Results from the Survey of Antibiotic Resistance (SOAR) 2015-17 in the Middle East (Kuwait, Lebanon and Saudi Arabia): data based on CLSI, EUCAST (dose-specific) and pharmacokinetic/pharmacodynamic (PK/PD) breakpoints.

OBJECTIVES: To determine antibiotic susceptibility of Streptococcus pneumoniae and Haemophilus influenzae isolates from community-acquired respiratory tract infections (CA-RTIs) collected in 2015-17 from Kuwait, Lebanon and Saudi Arabia. METHODS: MICs were determined by CLSI broth microdilution and susceptibility was assessed using CLSI, EUCAST (dose-specific) and pharmacokinetic/pharmacodynamic (PK/PD) breakpoints. RESULTS: A total of 139 S. pneumoniae isolates were collected from four centres in Kuwait, Lebanon and Saudi Arabia in 2015-17 and 55 H. influenzae isolates were collected and analysed from Saudi Arabia over the same time period. Pneumococci from all three countries were commonly non-susceptible to penicillin based on CLSI oral or low-dose IV penicillin using EUCAST breakpoints (39% in Kuwait to 57.1% in Lebanon) but by CLSI IV and EUCAST high-dose breakpoints most isolates were susceptible (∼90% in Kuwait and Saudi Arabia, and 100% in Lebanon). Isolates from Lebanon were highly susceptible to most other antibiotics (>90%) except cefaclor, oral cefuroxime and cefpodoxime (EUCAST breakpoints only). Overall, susceptibility was significantly lower in Kuwait and Saudi Arabia than Lebanon. Although all H. influenzae isolates (Saudi Arabia only) were ß-lactamase negative, 3.6% and 12.7% were ampicillin resistant by CLSI and EUCAST breakpoints, respectively. Otherwise susceptibility was high in H. influenzae. The application of different EUCAST breakpoints for low and higher doses for some of the antibiotics (amoxicillin, amoxicillin/clavulanic acid, ampicillin, penicillin, ceftriaxone, clarithromycin, erythromycin, levofloxacin and trimethoprim/sulfamethoxazole) allowed, for the first time in a SOAR study, the effect of raising the dosage on susceptibility to be quantified. CONCLUSIONS: Relatively low antibiotic susceptibility was observed in S. pneumoniae from Kuwait and Saudi Arabia in contrast to Lebanon, where rates of susceptibility were generally higher. Isolates of H. influenzae from Saudi Arabia were susceptible to most antibiotics. These factors are important in decision making for empirical therapy of CA-RTIs.

Retrospective analysis of pemphigoid gestationis in 32 Saudi patients - Clinicopathological features and a literature review.

BACKGROUND AND OBJECTIVES: Pemphigoid gestationis (PG) is a rare autoimmune-mediated blistering disease that mainly affects pregnant women in their 2nd or 3rd trimester and immediate postpartum period. In addition to the clinical assessment, the diagnosis of PG is usually confirmed by histological and immunological studies. PG usually flares up at the time of delivery and spontaneously improves postpartum. Prompt recognition and appropriate management may reduce morbidity associated with this disorder. This study aimed to determine the clinical, histopathological features and treatment of PG of Saudi patients. MATERIALS AND METHODS: A retrospective study of 32 patients with pemphigoid gestationis (PG) was conducted from 1990 to 2014 at King Khalid University Hospital and Derma Medical Center, Riyadh, Saudi Arabia. Data regarding epidemiology, medical histories, clinical course, diagnostic test results and management were collected and analyzed. RESULTS: A total of 32 patients with PG were analyzed. The mean age was 31.9 years. Seventy-four percent of the patients were multigravidas, and 2 patients were primigravidas. One hundred percent of the cases were singleton pregnancies. Eighty-four percent of the cases had the onset of PG during the 2nd and 3rd trimesters. One hundred percent of patients complained of pruritus, and 94% reported this as the first symptom. Erythematous plaques and vesiculobullous eruption were the most common skin presentation. The primary sites of involvement were the abdomen, trunk, lower (mainly thighs) and upper limbs. The face and mucus membranes were rarely involved. Fifty percent of patients had recurrent symptoms with their next pregnancy. Direct immunofluorescence revealed a linear deposition of the third component of the complement along the basement membrane zone in all cases (C3),while most of the cases showed positive linear deposition of IgG. Seventy five percent of our patients had a good response to oral corticosteroids, and only one patient needed IVIG. The vast majority of the patients (61%) became free of symptoms within 1-2 months of treatment. In 53% of the patients, maternal and fetal outcomes were good with no complications. Six pregnancies were complicated by preterm labor, 2 experienced IUGR (intrauterine growth restriction), and 2 had an abortion or stillbirth. CONCLUSION: Our study does not differ dramatically when comparing the onset of PG, the high frequency of multigravida women, the clinical course and good patient outcomes but we observed that the first attack extended from primigravida to 11th pregnancy and slight increase in recurrence rate. Finally the timely diagnosis and appropriate management of PG may improve both maternal and neonatal outcome.

Therapeutic efficacy of chloroquine against uncomplicated, Plasmodium falciparum malaria in south-western Saudi Arabia.

The results of annual random screening indicated that Plasmodium falciparum strains showing chloroquine (CQ) resistance in vitro became increasingly common in the Jazan region of south-western Saudi Arabia between 1986 and 1998 (chi(2) for trend = 50.027; P < 0.001). This worrying trend and the emergence of a micro-epidemic in 1997-1998 prompted an assessment of the therapeutic efficacy of CQ against uncomplicated, P. falciparum malaria in the area. The in-vivo testing of sensitivity to CQ was carried out in 291 clinically manifest, microscopically positive cases of P. falciparum malaria. Most of these patients (88%) were successfully treated with a single standard regimen of CQ therapy. The other 36 patients (12%) showed early treatment failure or a poor response to the CQ, although all of these were then successfully treated with a single standard dose of sulfadoxine-pyrimethamine (Fansidar), as a replacement therapy. Those unsuccessfully treated with CQ were generally younger (t = 2.625; P = 0.01) and tended to have higher body temperatures (t = -2.62; P = 0.012) and higher levels of parasitaemia at initial presentation (P > 0.000) than those who responded well to the drug. Although CQ remains a reasonably effective drug for the treatment of malaria in the Jazan region, and therefore will be kept as the first-line drug for the foreseeable future, failure of CQ efficacy must be carefully monitored in the area.

Toxicity studies in mice of common spices, Cinnamomum zeylanicum bark and Piper longum fruits.

Acute (24 hours) and chronic (90 days) oral toxicity studies on the ethanolic extracts of common spices Cinnamomum zeylanicum Nees bark and Piper longum L. fruits were carried out in mice. Acute dosages were 0.5, 1.0 and 3 g/kg while the chronic dosage was 100 mg/kg/day. All external morphological, hematological and spermatogenic changes, in addition to body weight and vital organ weights, were recorded. The extracts of both the plants caused no significant acute or chronic mortality compared to the control during this study. During chronic treatment there was no significant change in the pre- and post treatment body weight of the test animals while the weight gain in the control group was significant. C. zeylanicum treatment caused reduction in liver weight while P. longum caused a significant increase in the weight of the lungs and spleen of the treated animals compared to the control. Hematological studies revealed a significant fall in hemoglobin level of C. zeylanicum treated animals. Both of the extracts induced a significant increase in reproductive organ weights, sperm motility, sperm count and failed to illicit any spermatotoxic effect.

Biochemical basis of sodium valproate hepatotoxicity and renal tubular disorder: time dependence of peroxidative injury.

Mice fed with sodium valproate for 7, 14 and 21 days were evaluated for hepatotoxicity and renal tubular disorder. The drug was administered as an aqueous solution with an increasing concentration up to five days gradually reaching up to 0.71% w/v, which persisted throughout the study period. Mice fed with sodium valproate for 7, 14 and 21 days showed, marked hepatic injury and renal tubular disorder, evidenced by increased levels of malondialdehyde as a measure of lipid peroxidation. Administration of sodium valproate affected the glutathione contents both in liver and kidney tissue at all the three time points. However, this reduction in glutathione concentration was more pronounced in kidney when compared to control group. These results support the hypothesis that lipid peroxidation mediates the effect of sodium valproate on liver and kidney. Furthermore, the valproate induced toxicity is time related and the increase in lipid peroxide levels and depletion of glutathione occur time dependent even if the dose is clinically appropriate.

Integration of schistosomiasis-control activities into the primary-health-care system in the Gizan region, Saudi Arabia.

A few decades ago, the prevalence of Schistosoma haematobium infection in the human inhabitants of the Gizan region of Saudi Arabia was very high (43%-91%). A vertical programme for the control of the disease, by case finding, treatment of infected individuals and by chemical snail control, was begun in 1974 and led to significant reductions in prevalence in most areas. In 1989 the control activities were gradually integrated into the primary-health-care (PHC) system. Several schools in the area recently participated in the detection of ova (among schoolchildren and neighbouring communities) and organized health-education sessions. The records taken during the vertical and PHC programmes indicate that there were more diagnoses and higher chemotherapy coverage in the latter. The PHC programme has maintained the overall prevalence of infection at an extremely low level (< 1%) and the infection has been completely eradicated in several areas. The participation of schools proved to be particularly useful in terms of population coverage and health education.

PIP: A few decades ago, 43-91% of people living in the Gizan region of Saudi Arabia were infected with Schistosoma haematobium, the dominant schistosome in the region and one which is endemic in several provinces. However, a vertical disease control program comprised of case finding, the treatment of infected individuals, and chemical snail control launched in 1974 led to significant reductions in prevalence in most areas. By 1988, the overall prevalence of S. haematobium infection in Gizan had fallen to 1.6%. As the infection rate dropped to about 1% in many areas, the use of the vertical approach became less economically justifiable, and in 1989, control activities were gradually integrated into the primary health care (PHC) system. Several schools in the area recently participated in the detection of ova among schoolchildren and in neighboring communities, as well as in health education sessions. Records taken during the vertical and PHC programs indicate that there were more diagnoses and a higher degree of chemotherapy coverage in the PHC programs. The PHC program has maintained the overall prevalence of infection at under 1% and infection has been completely eradicated in several areas. The schools' participation was particularly helpful in terms of population coverage and health education.

Evaluation of the antiinflammatory activity of sodium valproate in rats and mice.

1. Treatment of rats with sodium valproate (100, 200 and 400 mg/kg i.p.) reduced the paw oedema induced by carrageenan by 36, 15 and 48%, respectively, within 3 h . 2. The effect produced by the higher dose (400 mg/kg) was equivalent to that produced by indomethacin (100 mg/kg). At 100 and 400 mg/kg, sodium valproate decreased the granuloma formation by a significant level. Similar doses of sodium valproate did not affect the rectal temperature in yeast-fevered mice, except with a dose of 200 mg/kg, which showed a significant decrease at 180 and 240 min posttreatment. 3. In comparison, sodium salicylate reduced the hyperthermia very significantly throughout the study period. 4. In normothermic mice, the rectal temperature changed only with a 400 mg/kg dose, but did not respond to lower SV doses. 5. The results indicate that sodium valproate, useful clinically as an epileptic drug, may have a potential therapeutic use as a mild antiinflammatory agent.

Effect of (-)-cathinone, a psychoactive alkaloid from khat (Catha edulis Forsk.) and caffeine on sexual behaviour in rats.

The effect of (-)-cathinone, caffeine and their combinations was studied on the sexual behaviour of male rats. Male sexual activities were assessed by recording the erectile responses (grooming of genitalis, yawning/stretching and homosexual mounting), in the absence of females. The copulatory behaviour was observed by caging males with receptive females brought into oestrus with s.c. injection of oestradiol benzoate and progesterone. The copulatory pattern of male rats (mounting, intromissions, ejaculations and refractory period) was recorded. The oral treatment of cathinone (5 mg kg-1 day-1), caffeine (50 mg kg-1 day-1) and their combinations for 15 days increased arousal (motivation) in male rats as evidenced by increased mounting performance and anogenital investigatory behaviour. However, erectile and ejaculatory responses, measured in the present study, showed no stimulant effect. It is conceivable from the present results that cathinone, the psychostimulant constituent of khat modified masculine pattern behaviour and caffeine also changed the effect of cathinone when administered concomitantly. However, our data provide no evidence that cathinone could be considered as an aphrodisiac.

Effect of ambrein, a major constituent of ambergris, on masculine sexual behavior in rats.

The effect of ambrein, a major constituent of ambergris, was studied on the sexual behavior of male rats. The rats were administered ambrein in doses of 100 and 300 mg/kg body weight. Male sexual activities were assessed by recording the erectile responses (penile erection) and homosexual mountings in the absence of female. The copulatory studies were carried out by caging males with receptive females brought into estrus with subcutaneous injections of estradiol benzoate and progesterone. The copulatory pattern of treated male rats (mountings, intromissions, ejaculations and refractory period), the pendiculations (yawns/stretches) and orientation activities towards females, the environment and themselves, were recorded. Ambrein produced recurrent episodes of penile erection, a dose-dependent, vigorous and repetitive increase in intromissions and an increased anogenital investigatory behavior, identifying the drug used in the present study as a sexual stimulant. It is conceivable from the present results that the ambrein-modified masculine sexual behavior in male rats supports the folk use of this drug as an aphrodisiac.

Comparative skin testing with PPD tuberculin, Mycobacterium avium and M. scrofulaceum sensitin in schoolchildren in Saudi Arabia.

SETTING: Jizan region, Saudi Arabia. OBJECTIVE: To test methodology for studies of tuberculin sensitivity and effectiveness of BCG vaccination programme. DESIGN: School children (n = 315) aged 6-12 years simultaneously tested intradermally with PPD tuberculin RT23, 2TU and 0.1 microgram Mycobacterium avium or M. scrofulaceum sensitin. Presence of BCG scar as evidence of previous BCG vaccination. Cervical lymph nodes palpated. RESULTS: BCG coverage was 75%. The prevalences of positive reactions (induration > or = 6 mm) were higher among children with than without scar. Prevalences of positive reactions to PPD and M. scrofulaceum sensitin were higher among girls than boys. In children with scar, the mean size of positive reactions to PPD was larger among girls than boys, and the prevalence of positive reactions was smaller in this group among children with than without palpable cervical lymph nodes. The sizes of reactions both to M. avium and to M. scrofulaceum sensitin were correlated to the size of the tuberculin reactions. Previous admission to hospital was reported less often by children with than without scar. CONCLUSIONS: The technique applied and training of staff was satisfactory. In further studies, however, we will apply three simultaneous tests to each person.

Pharmacological and safety evaluation studies on Lepidium sativum L., Seeds.

An ethanolic extract of Cress (Lepidium sativum L.) seeds has been studied for anti-inflammatory, antipyretic and analgesic activities and to evaluate the safety of their acute and chronic use in rodents. The extract significantly inhibited carrageenan-induced paw edema and reduced the yeast-induced hyperpyrexia. It also prolonged the reaction time of mice on the hot plate. However, the extract exacerbated indomethacin-induced gastric mucosal damage. The coagulation studies showed a significant increase in fibrinogen level and an insignificant decrease in prothrombin time, confirming its coagulating property. The toxicity tests showed that the administration of extract in single doses of 0.5 to 3.0g/kg did not produce any adverse effects or mortality in mice, whereas the animals treated with extract (100 mg/kg/day) for a period of 3 months in drinking water showed no symptoms of toxicity except a statistically insignificant higher mortality rate. These findings suggest that the seeds of Cress (L. sativum) possess significant anti-inflammatory, antipyretic, analgesic and coagulant activities, and are free from serious side or toxic effects.

The quipazine- and TFMPP-increased conditioned avoidance response in rats: role of 5HT1C/5-HT2 receptors.

The role of serotonin (5-HT) in the acquisition of the conditioned avoidance response was investigated. The effects of different serotonin agonists and antagonists, administered prior to learning sessions, were studied in groups of naive rats using the two-way shuttle box. Quipazine, an agonist at 5-HT1B/1C/2 receptors, significantly increased avoidance responding in a dose-dependent manner (1.25-10 mg/kg, s.c.). The putative 5-HT1B/1C receptor agonist TFMPP (1-[m-trifluoromethylphenyl] piperazine) at doses of 1.25 and 2.5 mg/kg (s.c.), increased acquisition of conditioned avoidance but showed no significant difference from control at doses of 5 and 10 mg/kg. The 5-HT1A agonist, buspirone, significantly decreased acquisition of conditioned avoidance. Increased acquisition of conditioned avoidance induced by either quipazine or TFMPP was effectively antagonized by the mixed 5-HT 1C/2 receptor antagonists, ketanserin (0.2 and 2 mg/kg, s.c.) and mianserin (1 mg/kg, s.c.). In contrast, spiperone (5-HT1A/2 receptors antagonist: 0.2 mg/kg, s.c.) only inhibited the increased acquisition induced by TFMPP. On the other hand, the 5-HT1A/1B receptors antagonist, pindolol, failed to antagonize the increase in acquisition of conditioned avoidance caused by quipazine or TFMPP. These results suggest that quipazine increases the conditioned avoidance behaviour by an action that might be mediated through stimulation of 5-HT1C receptors. The acquisition of conditioned avoidance induced by TFMPP, which was blocked by ketanserin, mianserin and spiperone but not by pindolol, suggests the involvement of 5-HT1C/2 receptors in the action of TFMPP.

Protective effect of Swertia chirata against indomethacin and other ulcerogenic agent-induced gastric ulcers.

The effect of Swertia chirata has been studied on experimentally induced gastric ulcers in rats. The ethanolic extract of chirata significantly reduced the intensity of gastric mucosal damage induced by indomethacin and necrotizing agents. It produced a significant decrease in gastric secretion in pylorus-ligated rats. The extract inhibited acetylcholine-induced contraction of guinea pig ileum, suggesting its anti-cholinergic activity. Pretreatment of rats with the extract significantly prevented ethanol-induced gastric wall mucus depletion and restored the non-protein sulfhydryl (NP-SH) content in the glandular stomachs. These findings support the use of chirata for the treatment of gastric ulcers in traditional medicine.

Toxicity studies on Alpinia galanga and Curcuma longa.

Acute (24 h) and chronic (90 days) oral toxicity studies on the ethanolic extracts of the rhizomes of Alpinia galanga and Curcuma longa were carried out in mice. Acute dosages were 0.5, 1.0, and 3 g/kg body weight while the chronic dosage was 100 mg/kg/day as the extract. All external morphological, hematological, and spermatogenic changes, in addition to body weight and vital organ weights were recorded. During this investigation no significant mortality as compared to the controls was observed. The weight gain in the A. galanga treated animals was significant as in the control group while the C. longa-treated animals gained no significant weight after chronic treatment. C. longa treatment induced significant changes in heart and lungs weights upon chronic treatment. Hematological studies revealed a significant rise in the RBC level of A. galanga-treated animals and a significant fall in the WBC and RBC levels of the C. longa-treated animals as compared to the controls. The gain in weights of sexual organs and increased sperm motility and sperm counts were observed in both groups of extract-treated male mice, however, these changes were highly significant in the A. galanga-treated group. Both extracts failed to show any spermatotoxic effects.

Effect of praziquantel and oxamniquine on prostacyclin synthesis by the rat arterial and myometrial tissues.

1. The influence of the two antischistosomal drugs (+/-) praziquantel and (+/-) oxamniquine on PGI2 synthesis by the male rat thoracic aorta and day-20 pregnant rat myometrium in vitro was investigated using a rat platelet antiaggregatory bioassay method. 2. Pretreatment of the tissues with praziquantel (64-512 microM) or oxamniquine (36-288 microM) for 30 min at 37 degrees C significantly inhibited basal PGI2 synthesis in a concentration-dependent manner (P less than 0.005, n = 5-6). 3. Both drugs failed to inhibit PGI2 synthesis in presence of exogenous arachidonic acid (AA) (16.6 microM). 4. Furthermore, they did not antagonize AA (4 nmol kg-1)-induced hypotension in urethane-anaesthetized rats. Thus, the drugs seemed to act via inhibition of phospholipase A2 enzyme (PLA2). 5. The highly lipophilic drugs may interact with membrane phospholipids resulting in prevention of interaction between the substrates and the enzyme's active site.

Toxicity studies in mice of ethanol extracts of Foeniculum vulgare fruit and Ruta chalepensis aerial parts.

Acute (24-h) and chronic (90-day) oral toxicity studies on the ethanolic extracts of Foeniculum vulgare fruit and Ruta chalepensis aerial parts were carried out in mice. Acute dosages were 0.5, 1.0 and 3 g/kg while the chronic dosage was 100 mg/kg per day of extract. All external morphological, haematological and spermatogenic changes, in addition to body and vital organ weights were recorded. The extracts caused no significant acute or chronic mortality as compared to controls during this investigation. The treated male mice gained significant weight during chronic treatment while a loss or no significant change in weight was noticed in the female mice treated with the same extracts. Haematological studies revealed a significant fall in RBC level of R. chalepensis-treated animals. Both the extracts failed to show spermatotoxic effects.

Influence of chemotherapeutic agents on prostacyclin synthesis. II. Effects of tetracycline and penicillin G on prostacyclin synthesis by the rat thoracic aorta and myometrial tissues.

The influence of the two antibiotics tetracycline hydrochloride (T) and penicillin G sodium (P) on PGI2 synthesis by the male rat thoracic aorta and day-20 pregnant rat myometrium was investigated in vitro using a rat platelet antiaggregatory bioassay method. Pretreatment of the tissues for 30 min at 37 degrees C with T (21-168 microM) or P (28-224 microM) significantly inhibited PGI2 synthesis in absence or presence of exogenous arachidonic acid (AA) (16.6 microM), (P less than 0.01, n = 5-6). Furthermore, pretreatment of rats with the two drugs (T 11 and P 175 mu mole kg-1 for 30 min) significantly antagonised AA (4 n mole kg-1)-induced hypotension in urethane-anaesthetised rats. They also (T 0.5-4 and P 1-6 microM) antagonised AA-induced aggregation in rabbit citrated platelet-rich plasma. T failed to affect ADP-induced aggregation to any significant level whereas P (3-6 microM) reduced ADP-induced aggregation. The drugs seemed to interfere with the action of the PG endoperoxide synthase (or PG cyclooxygenase) enzyme resulting in decreased formation of PGG2 and PGH2. Such an effect may have resulted from the induced formation of toxic [OH-] radicals and/or inhibition of O2 uptake by the tissues under the influence of the drugs. The demonstrated inherent property of these two antibiotics to inhibit the synthesis of the potent vasodilator, platelet antiaggregatory, anticonvulsant and inhibitor of gastric acid secretion--PGI2, may partly contribute towards better understanding of the biochemical mechanisms that underlie some of the previously known but poorly understood actions of these antibiotics. Furthermore, since good evidence exists for the involvement of excessive uterine prostaglandin synthesis in dysmenorrhoea and premature deliveries, it is suggested that the potential benefits of T or P in these two disorders be investigated.

Effect of Salvia haematodes on sexual behaviour of male rats.

The effect of an ethanolic extract of Salvia haematodes roots was studied on the sexual behaviour of male rats. In the initial experiments, male sexual responses were assessed by recording penile erection, licking and grooming of genitals and copulatory movement in absence of females. In the second set, copulatory behaviour was observed by caging males with a receptive female brought into estrus with s.c. injection of estradiol benzoate and progesterone. The frequencies of mounting and intromission and latency of the ejaculation were recorded. The results show that the extract (500 mg/kg, orally) produced a significant increase in episodes of penile erection. The drug was found to enhance the orientation of males towards the female by increased anogenital investigatory behaviour and enhanced licking and grooming of the genitals. The extract also increased the ejaculation latency. These findings support the folk use of this plant as aphrodisiac and for the treatment of premature ejaculation.

Effects of N-methyl- and N-isobutyl-1,2-diphenyl ethanol amines on the spontaneous and evoked contractions in the rat isolated uterus.

1. The effects of N-methyl- and N-isobutyl-1,2-diphenyl ethanol amine (compounds M & E), respectively and diltiazem (D) were examined on the spontaneous and evoked uterine contractions of pregnant rats in vitro. 2. Addition of compound M (75-300 microM), compound E (15-60 microM) or D (100-400 nM) to the uterine tissues, inhibited the spontaneous contractions in a dose-dependent manner. The potency order was D greater than E greater than M. 3. The inhibitions were reversed by elevating the extracellular Ca2+ concentration by 20 mM. The compounds also antagonised CaCl2-evoked contractions. 4. Treatment of rats with either compound during pregnancy days (1-16) did not affect the implantation process and did not induce any teratogenicity. 5. The uterine inhibitory effects of the compounds may be due to blockade of uterine Ca2+ channels.

Influence of diethylcarbamazine and mefloquine on PGI2 synthesis by the rat thoracic aorta and myometrial tissues.

1. The influence of the antifilarial drug diethylcarbamazine citrate (D) and DL-erythro mefloquine hydrochloride (Mf) on PGI2 synthesis by the male rat thoracic aorta and day-20 pregnant rat myometrium was investigated in vitro using a rat platelet antiaggregatory bioassay method. 2. Pretreatment of the tissues with D (25.5-204 microM) or Mf (24-192 microM) for 30 min at 37 degrees C significantly inhibited PGI2 synthesis in a concentration-dependent manner. 3. D exhibited its inhibitory effect even in presence of exogenous arachidonic acid (AA) (16.6 microM) whereas Mf lost its inhibitory effect in presence of AA. 4. Pretreatment of urethane-anaesthetized rats with D (32 mumol kg-1) but not Mf (7.5 mumol kg-1) for 30 min significantly antagonized AA (4 nmol kg-1)-induced hypotension. 5. Furthermore, D (0.25-0.5 microM) antagonized AA-induced aggregation in rabbit platelet-rich plasma without affecting that of ADP. 6. D seemed to interfere with the action of the PG endoperoxide synthase (PG cyclooxygenase) whereas Mf seemed to interfere with the action of phospholipase A2 (PLA2) enzyme. 7. D may have exerted its effect via release of toxic O2 radicals whereas Mf effect may have been due to an interaction with PLA2 substrate phospholipids. 8. The demonstrated inherent property of these two drugs to inhibit the synthesis of the potent vasodilator, platelet antiaggregatory, anticonvulsant and antiinflammatory mediator PGI2 may partly contribute towards better understanding of the biochemical mechanisms that underly some of the previously known but poorly understood actions of these drugs.