• Publication type
• Meeting Abstract MeSH

OBJECTIVES: This case series evaluated the clinical efficacy of the novel "lateral approach" combined with an enamel matrix derivative (EMD) and bone grafting in the regenerative surgical treatment of intrabony defects associated with an edentulous ridge. MATERIAL AND METHODS: The innovative flap, called the "lateral approach," is explicitly designed for regeneration of unchallenged isolated intrabony defects associated with edentulous alveolar ridges. The flap is defined by a curved vertical incision on the buccal side opposite the treated defect and a sulcular incision on the buccal and defect-associated sides, promoting uneventful healing and regeneration while minimizing complications. Seven intrabony defects (one per patient) distal to the lower second molar were treated using the "lateral approach" combined with EMD and grafting with deproteinized bovine bone mineral. The primary outcome was clinical attachment level (CAL) change. As additional parameters, pocket probing depth (PPD) reduction and complication rate were analyzed. All the outcomes were assessed 6 months post-surgery and compared with the baseline values. RESULTS: Primary wound healing occurred in 100% of cases, and no complications were reported. At the 6-month re-evaluation, the initial median CAL of 6 mm (interquartile range 5-8 mm) was reduced to 3 mm (3-5 mm). The corresponding median PPD was reduced from 6 mm (IQR 6-8 mm) to 4 mm (IQR 3-5 mm). These differences were statistically significant (p < 0.05). CONCLUSIONS: The "lateral approach" is a technique for the surgical treatment of intrabony defects associated with the edentulous ridge. Within the limitations of the study, this method seems to be suitable for distal intrabony defects in the lower second molars, which frequently develop after third molar extraction.

• MeSH
• Alveolar Ridge Augmentation * methods   MeSH
• Jaw, Edentulous surgery   MeSH
• Surgical Flaps transplantation   MeSH
• Adult MeSH
• Wound Healing MeSH
• Bone Substitutes therapeutic use   MeSH
• Middle Aged MeSH
• Humans MeSH
• Prospective Studies MeSH
• Dental Enamel Proteins therapeutic use   MeSH
• Bone Regeneration MeSH
• Alveolar Bone Loss * surgery   MeSH
• Guided Tissue Regeneration, Periodontal methods   MeSH
• Aged MeSH
• Bone Transplantation methods   MeSH
• Treatment Outcome MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

Článek se soustředí na farmakoterapii farmakorezistentní schizofrenie. Nejprve je uvedena definice farmakorezistentní schizofrenie a způsoby vyloučení pseudorezistence. Detailněji jsou rozebrány možnosti léčby, tj. změna stávající léčby, augmentace a kombinace antipsychotik. Na závěr je krátce zmíněna perspektivní léčba.

The paper is focused on pharmacotherapy of treatment-resistant schizophrenia and exclusion of pseudoresistance. The treatment options including switch, augmentation and combination of antipsychotics are described. Finally, perspective substances are briefly mentioned.

• MeSH
• Antipsychotic Agents MeSH
• Clozapine therapeutic use   MeSH
• Drug Therapy, Combination MeSH
• Drug Resistance * MeSH
• Humans MeSH
• Schizophrenia, Treatment-Resistant * drug therapy   MeSH
• Drug Synergism MeSH
• Check Tag
• Humans MeSH
• Publication type
• Review MeSH

Publikace se zaměřuje na různá témata napříč lékařstvím, lidskou anatomií a kulturní antropologií. Určeno široké veřejnosti.; Vědění i veselí je možno sdílet různě. Konvenčně i nekonvenčně, písmem i obrazem, pojmy i pocity, suše i šťavnatěji. Podrobné informace lze nyní získat o kdečem snadno, zpravidla však nikoli je prožít s všetečnou radostí. Již Karel Havlíček (míněno Borovský) a mnozí s ním naznačili, že leccos podstatného lze popsat také v rýmu, jistě i obyčejnou rýmu, což prospívá vtipu a šprýmu. Za života se člověk až do smrti bez těla neobejde. A bez mysli to také nestojí za nic. Obojí může někdy pomoci udržovat medicína. Popsat nástroje života, smrti a medicíny po součástkách a v součástech jinak, než je běžné, se možná nesluší ve vědě, naopak vědění to prospívá. Autoři se desítky let věnují vědecké antropologii a klinické medicíně, ale po pracovní době sobě i vědě rádi odlehčí i jinak. Třeba touto přilnavou knížkou O životě, smrti a medicíně s humorem, která ke čtenáři přilne a nepustí, protože od něj neočekává mentální výkon, hledání smyslu života ani vážnost. Jak prolínat ironii s fakty a fakta s ironií, tím se zde moří dva profesoři a četní originální profíci, malíři a grafici. Navíc je nutno skromně poznamenat, že vše v knize uvedené je čirá pravda, čímž se liší od mnohých jiných. Knížka bude též skvělým dárkem, jimž dárce obdarovanému odhalí hloubku a jedinečnost své vlastní osobnosti. Překvapí nepřipravené, snad nepohorší, zcela jistě nikoho ani nezarmoutí. V dnešním digitálním světě umožní konkurovat umělé inteligenci pouhým člověčenstvím a imaginací. Učiňme se četbou uvolněnějšími a skvělejšími!

• MeSH
• Anatomy MeSH
• Anthropology, Cultural MeSH
• Medicine MeSH
• Death MeSH
• Life MeSH
• Publication type
• Monograph MeSH
• Popular Work MeSH

• Conspectus
• Lékařské vědy. Lékařství
• NML Fields
• lékařství
• antropologie

Coriolus versicolor (CV), known in traditional Chinese medicine for over 2000 years, is currently used in China and Japan to reduce chemotherapy or radiotherapy side effects in cancer patients. Despite extensive research, its effects still need improvement. This study aimed to determine if combining CV extract with LY294002, an inhibitor of the phosphatidylinositol-3-kinase (PI3K) signalling pathway, enhances cancer cell treatment, potentially leading to a novel therapeutic approach. Three human cancer cell lines (MCF-7, HeLa, and A549) were treated with CV extract alone or combined with LY294002. Cell viability was assessed using MTT assays. Then, HeLa and MCF-7 cells most sensitive to the co-treatment were used to evaluate colony formation, apoptosis, cell cycle, cell migration and invasion, and phospho-PI3K expression. The results demonstrated that LY294002 enhanced the CV extract's anti-tumour effects by reducing cell viability and colony formation. The combined treatment with CV extract and LY294002 more effectively induced G0/G1 cell cycle arrest, promoted apoptosis, reduced cell invasion and migration, and inhibited phospho-PI3K expression compared to each agent alone. This study highlights the potent cytotoxic enhancement between CV extract and LY294002 on cancer cells, primarily by inhibiting phospho-PI3K expression. These findings suggest promising avenues for developing novel combination therapies targeting cancer.

• MeSH
• Apoptosis * drug effects   MeSH
• Cell Cycle drug effects   MeSH
• A549 Cells MeSH
• Chromones * pharmacology   MeSH
• Phosphatidylinositol 3-Kinases metabolism   MeSH
• HeLa Cells MeSH
• Phosphoinositide-3 Kinase Inhibitors * pharmacology   MeSH
• Humans MeSH
• MCF-7 Cells MeSH
• Morpholines * pharmacology   MeSH
• Cell Line, Tumor MeSH
• Cell Movement * drug effects   MeSH
• Cell Proliferation drug effects   MeSH
• Antineoplastic Agents pharmacology   MeSH
• Plant Extracts pharmacology   chemistry   MeSH
• Signal Transduction drug effects   MeSH
• Drug Synergism MeSH
• Cell Survival drug effects   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH

Hepatocellular carcinoma (HCC) cells critically depend on PARP1 and CHK1 activation for survival. Combining the PARP inhibitor (PARPi) olaparib with a CHK1 inhibitor (MK-8776, CHK1i) produced a synergistic effect, reducing cell viability and inducing marked oxidative stress and DNA damage, particularly in the HepG2 cells. This dual treatment significantly increased apoptosis markers, including γH2AX and caspase-3/7 activity. Both HCC cell lines exhibited heightened sensitivity to the combined treatment. The effect of drugs on the expression of proliferation markers in an olaparib-resistant patient-derived xenograft (PDX) model of ovarian cancer was also investigated. Ovarian tumors displayed reduced tissue growth, as reflected by a drop in proliferation marker Ki-67 levels in response to PARPi combined with CHK1i. No changes were observed in corresponding liver tissues using Ki-67 and pCHK staining, which indicates the absence of metastases and a hepatotoxic effect. Thus, our results indicate that the dual inhibition of PARP and CHK1 may prove to be a promising therapeutic approach in the treatment of primary HCC as well as OC tumors without the risk of liver metastases, especially in patients with olaparib-resistant tumor profiles.

• MeSH
• Apoptosis drug effects   MeSH
• Hep G2 Cells MeSH
• Checkpoint Kinase 1 metabolism   antagonists & inhibitors   MeSH
• Phthalazines * pharmacology   MeSH
• Carcinoma, Hepatocellular * drug therapy   pathology   metabolism   MeSH
• Liver drug effects   pathology   metabolism   MeSH
• Humans MeSH
• Mice MeSH
• Cell Line, Tumor MeSH
• Liver Neoplasms * drug therapy   pathology   metabolism   MeSH
• Ovarian Neoplasms * drug therapy   pathology   metabolism   MeSH
• Poly(ADP-ribose) Polymerase Inhibitors pharmacology   therapeutic use   MeSH
• Piperazines * pharmacology   MeSH
• DNA Damage drug effects   MeSH
• Cell Proliferation drug effects   MeSH
• Antineoplastic Combined Chemotherapy Protocols pharmacology   therapeutic use   adverse effects   MeSH
• Pyrazoles pharmacology   MeSH
• Pyrimidines MeSH
• Drug Synergism * MeSH
• Cell Survival drug effects   MeSH
• Xenograft Model Antitumor Assays * MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Mice MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

Platinum(IV) compounds possess distinct properties that set them apart from platinum(II) compounds. Often designed as prodrugs, they are reduced within cancer cells to their active platinum(II) form, enabling their cytotoxic effects. Their versatility also lies in their ability to be functionalized and conjugated with bioactive molecules to enhance cancer cell targeting. This report introduces new prodrugs that combine antitumor cisplatin with axially coordinated eugenol, leveraging their synergistic action to target cancer stem cells. A third bioactive ligand, 4-phenylbutyrate or octanoate, was added to further enhance biological activity, creating 'triple action' prodrugs. These new platinum(IV) prodrugs offer a novel approach to cancer therapy by improving targeting, increasing efficacy, overcoming drug resistance, and reducing tumor invasiveness while sparing healthy tissue.

• MeSH
• Cisplatin * pharmacology   MeSH
• Eugenol * pharmacology   MeSH
• Humans MeSH
• Cell Line, Tumor MeSH
• Neoplastic Stem Cells * drug effects   pathology   MeSH
• Colonic Neoplasms * drug therapy   pathology   MeSH
• Prodrugs * pharmacology   chemistry   MeSH
• Antineoplastic Agents * pharmacology   chemistry   MeSH
• Drug Synergism MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

The emergence of biofilm-induced drug tolerance poses a critical challenge to public healthcare management. Pseudomonas aeruginosa, a gram-negative opportunistic bacterium, is involved in various biofilm-associated infections in human hosts. Towards this direction, in the present study, a combinatorial approach has been explored as it is a demonstrably effective strategy for managing microbial infections. Thus, P. aeruginosa has been treated with cuminaldehyde (a naturally occurring phytochemical) and gentamicin (an aminoglycoside antibiotic) in connection to the effective management of the biofilm challenges. It was also observed that the test molecules could show increased antimicrobial activity against P. aeruginosa. A fractional inhibitory concentration index (FICI) of 0.65 suggested an additive interaction between cuminaldehyde and gentamicin. Besides, a series of experiments such as crystal violet assay, estimation of extracellular polymeric substance (EPS), and microscopic images indicated that an enhanced antibiofilm activity was obtained when the selected compounds were applied together on P. aeruginosa. Furthermore, the combination of the selected compounds was found to reduce the secretion of virulence factors from P. aeruginosa. Taken together, this study suggested that the combinatorial application of cuminaldehyde and gentamicin could be considered an effective approach towards the control of biofilm-linked infections caused by P. aeruginosa.

• MeSH
• Anti-Bacterial Agents * pharmacology   MeSH
• Benzaldehydes * pharmacology   MeSH
• Biofilms * drug effects   MeSH
• Cymenes pharmacology   MeSH
• Virulence Factors MeSH
• Gentamicins * pharmacology   MeSH
• Humans MeSH
• Microbial Sensitivity Tests * MeSH
• Pseudomonas aeruginosa * drug effects   physiology   MeSH
• Drug Synergism MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH

The current global scenario presents us with a growing increase in infections caused by fungi, referred to by specialists in the field as a "silent epidemic", aggravated by the limited pharmacological arsenal and increasing resistance to this therapy. For this reason, drug repositioning and therapeutic compound combinations are promising strategies to mitigate this serious problem. In this context, this study investigates the antifungal activity of the non-toxic, low-cost and widely available cationic polyelectrolyte Poly(diallyldimethylammonium chloride) (PDDA), in combination with different antifungal drugs: systemic (amphotericin B, AMB), topical (clioquinol, CLIO) and oral (nitroxoline, NTX). For each combination, different drug:PDDA ratios were tested and, through the broth microdilution technique, the minimum inhibitory concentration (MIC) of these drugs in the different ratios against clinically important Candida species strains was determined. Overall, PDDA combinations with the studied drugs demonstrated a significant increase in drug activity against most strains, reaching MIC reductions of up to 512 fold for the fluconazole resistant Candida krusei (Pichia kudriavzevii). In particular, the AMB-PDDA combination 1:99 was highly effective against AMB-resistant strains, demonstrating the excellent profile of PDDA as an adjuvant/association in novel antifungal formulations with outdated conventional drugs.

• MeSH
• Amphotericin B pharmacology   MeSH
• Antifungal Agents * pharmacology   MeSH
• Candida * drug effects   MeSH
• Drug Resistance, Fungal MeSH
• Candidiasis microbiology   drug therapy   MeSH
• Quaternary Ammonium Compounds * pharmacology   MeSH
• Humans MeSH
• Microbial Sensitivity Tests * MeSH
• Pichia MeSH
• Polyelectrolytes pharmacology   MeSH
• Polyethylenes pharmacology   chemistry   MeSH
• Drug Synergism MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH

Background/Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a growing global health problem closely linked to dietary habits, particularly high fructose consumption. This study investigates the combined effects of fructose and common food preservatives (sodium benzoate, sodium nitrite, and potassium sorbate) on the development and progression of MASLD. Methods: We utilized a human microbiota-associated mouse model, administering 10% fructose with or without preservatives for 11 weeks. Liver histology, hepatic gene expression (microarray analysis), biochemical markers, cytokine profiles, intestinal permeability, and gut microbiome composition (16S rRNA and Internal Transcribed Spacer (ITS) sequencing) were evaluated. Results: Fructose and potassium sorbate synergistically induced liver pathology characterized by increased steatosis, inflammation and fibrosis. These histological changes were associated with elevated liver function markers and altered lipid profiles. The treatments also induced significant changes in both the bacterial and fungal communities and disrupted intestinal barrier function, leading to increased pro-inflammatory responses in the mesenteric lymph nodes. Liver gene expression analysis revealed a wide range of transcriptional changes induced by fructose and modulated by the preservative. Key genes involved in lipid metabolism, oxidative stress, and inflammatory responses were affected. Conclusions: Our findings highlight the complex interactions between dietary components, gut microbiota, and host metabolism in the development of MASLD. The study identifies potential risks associated with the combined consumption of fructose and preservatives, particularly potassium sorbate. Our data reveal new mechanisms that are involved in the development of MASLD and open up a new avenue for the prevention and treatment of MASLD through dietary interventions and the modulation of the microbiome.

• MeSH
• Gene Expression drug effects   MeSH
• Fructose * adverse effects   MeSH
• Liver * metabolism   drug effects   MeSH
• Sorbic Acid pharmacology   MeSH
• Disease Models, Animal MeSH
• Mice, Inbred C57BL MeSH
• Mice MeSH
• Food Preservatives * pharmacology   adverse effects   MeSH
• Gastrointestinal Microbiome * drug effects   MeSH
• Drug Synergism MeSH
• Fatty Liver MeSH
• Animals MeSH
• Check Tag
• Male MeSH
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH