Low-dose oral hydroxychloroquine led to impaired vision in a child with renal failure: Case report and literature review.

INTRODUCTION: Hydroxychloroquine (HCQ) has received much attention in the treatment of coronavirus disease 2019 recently. However, it can cause irreversible vision loss. Few cases have been reported in pediatric patient with HCQ-related adverse reactions. Appropriate administration and early disease recognition are important for reducing the adverse drug reactions of HCQ. PATIENT CONCERNS: We report a case of a 14-year-old Chinese girl who sought treatment for rapidly decreasing vision in the left eye over 3 days. The simulation results of the population pharmacokinetic model of HCQ revealed that the plasma concentration of HCQ abnormally increased before the visual acuity of the eye decreased. DIAGNOSIS: She was diagnosed as HCQ related drug adverse reaction. INTERVENTIONS: The daily dose of HCQ for this patient was adjusted from 100 mg/d to 50 mg/d. OUTCOMES: Follow-up for 6 months showed no more vision loss recurrence. However, the existing decreased visual acuity of the eye did not recover either. CONCLUSION: Although decreased visual acuity is an infrequent symptom, ophthalmologists should be aware of the possibility of HCQ concentration enrichment and consider minimizing HCQ use when a child with renal hypofunction seeks treatment for shortsightedness.

Structural characterization, hypoglycemic effects and antidiabetic mechanism of a novel polysaccharides from Polygonatum kingianum Coll. et Hemsl.

The rhizome of Polygonatum kingianum has been used as a traditional medicine in China. In this study, a novel polysaccharides (PKPs-1) was isolated from P. kingianum and characterized by its molecular weight, primary structure. The hypoglycemic activity of PKPs-1was investigated by in vitro assay with the HepG2 cell line and in vivo test using STZ-induced diabetic mice. Results showed that the average molecular weight of PKPs-1 was 14.05 kDa and is composed mainly of glucose and mannose. Methylation analysis indicated that this polysaccharides fraction consisted mainly of ß1,2-link glucose. Besides, PKPs-1 exhibited significant anti-hyperglycemic activity on STZ-induced mice, improved insulin tolerance, and affected the metabolism of serum lipids. Results of real-time quantitative PCR (RT-PCR) showed that PKPs-1 significantly increased the expression of insulin receptor substrate-1 (IRS-1), phosphoinositide 3-kinase (PI3K) and protein kinase B (AKT), indicating that PKPs-1 regulates glucose metabolism by activating the PI3K/AKT signaling pathway. This study provides new insights for investigating the hypoglycemic effects of PKPs-1 and suggests that PKPs-1 could be a promising functional food or medicine for treating T2DM.

Oligosaccharides from depolymerized fucosylated glycosaminoglycan: Structures and minimum size for intrinsic factor Xase complex inhibition.

Fucosylated glycosaminoglycan (FG), a structurally complex glycosaminoglycan found up to now exclusively in sea cucumbers, has distinct anticoagulant properties, notably a strong inhibitory activity of intrinsic factor Xase complex (FXase). Knowledge of the FG structures could facilitate the development of a clinically effective intrinsic FXase inhibitor for anticoagulant drugs. Here, a new fucosylated glycosaminoglycan was obtained from the widely traded sea cucumber Bohadschia argus The precise structure was deduced as {→4)-[l-Fuc3S4S-α-(1→3)-]-d-GlcA-ß-(1→3)-d-GalNAc4S6S-ß-(1} through analysis of its chemical properties and homogeneous oligosaccharides purified from its ß-eliminative depolymerized products. The B. argus FG with mostly 3,4-di-O-sulfated fucoses expands our knowledge on FG structural types. This ß-elimination process, producing oligosaccharides with well-defined structures, is a powerful tool for analyzing the structure of complex FGs. Among these oligosaccharides, an octasaccharide displayed potent FXase inhibitory activity. Compared with oligosaccharides with various degrees of polymerization (3n and 3n - 1), our analyses reveal that the purified octasaccharide is the minimum structural unit responsible for the potent selective FXase inhibition, because the d-talitol in the nonsaccharide is unnecessary. The octasaccharide with 2,4-di-O-sulfated fucoses is more potent than that of one with 3,4-di-O-sulfated fucoses. Thus, sulfation patterns can play an important role in the inhibition of intrinsic factor Xase complex.

Structural analysis and anticoagulant activities of three highly regular fucan sulfates as novel intrinsic factor Xase inhibitors.

Fucoidan or fucan sulfate, a sulfated polysaccharide from algae or echinoderm mainly containing fucoses, possesses complex chemical structure and various biological activities. Herein, three fucan sulfates consisted of distinctive simplest repeating units were isolated from Holothuria fuscopunctata, Thelenota ananas and Stichopus horrens. The structural sequences of these fucan sulfates from H. fuscopunctata, T. ananas and S. horrens are →4-α-l-Fucp-(3SO3-)-1→, →4-α-l-Fucp-(2SO3-)-1→ and →3-α-l-Fucp-(2SO3-)-1→, respectively, revealing the existence of the highly regular homogeneous fucan sulfates and their structural diversity in the sea cucumber species for the first time. Pharmacological assays indicated their specific sulfation pattern and position of the glycosidic linkage may contribute to the anticoagulant action. Further mechanism analysis suggested that these fucan sulfates may exhibit strong inhibition of the intrinsic coagulation pathway by targeting the intrinsic coagulation factor Xase. Our results provide novel information to enrich knowledge on structural types of fucan sulfate and to illustrate its functionality.

Precise structures of fucosylated glycosaminoglycan and its oligosaccharides as novel intrinsic factor Xase inhibitors.

Selective inhibition of the endogenous coagulation pathway is a promising strategy for developing new anticoagulants. Fucosylated glycosaminoglycan (FG), a structurally complex glycosaminoglycan, has distinct anticoagulant properties, especially the strong intrinsic factor Xase inhibitory activity that is recognized as a new target with potential physiological and therapeutic applications. Detailed knowledge of FG structures is necessary for developing a clinically effective intrinsic FXase inhibitor. However, challenges remain to elucidate FG structures as a basis for pharmaceutical development. Herein, using the highly selective ß-elimination method, oligosaccharides with regular structures were prepared from the depolymerization products. Analysis of oligosaccharides further confirmed the precise structural sequence of the FG. Furthermore, biological activity assay suggested that these pure homogeneous oligosaccharides, particularly an octasaccharide, exhibit strong inhibition of the intrinsic coagulation pathway by inhibiting human intrinsic factor Xase. Our finding is significant for discovery of a new class of anticoagulant agents as intrinsic factor Xase inhibitors.

Structural analysis and biological activity of a highly regular glycosaminoglycan from Achatina fulica.

Edible snails have been widely used as a health food and medicine in many countries. A unique glycosaminoglycan (AF-GAG) was purified from Achatina fulica. Its structure was analyzed and characterized by chemical and instrumental methods, such as Fourier transform infrared spectroscopy, analysis of monosaccharide composition, and 1D/2D nuclear magnetic resonance spectroscopy. Chemical composition analysis indicated that AF-GAG is composed of iduronic acid (IdoA) and N-acetyl-glucosamine (GlcNAc) and its average molecular weight is 118kDa. Structural analysis clarified that the uronic acid unit in glycosaminoglycan (GAG) is the fully epimerized and the sequence of AF-GAG is →4)-α-GlcNAc (1→4)-α-IdoA2S (1→. Although its structure with a uniform repeating disaccharide is similar to those of heparin and heparan sulfate, this GAG is structurally highly regular and homogeneous. Anticoagulant activity assays indicated that AF-GAG exhibits no anticoagulant activities, but considering its structural characteristic, other bioactivities such as heparanase inhibition may be worthy of further study.

Structural analysis of a homogeneous polysaccharide from Achatina fulica.

Edible snails have been widely used as a health food and medicine in many countries. In our study, a water-soluble polysaccharide (AF-1) was isolated and purified from Achatina fulica by papain enzymolysis, alcohol precipitation and strong anion exchange chromatography. Structureof the polysaccharide was analyzed and characterized by chemical and instrumental methods, such as Fourier transform infrared spectroscopy, high performance liquid chromatography, analysis of monosaccharide composition, methylation analysis, and nuclear magnetic resonance (NMR) spectroscopy (1H, 13C, COSY, TOCSY, NOESY, HSQC and HMBC). Chemical composition analysis indicated that AF-1 is composed of glucose (Glc) and its average molecular weight is 1710kDa. Structural analysis suggested that AF-1 is mainly consisted of a linear repeating backbone of (1→4) linked α-d-Glc p residues with one branch, α-d-Glc p, attached to the main chain by (1→6) glycosidic bonds at every five main-chain units. Further studies on biological activities of the polysaccharide are currently in progress.

[HPLC Analyzed the Iridoid Glycosides of Qingyedan Commonly Used in Folk Medicine in Yunnan].

Objective: To compare the contents of iridoid glycosides in Qingyedan medicinal materials,and to provide the scientific basis for using resources of Qingyedan and rationality of original plant medicinal. Methods: The contens of three iridoid glycosides,including swertiamarin,gentiopicroside and sweroside in Qingyedan medicinal materials were determined by HPLC. Results: The constituents of 30 samples in nine species were significant difference. And the contents of iridoid glycosides in Swertia bimaculata,Swertia tenuis and Swertia pubescens were reported for the first time. Conclusion: The results show that the contents of iridoid glycosides in Qingyedan medicinal materials have a significant difference due to the different species and producing areas. Therefore, these medicinal plants should not be used as alternative medicines for clinical application. Swertiamarin and sweroside can be selected as quality control components, this method is an effective method to identify and control the quality of Qingyedan materials.