Effect of Gentiana olivieri on experimental epilepsy models

Mustafa Aslan, Didem Deliorman Orhan, Nilufer Orhan

Pharmacognosy Magazine 2011 7(28):344-349

Background: Flowering herbs of Gentiana olivieri Griseb. (Gentianaceae) are widely used as bitter tonic, stomachic, stimulant of appetite, antipyretic, anticonvulsant, antidiabetic and for mental problems in the different regions of Turkey. Objective: To establish the anticonvulsant activity potential of G. olivieri. Materials and Methods: In this work, the ethanol extract of G. olivieri was tested in three doses (200, 750 and 1000 mg/kg) for anticonvulsant activity against seizures produced in mice by pentylenetetrazole (PTZ), picrotoxin (PIC) and maximal electroshock (MES). Neurotoxicity of the ethanol extract was also determined by the Rota rod test to evaluate the safety. Ethosuximide (150 mg/kg), diazepam (0.5 mg/kg) and carbamazepine (30 mg/kg) were used as reference drugs. Results: Intraperitonally, injection of the extract significantly prolonged the onset of seizures at doses of 200 and 750 mg/kg, but did not alter the incidence of PTZ-induced seizures. Onset of PIC-induced seizures was delayed by the injection of the extract (1000 mg/kg). Moreover, only 750 mg/kg of the extract protected 25% of the mice against PIC-induced seizures. On the other hand, G. olivieri extract (200, 750 and 1000 mg/kg) showed a significant protective effect against MES-induced seizures. In the Rota rod test, the ethanol extract (200 mg/kg, ip) induced disturbance in motor coordination. Conclusion: The results indicate that G. olivieri has possessed anticonvulsant activity against MES-induced seizures in mice.

Influence of fungal elicitation on glycyrrhizin production in transformed cell cultures of Abrus precatorius Linn

Vijai Singh Karwasara, Priti Tomar, Vinod K Dixit

Pharmacognosy Magazine 2011 7(28):307-313

Background: Glycyrrhizin, obtained from Abrus precatorius (Indian liquorice), is a phytoconstituent of importance for pharmaceutical and food industries. Materials and Methods: High producing and fast growing cell lines of A. precatorius were developed by transformation with Agrobacterium tumefaciens for glycyrrhizin production. Its maximum transformation efficiency of 85% was obtained by infecting leaves with A. tumefaciens MTCC-431 supplemented with 50 μM acetosyringone. Thorough culture growth kinetics with sugar consumption profiles was established. Results: A twofold increase in glycyrrhizin productivity was obtained in transformed A. precatorius cell suspension cultures over the untransformed cultures. The fungal elicitors prepared from Aspergillus niger and Rhizopus stolonifer were tested at different concentrations to enhance glycyrrhizin production in transformed cell suspension cultures of A. precatorius. Maximum enhancement of 4.9- and 3.8-fold in glycyrrhizin contents, were obtained with A. niger (7.5% v/v) and R. stolonifer (5.0% v/v), respectively, on the 5th day after elicitor treatment. Conclusion: This study indicates the prospective of the amalgamation of elicitation methodology with transformed cell cultures for the large-scale production of glycyrrhizin.

Enhancement of the antibiotic activity of erythromycin by volatile compounds of Lippia alba (Mill.) N.E. Brown against Staphylococcus aureus

Helenicy N.H. Veras, Adriana R Campos, Fabíola F.G. Rodrigues, Marco A Botelho, Henrique D.M. Coutinho, Irwin R.A. Menezes, José Galberto M da Costa

Pharmacognosy Magazine 2011 7(28):334-337

Background: Lippia alba (Mill.) N.E. Brown, popularly known as "erva-cidreira," is commonly found in northeastern Brazil. The leaves tea is used to treat digestive disturbances, nausea, cough, and bronchitis. Objective: This work reports the chemical composition and erythromycin-modifying activity by gaseous contact against Staphylococcus aureus. Materials and Methods: The leaves of L. alba were subjected to hydrodistillation, and the essential oil extracted was examined with respect to the chemical composition, by gas chromatography-mass spectrometry (GC-MS), and the essential oil extracted was evaluated for antibacterial and antibiotic-modifying activity by gaseous contact. Results: The overall yield of essential oil obtained by hydrodistillation was 0.52%. The GC-MS analysis has led to the identification of the main components: geranial (31.4%) and neral (29.5%). It was verified that the essential oil interfered with erythromycin antibiotic activity against S. aureus ATCC 25923 was enhanced (221.4%) in the presence of 12% essential oil. The 3% essential oil increased the effect against S. aureus ATCC 25923 (41.6%) and S. aureus ATCC 6538 (58.3%). Conclusion: The essential oil of L. alba influences the activity of erythromycin and may be used as an adjuvant in antibiotic therapy against respiratory tract bacterial pathogens.

Bioactive constituents from Harpephyllum caffrum Bernh. and Rhus coriaria L

Marawan M Shabana, Aly M El Sayed, Miriam F Yousif, Abeer M El Sayed, Amany A Sleem

Pharmacognosy Magazine 2011 7(28):298-306

Background: The leaf ethanol extract of Harpephyllum caffrum Bernh. has evidenced medicinal value due to its hepatoprotective activity. It demonstrated inhibitory effects on test standard microbes approximated to 40% the potency of ofloxacin and fluconazole. The same extract evidenced in vitro cytotoxicity on human cell lines, liver carcinoma HEPG2, larynx carcinoma HEP2, and colon carcinoma HCT116 cell lines when compared to doxorubicin. Materials and Methods: Fractionation of the leaf ethanol extract led to the isolation of the polyphenols, ethyl gallate, and quercetin-3-O-rhamnoside, a hydrocarbon, hendecane, the fatty acid ester, methyl linoleate, and four triterpenoids, betulonic acid, 3-acetyl-methyl betulinate, lupenone and lupeol for the first time, in addition to the previously reported phenol acids and flavonoids, gallic acid, methyl gallate, quercetin, kaempferol, kaempferol-3-O-rhamnoside, kaempferol-3-O-galactoside, apigenin-7-O-glucoside, and quercetin-3-O-arabinoside. Results: The ethanol extract of the fruit of the genetically related Rhus coriaria L., known as sumac, afforded protocatechuic acid, isoquercitrin, and myricetin-3-O-α-L-rhamnoside from the fruits for the first time, in addition to the previously reported phenol acids and flavonoids, gallic acid, methyl gallate, kaempferol, and quercetin. Conclusion: The leaf ethanol extract of H. caffrum Bernh. exhibited variable anti-inflammatory, analgesic, and antipyretic activities, besides the hepatoprotective, in vitro cytotoxic and anti-microbial activities.

Xanthine oxidase inhibitory activity of the methanolic extracts of selected Jordanian medicinal plants

Mohammad M Hudaib, Khaled A Tawaha, Mohammad K Mohammad, Areej M Assaf, Ala Y Issa, Feras Q Alali, Talal A Aburjai, Yasser K Bustanji

Pharmacognosy Magazine 2011 7(28):320-324

Background: The search for novel xanthine oxidase (XO) inhibitors with a higher therapeutic activity and fewer side effects are desired not only to treat gout but also to combat various other diseases associated with the XO activity. At present, the potential of developing successful natural products for the management of XO-related diseases is still largely unexplored. In the present study, we have screened the methanolic extracts of various Jordanian medicinal plants for their XO inhibitory activities using an optimized protocol. Materials and Methods: The methanolic extracts of 23 medicinal plants, belonging to 12 families, were tested in vitro, at 200 μg/ml concentrations, for their XO inhibitory potential. The dose-dependent inhibition profiles of the most active plants were further evaluated by estimating the IC 50 values of their corresponding extracts. Results: Six plants were found most active (% inhibition more than 39%). These plants are Salvia spinosa L. (IC 50 = 53.7 μg/ml), Anthemis palestina Boiss. (168.0 μg/ml), Chrysanthemum coronarium L. (199.5 μg/ml), Achillea biebersteinii Afansiev (360.0 μg/ml), Rosmarinus officinalis L. (650.0 μg/ml), and Ginkgo biloba L. (595.8 μg/ml). Moreover, four more plants, namely Lavandula angustifolia Mill. (28.7% inhibition), Helianthemum ledifolium (L.) Mill. (28.4%), Majorana syriaca (L.) Kostel. (25.1%), and Mentha spicata L. (22.5%) showed a XO inhibitory activity in the range of 22-30%. Conclusion: The study showed that many of the tested plant species are potential sources of natural XO inhibitors that can be developed, upon further investigation, into successful herbal drugs for treatment of gout and other XO-related disorders.

Hepatoprotective and in vitro antioxidant effect of Carthamus tinctorious L, var Annigeri-2-, an oil-yielding crop, against CCl 4 -induced liver injury in rats

Mahadevappa Paramesha, Chapeyil K Ramesh, Venkatarangaiah Krishna, Yelegara S Ravi Kumar, Karur M.M. Parvathi

Pharmacognosy Magazine 2011 7(28):289-297

Background: The present investigation evaluates the hepatoprotective and in vitro antioxidant effect of methanolic extract and its isolated constituent, dehydroabietylamine, in Carthamus tinctorious L, var Annigeri-2-, an oil yielding crop. Materials and Methods: The hepatoprotective effects were estimated for the parameters viz, total bilirubin, total protein, serum alanine amino transaminase (ALT) and serum aspartate aminotransferase (AST) and alkaline phosphatase (ALP) and along with the pathological findings of hepatotoxicity. The in vitro antioxidant activity was evaluated by using free radical scavenging assays: DPPH, nitric oxide radical scavenging, hydroxyl radical, reducing power, ferrous ion chelating ability and total antioxidant capacity. Results: Both the methanolic extract (at 150 and 300 mg/kg bw) and dehydroabietylamine (at 50 mg/kg bw) showed significant liver protection against CCl 4 -induced liver damage that was comparable with the standard drug, silymarin (100 mg/kg bw), in reducing the elevated serum enzyme markers. The liver sections of the animals treated with dehydroabietylamine elicit a significant liver protection compared with the methanolic extract against CCl 4 -induced liver damage. Further, both the methanolic extract and dehydroabietylamine exhibited a considerable and dose-dependent scavenging activity of DPPH, nitric oxide and hydroxyl radical. Similarly, in the reducing power assay, the results were very persuasive. In addition, the Fe 2+ chelating activity and the total antioxidant assay established the antioxidant property of the methanolic extract and its isolated constituent. Among the two experimental samples, dehydroabietylamine proved to be more effective for the said parameters. Conclusion: The potent antioxidant and its correlative hepatoprotective activity of the methanolic extract and isolated constituent dehydroabietylamine is therefore attributed to its antioxidant and free radical scavenging activities.

Simultaneous determination of geniposide, chlorogenic acid, crocin1, and rutin in crude and processed fructus gardeniae extracts by high performance liquid chromatography

Enhong Ouyang, Chengrong Zhang, Xiaomeng Li

Pharmacognosy Magazine 2011 7(28):267-270

Background: Fructus Gardeniae, commonly used traditional Chinese medicine (TCM) called Zhizi in chinese, is derived from the dried fruit of Gardenia jasminoides Ellis of the Madder Family. To our knowledge, previously reported analytical methods were not developing for simultaneous determination of geniposide, chlorogenic acid, crocin1, and rutin in Fructus Gardeniae and its processed products of chaozheng pin (CZP) extracts. Materials and Methods: In this study, a HPLC method was developed for simultaneous determination four major active components in Fructus Gardeniae and its processed products. Results: The contents of geniposide, chlorogenic acid, crocin1, and rutin in Fructus Gardeniae samples analyzed were 2.492 – 4.242%, 0.162 – 0.407%, 0.417 -0.837%, and 0.116 – 0.251%, respectively. Conclusion: The developed method can be applied to the intrinsic quality control of Fructus Gardeniae.

Neuroprotective activity of the methanolic extract of Lonicera japonica in glutamate-injured primary rat cortical cells

Jin Bae Weon, Hye Jin Yang, Bohyoung Lee, Bo-Ra Yun, Ju Hee Ahn, Hyeon Yong Lee, Choong Je Ma

Pharmacognosy Magazine 2011 7(28):284-288

Background: We previously reported that the extracts of several Korean medicinal plants showed neuroprotective activity in glutamate-injured primary culutres of rat cortical cells. Objective: Among them, the effect of the methanolic extract of Lonicera japonica flower on the glutamate-induced neuronal cell death and its potential mechanism of action was investigated. Results: Treatment by the methanolic extract of L. japonica flower significantly protected neuronal cells against glutamate-induced excitotoxicity. It decreased the calcium influx that accompanies the glutamate induced excitotoxicity of neuronal cells, and inhibited the subsequent overproduction of nitric oxide, reactive oxygen species and peroxide to the level of control cells. In addition, it preserved cellular activity of superoxide dismutase, an antioxidative enzyme reduced by glutamate insult. Conclusions: According to this data, the methanolic extract of L. japonica flower significantly protected neuronal cells against glutamate excitotoxicity via antioxidative activity.

Phytochemical constituents and antioxidant activities of the whole leaf extract of Aloe ferox Mill.

Olubunmi Abosede Wintola, Anthony Jide Afolayan

Pharmacognosy Magazine 2011 7(28):325-333

Background: Aloe ferox Mill. (Asphodelaceae) is used in South Africa for the treatment of constipation among various ailments. Despite the extensive studies conducted on the antioxidant activities of the leaf gel and pulp extract of the plant, there is no information on the antioxidant properties of the whole leaf extract of the species. Materials and Methods: The antioxidant activities of ethanol, acetone, methanol and aqueous extracts of A. ferox were investigated spectrophotometrically against 1,1- diphenyl-2-picrylhydrazyl (DPPH), 2,2Ͳ-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) diammonium salt, hydrogen peroxide (H 2 O 2 ), nitric oxide (NO), lipid peroxidation and ferric reducing power. Total phenols, flavonoids, flavonols, proanthocyanidins, tannins, alkaloids and saponins were also determined using the standard methods. Results: The percentage compositions of phenols (70.33), flavonols (35.2), proanthocyanidins (171.06) and alkaloids (60.9) were significantly high in the acetone extract, followed by the ethanol extract with values of 70.24, 12.53, 76.7 and 23.76 respectively, while the least composition was found in the aqueous extract. Moreover, both flavonoids and saponins contents were appreciably high in both methanol and ethanol extracts, while others were very low. Tannins levels were, however, not significantly different (P > 0.05) in all the solvent extracts. At 0.5 mg/ml, the free radical scavenging activity of the methanol, acetone and ethanol extracts showed higher inhibition against ABTS, hydrogen peroxide and nitric oxide radicals. Whereas, scavenging activity of the extracts against DPPH* and lipid peroxidation were observed at a concentration of 0.016 and 0.118 mg/ml respectively in comparison to the butylated hydroxyltoluene (BHT), gallic acid and rutin. The ferric reducing potential of the extracts was concentration dependent and significantly different from that of vitamin C and BHT. Conclusion: The present study showed high level of radical scavenging activity by ethanol and methanol whole leaf extracts of A. ferox with higher antioxidant activities than acetone and aqueous extracts. The significant differences show that the whole leaf extract could be used as a potent antioxidant in medicine and food industries.

A high-performance molluscicidal ingredient against Oncomelania hupensis produced by a rhizospheric strain from Phytolacca acinosa Roxb

Danzhao Guo, Jun Chen, Yidan Liu, Hu Yao, Fang-An Han , Jing Pan

Pharmacognosy Magazine 2011 7(28):277-283

Background: Snail (Oncomelania hupensis) control is an important and effective preventive strategy in schistosomiasis control programs, and screening microbial molluscicidal agents is one of the most promising categories in biomolluscicides. Objective: To purify and identify the molluscicidal ingredient (MI) obtained from strain SL-30's exocellular broth. Materials and Methods: The active extracts extracted from SL-30's exocellular broth was purified on a silica gel column guided by molluscicidal activity assay against Oncomelania hupensis, then the MI was obtained. NMR spectroscopy and LC-MS/MS analysis was used to identify the molecular structure of the MI. Results: Molluscicidal activity bioassay showed that the MI exhibited significant molluscicidal activity with the LC 50 values of 0.101, 0.062, and 0.022 mg/L, respectively, in the case of exposure period of 24 h. From 1 H NMR, 13 C NMR, 1 H- 1 H COSY, and 1 H- 13 C HSQC spectra, partial important structure fragment was obtained, and the relative molecular weight of the MI showed 326 according to LC-MS analysis. Then, on these grounds, it was indicated that the molecular structure of the MI had a higher similarity to Gliotoxin with the molecular formula of C 13 H 14 N 2 O 4 S 2 . The quasi-molecular ion of m/z 325.45 was further analyzed by MS 2 as the parent ion, and two daughter ions obtained at m/z 295.11 [M-CH 2 OH]- and m/z 261.08 [M-CH 2 OH -2S]−.Conclusion: The MI was finally confirmed as Gliotoxin.

The preventive effect of N-butanol fraction of Nigella sativa on ethylene glycol-induced kidney calculi in rats

Mousa-Al-Reza Hadjzadeh, Abolfazl Khajavi Rad, Ziba Rajaei, Maryam Tehranipour, Nahid Monavar

Pharmacognosy Magazine 2011 7(28):338-343

Background: The current study was carried out to determine whether the aqueous-ethanolic extract or the butanolic fraction of Nigella sativa (NS) seeds could prevent or reduce calculi aggregation in experimental calcium oxalate nephrolithiasis in Wistar rats. Materials and Methods: Male Wistar rats were randomly divided into 5 groups: group A received tap drinking water for 28 days. Groups B, C, D and E received 1% ethylene glycol for induction of calcium oxalate (CaOx) calculus formation for 28 days. Rats in groups C, D and E also received aqueous-ethanolic extract of NS, N-butanol fraction and N-butanol phase remnant of NS, respectively, in drinking water at a dose of 250 mg/kg for 28 days. Urine concentration of oxalate, citrate, and calcium on days 0, 14, and 28, and also serum concentration of magnesium and calcium on days 0 and 28, were measured. On day 29, kidneys were removed for histopathologic study and examined for counting the calcium oxalate deposits in 10 microscopic fields. Result: Treatment of rats with N-butanol fraction and N-butanol phase remnant of NS significantly reduced the number and size of kidney calcium oxalate deposits compared with ethylene glycol group. Urinary concentration of oxalate in all experimental groups increased compared with control group on days 14 and 28, whereas the urine citrate concentration was lower in all experimental groups compared with control group on days 14 and 28. Conclusion: N-butanol fraction and N-butanol phase remnant of NS showed a beneficial effect on calcium oxalate deposition in the rat kidney. Therefore, the butanolic fraction of NS may be suggested for prevention of calcium oxalate calculi in humans.

Determination of 5-hydroxymethyl-2-furaldehyde of crude and processed fructus corni in freely moving rats using in vivo microdialysis sampling and liquid chromatography

Enhong Ouyang, Chengrong Zhang, Xiaomeng Li

Pharmacognosy Magazine 2011 7(28):271-276

Background: Fructus Corni is derived from the dry ripe sarcocarp of Cornus officinalis Sieb. et Zucc. 5-hydroxymethyl-2-furaldehyde (5-HMF) is an important active composition of the Fructus Corni. However, there have been no reports on the concentration of 5-HMF in freely moving rats using microdialysis coupled with HPLC. Materials and Methods: The concentration of 5-HMF in free-moving rats after intra-gastric (i.g.) administration of the water extract of Fructus Corni and JZP was analyzed by microdialysis coupled with high-performance liquid chromatographic (HPLC). Results: Results demonstrated that the concentration of 5-HMF in microdialysate was 1.4951 μg/l, but higher in rat microdialysate after i.g. administration of the aqueous extract of JZP (5.2662 μg/l). Conclusion: This method is proved to be rapid, accurate and simple. Real-time in vivo monitoring the concentration of 5-HMF provides the theoretical basis for further explaining the processing mechanism of Fructus Corni.

Antioxidative effects of cinnamomi cortex: A potential role of iNOS and COX-II

Jin-Won Chung, Jeong-Jun Kim, Sung-Jin Kim

Pharmacognosy Magazine 2011 7(28):314-319

Background: Cinnamomi cortex has wide varieties of pharmacological actions such as anti-inflammatory action, anti-platelet aggregation, and improving blood circulation. In this study, we tested to determine whether the Cinnamomi cortex extract has antioxidant activities. Materials and Methods: Antioxidative actions were explored by measuring free radical scavenging activity, NO levels, and reducing power. The mechanism of antioxidative action of Cinnamomi cortex was determined by measuring iNOS and COX-II expression in lipopolysaccharide (LPS) stimulated Raw cells. Results: Seventy percent methanolic extract of Cinnamomi cortex exerted significant 1,1-diphenyl–2–picrylhydrazyl (DPPH) free radicals and NO scavenging activities in a dose-dependent manner. More strikingly, the Cinnamomi cortex extract exerted dramatic reducing power activity (13-fold over control). Production of iNOS induced by LPS was significantly inhibited by the Cinnamomi cortex extract, suggesting that it inhibits NO production by suppressing iNOS expression. Additionally, COX-2 induced by LPS was dramatically inhibited by the Cinnamomi cortex extract. Conclusion: These results suggest that 70% methanolic extract of Cinnamomi cortex exerts significant antioxidant activity via inhibiting iNOS and COX-II induction.

Design and one-pot synthesis of new α-aminophosphonates and antimicrobial activity

Zahra Rezaei, Soghra Khabnadideh, Younes Ghasemi, Masomeh Fadaei, Zeinab Karimi

Journal of Pharmaceutical Negative Results 2011 2(2):78-86

Background: α-Aminophosphonates are bioisosters of amino acids and have several pharmacological effects. α-Aminophosphonates have been synthesized by various routes from reaction between an amine, an aldehyde, and phosphate compounds.
Materials and Methods: We synthesized 20 new α-aminophosphonates in the presence of FeCl3 in THF as a catalyst to facilitate the Manich-type reaction of aldehyde, amine and phosphite compounds to form the corresponding α-aminophosphonates in a one-pot, three-component reaction. In this study, the catalytic effect of ZnCl2 was also compared with FeCl3 in the synthesis of α-aminophosphonates. Results: The results showed that FeCl3 catalyzed the reaction in mild conditions to form α-aminophosphonates with high yields, but ZnCl2 did not give high yields of the compounds and the reaction took longer time in comparison to that taken by FeCl3 The chemical structures of all new compounds were confirmed by spectrophotometric methods (1HNMR, 13CNMR, IR). The compounds were investigated for antimicrobial activity against Escherichia coli, Bacillus subtilis, Salmonella typhi, Shigella sonnei, Proteus vulgaris, and Staphylococcus epidermidis. Conclusion: The new synthesized compounds did not show good antibacterial activity against the tested microorganisms

Insignificant difference between biofilm forming isolates of filtered water and non-filtered water

Sangita Revdiwala, Summaiya Mulla, Nrupal Chevli

Journal of Pharmaceutical Negative Results 2011 2(2):110-114

Aim: Biofilm formation is a developmental process with intercellular signals that regulate growth. Biofilms contaminate catheters, ventilators, and medical implants; they act as a source of disease for humans, animals, and plants. In this study we have done a quantitative assessment of biofilm formation in bacterial isolates, associated with the drinking water distribution system, in tryptic soya broth, with different incubation times. Materials and Methods: The study was carried out on 104 samples of water from different systems. The bacterial isolates were processed as per the microtiter plate method with only tryptic soya broth, and with varying concentrations of glucose, and were observed in response to time. Results: Out of the total of 104 samples of water, 63 were found to be bacteriologically positive and 24 of them were biofilm formers. Enterobacter spp. and Pseudomonas were maximally found to be biofilm producing. Conclusion: Biofilm formation depends on adherence of bacteria to various surfaces. Overhead plastic tanks and metal taps were the most common sources being infected. We must have a regular policy to get them clean so as to have affordable and safe drinking water.

Antacids incorporation in immediate release tablets failed to improve the stability of omeprazole in acidic media

HV Chavda, TM Chaudhary, CN Patel

Journal of Pharmaceutical Negative Results 2011 2(2):73-77

Background: The stability of omeprazole (OMZ) decreases in acidic medium. In this investigation, attempts have been made to develop oral tablet containing antacids/buffers to increase the pH of dissolution media for certain time. Materials and Methods: Tablet formulations were prepared by the direct compression technique. For the selection of superdisintegrant, Croscarmellose sodium, used initially was replaced with other superdisintegrants. The prepared tablets were evaluated for hardness, weight variation, thickness, friability, drug content, disintegration time and in vitro drug release studies. During the in vitro drug release studies, the pH of dissolution media was measured. Results and Discussion: All batches showed very short disintegration time, within 0.5-2 min except F1 and S5. Batch F7 was able to provide the immediate drug release. The study showed that the incorporation of antacid improved the pH of dissolution media, but failed to maintain it. Even though the high quantities of antacids were incorporated; the stability of drug in media was not improved. Other superdisintegrants did not show any significant changes in drug release or disintegration time. Bath F7 was stable for the period of 6 months at 40 o C / 75 %RH. Conclusions: Incorporation of higher quantities of antacids failed to retain the stability of OMZ in acidic media.

Sodium nitrite therapy fails to improve tissue perfusion in a mouse model of hind limb ischemia: Slight differences in methodology may be responsible casting suspicion on the reliability and predictive value of this model

Jeff S McKee, Benjamin D Brooks

Journal of Pharmaceutical Negative Results 2011 2(2):99-106

Background: The nude mouse model of hind limb ischemia is used to evaluate human-derived, cell-based therapeutics intended to promote tissue perfusion. The criticism of the mouse model of hind limb ischemia is the absence of a well-characterized positive control. The suitability of sodium nitrite (NaNO 2 ) was evaluated. The rationale for doing so was based on a report that NaNO 2 induced unprecedented tissue perfusion in wild-type mice using a similar model. The objective was to evaluate NaNO 2 to improve tissue perfusion in nude mice as well as their wild-type counterparts. Materials and Methods: The mice underwent surgically induced, unilateral hind limb ischemia, and received either NaNO 2 or a vehicle intraperitoneally, twice daily, for seven days. Hind limb tissue perfusion was evaluated on days one, four, seven, and fourteen post-surgery. Results: No increase in tissue perfusion was observed in the nude or wild-type mice treated with NaNO 2 when compared with the vehicle. Nude mice exhibited significantly lower tissue perfusion compared to wild-type mice, irrespective of the treatment. Conclusions: NaNO 2 failed to increase tissue perfusion and, therefore, did not appear suitable for use as a positive control in this model. This is in stark contrast to a previous report indicating that NaNO 2 significantly increased tissue perfusion in wild-type mice using a similar model. The exact cause is not known, but is probably due to differences in methodology employed between laboratories. The lower tissue perfusion in nude mice is a novel finding, suggesting this strain may have less pre-existing collateral vessels and/or a reduced capacity to form new vessels as compared to wild-type mice.

Effort toward the single pot synthesis of 6-(Biphenyl-4-yl)-2-[2-(indol-1-yl)ethyl]-4,5-dihydropyridazin-3(2H)-one from 6-(Biphenyl-4-yl)-2-[2-(indol-1-yl)ethyl]-4,5-dihydropyridazin-3(2H)-one

Mohammad Asif, Anita Singh, Lakshmayya

Journal of Pharmaceutical Negative Results 2011 2(2):69-72

Background: Many synthetic heterocyclic compounds are known to have different biological activities. Pyridazine and its derivatives are the important six membered heterocyclic compounds containing two N-hetero atoms. The pyridazine moiety is an important structural feature of many biologically active compounds. Pyridazine derivatives show diverse pharmacological properties. Aims and Objectives of the Study: The goal of this study, Pyridazine hold considerable interest relative to the preparation of organic intermediates and physiologically active compounds also. On the basis of its important in reported literature, we synthesized the 6-(Biphenyl-4-yl)-2-[2-(indol-1-yl)ethyl]-4,5-dihydropyridazin-3(2H)-one from 6-(Biphenyl-4-yl)-2-[2-(indol-1-yl)ethyl]-4,5-dihydro pyridazin-3(2H)-one in single step or pot reaction. Results : The important Observations and concrete implications of the study. The result showed that the compound 6-(Biphenyl-4-yl)-2-[2-(indol-1-yl) ethyl]-4,5-dihydropyridazin-3(2H)-one was not prepared by this method. The synthesis of compound has been confirmed by the spectral analysis namely IR, 1H NMR and Mass spectroscopy.

Reporting of sample size and power in negative clinical trials published in Indian medical journals

Jaykaran , Preeti Yadav, ND Kantharia

Journal of Pharmaceutical Negative Results 2011 2(2):87-90

Background and Aim: It is observed that negative clinical trials published in medical journals are poor in reporting of sample size calculation, various components of calculation of sample size. It is also observed that they are underpowered to detect the actual difference between the treatment outcomes. Because of scarcity of these data for Indian medical journals we designed this study to critically analyze the Indian medical journals for reporting of sample size, components of sample size and power. We calculated post hoc power for 30% and 50% difference between the treatment outcomes. Materials and Methods: All the negative clinical trials published in five Indian medical journals (Indian Journal of Pharmacology (IJP), Indian Pediatrics (IP), Indian Journal of Dermatology (IJD), Indian Journal of Dermatology, Vanereology and Leprology (IJDVL), and Journal of Postgraduate Medicine (JPGM)), between 2001 and 2008, were analyzed by each author for reporting of the sample size and components of the sample size. Post hoc power for 30% and 50% differences between the outcome was calculated by G Power software. All data were expressed as frequency, percentages, and 95% confidence interval around the percentages with the help of SPSS ver. 17. Results: The median sample size was observed to be 33 (range 9-85). Power was calculated in 28 (41.1%, 95% CI 30.2% to 53%) trials. The sample size was not calculated in 34 (50%, 95% CI 38.4% to 61.5%) trials. The full sample size was calculated in only 2 (2.9%, 95% CI 0.8% to 10.1%) trials. Post hoc power above 80% for 30% of difference was reported in 3 (4.4%, 95% CI 1.5% to 12%) trials and for 50% difference in outcome it was reported in 42 (61.7%, 95% CI 49.8% to 72.3) trials. Conclusion: Negative clinical trials published in five Indian journals are poor in reporting of sample size calculation. It is also observed that most of trials are underpowered to see the 30% and 50% difference between the outcomes. There is a need to generate more awareness regarding the sample size and power calculation

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