BACKGROUND: Syndrome of apparent mineralocorticoid excess (AME) is characterized by excessive MR stimulation despite low levels of aldosterone. 11Beta-hydroxysteroid dehydrogenase-2 (11βDSH-2) inactivates cortisol to cortisone, preventing cortisol-induced MR activation. Genetic defects in 11βDSH-2 cause AME through accumulation of cortisol in the distal nephron, leading to MR activation induced hypertension, hypokalemia and metabolic alkalosis. Acquired AME can occur due to the ingestion of glycyrrhizic acid, found in licorice root, which inhibits 11βDSH-2 and has additional effects on cortisol homeostasis through inhibition of 11βDSH-1.
METHODS: We present a case of acquired AME with a hyperadrenergic symptoms induced by ingestion of Advanced Liver Support, a nutritional supplement produced by Advanced BioNutritionals(R), in a 65-year-old Caucasian female who presented with accelerated hypertension, hypokalemia, metabolic alkalosis and adrenergic symptoms. Cessation of the licorice-containing supplement resulted in complete resolution of the patient\'s hypertension, symptoms and abnormal lab values. To our knowledge this is the first reported case of AME from this supplement, and the first to describe accompanying hyperadrenergic symptoms.
CONCLUSIONS: Glycyrrhizic acid is increasingly being found in unregulated nutritional supplements and has the potential to induce a reversable syndrome of AME. Acquired AME should be suspected in individuals who present with hypertension along with hypokalemia, metabolic alkalosis and low plasma renin and serum aldosterone levels.

Natural aglycones, a major ingredient accompanied by glycosides in plants, have played an important role in the treatment of various diseases. However, their bioavailability is limited by their poor water solubility. In contrast to previous efforts that required the use of new exotic materials which may raise concerns about biocompatibility, we report the first case of excipient-free nanodispersions in which an insoluble glycyrrhetinic acid (GA) assembled with its amphiphilic parent drug diammonium glycyrrhizinate (DG) into water-dispersible nanodispersions (130.8 nm for particle size and 91.74% for encapsulation efficiency). This strategy largely increased GA\'s water apparent solubility by hundreds of times to 549.0 μg/mL with a high cumulative dissolution percentage in vitro greater than 80% in 5 min. The study on the formation mechanism showed that the OH, C-O and C=O group stretching peaks shifted in the FTIR spectra of GA-DG nanodispersions, while the COOH peak (δ COOH 12.19 ppm) disappeared in the 1H NMR spectrum of GA-DG nanodispersions, indicating that carboxyl groups on GA may interact with the hydroxyl groups of DG in solution. Molecular dynamics simulations suggested that both hydrophobic interactions and hydrogen-bond interactions contribute to the coassembly of GA and DG molecules in aqueous solution. Oral pharmacokinetic studies in rats demonstrated that such nanodispersions have a significant increase in Cmax and AUC0-t of 2.45- and 3.45-fold compared with those for GA, respectively. Therefore, this strategy, employing amphiphilic glycosides as excipients to prepare nanodispersions, not using new materials, paves the way for the further application of hydrophobic aglycone drugs.

暂无摘要。

BACKGROUND: The aim of this study was to analyze the genetic abnormalities and clinical manifestations of Shwachman-Diamond syndrome (SDS).
METHODS: A Chinese infant with elevated transaminase and a novel mutation at of sbdsc.258 +2T>C and c.184a>Tc.292G>A.
METHODS: The female patient was 5 months\' old at onset, with elevated transaminase as the first manifestation accompanied by restricted growth and development and oily stool. After sequencing the blood samples from patients and their parents, the heterozygous mutations of sbdsc.258 +2T>C and c.184a>T were detected.
METHODS: After admission, the patient was provided compound glycyrrhizin, Newtide formula milk supplemented with probiotics, fat-soluble vitamins, oral medication to adjust the spleen and stomach, and other symptomatic treatments.
RESULTS: The stool traits improved, and the levels of liver function transaminases decreased compared with before.
CONCLUSIONS: SDS is a rare disease with a variety of clinical manifestations. Pancreatic exocrine dysfunction, blood system manifestations, and bone abnormalities are common clinical manifestations, and genetic testing is helpful for diagnosis.

暂无摘要。

Liver test abnormalities (LTA) are a frequent extracutaneous manifestation in generalized pustular psoriasis (GPP). Due to possible hepatotoxicity of systemic monotherapy, it is challenging to simultaneously achieve clinical remission and LTA normalization. However, evidence for therapy is lacking. The aim of this study was to assess the effectiveness of combination therapy of acitretin and glycyrrhizin in nine GPP patients with LTA. During the acute phase of GPP, a combination of acitretin (0.5 mg/kg/d PO) and glycyrrhizin (80 mg/d intravenous) was initiated. After 2 weeks, all the patients promptly achieved at least 77% improvement in the severity score of GPP, as well as a significant reduction of liver enzymes. The patients were continuously treated with tapered doses of acitretin (20-30 mg/d PO) and glycyrrhizin (150 mg/d PO), and presented stable conditions during the 12-month follow-up. In conclusion, we consider that the combination of acitretin plus glycyrrhizin is an effective and safe therapy in GPP patients with LTA.

BACKGROUND: Pyoderma gangrenosum (PG) is a phenomenon of cutaneous ulceration with unknown etiology. About half the cases have associated extracutaneous manifestations or associated systemic diseases. The most commonly associated systemic disorders include inflammatory bowel disease (IBD), hematologic malignancies, autoimmune arthritis, and vasculitis. This is a case report about giant PG with ulcerative colitis (UC), which is extremely rare.
METHODS: A 39-year-old female farmer with UC for the past 3 years presented with multiple painful ulcers, erosion, exudation, and crusting on the right leg for 1 month. A cutaneous examination showed diffusely distributed, multiple, well-defined, deep purulent ulcers on the right medial shank measuring 6 to 20 cm and sporadic worm-eaten ulceration on the right ectocnemial, with severe oozing and erosions. The ulcerations exhibited deep undermined borders, granulated tissue and a black eschar at the base. The right shank and feet were severely swollen, restricting movement. The arteria dorsalis pedis pulse was good, with normal sensation on the skin of the right shank and feet. Laboratory examinations showed a white cell count of 11.8 × 109/L, hemoglobin was 91 g/L, erythrocyte sedimentation rate was 82 mm/h, unelevated procalcitonin, serum C-reactive protein was 131.29 mg/L, and a negative tuberculin skin test. Enteroscopy demonstrated endoscopic evidence of UC. A skin lesion biopsy showed superficial erosion and scarring. Partial epidermal hyperplasia, partial epidermal atrophy and thinning, mild edema of the dermal papill. Most of the middle and lower part of the dermis, showed dense lymphocytes, histiocytes, multinucleated giant cells, and neutrophil infiltration. PG with UC was diagnosed based on clinical manifestations, laboratory examinations and enteroscopy results.
METHODS: She was treated with topical applications of povidone iodine and kangfuxin solution twice daily, methylprednisolone sodium succinate 40 mg and compound glycyrrhizin 60 mg via intravenous drip once a day, along with thalidomide 50 mg twice daily. The UC was controlled with mesalazine.
RESULTS: She required multiple therapies to achieve PG healing 3 months later. No PG recurrence was observed during the 1-year follow-up.
CONCLUSIONS: Recognizing the clinical features of PG and its pathogenic nature, ensuring timely management fundamental for preventing severe destruction and deformity, and control of associated diseases are important aspects of treatment. Combination therapy is essential for PG patients with IBD.

BACKGROUND: The on-line analysis of active pharmaceutical ingredients (APIs) during the extraction process in herbal medicine is a challenge. Establishing a reliable and robust model is a critical procedure for the industrial application of on-line near-infrared (NIR) technology.
OBJECTIVE: To evaluate the advantages of on-line NIR model development using system optimisation strategy, Glycyrrhiza uralensis Fisch was used as a case. The content of liquiritin and glycyrrhizic acid was monitored during pilot scale extraction process of Glycyrrhiza uralensis Fisch in three batches.
METHODS: High-performance liquid chromatography (HPLC) was used as reference method for content determination of liquiritin and glycyrrhizic acid. The quantitative models of on-line NIR were developed by system optimisation of processing trajectory. For comparison, the models were simultaneously developed by stepwise optimisation. Moreover, the modelling parameters obtained through system optimisation and stepwise optimisation were reused in three batches. Root mean square error of prediction (RMSEP) and residual predictive deviation (RPD) were used to assess the model quality.
RESULTS: The average values of RMSEP and RPD of systematic model for liquiritin in three batches were 0.0361, 4.1525 (first batch), 0.0348, 4.7286 (second batch) and 0.0311, 4.9686 (third batch), respectively. In addition, the modelling parameters of systematic model for glycyrrhizic acid in three batches were same, and the average values of RMSEP and RPD were 0.0665 and 5.2751, respectively. The predictive performance and robustness of systematic models for the three batches were better than the comparison models.
CONCLUSIONS: The work demonstrated that system optimisation quantitative model of on-line NIR could be used to determine the contents of liquiritin and glycyrrhizic acid during Glycyrrhiza uralensis Fisch extraction process.

BACKGROUND: Methotrexate (MTX) is an antimetabolite of folic acid, which is used for management of ectopic pregnancy. MTX-related toxicity may include cutaneous mucosal damage, bone marrow suppression, gastrointestinal disorders (gastritis, diarrhea, hematitis), liver and kidney function damage, pulmonary toxicity, cardiac toxicity, and nerve toxicity. However, it is not usual for vulvar edema induced by low-dose methotrexate.
UNASSIGNED: In this case report, we described a patient with severe vulvar edema and oral cavity ulceration and scalp ulceration induced by low-dose MTX treatment for ectopic pregnancy. Her presenting complaints were pain in the vulva, oral cavity, and scalp.
UNASSIGNED: The patient was diagnosed based on clinical findings for MTX toxic reactions.
METHODS: Vulva was disinfectioned with iodide and Kangfuxin solution, her mouth was rinsed with mouthwash. Three compound glycyrrhizin tablets were orally administered (3 times/day). After 10 days, the broken skin and mucous membrane healed.
RESULTS: The vulvar edema and oral cavity ulceration and scalp ulceration healed.
CONCLUSIONS: Our study demonstrated that even low-dose MTX can be induced skin and mucosal injury, patients and doctors should timely detection of drug toxicity reactions, immediately rescue, prompt discontinuation of medication, and symptomatic treatment to avoid accidental occurrence.

BACKGROUND: Glycyrrhizin is the main active component of licorice. Licorice and glycyrrhizin induced hypertension has been widely reported, yet licorice and glycyrrhizin induced hypertensive crisis has been rarely known.
METHODS: The case of this report was a 47-year-old woman, who took 225 mg of glycyrrhizin daily for 3 years due to primary biliary cholangitis. She was found to have a dramatically elevated blood pressure of about 230/110 mmHg without a history of hypertension and was referred to the emergency department.
METHODS: Hypokalemia, hypertensive retinopathy, and nephropathy were found during the following work-up. Since no other risk factors of hypertension were identified, she was suspected to have glycyrrhizin induced pseudo-hyperaldosteronism.
METHODS: Glycyrrhizin was discontinued. Intravenous sodium nitroprusside was used during the first few days. Nifedipine and irbesartan were taken after discharge, and the dosage was reduced gradually under supervision.
RESULTS: She stopped all the anti-hypertensive drugs 6 months since glycyrrhizin was stopped. Her blood pressure was about 110/60 mmHg after repetitive measurement. Her serum potassium and urine albumin/creatinine ratio were also normalized.
CONCLUSIONS: Licorice and glycyrrhizin induced hypertension due to pseudo-hyperaldosteronism has been widely reported, yet only 3 cases reported that excessive consumption of licorice could lead to hypertensive emergencies. This is the first case that glycyrrhizin induced hypertensive crisis with target organ impairment. By presenting this case, we remind clinicians of glycyrrhizin induced hypertension, a condition which could lead to medical emergencies.