JNK pathway is involved in the inhibition of inflammatory target gene expression and NF-kappaB activation by melittin

<p>Abstract</p> <p>Background</p> <p>Bee venom therapy has been used to treat inflammatory diseases including rheumatoid arthritis in humans and in experimental animals. We previously found that bee venom and melittin (a major component of bee venom) have anti-inflammatory effect by reacting with the sulfhydryl group of p50 of nuclear factor-kappa B (NF-κB) and IκB kinases (IKKs). Since mitogen activated protein (MAP) kinase family is implicated in the NF-κB activation and inflammatory reaction, we further investigated whether activation of MAP kinase may be also involved in the anti-inflammatory effect of melittin and bee venom.</p> <p>Methods</p> <p>The anti-inflammatory effects of melittin and bee venom were investigated in cultured Raw 264.7 cells, THP-1 human monocytic cells and Synoviocytes. The activation of NF-κB was investigated by electrophoretic mobility shift assay. Nitric oxide (NO) and prostaglandin E₂(PGE₂) were determined either by Enzyme Linked Immuno Sorbent Assay or by biochemical assay. Expression of IκB, p50, p65, inducible nitric oxide synthetase (iNOS), cyclooxygenase-2 (COX-2) as well as phosphorylation of MAP kinase family was determined by Western blot.</p> <p>Results</p> <p>Melittin (0.5–5 μg/ml) and bee venom (5 and 10 μg/ml) inhibited lipopolysaccharide (LPS, 1 μg/ml) and sodium nitroprusside (SNP, 200 μM)-induced activation of c-Jun NH2-terminal kinase (JNK) in RAW 264.7 cells in a dose dependent manner. However, JNK inhibitor, anthra [1,9-cd]pyrazole-6 (2H)-one (SP600215, 10–50 μM) dose dependently suppressed the inhibitory effects of melittin and bee venom on NF-κB dependent luciferase and DNA binding activity via suppression of the inhibitory effect of melittin and bee venom on the LPS and SNP-induced translocation of p65 and p50 into nucleus as well as cytosolic release of IκB. Moreover, JNK inhibitor suppressed the inhibitory effects of melittin and bee venom on iNOS and COX-2 expression, and on NO and PGE₂generation.</p> <p>Conclusion</p> <p>These data show that melittin and bee venom prevent LPS and SNP-induced NO and PGE₂production via JNK pathway dependent inactivation of NF-κB, and suggest that inactivation of JNK pathways may also contribute to the anti-inflammatory and anti-arthritis effects of melittin and bee venom.</p

Multifunctional-high resolution imaging plate based on hydrophilic graphene for digital pathology

In the present study, we showed that hydrophilic graphene can serve as an ideal imaging plate for biological specimens. Graphene being a single-atom-thick semi-metal with low secondary electron emission, array tomography analysis of serial sections of biological specimens on a graphene substrate showed excellent image quality with improved z-axis resolution, without including any conductive surface coatings. However, the hydrophobic nature of graphene makes the placement of biological specimens difficult; graphene functionalized with polydimethylsiloxane oligomer was fabricated using a simple soft lithography technique and then processed with oxygen plasma to provide hydrophilic graphene with minimal damage to graphene. High-quality scanning electron microscopy images of biological specimens free from charging effects or distortion were obtained, and the optical transparency of graphene enabled fluorescence imaging of the specimen; high-resolution correlated electron and light microscopy analysis of the specimen became possible with the hydrophilic graphene plate

Evaluation of the transporter-mediated herb-drug interaction potential of DA-9801, a standardized dioscorea extract for diabetic neuropathy, in human in vitro and rat in vivo

BACKGROUND: Drug transporters play important roles in the absorption, distribution, and elimination of drugs and thereby, modulate drug efficacy and toxicity. With a growing use of poly pharmacy, concurrent administration of herbal extracts that modulate transporter activities with drugs can cause serious adverse reactions. Therefore, prediction and evaluation of drug-drug interaction potential is important in the clinic and in the drug development process. DA-9801, comprising a mixed extract of Dioscoreae rhizoma and Dioscorea nipponica Makino, is a new standardized extract currently being evaluated for diabetic peripheral neuropathy in a phase II clinical study. METHOD: The inhibitory effects of DA-9801 on the transport functions of organic cation transporter (OCT)1, OCT2, organic anion transporter (OAT)1, OAT3, organic anion transporting polypeptide (OATP)1B1, OATP1B3, P-glycoprotein (P-gp), and breast cancer resistance protein (BCRP) were investigated in HEK293 or LLC-PK1 cells. The effects of DA-9801 on the pharmacokinetics of relevant substrate drugs of these transporters were also examined in vivo in rats. RESULTS: DA-9801 inhibited the in vitro transport activities of OCT1, OCT2, OAT3, and OATP1B1, with IC(50) values of 106, 174, 48.1, and 273 μg/mL, respectively, while the other transporters were not inhibited by 300 μg/mL DA-9801. To investigate whether this inhibitory effect of DA-9801 on OCT1, OCT2, and OAT3 could change the pharmacokinetics of their substrates in vivo, we measured the pharmacokinetics of cimetidine, a substrate for OCT1, OCT2, and OAT3, and of furosemide, a substrate for OAT1 and OAT3, by co-administration of DA-9801 at a single oral dose of 1,000 mg/kg. Pre-dose of DA-9801 5 min or 2 h prior to cimetidine administration decreased the C(max) of cimetidine in rats. However, DA-9801 did not affect the elimination parameters such as half-life, clearance, or amount excreted in the urine, suggesting that it did not inhibit elimination process of cimetidine, which is governed by OCT1, OCT2, and OAT3. Moreover, DA-9801 did not affect the pharmacokinetic characteristics of furosemide, as evidenced by its unchanged pharmacokinetic parameters. CONCLUSION: Inhibitory effects of DA-9801 on OCT1, OCT2, and OAT3 observed in vitro may not necessarily translate into in vivo herb-drug interactions in rats even at its maximum effective dose

A Case of Anaphylaxis to Chlorhexidine during Digital Rectal Examination

Chlorhexidine is widely used as an antiseptic and disinfectant in medical and non-medical environments. Although the sensitization rate seems to be low, its ubiquitous use raises the possibility of sensitization in many patients and medical care workers. We describe a patient with anaphylaxis during digital rectal examination with chlorhexidine jelly. Urticaria, angioedema, dyspnea, and hypotension developed within a few minutes of the rectal examination. The patient fully recovered after treatment with epinephrine and corticosteroids. Skin tests for chlorhexidine were undertaken 5 weeks later, showing positive prick and intradermal skin tests. Within 30 min of the skin test, the patient complained of febrile sensation, chest tightness, angioedema, and urticaria on the face and trunk. An enzyme allergosorbent test for latex was negative. We present this case to alert clinicians about hypersensitivity to chlorhexidine that could potentially be life-threatening. We suggest that chlorhexidine should be recognized as a causative agent of anaphylaxis during procedural interventions

Enhancement of carbamazepine removal rate using Tetradesmus obliquus KNUA061 and NaOCl and utilization of the resulting biomass

Pharmaceutical and personal care products (PPCPs) are discharged into receiving water bodies mainly from sewage treatment plants. Due to the inefficient removal in conventional wastewater treatment facilities, PPCPs have become a major concern to aquatic ecosystems, water quality, and public health worldwide since they cause harmful effects on aquatic life and human even at low doses. Among the PPCPs, carbamazepine (CBZ) is one of the most commonly prescribed anticonvulsant drugs and consumed more than 1,000 tons per year. Due to its structural complexity, CBZ is known as recalcitrant compound highly stable during wastewater treatment. Consequently, it has become one of the most frequently detected pharmaceuticals in waste water, surface water, and even drinking water. In this study, Korean indigenous microalgae strains were tested as eco-friendly and cost-effective solutions for CBZ removal. Based on the preliminary biological CBZ degradation tests, Tetradesmus obliquus KNUA061 demonstrating the best CBZ removal rate was selected for further experiments. In order to increase strain KNUA061's CBZ removal efficiency, NaOCl, which is widely accepted in the water purification process, was used as an additional stimulus to induce stress conditions. At around 20 μg L−1 CBZ, addition of 1.0 mg NaOCl resulted in approximately 20% of removal rate increase without suppressing cells growth. Roughly 90% of CBZ remained its original form and the composition of the transformed secondary metabolites was less than 10% during the biodegradation process by the microalga. Based on the results of the antioxidant enzyme activities, degree of lipid oxidation, and amino acid contents, it was concluded that the redox-defence system in microalgal cells may have been activated by the NaOCl treatment. Biomass analysis results showed that higher heating value (HHV) of strain KNUA061 biomass was higher than those of lignocellulosic energy crops suggesting that it could be utilized as a possible renewable energy source. Even though its biodiesel properties were slightly below the international standards due to the high PUFA contents, the biodiesel produced from T. obliquus KNUA061 could be used as a blending resource for transportation fuels. It was also determined that the microalgal biomass has acceptable feasibility as a sustainable dietary supplement feedstock due to its high essential amino acid contents

Динаміка та аналіз виробничого травматизму та професійних захворювань в Україні

Кожного року в Україні на виробництві травмується понад 10 тис. людей, з них гине понад 600 осіб. Оптимістична, на перший погляд, статистика, за якою травматизм на виробництві за роки незалежності України зменшився в десять разів, виявляється не такою вже й оптимістичною, коли аналізуються конкретні цифри

A Case of Anaphylaxis to Oral Minocycline

Minocycline is a semisynthetic tetracycline derivative that is often used in the treatment of acne vulgaris. To date, there has been only one case report of anaphylaxis to minocycline. We report here a case of anaphylaxis to oral minocycline. A 56-yr-old woman visited our hospital after three episodes of recurrent anaphylaxis. We performed an oral challenge test, the standard method for diagnosing drug allergies, with minocycline, one of the drugs she had taken previously. She developed urticaria, angioedema, nausea, vomiting, hypotension, and dyspnea within 4 min and was treated with intramuscular epinephrine, intravenous antihistamine and systemic corticosteroid. However, she presented similar symptoms at 50 min and at 110 min. In prescribing oral minocycline, physicians should consider the possibility of serious adverse reactions, such as anaphylaxis