Oncometabolites in urine - a new opportunity for detection and prognosis of the clinical progress of verified prostate cancer-a pilot study.

BACKGROUND: Oncometabolites provide a new approach towards the diagnostics and prognosis of the clinical progress of prostate cancer (PCa). This study is about the diagnostic and predictive value of a panel of urinary oncometabolites (ethanolamine, kynurenine, ß-alanine, α-alanine, leucine, isoleucine, γ-aminobutyric acid, and sarcosine) and correlation with prostate-specific antigen (PSA) and Gleason score in patients diagnosed with prostate cancer. METHODS: The participants in this cross-sectional study were divided into PCa group (101 patients who matched the including criteria, average age 71) and control group (52 individuals, with no evidence of malignancy, without oncological and other chronic diseases, and without prostate gland pathology, average age 40). The criteria to be included in the PCa group were as follows: i) being diagnosed with prostate cancer, based on digital rectal examination (DRE), prostate ultrasound investigation, or biopsy; ii) not being subjected to a surgical or any other treatment; iii) not having any other concomitant oncological diseases, renal failure, diabetes mellitus. The urinary concentration of the selected metabolites was established through high-performance liquid chromatography with tandem mass spectrometry detection (HPLC-MS/MS). RESULTS: The comparison of both groups established a significantly different elevated concentration of ethanolamine, sarcosine and kynurenine, and a significantly different decreased concentration of ß-alanine and isoleucine in PCa group. No changes of the values were detected in the PCa group with PSA levels below and above 10 ng/mL and Gleason score below and above 6 (p > 0.05). To test whether combination of several variables is more powerful in discriminating between PCa and control group multiple logistic regression analysis was performed. A model including ethanolamine, sarcosine, kynurenine, ß-alanine, and isoleucine demonstrated negative predictive power (NPP) 76.2% and positive predictive power (PPP) 81.8%. DISCUSSION: Urinary concentrations of ethanolamine, sarcosine, kynurenine, ß-alanine, and isoleucine in PCa group differ significantly from that of control group. New expanded population studies are needed to discuss our results.

Development and validation of an LC-MS/MS method for determination of 8-iso-prostaglandin f2 Alpha in human saliva.

Background: Increased formation of reactive oxygen species may be caused by the ion release of the metal alloys used in prosthetic dental restorations due to the corrosion process. As products of lipid peroxidation, isoprostanes can be used as a marker for oxidative stress in the body. There are two significant advantages of using isoprostanes as an oxidative stress marker - presence in all fluids in the body and low reactivity. Saliva provides noninvasive, painless, and cost-effective sample collection and can be used as an alternative testing medium of blood and urine. Methods: This study presents the development and validation of a sample LC-MS/MS method to quantify 8-isoprostaglandin F2-a in human saliva using salt-out assisted liquid-liquid extraction (SALLE). Results: The selected sample preparation procedure optimized chromatographic separation and mass detection provided high recovery and sensitivity of the analysis. The calibration curve was obtained in the predefined range 25-329 ng/L with R2 larger than 0.995. Normalized matrix varied between 89.7 % and 113.5%. The method showed sufficient accuracy and precision - accuracy in the range 89.7 %-113.9 %, and precision between 2.3% and 5.4%. Conclusions: The proposed method is validated according to current EMA/FDA industrial guidance for bioanalysis and offers an appropriate level of sensitivity and sufficient accuracy and precision.

Effects of Lacosamide Treatment on Epileptogenesis, Neuronal Damage and Behavioral Comorbidities in a Rat Model of Temporal Lobe Epilepsy.

Clinically, temporal lobe epilepsy (TLE) is the most prevalent type of partial epilepsy and often accompanied by various comorbidities. The present study aimed to evaluate the effects of chronic treatment with the antiepileptic drug (AED) lacosamide (LCM) on spontaneous motor seizures (SMS), behavioral comorbidities, oxidative stress, neuroinflammation, and neuronal damage in a model of TLE. Vehicle/LCM treatment (30 mg/kg, p.o.) was administered 3 h after the pilocarpine-induced status epilepticus (SE) and continued for up to 12 weeks in Wistar rats. Our study showed that LCM attenuated the number of SMS and corrected comorbid to epilepsy impaired motor activity, anxiety, memory, and alleviated depressive-like responses measured in the elevated plus maze, object recognition test, radial arm maze test, and sucrose preference test, respectively. This AED suppressed oxidative stress through increased superoxide dismutase activity and glutathione levels, and alleviated catalase activity and lipid peroxidation in the hippocampus. Lacosamide treatment after SE mitigated the increased levels of IL-1ß and TNF-α in the hippocampus and exerted strong neuroprotection both in the dorsal and ventral hippocampus, basolateral amygdala, and partially in the piriform cortex. Our results suggest that the antioxidant, anti-inflammatory, and neuroprotective activity of LCM is an important prerequisite for its anticonvulsant and beneficial effects on SE-induced behavioral comorbidities.

Anticonvulsant Effects of Topiramate and Lacosamide on Pilocarpine-Induced Status Epilepticus in Rats: A Role of Reactive Oxygen Species and Inflammation.

BACKGROUND: Status epilepticus (SE) is a neurological disorder characterized by a prolonged epileptic activity followed by subsequent epileptogenic processes. The aim of the present study was to evaluate the early effects of topiramate (TPM) and lacosamide (LCM) treatment on oxidative stress and inflammatory damage in a model of pilocarpine-induced SE. METHODS: Male Wistar rats were randomly divided into six groups and the two antiepileptic drugs (AEDs), TPM (40 and 80 mg/kg, i.p.) and LCM (10 and 30 mg/kg, i.p.), were injected three times repeatedly after pilocarpine administration. Rats were sacrificed 24 h post-SE and several parameters of oxidative stress and inflammatory response have been explored in the hippocampus. RESULTS: The two drugs TPM and LCM, in both doses used, succeeded in attenuating the number of motor seizures compared to the SE-veh group 30 min after administration. Pilocarpine-induced SE decreased the superoxide dismutase (SOD) activity and reduced glutathione (GSH) levels while increasing the catalase (CAT) activity, malondialdehyde (MDA), and IL-1ß levels compared to the control group. Groups with SE did not affect the TNF-α levels. The treatment with a higher dose of 30 mg/kg LCM restored to control level the SOD activity in the SE group. The two AEDs, in both doses applied, also normalized the CAT activity and MDA levels to control values. In conclusion, we suggest that the antioxidant effect of TPM and LCM might contribute to their anticonvulsant effect against pilocarpine-induced SE, whereas their weak anti-inflammatory effect in the hippocampus is a consequence of reduced SE severity.