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.

The Impact of Substitutions at Positions 1 and 8 of Fluoroquinolones on the Activity Against Mutant DNA Gyrases of Salmonella Typhimurium.

Although many drug-resistant nontyphoidal Salmonella (NTS) infections are reported globally, their treatment is challenging owing to the ineffectiveness of the currently available antimicrobial drugs against resistant bacteria. It is therefore essential to discover novel antimicrobial drugs for the management of these infections. In this study, we report high inhibitory activities of the novel fluoroquinolones (FQs; WQ-3810 and WQ-3334) with substitutions at positions R-1 by 6-amino-3,5-difluoropyridine-2-yl and R-8 by methyl group or bromine, respectively, against wild-type and mutant DNA gyrases of Salmonella Typhimurium. The inhibitory activities of these FQs were assessed against seven amino acid substitutions in DNA gyrases conferring FQ resistance to S. Typhimurium, including high-level resistant mutants, Ser83Ile and Ser83Phe-Asp87Asn by in vitro DNA supercoiling assay. Drug concentrations of WQ compounds with 6-amino-3,5-difluoropyridine-2-yl that suppressed DNA supercoiling by 50% (IC50) were found to be ∼150-fold lower than ciprofloxacin against DNA gyrase with double amino acid substitutions. Our findings highlight the importance of the chemical structure of an FQ drug on its antimicrobial activity. Particularly, the presence of 6-amino-3,5-difluoropyridine-2-yl at R-1 and either methyl group or bromine at R-8 of WQ-3810 and WQ-3334, respectively, was associated with improved antimicrobial activity. Therefore, WQ-3810 and WQ-3334 are promising candidates for use in the treatment of patients infected by FQ-resistant Salmonella spp.

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.

Effects of salso-bromo-iodine thermal water in children suffering from otitis media with effusion: a randomized controlled pilot study.

BACKGROUND: Otitis media with effusion (OME) is an ear disorder defined by the presence of fluid in the middle ear without signs or symptoms of acute infection. The aim of this randomised and controlled pilot study was to evaluate whether the treatment with a watery salsobromo- iodine solution, administered by nasal douche, could induce ear healing better than isotonic saline in children with OME. METHODS: The study was randomized, single-blind, and controlled. Study group (40 children) was treated with salso-bromo-iodine thermal water solution and Control group (40 children) was treated with isotonic saline; both compounds were administered by nasal nebulization with Rinowash nasal douche twice/day for 10 days a month for 3 consecutive months. Tympanogram and audiometry were performed at baseline and after treatment. RESULTS: Salso-bromo-iodine therapy shows better and statistically significant trend after treatment when compared to control group both for tympanogram results with greater improvement (represented by type C tympanogram; p = 0.031) and healing (represented by type A tympanogram; p < 0.001) and audiometric results, with higher presence of patients with normal hearing (p = 0.029) and lower among patients with moderate hypoacusis (p = 0.014). CONCLUSIONS: The current randomized-controlled pilot study demonstrated that watery salso-bromo-iodine solution was effective in the treatment of children with OME.

[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.

[The experience with the application of non-medicamental methods for the treatment of the patients presenting with gastroesophageal reflux disease].

The present study was designed to estimate the effectiveness of structural resonance electromagnetic therapy, acupuncture, and DMW therapy applied for the treatment of the patients presenting with gastroesophageal reflux disease. It was shown that acupuncture produced beneficial effect on the functional state of oesophagus and neurohumoral regulation of the lower oesophageal sphincter; moreover, it suppressed the acid-producing activity of the stomach. Structural resonance electromagnetic therapy, acupuncture, and DMW therapy decreased the level of vasoactive intestinal peptide in blood sera of the patients with this condition. These findings give reason to recommend acupuncture using corporal points (in the form of monotherapy in combination with a diet) to the patients presenting with gastroesophageal reflux disease and grade 0 and 1 oesophagitis (Savary-Miller classification). Structural resonance electromagnetic therapy (both alone and in combination with iodine-bromine baths) may be used to treat patients with gastroesophageal reflux disease and grade 0 oesophagitis. Such patients may be just as well managed using DMW therapy in combination with iodine-bromine baths. Patients presenting with grade 1 oesophagitisshoud be treated with the use of the above physical factors in combination with medicamental therapy.

[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.

[Short courses of iodine-bromine bath therapy and physical exercises for patients with coronary heart disease and concomitant cardiac rhythm disturbance].

The objective of this sanatorium-based study was to evaluate effect of short courses of iodine-bromine bath therapy and veloergometer exercises during 14 days on the working capacity, ventricular and supraventicular extrasystoles, painful and "silent" myocardial ischemia in patients with a combination of coronary heart disease (CHD), stable angina of functional class II, and grade II hypertensive disease (according to the WHO classification). The patients' conditions were monitored by means of spiroveloergometry and Holter ECG recordings. The study included a total of 108 patients. It was shown that short courses of iodine-bromine bath therapy and veloergometer exercises had training and anti-arrhythmic effect on the patients with concurrent coronary heart disease, stable angina, and hypertensive disease. The treatment improved their working capacity, enhanced coronary heart reserve, reduced the frequency of ventricular and supraventicular extrasystoles, decreased manifestations of painful and "silent" myocardial ischemia.

[Amplipulse-magnetotherapy and iodine-bromine waters in combined treatment of patients with chronic nonspecific salpingo-oophoritis].

Amplipulse-magnetotherapy was used as monotherapy and in combined treatment of 110 patients with chronic nonspecific salpingo-oophoritis (CNSO). Clinical assessment shows that transcerebral amplipulse-megnetotherapy (TAMT) has a positive effects on the course of CNSO, reproductive system and psychoemotional status of the patients. The addition of physical and balneological factors to TAMT enhances and prolongs neurotropic, endocrine, analgetic and anti-inflammatory effects of TAMT.

[Rationale for treating patients with hypertension and atherosclerosis of the lower extremities with iodine-bromine baths containing molecular iodine].

Higher therapeutic efficacy of iodine-bromine baths in conversion of iodine from an ionic form (standard iodine-bromine baths) into a molecular one is registered. This is explained by a 23.8 times increase in precipitation and a 4-times increase in iodine penetration into the body when it is molecular. A more effective function of the cardiovascular system, a stronger corrective effect on lipid metabolism, microcirculation in the absence of changes in a secretory function of the thyroid were registered.

[Effect of sulfur salt-bromine-iodine thermal waters on albumin and IgA concentrations in nasal secretions]. / Effetti indotti dalle acque termali sulfuree-salso-bromo-iodiche sulle concentrazioni di albumine e IgA secretorie del secreto nasale.

In chronic rhinopharyngotubaric phlogoses, the key pathogenic element sustaining phlogosis is a persistent modification of the biological, rheological features of the nasal mucus. For centuries sulphurous thermal waters have proved effective in clinically curing such phlogoses. In order to evaluate the effect of such sulphurous-salty-bromic-iodic thermal waters a randomized, double blind study was undertaken on a sampling of 50 patients. The effect such waters have on secretory IgA (sIgA) and albumin in the nasal secretions was tested against a placebo made of distilled water. Using the method of radial immunodiffusion, the response in the IgAs (mg/l) and albumin (mg/dl) concentrations in the nasal secretions was measured for 25 patients treated with the thermal waters and 25 patients treated with distilled water. The average concentrations were statistically compared using the Student t-test for paired samples. A significant increase (p < 0.0001) was seen in the mean IgAs concentration in the patients treated with the thermal waters. On the other hand, there was a weak, not statistically significant increase in the same data mean for the group treated with distilled water. The average increase in the albumin concentration in the nasal secretions proved significant in both cases although the significance was much more marked in the group treated with the thermal waters (p = 0.001) vs. the placebo group (p = 0.039).