94 research outputs found
Preclinical safety and tolerability of a repeatedly administered human leishmaniasis DNA vaccine.
The leishmaniases are a complex of vector-borne diseases caused by protozoan parasites of the genus Leishmania. LEISHDNAVAX is a multi-antigen, T-cell epitope-enriched DNA vaccine candidate against human leishmaniasis. The vaccine candidate has been proven immunogenic and showed prophylactic efficacy in preclinical studies. Here, we describe the safety testing of LEISHDNAVAX in naive mice and rats, complemented by the demonstration of tolerability in Leishmania-infected mice. Biodistribution and persistence were examined following single and repeated intradermal (i.d.) administration to rats. DNA vectors were distributed systemically but did not accumulate upon repeated injections. Although vector DNA was cleared from most other tissues within 60 days after the last injection, it persisted in skin at the site of injection and in draining lymph nodes. Evaluation of single-dose and repeated-dose toxicity of the vaccine candidate after i.d. administration to naive, non-infected mice did not reveal any safety concerns. LEISHDNAVAX was also well tolerated in Leishmania-infected mice. Taken together, our results substantiate a favorable safety profile of LEISHDNAVAX in both naive and infected animals and thus, support the initiation of clinical trials for both preventive and therapeutic applications of the vaccine
Growth Factors Regulate Expression of OsteoblastāAssociated Genes
Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141995/1/jper1345.pd
Novel Bradykinin Analogues Modified in the N-Terminal Part of the Molecule with a Variety of Acyl Substituents
In the current work we present some pharmacological characteristics of ten new analogues of bradykinin (ArgāProāProāGlyāPheāSerāProāPheāArg) modified in the N-terminal part of the molecule with a variety of acyl substituents. Of the many acylating agents used previously with B2 receptor antagonists, the following residues were chosen: 1-adamantaneacetic acid (Aaa), 1-adamantanecarboxylic acid (Aca), 4-tert-butylbenzoic acid (t-Bba), 4-aminobenzoic acid (Aba), 12-aminododecanoic acid (Adc), succinic acid (Sua), 4-hydroxybenzoic acid, 4-hydroxy-3-methoxybenzoic acid, 3-(4-hydroxyphenyl)propionic acid and 6-hydroxy-2-naphthoic acid. Biological activity of the compounds was assessed in the in vivo rat blood pressure test and the in vitro rat uterus test. Surprisingly, N-terminal substitution of the bradykinin peptide chain itself with aforementioned groups resulted in antagonists of bradykinin in the pressor test and suppressed agonistic potency in the uterotonic test. These interesting findings need further studies as they can be helpful for designing more potent B2 receptor blockers
HAE therapies: past present and future
Advances in understanding the pathophysiology and mechanism of swelling in hereditary angioedema (HAE) has resulted in the development of multiple new drugs for the acute and prophylactic treatment of patients with HAE. This review will recap the past treatment options, review the new current treatment options, and discuss potential future treatment options for patients with HAE
Could peak proteinuria determine whether patient with dengue fever develop dengue hemorrhagic/dengue shock syndrome? - A prospective cohort study
The carcinogenic effect of various multi-walled carbon nanotubes (MWCNTs) after intraperitoneal injection in rats
Airway exposure to multi-walled carbon nanotubes disrupts the female reproductive cycle without affecting pregnancy outcomes in mice
A fast, reliable and highly sensitive quantitative determination of the neurolepticum HR 375 in serum by means of HPTLC
A STUDY OF NEUROKININS AND OTHER OEDEMA-INDUCING MEDIATORS AND MECHANISMS IN THERMAL INJURY
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