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At least 919 records · Page 51Linked to original sources
PubMed1999

Hyperalgesia due to nerve injury: role of prostaglandins.

The hypothesis that prostaglandins contribute to hyperalgesia resulting from nerve injury was tested in rats in which the sciatic nerve was partially transected on one side. Subcutaneous injection of indomethacin (a classic inhibitor of cyclo-oxygenase) into the affected hindpaw relieved mechanical hyperalgesia for up to 10 days after injection. Subcutaneous injection of meloxicam or SC-58125 (selective inhibitors of cyclo-oxygenase-2) into the affected hindpaw also relieved mechanical hyperalgesia, but with a shorter time-course. Subcutaneous injection of SC-19220 (an EP1 prostaglandin receptor blocker) into the affected hindpaw produced significant relief of mechanical and thermal hyperalgesia. Comparable injections into the contralateral paw or abdomen had no effect on mechanical or thermal hyperalgesia, suggesting that the effects we observed were local rather than systemic. We conclude that prostaglandins, probably prostaglandin E1 or E2, contribute to the peripheral mechanisms underlying hyperalgesia following nerve injury. These data provide further evidence that inflammatory mediators contribute to neuropathic pain, and may warrant further study of peripherally administered non-steroidal anti-inflammatory drugs as a possible treatment for such pain in patients.

Animals↗
PubMed1970

Formation of mercapturic acids in rats after the administration of aralkyl esters.

1. Benzylmercapturic acid and hippuric acid were isolated from the urine of rats that had been injected subcutaneously with benzyl acetate. 2. 1-Menaphthylmercapturic acid and 1-naphthoic acid were isolated from the urine of rats after the subcutaneous injection of each of the following compounds: 1-menaphthyl alcohol and its acetate, propionate, butyrate and benzoate esters. 3. A quantitative method for determining 1-menaphthylmercapturic acid in urine was developed and used to measure the excretion of this compound in the urine of rats in the 4-day period after the subcutaneous injection of 1-menaphthyl alcohol and its acetate, propionate, butyrate and benzoate esters. 4. Chromatographic evidence was obtained for the presence of S-(1-menaphthyl)glutathione and S-(1-menaphthyl)-l-cysteine in bile collected from rats with cannulated bile ducts after the animals had been injected subcutaneously with each of the following compounds: S-(1-menaphthyl)glutathione, 1-menaphthyl acetate, propionate and butyrate. 5. Benzylmercapturic acid and 1-menaphthylmercapturic acid were isolated from the urine of rats that had been injected with sodium benzyl sulphate and sodium 1-menaphthyl sulphate respectively.

Acetates↗
PubMed1976

Inhibition of cerebral protein synthesis: performance at different times after passive avoidance training.

Inhibition of cerebral protein synthesis impairs long-term memory in a variety of species and tasks. Recently it was reported that subcutaneous injection of the protein synthesis inhibitor cycloheximide impaired short-term retention, measured 10 min after training in a passive avoidance task. To examine the possibility that inhibition of cerebral protein synthesis may sometimes disrupt short-term memory, mice were injected subcutaneously with cycloheximide (120 mg/kg) or anisomycin (150 mg/kg), or bitemporally with cycloheximide or anisomycin (100 mug/side) and given one training trial in a passive avoidance box. Subcutaneously injected cycloheximide reduced step-through latencies 10 min after training as reported previously, but anisomycin or bitemporally injected cycloheximide did not. All 4 drug groups exhibited impaired long-term memory. Since the results obtained at short intervals after training varied depending on the drug and route of injection, the impairment produced by subcutaneous cycloheximide at 10 min after training cannot be attributed to inhibition of cerebral protein synthesis. It is suggested that performance at short intervals after training reflects drug side effects on step-through behavior. By contrast, the impairment obtained at long intervals after training is consistent with the hypothesis that cerebral protein synthesis is required for formation of long-term memory.

Animals↗
PubMed1989

NovoSol Basal: pharmacokinetics of a novel soluble long acting insulin analogue.

OBJECTIVE: To determine the courses of absorption and the interindividual and intraindividual variations in absorption of iodine-125 labelled Ultratard HM and NovoSol Basal injected subcutaneously. DESIGN: Open randomised crossover study. Each patient was tested during two study periods of five days each, during which he or she received a subcutaneous injection of either 125I-NovoSol Basal or 125I-Ultratard HM on four consecutive days. The aim was to detect a reduction in intraindividual standard deviation by a factor of two with a probability 0.95, taking 0.05 as the level of significance. This required 24 degrees of freedom and led to the choice of four courses in each of eight patients. SETTING: Referrals to the diabetes research centre in Hvidøre, Copenhagen. PATIENTS: Eight insulin dependent (type I) diabetics with low or undetectable C peptide concentrations who were receiving a multiple insulin injection regimen. One patient withdrew immediately after recruitment. INTERVENTIONS: After an overnight fast patients received 96 nmol (16 IU insulin) of either 125I-NovoSol Basal or 125I-Ultratard HM injected subcutaneously into the thigh. To ensure that the insulin entered the subcutaneous fat at the same depth, ultrasonography was performed on each patient before the first injection. A different injection site on the thigh was used each day for four days in order to facilitate monitoring of the disappearance of four different depots in each patient. MAIN OUTCOME MEASURE: Residual activity at the injection site was measured roughly every two hours throughout the day. No radioactivity measurements were performed overnight (10 pm till 8 am). The residual radioactivity after the injection on the first day (upper right thigh) was recorded for five days, that after the injection on the second day (upper left thigh) for four days, after the injection on the third day (lower right thigh) for three days, and after the last injection (lower left thigh) for two days. RESULTS: NovoSol Basal was absorbed according to first order kinetics with a mean t50% of 35.3 (SEM 1.4) hours; Ultratard HM was absorbed after a lag phase and the corresponding t50% was 25.5 (2.5) hours. The intraindividual variations in t50% were significantly smaller with NovoSol Basal than with Ultratard HM (18.4% v 44.5%; p less than 0.001). Interindividual variations, however, were not significantly different (25.2% v 36.9%; p = 0.38). The total variation in t50% was substantially smaller with NovoSol Basal than with Ultratard HM (20.3% v 42.8%). CONCLUSIONS: NovoSol Basal seems to be an appreciable advance over Ultratard HM as a soluble insulin preparation for obtaining reproducible 24 hour insulin concentrations in the blood

Absorption↗
PubMed1996

A comparison of the skeletal effects of intermittent and continuous administration of calcitonin in ovariectomized rats.

The study was designed to compare the skeletal effects of intermittent and continuous administration of calcitonin (CT) in ovariectomized (OVX) rats. Female rats were sham operated or OVX at 3 months of age and treated for 6 weeks with vehicle or salmon CT. Sham-operated control rats were injected subcutaneously with vehicle on alternate days. One group of OVX rats was treated with vehicle intermittently by subcutaneous injection or continuously via Alzet osmotic minipumps. The remaining OVX rats were treated with CT by either subcutaneous injections (16 U/kg) on alternate days or by continuous infusion via minipumps at a daily dose of 8 U/kg. OVX rats treated with CT continuously were mildly hypocalcemic compared with all other groups. The proximal tibial metaphyses of vehicle-treated OVX rats were osteopenic with a cancellous bone volume at only 28% of the vehicle-treated control level. This bone loss was associated with increased indices of bone turnover such as osteoclast surface, osteoblast surface, and bone formation rate. Cancellous bone volume in OVX rats treated with CT either intermittently or continuously was significantly higher than that of vehicle-treated OVX rats, but lower than that of vehicle-treated control rats. Treatment of OVX rats with intermittent or continuous CT significantly decreased all indices of bone turnover compared with vehicle-treated OVX rats. However, osteoclast and osteoblast surfaces of OVX rats treated with CT continuously were still significantly higher than those of vehicle-treated control rats. These results indicate that intermittent and continuous administration of CT had similar skeletal effects in OVX rats. Both treatment regimens depressed bone turnover and partially prevented cancellous bone loss in the estrogen-deplete skeleton.

Analysis of Variance↗
PubMed1992

A surface protease and the invasive character of plague.

A 9.5-kilobase plasmid of Yersinia pestis, the causative agent of plague, is required for high virulence when mice are inoculated with the bacterium by subcutaneous injection. Inactivation of the plasmid gene pla, which encodes a surface protease, increased the median lethal dose of the bacteria for mice by a millionfold. Moreover, cloned pla was sufficient to restore segregants lacking the entire pla-bearing plasmid to full virulence. Both pla+ strains injected subcutaneously and pla- mutants injected intravenously reached high titers in liver and spleen of infected mice, whereas pla- mutants injected subcutaneously failed to do so even though they establish a sustained local infection at the injection site. More inflammatory cells accumulated in lesions caused by the pla- mutants than in lesions produced by the pla+ parent. The Pla protease was shown to be a plasminogen activator with unusual kinetic properties. It can also cleave complement C3 at a specific site.

Amino Acid Sequence↗
PubMed1982

Studies on the absorption of practically water-insoluble drugs following injection VI: Subcutaneous absorption from aqueous suspensions in rats.

The absorption characteristics and kinetics of practically water-insoluble drugs following subcutaneous injection of their aqueous suspensions were investigated in intact rats by the local clearance method and compared with those following intramuscular injection reported previously. The plot of the cube root of the residual fraction of the drug in the injection site versus time gave a good linear relationship under various experimental conditions. The absorption rate constant (j) increased with decreasing particle size. This increase was remarkable in the region of mean particle diameter less than 2-3 micrometers, while it was gradual or slight in the region above this. This phenomenon was explained by the fact that the in vivo spreading of particles of more than approximately 3 micrometers was still more limited by the network of the fibrous tissues. Between j and the initial drug concentration (C0) or injection volume (V0), the practically important relationship j alpha C0g V0h (g = -0.66 and h = -0.32) could approximately be derived from the experimental results. Comparison of j values among various compounds with different solubility (C's) in saline but with similar colloidal properties (particle size distribution and sedimentation volume) showed that a log j versus log C's plot gave a nearly straight line with a slope of approximately 0.5. All the results observed for the subcutaneous absorption were similar to those for intramuscular absorption and could reasonably be explained by the kinetic model proposed for intramuscular absorption.

Animals↗
PubMed1999

Routes of entry of Piscirickettsia salmonis in rainbow trout Oncorhynchus mykiss.

Since 1989, Piscirickettsia salmonis, the causal agent of piscirickettsiosis, has killed millions of farmed salmonids each year in southern Chile. The portal of entry for the pathogen was investigated by use of selected experimental infections in juvenile rainbow trout (12 g). The methods used were intraperitoneal injection, subcutaneous injection, patch contact on skin, patch contact on gills, intestinal intubation and gastric intubation. Cumulative mortalities at Day 33 post-inoculation were 98, 100, 52, 24, 24, and 2%, respectively. It was shown that intact skin and gills could be penetrated by P. salmonis. The high mortality obtained in subcutaneously injected fish indicated that skin injuries could facilitate the invasion of this pathogen. Results suggested that the main entry sites are through the skin and gills and that the oral route may not be the normal method by which P. salmonis initiates infection of salmonids.

Administration, Topical↗
PubMed1983

Pharmaceutical approach to subcutaneous dosage forms of insulin.

The present studies were undertaken to describe the dynamic nature of the degradation and absorption of insulin in the subcutaneous injection site and to develop agents which would stabilize this dosage form. [125I]Insulin with 0.2-U/kg of unlabeled insulin in 10 microliters of aqueous solution was injected subcutaneously in rats under the depilated skin of the back. At various times, radioactive skin tissue was extracted and assayed for insulin and/or its metabolites by gel filtration. Using these data, absorption and degradation rate constants of these substances were estimated according to a one-compartment model. Absorption rate constants of insulin and its metabolite of low molecular weight (monoiodotyrosine) were 0.021 min-1 and 0.107 min-1, respectively, while the degradation rate constant for insulin to monoiodotyrosine was 0.013 min-1. Thus, the bioavailability of insulin injected subcutaneously was lower than expected, suggesting the necessity of stabilizing methods. The protection of insulin from degradation at the site of injection was examined by the addition of various peptides. It was found that benzyloxycarbonyl-Gly-Pro-Leu-Gly was a good stabilizing agent, and remarkably inhibited insulin degradation. This inhibition was confirmed by the increase of immunoreactive insulin level and the decrease of the blood glucose level. We postulated that this peptide protects the injected insulin from degradation by inhibiting the peptidase present in subcutaneous tissue.

Animals↗
PubMed2000

Intra-individual variability of the metabolic effect of inhaled insulin together with an absorption enhancer.

OBJECTIVE: To study the metabolic effect and the variability of the effect elicited by inhalation of 87.2 U insulin powder combined with an absorption enhancer. The metabolic effect was compared with that of 10.2 U regular insulin injected subcutaneously and of 5.5 U regular insulin given intravenously RESEARCH DESIGN AND METHODS: In this single-center open euglycemic glucose clamp study 13 healthy male volunteers received 5 insulin administrations on separate study days: once as an intravenous dose, once as a subcutaneous injection, and 3 times by inhalation, in randomized order. Glucose infusion rates (GIRs) necessary to keep blood glucose concentrations constant at 5.0 mmol/l were determined over an 8-h period after administration. RESULTS: After inhalation of the insulin powder aerosol, the onset of action was substantially more rapid than after subcutaneous insulin injection, and maximal action was reached earlier (86+/-47 vs. 182+/-53 min, P<0.0001). The maximal glucose infusion rate after inhalation of insulin was comparable to that after subcutaneous insulin injection (9.2+/-2.6 vs. 8.8+/-2.8 mg x kg(-1) x min(-1), NS). The metabolic effect in the first 2 h after inhalation was significantly greater than that after subcutaneous insulin injection (amount of glucose infused: 0.88+/-0.25 vs. 0.59+/-0.20 g x kg(-1) x 120 min(-1), P<0.0001). However, the total metabolic effect after inhalation and subcutaneous injection was comparable (2.50+/-0.76 vs. 2.56+/-0.69 g x kg(-1) x 480 min(-1), NS). The relative bioefficacy of inhaled insulin calculated in relation to the data from the subcutaneous insulin application was 12.0+/-3.5% (absolute bioefficacy 10.1+/-3.1%) but was highest in the first 2 h after application (18.5+/-3.7%; absolute bioefficacy 8.2+/-4.1%). The intraindividual variability of the metabolic response induced by insulin inhalation was 14+/-9% for the maximal glucose infusion rate, 15+/-10% for the time-to-maximal effect, and 16+/-12% for the total amount of glucose infused. CONCLUSIONS: This feasibility study shows that inhaled insulin with an absorption enhancer has a pronounced metabolic effect compared with the results of a previous study of inhaled insulin without an enhancer. The intraindividual variability of the metabolic effect was comparable with that of inhaled and subcutaneously injected insulin.

Administration, Inhalation↗