ABSTRACT
Imatinib-induced ophthalmological side-effects, including conjunctiva hemorrhage and periorbital oedema, although very common and still remain relatively little understood. The present study investigated the effects of genetic polymorphisms of drug targets and membrane transporters on these side effects. We found that the minor allele of EGFR rs10258429 and SLC22A1 rs683369 were significant risk determinants of conjunctival hemorrhage with OR of 7.061 (95%CI=1.791-27.837, P=0.005 for EGFR rs10258429 CT+TT vs CC), and 4.809 (95%CI=1.267-18.431, P=0.021 for SLC22A1 rs683369 GG+CG vs CC). The minor allele of SLC22A5 rs274558 and ABCB1 rs2235040 were protective factors to periorbital oedema with OR of 0.313 (95%CI=0.149-0.656, P=0.002 for SLC22A5 rs274558 AA+AG vs GG), and 0.253 (95%CI=0.079-0.805, P=0.020 for ABCB1 rs2235040 CT vs CC). These results indicated that variants in EGFR, SLC22A1, SLC22A5 and ABCB1 influenced the incidence of Imatinib-induced ophthalmological toxicities, and polymorphism analyses in associated genes might be beneficial to optimize Imatinib treatment.
Subject(s)
Eye Diseases/genetics , Genetic Predisposition to Disease , Imatinib Mesylate/adverse effects , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , ATP Binding Cassette Transporter, Subfamily B/genetics , Alleles , ErbB Receptors/genetics , Eye Diseases/chemically induced , Eye Diseases/pathology , Female , Gene Frequency , Genotype , Humans , Imatinib Mesylate/administration & dosage , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/complications , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/pathology , Male , Middle Aged , Organic Cation Transporter 1/genetics , Polymorphism, Single Nucleotide , Solute Carrier Family 22 Member 5/geneticsABSTRACT
BACKGROUND: Thiopurine-induced leukopenia is the most common dangerous adverse event in Asians. NUDT15 R139C was recently proposed to be a promising biomarker for leukopenia with thiopurine therapy in Asians, but this has not been replicated in the Chinese population. AIM: To investigate the influence of NUDT15 R139C, thiopurine S-methyltransferase (TPMT), 6-TGN and 6-MMPR on thiopurine-induced leukopenia in Chinese patients with Crohn's disease. METHODS: Clinical and epidemiological characteristics were reviewed from medical records. NUDT15 R139C and TPMT were genotyped. 6-TGN/6-MMPR concentrations were measured with high-performance liquid chromatography (HPLC). RESULTS: A total of 253 patients were included, 65 (25.7%) of whom experienced leukopenia. The median follow-up with thiopurine treatment was 38.0 weeks (range, 1-192 weeks). NUDT15 R139C was strongly associated with the incidence of leukopenia (70.2% mutation vs. 12.8% wild type; P=8.61×10-19 ; odds ratio, 10.80; 95% CI, 5.89-19.83). However, TPMT genotype was not found to be correlated with the incidence of leukopenia (P = 0.44). In subgroup of NUDT15 wild type, there was significant difference of 6TGN concentration between patients with and without leukopenia (413.0 (174.2-831.4) vs. 279.7 (77.3-666.9) pmol/8 × 108 RBC, P = 0.0055). In contrast, no association was found in patients with NUDT15 R139C variant alleles (P = 0.26). 6-MMPR was not correlated with leukopenia (P = 0.84). CONCLUSIONS: In Chinese patients, it is strongly recommended to detect NUDT15 genotype rather than TPMT before initiating thiopurine drugs. 6TGN concentration should be routinely monitored in CD patients with NUDT15 wild type. As for CT genotype, starting at low dose and careful monitoring for leukopenia and 6TGN levels is recommended.
Subject(s)
Asian People/genetics , Crohn Disease/genetics , Leukopenia/genetics , Methyltransferases/genetics , Polymorphism, Genetic/genetics , Pyrophosphatases/genetics , Adolescent , Adult , Crohn Disease/blood , Crohn Disease/drug therapy , Female , Follow-Up Studies , Humans , Leukopenia/blood , Leukopenia/chemically induced , Male , Methyltransferases/blood , Middle Aged , Predictive Value of Tests , Risk Factors , Young AdultABSTRACT
A case of organophosphate (OP) poisoning was admitted to the emergency room. The patient accepted treatment with pralidoxime (PAM), atropine, and supporting therapy. It was observed that even after 22 h after treatment, 960 mg of atropine was not enough for the patient to be atropinized. However, a 160-mg follow-up treatment of anisodamine was quite enough for atropinization after 4 h. As a case report, more studies are required before any definite conclusion can be reached regarding the use of anisodamine as a potential substitute for high-dose atropine in cases of OP poisoning.
Subject(s)
Antidotes/therapeutic use , Organophosphate Poisoning/drug therapy , Solanaceous Alkaloids/therapeutic use , Atropine/therapeutic use , Cholinesterase Reactivators/therapeutic use , Female , Humans , Insecticides/poisoning , Middle Aged , Muscarinic Antagonists/therapeutic use , Pralidoxime Compounds/therapeutic useABSTRACT
Three new triterpenoid saponins, impatiprins A-C (1-3), together with a known triterpenoid (4) and two known triterpenoid saponins (5, 6), were isolated from the rhizomes of Impatiens pritzellii Hook. f. var. hupehensis Hook. f. The structures of 1-3 were determined by 1D and 2D NMR, FAB-MS techniques and chemical methods. Compounds 1 and 2 showed weak cytotoxicities against S-180, HeLa and HepG2 cell lines.
Subject(s)
Antineoplastic Agents, Phytogenic/isolation & purification , Impatiens/chemistry , Rhizome/chemistry , Saponins/isolation & purification , Triterpenes/isolation & purification , Animals , Humans , Magnetic Resonance Spectroscopy , Mass Spectrometry , Mice , Mice, Inbred BALB C , Saponins/chemistry , Saponins/pharmacology , Triterpenes/chemistry , Triterpenes/pharmacologyABSTRACT
Two new steroidal alkaloids, lichuanine (1) and lichuanisinine (2), were isolated from the bulbs of FritillariaLichuanensis P. Li et C.P. Yang. Their structures were determined to be (20S,25R)-5alpha, 14alpha-cevanine-3beta, 6beta-diol (1) and (20S,25S)-5alpha,14alpha-cevanine-3beta,6beta-diol-N-oxide (2) by means of spectral analysis and chemical evidence.
Subject(s)
Alkaloids/chemistry , Alkaloids/isolation & purification , Fritillaria/chemistry , Steroids/chemistry , Steroids/isolation & purification , Molecular Structure , Plant Stems/chemistryABSTRACT
A new ent-kaurane diterpenoid dimer, fritillebinide C(1) together with one known diterpenoid dimer fritillebinide B (2) were isolated from the bulbs of Fritillaria ebeiensis G.D. Yu et G.Q. Ji. Compound 1 has been determined to be ent-3beta-acetoxy-kauran-16beta,17-acetal ent-16beta-kauran-17(S)-aldehyde(1) by means of spectral analysis and chemical evidence.
Subject(s)
Diterpenes/chemistry , Liliaceae/chemistry , Chromatography , Dimerization , Diterpenes/isolation & purification , Magnetic Resonance Spectroscopy , Mass Spectrometry , Molecular Structure , Plant Structures/chemistryABSTRACT
A novel ent-kaurane diterpenoid dimer, fritillebinide B (1) together with one known diterpenoid dimer fritillebinide A (2) were isolated from the bulbs of Fritillaria eheiensis var. purpurea G.D. Yu et P. Li. Compound 1 has been established to be ent-3beta-acetoxy-kauran-16beta,17-acetal ent-16beta-kauran-17(R)-aldehyde (1) by means of spectral analysis and chemical evidence.
Subject(s)
Diterpenes/isolation & purification , Liliaceae/chemistry , Chromatography , Diterpenes/chemistry , Magnetic Resonance Spectroscopy , Molecular Structure , Plant Structures/chemistryABSTRACT
Two new ent-kauranoid diterpenoid dimers, fritillebin C (1) and fritillebin D (2), were isolated from the bulbs of Fritillaria ebeiensis G.D. Yu and G.Q. Ji. Their structures were determined to be ent-16beta-hydroxy-kauran-17-yl ent-16beta3-kauran-17-oate (1); ent-16alpha-hydroxy-kauran-17-yl ent-16beta-kauran-17-oate (2) by means of spectral analysis and chemical evidence.
