Xylene delays the development of Leydig cells in pubertal rats by inducing reactive oxidative species.

Xylene is a cyclic hydrocarbon, which is commonly used as a solvent in dyes, paints, polishes, and industrial solutions. It is a potential environmental pollutant. Here, we report the effect of xylene exposure on Leydig cell development in male rats during puberty. Xylene (0, 150, 750, and 1500 mg/kg) was gavaged to 35-day-old male Sprague Dawley rats for 21 days. Xylene significantly reduced serum testosterone levels at 750 and 1500 mg/kg without affecting serum luteinizing hormone and follicle-stimulating hormone levels. Xylene reduced the number of HSD11B1-positive Leydig cells at the advanced stage at 1500 mg/kg. At 750 and 1500 mg/kg, xylene also reduced the cell size and cytoplasm size. It down-regulated the expression of Leydig cell-specific genes (Lhcgr, Scarb1, Star, Cyp11a1, Hsd3b1, Cyp17a1, and Hsd11b1) and proteins. In addition, xylene significantly reduced the ratio of phosphorus-GSK-3ß (pGSK-3ß/GSK-3ß), phosphorus-ERK1/2 (pERK)/ERK1/2, and phosphorus-AKT1 (pAKT1)/AKT1, and SIRT1 levels in the testes. In vitro Leydig cell culture showed that xylene induced oxidative stress by increasing the production of reactive oxygen species and lowing antioxidant (Sod2), and inhibited the production of testosterone, and down-regulated the expression of genes related to steroidogenesis, while vitamin E reversed the xylene-mediated effect as an antioxidant. In conclusion, xylene exposure may disrupt the development of pubertal Leydig cells by increasing reactive oxygen species production and reducing the expression of GSK-3ß, ERK1/2, AKT1, and SIRT1.

Effect of Nectaroscordum koelzi Methanolic Extract on Acute and Chronic Inflammation in Male Mice.

INTRODUCTION: The present study deals with the effect of Nectaroscordum koelzi fruit extract on acute and chronic inflammation. METHODS: A total of 84 NMRI mice were used in this study. The effect of the extract on acute inflammation was analyzed by increasing vascular permeability via acetic acid and xylene induced ear edema among mice. The extract was evaluated in terms of effects on chronic inflammation by means of the cotton pellet test among mice. For the assessment of inflammation degree, the mice paw edema volume was measured by the plethysmometric test. RESULTS: The findings showed that the extract was effective on acute inflammation induced by acetic acid in mice. In the xylene ear edema, N. koelzi extract indicated a significant activity in mice. In the cotton pellet method, the methanol extract produced a significant reduction in comparison with the control and dexamethasone. Mice paw edema volume decreased with the extract. CONCLUSION: In general, the data from the experiments indicated that the methanol extract of N. koelzi has an anti-inflammatory effect on acute and chronic inflammation. However, the exact contributing mechanisms have not been investigated for the pharmacological effects.

Toxicological responses of BEAS-2B cells to repeated exposures to benzene, toluene, m-xylene, and mesitylene using air-liquid interface method.

In order to reduce exposure to toxic chemicals, the European REACH regulation (1907/2006) recommends substituting toxic molecules with compounds that are less harmful to human health and the environment. Toluene is one of the most frequently used solvents in industries despite its toxicity. The objective of this study is to better understand and compare the toxicity of toluene and its homologues in a bronchial cell model. Thus, human bronchial BEAS-2B cells were exposed to steams of toluene, m-xylene, mesitylene (1,3,5-trimethylbenzene), and benzene (20 and 100 ppm). Exposure was carried out using an air-liquid interface (ALI) system (Vitrocell) during 1 h/day for 1, 3, or 5 days. Cytotoxicity, xenobiotic metabolism enzyme gene expression, and inflammatory response were evaluated following cell exposures. BEAS-2B cell exposure to toluene and its homologues revealed the involvement of major (CYP2E1) and minor metabolic pathways (CYP1A1). A late induction of genes (EPHX1, DHDH, ALDH2, and ALDH3B1) was measured from Day 3 and can be linked to the formation of metabolites. An increase in the secretion level of inflammatory markers (TNF-α, IL-6, IL-8, MCP-1, and GM-CSF) was also observed. In parallel, regulation between inflammatory mediators and the expression of transmembrane glycoprotein mucin MUC1 was also studied. This in vitro approach with ALI system points out the relevance of conducting repeated exposures to detect potential late effects. The difference recorded after cell exposure to toluene and its homologues highlights the importance of substitution principle.

Necrotising fasciitis following accidental injection of intraoral xylene: a preventable medication error.

The most common cause of preventable mortality and morbidity to the patient in a healthcare system is medication error. Medication errors have got a significant impact on the patient health and healthcare system. These errors are multidisciplinary and can occur at various stages of drug therapy. Physicians, nursing staff, pharmacists, hospital administration all have an important role in preventing medication errors from recurring. The most common causes include wrong patient, wrong drug prescription, look-alike sound-alike drugs, faulty drug administration, wrong dosage, drug storage, delivery problem, lack of staff, patient and physician education and failure to monitor closely. This case illustrates the importance of incorporating protocol and cross-checking before administering a drug during the procedure. Here, we discuss a case of accidental intraoral injection of xylene instead of xylocaine (local anaesthetic agent), which was a sound-alike drug that resulted in significant morbidity to the patient.

Randomized controlled trial evaluating the antimicrobial efficacy of chlorhexidine gluconate and para-chloro-meta-xylenol handwash formulations in real-world doses.

Chlorhexidine gluconate-based soaps have become the gold standard for handwashing in critical care settings and para-chloro-meta-xylenol is an effective alternative antibacterial active ingredient. This study benchmarked 2 novel foaming handwashes, compared to a bland soap for antimicrobial effectiveness using the health care personnel handwash method at realistic soap doses (0.9 mL and 2.0 mL). To our knowledge, this is the first published efficacy study on realistic soap doses. Both soaps met Food and Drug Administration success criteria.

Effectiveness of surgical hand antisepsis using chlorhexidine digluconate and parachlorometaxylenol hand scrub: Cross-over trial.

BACKGROUND: Chlorhexidine and parachlorometaxylenol (PCMX) are antiseptics recommended for surgical hand antisepsis. To our knowledge, PCMX has not been evaluated for bactericidal efficacy "in vivo. METHODS: We conducted a randomized, double-blind, controlled crossover trial to compare the bacterial loads on fingertips and fingernails under laboratory conditions after use of antiseptic test products, including chlorhexidine digluconate 4%, PCMX 3%, and a reference solution of propan-1-ol 60% (P-1). We assessed bacterial load after a prewash with soft soap, immediately after application of an antiseptic, and 3 hours after application and wearing of sterile, powder-free gloves. Our procedures followed those specified by European Norm (EN) 12791 for evaluating surgical hand antiseptics and using cotton swab for fingertips and fingernails. RESULTS: Chlorhexidine digluconate 4% and PCMX 3% did not decrease bacterial load on the hands. The bactericidal performances of chlorhexidine digluconate 4% and PCMX 3% did not differ significantly. Chlorhexidine digluconate 4% and PCMX 3% increased bacterial load on the fingertips after participants had worn gloves for 3 hours. Fingernails had greater bacterial loads than skin on the fingertips. CONCLUSIONS: Chlorhexidine digluconate 4% and PCMX 3% had similar bactericidal efficacy, but they failed to meet the EN 12791 efficacy standard. Fingernails should be a particular focus of antisepsis in preparation for surgery.The trial was registered at ClinicalTrials.gov (ID: NCT02500758).

A novel diagnostic in situ derivatization kit for the simultaneous determination of 14 biomarkers of exposure to benzene, toluene, ethyl benzene and xylenes in human urine by isotope dilution liquid chromatography tandem mass spectrometry and kit optimization using response surface methodology.

Metabolite profiling can be used as a diagnostic measure for both short and long term co-exposure by individuals to benzene, toluene, ethylbenzene and xylenes (BTEX). A novel one pot derivatization in situ kit (OPDISK) was developed and optimized using a multivariate approach based on central composite design. The OPDISK was designed to simultaneously derivatize, in a urine sample matrix, a series of fourteen carboxylic acid and phenol-bearing urinary metabolites of BTEX to enhance their chromatographic analysis and sensitivity for detection by liquid chromatography - electrospray ionization - tandem mass spectrometry (LC-ESI-MS/MS). Using the reagent kit, the less responsive functional units on the molecules were converted to permanently positively-charged functional units. The kit was composed of three components, 2-fluoro-1-methylpyridinium p-toluenesulfonate (FMP), 3-carbinol-1-methylpyridinium iodide (CMP) and triethylamine (TEA) as a basic catalyst and, only after diluting a urine sample 20 fold with acetonitrile, was applied under mild conditions of room temperature and short reaction time of 20 min. The derivatized biomarkers were then directly analyzed using isotope dilution LC-ESI-MS/MS. The method was sensitive (limit of detection on column ranged from 1.4 pg to 3.1 ng), accurate (mean accuracy from 85% to 114%), and precise (mean coefficient of variation from 1% to 14%). The method results indicated a good linearity (R2 ≥ 0.990) for all metabolites. ClinChek® urine control samples were used successfully to demonstrate the accuracy of the method.

[Study on the health effects of occupational exposure to low concentrations of benzene].

Objective: The main purpose of this study was to ascertain whether (or not) exposure to benzene, toluene, xylene and ethylbenzene (BTXE) , under normal working conditions, was associated with any health effects. Methods: From January to December 2014, the workplaces concentrations of BTXE were measured of 71 enterprises in Suzhou Industrial Park. Occupational health examination were investigated on 764 employees who exposed to BTXE, as well as 4409 employees of the corresponding enterprises who unexposed to BTXE, and analyzed the data of the two groups. Results: A total of 6 monitoring sites in 3 enterprises BTXE concentrations excess of the standards, the unexposed group was under the limit of detection. The means of red blood cell count, hemoglobin, hematocrit, intermediate cell count and percentage of intermediate cells were significantly higher in exposed group than in unexposed group (P<0.05) . Conversely, platelet count was significantly lower in exposed group than in unexposed group (P<0.05) . The proportion of red blood cell volume, lymphocyte count and percentage of intermediate cells were significantly lower in exposed group than in unexposed group (P<0.05) . Both means and proportion of glutamic pyruvic transaminase and urea nitrogen were significantly higher in exposed group than in unexposed group (P<0.05) . The positive rate of protein, urine, urine red blood cell were significantly higher in exposed group than in unexposed group (P<0.05) . The abnormal rate of electrocardiogram, liver and kidney B scan were significantly higher in exposed group than in unexposed group (P<0.05) . Multivariate logistic regression analysis revealed that percentage of intermediate cells increased, urea nitrogen increased, urine protein positived, urine red blood cells positived in exposed group the OR values were 1.689, 3.291, 3.163 and 1.743 (P<0.05) . Conclusion: Occupational exposure to low concentrations of BTXE had a certain impact on the blood system and liver and kidney function of the employees, occupational health surveillance for such people should be strengthened.

On the use of Parylene C polymer as substrate for peripheral nerve electrodes.

Parylene C is a highly flexible polymer used in several biomedical implants. Since previous studies have reported valuable biocompatible and manufacturing characteristics for brain and intraneural implants, we tested its suitability as a substrate for peripheral nerve electrodes. We evaluated 1-year-aged in vitro samples, where no chemical differences were observed and only a slight deviation on Young's modulus was found. The foreign body reaction (FBR) to longitudinal Parylene C devices implanted in the rat sciatic nerve for 8 months was characterized. After 2 weeks, a capsule was formed around the device, which continued increasing up to 16 and 32 weeks. Histological analyses revealed two cell types implicated in the FBR: macrophages, in contact with the device, and fibroblasts, localized in the outermost zone after 8 weeks. Molecular analysis of implanted nerves comparing Parylene C and polyimide devices revealed a peak of inflammatory cytokines after 1 day of implant, returning to low levels thereafter. Only an increase of CCL2 and CCL3 was found at chronic time-points for both materials. Although no molecular differences in the FBR to both polymers were found, the thick tissue capsule formed around Parylene C puts some concern on its use as a scaffold for intraneural electrodes.

Patterning of functional human astrocytes onto parylene-C/SiO2 substrates for the study of Ca2+ dynamics in astrocytic networks.

OBJECTIVE: Recent literature suggests that astrocytes form organized functional networks and communicate through transient changes in cytosolic Ca2+. Traditional techniques to investigate network activity, such as pharmacological blocking or genetic knockout, are difficult to restrict to individual cells. The objective of this work is to develop cell-patterning techniques to physically manipulate astrocytic interactions to enable the study of Ca2+ in astrocytic networks. APPROACH: We investigate how an in vitro cell-patterning platform that utilizes geometric patterns of parylene-C on SiO2 can be used to physically isolate single astrocytes and small astrocytic networks. MAIN RESULTS: We report that single astrocytes are effectively isolated on 75 × 75 µm square parylene nodes, whereas multi-cellular astrocytic networks are isolated on larger nodes, with the mean number of astrocytes per cluster increasing as a function of node size. Additionally, we report that astrocytes in small multi-cellular clusters exhibit spatio-temporal clustering of Ca2+ transients. Finally, we report that the frequency and regularity of Ca2+ transients was positively correlated with astrocyte connectivity. SIGNIFICANCE: The significance of this work is to demonstrate how patterning hNT astrocytes replicates spatio-temporal clustering of Ca2+ signalling that is observed in vivo but not in dissociated in vitro cultures. We therefore highlight the importance of the structure of astrocytic networks in determining ensemble Ca2+ behaviour.

Effects of xylene on respiratory mucosa in rats / Efectos del xileno sobre la mucosa respiratoria de ratas

In this study we examined the effects histopathologic and immunohistochemical of xylene inhalation in rats by using light microscopy. Adult wistar albino rats were used in this study. Eight rats were in control group and 8 rats were in the experimental group. The experimental group was exposed to 300 ppm formaldehyde 3­5 min/day, 5 days/week for 8 weeks. The lining epithelium of respiratory mucosa showed a loss of ciliated cells with metaplasia of goblet cells, hyperplasia of squamous cells and edema, inflamation in sub epithelial area). In the group treated xylene. Disruption of cell-cell contact was observed. Weak expression of E-cadherin was observed between cells. The vascular endothelium of capillaries and venoles showed intense immunostaining for VEGF.

Se examinó el efecto histopatológico e inmunohistoquímico de la inhalación de xileno en ratas mediante el uso de microscopía de luz. Se utilizaron ratas albinas Wistar adultas. Ocho ratas formaron parte del grupo control y 8 del grupo experimental. El grupo experimental fue expuesto a 300 ppm de formaldehído, 3­5 min/día, 5 días/semana, durante 8 semanas. El epitelio de revestimiento de la mucosa respiratoria mostró una pérdida de células ciliadas con metaplasia de células caliciformes, hiperplasia de células escamosas y edema, con inflamación en la zona subepitelial. En el grupo tratado con xileno se observó una interrupción del contacto célula-célula. Se observó una débil expresión de E-cadherina entre las células. El endotelio vascular de los capilares y vénulas mostraron intensa inmunotinción de VEGF.

Anti-inflammatory and analgesic effects of Bi-yuan-ling granules.

Bi-yuan-ling granule (BLG) is a traditional Chinese medicine compound composed mainly of baicalin and chlorogenic acid. It has been demonstrated to be clinically effective for various inflammatory diseases such as acute rhinitis, chronic rhinitis, atrophic rhinitis and allergic rhinitis. However, the underlying mechanisms of BLG against these diseases are not fully understood. This study aimed to explore the anti-inflammatory and analgesic activities of BLG, and examine its protective effects on mouse acute lung injury (ALI). The hot plate test and acetic acid-induced writhing assay in Kunming mice were adopted to evaluate the pain-relieving effects of BLG. The anti-inflammatory activities of BLG were determined by examining the effects of BLG on xylene-caused ear swelling in Kunming mice, the cotton pellet-induced granuloma in rats, carrageenan-induced hind paw edema and lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice. The results showed that BLG at 15.5 mg/g could significantly relieve the pain by 82.5% (P<0.01) at 1 h after thermal stimulation and 91.2% (P<0.01) at 2 h after thermal stimulation. BLG at doses of 7.75 and 15.5 mg/g reduced the writhing count up to 33.3% (P<0.05) and 53.4% (P<0.01), respectively. Additionally, the xylene-induced edema in mice was markedly restrained by BLG at 7.75 mg/g (P<0.05) and 15.5 mg/g (P<0.01). BLG at 5.35 and 10.7 mg/g significantly reduced paw edema by 34.8% (P<0.05) and 37.9% (P<0.05) at 5 h after carrageenan injection. The granulomatous formation of the cotton pellet was profoundly suppressed by BLG at 2.68, 5.35 and 10.7 mg/g by 15.4%, 38.2% (P<0.01) and 58.9% (P<0.001), respectively. BLG also inhibited lung W/D ratio and the release of prostaglandin E2 (PGE2) in ALI mice. In addition, the median lethal dose (LD50), median effective dose (ED50) and half maximal inhibitory concentration (IC50) of BLG were found to be 42.7, 3.2 and 12.33 mg/g, respectively. All the findings suggest that BLG has significantly anti-inflammatory and analgesic effects and it may help reduce the damage of ALI.

Anti-Inflammatory Activity of Polysaccharide Fraction of Curcuma longa Extract (NR-INF-02).

The aim of the study was to investigate the safety and anti-inflammatory effects of polysaccharide fraction (F1) of Curcuma longa extract (NR-INF-02) in classical rodent models of inflammation. F1 was evaluated for its acute oral toxicity and found to be safe upto 5000 mg/kg body weight in rats. The anti-inflammatory activity of F1 was evaluated in acute (carrageenan - induced paw edema; xylene - induced ear edema) and chronic (cotton pellet - induced granuloma) models of inflammation. The results of the study demonstrated that F1 significantly (p ≤ 0.05) inhibited carrageenan-induced paw edema at 1 h and 3 h at doses of 11.25, 22.5 and 45 mg/kg body weight in rats. Also, F1 at doses of 15.75, 31.5 and 63 mg/kg significantly inhibited the xylene induced ear edema in mice. In a chronic model, F1 at 11.25, 22.5 and 45 mg/kg doses produced significant reduction of wet and dry weights of cotton pellets in rats. Overall results indicated that F1 of NR-INF-02 significantly attenuated acute and chronic inflammation in rodent models. This study emphasizes on the importance of Curcuma longa polysaccharide's role in acute and chronic inflammation.

Human inhalation exposures to toluene, ethylbenzene, and m-xylene and physiologically based pharmacokinetic modeling of exposure biomarkers in exhaled air, blood, and urine.

Urinary biomarkers of exposure are used widely in biomonitoring studies. The commonly used urinary biomarkers for the aromatic solvents toluene (T), ethylbenzene (E), and m-xylene (X) are o-cresol, mandelic acid, and m-methylhippuric acid. The toxicokinetics of these biomarkers following inhalation exposure have yet to be described by physiologically based pharmacokinetic (PBPK) modeling. Five male volunteers were exposed for 6 h in an inhalation chamber to 1/8 or 1/4 of the time-weighted average exposure value (TWAEV) for each solvent: toluene, ethylbenzene, and m-xylene were quantified in blood and exhaled air and their corresponding urine biomarkers were measured in urine. Published PBPK model for parent compounds was used and simulations were compared with experimental blood and exhaled air concentration data. If discrepancies existed, Vmax and Km were optimized. Urinary excretion was modeled using parameters found in literature assuming simply stoichiometric yields from parent compound metabolism and first-order urinary excretion rate. Alternative models were also tested for (1) the possibility that CYP1A2 is the only enzyme implicated in o-cresol and (2) a 2-step model for describing serial metabolic steps for mandelic acid. Models adapted in this study for urinary excretion will be further used to interpret urinary biomarker kinetic data from mixed exposures of these solvents.

Immuno-pathologic effects of oral administration of chlorpyrifos in broiler chicks.

This study sought to assess if chlorpyrifos (CPF) induced immunotoxic effects in orally-treated day-old broiler chicks. Groups of chicks received per os CPF diluted in xylene at 5, 10, and 20 mg/kg body weight (CPF-5, CPF-10, and CPF-20) orally daily for 15 days. Xylene and control groups received xylene alone (1 ml/kg BW) and physiological saline, respectively. At various times during/after the exposure regimens, different immune end-points were analyzed in the birds. Humoral immunity was examined by assessing antibody responses to sheep red blood cells. Cell-mediated immunity was measured via lymphoproliferative responses to avian tuberculin. Leukocyte phagocytic ability was measured using a carbon clearance assay. Results showed that CPF administered to broiler chicks caused a dose-dependent decrease in humoral immunity, cell-mediated immunity, and phagocytic activity. Dose- and time-related pathological changes were observed in bursa of Fabricius, spleen, and thymus in treated birds. These changes were mild, moderate, and severe, respectively, in the 5, 10, and 20 mg/kg CPF groups. The Bursa of Fabricius in treated birds showed increased inter-follicular connective tissue proliferation, severe moderate cytoplasmic vacuolation, edema, and degenerative changes such as pyknosis and fragmentation of nuclei that depleted the follicles of lymphoid cells. In the spleen, disorganization of follicular patterns, severe congestion, cytoplasmic vacuolation, degenerative changes, and hyperplasia of reticular cells were noted. The thymus in treated birds exhibited congestion, hyper-cellularity, and a presence of immature monocytes in the medullary region, as well as myoid cell necrosis. Taken together, these studies clearly demonstrated that chlorpyrifos could induce immunotoxicities in broiler birds.

δ-Amyrone, a specific inhibitor of cyclooxygenase-2, exhibits anti-inflammatory effects in vitro and in vivo of mice.

The whole plant of Sedum lineare Thunb has been used as traditional folk medicines for the treatment of sore throat, persistent hepatitis, jaundice and dysentery. δ-Amyrone (13(18)-Oleanen-3-one), a pentacyclic triterpene compound from S. lineare Thunb, was found to possess a potent anti-inflammatory effect in different inflammation model animals. Pretreatment with δ-Amyrone (i.p.) inhibited the ear edema in xylene-induced mouse ear edema. δ-Amyrone also decreased the level of nitric oxide (NO), prostaglandin E2 (PGE2), interleukin-6 (IL-6) and leukocyte numbers in acetic acid-induced peritonitis in vivo. To clarify the possible mechanism of δ-Amyrone, we investigated the effect of δ-Amyrone in lipopolysaccharide (LPS) induced peritoneal macrophages. The data indicated that δ-Amyrone notably inhibited IL-6, TNF-α and NO production. In addition, the result showed that δ-Amyrone may control the cyclooxygenase-2 (COX-2) regulation and not the cyclooxygenase-1 (COX-1) at protein levels. These results suggest that δ-Amyrone is a bioactive agent which possesses anti-inflammatory effects, which may be relevant to the regulation of COX-2.

[Effects of musk ketone at different concentrations on in vivo migration of exogenous rat bone marrow mesenchymal stem cells].

OBJECTIVE: To study the effects of musk ketone at different concentrations on in vivo migration of exogenous rat bone marrow mesenchymal stem cells (rBMSCs), thus screening out the optimal therapeutic dose. METHODS: Forty SD rats were randomly divided into 4 groups, 10 in each group. The rat model of skull defect was established using dental surgery. The primary rBMSCs were cultured by adherence screening method. The third passage cells were labeled by 10 micromol/L BrdU, and the labeled cells were injected into skull defect rats from the tail vein. Rats were administered with musk ketone at high, moderate and low concentration, respectively by gastrogavage, while equal volume of normal saline was administered to those in the blank control group by gastrogavage. Their skulls were taken out 14 days later, fixed, and decalcified. BrdU positive cells were counted under fluorescence microscope. RESULTS: After immunohistochemical processing, the gray scale analysis was preformed. There was statistical difference in the BrdU positive cell number between the blank control group and the low and moderate concentration musk ketone groups (P < 0.01). There was no statistical difference in the BrdU positive cell number between the blank control group and the high concentration musk ketone group (P > 0.05). CONCLUSION: Musk ketone could accelerate the in vivo migration of exogenous stem cells, with the optimal effects obtained at moderate and low concentrations.

Isofraxidin exhibited anti-inflammatory effects in vivo and inhibited TNF-α production in LPS-induced mouse peritoneal macrophages in vitro via the MAPK pathway.

Isofraxidin (IF) is a Coumarin compound that can be isolated from medicinal plants, such as Sarcandra glabra (Thunb.). Nakai is widely used in Asian countries for the treatment of anti-bacterial, anti-inflammatory and anti-tumour action. The present investigation was designed to evaluate the effect of IF on inflammation and nociception. In addition, we investigated a potential novel mechanism to explain the anti-inflammatory properties of IF. In vivo, xylene-induced mouse ear edema, carrageenan-induced rat paw edema, LPS-induced mouse endotoxic shock, acetic acid-induced mice writhing and formalin-induced mouse pain models were used to evaluate the anti-inflammatory activity of IF. In vitro, we examined the effects of IF inhibition on TNF-α production and the regulation of ERK1/2 and p38 phosphorylation activity in LPS-induced mouse peritoneal macrophages. Our results demonstrated that IF can significantly decrease xylene-induced ear edema, carrageenan-induced paw edema, acetic acid-induced writhing and formalin-induced pain. Moreover, IF greatly inhibited the production of TNF-α in the serum of LPS-stimulated mice and peritoneal macrophages, and it decreased phospho-p38 and ERK1/2 protein expression in LPS-stimulated mouse peritoneal macrophages. Overall, our data suggest that IF possesses significant analgesic and anti-inflammatory activities that may be mediated through the regulation of pro-inflammatory cytokines, TNF-α and the phosphorylation of p38 and ERK1/2.

Evaluation of neuropsychological symptoms and exposure to benzene, toluene and xylene among two different furniture worker groups in Izmir.

This study was conducted to determine whether there was any exposure to toluene, xylene and benzene and to assess the health impact of these solvents on workers in furniture enterprises in Karabaglar, Izmir. This cross-sectional study covered furniture enterprises in Karabaglar, Izmir. This study was comprised of an exposed group consisting of workers engaged in painting and varnishing and therefore exposed either directly or indirectly toluene, xylene and benzene in the workplace and the non-exposed group engaged in other aspects of production. While a total of 261 individuals completed questionnaires, 210 workers agreed to provide blood samples. Blood solvents levels were determined using gas chromatograph at Ege University, Intoxication Research and Application Centre. The modified EUROQUEST questionnaire was used to assess neuropsychological symptoms and neurological and general examination were performed. Occupational and exposure history, demographic and work-related information was collected. In this study of workers, blood toluene and benzene levels were found to be significantly higher among those engaged in painting and varnishing compared to those who perform other tasks. The average blood toluene and benzene concentrations among exposed workers were 6.95 times and 1.64 times respectively higher than those in the nonexposed groups. Smokers and participants who worked in excess of 8 hours/day had higher blood toluene and benzene levels. The most frequently work-related health complaints were back pain, allergies and asthma. No differences were found in the average scores in the neuropsychological symptoms questionnaire between exposed and non-exposed groups. Neurological examination of two individuals with these complaints revealed a loss of reflexes. The workers were unaware that they were being exposed to solvents at work. Tobacco smoke is a major source of internal exposure to benzene. Improving working conditions in furniture work places is a priority.

Synthesis and preliminary biological evaluation of capsaicin derivatives as potential analgesic drugs.

A series of capsaicin derivatives were designed and synthesized, including 10 compounds which are the combination of capsaicin and dihydro capsaicin with ibuprofen through bridge chain. Preliminary biological tests suggested that some compounds had both anti-inflammatory activity and analgesic activity. And their pungency was lower. Based on these results, some of these molecules can be considered as lead candidates for the further development of analgesic drugs.