Magnetic Circular Dichroism of meso-Phenyl-Substituted Pd-Octaethylporphyrins.

Absorption and magnetic circular dichroism (MCD) spectra have been measured and theoretically simulated for a series of palladium octaethylporphyrins substituted at the meso positions with phenyl groups (n = 0-4). Analysis of the spectra included the perimeter model and time-dependent density functional theory (TDDFT) calculations. With the increasing number of phenyl substituents, the molecule is transformed from a positive hard (ΔHOMO > ΔLUMO) to a soft (ΔHOMO ≈ ΔLUMO) chromophore. This is manifested by a drastic decrease of the absorption intensity in the 0-0 region of the Q-band and by the strongly altered ratio of MCD intensities in the Q and Soret regions. Such behavior can be readily predicted using perimeter model, by analyzing frontier orbital shifts caused by various perturbations: alkyl and aryl substitution, insertion of a metal, and deviations from planarity. TDDFT calculations confirm the trends predicted by the perimeter model, but they fail in cases of less symmetrical derivatives to properly reproduce the MCD spectra in the Soret region. Our results confirm the power of the perimeter model in predicting absorption and MCD spectra of large organic molecules, porphyrins in particular. We also postulate, contrary to previous works, that the isolated porphyrin dianion is not a soft chromophore, but rather a strongly positive-hard one.

Activity of Zn and Mg phthalocyanines and porphyrazines in amyloid aggregation of insulin.

Formation of the deposits of protein aggregates-amyloid fibrils in an intracellular and intercellular space-is common to a large group of amyloid-associated disorders. Among the approaches to develop of therapy of such disorders is the use of agents preventing protein fibrillization. Polyaromatic complexes-porphyrins and phthalocyanines-are known as compounds possessing anti-fibrillogenic activity. Here, we explore the impact of related macrocyclic complexes-phthalocyanines (Pc) and octaphenyl porphyrazines (Pz) of Mg and Zn-on aggregation of amyloidogenic protein insulin. Pz complexes are firstly reported as compounds able to affect protein fibrillization. The effect of Pc and Pz complexes on the kinetics and intensity of insulin aggregation was studied by the fluorescent assay using amyloid sensitive cyanine dye. This has shown the impact of metal ion on the anti-fibrillogenic properties of macrocyclic complexes-the effect on the fibrillization kinetics of Mg-containing compounds is much more pronounced comparing to that of Zn analogues. Scanning electron microscopy experiments have demonstrated that filamentous fibrils are the main product of aggregation both for free insulin and in the presence of macrocyclic complexes. However, those fibrils are distinct by their length and proneness to lateral aggregation. The Pc complexes cause the increase in variation of fibrils length 0.9 to 2.7 nm in opposite to 1.4 to 2.0 nm for free insulin, whereas Pz complexes cause certain shortening of the fibrils to 0.8 to 1.6 nm. The averaged size of the fibrils population was estimated by dynamic light scattering; it correlates with the size of single fibrils detected by scanning electron microscopy.

Therapeutic potential of phages in autoimmune liver diseases.

Autoimmune liver disease (ALD) poses a difficult medical challenge, as there is a significant number of patients in whom current therapy offers questionable or no benefit, yet its side effects may be serious, including the development of malignancy. Bacterial viruses (phages) have been recognized increasingly as immunomodulators contributing to immune homeostasis and curbing inflammation. Accumulating data suggest that phages may be useful in immunotherapy of ALD. Phages have been shown to down-regulate the expression and/or production and activity of factors associated with hepatic injury [reactive oxygen species, Toll-like receptor (TLR)-4 activation, nuclear factor kappa B (NF-κB) activation, proinflammatory and procoagulant activities of platelets] and up-regulate the expression and/or production of factors demonstrated as playing a protective role [interleukin (IL)-10, IL-1 receptor antagonist].

Resonance Raman spectroscopy study of protonated porphyrin.

Resonance Raman microscopy was used to study the resonance Raman scattering of the diacid (diprotonated form) of free-base porphyrin (21H,23H-porphine) in a crystal powder and KBr pellets. Intensive lines in the spectral range between 100÷1000cm-1 have been detected and assigned as spectral manifestation of out-of-plane modes. The Raman spectra were simulated by means of DFT methods and compared with the experimental data. It is evident from experimental and theoretical results that the activation of out-of-plane modes arises from saddle distortion of the porphyrin macrocycle upon formation of its diprotonated form.

[Crusted scabies induced by topical corticosteroids: A case report]. / Gale hyperkératosique favorisée par l'utilisation de dermocorticoïdes : à propos d'un cas.

The frequency of scabies is increasing in France. Crusted (or Norwegian) scabies is a very contagious form of scabies because of the huge number of mites in the skin. It is observed in patients suffering from immunodepression, motor or sensory deficiency, or mental retardation. The clinical presentation, except for the classic manifestation of scabies, is characterized by crusted lesions. Treatment is not easy and requires hospitalization. Topical corticosteroids are frequently used for children's dermatological diseases. Their long-term and inappropriate application in an infested scabies child can induce crusted scabies. We report on a case of an 8-year-old boy who developed crusted scabies induced by topical corticosteroid application. We discuss the therapeutic aspects of this severe form of scabies.

Phages in the global fruit and vegetable industry.

From recent articles, we have learned that phages can constitute a promising alternative in the food industry to eliminate bacterial pathogens from seedlings in greenhouse and field environments, as well as from fresh-cut food products. The fruit and vegetable industry requires quite a different approach than the meat or dairy industry. Several factors can inhibit efficacy of phage treatment such as plant watering or washing ready-to-eat products (water may dilute therapeutic doses), UV irradiation or extensive spreading of phytopathogens by wind, insects or even humans. Spontaneously occurring anomalous weather conditions in different parts of the world also may have an enormous impact on phage persistence in cultivations and on yields. Despite that, some phage preparations are commercially available and, without doubt, are much safer than chemical treatments. Along with increasing worldwide fruit and vegetable consumption, plant diseases and human foodborne illnesses are becoming a serious economic problem, resulting in a focus on optimization of phage treatment.

Application of microbiological quantitative methods for evaluation of changes in the amount of bacteria in patients with wounds and purulent fistulas subjected to phage therapy and for assessment of phage preparation effectiveness (in vitro studies).

PURPOSE: Quantitative microbiological studies may provide important information required for successful phage therapy (PT), however methods for PT monitoring of purulent wounds and fistulas has never been reported before. Therefore our goal was to determine and apply microbiological quantitative methods (MQMs) for monitoring experimental PT. METHODS: Samples from agar plates with growing bacteria were collected using dry and wet sterile compresses, or swabs. After shaking the sample in saline the amount of bacteria in suspension was determined. The method was standardized. The MQM using compress was applied for comparison of in vitro activity of phage preparations with other agents for wound rinsing. The usefulness of this swabbing method was tested in the Phage Therapy Unit for monitoring of experimental PT of patients with chronic wounds or purulent fistulas. RESULTS: Minimum, maximum and standard deviation values used for standardization of the studied method showed that data repeatability was good; thus the method was used for quantitation of bacteria taken both from plates in vitro and patients samples. Effectiveness of phage preparations was compared to gentamicin in vitro. Phages were as effective as antibiotics in reducing the amount of bacteria on agar plates, and this effect was not only due to simple mechanical removal of bacteria, but dependent on their antibacterial activity. We have also observed that the results of bacteria quantitation may correlate with the local status of a wound/fistula in a particular stage of PT. CONCLUSION: The standardized swabbing method of bacteria quantitation can be used for PT monitoring. Presented MQMs are simple and may help to monitor the therapy process and to decide on its duration, frequency and a kind of the phage applied. They can also be applied in other antibacterial treatment strategies.

Human peripheral blood CD8+ CD28- T cells of renal allograft recipients do not express FOXP3 protein.

INTRODUCTION: In recent studies, the FOXP3 molecule has been suggested to be a marker of a suppressor subset of human CD8+ CD28- T cells based on correlations between the level of its mRNA and allograft function. Because this transcriptional factor produces a protein, we suggest that these correlations should focus on the FOXP3 protein. The aim of our study was to evaluate whether FOXP3 protein was present in cells of the CD8+ CD28- population in the peripheral blood of renal allograft recipients and whether the level of CD8+ CD28- FOXP3+ cells correlated with allograft function. METHODS: The study was performed on 30 renal allograft recipients with uneventful stable courses (n=18) or biopsy-proven chronic rejection (n=12). The immunosuppression was based on cyclosporine (n=12) or rapamycin (n=9). Peripheral blood mononuclear cells isolated from recipient blood samples were labeled with anti-CD8 and anti-CD28 MAbs conjugated with fluorochromes. After incubation, washing, and labeling using a PE anti-human FOXP3 Kit, we determined the percentage of cells by flow cytometry. RESULTS: FOXP3 protein expression was not observed either in the CD8+ CD28- population, or the whole populations of CD8+ or CD28- cells among patient groups. CONCLUSIONS: The expression of FOXP3 protein in CD8+ CD28- cells seems to be of a questionable value as a diagnostic tool for allograft function, it is probably not a marker for the CD8+ CD28- T cell subset.

The influence of external factors on bacteriophages--review.

The ability of bacteriophages to survive under unfavorable conditions is highly diversified. We summarize the influence of different external physical and chemical factors, such as temperature, acidity, and ions, on phage persistence. The relationships between a phage's morphology and its survival abilities suggested by some authors are also discussed. A better understanding of the complex problem of phage sensitivity to external factors may be useful not only for those interested in pharmaceutical and agricultural applications of bacteriophages, but also for others working with phages.

[Extracorporeal membrane oxygenation and severe traumatic brain injury. Is the ECMO-therapy in traumatic lung failure and severe traumatic brain injury really contraindicated?]. / Extrakorporale Membranoxygenierung und schweres Schädel-Hirn-Trauma : Ist der ECMO-Einsatz bei polytraumatisierten ARDS-Patienten mit schwerem SHT wirklich noch kontraindiziert?

Veno-venous extracorporeal membrane oxygenation (ECMO) may be lifesaving in multiple injured patients with acute respiratory distress syndrome (ARDS) due to chest trauma. To prevent circuit thrombosis or thromboembolic complications during ECMO systemic anticoagulation is recommended. Therefore, ECMO treatment is contraindicated in patients with intracranial bleeding. The management of veno-venous ECMO without systemic anticoagulation in a patient suffering from traumatic lung failure and severe traumatic brain injury is reported.

[Testicular torsion: a tricky diagnosis]. / Torsion testiculaire: une urgence piège.

In common urological practice, testicular torsion is one of the most serious emergencies. Consequences can be devastating for the patient, both physically and psychologically. The primary care physician should be able to quickly identify the pathology and refer immediately the patient to a center with surgical facilities. Rapid diagnosis provides the best chances to save the patient's testicle, which may suffer irreversible damage as soon as 6 hours after the onset of the symptoms. History and clinical examination remain the cornerstones of the diagnosis, and are often sufficient to select patients who need surgical exploration. If time allows it, Doppler Ultrasound can often help distinguish torsion from other scrotal conditions, but cannot be considered as a 100% diagnostic tool.

[Robotic partial nephrectomy: development and advantages]. / Développement de la néphrectomie partielle robotisée: avantages.

Surgery is the first line of treatment of renal cell carcinoma. For small tumours confined to the kidney (< or = 4 cm), partial tumour resection has logically become the standard treatment. When technically feasible, partial nephrectomy may be applied to treat tumors less than 7 cm, according to 2010 recommendations of the European Association of Urology. In addition, nephron-sparing surgery has proven to positively impact on quality of life. Robotic-assisted laparoscopy partial kidney resection has recently emerged. Its indications are as yet undergoing validation, while open surgery still remains the gold standard. For the patients, the consequences of this minimally invasive evolution are evident: The comfort and postoperative recovery are respectively greater and faster compared to conventional open surgery.

"Medical writing" and ghostwriting as ethical challenges in medical communication.

In the past years, it has become increasingly apparent that ghostwriting may erode the public trust in medical science and scientific publishing. It is estimated that approximately 10% of articles published in reputed journals are ghostwritten, and this rate may be even higher in some medical specialties. Although this practice is rather universally condemned, the propriety of participation of professional writers in producing papers remains an open question. Although some believe this practice should also be banned, others argue that such stringent policy would increase nonpublication and rather encourage disclosure; but should medical writers be included as authors on the final version of manuscripts? These and other questions should be solved to maintain the high scientific and ethical standards of medical communication and public trust in medicine.

Eradication of Enterococcus faecalis by phage therapy in chronic bacterial prostatitis--case report.

The treatment of three patients suffering from chronic bacterial prostatitis who were qualified for an experimental phage therapy protocol managed at the Phage Therapy Unit in Wroclaw is described. They had previously been treated unsuccessfully with long-term targeted antibiotics, autovaccines, and laser biostimulation. Rectal application of phage lysates targeted against Enterococcus faecalis cultured from the prostatic fluid gave encouraging results regarding bacterial eradication, abatement of clinical symptoms of prostatitis, and lack of early disease recurrence.

Molecular modification of T4 bacteriophage proteins and its potential application - review.

Bacteriophage T4 is a virus with well-known genetics, structure, and biology. Such techniques as X-ray crystallography, cryo-EM, and three-dimensional (3D) image reconstruction allowed describing its structure very precisely. The genome of this bacteriophage was completely sequenced, which opens the way for the use of many molecular techniques, such as site-specific mutagenesis, which was widely applied, e.g., in investigating the functions of some essential T4 proteins. The phage-display method, which is commonly applied in bacteriophage modifications, was successfully used to display antigens (PorA protein, VP2 protein of vvIBDV, and antigens of anthrax and HIV) on T4's capsid platform. As first studies showed, the phage-display system as well as site-specific mutagenesis may also be used to modify interactions between phage particles and mammalian cells or to obtain phages infecting species other than the host bacteria. These may be used, among others, in the constantly developing bacteriophage therapy. All manipulations of this popular bacteriophage may enable the development of vaccine technology, phage therapy, and other branches of biological and medical science.

Rate of paraplegia and mortality in elective descending and thoracoabdominal aortic repair in the modern surgical era.

BACKGROUND: The risk of paraplegia and hospital death is the major concern in the surgical repair of descending and thoracoabdominal aortic pathologies. For specific indications, the evolving technology of endovascular stent grafting is becoming increasingly popular. We reviewed our results for elective surgical repair of various aortic pathologies with respect to this innovative therapeutic background. METHODS: From July 1993 to April 2006, 56 patients (mean age 55+/-16 years, range 25 to 80 years, 62.5% males) underwent elective surgical repair of the descending (n=37, 66.1%) and thoracoabdominal aorta (n=19, 33.9%), including seven reoperations and five cases of previous endovascular stent grafting. The underlying pathologies were: degenerative aneurysm (n=21), type B aortic dissection (n=24), and Marfan's syndrome with a chronic type B dissection and an increase in the diameter of the descending aorta (n=11), respectively. Most patients were operated using deep hypothermic circulatory arrest. RESULTS: Thirty-day mortality was 5.4 % (n=3). Two patients died of myocardial infarction, one after coronary stent occlusion. Another patient died due to ventricular disruption at the side of the left ventricular apical vent. The rate of paraplegia was 3.6% (n=2) with one case of complete and one of incomplete paraplegia. Survival at five years was 78%. CONCLUSIONS: If modern surgical principles are used in elective descending and thoracoabdominal aortic repair, surgery can be performed with a low postoperative risk for hospital death or paraplegia. These results should be taken into account when evaluating alternative therapeutic strategies in patients with similar pathologies.

The influence of immuosuppressive therapy on the development of CD4+CD25+ T cells after renal transplantation.

A growing number of studies suggest that CD4(+)CD25(+) T regulatory (Treg) cells play a significant role to downregulate the immune response to alloantigens. In this study, we investigated the possible influence of immunosuppressive therapy, including cyclosporine (CsA) or rapamycin (sirolimus), on the level of CD4(+)CD25(+), CD4(+)CD25(+)FOXP3(+), and CD4(+)CD25(+)CTLA-4(+) T cells in the peripheral blood of renal allograft recipients. The study was performed on renal allograft recipients who displayed uneventful stable courses (RAR-S; n = 15) versus biopsy-proven chronic rejection (RAR-CH; n = 12). The patients were divided based on the immunosuppressive protocol: group 1 (prednisone+CsA+Aza) and group II (prednisone+sirolimus). The control group consisted of 10 healthy blood donors. We examined the expression of CD4, CD25, CTLA-4, and Foxp3 in peripheral blood T cells. Flow cytometry was performed with a FACSCalibur (BD Biosciences) instrument with data analyzed using Cell Quest software. The percentage of CD4(+)CD25(+)Foxp3(+) T cells in rapamycin (sirolimus) treated patients did not differ from that observed in healthy individuals, but was significantly higher compared with CsA-treated patients. CsA therapy resulted in a reduction in the percentage of CD4(+)CD25(+)CTLA-4(+) and CD4(+)CD25(+)Foxp3(+) regulatory T cells after renal transplantation in both groups (RAR-S and RAR-CH) compared with patients treated with rapamycin or to healthy donors. The type of immunosuppressive therapy (with or without calcineurin inhibitors) may have an important role in tolerance induction and graft function.

Concept of optimisation of the radiation protection system in the nuclear sector: management of individual cancer risks and providing targeted health care.

The paper discusses the provision of targeted health care to nuclear workers in Russia based on radiation-epidemiological estimates of cancer risks. Cancer incidence rates are analysed for the workers of the Institute of Physical Power Engineering (the first nuclear installation in the world) who were subjected to individual dosimetric monitoring from 1950 to 2002. The value of excess relative risk for solid cancers was found to be ERR Gy(-1) = 0.24 (95% CI: -4.22; 7.96). It has been shown that 81.8% of the persons covered by individual dosimetric monitoring have potential attributive risk up to 5%, and the risk is more than 10% for 3.7% of the workers. Among the detected cancer cases, 73.5% of the individuals show an attributive risk up to 5% and the risk is in excess of 10% for 3.9% of the workers. Principles for the provision of targeted health care, given voluntary health insurance, are outlined.