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Changing environmental cues reduces tolerance to nicotine-induced anorexia.

Male rats on a 22-h food deprivation schedule were injected daily with a low dose of nicotine and allowed to drink sweetened milk for 10 min in a test cage in the colony room. Nicotine initially suppressed milk intake but complete tolerance developed within 10 days so that the amount of intake did not differ from saline controls. The role of temporal cues was tested on the next day by changing the timing of cues, and omitting others that normally preceded nicotine injection while keeping constant the physical environment within which injection and testing took place and the drug-test interval. Changing the timing of injection significantly suppressed milk intake. These results show that tolerance to the anorectic effects of a low dose of nicotine is partially dependent on the presence and timing of cues associated with tolerance acquisition.

Animals↗

Acebutolol in supraventricular arrhythmias.

The effect of intravenous acebutolol on supraventricular arrhythmias was evaluated in 20 patients, 5 with chronic obstructive pulmonary disease. A rapid ventricular rate in atrial fibrillation was slowed greater than 15% in all of 10 patients by acebutolol and in none of 5 patients by saline. A rapid ventricular rate in atrial flutter was slowed greater than 15% in all of 6 patients by acebutolol and in none of 3 patients by saline. Frequent premature atrial beats were abolished or reduced by greater than 75% in each of 2 patients by acebutolol and not in a patient by saline. Acebutolol converted multifocal atrial tachycardia to sinus rhythm in a patient. Digitalis-induced nonparoxysmal atrioventricular junctional tachycardia was not affected by saline but was abolished by acebutolol in a patient. Acebutolol was well tolerated in each of 5 patients with chronic obstructive pulmonary disease. Acebutolol is useful in the treatment of supraventricular arrhythmias.

Acebutolol↗

Effectiveness and duration of intramuscular antimotion sickness medications.

Motion sickness inhibits gastric motility, making the oral route ineffective for medications. The intramuscular route is an effective alternative. The rotating chair was used to produce the M 111 level of motion sickness on the Graybiel Symptom Scale. The intramuscular medications given 30 minutes before rotation were compared with placebo (saline, 1 mL) for effectiveness and duration in increasing the number of tolerated head movements. Average placebo number of head movements was 294. Promethazine 25 mg increased head movements by 78% (P < .05), with a duration of 12 hours. Scopolamine 0.2 mg increased head movements by 91% (P < .05), with a duration of 4 hours. The effect of caffeine 250 mg and ephedrine 25 mg was not significant. When combined with scopolamine, ephedrine produced an 32% additive effect. Scopolamine 0.08 mg, 0.1 mg, and 0.2 mg and also promethazine 12.5 mg and 25 mg were significant (P < .05). Promethazine appears to be the drug of choice for intramuscular use because of a longer duration and a high level of effectiveness. Scopolamine was of high effectiveness, but had a duration of 4 hours. It was eight times as potent by the intramuscular as by the oral route.

Caffeine↗

Biochemical markers of ethanol effects on brain.

Because sialic acid is a potential biochemical marker of membrane development or alteration, we compared acute and chronic ethanol effects on sialic acid. Experiments were conducted with 50 adult male Wistar rats (approximately 400 gm), housed in groups of five. Rats drank ad libitum a vitamin-fortified diet (Nutrament) that was adulterated with ethanol; ethanol intake averaged for each rat 10-18 gm/kg/day. Controls were fed an equal total volume, made isocaloric with sucrose. Rats were sacrificed weekly for four weeks, and an acute challenge dose of ethanol (2 gm/kg, intraperitoneally) was given 45 minutes before sacrifice of both control and ethanol-consuming rats. Some controls were challenged only with saline. We replicated our earlier findings of regional differences in sialic acid and in cerebellar deoxyribose (measured as a necessary adjunct in the autoanalyzer modification of the Warren-Delmotte methods). In the saline-challenged controls, levels of both compounds were higher at four weeks than after one week. Similar increases occurred also in the chronic ethanol-consuming group, but not in the ethanol-challenged controls, which had significantly lower values. Results in saline-challenged controls suggest that the chronic treatment either 1) created a tolerance which protected cells from damage by the challenge dose of ethanol, or 2) killed neurons, thus promoting proliferation of glial cells.

Alcohol Drinking↗

Successful repair of major retrohepatic vascular injuries without the use of shunt or sternotomy.

Injury to the retrohepatic veins and vena cava secondary to blunt abdominal trauma is often fatal. The purpose of this report is to describe the successful isolation and repair of retrohepatic vascular injuries without the use of median sternotomy or vena caval shunt. Two children with both hepatic vein and retrohepatic caval injuries from blunt trauma were treated by the following surgical approach: (1) bilateral subcostal incision with vertical midline extension; (2) packing of the liver and volume resuscitation with the Rapid Infusion System prior to vascular isolation; (3) isolation of the intrapericardial vena cava through a transdiaphragmatic pericardial window; (4) control of the suprarenal vena cava and porta hepatis; and (5) repair of vein lacerations with vascular occlusion and continuous saline irrigation for improved visualization despite continued venous bleeding. This approach was tolerated and allowed successful repair without shunting in these patients despite an average weight of 14 kg and the loss of 3 L and 23 L of blood, respectively. We attribute the success of this technique to rapid control of hemorrhage and volume resuscitation. This success suggests that the routine use of shunt or sternotomy is not necessary in these devastating injuries.

Child, Preschool↗

The effect of Naftidrofuryl on ethanol-induced liver damage in chronic alcoholic patients.

A prospective double-blind placebo-controlled trial of intramuscular Naftidrofuryl was carried out on 32 randomly selected hospitalized male alcoholic patients with clinical, biochemical and histological evidence of hepatic damage. Seventeen patients received the drug (40 mg in 5 ml i.m. three times daily for 6 days) and 15 patients received a placebo (5 ml in normal saline i.m. three times daily for 6 days). The drug was well tolerated and there were no adverse side-effects. Naftidrofuryl significantly improved the physiological function of the liver cells as reflected by indocyanine green (ICG) clearance by the liver (t = 2.61; p less than or equal to 0.02) and also caused a larger fall in raised serum levels of gamma glutamyl transpeptidase (GGT) than did the placebo injections. Overall clinical improvement (e.g. appetite, body weight, reduced liver size, general sense of well-being) was more clearly evident in patients of the treated group than in those of the placebo group. Naftidrofuryl, therefore, appears to be of benefit in ethanol-induced liver damage and more extensive long-term trials are suggested in patients with alcoholic liver disease (ALD).

Adult↗

Ketamine-induced changes in rat behaviour: A possible animal model of schizophrenia.

It was investigated whether subchronic application of 30 mg/kg ketamine (Ket) induces reliable changes in behaviour and parameters of dopaminergic, glutamatergic, and serotonergic neurotransmissions, which might be the basis of an animal model in schizophrenia research. To test this, rats were injected with 30 mg/kg ip Ket daily for five consecutive days. In response to the first Ket injection, there was a decrease in activity time representing an acute Ket effect. Following the fifth injection, there were no differences between Ket- and saline (sal)-injected control rats in activity time, which might be a tolerance reaction. The following experiments were performed 2 or 4 weeks after Ket treatment. There were no effects on anxiety in either vehicle or Ket-treated rats using either low or high illumination levels in the elevated plus-maze. In the social interaction test, both groups of rats spent comparable times in social contact. The percentage of nonaggressive behaviour was decreased in Ket-treated rats. Two weeks after completion of the treatment, there was no effect on prepulse inhibition (PPI). Four weeks after the final Ket injection, latent inhibition (LI) was disrupted. There was no difference in the animals' activity in reaction to apomorphine (Apo) administration. Ket-treated rats injected with 0.1 mg/kg MK-801 showed an enhancement in locomotor activity. Ket treatment leads to an increase in D2 receptor binding in the hippocampus and a decrease in glutamate receptor binding in the frontal cortex. The authors did not find any changes in D1 receptor binding. The density of dopamine transporters was increased in the striatum. The density of 5-HT transporters was increased in the striatum, the hippocampus, and the frontal cortex. The results suggest that subchronic treatment with subanaesthetic doses of Ket induce schizophrenia-related alterations, which might be a useful animal model in the study of this disease.

Anesthetics, Dissociative↗

Hypersaline nasal irrigation in children with symptomatic seasonal allergic rhinitis: a randomized study.

Recent evidence suggests that nasal irrigation with hypertonic saline may be useful as an adjunctive treatment modality in the management of many sinonasal diseases. However, no previous studies have investigated the efficacy of this regimen in the prevention of seasonal allergic rhinitis-related symptoms in the pediatric patient. Twenty children with seasonal allergic rhinitis to Parietaria were enrolled in the study. Ten children were randomized to receive three-times daily nasal irrigation with hypertonic saline for the entire pollen season, which had lasted 6 weeks. Ten patients were allocated to receive no nasal irrigation and were used as controls. A mean daily rhinitis score based on the presence of nasal itching, rhinorrea, nasal obstruction and sneezing was calculated for each week of the pollen season. Moreover, patients were allowed to use oral antihistamines when required and the mean number of drug assumption per week was also calculated. In patients allocated to nasal irrigation, the mean daily rhinitis score was reduced during 5 weeks of the study period. This reduction was statistically significantly different in the 3th, 4th and 5th week of therapy. Moreover, a decreased consumption of oral antihistamines was observed in these patients. This effect became evident after the second week of treatment and resulted in statistically significant differences during the 3th, 4th and 6th week. This study supports the use of nasal irrigation with hypertonic saline in the pediatric patient with seasonal allergic rhinitis during the pollen season. This treatment was tolerable, inexpensive and effective.

Administration, Intranasal↗

Phase I/II study of a short course of weekly cisplatin in patients with advanced solid tumours.

Twenty-five patients with advanced solid tumours were entered in a phase I/II study of six, weekly cycles of cisplatin. Nineteen patients were chemonaive and six were previously treated. The starting dose was 50 mg m-2 week-1. This dose could be escalated without major toxicity to 70 mg m-2 week-1. At a dose of 80 mg m-2 myelosuppression grade 3 occurred as well as grade 1 nephro- and neurotoxicity. The maximum tolerated dose was 85 mg m-2 with dose limiting thrombocytopenia. Hypertonic saline was effective in preventing nephrotoxicity. Ondansetron was a very effective antiemetic in the first weeks of treatment but its efficacy waned later on. Responses were observed in head and neck cancer, melanoma and mesothelioma. At the dose level of 80 mg m-2 the optimal dose intensity was reached. This schedule will be tested further in phase II studies.

Adult↗

Influence of environmental salinity on routine metabolic rate and critical oxygen tension of Cyprinodon variegatus.

We examined the influence of a wide range of environmental salinities on routine metabolic rate and critical oxygen tension in Cyprinodon variegatus, a common coastal resident of the western Atlantic Ocean and Gulf of Mexico. C. variegatus lives in ambient salinities ranging from freshwater to 142/1000, with fish used in this study obtained from a Gulf of Mexico salt marsh near Cedar Key, Florida. In a steady state experiment, routine metabolic rate and critical oxygen tension were determined at salinities ranging from 0/1000 to 100/1000. Measures of routine metabolic rate and critical oxygen tension were unaffected by changes in salinity between 0/1000 and 40/1000. However, routine metabolic rate declined and critical oxygen tension increased progressively at salinities above 40/1000. The reduction in routine metabolic rate and rise in critical oxygen tension correlates with a reduced ability of C. variegatus to osmoregulate effectively at high salinities. The variations in routine metabolic rate and critical oxygen tension at high salinities suggest that C. variegatus responds to high salinities by reducing energy expenditures, effectively increasing the time that individuals can tolerate hypersaline conditions.

Adaptation, Physiological↗

The effect of long-term vasodilatation on capillary growth and performance in rabbit heart and skeletal muscle.

The long-term effect of adenosine and of a new xanthine derivative, 1-(5-oxohexyl)-3-methyl-7-propylxanthine (HWA 285) on capillary density was studied in rabbits. Doses of both agents were established in acute experiments such that they would produce a prolonged increase in coronary and skeletal muscle blood flows without significantly affecting blood pressure or cardiac output. These doses were then chronically administered (3 to 5 weeks) by continuous intravenous infusion from portable infusion pumps carried by the rabbits. Control animals were infused with saline. Long-term administration of adenosine and HWA 285 was well tolerated by the animals. In the acute experiments, adenosine (42 mumol.h-1 iv) reduced the heart rate and produced an increase in coronary blood flow (studied using 15 micrometers radioactive microspheres) and conductance of 38% and 65% respectively, with increases in skeletal muscle of 65% and 92%. Blood pressure, cardiac output and cardiac minute work were not affected. HWA 285 (57 mumol.h-1) slightly but significantly increased blood pressure, but did not affect heart rate, cardiac output or minute work. Coronary and skeletal muscle blood flow were increased by 41% and 72%, with conductance increases of 33% and 62% respectively. The number of all capillaries present was studied in the heart and skeletal muscle using histochemical staining for alkaline phosphatase. Myocardial capillary density (capillaries per mm2, means +/- SE) was 3092 +/- 97 in the adenosine infused group and 2870 +/- 153 in the HWA 285 infused group compared with 2426 +/- 93 in the controls, ie an increase of 27% (p less than 0.001) and 18% (p less than 0.02) respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗

Passive Proton Conductance Is the Major Reason for Membrane Depolarization and Conductance Increase in Chara buckellii in High-Salt Conditions.

Chara buckellii G.O.A., a salt-tolerant alga, has a less negative membrane potential (Em) when cultured in saline medium (artificial Waldsea water) than when cultured in freshwater. The cell hyperpolarizes and membrane conductance (Gm) decreases when the external medium is changed from Waldsea control solution (WCS), a high-salt medium, to low-salt medium containing sufficient sorbitol to generate the same osmotic potential as WCS. Banding pattern and proton flux experiments show that C. buckellii has higher passive proton influx in the alkaline band in high-salt medium than in low-salt medium. Decrease of the passive proton influx by darkness or low external pH dramatically hyperpolarizes the membrane and decreases the conductance. The pH dependence curves of Em and Gm also indicate the existence of high passive proton conductance (GH) in C. buckellii. Ion substitution experiments show that Em and Gm of saltwater cells are not dependent on K+, Na+, Cl-, or SO42+. Mg2+ also affects Em and Gm, but its effect is probably on GH. We conclude that GH is the most important cause of the membrane depolarization and conductance increase in the saltwater alga C. buckellii.

Journal Article↗

The myth of pulmonary Raynaud's phenomenon: the contribution of pulmonary arterial vasospasm in patients with systemic sclerosis related pulmonary arterial hypertension.

OBJECTIVE: To investigate the contribution of cold induced pulmonary vasospasm by peripheral and central cold stimulus in exacerbating pulmonary arterial hypertension (PAH) in patients with systemic sclerosis undergoing cardiac catheterisation. METHODS: In a prospective pilot study, 21 patients with systemic sclerosis and catheter proven PAH had mean pulmonary artery pressure (mPAP), pulmonary vascular resistance (PVR), and cardiac output (CO) measured before and after peripheral (hand immersion into cold water at 10-15 degrees C for two minutes if tolerated) and central (direct cold water at 4 degrees C injected into the right atrium) cold pressor challenge. Markers of endothelial activation, platelet function, and nitric oxide degradation were measured in blood sampled from the pulmonary artery. RESULTS: 19 of the patients (mean (SD) age, 56 (4) years; baseline mPAP, 34 (8) mm Hg; PVR, 420 (87) dyne.s.cm(-5); CO, 6.4 (1.8) l/min) tolerated cold hand immersion for the maximum two minute duration. All 21 tolerated central cold pressor challenge (three to five injections of 10 ml saline boluses at 4 degrees C). There was no significant change in haemodynamics after cold challenge by either route of provocation. Levels of endothelin-1, von Willebrand factor, fibrinogen, and 3-nitrotyrosine were raised compared with control values in patients with systemic sclerosis but without PAH, but did not change significantly after peripheral cold challenge. CONCLUSIONS: Pulmonary vasospasm in response to peripheral and centrally administered cold pressor challenge is unlikely to contribute to persistence of pulmonary arterial hypertension in patients with systemic sclerosis.

Adult↗

[Evaluation of aroeira (Schinus terebinthifolius Raddi) extract on the healing process of gastroraphy in rats].

PURPOSE: To evaluate the healing process of gastric suture in rats using hydroalcoholic aroeira (Schinus terebinthifolius Raddi) extract. METHODS: Forty adult male rats, divided into two groups of 20 animals were operated and named as follows: aroeira group (Ga), and the control group (Gc). Each group was divided into two subgroups (SG) of 10 animals (SGa and SGc) according to the time of provoked death (three and seven days). The same surgical procedure was performed in all animals consisting in incision and simple suture of the stomach (Prolene(R) 6-0). The only difference was on the type of medical treatment. The aroeira group received a single 100 mg/kg of aroeira extract in an intraperitoneal dose and the animals from the control group received the same quantity in milliliters (ml) of the isotonic saline solution. The evaluated parameters were: macroscopic alterations, microscopic healing process and toleration to atmospheric air insufflation. RESULTS: All animals had good healing process of abdominal wall with no clinical evidence of infection, dehiscence, abscesses and peritonitis. Both groups presented adherences to gastric suture line area with surrounding organs, mainly the liver, lower intestines and the abdominal wall. Microscopic analysis showed only chronic inflammation significant difference between the aroeira and control groups on the third day of observation. Resistance tests did not present significant statistical differences in the studied groups. CONCLUSION: The use of aroeira (Schinus terebinthifolius Raddi) hydro-alcoholic extract did not alter the stomach healing process, considered on macroscopic, tensiometric and microscopic assessment.

Anacardiaceae↗

Development of a whole-sediment toxicity test using a benthic marine microalga.

An acute whole-sediment toxicity test with a benthic marine microalga was developed and optimized using flow cytometry to distinguish algae (based on their chlorophyll a autofluorescence) from sediment particles. Of seven benthic marine algae screened, the diatom Entomoneis cf punctulata was most suitable because of its tolerance of a wide range of water and sediment physicochemical parameters, including salinity, pH, ammonia, and sulfide. A whole-sediment and water-only toxicity test based on inhibition of esterase activity in this species was developed. Enzyme activity rather than growth was used as the test endpoint, as nutrient release from sediments has previously been found to stimulate algal growth, potentially masking contaminant toxicity. The sensitivity of the bioassay to a range of metals (copper, zinc, cadmium, lead, arsenic, manganese) and phenol in water-only exposures was compared to the standard 72-h growth rate inhibition test. The esterase enzyme inhibition test was sensitive to copper, with a 3-h inhibitory concentration to cause a 50% (IC50) reduction in a fluorescein diacetate fluorescence value of 97 +/- 39 microg Cu/L. A concentration-dependent response was also observed in the presence of sediment particles (copper tailings), with and without dilution, using a control clean sediment. The primary route of exposure to copper was via pore water rather than by direct contact with tailings particles. This is the first whole-sediment bioassay developed with a benthic alga suitable for sediment quality assessment in marine/estuarine systems, and its advantages and limitations are discussed.

Biological Assay↗

Bulimic vomiting alters pain tolerance and mood.

Bulimia, a disorder of episodic binging and purging, remains without a known etiology. A case report is presented of a patient who attributed bulimic episodes to efforts at inducing euphoria. Experimental pain tolerance was increased by bulimic vomiting, blocked by naloxone, but not by saline. Vomiting was also associated with falls in depression and anxiety. Plasma ACTH and cortisol, putative markers for beta-endorphin, also rose following vomiting. It is hypothesized that in some bulimics, the disorder arises by virtue of an addiction to one's own internally released endogenous opioid peptides.

Adrenocorticotropic Hormone↗

Liquid covering for superficial skin wounds and its effect on wound closure in guinea pigs.

An irrigatable bandage has been developed to hold fluid over a wound. Starting with superficial skin wounds on the back of guinea pigs, the bandage has been used to hold saline or phosphate-buffered saline containing antibiotics over the wound for up to 48 hours. Animals tolerated the bandage well for this period and bacterial contamination and wound maceration were not complications. The extent of reepithelialization with time was measured histologically under three separate conditions: wound exposed to air, wound covered and kept moist, and wound covered with liquid. By 24 hours 2 +/- 1%, 16 +/- 4% and 60 +/- 8% of the wound surface interfollicular areas showed some reepithelialization, respectively. On the average, at the same time these areas showed 15 +/- 2%, 19 +/- 2% and 37 +/- 1% coverage by epithelium. By these measurements, the liquid cover enhanced the rate of wound closure significantly.

Air↗

Effect of low level helium-neon (He-Ne) laser therapy in the prevention & treatment of radiation induced mucositis in head & neck cancer patients.

BACKGROUND & OBJECTIVES: Oral mucositis is a common debilitating complication of radiotherapy occurring in about 60 per cent of cancer patients. Considerable buccal toxicity of radiotherapy or chemotherapy in cancer patients to become discouraged and can affect their quality of life. In addition, such toxicity can alter the treatment plan. At present, there is no clinically appropriate prophylaxis efficacious antidote for mucositis. The low level laser (LEL) appears to be a simple, non-traumatic technique for the prevention and treatment of radiation induced mucositis. Therefore the present study was carried out to find out the effect of low-level helium-neon (He-Ne) laser in the prevention and treatment of radiation induced mucositis in head and neck cancer patients. METHODS: The patients with carcinoma of oral cavity with stages II-IV a being uniformly treated with curative total tumour dose of 66 Gy in 33 fractions over 6 wk were selected for the study. The patients were divided based on computer generated randamosization into laser (study group) and control groups with 25 patients in each group. Both study and control groups were comparable in terms of site of the lesion, stage of the cancer and histology. The study group patients were treated with He-Ne laser (wavelength 632.8 nm and output of 10mW) and control group patients were given oral analgesics, local application of anaesthetics, 0.9 per cent saline and povidine wash during the course of radiotherapy. RESULTS: All patients tolerated the laser treatment without any adverse effect or reactions. The result showed a significant difference in pain and mucositis (P<0.001) between the two groups. At the end of radiotherapy (after 6 wk) mean pain sure and mucositis grade were significantly lower (P<0.001) in the study group compared to control. INTERPRETATION & CONCLUSION: The low-level He-Ne laser therapy during the radiotherapy treatment was found to be effective in preventing and treating the mucositis in head and neck cancer patients. Further studies need to be done on a larger sample to find the mechanism.

Female↗