Quantification and validation of nine nonsteroidal anti‐inflammatory drugs in equine urine using gas chromatography–mass spectrometry for doping control

Nonsteroidal anti‐inflammatory drugs (NSAIDs) are commonly used in therapeutic doses in human and veterinary medicine for the treatment of inflammation, pain, and fever. A method for the simultaneous determination of nine NSAIDs, known as therapeutic prohibited substances, in equine urine was developed and fully validated according to the European Commission Decision 2002/657/EC and Association of Official Racing Chemists criteria. The validation was performed for naproxen, flunixin, ketoprofen, diclofenac, eltenac, meclofenamic acid, phenylbutazone, vedaprofen, and carprofen in equine urine in accordance with the International Screening Limits (ISL) regulated by International Federation of Horseracing Authorities. After basic hydrolysis, samples were extracted with a C18 cartridge using automated solid‐phase extraction. Several derivatization reagents were investigated, and trimethylphenylammonium hydroxide/methanol (20/80, v/v) was selected. Analyses were carried out using gas chromatography–mass spectrometry with selected ion monitoring mode, but the method can be applied to a large number of analytes. The within‐laboratory reproducibility was not more than 12.8% (≤15%), and mean relative recoveries ranged from 91.1% to 104.1% for inter‐day and intra‐day precision. The decision limits (CCα) and detection capabilities (CCβ) were evaluated at concentrations near the ISL for each therapeutic substance. The validation results demonstrated that the method is highly reproducible, easily applicable, and suitable for the analysis of some NSAIDs in equine urine that have not been previously published. Finally, the method was also applied to known positive samples.     

Effect of valproate on the plasma concentrations of aripiprazole in bipolar patients

Objective. There is very limited documentation available on the effects of valproate co-medication on the pharmacokinetics of aripiprazole in a naturalistic setting. The aim of the present study was to investigate the effect of co-medication with valproate on serum concentrations of aripiprazole in bipolar disorder patients in a clinical setting. Method. Plasma samples of bipolar disorder patients (n = 69) on a stable dose of aripiprazole 20 mg/day were analyzed by a liquid chromatography-mass spectrometry method in a routine therapeutic drug monitoring setting. Therapeutic drug monitoring was done for the entire study group before and after valproate co-administration. Results. We observed a statistically significant difference between the aripiprazole monotherapy and aripiprazole-valproate combination with respect to total aripiprazole plasma levels (p < 0.01). However, no statistically significant differences were noted in aripiprazole levels between the first week and the second week of valproate co-administration. Conclusion. In conclusion, concurrent treatment with valproate resulted in changes in the total aripiprazole plasma levels by 23%. But a lower total aripiprazole concentration during co-medication with valproate, caused by protein binding displacement, is reported being clinically insignificant in previous studies. The results from these studies are important in order to clarify clinical safety and efficacy.     

Clinical and pathological correlations of marrow PUMA and P53 expressions in myelodysplastic syndromes

p53 is a key regulator of apoptosis. p53 upregulated modulator of apoptosis (PUMA) is a critical mediator of p53‐dependent and independent apoptosis. The objective of this study was to evaluate the relationship of p53 and PUMA to the prognosis of MDS. Bone marrow biopsies of MDS patients at the time of diagnosis (n = 76) and at the time of transformation (n = 19) were included in the study group. The expression of p53 and PUMA was evaluated using immunohistochemistry. When compared to the control group, both p53 (p < 0.001) and PUMA (p = 0.012) expression levels were significantly higher in MDS group. In MDS group, there was a moderate positive correlation between p53 and PUMA expressions. PUMA expression was not correlated with event free and overall survival. However, overall survival was significantly lower in cases with p53 expression in more than 50% of the cells. There was an increase in PUMA expression in cases that showed transformation as compared to the initial diagnostic bone marrows but was not statistically significant. The correlation that existed between p53 and PUMA was lost in transformed cases. Our results showed that PUMA and p53 expressions are increased in MDS marrows compared to normal marrows. PUMA expression increases further during transformation while the expression of p53 is not significantly altered which suggests that PUMA alterations might be a late event during the evolution of MDS.     

Bronchial Hyper‐Reactivity in Migraine Without Aura: Is It a New Clue for Inflammation?

Objective.— We attempted to investigate the relationship between migraine without aura (MwoA) and bronchial hyper‐reactivity to postulate inflammation as an underlying mechanism in migraine. Background.— Comorbidity of migraine and atopic diseases such as asthma has been an argument for suspected immune system dysfunction in migraineurs. Methods.— Twenty patients with MwoA and 5 control subjects without history of atophy and asthma were included in study. Subjects with abnormal physical examination and chest radiographs were excluded. After a normal spirometry, methacholine bronchoprovocation test was performed in all subjects and controls according to 5 breath dosimeter methods. Results.— Sixteen of 20 patients and 2 of 5 control subjects were women. Mean ages were 37.5 (19‐56) and 33.8 (26‐43) years, respectively. Methacholine bronchoprovocation test was positive in 3 patients (15%) but was normal in all controls (0%). Conclusions.— The relationship between MwoA and bronchial hyper‐reactivity may help to postulate the inflammation in migraine as an underlying mechanism.     

Acute Transverse Myelitis at the Conus Medullaris Level After Rabies Vaccination in a Patient With Behcet's Disease

Abstract

Case report: A 25-year-old man with BehÇet's disease was admitted because of weakness of the lower limbs and difficulty in urination. He had received a rabies vaccination 2 months previous because he had been bitten by a dog.

Findings: Clinical and laboratory findings supported acute transverse myelitis. A hyperintense lesion and expansion at the level of conus medullaris was detected on spinal magnetic resonance imaging.

Conclusion: Although neurologic involvement is one of the main causes of mortality and morbidity in BehÇet's disease, the factors that aggravate the involvement of the nervous system are still unclear. Vaccination may have been the factor that had activated autoimmune mechanisms in this case. To our knowledge, involvement of the conus medullaris in BehÇet's disease after rabies vaccination has not been reported.     

Some Heavy Metals Accumulation in Tissues in <Emphasis Type="Italic">Capoeta umbla</Emphasis> (Heckel, 1843) from Uzuncayir Dam Lake (Tunceli,Turkey)

Concentrations of metals were determined in the gills, liver, kidney, heart and muscle in Capoeta umbla caught from six stations from the Munzur River system. Metal concentrations in the tissues tended to vary significantly among stations (p < 0.05). Liver (Cu, 10.10 ± 0.23–23.03 ± 9.37 ppm; Zn, 14.67 ± 3.01–21.82 ± 2.39 ppm; Cd, 18.04 ± 4.56–52.69 ± 10.65 ppb and Fe, 28.87 ± 6.78–115.11 ± 34.87 ppm) and kidney (Cu, 1.80 ± 0.25–3.70 ± 0.62 ppm; Zn, 20.81 ± 0.37–29.36 ± 0.70 ppm; Cd, 132.06 ± 5.29–639.51 ± 20.14 ppb and Fe, 24.40 ± 1.98–59.39 ± 1.97 ppm) tissues showed higher metal concentrations than other tissues. It seems that metal contamination in the river is too high for the health of fish and the people who eat them. The geographical locations of catch, season, nature of diet, and the size of fish used for analyses might lead to different metal concentration in the same fish species.