Phytochemical Estimation and Therapeutic Amelioration of Aesculus hippocastanum L. Seeds Ethanolic Extract in Gastric Ulcer in Rats Possibly by Inhibiting Prostaglandin Synthesis.

OBJECTIVE: To quantify phytochemicals using liquid chromatography and mass spectroscopy (LCMS) analysis and explore the therapeutic effect of Aesculus hippocastanum L. (AH) seeds ethanolic extract against gastric ulcers in rats. METHODS: Preliminary phytochemical testing and LCMS analysis were performed according to standard methods. For treatment, the animals were divided into 7 groups including normal control, ulcer control, self-healing, AH seeds low and high doses, ranitidine and per se groups. Rats were orally administered with 10 mg/kg of indomethacin, excluding the normal control group (which received 1% carboxy methyl cellulose) and the per se group (received 200 mg/kg AH seeds extract). The test group rats were then given 2 doses of AH seeds extract (100 and 200 mg/kg, respectively), while the standard group was given ranitidine (50 mg/kg). On the 11th day, rats in all groups were sacrificed, and their stomach was isolated to calculate the ulcer index, and other parameters such as blood prostaglandin (PGE2), tissue superoxide dismutase (SOD), catalase (CAT), malonyldialdehyde (MDA), and glutathione (GSH). All isolated stomach tissues were analyzed for histopathological findings. RESULTS: The phytochemical examination shows that the AH seeds contain alkaloids, flavonoids, saponins, phenolic components, and glycosides. LCMS analysis confirms the presence of quercetin and rutin. The AH seeds extract showed significant improvement in gastric mucosa conditions after indomethacin-induced gastric lesions (P<0.01). Further marked improvement in blood PGE2 and antioxidant enzymes, SOD, CAT, MDA and GSH, were observed compared with self-healing and untreated ulcer-induced groups (P<0.01). Histopathology results confirmed that AH seeds extract improved the mucosal layer and gastric epithelial membrane in treated groups compared to untreated ulcer-induced groups. CONCLUSIONS: LCMS report confirms the presence of quercetin and rutin in AH seeds ethanolic extract. The therapeutic effect of AH seeds extract against indomethacin-induced ulcer in rat model indicated the regenerated membrane integrity, with improved cellular functions and mucus thickness. Further, improved antioxidant enzyme level would help to reduce PGE2 biosynthesis.

Supplementation with Whey Protein, Omega-3 Fatty Acids and Polyphenols Combined with Electrical Muscle Stimulation Increases Muscle Strength in Elderly Adults with Limited Mobility: A Randomized Controlled Trial.

Age-related sarcopenia is a progressive and generalized skeletal muscle disorder associated with adverse outcomes. Herein, we evaluate the effects of a combination of electrical muscle stimulation (EMS) and a whey-based nutritional supplement (with or without polyphenols and fish oil-derived omega-3 fatty acids) on muscle function and size. Free-living elderly participants with mobility limitations were included in this study. They received 2 sessions of EMS per week and were randomly assigned to ingest an isocaloric beverage and capsules for 12 weeks: (1) carbohydrate + placebo capsules (CHO, n = 12), (2) whey protein isolate + placebo capsules (WPI, n = 15) and (3) whey protein isolate + bioactives (BIO) capsules containing omega-3 fatty acids, rutin, and curcumin (WPI + BIO, n = 10). The change in knee extension strength was significantly improved by 13% in the WPI + BIO group versus CHO on top of EMS, while WPI alone did not provide a significant benefit over CHO. On top of this, there was the largest improvement in gait speed (8%). The combination of EMS and this specific nutritional intervention could be considered as a new approach for the prevention of sarcopenia but more work is needed before this approach should be recommended. This trial was registered at the Japanese University Hospital Medical Information Network (UMIN) clinical trial registry (UMIN000008382).

Rutin and meloxicam attenuate paw inflammation in mice: Affecting sorbitol dehydrogenase activity.

Rutin, naturally occurring flavonoid, has reported to cover interesting multiple pharmacological properties. This study evaluated rutin or/and meloxicam effects in paw inflammation induced by formalin in mice. Mice were divided into four groups: I-Formalin group, II-Rutin 60 mg/kg (p.o.), III-Meloxicam 10 mg/kg (p.o.), plus IV-Combined rutin and meloxicam. Therapies were administered once a day for 7 days. The curative effects were assessed on inflammatory, oxidative stress, and apoptosis. Both rutin and/or meloxicam induced marked improvement in paw licking time on the 1st day and by combined treatment only on the 3rd day as well reduction in paw edema% on the 3rd day. Moreover, noticeable progress in liver malondialdehyde content, superoxide dismutase, and sorbitol dehydrogenase activities as well decline in paw interleukin-1ß level and extent of apoptosis. The results spot light on the good influence of combined rutin and meloxicam in formalin-induced mice paw inflammation to a better extent than either rutin or meloxicam lonely.

A Randomized, Clinical Trial to Evaluate Efficacy and Tolerability of Trypsin:Chymotrypsin as Compared to Serratiopeptidase and Trypsin:Bromelain:Rutoside in Wound Management.

INTRODUCTION: Systemic enzyme therapy can play an important role in maintaining normal inflammatory processes within the body and thereby helps support and speed up healing. In the course of the anti-inflammatory action, enzymes degrade damaged cells and necrotic material and, through the inactivation of mediators and toxic products, they restrict the edema and pain. METHOD: The study conducted at Grant Medical College, Mumbai, India was a clinical trial comparing the efficacy and tolerability of three oral enzyme treatment groups-oral tablets containing trypsin:chymotrypsin (TC) (Chymoral Forte®), serratiopeptidase (S) 5 mg oral tablets, and oral enzyme tablets containing trypsin 48 mg, bromelain 90 mg, and rutoside 100 mg (TBR)-to evaluate their healing potential in surgical wounds after orthopedic surgery. RESULTS: A total of 75 patients were screened, randomized, and divided into three groups in 1:1:1 ratio receiving either of the three treatments. In the TC group, erythema was significantly reduced from 3.44 on day 3 to 1.16 on day 10 (p < 0.01). There was significantly better reduction in erythema scores in the TC group as compared to S and TBR groups (p < 0.05) at each follow-up visit. Similarly reduction in the local irritation, wound discharge, edema, induration, and tenderness score with TC treatment at the end of the study was significantly higher than that observed in the other two groups. In addition TC showed significant reduction in pain on the VAS scale (p < 0.01). Global assessment of response to therapy for efficacy and tolerability was reported to be good to excellent in 88% and 92% of the patients on TC as compared to 12% and 8% with S and 12% and 8% with TBR. CONCLUSION: TC provides a better resolution of symptoms of inflammation after orthopedic surgery as compared to S and TBR, thus facilitating better wound healing. Further studies are warranted to confirm the findings. TRIAL REGISTRATION: Clinical Trial Registry of India (Reg. No. CTRI/2011/07/001920).

Rutoside and Hydrolytic Enzymes Do Not Attenuate Marathon-Induced Inflammation.

INTRODUCTION: Vigorous and prolonged exercise such as marathon running increases inflammatory markers and the risk of upper respiratory illness (URI) in athletes. Nutritional supplements are being tested as countermeasures of exercise-induced inflammation and immune dysfunction. METHODS: In this prospective randomized, double-blind, placebo-controlled phase I trial, healthy male runners (N = 138, age 42 ± 11 yr) were supplemented with rutoside (600-1200 mg·d) and hydrolytic enzymes (540-1080 mg·d bromelain, 288-576 mg·d trypsin) (WOB) or placebo (PL) for 1 wk before and 2 wk after the Munich Marathon 2013. Blood samples were collected 5 wk prerace and immediately, 24 h, and 72 h postrace and analyzed for inflammation biomarkers (interleukins [IL] 6 and 10, high-sensitivity C-reactive protein, and leukocytes). URI rates, assessed by the Wisconsin Upper Respiratory Symptom Survey, were compared between the study groups during the 2-wk period after the marathon race. URI was defined if the Wisconsin Upper Respiratory Symptom Survey score was equal or greater than seven, representing either one severe symptom or seven mild symptoms. RESULTS: Immediately postrace, the increase of IL-6 was not significantly different between the WOB and the PL groups (median [interquartile range]: WOB, 33.8 [22.5-58.8] ng·L; PL, 35.6 [24.8-61.29] ng·L; P = 0.758). No significant group differences were observed for increases of IL-10, high-sensitivity C-reactive protein, or leukocytes pre- to postrace (all P > 0.05). From race day until 2 wk after the marathon race, the percentage of individuals with at least one URI did not significantly differ between the groups (WOB, 50.0%; PL, 51.5%; P = 0.859). CONCLUSION: Supplementation with rutoside and hydrolytic enzymes before and after a marathon race did not attenuate postrace inflammation or decrease URI incidence in nonelite male marathon runners.

Intravenous rutin in rat exacerbates isoprenaline-induced cardiotoxicity likely due to intracellular oxidative stress.

OBJECTIVES: Rutin, quercetin-3-O-rutinoside, a natural flavonol glycoside, has shown various in vitro benefits with potential use treating human diseases, especially cardiovascular system disorders. Antioxidant properties are assumed to underlie the majority of these benefits. Yet rutin pro-oxidant properties have been reported as well. Our research group has recently shown aggravating effects on isoprenaline (ISO)-induced cardiotoxicity in Wistar:Han rats after 24 hours. METHODS: This study was designed to examine in more detail the reasons for the negative effects of rutin (11.5 and 46 mg/kg, i.v.) after administration of ISO (100 mg/kg, s.c.) in rats within 2 hours of continuous experiment and in the H9c2 cardiomyoblast-derived cell line. RESULTS: Like our previous findings, rutin did not (11.5 or 46 mg/kg, i.v.) reduce the ISO-induced mortality within 2 hours although the lower dose significantly reduced cardiac troponin T (cTnT) and partly improved the histological findings. In contrast, the higher dose increased the mortality in comparison with solvent (1.26% w/v sodium bicarbonate). This was not caused by any specific haemodynamic disturbances. It appears to be associated with oxidative stress as rutin enhanced intracellular reactive oxygen species formation in vitro and had the tendency to increase it in vivo. CONCLUSIONS: Rutin, likely due to its pro-oxidative effects, can exacerbate catecholamine cardiotoxicity depending on the dose used.

Gelatin-based microspheres crosslinked with glutaraldehyde and rutin oriented to cosmetics

ABSTRACT Glutaraldehyde (GTA) has been extensively used as a gelatin crosslinking agent, however, new natural ones have been suggested as more biocompatible. Polyphenols are possible candidates and the flavonols, such as rutin (RUT), also exhibit potential synergism with sunscreens and antioxidant agents used in cosmetics. In this work, gelatin microspheres (M0) were obtained and crosslinked with GTA 10 mM (MG) or RUT 10 mM (MR), dissolved in acetone:NaOH 0,01M (70:30 v/v). MG exhibited crosslinking extent of 54.4%. Gelatin, M0, MG and MR did not elicit any signs of skin damage, regarding the formation of erythema, the barrier function disruption and negative interference in the stratum corneum hydration. Oily dispersions containing M0, MG or MR, isolated or combined with benzophenone-3 or octyl methoxycinnamate, suggested that the microspheres, at a 5.0% w/w, had no additional chemical or physical photoprotective effect in vitro. Crosslinking with RUT had occurred, but in a lower degree than GTA. Microspheres had not improved sun protection parameters, although, non-treated gelatin interfered positively with the SPF for both UV filters. The in vivo studies demonstrated that these materials had very good skin compatibility.

Acute and Subacute Toxicity Studies on Rutin-Rich Tartary Buckwheat Dough in Experimental Animals.

In order to investigate the toxicity of rutin-rich dough from the Tartary buckwheat variety 'Manten-Kirari,' acute and subacute toxicity studies (10,000 and 5,000 mg/kg flour, respectively) were performed using rats. In the acute toxicity study, no toxic symptoms were observed and no rats died during the test. Body weight in the 'Manten-Kirari'-treated group was not significantly different when compared with that of the control group. On pathologico-anatomic observation, no unusual symptoms were observed in the 'Manten-Kirari'-treated group when compared with the control group. In the subacute toxicity study, no toxic symptoms were observed and no rats died during the test. Body weight and food intake in the 'Manten-Kirari'-treated and common buckwheat groups were not significantly different when compared with the control group. However, some investigated properties, such as urine protein and serum albumin, were significantly different in the 'Manten-Kirari' and common buckwheat groups when compared with the control group. However, these changes were not caused by toxicity, but by transient changes. On pathologico-anatomic observation, some abnormalities were observed in the liver, kidneys, heart, lung, bronchi and pituitary gland in some rats. However, the incidental rates in the 'Manten-Kirari' and common buckwheat groups did not differ when compared to controls. Therefore, these abnormalities may be caused by natural generation. Based on these results, we concluded that dough at a dose of 5,000 mg flour/kg is at a non effect level.

Rutin (quercetin rutinoside) induced protein-energy malnutrition in chronic kidney disease, but quercetin acted beneficially.

Nutraceutically, much of the literature has indicated that an aglycon and its related glycoside would act similarly. However, controversial reports are accumulating. We hypothesize that rutin (RT) and quercetin (QT) pharmacodynamically could act differently. To confirm this, doxorubicin (DR) (8.5 mg/kg) was used to induce rat chronic kidney disease (CKD) and then treated with QT and RT (each 70 mg/kg body weight per day) for 13 weeks. QT exhibited better body weight gaining effect (420 ± 45) vs RT, 350 ± 57 g/rat (p < 0.001). DR raised the ratio kidney-to-body weight (%) to 0.82 (p < 0.001) vs RT, 0.62 (p < 0.01), and QT, 0.35 (p < 0.01). DR reduced the glomerular filtration rate to 25.2 vs RT, 48 ± 11.3; QT, 124.7 ± 12.8 (p < 0.001) and the control, 191.5 ± 15.7 mL/h (p < 0.001). DRCKD reduced hematocrit to 29 ± 5; RT, to 28 ± 5 (p < 0.05); QT, to 36 ± 6 vs the control 37.5 ± 4%, (p < 0.01). DRCKD reduced the serum albumin (s-Ab) to 2.1 ± 0.2 (p < 0.001); QT, to 2.7 ± 0.2 (p < 0.05) vs the normal 4.3 ± 0.5 g/dL, yet RT was totally ineffective. DRCKD raised serum cholesterol level to 340 ± 30; vs RT, 260 ± 12; QT, 220 ± 25; and the normal value, 70 ± 25 mg/dL. DRCKD increased serum triglyceride to 260 ± 15 (p < 0.001), RT and QT restored it to 170 ± 25 and 200 ± 15 (p < 0.05) vs the normal 26-145 mg/dL. DRCKD elevated blood urea nitrogen to 38 ± 3 vs RT, to 98 ± 6 mg/dL (p < 0.001), implicating "protein-energy malnutrition". RT stimulated serum creatinine (sCr) production to reach 6.0 ± 0.9 mg/dL (p < 0.001). QT did not alter the sCr level. RT but not QT induced uremia and hypercreatininemia. DR significantly downregulated Bcl-2, but highly upregulated Bax, Bad, and cleaved caspase-3, implicating the intrinsic mitochondrial pathway. DR damaged DNA, but QT completely rescued such an effect and recovered renal amyloidosis and collagen deposition. Conclusively, RT and QT act differently, and RT is inferior to QT with respect to treating CKD.

An open-label pilot study of a formulation containing the anti-inflammatory flavonoid luteolin and its effects on behavior in children with autism spectrum disorders.

BACKGROUND: Accumulating evidence suggests an association between autism spectrum disorders (ASD) and inflammation in brain regions related to cognitive function. The natural flavonoid luteolin has antioxidant, anti-inflammatory, mast cell-blocking, and neuroprotective effects. It was shown to improve cognitive performance in a mouse model of ASD, but its effect in humans has not been adequately studied. OBJECTIVES: The goal of this study was to assess the effectiveness and tolerability in white children with ASD of a dietary supplement containing 2 flavonoids (>95% pure), luteolin (100 mg/capsule, from chamomile) and quercetin (70 mg/capsule), and the quercetin glycoside rutin (30 mg/capsule) from the Sophora japonica leaf, formulated in olive kernel oil to increase oral absorption. METHODS: Fifty children (4-10 years old; 42 boys and 8 girls) with ASD were enrolled in a 26-week, prospective, open-label trial at the 2nd University Department of Psychiatry at "Attikon" General Hospital, Athens, Greece. Children were referred for the study by their respective physicians or came from the practice of the senior author. ASD diagnosis by clinical assessment was based on the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision, symptom list and corroborated by using the Autism Diagnostic Observation Schedule. The dose of the study formulation used was 1 capsule per 10 kg weight per day with food. The primary outcome measures were the age-equivalent scores in the Vineland Adaptive Behavior Scales domains. Secondary outcomes included the Aberrant Behavior Checklist, the Autism Treatment Evaluation Checklist, and the Clinical Global Impression-Improvement score. Data were measured at baseline, week 18, and week 26. Parents were interviewed for any possible improvements they noticed and instructed to report any unusual adverse events. RESULTS: A total of 40 children completed the protocol. There was a significant improvement in adaptive functioning as measured by using the VABS age-equivalent scores (8.43 months in the communication domain, 7.17 months in daily living skills, and 8 months in the social domain; P < 0.005), as well as in overall behavior as indicated by the reduction (26.6%-34.8%) in Aberrant Behavior Checklist subscale scores. Age, sex, and history of allergies had no effect on the results, whereas the initial level of functioning or difficulty did predict the final outcome in most of the measures used. There was a transient (1-8 weeks) increased irritability in 27 of the 50 participants. CONCLUSIONS: These results are encouraging in that the combination of the flavonoids luteolin and quercetin seemed to be effective in reducing ASD symptoms, with no major adverse effects. ClinicalTrials.gov identifier: NCT01847521.

Antioxidant activity and cytotoxicity of Cyrtosperma johnstonii extracts on drug sensitive and resistant leukemia and small cell lung carcinoma cells.

CONTEXT: The number of patients with cancer is increasing. New therapeutic agents to overcome drug-resistant tumors are urgently needed. Cyrtosperma johnstonii N.E. Br. (Araceae) is used for treatment of cancer in Thai traditional medicine. This study aimed to evaluate antioxidant activity and cytotoxicity of C. johnstonii extracts on human cancer cells. MATERIALS AND METHODS: Dried powder of C. johnstonii rhizomes was extracted with several solvents. The 0.1 mg/ml extract solution was tested for antioxidant activity by 2,2'-azinobis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) and ferric reducing antioxidant power (FRAP) assays. Color formation from 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide was used to determine cell viability. Standardization of the extract was performed by high-performance liquid chromatography (HPLC) with photodiode array detector at 254 and 360 nm. Cell cycle arrest was evaluated by flow cytometry after 5 min, 12 h and 24 h treated with 20 µg/ml of the acetone extract. RESULTS: The acetone extract exhibited the highest phenolic content and antioxidant activity (TEAC and EC values = 19.2 ± 0.14 and 19.2 ± 0.31 mM/mg, respectively). The IC50 values for leukemia ranged from 11 ± 1 to 29 ± 3 µg/ml and from 5 ± 2 to 6 ± 0 µg/ml for small cell lung carcinoma cells. Cell cycle arrest occurred at the G2/M phase followed by apoptosis. HPLC analysis revealed that rutin is the major constituents of the extract. DISCUSSION AND CONCLUSION: The acetone extract of C. johnstoni is a promising source of natural antioxidants and anticancer. The extract inhibits cancer cells effectively with less effect on normal cells.

Hypoglycaemic effect of Melothria heterophylla in streptozotocin-induced diabetic rats.

CONTEXT: In the Indian traditional system of medicine, Melothria heterophylla (Lour.) Cogn., (Cucurbitaceae) is prescribed for the treatment of diabetes mellitus. OBJECTIVE: In the present study, the antidiabetic effect of ethanol extract of Melothria heterophylla (EEMH), and its active isolated constituents were investigated in streptozotocin (STZ)-induced diabetic Swiss albino rats. METHOD: Successive Soxhlet extraction of the dried total aerial parts with petroleum ether for defatting and then with ethanol (95%) to obtain ethanol extract, which was concentrated under reduced pressure. Hyperglycemia was induced in rats by STZ (50 mg/kg, body weight). Twenty-four hours after STZ induction, respective groups of diabetic rats received EEMH (200 and 400 mg/kg, body weight), gallic acid (GA) (2 and 4 mg/kg, body weight), and rutin (RU) (2 and 4 mg/kg, body weight), respectively, orally daily for 15 days. Glibenclamide (0.5 mg/kg, orally) served as reference. Blood glucose levels and change in body weight were measured on every 5(th) day during 15 days of treatment. Biochemical parameters, viz., serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), alkaline phosphatase (ALP) and serum insulin, were measured. RESULTS: EEMH and its active constituents significantly (p < 0.01) normalized blood glucose levels and serum biochemical parameters as compared to those of STZ controls. Both GA (4 mg/kg) and RU (4 mg/kg) exhibited maximum glucose lowering effect (69.1 and 66.7%, respectively) in diabetic rats compared to the other dose (2 mg/kg) at the end of the study. EEMH, gallic acid and RU also showed significant increase in serum insulin, and body weight of STZ-induced diabetic rats. CONCLUSION: Therefore, ethanol extract of Melothria heterophylla, GA and RU demonstrated remarkable antidiabetic activity in STZ-induced diabetic rats.

Severe liver dysfunction possibly caused by the combination of interferon beta-1b therapy and melilot (sweet clover) supplement.

WHAT IS KNOWN AND OBJECTIVE: We report a case of severe liver dysfunction exacerbated after interferon beta (IFNB)-1b injection in a patient with multiple sclerosis (MS) who had been taking a melilot (sweet clover) supplement. Although IFNB-1b therapy for MS can cause mild liver dysfunction, severe hepatotoxicity attributable to supplement use has been reported. CASE SUMMARY: A 23-year-old Japanese woman taking a melilot supplement containing coumarin at 10 mg/day for 3 years was admitted to our hospital to receive IFNB-1b therapy for MS. Fourteen days after subcutaneous injection of IFNB-1b every other day, her aspartate transaminase (AST) and alanine aminotransferase (ALT) levels were elevated at 235 and 681 IU/L, respectively. After the discontinuation of IFNB-1b therapy and supplement intake, AST and ALT returned to normal levels. Later, she started receiving an intramuscular injection of IFNB-1a weekly without supplement intake. She was able to continue IFNB-1a therapy this time, showing a slight elevation of AST level at 61 IU/L. WHAT IS NEW AND CONCLUSION: The combination of IFNB-1b therapy and melilot supplement intake may cause severe liver dysfunction in patients with MS. Given the doubtful value of the supplement, we suggest that it should be avoided by patients receiving interferon therapy.

[Impact of exogenous proteolytic enzymes on immunogenesis in patients with urogenital infections].

The use of systemic enzyme therapy in combination with antibiotics in the treatment of urogenital chlamydia infection in patients of both sexes proved to improve the therapeutic efficacy and to reduce the risk of the side effects.

[Systemic enzymotherapy in the combined treatment of infectious endocarditis in drug addicts].

The aim of this study was to elucidate effects of systemic enzymotherapy on the clinical course of infectious endocarditis and the frequency of thromboembolic complications in drug addicts compared with controls. Another objective was to develop an optimal regime of enzymotherapy depending on the severity of the disease. Inclusion of wobenzyme in the combined treatment of infectious endocarditis permitted to accelerate the achievement of clinical improvement, normalize blood rheologic characteristics, reduce severity of intoxication and systemic inflammation, decrease the frequency of septic thromboembolia of the pulmonary artery.

[EFFECT OF THE POLYENZYME DRUG WOBENZYM ON THE ACTIVITY OF A DESTRUCTIVE INFLAMMATORY PROCESS IN THE COMPLEX THERAPY OF PULMONARY TUBERCULOSIS].

Ninety patients with new-onset pulmonary tuberculosis were examined prior to therapy The patients were randomized into 2 groups: 1) 20 patients receiving the standard antibiotic therapy regimen; 2) 70 patients taking the standard antibiotic therapy and the polyenzyme drug Wobenzym. The use of the latter in the complex therapy of patients with pulmonary tuberculosis was shown to cause an increase in the activity of the destructive inflammatory process and to regulate the function of the immune system as compared with those during the standard therapy.

Study of efficacy and safety of a new local cream ('healer') in the treatment of chronic anal fissure: a prospective, randomized, single-blind, comparative study.

OBJECTIVES: To determine the efficacy and safety of 'healer' cream as monotherapy in the treatment of acute and chronic anal fissure. STUDY DESIGN: A prospective, randomized, single blinded, comparative trial. METHODS: Sixty patients suffering from anal fissure were included in the study. Patients were randomly divided into three groups: group A: treated with 'healer' local cream application 3 times daily; group B: treated with nitroglycerine 0.25% local cream 3 times daily; group C: treated with a lidocaine 2% cream applied locally 3 times daily. All the followings were followed up and compared between groups. (1) Visual pain analogue score after defecation; (2) severity of straining and discomfort during defecation; (3) frequency of ulcer healed at 30 days; (4) any side effects or complications. RESULTS: The pain scoring after defecation was significantly reduced in the three treatment groups. The group treated with 'healer' isosorbide-di-nitrate showed the greatest reduction of the visual pain analogue score median from 9 before treatment to 3 & 1 after 10 and 20 days respectively, while the median visual pain analogue score in group B treated with nitroglycerine cream was 9 reduced to 4 & 2 after 10 and 20 days respectively, and the median visual pain analogue score in lidocaine group only dropped from 9 to 6 and 4, respectively. The reduction of both pain scoring and defecation scoring with 'healer' was statistically significantly greater than the other two treatments by Kruskal-Wallis test, P<0.001. The number of patients experiencing complete relief and passing stools easily after 10 days was significantly higher in 'healer' group, by Pearson Chi square = 22.94, P<0.001. After 30 days, the fissures were healed in 18 (90%) of 20 patients in the 'healer' group and in 12 (60%) of 20 in the nitroglycerin group, while only 6 (30%) of patients treated with lidocaine cream had their fissures healed by the 30 days treatment. Chi square = 15 (P = 0.001). CONCLUSION: 'Healer' is a promising effective and safe line of treatment in acute and chronic anal fissure. The characteristic pharmacokinetics of isosorbide-di-nitrate leads to a better effect than nitroglycerin in healing (more prolonged action). Also the less fast absorption than nitroglycerin leading to a smoother dose concentration curve, may be the cause that headache is less frequent and less severe in 'healer' treatment versus nitroglycerin.

Study of efficacy and safety of a new local cream ("healer") in the treatment of chronic anal fissure: a prospective, randomized, single-blind, comparative study / Estudo da eficácia e segurança de novo creme cicatrizante para o tratamento da fissura anal crônica: estudo prospectivo, randomizado, simples-cego e comparativo

OBJECTIVES: To determine the efficacy and safety of "healer" cream as monotherapy in the treatment of acute and chronic anal fissure. STUDY DESIGN: A prospective, randomized, single blinded, comparative trial. METHODS: Sixty patients suffering from anal fissure were included in the study. Patients were randomly divided into three groups: group A: treated with "healer" local cream application 3 times daily; group B: treated with nitroglycerine 0.25 percent local cream 3 times daily; group C: treated with a lidocaine 2 percent cream applied locally 3 times daily. All the followings were followed up and compared between groups. (1) Visual pain analogue score after defecation; (2) severity of straining and discomfort during defecation; (3) frequency of ulcer healed at 30 days; (4) any side effects or complications. RESULTS: The pain scoring after defecation was significantly reduced in the three treatment groups. The group treated with "healer" isosorbide-di-nitrate showed the greatest reduction of the visual pain analogue score median from 9 before treatment to 3 & 1 after 10 and 20 days respectively, while the median visual pain analogue score in group B treated with nitroglycerine cream was 9 reduced to 4 & 2 after 10 and 20 days respectively, and the median visual pain analogue score in lidocaine group only dropped from 9 to 6 and 4, respectively. The reduction of both pain scoring and defecation scoring with "healer" was statistically significantly greater than the other two treatments by Kruskal-Wallis test, P<0.001. The number of patients experiencing complete relief and passing stools easily after 10 days was significantly higher in "healer" group, by Pearson Chi square = 22.94, P<0.001. After 30 days, the fissures were healed in 18 (90 percent) of 20 patients in the "healer" group and in 12 (60 percent) of 20 in the nitroglycerin group, while only 6 (30 percent) of patients treated with lidocaine cream had their fissures healed by ...

OBJETIVOS: Determinar a eficácia e segurança de "creme cicatrizante" (dinitrato de isosorbida 1 por cento; lidocaína 2 por cento; rutosídios 5 por cento em base de creme anti-séptico) como monoterapia no tratamento da fissura anal aguda ou crônica. METODOLOGIA: Estudo prospectivo, randomizado, simples-cego, comparativo. Foram incluídos 60 pacientes com fissura anal. Foram divididos randomicamente em três grupos: grupo A: tratados com "creme cicatrizante", grupo B: tratados com creme de nitroglicerina 0,25 por cento e grupo C: tratados com creme de lidocaína 2 por cento aplicado. Em todos foi feita aplicação local 3 vezes ao dia. Os seguintes parâmetros foram aferidos: 1) escore analógico visual de dor após defecação, 2) severidade de esforço e desconforto para evacuar, 3) frequência da cicatrização após 30 dias, 4) presença de efeitos colaterais ou complicações. RESULTADOS: O escore de dor após a defecação foi reduzido significativamente nos três grupos. O grupo tratado com creme cicatrizante mostrou grande redução do escore médio de 9 para 3 e 1 após 10 e 20 dias de tratamento, respectivamente, enquanto que a média do grupo B foi reduzida de 9 para 4 e 2 e do grupo C de 9 para 6 e 4 após 10 e 20 dias de tratamento, respectivamente. A redução tanto da dor como do desconforto evacuatório com o uso de "creme cicatrizante" foi significativo em comparação com os outros cremes pelo teste de Kruskal-Wallis, P<0,001. O número de pacientes que referiram alívio completo e passagem fácil da fezes após 10 dias de tratamento foi maior e significativo no grupo A pelo teste Pearson, P<0,001. Após 30 dias, as fissuras estavam cicatrizadas em 18 (90 por cento) pacientes do grupo A, em 12 (60 por cento) do grupo B e em apenas 6 (30 por cento) do grupo C. Qui ao quadrado = 15 (P = 0,001). CONCLUSÃO: O "creme cicatrizante" é um tratamento que promete ser promissor e seguro na fissura anal aguda ou crônica. A característica farmacocinética do creme leva ...