Therapeutic evaluation of free and liposome-loaded furazolidone in experimental visceral leishmaniasis.

Drug delivery systems are promising pharmaceutical formulations used to improve the therapeutic index of drugs. In this study, we developed a liposomal formulation of furazolidone that targets Leishmania (Leishmania) chagasi amastigotes in a hamster model. Using laser scanning confocal microscopy, it was demonstrated that the liposomal drug co-localised with L. (L.) chagasi amastigotes within macrophages. Liposomal furazolidone administered intraperitoneally at 0.5mg/kg for 12 consecutive days reduced spleen (74%) and liver (32%) parasite burden at a 100-fold lower dose than the free drug. Free furazolidone (50mg/kg) also effectively reduced spleen (82.5%) and liver (85%) parasites; its in vitro activity against promastigotes and intracellular amastigotes demonstrated a high degree of parasite selectivity. Thus, furazolidone, both in the free and liposome-loaded formulation, is an effective inhibitor of L. (L.) chagasi, representing a possible cost-effective drug candidate for the treatment of visceral leishmaniasis.

Quadruple therapy with furazolidone for retreatment in patients with peptic ulcer disease.

AIM: To establish the efficacy and safety of a 7-d therapeutic regimen using omeprazole, bismuth subcitrate, furazolidone and amoxicillin in patients with peptic ulcer disease who had been previously treated with other therapeutic regimens without success. METHODS: Open cohort study which included patients with peptic ulcer who had previously been treated unsuccessfully with one or more eradication regimens. The therapeutic regimen consisted of 20 mg omeprazole, 240 mg colloidal bismuth subcitrate, 1000 mg amoxicillin, and 200 mg furazolidone, taken twice a day for 7 d. Patients were considered as eradicated when samples taken from the gastric antrum and corpus 12 wk after the end of treatment were negative for Helicobacter pylori (H pylori) (rapid urease test and histology). Safety was determined by the presence of adverse effects. RESULTS: Fifty-one patients were enrolled. The eradication rate was 68.8% (31/45). Adverse effects were reported by 31.4% of the patients, and these were usually considered to be slight or moderate in the majority of the cases. Three patients had to withdraw from the treatment due to the presence of severe adverse effects. CONCLUSION: The association of bismuth, furazolidone, amoxicillin and a proton-pump inhibitor is a valuable alternative for patients who failed to respond to other eradication regimens. It is an effective, cheap and safe option for salvage therapy of positive patients.

Failure of Helicobacter pylori treatment after regimes containing clarithromycin: new practical therapeutic options.

UNLABELLED: Failure of Helicobacter pylori treatment is a growing problem in daily practice. AIM: To evaluate the efficacy of two new regimes as second-line options in a randomized and prospective study. METHODS: Patients in whom a first eradication regime containing clarithromycin had failed were included. After performing gastroscopy and a 13C-urea breath test (UBT), the patients were randomized to receive a combination of 20 mg of rabeprazole, 500 mg of levofloxacin, and 200 mg (two tablets) of furazolidone administered once daily for 10 days (RLF) or the combination of 20 mg of rabeprazole, 120 mg (two tablets) of bismuth subcitrate, 100 mg of doxycycline, and 200 mg of furazolidone, administered twice daily for 10 days (RBDF). Clinical examinations and new UBT were performed 60 days after therapy. RESULTS: Sixty patients were included (mean age, 46 years, 57% females). Two patients were excluded: one because of adverse effects and another as a result of protocol violation. Compliance was similar in both groups (90% took all medications correctly). Side-effects (96% mild) were observed in 87% of the patients and were comparable between groups, except diarrhea, which was more frequent in group RLF (p= .025). Intention-to-treat cure rates were 77% (95% confidence interval (CI): 62-93%) in the RLF group and 83% (95% CI: 68-97%) in the RBDF group (p= .750). Per-protocol cure rates were 80% (95% CI: 65-95%) in the RLF group and 82% (95% CI: 67-96%) in the RBDF group (p= 1.0). CONCLUSIONS: Both once-daily triple (rabeprazole, levofloxacin, and furazolidone) and twice-daily quadruple therapy (rabeprazole, bismuth subcitrate, doxycycline, and furazolidone) for 10 days achieved encouraging results. Subsequent studies should be performed to evaluate antibiotic resistance, doses, dosing intervals, duration of treatment, and safety of these two regimes.

New once-daily, highly effective rescue triple therapy after multiple Helicobacter pylori treatment failures: a pilot study.

BACKGROUND: Helicobacter pylori treatment failure is a growing problem in daily practice. AIM: To determine the efficacy of the combination of rabeprazole, levofloxacin and furazolidone as a rescue therapy. METHODS: Duodenal ulcer patients previously submitted, without success, to at least two H. pylori treatment regimens were included. Gastroscopy (urease test, histological examination and culture) and (13)C-urea breath test were performed. All patients received a combination of rabeprazole 20 mg, levofloxacin 500 mg and furazolidone 200 mg (two tablets) administered in a single dose in the morning for 10 days. Clinical examination and a new (13)C-urea breath test were performed 90 days after therapy. RESULTS: Twelve patients (eight females and four males), mean age 43 (30-58) years were included. Two patients failed to complete the treatment because of nausea and vomiting. Ten patients completed the study and took all the medications as advised. Culture was obtained in six patients: 100 and 83% of the samples were sensitive to furazolidone and levofloxacin, respectively. Per-protocol and intention-to-treat eradication rates were 100 and 83% (P = 0.019). CONCLUSIONS: the combination of rabeprazole, levofloxacin and furazolidone in a single daily dose for 10 days constitutes a highly-effective and low-cost alternative as a third-line therapy in patients infected with H. pylori.

Once-daily, low-cost, highly effective Helicobacter pylori treatment to family members of gastric cancer patients.

BACKGROUND: Helicobacter pylori eradication in family members of gastric cancer patients is now widely accepted, although problems related to costs and compliance persist. AIM: To compare the efficacy, tolerability and long-term re-infection rates of two once-daily regimens for the eradication of H. pylori in family members of gastric cancer patients. METHODS: 106 first-degree family members of gastric cancer patients were recruited and submitted to the 13C-urea breath test (UBT) to detect H. pylori. If positive, they were randomly allocated to receive a combination of lanzoprazole 30 mg, clarithromycin OD (extended-release formulation) 500 mg and furazolidone 400 mg, once daily, in the morning, for 7 days (Group A) or the same regimen with only 200 mg furazolidone (Group B). Eradication was confirmed by urea breath test performed 6 weeks after treatment. 13C-urea breath test was repeated at 944 (784-1258) days after treatment in successfully treated participants to look for re-infection. RESULTS: Twenty-five participants were H. pylori negative and two H. pylori-positive individuals refused to sign the informed consent and were excluded. Therefore, 79 participants were studied. Forty participants were allocated to Group A and 39 to Group B. All participants completed treatment. Adverse effects, mostly mild, were observed in 18% of Group A and 18% of Group B (N.S.). The intention-to-treat eradication rate was 87.5% in Group A and 61.5% in Group B (P = 0.006). The mean annual re-infection rate was 3%. CONCLUSIONS: The combination of lanzoprazole 30 mg, one tablet of clarithromycin OD (extended release formulation) 500 mg and furazolidone 400 mg, once daily for 7 days, constitutes an inexpensive, safe and effective alternative for anti-H. pylori therapy in family members of gastric cancer patients.

Factors associated with treatment failure of Helicobacter pylori infection in a developing country.

BACKGROUND: Although no regimen can eradicate in 100% of patients, factors that may affect the eradication rates have been poorly studied. GOAL: To evaluate factors associated with treatment failure. STUDY: One hundred patients were treated with pantoprazole plus clarithromycin and furazolidone for eradication. Clarithromycin and furazolidone resistance was evaluated by the agar dilution method. Point mutations in 23S rRNA genes related to clarithromycin resistance were investigated by polymerase chain reaction and restriction length fragment polymorphism and A by polymerase chain reaction. The data were analyzed by logistic regression. RESULTS: eradication occurred in 85 of 97 patients who completed the treatment (87.6%; 95% CI = 79.0-93.1). All strains were susceptible to furazolidone, and nine were resistant to clarithromycin (A2142G or A2143G mutation was detected in all of them). The treatment failure was significant and independently associated with clarithromycin resistance (OR = 7.79; 95% CI = 1.73-35.01), A-negative status (OR = 4.81; 95% CI = 1.14-20.14), and male gender (OR = 4.20; 95% CI = 1.01-17.78), but not with the type of disease, mean age, smoking, alcohol consumption, and the degree of the antral and oxyntic gastritis. CONCLUSION: Resistance to clarithromycin, A-negative status, and gender were predictive factors of eradication failure.

Omeprazole, clarithromycin and furazolidone for the eradication of Helicobacter pylori in patients with duodenal ulcer.

AIM: To evaluate the efficacy of omeprazole plus clarithromycin and furazolidone in Helicobacter pylori eradication and duodenal ulcer healing in Brazilian patients. METHODS: Forty H. pylori-positive patients with duodenal ulcer were randomized to receive 20 mg omeprazole o.m. or b.d. for 1 month plus 500 mg clarithromycin (b.d. ) and 200 mg furazolidone (b.d.) for 1 week. RESULTS: Three months after the end of the treatment the eradication rates were 90% by intention-to-treat analysis, and 97% by per protocol analysis. Mild side-effects were observed in 25 patients, none of whom abandoned the protocol. No difference was observed between the 20 mg and 40 mg omeprazole daily doses. Cure or significant improvement of the symptoms and of the histological alterations were observed after H. pylori eradication. CONCLUSION: Our results demonstrate that clarithromycin and furazolidone in combination with omeprazole are a good alternative for H. pylori eradication in Brazilian patients with duodenal ulcer.

Eficacia de la terapia cuádruple en la erradicación del Helicobacter pylori y la prevención de la úlcera duodenal recidivante / Efficacy of quadruple therapy for eradication of Helicobacter pylori and prevention of recurring duodenal ulcer

Objetivo. El objetivo de nuestro estudio fue evaluar la eficacia del tratamiento con ranitidina asociada a tres antibióticos para la erradicación del Helicobacter pylori (Hp) contra el tratamiento de mantenimiento con ranitidina en la prevención de la recidiva de la úlcera duodenal (UD) durante un seguimiento de 12 meses. Antecedentes. Se han efectuado numerosos estudios sobre la erradicación del Hp en la mucosa gástrica y la prevención de la UD recidivante, sin embargo, no se ha establecido aún un tratamiento óptimo. Métodos. Nosotros efectuamos un estudio prospectivo y comparativo con 51 pacientes portadores de UD activa diagnosticada por endoscopía y que fueron distribuidos al azar en dos grupos. El grupo A (26 pacientes) recibió ranitidina 300 mg/día + metronidazol 1.5 g/día + furoxona 300 mg/día por cinco días durante 12 meses. En ambos grupos efectuamos endoscopía de control a las ocho semanas de iniciado el tratamiento, así como a los seis y 12 meses de su inclusión en el protocolo o antes en caso de presentar manifestaciones clínicas de recidiva de la UD. En cada endoscopía se tomaron dos biopsias del antro gástrico para la detección histológica del Hp mediante tinción de Giemsa así como de hematoxilina y eosina. Todos los pacientes dieron su consentimiento para participar en la investigación ésta fue aprobada por el Comité de Etica de nuestro hospital. El análisis estadístico se efectuó mediante X2. Resultados. Después de ocho semanas, las ulceras de todos los pacientes se encontraban cicatrizadas. El porcentaje de erradicación del Hp fue de 24/26 (92 por ciento) en el grupo A y ninguno en el grupo B(p<0.001). La reubfeccuñib por Hp ocurrió en 9/24 (37.5) durante el periodo control de 12 meses (grupo A) y de éstos un paciente tuvo recidiva de la UD. Por el contrario, los 25 pacientes del grupo B fueron persistentes positivos para el Hp y siete sufrieron recidiva de la UD (p<0.05). Ambos tratamientos fueron bien tolerados. Conclusiones. La terapia combinada de amoxicilina, metronizadol, furoxona y ranitidina es altamente efectiva para la erradicación del Hp y la prevención de la recidiva de la UD. Nuestros resultados son similares a los reportados con otros esquemas terapéuticos

[Efficacy of quadruple therapy in the eradication of Helicobacter pylori and prevention of recurrent duodenal ulcer]. / Eficacia de la terapia cuádruple en la erradicación del Helicobacter pylori y la prevención de la úlcera duodenal recidivante.

OBJECTIVE: We studied during a 12-months follow-up the effect of the eradication of Helicobacter pylori (Hp) on the recurrence of duodenal ulcer (DU). BACKGROUND: The eradication of Hp from the gastric mucosa has been the objective of numerous therapeutic trials for preventing DU recurrence; however, an optimal treatment has not yet been established. METHODS: 51 patients with Hp infection and active DU confirmed by endoscopy were randomized in two groups. All patients received ranitidine 300 mg daily for eight weeks. Group A (26 patients) received a 5 day course of amoxycillin 500 mg t.i.d., metronidazole 500 mg t.i.d., and furoxone 100 mg t.i.d., during the 3rd week. After ranitidine treatment, none patient of this group received further treatment. Group B (25 patients) received 150 mg of ranitidine daily during 12 months. Endoscopy was performed at the end of the first eight weeks of the ranitidine treatment as well as at the 6th and 12th month of follow-up or sooner if symptoms recurred. Two biopsies were taken from gastric antrum at each endoscopy examination for Hp detection with Giemsa and hematoxylin/eosine stains. Each patient gave informed consent and this trial was approved by the regional Ethics Committee. Statistical analysis was performed using chi 2 test. RESULTS: After eight weeks of ranitidine treatment, the ulcer of all patients from both groups was healed. The percentage of Hp eradication was 92% (24/26 pt) in group A and none in group B (p < 0.001). Recurrence of Hp infection occurred in 9/24 patients (37.5%) during a 12 months follow-up (group A) and of these, one patient had recurrence of DU. In contrast, all 25 patients of group B were persistently Hp positive and 7 developed recurrent DU (p < 0.05). Both treatments were well tolerated. CONCLUSIONS: The combined therapy with amoxycillin, metronidazole, furoxone and ranitidine is highly effective in both Hp eradication and prevention of DU recurrence.

Acid suppression with ranitidine plus oral triple therapy improves ulcer healing but not Helicobacter pylori eradication.

BACKGROUND/AIMS: To evaluate whether the addition of 2 weeks of ranitidine to a 1-week oral triple therapy (OTT) regimen improved ulcer healing and H. pylori eradication. METHODOLOGY: Two hundred and eleven consecutive patients with an endoscopic diagnosis of active duodenal ulcer (DU) and a positive antrum biopsy for H. pylori were enrolled. Those attending the Hospital Vera Cruz (Group A, n=142) received a 14-day course of ranitidine (150 mg after breakfast and dinner) plus a 1-week OTT, consisting of bismuth subcitrate, (240 mg after the 3 meals), tetracycline (500 mg, 10 min before the three meals and at bedtime), and furazolidone (200 mg after breakfast and dinner). Patients from the Hospital das Clinicas (Group B, n=69) received the same OTT as Group A but without ranitidine. Patients underwent endoscopy again on average 40 days (range: 30-60 days) after completing therapy in order to assess ulcer healing and H. pylori status. RESULTS: Both schedules were equally efficient in eradicating H. pylori with 90% (128/142) eradication in group A, and 84% (58/69) in group B (p=0.2). In contrast, the addition of ranitidine to OTT improved ulcer healing when compared with OTT alone (96%, 137/142, vs. 70%, 48/69; p<0.001). CONCLUSIONS: Our results demonstrate that the association of acid suppression, obtained with 2 week ranitidine administration with OTT improved ulcer healing but did not enhance H. pylori eradication.

Five day and ten day triple therapy (amoxicillin, furazolidone and metronidazole) in the treatment of duodenal ulcer.

This investigation aimed to compare bacterial eradication and healing in patients with active duodenal ulcer treated with a combination of furazolidone 600 mg/day and metronidazole 750 mg/day and amoxicillin 1.5 and g/day for 5 (TT5) or 10 (TT10) days. Fifty four (TT5 = 28 and TT10 = 26) patients were included in the study. Ulcer healing was observed in 77.8% of TT5 Group and in 75% of TT10 Group at week 4. H pylori eradication was observed in 51.9% and 65% respectively (p > 0.05). When all patients were grouped, a significantly healing rate was observed in those eradicated as compared to those not eradicated (p = 0.03). We concluded that extending the treatment to 10 days did not significantly influence the results of ulcer healing and eradication of Helicobacter pylori.

Tratamento do "Helicobacter pylori" em pacientes resistentes ao esquema Belo Horizonte (EBH) / Treatment of \"Helicobacter pylori\" in patients resistant to Belo Horizonte scheme

Foram estudados 150 pacientes com úlcera duodenal endoscopicamente comprovada em qualquer estádio da classificaçao de Sakita e resistentes ao EBH. Os pacientes foram aleatoriamente distribuídos em três grupos terapêuticos utilizando omeprazol, subcitrato de bismuto coloidal, amoxicilina e furazolidona. O grupo II, que utilizou omeprazol 20 mg uid x sete dias, associado a amoxicilina 500mg + furazolidona 200mg + SBC 120mg qid x sete dias, foi o que apresentou melhor índice de erradicaçao, com 64,4 por cento. Ocorreram altas taxas de efeitos colaterais nos três grupos, porém leves em sua maioria, e mais freqüentes nos esquemas de 14 dias.

Efecto de la furazolidona sobre el glutatión sanguíneo del pollo de engorda / Effec of furazolidone on chicks blood glutathione

El objetivo de este trabajo fue establecer si la furazolidona utiliza el sistema detoxificante de glutatión en el organismo, mediante la determinación de la cantidad (µmol/ml de sangre) de glutatión total (GT), glutatión oxidado (GSSG), y glutatión reducido (GSH) durante las 5 semanas de vida del pollo de engorda que no consumió aditivos (testigo), comparado con los niveles de GT, GSSG y GSH sanguíneo de las aves que consumieron furazolidona durante las 5 primeras semanas de vida. Hubo diferencia significativa entre el GT (µmol/ml de sangre) y el peso corporal de pollos del grupo testigo y el que consumió furazolidona (55 ppm en el alimento) (R²= -0.709; P< 0.05, y = 2.15 - 0.607x y R²=-0.820 P< 0.05, y = 2.17 -0.61x respectivamente) hubo diferencia significativa (P< 0.05) entre el peso de los pollos del grupo testigo y el de los que consumieron furazolidona (751.3 vs 884.35 g respectivamente)

Duodenal ulcer and eradication of Helicobacter pylori in a developing country. An 18-month follow-up study.

Forty-eight patients with endoscopically proven duodenal ulcer (DU) and Helicobacter pylori infection detected by 14C-urea breath test (BT) were assigned to 5 days of treatment with furazolidone, metronidazole, and amoxicillin in addition to eventual classical anti-ulcer agents if necessary. Clinical evaluation and BT were repeated at 2, 6, and 18 months after therapy to determine H. pylori eradication or reinfection. Endoscopy was also repeated at 6 and 18 months after treatment to detect DU relapse. In 29 (60%) patients H. pylori had been eradicated at 2 months after therapy, and in 19 (40%) infection persisted. After successful eradication, 6 of 29 (20.7%) were reinfected. All 24 patients who were negative at the 18-month evaluation were asymptomatic, free of anti-ulcer drugs, and with healed ulcers, whereas among the 19 positive patients followed up, 11 (57%) continued to be symptomatic and still using anti-ulcer agents (p less than 0.010), and 10 (53%) showed active ulcers at endoscopy (p less than 0.010). H. pylori eradication is clearly followed by long-term remission of DU. Reinfection may be an additional problem in treating DU patients in developing countries.

Que Hay de Nuevo en Giardiasis / What is New about Giardiasis

Se revisan los aspectos clinicos mas importantes de la literatura sobre giardiasis en funcion de su utilidad para el medico y de su implicacion en la investigacion, haciendose enfasis en el empleo del microscopio electronico de rastreo en el estudio de las lesiones intestinales; se discuten: la multiplicidad de las manifestaciones causadas por esta enfermedad; la presencia de endosimbiotes en trofozoitos y quistes de Giardia lamblia: las publicaciones mas recientes sobre transmision; las diversas alteraciones funcionales e histologicas del intestino; las relaciones de este parasito con diversos sindromes de inmunodeficiencia; su relacion con cuadros de malabsorcion secundaria a la malnutricion proteica primaria severa; la relacion con los estados de hipoclorhidria y aclorhidria, y la relacion posible de esta parasitosis con una flora bacteriana intestinal anormal concomitante