Toxicokinetics of an environmentally relevant mixture of dioxin-like PHAHs with or without a non-dioxin-like PCB in a semi-chronic exposure study in female Sprague Dawley rats

Female Sprague Dawley rats were treated subcutaneously for 20 weeks with an environmentally relevant mixture of dioxin-like PHAHs with (PHAH+) or without (PHAH-) 2,2',4,4',5,5'-hexachlorobiphenyl. The hepatic retention (% of given dose) of the various PHAH congeners differed considerably and in the following order: 2,3,4,7,8-pentachlorodibenzofuran (30.5-43.1%), 3,3',4,4',5-pentachlorobiphenyl (12.8-17.6%), 1,2,3,7,8-pentachlorodibenzo-p-dioxin (6.9-10.8%), 2,3,7,8-tetrachlorodibenzo-p-dioxin (3.2-4.5%), 2,3,3',4,4',5-hexachlorobiphenyl (1.0-1.7%), 2,2',4,4',5,5'-hexachlorobiphenyl (0.5-0.8%) and 2,3',4,4',5-pentachlorobiphenyl (0.2-0.4%). A decrease of the hepatic retention of 2,3,7,8-TCDD, 1,2,3,7,8-PeCDD and 2,3,4,7,8-PeCDF was found at increasing doses of the PHAH+ mixture. 2,2',4,4',5,5'-Hexachlorobiphenyl increased the hepatic retention (1.3-2 times) of all congeners in the PHAH+ group, compared to the TEQ equivalent dosed PHAH- group. No interactions were observed on the ethoxyresorufin-O-deethylase activity.     

The surface-active compounds of a Pseudomonas sp. S-27 culture

Pseudomonas species S-27 was grown on various substrates. It was established that the Pseudomonas species S-27 strain can produce biosurfactants of ramnolipid nature decreasing the surface and interfacial tension to 29.2 and 0.05 mN/m. respectively, as well as a biopolymer stabilizing the emulsions with hydrocarbons and oils. The biosurfactant and bioemulsifier synthesis is shown to depend of the substrate nature.     

Lack of association between antiphospholipid antibodies and first-trimester spontaneous abortion: prospective study of pregnancies detected within 21 days of conception

OBJECTIVE: To determine the role of antiphospholipid antibodies and anticardiolipin antibodies in first-trimester losses, addressing experimental pitfalls that preclude excluding the possibility that these antibodies reflect merely the selection bias of studying couples only after they have already experienced losses. DESIGN: Given that retrospective studies cannot exclude the possibility that such antibodies arise as a result of the fetal death, blood samples were obtained either before pregnancy or very early in pregnancy. Sera were obtained within 21 days of conception. SETTING: Multicenter university-based hospitals (National Institute of Child Health and Human Development collaborative study). PATIENT(S): Subjects for the current study were 93 women who later experienced pregnancy loss (48 diabetic; 45 nondiabetic), matched 2:1 with 190 controls (93 diabetic and 97 nondiabetic) who subsequently had normal live-born offspring. INTERVENTION(S): Sera from these 283 women were analyzed for antiphospholipid antibodies by enzyme immunoassay. In 260 of the 283 women (87 with pregnancy losses; 173 with live-born infants), sera were also available to perform assays for anticardiolipin antibodies by enzyme immunoassay. MAIN OUTCOME MEASURE(S): Pregnancy losses. RESULT(S): No association was observed between pregnancy loss and the presence of antiphospholipid antibodies or anticardiolipin antibodies. Levels of antiphospholipid antibodies were 6-19 PL/mL in 62.4% of the pregnancies that ended in losses and > or = 20 PL/mL in 5.4%; among pregnancies resulting in live-born infants, the percentages were 56.8% and 6.8%, respectively. Of the pregnancies that ended in a loss, 5.7% had anticardiolipin antibodies > or = 16 GPL/mL, compared with 5.2% of those ending in a live birth. CONCLUSION(S): This prospective study suggests that anticardiolipin antibodies and antiphospholipid antibodies are not associated with an increased risk for first-trimester pregnancy loss.     

A non-pungent resiniferatoxin analogue, phorbol 12-phenylacetate 13 acetate 20-homovanillate, reveals vanilloid receptor subtypes on rat trigeminal ganglion neurons

Capsaicin, the vanilloid responsible for the pungent taste of hot peppers, binds to receptors found primarily in polymodal nociceptors. Capsaicin initially stimulates polymodal nociceptors and subsequently inhibits them from responding to a variety of stimuli. This property makes it useful clinically as an analgesic and anti-inflammatory compound. There is mounting, albeit indirect, evidence for the existence of several subtypes of vanilloid receptors. One such piece of evidence comes from studying analogues of capsaicin, such as phorbol 12-phenylacetate 13 acetate 20-homovanillate. This compound binds to (capsaicin) vanilloid receptors on sensory neurons, but unlike capsaicin it is non-pungent and does not produce hypothermia. To determine how sensory neurons respond to phorbol 12-phenylacetate 13 acetate 20-homovanillate, and to compare these responses with those evoked by capsaicin, whole-cell patch-clamp measurements were performed on cultured rat trigeminal ganglion neurons. It was found that 63% of the neurons held at -60 mV were activated by 3 microM, phorbol 12-phenylacetate 13 acetate 20-homovanillate, and 87% of these were also activated by 1 microM capsaicin. In a given neuron, phorbol 12-phenylacetate 13 acetate 20-homovanillate, like capsaicin, could activate kinetically distinct inward currents. The current-voltage curves characterizing phorbol 12-phenylacetate 13 acetate 20-homovanillate responses were asymmetric and had reversal potentials at -5.8 +/- 6.0 mV and 10.4 +/- 4 mV. The averaged dose-response curves for phorbol 12-phenylacetate 13 acetate 20-homovanillate were fit to the Hill equation and had binding constants (K(1/2)s) of 2.73 microM and 0.96 microM and Hill coefficients (ns) of approximately 1 for a rapidly- and slowly-activating current, respectively. These parameters are consistent with those obtained from binding experiments and calcium-influx experiments on sensory nerves. Repeated applications of phorbol 12-phenylacetate 13 acetate 20-homovanillate every 3 min caused a complete reduction in the rapidly-activating currents leaving only a reduced slowly-activating current. This provides strong evidence for the independence of these currents and the existence of subtypes of vanilloid receptors. Additional evidence for the existence of receptor subtypes is that 10 microM capsazepine, a specific and competitive inhibitor of capsaicin-evoked responses, did not inhibit the phorbol 12-phenylacetate 13 acetate 20-homovanillate-induced currents in some neurons and partially inhibited them in other neurons. Thus, there are capsazepine-sensitive and capsazepine-insensitive subtypes of vanilloid receptors. In summary, we have obtained electrophysiological and pharmacological evidence for distinct subtypes of vanilloid receptors.     

Gastric antrectomy with selective gastric vagotomy does not influence gallbladder motility during interdigestive and postprandial periods

Fasting gastrointestinal motility and gallbladder motility during the interdigestive state and in the postprandial period was studied in eight patients who were operated for ulcer disease with an antrectomy and selective gastric vagotomy. Nocturnal motility recording revealed all three phases of the migrating motor complex (MMC) in all but one patient, where no phase III activity was recorded. In the rest of the patients 3-10 events with phase III activity were recorded. At scintigraphy ([75Se]HCAT) a cyclic gallbladder filling and emptying in relation to the MMC cycle was found. Episodes with emptying were confined to phase II and a total of 13 episodes with a median duration of 25 min (range 10-70 min) were observed. A median of 10.7% (6.1-17.7%) of the gallbladder contents was emptied. In a control group of eight healthy young men the values were 13.5 min (9-36 min) and 6.9% (3.7-31.1%), respectively. These differences were not significant. During the postprandial period, a lag period in gallbladder emptying of median 15 min (5-20 min) was observed when food ingestion took place during phase I of the MMC. Thereafter a gradual emptying occurred with a rate of 0.95% min (0.71-1.15%/min). In a control group of healthy young males, the lag period was 13.5 min (9-22.5 min) and the emptying rate 0.61%/min (0.08-0.77%/min). When food ingestion occurred during phase II of the MMC, the lag period of gallbladder emptying in the patient group was median 0 min (0-5 min) and the emptying rate was 0.77%/min (0.33-0.86%/min). The values in the control group were 0 min (-9 to 13.5 min) and 0.76%/min (0.54-2.25%/min), respectively. These differences between the patients and controls were not significant. In conclusion, antrectomy and selective gastric vagotomy do not influence fasting gastrointestinal motility or gallbladder motility during the interdigestive state or in the postprandial period.     

Amphetamines in hair by enzyme-linked immunosorbent assay

Human hair was collected from the occipital crown region of the head from several subjects; these hair samples were presumptively positive for amphetamines by a previously evaluated immunoassay. Hair was washed briefly with methanol to remove external contamination, then extracted with hot methanol for 2 h to recover the drugs. The extracts were evaporated to dryness, reconstituted in buffer, and analyzed using a new enzyme-linked immunosorbent assay (ELISA) technique adapted for the detection of amphetamines in hair. Gas chromatography-mass spectrometry was used as the reference technique. Cross-reactivity of several related compounds was evaluated by equating the inverse of the ligand concentration at 50% antibody binding to the affinity constant for each compound. The ratio of a compound's affinity constant to that for d-methamphetamine was used to derive percent crossreactivity. These experiments yielded values of 30.8% for d-amphetamine, 7.4% for I-methamphetamine, 4.3% for phentermine, 2.9% for I-amphetamine, and <1% for ephedrine, methylenedioxyamphetamine, and methylenedioxymethamphetamine. Cross-reactivity of unrelated compounds was found to be non-existent. The optimum cutoff concentration was determined by receiver operating characteristic curve analysis to be 300 pg/mg and the observed limit of detection was 60 pg/mg. Intra-assay precision at 300 pg/mg was 3.3% (coefficient of variation, CV), and the interassay CV was 10.5%. The sensitivity and specificity of the method were 83% and 92%, respectively.