Determination of antimicrobial activity of Cefaclor on common respiratory tract pathogens in Pakistan.

OBJECTIVE: To determine the antimicrobial activity of Cefaclor against common respiratory tract pathogens isolated from patients in Pakistan. SETTING: Department of Microbiology, Liaquat National Postgraduate Medical Centre, Karachi. METHOD: A laboratory analysis was done on 466 isolates of respiratory tract pathogens collected from 13 laboratories from all over Pakistan. Antibiotic sensitivity test was done by Kirby Bauer disc diffusion method and MIC of Cefaclor was determined by 'E' test. RESULT: Of the 163 Streptococcus pneumoniae, 87 Moraxella catarrhalis and 216 Haemophilus influenzae > 95% isolates were susceptible to Cefaclor. The MIC 90 of all these pathogens were < 2 ug. CONCLUSION: Resistance of respiratory tract pathogens to the 2nd generation Cephalosporin, Cefaclor is very low. MIC 90 of Cefaclor against all three common respiratory tract pathogens is < 2 ug, which indicates that Cefaclor would be effective in more than 90% of cases infected with these bacteria.

Phosmet induces up-regulation of surface levels of the cellular prion protein.

Chronic (2 day) exposure of human neuroblastoma cells to the organophosphate pesticide phosmet induced a marked concentration-dependent increase in the levels of PrP present on the cell surface as assessed by biotin labelling and immunoprecipitation. Levels of both phospholipase C (PIPLC)-releasable and non-releasable forms of PrP were increased on the plasma membrane. These increases appear to be due to post-transcriptional mechanisms, since PrP mRNA levels as assessed by Northern blotting were unaffected by phosmet treatment. These data raise the possibility that phosmet exposure could increase the susceptibility to the prion agent by altering the levels of accessible PrP.

Comparison of neurite outgrowth with neurofilament protein subunit levels in neuroblastoma cells following mercuric oxide exposure.

1. The objectives of the study were to establish that inhibition of neuronal differentiation in culture (assessed by neurite outgrowth) can be used as a broad spectrum in vitro measure of neurotoxicity. 2. To establish whether a rapid measure of neurite outgrowth could be used. Thus the study examined the relationship between the degree of neurite outgrowth assessed directly by image analysis and neurofilament protein subunit levels measured by an ELISA. 3. SKNSH neuroblastoma cells, exposed for up to 6 days to mercuric chloride during initiation and continuation of differentiation, had lower levels of neurofilament proteins than unexposed cells. 4. Preliminary data from parallel examinations of neurite outgrowth assessed by image analysis and neurofilament protein subunit levels assessed by ELISA support a correlation when neurofilament protein levels are decreased by sub-cytotoxic doses of mercuric chloride in SKNSH cells.

Use of neurite outgrowth as an in vitro method of assessing neurotoxicity.

This work shows that the neurotoxic excitatory amino acids beta-N-methylamino alanine, BMAA, and kainate, modulate neurite outgrowth; this was assessed by measuring the levels of two separate neurofilament proteins (68 kD and 160 kD), in a mouse neuroblastoma cell line, (NB41A3). BMAA has been proposed to be the exogenous excitotoxin in Guam disease or amyotrophic lateral sclerosis (ALS/parkinsonian/dementia; Guam ALS-PD). Kainate is a glutamate analogue which causes excitotoxic damage associated with excessive entry of calcium into neurons. The results show that at low doses (10(-9) to 10(-7) M) both BMAA and kainate decrease the concentration of the two neurofilament proteins. However at high doses (10(-6) to 10(-5) M) they cause an apparent accumulation of the neurofilament proteins; the effect is more marked with BMAA. These results support the continued development of an in vitro test for neurotoxicity based on neurite outgrowth.

In vitro tests of neurotoxicity.

This review presents some of the newer techniques in the rapidly advancing area of neurotoxicity testing in vitro. They are not described at length, and more details can be obtained from the cited references. In vitro testing offers the possibility of relatively inexpensive screening of large numbers of pharmaceutical compounds, formulations, and environmental substances. The level of sophistication attained in this field may soon allow much more accurate safety limits to be set, as specific mechanisms of neurotoxicity are elucidated.

l-BMAA and kainate-induced modulation of neurofilament concentrations as a measure of neurite outgrowth: Implications for an in vitro test of neurotoxicity.

This work shows that the neurotoxic excitatory amino acid analogues beta-N-methyl-l-amino-alanine (l-BMAA) and kainate, modulate neurite outgrowth. This was assessed indirectly by measuring the levels of two different neurofilament proteins (68 kDa and 160 kDa) in a mouse neuroblastoma cell line (NB41A3). The results of this study show that at low doses (10(-9)-10(-7)m) both l-BMAA and kainate decrease the concentration of the two neurofilament proteins but that at high doses (10(-6)-10(-5)m) they cause an apparent accumulation; the effect is more marked with l-BMAA. The sensitivity of the neurofilaments to low doses (10(-8)m) of the latter suggests that this test may be useful as a general in vitro test of neurotoxicity. In addition, these in vitro observations may shed light on the formation of the 'neurofibrillary tangles' commonly found in the brains of patients who have had Guam disease and/or Alzheimer's disease.

Biological properties of streptococcal cell-wall particles. 3. Dermonecrotic reaction to cell-wall mucopeptides.

Abdulla, Essa M. (University of North Carolina School of Medicine, Chapel Hill), and John H. Schwab. Biological properties of streptococcal cell-wall particles. III. Dermonecrotic reaction to cell-wall mucopeptides. J. Bacteriol. 91:374-383. 1966.-Intradermal injection of rabbits and guinea pigs with mucopeptide suspensions produced an acute necrotic lesion which reached maximal severity within 24 hr and gradually subsided with scar formation. Necrosis was evident within 4 hr after injection of 100 mug, and an indurated area (10 x 10 mm) was produced with as little as 5.0 mug. Mucopeptides from six bacterial strains were studied. Comparison of cell walls and derived mucopeptides showed that the acute necrotic lesion tended to be more severe as the residual polysaccharide was decreased. Hyperimmunization with mucopeptide reduced the acute reaction, with evidence of immunological specificity. Incubation with lysozyme also modified the reaction in relation to extent of digestion. Toxicity was related to particle size, since extended sonic vibration decreased activity. Histological sections showed intense accumulations of polymorphonuclear leukocytes, along with altered collagen. A chronic nodular lesion appeared about 7 days after injection of the intact cell-wall fragments. In contrast to the acute necrotic reaction, this lesion was rarely produced by the mucopeptide separated from polysaccharide.