D-Cycloserine in the Treatment of Pulmonary Tuberculosis Resistant to the Standard Drugs

Ruiz, Ramón Ceres

doi:10.1378/chest.45.2.181

Cited by 8 publications

(2 citation statements)

References 2 publications

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“…Mycobacteria combine β‐lactamase production (Chambers et al , 1995) with their ability to adopt an alternative, penicillin‐insensitive stem peptide cross‐linking mode in stationary phase, a strategy that is likely relevant in vivo (Goffin & Ghuysen, 2002). Other than the use of d ‐cycloserine, which inhibits stem peptide synthesis (Cáceres et al , 1997), as a second‐line agent in drug‐resistant cases (Ruiz, 1964), the inhibition of mycobacterial peptidoglycan has not been exploited clinically. The biosynthesis of meso ‐DAP represents a potentially useful node of mycobacterial cell wall physiology for chemical intervention as the di‐amino acid is strictly required for all peptidoglycan stem peptide cross‐linking (Wietzerbin et al , 1974).…”

Section: Discussionmentioning

confidence: 99%

Characterization ofMycobacterium tuberculosisdiaminopimelic acid epimerase: paired cysteine residues are crucial for racemization

Usha

Dover

Roper

et al. 2008

FEMS Microbiology Letters

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Recently, the overproduction of Mycobacterium tuberculosis diaminopimelic acid (DAP) epimerase MtDapF in Escherichia coli using a novel codon alteration cloning strategy and the characterization of the purified enzyme was reported. In the present study, the effect of sulphydryl alkylating agents on the in vitro activity of M. tuberculosis DapF was tested. The complete inhibition of the enzyme by 2-nitro-5-thiocyanatobenzoate, 5,5'-dithio-bis(2-nitrobenzoic acid) and 1,2-benzisothiazolidine-3-one at nanomolar concentrations suggested that these sulphydryl alkylating agents modify functionally significant cysteine residues at or near the active site of the epimerase. Consequently, the authors extended the characterization of MtDapF by studying the role of the two strictly conserved cysteine residues. The putative catalytic residues Cys87 and Cys226 of MtDapF were replaced individually with both serine and alanine. Residual epimerase activity was detected for both the serine replacement mutants C87S and C226S in vitro. Kinetic analyses revealed that, despite a decrease in the K(M) value of the C87S mutant for DAP that presumably indicates an increase in nonproductive substrate binding, the catalytic efficiency of both serine substitution mutants was severely compromised. When either C87 or C226 were substituted with alanine, epimerase activity was not detected emphasizing the importance of both of these cysteine residues in catalysis.

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Section: Discussionmentioning

confidence: 99%

Characterization ofMycobacterium tuberculosisdiaminopimelic acid epimerase: paired cysteine residues are crucial for racemization

Usha

Dover

Roper

et al. 2008

FEMS Microbiology Letters

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“…DCS is a relatively safe broad‐spectrum antibiotic [101–104] and has been used for several decades in the clinic to treat tuberculosis and urinary tract infections at a dosage of around 500–1000 mg/day [105,106]. In studies on healthy males [107] and patients [108], DCS administered at doses of 15–250 mg/day did not result in any side effects.…”

Section: Role Of Dcs In Neuronal Behaviormentioning

confidence: 99%

Potential of D‐cycloserine in the treatment of behavioral and neuroinflammatory disorders in Parkinson's disease and studies that need to be performed before clinical trials

Pawlak

Chen

Wu³

et al. 2012

The Kaohsiung J of Med Scie

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Hyperactivation of glutamatergic N-methyl-D-aspartate (NMDA) receptors has been implicated in the excitotoxicity and pathophysiology of Parkinson's disease (PD). NMDA receptor blockers have been used clinically to treat dementia, but their efficacy is controversial. Modulation of NMDA receptors might improve neuroinflammation and cognitive deficits in PD. D-cycloserine (DCS), a partial agonist binding to the glycine binding site of NMDA receptors, has been demonstrated to improve cognitive function in primates and rodents. Our previous study showed that DCS can reduce motor, emotional, and cognitive dysfunctions, as well as neuroinflammation and neurodegeneration in a PD animal model and may therefore have potential for the treatment of neuroinflammation and cognitive dysfunction in patients with PD. In addition, increased expression of cyclooxygenase type-2 (COX-2) has been observed in dopaminergic neurons and activated microglia in the brain of both PD patients and PD animal models. COX-2 inhibitors can suppress activation of microglia and protect dopaminergic neurons from degeneration. Thus, a combination of DCS and COX-2 inhibitors might prove useful in suppressing neuroinflammation and cognitive deficits in PD.

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GABA Synapses, Depression, and Antidepressant Drugs

Lloyd

Pichat

1987

Clinical Pharmacology in Psychiatry

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D-Cycloserine in the Treatment of Pulmonary Tuberculosis Resistant to the Standard Drugs

Cited by 8 publications

References 2 publications

Characterization ofMycobacterium tuberculosisdiaminopimelic acid epimerase: paired cysteine residues are crucial for racemization

Characterization ofMycobacterium tuberculosisdiaminopimelic acid epimerase: paired cysteine residues are crucial for racemization

Potential of D‐cycloserine in the treatment of behavioral and neuroinflammatory disorders in Parkinson's disease and studies that need to be performed before clinical trials

GABA Synapses, Depression, and Antidepressant Drugs

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