +/- 0.3 cm to 1.2 +/- 0.3 cm in the Laparoscopic and Open Cholecystectomy groups, respectively. The total time cycle of diaphragmatic motion decreased significantly in the two groups. The DIA also decreased significantly during deep breathing after cholecystectomy from 6.0 +/- 0.8 cm to 3.0 +/- 1.8 cm and from 6.1 +/- 1.3 cm to 3.1 +/- 1.6 cm in the Laparoscopic and Open Cholecystectomy groups, respectively. The six patients who underwent spirometric examination showed, during quiet breathing, a significant decrease in DIA without change in tidal volume, i.e., 0.51 +/- 0.08 L to 0.45 +/- 0.08 L. We found a significant decrease in DIA after cholecystectomy and a significant interindividual correlation between DIA during deep inspiration and inspiratory capacity. Using M-mode sonography techniques, we were able to demonstrate changes in diaphragmatic mobility after laparoscopic or open cholecystectomy. IMPLICATIONS: Cholecystectomy at times results in impaired respiratory and diaphragmatic functions. The techniques currently used to study these repercussions are both laborious and invasive. Our sonographic technique is completely noninvasive and can be used to study diaphragm morphology and movement in real time.

Adult↗
PubMed2025

Carafe enables high quality in silico spectral library generation for data-independent acquisition proteomics.

Data-independent acquisition (DIA)-based mass spectrometry is becoming an increasingly popular mass spectrometry acquisition strategy for carrying out quantitative proteomics experiments. Most of the popular DIA search engines make use of in silico generated spectral libraries. However, the generation of high-quality spectral libraries for DIA data analysis remains a challenge, particularly because most such libraries are generated directly from data-dependent acquisition (DDA) data or are from in silico prediction using models trained on DDA data. In this study, we developed Carafe, a tool that generates high-quality experiment-specific in silico spectral libraries by training deep learning models directly on DIA data. We demonstrate the performance of Carafe on a wide range of DIA datasets, where we observe improved fragment ion intensity prediction and peptide detection relative to existing pretrained DDA models. To make Carafe more accessible to the community, we have integrated Carafe into the widely used Skyline tool.

Journal Article↗
PubMed2000

Improved patient acceptability with a transdermal drug-in-adhesive oestradiol patch.

The aim of this trial was to assess the relative patient acceptability of two transdermal oestradiol patches used in treatment of oestrogen deficiency in postmenopausal women. Thirty-five hysterectomised postmenopausal women with no previous experience of transdermal oestradiol delivery systems received treatment with either once-weekly drug-in-adhesive (DIA) patches or twice-weekly reservoir patches for 4 weeks, and were then switched to the alternative treatment for a further 4 weeks. At the end of the study, the patients completed a questionnaire to assess their relative preference for a number of characteristics of the 2 transdermal systems and, where possible, their preference for transdermal compared with oral hormone replacement therapy. Thirty-one patients completed the study; four withdrew during treatment with the reservoir patch. The DIA patch was preferred for being 'easiest to remember to apply' by 80% of patients (p < 0.01), 'easiest to open' and 'easiest to apply' by 68% (p = 0.025), and as having 'best cosmetic appearance' by 65% (p = 0.05) and 'best overall skin adhesion' by 61% (p < 0.01). While 10% of patients rated the reservoir patch as 'least irritating to the skin' (p = 0.03), only one patient found this patch 'most comfortable to wear' (p < 0.01). The DIA patch was selected by 87% of patients as their preferred treatment overall (p = 0.001). Ninety-one per cent of 22 responding patients were at least as confident of treatment with transdermal patches as with oral hormone replacement therapy (p = 0.006) and 74 % of 27 responders preferred transdermal to oral treatment (p = 0.004). The DIA patch appears to be more acceptable to patients than the reservoir patch as a transdermal oestradiol delivery system for the treatment of postmenopausal oestrogen deficiency. Characteristics of the DIA patch which may account for improved patient acceptance include ease of remembering once-weekly patch application, improved cosmetic appearance and comfort, and better adhesion.

Administration, Cutaneous↗
PubMed1989

Histochemical characteristics of human expiratory and inspiratory intercostal muscles.

The relative occurrence of slow-twitch (ST) and fast-twitch (FTa and FTb) fibers, fiber size, and capillary supply in internal (INT) and external intercostal muscles (EXT), the costal diaphragm (DIA), and vastus lateralis muscle (VAS) was examined post-mortem in eight healthy males. The relative occurrence of ST fibers in INT [64 +/- 3% (SE)] and EXT (62 +/- 3%) was similar but higher than in DIA (49 +/- 3%) and VAS (40 +/- 6%; P less than 0.05). The occurrence of FTa fibers in expiratory INT (35 +/- 3%) was higher than in inspiratory INT and EXT (17 +/- 1%; P less than 0.05) but similar to DIA (28 +/- 6%) and VAS (32 +/- 2%). Accordingly, expiratory INT had fewer FTb fibers (1 +/- 1%) than the others (P less than 0.05). Expiratory INT had a 60% larger fiber area than inspiratory INT and EXT and DIA (P less than 0.05), but the area was similar to that of VAS. The number of capillaries per fiber was higher in expiratory INT (2.3 +/- 0.1) than in inspiratory INT and EXT (1.6 +/- 0.1), DIA (1.9 +/- 0.1), and VAS (1.8 +/- 0.2; P less than 0.05). The results suggest that the occurrence of many large capillary-rich FTa fibers in expiratory INT is bound to function (expiratory vs. inspiratory) rather than to anatomy (INT vs. EXT).

Adenosine Triphosphatases↗
PubMed1990

Upper airway muscle and diaphragm responses to hypoxia in the piglet.

The neonatal ventilatory response to hypoxia is characterized by initial transient stimulation and subsequent respiratory depression. It is unknown, however, whether this response is also exhibited by the upper airway muscles that regulate nasal, laryngeal, and pharyngeal patency. We therefore compared electromyogram (EMG) amplitudes and minute EMGs for the diaphragm (DIA), alae nasi (AN), posterior cricoarytenoid (PCA), and genioglossus (GG) muscles in 12 anesthetized spontaneously breathing piglets during inhalation of 12% O2 over 10 min. Minute EMG for the DIA responded to hypoxia with an initial transient increase and subsequent return to prehypoxia levels by 10 min. Hypoxia also stimulated all three upper airway muscles. In contrast to the DIA EMG, however, AN, PCA, and GG EMGs all remained significantly above prehypoxia levels after 10 min of hypoxia. We have thus demonstrated that the initial stimulation and subsequent depression of the DIA EMG after 12% O2 inhalation contrast with the sustained increase in AN, PCA, and GG EMGs during hypoxia. We speculate that 1) central inhibition during neonatal hypoxia is primarily distributed to the motoneuron pools regulating DIA activation and 2) peripheral chemoreceptor stimulation and/or central disinhibition induced by hypoxia preferentially influence those motoneuron pools that regulate upper airway muscle activation, causing the different hypoxic responses of these muscle groups in the young piglet.

Animals↗
PubMed1994

Mechano- and chemoreceptor modulation of respiratory muscles in response to upper airway negative pressure.

To investigate the influence of phasic pulmonary stretch receptors (n = 6) and chemoreceptors (n = 7) on the reflex response of the genioglossus (GG) muscle and diaphragm (DIA) to upper airway (UAW) negative pressure, we measured the response of the GG and DIA electromyogram (EMG) to three challenges: 1) negative pressure applied to the UAW during normoxia and hypercapnia, 2) end-expiratory tracheal occlusion, and 3) application of UAW negative pressure simultaneous with tracheal occlusion in spontaneously breathing tracheotomized anesthetized cats. Peak GG EMG was greatest when UAW negative pressure and end-expiratory tracheal occlusion were combined. No GG EMG activity was seen when UAW negative pressure was applied alone unless the animal was vagotomized or hypercapnic. DIA EMG increased in response to UAW negative pressure combined with occlusion. However, the increase in peak GG EMG was significantly greater than for the DIA with the same challenge. DIA EMG amplitude increased in response to occlusion alone but did not change when UAW negative pressure was applied alone. In the cat, phasic feedback from phasic pulmonary stretch receptors is a potent inhibitor of reflex activation of the GG in response to negative pressure applied to the UAW, which can be overridden by an increase in chemoreceptor drive.

Animals↗