Avaliação da atividade protetora gástrica do extrato hidroalcoólico da semente de girassol em ratas / Evaluation of the gastroprotective activity of hydroalcoholic extract of sunflower seed in rats

JUSTIFICATIVA E OBJETIVOS: Avaliar a proteção gástrica do extrato hidroalcoólico da semente de girassol (EHSG) em relaçãoao estresse, ao uso de indometacina e etanol. MÉTODO: Foi realizado um estudo experimental envolvendo 90 ratas (Rattus norvegicus albinus), da linhagem Wistar, fêmeas, com peso corporal médio de 150-230 g, divididos em 18 grupos distintos os quais receberam os seguintes tratamentos: EHSG:250 mg/kg, 500 mg/kg, 1000 mg/kg e 2000 mg/kg; etanol 0,5mL; cimetidina 60 mg/kg; indometacina 20 mg/kg; água 1 mL. Os dados foram analisados utilizando o programa Grand PadPrism 5 com aplicação de testes estatísticos considerando o nível de significância de 5%. RESULTADOS: O EHSG apresenta proteção contra as lesões gástricas em ratas, nas doses de 250 e 1000 mg, tanto no modelo pelo estresse, quanto na indução por etanol e indometacina. CONCLUSÃO: Os dados obtidos no presente estudo mostram que o EHSG apresenta proteção gástrica em determinadas doses.

BACKGROUND AND OBJECTIVES: To evaluate the gastric protection hidroalcoólico extract the sunflower seed (EHSG) in relation to stress, the use of indomethacin and ethanol. METHOD: We conducted an experimental study involving 90 rats (Rattus norvegicus albinos), Wistar, females, mean body weight of 150-230 g were divided into 18 distinct groups which received the following treatments: EHSG: 250mg/kg , 500 mg/kg, 1000 mg/kg and 2000 mg/kg; 0.5 mL ethanol, cimetidine 60 mg/kg, 20 mg/kg indomethacin; 1 mL water. Data were analyzed using the GrandPad Prism 5 with application of statistical tests, the significance level of 5%. RESULTS: The EHSG has protective against gastric injury in rats at doses 250 mg and 1000, both in the model by stress, as in the induction by ethanol and indomethacin. CONCLUSION: The data obtained in this study show that has EHSG gastric protection in certain doses.

Oral ulceration and bleeding associated with pancreatic enzyme supplementation in a German shepherd with pancreatic acinar atrophy.

A 20-month-old German shepherd with primary pancreatic acinar atrophy and exocrine pancreatic insufficiency that was treated with pancreatic enzyme supplementation, vitamin B12, and cimetidine developed oral bleeding. Following discontinuation of the cimetidine, increased preincubation of the enzymes with the food, and symptomatic therapy for the ulceration, the dog's condition improved.

Adverse haematological effects of vinblastine, prednisolone and cimetidine treatment: a retrospective study in fourteen dogs with mast cell tumours.

Vinblastine toxicity is poorly documented in dogs. The aim of this study was to investigate the haematological alterations in dogs treated with vinblastine and prednisolone. Fourteen dogs with mast cell tumours (MCT) were selected on at least one of the following criteria: lymph node infiltration, surgical margin infiltration, grade II MCTs with Ki-67 >10%, and grade III MCTs. Starting 15 days after surgery, the dogs were given vinblastine (2 mg/m2 i.v. four times weekly, then twice monthly for 2 months) and prednisolone (2 mg/kg/day p.o.). An EDTA blood sample was collected weekly for complete blood count (CBC). A total of 98 doses of vinblastine were given to the 14 dogs and 114 CBC were performed. Abnormal haematological findings were observed in 12 CBCs from five dogs, which represent a prevalence of 20% of the total CBCs performed in these animals. The most prevalent abnormal finding was thrombopenia (9/12) most often with grade I toxicity (6/9). In conclusion, the risk of occurrence of adverse haematological effects resulting from vinblastine-prednisolone treatment seems limited in dogs with MCT and it should not be overestimated.

Drug interactions of clinical significance for the dermatologist: recognition and avoidance.

While it would be impossible for any dermatologist to remember all potential drug interactions, knowledge of the mechanisms of drug interactions can help reduce the risk of serious adverse outcomes. Most drugs are associated with interactions but the majority do not produce significant outcomes. Dealing with drug interactions is a challenge in all clinical practice, including dermatology. New information continues to appear, and dermatologists need to know about the drugs they use.This article focuses on the mechanisms of drug interactions. In particular, the life of a drug in terms of absorption, distribution, metabolism and excretion are reviewed with the focus on points of importance and relevance to drug interactions. The most clinically important drug interactions in dermatological practice are caused by alterations in drug metabolism. The contributions of P-glycoprotein, pharmacogenetic variation and genetic polymorphisms to drug interactions are highlighted, and the best evidence for drug interactions involving drug classes relevant to the dermatologist is presented. Since the initial evidence for clinically relevant drug interactions comes from case reports, prescribing physicians can have a major role in collating information on interactions. By understanding the mechanisms behind drug interactions and staying alert for toxicities, we can help make drug therapy safer and reduce the fear of drug interactions.

The consequences of H2 receptor antagonist--piroxicam coadministration in patients with joint disorders.

A randomised crossover study was performed in subjects with rheumatoid arthritis (or other arthropathies) to investigate if any alteration in the steady pharmacokinetics of the NSAID piroxicam (a drug which is extensively metabolised via cytochrome P450) or its major metabolites occurred as a result of coadministering either cimetidine or nizatidine. Twelve females and 2 males with mean age, weight, and albumin concentrations of 58 years, 61 kg, and 40 g.L-1 respectively, completed the study. Comparisons were made between the following parameters: plasma piroxicam AUCs [AUC0-24(P)], plasma 5-hydroxypiroxicam AUCs [AUC0-24(5-OHP)], the ratio of these i.e. AUC0-24(5-OHP):AUC0-24(p), the % piroxicam daily dose excreted in urine as 5-hydroxypiroxicam (before and after glucuronidase incubation); and the mean of the steady state trough piroxicam, and 5-hydroxypiroxicam concentrations (obtained during each study phase in addition to the wash-out period). A statistically significant difference as a result of initiating either cimetidine or nizatidine was obtained only for the ratio AUC0-23(5-OHP):AUC0-24(P). This was indicative of a weak potential to inhibit piroxicam hydroxylation. No clinically significant alteration in the steady state pharmacokinetics of piroxicam occurred in these subjects as a result of cimetidine or nizatidine coadministration. Consequently it is unlikely that any adverse events would arise from these combinations.

Effect of autolymphocyte therapy on survival and quality of life in patients with metastatic renal-cell carcinoma.

To assess the value of autolymphocyte therapy (ALT) in the treatment of metastatic renal-cell carcinoma, 90 patients were randomised to receive every month for six months oral cimetidine plus an infusion of autologous peripheral blood lymphocytes activated in vitro by a previously generated autologous lymphokine mixture, or cimetidine alone. The median follow-up was 15 months. Survival time for the autolymphocyte group was approximately 2.5 times that for the cimetidine group (p = 0.008). Patients who had greater than 500 pg interleukin-1 (IL-1) per ml autologous lymphokine mixture had a six-fold survival advantage over those with less than 500 pg/ml (p less than 0.00005). Men treated with ALT had a four-fold survival advantage (p = 0.001) over men who received cimetidine only. Infusion of the cultured autolymphocytes was accompanied by mild, self-limited fever in 11 of the 45 ALT patients, and by only one instance in which fever was accompanied by tachypnoea and hypotension.

Omeprazole (20 mg daily) versus cimetidine (1200 mg daily) in duodenal ulcer healing and pain relief.

We conducted a double-blind, randomized, parallel group study in 169 patients with acute duodenal ulcers to compare omeprazole, 20 mg daily, with cimetidine, 600 mg twice daily. After 2 wk, 58% of the omeprazole-treated patients and 46% of the cimetidine-treated patients were completely healed (p = 0.056). After 4 and 6 wk 84% and 88% healed with omeprazole, and 80% and 89% healed with cimetidine (p = NS). After 2 wk, pain was completely gone in 62% of the omeprazole-treated patients versus 46% of the cimetidine-treated patients (p = 0.04). Clinical or laboratory adverse events were reported in 6 (7%) of the omeprazole-treated patients and 11 (13%) of the cimetidine-treated patients (p = NS). An adverse event caused withdrawal of 1 patient on omeprazole (anxiety and depression) and 2 patients on cimetidine (diarrhea and fall in hemoglobin). We conclude that omeprazole (20 mg daily) resulted in a trend toward more rapid ulcer healing compared with a relatively high dose of cimetidine (600 mg b.i.d.), and was preferred by patients for relief of ulcer pain.

A new series of oral medications for chronic (cancer) pain relief.

This new program of pain medication provides more even pain relief, avoiding the peaks and valleys of the traditional injections. Patients remain lucid, slightly euphoric, and pain free--even from deep pain. The family is capable of coping and treating the patient in their home, without having to contend with anger, hostility, and frustration. The patients are cooperative, not as demanding, and for the most part, are able to verbalize freely about their impending death to family members and friends in such a manner that when death does occur, it is peaceful . We have not encountered any addiction/habituation problems. We have not experienced any failures as long as the patient could take the oral medication. With continuous examination and evaluation, we have avoided any adverse drug reactions by tailoring the cocktail to the patient's needs and responses on a continuous basis. When changing from injections or other medications to the cocktail program, or when changing from one cocktail to another, the patient is assured that the old medication is available on demand. Should a patient become anxious or fearful that his cocktail will not always work, he is assured that there are others that will. A pain-free patient relieves the anxiety of the family, an important and welcome fact to be considered. By monitoring such factors as dosage, volume, taste, texture, and color, as well as offering other flavoring (cinnamon, lemon, cherry), we have not experienced any patient refusal. Once on the program, their self-respect is regained and their personal pride and sense of well-being are reestablished.(ABSTRACT TRUNCATED AT 250 WORDS)

The intragastric host-mediated assay for the assessment of the formation of direct mutagens in vivo.

The intragastric host-mediated assay (h.m.a.) was devised and carried out with a view to assessing the formation of direct mutagens in the gastrointestinal tract of mammals. The h.m.a. consists in the injection of nitrosable compounds, NaNO2 and cells of the yeast S. pombe, by gavage into the animals' stomachs and in the recovery of the target cells from the faeces for mutation-induction analysis. Methylurea was chosen as a model nitrosable compound, and the effects of nitrosation modulators such as ascorbic acid and thiocyanate were studied. Cimetidine, a drug nitrosable in vitro, was tested with the system. Positive results were obtained only at very large doses and in artificially produced low pH. The new host-mediated assay seems to be efficient in revealing the formation, in vivo, of direct, short-living mutagens.

The deleterious effects of high dose cimetidine in acute thermal injury.

Pharmacological doses of cimetidine have been reported to reduce oedema formation in murine burn models. Sprague-Dawley rats subjected to a 30 per cent full-thickness burn were treated with cimetidine (200 mg/kg) pre and post burn. Untreated, burned animals and sham-burned animals were also studied. No beneficial effects of cimetidine were demonstrated. Cimitidine increased the water content in lung, stomach and eschar of burned animals. No differences were seen in serum or urine electrolytes, or extrarenal water loss. Cimetidine did reduce serum hyperosmolality seen in unresuscitated burned animals. Multiple doses of cimetidine following thermal injury were associated with a significant increment in mortality rate.

Influence of smoking on healing rate of duodenal ulcer in response to cimetidine or high-dose antacid.

Fifty consecutive patients with symptomatic endoscopically proven duodenal ulcer were randomized double-blind to Mylanta II or cimetidine treatment schedules. Smoking habits were noted, but patients were not advised to alter these. Healing was determined by reendoscopy at 6 wk. Eighty percent of patients on active cimetidine and 52% on active Mylanta II had healed at 6 wk (not significantly); 85% of nonsmokers healed compared to 44% of smokers (p less than 0.03). In smokers, cimetidine achieved healing in 50%, Mylanta II in 39% (not significantly); while in nonsmokers, cimetidine achieved healing in 100%, Mylanta II in 67% (not significantly). These results indicate a significant and equally adverse effect of smoking on the healing rate of duodenal ulcer achieved by either cimetidine or Mylanta II.

Effectiveness of cimetidine as an adjunct to supplemental pancreatic enzymes in patients with cystic fibrosis.

The effectiveness and safety of the use of cimetidine as an adjunct to pancreatic enzymes was evaluated in eight patients with cystic fibrosis having pancreatic insufficiency. Cimetidine (300 mg, three times a day) was given for a 6-week period during which the patients demonstrated a significant weight gain (P < 0.05) and reduction of steatorrhea (P < 0.01). Data suggesting an early correction of the abnormal fatty acid composition of plasma lipids were observed. No side effects were apparent during the clinical trial. These results demonstrate the beneficial effects of the use of cimetidine in patients with cystic fibrosis and indicate the need for long-term clinical trials.