Heterobostrychus aequalis (Waterhouse, 1884) (Coleoptera: Bostrichidae): Its interception at the Harbor of Rio de Janeiro and relevance as a quarentine pest (A1)

Heterobostrychus aequalis (Waterhouse, 1884) (Coleoptera: Bostrichidae) is considered a severe pest for wood and wood products in regions where it is established. In Brazil, so far, there are no records of its establishment. Therefore, this work reports the interception of this Bostrichidae in the Harbor of Rio de Janeiro, on pallet wood from India. It also defends the maintenance of this insect as an absent quarantine pest (A1), by the Ministry of Agriculture, Livestock and Supply. It also conducts a discussion that addresses the efficiency of wood treatments, usually used to prevent the spread of quarantine pests in environments where there is international transit of wood, demonstrating that they may not be efficient in this regard, especially for insect species that have the capacity to lay eggs on dry wood. In this context, it also suggests population monitoring, combined with inspections, as an aid measure for the early detection of this pest in an environment where there is international transit of wood.

The Pharmacology and Clinical Efficacy of Antiseizure Medications: From Bromide Salts to Cenobamate and Beyond.

Epilepsy is one of the most common and disabling chronic neurological disorders. Antiseizure medications (ASMs), previously referred to as anticonvulsant or antiepileptic drugs, are the mainstay of symptomatic epilepsy treatment. Epilepsy is a multifaceted complex disease and so is its treatment. Currently, about 30 ASMs are available for epilepsy therapy. Furthermore, several ASMs are approved therapies in nonepileptic conditions, including neuropathic pain, migraine, bipolar disorder, and generalized anxiety disorder. Because of this wide spectrum of therapeutic activity, ASMs are among the most often prescribed centrally active agents. Most ASMs act by modulation of voltage-gated ion channels; by enhancement of gamma aminobutyric acid-mediated inhibition; through interactions with elements of the synaptic release machinery; by blockade of ionotropic glutamate receptors; or by combinations of these mechanisms. Because of differences in their mechanisms of action, most ASMs do not suppress all types of seizures, so appropriate treatment choices are important. The goal of epilepsy therapy is the complete elimination of seizures; however, this is not achievable in about one-third of patients. Both in vivo and in vitro models of seizures and epilepsy are used to discover ASMs that are more effective in patients with continued drug-resistant seizures. Furthermore, therapies that are specific to epilepsy etiology are being developed. Currently, ~ 30 new compounds with diverse antiseizure mechanisms are in the preclinical or clinical drug development pipeline. Moreover, therapies with potential antiepileptogenic or disease-modifying effects are in preclinical and clinical development. Overall, the world of epilepsy therapy development is changing and evolving in many exciting and important ways. However, while new epilepsy therapies are developed, knowledge of the pharmacokinetics, antiseizure efficacy and spectrum, and adverse effect profiles of currently used ASMs is an essential component of treating epilepsy successfully and maintaining a high quality of life for every patient, particularly those receiving polypharmacy for drug-resistant seizures.

Slow-binding reversible inhibitor of acetylcholinesterase with long-lasting action for prophylaxis of organophosphate poisoning.

Organophosphorus (OP) compounds represent a serious health hazard worldwide. The dominant mechanism of their action results from covalent inhibition of acetylcholinesterase (AChE). Standard therapy of acute OP poisoning is partially effective. However, prophylactic administration of reversible or pseudo-irreversible AChE inhibitors before OP exposure increases the efficiency of standard therapy. The purpose of the study was to test the duration of the protective effect of a slow-binding reversible AChE inhibitor (C547) in a mouse model against acute exposure to paraoxon (POX). It was shown that the rate of inhibition of AChE by POX in vitro after pre-inhibition with C547 was several times lower than without C547. Ex vivo pre-incubation of mouse diaphragm with C547 significantly prevented the POX-induced muscle weakness. Then it was shown that pre-treatment of mice with C547 at the dose of 0.01 mg/kg significantly increased survival after poisoning by 2xLD50 POX. The duration of the pre-treatment was effective up to 96 h, whereas currently used drug for pre-exposure treatment, pyridostigmine at a dose of 0.15 mg/kg was effective less than 24 h. Thus, long-lasting slow-binding reversible AChE inhibitors can be considered as new potential drugs to increase the duration of pre-exposure treatment of OP poisoning.

Protective effects and potential mechanisms of (2-Carboxyethyl) dimethylsulfonium Bromide (Br-DMPT) on gill health status of on-growing grass carp (Ctenopharyngodon idella) after infection with Flavobacterium columnare.

In this study, the protective effects and potential mechanisms of (2-Carboxyethyl) dimethylsulfonium Bromide (Br-DMPT) were evaluated in relation to the gill health status of on-growing young grass carp (Ctenopharyngodon idella). A total of 450 grass carp (216.49 ± 0.29 g) were randomly distributed into five treatments of three replicates each (30 fish per replicate) and were fed diets supplemented with gradational Br-DMPT (0-520.0 mg/kg levels) for 60 days. Subsequently, the fish were challenged with Flavobacterium columnare for 3 days, and the gills were sampled to evaluate antioxidant status and immune responses evaluation. Our results showed that, when compared to the control group, dietary supplementation with appropriate Br-DMPT levels resulted in the following: (1) decreased gill rot morbidity and improved gill histological symptoms after exposure to F. columnare (P < 0.05); (2) improved activities and gene expression levels (except GSTP2 gene) of antioxidant enzymes and decreased oxidative damage parameter values (reactive oxygen species, malondialdehyde and protein carbonyl) (P < 0.05), which may be partially associated with the nuclear factor-erythroid 2-related factor 2 (Nrf2) signalling pathway (P < 0.05); (3) increased lysozyme (LZ) and acid phosphatase (ACP) activities and complement 3 (C3), C4 and immunoglobulin M (IgM) contents, and upregulated genes expressions of antibacterial peptides (liver-expressed antimicrobial peptide-2A, -2B, hepcidin, ß-defensin and mucin2) (P < 0.05); (4) upregulated gene expressions of anti-inflammatory cytokines (except IL--4/13B) that may be partially to the TOR/(S6K1, 4E-BP1) signalling pathway, and downregulated gene expressions of pro-inflammatory cytokines (except IL-12P35) may be partially to the IKK ß, γ/IκBα/NF-kB) signalling pathway (P < 0.05). Taken together, our results indicate that dietary supplementation with appropriate amounts of Br-DMPT may effectively protect on-growing grass carp from F. columnare by strengthening gill antioxidant capacity and immunity. Furthermore, based on measures of combatting gill rot, antioxidant indices (MDA) and immune indices (LZ), the dietary Br-DMPT supplementation levels for on-growing grass carp are recommended to be 291.14, 303.38 and 312.01 mg/kg diet, respectively.

Population Pharmacokinetic Analysis of Fluticasone Furoate/Umeclidinium Bromide/Vilanterol in Patients with Chronic Obstructive Pulmonary Disease.

BACKGROUND: Population pharmacokinetic methods were used to characterize the pharmacokinetics of fluticasone furoate (FF), umeclidinium (UMEC), and vilanterol (VI) in patients with chronic obstructive pulmonary disease (COPD) when administered as a fixed-dose combination via a single closed inhaler. METHODS: Plasma concentration data from three studies were analyzed using non-linear mixed-effects modeling in NONMEM®. RESULTS: The pooled dataset consisted of 2948, 2589, and 3331 FF, UMEC, and VI observations from 714, 622, and 817 patients with COPD, respectively. There were 41%, 13%, and 21% of observations below the quantification limit for FF, UMEC, and VI, respectively. The pharmacokinetics of FF, UMEC, and VI were all adequately described by a two-compartment model with first-order absorption. The following covariates were statistically significant, but none were considered to be clinically relevant. For FF, Japanese heritage and FF/VI treatment on apparent inhaled clearance (CL/F) with FF CL/F 35% lower in patients of Japanese heritage across all treatments and FF CL/F 42% higher in patients with COPD following FF/VI administration. This is in line with the product label. For UMEC, weight, age, and smoking status on CL/F and weight on apparent volume of distribution (V2/F) with every 10% increase in age from 60 years of age leading to approximately a 6% decrease in UMEC CL/F and every 10% increase in weight from 70 kg leading to approximately a 6% increase in UMEC CL/F and approximately an 8% increase in UMEC V2/F. For a subject with COPD who smoked, UMEC CL/F was 28% higher. For VI, weight on CL/F and smoking status on V2/F with an approximately 4% increase in VI CL/F for every 10% increase in weight from 70 kg, and for a subject with COPD who smoked, VI V2/F was 46% higher. The majority of these covariates have been previously identified in historical analyses. None of these effects were clinically relevant in terms of systemic exposures and do not warrant dose adjustment. CONCLUSIONS: All FF, UMEC, and VI plasma concentrations were well interspersed with historical data and were all adequately described by a two-compartment model with first-order absorption. There were no clinically relevant differences in FF, UMEC, or VI systemic exposures when administered as FF/UMEC/VI, FF/VI + UMEC, or the dual combinations FF/VI and/or UMEC/VI.

The effects of high intensity exercise on learning and memory impairments followed by combination of sleep deprivation and demyelination induced by etidium bromide.

Introduction: Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system. Cognitive impairments occurs in MS patients including learning and memory impairments. More than 50% of MS patients suffer from sleep problems. It has been suggested that in animal models exercise has direct neuroprotective effects on MS and sleep deprivation (SD). In this research, MS impairments were induced using a demyelination model as an indicator of MS disease. Also induction of SD was done using multiple platform. In order to focus on the research question, combination of MS model with SD was studied. In this study, the impact of treadmill exercise on learning and memory impairments was investigated. Material and methods: Male wistar rats were used in the present study. Exercise groups exercised daily for 1 h/day for 10 consecutive days with treadmill (speed: 18 m/min and inclination: 25°). The multiple platform method was applied for the induction of a 72 h SD. The cognitive functions were evaluated using Morris water maze (MWM) and open field tests. Animals were anaesthetized with a certain dose of ketamine and xylazin. After full anesthesia, the rat was placed on rat stereotaxic instrument in the skull-flat position. Demyelination was induced bilaterally by direct single injection of 3 µl of 0.01% ethidium bromide in sterile 0.9% saline at the rate of 1 µl/min into the hippocampal formation. The dose was injected using appropriate stereotaxic coordinates. Results: All of the learning and memory indices in the MWM task showed that SD and hippocampal demyelination destroy learning and memory. It seems that exercise can modulate the destructive effects of SD and demyelination on learning and memory at the behavioral level.

Dioctadecyldimethylammonium bromide (DODAB-BF) as a new adjuvant for maternal-fetal immunization in mice against Neisseria meningitidis: evaluation of humoral response.

Neisseria meningitidis bacterium is a Gram-negative diplococcus. Among their serogroups, the B is one of the main causes of invasive meningococcal disease. Newborns and children are particularly susceptible to this infection because of their immune systems that are still maturing and relatively inexperienced. Thus, further studies on the use of maternal immunization for protection against this disease are needed. The purpose of this study was to evaluate the potential immunogenic antigens from the outer membrane of N. meningitidis serogroup B in outbred mice and the influence of maternal immunization in the offspring, and analyze the adjuvant effect of bilayer fragments of dioctadecyldimethylamonium bromide (DODAB-BF) and hydroxide aluminium (alum) in enhancing antibodies production and transference to offspring. IgG and IgG1, IgG2a and IgG2b subclasses of antibodies in serum from immunized mice and controls were quantified and compared. Immunization by subcutaneous and intramuscular routes exhibited evidence of IgG, and both adjuvants promoted the production of IgG1 and IgG2b that were transferred to the offspring. These antibodies also showed specificity with the outer membrane vesicles from homologous strain and were capable to cross react with different strains. The use of DODAB-BF seems to enhance immune response on mothers and offspring and may have immunological advantages.

Imepitoin withdrawal in dogs with idiopathic epilepsy well-controlled with imepitoin and phenobarbital and/or potassium bromide does not increase seizure frequency.

Phenobarbital or potassium bromide (KBr) add-on treatment decreases the average monthly seizure frequency in dogs with idiopathic epilepsy resistant to a maximum dose of imepitoin. The importance of continued administration of imepitoin in these dogs is currently unknown. The goal of this study was to assess whether imepitoin withdrawal would destabilize epileptic seizure control. In this prospective clinical trial epileptic seizure control was evaluated by comparing the monthly seizure frequency of 13 dogs with well-controlled idiopathic epilepsy receiving a combination of imepitoin and phenobarbital (n=4), imepitoin and KBr (n=7), and imepitoin, phenobarbital and KBr (n=2) during a period of 3-6 months (pre-withdrawal period), with a follow-up period of 9-12 months after withdrawal of imepitoin (post-withdrawal period). Adverse effects were also recorded before and after withdrawal of imepitoin. Imepitoin was tapered off over 3 months as follows: 20mg/kg twice daily for 1 month, then 10mg/kg twice daily for 1 month, then once daily for 1 month. Withdrawal of imepitoin did not increase monthly seizure frequency (P=0.9). Moreover, all owners reported improvement in the adverse effects experienced by their dog after withdrawal of imepitoin. Imepitoin withdrawal in epileptic dogs that were well-controlled with imepitoin and phenobarbital and/or KBr did not worsen epileptic seizure control, and possibly decreased antiepileptic treatment-related adverse effects. However, a worsening of seizure frequency could occur in individual cases.

Development of a novel resin-based dental material with dual biocidal modes and sustained release of Ag+ ions based on photocurable core-shell AgBr/cationic polymer nanocomposites.

Research on the incorporation of cutting-edge nano-antibacterial agent for designing dental materials with potent and long-lasting antibacterial property is demanding and provoking work. In this study, a novel resin-based dental material containing photocurable core-shell AgBr/cationic polymer nanocomposite (AgBr/BHPVP) was designed and developed. The shell of polymerizable cationic polymer not only provided non-releasing antibacterial capability for dental resins, but also had the potential to polymerize with other methacrylate monomers and prevented nanoparticles from aggregating in the resin matrix. As a result, incorporation of AgBr/BHPVP nanocomposites did not adversely affect the flexural strength and modulus but greatly increased the Vicker's hardness of resin disks. By continuing to release Ag+ ions without the impact of anaerobic environment, resins containing AgBr/BHPVP nanoparticles are particularly suitable to combat anaerobic cariogenic bacteria. By reason of the combined bactericidal effect of the contact-killing cationic polymers and the releasing-killing Ag+ ions, AgBr/BHPVP-containing resin disks had potent bactericidal activity against S. mutans. The long-lasting antibacterial activity was also achieved through the sustained release of Ag+ ions due to the core-shell structure of the nanocomposites. The results of macrophage cytotoxicity showed that the cell viability of dental resins loading less than 1.0 wt% AgBr/BHPVP was close to that of neat resins. The AgBr/BHPVP-containing dental resin with dual bactericidal capability and long term antimicrobial effect is a promising material aimed at preventing second caries and prolonging the longevity of resin composite restorations.

Efficacy of potassium bromide in the treatment of drug-resistant epilepsy: a case of new-onset refractory status epilepticus.

A 40-year-old man presented with a series of generalized tonic-clonic seizures after febrile illness. He developed status epilepticus and required mechanical ventilation with anesthetics. Steroid pulse, intravenous immunoglobulin, and immunoadsorption therapy were administrated, and the status epilepticus improved; however, drug-resistant seizures remained. Despite the use of several antiepileptic drugs, seizures frequently occurred. Additional administration of potassium bromide resulted in significant suppression of seizures. Potassium bromide is regarded as an effective medication for pediatric refractory epilepsy after encephalitis. The present case is considered to be new-onset refractory status epilepticus (NORSE) syndrome based on clinical features, and potassium bromide could be effective in treating adult refractory epilepsy, such as NORSE syndrome.

Evaluation of the Most Frequently Prescribed Extemporaneously Compounded Veterinary Medications at a Large Independent Community Pharmacy.

Extemporaneous drug formulation is essential to provide optimal pharmaceutical care to veterinary patients. The need for this is exacerbated by the fact that commercially produced veterinary-specific products, without a human indication, require specialty veterinary manufacturing facilities and a new animal drug application process to gain marketing approval. This study examined the prescription patterns of extemporaneously compounded veterinary preparations in the compounding department at a large independent community pharmacy. Data was obtained from a total of 1348 prescriptions requiring extemporaneous compounding over the course of a two-year period (2014-2015). A database was constructed and each compounded prescription was allocated to a therapeutic category based on the American Hospital Formulary Service Drug Information. Data analysis showed that the most commonly prescribed preparations belonged to the central nervous system (39%), anti-infective agents (21%), and hormones (12%) therapeutic categories. Overall, suspensions were the most dispensed (47%), extemporaneously compounded dosage forms followed by solutions (28%), and capsules (10%). The majority (88%) of compounded preparations were administered by the oral route. The top three drugs that are compounded for veterinary medicine were (1) potassium bromide oral solution for canine epilepsy, (2) methimazole solution used to treat hyperthyroidism in cats, and (3) metronidazole suspension, an antibiotic for the treatment of diarrhea and other infections in dogs and cats. Remarkably, our findings are in good agreement with previously published survey data on the top drugs that are compounded for veterinary medicine. In the era of personalized medicine, veterinary extemporaneous compounding for specialized needs will continue to play an important role providing optimum therapy for veterinary patients.

Bromoderma mimicking pyoderma gangrenosum caused by commercial sedatives.

Bromoderma is a rare skin disorder caused by bromide intake. It presents as single or multiple papillomatous nodules or plaques, and ulcers studded with small pustules on the face or limbs. The clinical features of bromoderma are similar to those of pyoderma gangrenosum. A 41-year-old Japanese woman was diagnosed with pyoderma gangrenosum 11 years prior to presentation. Pyoderma had repeatedly appeared over her entire body despite treatment. She also frequently complained of syncopal episodes. She was admitted to our hospital after loss of consciousness and an episode of generalized convulsion. Laboratory tests revealed a negative serum anion gap and hyperchloremia. Her serum bromide level was significantly elevated, suggesting bromide intoxication. The patient had a 10-year history of high serum bromide levels. After the intake of bromide-containing sedatives was stopped, there was no recurrence of pyoderma in the absence of treatment. In conclusion, this case was diagnosed as bromoderma with commercial sedative-induced bromide intoxication. Although the US Food and Drug Administration have banned the use of bromides, over-the-counter (OTC) treatments containing bromides are still used in Japan and other countries. Long-term use of OTC medicines containing bromvalerylurea may result in the development of bromoderma. If unclarified neurological or psychiatric symptoms are associated with pyoderma, we propose measurement of the patient's serum chloride concentration. Determination of hyperchloremia is helpful for the diagnosis of chronic intoxication with bromides.

Effect of chronic administration of phenobarbital, or bromide, on pharmacokinetics of levetiracetam in dogs with epilepsy.

BACKGROUND: Levetiracetam (LEV) is a common add-on antiepileptic drug (AED) in dogs with refractory seizures. Concurrent phenobarbital administration alters the disposition of LEV in healthy dogs. HYPOTHESIS/OBJECTIVES: To evaluate the pharmacokinetics of LEV in dogs with epilepsy when administered concurrently with conventional AEDs. ANIMALS: Eighteen client-owned dogs on maintenance treatment with LEV and phenobarbital (PB group, n = 6), LEV and bromide (BR group, n = 6) or LEV, phenobarbital and bromide (PB-BR group, n = 6). METHODS: Prospective pharmacokinetic study. Blood samples were collected at 0, 1, 2, 4, and 6 hours after LEV administration. Plasma LEV concentrations were determined by high-pressure liquid chromatography. To account for dose differences among dogs, LEV concentrations were normalized to the mean study dose (26.4 mg/kg). Pharmacokinetic analysis was performed on adjusted concentrations, using a noncompartmental method, and area-under-the-curve (AUC) calculated to the last measured time point. RESULTS: Compared to the PB and PB-BR groups, the BR group had significantly higher peak concentration (Cmax ) (73.4 ± 24.0 versus 37.5 ± 13.7 and 26.5 ± 8.96 µg/mL, respectively, P < .001) and AUC (329 ± 114 versus 140 ± 64.7 and 98.7 ± 42.2 h*µg/mL, respectively, P < .001), and significantly lower clearance (CL/F) (71.8 ± 22.1 versus 187 ± 81.9 and 269 ± 127 mL/h/kg, respectively, P = .028). CONCLUSIONS AND CLINICAL IMPORTANCE: Concurrent administration of PB alone or in combination with bromide increases LEV clearance in epileptic dogs compared to concurrent administration of bromide alone. Dosage increases might be indicated when utilizing LEV as add-on treatment with phenobarbital in dogs.

Pharmacokinetics of bromide in adult sheep following oral and intravenous administration.

OBJECTIVE: To determine the pharmacokinetics of bromide in sheep after single intravenous (IV) and oral (PO) doses. PROCEDURE: Sixteen Merino sheep were randomly assigned to two treatment groups and given 120 mg/kg bromide, as sodium bromide IV or potassium bromide PO. Serum bromide concentrations were determined by colorimetric spectrophotometry. RESULTS: After IV administration the maximum concentration (Cmax ) was 822.11 ± 93.61 mg/L, volume of distribution (Vd ) was 0.286 ± 0.031 L/kg and the clearance (Cl) was 0.836 ± 0.255 mL/h/kg. After PO administration the Cmax was 453.86 ± 43.37 mg/L and the time of maximum concentration (Tmax ) was 108 ± 125 h. The terminal half-life (t½ ) of bromide after IV and PO administration was 387.93 ± 115.35 h and 346.72 ± 94.05 h, respectively. The oral bioavailability (F) of bromide was 92%. No adverse reactions were noted in either treatment group during this study. The concentration versus time profiles exhibited secondary peaks, suggestive of gastrointestinal cyclic redistribution of the drug. CONCLUSIONS AND CLINICAL RELEVANCE: When administered PO, bromide in sheep has a long half-life (t½ ) of approximately 14 days, with good bioavailability. Potassium bromide is a readily available, affordable salt with a long history of medical use as an anxiolytic, sedative and antiseizure therapy in other species. There are a number of husbandry activities and flock level neurological conditions, including perennial ryegrass toxicosis, in which bromide may have therapeutic or prophylactic application.

Single-dose pharmacokinetics of bupropion hydrobromide and metabolites in healthy adolescent and adult subjects.

Data from 2 pediatric single-dose studies, conducted at the same center, were combined to evaluate exposure levels of bupropion and metabolites in adolescents 12-17 years old, compared with adults > 18 years. Pharmacokinetic analyses of bupropion and its metabolites were performed using normalization and pharmacological/convulsive weighting methods on exposure. When compared with adults (>18 years), subjects 12-14 years had an increase in weight-normalized exposure to bupropion (ie, Cmax , 78%; AUC0-t , 83%; and AUCinf , 85%). Variability in this younger age group was also higher, with observations of a 3- to 4-fold increase in exposure. When the changes in metabolites were accounted within pharmacological and convulsive-weighted exposures, the relative ratio of 12-14 years to adults in body weight-normalized Cmax was 127% and 110%, respectively. Subjects 15-17 years did not exhibit a difference in exposure compared with adults. The influence of age on bupropion pharmacokinetics demonstrates that, in general, healthy adolescent subjects cannot be considered smaller healthy adult subjects; the increase in exposure is inversely related to age and appears to be solely associated with bupropion, not with its metabolites. Because there are no clinical safety and efficacy data of bupropion in adolescents, this data may shift its risk-benefit profile.

Epilepsy of infancy with migrating focal seizures: six patients treated with bromide.

PURPOSE: We present six patients with epilepsy of infancy with migrating focal seizures (EIMFS) and provide a comprehensive evaluation of potassium bromide therapy. METHOD: Between February 1, 2007 and July 31, 2012, six patients who met the diagnostic criteria of EIMFS were treated with potassium bromide. Potassium bromide was added to other antiepileptic drugs (AEDs) in doses ranging from 30 to 80 mg/kg/day. Plasma bromide concentration was monitored. A therapeutic bromide concentration between 75 and 125 mg/dL was considered to be ideal. RESULTS: Four of six children responded well to bromide. One of these patients became seizure free, but remained severely mentally impaired. Two boys, currently 4 and 6 years of age, respectively, have monthly seizures as well as axial hypotonia and severe language impairment. The fourth child responded well to bromide, having only weekly seizures and moderate psychomotor retardation. The patient who became seizure free improved visual contact and head control. In the other three patients with good control, the seizures became focal without secondary generalization and status epilepticus and hospital admission was not required. The remaining two patients did not respond well to bromide. Adverse effects were seen in three cases: vomiting in one, drowsiness in another, and acneiform eruption in the face in the remaining patient. Adverse effects resolved with dose reduction. CONCLUSION: Early treatment with bromides should be considered in EIMFS to control the seizures and status epilepticus and to avoid progressive cognitive impairment. Potassium bromide is an old AED. Plasma concentration monitoring should be considered.

Serum bromide concentrations following loading dose in epileptic dogs.

OBJECTIVE: To determine serum bromide concentrations following an oral loading dose in dogs. METHODS: Retrospective review of clinical records of dogs suffering from seizures that were treated with bromide. A loading dose of 600 mg/kg potassium bromide was administered orally in 17 to 48 hours together with a maintenance dose of 30 mg/kg/day. Blood samples were collected within 24 hours after completing the protocol and serum bromide concentrations were determined by ultra-violet gold chloride colorimetric assay. RESULTS: Thirty-eight dogs were included in the study. The median age was 3 (range, 0 · 2 to 10) years and bodyweight 21 · 8 (3 · 45 to 46 · 2) kg. The median serum bromide concentration was 1 · 26 (0 · 74 to 3 · 6) mg/mL. Thirty-two dogs (84 · 2%) had serum bromide concentrations within the therapeutic interval (1 to 3 mg/mL). The serum concentration in five dogs (13 · 2%) was just under the minimal therapeutic value and in one dog (2 · 6%) it exceeded the maximal therapeutic value (3 · 6 mg/mL). CLINICAL RELEVANCE: Following this oral loading dose protocol, serum bromide concentrations reach the therapeutic range in the majority of dogs. This indicates that the suggested protocol is effective in achieving therapeutic concentrations rapidly in epileptic dogs.

[Rehabilitation of the patients presenting with oesophageal achalasia following balloon cardiodilation].

The present study involved a total of 25 patients presenting with oesophageal achalasia who had undergone balloon cardiodilation. The complex of rehabilitative measures concluded the application of an ultrahigh-frequency electromagnetic fields (decimeter wave (DMW) therapy) to the collar region and general iodine bromide baths. The treatment resulted in the elimination of dysphagia syndrome during consumption of solid food in 80% of the patients. Simultaneously, the oesophagogastroscopic study revealed the improvement of the state of oesophageal mucosa. Moreover, the thyrotropin level was normalized. The positive effect of such rehabilitative treatment persisted during 6-8 months.

Short-term effects of combined treatment with potassium bromide and methimazole in patients with Graves' disease.

BACKGROUND: Potassium bromide is used as a sedative and an anti-epileptic drug for children and adolescents. Rodent animal studies have shown that bromide ions inhibit thyroid hormone synthesis by decreasing the iodine concentration in thyroid tissue. AIM: To observe the short-term clinical effects of combined treatment with potassium bromide and methimazole in patients with Graves' disease. MATERIALS AND METHODS: Sixty patients with Graves' diseases were randomized in groups. Thirty patients in the combined treatment group were treated with methimazole (10 mg, tid) and potassium bromide (1 g, tid); 30 patients in the methimazole only group were treated with methimazole (10 mg, tid) and starch placebo (1 g, tid). All the patients were treated with metoprolol tartrate (25 mg, bid) to control the symptoms and signs of hyperthyroidism. Patients were treated for one month. Clinical symptoms and potential side effects were monitored. Serum thyroid hormone levels were measured before and after the treatments. RESULTS: Clinical hyperthyroidism symptoms were improved in both groups, with or without potassium bromide. Patients in the combined treatment group displayed improved clinical hyperthyroidism symptoms 10 days earlier on average (p<0.05). Furthermore, blood thyroid hormone levels decreased to normal levels in 93% (28/30) of patients in the combined treatment group, compared with only 37% (5/30) of patients in the methimazole only group (p<0.05). CONCLUSIONS: Treatment of patients with Graves' disease with a novel combination therapy consisting of potassium bromide and methimazole resulted in a rapid improvement in clinical symptoms and decreased blood thyroid hormone levels to homeostatic levels faster than methimazole treatment alone.