Východiska: V literatuře nejsou žádné zmínky o souběžné chemoradioterapii při karcinomu žaludku s peritoneálními oligometastázami. Popis případu: Muž ve věku 70 let s karcinomem žaludku a peritoneálními oligometastázami byl léčen adaptivní radioterapií a souběžně perorálně podávaným S-1. Po radioterapii bylo podávání S-1 přerušeno a o 2 roky později byla zaznamenána kompletní regrese tumoru bez rekurence metastáz v průběhu 6 let po radioterapii. Závěr: Karcinom žaludku s peritoneálními metastázami je možné léčit souběžně adaptivní radioterapií a perorálně podávaným S-1 s kurativním záměrem.
Background: There are no reports of concurrent chemoradiotherapy for gastric cancer with peritoneal oligometastases. Case description: A 70-year-old man with gastric cancer and peritoneal oligometastases received concurrent adaptive radiotherapy and oral S-1. After radiotherapy, S-1 was discontinued, and 2 years later the tumor had completely regressed, with no recurrence or metastasis 6 years after radiotherapy. Conclusion: Peritoneal oligometastatic gastric cancer may be a candidate for curative treatment with concurrent adaptive radiotherapy and oral S-1.
- MeSH
- chemoradioterapie metody MeSH
- ftorafur aplikace a dávkování terapeutické užití MeSH
- kyselina oxonová aplikace a dávkování terapeutické užití MeSH
- lidé MeSH
- metastázy nádorů terapie MeSH
- nádory žaludku * diagnóza patologie terapie MeSH
- peritoneální nádory sekundární terapie MeSH
- protokoly protinádorové léčby MeSH
- senioři MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- Publikační typ
- kazuistiky MeSH
INTRODUCTION: The widespread importance of the synthesis and modification of anticancer agents has given rise to many numbers of medicinal chemistry programs. In this regard, triazine derivatives have attracted attention due to their remarkable activity against a wide range of cancer cells. This evaluation covers work reports to define the anticancer activity, the most active synthesized compound for the target, the SAR and, when described, the probable MOA besides similarly considered to deliver complete and target-pointed data for the development of types of anti-tumour medicines of triazine derivatives. Triazine scaffold for the development of anticancer analogues. Triazine can also relate to numerous beneficial targets, and their analogues have auspicious in-vitro and in-vivo anti-tumour activity. Fused molecules can improve efficacy, and drug resistance and diminish side effects, and numerous hybrid molecules are beneath diverse stages of clinical trials, so hybrid derivatives of triazine may offer valuable therapeutic involvement for the dealing of tumours. OBJECTIVE: The objective of the recent review was to summarize the recent reports on triazine as well as its analogues with respect to its anticancer therapeutic potential. CONCLUSION: The content of the review would be helpful to update the researchers working towards the synthesis and designing of new molecules for the treatment of various types of cancer disease with the recent molecules that have been produced from the triazine scaffold. Triazine scaffolds based on 1,3,5-triazine considerably boost molecular diversity levels and enable covering chemical space in key medicinal chemistry fields.
- MeSH
- antitumorózní látky * farmakologie chemie terapeutické užití MeSH
- léky antitumorózní - screeningové testy MeSH
- lidé MeSH
- nádory farmakoterapie MeSH
- triaziny * farmakologie chemie terapeutické užití MeSH
- vyvíjení léků metody MeSH
- vztahy mezi strukturou a aktivitou MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Coccidiosis is a protozoan intestinal disease that reduces the production of the sheep industry and causes large economic losses for sheep. Although chemically synthesised drugs are routinely employed to treat coccidiosis in sheep, the anticoccidial drug resistance and drug residues in edible meat have prompted an urgent search for alternatives. Herein, the anticoccidial properties of diclazuril, a conventional anticoccidial drug, and Allium sativum, Houttuynia cordata and Portulaca oleracea were assessed. Forty 45-day-old lambs naturally infected with Eimeria spp. were selected and randomly divided into five groups. The results showed that the sheep treated for coccidiosis had considerably decreased average daily gain (ADG) during both administration and withdrawal of the drug compared to the control group. Furthermore, at days 14, 21, 28 and 35, respectively, the three herbs and diclazuril had similar anticoccidial effects, with lower oocysts per gram (OPG) than the control group. On day 78, OPG in the three herbal groups was significantly lower than in the diclazuril group. In addition, the abundance and composition of the gut microbiota were changed in sheep treated with the three herbs and diclazuril compared to the untreated sheep. Moreover, some intestinal microorganisms have a correlation with OPG and ADG when using Spearman correlation analysis. In summary, our results suggest that all three herbs produce anticoccidial effects similar to diclazuril and modulate the balance of gut microbiota in growing lambs.
- MeSH
- Eimeria účinky léků fyziologie MeSH
- kokcidiostatika farmakologie aplikace a dávkování MeSH
- kokcidióza * veterinární farmakoterapie parazitologie MeSH
- léky rostlinné čínské farmakologie aplikace a dávkování MeSH
- nemoci ovcí * parazitologie farmakoterapie MeSH
- oocysty účinky léků MeSH
- ovce MeSH
- střevní mikroflóra * účinky léků MeSH
- triaziny farmakologie aplikace a dávkování MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
DRESS syndróm je závažná, potencionálne letálna, reakcia alergického typu, ktorá sa môže prejaviť u predisponovaného jedinca niekoľko týždňov po užívaní lieku. Je dôležité na ňu myslieť, ak sa u pacienta, ktorý je liečený suspektným liekom, objavia vysoké teploty, exantém spolu s postihnutím vnútorných orgánov a charakteristickými hematologickými zmenami. Liečba spočíva vo vynechaní príslušného lieku, vo vysokých dávkach kortikoidov, prípadne s intravenóznymi imunoglobulínmi, a v komplexnej terapii orgánového postihnutia. Autorky prezentujú kazuistiku 12-ročnej pacientky na liečbe lamotrigínom, u ktorej došlo k rozvoju febrilít, morbiliformného exantému, k hematologickým a hepatálnym zmenám.
DRESS syndrome is a serious, potentially lethal hypersensitivity reaction that may manifest itself in a predisposed individual several weeks after taking the drug. It is important to keep it in mind in a patient who is being treated with suspected drug who develops high fevers, rash along with involvement of internal organs and typical hematological changes. Treatment consists of discontinuation of the drug, high doses of corticosteroids, possibly with intravenous immunoglobulins and complex therapy of affected organs. The authors present a case report of a 12-years-old girl under lamotrigine treatment with the development of fever, morbilliform rash, hematological and liver changes.
- MeSH
- diferenciální diagnóza MeSH
- lamotrigin škodlivé účinky terapeutické užití MeSH
- léková dermatitida diagnóza etiologie farmakoterapie MeSH
- lékový hypersenzitivní syndrom * diagnóza farmakoterapie genetika MeSH
- lidé MeSH
- mladiství MeSH
- mortalita MeSH
- nežádoucí účinky léčiv komplikace MeSH
- Check Tag
- lidé MeSH
- mladiství MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
Ochorenie COVID-19 (coronavirus disease 2019; COVID-19), zapríčinené koronavírusom 2, spôsobujúcim ťažký akútny respiračný syndróm (Severe Acute Respiratory Syndrome Coronavirus 2; SARS-CoV-2), sužuje ľudskú populáciu od prelomu rokov 2019 a 2020, kedy boli vo Wu-chane, v najväčšej metropole a hlavnom meste provincie Chu-pej v strednej Číne, potvrdené prvé prípady infikovania sa týmto patogénom. Od tohto obdobia bolo v liečbe pacientov s COVID-19 navrhnutých a využitých mnoho farmakoterapeutických modalít. Triazavirín (TZV; riamilovir) je syntetické netoxické antiviroticky širokospektrálne účinkujúce liečivo patriace do skupiny azolotriazínov. V kontexte vedomostí o morfológii, štruktúre viriónu, genóme, replikačnom cycle a funkciách jednotlivých proteínov v SARS-CoV-2 a aj v súlade s vykonanými analýzami in silico bolo publikovaných niekoľko hypotéz a návrhov so zámerom využiť TZV v liečbe COVID-19. Výsledky a závery vyplývajúce z dobre známeho randomizovaného klinického skúšania, evidovaného pod registračným číslom ChiCTR2000030001, ktoré bolo realizované v Číne v roku 2020, však indikovali nielen efektívne anti- SARS-CoV-2-pôsobenie tohto azaanalógu guanínu, ale aj niektoré obmedzenia v kontexte všeobecnej interpretovateľnosti a uplatniteľnosti formulovaných výstupov. Primárny zámer tejto prehľadovej publikácie spočíval preto v načrtnutí komplexnejšieho pohľadu na farmakoterapeutické intervencie proti COVID-19/- SARS-CoV-2, ktoré sú založené na využití TZV. Pozornosť bola sústredená na relevantné výsledky a závery z klinických skúšaní a praktické skúsenosti definujúce nielen reálne benefity zvolených terapeutických stratégií, ktoré zahŕňajú zmienené antivirotikum, ale aj niekoľko úskalí s nimi spojených.
Coronavirus disease 2019 (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has plagued the human population as 2019 turned into 2020, when first cases were confirmed to be infected with the pathogen in Wuhan City, the largest mega-city and capital of Hubei Province in Central China. Since this time, many pharmacotherapeutic modalities were suggested and used to treat the patients suffering from COVID-19. Triazavirin (TZV; riamilovir) is a synthetic non-toxic broad-spectrum antiviral drug belonging into an azolotriazine class. Several hypotheses and suggestions based on the knowledge about morphology, structure of virion, genome, replication cycle and functions of particular proteins within SARS-CoV-2 as well as in silico analyzes were published aiming to employ TZV for the treatment of COVID-19. Results and conclusions from a well-known randomized controlled trial registered under the Registration No. ChiCTR2000030001, which was carried out in China in 2020, indicated not only the anti-SARS-CoV-2 efficacy of given aza analogue of guanine but also some limitations of these outcomes in the context of their general interpretability and applicability. Thus, a primary aim of this review article was to provide more complex view on pharmacotherapeutic interventions based on TZV against COVID-19/SARS-CoV-2. The focus was on relevant results and conclusions from clinical trials as well as practical experiences with given antiviral agent considering not only real benefits of chosen therapeutic strategies but also several obstacles connected with them.
- Klíčová slova
- triazavirin, riamilovir,
- MeSH
- antivirové látky farmakologie terapeutické užití MeSH
- COVID-19 * MeSH
- farmakoterapie COVID-19 MeSH
- lidé MeSH
- randomizované kontrolované studie jako téma MeSH
- triaziny farmakologie terapeutické užití MeSH
- triazoly farmakologie terapeutické užití MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
OBJECTIVE: To analyse the concentrations of lamotrigine in maternal serum, colostrum, and serum of breastfed newborns, and to evaluate the effect of comedication with enzyme-inducing antiseizure medication and valproic acid. METHODS: This cohort study collected data from 158 women and 143 breastfed newborns. Maternal serum, milk (i.e., colostrum), and newborn serum samples were collected between the 2nd and 5th postnatal days, and lamotrigine concentrations were measured by high-performance liquid chromatography. RESULTS: The median lamotrigine concentrations were 2.7 mg/L in maternal serum, 1.4 mg/L in milk, and 1.7 mg/L in newborn serum. The median milk/maternal serum concentration ratio was 0.60, the median newborn/maternal serum concentration ratio was also 0.60, and the median newborn serum/milk concentration ratio was 1.00. A significant correlation was observed between milk and maternal serum concentrations and between newborn serum and milk concentrations, maternal serum concentrations, maternal daily dose, and dose related to maternal body weight. CONCLUSIONS: Exposure to lamotrigine in breastfed newborns is lower than exposure during pregnancy. However, by the same dose by the same mother, lamotrigine concentrations in both maternal serum and milk increase significantly after delivery. This finding, together with the immature function of eliminating enzymes in newborns, may be the reason for reaching concentrations in the reference range used for the general epileptic population in breastfed newborns. Therapeutic monitoring of breastfed newborns serum concentrations of lamotrigine is not mandatory; however, if signs of possible adverse events are noted, newborn serum concentrations should be analysed.
- MeSH
- antikonvulziva terapeutické užití MeSH
- kohortové studie MeSH
- kojení * MeSH
- kolostrum chemie MeSH
- lamotrigin farmakologie MeSH
- lidé MeSH
- mateřské mléko chemie MeSH
- matky * MeSH
- novorozenec MeSH
- poporodní období MeSH
- těhotenství MeSH
- Check Tag
- lidé MeSH
- novorozenec MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Klíčová slova
- Imeglimin,
- MeSH
- hypoglykemika * farmakologie terapeutické užití MeSH
- lidé MeSH
- triaziny farmakologie terapeutické užití MeSH
- Check Tag
- lidé MeSH
Simple molecular descriptors of extensive series of 1,3,5-triazinyl sulfonamide derivatives, based on the structure of sulfonamides and their physicochemical properties, were designed and calculated. These descriptors were successfully applied as inputs for artificial neural network (ANN) modelling of the relationship between the structure and biological activity. The optimized ANN architecture was applied to the prediction of the inhibition activity of 1,3,5-triazinyl sulfonamides against human carbonic anhydrase (hCA) II, tumour-associated hCA IX, and their selectivity (hCA II/hCA IX).
- MeSH
- antigeny nádorové metabolismus MeSH
- inhibitory karboanhydras chemie metabolismus MeSH
- karboanhydrasa II antagonisté a inhibitory metabolismus MeSH
- karboanhydrasa IX antagonisté a inhibitory metabolismus MeSH
- lidé MeSH
- neuronové sítě (počítačové) * MeSH
- racionální návrh léčiv MeSH
- sulfonamidy chemie metabolismus MeSH
- triaziny chemie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Na úrovni farmakokinetiky jsou lékové interakce antiepileptik spojeny obvykle s enzymatickou indukcí nebo inhibicí. Méně časté jsou interakce v oblasti absorpce, vazby na plazmatické bílkoviny nebo renální exkrece. Farmakodynamické interakce antiepileptik s dalšími látkami se zřídka týkají synergismu s možností snížení dávek, spíše se zvyšuje incidence vedlejších účinků. Čistě farmakodynamické interakce byly popsány u oxcarbazepinu, perampanelu a pregabalinu.
Drug interactions of antiepileptic drugs are mostly connected with enzymatic induction or inhibition. The interaction on level of absorption, plasma-protein binding of renal excretion is less frequent. Pharmacodynamic interaction of antiepileptics with other drugs is seldom synergistic with a possibility of declination of dose. The increase of adverse drug reactions is more common. Purely pharmacodynamic interaction was described with oxcarbazepin, perampanel and pregabalin. The new antiepileptics have lower interaction potential - most of them are excreted either via kidney or extrahepatal (e. g. gabapentin, lacosamide, levetiracetam, topiramate, vigabatrin). Enzymatic induction is either not present or minimal. The inductive effect is necessary to be taken into account in carbamazepine, phenytoin and phenobarbital. Inhibitive effect is held in valproic acid and felbamate. The interactive potential among newer antiepileptics is the highest in lamotrigine, oxcarbazepine and rufinamide. Drug interactions were not found in lacosamide, pregabalin, stiripentol and vigabatrin.
- MeSH
- antikonvulziva * farmakokinetika krev MeSH
- fenobarbital farmakokinetika MeSH
- fenytoin farmakokinetika MeSH
- gabapentin farmakokinetika MeSH
- karbamazepin farmakokinetika MeSH
- kyselina valproová farmakokinetika MeSH
- lamotrigin farmakokinetika MeSH
- lékové interakce * MeSH
- lidé MeSH
- primidon farmakokinetika MeSH
- topiramat farmakokinetika MeSH
- Check Tag
- lidé MeSH
Kromě rizika selhání antikoncepce, které hrozí u eslikarbazepinu, felbamátu, fenobarbitalu, fenytoinu, karbamazepinu, oxcarbazepinu, perampanelu, primidonu, rufinamidu a vyšších hladin topiramátu, má klinický význam rovněž vliv antikoncepce na hladinu lamotriginu a případně topiramátu. Estrogenní komponenta výrazně snižuje hladinu lamotriginu s nutností navýšit dávky. V týdnu bez antikoncepce pak stoupá riziko nežádoucích účinků spojených s vysokou hladinou lamotriginu. Podání čistě progestinové antikoncepce při léčbě lamotriginem může způsobit selhání antikoncepce z důvodu mírného zvýšení clearance progestinu. Vliv na hormonální antikoncepci nemají klonazepam, etosuximid, gabapentin, kys. valproová, lacosamid, levetiracetam, pregabalin, retigabin, tiagabin, vigabatrin, zonisamid. Nebylo hodnoceno a nepředpokládá se u klobazamu. U stiripentolu a sulthiamu je předpokládán vzestup hladiny kontraceptiva a možná potřeba redukce dávky.
The metabolism of contraceptives is enhanced and thereby contraceptive failure might occur in combination with carbamazepine, eslicarbazepine, felbamate, phenobarbital, phenytoin, oxcarbazepine, perampanel, primidone, rufinamide or higher levels of topiramate. Estrogen component considerably declines lamotrigine level with the necessity to increase the dose. Lamotrigine concentrations consequently significantly increase during the hormonal contraceptive washout week and may be associated with intermittent lamotrigine-related toxicity. Lamotrigine produces a modest reduction in the progesterone level which might result in contraceptive failure in patients using the progesterone-only pill. The metabolism of hormonal contraceptives is no affected with: clonazepam, ethosuximide, gabapentin, lacosamide, levetiracetam, pregabalin, retigabine, tiagabine, vigabatrin, valproic acid, zonisamid. The effect has not been evaluated in clobazam. A pharmacokinetic interaction would not be anticipated. It is not known whether stiripentol or sulthiame affect hormonal contraception, but they can increase plasma level of hormonal contraceptives and thus necessitate lower doses to be prescribed.
- MeSH
- antikonvulziva * farmakologie MeSH
- hormonální antikoncepce MeSH
- kontraceptiva hormonální farmakologie MeSH
- lamotrigin farmakologie MeSH
- léková kontraindikace MeSH
- lékové interakce * MeSH
- lidé MeSH
- topiramat farmakologie MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
