Behavioral and Neuronal Effects of Inhaled Bromine Gas: Oxidative Brain Stem Damage.

The risk of accidental bromine (Br2) exposure to the public has increased due to its enhanced industrial use. Inhaled Br2 damages the lungs and the heart; however, adverse effects on the brain are unknown. In this study, we examined the neurological effects of inhaled Br2 in Sprague Dawley rats. Rats were exposed to Br2 (600 ppm for 45 min) and transferred to room air and cage behavior, and levels of glial fibrillary acidic protein (GFAP) in plasma were examined at various time intervals. Bromine exposure resulted in abnormal cage behavior such as head hitting, biting and aggression, hypervigilance, and hyperactivity. An increase in plasma GFAP and brain 4-hydroxynonenal (4-HNE) content also was observed in the exposed animals. Acute and delayed sympathetic nervous system activation was also evaluated by assessing the expression of catecholamine biosynthesizing enzymes, tryptophan hydroxylase (TrpH1 and TrpH2), and tyrosine hydroxylase (TyrH), along with an assessment of catecholamines and their metabolites. TyrH was found to be increased in a time-dependent manner. TrpH1 and TrpH2 were significantly decreased upon Br2 exposure in the brainstem. The neurotransmitter content evaluation indicated an increase in 5-HT and dopamine at early timepoints after exposure; however, other metabolites were not significantly altered. Taken together, our results predict brain damage and autonomic dysfunction upon Br2 exposure.

Bromine inhalation mimics ischemia-reperfusion cardiomyocyte injury and calpain activation in rats.

Halogens are widely used, highly toxic chemicals that pose a potential threat to humans because of their abundance. Halogens such as bromine (Br2) cause severe pulmonary and systemic injuries; however, the mechanisms of their toxicity are largely unknown. Here, we demonstrated that Br2 and reactive brominated species produced in the lung and released in blood reach the heart and cause acute cardiac ultrastructural damage and dysfunction in rats. Br2-induced cardiac damage was demonstrated by acute (3-24 h) increases in circulating troponin I, heart-type fatty acid-binding protein, and NH2-terminal pro-brain natriuretic peptide. Transmission electron microscopy demonstrated acute (3-24 h) cardiac contraction band necrosis, disruption of z-disks, and mitochondrial swelling and disorganization. Echocardiography and hemodynamic analysis revealed left ventricular (LV) systolic and diastolic dysfunction at 7 days. Plasma and LV tissue had increased levels of brominated fatty acids. 2-Bromohexadecanal (Br-HDA) injected into the LV cavity of a normal rat caused acute LV enlargement with extensive disruption of the sarcomeric architecture and mitochondrial damage. There was extensive infiltration of neutrophils and increased myeloperoxidase levels in the hearts of Br2- or Br2 reactant-exposed rats. Increased bromination of sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) and increased phosphalamban after Br2 inhalation decreased cardiac SERCA activity by 70%. SERCA inactivation was accompanied by increased Ca2+-sensitive LV calpain activity. The calpain-specific inhibitor MDL28170 administered within 1 h after exposure significantly decreased calpain activity and acute mortality. Bromine inhalation and formation of reactive brominated species caused acute cardiac injury and myocardial damage that can lead to heart failure. NEW & NOTEWORTHY The present study defines left ventricular systolic and diastolic dysfunction due to cardiac injury after bromine (Br2) inhalation. A calpain-dependent mechanism was identified as a potential mediator of cardiac ultrastructure damage. This study not only highlights the importance of monitoring acute cardiac symptoms in victims of Br2 exposure but also defines calpains as a potential target to treat Br2-induced toxicity.

Bromofatty aldehyde derived from bromine exposure and myeloperoxidase and eosinophil peroxidase modify GSH and protein.

α-Chlorofatty aldehydes (α-ClFALDs) and α-bromofatty aldehydes (α-BrFALDs) are produced in activated neutrophils and eosinophils. This study investigated the ability of α-BrFALD and α-ClFALD to react with the thiols of GSH and protein cysteinyl residues. Initial studies showed that 2-bromohexadecanal (2-BrHDA) and 2-chlorohexadecanal (2-ClHDA) react with GSH producing the same fatty aldehyde-GSH adduct (FALD-GSH). In both synthetic and cellular reactions, FALD-GSH production was more robust with 2-BrHDA compared with 2-ClHDA as precursor. NaBr-supplemented phorbol myristate acetate (PMA)-activated neutrophils formed more α-BrFALD and FALD-GSH compared with non-NaBr-supplemented neutrophils. Primary human eosinophils, which preferentially produce hypobromous acid and α-BrFALD, accumulated FALD-GSH following PMA stimulation. Mice exposed to Br2 gas had increased levels of both α-BrFALD and FALD-GSH in the lungs, as well as elevated systemic plasma levels of FALD-GSH in comparison to mice exposed to air. Similar relative reactivity of α-ClFALD and α-BrFALD with protein thiols was shown using click analogs of these aldehydes. Collectively, these data demonstrate that GSH and protein adduct formation are much greater as a result of nucleophilic attack of cysteinyl residues on α-BrFALD compared with α-ClFALD, which was observed in both primary leukocytes and in mice exposed to bromine gas.

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 evaluation of the effectiveness of electrophoresis in the form of Polymineral wipes on the basis of iodine- bromine natural water in the young children suffering from the consequences of perinatal lesions in the central nervous system].

UNLABELLED: The background: the increased frequency of serious consequences of perinatal lesions in the central nervous system of the young children dictates the necessity to develop the effective methods of physiotherapy for the early-stage rehabilitation of such patients on the basis of an objective assessment of the adaptive reserves of the organism. MATERIAL AND METHODS: The present study involved 53 children at the age from 1 to 12 months presenting with the consequences of perinatal lesions to the central nervous system. Thirty of the children were treated with the use of electrophoresis in the form of Polymineral wipes on the basis of natural iodine-bromine water. The group of comparison was comprised of 23 children treated without physiotherapy. We estimated the clinical effectiveness and the level of adaptive resources based on the results of blood count measurements (the type of non-specific adaptive reaction and the reactivity level); in addition, the electro-acupuncture test was carried out with the use of the hardware-software complex for bioresonance (MOR) therapy. RESULTS: The clinical effectiveness of an electrophoresis in the form of Polymineral wipes on the basis of natural iodine-bromine water used for the treatment of the newborn infants with the consequences of perinatal lesions to the central nervous system amounted to 93.3%. The rearrangement of the adaptive reactions was apparent as the increase in the proportion of the antistress reactions from 63.3% to 86.7%, the decrease in the frequency of the reactivation reaction by a factor of 3.7, and the reduction of the reactivity level by a factor of 3.0. The repeated study with the use of the MORA-test revealed normalization of the altered indicators in all the children with the initially reduced or enhanced values of these indicators. In the comparison group, dynamics of clinical symptoms was less apparent, and the assessment of the adaptative resources revealed their decrease in 78.3% of the cases. CONCLUSION: The present study confirmed the beneficial effect of electrophoresis in the form of Polymineral wipes on the basis of natural iodine-bromine natural water on the dynamics of clinical symptoms and adaptive reserves in the infants suffering from the consequences of perinatal lesions to the central nervous system. The determination of the type of the nonspecific adaptive reaction and the level of reactivity in combination with the MORA-test can be a method for the assessment of the effectiveness and adequacy of physiotherapeutic modalities for the young children.

Simple radiosensitizing of hypoxic tumor tissues by N2O/Br(-) mixture.

The radiosensitization model of hypoxic tumor tissues based on the N2O/Br(-) mixture is described. The well-documented radiolysis of water in the presence of N2O and Br(-) ions at a low concentration supports this model. An aqueous solution saturated with N2O gas during the radiolysis generates OH radicals in a large extent. In N2O/Br- media at pH<9, Br2 is formed. Br2 hydrolyzes in an aqueous solution to form a very reactive hypobromous (HOBr) acid. Such process is described by the following chemical reaction: H2O + Br(-) + N2O + ionizing radiation (IR) --> HOBr + OH(-). In vivo formed HOBr as a long-lived product with a high biological activity induces the hypoxic tumor cell damage via many unique mechanisms. A local application or inhalation of an N2O-O2 mixture before or during the radiotherapy to enhance the saturation of tissues with N2O is a key prerequisite. Since the extracellular concentration of Br(-) ions is very low (0.02-0.05 mM), an oral or local application of NaBr should be used to shift the extracellular concentration of Br(-) ions to the mM region.

[The clinical results and lipid peroxidation dynamics in the patients presenting with psoriasis treated by the applications of a natural highly mineralized bromine-iodine brine].

The authors report the results of the treatment of 64 patients presenting with psoriasis by the applications of a natural highly mineralized bromine-iodine brine. The method has been shown to be highly efficacious and safe. It allowed the clinical remission and marked improvement of the patients' clinical conditions to be achieved in 48 (77.4%) cases compared with 10 (27.8%) cases among the patients of the control group. Exacerbation was documented in a single patient with psoriatic erythrodermia. All the patients showed the normal results of general and biochemical clinical analyses of blood and urea throughout the study period. The applications of the natural highly mineralized bromine-iodine brine exerted the normalizing action on seven of the 8 characteristics of the lipid peroxidation process. It is maintained that the high effectiveness of the method in question can be accounted not only by the reflectory and humoral mechanisms of action of highly mineralized bromine-iodine brine but also by the marked exhaustion of the functional reserves of the mast cells under effect of the applications. It is concluded that an advantage of the proposed approach over standard balneotherapeutic procedures consists of the possibility to employ it not only at the base of a spa and health resort facility but also in a different setting with the involvement of the patients suffering from progressive psoriasis.

Photodynamic properties and photoinactivation of Candida albicans mediated by brominated derivatives of triarylmethane and phenothiazinium dyes.

The photodynamic activity of brominated derivatives of New Fuchsin and Azure B was studied in solution and in cell suspensions of Candida albicans. The spectroscopic and photodynamic properties of these photosensitizers were compared with those of Crystal Violet and Azure B, which represent active photosensitizer related to each family of compounds. Triarylmethane derivatives absorb intensely with a band centered at ∼ 570 nm, while the phenothiazinium dyes at ∼ 650 nm. Photooxidation of 9,10-dimethylanthracene was observed using phenothiazinium compounds indicating the formation of singlet molecular oxygen, while it was not detected using triarylmethane agents. However, triarylmethane dyes were able to photooxidize l-tryptophan. In yeast cell suspensions, the photosensitized inactivation of C. albicans increases with photosensitizer concentration, causing a ∼ 5 log decrease of cell survival, when the cultures are treated with 20 µM of Crystal Violet and irradiated for 60 min. Under these conditions, the photodynamic activity of 50 µM Azure B induced a ∼ 3 log decrease of cell survival. Studies of photodynamic action mechanism indicated that photoinactivation of C. albicans cells induced by triarylmethane compounds involves mainly type I photoprocess. Although, phenothiazinium derivatives produce singlet molecular oxygen, a contribution of other reactive oxygen species cannot be discarded in the photoinactivation of C. albicans.

A dynamic system for delivering controlled bromine and chlorine vapor exposures to weanling swine skin.

CONTEXT: Assessing the hazards of accidental exposure to toxic industrial chemical (TIC) vapors and evaluating therapeutic compounds or treatment regimens require the development of appropriate animal models. OBJECTIVE: The objective of this project was to develop an exposure system for delivering controlled vapor concentrations of TICs to the skin of anesthetized weanling pigs. Injury levels targeted for study were superficial dermal (SD) and deep dermal (DD) skin lesions as defined histopathologically. MATERIALS AND METHODS: The exposure system was capable of simultaneously delivering chlorine or bromine vapor to four, 3-cm diameter exposure cups placed over skin between the axillary and inguinal areas of the ventral abdomen. Vapor concentrations were generated by mixing saturated bromine or chlorine vapor with either dried dilution air or nitrogen. RESULTS: Bromine exposure concentrations ranged from 6.5 × 10(-4) to 1.03 g/L, and exposure durations ranged from 1 to 45 min. A 7-min skin exposure to bromine vapors at 0.59 g/L was sufficient to produce SD injuries, while a 17-min exposure produced a DD injury. Chlorine exposure concentrations ranged from 1.0 to 2.9 g/L (saturated vapor concentration) for exposures ranging from 3 to 90 min. Saturated chlorine vapor challenges for up to 30 min did not induce significant dermal injuries, whereas saturated chlorine vapor with wetted material on the skin surface for 30-60 min induced SD injuries. DD chlorine injuries could not be induced with this system. CONCLUSION: The vapor exposure system described in this study provides a means for safely regulating, quantifying and delivering TIC vapors to the skin of weanling swine as a model to evaluate therapeutic treatments.

Dietary iodine and bromine intakes in Ukrainian subjects.

Dietary iodine and bromine intakes in Ukrainian subjects were estimated in relation to the health effects on inhabitants after the Chernobyl accident. Two hundred and eighty-six total diets were collected from twenty-five regions for Ukrainians by a duplicate portion study. Iodine and bromine were rapidly determined by inductively coupled plasma mass spectrometry after chemical separation. The range, median, and geometric mean of iodine intakes were 2.86-698, 44.7, and 48.1 microg per person per day, respectively. Those of bromine were 0.627-16.9, 2.97, and 2.92 mg per person per day, respectively. Daily intakes of both elements in Ukrainians were lower than previously reported values. The iodine intake in areas contaminated by the Chernobyl accident was lower than that in non-contaminated areas. The low iodine intake in both areas would be related to the high prevalence of goiters throughout the whole country. The low bromine intakes indicated Ukrainians were not exposed to bromine-containing foods.

The effect of selected aromatic bromine derivatives on the activity of glutathione peroxidase and transferase.

OBJECTIVES: Glutathione (GSH) is an important element of antioxidative barrier. Its biological function consists in eliminating oxygen free radicals. It also acts as a co-substrate in numerous enzymatic reactions catalyzed by glutathione peroxidase (GPx) and glutathione S-transferase (GST). In our study we attempted to assess the effect of hexabromobenzene (HBB) and its metabolites on the level of GSH and related enzymes, GPx and GST. MATERIALS AND METHODS: The experiments were performed on female Wistar rats. The investigated compounds (HBB, 1,2,4,5-tetraBB, 1,2,4- and 1,3,5-triBB) were administered intragastrically in three different doses (HBB: 15, 75, and 375 mg/kg; 1,2,4,5-tetraBB and 1,2,4-triBB: 8, 40, and 200 mg/kg; 1,3,5-triBB: 12, 60, and 300 mg/kg) for 7, 14, 21 or 28 days. GSH level and activity of GST and GPx were determined in the obtained material. RESULTS: The highest activity of GPx and GSTwas observed after a 7-fold administration of all investigated compounds. Prolonged time of exposure caused the return to the control values. CONCLUSIONS: The study revealed that repeated exposure to aromatic bromine derivatives increases GPx and GST activity only in the initial phase of the experiment.

Effect of long-term administration of arsenic (III) and bromine with and without selenium and iodine supplementation on the element level in the thyroid of rat.

The aim of this study was to evaluate the influence of arsenic and bromine exposure with or without iodine and selenium supplementation on the element level in the thyroid of rats. Four major groups of Wistar female rats were fed with respective diets: group A - standard diet, group B - iodine rich diet (10 mg I/kg food), group C - selenium rich diet (1 mg Se/kg) and group D - iodine and selenium rich diet (as in group B and C). Each group was divided into four subgroups per 7 animals each receiving either NaAsO(2) ip (6.5 mg.kg(-1) twice a week for two weeks and 3.25 mg.kg(-1) for six weeks) or KBr in drinking water (58.8 mg.l(-1)) for 8 weeks or combined administration of both substances. Remaining subgroup served as controls. After 8 weeks thyroid glands were analyzed by ICP-MS for As, Br, Se, and I content. The exposition of rat to arsenic or bromine causes the accumulation of these elements in the thyroid gland ( approximately 18 ppm of As, approximately 90 ppm of Br) and significantly affects iodine and selenium concentration in the thyroid. In iodine and/or selenium supplemented rats the bromine intake into the thyroid was lowered to approximately 50% of the level in unsupplemented animals. Also selenium thyroid level elevated due to KBr administration was lowered by iodine supplementation in the diet. The accumulation of arsenic in the thyroid was not influenced by selenium or iodine supplementation; however, As(III) administration increased iodine thyroid level and suppressed selenium thyroid level in selenium or iodine supplemented group of animals.

Reactive airways dysfunction and systemic complaints after mass exposure to bromine.

Occasionally children are the victims of mass poisoning from an environmental contaminant that occurs due to an unexpected common point source of exposure. In many cases the contaminant is a widely used chemical generally considered to be safe. In the following case, members of a sports team visiting a community for an athletic event were exposed to chemicals while staying at a local motel. Bromine-based sanitizing agents and other chemicals such as hydrochloric acid, which were used in excess in the motel's swimming pool, may have accounted for symptoms experienced by the boy reported here and at least 16 other adolescents. Samples of pool water contained excess bromine (8.2 microg/mL; ideal pool bromine concentration is 2-4 microg/mL). Symptoms and signs attributable to bromine toxicity included irritative skin rashes; eye, nose, and throat irritation; bronchospasm; reduced exercise tolerance; fatigue; headache; gastrointestinal disturbances; and myalgias. While most of the victims recovered within a few days, the index case and several other adolescents had persistent or recurrent symptoms lasting weeks to months after the exposure.

Effect of route of administration in the micronucleus test with potassium bromate.

The effect of intraperitoneal injection (i.p.) versus oral gavage administration (p.o.) of potassium bromate was examined using the micronucleus test in 2 strains of male mice (MS/Ae and CD-1). First, a small acute toxicity test and a pilot micronucleus experiment were performed to determine the appropriate dose range and sampling time for the full-scale micronucleus test. The full-scale test was carried out using doses of 18.8, 37.5, 75, and 150 mg/kg in the i.p. test and of 37.5, 75, 150, and 300 mg/kg in the p.o. test. The sampling time was 24 h for both mouse strains. Potassium bromate induced micronucleated polychromatic erythrocytes (MNPCEs) dose-dependently by both routes of administration in both mouse strains. No distinct difference in route of administration was observed in the test with MS/Ae mice. In CD-1 mice more MNPCEs were induced by the i.p. route than by the p.o. route.

Oral administration of the renal carcinogen, potassium bromate, specifically produces 8-hydroxydeoxyguanosine in rat target organ DNA.

Following oral administration of a renal carcinogen, potassium bromate (KBrO3), to the rat, a significant increase of 8-hydroxydeoxyguanosine (8-OH-dG) in kidney DNA was observed. In the liver, a non-target tissue, the increase in 8-OH-dG was not significant. The non carcinogenic oxidants, NaCIO and NaCIO2, had no effect on 8-OH-dG formation in kidney DNA. These results suggest that formation of 8-OH-dG in tissue DNA is closely related to KBrO3 carcinogenesis.

Blood bromine levels in a Pacific atoll population.

Serum and red cells from 20 Marshallese on two atolls and from 10 subjects in New York were compared for their elemental composition employing an energy dispersive X-ray fluorescence technique. The elements analyzed in serum included Cl, Zn, and Br, whereas red cells were analyzed for Cl, K, Fe, Zn, Br, and Rb. Both Marshallese groups showed statistically significant (P less than 0.01) elevations in serum Br (51 and 96%) and in red cell Br (393 and 478%) as compared to the New York group. The Marshallese Br/Cl ratio in serum and in red cells was elevated when compared to that of the New York group, whereas the Rb/K ratios were equivalent. The red cell Br/serum Br ratio was also elevated in the Marshallese subjects. There were no similar differences noted among the other elements tested. Drinking liquids in the Marshall Islands were analyzed for Br but did not provide a clear source for the elevated Br levels.