Image-Based In Vitro Screening Reveals the Trypanostatic Activity of Hydroxymethylnitrofurazone against Trypanosoma cruzi.

Hydroxymethylnitrofurazone (NFOH) is a therapeutic candidate for Chagas disease (CD). It has negligible hepatotoxicity in a murine model compared to the front-line drug benznidazole (BZN). Here, using Trypanosoma cruzi strains that express bioluminescent and/or fluorescent reporter proteins, we further investigated the in vitro and in vivo activity of NFOH to define whether the compound is trypanocidal or trypanostatic. The in vitro activity was assessed by exploiting the fluorescent reporter strain using wash-out assays and real-time microscopy. For animal experimentation, BALB/c mice were inoculated with the bioluminescent reporter strain and assessed by highly sensitive in vivo and ex vivo imaging. Cyclophosphamide treatment was used to promote parasite relapse in the chronic stage of infection. Our data show that NFOH acts by a trypanostatic mechanism, and that it is more active than BZN in vitro against the infectious trypomastigote form of Trypanosoma cruzi. We also found that it is more effective at curing experimental infections in the chronic stage, compared with the acute stage, a feature that it shares with BZN. Therefore, given its reduced toxicity, enhanced anti-trypomastigote activity, and curative properties, NFOH can be considered as a potential therapeutic option for Chagas disease, perhaps in combination with other trypanocidal agents.

The Effects of Nitrofurazone on Wound Healing in Thoracoabdominal Full-thickness Skin Defects.

INTRODUCTION: The use of topical antibiotics on wound healing has been a matter of debate for many years because of the effectiveness. OBJECTIVE: The aim of this study is to investigate the potential effects of topical nitrofurazone, an antibacterial agent, on the healing of full-thickness skin defects created in a laboratory setting. MATERIALS AND METHODS: A total of 42 adult male Sprague Dawley rats were divided into 2 groups: group A (control group; n = 21) and group B (nitrofurazone group; n = 21). Circular full-thickness skin defects about 1 cm x 1 cm in size were formed in the left thoracoabdominal regions of all rats. Local physiological saline was applied to the wound once daily in the control group, and a thin layer of nitrofurazone cream was applied to the wound topically once daily in the nitrofurazone group. The defect sizes of all rats were photographed at baseline and days 3, 7, and 10 of the experiment, and wound size reduction was measured macroscopically on the computer to calculate the healing rates. A total of 7 rats from each group were euthanized on days 3, 7, and 10, and their defected regions were resected. The removed specimens were evaluated histopathologically and scored for inflammatory cells, collagen accumulation, granulation tissue formation, reepithelization, and features of the skin defect (eg, layers of the skin affected, size, whether it involves any abscess-necrosis). Statistical significance was set at P ⟨ .05. RESULTS: The healing rate had higher values in group B at days 7 and 10 of the experiment (P ⟨ .001). A comparison of the group scores showed that there were statistically significant differences in favor of group B. No statistically significant difference was found between the 2 groups with respect to granulation tissue formation. CONCLUSIONS: Topically applied nitrofurazone produced positive effects accelerating the wound healing process.

A new medium-throughput screening design approach for the development of hydroxymethylnitrofurazone (NFOH) nanostructured lipid carrier for treating leishmaniasis.

Hydroxymethilnitrofurazone (NFOH) is a nitrofurazone derivative and has potential use in treating leishmaniasis. However, due to low water solubility and bioavailability, NFOH has failed in in vivo tests. Nanostructured lipid carrier (NLC) is an alternative to overcome these limitations by improving pharmacokinetics and modifying drug delivery. This work is focused on developing a novel NFOH-loaded NLC (NLC-NFOH) using a D-optimal mixture statistical design and high-pressure homogenization, for oral administration to treat leishmaniasis. The optimized NLC-NFOH consisted of Mygliol® 840, Gelucire® 50/13, and Precirol® ATO 5 as lipids. These lipids were selected using a rapid methodology Technobis Crystal 16 T M, microscopy, and DSC. Different tools for selecting lipids provided relevant scientific knowledge for the development of the NLC. NLC-NFOH presented a z-average of 198.6 ±â€¯5.4 nm, PDI of 0.11 ±â€¯0.01, and zeta potential of -13.7 ±â€¯0.7 mV. A preliminary in vivo assay was performed by oral administration of NLC-NFOH (2.8 mg/kg) in one healthy male Wistar rat (341 g) by gavage. Blood from the carotid vein was collected, and the sample was analyzed by HPLC. The plasma concentration of NFOH after 5 h of oral administration was 0.22 µg/mL. This same concentration was previously found using free NFOH in the DMSO solution (200 mg/kg), which is an almost 100-fold higher dose. This study allowed a design space development approach of the first NLC-NFOH with the potential to treat leishmaniasis orally.

Exantema fijo medicamentoso por paracetamol. Caso clínico con revisión bibliográfica / Fixed drug eruption with acetaminophen. Clinical case with bibliographic review

El exantema fijo medicamentoso es una toxicodermia caracterizada por la aparición de una lesión cutánea en forma de mácula de color rojizo o violáceo, redonda u oval, edematosa, bien delimitada, y que presenta recurrencias tras la administración del agente causal, generalmente un fármaco. Puede ser producido por una gran variedad de fármacos, entre ellos el paracetamol. El paracetamol es un medicamento con propiedades analgésicas y antipiréticas ampliamente conocido y utilizado por su amplio margen de seguridad y elevada biodisponibilidad. Sin embargo, se han descrito reacciones cutáneas adversas de diferentes tipos e intensidad tras su administración, fundamentalmente urticaria y angioedema, y con menor frecuencia eritema multiforme, necrólisis epidérmica tóxica, exantema fijo y púrpura de Henoch-Schönlein. Se presenta el caso de un usuario tipo con exantema fijo medicamentoso relacionado con el consumo de paracetamol. Se ha realizado una revisión bibliográfica sobre los diversos hallazgos clínicos y el diagnóstico diferencial entre las diferentes toxicodermias, así como el manejo y abordaje de las lesiones basado en el concepto TIME

Fixed drug eruption is a toxicodermia characterized by the appearance of a well-circumscribed reddish or violet, circular or oval, edematous skin lesion which can present recurrences after taking the causal agent, usually a drug. It can be produced by a wide variety of drugs, including acetaminophen. Acetaminophen is a drug with analgesic and antipyretic properties widely known and used for its wide range of safety and high bio-availability. However, different types and intensity of adverse skin reactions have been reported following administration, mainly urticaria and angioedema, and less frequently erythema multiforme, toxic epidermal necrolysis, fixed exanthema and Henoch-Schönlein purpura. We present the case of a role model user with fixed drug exanthema after acetaminophen consumption. A bibliographic review has been made on the various clinical findings and the differential diagnosis between different toxicodermias, as well as the management and approach of the lesions based on the TIME concept

Quemadura por pegamento de cianocrilato / Cyanoacrylate glue burn

Las quemaduras químicas representan un porcentaje muy pequeño dentro del total de las causas de quemaduras en niños. Dentro de estas, las producidas por pegamentos compuestos por cianocrilato presentan unas características que las hacen más complejas de manejar. El cianocrilato es una resina acrílica que polimeriza rápido, por lo que los pegamentos que lo contienen pueden unir dos superficies fuertemente en apenas un minuto. Presentamos el caso de una niña atendida en nuestro centro de salud por las lesiones producidas al contacto con este 'superpegamento' (AU)

An in vivo comparison of commonly used topical antimicrobials on skin graft healing after full-thickness burn injury.

Topical antimicrobials are frequently used for local control of infections in burn patients. It has been postulated that these agents retard wound healing. There are limited data about the effects of topical antimicrobial agents on skin graft healing. In this study, we aimed to evaluate the effects of nitrofurazone, 1% silver sulfadiazine, and povidone-iodine on skin graft healing. Forty male rats were used in this study. A meshed skin graft, placed on an excised burn wound, was used as a model to compare topical agents with a control group. Skin graft survival rates, closure of meshed graft interstices (based on physical parameters, namely epithelialization and wound contraction), and histological changes were analyzed. Graft take was more than 85% in all groups. There was no difference between the mean values of the percent graft survival for each group (P > .05). Epithelialization occurred significantly earlier in animals in the nitrofurazone group (P < .05). There was no significant difference between groups in wound contraction rates (P >.05). There was no histological difference between the biopsy specimens of skin grafts. In specimens obtained from the interstices of the meshed graft, no significant differences were found among the groups regarding the wound healing parameters (P > .05). We found that nitrofurazone, silver sulfadiazine, and povidone-iodine had no negative effect on graft healing and take in noncontaminated burn wounds.

Hepatotoxicity in mice of a novel anti-parasite drug candidate hydroxymethylnitrofurazone: a comparison with Benznidazole.

BACKGROUND: Treatment of Chagas disease, caused by Trypanosoma cruzi, relies on nifurtimox and benznidazole (BZL), which present side effects in adult patients, and natural resistance in some parasite strains. Hydroxymethylnitrofurazone (NFOH) is a new drug candidate with demonstrated trypanocidal activity; however, its safety is not known. METHODS: HepG2 cells dose response to NFOH and BZL (5-100 µM) was assessed by measurement of ROS, DNA damage and survival. Swiss mice were treated with NFOH or BZL for short-term (ST, 21 d) or long-term (LT, 60 d) periods. Sera levels of cellular injury markers, liver inflammatory and oxidative stress, and fibrotic remodeling were monitored. RESULTS: HepG2 cells exhibited mild stress, evidenced by increased ROS and DNA damage, in response to NFOH, while BZL at 100 µM concentration induced >33% cell death in 24 h. In mice, NFOH ST treatment resulted in mild-to-no increase in the liver injury biomarkers (GOT, GPT), and liver levels of inflammatory (myeloperoxidase, TNF-α), oxidative (lipid peroxides) and nitrosative (3-nitrotyrosine) stress. These stress responses in NFOH LT treated mice were normalized to control levels. BZL-treated mice exhibited a >5-fold increase in GOT, GPT and TNF-α (LT) and a 20-40% increase in liver levels of MPO activity (ST and LT) in comparison with NFOH-treated mice. The liver inflammatory infiltrate was noted in the order of BZL>vehicle≥NFOH and BZL>NFOH≥vehicle, respectively, after ST and LT treatments. Liver fibrotic remodeling, identified after ST treatment, was in the order of BZL>vehicle>NFOH; lipid deposits, indicative of mitochondrial dysfunction and in the order of NFOH>vehicle>BZL were evidenced after LT treatment. CONCLUSIONS: NFOH induces mild ST hepatotoxicity that is normalized during LT treatment in mice. Our results suggest that additional studies to determine the efficacy and toxicity of NFOH are warranted.

Efficacy of intraoperative surgical irrigation with polihexanide and nitrofurazone in reducing bacterial load after nail removal surgery.

BACKGROUND: A common challenge of nail avulsion surgery is the associated bacterial contamination and infection that can manifest. The toe has a difficult anatomy to antiseptically prepare and properly maintain throughout the surgical procedure, lending to this widespread problem. OBJECTIVE: We conducted a controlled, prospective randomized study to examine the antiseptic efficacy of 3 intraoperative irrigation methods during nail avulsion surgery. METHODS: We compared intraoperative antiseptic irrigation using 0.9% saline solution (24 patients), 0.2% nitrofurazone (22 patients), and 0.1% polihexanide (25 patients). Swab samples were taken from each patient at 5 distinct stages throughout the surgical procedure, and bacterial culture analysis was performed (positive culture rate, total inocula count, reduction of bacterial load, and identification of specific micro-organisms). RESULTS: All 3 intraoperative irrigation methods reduced the total bacterial load, but polihexanide was significantly more effective. Furthermore, no patient from the polihexanide group developed postoperative infection. The reduction in bacterial load was lost for all 3 methods after partial nail avulsion surgery, returning to similar values as the initial presurgical bacterial load. An intraoperative irrigation step after partial nail avulsion with saline, nitrofurazone, and polihexanide was effective in reducing the bacterial load by 95.2%, 96.6%, and 99.5%, respectively. LIMITATIONS: Our patients underwent phenol-based nail avulsion, resulting in no bacterial load after complete nail removal because of the intrinsic antiseptic nature of the phenol. CONCLUSIONS: Intraoperative irrigation with 0.1% polihexanide substantially reduced the bacterial load and subsequent infections, highlighting the importance of an irrigation step in nail avulsion surgery.

Wound healing properties of Indian propolis studied on excision wound-induced rats.

CONTEXT: In traditional medicine propolis is widely used for the treatment of various ailments including ulcer and wound healing. The phytochemical screening of Indian propolis indicates the presence of biologically active ingredients in appreciable amounts. In the absence of systematic evaluation of wound healing properties of Indian propolis in the literature, the present study was undertaken. OBJECTIVE: The aim of this study was to evaluate the wound healing potential of Indian propolis on excision wounds induced in experimental rats. MATERIALS AND METHODS: Excision wounds were created in male Wistar rats and were treated with Indian propolis ointment (nitrofurazone was used as a reference drug - widely used for wound healing) for a period of 14 days. Control rats were treated with petroleum jelly. The parameters analyzed include wound contraction, hydroxyproline, hexosamine, uronic acid, total protein, DNA, and RNA. RESULTS: Topical application of propolis ointment for 14 days significantly improved the wound contraction when compared to the control group of rats. The determination of hydroxyproline, hexosamine, uronic acid, DNA, RNA and protein levels in the wound matrix revealed the pro-healing effects of propolis. The results obtained were comparable with nitrofurazone. DISCUSSION AND CONCLUSION: It appears that the ethanol extract of Indian propolis possesses significant pro-healing activity by accelerating the healing process at various phases of tissue repair. The presence of biologically active ingredients such as flavonoids, phenolic acids, terpenes, benzoic acids, amino acids and vitamins, etc. in Indian propolis may readily account for the observed prophylactic action of propolis in wound healing.

Hydroxymethylnitrofurazone is active in a murine model of Chagas' disease.

The addition of a hydroxymethyl group to the antimicrobial drug nitrofurazone generated hydroxymethylnitrofurazone (NFOH), which had reduced toxicity when its activity against Trypanosoma cruzi was tested in a murine model of Chagas' disease. Four groups of 12 Swiss female mice each received 150 mg of body weight/kg/day of NFOH, 150 mg/kg/day of nitrofurazone (parental compound), 60 mg/kg/day of benznidazole (BZL), or the solvent as a placebo. Treatments were administered orally once a day 6 days a week until the completion of 60 doses. NFOH was as effective as BZL in keeping direct parasitemia at undetectable levels, and PCR results were negative. No histopathological lesions were seen 180 days after completion of the treatments, a time when the levels of anti-T. cruzi antibodies were very low in mice treated with either NFOH or BZL. Nitrofurazone was highly toxic, which led to an overall rate of mortality of 75% and necessitated interruption of the treatment. In contrast, the group treated with its hydroxymethyl derivative, NFOH, displayed the lowest mortality (16%), followed by the BZL (33%) and placebo (66%) groups. The findings of histopathological studies were consistent with these results, with the placebo group showing the most severe parasite infiltrates in skeletal muscle and heart tissue and the NFOH group showing the lowest. The present evidence suggests that NFOH is a promising anti-T. cruzi agent.

Oral myiasis caused by Cochliomyia hominivorax treated nonsurgically with nitrofurazone: report of 2 cases.

Accidental oral myiasis are caused by ingestion of fly's eggs or direct oviposition over a compromised area of the host. Here the authors report 2 cases of accidental oral myiasis caused by direct oviposition over an edentulous area in the first patient and in the periodontium in the second patient. Both cases were treated successfully with topical applications of nitrofurazone during a 3-day period. No surgical procedures were required. Flushing the wound with nitrofurazone caused the maggots to endure a liquid-filled anaerobic environment. Healing was uneventful in the 2 cases presented and no adverse reactions were observed during the treatment after 2 months of follow-up. The maggots of both patients were identified as Cochliomyia hominivorax.

Wound healing and protease inhibition activity of Bacoside-A, isolated from Bacopa monnieri wettest.

Bacopa monnieri (L.) Wettest. (Scrophulariaceae) is a well-known medicinal herb. In the Indian system of medicine it is known as Brahmi (Sanskrit) and Indian water hyssop. Methanolic extract of Bacopa monnieri and its isolated constituent Bacoside-A were screened for wound healing activity. Bacoside-A was screened for wound healing activity by excision, incision and dead space wound on Swiss albino rats. Significant wound healing activity was observed in both extract and the Bacoside-A treated groups. The SDS-PAGE caseinolytic zymogram analysis of inhibition of matrix metalloproteases (MMPs) enzyme from the excision wound by Bacoside-A, an isolated constituent, was done with the concentrations 100 and 200 micromg/ml. In Bacoside-A treated groups, epithelialization of the excision wound was faster with a high rate (18.30 +/- 0.01 days) of wound contraction. The tensile strength of the incision wound was increased (538.47 +/- 0.14 g) in the Bacoside-A treated group. In the dead space wound model, the weight of the granuloma was also increased (89.15 +/- 0.08 g). The histological examination of the granuloma tissue of the Bacoside-A treated group showed increased cross-linking of collagen fibers and absence of monocytes. The wound healing activity of Bacoside-A was more effective in various wound models compared to the standard skin ointment Nitrofurazone.

Prophylaxis and treatment of Chagas disease in renal transplant donor and recipient: case report.

Chagas disease is a prevalent zoonosis in Latin America, caused by the protozoa Trypanosoma cruzi and transmitted by Triatoma infestans. Part of the infectious cycle consists of chronic subclinical parasitemia, causing in the long term end-organ damage. Amastigotes have been isolated from various organs including native and allograft renal parenchyma; thus, transplantation plus immunosuppression therapy is another mode of disease transmission and reactivation. Herein, we report 2 successful kidney transplantations cases in which either infection or reactivation was averted using prophylactic nitroderivates.

Oral myiasis caused by Cochliomyia hominivorax treated with ivermectin and nitrofurazone: case report.

Myiasis is the infestation of tissues and organs of animals and humans by certain dipteran fly larvae. This phenomenon is well-documented, especially among animals and people in tropical and subtropical areas. Oral myiasis is a rare condition that can be caused by several species of dipteran fly larvae. When the larvae are removed from the mouth, the tissues seem to recover with no subsequent complications and no need for further treatment. This article presents a case involving a patient with oral myiasis caused by Cochliomyia hominivorax and treated with ivermectin and nitrofurazone.

Atividade terapêutica do 5-nitrofuraldeído-semicarbazona (nitrofurazona) em esquemas de duração prologada na infeccção experimental do camundongo pelo Trypanosoma cruzi / Therapeutic activity of 5-nitrofuraldeído-semicarbazone (nitrofurazone) in schemes prolong the duration of infectious disease in experimental mice by Trypanosoma cruzi

Revisões históricas aos avanços científicos para o controle da doença, o Simpósio Internacional Comemorativo do Centenário da Descoberta da Doença de Chagas (1909-2009).

Effectiveness of a honey dressing for healing pressure ulcers.

OBJECTIVE: To compare the effect of a honey dressing vs an ethoxy-diaminoacridine plus nitrofurazone dressing in patients with pressure ulcers. DESIGN: This 5-week randomized clinical trial evaluated the effect of a honey dressing on pressure ulcer healing. SETTING AND SUBJECTS: Thirty-six patients with a total of 68 stage II or III pressure ulcers referred from a university hospital in Izmir were enrolled in the study. Twenty-six subjects completed the trial. INSTRUMENTS: Ulcers were measured with acetate tracings and Pressure Ulcer Scale for Healing (PUSH) evaluations. METHODS: Fifteen patients with 25 pressure ulcers were treated with honey dressings, and 11 patients with 25 pressure ulcers were treated with ethoxy-diaminoacridine plus nitrofurazone dressings. Wound healing was assessed weekly using the PUSH tool, version 3.0. The primary outcome measure was the change in PUSH tool scores in each group at 5 weeks. RESULTS: The two groups were statistically similar with regard to baseline and wound characteristics. After 5 weeks of treatment, patients who were treated by honey dressing had significantly better PUSH tool scores than subjects treated with the ethoxy-diaminoacridine plus nitrofurazone dressing (6.55 +/- 2.14 vs 12.62 +/- 2.15, P < .001). CONCLUSION: By week 5, PUSH tool scores showed that healing among subjects using a honey dressing was approximately 4 times the rate of healing in the comparison group. The use of a honey dressing is effective and practical.

Cura de ampollas por fricción. A propósito del camino de Santiago / The treatment of blisters caused by friction while hiking the road to Santiago

Se recoge una experiencia práctica de tratamiento de ampollas por fricción en los pies de peregrinos del Camino de Santiago. En el diseño del plan de tratamiento se consideraron las peculiaridades de una marcha que se prolonga durante días: criterios de comodidad, seguridad y prevención de complicaciones. Los sujetos de estudio son peregrinos, compañeros de viaje de los autores. Como principales características diferenciales del método propuesto se destacan el desbridamiento precoz de la piel de la ampolla, la utilización de una cura húmeda con nitrofurazona y la fijación con un vendaje. Siguiendo este método se atendieron 16 lesiones, realizándose un total de 112 curas, registrando una evolución favorable en seis días y sin diferencias significativas en la mejoría de la lesión

this article deals with a practical experience treating blisters caused by friction on feet of pilgrims who hiked the Road to Santiago. To design this treatment plan, the authors considered the peculiarities a hike which lasts to over many days has: comfort criteria, security and prevention of complications. The study subjects were pilgrims, traveling companions of teh authors. these stand out as main differentiating characteristics of this proposed treatment, the precocious debridement of the skin of the blister, the use of a wer cure which has nitrofurazone in it and the application of a banage. following this procedure, the authors of this study tended to 16 lesions, carrying out a total of 112 cures which showed a favourable evolution within six days and no significant differences in the improvement of the lesion

Effect of low-level helium-neon laser therapy on the healing of third-degree burns in rats.

This paper presents the results of a study on the effects of low-level helium-neon laser therapy (LL He-Ne LT) on the healing of burns. Seventy-eight adult male rats, having been subjected to third-degree burns, were randomly divided into four groups: two laser treated groups (n=20, each), one control group (n=19) and one nitrofurazone treated group (n=19). In the two laser treated groups, the burns were treated on a daily basis with LL He-Ne LT with an energy density of 1.2 and 2.4 J/cm(2), respectively. The response to treatment was assessed histologically at 7, 16 and 30 days after burning, and microbiologically at day 15. Analysis of variance showed that the mean of blood vessel sections in the 1.2J/cm(2) laser group was significantly higher than those in the other groups and the mean of the depth of new epidermis in the 2.4 J/cm(2) laser group on day 16 was significantly lower than in the nitrofurazone treated group (P=0.025, P=0.047, respectively). When Staphylococcus aureus and Pseudomonas aeruginosa grew in more than 50% of samples obtained from control group, there were no S. aureus and P. aeruginosa in the samples of 2.4 J/cm(2) laser group. It is concluded that LL He-Ne LT induced the destruction of S. aureus and P. aeruginosa in third-degree burns of rats, yet at the same time our histological findings showed that LL He-Ne LT caused a significant increase in the mean of blood vessel sections on day 7 after third degree burns and a decrease in the mean of the depth of new epidermis on day 16 after the same burns in rats.

Use of broad-spectrum antimicrobials in the eradication of unknown aquatic pathogens in a zebrafish larval rearing system.

A zebrafish larval rearing system experienced a surge in mortality rates soon after the introduction of new stocks. A comprehensive water analysis of pH, nitrites, nitrates, ammonia, chlorine, carbonate hardness, general hardness, and conductivity identified no anomalies. Observations via light microscopy of affected fry revealed consistent signs of impaired mobility, blood clotting, and eventual heart hemorrhage resulting in the death of 90 to 100% of the fry by the age of 2 weeks. Collection of sufficient tissue samples for a histological investigation proved problematic due to the fry's diminutive size. Because a causal agent could not be isolated satisfactorily, the use of a broad-spectrum antibiotic was deemed necessary. After considering many broad-spectrum antibiotics for treatment, we implemented a two-tiered approach for treatment. The rearing system was treated with a nitrofurazone derivative, whereas the adult populations were treated using multi-antibiotic food pellets. The rearing system was treated for 3 weeks, and the adult population was treated for 2 weeks. After the completion of the antibiotic treatments, the biological filters of all of the medicated systems were seeded with nitrifying bacterial cultures. Upon the maturation of the rearing systems' biological filters, mortality rates returned to pre-outbreak levels. There have been no re-occurrences of the fish mortality since the completion of treatment. This epidemic provided some valuable lessons, lessons that if followed, will ensure faster response to unknown pathogens in the future.