A. N. Chakrabarty

The anti-bacterial action of diclofenac shown by inhibition of DNA synthesis

Most strains of Gram-positive and Gram-negative bacteria were inhibited by 50-100 mg/l of the anti-inflammatory agent, diclofenac sodium (Dc). In vivo test using 30 or 50 microg Dc per 20 g mouse (Swiss Albino variety) significantly (P <0.001) protected the animals when challenged with 50 MLD of a virulent Salmonella typhimurium. The anti-bacterial action of Dc was found to be due to inhibition of DNA synthesis which was demonstrated using 2 micro Ci (3H) deoxythymidine uptake.

Trifluoperazine: a broad spectrum bactericide especially active on staphylococci and vibrios

Trifluoperazine showed some significant antimicrobial activity when tested against 293 strains from two Gram-positive and eight Gram-negative genera. Minimum inhibitory concentrations of the drug were measured using an agar dilution technique. Forty six of 55 strains of Staphylococcus aureus were inhibited by 10-50 microg/ml of trifluoperazine. This drug also inhibited strains of Shigella spp., Vibrio cholerae and V. parahaemolyticus at a concentration of 10-100 microg/ml. Other bacteria including Pseudomonas spp. were moderately sensitive to trifluoperazine. In the in vivo studies this compound offered significant protection to Swiss albino mice at a concentration of 30 microg/mouse (P<0.001) when challenged with 50 median lethal dose of Salmonella typhimurium NCTC 74.

Antimycobacterial activity of methdilazine (Md), an antimicrobic phenothiazine

Methdilazine (Md) could inhibit various Mycobacterium spp. at 5–15 μg/ml concentrations in vitro as well as in vivo. When Md was tested in combination with streptomycin (Sm), rifampicin (Rf) or methyl‐DOPA (m‐D), it showed synergistic effects only with respect to methyl‐DOPA.

Antimicrobial potentiality of a new non-antibiotic : the cardiovascular drug oxyfedrine hydrochloride

Ten cardiovascular drugs, having diverse pharmacological action, were screened for possible antimicrobial property against known eight sensitive bacteria, belonging to Gram positive and Gram negative types. Although five drugs failed to show antimicrobial activity and three had moderate antimicrobial action, oxyfedrine HCl and dobutamine were seen to possess pronounced antimicrobial property. Oxyfedrine was further tested in vitro against 471 strains of bacteria from two Gram positive and fourteen Gram negative genera. The minimum inhibitory concentration (MIC) of oxyfedrine was determined by agar dilution method, which ranged from 50-200 microg/ml in most of the strains, while some strains were inhibited at even lower concentrations. In animal experiments, this compound was capable of offering significant protection to Swiss strain of white mice, challenged with 50 median lethal dose (MLD) of a virulent strain of Salmonella typhimurium at concentrations of 15, 30 and 60 microg/mouse. The in vivo results were highly significant according to chi-square test.

Antimycobacterial activity of the antiinflammatory agent diclofenac sodium, and its synergism with streptomycin

Diclofenac sodium, an antiinflammatory agent, exhibited remarkable inhibitory action against both drug sensitive and drug resistant clinical isolates of Mycobacterium tuberculosis, as well as other mycobacteria. This drug was tested in vitro against 45 different strains of mycobacteria, most of which were inhibited by the drug at 10-25 µg/ml concentration. When tested in vivo, diclofenac, injected at 10 µg/g body weight of a Swiss strain of white mice, could significantly protect them when challenged with 50 median lethal dose of M. tuberculosis H37 Rv 102. According to c2 test, the in vivo data were highly significant (p<0.01). Diclofenac was further tested for synergism with the conventional antimycobacterial drug streptomycin against M. smegmatis 798. When compared with their individual effects, synergism was found to be statistically significant (p<0.05). By the checkerboard assessment procedure, the fractional inhibitory concentration index of this combination was found to be 0.37, confirming synergism.

Screening for anti-HIV drugs that can combine virucidal and virustatic activities synergistically

Chlorcyclizine HCl and ciprofloxacin HCl were shown to have anti-HIV activity. They possess virustatic and virucidal activities against HIV, a murine retrovirus (RV) and several other RNA and DNA viruses. These drugs were screened from a large number of compounds on the basis of in vitro mutagenicity and antimetabolite detection tests. Subsequent studies were based on different exo vivo cell cultures. These two compounds were then tested on an animal model, following standard test protocols, using another retrovirus, maintained as Ehrlichs ascites cell tumour virus (EACTV). The animal mortality and protection tests corroborated the findings obtained in vitro, suggesting that these drugs acted synergistically against HIV, exhibiting both virucidal and virustatic properties.

Paradoxical Inhibition among Bacteria. Characterization of the Phenomenon and Nature of the Genetic Process

The phenomenon of paradoxical inhibition (p.i.) manifests itself as well-defined growth of a sensitive bacterium in the centre of the zone of inhibition overlying an area of growth of the inhibitory bacterium. Bacteriocin typing medium (BTM) for Vibrio cholerae elicited p.i. for this group only. A medium for paradoxical inhibition (MPI) was devised which supported the development of p.i. among members of Enterobacteriaceae, Vibrio and Alcaligenes spp. at high frequency. The reacting pair of strains could belong either to the same or to different genera. Colonies of non-bacteriocinogenic strains derived from the central area of p.i. showed acquisition of bacteriocinogeny at high frequency. Acquisition was rapid in the beginning (up to 4 h) followed by a decline and virtual disappearance of bacteriocinogeny by 18 h on MPI, but was substantially retained on BTM. The overall frequency of acquisition among cell populations of different strains varied between 10-1 and 10-4, and the acquired characters were stable. Acquisition did not require either cell contact or participation of phages, but depended upon extracellular diffusable agents that were DNase sensitive and RNase resistant. A mutational basis for such acquisition could be ruled out, and the process of gene transfer was considered to be transformation. The extra-chromosomal nature of the determinants of bacteriocinogeny in the bacteria studied was suggested by effective elimination of these markers by sodium dodecyl sulphate and acridine orange.

Incidence and Elimination of R Plasmids in Vibrio cholerae

Of 124 strains of Vibrio cholerae, 32 were multiply resistant to antibiotics. This resistance appeared to be determined by R plasmids on the basis of their effective elimination by sodium dodecyl sulfate, acridine orange, ethidium bromide, and ultraviolet radiation.

Possible Human Health Hazards from Outbreak of Epizootic Ulcerative Syndrome (EUS) in Fish in the Asia-Pacific Region

Acid fast rods, constituting chemoautotrophic nocardioform bacteria, could be repeatedly cultivated and isolated and propagated indefinitely in vitro from fish actinomycotic macrophage granuloma from the massive epizootics of ulcerative disease syndrome of fish in eastern India during 1988-90. The possible human hazards of zoonotic actinomycotic infections as a result of handling and consumption of such fish are assessed.

Immunochemical studies on a polysaccharide from Shigella dysenteriae type 2

The polysaccharide isolated from Shigella dysenteriae type 2, strain NCTC 566, on Smith degradation and graded hydrolysis yielded three oligosaccharides which were characterised using methylation studies. Using homologous rabbit antiserum and the monosaccharides that constituted the polysaccharide and the oligosaccharides isolated from it and the cross-reactions in some type-specific pneumococcal antisera, immunochemical specificities of different sugar groupings in the polysaccharide molecule were determined. These results indicated that N-acetylglucosamine was the immunodominant sugar in the polysaccharide and the oligosaccharide isolated from the Smith-degraded product and having the structure (formula; see text) gave maximum inhibition of the specific precipitation.