-
1.
Molybdenum improves 2-acetyl-1-pyrroline, grain quality traits and yield attributes in fragrant rice through efficient nitrogen assimilation under cadmium toxicity.
Imran, M, Hussain, S, Rana, MS, Saleem, MH, Rasul, F, Ali, KH, Potcho, MP, Pan, S, Duan, M, Tang, X
Ecotoxicology and environmental safety. 2021;:111911
Abstract
Cadmium (Cd) toxicity causes severe perturbations in nitrogen (N) uptake and assimilation, and thereby interrupts normal plant growth. Molybdenum (Mo), a necessary trace element, plays important roles in N metabolism through regulating N assimilatory enzymes activities and expressions in higher plants. Taking this into account, a pot experiment was performed to explore the role of Mo in alleviating Cd-induced inhibitory effects on physio-biochemical processes, N metabolism, yield attributes and grain quality characters of two fragrant rice cultivars; Guixiangzhan and Meixiangzhan-2. Both the fragrant rice cultivars were treated with two levels of each Cd concentrations (0 and 100 mg/kg) and Mo treatments (0 and 0.15 mg/kg). The results revealed that Cd toxicity significantly reduced (p < 0.05) plant dry biomass, gaseous exchange attributes, chlorophyll contents, N utilizing and assimilatory enzymes activities, 2-acetyl-1-pyrroline (2AP) contents and grain yield in both cultivars; however, more severe inhibitions were observed in Meixiangzhan-2 than Guixiangzhan. Nevertheless, Mo application alleviated Cd stress and enhanced 2AP content and grain yield by 75.05% and 67.94% in Guixiangzhan and 87.71% and 83.51% in Meixiangzhan-2, respectively compared with no Mo application. Moreover, Mo application improved photosynthesis, chloroplast configuration, soluble protein and proline contents and also strengthened the N assimilatory pathway through efficient NO3- utilization, higher nitrate reductase, nitrite reductase, glutamine synthetase and glutamate synthase activities and transcript levels under Cd stress. Collectively, our results imply that Mo-induced enhancement in N utilization and assimilation improved yield and grain quality characters of fragrant rice cultivars under Cd stress.
-
2.
Lanthanum (La) improves growth, yield formation and 2-acetyl-1-pyrroline biosynthesis in aromatic rice (Oryza sativa L.).
Luo, H, Chen, Y, He, L, Tang, X
BMC plant biology. 2021;(1):233
Abstract
BACKGROUND Lanthanum (La) is a rare earth element that can influence plant growth and development. However, the effect of La on growth, yield formation and 2-acetyl-1-pyrroline (2-AP, a key compound responsible for the aroma of rice) biosynthesis in aromatic rice (Oryza sativa L. subsp. japonica Kato) has not been reported. Therefore, the present study investigated the effects of La on growth, photosynthesis, yield formation and 2-AP biosynthesis in aromatic rice through three experiments. RESULTS Two pot experiments and a two-year field trial were conducted with different rates of La application (20-120 LaCl3 mg kg-1 and 12 kg ha-1 LaCl3), and treatments without La application were used as controls. The results showed that the application of LaCl3 at 80 and 100 mg kg-1 and at 12 kg ha-1 greatly increased the 2-AP content (by 6.45-43.03%) in aromatic rice seedlings and mature grains compared with the control. The La treatments also increased the chlorophyll content, net photosynthetic rate and total aboveground biomass of rice seedlings. Higher antioxidant enzyme (superoxide, peroxidase, and catalase) activity was detected in the La treatments than in the control. The La treatments also increased the grain yield, grain number per panicle and seed-setting rate of aromatic rice relative to the control. Moreover, the grain proline and γ-aminobutyric acid contents and the activity of betaine aldehyde dehydrogenase significantly decreased under the La treatment. The application of La to soil enhanced the activity of proline dehydrogenase by 20.62-56.95%. CONCLUSIONS La improved the growth, yield formation and 2-AP content of aromatic rice and enhanced 2-AP biosynthesis by increasing the conversion of proline to 2-AP and decreasing the conversion of GABald to GABA.
-
3.
Effects of pirenzepine on vonoprazan-induced gastric acid inhibition and hypergastrinemia.
Suzuki, T, Higuchi, T, Kagami, T, Uotani, T, Yamade, M, Tani, S, Hamaya, Y, Iwaizumi, M, Osawa, S, Sugimoto, K, et al
European journal of clinical pharmacology. 2021;(7):971-978
Abstract
BACKGROUND Compared to proton pump inhibitors, vonoprazan exerts a greater inhibitory effect on gastric acid secretion and is useful for treating acid-related diseases, such as gastro-esophageal reflux disease. However, there is a problem that vonoprazan causes hypergastrinemia, which confers a risk of carcinoid tumor. A previous report demonstrated that pirenzepine, an M1 muscarinic receptor antagonist, enhances the acid inhibitory effects while suppressing hypergastrinemia induced by omeprazole. Here, we examined whether pirenzepine enhances the gastric acid inhibitory effects of vonoprazan without further increasing serum gastrin levels. METHODS Eleven healthy volunteers were subjected to 24-h intragastric pH monitoring and serum gastrin measurements on day 7 of three different regimens: pirenzepine 75 mg alone, vonoprazan 10 mg alone, and vonoprazan 10 mg plus pirenzepine 75 mg administered in a randomized crossover fashion. RESULTS Median pH 4 holding time ratios (range) achieved with pirenzepine 75 mg, vonoprazan 10 mg, and vonoprazan 10 mg plus pirenzepine 75 mg were 6.9% (2.4-32.8%), 88.4% (54.6-100%), and 84.2% (40.3-100%), respectively. Respective serum gastrin levels were 79 (75-210) pg/ml, 310 (110-870) pg/ml, and 170 (140-930) pg/ml. In cases with hypergastrinemia (gastrin ≥ 200 pg/ml) induced by vonoprazan 10 mg alone, concomitant treatment with pirenzepine significantly reduced serum gastrin levels from 370 to 180 pg/ml (P = 0.028). CONCLUSION Although pirenzepine does not enhance acid inhibition, it does improve hypergastrinemia induced by vonoprazan to some extent.
-
4.
Evaluation of Potential Drug-Drug Interaction Risk of Pexidartinib With Substrates of Cytochrome P450 and P-Glycoprotein.
Zahir, H, Kobayashi, F, Zamora, C, Gajee, R, Gordon, MS, Babiker, HM, Wang, Q, Greenberg, J, Wagner, AJ
Journal of clinical pharmacology. 2021;(3):298-306
-
-
Free full text
-
Abstract
Pexidartinib is approved for treatment of adults with symptomatic tenosynovial giant cell tumor. In vitro data showed pexidartinib's potential to inhibit and induce cytochrome P450 (CYP) 3A, inhibit CYP2C9, CYP2C19 and P-glycoprotein (P-gp). Herein, 2 open-label, single-sequence, crossover studies evaluated the drug-drug interaction potential of pexidartinib on CYP enzymes (CYP2C9, CYP2C19, and CYP3A) and P-gp. Thirty-two subjects received single oral doses of midazolam (CYP3A substrate) and tolbutamide (CYP2C9 substrate) alone and after single and multiple oral doses of pexidartinib. Twenty subjects received single oral doses of omeprazole (CYP2C19 substrate) and digoxin (P-gp substrate) alone or with pexidartinib. Analysis of variance was conducted to determine the effect of pexidartinib on various substrates' pharmacokinetics. No drug-drug interaction was concluded if the 90% confidence interval of the ratio of test to reference was within the range 80% to 125%. Coadministration of single and multiple doses of pexidartinib resulted in 21% and 52% decreases, respectively, in the area under the plasma concentration-time curve from time zero to the last measurable time point (AUClast ) of midazolam, whereas AUClast values of tolbutamide increased 15% and 36%, respectively. Omeprazole exposure decreased on concurrent administration with pexidartinib, the metabolite-to-parent ratio was similar following omeprazole administration alone vs coadministration with pexidartinib; pexidartinib did not affect CYP2C19-mediated metabolism. Maximum plasma concentrations of digoxin slightly increased (32%) with pexidartinib coadministration; no significant effect on digoxin AUClast . These results indicate that pexidartinib is a moderate inducer of CYP3A and a weak inhibitor of CYP2C9 and does not significantly affect CYP2C19-mediated metabolism or P-gp transport.
-
5.
Pyroluria: Fact or Fiction?
Warren, B, Sarris, J, Mulder, RT, Rucklidge, JJ
Journal of alternative and complementary medicine (New York, N.Y.). 2021;(5):407-415
Abstract
Objective: The term "Mauve factor" (pyrroluria) dates back to 1958 when Dr. Abram Hoffer defined the condition as elevated levels of pyrroles in the urine, currently called hydroxyhemepyrrolin-2-one (HPL). It was suggested that the raised pyrrole levels lead to depletions in zinc and vitamin B6, which, in turn, were hypothesized to result in a range of psychiatric disorders, such as schizophrenia, anxiety, and depression. Treatment implications are supplementation with zinc and B6. This article aimed to review the scientific literature associating pyrroluria with psychiatric symptoms, explore the validity of HPL testing, explore the role of nutrients as treatment options for pyrroluria, and discuss future research directions. Methods: A PRISMA review was conducted using search results from electronic databases PubMed, MEDLINE, PsycINFO, EMBASE from inception to February 2020 using the following keywords: hydroxyhemepyryrrolin (HPL), kryptopyrrole (KP), mauve factor, pyroluria, pyrroluria, monopyrroles. Article reference lists were also scanned and included where relevant. Results: Seventy-three articles were identified of which only three studies identified significantly higher HPL levels in a psychiatric population compared with controls, and there were no placebo-controlled treatment trials directed at pyrroluria. The other 13 clinical studies either showed no association or did not provide adequate data to show group differences in HPL levels. Despite an extensive history of practitioners diagnosing and treating a wide variety of mental health conditions associated with pyrroluria as well as clinical observations of elevated HPL being associated with psychiatric disorders, there was no clear research that showed the following: (1) elevated HPL is robustly associated with increased mental health symptoms, (2) elevated HPL in urine is associated with increased urine excretion of zinc and B6, and (3) high-dose zinc and B6 are an efficacious treatment for mental health problems associated with elevated HPL. Conclusions: Elevated HPL is a clinically observed, but poorly researched biomarker with unclear associations with mental disorders. Based on current evidence, HPL testing is not recommended as a screening or treatment tool. Further research is required in the following areas: establishment of which specific clinical populations exhibit elevated HPL, validation of the chemistry and validity of testing, and controlled trials to establish efficacy of high-dose zinc and B6 as treatment of elevated pyrroles.
-
6.
Efficacy of vonoprazan against bleeding from endoscopic submucosal dissection-induced gastric ulcers under antithrombotic medication: A cross-design synthesis of randomized and observational studies.
Hidaka, Y, Imai, T, Inaba, T, Kagawa, T, Omae, K, Tanaka, S
PloS one. 2021;(12):e0261703
Abstract
Vonoprazan, a potassium-competitive acid blocker, is expected to be superior to proton pump inhibitors (PPIs) in preventing post-endoscopic submucosal dissection (ESD)-induced gastric bleeding. However, the results of randomized controlled trials (RCTs) and observational studies on the efficacy of vonoprazan have been inconsistent. This study aimed to evaluate the effectiveness of vonoprazan in antithrombotic drug users, a population that has been excluded from RCTs. Treatment effects were assessed using cross-design synthesis, which can be adjusted for differences in study design and patient characteristics. We used data from an RCT in Japan (70 patients in the vonoprazan group and 69 in the PPI group) and an observational study (408 patients in the vonoprazan group and 870 in the PPI group). After matching, among the antithrombotic drug users in the observational study, post-ESD bleeding was noted in 8 out of 86 patients in the vonoprazan group and 18 out of 86 patients in the PPI group. After pooling the data from the RCT and observational study, the risk difference for antithrombotic drug users was -14.6% (95% CI: -22.0 to -7.2). CDS analysis suggested that vonoprazan is more effective than PPIs in preventing post-ESD bleeding among patients administered antithrombotic medications.
-
7.
Light and water treatment during the early grain filling stage regulates yield and aroma formation in aromatic rice.
Li, Y, Liang, L, Fu, X, Gao, Z, Liu, H, Tan, J, Potcho, MP, Pan, S, Tian, H, Duan, M, et al
Scientific reports. 2020;(1):14830
Abstract
The effect of light and water on aromatic rice remain largely unclear. A pot experiment was conducted to investigate the influences of light-water treatments (CK: natural light and well-watered conditions, WS: natural light and water-stressed conditions, LL: low light and well-watered conditions, LL-WS: low light and water-stressed treatment) on yield and 2-acetyl-1-pyrroline (2AP) formation in aromatic rice. Compared with CK, the light-water treatments decreased grain yield (10.32-39.19%) due to reductions in the filled grain percentage and total dry weight, in the regulation of biomass distribution, and in the attributes of gas exchange and antioxidant response parameters. The 2AP content in grains increased in the LL treatment (5.08-16.32%) but decreased in the WS treatment compared with that in CK. The changes in 2AP were associated with changes in 2AP formation-related traits and element content. Low light and water stress led to yield declines in aromatic rice, but low light alleviated the decrease in 2AP content caused by water stress.
-
8.
Effect of probiotics during vonoprazan-containing triple therapy on gut microbiota in Helicobacter pylori infection: A randomized controlled trial.
Kakiuchi, T, Mizoe, A, Yamamoto, K, Imamura, I, Hashiguchi, K, Kawakubo, H, Yamaguchi, D, Fujioka, Y, Nakayama, A, Okuda, M, et al
Helicobacter. 2020;(3):e12690
Abstract
BACKGROUND Probiotics are beneficial to patients with Helicobacter pylori infections by modulating the gut microbiota. Biofermin-R (BFR) is a multiple antibiotic-resistant lactic acid bacteria preparation of Enterococcus faecium 129 BIO 3B-R and is effective in normalizing the gut microbiota when used in combination with antibiotics. This study aimed to determine the effect of BFR in combination with vonoprazan (VPZ)-based therapy on gut microbiota. METHODS Patients with positive urinary anti-H pylori antibody test (primary test) and fecal H pylori antigen test (secondary test) were examined. Patients in group 1 (BFR- ) received VPZ (20 mg twice daily), amoxicillin (750 mg twice daily), and clarithromycin (400 mg twice daily) for 7 days. Patients in group 2 (BFR+ ) received BFR (3 tablets/day) for 7 days, in addition to the aforementioned treatments. Following treatment, the relative abundance, α-diversity, and β-diversity of gut microbiota were assessed. RESULTS Supplementation with BFR prevented the decrease in a-diversity after eradication therapy (Day 7). β-diversity was similar between groups. The incidence rate of diarrhea was non-significantly higher in the BFR- than in the BFR+ group (73.1% vs 56.5%; P = .361). Stool consistency was comparable in the BFR+ group on Days 7 and 1 (3.86 ± 0.95 vs 3.86 ± 1.46; P = .415). CONCLUSION Biofermin-R combined with VPZ-based therapy resulted in higher microbial α-strain diversity and suppressed stool softening during H pylori eradication therapy.
-
9.
Tofacitinib for ulcerative colitis: results of the prospective Dutch Initiative on Crohn and Colitis (ICC) registry.
Biemans, VBC, Sleutjes, JAM, de Vries, AC, Bodelier, AGL, Dijkstra, G, Oldenburg, B, Löwenberg, M, van Bodegraven, AA, van der Meulen-de Jong, AE, de Boer, NKH, et al
Alimentary pharmacology & therapeutics. 2020;(9):880-888
-
-
Free full text
-
Abstract
BACKGROUND Tofacitinib is a Janus kinase inhibitor approved for the treatment of ulcerative colitis (UC). AIM: To evaluate effectiveness, safety and use of tofacitinib in daily practice. METHODS UC patients initiating tofacitinib were prospectively enrolled in 15 hospitals in the Netherlands. Corticosteroid-free clinical remission (short clinical colitis activity index [SCCAI] ≤2), biochemical remission (faecal calprotectin level ≤250 µg/g), combined corticosteroid-free clinical and biochemical remission, predictors of remission, safety outcomes, treatment dose and effect on lipids were determined at weeks 12 and 24. Endoscopic outcomes were evaluated in centres with routine endoscopic evaluation. RESULTS In total, 123 UC patients (95% anti-TNF, 62% vedolizumab and 3% ustekinumab experienced) were followed for a median duration of 24 weeks (interquartile range 12-26). The proportion of patients in corticosteroid-free clinical, biochemical, and combined corticosteroid-free clinical and biochemical remission rate at week 24 was 29% (n: 22/77), 25% (n: 14/57), and 19% (n: 11/57) respectively. Endoscopic remission (Mayo = 0) was achieved in 21% of patients at week 12 (n: 7/33). Prior vedolizumab exposure was associated with reduced clinical remission (odds ratio 0.33, 95% confidence interval [CI] 0.11-0.94). At week 24, 33% (n: 14/42) of patients still on tofacitinib treatment used 10 mg twice daily. In total, 33 tofacitinib-related adverse events (89 per 100 patient years) occurred, 7 (6% of total cohort) resulted in discontinuation. Cholesterol, HDL and LDL levels increased during induction treatment by 18% (95% CI 9-26), 18% (95% CI 8-28) and 21% (95% CI 14-39) respectively. CONCLUSION Tofacitinib is an effective treatment for UC after anti-TNF and vedolizumab failure. However, a relatively high rate of adverse events was observed resulting in discontinuation in 6% of patients.
-
10.
Efficacy and safety of saroglitazar in managing hypertriglyceridemia in type-2 diabetes: A meta-analysis.
Dutta, D, Bhattacharya, S, Surana, V, Aggarwal, S, Singla, R, Khandelwal, D, Sharma, M
Diabetes & metabolic syndrome. 2020;(6):1759-1768
Abstract
BACKGROUND AND AIMS Saroglitazar is commonly used in India for managing hypertriglyceridemia in diabetes. This meta-analysis evaluated the efficacy and safety of saroglitazar in hypertriglyceridemia. METHODS Electronic databases were searched for RCTs involving diabetes patients receiving saroglitazar in intervention arm, and placebo/lipid/diabetes medication in the control arm. Primary outcome was to evaluate change in serum triglyceride and HbA1c. Secondary outcomes were to evaluate changes in other lipid parameters, glycaemia and adverse effects. Analysis for lipid and glycaemic parameters were done separately for controls receiving anti-lipid medications (statins/fibrates) [active control group (ACG)] and those receiving placebo/diabetes medications [passive control group (PCG)]. RESULTS Following 12 weeks therapy, individuals receiving saroglitazar had significantly lower triglycerides when compared to PCG [MD -71.67 mg/dl (95% CI: -123.67 to -19.66 mg/dl); P < 0.01; I2 = 91% (considerable heterogeneity); low certainty of evidence (LCE)], but not ACG [MD -37.38 mg/dl (95% CI: -84.55-9.79 mg/dl; P = 0.12; I2 = 98% (considerable heterogeneity); LCE]. Individuals receiving saroglitazar had significantly lower fasting glucose when compared to PCG [MD -24.61 mg/dl (95% CI: -44.13 to -5.09 mg/dl); P = 0.01; I2 = 65% (moderate heterogeneity); LCE], but not ACG [MD -13.5 mg/dl (95% CI: -33.1-6.10 mg/dl; P = 0.18; I2 = 98% (considerable heterogeneity); LCE]. HbA1c, total cholesterol, LDL-C, apolipoprotein-B and HDL-C were not significantly different among study groups. Creatinine was significantly higher in patients receiving saroglitazar as compared to controls [MD 0.12 mg/dl (95% CI: 0.04-0.21 mg/dl); P < 0.01; I2 = 29% (low heterogeneity); high certainty of evidence]. CONCLUSION This meta-analysis reinforces the excellent triglyceride lowering of saroglitazar, but highlights significant increase in creatinine.