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Rationale: Maleic acid is an industrial-grade chemical that is often used in adhesives, stabilizers, and preservatives. It is unknown whether long-term consumption of maleic acid modified starch is harmful to humans. However, many studies have indicated that maleic acid causes renal tubular damage in animal models, even as the associated pathways remain unclear. Sequential window acquisition of all theoretical fragment ion spectra (SWATH) is the most innovative of the label-free quantitative technologies which have better quantification performance. Therefore, SWATH technology was used to investigate the effect of maleic acid on the rat kidney proteome in this study., Methods: Sprague-Dawley(SD) rats were treated with 0 mg/kg (control), 6 mg/kg (low-dose), 10 mg/kg (medium-dose), and 60 mg/kg (high-dose) of maleic acid. After kidney protein extraction, 28% SDS-PAGE was used, followed by in-gel digestion and desalting. Next, the samples were analyzed with ultra-performance liquid chromatography (UPLC) coupled with quadrupole time-of-flight mass spectrometry (Q-TOF MS), and data-dependent acquisition (DDA) and SWATH technology were also used. The gene ontology and pathway analysis were accomplished. Ultimately, these protein biomarkers were validated by using scheduled high-resolution multiple reaction monitoring (sMRM HR )., Results: Comparisons of the control group with the other three groups revealed that 95, 130, and 103 proteins were expressed at significantly different levels in the control group and in the low-dose, medium-dose, and high-dose groups, respectively. According to the gene ontology analysis, the major processes that these proteins were involved in were metabolic processes, biological regulation, cellular processes, and responses to stimuli; the major functions that these proteins were involved in were binding, hydrolase activity, catalytic activity, and oxidoreductase activity; and the major cellular components hat they were involved in were the cytoplasm, extracellular region, membrane, and mitochondria. According to the KEGG pathway analysis, these proteins were involved in 35 pathways, five of which, the carbohydrate metabolism, folate biosynthesis, renal tubular resorption, amino acid metabolism, and Ras signaling pathways, are discussed in this study. Ultimately, 19 proteins involved in 12 important pathways were validated by sMRM HR ., Conclusions: It was demonstrated that maleic acid caused insufficient energy production, which might lead to a decrease in the activity of the sodium-potassium ATP pump and hydrogen ion ATP pump, which could in turn have caused renal tubular resorption and hydrogen ion regulation to be blocked, thus leading to the accumulation of hydrogen ions in the renal tubules, which would then result in renal tubular acidification followed finally by Fanconi syndrome., (© 2019 John Wiley & Sons, Ltd.)

Maleic acid (MA)-induced nephropathy that is characterized by proteinuria, glycosuria, phosphaturia and a deficient urinary acidification and concentration. Sulforaphane (SF) is an indirect antioxidant that shows nephroprotective effects. The aim of the present work was to test the pre-treatment with SF against the MA-induced nephropathy. Wistar rats (230-260 g) were separated in the following groups: control, MA (which received 400 mg/kg of MA), SF + MA (which received MA and 1 mg/kg of SF each day for four days) and SF (which only received SF). MA induced proteinuria, an increase in urinary excretion of N-acetyl-β-d-glucosaminidase, and a decrease in plasma glutathione peroxidase activity, renal blood flow, and oxygenation and perfusion of renal cortex. All these impairments correlated with higher levels of oxidative damage markers and exacerbated superoxide anion production on renal cortex. Moreover, MA impaired mitochondrial bioenergetics associated to complex I, mitochondrial membrane potential and respiratory control index and increased the mitochondrial production of hydrogen peroxide. Further it disrupted mitochondrial morphology. SF prevented all the above-described alterations. In conclusion, the protective effect of SF against MA-induced nephropathy is associated with preservation of mitochondrial bioenergetics, amelioration of oxidative stress and improvement of renal hemodynamics and renal cortex oxygenation., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Maleic acid has been shown to be used as a food adulterant in the production of modified starch by the Taiwan Food and Drug Administration. Due to the potential toxicity of maleic acid to the kidneys, this study aimed to develop an analytical method to investigate the pharmacokinetics of maleic acid in rat blood and kidney cortex. Multiple microdialysis probes were simultaneously inserted into the jugular vein and the kidney cortex for sampling after maleic acid administration (10 or 30 mg/kg, i.v., respectively). The pharmacokinetic results demonstrated that maleic acid produced a linear pharmacokinetic phenomenon within the doses of 10 and 30 mg/kg. The area under concentration versus time curve (AUC) of the maleic acid in kidney cortex was 5-fold higher than that in the blood after maleic acid administration (10 and 30 mg/kg, i.v., respectively), indicating that greater accumulation of maleic acid occurred in the rat kidney.

Background: Chloroquine has been the treatment of choice for acute vivax malaria for more than 60 years. Malaria caused by Plasmodium vivax has recently shown resistance to chloroquine in some places. This study compared the efficacy and safety of fixed dose combination (FDC) of arterolane maleate and piperaquine phosphate (PQP) with chloroquine in the treatment of uncomplicated vivax malaria., Methods: Patients aged 13-65 years with confirmed mono-infection of P. vivax along with fever or fever in the previous 48 h were included. The 317 eligible patients were randomly assigned to receive FDC of arterolane maleate and PQP (n = 159) or chloroquine (n = 158) for 3 days. Primaquine was given as an anti-relapse measure on day 3 and continued for 14 consecutive days. Primary efficacy analysis included assessment of the proportion of aparasitaemic and afebrile patients at 72 h. Safety endpoints were analysis of adverse events, vital signs, laboratory data, and abnormalities on electrocardiograph. Patients participated in the study for at least 42 days., Results: In per protocol population, the proportion of aparasitaemic and afebrile patients at 72 h was 100% (140/140) in the FDC of arterolane maleate and PQP group, and 99.3% (145/146) in the chloroquine group (Fisher, p > 0.9999). In intent to treat population, the corresponding value was reported to be 96.9% (154/159) in the FDC of arterolane maleate and PQP group and 98.7 % (156/158) in the chloroquine group (Fisher, p = 0.4479). The median parasite clearance time was 24 h in FDC of arterolane maleate and PQP group and 26 h in chloroquine group (Log-rank, p = 0.2264). Similarly, median fever clearance time was 24 h in both the groups (Log-rank, p = 0.7750). In PP population, day 28 cure rates were 100 % in both the groups (95% CI (96.52, 100.0 for FDC of arterolane maleate and PQP and 96.73, 100.0 in chloroquine group)). Incidence of adverse events was 82.4% in the FDC of arterolane maleate and PQP group and 85.4% in the chloroquine group. Most of the adverse events were mild to moderate in intensity. The commonly reported clinical adverse events in the FDC of arterolane maleate and PQP versus chloroquine group were vomiting (5.0 vs 5.1%), headache (1.3 vs 3.2%) and prolonged QT (1.9 vs 3.2%). No deaths were reported. The pharmacokinetic analysis indicates that arterolane maleate is well absorbed and has a relatively short t1/2 of 3.2 h. Piperaquine is also well absorbed after oral administration with a t1/2 of about 228.33 h., Conclusions: The study showed that FDC of arterolane maleate and PQP effectively cured vivax malaria and attained acceptable level of cure up to day 28. Both the groups showed similar safety profile. Trial Registration Clinical Trial Registry India: CTRI/2011/11/002129.

Phthalate plasticizers such as di(2-ethylhexyl) phthalate (DEHP) are being phased out of many consumer products because of their endocrine disrupting properties and their ubiquitous presence in the environment. The concerns raised from the use of phthalates have prompted consumers, government, and industry to find alternative plasticizers that are safe, biodegradable, and have the versatility for multiple commercial applications. We examined the toxicogenomic profile of mono(2-ethylhexyl) phthalate (MEHP, the active metabolite of DEHP), the commercial plasticizer diisononyl cyclohexane-1,2-dicarboxylate (DINCH), and three recently proposed plasticizers: 1,4-butanediol dibenzoate (BDB), dioctyl succinate (DOS), and dioctyl maleate (DOM), using the immortalized TM4 Sertoli cell line. Results of gene expression studies revealed that DOS and BDB clustered with control samples while MEHP, DINCH and DOM were distributed far away from the control-DOS-BDB cluster, as determined by principle component analysis. While no significant changes in gene expression were found after treatment with BDB and DOS, treatment with MEHP, DINCH and DOM resulted in many differentially expressed genes. MEHP upregulated genes downstream of PPAR and targeted pathways of cholesterol biosynthesis without modulating the expression of PPAR's themselves. DOM upregulated genes involved in glutathione stress response, DNA repair, and cholesterol biosynthesis. Treatment with DINCH resulted in altered expression of a large number of genes involved in major signal transduction pathways including ERK/MAPK and Rho signalling. These data suggest DOS and BDB may be safer alternatives to DEHP/MEHP than DOM or the commercial alternative DINCH.

Background and Purpose: Dimethyl fumarate (DMF) is a newly approved drug for the treatment of relapsing forms of multiple sclerosis and relapsing-remitting multiple sclerosis. Here, we investigated the effects of DMF and its metabolites mono-methylfumarate (MMF and methanol) on different gastrointestinal cancer cell lines and the underlying molecular mechanisms involved., Experimental Approach: Cell viability was measured by the MTT or CCK8 assay. Protein expressions were measured by Western blot analysis. LDH release, live- and dead-cell staining, intracellular GSH levels, and mitochondrial membrane potential were examined by using commercial kits., Key Results: DMF but not MMF induced cell necroptosis, as demonstrated by the pharmacological tool necrostatin-1, transmission electron microscopy, LDH and HMGB1 release in CT26 cells. The DMF-induced decrease in cellular GSH levels as well as cell viability and increase in reactive oxygen species (ROS) were inhibited by co-treatment with GSH and N-acetylcysteine (NAC) in CT26 cells. DMF activated JNK, p38 and ERK MAPKs in CT26 cells and JNK, p38 and ERK inhibitors partially reversed the DMF-induced decrease in cell viability. GSH or NAC treatment inhibited DMF-induced JNK, p38, and ERK activation in CT26 cells. DMF but not MMF increased autophagy responses in SGC-7901, HCT116, HT29 and CT26 cancer cells, but autophagy inhibition did not prevent the DMF-induced decrease in cell viability., Conclusion and Implications: DMF but not its metabolite MMF induced necroptosis in colon cancer cells through a mechanism involving the depletion of GSH, an increase in ROS and activation of MAPKs., (© 2015 The British Pharmacological Society.)

Previously, we prepared a pirarubicin (THP)-encapsulated micellar drug using styrene-maleic acid copolymer (SMA) as the drug carrier, in which active THP was non-covalently encapsulated. We have now developed covalently conjugated SMA-THP (SMA-THP conjugate) for further investigation toward clinical development, because covalently linked polymer-drug conjugates are known to be more stable in circulation than drug-encapsulated micelles. The SMA-THP conjugate also formed micelles and showed albumin binding capacity in aqueous solution, which suggested that this conjugate behaved as a macromolecule during blood circulation. Consequently, SMA-THP conjugate showed significantly prolonged circulation time compared to free THP and high tumor-targeting efficiency by the enhanced permeability and retention (EPR) effect. As a result, remarkable antitumor effect was achieved against two types of tumors in mice without apparent adverse effects. Significantly, metastatic lung tumor also showed the EPR effect, and this conjugate reduced metastatic tumor in the lung almost completely at 30 mg/kg once i.v. (less than one-fifth of the maximum tolerable dose). Although SMA-THP conjugate per se has little cytotoxicity in vitro (1/100 of free drug THP), tumor-targeted accumulation by the EPR effect ensures sufficient drug concentrations in tumor to produce an antitumor effect, whereas toxicity to normal tissues is much less. These findings suggest the potential of SMA-THP conjugate as a highly favorable candidate for anticancer nanomedicine with good stability and tumor-targeting properties in vivo., (© 2014 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.)

Objective: LB80380, a dipivoxil ester prodrug of LB80331, is a novel antiviral agent for the treatment of chronic hepatitis B. The aim of this study was to compare the pharmacokinetic differences after single oral administrations of the free base and maleate formulations of LB80380 in healthy male subjects., Methods: An open-label, single- dose, randomized-sequence, 2-treatment crossover study was conducted in 32 Korean male volunteers. Subjects received either a combination of 60 and 90 mg tablets of the free base LB80380 formulation or a 183 mg (150 mg as a free base) tablet of the maleate LB80380 formulation. Then, after a 14- day washout period, each subject received the other formulation. Plasma and urine concentrations of LB80331 and LB80317 (active metabolites of LB80380) were measured by validated liquid chromatographytandem mass spectrometry assays. A safety assessment, which included vital signs, adverse events, electrocardiograms and clinical laboratory tests, was performed for each subject., Results: A total of 32 healthy subjects was enrolled, and 26 subjects completed the study. Single oral administrations of LB80380 maleate tablets did not result in clinically significant differences in the safety profile compared to the LB80380 free base tablets. The 90% confidence intervals (CIs) for the geometric mean ratios of Cmax and AUClast for LB80331 of the two treatments (maleate versus free base formulation) were 0.986 - 1.1240 and 0.9848 - 1.0533, respectively. The 90% CIs for the geometric mean ratios of Cmax and AUClast for LB80317 were 0.8379 - 0.9696 and 0.7224 - 0.9196., Conclusions: In healthy male subjects, the 183 mg LB80380 maleate tablet was pharmacokinetically equivalent to the 60 and 90 mg LB80380 free base tablets.

Objective: To evaluate the efficacy and safety of entecavir (ETV) maleate versus ETV in Chinese patients with hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB)., Methods: This was a randomized, double-blind, double-dummy, controlled, multicenter study. Patients were randomly assigned to receive 48 weeks of treatment with 0.5 mg/day ETV (group A; n = 26) or 0.5 mg/day ETV maleate (n = 31). Hepatitis B virus (HBV) DNA levels were measured at weeks 12, 24, and 48 by the Roche Cobas Ampliprep/Taqman PCR assay. Adverse events (AE) were recorded., Results: Baseline characteristics were similar between the two groups. At weeks 12, 24, and 48, the mean HBV DNA level had similarly decreased from baseline in both groups (A: by 4.24, 4.61 and 4.88 log10 IU/mL vs. B: 4.01, 4.50 and 4.99 log10 IU/mL, respectively; all P more than 0.05). Patients who achieved undetectable levels of serum HBV DNA (less than 20 IU/mL) at week 48 were similar in the two groups (A: 69.23% vs. B: 80.65%; P more than 0.05). Both groups achieved similar normalization of ALT at week 48 (A: 96.00% vs. B: 83.87%; P more than 0.05). The overall AE incidence was similar for the two groups (A: 22.22% vs. B: 9.38%; P more than 0.05)., Conclusion: Entecavir maleate and entecavir showed similar efficacy and safety in patients with HBeAg-negative CHB.

Human skin is exposed to a large variety of cosmetic allergens. Most allergic contact dermatitis occurs after exposure to fragrance, preservatives, and hair dyes. Such reactions can often be occult. As a result, a high index of suspicion is needed in assessing the patient with facial or cosmetic dermatitis. This contribution looks at why such a large number of chemicals are in everyday usage, at how dermatologists monitor trends in allergy to cosmetics, and at a number of new and emerging allergens to consider in the assessment of suspected cosmetic allergy., (Copyright © 2011 Elsevier Inc. All rights reserved.)

This study evaluated the potential utility of albuminuria as a "biomarker" of acute kidney injury (AKI) and tested whether AKI induces renal expression of the normally silent albumin gene. Urine albumin concentrations were measured in mice with five different AKI models (maleate, ischemia-reperfusion, rhabdomyolysis, endotoxemia, ureteral obstruction). Albumin gene induction in renal cortex, and in antimycin A-injured cultured proximal tubular cells, was assessed (mRNA levels; RNA polymerase II binding to the albumin gene). Albumin's clinical performance as an AKI biomarker was also tested (29 APACHE II-matched intensive care unit patients with and without AKI). Results were contrasted to those obtained for neutrophil gelatinase-associated lipocalin (NGAL), an established "AKI biomarker" gene. The experimental and clinical assessments indicated albumin's equivalence to NGAL as an AKI biomarker (greater specificity in experimental AKI; slightly better receiver-operating curve in humans). Furthermore, experimental AKI markedly induced the albumin gene (mRNA/RNA polymerase II binding increases; comparable to those seen for NGAL). Albumin gene activation in patients with AKI was suggested by fivefold increases in RNA polymerase II binding to urinary fragments of the albumin gene (vs. AKI controls). Experimental AKI also increased renal cortical mRNA levels for α-fetoprotein (albumin's embryonic equivalent). A correlate in patients was increased urinary α-fetoprotein excretion. We conclude that AKI can unmask, in the kidney, the normally silent renal albumin and α-fetoprotein genes. In addition, the urinary protein data independently indicate that albuminuria, and perhaps α-fetoprotein, have substantial utility as biomarkers of acute tubular injury.

Importance of the Field: Chronic obstructive pulmonary disease (COPD) is a partially reversible, progressive obstructive disorder. Bronchodilators are the mainstay of treatment since they improve lung function and patient-reported outcomes and reduce acute exacerbations. Long-acting inhaled bronchodilators (at present including the once-daily antimuscarinic tiotropium, and the twice-daily beta(2)-agonists formoterol and salmeterol) are recommended as first-line treatment for patients with persistent symptoms. Indacaterol maleate has been developed as a new once-daily inhaled beta(2)-selective agonist., Areas Covered in This Review: This article reviews the published literature on the pharmacologic properties and the Phase II and III trials that have evaluated the safety and efficacy of this new agent., What the Reader Will Gain: The reader will obtain an appreciation of the safety and efficacy of indacaterol and the role that it might play in the future management of COPD of varying severity., Take Home Message: Indacaterol is a new, once-daily beta(2)-agonist with an onset of action within 5 min and a duration of bronchodilation of at least 24 h. In doses of 150 and 300 microg, it has sustained benefits over 6 - 12 months with respect to both bronchodilation and patient-reported outcomes and is well-tolerated with an acceptable safety profile.

This study sought to monitor changes in the topography, morphology, and radiographic profiles of human permanent teeth that had been exposed to citrus fruit juices. The effect of long-term exposure was monitored for a prolonged duration of 20 weeks according to set criteria. Topographic and morphologic changes were observed at weekly intervals following challenge by test fluids (orange, lemon, and grapefruit juices) and compared with control fluids (acetic acid and water). The qualitative changes in the specimens' topography and the morphology of citrus fruit juices and control fluids are described as a function of time, in specific details. The digitized radiographic images obtained at four-week intervals were analyzed and the changes were assessed. The results indicated that orange juice specimens demonstrated the mildest changes, while lemon juice specimens displayed the most severe damage to the coronal segments of the teeth. This damage manifested as loss of cusp height, cervical enamel, and coronal radius, as well as reduction of enamel cap height. Of the tested and control fluids, lemon juice displayed the most eros ion, followed by acetic acid, grapefruit juice, orange juice, and water, which had no effect. Continued immersion in the four acidic fluids led to varying degrees of enamel loss progression.

Dicaprylyl maleate (DCM) has been reported rarely as a cause of allergic contact dermatitis. The objectives of this study were to identify patients from multiple centres with allergy to DCM in cosmetic products confirmed by patch testing and, in addition, to investigate the effect of testing with aged DCM. This is an international multicentre study of 22 patients with 26 reactions to products containing DCM. Patch testing was carried out to ingredients including DCM obtained from the manufacturer. Further testing was carried out with deliberately aged DCM in a sample of patients. 22 patients had clinical and positive patch test reactions at 4 days to a total of 26 cosmetic products containing DCM. 5 patients did not react to DCM prepared by the manufacturer from concurrent factory stock but did have positive reactions to a deliberately aged batch of DCM. DCM is an emerging cosmetic allergen. Testing with aged material yields a greater number of positive results. Co-operation between cosmetics manufacturers and clinicians is important in the identification of new allergens.

Objective: The purpose of this study was to evaluate the clinical performance and longevity of Tetric Ceram and Syntac Sprint restorations in stress-bearing areas performed in general practice., Method and Materials: The light-curing resin composite Tetric Ceram in combination with the bonding material Syntac Sprint were used as restorative materials in three public dental health clinics. All the restorations were done by general practitioners in an ordinary patient pool attending a public health clinic. Before starting, the general practitioners were instructed and trained in performing the restorations according to a standardized clinical procedure, and the evaluations were done according to United States Public Health Service criteria. One hundred forty-eight restorations (27 Class I, 121 Class II) were done in 123 patients. After 2 years, 140 restorations (95%) could be assessed. Color slides and bitewings were taken to supplement the clinical evaluations of color match, marginal discoloration, secondary caries, and marginal adaptation. Wear of the restorations was evaluated according to the Leinfelder method., Results: After 2 years, 7 out of 148 restorations had failed, giving a failure rate of 5% of the tested materials. Five restorations failed due to hypersensitivity, one to secondary caries, and one to fracture. The wear rate was low (mean 37 microm) and did not result in any replacement., Conclusion: This 2-year study showed that clinically satisfactory results could be obtained using resin composite Class I and II restorations in stress-bearing areas done in general practice on an ordinary clientele when the clinical procedure is standardized.

Polyelectrolyte complex films were prepared with polyethyleneoxide-maleic acid copolymer and chitosan using a casting/solvent evaporation method. The films were examined in terms of their IR spectra, surface and cross-section morphologies, cytotoxicity, and swelling behavior at different pH levels. To assess the potential of these films as a biomedical device, the profiles of the release of model drug from the CS/PEOMA films were examined at pH 4.8. The surface morphology of the films was quite smooth and uniform, and the cross-sectional morphology was dense and homogeneous. The swelling behaviors of CS/PEOMA films were found to depend on the pH of the solution as well as on the CS/PEOMA composition. Drug release from different CS/PEOMA films at pH 4.8 was found to be dependent on film composition. The results showed the potential applicability of CS/PEOMA film as a drug delivery vehicle.

Allergic contact dermatitis from esters of fumaric acid or esters of maleic acid is rare. The case of a chemist with allergic reactions to esters both of fumaric acid and of maleic acid is presented. Extremely high sensitivity of the patient to diethyl fumarate was noted. The formation of identical complete antigens from esters of these two cis-trans isomeric acids may be an explanation of the patient's double allergy. This is discussed from a stereochemical point of view. These stereochemical considerations point to a general mechanism where cis-trans isomeric alpha,beta-unsaturated carbonyl compounds are converted into the same complete antigen., (Copyright 2003 S. Karger AG, Basel)

Unsaturated polyester (UP) cement caused allergic contact dermatitis in car repair work. The resin was a condensate of polyols and maleic anhydride with reactive solvent, auxiliary substances, and inorganic reinforcement substances. To identify the causative chemicals, the cement was tested on a sensitized patient. For analysis, samples of the resin were eluted with acetone and eluted with hexane to precipitate inorganic material and large polyester molecules. The eluate was evaporated. The remainder, dissolved in acetone, was separated into fractions on silica plates by thin layer chromatography (TLC). On the developed (hexane/chloroform, 15/85) plates, 20 bands were obtained under UV-light at 254 nm. Samples of the bands were scraped and used for patch testing. The scraping at a retention factor (Rf) of 0.24 caused a skin reaction. The bands at this retention were removed from six plates, combined, eluted with acetone and purified again by TLC. The purified fraction mixed in petrolatum in the dilution series was used for conclusive patch testing on the patient. An allergic reaction was induced at down to 0.003% wt/wt. According to MS and IR analyses, the isolated compound was diethyleneglycol maleate (DEGM, MW204). In addition to the resin part, the sanding dust also contained this monomer.

The aim of this study was to investigate the efficacy and tolerability of intranasally applied dimetindene (CAS 3614-69-5) 0.1% spray in children suffering from seasonal allergic rhinitis. A total of 100 children under 14 years with acute seasonal allergic rhinitis participated in this randomised, single-blind, reference-controlled, multi-center, parallel group study with two treatment groups. The study took place between 2nd April and 16th September 1996 during the pollen season. Patients were examined at enrollment (day 1), day 8 and day 15. Patients kept diary throughout the 2-week treatment phase. Patients were randomised to receive either dimetindene 0.1% (Fenistil Nasal Spray) or a levocabastine (CAS 79516-68-0) 0.05% solution as reference medication. Both medications were supplied in similar outer packages. A single-blind approach was chosen, because the reference medication levocabastine requires two spray puffs per nostril as a single dose, whereas for dimetindene maleate solution a single spray puff per nostril is sufficient. Dimetindene 0.1% was applied with 1 spray puff (= 0.14 mg dimetindene) in each nostril and levocabastine with 2 spray puff (= 0.10 mg levocabastine) in each nostril every day in the morning before leaving the house and in the evening before going to bed. Additional administration of the spray was allowed up to 4 times a day if needed. Efficacy was assessed as change in severity of characteristic symptoms associated with pollen rhinitis: nasal rhinorrhea, nasal itching, nasal sneezing and nasal congestion. In addition, changes in ocular symptoms, lacrimation, ocular itching and red eyes, global physician's assessment of efficacy at the end of treatment were assessed. The primary criterion change of total nasal symptom severity score between day 1 and day 3 resulted in a statistically equivalent and therapeutically relevant symptom reduction for the two treatments. All secondary criteria showed a similar reduction in symptoms, thus underlining the consistency of the findings. Both nasal sprays were well tolerated. It is concluded from these results that dimetindene 0.1% nasal spray solution is a safe and efficient treatment option for children under 14 years suffering from seasonal allergic rhinitis.

We report a case of severe peristomal dermatitis that was refractory to conventional treatments. Patch testing revealed positive allergies to myroxylon perulase (balsam of Peru), propylene glycol, Stomahesive paste, and Gantrez. This is the second reported case of patch-test-positive peristomal allergy to Gantrez.

Styrene-maleic acid neocarzinostatin (SMANCS) sometimes causes hepatic vascular side effects, including arterial stricture, obstruction, and arterio-portal shunt. A total of 128 intra-arterial SMANCS injection treatments, performed for 89 patients with hepatocellular carcinoma, were analyzed to determine the relationship between angiographic findings and subsequent hepatic vascular injuries. After SMANCS therapy, hepatic arterial stricture or obstruction occurred in 5 patients (5/128; 3.9%), arterio-portal shunting in 12 (12/128; 9.4%), liver shrinkage in 4 (4/128; 3.1%), and cholangitis or biloma in 2 (2/128; 1.6%). Among 23 patients whose plain abdominal X-ray films just after SMANCS injection showed Lipiodol retention in the hepatic artery, 5 patients developed arterial obstruction, 10 developed arterio-portal shunt, and 2, cholangitis or biloma. Among 26 patients with Lipiodol retention in the portal vein, 4 developed hepatic lobe atrophy with aggravation of liver function. Among 3 patients with Lipiodol retention in both the hepatic artery and the portal vein, 1 developed arterio-portal shunt. In 76 treatments without excessive Lipiodol retention, only 1 of the patients developed arterio-portal shunt. Excessive retention of Lipiodol in hepatic vascular beds just after SMANCS therapy was significantly associated with future vascular side effects (22/52 vs 1/76; P < 0.0001). Lipiodol retention in arteries just after SMANCS injection was closely associated with subsequent arterial obstruction or arterio-portal shunt, and Lipiodol retention in the portal vein was related to subsequent hepatic lobe atrophy.

The role of a hot water extract of black tea (Camellia sinensis (L). O. Kuntze Theaceae) in the gastric cytoprotective mechanisms was studied using gastric mucosal lesions produced by various ulcerogens in rats as an experimental model. Prior oral administration of black tea extract (BTE) at 20 ml/kg, i.g. once a day for 7 days significantly reduced the incidence of gastric erosions and severity induced by ethanol, diethyldithiocarbamate (DDC) and diethylmaleate (DEM). This treatment also favorably altered the changes in acid and peptic activity of gastric juice in these ulcerogen-treated animals. Singular administration of succimer (60 mg/kg, i.g.), the standard sulfhydryl containing antiulcer drug used as a reference drug, was also effective. The levels of glutathione and glutathione peroxidase were significantly decreased after treatment with ethanol, DDC and DEM, and this decrease was prevented by BTE pretreatment in the aforesaid manner. Other major features of BTE-induced reversal of ulcerogenic agents include a significant decrease in the protein content and a marked increase in hexosamine and sialic acid content. These results suggest a major role for glutathione, an endogenous antioxidant, in the cytoprotection against ulceration afforded by BTE.

Scotchbond MP and ART Bond were used without intentional enamel etching to bond a total of 43 resin composite restorations in Class V 'abrasion/ erosion' lesions. The cumulative loss rates after 6 months, 1 year, and 2 years, respectively, were Scotchbond MP: 9, 14, 27 per cent; and ART Bond: 0, 5, 5 per cent. These data were not compared because each material was used on different patients. The results support the higher bond strength to dentine in the laboratory of Scotchbond MP compared with its predecessor Scotchbond 2. There was a slight but clinically insignificant amount of enamel marginal staining for both products after 2 years, confirming the necessity to etch the enamel for effective marginal sealing.

The clinical requirements of dentin bonds are that they should be non-permeable to oral fluids, seal dentinal tubules, protect the pulp, and be long lasting and durable. Dentin bonding systems that use acidic agents to remove the smear layer are currently being used. Acid conditioning not only removes the smear layer, but also demineralizes the surface of the intertubular dentin and produces intratubular demineralization and funnelling. A dentin bond is produced when hydrophillic resin monomers infiltrate the dentinal tubules and collagen of the demineralized intertubular zone, producing a hybrid layer. The use of a critical point drying technique and SEM allows a clear visualization of the structure of the hybrid layer. This study showed that currently used hydrophillic resin monomers are unable to completely infiltrate the demineralized zone, and it is speculated that this failure could contribute to microleakage and influence the long-term durability of the bond. It is also apparent that these bonds depend on the mechanical investment of collagen by the infiltrating monomer. Since none of the unfilled resins tested seem capable of completely infiltrating the demineralized collagenous zone, the degree of demineralization produced by the commercial acid concentrations in current use is questioned. More dilute acids than those available commercially are shown to reduce both the degree and depth of demineralization, and we suggest that the resultant thinner layer may lend itself to more complete resin infiltration of the collagen.

In this study, the effect of enamel etching resulting in permanently lost enamel was investigated. Phosphoric acid and maleic acid were used as etchants. Also the etch duration was varied. The results of the study show that phosphoric acid removed significantly more enamel than maleic acid. The relationship found between the loss of enamel and the etch duration suggested that a diffusion controlled mechanism plays a role in the case of both acids. Morphological information obtained by scanning electron microscopy indicated that the surface structure resulting from etching with phosphoric acid and maleic acid is similar.

6 men contracted occupational allergic contact dermatitis from unsaturated polyester (UP) cements. 4 of the men were employed in car repair painting and the remaining 2 in mold manufacturing. The exposure time to UP cements ranged from 6 to 32 years before onset of skin symptoms. All patients had eczema on their hands; in addition, 4 had skin symptoms on airborne areas, i.e., wrists, neck and face. All 6 patients developed allergic reactions when patch tested with UP resin at 0.5-10% in petrolatum (pet.). None of the tested patients reacted to auxiliary or cross-linking chemicals of the cements. Diethylene glycol maleate (DGM) was purified and identified from the UP resin of a cement. 1 patient reacting to UP resin was also patch test positive to DGM and he produced an allergic reaction to DGM down to a concentration of 0.0032% pet. DGM was found in both uncured and cured UP resin. None of the patients could continue their work with UP cements after their sensitization.

10 of 20 workers in an envelope-making factory developed contact dermatitis. The cause was dibutyl maleinate, which was added to a polyvinylacetate glue. Dibutyl maleinate is a strong sensitizer and should be withdrawn from industrial use.

Two patients, who developed eczematous eruptions beneath Curad-brand medical adhesive plastic bandages, were found to have allergic contact dermatitis to N-dodecyl maleamic acid. N-dodecyl maleamic acid is a monomer used in the production of the adhesive in Curad bandages. Our patients were also sensitive to several closely related chemical compounds. We discuss the chemical requisite for allergenicity of these compounds. These are the first documented cases of allergic contact dermatitis from dodecyl maleamic acid.

Injection of a polymer, styrene maleic anhydride (SMA), into the lumen of the vas deferens of rats, was observed to have effective and reversible contraception. The safety evaluation of the polymer, for 90 days, was carried out in Charles Foster male rats. There have been no significant changes in any of the toxicity parameters in the test animals as compared to the control animals. Hence, it is concluded that the compound is non-toxic to rodents.

Acceleration of technical development results in growing difficulties to trace allergens. In this respect rare allergens as well as hidden sources of well-known allergens not infrequently cause persistence of allergic dermatitis. Examples are presented for di-ethyl-ester of maleic acid, hydroxylammoniumhydrochloride, N-methyl-p-aminophenol, 2-hydroxy-3-naphtoic acid o-aniside and N-acetoacetyl-benzylamide.

In the monkey, the action of four renal toxics : lead acetate, sodium maleate, cadmium chloride and sodium chromate was compared. Tubulopathies were obtained only with cadmium chloride and sodium chromate with in the best cases about 16 mg/l of beta2-microglobulin (beta2m) in the urine. Monkey and human beta2m have the same molecular weight and are antigenically similar. However, they differed in electrophoretic mobility, the monkey beta2m being slightly more cathodic.

Maleate administration produces features that closely resemble the Fanconi syndrome. To determine whether this dysfunction is caused by maleate or its metabolite, maleyl-CoA, which is produced in the succinyl-CoA transferase reaction, the effect of pretreatment with acetoacetate on the maleate dysfunction was tested in rats, Infusion of acetoacetate, 90 mu mol . min-1 . kg body wt-1 protects the kidney from maleate action, whereas administration of propionate, a monocarboxylic anion and CoA-dependent metabolite resembling the anion of acetoacetate, has no effect on maleate-induced renal dysfunction. Maleate (100 mg/kg body wt) alone lowered kidney ATP concentration by 44%, whereas maleate with acetoacetate did not prevent the decreased renal ATP (42%), while glucosuria, phosphaturia, calciuria, and bicarbonaturia were significantly diminished. Similar changes in renal ATP level were observed in rats treated with propionate or propionate and maleate in combination. These experiments demonstrate that maleate per se is not inhibitory but that its metabolite, presumably maleyl-CoA, may inhibit tubule function.