Infant exposure to environmental tobacco smoke: Jordan University hospital-based study.

To study exposure to environmental tobacco smoke during the first year of life, 220 infants attending the outpatient paediatric clinic of the University of Jordan for routine visits with their mothers were recruited to the study. Mothers completed a questionnaire about smoking habits of household members, and urine samples were obtained from infants for analysis of cotinine levels. A total of 60.0% of infants were reported to be exposed to passive smoking at home and 36.4% had detectable levels of urine cotinine (mean 7.1 ng/mL, range 0.27-41 ng/mL). Detectable saliva cotinine levels in 8/20 mothers of neonates (1-2 days old) suggested in utero exposure. Recommendations are made to protect this vulnerable population from tobacco smoke exposure.

Delay of ovulation by meloxicam in healthy cycling volunteers: A placebo-controlled, double-blind, crossover study.

This study aimed to assess the effect of meloxicam on female ovulation. Twenty consented fertile females were monitored for 4 menstrual cycles: a baseline cycle, 2 treatment cycles, and a washout cycle between treatment cycles. In the first cycle visit, transvaginal ultrasound was performed, a blood sample for progesterone and meloxicam analysis was withdrawn, and volunteers were given a luteinizing hormone (LH) urine test kit and meloxicam or placebo. Volunteers started the treatment on the following day and asked to return the day the LH kit was positive to detect the dominant follicle. At subsequent visits, transvaginal ultrasound and progesterone and meloxicam levels were investigated. Compared to placebo, a 5-day delay in follicle rupture, a 55.7% increase in the mean maximum follicle diameter, and 33.5% decrease of plasma progesterone level were observed in the meloxicam-treated group. Such demonstrated meloxicam effects were reversed in participants who were randomized to meloxicam first and then placebo. Only minor side effects were reported by volunteers during the course of treatment. It is concluded that meloxicam resulted in a reversible delay of ovulation, an increase in follicular diameter, and a decrease in plasma progesterone level.

Further investigation on meloxicam contraceptivity in female rabbits: luteinizing unruptured follicles, a microscopic evidence.

Meloxicam, a selective cyclooxygenase-2 inhibitor, was administered orally or intravaginally, to sperm-positive female rabbits to assess its effect on ovulation. A single oral dose (20 mg/kg), administered 5 h postcoitus resulted in 100% contraceptive rate. On the other hand, for females receiving meloxicam suppositories (14.9 mg/kg), 5 h postcoitus, the contraceptive rate was 62.5% compared to placebo. The decrease in the contraceptive effect of meloxicam suppository may be due to the rejection of the dose by some females. Corpora lutea, maternal plasma progesterone, ovary fresh weight and maternal body weight gain were not affected by meloxicam treatment compared to placebo. Histopathologically, the surface of the ovary of meloxicam-treated females appears irregular and dilated due to the presence of different-sized cysts. Some of the cystic follicles were retained ova. Further, immunohistochemical stains for estrogen and progesterone receptors showed positive staining in granulosa cells and the wall of the unruptured follicle. It is concluded that contraceptive effect of meloxicam in female rabbits resulted in a failure of follicular rupturing.

Meloxicam inhibits rabbit ovulation.

The nonsteroidal antiinflammatory, selective cyclo-oxygenase-2 (COX-2) inhibitor, meloxicam, was tested to assess its effect on rabbit ovulation. Meloxicam in different doses was administered intraperitoneally (ip) to adult female Californian rabbits at 2, 5, 8, and 24 h postcoitus with sperm-positive rabbits. Rabbits were killed on Day 10 of gestation. Meloxicam produced significant inhibition of ovulation in rabbits. This inhibition of ovulation by meloxicam was dose- and time-dependent. Ovulation in rabbits was completely inhibited by a single ip administration of meloxicam (20 mg/kg) when the drug was administered at 2 and 5 h postcoitus, whereas neither ovulation nor implantation were inhibited (pregnancy rate 75%) by the same dose administered 24 h postcoitus (approximately 14 h post ovulation). Further, ovulation was completely inhibited by 10 mg/kg of meloxicam when the drug was administered at 5 or 8 h postcoitus, but there was less inhibition of ovulation when 10 mg/kg of the drug was administered at 2 or 24 h postcoitus (pregnancy rate 25 and 80%, respectively). Corpora lutea, maternal plasma progesterone, ovary fresh weight, and maternal body weight gain were affected by meloxicam treatment. Histopathological findings observed in the ovaries of treated rabbits included microscopic dilatation of graffian follicles, particularly mature follicles. Some of the follicles were cystically dilated in addition to severe hemorrhage within the follicles which lost ova. These results show that ovulation can be inhibited in rabbits by meloxicam. Further studies are needed to assess the value of selective COX-2 inhibitors as potential nonhormonal contraceptive agents.

Effects of Inula viscosa leaf extracts on abortion and implantation in rats.

The anti-implantation and mid-term abortifacient effects exhibited by administration of Inula viscosa leaf extracts, were studied in rats. The aqueous extract administered i.p. on day 1-6 of gestation, totally diminished fetal implantation and caused a significant (P<0.05) reduction in the number of corpora lutea and blood progesterone levels. Meanwhile, administration on day 13-15 of gestation exhibited mid-term abortion. Furthermore, petroleum ether and dichloromethane, but not methanol, extracts exhibited pronounced abortifacient effects. The results of this study are in agreement with the traditional reputation of this plant as abortifacient. Further, the plant possesses anti-implantational and luteolytic effects.

Effects of castor bean extract and ricin A-chain on ovulation and implantation in rabbits.

The anti-implantation and antiovulation effects of castor bean extract (CBE) and ricin A-chain (RAC) were evaluated in rabbits. Both CBE and RAC, administered intraperitoneally on days 5-9 of pregnancy, exhibited a pronounced decrease in maternal body weight gain and in death of all fetuses. A significant (p < 0.01) decrease of implantation sites resulted after rabbits were treated with RAC on the first 6 consecutive days of pregnancy. When female rabbits were treated with RAC for 10 consecutive days followed by human chorionic gonadotropin (hCG) (50 IU/kg intravenously), there was a 30% reduction in the number of corpora lutae. These data clearly indicate that CBE and RAC possess potent effects on implantation and ovulation in rabbits. The protein contents of castor bean extract, separated by polyacrylamide gel electrophoresis, revealed the presence of several protein bands, ricin toxin being a major constituent of the extract.

The bioequivalence study of folifer-Z: a new formulation of sustained-release iron and zinc.

The bioequivalence of Folifer-Z tablets, a new sustained-release iron and zinc formulation was evaluated and compared to that of Fefol-Z capsules in 30 healthy male subjects. Each subject received a single oral dose of either product according to a randomized two-way crossover design. A washout period of 1 week was allowed after each treatment. Blood samples were obtained over a 24-h period, and iron and zinc concentrations were measured. The pharmacokinetic parameters of Folifer-Z were Cmax (103 +/- 46.2 micrograms/dl), Tmax (5.93 +/- 2.94 h) and AUC0-24 h (1937 +/- 706 micrograms/dl per h), whereas the corresponding Fefol-Z values were Cmax (109 +/- 41.5 micrograms/dl), Tmax (6.64 +/- 2.54) and AUC0-24 h (1865 +/- 699 micrograms/h per dl). Analysis of variance on log-transformed data for Cmax and AUC0-24 h revealed lack of significant differences among the two formulations. The mean relative bioavailability of AUCtest/AUCreference was 1.07 (90% confidence interval range: 99-115%) and for Cmax test/Cmax reference was 0.96 (90% confidence interval range: 88-105%). Regarding the zinc results, the pharmacokinetic parameters of Folifer-Z values were Cmax (101 +/- 20.7 micrograms/dl), Tmax (4.86 +/- 1.53 h) and AUC0-24 h (1944 +/- 202 micrograms/h per dl), while the corresponding Fefol-Z values were Cmax (102 +/- 20.7), Tmax (4.93 +/- 1.51) and AUC0-24 h (1953 +/- 200). Analysis of variance on log-transformed zinc data for Cmax, Tmax and AUC0-24 h revealed lack of significant difference among the two formulations. The mean relative bioavailability of AUCtest/AUCreference was 0.98 (90% confidence interval range; 95-101%) and for Cmax test/Cmax reference was 0.92 (90% confidence interval range: 89-96%). The results also indicate a possible inhibition of zinc absorption by iron content of both formulations. It is concluded that Folifer-Z product is bioequivalent to Fefol-Z product.

Aspects of microbiological and chemical quality of turmus, lupin seeds debittered by soaking in water.

Eleven species of spherical lactic acid bacteria (LAB) belonging to the genera Leuconostoc, Lactococcus, Enterococcus and Pediococcus were the predominant microorganisms in 40 samples of turmus, ready-to-eat lupin seeds debittered by boiling and soaking in water. The average counts of the LAB in the 20 winter samples and the 20 summer samples were 7.4 and 8.7 log CFU/g, respectively. The averages of the Enterobacteriaceae counts were 5.1 and 6.6 log CFU/g, respectively, and the 11 species isolated belonged to the genera Enterobacter, Citrobacter, Escherichia and Klebsiella. The average yeast counts in winter and summer samples were 3 and 3.2 log CFU/g, respectively, and the 5 species isolated were in the genera Saccharomyces, Cryptococcus, Rhodotorula and Candida. Although Salmonella was not isolated from any sample and the Staphylococcus aureus count in all samples was < 1 log CFU/g, microbial hazards could be associated with the high Enterobacteriaceae counts and the presence of Escherichia coli. Total alkaloid concentration in 30% of the samples examined was higher than 0.02%, thus making the seeds a potential chemical hazard. Boiling the turmus directly before consumption and discarding the seeds with a bitter taste may help in avoiding some of the microbial and chemical hazards which could be associated with turmus consumption.

Toxicity of a new antismoking mouthwash 881010 in rats and rabbits.

Male and female rats and rabbits were used in this study to investigate the acute and subchronic toxicity of a new antismoking (A.S.) mouth wash (0.5% silver nitrate as the active ingredient). The LD50 values for i.p. administration in male and female rats were 35.7 and 37.2 mg/kg body weight, respectively. The corresponding values in male and female rabbits were 113 and 128 mg/kg body weight, respectively. The oral LD50 values of the mouthwash in male and female rats were 428 and 433 mg/kg body weight, respectively. The corresponding values in male and female rabbits were 1261 and 1320 mg/kg body weight, respectively. Postmortem and histopathological examination revealed congestion, edema, hemorrhage, and mucosal necrosis with brown pigment deposition in the upper gastrointestinal and respiratory tracts for the orally treated animals and ascitis, peritoneal fat necrosis, and pigment deposition in i.p. administered animals. Subchronic toxicity involved administration of low (1.5 mg/kg), intermediate (15 mg/kg), and high (150 mg/kg) doses of A.S. mouthwash by swabbing the oral cavity daily for 30 consecutive days. Body weight, hematologic observations, and histopathological examination showed no significant differences between control and treated animals, except for dark coloration in teeth and increased platelet counts in treated rats.

Effect of chronic cocaine administration on amino acid uptake in rat placental membrane vesicles.

This study evaluated the effects of chronic exposure to cocaine during pregnancy on amino acid uptake in placental membrane vesicles. Pregnant rats received 62 mg/kg of cocaine hydrochloride by intraperitoneal (IP) injection as a divided daily dose on gestation days 8-19 inclusive. Fetal body weights were significantly decreased by 19% in the cocaine group, while placental weights were unchanged. Placental apical membrane vesicles were prepared from control and cocaine-treated animals, and marker enzyme enrichments for alkaline phosphatase and [3H]-dihydroalprenolol binding did not differ between cocaine and control groups. Rates of uptake (10 sec) of selected radiolabeled amino acids were measured utilizing a rapid filtration technique. Na(+)-dependent apical membrane [3H]-glutamine transport (50 microM) was reduced by 95% (p < 0.05) in cocaine-treated compared to control placentas. Uptake of 50 microM [3H]-methyl aminoisobutyric acid (MeAIB) into apical membranes was also decreased by 43% (p < 0.05) in cocaine membranes. Na(+)-independent [3H]-arginine transport (10 microM), however, did not differ between control or cocaine-treated groups. In summary, chronic cocaine administration selectively inhibited the transport of glutamine and MeAIB into apical membrane vesicles, but had minimal effect on arginine transport. We postulate that this diminution in uptake may contribute to the fetal growth retardation noted in our model.

Fetoplacental growth and placental protein synthesis in rats after chronic maternal cocaine administration.

This study evaluated the effects of chronic exposure to cocaine during pregnancy on the morphology and function of the placenta. Pregnant rats received either 45 or 60 mg/kg of cocaine hydrochloride by i.p. injection as a divided daily dose on days 8 to 18 of gestation. The maternal weight gain decreased by 20% to 24% (P < .05) in the two cocaine treatment groups, whereas the placental weight was not significantly altered. Fetal growth showed a dose-related decrease in the 45- and 60-mg/kg cocaine treatment groups; fetal body weights and length were significantly decreased by 5% to 10%. The plasma levels of cocaine were 0.79 and 1.09 micrograms/ml in the 45- and 60-mg treatment dose groups, respectively; the level in the fetal plasma was 3-fold higher in the latter group. Placental tissue explants were cultured in the presence of [35S]-methionine to investigate whether cocaine exposure altered placental protein synthesis. Secreted proteins were analyzed by polyacrylamide gel electrophoresis followed by fluorography or by western blotting and immunostaining with antibodies to placental prolactin-like proteins-B and -C and growth hormone-related protein-1. The data showed that there were no quantitative or qualitative changes in placental peptide hormone secretion as a result of the cocaine treatment. These data indicate that chronic cocaine exposure in the pregnant rat is associated with fetal growth retardation in the absence of alterations in placental morphology or secretory protein synthesis.

Dermal and inhalation exposure to dimethoate.

Dermal and respiratory exposure and plasma acetylcholinesterase (ChE) activity were monitored on six workers spraying tomato crops under plastic houses with dimethoate [O,O-dimethyl S-(N-methylcarbamoylmethyl) phosphorodithoate]. The mean dermal exposure was 914 mg/day and the mean respiratory exposure was 17 mg/day. The maximum dose received by the spraymen was 18.2 mg/day. It was estimated that 84% of the dermal exposure was to the forearms and hands. Of the body areas monitored, the back of the neck received the least rate of exposure. The results also show a reduction in plasma ChE among spraymen. The mean difference was 37.1% less than the preexposure values, which exceeds the limits set by the World Health Organization.

Direct relaxant effects of garlic juice on smooth and cardiac muscles.

The effects of garlic juice on smooth and cardiac muscles of rabbit and guinea pig were tested in vitro using isolated segments of aorta, trachea and intestines and isolated rabbit hearts. Garlic juice inhibited the contractions of rabbit and guinea pig aortic rings induced by norepinephrine in Ca(2+)-free and Ca(2+)-containing Krebs-Henseleit solutions. Also, garlic juice inhibited the contractions of rabbit and guinea pig tracheal smooth muscles induced by acetylcholine and histamine, respectively, in both Ca(2+)-free and Ca(2+)-containing Krebs-Henseleit solutions. Furthermore, garlic juice inhibited the spontaneous movements of rabbit jejunum and guinea pig ileum and inhibited the force of contraction of isolated rabbit hearts in a concentration-dependent manner. All inhibitions were reversible. These data suggest that the hypotensive action of garlic juice may be due, at least in part, to a direct relaxant effect on smooth muscles.

Pesticide mortality. A Jordanian experience.

During the 13-year period of 1973-1985, at least 329 deaths in Jordan resulted from poisoning by pesticides. Organophosphates were the major compounds incriminated in 93.6% of the cases. The annual mortality rate compared with that of other countries is relatively high, and was 5.97%, 17.35%, and 2.6% per 1 million people in 1973, 1979, and 1985, respectively. The annual mortality rates due to suicidal and accidental poisoning are 61% and 35.3%, respectively: 74% of the accidentally poisoned group are children less than 10 years, while 60.7% of the suicides are 15-24 years of age. To minimize such high mortality rates from pesticide poisoning, Jordan needs to adopt more protective measures by rigorous regulation.

Hypoglycemic effects of Teucrium polium.

Teucrium polium has a folk reputation as a hypoglycemic agent. The hypoglycemic activity of an aqueous decoction of plant aerial parts was tested in normoglycemic and streptozotocin-hyperglycemic rats. Results indicate that this extract caused significant reductions in blood glucose concentration 4 h after intravenous administration and 24 h after intraperitoneal administration. This effect could be due to enhancement of peripheral metabolism of glucose rather than an increase in insulin release.

Formation of benzo[a]pyrene-DNA adducts by microsomal enzymes: comparison of maternal and fetal liver, fetal hematopoietic cells and placenta.

The formation of benzo[a]pyrene (BP)-DNA adducts was studied in vitro in the presence of microsomes prepared from the isolated labyrinth zone of the rat placenta, the hematopoietic erythroblast cells of the fetal liver, the fetal liver, as well as the maternal liver. Pregnant rats received beta-naphthoflavone (beta NF; 15 mg/kg, i.p.) on day 17 gestation. One day later, placentae, fetal and maternal livers were obtained and hematopoietic erythroblast cells were separated from hepatocytes in the fetal livers. The respective microsomal fractions were incubated in the presence of calf thymus DNA, NADPH-regenerating system and [3H]BP (300 microCi) at 37 degrees C for 30 min. Following beta NF pretreatment, the levels of covalent binding (pmol/mg DNA/mg microsomal protein) for maternal liver, fetal liver, placenta and erythroblast cells were: 28.4, 2.4, 0.31 and 3.9, respectively, with the hematopoietic erythroblast cells being the most active among fetal tissue preparations. The extent of transplacental induction compared to control was greatest in the hematopoietic cells (18-fold) followed by fetal liver (16-fold) and labyrinth zone (5-fold). Further experiments characterized the BP-DNA adducts formed by induced microsomes. DNA was isolated, purified and digested sequentially with DNase I, snake venom phosphodiesterase type II and alkaline phosphatase type III. The deoxynucleoside-BP adducts were purified on a Sephadex LH-20 column and then separated on HPLC and the adducts were quantitated radiometrically. Seven distinct adducts were separated on HPLC and named A-G in order of elution. Adduct B was prominent in all preparations (22-55% total radioactivity). The adduct profile and retention time for peak B is similar to that reported for the adduct formed by microsomal activation of 9-hydroxy BP. Peak D constituted a major fraction (19%) in maternal liver profiles in comparison with the three fetal tissue preparations (8%). In subsequent experiments, peak D was shown to be derived from reaction of (+/-)7 beta,8 alpha-dihydroxy-9 alpha,10 alpha-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE) with DNA. Peak C was unique to erythroblast cell and labyrinth profiles, while peak G was specific for maternal liver and fetal liver profiles. These results demonstrate that fetal liver and its hematopoietic cells are significant sites of BP bioactivation which may contribute to the fetal toxicity of polyaromatic hydrocarbons.

Extraction of omega- and omega-1-hydroxylauric acids with ethyl acetate results in formation of acetoxy products.

In studies of the regiospecific metabolism of lauric acid by monooxygenase enzymes, incubation medium from the reaction of [14C] lauric acid and microsomes is routinely acidified and extracted with ethyl ether. Separation of products by HPLC shows the formation of omega(12)- and omega-1(11)-hydroxylauric acids by rat liver microsomes. In a comparison of several extraction solvents, we observed that the extraction of incubation media with ethyl acetate alone was associated with the appearance of a major new metabolite peak concomitant with loss of the 12- and 11-hydroxylaurate peaks by 62 and 23%, respectively. No difference was observed between extraction procedures in the per cent recovery of radiolabel. Similar results were observed with extraction of lauric acid metabolites formed by fish liver microsomes. Acidification of the incubation media prior to ethyl acetate extraction prevented formation of the new metabolite peak. In experiments to identify the new metabolite(s), 11- and 12-hydroxylaurate products formed by rat liver microsomes were acetylated and found to show an HPLC retention time similar to that of the unknown metabolite peak formed with ethyl acetate extraction. Mass spectrometric analysis further showed that the methyl esters of 11- and 12-acetoxylauric acids were very similar to that of the methyl ester derivative of the unknown metabolite fraction. Thus, data indicate that the acetoxy derivatives of 11- and 12-hydroxylauric acids were formed by direct reaction of ethyl acetate with the laurate products formed by microsomal monooxygenase enzymes. This extraction procedure can produce a major shift in the amount and ratio of omega- and omega-1-hydroxylaurates measured in the incubation media.

Suicide by xylene ingestion. A case report and review of literature.

A 27-year-old male committed suicide by ingestion of a large quantity of xylene. The presence of xylene in the tissues of the victim was confirmed by chromatographic and spectrometric techniques. High levels of xylene were detected in blood (11 mg/dl), gastric contents (880 mg/dl), and duodenal contents (3,300 mg/dl). Histological examination of the lungs showed severe congestion and acute pulmonary edema. Review of the relevant literature is presented.

Induction of cytochrome P-450c in hematopoietic cells of fetal liver.

The transplacental inductive effect of beta-naphthoflavone (beta NF) on cytochrome P-450 isozymes was studied in separate hematopoietic and hepatocyte cells from fetal rat liver. Two fractions of dispersed fetal liver cells were isolated by Ficoll-Paque centrifugation and shown by histologic examination to be enriched in erythroblasts and hepatocytes, respectively. beta NF treatment increased ethoxyresorufin-O-deethylase activity 250-fold in both erythroblast and hepatocyte cell fractions. Polyacrylamide gel electrophoresis and immunostaining techniques showed the induction of cytochrome P-450c, but not P-450d, in erythroblast and hepatocyte fractions.

Differential induction of ethoxyresorufin-O-deethylase in tissues of the rat placenta.

The placenta of the rat during late gestation is comprised of the yolk sac membranes, labyrinth and basal zone, which are of fetal origin, and the decidua basalis, which is derived maternally. Studies investigated whether the placental monooxygenase activity induced by administration of beta-naphthoflavone (beta-NF) and 3-methylcholanthrene (3-MC) to pregnant rats was localized differentially in these separate portions of the organ. Ethoxyresorufin-O-deethylation (EROD) was measured by fluorometric assay in homogenates of the respective placental tissues and of intact fetuses. EROD was very low or undetectable in feto-placental homogenates from untreated control animals. The administration of beta-NF and 3-MC increased EROD activity 50-fold over control in labyrinth and fetal homogenates, 10- to 15-fold in decidua, 8- to 20-fold in fetal membranes and 8-fold in basal zone preparations. The apparent Km value for ethoxyresorufin was significantly lower than control for EROD in labyrinth preparations from both beta-NF- and 3-MC-treated animals. Enzyme activity in labyrinth homogenates was maximally induced by 3-MC treatment for 1 to 3 days. In contrast, EROD activity was maximal after 1 to 2 days beta-NF administration, but declined markedly with longer duration of treatments. Subsequent studies compared the in vitro effects of alpha-naphthoflavone (alpha-NF) and beta-NF on induced EROD in feto-placental homogenates. The two benzoflavones were found to be equipotent as inhibitors with IC50 values less than 1 microM for labyrinth, maternal liver and fetal preparations.(ABSTRACT TRUNCATED AT 250 WORDS)