Effects of verapamil on in vitro intracellular accumulation and retention of daunorubicin in blast cells from patients with acute nonlymphocytic leukemia

Blood ◽  
1986 ◽  
Vol 68 (1) ◽  
pp. 83-88 ◽  
Author(s):  
DD Ross ◽  
CC Joneckis ◽  
CA Schiffer
Keyword(s):  
T Test ◽  
Acute Nonlymphocytic Leukemia ◽  
Free Medium ◽  
Intracellular Accumulation ◽  
Time Curve ◽  
Population Mean ◽  
Small Increment ◽  
Blast Cells ◽  
Paired T Test

Abstract The effects of verapamil on the intracellular pharmacokinetics of daunorubicin (DNR) in blast cells from the bone marrows of patients with acute nonlymphocytic leukemia (ANLL) were studied to determine whether verapamil was capable of enhancing intracellular accumulation and retention of DNR in ANLL, as has been observed in murine P388 cells resistant to DNR. Seventeen marrows from ANLL patients were studied, 13 of which were from patients who were considered to be clinically refractory to DNR. We took care to include such patients in this study since, in the P388 model, verapamil enhancement of DNR uptake is observed only in cells resistant to DNR. Intracellular accumulation of DNR was studied by exposing blast cells to DNR (1 microgram/mL) +/- verapamil (6.6 mumol/L) for up to 4 hours. Following a 2-hour exposure of cells to DNR +/- verapamil, intracellular retention of DNR was studied by incubating the cells in DNR-free medium for 3 hours. Intracellular DNR/10(6) cells was quantified by fluorometry. In 12 of 15 patient marrows, verapamil failed to enhance intracellular accumulation of DNR. Three patient marrows had a very small increment in DNR uptake in response to verapamil (approximately 14% greater than DNR alone) that was significant (P less than .05) by paired t test. Intracellular retention of DNR (t 1/2) and the area under the intracellular DNR v time curve (AUC) were studied in 17 patients marrow specimens. No significant alterations in these parameters were observed in response to verapamil. These data indicate either that verapamil did not substantially enhance DNR uptake or retention in blast cells obtained from ANLL patients who are clinically resistant to DNR, or that the frequency of DNR-resistant cells (ie, verapamil-responsive cells) among the blast cells obtained from these patients was too low to influence the population mean of intracellular DNR as measured in these studies.

scholarly journals Effects of verapamil on in vitro intracellular accumulation and retention of daunorubicin in blast cells from patients with acute nonlymphocytic leukemia

Blood ◽  
1986 ◽  
Vol 68 (1) ◽  
pp. 83-88
Author(s):  
DD Ross ◽  
CC Joneckis ◽  
CA Schiffer
Keyword(s):  
T Test ◽  
Acute Nonlymphocytic Leukemia ◽  
Free Medium ◽  
Intracellular Accumulation ◽  
Time Curve ◽  
Population Mean ◽  
Small Increment ◽  
Blast Cells ◽  
Paired T Test

The effects of verapamil on the intracellular pharmacokinetics of daunorubicin (DNR) in blast cells from the bone marrows of patients with acute nonlymphocytic leukemia (ANLL) were studied to determine whether verapamil was capable of enhancing intracellular accumulation and retention of DNR in ANLL, as has been observed in murine P388 cells resistant to DNR. Seventeen marrows from ANLL patients were studied, 13 of which were from patients who were considered to be clinically refractory to DNR. We took care to include such patients in this study since, in the P388 model, verapamil enhancement of DNR uptake is observed only in cells resistant to DNR. Intracellular accumulation of DNR was studied by exposing blast cells to DNR (1 microgram/mL) +/- verapamil (6.6 mumol/L) for up to 4 hours. Following a 2-hour exposure of cells to DNR +/- verapamil, intracellular retention of DNR was studied by incubating the cells in DNR-free medium for 3 hours. Intracellular DNR/10(6) cells was quantified by fluorometry. In 12 of 15 patient marrows, verapamil failed to enhance intracellular accumulation of DNR. Three patient marrows had a very small increment in DNR uptake in response to verapamil (approximately 14% greater than DNR alone) that was significant (P less than .05) by paired t test. Intracellular retention of DNR (t 1/2) and the area under the intracellular DNR v time curve (AUC) were studied in 17 patients marrow specimens. No significant alterations in these parameters were observed in response to verapamil. These data indicate either that verapamil did not substantially enhance DNR uptake or retention in blast cells obtained from ANLL patients who are clinically resistant to DNR, or that the frequency of DNR-resistant cells (ie, verapamil-responsive cells) among the blast cells obtained from these patients was too low to influence the population mean of intracellular DNR as measured in these studies.

Long-term proton pump induced hypergastrinaemia does induce lineage-specific restitution but not clonal expansion in benign Barrett's oesophagus in vivo

Gut ◽  
2009 ◽  
Vol 59 (2) ◽  
pp. 156-163 ◽  
Author(s):  
Jolanta A Obszynska ◽  
Paul A Atherfold ◽  
Manoj Nanji ◽  
Deborah Glancy ◽  
Sonia Santander ◽  
...  
Keyword(s):  
Proton Pump ◽  
Biological Effects ◽  
T Test ◽  
Barrett’S Oesophagus ◽  
Segment Length ◽  
Term Therapy ◽  
Barrett's Oesophagus ◽  
Paired T Test

BackgroundBarrett's oesophagus is a common premalignant lesion caused partly by acid reflux. Although the requisite therapy, proton pump inhibitors (PPIs), have been implicated in the progression of Barrett's oesophagus in animal models, harmful effects of prolonged PPI therapy in Barrett's oesophagus is both inconclusive and controversial. We therefore aimed to test the role of PPI-induced hypergastrinaemia in vitro and see whether any biological parameters were useful surrogates of long-term therapy in man.MethodsWe undertook detailed serological and tissue assessment of gastrin and CCK2 receptors in 90 patients randomised to different doses of PPI therapy during a detailed 2-year follow-up. We also undertook a comprehensive study of cell models to study the consequential biological effects of gastrin on the mucosa.ResultsGastrin and its cognate receptor CCK2R were expressed highest in the stomach, then less in Barrett's oesophagus and least in squamous oesophagus (SqE) (n=20 paired t-test, p<0.01). Analysis of the change in Barrett's oesophagus segment length change in 70 patients who were randomised to high or low PPI dose showed no difference over 2 years (n=70 t-test, p=0.8). Prolonged PPI use did, however, increase the serum gastrin, (36 pg/ml±57 pg/ml to 103 pg/ml±94 pg/ml (paired t test, p<0.05)). In vitro gastrin also induced changes in OE33(E)cckr Barrett's oesophagus cells, but not OE21(E)cckr squamous cells, transfected with CCK2R; migration was induced by 1 ng/ml of gastrin but proliferation only increased with 100 ng/ml (paired t-test, p<0.01) and both were abolished by antagonists.ConclusionWhile the short-term effects of gastrin enhance epithelial restitution in Barrett's oesophagus (but not squamous mucosa) there is no clinical evidence that Barrett's oesophagus length expands over time. This study, which is the largest and longest term randomised controlled trial of gastrin biology in Barrett's oesophagus, is further proof of the clinical safety of PPI therapy.

scholarly journals Recombinant gamma interferon induces hypertriglyceridemia and inhibits post-heparin lipase activity in cancer patients.

1986 ◽  
Vol 164 (4) ◽  
pp. 1093-1101 ◽  
Author(s):  
R Kurzrock ◽  
M F Rohde ◽  
J R Quesada ◽  
S H Gianturco ◽  
W A Bradley ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Lipase Activity ◽  
T Test ◽  
Activated Macrophages ◽  
Very Low Density Lipoproteins ◽  
Cholesterol Levels ◽  
Macrophage Activator ◽  
Regulate Lipid Metabolism ◽  
Paired T Test

Animals suffering from malignancy or chronic infection develop characteristic metabolic abnormalities, including a well-defined hypertriglyceridemic state. These abnormalities have been attributed to release of one or more mediators from activated macrophages. We report that cancer patients receiving RIFN-gamma, a potent macrophage activator, at doses of greater than or equal to 0.25 mg/m2/d i.m. show marked increases in triglyceride but not in cholesterol levels (pretreatment triglyceride level of 180 +/- 190 mg/dl [mean +/- SD] vs. a day-14 level of 370 +/- 242 mg/dl, n = 23, p less than 0.001 by the paired t test). This hypertriglyceridemia was characterized by an increase in very low-density lipoproteins and a decrease in plasma post-heparin lipase activity, consistent with defective triglyceride clearance (mean pretreatment lipase level of 2.1 mumol/ml/h vs. a day-14 level of 1.2 mumol/ml/h, n = 6, p = 0.02 by the paired t test). rIFN-gamma did not directly inhibit lipoprotein lipase enzymatic activity in vitro. Other possible mechanisms of action, such as suppression of lipase by an rIFN-gamma-induced mediator released from activated macrophages, or a direct effect of interferon on lipase biosynthesis, require further investigation. Our observations provide evidence that factors produced by the immune system can regulate lipid metabolism in man.

Testing the metabolic hypothesis of O2 chemoreception in the cat carotid body in vitro

1994 ◽  
Vol 76 (3) ◽  
pp. 1317-1323 ◽  
Author(s):  
D. G. Buerk ◽  
R. Iturriaga ◽  
S. Lahiri
Keyword(s):  
Carotid Body ◽  
Energy State ◽  
High Energy ◽  
T Test ◽  
Sensory Response ◽  
O2 Consumption ◽  
High Energy State ◽  
Metabolic Hypothesis ◽  
Paired T Test

It is known that oligomycin reduces the oxidative phosphorylation high-energy state or high-energy intermediates by inhibiting the formation of ATP without directly inhibiting electron transport, whereas metabolic uncouplers dissipate the high-energy state without net production of ATP. The metabolic hypothesis for O2 chemoreception in the carotid body (CB) predicts that 1) oligomycin should diminish O2 consumption and attenuate O2 chemoreception and 2) uncouplers should reverse the effect of oligomycin by increasing O2 consumption without restoring O2 chemoreception. These predictions were tested by simultaneously measuring CB chemosensory discharge from the sinus nerve and the rate of tissue O2 disappearance (dPO2/dt) during interruption of perfusate flow in perfused-superfused cat CB preparations (n = 9). O2 consumption was calculated from dPO2/dt. Flow-interruption responses were measured before and after oligomycin (1-microgram bolus) and subsequently after dinitrophenol (50 microM). Chemosensory responses to bolus injections of hypercapnic Tyrode solution, cyanide, or nicotine were also tested periodically. Oligomycin diminished dPO2/dt from -2.67 +/- 0.30 to -2.02 +/- 0.19 (SE) Torr/s (P < 0.004, paired t test) and reduced the maximal sensory response from 196 +/- 43 to 124 +/- 12 impulses/s (P < 0.002, paired t test) while augmenting the initial response to CO2. Dinitrophenol reversed the metabolic depressant effect of oligomycin but further suppressed the chemosensory response. These results confirm the above predictions and strengthen the metabolic hypothesis for O2 chemoreception in the CB.

scholarly journals Λειτουργική ικανότητα υπερπληθυσμών λεμφoκυττάρων ασκιτικού υγρού ασθενών με καρκίνο των ωοθηκών

2013 ◽  
Author(s):  
Νικόλαος Πισταμαλτζιάν
Keyword(s):  
Ex Vivo ◽  
T Test ◽  
P Value ◽  
Paired T Test

Η προθυμοσίνη α (προΤα) είναι ένα ισχυρά όξινο πολυπεπτίδιο, 109 αμινοξικών καταλοίπων, με ανοσοενισχυτική δράση in vitro και in vivo. Οι ανοσοδραστικές της ιδιότητες, οφείλονται στο καρβοξυτελικό της δεκαπεπτίδιο, προΤα(100-109).Στην διατριβή, διερευνήθηκε η in vitro επίδραση των προΤα/προΤα(100-109), συνεργιστικά με ιντερλευκίνη–2, στις ανοσολογικές απαντήσεις λεμφοκυττάρων απομονωμένων από ασκιτικό υγρό ασθενών με καρκίνο ωοθηκών. Απομονωθέντα λεμφοκύτταρα, από 33 ασθενείς με καρκίνο ωοθηκών σταδίου ΙΙΙC (FIGO), χωρίς προηγούμενη έκθεση σε χημειοθεραπεία, επωάστηκαν ex vivo με προΤα, και προΤα(100–109), συνεργιστικά με χαμηλές συγκεντρώσεις ιντερλευκίνης–2, στα πλαίσια μικτής καλλιέργειας λεμφοκυττάρων/καρκινικών κυττάρων. Ως μέτρο σύγκρισης υπήρξαν κύτταρα που επωάστηκαν παρουσία ιντερλευκίνης–2 μόνο. Τα λεμφοκύτταρα ενεργοποιούνταν εβδομαδιαία, επί 3 εβδομάδες, με εγχύσεις αυτόλογων καρκινικών κυττάρων. Στις ημέρες 7, 14, 21 γίνονταν έλεγχος του ανοσοφαινότυπου των σχετιζόμενων με τον όγκο λεμφοκυττάρων (TALs) με τη μέθοδο της κυτταρομετρίας ροής, αλλά και της δραστικότητας τους με τη δοκιμασία κυτταροτοξικότητας. Για τη δοκιμασία της κυτταροτοξικότητας, χρησιμοποιήθηκαν ως στόχοι αυτόλογα καρκινικά κύτταρα και K562 κύτταρα. Οι στόχοι συνδέονταν με 51Cr (18 ώρες συνεπώασης, σε μια αναλογία εκτελεστών : στόχων 40:1), και γίνονταν μέτρηση της εκλυόμενης ραδιενέργειας από μετρητή γ-ακτινοβολίας. Για τον προσδιορισμό του ανοσοφαινότυπου χρησιμοποιήθηκαν anti-CD45, anti-CD56, anti-CD3, anti-CD4 και anti-CD8 μονοκλωνικά αντισώματα συνδεδεμένα με τις χρωστικές φλουορεσκεΐνη, R-φυκοερυθρίνη και R–φυκοερυθρίνη/Cychrome5. Για την κυτταρομετρία ροής, χρησιμοποιήθηκε κυτταρόμετρο BD FACS Calibur. Τα δεδομένα αναλύθηκαν με λογισμικό CellQuest. Για τη στατιστική επεξεργασία χρησιμοποιήθηκε το paired t–test, με αμφίπλευρα επίπεδα σημαντικότητας και p-value = 0,05. Για την ανάλυση χρησιμοποιήθηκε το SPSS v13.0. Συνολικά, τα πειραματικά δεδομένα υποδεικνύουν πως η προΤα και το προΤα(100-109) ενισχύουν σημαντικά την ειδική – για – το αντιγόνο κυτταροτοξικότητα των TALs, έναντι των αυτόλογων καρκινικών κυττάρων in vitro ( ~20% έναντι 12.5%, p = 0.001 για την ημέρα 7 και ~18% έναντι 11%, p=0.003 για την ημέρα 14), εμφανίζοντας μια λιγότερο ισχυρή επίδραση στην ικανότητα των ΝΚ κυττάρων, να λύουν ευαίσθητους σε αυτά στόχους (p=0.073). Η επίδραση της προθυμοσίνης α και του προΤα(100-109) είναι πιο ισχυρή τις ημέρες 7-14, και μειώνεται σημαντικά την ημέρα 21. Η δράση της προθυμοσίνης α είναι ταυτόσημη με αυτή του προΤα(100-109). Η χρήση δεκαπεπτιδίου με αναδιαταγμένη αλληλουχία αμινοξέων δεν προκάλεσε ανοσοενίσχυση, αποδεικνύοντας έτσι την ειδική για την αλληλουχία δράση του προΤα(100-109). Η συγκεκριμένη μελέτη παρουσιάζει για πρώτη φορά, την ανοσοενισχυτική δράση της προΤα και του προΤα(100-109) σε λεμφοκύτταρα ασκιτικού υγρού ασθενών με καρκίνο των ωοθηκών. Δεν υπήρξε κάποια συσχέτιση με την ηλικία, τον ιστολογικό τύπο ή την θεραπευτική ανταπόκριση.Συμπερασματικά, η προθυμοσίνη α και το ανοσοδραστικό καρβοξυτελικό δεκαπεπτίδιο προΤα(100-109), ενισχύουν σημαντικά την λυτική ικανότητα των TALs. Παρουσία καρκινικών αντιγόνων, ενισχύουν την μειωμένη κυτταροτοξικότητα των TALs έναντι των αυτόλογων καρκινικών κυττάρων, αναστρέφοντας την ισχυρή ανοσοκατασταλτική επίδραση που ασκεί σε αυτά, το περιβάλλον του ασκίτη ασθενών με καρκίνο των ωοθηκών.

ALTERATION OF THE END-PLANE ANGLE IN PRESS-FIT CYLINDRICAL STEM RADIAL HEAD PROSTHESIS: AN IN VITRO STUDY

Hand Surgery ◽  
2012 ◽  
Vol 17 (01) ◽  
pp. 19-24 ◽  
Author(s):  
Suriya Luenam ◽  
Piti Chalongviriyalert ◽  
Arkaphat Kosiyatrakul ◽  
Chusak Thanawattano
Keyword(s):  
Radial Head ◽  
T Test ◽  
Radial Head Prosthesis ◽  
Plane Angle ◽  
Radial Head Replacement ◽  
Press Fit ◽  
Before And After ◽  
The Mean ◽  
Paired T Test

Purpose: Many studies comparing the morphology of native radial head with the prosthesis have been published. However, there is limited information regarding the postoperative alignment of the articular surface following the radial head replacement. The purpose of this study is to evaluate the alteration of the end-plane angle in the modular radial head prosthesis with a press-fit cementless cylindrical stem. Methods: The study used 36 cadaveric radii. The press-fit size prosthesis with cylindrical stem was inserted into each specimen. The end-plane angles of the radial head before and after prosthetic replacement, were measured in coronal and sagittal planes with a digital inclinometer. The data were analyzed by paired t-test. Results: From paired t-test, there were statistically symmetrical end-plane angles before and after radial head replacement in both coronal and sagittal planes (p-value < 0.01). The mean of radial head end-plane angle alteration in the coronal plane was 3.62° (SD, 2.76°) (range, 0.3°–8.9°). In the sagittal plane, the mean of alteration was 5.85° (SD, 3.56°) degrees (range, 0.3° – 14.2°). Conclusion: The modular radial head prosthesis with cylindrical stem is in vitro able to restore the native end-plane angles of radial heads statistically when used in a press-fit fashion.

CLL Cell Viability Promoted by Myosin Heavy Chain IIA Exposed Apoptotic Cells is BTK-dependent

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1767-1767
Author(s):  
Charles C. Chu ◽  
Lu Zhang ◽  
Xiaoxuan Cui ◽  
Amanda R. Magli ◽  
Xiao-Jie Yan ◽  
...  
Keyword(s):  
Cell Viability ◽  
B Cell ◽  
Heavy Chain ◽  
T Test ◽  
Apoptotic Cells ◽  
Mutation Status ◽  
Large Patient ◽  
Bcr Signaling ◽  
Paired T Test

Abstract Abstract 1767 B-cell chronic lymphocytic leukemia (CLL) is a clonal CD5+CD19+ B-lymphocyte cancer with a B cell receptor (BCR) immunoglobulin heavy chain variable (IGHV) gene sequence that may be classified as unmutated (U-CLL) or mutated (M-CLL) depending on the level of IGHV mutation. Because U-CLL patients have a worse clinical prognosis than M-CLL patients, the structure of the BCR and the signaling consequences of BCR occupancy by antigen are considered crucial to disease development and possibly progression. Moreover, nearly one third of CLL patients express a CLL BCR that is virtually identical in sequence (stereotyped) to other CLL patient subgroups, an incidence that is extraordinarily unlikely by random chance, suggesting that common antigens could bind to these CLL BCRs and initiate signaling. Apoptotic autoantigens may be a source of such antigens. Indeed, CLL BCRs expressed as native or recombinant monoclonal antibodies (mAbs) can recognize autoantigens, such as nonmuscle myosin heavy chain IIA (myosin), actin, vimentin, cofilin-1, filamin B, insulin, DNA, IgG, myoglobin, thyroglobulin, cardiolipin, and oxidized low-density lipoprotein. These molecules are generally intracellular and may be exposed on the cell surface during apoptosis, permitting binding to CLL BCRs. Indeed, intracellular myosin is exposed on the surface of a subset of apoptotic cells, termed MEACs (myosin exposed apoptotic cells). Furthermore, MEACs bind to over 60% of CLL mAbs tested, supporting the idea that multiple autoantigens exposed on MEACs may stimulate CLL cells. This binding may furnish signals beneficial to the leukemic cell, because MEAC binding correlates with shorter patient survival. To test this hypothesis, the effect of MEAC binding on spontaneous CLL cell apoptosis was tested after co-culture of CLL peripheral blood mononuclear cells from a large patient cohort with MEACs (3:1–5:1 ratio) for 2–4 days using flow cytometry and AnnexinV and 7-actinomycin D staining to measure apoptosis in CD19+CD3− cells. A typical wide range of spontaneous apoptosis was observed (median = 26.98% (5.93%–91.35%) AnnexinV+). In this large patient cohort (n=64, with some patient samples tested 2–8 times), co-culture of CLL cells with MEACs resulted in a decrease in apoptosis in all patient samples as compared to cultures without MEACs (median = 18.58% (2.49%–76.35%) AnnexinV+), a highly significant result (P=0.0001, two-tailed paired t-test). In this cohort, U-CLL patients (n=23) had a slightly higher median decrease in apoptosis (30.39%) than M-CLL patients (n=33, 22.69%), but this was not significant (P=0.3940, two-tailed unpaired t-test with Welch's correction). Furthermore, no apparent correlation between MEAC co-culture responsiveness and in vitro MEAC binding was observed in the 9 CLL patient samples exhibiting stereotyped CLL BCR. Finding that MEAC co-culture affects all CLL cells regardless of IGHV mutation status or stereotypy contrasts with MEAC binding to CLL mAbs in vitro, for which there is a marked preference for U-CLL and stereotyped mAbs. One possible explanation for the conflicting result is that CLL cells with BCRs that do not bind MEACs well receive an additional non-Ig receptor signal that boosts the BCR signal to make it near equivalent to the signal from BCRs on cells that bind MEACs well. In this model, inhibition of BCR signaling would abrogate the decrease in apoptosis produced by MEAC co-culture in all CLL cases. To test this, Bruton tyrosine kinase (BTK) inhibitors, ibrutinib or LFM-A13, were added to these co-cultures (n=12 and 18, respectively). Both inhibitors significantly abrogated the MEAC co-culture increase in viability (ibrutinib, P=0.0005; LFM-A13, P=0.0007; two-tailed paired t-test). Ibrutinib and LFM-A13 inhibited all samples regardless of IGHV mutation status (stereotyped BCR samples were not tested). In conclusion, these results are consistent with the theory that antigenic stimulation of CLL cells via the BCR promotes CLL cell viability and may influence the level of disease activity. MEACs may be a source of such antigenic stimulation. Interference with BCR signaling via BTK inhibition prevents this stimulation and may be one of the explanations for the clinical success of BCR signaling inhibitors in treating CLL. Disclosures: Barrientos: Gilead and Pharmacyclics: Research Funding.

Broth Microdilution and E-Test for Determining Fluoroquinolone Activity against Streptococcus Pneumoniae

2002 ◽  
Vol 36 (3) ◽  
pp. 416-422 ◽  
Author(s):  
Michael B Kays ◽  
Melissa A Graff
Keyword(s):  
Streptococcus Pneumoniae ◽  
T Test ◽  
Rank Test ◽  
Broth Microdilution ◽  
Signed Rank ◽  
Significant Difference ◽  
Wilcoxon Signed Rank Test ◽  
Signed Rank Test ◽  
Paired T Test

OBJECTIVE: To compare broth microdilution and E-test minimum inhibitory concentrations (MICs) of 4 fluoroquinolones against Streptococcus pneumoniae and to determine the effect of these in vitro MIC methods on the calculation of AUC0–24/MIC ratios. METHODS: Levofloxacin, gatifloxacin, moxifloxacin, and gemifloxacin MICs were determined by broth microdilution (incubated in air) and E-test (incubated in CO2) for 100 clinical isolates of S. pneumoniae. MIC50, MIC90, and geometric mean MIC were calculated. Steady-state serum concentration—time profiles were simulated for once-daily, oral dosing of levofloxacin 500 mg, gatifloxacin 400 mg, moxifloxacin 400 mg, and gemifloxacin 320 mg. After correcting for protein binding, AUC0–24 of unbound drug was calculated for each regimen, and AUC0–24/MIC ratios were calculated using MIC data from both in vitro methods. Differences in MICs between methods were determined for each agent using the paired t-test (after logarithmic transformation of MICs) and the Wilcoxon signed-rank test. Differences in AUC0–24/MIC ratios were also determined using the paired t-test and the Wilcoxon signed-rank test. The level of significance for all analyses was p < 0.05. RESULTS: Broth microdilution and E-test MICs were within ± 1 log2 dilution for 94%, 93%, 61%, and 35% of the isolates for levofloxacin, gatifloxacin, moxifloxacin, and gemifloxacin, respectively. Broth microdilution MICs were significantly lower than E-test MICs for all 4 agents (p < 0.001). However, a categorical change in susceptibility was seen for only 1 isolate with gatifloxacin and moxifloxacin (intermediate by broth microdilution, resistant by E-test). AUC0–24/MIC ratios were significantly higher for each regimen when MICs were determined by broth microdilution compared with E-test (p < 0.001). CONCLUSIONS: There is a significant difference in the activity of the newer fluoroquinolones against S. pneumoniae when MICs are determined by broth microdilution and E-test. When evaluating fluoroquinolone activity and pharmacodynamics against this organism, clinicians must be aware that MIC testing methodology may have a significant impact on the results.

Abnormal epithelial transport in cystic fibrosis jejunum

1991 ◽  
Vol 260 (5) ◽  
pp. G758-G763 ◽  
Author(s):  
E. V. O'Loughlin ◽  
D. M. Hunt ◽  
K. J. Gaskin ◽  
D. Stiel ◽  
I. M. Bruzuszcak ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Epithelial Transport ◽  
Clinical Manifestations ◽  
T Test ◽  
Electrolyte Transport ◽  
Ionophore A23187 ◽  
Ussing Chambers ◽  
Cl Secretion ◽  
Paired T Test

Abnormal epithelial electrolyte transport has been identified in a range of cystic fibrosis (CF) organs and appears to account for the various clinical manifestations of the disease. The aim of this study was to further define the Cl- secretion defect in CF jejunum. Excised jejunum was obtained from 11 CF patients and 12 controls. Transport studies were performed on stripped epithelium in vitro under short-circuited conditions in Ussing Chambers. 3-Isobutyl-1-methylxanthine (IBMX) (300 microM) significantly increased Cl- secretion in control (-2.3 +/- 0.6 to -3.3 +/- 0.7 mueq.cm-2.h-1; P less than 0.01, paired t test; n = 5 subjects) but not in CF jejunum (-0.5 +/- 0.3 to -0.1 +/- 0.4; n = 4). However in contrast to control jejunum, net Na+ absorption in CF jejunum was higher in the IBMX (1.3 +/- 0.5 mueq.cm-2.h-1) compared with basal periods (0.6 +/- 0.3; P less than 0.05, paired t test). IBMX stimulation of tissue adenosine 3',5'-cyclic monophosphate (cAMP) was similar in both control and CF jejunum. A range of secretagogues known to induce secretion in mammalian intestine, including dibutyryl cAMP (DBcAMP), DBcGMP, Ca2+ ionophore A23187, and the protein kinase C activator 4 beta-phorbol 12,13-dibutyrate, failed to induce secretion in CF jejunum. In conclusion, CF jejunum failed to exhibit Cl- secretion and also demonstrated abnormalities of Na+ absorption. These results support the view that the defect lies at a site distal to the intracellular messengers. Moreover, these abnormalities of intestinal electrolyte transport may account for some of the gastrointestinal manifestations of the disease such as meconium ileus and distal intestinal obstruction syndrome.

scholarly journals Bifidogenic and butyrogenic effects of young barely leaf extract in an in vitro human colonic microbiota model

AMB Express ◽  
2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Daisuke Sasaki ◽  
Kengo Sasaki ◽  
Yasushi Kadowaki ◽  
Yasuyuki Aotsuka ◽  
Akihiko Kondo
Keyword(s):  
Leaf Extract ◽  
T Test ◽  
Isoleucine Leucine ◽  
Colonic Microbiota ◽  
Health Promoting ◽  
Barley Leaf ◽  
Vitro Model ◽  
Dunnett's Test ◽  
Paired T Test

Abstract Young barley leaf extract (YBL) contains beneficial substances such as fructans, minerals, and vitamins. The effects of YBL administration on the human colonic microbiota and its production of metabolites were evaluated using an in vitro model culture system. Fermentations were started by inoculating fecal samples from nine healthy subjects, with or without 1.5% YBL. Bacterial 16S rRNA sequencing results confirmed that YBL administration significantly increased the relative abundances of bacteria related to the genus Bifidobacterium (p = 0.001, paired t-test) and those of the genera Faecalibacterium, Roseburia, Unclassified Ruminococcaceae, and Lachnospira (p = 0.013, p = 0.019, p = 0.028, and p = 0.034, respectively, paired t-test). Increased abundances of the latter genera corresponded to increased butyrate production in human colonic microbiota models following fermentation with 1.5% YBL, when compared to fermentation without 1.5% YBL (p = 0.006, Dunnett’s test). In addition, YBL administration significantly increased the production levels of amino acids such as lysine, glutamate, serine, threonine, alanine, isoleucine, leucine, valine, and phenylalanine. Therefore, our results showed the health-promoting bifidogenic and butyrogenic effects of YBL.

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