Bromine Substitution Improves the Photothermal Performance of π-Conjugated Phototheranostic Molecules.

NIR-II fluorescence imaging-guided photothermal therapy (PTT) has been widely investigated due to its great application potential in tumor theranostics. PTT is an effective and non-invasive tumor treatment method that can adapt to tumor hypoxia; nevertheless, simple and effective strategies are still desired to develop new materials with excellent PTT properties to meet clinical requirements. In this work, we developed a bromine-substitution strategy to enhance the PTT of A-D-A'-D-A π-conjugated molecules. The experimental results reveal that bromine substitution can notably enhance the absorptivity (ϵ) and photothermal conversion efficiency (PCE) of the π-conjugated molecules, resulting in the brominated molecules generating two times more heat (ϵ808 nm ×PCE) than their unsubstituted counterpart. We disclose that the enhanced photothermal properties of bromine-substituted π-conjugated molecules are a combined outcome of the heavy-atom effect, enhanced ICT effect, and more intense bromine-mediate intermolecular π-π stacking. Finally, the NIR-II tumor imaging capability and efficient PTT tumor ablation of the brominated π-conjugated materials demonstrate that bromine substitution is a promising strategy for developing future high-performance NIR-II imaging-guided PTT agents.

Unimolecular micelles from star-shaped block polymers by photocontrolled BIT-RDRP for PTT/PDT synergistic therapy.

Unimolecular micelles (UIMs) exhibit promising potential in the precise diagnosis and accurate treatment of tumor tissues, a pressing problem in the field of medical treatment, because of their perfect stability in the complex and variable microenvironment. In this study, porphyrin-based four-armed star-shaped block polymers with narrow molar mass dispersity (D = 1.34) were facilely prepared by photocontrolled bromine-iodine transformation reversible-deactivation radical polymerization (BIT-RDRP). A photothermal conversion dye, ketocyanine, was covalently linked onto the PEG and then introduced into the polymers through a "grafting onto" strategy to obtain polymeric nanomaterial, THPP-4PMMA-b-4P(PEGMA-co-APMA)@NIR-800, with dual PTT/PDT function. The resulting polymers could form monodispersed UIMs in the water below critical aggregation concentration, meanwhile maintaining the capacities of singlet oxygen release and photothermal conversion. Importantly, the UIMs displayed excellent biocompatibility while exerting superior PTT and/or PDT therapeutic effects under the irradiation of specific wavelengths of light, according to in vitro cellular experiments, which is expected to become a new hot spot for cancer therapy and anti-tumor research. Overall, stable and powerful UIMs with dual PTT/PDT function is provided, which are expected to be competitive candidates in cancer therapy.

Bromamine T, a stable active bromine compound, prevents the LPS­induced inflammatory response.

Inflammation is the most common cause of most acute and chronic debilitating diseases. Towards unveiling novel therapeutic options for patients with such complications, N­bromotaurine (TauNHBr) has emerged as a potential anti­inflammatory agent; however, its therapeutic efficacy is hindered due to its relatively poor stability. To address this challenge, the present study focused on examining the effects of a stable active bromine compound, named bromamine T (BAT). The present study examined the protective properties of BAT against lipopolysaccharide (LPS)­mediated inflammation in vitro, by using LPS­stimulated murine J774.A1 macrophages (Mφs), as well as in vivo, by using a murine LPS­mediated air­pouch model. Additionally, its efficacy was compared with that of taurine, a known potent anti­inflammatory molecule. In LPS­stimulated J774A.1 Mφs, BAT and taurine were very effective in reducing the secretion of pro­inflammatory mediators. The in vitro experiments indicated that LPS­mediated inflammation was attenuated due to the protective properties of BAT and of taurine, probably through the inhibition of phosphorylated p65 NF­κB subunit (Ser 536) nuclear translocation. The in vivo experiments also revealed that BAT and taurine inhibited LPS­mediated inflammation by reducing total cell/polymorphonuclear cell (PMN) infiltration in the air­pouch and by decreasing pouch wall thickness. The analysis of exudates obtained from pouches highlighted that the inhibitory effects of BAT and taurine on the secretion of pro­inflammatory cytokines were similar to those observed in vitro. Notably, the effect of BAT at the highest concentration tested was superior to that of taurine at the highest concentration. Taken together, the findings of the present study indicate that BAT prevents the LPS­induced inflammatory response both in vitro and in vivo.

[The multifunctional therapy of various forms of irritable bowel syndrome]. / Mnogofunktsional'naya terapiya pri razlichnykh formakh sindroma razdrazhennogo kishechnika.

Irritable bowel syndrome (IBS) is a pathological condition characterized by heterogeneous etiology, pathogenesis, and clinical symptoms. These characteristics dictate the necessity of prescribing multiple medications for the treatment of IBS. Such compulsory polypharmacy inadvertently enhances the risk of adverse reactions to the treatment, increases its cost, and impairs compliance on the part of the patients. The objective of the present study was to evaluate the effectiveness of the administration of the clorine-bromine brine with the use of sinusoidal modulated current electrophoresis (SMC-phoresis) for the treatment of different forms of IBS. THE PATIENTS AND METHODS: We examined and treated 80 patients with different forms of IBS. The patients were divided into two equal groups comprised of 40 patients each. The patients of the study group were treated with the use of SMС-phoresis of the bromine-chlorine brine based at the «Varzi-yatchi¼ spa and health resort (the Udmurt Republic) making use of the sparing or stimulating techniques depending on the type of IBS. Each therapeutic course consisted of 10-12 sessions. The patients in the group of comparison received the standard pharmaceutical treatment for IBS (myotropic anti-spasmodics and lactulose). The emphasis was laid on the evaluation of dynamics of the intestinal motor function in different variants of IBS with the use of the EGS-4M apparatus based on the GSRS questionnaire (Gastrointestinal Symptom Rating Scale). Special attention was given to the interpretation of the main gastrointestinal syndromes and the evaluation of the quality of life of the patients in the course of the treatment and after its completion. RESULTS: Тhe main symptoms of IBS after a course of SMC-phoresis with the natural brine were significantly less pronounced compared to those in the patients managed by means of standard pharmacotherapy. Positive dynamics in the clinical picture of the disease had beneficial influence on the quality of life of the patients which approached that of the healthy subjects in the group of comparison. The results of colonography suggested the presence of various types of disturbances of motor function of the intestines. SMC-phoresis of the natural chlorine-bromine brine had a positive influence on dyskinesia associated with diarrhea and constipation associated with IBS, while the effect of the standard pharmaceutical treatment was unidirectional and significantly inferior to it in terms of efficiency. CONCLUSION: The use of complementary therapy can provide a better clinical outcome of IBS and to a greater extent improve the quality of life of the patients presenting with various forms of this pathology.

[Balneotherapy to the treatment of patients with hysteromyoma].

Patients with hysteromyoma are treated by radon therapy and balneotherapy with the use of iodine-bromine water. Radon therapy is known to produce a more pronounced effect than drinking of iodine-bromine water. At the same time, the latter treatment activates hyperemic processes in the skin and mucous membranes and thereby decreases density of myometrial nodular lesions and compact foci. It is concluded that radon therapy and the use of iodine-bromine water are the methods of choice for balneotherapy of patients with hysteromyoma.

Radioactive derivatives of 2-methyl-1, 4-naphthoquinol bis (diphosphate salt) as anti-cancer drugs with high LET radiations.

From the results of the alpha-particle track autoradiography, the alkaline phosphatase studies, the biodistribution investigations and the therapeutic experiments with the transplanted Franks and Hemmings (1978) adenocarcinoma of the rectum in mice, an important finding is the striking selectivity of the uptake of the compound 6-211 At-astato-2-methyl-1, 4-naphthoquinol bis (diphosphate salt), after intraperitoneal injection into the tumour cell nuclei and in many cases into the nuclei of tumour stem cells, together with negligible uptake into normal colon and narrow. The compound, 6-211 At-astato-2-methyl-1, 4-naphthoquinol bis (diphosphate salt) has been found to cure about two-thirds of the transplanted adenocarcinoma of the rectum in mice after a single intra-peritoneal injection of 3-4 microCi. This approach can be regarded as a form of metabolically-directed drug targetting on to a tumour product which is an enzyme, an alkaline phosphatase isozyme, present in the cells of some tumours. The compound is being studied further from the point of view of possible human therapeutic applications.

Bromocriptine treatment of acromegaly.

The effects of oral bromocriptine in acromegaly have been studied. A dose of 5 mg six-hourly suppressed circulating growth hormone (GH) levels in nine out of 11 patients treated for seven to 11 weeks. This was associated with considerable clinical improvement in all patients, with abolition of excessive sweating, reduction in soft-tissue thichening, loosening of rings, decrease in shoe size, improvement in facial features, and loosening of dentures. Metabolic changes included improvement in glucose tolerance and reduction in hydroxyproline excretion. Unlike the actions of growth hormone release inhibiting hormone the suppression of GH was not accompanied by a reduction in insulin or glucagon secretion, though prolactin levels were suppressed. Side effects other than mild constipation were not seen when the full dose regimen was reached by slowly increasing the dose from 2-5 mg once daily. Bromocriptine holds promise as a safe and orally effective medical treatment to augment surgical or radiotherapeutic measures directed at the pituitary tumour. Its efficacy during longterm administration remains to be established.

[Behavior of the immunoglobin level in the serum of patients with ovarian neoplasms]. / Verhalten des Immunglobulinspiegels im Blutserum bei Patientinnen mit Carcinoma ovarii

In 18 patients with the histological proved Ca ovarii we have examined the level of serum immunoglobulins IgG, IgA and IgM in blood during the combined therapy by two cytostatics (Cyclophosphamide, Cytembena) in a week's intervals. The serum immunoglobins IgG, IgA, IgM was followed by the simple radial immunodiffusion technic by Manchini in 2% agar gel with the standard fa Sevac (CSSR). The level of IgG sank at least 10% in 10 patients, the level of IgA and IgG in 9 patients. We have also followed every month the level of the serum immunoglobins at the long times administration of several peroral doses of Cyclophosphamid in 9 patients. At this long times administration the serum immunoglobins IgG and IgA were found responsible in their reduced synthesis than the IgM.

[Determination of the nucleolar coefficient in lymphocytes in chemotherapeutically treated patients with ovarian carcinoma]. / Bestimmung des Nukleolarkoeffizienten in den Lymphozyten bei chemotherapeutisch behandelten Patientinnen mit Ovarialkarzinom

At the total evaluation of the base values of lymphocytes in the patients with Ca ovariorum a lower number of lymphocytes was found than in the healthy population. At the same time the lymphocytes in the patients with Ca contained a lower number of nucleoli which are capable of the synthesis RNA (i.e. nucleoli ringsingers and active) and a higher number of nucleoli irreversible unable of the synthesis of RNA, i.c. micronucleoli. So the value of the nucleolar coefficient was rised, too, in these patients. It seems, that the described changes were dependent of the clinic condition of our patients, in some cases they preceded the state. This method is utilised at the IInd Obstetric Gynaec. Clin. in Prague for the long time cytostatic therapy.