Research Interest: Molecular mechanisms of Leptospira pathogenesis
Leptospirosis is an important global human and veterinary
health problem caused by pathogenic Leptospira species. There
is a reported 27/100,000 incidence rate in Jamaica, where
two endemic strains are responsible for most of the human
seroconversions. Leptospira virulence factors such as haemolysins,
LPS, glycolipoprotein, peptidoglycan, heat shock proteins
and flagellin have been shown to be involved in the pathogenic
process; however, our knowledge of their in vivo (or host)
expression during the infection process still represents a
gap in our understanding of the pathogenesis of this organism.
Current research underway involves identification and characterization
of Leptospira virulence-associated genes (regulated by the
recA gene) that are expressed during infection (in vivo).
Effect of exogenous nitric oxide in insulin-mediated
signal transduction pathways
Nitric oxide (NO) is an important bioactive signalling molecule
that mediates a variety of normal physiological functions.
Collaborative research with Dr. D. Ragoobirsingh has established
that exogenous NO (from SNAP and GSNO) inhibits insulin binding
to its receptor on mononuclear leukocytes, which was attributed
to decreased insulin receptor sites per cell.
Subsequent work has demonstrated that in vitro exogenous
NO significantly inhibited glucose uptake and expression of
insulin receptor substrate-1 (IRS-1) in primary skeletal,
adipose and hepatic tissue obtained from Sprague-Dawley rats.
We are characterizing the in vitro effects of NO on phosphorylation
of tyrosine residues in the insulin receptor, serine and tyrosine
residues of IRS-1, and on the content and translocation of
glucose transporters GLUT1 and GLUT4 in isolated adipose,
skeletal muscle and liver cells from Sprague-Dawley rats.
Comparisons with dexamethasone-induced insulin resistance
are also being investigated.
Antibiotic resistance patterns and mechanisms of
pathogenicity of clinical isolates
The antibiotic resistance patterns and mechanisms of pathogenicity
are being investigated in clinical isolates of Pseudomonas
aeruginosa and Staphylococcus aureus (including MRSA), and
veterinary isolates of E. coli.
Recent publications
1. P.D. Brown & P.N.Levett (1997). Differentiation of
Leptospira species and serovars by PCR-restriction enzyme
analysis, arbitrarily primed PCR, and low stringency PCR.
J. Med. Microbiol. 46: 173-181.
2. P.N.Levett, P.D.Brown, S.Hector, M.M.Scantlebury, T.C.Roach
(1999). Clustering of cases of Mycobacterium fortuitum infection
investigated by molecular typing. West Indian Med. J. 48:
16-19.
3. P.D.Brown, D.G. Carrington, C. Gravekamp, H. van de Kemp,
C.N. Edwards, S.R. Jones, P.R. Prussia, S. Garriques, W.J.
Terpstra, P.N. Levett. (2003). Direct detection of leptospiral
material in human postmortem samples. Res. Microbiol. 154(8):
581-586.
4. D.Ragoobirsingh, D.McGrowder, T.Dasgupta & P.D.Brown
(2004). The effect of nitric oxide on glucose metabolism.
Mol. Cell. Biochem. 263: 29-34.
5. P.D.Brown, A.Izundu (2004). Antibiotic resistance in clinical
isolates of Pseudomonas aeruginosa in Jamaica. Rev Panam Salud
Publica/Pan Am. J. Public Health 16(2): 125-130.
6. P.D.Brown (2005). Leptospira spp. Encyclopedia of Medical
Genomics and Proteomics, DOI: 10.1081/E-EDGP-120020875 (Review)
7. D.McGrowder, D.Ragoobirsingh & P.Brown (2006). Acute
effects of exogenous nitric oxide on glucose uptake in skeletal
muscle of normoglycaemic and diabetic rats. Med. Sci. Monit.
12(1): BR28-35.
8. T.Miles, W.McLaughlin & P.D.Brown (2006). Antimicrobial
resistance of Escherichia coli from broiler chickens and humans.
BMC Vet. Res. 2:7
9. S.Badal, P.D.Brown & D.Ragoobirsingh (2006). Exogenous
nitric oxide inhibits IRS-1 expression in rat hepatocytes
and skeletal myocytes. J. Biomed. Sci. DOI: 10.1007/s11373-006-9073-y
10. K.Barrett, D.McGrowder, P.Brown & D.Ragoobirsingh.
Increased PC-1 phosphodiesterase activity and inhibition of
glucose uptake in adipocytes of type 2 diabetic rats. Mol.
Cell. Biochem. [in press]
11. D.McGrowder, K.Barrett, P.Brown & D.Ragoobirsingh.
Exogenous nitric oxide inhibits glucose uptake in peripheral
tissues of diabetic rat model. Diabetologia Croatica. [in
press]
12. D.McGrowder, D.Ragoobirsingh & P.Brown. Therapeutic
uses of nitric-oxide-donating drugs in the treatment of cardiovascular
diseases. Int. J. Pharmacol. [Review; in press]
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