A polyisoprenylated ketone named enervosanone has been isolated from the stem bark of Calophyllum enervosum together with three known compounds, cambogin, osajaxanthone and epicatechin. Their structures were determined by spectroscopic analysis. The antimicrobial evaluations of the isolated compounds were also reported.
Exposure of Plasmodium falciparum to increasing sublethal drug concentrations followed by drug treatment led to the development of many resistant parasites. Therefore, the susceptibility of these clones to the type II antifolate drugs, cycloguanil and pyrimethamine, before and after subculturing them in vitro for a period of 3 years, was studied.
Fragaria chiloensis fruit has a short postharvest life mainly due to its rapid softening. In order to improve its postharvest life, preharvest applications of methyl jasmonate (MeJA) and chitosan were evaluated during postharvest storage at room temperature. The quality and chemical parameters, and protection against decay were evaluated at 0, 24, 48 and 72 h of storage from fruits of two subsequent picks (termed as first harvest and second harvest). In general, fruits treated with MeJA and chitosan maintained higher levels of fruit firmness, anthocyanin, and showed significant delays in decay incidence compared to control fruit. MeJA-treated fruits exhibited a greater lignin content and SSC/TA ratio, and delayed decay incidences. Instead, chitosan-treated fruits presented higher antioxidant capacity and total phenol content. In short, both the elicitors were able to increase the shelf life of fruits as evidenced by the increased levels of lignin and anthocyanin, especially of the second harvest.
The present study reports a bioassay-guided isolation of β-caryophyllene from the essential oil of Aquilaria crassna. The structure of β-caryophyllene was confirmed using FT-IR, NMR and MS. The antimicrobial effect of β-caryophyllene was examined using human pathogenic bacterial and fungal strains. Its anti-oxidant properties were evaluated by DPPH and FRAP scavenging assays. The cytotoxicity of β-caryophyllene was tested against seven human cancer cell lines. The corresponding selectivity index was determined by testing its cytotoxicity on normal cells. The effects of β-caryophyllene were studied on a series of in vitro antitumor-promoting assays using colon cancer cells. Results showed that β-caryophyllene demonstrated selective antibacterial activity against S. aureus (MIC 3 ± 1.0 µM) and more pronounced anti-fungal activity than kanamycin. β-Caryophyllene also displayed strong antioxidant effects. Additionally, β-caryophyllene exhibited selective anti-proliferative effects against colorectal cancer cells (IC50 19 µM). The results also showed that β-caryophyllene induces apoptosis via nuclear condensation and fragmentation pathways including disruption of mitochondrial membrane potential. Further, β-caryophyllene demonstrated potent inhibition against clonogenicity, migration, invasion and spheroid formation in colon cancer cells. These results prompt us to state that β-caryophyllene is the active principle responsible for the selective anticancer and antimicrobial activities of A. crassnia. β-Caryophyllene has great potential to be further developed as a promising chemotherapeutic agent against colorectal malignancies.
There are no definite reports regarding the effects of chronic fluoxetine on animal models of epilepsy. Since chronically administered fluoxetine, in comparison to acutely administered fluoxetine has different effects on CNS, the present study was undertaken to investigate the effect of acute and chronic fluoxetine pretreatment, on a median anticonvulsant dose (ED50) of phenytoin in male ICR albino mice. Additionally, the effects of fluoxetine pretreatment on median convulsive current (CC50) in the presence and absence of phenytoin were investigated and results were compared. The maximal electroshock seizure (MES) test was used to estimate the ED50of phenytoin. The electroshock threshold test was used to estimate CC50. ED50and CC50values were calculated by probit analysis. The effects of the chronic and acute fluoxetine groups on the ED50of phenytoin were significantly different (P<0.05), and on CC50this difference was not statistically significant. Chronic fluoxetine insignificantly increased the ED50of phenytoin and decreased the CC50while acute fluoxetine decreased the ED50of phenytoin and increased the CC50. Our results indicate that chronic fluoxetine does not have an antiepileptic property and it may have dubious proconvulsant properties, contrary to acute fluoxetine.
The effects of 2% and 4% sevoflurane in oxygen and nitrous oxide for induction of anaesthesia in 60 unpremedicated elderly patients was compared to those obtained during an intravenous Thiopentone induction. Intravenous induction induced anaesthesia in 27 +/- 5 seconds, significantly faster than a 2% or 4% sevoflurane induction (109 +/- 36 and 71 +/- 24 seconds respectively). One patient in both the thiopentone and 2% sevoflurane groups, and 2 patients in the 4% sevoflurane group coughed during induction. The postinduction reduction in mean arterial pressure was greatest in the thiopentone group followed by the 4% and the 2% sevoflurane groups. Heart rate changes were minimal in all groups. We conclude that 2% or 4% sevoflurane offered suitable conditions for induction of anaesthesia in the elderly with minimal cardiovascular derangement.
Plant styryl-lactone derivatives isolated from Goniothalamus sp. are potential compounds for cancer chemotherapy. In this study, we have examined the mechanisms of apoptosis induced by altholactone, a stryl-lactone isolated from the Malaysian plant G. malayanus on human HL-60 promyelocytic leukemia cells. Flow cytometric analysis of the externalization of phosphatidylserine (PS) using the annexin V/PI method on altholactone treated HL-60 cells showed a concentration-dependent increase of apoptosis from concentrations ranging from 10.8 (2.5 microg/ml) to 172.4 microM (40 microg/ml). Pre-treatment with the antioxidant N-acetylcysteine (1 mM) completely abrogated apoptosis induced by altholactone, suggesting for the involvement of oxidative stress. Further flow cytometric assessment of the level of intracellular peroxides using the fluorescent probe 2',7'-dichlorofluorescein diacetate (DCFH-DA) confirmed that altholactone induced an increase in cellular oxidative stress in HL-60 cells which was suppressed by N-acetylcysteine. In summary, our results demonstrate for the first time that altholactone induced apoptosis in HL-60 cells occurs via oxidative stress.
Crude extracts (methanol) of various parts, viz. the leaves, fruits, roots, stem and trunk bark, of Garcinia atroviridis were screened for antimicrobial, cytotoxic, brine shrimp toxic, antitumour-promoting and antioxidant activities. The crude extracts exhibited predominantly antibacterial activity with the root extract showing the strongest inhibition against the test bacteria at a minimum inhibitory dose (MID) of 15.6 microg/disc. Although all the extracts failed to inhibit the growth of most of the test fungi, significant antifungal activity against Cladosporium herbarum was exhibited by most notably the fruit (MID: 100 microg), and the leaf (MID: 400 microg) extracts. None of the extracts were significantly cytotoxic, and lethal towards brine shrimps. The root, leaf, trunk and stem bark extracts (except for the fruits) showed strong antioxidant activity exceeding that of the standard antioxidant, alpha-tocopherol. Antitumour-promoting activity (>95% inhibition) was shown by the fruit, leaf, stem and trunk bark extracts.
Eight hundred and fifty-six strains of Mycobacterium tuberculosis from previously untreated patients with pulmonary tuberculosis from various states in West Malaysia were studied during the period 1984 to 1987. All the strains were tested for in vitro susceptibility to the anti-tuberculosis drugs isoniazid (INH), streptomycin (SM), rifampicin (RMP) and ethambutol (ETB). One hundred and twenty-one of the isolates (14.18%) were resistant to 1 drug while 17 (1.97%) were resistant to 2 drugs. No strain was found to be resistant to more than 2 drugs. The prevalence of primary resistance to INH was 4.20%, SM was 7.59%, RMP was 0.95% and ETB was 1.44%. In 1.86% of isolates, resistance was noted to both INH and SM, while 0.11% were resistant to both RMP and ETB. There was no significant difference in distribution of resistant bacilli between the sexes (p > 0.01).
Six clones were derived from each Plasmodium falciparum isolate obtained from Malaysia, Africa and Thailand and were characterized against type II antifolate drugs, cycloguanil and pyrimethamine using the modified in vitro microtechnique. Results showed that these isolates were of a heterogeneous population, with 50% inhibitory concentrations of Gombak A clones at 0.0151-0.1450 and 0.0068-0.1158 microM, Gambian clones at 0.0056-0.1792 and 0.0004-0.0068 microM and TGR clones at 0.0103-0.0703 and 0.0776-0.3205 microM against cycloguanil and pyrimethamine, respectively. All clones displayed similar susceptibilities as their parent isolates except A/D3, A/D5, A/G4 and A/H7 clones which were sensitive to cycloguanil at 0.0735, 0.0151, 0.0540 and 0.0254 microM but Gm/B2 clone was resistant at 0.1792 microM, respectively. However, A/D3, TGR/B4, TGR/B7, TGR/C4, TGR/C7 and TGR/H2 clones were resistant to pyrimethamine at 0.1158, 0.1070, 0.1632, 0.1580, 0.2409 and 0.3205 microM, respectively. Further results indicated that they were pure clones compared to their parent isolates as their drug susceptibility studies were statistically different (p < 0.05).
Measurement of rates of propulsion in the small intestine in control and experimental groups of male Sprague-Dawley rats (200-250 g) were carried out as a means of assessing antidiarrhoeal activity of aqueous extracts of the leaf of Psidium guajava (L.), using morphine as the standard drug of reference. Hyperpropulsion (diarrhoea) was induced by gavaging rats in a control group with Microlax, using phenol red mixed into it as a marker in the intestine, and the mean rate of the hyperpropulsion was determined. The normal rate of propulsion, defined as the percentage of the length of the ileum traversed by the front of the dye in 1 h after gavaging animals with a liquid paraffin-phenol red meal, was also determined in another control group. In experimental groups pretreated with enteral administration of either morphine or aqueous extracts, 1 h before the challenge with Microlax, the percentage inhibition to the hyperpropulsive rate (antidiarrhoeal activity) was calculated. Both morphine and the extracts produced a dose-response relationship in their antidiarrhoeal effects. A dose of 0.2 ml/kg fresh leaf extract produced 65% inhibition of propulsion. This dose is equiactive with 0.2 mg/kg of morphine sulphate. The antidiarrhoeal action of the extract may be due, in part, to the inhibition of the increased watery secretions that occur commonly in all acute diarrhoeal diseases and cholera.
Plasmodium falciparum isolates from Malaysia, Africa and Thailand were cultured in vitro following the method of Trager and Jensen and subsequently cloned using the limiting dilution method of Rosario. These clones were presently characterized against three schizonticidal drugs, chloroquine, mefloquine and quinine, using the modified in vitro microtechnique. Results showed that all the clones derived from Gombak A isolate were chloroquine-resistant with average IC50 values ranging at 0.1377-1.0420 microM (0.007-0.058 mefloquine activity), sensitive to mefloquine at 0.0032-0.0103 microM and quinine at 0.0025-0.0428 microM (0.075-3.080 mefloquine activity). Similarly, the TGR clone displayed resistance to chloroquine at 0.1715-0.5875 microM (0.002-0.029 mefloquine activity) but were also sensitive to mefloquine at 0.0008-0.0058 microM and quinine at 0.0055-0.0700 microM (0.055-0.202 mefloquine activity). In contrast, four out of six Gambian clones were sensitive to chloroquine at 0.0047-0.0172 microM (0.122-0.617 mefloquine activity) but all were sensitive to mefloquine at 0.0008-0.0029 and 0.0016-0.0102 microM (0.096-1.813 mefloquine activity). In general, most of the clones displayed susceptibility patterns similar to that of their parent isolates against the three schizonticidal drugs except Gm/B2 and Gm/H5 Gambian clones were chloroquine-resistant at 0.3427 microM (0.006 mefloquine activity) and 0.2260 microM (0.004 mefloquine activity), respectively. Further results indicated that they were pure clones compared to their parent isolates as their schizonticidal drug susceptibilities were statistically different (p < 0.05) except Gm/C6 and TGR/B7 clones against mefloquine (p < 0.05).
A comparative effect of propranolol and nifedipine administered individually and in combination at graded dose levels; and that of phenytoin at 30 mg kg-1 on maximal electroshock (MES)-induced seizure in mice was investigated. Propranolol in doses of 10 mg kg-1 and 20 mg kg-1, and nifedipine in doses of 8 mg kg-1 and 16 mg kg-1 significantly modified MES activity. Propranolol (40 mg kg-1), and a combination of propranolol (20 mg kg-1) and nifedipine (8 mg kg-1), produced antiMES activity, which was comparable to that of phenytoin (30 mg kg-1). In mice treated with propranolol and nifedipine combination, the tonic flexor and tonic extensor phase ratios (F/E ratio) were significantly higher than individual drug responses. Our findings suggest that a combination of propranolol and nifedipine has either synergistic or an additive effect in controlling MES-induced seizures in mice.
Cyclic AMP phosphodiesterase (PDE) partially purified from roots of Vigna mungo exhibited optimum activity at pH 5.5 to 6.0 and maximum enzyme activity at 50 degrees C. Levels of PDE activity in roots remained relatively constant from the first to the eleventh day after germination; on the twelfth day there was a 400% increase in PDE activity. The enzyme was stable for at least 48 hours at 28 degrees C, retaining 92% of its original activity. Plant growth hormones including gibberellic acid, indoleacetic acid and kinetin at 1.0 and 10.0 microM concentrations did not have any significant effect on enzyme activity. Nucleotides tested including cyclic 2'3' AMP, cyclic 2'3' GMP completely abolished enzyme activity at 1.0mM while cyclic 3'5' GMP, cyclic 3'5' GMP, 2'deoxy 5' ATP, 2'deoxy 5'GTP and 5'ADP were also inhibitory to the enzyme. The enzyme was stimulated by Mg2+, Fe2+ and NH4+ while Cu2+ and Fe3+ were inhibitory. Theophylline, caffeine, phosphate, pyrophosphate and EDTA were inhibitory to the enzyme.
170 clinical isolates of Pseudomonas aeruginosa were tested for in vitro susceptibility to gentamicin, amikacin, tobramycin, netilmicin, kanamycin, streptomycin, cefotaxime, ceftriaxone, cefoperazone, ceftazidime, moxalactam, azlocillin, piperacillin and ticarcillin. Against 93 gentamicin-sensitive strains, the most active antibiotics were in descending order, ceftazidime, tobramycin, gentamicin, amikacin, and the ureidopenicillins. Against 77 gentamicin-resistant strains, only ceftazidime, amikacin and moxalactam had mode minimum inhibitory concentrations within achievable peak serum levels after standard therapeutic dosage. There was no correlation between cephalosporin resistance and aminoglycoside resistance except for cefoperazone, which, together with the ureidopenicillins and ticarcillin, showed marked decrease in activity against gentamicin-resistant strains.
Six clones were derived from each Malaysian Plasmodium falciparum isolate and characterized for their susceptibilities against type II antifolate drugs, cycloguanil and pyrimethamine. Results showed that these isolates were of a heterogeneous population, with average IC50 values of Gombak C clones at 0.012-0.084 microM and 0.027-0.066 microM, ST 9 clones at 0.019-0.258 microM and 0.027-0.241 microM, ST 12 clones at 0.015-0.342 microM and 0.012-0.107 microM, ST 85 clones at 0.022-0.087 microM and 0.024-0.426 microM, and ST 148 clones at 0.027-0312 microM and 0.029-0.690 microM against cycloguanil and pyrimethamine, respectively. Generally, most of these clones displayed susceptibility patterns similar to their parent isolates except ST 9/A4, ST 9/A7, ST 9/B5, ST 9/D9, ST 9/D10, ST 148/A4, ST 148/A5, ST 148/A7, ST 148/F7, ST 148/F8 clones, which were sensitive at 0.027 microM, 0.019 microM, 0.022 microM, 0.063 microM, 0.037 microM, 0.031 microM, 0.042, microM, 0.042 microM, 0.062 microM, and 0.027 microM, whereas, ST 12/D7 clone was resistant at 0.342 microM, against cycloguanil respectively. However, ST 9/A4, ST 9/D8, ST 12/D5, ST 85/A5, ST 85/B3, ST 85/B4, ST 85/D3, ST 85/D7, ST 148/A6, and ST 148/A7 clones were resistant to pyrimethamine at 0.158 microM, 0.241 microM, 0.107 microM, 0.223 microM, 0.393 microM, 0.402 microM, 0.426 microM, 0.115 microM, 0.690 microM, and 0.520 microM, respectively.
Since thrombi continue to incorporate fibrin during lysis we tested the effect of pretreatment with ancrod, a defibrinating agent from Malaysian pit viper venom, on thrombolysis with urokinase and streptokinase. Thrombi were induced by copper-coils in the carotid arteries of the dogs, weighed after 1 hour and inserted into the femoral arteries of the same animals. They were then exposed for 15 min to iv boluses of streptokinase 10,000 U/kg, urokinase 10,000 U/kg and urokinase 25,000 U/kg with or without pretreatment with ancrod. Ancrod depleted fibrinogen within 5 min and enhanced the lytic effect of streptokinase from 25 +/- 8% to 59 +/- 13% (p less than .05), urokinase 10,000 U/kg from 16 +/- 11% to 66 +/- 18% (p less than .01) and urokinase 25,000 U/kg from 27 +/- 17% to 85 +/- 8% (p less than .001) of the initial thrombus weight. Ancrod itself did not activate plasminogen to plasmin. We conclude that ancrod enhances thrombolysis probably by depleting fibrinogen and preventing new fibrin incorporation into the thrombus during lysis.