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At least 253 records · Page 14Linked to original sources
PubMed2004

Adenovirus vectors targeting alphaV integrin or heparan sulfate receptors display different distribution of transgene activity after intramuscular injection.

BACKGROUND: Modification of the fiber proteins in replication-deficient adenoviral (Ad) vectors through incorporation of specific receptor-binding motifs may represent a strategy to enhance their tissue targeting capabilities. METHODS: In this study, we compared an unmodified Ad (GV10) with two mutated vectors obtained by insertion of specific target sequences that redirect binding, either toward alpha(V) integrin (RGD) or heparan sulfate (UTV) cellular receptors, for reporter gene expression spatial distribution in the rabbit skeletal muscle. In a first series of experiments, injection volume was kept constant and activity of a lacZ transgene was evaluated 48 h after injection of the Ad vectors at different doses. In separate experiments, the effects of different volumes of injection at a constant dose of Ad vector were monitored. RESULTS: All vectors evaluated showed a significant increase in the number of lacZ-positive muscle segments, with increasing vector dose. However, in muscles treated with the UTV vector, fewer muscle fibers were beta-gal-positive than in GV10 or RGD vector treated animals. In fact, total beta-gal activity increased in a dose-dependent fashion in the GV10- and RGD-treated muscles, but not in the UTV-treated ones. Remarkably, in samples from UTV-treated animals, a volume-dependent enhancement of transgene expression was observed during experiments performed at the same dose and different injection volumes. CONCLUSIONS: The results of the present study demonstrate that altering Ad affinity for cellular receptors modulates the level and distribution of transgene activity, conferring characteristics that may allow for treatment customization.

Adenoviridae↗
PubMed1979

Comparison of serum levels after intramuscular injections of 2% and 10% cis(Z)-flupentixol decanoate in Viscoleo to schizophrenic patients.

The serum concentrations of cis(Z)-flupentixol after injection of 2% and 10% cis(Z)-flupentixol decanoate in Viscoleo (Depixol injection, Fluanxol Depot) have been investigated in a crossover study with eight schizophrenic patients. No statistically significant difference was found between the two preparations when the data from individual days or areas under the serum concentration curves were considered. For the individual patients a difference was found between the two treatments in six cases; one preparation gave the higher serum concentration in four cases and the other preparation in two cases. Thus, the difference found within individual patients reflects the intraindividual variation rather than a difference between preparations. The maximum serum concentration was seen at 4 or 7 days after injection. The maximum/minimum fluctuation ratio indicates that dosage intervals longer than 2 weeks seem reasonable for most of the patients. The similarity in the serum concentrations, no matter which concentration of flupentixol decanoate solution was given, indicates that a dispersal and possibly a metabolic breakdown of the oil depot takes place in the muscle.

Adult↗
PubMed1976

125I-labelled botulinum A neurotoxin: pharmacokinetics in cats after intramuscular injection.

1. On unilateral injection of sublethal doses of 125I-botulinum A neurotoxin (BTA) into one gastrocnemius muscle of the cat we found after 48 h: a) A disto-proximal gradient of radioactivity (RA) had developed in the sciatic nerve of the injected side. b) The ventral roots of the spinal cord half segments supplying the injected muscle showed a higher RA than the ventral roots of the contralateral control side. c) The spinal cord half segments innervating the injected muscle had a RA much higher than the corresponding segments of the contralateral side. However, a small rise of RA was also observed in the contralateral half segments. 2. In histoautoradiographs of the (ligatured) ventral roots the RA was strictly confined to the intraaxonal space of a few nerve fibres. 3. On injection of equal doses of 125I-BTA into either gastrocnemius muscle we found after 38 h: a) Direct stimulation of only one of the injected muscle caused the RA to reach a higher level in the spinal cord half segments ipsilateral to the stimulated muscle than in the spinal cord half segments of the non-stimulated side. b) Unilateral stimulation of one gastrocnemius nerve under the influence of gallamine or unilateral antidromic stimulation of the dorsal roots L7, S1 failed to cause a difference in RA between stimulated and non-stimulated side.

Animals↗
PubMed1989

Demonstration of ricin within the mammalian para-aortic lymph node. I. Comparison of the localization, after intramuscular injection, with three immunocytochemical methods.

Following a supralethal injection of ricin into thigh muscle of the adult rat, the toxin was demonstrated post-mortem in the para-aortic lymph node, ipsilateral to the side of injection. The relative merits of two immunoenzyme methods, peroxidase anti-peroxidase (PAP) and avidin-biotin-peroxidase complex (ABC) and a silver-enhanced immunogold method (IGSS) were assessed in the detection of ricin in the lymph node tissue. The toxin was clearly seen to be located in association with histiocytes found both within and lining the sinuses of the nodes and also, in some cases, in the subcapsular sinus of the node; the toxin was not demonstrable within lymphoid follicles by light microscopy. However, using electron microscopy and the IGSS technique, cells carrying discrete particles of gold could be visualized within follicular areas. The IGSS and ABC-peroxidase methods were both found to give excellent results without background staining at the light microscopy level. However, when these techniques were used prior to embedding and viewing by electron microscopy, the IGSS technique proved to be far superior.

Animals↗
PubMed1991

Efficacy and tolerability of a long-acting intramuscularly injectable depot preparation of bromocriptine: the results of a double blind study.

The tolerability and efficacy of a long-acting im applicable form of bromocriptine (Parlodel LAR) was tested in a double-blind approach in 20 patients with hyperprolactinemia or prolactinoma, 17 of them complaining of persistent side effects on oral treatment with dopamine agonists. The study-code revealed similar characteristics for age, sex, weight, clinical symptoms and previous therapy in both groups but prolactin serum levels were higher in the verum group even though the difference was not significant. In all 10 patients receiving Parlodel LAR prolactin serum concentrations were significantly suppressed and tumor size was reduced in 5 of the 9 patients with visible tumors when controlled after 28 days. In contrast, no significant change in serum prolactin levels was observed in the placebo group and tumor size of all visible tumors was not altered. Side effects typically reported for dopamine agonists started 3 h after application in the verum group and were significantly different to the unspecific side effects reported in the placebo group during the first 72 h. Thereafter systemic tolerability was indistinguishable between both groups. The local tolerability at the injection site was excellent for both, Parlodel LAR and placebo.

Adolescent↗