Second generation triazoles are widely used as first-line drugs for the treatment of invasive fungal infections, including aspergillosis and candidiasis. This class, along with itraconazole, voriconazole, posaconazole, and isavuconazole, is characterized by a broad range of activity, however, individual drugs vary considerably in safety, tolerability, pharmacokinetics profiles, and interactions with concomitant medications. The interaction may be encountered on the absorption, distribution, metabolism, and elimination (ADME) step. All triazoles as inhibitors or substrates of CYP isoenzymes can often interact with many drugs, which may result in the change of the activity of the drug and cause serious side effects. Drugs of this class should be used with caution with other agents, and an understanding of their pharmacokinetic profile, safety, and drug-drug interaction profiles is important to provide effective antifungal therapy. The manuscript reviews significant drug interactions of azoles with other medications, as well as with food. The PubMed and Google Scholar bases were searched to collect the literature data. The interactions with anticonvulsants, antibiotics, statins, kinase inhibitors, proton pump inhibitors, non-nucleoside reverse transcriptase inhibitors, opioid analgesics, benzodiazepines, cardiac glycosides, nonsteroidal anti-inflammatory drugs, immunosuppressants, antipsychotics, corticosteroids, biguanides, and anticoagulants are presented. We also paid attention to possible interactions with drugs during experimental therapies for the treatment of COVID-19.
Background: We aimed to assess a liposomal fat-soluble vitamin formulation containing vitamin K2 with standard treatment in cystic fibrosis (CF). Methods: A multi-center randomized controlled trial was carried out in 100 pancreatic-insufficient patients with CF. The liposomal formulation contained vitamin A as retinyl palmitate (2667 IU daily) and beta-carotene (1333 IU), D3 (4000 IU), E (150 IU), K1 (2 mg), and K2 as menaquinone-7 (400 µg). It was compared with the standard vitamin preparations in the closest possible doses (2500 IU, 1428 IU, 4000 IU, 150 IU, 2.14 mg, respectively; no vitamin K2) over 3 months. Results: Forty-two patients finished the trial in the liposomal and 49 in the control group (overall 91 pts: 22.6 ± 7.6 years, 62.6% female, BMI 19.9 ± 2.8 kg/m2, FEV1% 70% ± 30%). The main outcome was the change of vitamin status in the serum during the study (liposomal vs. standard): all-trans-retinol (+1.48 ± 95.9 vs. −43.1 ± 121.4 ng/mL, p = 0.054), 25-hydroxyvitamin D3 (+9.7 ± 13.4 vs. +2.0 ± 9.8 ng/mL, p = 0.004), α-tocopherol (+1.5 ± 2.5 vs. −0.2 ± 1.6 µg/mL, p < 0.001), %undercarboxylated osteocalcin (−17.2 ± 24.8% vs. −8.3 ± 18.5%, p = 0.061). The secondary outcome was the vitamin status at the trial end: all-trans-retinol (370.0 ± 116.5 vs. 323.1 ± 100.6 ng/mL, p = 0.045), 25-hydroxyvitamin D3 (43.2 ± 16.6 vs. 32.7 ± 11.5 ng/mL, p < 0.001), α-tocopherol (9.0 ± 3.1 vs. 7.7 ± 3.0 µg/mL, p = 0.037), %undercarboxylated osteocalcin (13.0 ± 11.2% vs. 22.7 ± 22.0%, p = 0.008). Conclusion: The liposomal fat-soluble vitamin supplement containing vitamin K2 was superior to the standard form in delivering vitamin D3 and E in pancreatic-insufficient patients with CF. The supplement was also more effective in strengthening vitamin K-dependent carboxylation, and could improve vitamin A status.
This study aims to assess the effect of an increase in daily physical activity to prevent cognitive decline, sustain brain volumes and maintain healthy biomarker levels in previously inactive (< 7,000 steps/day) mild cognitive impairment (MCI) subjects aged 50-65 years. In total, 198 subjects with MCI (assessed using the Montreal Cognitive Assessment test) will be recruited and randomised into two groups: active and passive. The active group will be instructed, encouraged and motivated to increase their physical activity to a moderate level (≥ 10,000 steps/day), while the passive group should maintain their normal activity levels. All subjects will undergo cognitive assessment, neuroimaging and biomarker tests before and after a one-year intervention. During the intervention, physical activity will be measured by the Fitbit Inspire HR wristband. The study was registered in the German Clinical Trials Register database (registration no. DRKS00020943, date of registration: 09.03.2020, protocol version: 1.0).
Zespół Klippla-Trénaunaya to rzadki zespół charakteryzujący się występowaniem malformacji naczyń włosowatych i żylnych oraz przerostem kończyn z obecnością lub bez malformacji limfatycznych. Zmiany te najczęściej występują od urodzenia lub mogą być zauważalne we wczesnym dzieciństwie. Zespół Klippla-Trénaunaya zwykle występuje sporadycznie. Aktualne badania nad patogenezą tego zespołu wskazują na istotną rolę mutacji genu PIK3CA. Dzięki odkryciu patomechanizmu powstawania zespołu Klippla-Trénaunaya i roli szlaku mTOR istnieją potencjalne możliwości leczenia tego zespołu sirolimusem. W zespole Klippla-Trénaunaya mogą współwystępować zaburzenia neurologiczne takie jak: udar krwotoczny, udar niedokrwienny, padaczka, malformacje naczyniowe ośrodkowego układu nerwowego, przerost jednej półkuli mózgu. Celem tej pracy jest przedstawienie przypadku 17-letniej pacjentki z zespołem Klippla-Trénaunaya i porównanie jej obecnego stanu z obrazem klinicznym w chwili rozpoznania w wieku 6 lat oraz przegląd aktualnej literatury na ten temat.
Eosinophils are found in the mucosa of the healthy gastrointestinal tract, but they also often accompany gastrointestinal diseases. We hypothesized that a positive correlation exists between blood eosinophil count and colonic eosinophil mucosal density in children. Electronic health records regarding 181 colonoscopies, performed with biopsy in the years 2019–2022, were screened for information on blood and colonic eosinophil count, age, sex, diagnoses, weight, height, white blood cell (WBC) count, serum C-reactive protein (CRP), and total IgE concentration. The median age (IQR) of the 107 included children (109 colonoscopies) was 12.4 years (8.1–15.5); 32 presented with blood eosinophilia (29.3%). The median eosinophil density/high-power field in the colonic mucosa was 22.5 (9–31). We found a weak correlation between colonic mucosal eosinophil density and blood eosinophil count (r = 0.295, 95% CI 0.108–0.462, p = 0.0018). This association was more pronounced in patients with elevated CRP (r = 0.529, 95% CI 0.167–0.766, p = 0.0054) and older than 12.4 years (r = 0.448, 95% CI 0.197–0.644, p = 0.00068). Peripheral blood eosinophilia might hint at increased mucosal colonic eosinophil density, especially in older children and in the presence of systemic inflammation. However, it seems unlikely that blood and colonic eosinophilia are strongly linked in younger children. Studies in adults are warranted.
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