Several studies have shown that plants can absorb various micropollutants. The behavior of micropollutants from wastewater treatment plant resources was comprehensively investigated in raised beds in which either a mixture of vegetables or maize was grown. The beds were either irrigated with treated wastewater or enriched with sewage sludge or composted sewage sludge. Over the year, samples of wastewater, water drained from the beds, soils and plants were analyzed. Of the seventy-five analyzed substances, fifty-four, thirty-three and twenty-seven were quantified in wastewater, sewage sludge, and composted sludge, respectively. Alarmingly, approximately 20 % of the compounds from wastewater were also detected in the solutions leached from the beds irrigated with wastewater (e.g., gabapentin, tramadol, sertraline, carbamazepine, its metabolites, and benzotriazoles). In addition, a gradual increase in the content of four substances (telmisartan, venlafaxine, carbamazepine, citalopram) was recorded in these beds. The compounds from both biosolids used for soil enrichment tended to remain in the soils (e.g., telmisartan, venlafaxine, sertraline, its metabolite, citalopram, and its metabolite). Only four compounds (sertraline and three benzotriazoles) leached from these beds. Uptake of some chemicals (e.g., gabapentin, tramadol, carbamazepine and its metabolite, and venlafaxine and its metabolite) and their accumulation in plant tissues was observed mainly in vegetables grown on beds irrigated with wastewater. However, daily consumption values for edible plant parts and individual compounds did not indicate a direct threat to human health. Results of this innovative study show possible risks associated with the use of these resources in agriculture. Of particular concern is the possible micropollutants percolation towards groundwater, including those for which high sorption and thus low mobility in the soil environment is expected, such as sertraline. Soil and crop contamination cannot be neglected either.

• Klíčová slova
• Biosolids, Composts, Human health risk, Pharmaceuticals, contaminants' leaching from soils, contaminants' uptake by plants,
• MeSH
• citalopram MeSH
• gabapentin MeSH
• karbamazepin metabolismus   MeSH
• látky znečišťující půdu * analýza   MeSH
• lidé MeSH
• odpadní voda MeSH
• odpadní vody chemie   MeSH
• půda MeSH
• sertralin MeSH
• telmisartan MeSH
• tramadol * MeSH
• venlafaxin hydrochlorid MeSH
• voda MeSH
• zelenina metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• citalopram MeSH
• gabapentin MeSH
• karbamazepin MeSH
• látky znečišťující půdu * MeSH
• odpadní voda MeSH
• odpadní vody MeSH
• půda MeSH
• sertralin MeSH
• telmisartan MeSH
• tramadol * MeSH
• venlafaxin hydrochlorid MeSH
• voda MeSH

BACKGROUND: Painful diabetic neuropathy is an important therapeutic challenge as the efficacy of analgesic drugs in this setting is still unsatisfactory. Monotherapy with available treatments is often not sufficient and a combination of drugs is necessary. Trazodone (TRZ) is a compound with a multi-modal mechanism of action, being a serotonin-2 antagonist/reuptake inhibitor developed and approved for the treatment of depression in several countries. Previous clinical trials suggest a possible beneficial effect of low doses of trazodone for the treatment of patients affected by painful diabetic neuropathy. OBJECTIVE: This phase II study was designed to collect data on the efficacy and safety of low doses of TRZ combined with gabapentin after 8 weeks of treatment in patients affected by painful diabetic neuropathy. METHODS: This was a randomized, double-blind, placebo-controlled, multi-center, international, prospective study. Male and female diabetic patients aged 18-75 years and affected by painful diabetic neuropathy were eligible for enrollment. Subjects were randomized (1:1:1 ratio) to TRZ30 (10 mg three times daily for 8 weeks) or TRZ60 (20 mg three times daily for 8 weeks) or placebo. Gabapentin as background therapy was administered in open-label conditions to all patients. The primary endpoint was the change from baseline of the Brief Pain Inventory Short Form item 5 to week 8. Secondary endpoints included the other Brief Pain Inventory Short Form items, and the assessment of anxiety, sleep, quality of life, patient's improvement, and safety. RESULTS: One hundred and forty-one patients were included in the intention-to-treat population: 43 allocated to the TRZ30 group, 50 to the TRZ60 group, and 48 to the placebo group. After 8 weeks, the mean changes of Brief Pain Inventory Short Form item 5 from baseline were - 3.1, - 2.6, and - 2.5 in the TRZ30, TRZ60, and placebo groups, respectively. No statistically significant differences between groups were seen. Nevertheless, a better trend was observed for TRZ30 vs placebo (95% confidence interval - 1.30, 0.15; p = 0.1179), on top of the background effect of gabapentin administered to all study groups. 62.8% of patients achieved a ≥ 50% reduction in the TRZ30 group, 54% in the TRZ60 group, and 45.8% in the placebo group. At the same time, a statistically significant improvement was observed in Brief Pain Inventory Short Form item 6 for TRZ30 vs placebo (95% confidence interval - 1.54, - 0.07; p = 0.0314). No serious adverse event occurred during the trial and the most frequent treatment-emergent adverse events involved nervous system, QT prolongation, and gastrointestinal disorders. CONCLUSIONS: All treatment groups showed a clinically meaningful pain improvement; nevertheless, patients in the TRZ30 treatment group reported better efficacy outcomes. This finding suggests that low doses of TRZ could be useful for treating painful diabetic neuropathy, and support further adequately powered confirmatory trials investigating the efficacy of TRZ. CLINICAL TRIAL REGISTRATION: NCT03202979, date of registration: 29/06/2017.

• MeSH
• analgetika aplikace a dávkování   škodlivé účinky   MeSH
• diabetické neuropatie farmakoterapie   MeSH
• dvojitá slepá metoda MeSH
• gabapentin aplikace a dávkování   MeSH
• kombinovaná farmakoterapie MeSH
• kvalita života MeSH
• lidé středního věku MeSH
• lidé MeSH
• pilotní projekty MeSH
• prospektivní studie MeSH
• selektivní inhibitory zpětného vychytávání serotoninu aplikace a dávkování   škodlivé účinky   MeSH
• senioři MeSH
• trazodon aplikace a dávkování   škodlivé účinky   MeSH
• výsledek terapie MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze II MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH
• srovnávací studie MeSH
• Názvy látek
• analgetika MeSH
• gabapentin MeSH
• selektivní inhibitory zpětného vychytávání serotoninu MeSH
• trazodon MeSH

BACKGROUND: There are limited data on the effects of GBP on bone and no data for PGB. Some data suggest that there is a significant influence of sex hormone balance on the susceptibility of bone to antiepileptic drug-induced bone loss. METHODS: Forty-eight male Wistar rats were divided into six groups that were subjected to two surgeries, sham (noORX) or real orchidectomy (ORX), and were fed three diets, a SLD, a SLD enriched with GBP or a SLD enriched with PGB. Dual energy X-ray absorptiometry was used to measure the bone mineral density. The concentrations of bone turnover markers were assayed. The femurs were biomechanically tested. RESULTS: Significant reductions in bone mineral density, weight and biomechanical strength were observed in ORX animals. GBP or PGB exposure did not cause significant alterations in bone mineral density or biomechanical strength. No changes in bone turnover markers were observed, except for RANKL. A significant increase was found in the ORX GBP and ORX PGB groups. Within the orchidectomized animal group, RANKL levels were significantly higher in the ORX PGB group than in the ORX GBP group. CONCLUSIONS: Because neither GBP nor PGB affected bone mineral density or mechanical bone strength, both of these antiepileptic drugs could be considered drugs with lower risks to bone health. A shift in RANKL levels indicates that the effects of GBP and PGB on osteoclast activity may be dependent on the hormonal status of animals.

• Klíčová slova
• Amino-terminal propeptide of procollagen type I, Bone alkaline phosphatase, Bone mineral density, Receptor activator of nuclear factor-kappa B ligand,
• MeSH
• absorpční fotometrie metody   MeSH
• alkalická fosfatasa metabolismus   MeSH
• antikonvulziva farmakologie   MeSH
• biomechanika účinky léků   MeSH
• femur účinky léků   metabolismus   MeSH
• gabapentin farmakologie   MeSH
• kostní denzita účinky léků   MeSH
• krysa rodu Rattus MeSH
• orchiektomie metody   MeSH
• osteoprotegerin metabolismus   MeSH
• potkani Wistar MeSH
• pregabalin farmakologie   MeSH
• prospektivní studie MeSH
• remodelace kosti účinky léků   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• alkalická fosfatasa MeSH
• antikonvulziva MeSH
• gabapentin MeSH
• osteoprotegerin MeSH
• pregabalin MeSH

Ligands of auxiliary α2δ subunit of voltage-dependent calcium channels (VDCCs) decrease elevated L-type VDCCs surface expression in arterial myocytes and arterial constriction in spontaneously hypertensive rats (SHR). However, their effect on blood pressure (BP) is unclear. In this study, we investigated the hemodynamic response to acute and chronic administration of gabapentin, a ligand of auxiliary α2δ subunit of VDCCs, in adult SHR with established neurogenic hypertension. The acute gabapentin administration lowered BP and heart rate more in conscious SHR than Wistar-Kyoto rats. Both nifedipine (L-type VDCCs blocker) and ω-conotoxin GVIA (N-type VDCCs blocker) also decreased BP more in SHR, but only gabapentin and ω-conotoxin GVIA abolished the nitroprusside-induced reflex tachycardia of baroreceptor-heart rate control. Hypotensive effect of gabapentin was accompanied by a reduction of (1) plasma norepinephrine level, (2) depressor response to ganglionic blocker pentolinium, (3) power of low frequency component of systolic BP variability, and (4) pressor response of mesenteric vascular bed to periarterial nerve stimulation, suggesting the decrease of peripheral sympathetic nerve transmission. Moreover, gabapentin effects on BP and baroreflex were absent in sympathectomized rats. In conclusion, the acute (but not chronic) administration of gabapentin lowered BP more in SHR than in Wistar-Kyoto rats. Besides the known L-type VDCCs involvement in the vascular effect of gabapentin, our data revealed the important role of N-type VDCCs in acute gabapentin effect on sympathetic control of BP. Gabapentin-induced changes of sympathetic nerve transmission indicated major hemodynamic mechanism of the acute response to this drug.

• Klíčová slova
• baroreflex, calcium channels, gabapentin, sympathectomy, sympathetic nervous system,
• MeSH
• analgetika farmakologie   MeSH
• blokátory kalciových kanálů farmakologie   MeSH
• druhová specificita MeSH
• gabapentin farmakologie   MeSH
• hypertenze patofyziologie   MeSH
• krevní tlak účinky léků   fyziologie   MeSH
• nifedipin farmakologie   MeSH
• potkani inbrední SHR MeSH
• potkani inbrední WKY MeSH
• srdeční frekvence účinky léků   fyziologie   MeSH
• sympatický nervový systém účinky léků   fyziologie   MeSH
• vápníkové kanály - typ L metabolismus   MeSH
• vápníkové kanály - typ N metabolismus   MeSH
• vědomí MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• analgetika MeSH
• blokátory kalciových kanálů MeSH
• gabapentin MeSH
• nifedipin MeSH
• vápníkové kanály - typ L MeSH
• vápníkové kanály - typ N MeSH

A simple, sensitive and robust method for simultaneous determination of antiepileptic drugs (gabapentin, pregabalin and vigabatrin) in human serum using GC-MS was developed and validated for clinical toxicology purposes. This method employs an emerging class of derivatization agents - alkyl chloroformates allowing the efficient and rapid derivatization of both the amino and carboxylic groups of the tested antiepileptic drugs within seconds. The derivatization protocol was optimized using the Design of Experiment statistical methodology, and the entire sample preparation requires less than 5 min. Linear calibration curves were obtained in the concentration range from 0.5 to 50.0 mg/L, with adequate accuracy (97.9-109.3%) and precision (<12.1%). The method was successfully applied to quantification of selected γ-aminobutyric acid analogs in the serum of patients in both therapeutic and toxic concentration ranges.

• MeSH
• aminy analýza   krev   MeSH
• antikonvulziva analýza   krev   MeSH
• design s pomocí počítače MeSH
• formiáty chemie   MeSH
• GABA analogy a deriváty   analýza   krev   MeSH
• gabapentin MeSH
• kalibrace MeSH
• kyseliny cyklohexankarboxylové analýza   krev   MeSH
• lidé MeSH
• plynová chromatografie s hmotnostně spektrometrickou detekcí MeSH
• pregabalin analýza   krev   MeSH
• vigabatrin analýza   krev   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• aminy MeSH
• antikonvulziva MeSH
• formiáty MeSH
• GABA MeSH
• gabapentin MeSH
• hexylchloroformate MeSH Prohlížeč
• kyseliny cyklohexankarboxylové MeSH
• pregabalin MeSH
• vigabatrin MeSH

BACKGROUND: Nocturnal sleep of patients suffering from various forms of dementia is often impaired by nocturnal agitation or nocturnal wandering. Anticonvulsives such as carbamazepine or valproate are reported to have some therapeutic efficacy, but there is little information about other drugs suitable for treatment of this condition. CASE REPORT: Our patient, a 77-year-old Czech woman with incipient vascular dementia, received gabapentin 400mg at bedtime for 6 months and showed convincing improvement. CONCLUSIONS: Gabapentin was very effective in treating nocturnal agitation.

• MeSH
• aminy terapeutické užití   MeSH
• anxiolytika terapeutické užití   MeSH
• demence komplikace   farmakoterapie   MeSH
• GABA terapeutické užití   MeSH
• gabapentin MeSH
• kyseliny cyklohexankarboxylové terapeutické užití   MeSH
• lidé MeSH
• psychomotorický neklid komplikace   farmakoterapie   MeSH
• senioři MeSH
• tma * MeSH
• Check Tag
• lidé MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• práce podpořená grantem MeSH
• Názvy látek
• aminy MeSH
• anxiolytika MeSH
• GABA MeSH
• gabapentin MeSH
• kyseliny cyklohexankarboxylové MeSH

PURPOSE: To study the anticonvulsant effects of gabapentin (GBP) in immature animals. METHODS: Motor seizures were induced by pentylenetetrazol in 7-, 12-, 18-, 25-day-old, and adult rats. Animals pretreated with GBP (15, 30, or 60 mg/kg i.p.) were compared with controls. The incidence and latency of two types of seizures [minimal (i.e., clonic)] and generalized tonic-clonic (GTCS) were recorded, and seizure severity was scored. RESULTS: GBP suppressed or at least restricted the tonic phase of GTCS at all the developmental stages studied. In addition, minimal seizures were suppressed in 18-day-old rats. Both effects exhibited a tendency to a U-shaped dose-response curve. CONCLUSIONS: Anticonvulsant effects of GBP were demonstrated in immature and in adult rats.

• MeSH
• acetáty farmakologie   MeSH
• aminy * MeSH
• antikonvulziva farmakologie   MeSH
• chování zvířat účinky léků   fyziologie   MeSH
• epilepsie generalizovaná chemicky indukované   prevence a kontrola   MeSH
• epilepsie tonicko-klonická chemicky indukované   prevence a kontrola   MeSH
• GABA * MeSH
• gabapentin MeSH
• krysa rodu Rattus MeSH
• kyseliny cyklohexankarboxylové * MeSH
• mozek účinky léků   růst a vývoj   MeSH
• pentylentetrazol * MeSH
• potkani Wistar MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• záchvaty chemicky indukované   prevence a kontrola   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• acetáty MeSH
• aminy * MeSH
• antikonvulziva MeSH
• GABA * MeSH
• gabapentin MeSH
• kyseliny cyklohexankarboxylové * MeSH
• pentylentetrazol * MeSH