Reliability of 18F-FDG PET Metabolic Parameters Derived Using Simultaneous PET/MRI and Correlation With Prognostic Factors of Invasive Ductal Carcinoma: A Feasibility Study.

OBJECTIVE: The objective of our study was to correlate semiquantitative PET parameters-standardized uptake value (SUV) and total lesion glycolysis (TLG)-derived in simultaneous PET/MRI using MRI-based attenuation correction with clinical and histopathologic prognostic factors in patients with breast cancer. MATERIALS AND METHODS: Eighty-two invasive ductal carcinomas in 69 women were included in the study. All the subjects underwent whole-body (WB) PET/MRI (supine WB mode) and dedicated PET/MRI of the breast (prone breast imaging mode) for staging on a simultaneous PET/MRI system. The SUV and TLG values were calculated from 18F-FDG PET data using MRI-based attenuation correction (2-point Dixon sequence for tissue segmentation). Relationships between SUV and TLG values and clinical and histopathologic parameters (i.e., tumor size, tumor grade, Ki-67 status, and hormonal receptor expression status) were evaluated using Spearman correlation coefficient analysis. RESULTS: A significant correlation was observed between mean SUV (SUVmean) and maximum SUV (SUVmax) values derived with WB PET and regional PET of the breasts performed simultaneously with MRI (r = 0.88 and 0.89, respectively). A significant difference (p < 0.05) was observed in SUVmean, SUVmax, and TLG values between the grades and molecular subtypes of breast cancer. High SUVmean, SUVmax, and TLG values were found to correlate with larger tumor size (p < 0.01), higher proliferation index (p < 0.05), higher grade (p < 0.01), and triple-negative hormonal receptor status (p < 0.01, p < 0.05). CONCLUSION: Semiquantitative FDG parameters derived with MRI-based attenuation correction in simultaneous PET/MRI are reliable and correlate with clinicopathologic features such as grade as well as subtype and thus could be used in the prognostication of breast cancer.

Anti-Helicobacter pylori potential of artemisinin and its derivatives.

The antimalarial drug artemisinin from Artemisia annua demonstrated remarkably strong activity against Helicobacter pylori, the pathogen responsible for peptic ulcer diseases. In an effort to develop a novel antimicrobial chemotherapeutic agent containing such a sesquiterpene lactone endoperoxide, a series of analogues (2 natural and 15 semisynthetic molecules), including eight newly synthesized compounds, were investigated against clinical and standard strains of H. pylori. The antimicrobial spectrum against 10 H. pylori strains and a few other bacterial and fungal strains indicated specificity against the ulcer causing organism. Of five promising molecules, a newly synthesized ether derivative ß-artecyclopropylmether was found to be the most potent compound, which exhibited MIC range, MIC(90), and minimum bactericidal concentration range values of 0.25 to 1.0 µg/ml, 1.0 µg/ml, and 1 to 16 µg/ml, respectively, against both resistant and sensitive strains of H. pylori. The molecule demonstrated strong bactericidal kinetics with extensive morphological degeneration, retained functional efficacy at stomach acidic pH unlike clarithromycin, did not elicit drug resistance unlike metronidazole, and imparted sensitivity to resistant strains. It is not cytotoxic and exhibits in vivo potentiality to reduce the H. pylori burden in a chronic infection model. Thus, ß-artecyclopropylmether could be a lead candidate for anti-H. pylori therapeutics. Since the recurrence of gastroduodenal ulcers is believed to be mainly due to antibiotic resistance of the commensal organism H. pylori, development of a candidate drug from this finding is warranted.

Cyclo-oxygenase-1 inhibition increases acid secretion by modulating H+,K+-ATPase expression and activation in rabbit parietal cells.

1. In the present study, we evaluated the role of cyclo-oxygenase (COX)-1 and COX-2 on gastric acid secretion in rabbit isolated parietal cells and gastric glands by examining [(14)C]-aminopyrine uptake, prostaglandin (PG) E(2) synthesis and COX-1, COX-2 and proton pump expression at baseline and after treatment with various concentrations of specific COX-1 (SC-560), COX-2 (5,5-dimethyl-3-(3-fluorophenyl)-4-(4-methyl-sulphonyl)phenyl-2 (5H)-furanone; DFU) and non-specific COX (indomethacin) inhibitors. 2. In parietal cells, SC-560 and indomethacin, over the concentration range 10(-8) to 10(-4) mol/L, dose-dependently increased basal and 10(-4) mol/L histamine-stimulated aminopyrine uptake and inhibited PGE(2) synthesis, whereas DFU (10(-8) to 10(-5) mol/L) had no effect. However, at 10(-4) mol/L, DFU augmented histamine-stimulated aminopyrine uptake by 135% and inhibited PGE(2) synthesis by 39%, indicating an inhibition of COX-1 at this higher concentration. 3. The SC-560-, DFU- and indomethacin-induced augmentation of histamine-stimulated aminopyrine uptake was reduced to basal levels after 10(-5) mol/L lansoprazole treatment in parietal cells and gastric glands, whereas 10(-4) mol/L ranitidine only partially inhibited such augmentation. 4. Only COX-1 was detected in parietal cells. However, both COX-1 and COX-2 were expressed in gastric glands, with relative protein density of COX-1 being sixfold higher than that of COX-2. Protein levels of COX-1 in parietal cells and those of COX-1 and COX-2 in gastric glands remained unchanged, regardless of inhibitor treatment, either alone or with histamine. 5. Parietal cell proton pump expression was significantly enhanced by 10(-5) mol/L SC-560 and 10(-4) mol/L indomethacin (by 29 and 31%, respectively) and pump activity was enhanced by 61 and 65%, respectively. In contrast, 10(-5) mol/L DFU had no effect. 6. In conclusion, the data indicate that inhibition of COX-1- but not COX-2-derived PGE(2) synthesis is involved in augmentation of non-steroidal anti-inflammatory drug-induced gastric acid secretion in parietal cells by enhancing expression and activation of the proton pump.

Detection and quantification of ppb level potassium in biological samples in the presence of high sodium by ion chromatographic method.

Employing a silica gel column modified with carboxyl groups and an eluent consisting of 4.0mM tartaric acid and 0.75mM dipicolinic acid in 2% acetone, an otherwise difficult quantification of K(+) at ppb level in presence of 6000ppm NaCl was achieved by incorporating 0.75mM 18-crown-6 ether in the mobile phase and subtracting the blank NaCl signal from each chromatogram. Optimized analytical conditions were established in terms of relative standard deviation (%) of retention time, peak area and calibration equations, and also by peak asymmetry factor. The net efflux of K(+) into the gastric lumen under in vitro conditions of acid secretion was investigated in Ussing chamber model. The effects of the physiological secretagogue histamine and the antisecretory agents cimetidine, omeprazole and SCH28080 were studied. The decline of K(+) efflux in presence of cimetidine, and the rise of the same in the presence of omeprazole and SCH28080 were conspicuously discernible, thereby validating the usefulness of ion chromatography based K(+) quantification method under biological experimental conditions.

Patterns of epidermal growth factor receptor testing across 111 tertiary care centers in India: Result of a questionnaire-based survey.

BACKGROUND: We conducted a survey of 111 medical oncologists across India to understand the current pattern of epidermal growth factor receptor (EGFR) mutation testing at their respective centers. METHODS: Medical oncologists from 111 institutes across India were interviewed face to face using a structured questionnaire. They were divided into two groups - Group 1 with in-house EGFR testing and Group 2 who send samples to central/commercial laboratories outside their institutions. Answers of the two groups were analyzed to see the prevailing patterns of EGFR testing and differences between the two groups if any. RESULTS: Ninety-five percent (105/111) of medical oncologists recommended testing for EGFR mutations in patients with adenocarcinoma histology and 40% (44/111) recommended EGFR testing in squamous cell histology. The average time duration to get EGFR test results was 10 days in Group 1 centers versus 18 days in Group 2 centers. Ninety-six percent (106/111) of the medical oncologists from Group 1 centers requested for factoring additional sample for biomarker testing compared to 69% (77/111) of the oncologists from Group 2 centers. Sixty-nine percent (77/111) of medical oncologists in Group 1 centers would prefer to wait for the test results before initiating treatment compared to 46% (51/111) in Group 2. EGFR tyrosine-kinase inhibitors were used in only approximately 60% of patients with diagnosed EGFR mutation in the first line. For patients in whom chemotherapy was initiated while waiting for test results, 50% (56/111) of medical oncologists would prefer to complete 4-6 cycles before switching to targeted therapy. At the time of progression, rebiopsy was possible in approximately 25% of the patients. CONCLUSIONS: Turnaround time for molecular testing should improve so that eligible patients can benefit from targeted therapies in the first line. There is a need to increase the awareness among pulmonologists, oncologists, and interventional radiologists regarding the importance of adequate samples required for molecular tests.

Woodfordia fruticosa: traditional uses and recent findings.

Woodfordia fruticosa Kurz of the family Lythraceae is a plant of tropical and subtropical region with a long history of medicinal use. A wide range of chemical compounds including tannins (especially those of macrocyclic hydrolysable class), flavonoids, anthraquinone glycosides, and polyphenols have been isolated from this species in recent times. Extracts and metabolites of this plant, particularly those from flowers and leaves, possess useful pharmacological activities. A comprehensive account of the chemical constituents and the biological activities is presented and a critical appraisal of the ethnopharmacological issues is included in view of the many recent findings of importance on this plant.

On the potential of Tephrosia purpurea as anti-Helicobacter pylori agent.

AIM OF THE STUDY: Since Tephrosia purpurea (Linn.) Pers. (Fabaceae) has traditional use in curing different types of wounds including gastroduodenal ulcers, it was of interest to evaluate the in vitro anti-Helicobacter pylori activity profile of the plant extract and its fractions with a view to examining its therapeutic potential, if any. MATERIALS AND METHODS: Employing clinical isolates and standard strains of Helicobacter pylori, the extract and fractions were bioevaluated in terms of MIC and MBC values, acid stability, time-kill kinetics, drug resistance, and synergistic potential. RESULTS: The methanolic extract showed promising activity against clinical isolates and standard strains of Helicobacter pylori, including metronidazole-resistant strains. Fractionation of the extract revealed the n-hexane and chloroform fractions to possess marked activity. The extract and the less polar fractions remained functionally active in acidic condition similar to stomach environment, exhibited consistent bacteriostatic activity during repeated exposure, and demonstrated synergism, complete or partial, even with antibiotic-resistant strains. CONCLUSION: Apolar fractions of Tephrosia purpurea may have therapeutic potential in combating Helicobacter pylori mediated gastroduodenal disorders.

Melatonin protects against gastric ulceration and increases the efficacy of ranitidine and omeprazole in reducing gastric damage.

The antiulcer effect of melatonin on gastric lesions caused by restraint-cold stress was studied with the intent of determining the mechanism of action of this agent. Melatonin dose-dependently prevented restraint-cold stress-induced gastric damage with around 90% inhibition at a dose of 60 mg/kg BW. When compared with already marketed antiulcer drugs such as ranitidine and omeprazole, melatonin was found to be more effective than ranitidine but less effective than omeprazole in preventing stress ulcer. As stress-induced gastric lesions are mainly caused by oxidative damage because of hydroxyl radicals (*OH), the effect of melatonin in scavenging the.OH generated during stress conditions in vivo as well as in an in vitro model system were studied. The results indicate that melatonin caused an 88% reduction of endogenous *OH during stress in vivo, an observation confirmed in an established in vitro system. Furthermore, a decrease in the activity of gastric peroxidase (GPO) and an increase in the gastric mitochondrial superoxide dismutase (Mn-SOD) activity because of restraint-cold stress was attenuated by melatonin pretreatment indicating that the indole possibly exerts its gastroprotective effects through its direct as well as indirect antioxidant activities. Moreover, in separate experiments, cotreatment of rats with melatonin and ranitidine or omeprazole was found to protect against stress ulceration in doses at which either of these alone could not protect the stomach. The findings raise the possibility of melatonin being considered as an effective gastroprotective agent individually or as a cotreatment with either ranitidine and omeprazole.