Covalent Immobilization of Organic Photosensitizers on the Glass Surface: Toward the Formation of the Light-Activated Antimicrobial Nanocoating

Two highly efficient commercial organic photosensitizers—azure A (AA) and 5-(4-aminophenyl)-10,15,20-(triphenyl)porphyrin (APTPP)—were covalently attached to the glass surface to form a photoactive monolayer. The proposed straightforward strategy consists of three steps, i.e., the initial chemical grafting of 3-aminopropyltriethoxysilane (APTES) followed by two chemical postmodification steps. The chemical structure of the resulting mixed monolayer (MIX_TC_APTES@glass) was widely characterized by X-ray photoelectron (XPS) and Raman spectroscopies, while its photoactive properties were investigated in situ by UV–Vis spectroscopy with α-terpinene as a chemical trap. It was shown that both photosensitizers retain their activity toward light-activated generation of reactive oxygen species (ROS) after immobilization on the glassy surface and that the resulting nanolayer shows high stability. Thanks to the complementarity of the spectral properties of AA and APTPP, the effectiveness of the ROS photogeneration under broadband illumination can be optimized. The reported light-activated nanocoating demonstrated promising antimicrobial activity toward Escherichia coli (E. coli), by reducing the number of adhered bacteria compared to the unmodified glass surface.     

Fatal rituximab‐associated lung injury syndrome in a patient treated with rituximab for recurrence of post‐transplant nephrotic syndrome

Rituximab (anti‐B CD20 ab.) in recently widely used in renal transplantation. Case history: A 10‐yr‐old patient with end‐stage renal failure due to multidrug‐resistant NS was transplanted with renal graft from deceased donor and presented immediate recurrence of NS. PF was started on day 3 and patient received MP pulses, however with no effect. Rituximab (4 × 375 mg/m²) was administered. Chest radiographs taken at that time were normal. Partial remission was achieved and the patient was discharged in good condition. Sequential recurrence appeared two wk afterward. Twelve sessions of PF were performed and six pulses of MP were given, effecting a partial remission. Three months after the last dose of rituximab, patient was admitted with increasing respiratory failure, requiring mechanical ventilation. Infectious background, including CMV, BKV, mycoplasma, and pneumocystis, was not confirmed. The patient was treated with MP pulses, IVIG, and a variety of antibiotics. Ground‐glass opacity was confirmed on lung CT images. Respiratory failure worsened, despite aggressive ventilation and patient passed away after three wk at ICU. A destruction of alveolar epithelium and extended pulmonary fibrosis was confirmed in the autopsy report. The case represents a fatal RALI.     

Proteasome 20S in multiple myeloma: comparison of concentration and chymotrypsin-like activity in plasma and serum

The ubiquitin-proteasome system is relevant in the pathobiology of many haematological malignancies, including multiple myeloma. The assessment of proteasome concentration and chymotrypsin-like (ChT-L) activity might constitute a new approach to diagnosis, prognosis and monitoring of anticancer treatment of patients with haematological malignancies and other diseases. The aim of our study was to determine which material, plasma or serum, is better for measuring chymotrypsin-like (ChT-L) activity and proteasome concentration. We analysed proteasome concentration and chymotrypsin-like (ChT-L) activity in 70 plasma and serum samples drawn from 28 patients at different treatment stages for multiple myeloma (MM) and 31 healthy volunteers. Proteasome ChT-L activity and concentration in multiple myeloma patients were significantly higher in plasma compared to serum. In this group we observed significant and positive correlations both between the plasma and serum proteasome ChT-L activity and plasma and serum proteasome concentration. The higher values of proteasome concentration and ChT-L activity in plasma than in serum and their better correlations with parameters of tumour load and prognosis suggest that plasma constitutes a better biological material for measuring ChT-L activity and proteasome concentration than serum in multiple myeloma patients.     

Congenitally corrected transposition of the great arteries with coexisting stenosis of pulmonary trunk valve and ventricular septum defect in a 55-year-old woman--a case report

Congenitally corrected transposition of the great arteries (CCTGA) is a rare cardiac malformation. This anomaly is characterised by atrioventricular as well as ventriculoarterial discordance. Isolated CCTGA may cause no symptoms until adult life. Most CCTGA cases with concomitant cardiac abnormalities are symptomatic and are therefore usually diagnosed in childhood. In the majority of patients, congestive heart failure secondary to right ventricular dysfunction occurring by the fifth or sixth decade enables diagnosis. We present an oligosymptomatic 55-year-old woman with corrected transposition of the great arteries and coexisting stenosis of pulmonary trunk valve and ventricular septum defect.     

Glutamate receptor ligands attenuate allodynia and hyperalgesia and potentiate morphine effects in a mouse model of neuropathic pain

Recent studies have indicated that metabotropic glutamate receptors mGluR5, mGluR2/3 and mGluR7 are present in the regions of central nervous system important for nociceptive transmission, but their involvement in neuropathic pain has not been well established. We demonstrated that acute and chronic administration of MPEP (mGluR5 antagonist), LY379268 (mGluR2/3 agonist), and AMN082 (mGluR7 agonist) attenuated allodynia (von Frey test) and hyperalgesia (cold plate test) as measured in Swiss albino mice on day seven after chronic constriction injury (CCI) to the sciatic nerve. Moreover, single administration of MPEP (30 mg/kg; i.p.) or LY379268 (10mg/kg; i.p.) injected 30 min before morphine potentiated morphine's effects (20mg/kg; i.p.) in the mouse CCI model, as measured by both the tests mentioned above. However, a single administration of AMN082 (3mg/kg; i.p.) potentiated the effects of a single morphine injection (20mg/kg; i.p.) in the von Frey test only. Chronic administration (7 days) of low doses of MPEP, LY379268 or AMN082 (all drugs at 3mg/kg; i.p.) potentiated the effects of single doses of morphine (3, 10, and 20mg/kg; i.p.) administered on day seven; however, AMN082 only potentiated the effect in the cold plate test. Additionally, the same doses of MPEP and LY379268 (but not AMN082) chronically co-administered with morphine (40 mg/kg; i.p.) attenuated the development of morphine tolerance in CCI-exposed mice. Our data suggest that mGluR5, mGluR2/3, and mGluR7 are involved in injury-induced plastic changes in nociceptive pathways and that the mGluR5 and mGluR2/3 ligands enhanced morphine's effectiveness in neuropathy, which could have therapeutic implications.     

Minocycline and pentoxifylline attenuate allodynia and hyperalgesia and potentiate the effects of morphine in rat and mouse models of neuropathic pain

Recent research has shown that microglial cells which are strongly activated in neuropathy can influence development of allodynia and hyperalgesia. Here we demonstrated that preemptive and repeated i.p., administration (16 h and 1 h before injury and then after nerve ligation twice daily for 7 days) of minocycline (15; 30; 50 mg/kg), a potent inhibitor of microglial activation, significantly attenuated the allodynia (von Frey test) and hyperalgesia (cold plate test) measured on day 3, 5, 7 after chronic constriction injury (CCI) in rats. Moreover, the 40% improvement of motor function was observed. In mice, i.p., administration of minocycline (30 mg/kg) or pentoxifylline (20 mg/kg) according to the same schedule also significantly decreased allodynia and hyperalgesia on day 7 after CCI. Antiallodynic and antihyperalgesic effect of morphine (10 mg/kg; i.p.) was significantly potentiated in groups preemptively and repeatedly injected with minocycline (von Frey test, 18 g versus 22 g; cold plate test, 13 s versus 20 s in rats and 1.2 g versus 2.2 g; 7.5 s versus 10 s in mice; respectively) or pentoxifylline (1.3 g versus 3 g; 7.6 s versus 15 s in mice; respectively). Antiallodynic and antihyperalgesic effect of morphine (30 μg; i.t.) given by lumbar puncture in mice was also significantly potentiated in minocycline-treated group (1.2 g versus 2.2 g; 7.5 s versus 11 s; respectively). These findings indicate that preemptive and repeated administration of glial inhibitors suppresses development of allodynia and hyperalgesia and potentiates effects of morphine in rat and mouse models of neuropathic pain.     

Cost-effectiveness of strong opioids focussing on the long-term effects of opioid-related fractures: a model approach

Opioid analgesics are known to impact on the central nervous system (CNS). These CNS side effects, such as dizziness and confusion, have been shown to lead to an increased risk of falling with subsequent fractures in elderly patients being treated with opioids. The risk of experiencing fractures has been shown to be dependent on the substance administered. Therefore, a health economic model was developed to investigate the cost-effectiveness of the most commonly used strong opiods in Germany, focussing on opioid-related fractures. By means of a Markov model, the consequences of hip, spine and forearm fractures due to the prior administration of transdermal (TD) buprenorphine, TD fentanyl, oral oxycodone as well as oral morphine were assessed from the perspectives of the German statutory health insurance (SHI) and the German social security (GSS) system over a time horizon of 6 years. The most frequently prescribed strength/package-size combinations of these opioids were taken into consideration, including generics where available. The results of the present analysis predict that TD buprenorphine is dominant compared to TD fentanyl and oxycodone by showing better effects [life years gained/quality adjusted life years (QALY) gained] at lower cost. From the SHI perspective, the incremental cost-effectiveness ratio (ICER) compared to morphine is € 6,801.61 per life year gained, and € 7,766.11 per QALY gained. From the GSS perspective, the ICER is € 2,496.77 per life year gained and € 2,850.83 per QALY gained. The model is robust regarding probabilistic variations of all parameters in the sensitivity analyses. Focussing on fractures due to the prior administration of strong opioids, TD buprenorphine is less costly and more effective than TD fentanyl and oxycodone and represents a cost-effective treatment option versus morphine in patients with chronic pain from both the SHI and GSS perspective in Germany.     

Polymorphisms in the growth hormone receptor: a case-control study in breast cancer

The human growth hormone receptor (GHR) mediates the effects of growth hormone (GH1), starting a signalling cascade that is involved in the regulation of proliferation, differentiation and apoptosis. Recently, an isoform of the GHR gene lacking exon 3 (GHRd3) was associated with accelerated responsiveness to growth hormone. In this study, we investigated the association of the GHRd3 polymorphism with breast cancer risk and performed a haplotype analysis with 3 additional single nucleotide polymorphisms (SNPs) (Gly186Gly, Cys440Phe and Ile544Leu) in the GHR coding region in a Polish cohort. We did not observe any effect of the 4 polymorphisms on breast cancer risk. Neither did the 3 most common haplotypes influence breast cancer risk. However, a rare haplotype (dGGC), containing the GHRd3 allele, was associated with a decreased breast cancer risk (OR 0.30, 95% CI 0.11-0.80).