DARU Journal of Pharmaceutical Sciences
Year:2004 | Volume:12 | Issue:4|Papers Count:8

The aerial part of Pineapple weed (Matricaria matricarioides), an adulterant of Chamomile, was investigated for its chemical constituents. Nine compounds were isolated and identified as two spiroethers [cis - en - yn - dicycloether 1 and trans - en - yn - dicycloether 2], three coumarins [7 - methoxycoumarin (Herniarin) 3, umbelliferone 4 and 7 - methoxy - 3, 4 -dihydrocoumarin 5], phytol 6, luteolin - 7 - glucoside 7, (Z) - 2 - ß - D - Glucopyranosyloxyl - 4 - methoxycinnamic acid 8, and (E) - 2 - ß -D-Glucopyranosyloxyl - 4 -methoxycinnamic acid 9. By GC-MS analysis, the major components of the steam distilled volatile oil were identified as trans-en-yn-dicycloether and cis-en- yn-dicycloether, with the trans-form being more abundant than the cis-form. The results indicated some similarities between the constituents of Pineapple weed and those of German Chamomile. All these nine compounds are reported for the first time from Pineapple weed growing in Newfoundland. Compound 5 is reported from this plant genus for the first time.

In this study the antinoiciceptive and histopathological effects of the methanolic extract of fumaria parviflora Lam. in animal models was investigated. For this purpose, the antinociceptive effects of percolated and soxhlet extracts were evaluated in mice subjected to acute thermal (hot-plate) and persistent chemical (formalin) pain stimuli. Intraperitoneal (i.p.) injection of the percolated extract evoked significant antinociceptive effects at a dose of 100 mg/kg in the second phase of formalin test. The maximum antinociceptive effect was induced by the dose of 300 mg/kg that was significant in both phases of formalin test. Dose of 400 mg/kg of the percolated extract induced acute adverse effects such as diarrhea, polyurea, malasia and hyperventilation in mice. Soxhlet extract of F. parviflora (300 mg/kg, i.p.) also showed significant effects in the both phases of formalin test. The most effective dose of the percolated extract as well as the soxhlet extracts (300 mg/kg, i.p.) were evaluated in hot plate test. The results showed that only percolated extract had significant antinociceptive effect in hot-plate. Pretreatment of mice with naloxane, an opioid antagonist did not change antinociceptive effect of percolated extract in formalin test, but in hot-plate it increased extract’s effect after the first 15 minutes. In histopathological evaluation of liver, toxic dose of percolated extract (400 mg/kg) caused degeneration, necrosis and regeneration of hepatic cells. The study of ulcerogenic effects of oral percolated extract on stomach in rats showed that this adverse effect was significantly lower in comparison with the same dose of indomethacin. These results showed F. parviflora is relatively safe for use and it is a good candidate for further studies to determine its effective and probable toxic compound(s).

The purpose of this study was to assess the influence of acute manic phase on the steady state pharmacokinetics of carbamazepine (CBZ) in bipolar patients. Forty one acutely manic and 76 epileptic patients entered this prospective study. CBZ apparent oral clearance (CL/F) values were calculated in both groups and were compared with each other. CBZ clearance is affected by different factors such as age, body weight, dosage and the use of concurrent medications. However, since these factors were similar between the two groups, our results could not be affected by these confounding factors.Comparison between epileptic and manic patients showed that CL/F values in acutely manic patients were significantly higher than epileptic patients (0.128 ± 0.016 vs. 0.112 ± 0.0147 L/hr/kg, p< 0.0001). As a result, acutely manic patients require more CBZ dosages to achieve serum concentrations comparable with those found in epileptic patients. Increased CBZ clearance in acutely manic patients may be related to increase of catecholamine and sympathetic activity in these patients. This results in increased hepatic blood flow which may affect the hepatic clearance of drug. Besides, due to the abnormalities in membrane transport of acutely manic patients, it may be suggested that cellular uptake of the drug and its volume of distribution may be affected. Since our study is a preliminary investigation in this field, further detailed pharmacokinetic study in acutely manic patients are warranted to confirm results of this study.

Omeprazole, a proton pump inhibitor, effectively suppresses the gastric acid secretion in the parietal cells of stomach. Pharmacokinetics and relative bioavailability of generic products of omeprazole were compared with innovator product, Losec. Twelve healthy adult volunteers participated in the study which was conducted according to a randomized, open-label single dose Latin square cross over design. The preparations were compared using area under the plasma concentration – time curve (AUC), peak plasma concentration (Cmax), and time to reach peak plasma concentration (tmax). The two generic capsules proved to be bioequivalent with brand-name omeprazole with regard to the pharmacokinetic parameters Cmax, AUC0-t, AUC0-inf and tmax. Moreover the parametric confidence intervals (90%) for the ratio of the Cmax, AUC0-8 and AUC0-∞ values lie between 0.8-1.2. The test formulations were found bioequivalent to the reference formulation by the one-way ANOVA test procedure. On the basis of these results, the 3 formulations were considered to be bioequivalent. Two subjects demonstrated increase in AUCs and high Cmax after administration of either product which may attribute to the ethnic disposition of omeprazole in these subjects.

Ocular infections may arise from topical ophthalmic medications. A standard imposed by the British Pharmaceutical Codex implies that eye drops should be discarded after 1-day use when these remedies are used in outpatient departments. In this study the bioburden rates arising from 2, 4 and 7 days’ use were evaluated and compared with those of 1 day’s use to determine whether it is possible to extend the period of use of preserved eye drops in outpatient departments. A total of 200 eye drops were taken from outpatient departments of Farabi Eye Hospital after 1, 2, 4 and 7 days’ use and the contamination rates of the residual contents, caps and droppers were determined using conventional techniques. High biobudren rates were obtained in all the samples tested. Although the overall recorded incidences of microbial contamination in the 2 and 4-day drops were not considerably different from those of first day (P>0.01) but those of 7 days’ use were significant (P<0.01). However, when contamination rate of drop contents was taken into account there was a significant difference between 4 and 7 days’ use compared to 1-day drops. Most of the isolated organisms were either of human flora types of Gram-positive bacteria or air-borne fungi. It is concluded that the use of eye drops for outpatient practice may be extended up to 2 days; yet, care should be taken to reduce the overall contamination rates of these preparations for prevention of ocular nosocomial infections.

In this study, the effect of phenytoin cream on linear incisional wound healing was investigated. Thirty male Wistar rats were subjected to a linear 3cm incision made over the skin of the back. The animals were randomly divided into 3 experimental, control, cold cream and treatment groups. Control group did not receive any drug or cold cream. Cold cream group received topical cold cream once a day from the beginning of experiments until the day that wounds were closed. Treatment group were treated topically by 1% phenytoin cream at the same time. For computation of the percentage of wound healing, the area of the wound was measured at the beginning of experiments and the next 2,4,6,8,10,12,14 and 16 days.The percentage of the healing wounds was calculated by Walker formula after measurement of the wound area. Results showed that there weren’t statistically significant differences between treatment and cold cream animals (P>0.05) in most of the days. It is concluded that phenytoin has possibly no significant effect on the rate of wound closing in acute wound model of incision in rat. Therefore further study is required for detection of the role of phenytoin on wound healing and the related parameters in various kinds of experimental wound models.

In this study effect of recombinant human leukemia inhibitory factor on invitro development of 2 cells embryos and isolated blastomeres derived from mouse 2 cell embryos were investigated. Female ICR mice that were between 8 to 10 weeks old received intraperitoneal injection of 7.5 IU of PMSG for super ovulation followed by intraperitoneal administration of 7.5 IU of HCG 48 hours later. The mice were then mated to mature ICR male mice and were checked for vaginal plugs after 13-14 hours. Mice were killed 46-48 hours after HCG injection by cervical dislocation, their oviducts were removed and flushing 2 cell embryos were collected. The zona pellucida of 2 cell embryos were removed by Acid Tyrod solution and blastomeres separated with oocyte preparation pipette and then all embryos and blastomeres were cultured in Potassium Simplex Optimized Medium (KSOM) +Aminoacid (AA) different amounts of rhLIF (500IU/ml, 1000IU/ml and 1500IU/ml). Some embryos and individual blastomere also were cultured without rhLIF as control group. All samples were cultured in an incubator at 370C with 0.05 CO2 for 120 hours. The rate of embryo and individual blastomeres which reached to 2 cell, 4 cell, 8 cell and 9-16 cell were the same in all groups. However in further developmental stages, morula and blastocyst between experimental and control groups were significantly different. Therefore it may be concluded that: cultivation of isolated blastomers up to the blastocyst stage with rhLIF has stimulatory effect on the preimplantation stage (morula and blastocyst) but it has no stimulatory and inhibitory effects when was added to culture media at the early cleavage stage.

The kinetic characteristics, of interaction between hK6 (human Kallikrein) and soybean (BBI), protease inhibitor and antitumor agent, in the presence of substrate (Phenylalanine –Serine-Arginine)-(7-amino-4- methyl-coumarin) (FSR-AMC) were investigated. The hK6 were found to bind soybean in two reversible steps, by slow binding inhibition mechanism. The Ki of the first step binding was 13 nM and Ki* of the second binding step was 1.6 nM. The microcopic rate constants were calculated as follows: 311 M-1.S-1 for k3 , 0.04×10-6 M-1.S-1 for k –3 , 0.2×10-6 S-1 for k 4 and 0.025×10-6 S-1 for k-4 respectively. The results suggested that the interaction mechanism between hK6 and soybean was like that of trypsin with this inhibitor but with rather lower inhibitory constants values.