Oral fish oil positively influences nutritional-inflammatory risk in patients with haematological malignancies during chemotherapy with an impact on long-term survival: a randomised clinical trial.

BACKGROUND: Studies suggest that the ingestion of fish oil (FO), a source of the omega-3 polyunsaturated fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), can reduce the deleterious side-effects of chemotherapy. The aim of this randomised clinical trial was to evaluate the effect of supplementation with oral FO for 9 weeks on nutritional parameters and inflammatory nutritional risk in patients with haematological malignancies during the beginning of chemotherapy. METHODS: Twenty-two patients with leukaemia or lymphoma were randomised to the unsupplemented group (UG) (n = 13) or supplemented group (SG) (n = 9). SG received 2 g/day of fish oil for 9 weeks. Nutritional status, serum acute-phase proteins and plasma fatty acids were evaluated before (T0) and after (T1) the intervention period. Data were analysed using two models; model 1, comprising data from all patients included in the study, and model 2, comprising data from UG patients with no increase in the proportions of EPA and DHA in plasma and data from SG patients showing an at least 100% increase in plasma EPA and DHA. RESULTS: SG showed an increased plasma proportion of EPA and DHA in both models. In model 2, C-reactive protein (CRP) and CRP/albumin ratio showed larger reductions in the SG. Overall long-term survival in both models (465 days after the start of the chemotherapy) was higher in the group ingesting fish oil (P < 0.05). CONCLUSIONS: These findings indicate an improved nutritional-inflammatory risk and potential effects on long-term survival in patients with haematological malignancies supplemented with FO during the beginning of chemotherapy.

Comparative in vitro and in vivo evaluations of oral sustained-release formulations of diclofenac sodium in beagle dogs.

PURPOSE: Two sustained release formulations (microspheres and Voltaren SR75) were evaluated for their drug release characteristics in dissolution (in vitro study) and after oral administration to beagle dogs (in vivo study) by HPLC. METHODS: The dissolution study was carried out according to the paddle method and the pharmacokinetic study was conducted using HPLC analysis in a crossover design in six female beagle dogs after oral administration of 75 mg diclofenac sodium (DFS). RESULTS: The dissolution profiles showed 45% release for Voltaren SR75 and around 95% for the microspheres. Oral administration of DFS resulted in AUC(0-24) and Cmax values of 20.4 microg h/mL and 3.04 microg/mL for microspheres and 33.5 microg h/mL and 5.59 microg/mL for Voltaren, respectively. The Tmax was 3.0 h for both formulations. A significant difference in AUC(0-24) and Cmax was observed for DFS absorption from microspheres and Voltaren. CONCLUSIONS: The results from the dissolution assay demonstrated the faster release of diclofenac sodium from microspheres. The bioavailability of DFS in microspheres was about 61% that of Voltaren, for the parameters AUC and Cmax, and they are therefore not bioequivalent to Voltaren in relation to the extent of absorption. However, the rate of drug absorption (Tmax) was similar for the two formulations.

True hermaphroditism-the importance of ultrasonic assessment.

Intersex states are associated with rare syndromes within a wide clinical spectrum, true hermaphroditism being the rarest of them all. It is a condition that is characterized by ovotestis, i.e. the presence of ovarian and testicular tissues in the same individual, either in separate gonads or in the same gonad. Diagnostic investigation of hermaphroditism involves ultrasound examination of the gonads, karyotype analysis and histological studies. We report the case of a 21-year-old individual with true hermaphroditism, in whom ovotestis was diagnosed on ultrasonography and which was later confirmed by anatomopathological study of the gonads. The role of ultrasound in the initial diagnostic investigation of intersex states, especially true hermaphroditism, is discussed.

Nitroflurbiprofen, a new nonsteroidal anti-inflammatory, ameliorates structural injury in the remnant kidney.

Cyclooxygenase derivatives and nitric oxide (NO) may influence the pathogenesis of progressive nephropathies. We investigated the effect of nitroflurbiprofen (NOF), a NO-releasing nonsteroidal anti-inflammatory drug (NSAID) without gastrointestinal toxicity, in rats with 5/6 ablation (NX). The following four groups were studied: Sham, sham-operated rats; Sham + NOF, Sham receiving oral NOF two times daily; NX, rats subjected to NX; and NX + NOF, NX receiving NOF. NOF was barely detected in plasma but released the parent compound flurbiprofen. At 30 days, glomerular hydraulic pressure (PGC) was 76 +/- 3 mmHg in NX (52 +/- 1 in Sham, P < 0.05). NOF slightly reduced PGC to 69 +/- 2 mmHg in NX + NOF (P > 0.05 vs. NX). Glomerular volumes behaved similarly. At 60 days, tail cuff pressure was 152 +/- 6 mmHg, glomerulosclerosis index was 22.1 +/- 9.5, and interstitial fractional area was 9.9 +/- 1.2% in NX. NOF reduced these parameters to 137 +/- 4 mmHg, 3.5 +/- 0.7, and 6.4 +/- 0.8%, respectively (P < 0.05), without causing growth stunting or anemia. These beneficial effects could not be ascribed to NO donation and may reflect cyclooxygenase inhibition. This is the first evidence that chronic NSAID treatment may ameliorate progressive nephropathies.

Comparative bioavailability of two atenolol tablet formulations in healthy male volunteers after a single dose administration.

The bioavailability of 2 atenolol tablet formulations (Angipress from Laboratórios Biosintética, and Atenol from Wellcome ICI Laboratory, Brazil) were compared in 18 healthy male volunteers who received a single 50 mg dose of each atenolol formulation. The study was conducted following an open randomized 2-period crossover design with a 14-day washout interval between doses. Plasma samples were obtained over a 24-hour interval and atenolol concentrations were determined by HPLC with fluorimetric detection. From the plasma atenolol concentration vs time curves the following pharmacokinetic parameters were obtained: AUC(zero-24) (area under the concentration vs time curves from 0-24 h), ke (terminal elimination constant), t1/2 (terminal first order elimination half-life), AUC (area under the concentration vs time curves extrapolated to infinity), Cmax (maximum achieved concentration), Tmax (time to achieve Cmax) and Cmax/AUC. All these variables were analyzed using both parametric and nonparametric statistics. Geometric mean Angipress/Atenol individual percent ratios were 99.6% for AUC(zero-24), 99.7% for AUC, 98.0% for Cmax, 102.8% for t1/2, 97.2% for ke and 97.8% for Cmax/AUC, with all their 90% confidence intervals within the bioequivalence range 80-125%, thus showing similar patterns of absorption and disposition. Arithmetic mean for individual Tmax differences was 0.8 h, and the 90% confidence interval did not include the zero value. Based on these results and in accordance with the European Union and the US Food and Drug Administration bioequivalence requirements we conclude that both atenolol formulations are bioequivalent for both the extent and the rate of absorption.

Tratamiento quirúrgico de la úlcera gastroduodenal sangrante / Surgical treatment in the management of bleeding gastroduodenal ulcers

La cirugía de la úlcera péptica ha disminuido pero las complicaciones como la estenosis duodenal,hemorragia y perforación siguen requiriendo tratamiento quirúrgico.El sesenta coma nueve por ciento de los operados había sido internados de urgencia.El tratamiento médico de la hemorragia ha mejorado pero el uso de sustancias esclerosantes como el alcohol hace que se vean casos con duodenos alterados y hasta perforaciones.Es importante valorar las alteraciones que producen como necrosis y retardos en la cicatrización.Laa hemostasia directa como procedimiento quirúrgico es válido requiriéndose estar seguro del lugar de sangrado y de la hemostasia.La operaciónm de Weinberg es una buena opción en un buen número de casos de úlcera duodenal (treinta y dos coma cinco por ciento, 13/49).Los procedimientos en la detención de la hemorragia pero deben usarse como segunda opción ya que incrementa la morbilidad,mortalidad y secuelas alejadas.La mortalidadfue del diecisiete coma cinco por ciento lo que justifica por tratarse de pacientes en donde ele tratamiento médico ha fracasado, politranfundidos,en malas condiciones y operados de urgencia.En nuestra serie todos los fallecidos tenían más de 50 años

Tratamiento quirúrgico de la úlcera gastroduodenal sangrante / Surgical treatment in the management of bleeding gastroduodenal ulcers

La cirugía de la úlcera péptica ha disminuido pero las complicaciones como la estenosis duodenal,hemorragia y perforación siguen requiriendo tratamiento quirúrgico.El sesenta coma nueve por ciento de los operados había sido internados de urgencia.El tratamiento médico de la hemorragia ha mejorado pero el uso de sustancias esclerosantes como el alcohol hace que se vean casos con duodenos alterados y hasta perforaciones.Es importante valorar las alteraciones que producen como necrosis y retardos en la cicatrización.Laa hemostasia directa como procedimiento quirúrgico es válido requiriéndose estar seguro del lugar de sangrado y de la hemostasia.La operaciónm de Weinberg es una buena opción en un buen número de casos de úlcera duodenal (treinta y dos coma cinco por ciento, 13/49).Los procedimientos en la detención de la hemorragia pero deben usarse como segunda opción ya que incrementa la morbilidad,mortalidad y secuelas alejadas.La mortalidadfue del diecisiete coma cinco por ciento lo que justifica por tratarse de pacientes en donde ele tratamiento médico ha fracasado, politranfundidos,en malas condiciones y operados de urgencia.En nuestra serie todos los fallecidos tenían más de 50 años

Influence of gastric acid secretion blockade and food intake on the bioavailability of a potassium diclofenac suspension in healthy male volunteers.

The bioavailability of a single dose of a potassium diclofenac (KDIC) suspension (Flogan, Merck, 7ml, 105 mg) was studied in 13 healthy male volunteers in the fasting state (placebo phase, PLA), after gastric acid secretion blockade (subacute pretreatment with omeprazole, OME phase) and after food intake (FOOD phase). A 14-day washout period between phases was adopted. Serum samples were obtained over a 24 hour interval and the diclofenac concentrations were determined by high pressure liquid chromatography with ultraviolet detection. From the serum diclofenac concentration vs time curves, the AUC[0-infinity] (area under the concentration vs time curves from 0 to infinity), Cmax (maximum achieved concentration), tmax (time to achieve Cmax), Ke (terminal first order elimination constant), half-life values (t1/2) and AUC[0-infinity]/t1/2 ratio as an index of diclofenac clearance, were obtained. All these variables were analyzed using both parametric and non-parametric statistics. In the presence of food, KDIC absorption was delayed (as shown by lower Cmax and greater tmax values) and decreased (as shown by lower AUC[0-infinity] values), and the serum diclofenac concentration vs time curves showed a biphasic pattern. Omeprazole pretreatment did not change the absorption parameters. Both of these treatments altered the diclofenac clearance, as assessed by the AUC[0-infinity]/t1/2, t1/2 and Ke values, although the changes were not considered to be clinically significant, because of the wide therapeutic range for diclofenac. The delay in the rate of diclofenac absorption produced by food intake was not due to an increase in the gastric pH, and could be of particular importance when rapid analgesia is desired.

Effects of hydroalcoholic extracts of Portulaca pilosa and Achyrocline satureioides on urinary sodium and potassium excretion.

Porulaca pilosa has been used in Brazil as a traditional remedy to cause diuresis, antipyresis and analgesia. Achyrocline satureioides has been used in folk medicine as antiinflammatory, hypoglycemic, sedative and to treat gastrointestinal disorders such as diarrhea and dysentery suggesting that it may affect salt and water reabsorption by the gastrointestinal tract. In the current study, hydroalcoholic extracts of both plants were investigated in order to examine their renal effects. The results support the claim that extracts of P. pilosa present renal effects but not the popular belief that it affects diuresis. It has also been provided that, in rats, it causes an increase in K excretion without a concomitant change in water diuresis or Na excretion. Our findings also support the popular belief that A. satureioides does not apparently have renal effects and it might change renal ion transport based on observations that it affects gastrointestinal reabsorption.

Preliminary pharmacologic evaluation of crude whole plant extracts of Elephantopus scaber. Part I: In vivo studies.

Elephantopus scaber has been used in Brazil as a traditional remedy to cause diuresis, antipyresis and to eliminate bladder stones. In the current study, aqueous and hydroalcoholic extracts of whole plants were tested for acute toxicity, analgesic, antipyretic, antiinflammatory, cardiovascular, diuretic and constipating activities. Both extracts (0.3-6 g/kg i.p.) induced writhing, loss of muscle tone, ataxia, prostration and death in mice. No analgesic effects of these extracts were detected using mouse hot-plate and acetic acid-induced writhing tests. Both extracts failed to modify diuresis or carrageenan-induced rat paw edema. In contrast, given intraperitoneally, both reduced brewer's yeast-induced hyperthermia in rats, but when given orally did not affect it. Moreover, the aqueous extract decreased the intestinal transit time in mice while the hydroalcoholic extract increased it. Finally, these extracts, given intravenously, reduced blood pressure and heart rate in rats; these effects could be blocked by atropine but not by co-administration of pyrilamine and cimetidine.

Effects of age on behavioral and physiological responses to carbaryl in rats.

Motor, sensory and thermoregulatory functions were examined in young (3 months) and mature (12 months) rats following PO administration of single low doses (10 and 50 mg/kg) of carbaryl, a carbamate insecticide, and these effects were related to blood cholinesterase activity. Carbaryl 50 mg/kg decreased the frequency of ambulation in the open-field arena within 30 min while it enhanced the duration of haloperidol-induced catalepsy in both young and mature rats. Administration of carbaryl also resulted in an increased nociceptive threshold to thermic stimuli mainly in mature rats. An age-related reduction in body temperature was observed at 30, 60 and 90 min after injection. Activity of blood cholinesterase was reduced in young and mature rats at 30 and 60 min following carbaryl exposure. These results indicate that carbaryl can induce an age-related impairment on some behavioral and autonomic functions in rats correlated to the inhibition of cholinesterase activity.

Behavioral and biochemical changes following repeated administration of carbaryl to aging rats.

Motor, sensory and thermoregulatory functions were examined in aging rats (12 months) following two schedules of repeated po administration of the carbamate insecticide carbaryl and these effects were assessed in terms of blood cholinesterase activity. Administration of carbaryl (50 mg/kg) by gavage daily for 30 days resulted in a reduction of locomotor activity in the open-field and in an inhibition of cholinesterase activity within 30 min after the last treatment. Twenty-four h later, only the locomotor effect was evident. After 90 days of exposure to carbaryl in drinking water, no significant effects were observed. These findings suggest that repeated administration of carbaryl to aging rats can induce an impairment of motor function and a reduction of cholinesterase activity, while tolerance develops in some other parameters.

Behavioral and biochemical changes following reapeted administration of carbaryl to aging rats

Motor, sensory and thermoregulatoty function were examined in aging rats (12 months) following two schedules of repated po adminstration of the carbamate insecticide carbaryl and these effects were assessed in terms of blood cholinesterase activity. Administration of carbaryl (50 mg/Kg) by gavage daily for 30 days resulted in a resultad in a reduction of locomotor activity in thre open-field and an inhibition of cholinesterase activity within 30 min after the last treatment. Twenty-for h later, only the locomotor effect was evident. After 90 days of exposure to carbaryl in drinking water, no significant effects were observed. These findings suggest that repeated administration of carbaril to aging rats can induce an impairment of motor function and a reduction of cholinesterase activity, while tolerance develops in some other parameters

Effects of d,1-propranolol and haloperidol on aggressive behavior induced in mice by isolation and isolation plus amphetamine treatment.

We measured the aggressive behavior of isolated mice treated or not with d,1-amphetamine (6.0 mg/kg, ip) and injected with different doses of d,1-propranolol (10.0, 20.0 or 30.0 mg/kg, ip) or haloperidol (0.5 or 1.0 mg/kg). d,1-Amphetamine (6.0 mg/kg, ip) decreased the aggressiveness of the isolated mice and induced stereotyped behavior. Haloperidol antagonized amphetamine-induced stereotypy, increased the latency to the 1st attack and decreased duration of fighting and frequency of attacks in mice treated or not with amphetamine. d,1-Propranolol did not change stereotypy but decreased aggressiveness in a dose-dependent way, being more effective against aggression induced by isolation per se. These results are discussed in terms of the interference of the drugs with the activity of either catecholaminergic neurons or midbrain reticular formation. The latter effect seems to be the most likely explanation for the observed anti-aggressive effects of haloperidol and d-1, propranolol.

Tratamiento quirurgico de la hernia hiatal. / Surgical treatment of hiatal hernia

Se presentan 61 pacientes portadores de hernia hiatal sometidos a tratamiento quirurgico, con 88,5% de resultados excelentes. Se consideran las distintas tecnicas empleadas, reservandose la utilizacion de la gastropexia anterior en pacientes seleccionados

Tratamiento quirurgico de la hernia hiatal. / Surgical treatment of hiatal hernia

Se presentan 61 pacientes portadores de hernia hiatal sometidos a tratamiento quirurgico, con 88,5% de resultados excelentes. Se consideran las distintas tecnicas empleadas, reservandose la utilizacion de la gastropexia anterior en pacientes seleccionados