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PubMed1998

Colchicine: 1998 update.

OBJECTIVE: To present an update of the use of colchicine in patients with familial Mediterranean fever (FMF) and other rheumatic and nonrheumatic diseases. DATA SOURCES: Published studies on colchicine retrieved from MEDLINE searches from 1987 to 1997 and reports presented at national and international meetings. STUDIES SELECTION AND EXTRACTION: All studies were reviewed by the authors. Reports addressing the topics of colchicine pharmacokinetics, biological effects, indications for use, and side effects were selected. DATA SYNTHESIS: Colchicine is an alkaloid that may interfere with microtubule formation, thereby affecting mitosis and other microtubule-dependent functions. It has a bioavailability of 25% to 50% when administered orally. Colchicine and its metabolites are excreted through the urinary and biliary tracts. It may be used while breast feeding; however, amniocentesis should be performed when used in pregnancy. The drug may be given to children with FMF. The efficacy of colchicine has been proved in FMF, gout, Behcet's disease, and cirrhosis. Its place in the treatment of scleroderma, sarcoidosis, and skin disorders remains to be determined. Gastrointestinal side effects occur early and are most common manifestations of colchicine toxicity. Severe colchicine toxicity results in multiple organ failure, convulsions, coma, and death. Potentially, effective treatment with Fab anti-colchicine antibodies unfortunately is unavailable; therefore, treatment is supportive. CONCLUSIONS: Colchicine is a relatively safe and effective medication for several disorders when used in appropriate dosage in patients with normal kidney and liver function.

Behcet Syndrome↗
PubMed1993

Effect of antihypertensive therapy on the kidney in patients with diabetes: a meta-regression analysis.

OBJECTIVE: To assess the relative effect of different antihypertensive agents on proteinuria and renal function in patients with diabetes. DATA SOURCES: We used MEDLINE and bibliographies in recent articles to identify studies of the effects of antihypertensive agents on renal function in patients with diabetes. STUDY SELECTION: We selected 100 controlled and uncontrolled studies that provided data on renal function, proteinuria, or both, before and after treatment with an antihypertensive agent. DATA EXTRACTION: Data on blood pressure, renal function, proteinuria, patient characteristics (for example, age, sex, and type of diabetes), and study design (for example, random allocation and the use of a placebo) were extracted from selected studies. DATA SYNTHESIS: Multiple linear regression analysis indicated that angiotensin-converting enzyme (ACE) inhibitors decreased proteinuria independent of changes in blood pressure, treatment duration, and the type of diabetes or stage of nephropathy, as well as study design (P < 0.0001). Reductions in proteinuria from other antihypertensive agents could be entirely explained by changes in blood pressure. Blood pressure reduction in itself was associated with a relative increase in glomerular filtration rate (regression coefficient [+/- SE], 3.70 +/- .92 mL/min for each reduction of 10 mm Hg in mean arterial pressure; P = 0.0002); however, compared with other agents, ACE inhibitors had an additional favorable effect on glomerular filtration rate that was independent of blood pressure changes (3.41 +/- 1.71 mL/min; P = 0.05). CONCLUSION: Angiotensin-converting enzyme inhibitors can decrease proteinuria and preserve glomerular filtration rate in patients with diabetes. These effects occur independent of changes in systemic blood pressure.

Adolescent↗
PubMed1999

Scanning electron microscopy study of the effect of tetracycline HCl on smear layer removal and fibrin network formation.

Scanning electron microscopy (SEM) was used to evaluate root surface characteristics of human teeth affected with periodontitis following periodontal instrumentation and topical application of tetracycline HCl (TTC-HCl; pH 1.6; 4 min). Specimens were randomly assigned to periodontal instrumentation alone (control 1); periodontal instrumentation plus TTC-HCl (test 1); periodontal instrumentation plus trypsin solution after extraction (control 2); and periodontal instrumentation plus TTC-HCl plus trypsin solution after extraction (test 2). Tetracycline solution was applied with a cotton pellet. Twenty-two single root periodontitis affected human teeth scheduled for extraction were selected. Mucoperiosteal flaps were raised, root surfaces were mechanically and chemically treated, flaps were repositioned and maintained in place for 20 min. Teeth were extracted, rinsed and placed in cold phosphate buffer solution (PBS) and control 2 and test 2 groups were treated with trypsin solution. Specimens were examined using SEM. Smear layer was successfully removed, exposing dentinal tubules; however, fibrin network formation in situ was not improved by application of TTC-HCl.

Anti-Bacterial Agents↗
PubMed1992

Evaluation of latex allergy in patients with meningomyelocele.

Seventy-six patients with meningomyelocele were evaluated for latex sensitivity by medical history and epicutaneous skin testing. Four different latex glove extracts, two nonlatex glove extracts, cornstarch, selected inhalant antigens, and negative and positive controls were used for skin testing. Forty-nine patients (64.5%) were skin test positive to latex extracts (latex-positive group). Twenty-four patients (49%) of the latex-positive group and none of the latex-negative group had histories of immediate reactions to latex products (P less than .001). The latex-positive group had a higher mean number of surgical procedures, 12.67 +/- 11.27, compared with 6.89 +/- 6.55 (P less than .001) in the latex-negative group. Twenty-three of the latex-positive patients (47%) used latex products daily compared to seven patients (26%) in the latex-negative group (P = .073). Twenty latex-positive patients (41%) had atopy compared with five patients (19%) of the latex negative group (P = .041). There was no significant difference between the two groups in age, sex, daily catheterization, or positive skin tests to cornstarch. All 76 patients tested negative to the nonlatex glove extracts. Ten control subjects tested negative for all latex and nonlatex glove extracts.

Adolescent↗
PubMed1996

Pesticide residue analyses in plant material by chromatographic methods: clean-up procedures and selective detectors.

This paper deals with the analysis of pesticide residues by chromatographic methods in samples of plant origin. Emphasis is put on the isolation and clean-up steps of the sample preparation for GC or LC determination. The problems of the extraction solvent selection and clean-up procedures using different types of adsorption column chromatography or gel permeation chromatography are discussed. Attention is also given to alternative techniques such as supercritical fluid extraction (SFE), matrix solid-phase dispersion (extraction) (MSPD) and sweep co-distillation that are used for sample processing prior to GC and LC analysis. Currently, pesticide residue analyses are typically multi-residue procedures with highly sensitive methods. Consumption of costly and toxic solvents is being minimized and fully automated analytical procedures can be expected in the future.

Chromatography↗
PubMed1993

Mapping of a sequence essential for the nuclear transport of the Xenopus ribosomal transcription factor xUBF using a simple coupled translation-transport and acid extraction approach.

The amino acid sequences directing the nuclear transport of the RNA polymerase I transcription factor xUBF have been studied by a novel combination of in oocyte-coupled translation-nuclear transport and selective HCl extraction. Synthetic mRNA was used to direct the translation of labeled xUBF and its mutants in microinjected oocytes. After manual dissection of nuclei and cytoplasm, labeled xUBF and mutants were isolated essentially pure by HCl extraction. Using deletion mutations, a sequence essential, but not necessarily sufficient, for nuclear transport was mapped to a 29-amino-acid segment lying between the most carboxy-terminal putative HMG-box DNA-binding domain, HMG-box 5, and the highly acidic carboxy-terminal domain. It was shown that deletion of only 5 amino acids from this segment eliminated xUBF transport, and it could be deduced that at least 11 of the 29 amino acids were essential for nuclear transport. The segment of xUBF necessary for nuclear transport contains a sequence conforming to the bipartite nuclear transport motif consensus, but this sequence in itself was insufficient for nuclear transport.

Amino Acid Sequence↗
PubMed2005

Osteotomy for treating knee osteoarthritis.

BACKGROUND: Patients with unicompartmental osteoarthritis of the knee can be treated with a correction osteotomy. The goal of the correction osteotomy is to transfer the load bearing from the pathologic to the normal compartment of the knee. A successful outcome of the osteotomy relies on proper patient selection, stage of osteoarthritis, achievement and maintenance of adequate operative correction. OBJECTIVES: To assess the effectiveness and safety of an osteotomy for treating osteoarthritis of the knee. SEARCH STRATEGY: The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE (Current contents, Health STAR) were searched up until October 2002 for controlled clinical trials. The reference lists of publications in the identified trials were also screened. SELECTION CRITERIA: Extracted studies were included in the final analysis if they met the pre-defined inclusion criteria: 1) a randomised controlled clinical trial or a controlled clinical trial 2) all patients had unicompartmental osteoarthritis of the medial or lateral compartment of the knee 3) the intervention in one of the studied groups was a high tibial osteotomy or a distal femoral osteotomy. DATA COLLECTION AND ANALYSIS: Two reviewers independently selected the trials, assessed the methodological quality using a validated tool and extracted the data. The planned analysis was to pool the results where appropriate, however, due the heterogeneity of the studies, pooling of the outcome measures was not possible. Results are described for each study and presented as a best evidence synthesis. MAIN RESULTS: Following the search strategy and applications of selection criteria, eleven studies were included in this review. All the studies concerned a valgus high tibial osteotomy (HTO) for medial compartment osteoarthritis of the knee. Four studies compared two techniques of HTO. One study compared HTO alone versus HTO with additional treatment. Four studies compared within the same type of HTO, different per-operative conditions (two studies) or two different types of post-operative treatment (two studies). Two studies compared HTO with unicompartmental joint replacement. No study compared an osteotomy with conservative treatment. Most studies showed improvement of the patient (less pain and improvement of function scores) after osteotomy surgery, but in the majority of the studies there was no significant difference with other operative treatment (other technique of HTO/ unicompartmental joint replacement). Overall, the methodological quality was low. AUTHORS' CONCLUSIONS: Based on 11 studies, of which 6 were high quality, we conclude that there is silver level evidence that valgus HTO improves knee function and reduces pain. There is no evidence whether an osteotomy is more effective than conservative treatment and the results so far do not justify a conclusion about effectiveness of specific surgical techniques.

Humans↗
PubMed2006

Determination of sulfonylurea herbicides in water and food samples using sol-gel glass-based immunoaffinity extraction and liquid chromatography-ultraviolet/diode array detection or liquid chromatography-tandem mass spectrometry.

Immunoaffinity supports (IAS) were prepared using broad specific polyclonal anti-sulfonylurea (SU) antibodies immobilized in sol-gel glass. Two different kinds of supports were applied, crushed sol-gel monoliths and sol-gel-coated highly porous silica particles. Both were used for the quantitative enrichment of SUs in natural water and food samples followed by high-performance liquid chromatography-ultraviolet/diode array detection (HPLC-UV/DAD) and tandem mass spectrometry (LC-MS/MS), respectively. Loading, washing, and elution conditions of IAS were optimized. The capacity of supports was determined for 30 SUs and compared with the cross-reactivity pattern of the direct competitive enzyme-linked immunosorbent assay. The capacities correlated well with the affinity to individual SU compounds. Even analytes to which the polyclonal antibodies showed only a lower cross-reactivity could be enriched to a certain degree, if a sufficient capacity of IAS was provided. The IAS could be reused at least 10 times without a loss of effectiveness. Recovery of 16 selected SUs extracted from spiked water and food samples was dependent on the affinity of both immobilized antibodies to single compounds and matrix interferences. In water, 13 SUs showed recoveries higher than 80% when immunoaffinity extraction was used in combination with LC-UV/DAD. On the basis of the enrichment of 200 mL of aqueous sample, corresponding limit of detection (LOD) values ranged between 20 and 100 ng/L. The recoveries of 10 SUs, which were extracted from 10 g of potato spiked at a 10 microg/kg level, were higher than 75%. For grain samples, recoveries were at the same order for at least five SU herbicides. The LOD of LC-MS/MS measurements was about 1 order of magnitude higher, i.e., gave LODs between 1.1 and 6.9 microg/kg of food sample, depending on the compound and extraction procedure. These LODs provide evidence that the main advantage of the prepared IAS is their high selectivity for group specific recognition of SUs as compared to other nonspecific solid phase extraction materials.

Chromatography, High Pressure Liquid↗
PubMedDate not supplied

Analysis of bisdesmosidic saponins in Saponaria vaccaria L. by HPLC-PAD-MS: identification of new quillaic acid and gypsogenin 3-O-trisaccharides.

A high-performance liquid chromatographic method using photodiode array and single quadrupole electrospray mass detection for analysis and profiling of bisdesmosidic saponins in Saponaria vaccaria seed was developed. Profiles of seed extract from three different plant sources were obtained and found to contain the same saponins, albeit in different proportions. Several known saponins were identified by selected ion extraction of quasi-molecular ions from the total ion chromatogram and confirmed by their mass spectra. Application of high cone voltages afforded mass spectra containing key diagnostic fragments and relatively strong singly charged quasi-molecular ions. In addition to previously identified saponins, several new quillaic acid and gypsogenin bisdesmosides could be detected via mass spectral analysis. Five of these were tentatively identified as pentose homologues of known saponins, having an added xylosyl residue linked to the 3-O-glucuronyl group (1 --> 3). The stereochemistry and identity of the xylosyl linkage in the new saponins was determined by chemical means. Previously reported vaccaric or segetalic acid-type bisdesmosides could not be detected in any of the extracts.

Carbohydrate Conformation↗
PubMed1997

Effects of amiodarone on thyroid function.

PURPOSE: To review the literature on the effects of amiodarone on thyroid physiology and management of amiodarone-induced thyroid disease. DATA SOURCES: English-language articles identified through a MEDLINE search (for 1975 to 1995, using the terms amiodarone and thyroid) and selected cross-referenced articles. STUDY SELECTION: Articles on the effects of amiodarone on thyroid physiology and function tests and occurrence, recognition, and management of amiodarone-induced thyroid disease. DATA EXTRACTION: Data were manually extracted from selected studies and reports; emphasis was placed on information relevant to the practicing clinician. DATA SYNTHESIS: Amiodarone can have many effects on thyroid function test results, even in the absence of hyperthyroidism or hypothyroidism. It may cause an increase in serum levels of thyroxine, reverse triiodothyronine, and thyroid-stimulating hormone and a decrease in serum triiodothyronine levels. Thyrotoxicosis occurs in some patients and is related to several pathogenetic mechanisms. It often present dramatically with obvious clinical manifestations and further changes in thyroid function test results. Medical options include therapy with thionamides, perchlorate, and prednisone. Radioactive iodine is of little use. Thyroidectomy is effective and is the only measure that consistently allows continued use of amiodarone. Unlike thyrotoxicosis, hypothyroidism is related to a persistent Wolff-Chaikoff effect and often has a vague presentation. The goal of treatment of amiodarone-induced hypothyroidism is to bring serum thyroxine levels to the upper end of the normal range, as often seen in euthyroid patients who are receiving amiodarone. CONCLUSIONS: Thyroid dysfunction commonly occurs with amiodarone therapy. It may be difficult to recognize the dysfunction because of the many changes in thyroid function test results that occur in euthyroid patients who are receiving amiodarone. Effective strategies exist for the management of hyperthyroidism and hypothyroidism; these should be tailored to the needs of the individual patient.

Amiodarone↗
PubMedDate not supplied

Immediate mandibular rehabilitation with endosseous implants: simultaneous extraction, implant placement, and loading.

PURPOSE: This report of a clinical patient series indicates the relative safety and illustrates the procedures involved in the extraction of remaining teeth followed by immediate implant placement and loading with a simple acrylic resin fixed denture. MATERIALS AND METHODS: Ten consecutive patients who selected tooth extraction and implant-supported fixed denture rehabilitation of the mandible were treated using a 1-visit approach for extraction, implant placement, and restoration. Healthy individuals (10 women) were treated under local anesthesia. Fifty-four implants were placed in 10 patients. Five or 6 Astra Tech implants (11 or 13 mm long) were placed into the edentulous parasymphyseal region of the mandible. Four to 6 implants (48 of 54) were immediately loaded by the fabrication of a simple acrylic resin fixed denture. The criterion for loading was clinical judgment of primary stability, ie, the absence of axial or lateral mobility with physical resistance to rotation. Patients were recalled at 1, 3, and 12 weeks. At 12 weeks, impressions were made for the fabrication of a screw-retained fixed denture. The fixed dentures were completed using conventional fabrication and prosthetic techniques. RESULTS: After a period of 6 to 18 months, all 54 implants had survived and were considered 100% successful by independent testing of mobility and radiographic evidence of osseointegration. There were no surgical complications. Fracture and debonding of the acrylic resin provisional denture occurred for 1 patient during the first 12 weeks of treatment. DISCUSSION: Advantages to extraction with simultaneous replacement include the maintenance of vertical dimension, elimination of reline procedures and interim denture therapy, and potential improvement of soft tissue healing. CONCLUSION: This therapeutic approach simplifies patient care without apparent additional risk.

Adult↗
PubMed1998

An algorithm to detect Chlamydia trachomatis by polymerase chain reaction on specimens extracted for enzyme immunoassay.

Amplification assays for detecting Chlamydia trachomatis have been shown to be more sensitive than enzyme immunoassay (EIA) by many investigators. In this study, we have developed an algorithm for performing PCR (COBAS AMPLICOR) on selected specimens extracted for EIA (ACCESS) with sample-to-cutoff (s/co) values between 0.25 and 0.99. Furthermore, we have shown that these specimens can be utilized for PCR without encountering any inhibition problems. In our investigation, 230 out of 6,558 urethral and cervical swabs submitted for C. trachomatis screening by EIA over a period of 9 months, had s/co values ranging between of 0.25 and 0.99. Ninety (39.1%) of these specimens tested positive by PCR. These specimens were stable and gave reproducible PCR results before and after storage for a period of 9 months. This testing algorithm offers an effective way of detecting C. trachomatis with selective use of PCR while increasing the sensitivity of the EIA screening system.

Algorithms↗
PubMed2002

Selective separation of hydroxide from alkaline nuclear tank waste by liquid-liquid extraction with weak hydroxy acids.

Recovery and recycle of caustic reagents in industrial processes offer potential means of pollution prevention, as investigated herein for particular needs related to the cleanup of alkaline nuclear waste. Specifically, the recovery of hydroxide from alkaline media by liquid-liquid extraction can be effected utilizing weak hydroxy acids, as demonstrated for NaOH utilizing a series of lipophilic fluorinated alcohols and alkylated phenols dissolved in 1-octanol. Extraction efficiency follows the expected order of acidity of the hydroxy acids, the phenols being the most efficient extractants among the compounds tested. After extraction, NaOH is effectively recoverable from the organic phase upon contact with water. The weakest hydroxy acids are the most efficiently stripped, NaOH recovery being nearly quantitative in a single contact. In competitive extraction experiments, good selectivity for hydroxide recovery over other anions such as nitrate and chloride was demonstrated. Since the order of extraction favors larger anions, the exceptional preference for hydroxide implies that the extraction occurs by deprotonation of the hydroxy acids in a cation-exchange process. Stripping therefore occurs by hydrolysis to regenerate the neutral hydroxy acid, liberating NaOH to the aqueous phase. Since hydroxide equivalents rather than actual hydroxide ions are transferred to the solvent, the process is termed "pseudohydroxide extraction." Hydroxide recovery from a simulant of alkaline nuclear tank waste (Hanford DSSF simulant) was also demonstrated in repeated extraction and stripping cycles.

Cations↗
PubMed2003

Application of 3D-Jury, GRDB, and Verify3D in fold recognition.

In CASP5, the BioInfo.PL group has used the structure prediction Meta Server and the associated newly developed flexible meta-predictor, called 3D-Jury, as the main structure prediction tools. The most important feature of the meta-predictor is a high (86%) correlation between the reported confidence score and the quality of the selected model. The Gene Relational Database (GRDB) was used to confirm the fold recognition results by selecting distant homologues and subsequent structure prediction with the Meta Server. A fragment-splicing procedure was performed as a final processing step with large fragments extracted from selected models using model quality control provided by Verify3D. The comparison of submitted models with the native structure conducted after the CASP meeting showed that the GRDB-supported structure prediction led to a satisfactory template fold selection, whereas the fragment-splicing procedure must be improved in the future.

Amino Acid Sequence↗
PubMed2006

Iron fractionation for corrosion products from natural gas pipelines by continuous-flow sequential extraction.

The forms and quantities of iron species in corrosion product samples from natural gas pipelines were examined, using a continuous-flow sequential extraction system. Sequential extraction consists of four steps that dissolve water soluble iron (FeSO4), acid soluble iron (FeCO3), reducible iron (Fe-(oxyhydr)oxides) and oxidisable iron (FeS2) fractions, respectively. Selectivity of extracting reagents for particular iron species was evaluated by determination of co-extracted anions, using ion chromatography, and evolved CO2, using indirect flame atomic absorption spectrometer (FAAS). Iron was found predominantly in the reducible fraction (61-99%), indicating that Fe-(oxyhydr)oxides are the major constituents of the corrosion products.

Journal Article↗
PubMed2002

Cancer prevention and therapy with kiwifruit in Chinese folklore medicine: a study of kiwifruit extracts.

Kiwi gold fruits were extracted successively with hexane, acetone, methanol and 70% methanol, and further fractionated by silica gel and ODS column chromatographies for the assays of various biological activities. Five fractions H1, H2 (hexane extract), Al, A2 (acetone extract) and M2 (methanol extract) showed selective cytotoxic activity against human oral tumor cell lines, which was more sensitive than human gingival fibroblasts. More hydrophilic fractions [70M3, 70M4, 70M5] of 70% methanol extract displayed higher anti-HIV activity, radical generation and O2- scavenging activity. The antibacterial activity of 70% methanol extracts [70M0, 70M1, 70M2, 70M3, 70M4] was generally lower than that of more lipophilic fractions (hexane, acetone, methanol extracts), although each fraction did not show any specific antimicrobial action. All fractions were inactive against Helicobacter pylori. These results demonstrate that gold kiwifruit extracts contain valuable, various bioactive materials, which can be separated with each other.

Actinidia↗
PubMed1977

The role of the liver in glucagon metabolism.

Total plasma immunoreactive pancreatic glucagon (IRG) was measured in samples taken simultaneously from the proximal portal vein and superior vena cava of 26 healthy rats. The portal-peripheral ratio of IRG was 2.80+/-0.25, the portal-peripheral difference (Delta) 124+/-15 pg/ml, and percentage extraction 58+/-3. Gel filtration of paired portal and peripheral vein samples showed that reduction in the 3,500-dalton IRG component (glucagon) in peripheral samples accounted for almost all the differences, there being minimal and inconsistent changes in the high molecular weight (>40,000) fraction. The portal-peripheral ratio of the 3,500-dalton glucagon was 5.24+/-1.10, the portal-peripheral difference 130+/-33 pg/ml, and the percentage extraction 81+/-5. To study the transhepatic differences in the 9,000-dalton "proglucagon-like" material, the experiment was repeated in nine rats 24 h after bilateral nephrectomy, a procedure which increases plasma levels of this fraction. The portal-peripheral ratio for plasma IRG in these rats was 1.48+/-0.12, the portal-peripheral difference 140+/-29 pg/ml, and percentage extraction 28+/-5. Gel filtration revealed no consistent differences between portal and peripheral concentrations of the 9,000- and >40,000-dalton components, which comprised 40 and 13%, respectively, of the mean IRG level of 492+/-35 pg/ml. In contrast, there were marked differences between portal and peripheral levels of the 3,500-dalton component the ratio being 3.42+/-0.63, the portal-peripheral difference 182+/-32 pg/ml, and percentage extraction 64+/-5. Similar studies in a healthy dog, in which species there are significant circulating levels of the 9,000-dalton IRG component, confirmed the selective hepatic extraction of the 3,500-dalton fraction. We conclude that the various IRG fractions are metabolized differently by the liver, and that portal-peripheral ratios based on direct assay of plasma IRG will vary depending on the percentage glucagon immunoreactivity in each fraction; the greater the combined contribution of fractions other than the 3,500-dalton component to total plasma IRG, the lower will be the ratio. Because of the heterogeneity of circulating IRG and significant differences in the metabolism of its various components, gel filtration of plasma samples is necessary for precise quantitation of the hepatic uptake of each particular fraction.

Animals↗
PubMed1994

[Studies on antiulcer agents. I. The effects of various methanol and aqueous extracts of crude drugs on antiulcer activity].

The antiulcer activities of 59 methanol and aqueous extracts obtained from 59 crude drugs on the ethanol-HCl-induced ulceration in rats were investigated. Among them 15 extracts were selected and they were further examined for their effects on indomethacin-, aspirin- and the water-immersion stress-induced ulcer. From these results, the methanol extract of root of Iris germanica was found to, show potent antiulcer activities. The above methanol extract was separated into 3 portions by solvent extraction, and the ether soluble portion was fractionated into 5 fractions (1 to 5) by chromatography. Fractions 4 and 5 showed significant antiulcer activities. Fraction 4 was further purified and the obtained gamma-irigermanal exhibited a potent antiulcer activity. However, further investigations are required to understand the mechanism.

Animals↗