Investigation of the efficacy of epidermal growth factor, boric acid and their combination in cartilage injury in rats: An experimental study.

OBJECTIVES: In this study, we aimed to determine the bioefficacy of epidermal growth factor (EGF), boric acid (BA), and their combination on cartilage injury in rats. MATERIALS AND METHODS: In in vitro setting, the cytotoxic effects of BA, EGF, and their combinations using mouse fibroblast cell (L929), human bone osteosarcoma cell (Saos-2), and human adipose derived mesenchymal stem cells (hAD-MSCs) were determined by applying MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] test. In in vivo setting, 72 rats were randomly divided into four groups. A standard chondral defect was created and microfracture was performed in all groups. Group A was determined as the control group. In addition to the standard procedure, Group B received 100 ng/mL of EGF, Group C received a combination of 100 ng/mL of EGF and 10 µg/mL of BA combination, and Group D 20 µg/mL of BA. RESULTS: The cytotoxic effect of the combinations of EGF dilutions (1, 5, 10, 25, 50, 100, 200 ng/mL) with BA (100, 300, 500 µg/mL) was observed only in the 72-h application period and in Saos-2. The cytotoxic effect of BA was reduced when combined with EGF. There was no significant difference in the histopathological scores among the groups (p=0.13). CONCLUSION: Our study showed that EGF and low-dose BA application had a positive effect on cartilage healing in rats. Significant decreases in recovery scores were observed in the other groups. The combination of EGF and BA promoted osteoblast growth. Detection of lytic lesions in the group treated with 20 µg/mL of BA indicates that BA may have a cytotoxic effect.

Success in treating wounds with local boric acid: a case study.

Wounds are difficult to treat in patients with diabetes, affecting their quality of life (QoL) and requiring a multidisciplinary approach to their treatment. In addition to systemic treatments such as intravenous antibiotics and debridement, local therapies used in appropriate cases help prevent situations that may result in the need for amputation. Boric acid, an easily accessible agent in local wound care, was considered for use in wounds because of its bactericidal and fungicidal properties, as well as its positive effects on angiogenesis, collagen synthesis and re-epithelialisation. While there are data on the use of boric acid solution in the treatment of hard-to-heal wounds in the literature, its use in wounds is limited. Moreover, although 2-3% boric acid solutions have been used in previous studies, boric acid powder (BAP) was used in this present case study. In this article, BAP was used in the treatment of two patients with diabetic wounds. The application of BAP effectively cleared the necrosis and accelerated wound healing. Boric acid is easily accessible, easy to use and an effective agent that should be considered because of its beneficial effects on wounds patients when used in addition to systemic therapy.

Investigating effects of locally applied boric acid on fracture healing with and without low-level laser therapy.

This study aimed to investigate the effects on fracture healing of locally applied boric acid (BA) with and without low-level laser therapy (LLLT). A unicortical femoral defect was surgically created on the anterolateral surface of proximal femur of each subject. The subjects, totaling 56 Wistar albino rats, were randomly allocated into four groups (n = 14 each): control, LLLT (λ = 905 µm, 10,000 Hz, 25 mW, and peak power 25 W), BA (40 mg/kg), and BA + LLLT groups. On the 30th day, the highest radiological score was recorded for the BA + LLLT group (3.63 [2-4]), followed by the BA (3.38 [2.75-3.75]), control (3 [2-3.25]), and LLLT (2.5 [1.25-3]) groups. On days 15 and 30 post-surgery, malondialdehyde levels were significantly lower among the BA + LLLT group compared to the control group (p < 0.001). On day 30, superoxide dismutase, catalase, and alkaline phosphatase levels were highest in the BA + LLLT group compared to the control group (p < 0.001). When the histopathological, immunofluorescence, and immunohistochemical findings on the 15th and 30th days were compared with the control group, a statistically significant difference was found for the BA and BA + LLLT groups (p ˂ 0.05). This study suggests that locally applied BA with LLLT may accelerate fracture healing.

Therapeutic Effects of Boric Acid in a Septic Arthritis Model Induced by Escherichia coli in Rats.

The study aimed to evaluate the therapeutic effect of boric acid (BA) in experimentally induced septic arthritis. A total of 30 rats, 6 rats in each group (5 groups), were used in the study. No treatment was applied to the rats in the control group. Only BA was administered intraperitoneally (IP) to the rats in the bor group. Escherichia coli was administered at a single dose of 25 µL, 1 × 1010 cfu/rat from the right foot pad of the rats, via intra-articular route, to the mice in the arthritis, arthritis-bor, and arthritis-antb groups. Then, BA at a dose of 50 mg/kg and cefazolin at a dose of 25 mg/kg were administered to the rats in the arthritis-bor and arthritis-antb groups, respectively, for 7 days via the IP route. At the end of the study, all animals were euthanized following the ethical rules. Blood and tissue samples were taken from the rats for biochemical and histopathological analyses. The levels of GSH, MDA, Endoglin, Endocan, and TNF-ß markers were measured in the blood samples taken. A significant decrease was observed in MDA and Endoglin levels in the boric acid-administered group compared with the arthritis group, while a significant increase was observed at the GSH level. Histopathologically, it was determined that the reactive surrounding tissue response in the bor group was significantly reduced. As a result, a significant decrease in inflammation was found biochemically and histopathologically in the groups treated with BA.

Data on Safety of Intravaginal Boric Acid Use in Pregnant and Nonpregnant Women: A Narrative Review.

ABSTRACT: Intravaginal boric acid (IBA) represents one of the only options available to treat azole-resistant vulvovaginal candidiasis (VVC) and is included as part of multiple national guidelines (including the United Kingdom and the United States) for the treatment of VVC or recurrent bacterial vaginosis. Novel products using IBA are under development for treatment and suppression of VVC and bacterial vaginosis. Use of over-the-counter or clinician-prescribed IBA in reproductive-aged women is already widespread and may increase further if drug resistance in VVC rises. However, IBA is not a Food and Drug Administration-approved drug, and safety data are sparse. Given these factors, it is important to understand the currently available data on the safety of IBA use. Herein, we set out to synthesize human and animal data (converting, where appropriate, dose and serum values to standard units to facilitate comparison) to answer 2 key questions: (1) What are the data on the safety of IBA use for women? and (2) What are the data on the safety of IBA use in pregnancy? We find that, despite gaps, available data suggest IBA use is safe, at least when used in doses commonly described in the literature as being prescribed by clinicians. Information on harms in pregnancy is limited, and data remain insufficient to change current guidelines, which recommend IBA avoidance in pregnancy.

Promising potential of boron compounds against Glioblastoma: In Vitro antioxidant, anti-inflammatory and anticancer studies.

Glioblastoma (GB) is the most common and aggressive primary malignant astrocytoma correlated with poor patient survival. There are no curative treatments for GB, and it becomes resistant to chemotherapy, radiation therapy, and immunotherapy. Resistance in GB cells is closely related to their states of redox imbalance, and the role of reactive oxygen species and its impact on cancer cell survival is still far from elucidation. Boron-containing compounds, especially boric acid (BA) and borax (BX) exhibited interesting biological effects involving antibacterial, antiviral, anti-cancerogenic, anti-mutagenic, anti-inflammatory as well as anti-oxidative features. Recent studies indicated that certain boron compounds could be cytotoxic on human GB. Nevertheless, there is gap of knowledge in the literature on exploring the underlying mechanisms of anti-GB action by boron compounds. Here, we identified and compared the potential anti-GB effect of both BA and BX, and revealed their underlying anti-GB mechanism. We performed cell viability, oxidative alterations, oxidative DNA damage potential assays, and explored the inflammatory responses and gene expression changes by real-time PCR using U-87MG cells. We found that BA and BX led to a remarkable reduction in U-87MG cell viability in a concentration-dependent manner. We also found that boron compounds increased the total oxidative status and MDA levels along with the SOD and CAT enzyme activities and decreased total antioxidant capacity and GSH levels in U-87MG cells without inducing DNA damage. The cytokine levels of cancer cells were also altered. We verified the selectivity of the compounds using a normal cell line, HaCaT and found an exact opposite condition after treating HaCaT cells with BA and BX. BA applications were more effective than BX on U-87MG cell line in terms of increasing MDA levels, SOD and CAT enzyme activities, and decreasing Interleukin-1α, Interleukin-6 and Tumor necrosis factor- α (TNF- α) levels. We finally observed that anticancer effect of BA and BX were associated with the BRAF/MAPK, PTEN and PI3K/AKT signaling pathways in respect of downregulatory manner. Especially, BA application was found more favorable because of its inhibitory effect on PIK3CA, PIK3R1, PTEN and RAF1 genes. In conclusion, our analysis indicated that boron compounds may be safe and promising for effective treatment of GB.

Boric acid as a promising agent in the treatment of ovarian cancer: Molecular mechanisms.

PURPOSE: The aim of this study is to determine the therapeutic effects of boric acid cell proliferation, invasion, migration, colony formation, cell cycle and apoptosis mechanisms in ovarian cancer cell line under in vitro conditions. METHODS: MDAH-2774 ovarian cancer cells were employed. Real-time PCR test was used to investigate changes in genes and proteins of cell cycle and apoptosis and identified miRNAs under the addition of boric acid. The apoptosis rates were calculated by TUNEL assay. Matrigel invasion, colony formation and Wound healing tests were used to determine invasion and migration. Oxidative stress index value was calculated for oxidative stress. RESULTS: Boric acid inhibited cell proliferation, invasion, migration and colony formation, but induces apoptosis and oxidative stress. Also, the expression of miRNA-21, miRNA-200a, miRNA-130a and mi-RNA-224 (which are indicators of poor prognosis of ovarian cancer) decreased significantly. CONCLUSION: The potential of boric acid as a natural molecule may supports its effectiveness in reducing adverse effects arising from conventional ovarian cancer treatments.

Comparison of Subgingival Irrigation Effect of Boric Acid 0.5% and Povidone-Iodine 0.1% on Chronic Periodontitis Treatment.

PURPOSE: To comparatively evaluate the effect of a 5% boric acid (BA) irrigant on periodontal condition, bacterial level and oral neutrophil numbers with a 1% povidone iodine (PVP-I) irrigant as an adjunct to scaling and root planing (SRP) in chronic periodontitis (CP) treatment. MATERIALS AND METHODS: A single-masked, randomised clinical trial with 36 CP patients was conducted at the Faculty of Odonto-Stomatology, University of Medicine and Pharmacy, Ho Chi Minh City, Vietnam. Subjects were randomly divided into two treatment groups: 1) SRP plus PVP-I 0.1% irrigant and 2) SRP plus BA 0.5% irrigant. Clinical measurements, including the plaque index (PI), gingival index (GI), bleeding on probing (BOP), probing depth (PD), clinical attachment level (CAL), bacterial level in subgingival plaque (BANA test) and the quantification of oral neutrophils were evaluated at baseline, 4, 6 and 8 weeks after treatment (T0, T4, T6 and T8). RESULTS: Whole-mouth (PI, GI, BOP, PD, CAL and PD) parameters, bacterial level in subgingival plaque and number of oral neutrophils decreased statistically significantly after treatment compared to baseline in both groups (p < 0.01). Between the two groups, whole-mouth PI, GI, BOP, PD and CAL reduction in the BA 0.5% group were higher than those in the PVP-I 0.1% group, but statistical significance was found only for GI and BOP after treatment (p < 0.05). The PD and CAL reductions for moderately deep pockets (PD ≥ 5 mm and < 7 mm) were significantly greater in group 2 compared to group 1 after treatment compared to baseline (p < 0.01). This difference was not found for deep pockets (PD ≥ 7 mm). CONCLUSION: The results of this study suggest that BA 0.5% could be an alternative to PVP-I 0.1%, and might be more favourable because it provided superior results regarding whole-mouth BOP, GI as well as PD and CAL reduction for moderately deep pockets after CP treatment.

Treatment of chronic wounds with polyurethane sponges impregnated with boric acid particles: A randomised controlled trial.

The objective of this study was to investigate the effectiveness of the sponge with boric acid particles combined with the negative pressure wound treatment (NPWT) system for chronic wounds with tissue defects. Our study was designed as a prospective randomised study. One hundred patients who were planned to have NPWT due to chronic wounds were included in this study from Orthopaedics and Traumatology and Plastic Surgery clinics. Patients were divided into two groups. In the first group, a new method, boric acid impregnated sponge, combined with the NPWT system, was used, and in the second group, sponge with silver nitrate was used. Besides the wide-broad spectrum antibacterial properties of silver nitrate, the antimicrobial, angiogenetic, and epithelial effects of boric acid were aimed to investigate by macroscopically and histopathologically. Thirty-six patients in the silver nitrate group and 44 patients in the boric acid group completed the study. A decrease in wound size and granulation was observed in both groups. Macroscopically, a decrease in wound size reduction, epithelialization and granulation were more prominent in the first group in which boric acid impregnated sponge was used than the second group in which silver sponge was used. Moreover, microscopically, the number of fibroblasts, collagen synthesis, and angiogenesis were significantly increased in Group 1. In this clinical study, the broad-spectrum antimicrobial properties of boric acid and its positive effect on the cells responsible for wound healing were found to be more pronounced compared to silver nitrate sponges. A combination of boric acid sponges with the NPWT system may be an alternative method for chronic wounds.

Suitability of boric acid as a boron drug for boron neutron capture therapy for hepatoma.

Hepatoma is the second leading cause of cancer death worldwide. Due to the poor outcomes of patients with late diagnosis, newer treatments for hepatoma are still needed. As an emerging therapy, boron neutron capture therapy (BNCT) may be an effective solution in hepatoma management. In this study, boric acid (BA) was used as the boron drug for in vivo analysis of action mechanism. The N1S1 single liver tumor-bearing rat and the VX2 multifocal liver tumor-bearing rabbit models were used to investigate the retention status of BA in the tumor regions during BNCT. The autoradiographic examination showed BA can localize specifically not only in the hepatoma cells but also in tumor blood vessels. Our findings indicate that superior hepatoma targeting could be achieved in BA-mediated BNCT, which supports BA to be a suitable boron drug for BNCT for hepatoma.

Analysis of DNA Damage Responses After Boric Acid-mediated Boron Neutron Capture Therapy in Hepatocellular Carcinoma.

BACKGROUND: Boron neutron capture therapy (BNCT) selectively kills tumor cells while sparing adjacent normal cells. Boric acid (BA)-mediated BNCT showed therapeutic efficacy in treating hepatocellular carcinoma (HCC) in vivo. However, DNA damage and corresponding responses induced by BA-mediated BNCT remained unclear. This study aimed to investigate whether BA-mediated BNCT induced DNA double-strand breaks (DSBs) and to explore DNA damage responses in vitro. MATERIALS AND METHODS: Huh7 Human HCC cells were treated with BA and irradiated with neutrons during BA-BNCT. Cell survival and DNA DSBs were examined by clonogenic assay and expression of phosphorylated H2A histone family member X (γH2AX), respectively. The DNA damage response was explored by determining the expression levels of DNA repair- and apoptosis-associated proteins and conducting a cell-cycle analysis. RESULTS: DNA DSBs induced by BA-mediated BNCT were primarily repaired through the homologous recombination pathway. BA-mediated BNCT induced G2/M arrest and apoptosis in HCC. CONCLUSION: Our findings may enable the identification of radiosensitizers or adjuvant drugs for potentiating the therapeutic effectiveness of BA-mediated BNCT for HCC.

The propolis and boric acid can be highly suitable, alone/or as a combinatory approach on ovary ischemia-reperfusion injury.

PURPOSE: Ovarian ischemia-reperfusion (IR) damage continues to be a serious infertility problem. The oxidative stress plays central role in the development of IR injuries. Activation of antioxidants decreases IR injuries; however, the efficacy of antioxidant agents remains controversial. Unfortunately, there has been no evidence for medicinal use of boric acid (BA) and propolis (Prop) on ovarian IR injury on rats so far. This study will provide to reveal the potential applications of the Prop and BA in ovarian IR therapy. METHODS: The Sprague-Dawley rats were randomized into five groups: I-control, II-IR, 3 h of ischemia and 3 h of reperfusion, III and IV-a signal dose of oral BA (7 mg/kg) and Prop (100 mg/kg) alone 1 h before induction of IR, V-Prop and BA together 1 h before induction of IR. SOD (superoxide dismutase), CAT (catalase), GSH (glutathione), MPO (myeloperoxidase), MDA (malondialdehyde), and IL-6 (interleukin-6) levels were quantified by ELISA and the TNF-α (tumor necrosis factor-α), 8-OHdG (8-hydroxylo-2'-deoxyguanosin) and Caspase-3 expressions were performed by immunohistochemical analyses. RESULTS: BA and Prop pretreatment significantly reduced MPO, MDA, and IL-6 levels and pathologic score in IR rats, with no effects in control group. These agents used in therapy also decreased TNF-α, 8-OHdG and Caspase-3 protein expressions increased by IR. Furthermore, BA and Prop combination showed significant ameliorative effects on ovary injury caused by IR through acting as an antioxidant, anti-inflammatory and antiapoptotic agent. CONCLUSION: BA and Prop alone and especially in combination could be developed as therapeutic agents against ovary IR injury.

Boric acid and probiotics in bacterial and fungal vulvovaginitis as an effective therapeutic option / Ácido bórico y probióticos en vulvovaginitis bacteriana y fúngica como opción terapéutica eficaz

Objective: To demonstrate that vaginal application of boric acid and probiotics is effective for the treatment of vulvovaginitis and can be considered not only an alternative option, but also a first-line treatment.Material and methods: We performed a multicenter, open-label, pilot trial with random allocation to the study treatment (150 mg boric acid + Lactobacillus gasseri and Lactobacillus rhamnosus) or active control treatment (clotrimazole in candida vulvovaginitis and clindamycin in bacterial vulvovaginitis). All treatments were administered vaginally. The study population comprised 48 women aged >18 years with a suspected diagnosis of vulvovaginitis. We excluded patients who were menstruating or breastfeeding and patients who were pregnant (or planning to become pregnant) at baseline. We also excluded patients who had taken antibiotic treatment or probiotic prophylaxis in the previous 2 weeks and treatments that could interfere with the study. Similarly, we excluded patients infected by Chlamydia trachomatis, Trichomonas vaginalis, Neisseria gonorrhoeae, or Herpes simplex. Follow-up lasted 12 weeks and included 3 face-to-face contacts and 2 telephone calls. Results: Almost all patients (97.9%) were of childbearing age, 100% were sexually active, 77.1% had a history of vulvovaginitis, and 41.7% had recurrent vulvovaginitis. After treatment, the cure rate was 60.9% in the study treatment group and 62.5% in the control group. Vulvovaginitis improved in 39.1% and 33.3%, respectively, and no response was observed in 0% and 4.2% respectively, with no significant differences between the treatments. The Sobel score improved significantly (p<0.05) after 2 weeks of follow-up (study treatment, baseline=5.83±1.6 and 2 weeks=1.00±1.90; control treatment, baseline=6.13±3.03 and 2 weeks=1.30±2.72), although there were no significant differences between the groups. Conclusions: Administration of boric acid and probiotics for treatment of vulvovaginitis proved to be as effective as the standard treatment for candida and bacterial vulvovaginitis. Larger studies are needed to confirm our findings

Objetivo: Demostrar que la administración vaginal de ácido bórico y probióticos en vulvovaginitis oportunistas es un tratamiento eficaz, no solo como opción alternativa, sino también como primera opción terapéutica. Material y métodos: Ensayo piloto multicéntrico, abierto, con asignación aleatoria al tratamiento en estudio (150mg ácido bórico + L.gasseri y L.rhamnosus, AB+P) o al control (C) activo (clotrimazol en vulvovaginitis candidiásica y clindamicina en vulvovaginitis bacteriana), todos vía vaginal. Se incluyó 48 mujeres > 18 años, con diagnóstico de sospecha de vulvovaginitis. Se excluyó pacientes con menstruación, con lactancia, embarazadas (o susceptibles de embarazo) al inicio del estudio, con tratamiento antibiótico o profilaxis con probióticos en las 2 semanas previas y tratamientos que pudieran interferir. Se excluyó pacientes con infección por Chlamydia trachomatis, Trichomona vaginalis, Neisseria gonorrhoeae o Herpes simplex. Se siguieron 12 semanas con 3 controles presenciales y 2 telefónicos. Resultados: 97,9% estaban en edad fértil, 100% eran sexualmente activas, 77,1% tenía antecedentes de vulvovaginitis y 41,7% sufría vulvovaginitis recurrentes. Tras el tratamiento, se logró resolución en un 60,9% con AB+P y un 62,5% con C, mejoría en 39,1% y 33,3% y ausencia de respuesta en 0% y 4,2% respectivamente, sin diferencias significativas entre tratamientos. Sobel score mostró mejoría significativa (p<0,05) tras 2 semanas de seguimiento (AB+P: basal=5,83±1,6 y 2sems=1,00±1,90, C: basal=6,13±3,03 y 2sems=1,30±2,72) sin diferencias entre grupos. Conclusiones: El tratamiento de vulvovaginitis con ácido bórico y probióticos resultó un recurso terapéutico igual de eficaz que los tratamientos estándar para vulvovaginitis candidiásica y bacteriana. Estudios más amplios podrían confirmarlo

Safety and Efficacy of a Novel Vaginal Anti-infective, TOL-463, in the Treatment of Bacterial Vaginosis and Vulvovaginal Candidiasis: A Randomized, Single-blind, Phase 2, Controlled Trial.

BACKGROUND: Bacterial vaginosis (BV) and vulvovaginal candidiasis (VVC) present serious reproductive health risks and management challenges, with poor control attributed to survival of treatment-resistant biofilm communities. Boric acid is used in various regimens for non-albicans VVC and recurrent BV. We investigated safety and efficacy of a novel boric acid-based vaginal anti-infective with enhanced antibiofilm activity (TOL-463) in treating BV and VVC. METHODS: In this phase 2 randomized, investigator-blinded trial conducted at 2 sexual health clinics, women with BV or VVC were randomly assigned (1:1) to 7 nights of TOL-463 vaginal gel or insert. The primary test of cure (TOC) was clinical cure at day 9-12; safety was assessed at TOC and day 21-30. RESULTS: One hundred six participants (53 with BV, 36 VVC, 17 both) were enrolled; most were African American (69%). Clinical cure rate of BV at TOC was 59% (95% confidence interval [CI], 41%-75%) for TOL-463 insert and 50% (95% CI, 31%-69%) for TOL-463 gel, and for VVC, 92% (95% CI, 67%-99%) for TOL-463 insert and 81% (95% CI, 57%-93%) for TOL-463 gel. Both products were safe and well tolerated with no secondary cases of VVC; vulvovaginal burning was the most common adverse event (9.6%). CONCLUSIONS: TOL-463, especially in vaginal insert form, is effective and safe in treating BV and VVC. Future studies should assess the potential role of TOL-463 as a biofilm disrupter in enhancing likelihood of cure relative to approved therapies, reducing recurrence rates, and combined with traditional antimicrobials. CLINICAL TRIALS REGISTRATION: NCT02866227.

Antifibrotic Effect of Boric Acid in Rats with Epidural Fibrosis.

BACKGROUND: Epidural fibrosis is a major problem after spine surgery, with some patients having recurrent symptoms secondary to excessive formation of scar tissue resulting in neurologic compression. We used a rat laminectomy model to determine if topical application of boric acid could be helpful in the prevention of epidural fibrosis. METHODS: Rats were randomly assigned to 2 control and 2 experimental groups (n = 8 for each group). The negative control group received no surgery, and the positive control group underwent laminectomy only. Experimental groups were classified according to the study agents applied onto the dura mater after laminectomy at the L3 level: 2.5% boric acid solution and 5% boric acid solution. The extent of epidural fibrosis was assessed 4 weeks later macroscopically and histopathologically. RESULTS: Boric acid reduced epidural fibrosis in rats after laminectomy. The effect of 5% boric acid solution was more pronounced (P < 0.05) compared with the 2.5% solution. CONCLUSIONS: The antifibrotic effect of boric acid solution for the prevention of epidural fibrosis suggests that boric acid should be further evaluated in future studies for the prevention of epidural fibrosis.

Effects of boric acid on bone formation after maxillary sinus floor augmentation in rabbits.

PURPOSE: Augmentation of the maxillary sinus floor with bone grafting is commonly used for successful treatment of edentulous posterior maxilla with dental implants, and it is essential to maintain good bone volume and quality for long-term success of dental implants. The aim of this experimental study was to investigate the local and systemic effects of boric acid on new bone formation after maxillary sinus floor augmentation (MSFA). MATERIALS AND METHODS: Twenty-four male, New Zealand rabbits were randomly divided into three groups with eight rabbits each, and bilateral MSFA was performed in each animal. An autogenous bone/xenograft mixture was used to augment the maxillary sinuses in each group. Group 1 was determined as control with no additional materials, whereas 3 mg/kg boric acid (BA) was added to the mixture in group 2, and 3 mg/kg boric acid solution added to drinking water daily in group 3. RESULTS: The animals were sacrificed and also histologic, histomorphometric, and immunnohistochemical analyses were performed at weeks 4 and 8. At week 4, bone regeneration was better in the local BA group than in the control and systemic BA groups (p < 0.05). However, no significant difference was found among the groups in terms of bone regeneration at the end of week 8 (p > 0.05). CONCLUSION: Significant higher new bone formation was revealed by BA at early healing especially with local application. BA may be a therapeutic option for improving the bone regeneration.

Several effects of boron are induced by uncoupling steroid hormones from their transporters in blood.

Boron is increasingly added to food supplements due to multiple effects that have been reported in mammals after boric acid administration. Among these effects are inflammatory process control, bone and muscle strength enhancement, protein expression regulation, and a decreased risk of developing some pathologies in which these processes are key, such as osteoporosis, dermatological inflammatory non-infectious maladies and diseases affecting the central nervous system. Experimental data have suggested that steroid hormone levels in plasma change after boric acid administration, but a clear mechanism behind these variations has not been established. We analyzed possibilities for these changes and hypothesized that boric acid disrupts the interactions between steroid hormones and several carriers in plasma. In particular, we proposed that there is an uncoupling of the interactions between sex hormone binding globulin (SHBG) and estrogens and testosterone and that there are alterations in the binding of hydrophobic ligands by other carrier proteins in plasma. Further experimental and computational studies are required to support the hypothesis that boric acid and probably other boron-containing compounds can displace steroid hormones from their plasma carriers. If such phenomena are confirmed, boron administration with a clear mechanism could be employed as a therapeutic agent in several diseases or physiological events that require modulation of steroid hormone levels in plasma.

Current treatment options for vulvovaginal candidiasis caused by azole-resistant Candida species.

INTRODUCTION: Clinicians are increasingly challenged by patients with refractory vulvovaginal candidiasis (VVC) caused by azole-resistant Candida species. Fluconazole resistant C.albicans is a growing and perplexing problem following years of indiscriminate drug prescription and unnecessary drug exposure and for which there are few therapeutic alternatives. Regrettably, although the azole class of drugs has expanded, new classes of antifungal drugs have not been forthcoming, limiting effective treatment options in patients with azole resistant Candida vaginitis. AREAS COVERED: This review covers published data on epidemiology, pathophysiology and treatment options for women with azole-resistant refractory VVC. EXPERT OPINION: Fluconazole resistant C.albicans adds to the challenge of azole resistant non-albicans Candida spp. Both issues follow years of indiscriminate drug prescription and unnecessary fluconazole exposure. Although an understanding of azole resistance in yeast has been established, this knowledge has not translated into useful therapeutic advantage. Treatment options for such women with refractory symptoms are extremely limited. New therapeutic options and strategies are urgently needed to meet this challenge of azole drug resistance.

The Effect of Boric Acid and Borax on Oxidative Stress, Inflammation, ER Stress and Apoptosis in Cisplatin Toxication and Nephrotoxicity Developing as a Result of Toxication.

The development of treatment protocols that can reduce side effects in chemotherapy applications is extremely important in terms of cancer treatment. In this context, it was aimed to investigate the effects of boric acid and borax on cisplatin toxicity (nephrotoxicity) in rats. In the experimental phase, eight groups were formed from rats. Boric acid and borax were given to the treatment groups with three different doses using gavage. On the fifth day of the study, cisplatin (10 mg/kg) was administered to all rats except the control group. At the end of the study, oxidative stress-related (GSH, MDA, PCO, GPx, 8-OHdG), inflammation-related (TNF-α, IL-1ß, IL-18, MCP-1, ICAM, TGF-ß), apoptosis-related (p53, caspase 1, 3, 8, 12, bcl-2, bcl-xL, NFkB), and ER stress-related (GRP78, ATF-6, PERK) basic parameters were analyzed in serum, erythrocyte, and kidney tissues. Kidney tissues were also examined by histopathological and immunohistochemical methods. Borax and boric acid at different doses decreased inflammation and oxidative stress caused by cisplatin toxicity and increased ER stress. As a result of the treatments applied to experimental animals, it was determined that boric acid and borax reduced apoptotic damage in kidney tissue, but the decrease was statistically significant only in 200 mg/kg boric acid-administered group. In the study, low anti-apoptotic effects of borate doses with the anti-inflammatory and antioxidant effect may be due to increased ER stress at the relevant doses. Further studies on the effects of boron compounds on ER stress and apoptotic mechanisms may clarify this issue. Thus, possible side effects or if there are new usage areas of borone compounds which have many usage areas in clinics can be detected.