The proposal that calcium antagonists have different sites of action has been tested by attempting to reverse their inhibitory effects with a dihydropyridine which augments Ca2+ entry into cells, Bay K 8644. Bay K 8644 (1-1000 nmol/l) increased the sensitivity to Ca2+ of K+-depolarized taenia preparations from the guinea-pig caecum. Thus Bay K 8644 augmented established submaximal Ca2+-induced contractions and also shifted cumulative concentration-response curves to Ca2+ to the left, even in the presence of an optimal K+-depolarization. The inhibitory effects of nifedipine (10 nmol/l), verapamil (0.2 mumol/l), diltiazem (1 mumol/l) and diclofurime (1 mumol/l) on Ca2+-induced contractions were reversed by Bay K 8644 (1-1000 nmol/l). In contrast, Bay K 8644 did not reverse the effects of cinnarizine (1 mumol/l), flunarizine (1 mumol/l), fendiline (3 mumol/l), prenylamine (3 mumol/l), pimozide (1 mumol/l), bepridil (3 mumol/l), perhexiline (10 mumol/l) or the calmodulin antagonist W-7 (200 mumol/l). Bay K 8644 (1-100 nmol/l) was less effective at reversing the effects of nisoldipine (10 nmol/l), a slowly dissociating dihydropyridine, than the effects of nifedipine. However, preincubation with Bay K 8644 (1 mumol/l) protected the taenia from the inhibitory effects of nisoldipine (10 nmol/l). These findings are compatible with interactions of nisoldipine and Bay K 8644 at a common site. Taenia preparations incubated with Bay K 8644 (1 mumol/l) were protected from the inhibitory effects of nifedipine (10 nmol/l), nisoldipine (10 nmol/l) and to a lesser extent verapamil (0.2 mumol/l) and diltiazem (1 mumol/l).(ABSTRACT TRUNCATED AT 250 WORDS)

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This study aimed at evaluating in outpatients an algorithm for the laboratory diagnosis of Clostridioides (Clostridium) difficile infection (CDI), i.e., enzyme immunoassays (EIAs) detecting bacterial glutamate dehydrogenase (GDH) and toxin A/B, followed by polymerase chain reaction (PCR) analyses of samples with discordant EIA results.In total, 9802 examinations of stool samples by GDH and toxin EIAs performed in 7263 outpatients and 488 inpatients were analyzed retrospectively. Samples with discordant EIA results had been tested by a commercially available PCR assay detecting genes of the C. difficile-specific triose phosphate isomerase (tpi) and toxin B (tcdB). Concordant EIA results (686 C. difficile-positive, 8121 negative) were observed for 8807 (89.8%; 95% CI, 89.2–90.4%) samples. Of 958 samples with discordant EIA results, 895 were analyzed using PCR and 580 of 854 GDH-positive/borderline, toxin-negative samples (67.9%; 95% CI, 64.7–71.0%) were positive for tpi and tcdB, while 274 samples (32.1%; 95% CI, 29.0–35.3%) were tcdB-negative. In contrast, 35 of 41 GDH-negative, toxin-positive/borderline samples (85.4%; 95% CI, 71.2–93.5%) were tcdB-negative. Still, 6 samples (14.6%; 95% CI, 6.5–28.8%) yielded positive PCR results for both genes.In conclusion, around 90% of the samples were analyzed appropriately by only applying EIAs. Approximately one third of the PCR-analyzed samples were tcdB-negative; thus, patients most likely did not require CDI treatment.