Clinicopathologic features and treatment outcome of urinary bladder neoplasm.

More than ninety percent of bladder neoplasm is Transitional Cell Carcinoma (TCC). About 85% of patients present with symptom of painless haematuria. However haematuria is quite often intermittent so that a negative result has little meaning in ruling out the presence of bladder cancer. The present study was conducted to observe the natural history of different clinicopathologic stages of bladder cancer after transurethral resection bladder tumor (TURBT), either intravescical chemotherapy (IVC) or immunotherapy with BCG and of other forms of therapy like radio-chemotherapy (RCT) and radical surgery in few cases. A consecutive series of 52 cases with different grades and stages of bladder cancer patients were studied. Those who were noncompliant with surgery were sent for RCT. The age range of the patients was 34 to 75 with mean 53 year. Macroscopic haematuria, flank pain, microscopic haematuria, bladder irritability was found in 43(82.7%), 06(11.5%), 03(5.8%), 32(61.5%) cases respectively and coincidental ureteral TCC with hydronephrosis was found in 04(7.7%) cases for whom radical nephreureterectomy and cystectomy with ileal conduit was done. Amongst the other muscle invasive tumor only three cases were compliant to do radical surgery; rest were advised to consult with oncologist for possible RCT. Superficial bladder cancer was 19(36.5%) and invasive bladder cancer was 33(63.5%). TURBT and IVT were offered for all superficial bladder tumors. Of them 06(31.5%) patients showed recurrence during the study period. More recurrences occur in IVC group (35.7%) than immunotherapy with BCG group (20%) Re-TURBT and stage wise treatment was offered to them. All recurrent cases were G-3 tumor and were multifocal. Recurrence rate is about 30%. Screening program and structured referral system should be developed to have early diagnosis for prompt treatment and best prognosis.

Influence of aqueous extract from Neurada procumbens L. on blood pressure of rats.

Neurada procumbens is a desert plant in the Arabian Peninsula. It has been considered edible by Bedouin and has been used traditionally as a medicinal herb. During a screening test of Arabian plants, the aqueous extract of Neurada procumbens increased the blood pressure of anaesthetized normotensive rats when it was administered orally. Further studies proved it elevated the blood pressure of conscious SHR, and produced vasoconstriction on the aortic strips of rats in vitro, which was reduced partially by phentolamine. This study demonstrates that the aqueous extract of the plant has an effect of increasing blood pressure that might be mediated through alpha-adrenergic receptors. Though more investigations are needed to prove its effect in humans, the present study warns that Neurada procumbens might not be so safe as it has been considered, and people, especially those with cardiovascular diseases, should be careful when they use the plant.

Anti-nociceptive and anti-inflammatory properties of Caralluma arabica.

In the present study, a 10% ethanolic extract of Caralluma arabica at the doses of 200 and 400 mg/kg was evaluated for the antinociceptive activity using the hot plate and acetic acid induced abdominal constrictions in mice and tail flick method in rats. Oral and topical application of C. arabica extract was assessed in the present study for anti-inflammatory properties using carrageenan-induced rat paw oedema. Anti-inflammatory activity was also evaluated using cotton pellet granuloma method. C. arabica extract showed significant Anti-nociceptive properties in all the models studied. C. arabica extract significantly reduced the increase in hind paw volume induced by carrageenan injection when used orally or topically. Results of the present study confirm the use of C. arabica traditionally for the treatment of painful and inflammatory conditions and indicate transdermal absorption of the plant extract.

Neuropharmacological actions of Portulaca oleraceae L v. sativa (Hawk).

Portulaca oleracea L v. sativa (family: Portulacaceae) is a warm-climate annual, cultivated in the Arabian peninsula and used traditionally for alleviating pain and swelling. It was observed that a 10% ethanolic extract of this plant produced restriction of movement in animals during the routine screening studies. Therefore the effects of the extract on the locomotor activity, threshold to noxious stimulus, anti-convulsant activity and relaxant effects on the skeletal muscle were studied. The extract, on intraperitoneal administration, showed a significant reduction in the locomotor activity in mice, anti-nociceptive activity in rats using Tail Flick Method, an increase in the onset time of pentylenetetrazole-induced convulsions in mice and muscle relaxant activity in in vitro (rat hemidiaphragm) and in vivo (grip strength) experiments. The anti-nociceptive activity of the extract in rats was attenuated by naloxone pre-treatment indicating the involvement of opioid receptors in its anti-nociceptive effects. It is indicated from the results of the present study that P. oleracea v. sativa possesses varied effects on both the central and peripheral nervous system and the plant should be exhaustively studied for other neuropharmacological effects.

Anti-inflammatory and anti-ulcer activity of Calligonum comosum in rats.

The 10% ethanol extract of the aerial parts of Calligonum comosum (50--400 mg/kg, i.p.) significantly reduced the increase in hind paw oedema induced by carrageenan in rats. Following sub-acute oral administration of the extract (50 and 100 mg/kg, daily for 14 days), a significant anti-inflammatory activity in the cotton pellet model was observed. Pre-treatment with the extract (100, 200 and 400 mg/kg) produced a significant and dose-dependent inhibition to the acute gastric ulcers induced by phenylbutazone, indomethacin, 0.2 N NaOH and 80% ethanol.

The analgesic and anti-inflammatory effects of Portulaca oleracea L. subsp. Sativa (Haw.) Celak.

Many ethnic groups have used different species of Portulaca oleracea L., a member of the Family Portulacaceae, as vegetable and also herbal medicine against several diseases for many centuries. A review of the records in both folkloric and scientific literature indicates that Portulaca has many medicinal uses. After our previous preliminary screening of three species of the family for analgesic and anti-inflammatory properties, Portulaca oleracea L. subsp. sativa (Haw.) Celak. (a cultivar) was chosen for further work due to its abundant availability from reliable sources. The 10% ethanolic extract of the aerial parts (dried leaves and stem) showed significant anti-inflammatory and analgesic after intraperitoneal and topical but not oral administration when compared with the synthetic drug, diclofenac sodium as the active control. Results indicate this cultivar species of Portulaca also possesses some of the claimed traditional uses of the wild species in the relief of pain and inflammation.

Evaluation of the teratogenic potential of pyrazinamide in Wistar rats.

We have tested Pyrazinamide (PZA), an essential component of modern short-course tuberculosis treatment regimen, for teratogenicity using Wistar rats. The drug was given by oral intubation from 6-15 days of gestation, at doses of 0, 25, 100 and 500 mg/kg body weight per day. Reduction in body weight and food consumption were observed in the treated dams. On day 20 of gestation, all the dams were killed by cervical dislocation and signs of maternal toxicity, reproductive indices and fetal measurements were recorded. Dams given doses of 100 and 500 mg/kg had significantly higher incidence of reabsorbed fetuses, reduced litter size, and impaired neonatal growth than those given no PZA or only 25 mg/kg dose. External visceral and skeletal examination of all fetuses of PZA-treated dams showed several types of variations which were neither dose related nor having a consistent pattern. However, these variations occurred mostly in the dams treated with the dose of 500 mg/kg. In conclusion, these data show that in Wistar rats, only high doses of PZA (100 and 500 mg/kg) produced fetotoxicity. No evidence of teratogenic effect of the drug was observed.

Effect of acute administration of fish oil (omega-3 marine triglyceride) on gastric ulceration and secretion induced by various ulcerogenic and necrotizing agents in rats.

The fish oil commercially known as Marine-25 (omega-3 marine triglyceride) is an eicosapentaenoic acid (EPA)-rich oil. It was investigated for its ability to inhibit gastric secretion and to protect the gastric mucosa against the injuries caused by pyloric ligation, non-steroidal anti-inflammatory drugs (NSAIDs--aspirin and indomethacin), reserpine, hypothermic restraint stress and necrotizing agents [0.6 M HCl 0.2 M NaOH or 80% (v/v) aqueous ethanol]. The results showed that the fish oil, at a dose of 5 or 10 ml/kg body weight, provided significant protection in the various experimental models used. It produced a significant inhibition of gastric mucosal damage induced by pyloric ligation, NSAIDs, reserpine or hypothermic restraint ulcers. Fish oil also exerted a significant inhibitory action on gastric mucosal lesions produced by various necrotizing agents. Our findings show that fish oil rich in eicosapentaenoic acid possesses both antisecretory and antiulcerogenic effects.

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.

Evaluation of teratogenic potential of khat (Catha edulis Forsk.) in rats.

The embryotoxic and teratogenic effects of khat (Catha edulis Forsk.), a plant chewed by the people of Eastern Africa and Southern Arabia to attain a state of euphoria and stimulation, was studied in Wistar rats. Methanolic extract of khat was administered orally by gavage to rats during days from 6 to 15 of gestation at doses of 0, 125, 250 and 500 mg/kg. body weight/day. Khat reduced the food consumption and maternal weight gain and also lowered the food efficiency index, as compared to control mothers. On day 20 of gestation, all dams were sacrificed by cervical dislocation, cesarean sections were performed and maternal and fetal toxicities were assessed. The administration of khat had no effect on fetal sex ratio. However, at a dose of 125 mg/kg body weight and above, it produced a significant increase in resorptions and fetal wastage. Khat administration in utero also reduced the litter size and caused intrauterine growth retardation. External, visceral and skeletal examination of the fetus of treated dams showed several types of malformations and variations in all the groups of animals. However, a consistent tendency of abnormalities was observed in the highest dosed (500 mg/kg) group. The data of the present study revealed that khat retarded fetal growth and induced terata. The present observations indicate that khat possesses both embryotoxic as well as teratogenic properties. The developmental toxicities of khat are dose-related.

The effect of maternal administration of enalapril on fetal development in the rat.

Enalapril (MK, 421), an angiotensin converting enzyme inhibitor, was tested for teratogenicity using Wistar rats. The drug was given by oral intubation, from 6-15 days of gestation, at the doses of 0, 3, 10 and 30 mg/kg/day. Reduction in body weight and food consumption were observed in the treated dams. However, food efficiency index, assessed at different periods of gestation was found to be unaffected. On day 20 of gestation, all the dams were sacrificed by cervical dislocation and sign of maternal toxicity, reproduction indices and fetal measures were recorded. The dams treated with enalapril at only the doses of 10 and 30 mg/kg, produced significant decrease in numbers of implants, litter size and incidence of reabsorbed fetuses, and also reduced neonatal growth. No such effects were observed at the lowest dose level (3 mg/kg) used. External, visceral and skeletal examinations of the fetuses of enalapril-treated dams showed several types of variations in all groups, but no consistent pattern were observed. However, a slight increase in skeletal variations was seen with the highest dose (30 mg/kg) group. The data of the present study under the conditions described herein and at the doses employed, revealed no evidence of teratogenesis, but numerous deleterious effects on the fetus were evident.

The effect of maternal administration of captopril on fetal development in rat.

Captopril an angiotensin converting enzyme (ACE) inhibitor, was evaluated for teratogenic potential in Wistar rats. The drug was administered daily from 6 to 15 day of gestation by gavage (0, 3, 10 and 30 mg/kg/day) and perinatal studies were conducted. Captopril decreased food consumption and suppressed gain in body weight. However, no alteration in food efficiency index was observed. The treatment of rats with captopril in doses of 10 and 30 mg/kg, significantly reduced the mean number of implants per litter size and produced intrauterine growth retardation. The incidence of external and visceral malformations were neither dose related nor significantly different from those of controls. In addition, animal treated with these dose levels showed decreased ossification of digits, sternum and skull of the offsprings. The data of the present study indicates that captopril was not found to be teratogenic to Wistar rats. However, adverse effects on intrauterine growth, fetal ossification, neonatal growth and survival rate were seen among the pups.

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.

An evaluation of the male reproductive toxicity of cathinone.

(-)-Cathinone is the major psychoactive component of khat plant (Catha edulis Forssk.). Khat has been shown to produce reproductive toxicity in human beings and experimental animals. However, the chemical constituents of khat leaves responsible for sexual dysfunction are not known. In the present study cathinone enantiomers have been investigated for their reproductive toxicity in rats. Cathinone produced a dose-dependent decrease in food consumption and suppressed the gain in body weight. There was a significant decrease in sperm count and motility and increase in the number of abnormal sperms in cathinone treated animals. Histopathological examination of testes revealed degeneration of interstitial tissue, cellular infiltration and atrophy of Sertoli and Leydig's cells in cathinone treated animals. Cathinone also produced a significant decrease in plasma testosterone levels of the rats. Although both enantiomers of cathinone produced deleterious effects on male reproductive system, (-)-cathinone was found to be more toxic. From this study it may be concluded that the cathinone content in khat may be partially or totally responsible for the reproductive toxicity in khat chewers.

Effect of khatamines and their enantiomers on plasma triiodothyronine and thyroxine levels in normal Wistar rats.

The effect of cathinone and N-formylnorephedrine, two psychoactive amines of khat (Catha edulis Forsk.) and their enantiomers have been studied on plasma levels of triiodothyronine (T3) and thyroxine (T4) in male Wistar rats. The rats were injected with 5, 10 and 30 mg/kg, body weight of four khatamines and the blood samples were collected 2 h after their administration. In the separate set of experiments the effect of these khatamines at 1, 2 and 4 h after their administration was also examined. All the khatamines failed to produce a significant dose dependent increase in T3 and T4 levels in the dose of 5 mg/kg. However, all of these compounds produced a significant dose dependent increase in T3 and T4 levels at higher doses but only T4 levels were increased following the dose of 10 mg/kg. Our studies on the effect of khatamines in T3 and T4 levels at various times showed a significant increase in T4 levels in all the four groups treated with various khatamines and the peak effect was observed at 2 h in case of (-)- and (+)-cathinone and 4 h in case of (-) and (+)N-formylnorephedrine. This study suggests that the symptoms observed in khat chewers including hyperthermia, anorexia, and metabolic changes may to some extent be attributed to the thyroid stimulating effect of khatamines. However, further studies are needed to establish the mechanism of release of thyroid hormones by these compounds and their involvement in the pharmacological effects.

Comparative study of cathinone and amphetamine on brown adipose thermogenesis.

The effect of cathinone and amphetamine on brown adipose tissue thermogenesis and its modification with propranolol and timolol has been studied in rats. Both cathinone and amphetamine produced significant dose dependent increases in intracapsular brown adipose tissue (IBAT) and rectal temperatures. Amphetamine was found to be three times more potent as compared to cathinone, on a dose basis. Pretreatment of animals with propranolol and timolol individually inhibited cathinone and amphetamine induced hyperthermia. These findings suggest the involvement of beta adrenergic receptors in cathinone and amphetamine induced thermogenesis.

Post-coital antifertility activity of the seeds of Coriandrum sativum in rats.

Effect of the aqueous extract of fresh coriander (Coriandrum sativum) seeds has been studied on female fertility in rats. Parameters included effects on oestrus cycle, implantation, foetal loss, abortion, teratogenicity and serum progesterone levels on days 5, 12 and 20 of the pregnancy. The extract at doses of 250 and 500 mg/kg orally produced a dose-dependent significant anti-implantation effect, but failed to produce complete infertility. Treatment of animals during day-8 to day-12 and day-12 to day-20 of the pregnancy did not produce any significant abortifacient activity. There was no significant change in the weight and length of the foetuses delivered by rats treated with the extract and no abnormalities were seen in the organs of the offsprings. The extracts produced a significant decrease in serum progesterone levels on day-5 of pregnancy which may be responsible for the anti-implantation effect observed in this study.

Quantitative studies on acetylcholinesterase in seven species of digenetic trematodes.

Quantitative estimation of absolute levels and in vitro release of acetylcholinesterase (AChE) in seven species of digenetic trematodes: Isoparorchis hypselobagri from the swim bladder of catfish, Wallago attu; Srivastavaia indica and Gastrothylax crumenifer from the rumen, and Gigantocotyle explanatum from the liver of the water buffalo, Bubalus bubalis; Fasciolopsis buski, Echinostoma malayanum from the small intestine and Gastrodiscoides hominis from the caecum of the pig, Sus scrofa revealed that the enzyme is present in remarkably high quantities in species which inhibit gastrointestinal tract compared with those that parasitize liver and swim bladder. The rate of in vitro release of AChE also varies with the species which supports the view that such differential secretion probably takes place in situ as well to counteract peristalsis and it is a biochemical adaptation on the part of these trematodes.