Efficacy and safety of boric acid as a preventive treatment against Saprolegnia infection in Nile tilapia (Oreochromis niloticus).

Saprolegniosis is a worldwide fungal-like infection affecting freshwater fishes and their eggs. Reports show high mortalities and subsequent economic losses annually from Saprolegnia infections. Most therapeutants against Saprolegnia spp. infections are inefficient and some have negative impact on the environment. In this study, we have investigated the ability of boric acid (BA) to prevent Saprolegnia infection in Nile tilapia (Oreochromis niloticus). BA inhibited radial growth of Saprolegnia hyphae in vitro. Complete in vitro growth inhibition was found at a concentration of ≥0.6 g/L. Inhibitory effects were also observed in vivo when Nile tilapia were experimentally challenged with Saprolegnia spores and followed over 10 days post challenge and under continuous exposure to different BA concentrations. No signs of saprolegniosis were observed in fish treated with BA at concentrations of 0.4 g/L and above. Comet assay revealed that BA has low toxicity in tilapia continuously exposed to concentrations of 0.2-0.6 g/L for 96 h. Additionally, no significant histomorphological changes were observed in BA-treated fish compared to non-treated controls. Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) enzyme levels indicated reduction in systemic tissue damage associated with Saprolegnia infection. This study demonstrates the potential of BA as a prophylactic measure against Saprolegnia infection in tilapia, and we recommend additional studies on environmental impact.

Cardiac arrest induced by the intentional ingestion of boric acid and mirtazapine treated by percutaneous cardiopulmonary bypass: a case report.

BACKGROUND: Mirtazapine has a good tolerability and safety profile that demonstrates several benefits over other antidepressants and it is associated with few fatalities. Boric acid is an odorless white powder that is generally not recognized as a poisonous substance. We report a case of cardiac arrest induced by the intentional ingestion of mirtazapine, boric acid, and sennosides, by a patient who required percutaneous cardiopulmonary bypass. CASE PRESENTATION: Our patient was a 49-year-old Japanese woman with a history of depression; she was found in an unconscious state after ingesting boric acid (unknown amount), mirtazapine (1950 mg), and sennosides (780 mg). On arrival, she was in a deep coma with marked hypotension induced by atrial fibrillation, tachycardia, and diffuse hypokinetic cardiac motion. She had systemic diffuse erythema. Her serum concentrations of boric acid and mirtazapine on arrival were 560.49 mg/L and 1270 ng/mL, respectively. She experienced repeated cardiac arrest, and was therefore treated with tracheal intubation, mechanical ventilation, percutaneous cardiopulmonary bypass, and continuous hemodialysis filtration. Stable circulation and respiration and a normal kidney function were finally obtained and she was transferred to a local medical facility in a persistent unconscious state. CONCLUSIONS: This is the first case of a return of spontaneous circulation after cardiac arrest induced by the intentional ingestion of boric acid and mirtazapine, requiring percutaneous cardiopulmonary bypass for survival. To maintain cerebral perfusion during percutaneous cardiopulmonary bypass, even in a prolonged state of cardiac arrest induced by overdose, is medically, ethically, and economically challenging.

Intravaginal boric acid: is it an alternative therapeutic option for vaginal trichomoniasis?

OBJECTIVES: Trichomoniasis, caused by Trichomonas vaginalis (TV), is the most common curable sexually transmitted infection worldwide. Current guidance in the UK is to treat TV with a nitroimidazole antibiotic. The high prevalence of TV, high rate of antibiotic resistance and limited tolerability to nitroimidazoles suggest that alternative treatment regimens are needed. Intravaginal boric acid (BA) has been used safely for the treatment of candida vulvovaginitis and bacterial vaginosis, and in vitro studies suggest BA is active against TV. We review the evidence for the efficacy of BA in patients with TV. METHODS: MEDLINE, EMBASE, CINAHL, AMED, HMIC and BNI and Grey literature databases, The Cochrane Library, Trial Registers, conference abstracts and proceedings were searched. Inclusion criteria were women aged 16 years or over with microbiological confirmation of TV infection and using BA as treatment. There were no restrictions on language, publication date or study design. The in vitro evidence for BA activity against TV was also reviewed. RESULTS: No randomised controlled trials or case series were found. Four case reports demonstrated TV clearance with BA using a variety of dose regimens (dose 600 mg alternate nights to 600 mg two times per day; duration 1-5 months). In vitro studies suggest that BA has activity against TV which is independent of its effect on pH. DISCUSSION: Further evaluation of BA for the treatment of uncomplicated TV is required, but it may be useful when therapeutic options are limited. If shown to be safe and effective, intravaginal BA might provide a well-tolerated alternative anti-infective treatment which reduces community exposure to systemic antibiotics.

18F-Tetrafluoroborate, a PET Probe for Imaging Sodium/Iodide Symporter Expression: Whole-Body Biodistribution, Safety, and Radiation Dosimetry in Thyroid Cancer Patients.

We report the safety, biodistribution, and internal radiation dosimetry, in humans with thyroid cancer, of 18F-tetrafluoroborate (18F-TFB), a novel PET radioligand for imaging the human sodium/iodide symporter (hNIS). Methods: Serial whole-body PET scans of 5 subjects with recently diagnosed thyroid cancer were acquired before surgery for up to 4 h after injection of 184 ± 15 MBq of 18F-TFB. Activity was determined in whole blood, plasma, and urine. Mean organ-absorbed doses and effective doses were calculated via quantitative image analysis and using OLINDA/EXM software. Results: Images showed a high uptake of 18F-TFB in known areas of high hNIS expression (thyroid, salivary glands, and stomach). Excretion was predominantly renal. No adverse effects in relation to safety of the radiopharmaceutical were observed. The effective dose was 0.0326 ± 0.0018 mSv/MBq. The critical tissues/organs receiving the highest mean sex-averaged absorbed doses were the thyroid (0.135 ± 0.079 mSv/MBq), stomach (0.069 ± 0.022 mSv/MBq), and salivary glands (parotids, 0.031 ± 0.011 mSv/MBq; submandibular, 0.061 ± 0.031 mSv/MBq). Other organs of interest were the bladder (0.102 ± 0.046 mSv/MBq) and kidneys (0.029 ± 0.009 mSv/MBq). Conclusion: Imaging using 18F-TFB imparts a radiation exposure similar in magnitude to many other 18F-labeled radiotracers. 18F-TFB shows a biodistribution similar to 99mTc-pertechnetate, a known nonorganified hNIS tracer, and is pharmacologically and radiobiologically safe in humans. Phase 2 trials for 18F-TFB as an hNIS imaging agent are warranted.

BASIC study: is intravaginal boric acid non-inferior to metronidazole in symptomatic bacterial vaginosis? Study protocol for a randomized controlled trial.

BACKGROUND: Bacterial vaginosis is associated with increased transmission of sexually transmitted infections, preterm labor, post-surgical infections, and endometritis. Current treatment for symptomatic bacterial vaginosis includes antibiotics, such as metronidazole, which are 70-80 % effective at one month after treatment and result in high recurrence rates and secondary candida infections. Intravaginal boric acid has been used for over a hundred years to treat vaginal infections, such as bacterial vaginosis. Boric acid is inexpensive, accessible, and has shown to be an effective treatment for other infections, such as vaginal candidiasis. To date, there has been no clinical trial evaluation of boric acid effectiveness to treat bacterial vaginosis. METHODS/DESIGN: The BASIC (Boric Acid, Alternate Solution for Intravaginal Colonization) trial is a randomized, double-blinded, multicenter study. The study will enroll a minimum of 240 women of 16-50 years of age who are symptomatic with bacterial vaginosis. Eligible participants will have Amsel and Nugent scores confirming bacterial vaginosis. Women who are pregnant or menopausal or have other active co-infections will be excluded. Consenting participants who meet exclusion and inclusion criteria will be randomly assigned to one of three treatment groups: boric acid, metronidazole, or an inert placebo. Self-administration of treatment intravaginally for 10 days will be followed by clinical assessment at 7 and 30 days (days 17 and 40, respectively) after the end of the treatment phase. Primary outcome is a non-inferiority, per-protocol comparison of the effectiveness of boric acid with that of metronidazole at day 17, as measured by the Nugent score in 16-50 year olds. Secondary outcomes include: non-inferiority, intention-to-treat comparison of effectiveness of boric acid with that of metronidazole at day 17, analysis for both per-protocol and intention-to-treat at day 40, and safety considerations, including adverse effects requiring patient discontinuation of treatment. DISCUSSION: This study will be the first to determine whether intravaginal boric acid is non-inferior to metronidazole in the treatment of bacterial vaginosis in symptomatic women. TRIAL REGISTRATION: ClinicalTrials.gov NCT00799214, registered online Nov 10, 2008.

Dermatitis toxica faciei after boric acid.

An adverse toxic reaction to the topical application of a 2% boric acid solution is described in a 2-year-old girl. Topical boric acid is licensed for use in children above the age of 10 in the Czech Republic. However, it can be bought over the counter and it is very often used in younger children. Due to its fast absorption and slow elimination, there is a high risk of systemic side effects. On the other hand, topical side effects are not reported in the present literature.

Mitochondrial dysfunction is involved in the toxic activity of boric acid against Saprolegnia.

There has been a significant increase in the incidence of Saprolegnia infections over the past decades, especially after the banning of malachite green. Very often these infections are associated with high economic losses in salmonid farms and hatcheries. The use of boric acid to control the disease has been investigated recently both under in vitro and in vivo conditions, however its possible mode of action against fish pathogenic Saprolegnia is not known. In this study, we have explored the transformation in Saprolegnia spores/hyphae after exposure to boric acid (1 g/L) over a period 4-24 h post treatment. Using transmission electron microscopy (TEM), early changes in Saprolegnia spores were detected. Mitochondrial degeneration was the most obvious sign observed following 4 h treatment in about 20% of randomly selected spores. We also investigated the effect of the treatment on nuclear division, mitochondrial activity and function using confocal laser scanning microscopy (CLSM). Fluorescence microscopy was also used to test the effect of treatment on mitochondrial membrane potential and formation of reactive oxygen species. Additionally, the viability and proliferation of treated spores that correlated to mitochondrial enzymatic activity were tested using an MTS assay. All obtained data pointed towards changes in the mitochondrial structure, membrane potential and enzymatic activity following treatment. We have found that boric acid has no effect on the integrity of membranes of Saprolegnia spores at concentrations tested. It is therefore likely that mitochondrial dysfunction is involved in the toxic activity of boric acid against Saprolegnia spp.

External auditory canal stenosis due to the use of powdered boric acid.

Acquired stenosis of the external auditory canal (EAC) may occur because of chronic external otitis, recurrent chronic catarrhal otitis media associated with tympanic membrane perforation, chronic dermatitis, tumors, and trauma. Stenosis occurs generally at the one-third bone part of the external auditory canal. In this article, we present 3 cases of acquired EAC stenosis due to the previous powdered boric acid application. Besides the presentation of surgical intervetions in these cases, we want to notify the physicians not to use or carefully use powdered boric acid because of the complication of EAC stenosis.

Human environmental and occupational exposures to boric acid: reconciliation with experimental reproductive toxicity data.

The reproductive toxicity of boric acid and borates is a matter of current regulatory concern. Based on experimental studies in rats, no-observed-adverse-effect levels (NOAELs) were found to be 17.5 mg boron (B)/kg body weight (b.w.) for male fertility and 9.6 mg B/kg b.w. for developmental toxicity. Recently, occupational human field studies in highly exposed cohorts were reported from China and Turkey, with both studies showing negative results regarding male reproduction. A comparison of the conditions of these studies with the experimental NOAEL conditions are based on reported B blood levels, which is clearly superior to a scaling according to estimated B exposures. A comparison of estimated daily B exposure levels and measured B blood levels confirms the preference of biomonitoring data for a comparison of human field studies. In general, it appears that high environmental exposures to B are lower than possible high occupational exposures. The comparison reveals no contradiction between human and experimental reproductive toxicity data. It clearly appears that human B exposures, even in the highest exposed cohorts, are too low to reach the blood (and target tissue) concentrations that would be required to exert adverse effects on reproductive functions.

Boric acid for recurrent vulvovaginal candidiasis: the clinical evidence.

BACKGROUND: Recurrent vulvovaginal candidiasis (VVC) remains a challenge to manage in clinical practice. Recent epidemiologic studies indicate that non-albicans Candida spp. are more resistant to conventional antifungal treatment with azoles and are considered as causative pathogens of vulvovaginal candidiasis. METHODS: We searched PubMed and Scopus for studies that reported clinical evidence on the intravaginal use of boric acid for vulvovaginal candidiasis. RESULTS: We identified 14 studies (2 randomized clinical trials [RCTs], 9 case series, and 4 case reports) as eligible for inclusion in this review. Boric acid was compared with nystatin, terconazole, flucytosine, itraconazole, clotrimazole, ketoconazole, fluconazole, buconazole, and miconazole; as monotherapy, boric acid was studied in 7 studies. The mycologic cure rates varied from 40% to 100% in patients treated with boric acid; 4 of the 9 included case series reported statistically significant outcomes regarding cure (both mycologic and clinical) rates. None of the included studies reported statistically significant differences in recurrence rates. Regarding the adverse effects caused by boric acid use, vaginal burning sensation (<10% of cases), water discharge during treatment, and vaginal erythema were identified in 7 studies. CONCLUSIONS: Our findings suggest that boric acid is a safe, alternative, economic option for women with recurrent and chronic symptoms of vaginitis when conventional treatment fails because of the involvement of non-albicans Candida spp. or azole-resistant strains.

Nonclinical safety evaluation of boric acid and a novel borate-buffered contact lens multi-purpose solution, Biotrue™ multi-purpose solution.

Multipurpose solutions (MPS) often contain low concentrations of boric acid as a buffering agent. Limited published literature has suggested that boric acid and borate-buffered MPS may alter the corneal epithelium; an effect attributed to cytotoxicity induced by boric acid. However, this claim has not been substantiated. We investigated the effect of treating cells with relevant concentrations of boric acid using two cytotoxicity assays, and also assessed the impact of boric acid on corneal epithelial barrier function by measuring TEER and immunostaining for tight junction protein ZO-1 in human corneal epithelial cells. Boric acid was also assessed in an in vivo ocular model when administered for 28 days. Additionally, we evaluated Biotrue multi-purpose solution, a novel borate-buffered MPS, alone and with contact lenses for ocular compatibility in vitro and in vivo. Boric acid passed both cytotoxicity assays and did not alter ZO-1 distribution or corneal TEER. Furthermore, boric acid was well-tolerated on-eye following repeated administration in a rabbit model. Finally, Biotrue multi-purpose solution demonstrated good ocular biocompatibility both in vitro and in vivo. This MPS was not cytotoxic and was compatible with the eye when administered alone and when evaluated with contact lenses. We demonstrate that boric acid and a borate-buffered MPS is compatible with the ocular environment. Our findings provide evidence that ocular effects reported for some borate-buffered MPS may be incorrectly attributed to boric acid and are more likely a function of the unique combination of ingredients in the MPS formulation tested.

The ototoxic effect of boric acid solutions applied into the middle ear of guinea pigs.

This study analyzed the ototoxic effects of boric acid solutions. Boric acid solutions have been used as otologic preparations for many years. Boric acid is commonly found in solutions prepared with alcohol or distilled water but can also be found in a powder form. These preparations are used for both their antiseptic and acidic qualities in external and middle ear infections. We investigated the ototoxic effect of boric acid solutions on guinea pigs. We are unaware of any similar, previously published study of this subject in English. The study was conducted on 28 young albino guinea pigs. Prior to application of the boric acid solution under general anesthesia, an Auditory Brainstem Response (ABRs) test was applied to the right ear of the guinea pigs. Following the test, a perforation was created on the tympanic membrane of the right ear of each guinea pig and small gelfoam pieces were inserted into the perforated area. Test solutions were administered to the middle ear for 10 days by means of a transcanal route. Fifteen days after inserting the gelfoams in all of the guinea pigs, we anasthesized the guinea pigs and removed the gelfoams from the perforated region of the ear and then performed an ABRs on each guinea pig. The ABRs were within the normal range before the applications. After the application, no significant changes were detected in the ABRs thresholds in neither the saline group nor the group administered boric acid and distilled water solution; however, significant changes were detected in the ABRs thresholds of the Gentamicine and boric acid and alcohol solution groups. We believe that a 4% boric acid solution prepared with distilled water can be a more reliable preparation than a 4% boric acid solution prepared with alcohol.

Drugs during lactation accenting boron exposure.

OBJECTIVES: The benefits of breastfeeding are generally accepted. Risk of drug usage for baby due to lactation is well assessed minimally in certain cases. However, information given about drugs are often insufficient, frustrating, and not recommending lactation. In Czech Teratology Information Service (CZTIS) counselling we use these information. RESULTS: We have given advice in 58 cases inquiring the CZTIS about the risk of drug exposure during lactation. The most frequent queries were on chronic disease treatment following the drug exposure during pregnancy. Remaining cases were associated with acute infections. Mothers suffered from idiopathic bowel disease and psychiatric patients want to be informed before delivery about possibility to breastfeed their babies. Treatment of epilepsy, another frequent disease, is associated with better level of knowledge of both, neurologists and patients. Breastfeeding is recommended according to management in care of epileptic women. CONCLUSION: In our counselling we consider the factors which are involved in drug transfer in the milk and mechanisms and steps of transfer as well. We follow the classification of drugs during lactation by their effect on infants: absolutely contraindicated, temporary cessation of breastfeeding, drugs of special concern and drugs compatible with breastfeeding.

Chemesthetic responses to airborne mineral dusts: boric acid compared to alkaline materials.

OBJECTIVES: (1) To assess the relation between occupationally relevant exposures to dust of boric acid and magnitude of feel in the eye, nose, and throat during activity (pedaling) equal to light industrial work. (2) To compare feel from the dust of boric acid with that of the alkaline dusts calcium oxide and sodium tetraborate pentahydrate (sodium borate). (3) To chart how magnitude of feel changes with time in exposures up to 3/4 h. METHODS: Twelve subjects, six males and six females, participated in duplicate sessions of exposure to 2.5, 5, and 10 mg m(-3) of boric acid, 10 mg m(-3) of sodium borate, 2.5 mg m(-3) of calcium oxide presented as calcium oxide alone or diluted with hydrated calcium sulfate, and 0 mg m(-3) (blank). Exposures occurred in a plastic dome suspended over the head and closed around the neck with rubber dam. Measurements pre- and post-exposure included nasal secretion and nasal resistance. Measurements during exposure included rated magnitude of feel in the eye, nose, and throat, and respiration (Respitrace System). Six concentrations of carbon dioxide ranging from just below detectable to sharply stinging gave subjects references for their ratings. RESULTS: In general, feel increased for periods up to half an hour, then either declined or held at a plateau. Each material had a temporal signature. The nose led with the highest feel, followed by the throat, then the eyes. This hierarchy proved weakest for boric acid; at one level of exposure, magnitude in the throat overtook that in the nose. Accompanying measures implied that change of feel with time occurred neither because of an increase in dilution of the dissolved dusts in newly secreted mucus nor an increase of consequence in nasal resistance. Most likely, sensory adaptation determined the change. Boric acid of 10 mg m(-3) fell slightly and insignificantly below 10 mg m(-3) sodium borate in feel. Boric acid, though, showed a relatively flat dose-response relationship, i.e., a change in level caused little change in feel. CONCLUSIONS: The time-constant for feel from dusts lies on the order of tens of minutes. A flat concentration-response function for boric acid and a notable response from the throat suggests that perceived dryness, not mediated by acidity but perhaps by osmotic pressure, may account for the feel evoked at levels of exposure at or below 10 mg m(-3). More acidic dusts that could actually change nasal pH may trigger sensations differently.

Prevalence of Candida glabrata and its response to boric acid vaginal suppositories in comparison with oral fluconazole in patients with diabetes and vulvovaginal candidiasis.

OBJECTIVE: A large proportion of vulvovaginal candidiasis (VVC) in diabetes is due to non-albicans Candida species such as C. glabrata and C. tropicalis. Observational studies indicate that diabetic patients with C. glabrata VVC respond poorly to azole drugs. We evaluated the response to oral fluconazole and boric acid vaginal suppositories in diabetic patients with VVC. RESEARCH DESIGN AND METHODS: A total of 112 consecutive diabetic patients with VVC were block randomized to receive either single-dose oral 150-mg fluconazole or boric acid vaginal suppositories (600 mg/day for 14 days). The primary efficacy outcome was the mycological cure in patients with C. glabrata VVC in the two treatment arms. The secondary outcomes were the mycological cure in C. albicans VVC, overall mycological cure irrespective of the type of Candida species, frequencies of yeast on direct microscopy, and clinical symptoms and signs of VVC on the 15th day of treatment. Intention-to-treat (ITT; n = 111) and per-protocol (PP; n = 99) analyses were performed. RESULTS: C. glabrata was isolated in 68 (61.3%) and C. albicans in 32 (28.8%) of 111 subjects. Patients with C. glabrata VVC showed higher mycological cure with boric acid compared with fluconazole in the ITT (21 of 33, 63.6% vs. 10 of 35, 28.6%; P = 0.01) and PP analyses (21 of 29, 72.4% vs. 10 of 30, 33.3%; P = 0.01). The secondary efficacy outcomes were not significantly different in the two treatment arms in the ITT and PP analyses. CONCLUSIONS: Diabetic women with C. glabrata VVC show higher mycological cure with boric acid vaginal suppositories given for 14 days in comparison with single-dose oral 150-mg fluconazole.