Identification of late asthmatic reactions following specific inhalation challenge.

Specific inhalation challenge (SIC) is the reference standard for the diagnosis of occupational asthma. Current guidelines for identifying late asthmatic reactions are not evidence based. OBJECTIVES: To identify the fall in forced expiratory volume in 1 s (FEV1) required following SIC to exceed the 95% CI for control days, factors which influence this and to show how this can be applied in routine practice using a statistical method based on the pooled SD for FEV1 from three control days. METHODS: Fifty consecutive workers being investigated for occupational asthma were asked to self-record FEV1 hourly for 2 days before admission for SIC. These 2 days were added to the in-hospital control day to calculate the pooled SD and 95% CI. RESULTS: 45/50 kept adequate measurements. The pooled 95% CI was 385 mL (SD 126), or 14.2% (SD 6.2) of the baseline FEV1, but was unrelated to the baseline FEV1 (r=0.06, p=0.68), or gender, atopy, smoking, non-specific reactivity or treatment before or during SIC. Thirteen workers had a late asthmatic reaction with ≥2 consecutive FEV1 measurements below the 95% CI for pooled control days, 4/13 had <15% and 9/13 >15% late fall from baseline. The four workers with ≥2 values below the 95% CI all had independent evidence of occupational asthma. CONCLUSION: The pooled SD method for defining late asthmatic reactions has scientific validity, accounts for interpatient spirometric variability and diurnal variation and can identify clinically relevant late asthmatic reactions from smaller exposures. For baseline FEV1 <2.5 L, a 15% fall is within the 95% CI.

Behaviour of Vascular Smooth Muscle Cells on Amine Plasma-Coated Materials with Various Chemical Structures and Morphologies.

Amine-coated biodegradable materials based on synthetic polymers have a great potential for tissue remodeling and regeneration because of their excellent processability and bioactivity. In the present study, we have investigated the influence of various chemical compositions of amine plasma polymer (PP) coatings and the influence of the substrate morphology, represented by polystyrene culture dishes and polycaprolactone nanofibers (PCL NFs), on the behavior of vascular smooth muscle cells (VSMCs). Although all amine-PP coatings improved the initial adhesion of VSMCs, 7-day long cultivation revealed a clear preference for the coating containing about 15 at.% of nitrogen (CPA-33). The CPA-33 coating demonstrated the ideal combination of good water stability, a sufficient amine group content, and favorable surface wettability and morphology. The nanostructured morphology of amine-PP-coated PCL NFs successfully slowed the proliferation rate of VSMCs, which is essential in preventing restenosis of vascular replacements in vivo. At the same time, CPA-33-coated PCL NFs supported the continuous proliferation of VSMCs during 7-day long cultivation, with no significant increase in cytokine secretion by RAW 264.7 macrophages. The CPA-33 coating deposited on biodegradable PCL NFs therefore seems to be a promising material for manufacturing small-diameter vascular grafts, which are still lacking on the current market.

Sensitization and cross-reactivity patterns of contact allergy to diisocyanates and corresponding amines: investigation of diphenylmethane-4,4'-diisocyanate, diphenylmethane-4,4'-diamine, dicyclohexylmethane-4,4'-diisocyanate, and dicylohexylmethane-4,4'-diamine.

BACKGROUND: Isocyanates are used in polyurethane production. Dermal exposure to isocyanates can induce contact allergy. The most common isocyanate is diphenylmethane diisocyanate used for industrial purposes. The isomer diphenylmethane-4,4'-diisocyanate (4,4'-MDI) is used in patch testing. Diphenylmethane-4,4'-diamine (4,4'-MDA) is its corresponding amine. Concurrent reactions to 4,4'-MDI and 4,4'-MDA have been reported, as have concurrent reactions to 4,4'-MDI and dicyclohexylmethane-4,4'-diisocyanate (4,4'-DMDI). OBJECTIVES: To investigate the sensitization capacities and the cross-reactivity of 4,4'-MDI, 4,4'-MDA, 4,4'-DMDI, and dicyclohexylmethane-4,4'-diamine (4,4'-DMDA). METHODS: The guinea-pig maximization test (GPMT) was used. RESULTS: The GPMT showed sensitizing capacities for all investigated substances: 4,4'-MDI, 4,4'-MDA, 4,4'-DMDI, and 4,4'-DMDA (all p < 0.001). 4,4'-MDI-sensitized animals showed cross-reactivity to 4,4'-MDA (p < 0.001) and 4,4'-DMDI (all p < 0.05). 4,4'-MDA-sensitized animals showed cross-reactivity to 4,4'-DMDA (p = 0.008). CONCLUSION: All of the investigated substances were shown to be strong sensitizers. Animals sensitized to 4,4'-MDI showed cross-reactivity to 4,4'-MDA and 4,4'-DMDI, supporting previous findings in the literature. The aromatic amine 4,4'-MDA showed cross-reactivity to the aliphatic amine 4,4'-DMDA.

Abuse potential of gabapentin in dentistry.

Gabapentin is an anticonvulsant drug widely prescribed for various ailments, including orofacial pain. It was once thought to have no potential for abuse; however, the last decade has seen a dramatic rise in the nonmedical use of gabapentin, particularly among opioid-dependent patients. Gabapentin is sedating and interacts with other sedating medications such as opioids, which can lead to impairment and accidents and may raise the risk of overdose. Dentists must be aware of the potential for abuse of gabapentin and weigh its benefits against its risks when prescribing the drug.

Potential harmful effects of dietary supplements in sports medicine.

PURPOSE OF REVIEW: The purpose of this article is to collect the most recent data regarding the safety of well-known or emerging dietary supplements used by athletes. RECENT FINDINGS: From January 2014 to April 2016, about 30 articles have been published in the field. New data show that 90% of sports supplements contain trace of estrogenic endocrine disruptors, with 25% of them having a higher estrogenic activity than acceptable. About 50% of the supplements are contaminated by melamine, a source of nonprotein nitrogen. Additional data accumulate toward the safety of nitrate ingestion. In the last 2 years, the safety of emerging supplements such as higenamine, potentially interesting to lose weight, creatine nitrate and guanidinoacetic acid has been evaluated but still needs further investigation. SUMMARY: The consumption of over-the-counter supplements is very popular in athletes. Although most supplements may be considered as safe when taking at the recommended doses, athletes should be aware of the potential risks linked to the consumption of supplements. In addition to the risks linked to overdosage and cross-effects when combining different supplements at the same time, inadvertent or deliberate contamination with stimulants, estrogenic compounds, diuretics or anabolic agents may occur.

Antiepileptic drugs (AEDs) during pregnancy and risk of congenital jaw and oral malformation.

In the United States, an estimate of 1.3 million women suffering from epilepsy are in their childbearing age. Potential teratogenicity of antiepileptic drugs (AEDs) is of concern to these women considering pregnancy because discontinuing pharmacotherapy during pregnancy may not be advised due to the risk of seizures that may be dangerous to the mother as well as the fetus. Using a Relational Online Analytical Processing (ROLAP) software licensed by Simultek, we searched for medications reported for congenital jaw and oral cavity malformation on the FDA Adverse Event Reporting System (AERS), a voluntary adverse event reporting program that contains over 55 million adverse event reports of medical products in the United.States. Our results indicate that various forms of valproic acid, and more importantly, newer generation antiepileptic agents including lamotrigine, topiramate, and gabapentin show signals for either congenital jaw or oral malformation. Although teratogenic potential of valproic acid has long been confirmed, information on teratogenicity of the newer generation antiepileptic drugs is relatively scarce and inconclusive. Early safety signals on the teratogenic potential of AEDs detected in this study are crude statistics that do not establish causation nor exclude confounding. The results require validation and further investigation via properly controlled epidemiological studies.

Gabapentin and pregabalin in the treatment of fibromyalgia: a systematic review and a meta-analysis.

WHAT IS KNOWN AND OBJECTIVES: Fibromyalgia (FBM) is a common chronic pain disorder affecting up to 2% of the general population. Current treatment options are mostly symptom-based and limited both in efficacy and number. Two promising alternatives are gabapentin (GP) and pregabalin (PB). We aimed to estimate the efficacy and safety/tolerability of the two compounds in FBM through a systematic review and a meta-analysis of relevant randomized double-blind placebo-controlled (RCT) were performed. DATA SOURCES, EXTRACTION AND ANALYSIS: A literature search was conducted through MEDLINE, EMBASE, Cochrane CENTRAL and the reference lists of relevant studies. Responders to treatment (>30% reduction in mean pain score) and dropouts due to lack of efficacy were used as primary outcome measures. Dropout rates and incidence of common adverse outcomes were also investigated. Four RCTs, reporting data on 2040 patients, were reviewed and three of them using PG were included in the meta-analysis. RESULTS: Pregabalin at a dose of 600, 450 and 300 mg per day is effective in FBM compared to placebo (NNT: 7, upper 95% CI: 12, 450 mg). A number of adverse events (AE), such as dizziness, somnolence, dry mouth, weight gain, peripheral oedema, is consistently associated with treatment at any dose and could lead one out of four patients to quit treatment (NNH: 6, lower 95% CI: 4, 600 mg). Indirect comparison meta-analysis suggests that PB at a dose of 450 mg per day could result in more responders than at 300 mg, but this result needs to be interpreted with caution as there were no significant differences between 600 and 300 mg or between 600 and 450 mg. Data on GP is limited. WHAT IS NEW AND CONCLUSIONS: The analysis indicates that PB at a dose of 450 mg per day is most likely effective in treating FBM, although AE are not negligible. Further evidence is necessary for more conclusive inferences.

Morphine, gabapentin, or their combination for neuropathic pain.

BACKGROUND: The available drugs to treat neuropathic pain have incomplete efficacy and dose-limiting adverse effects. We compared the efficacy of a combination of gabapentin and morphine with that of each as a single agent in patients with painful diabetic neuropathy or postherpetic neuralgia. METHODS: In this randomized, double-blind, active placebo-controlled, four-period crossover trial, patients received daily active placebo (lorazepam), sustained-release morphine, gabapentin, and a combination of gabapentin and morphine--each given orally for five weeks. The primary outcome measure was mean daily pain intensity in patients receiving a maximal tolerated dose; secondary outcomes included pain (rated according to the Short-Form McGill Pain Questionnaire), adverse effects, maximal tolerated doses, mood, and quality of life. RESULTS: Of 57 patients who underwent randomization (35 with diabetic neuropathy and 22 with postherpetic neuralgia), 41 completed the trial. Mean daily pain (on a scale from 0 to 10, with higher numbers indicating more severe pain) at a maximal tolerated dose of the study drug was as follows: 5.72 at baseline, 4.49 with placebo, 4.15 with gabapentin, 3.70 with morphine, and 3.06 with the gabapentin-morphine combination (P<0.05 for the combination vs. placebo, gabapentin, and morphine). Total scores on the Short-Form McGill Pain Questionnaire (on a scale from 0 to 45, with higher numbers indicating more severe pain) at a maximal tolerated dose were 14.4 with placebo, 10.7 with gabapentin, 10.7 with morphine, and 7.5 with the gabapentin-morphine combination (P<0.05 for the combination vs. placebo, gabapentin, and morphine). The maximal tolerated doses of morphine and gabapentin were lower (P<0.05) with the combination than for each drug as single agent. At the maximal tolerated dose, the gabapentin-morphine combination resulted in a higher frequency of constipation than gabapentin alone (P<0.05) and a higher frequency of dry mouth than morphine alone (P<0.05). CONCLUSIONS: Gabapentin and morphine combined achieved better analgesia at lower doses of each drug than either as a single agent, with constipation, sedation, and dry mouth as the most frequent adverse effects.

Stearylamine-bearing cationic liposomes kill Leishmania parasites through surface exposed negatively charged phosphatidylserine.

OBJECTIVES: Lipid-associated formulations of antileishmanial agents have proved to be more effective therapies with reduced toxicities. Previous studies from our group and others revealed that liposomes bearing phosphatidylcholine and stearylamine (SA) themselves kill Leishmania and other protozoan parasites in vitro and in vivo, without causing any adverse effect on host. In the present study, we offer detailed insights into the mechanism of action of these liposomes. METHODS: Mechanism study was carried out using fluorometric, confocal and electron microscopic methods. RESULTS: Herein, we provide evidence for induction of membrane disruption by specific interaction with surface phosphatidylserine (PS) of Leishmania promastigotes and amastigotes, phospholipids normally not found on mammalian cell surface, with SA-containing liposomes. Cell surface PS on different forms of Leishmania facilitated liposome-induced parasite killing. The target selectivity of the liposomes was further proved through inhibition of antileishmanial activity with annexinV, and strong affinity with anionic PS rather than phosphatidic acid-containing liposomes for leishmanicidal activity. CONCLUSIONS: SA-bearing liposomes specifically kill Leishmania, but are non-toxic to murine peritoneal macrophages and human erythrocytes.

Gabapentin for hot flashes in 420 women with breast cancer: a randomised double-blind placebo-controlled trial.

BACKGROUND: Most women receiving systemic therapy for breast cancer experience hot flashes. We undertook a randomised, double-blind, placebo-controlled, multi-institutional trial to assess the efficacy of gabapentin in controlling hot flashes in women with breast cancer. METHODS: 420 women with breast cancer who were having two or more hot flashes per day were randomly assigned placebo, gabapentin 300 mg/day, or gabapentin 900 mg/day by mouth in three divided doses for 8 weeks. Each patient kept a 1-week, self-report diary on the frequency, severity, and duration of hot flashes before the start of the study and during weeks 4 and 8 of treatment. Analyses were by intention to treat. FINDINGS: Evaluable data were available on 371 participants at 4 weeks (119 placebo, 123 gabapentin 300 mg, and 129 gabapentin 900 mg) and 347 at 8 weeks (113 placebo, 114 gabapentin 300 mg, and 120 gabapentin 900 mg). The percentage decreases in hot-flash severity score between baseline and weeks 4 and 8, respectively were: 21% (95% CI 12 to 30) and 15% (1 to 29) in the placebo group; 33% (23 to 43) and 31% (16 to 46) in the group assigned gabapentin 300 mg; and 49% (42 to 56) and 46% (34 to 58) in the group assigned gabapentin 900 mg. The differences between the groups were significant (p=0.0001 at 4 weeks and p=0.007 at 8 weeks by ANCOVA for overall treatment effect, adjusted for baseline values); only the higher dose of gabapentin was associated with significant decreases in hot-flash frequency and severity. INTERPRETATION: Gabapentin is effective in the control of hot flashes at a dose of 900 mg/day, but not at a dose of 300 mg/day. This drug should be considered for treatment of hot flashes in women with breast cancer.

Target analysis of primary aromatic amines combined with a comprehensive screening of migrating substances in kitchen utensils by liquid chromatography-high resolution mass spectrometry.

An analytical strategy including both the quantitative target analysis of 8 regulated primary aromatic amines (PAAs), as well as a comprehensive post-run target screening of 77 migrating substances, was developed for nylon utensils, using liquid chromatography-orbitrap-high resolution mass spectrometry (LC-HRMS) operating in full scan mode. The accurate mass data were acquired with a resolving power of 50,000 FWHM (scan speed, 2 Hz), and by alternating two acquisition events, ESI+ with and without fragmentation. The target method was validated after statistical optimization of the main ionization and fragmentation parameters. The quantitative method presented appropriate performance to be used in official monitoring with recoveries ranging from 78% to 112%, precision in terms of Relative Standard Deviation (RSD) was less than 15%, and the limits of quantification were between 2 and 2.5 µg kg(-1). For post-target screening, a customized theoretical database was built for food contact material migrants, including bisphenols, phthalates, and other amines. For identification purposes, accurate exact mass (<5 ppm) and some diagnostic ions including fragments were used. The strategy was applied to 10 real samples collected from different retailers in the Valencian Region (Spain) during 2014. Six out of eight target PAAs were detected in at least one sample in the target analysis. The most frequently detected compounds were 4,4'-methylenedianiline and aniline, with concentrations ranging from 2.4 to 19,715 µg kg(-1) and 2.5 to 283 µg kg(-1), respectively. Two phthalates were identified and confirmed in the post-run target screening analysis.

Historical and modern epidemiological studies on populations exposed to N-substituted aryl compounds.

The historical exposures to aromatic amines of various occupational groups are briefly reviewed. Modern studies indicate that other occupational groups might have risks worth investigating; these include machinists and workers in the chemical industry. Details of a recent investigation into the exposure of dye workers are given which indicate a lowered risk in recent years since the introduction of safety measures. Nonoccupational exposures to the aromatic amines are also discussed. They include cigarette smoking and phenacetin abuse, the former being a potent causal agent in bladder cancer.

Long-term effects of Meridol and chlorhexidine mouthrinses on plaque, gingivitis, staining, and bacterial vitality.

The aim of the present study was to compare the effect on plaque growth and gingival response of Meridol, an amine/stannous fluoride solution, during a three-month investigation, with those of a placebo preparation as a negative control and a chlorhexidine solution as a positive control, in a double-blind study. After having their teeth professionally cleaned, 36 volunteers continued their usual oral hygiene for a period of two weeks. Their teeth were then polished again (month 0) after which they rinsed twice daily (morning and evening) with one of the three mouthrinses in addition to their habitual toothcleaning. After three months of rinsing, plaque indices remained lowest in the chlorhexidine group, although the subjects using Meridol had indices significantly lower than those of individuals rinsing with the placebo solution. The gingival index scores in the Meridol group were higher than in the chlorhexidine group and lower than in the placebo group. The plaque vitality scores showed a bactericidal effect in vivo with chlorhexidine and Meridol during the entire experiment. The use of Meridol resulted in more toothstaining than with the placebo, but significantly less than with chlorhexidine. This study demonstrated that Meridol reduced plaque accumulation, retarded gingivitis development, possessed a definite bactericidal action, and produced only slight toothstaining.

Health hazards of tertiary amine catalysts.

Tertiary amine catalysts are widely employed in foundry and polyurethane foam manufacture operations. These highly reactive amines have been associated with graphic disturbances in vision and systemic health effects. Prominent among the reported effects on vision are mydriasis (dilated pupils), cycloplegia (loss of accommodation), and corneal edema, which may result in hazy (looking through smoke) or blurry (out of focus) vision and halo perception. Systemic symptoms, possibly due to a release of endogenous histamine, are consistent with pharmacologic actions of amines and have also been described. These symptoms, as well as the disturbances in vision, are transient. Nevertheless, employees who work with or around machinery, or drive vehicles, may be at an increased risk of accident and injury when experiencing these symptoms.

The effectiveness of an amine fluoride/stannous fluoride dentifrice on the gingival health of teenagers: results after six months.

The objectives of the present study included examining the effect of non-supervised tooth brushing with an amine fluoride/stannous fluoride (AmF/SnF2) dentifrice on gingival health of teenagers in a field trial over six months. Jerusalem high-school adolescents (246) participated in a double-blind study with a NaF dentifrice serving as control. No oral hygiene instruction or supervision was given. Examinations took place at baseline, three weeks, three months and six months. In all examinations, no differences were revealed for plaque levels. Other results indicated a consistent advantage for the AmF/SnF2 group. Gingival Index (GI) scores were significantly lower in the test group at the three month examination (GI = 0.85, compared to GI = 0.89; p = 0.036) and at the six month examination (GI = 0.72, compared to 0.78; p = 0.042) than among controls. Mean bleeding on probing scores were lower in the AmF/SnF2 than in the control group at the six month examination (0.53, compared to 0.63; p = 0.041). No side effects, including staining, were reported, nor found, among the AmF/SnF2 group. In addition to the well established caries preventive role of fluoride dentifrice, these data indicate an additional and important public health role of a AmF/SnF2 dentifrice, in preventing gingivitis.

[Wedge-shaped defects of the neck of the tooth in regular brushing with an amine fluoride gel]. / Keilförmige Zahnhalsdefekte bei regelmässiger Bürstapplikation eines aminfluoridhaltigen Gelees.

Gingival recession and wedge-shaped defects are caused mainly by incorrect tooth brushing procedures. The aim of this epidemiologic study was to determine if in addition there is a relationship to the regular use of an amine fluoride gel (pH 5.2) applied by a toothbrush. In a regression analysis, the effect of age, sex, education, toothbrushing frequency, gingival bleeding (PBI) and use of the gel on the occurrence of wedge-shaped defects was investigated. Similarly, the influence of these variables on the occurrence of gingival retraction without any hard tissue defect was investigated. Both types of lesions showed a statistically significant relationship to age and PBI. Moreover, use of the amine fluoride gel was significantly and negatively correlated with the occurrence of wedge-shaped defects.

Clinical Inquiry: Do venlafaxine and gabapentin control hot flashes in women with a history of breast cancer?

Venlafaxine reduces hot flashes more than placebo in women with a history of breast cancer; adverse effects include dry mouth and constipation.

Validation of a liquid chromatography-mass spectrometry method for determining the migration of primary aromatic amines from cooking utensils and its application to actual samples.

Many cooking utensils are made of nylon, a material that may incorporate azodyes and where primary aromatic amines (PAAs) are the starting substances. Moreover, aromatic amines may also be present as technical impurities. Another source of PAAs could be aromatic isocyanates used as monomers in the production of polyurethanes. The aim of this work was to validate a simple LC-MS/MS method for the determination of eight primary aromatic amines (m-phenylenediamine, 2,6- and 2,4-toluenediamine, 1,5-diaminonaphthalene, aniline, 4,4'-diaminonaphenylether, 4,4'-methylenedianiline and 3,3'-dimethylbenzidine) in the aqueous food simulant 3% acetic acid (w/v). The detection limits calculated were adequate with respect to present legislation. The method was validated at four concentration levels (2, 5 10 and 20 microg kg(-1)). Global internal reproducibility was in the range 5.6-21.4% (RSD(R)) depending on the compound and concentration. Mean recoveries for all levels varied between 89 and 100%, depending on the amine. A total of 39 samples of cooking utensils were analyzed using the described method and the results obtained after the third migration test were not compliant in approximately half of the samples.