Urogenital tuberculosis, the cause of ineffective antibacterial therapy for urinary tract infections

Background: Urogenital tuberculosis (UGTB) is one of the great imitators; it is commonly masked by urinary tract infections (UTIs). We aimed to estimate how many UGTB patients were among patients with a long history of UTIs. Material and Methods: A total of 244 patients with recurrent UTIs and suspected UGTB were enrolled in an open, noncomparative prospective study. Their urine and expressed prostate secretion or ejaculate were cultured (a total of 1446 samples), and 421 isolates with growth of ⩾10 4 colony-forming units (CFU)/ml were investigated for drug resistance. Typically, UGTB diagnosis is made by individual case. Results: All 244 patients had a long history of recurrent UTIs (on average, 7.9 ± 3.4 years); all received at least five courses of antibacterial therapy without good result. UGTB was diagnosed in 63 (25.8%), and in 41 of these (65.1%), there was comorbidity of UTI and UGTB. Of 1446 samples investigated, 421 (29.1%) were positive, and 1025 were negative. Escherichia coli was found in 57.3% of gram-negative microflora and in 29.0% only among all uropathogens. E. coli was resistant to amoxicillin/clavulanate in 51.5–57.1%, to cefotaxime in 50.0–52.0%, to gentamycin in 33.3–59.5%, to ciprofloxacin in 63.2–66.7%, to levofloxacin in 54.8–45.2%, and to nitrofurantoin in 23.5–20.8% in 2015 and 2016, respectively. If, in 2015, all isolates of E. coli were susceptible to imipenem, in 2016, 7.1% of strains were resistant to this antibiotic. Level of drug-resistance was higher in 2016, excluding only levofloxacin and nitrofurantoin. Conclusions: Total prevalence of UGTB among UTI patients with poor results of antibacterial therapy was 25.8%. Comorbidity of UTI and UGTB was diagnosed in 65.1%

Composite Bone Cements with Enhanced Drug Elution

Antibiotic-loaded bone cement (ALBC) has become an indispensable material in orthopedic surgery in recent decades, owing to the possibility of drugs delivery to the surgical site. It is applied for both infection prophylaxis (e.g., in primary joint arthroplasty) and infection treatment (e.g., in periprosthetic infection). However, the introduction of antibiotic to the polymer matrix diminishes the mechanical strength of the latter. Moreover, the majority of the loaded antibiotic remains embedded in polymer and does not participate in drug elution. Incorporation of the various additives to ALBC can help to overcome these issues. In this paper, four different natural micro/nanoscale materials (halloysite, nanocrystalline cellulose, micro- and nanofibrillated cellulose) were tested as additives to commercial Simplex P bone cement preloaded with vancomycin. The influence of all four materials on the polymerization process was comprehensively studied, including the investigation of the maximum temperature of polymerization, setting time, and monomer leaching. The introduction of the natural additives led to a considerable enhancement of drug elution and microhardness in the composite bone cements compared to ALBC. The best combination of the polymerization rate, monomer leaching, antibiotic release, and microhardness was observed for the sample containing nanofibrillated cellulose (NFC)

Inhibitory Effects of 5-Fluorouracil on the Growth of 4-Hydroxytamoxifen-Resistant and Sensitive Breast Cancer Cells

Cancer is one of the leading causes of death worldwide, accounting for about 10 million deaths a year, or nearly one in six deaths. The most common types of cancer are breast, colorectal, lung, and prostate cancers. Prolonged application of hormone drugs leads to the development of resistance. The development of agents with high activity against resistant cells is a challenge. It is important to create novel targeted compounds and search for active molecules among those previously developed. The study aimed to evaluate the sensitivity of 4-hydroxytamoxifen-resistant cells to 5-fluorouracil (5-FU) and analyse the signalling pathways that are regulated by 5-FU in breast cancer cells. Antiproliferative activity of compounds was assessed by the MTT assay, and immunoblotting was used to evaluate the expression of proteins in breast cancer cells. Activity of 5-FU was evaluated on parental MCF7 cells and a cell subline with resistance to 4-hydroxytamoxifen (HT), named MCF7/HT. The MCF7/HT cells showed high sensitivity to 5-FU. Expression of oestrogen receptor α (ERα, a key driver of breast cancer growth) in MCF7 and MCF7/HT cells was not sensitive to 5-FU treatment. In both parental and resistant cells, 5-FU induced changes in the activity of several signalling proteins. 5-FU activated AKT, extracellular signal-regulated kinase 1/2 (ERK 1/2) and upregulated cyclin D1 expression. The data suggest that 5-FU should be further investigated as a chemotherapeutic for hormone-resistant cancers; the combination of 5-FU with novel apoptosis inducer LCTA-3344 is considered effective to inhibit the growth of breast cancer cells, including those that are hormone-resistant

Quantum transport at Dirac point enables graphene for terahertz heterodyne astronomy

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