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.

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.

[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.

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.

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.

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.

[Relationship between the structure and estroginic activity of bromine- and silyl-substitutes of estradiol]. / Zavisimost' mezhdu stroeniem i éstrogennoi adtivnost'iu brom- i sililzameshchennykh éstradiola.

Comparative study of the estrogen properties of 2- and 4-brom and silyl-substituted estradiol administered subcutaneously and orally was carried out on sexually immature female rats. In comparison with initial estrogen, estradiol, silyl-group (SiMe3) substituted in the 4th position diminished the estrogen activity after subcutaneous injection but improved it considerably when given orally. Introduction of silyl radical in the 2nd position or of bromine in the 2nd and 4th positions of the estradiol molecule led to practically complete loss of the estrogenic activity irrespective of the method of administration of these compounds.

Long-term treatment of galactorrhoea and hypogonadism with bromocriptine.

Seventeen women and four men with galactorrhoea and associated hypogonadism have been treated with bromocriptine for 2 to 28 months. In 18 patients the gonadal status became normal as the galactorrhoea improved. The gonadally unresponsive patients had either pituitary tumours or premature menopause. Prolactin levels fell with treatment; withdrawal of the drug was associated with an increase in serum prolactin and a recurrence of the galactorrhoea and hypogonadism. Two patients tried to become pregnant on treatment and both succeeded. Raised prolactin levels appear to block the actions of the gonadotrophins at a gonadal level rather than prevent their synthesis or release; lowering prolactin secretion with bromocriptine allows resumption of normal gonadal function. Bromocriptine appears to be the treatment of choice for inappropriate lactation in association with hypogonadism on a long-term basis.