Contact dermatitis caused by glucose sensors, insulin pumps, and tapes: Results from a 5-year period.

BACKGROUND: The number of patients with contact dermatitis from glucose sensors and insulin infusion sets is increasing. Patch testing is challenging because of a lack of information concerning the constituent materials of medical devices. OBJECTIVES: To report on products and causes of allergic reactions to glucose sensors or insulin infusion sets over a 5-year period and suggest a short screening series. METHODS: Analysis of patch test data from consecutive patients suspected of allergic contact dermatitis (ACD) to glucose sensors and/or insulin infusion sets from 2015-2019. RESULTS: Patient numbers increased from 4 to 15 per year; 30/38 (78.9%) were children. In 29 (76.3%), a diagnosis of allergic/probable ACD was established, mostly due to the tapes of the device or allergens in these tapes (n = 23) followed by allergens in the device housing (n = 10). Isobornyl acrylate, abitol, and colophonium were the most common allergens. Information from manufacturers was often difficult to obtain and, if accessible, inadequate. For this reason, the diagnosis was delayed for more than 1.5 years in 12 (31%) patients. CONCLUSIONS: The increasing number of patients, mostly children, with ACD from devices used in treatment of type 1 diabetes demonstrates the importance of this problem. Allergies can easily be overlooked, due to the lack of mandatory labeling of the constituent materials of the devices.

Prospective study of the effect of sulfotanshinone sodium combined with tirofiban on vascular endothelial function and indicators of plaque stability in elderly patients with acute coronary syndrome.

WHAT IS KNOWN AND OBJECTIVE: This study aimed to explore the effect of sulfotanshinone sodium injection combined with tirofiban on vascular endothelial function and indicators of plaque stability in elderly patients with acute coronary syndrome (ACS). METHODS: We designed a prospective study and enrolled 169 patients with ACS who were admitted to our hospital as subjects. Patients treated with sulfotanshinone sodium injection combined with tirofiban (n = 99) were allocated to the research group (RG), and the remaining patients treated with tirofiban alone were allocated to the control group (n = 70; CG). The two groups were compared in terms of treatment efficacy, adverse reactions, vascular endothelial function, changes in plaque stability indicator levels, prognosis, recurrence rate, and quality of life after the treatment. RESULTS AND DISCUSSION: Treatment response rate, SOD and ET-1 levels, and quality-of-life score were markedly lower in RG than in CG (all P < .05). The incidence of adverse reactions; levels of CD63p, CD62p and GP IIb/IIIa; changes in plaque stability indicator levels; and recurrence rate were markedly higher in RG than in CG (all P < .05). There was no significant difference in 3-year survival rate between the two groups (P > .05). WHAT IS NEW AND CONCLUSION: Compared with tirofiban alone, sulfotanshinone sodium injection combined with tirofiban had superior efficacy and safety in the treatment of ACS. It can effectively reduce recurrence rate and improve quality of life in ACS, making it a strong candidate for popular clinical application.

HLA-A*02:01 allele is associated with tanshinone-induced cutaneous drug reactions in Chinese population.

Tanshinone, a widely used Chinese patent medicine, has been confirmed to have various kinds of pharmacological effects although frequently causing cutaneous adverse drug reactions (cADRs). We aim to identify whether human leukocyte antigen (HLA) class I alleles are associated with tanshinone-induced cADRs in Han Chinese. The association study including 18 patients with tanshinone-induced cADRs, 67 tanshinone-tolerant volunteers, and two general population databases consisted of 10,689 and 169,995 healthy subjects was performed. The frequency of tanshinone-induced cADRs patients carrying HLA-A*02:01 was significantly higher when compared with the general control groups (OR = 6.25, Pc = 7.20 × 10-5; OR = 7.14, Pc = 8.00 × 10-6), and with the tolerant group (OR = 5.09, Pc = 0.024). The molecular docking assay confirmed high affinity of the ingredients of tanshinone towards HLA-A*02:01 (≤-7.5 kcal/mol). The result suggested HLA-A*02:01 may work as a promisingly predictive marker for tanshinone personalized therapy in Han Chinese.

Traditional Chinese medicine versus regular therapy in Henoch-Schönlein purpura nephritis in children: study protocol for a randomized controlled trial.

BACKGROUND: Henoch-Schönlein purpura nephritis (HSPN) is the most common secondary glomerular disease in children. Currently, the treatment for HSPN is always selected based on the Kidney Disease Improving Global Outcomes guidelines; however, this approach may lead to undertreatment, especially in patients with persistent proteinuria that does not reach nephrotic levels and/or hematuria and those with a pathological classification between grades 1 and 3 according to the International Study of Kidney Disease in Children. This study was performed to evaluate the curative effect and safety of a traditional Chinese medicine (TCM) integrated treatment program in this type of HSPN. METHODS: This multicenter, open-label, large-sample, randomized controlled trial was performed in China and included 500 children with HSPN exhibiting mild pathological patterns. The treatment group to control group ratio was 2:1, and each group was further stratified into two types, light and heavy, according to urinary protein quantification and pathological type. The treatment group received tripterygium glycosides (TGs), tanshinone IIa sodium sulfonate injection, and Chinese herbs selected based on syndrome differentiation in TCM. The heavy and light subgroups received treatment courses and dosages of TG. In the control groups, the light group received benazepril hydrochloride tablets, low molecular weight heparin calcium injection, dipyridamole tablets, and a Chinese medicine placebo, while the heavy group received the same treatment plus prednisone. All groups were treated for 3 months and then followed up for 9 months. The efficacy and safety of the treatments were then evaluated among the groups. DISCUSSION: Currently, few treatments are available for HSPN patients with mild pathological patterns indicating light to moderate proteinuria and/or hematuresis. In this large-sample study, we provide a new approach for HSPN that includes an integrated treatment program that incorporates TCM. TRIAL REGISTRATION: Clinical Trials.gov, NCT03591471 . Re-registered on 19 July 2018.

Occupational allergic contact dermatitis caused by colophonium.

BACKGROUND: Colophonium is a common contact allergen that is present not only in household products but also in occupational settings. OBJECTIVES: To describe the sources of occupational exposure to colophonium and the occupations at risk of colophonium allergy. METHODS: We reviewed patch test files from the years 2002 to 2017 at the Finnish Institute of Occupational Health for patients with allergic reactions to colophonium and abietic acid. We analysed the patch test, occupation and exposure data of 39 patients diagnosed with occupational allergic contact dermatitis (OACD) caused by colophonium. RESULTS: Of the patients examined for suspected occupational dermatitis, 4.6% (n = 118) reacted positively to colophonium. The majority of the OACD patients worked in the wood industry, as machinists, or were involved in soldering or agriculture. The most common occupational sources of exposure were coniferous wood and wood-derived materials, followed by glues, metalworking fluids, and soldering materials. Colophonium is not always mentioned in safety data sheets (SDSs), and the sources of colophonium exposure are often materials for which there are no SDSs. CONCLUSION: OACD caused by colophonium is quite common and occurs in a variety of occupations. SDSs provide poor information for exposure assessment. Patch testing with the patient's own materials was often useful in establishing the diagnosis.

[The Efficacy of Rebamipide or Ecabet Sodium Supplementation for Helicobacter pylori Eradication Therapy Compared with Quadruple (Concomitant) Regimen].

Background/Aims: Although some previous studies reported that a treatment combined with mucoprotective agent could improve the eradication rate in dual or triple therapy, there are other reports that question the efficacy of combining these drugs in concomitant therapy (CoCTx). The aim of this study was to investigate the effects of rebamipide or ecabet on the Helicobacter pylori (H. pylori) eradication combined with CoCTx. Methods: We retrospectively reviewed the medical records of 277 patients with proven H. pylori infection. They were assigned to one of 3 regimens for 10 days, twice daily: (a) CoCTx (n=118): lansoprazole 30 mg, amoxicillin 1 g, metronidazole 500 mg, and clarithromycin 500 mg; (b) CoCTx+rebamipide (100 mg) (n=85); (c) CoCTx+ecabet (1 g) (n=74). Results: The baseline characteristics were not significantly different. H. pylori eradication rates were 82.2% (97/118) in CoCTx, 90.6% (77/85) in CoCTx+rebamipide, and 89.2% (66/74) in CoCTx+ecabet (p=0.17), which were statistically insignificant. Overall adverse events were more frequently reported in the CoCTx+rebamipide (50.6%. 43/85) and CoCTx+ecabet (44.6%, 33/74) groups than in the CoCTx (32.2%, 38/118) (p = 0.03) group. Drug compliances were not different between three groups (CoCTx: 95.8%, 113/118; CoCT+rebamipide: 92.9%, 79/85; CoCTx+ecabet 98.6%,73/74) (p=0.209). Multivariate analysis showed that the risk of eradication failure was significantly increased with decreased drug compliance (odds ratio 3.52, 95% confidence interval 1.00-12.32; p=0.05). Conclusions: Addition of these mucoprotective agent was not superior to CoCTx alone for eradicating H. pylori infection with frequent adverse events. Rather, drug compliance is the most related factor affecting the eradication rate. Our data suggest the importance of drug compliance over the drugs used.

Involvement of allelopathy in inhibition of understory growth in red pine forests.

Japanese red pine (Pinus densiflora Sieb. et Zucc.) forests are characterized by sparse understory vegetation although sunlight intensity on the forest floor is sufficient for undergrowth. The possible involvement of pine allelopathy in the establishment of the sparse understory vegetation was investigated. The soil of the red pine forest floor had growth inhibitory activity on six test plant species including Lolium multiflorum, which was observed at the edge of the forest but not in the forest. Two growth inhibitory substances were isolated from the soil and characterized to be 15-hydroxy-7-oxodehydroabietate and 7-oxodehydroabietic acid. Those compounds are probably formed by degradation process of resin acids. Resin acids are produced by pine and delivered into the soil under the pine trees through balsam and defoliation. Threshold concentrations of 15-hydroxy-7-oxodehydroabietate and 7-oxodehydroabietic acid for the growth inhibition of L. multiflorum were 30 and 10µM, respectively. The concentrations of 15-hydroxy-7-oxodehydroabietate and 7-oxodehydroabietic acid in the soil were 312 and 397µM, respectively, which are sufficient concentrations to cause the growth inhibition because of the threshold. These results suggest that those compounds are able to work as allelopathic agents and may prevent from the invasion of herbaceous plants into the forests by inhibiting their growth. Therefore, allelopathy of red pine may be involved in the formation of the sparse understory vegetation.

Relevance of carnosic acid to the treatment of several health disorders: Molecular targets and mechanisms.

Carnosic acid is a phenolic diterperne compound found in abundance in sage and rosemary, which are both widely used in traditional medicine. Research over the past decade indicates that carnosic acid has multiple bioactive properties including antioxidant, anti-inflammatory and anticancer activities among others. This review summarizes the current in vitro and in vivo data about the efficacy of carnosic acid in the prevention or treatment of various experimental health disorders. The analysis of the literature allows an insight into the participation of numerous signaling pathways modulated by carnosic acid, into its synergistic potential and, thus, into the divergence in cellular mechanisms of action of this molecule.

Tanshinone IIA attenuates renal fibrosis and inflammation via altering expression of TGF-ß/Smad and NF-κB signaling pathway in 5/6 nephrectomized rats.

PURPOSE: In traditional Chinese medicine, Tanshinone IIA is used to treat chronic kidney disease (CKD). However, its biological activity and mechanism of action in renal fibrosis and inflammation are not fully identified. The current study was conducted to determine the effects of Tanshinone IIA treatment on CKD by assessing potential modulation of the TGF-ß/Smad and NF-κB signaling pathway. METHODS: CKD was produced in rats by 5/6 nephrectomy. They were then divided into the following groups: control (sham operation); CKD (5/6 nephrectomy); 5/6 nephrectomy+Tanshinone IIA (10mg/kg in average, once a day for 16 weeks). Serum and urine samples were obtained from animals in each group, and serum creatinine (Scr), blood urea nitrogen (BUN) levels and 24h urinary protein excretion were measured. Tissue samples from the kidney were used for morphometric studies (Masson's trichrome). The expression of fibronectin protein and collagen types I, III, IV, and TGF-ß, TNF-α, CXCL-1, MCP-1, RANTES mRNA were evaluated using immunohistochemistry and RT-PCR analysis; the TGF-ß/Smad and NF-κB signaling pathway was detected by immunohistochemistry and Western blot analysis. RESULTS: The following effects were observed in CKD rats treated with Tanshinone IIA: (1) marked improvements in Scr, and 24h urine protein excretion; (2) significant reductions in protein and mRNA levels of fibronectin, collagen III, and collagen IV and TNF-α, MCP-1, and CXCL-1; (3) significantly inhibited the TGF-ß/Smad and NF-κB signaling activation. CONCLUSIONS: These results suggest that Tanshinone IIA suppresses renal fibrosis and inflammation via altering expression of TGF-ß/Smad and NF-κB pathway in the remnant kidney, thus supporting the potential of Tanshinone IIA as a new therapeutic agent for slowing the progression of CKD.

Carnosic acid induces autophagic cell death through inhibition of the Akt/mTOR pathway in human hepatoma cells.

The therapeutic goal of cancer treatment is now geared towards triggering tumour-selective cell death with autophagic cell death being required for the chemotherapy of apoptosis-resistant cancer. In this study, Carnosic acid (CA), a polyphenolic diterpene isolated from Rosemary (Rosemarinus officinalis), significantly induced autophagic cell death in HepG2 cells. Ca treatment caused the formation of autophagic vacuoles produced an increasing ratio of LC3-II to LC3-I in a time- and dose-dependent manner but had no effect on the levels of autophagy-related protein ATG6 and ATG13 expression. Autophagy inhibitors, 3-methyladenine (3-MA), chloroquine and bafilomycin A1, or ATG genes silencing in HepG2 cells significantly inhibited CA-induced autophagic cell death. The CA treatment decreased the levels of phosphorylated Akt and mTOR without any effects on PI3K or PTEN. Most importantly, overexpression of Akt and knockdown of PTEN attenuated autophagy induction in CA-treated cells. Taken together, our results indicated that CA induced autophagic cell death through inhibition of the Akt/mTOR pathway in human hepatoma cells. These findings suggest that CA has a great potential for the treatment of hepatoma via autophagic induction.

Acute and 30-day oral toxicity studies of administered carnosic acid.

PURPOSE: Increasing interest in carnosic acid (CA) is due to its pharmacological properties. The aim of this study was to evaluate the acute and 30-day oral toxicity of CA. METHODS: The acute oral toxicity study in Kuming mice design followed the OECD-guidelines 423, and a 30-day chronic oral toxicity study in Wistar rats based on the enhanced OECD test guideline 407 were performed. RESULTS: The oral lethal dose (LD50) for mice was 7100 mg/kg of body weight in the acute toxicity study. The histopathological changes were observed in the heart, liver and kidney for the survival mice treated with a single dose CA. For the sub chronic toxicity study, CA administered for 30 days produced slightly reductions in the weight gain pattern, which did not reach the significant level when compared with the control values. With respect to serum biochemistry test, decreased total serum protein levels, but conversely increased aspartate aminotransferase (AST) levels were detected in the high-dose and moderate-dose groups. Histopathologically, light pathological changes were observed in the heart, liver, and kidney of rats treated with the high-dose CA. CONCLUSION: The present work suggests that a short-term oral administration of CA has a relatively low toxicity profile.

In vitro hepatotoxicity and cytochrome P450 induction and inhibition characteristics of carnosic acid, a dietary supplement with antiadipogenic properties.

Carnosic acid is a phenolic diterpene isolated from rosemary (Rosmarinus officinalis), which may have anticancer, antiadipogenic, and anti-inflammatory properties. Recently, carnosic acid was shown to prevent weight gain and hepatic steatosis in a mouse model of obesity and type II diabetes. Based on these results, carnosic acid has been suggested as a potential treatment for obesity and nonalcoholic fatty liver disease; however, little is known about the safety of carnosic acid at doses needed to elicit a pharmacological effect. For this reason, hepatotoxicity and cytochrome P450 inhibition and induction studies were performed in primary human hepatocytes and microsomes. Measuring cellular ATP, carnosic acid showed a dose-dependent increase in hepatotoxicity with an EC(50) value of 94.8 ± 36.7 µM in three human hepatocyte donors without a concurrent increase in the apoptosis markers caspase-3/7. In human liver microsomes, carnosic acid did not exhibit significant time-dependent inhibition for any of the cytochrome P450 enzymes investigated, although it did inhibit CYP2C9- and CYP3A4-catalyzed reactions with K(i) values of 9.2 and 4.3 µM, respectively. Carnosic acid also induced CYP2B6 and CYP3A4 mRNA and enzyme activity in a dose-dependent manner. At 10 µM, carnosic acid increased CYP2B6 enzyme activity 61.6 and 49.3% in two donors compared with phenobarbital, and it increased CYP3A enzyme activity 82.6 and 142% compared with rifampicin. These results indicate the potential for drug interactions with carnosic acid and illustrate the need for an appropriate safety assessment before being used as a weight loss supplement.

Safety and tolerability of bismuthyl ecabet suspension, a novel anti-ulcer agent, following single and multiple oral dose administration in healthy Chinese subjects.

BACKGROUND: Bismuthyl ecabet is a combination of sulfodehydroabietic acid and bismuth, which forms a new type of salt that is useful in treating peptic ulcers and gastritis. OBJECTIVE: This study was designed to assess the safety and tolerability of bismuthyl ecabet suspension in healthy Chinese subjects. METHODS: For the study 77 volunteers were randomized into single- or multiple-dose groups for oral administration of bismuthyl ecabet 200-1600 mg once daily or 1200 mg twice daily for 7 days. Safety and tolerability were assessed by adverse events, physical examination and serum biochemistry. RESULTS: In both the single- and multiple-dose studies, no severe adverse events were observed in any of the volunteers. The main adverse events caused by the drug in single-dose groups were an increase in serum alanine transaminase (ALT), γ-glutamyl transpeptidase, blood urea nitrogen, total bilirubin and skin rash. The numbers of adverse events judged to be possibly related to the drug were 2/18 in the 400 mg, 2/18 in the 800 mg, 1/8 in the 1200 mg, and none in the 200 or 1600 mg dose groups. In the multiple-dose studies, an increased serum ALT and aspartate transaminase (AST) was found in one subject after 7 days of administration of the drug. All serum biochemistry returned to normal levels and skin rash resolved after 7 days without any special treatment. CONCLUSION: Bismuthyl ecabet was shown to be safe and well tolerated in healthy Chinese subjects. The oral dosing regimen selected for subsequent phase II/III clinical trials was 800 mg twice daily.

Upregulation of endogenous neurotrophin levels in the brain by intranasal administration of carnosic acid.

The potential of intranasally administered carnosic acid to enhance the endogenous levels of neurotrophins [nerve growth factor and brain-derived neurotrophic factor] in the brain was investigated. Hydroxypropyl-ß-cyclodextrin (HP-ß-CD) was used to enhance the aqueous solubility of carnosic acid. The effect of different concentrations of chitosan on the permeation of carnosic acid was investigated across the bovine olfactory mucosa using Franz diffusion cell setup. The formulations were administered [intranasal (i.n.)/subcutaneous route] in Sprague-Dawley rats, and the neurotrophins were sampled from the brain by microdialysis after the treatment period and measured by enzyme-linked immunosorbent assay. Phase solubility studies revealed that the solubility of carnosic acid was enhanced significantly with increase in the concentration of HP-ß-CD. The neurotrophin levels were enhanced significantly upon i.n. administration of carnosic acid with chitosan, which was approximately 1.5-2-fold more over the parenteral route. Nose-to-brain delivery of carnosic acid along with chitosan is a potential approach for treating disorders associated with depletion of neurotrophins.

Quadruple therapy with ecabet sodium, omeprazole, amoxicillin and metronidazole is effective for eradication of Helicobacter pylori after failure of first-line therapy (KDOG0201 Study).

BACKGROUND AND OBJECT: An antiulcer agent, ecabet sodium, is active against Helicobacter pylori. The aim of the present study was to clinically examine whether eradication therapy, which includes ecabet sodium, is effective in eradication of H. pylori after failure of first-line therapy. METHODS: Patients with peptic ulcer who failed with first-line triple eradication therapy containing clarithromycin received quadruple therapy with omeprazole (20 mg, twice daily), amoxicillin (750 mg, twice daily), metronidazole (500 mg, twice daily) and ecabet sodium (1000 mg, twice daily) for 14 days. Eradication of H. pylori was judged by 13C-urea breath test 8 weeks later. RESULTS: Fifty-two patients (36 men and 16 women) were included. Their mean age was 51.4 years (range 28-73). One patient dropped out because of diarrhoea. The eradication rate was 98.0% (50/51) according to the per-protocol analysis and 96.2% (50/52) according to the intention-to-treat analysis. Side effects occurred in seven patients, but none were serious. CONCLUSIONS: Quadruple therapy including ecabet sodium is useful as second-line eradication treatment for H. pylori.