Essential drugs policy in Bolivia

Since the publication of the WHO list of essential drugs 10years ago, there has been a growing volume of literature onthe topic. This paper on the experience of essential drugs policyin Bolivia is written in the belief that reports on attemptsto implement drugs policies in individual countries are oneof the most instructive sources of information. Coming intopower in 1982, the democratic Bolivian government set up a centrally-controlledagency to be responsible for the procurement and distributionof drugs, with a view to making basic drugs available throughoutthe country. Despite limited technical and institutional resources,the policy proved administratively and organizationally practical.However problems arose at the political level both because theinterests of the industry and pharmacists were threatened andbecause there was disagreement within the government as to whetherdrugs should be seen as commercial goods or health aids. Theagency set up to implement the drug policy was abolished withintwo months of the neo-liberal government resuming power in 1985- emphasizing the symbolic importance of the agency in the overallhealth policy. Only when those concerned with drug policy atan international level concentrate on the political and culturalobstacles to essential drugs policies, and stop giving priorityto the practical issues of procurement and distribution, willtheir policies gain the credibility which is a prerequisitefor success.     

Conformation and dynamics of the chemotactic peptide formyl-L-methionyl-L-leucyl-L-phenylalanine in solution

Several conformational and dynamic features of the chemotactic peptide formyl-L-methionyl-L-leucyl-L-phenylalanine in solution have been delineated by investigations of NMR and IR spectroscopic parameters. Both 1D and 2D NMR experiments have been performed for detection of scalar and dipolar proton-proton connectivities, whereas ¹³C and ¹H relaxation parameters have been interpreted in terms of molecular dynamics. The main conformation appeared to be unfolded with the three hydrophobic side chains extending in divergent directions with respect to the backbone. The existence of relatively weak inter-molecular hydrogen bonds was demonstrated, involving the formamide end group, with increase in the hydrophobicity of the external surface.     

Preparation and properties of des-Tyr98 and des-Arg97-Tyr98 acylphosphatase (muscular isoenzyme)

Previous NMR reports indicated that Tyr⁹⁸, the C-terminal residue of the muscular form of acylphosphatase, is likely to be part of the enzyme's active site. In addition, there is evidence that an arginine residue participates to the catalyzed reaction, possibly as phosphate binding site. Among all Arg residues present in the muscular forms of acylphosphatase, four, i.e. Arg²³, Arg⁷⁴, Arg⁷⁷, and Arg⁹⁷, appear to be conserved in all species checked thus far. We prepared the des-Tyr⁹⁸ and des-Arg⁹⁷-Tyr⁹⁸ derivatives of the native acylphosphatase to investigate the properties of both modified enzymes. The enzyme lacking Tyr⁹⁸ was found to be catalytically less effective than the native one, whereas the des-Arg⁹⁷-Tyr⁹⁸ acylphosphatase was completely inactive. This evidence suggests that Arg⁹⁷ participates directly to the active site catalytic mechanism. Fluorescence and CD spectra revealed that the latter enzyme could have been undergone some conformational change that could account for the loss of activity; on the other hand, the one-dimensional NMR spectra of either native and des-Arg⁹⁷-Tyr⁹⁸ enzymes were strictly similar, thus demonstrating that the removal of the two C-terminal residues does not markedly affect the fold of the enzyme. The results reported are proof of a critical contribution of Arg⁹⁷ to the acylphosphatase active site; however, we cannot exclude that the function of this residue is merely to stabilize the active site conformation and dynamics.     

Influence of Different Protein Intake on Renal Growth in Young Rats

ABSTRACT. We have examined the effect of high protein intake on kidney growth and function in growing rats. The rats were kept on an isocaloric diet containing 12%, 21% and 50% protein, from weaning (16 days) until the time of investigation (18, 20, 24,40 or 80 days). There was no significant difference between the 12% and 21% protein groups in any of the parameters studied. 50% protein increased body weight (BW) and kidney weight (KW). The increase in kidney weight was already evident after 2 days and exeeded the increase in body weight in all age groups. At 24 days renal cortical DNA and the protein/DNA ratio were significantly increased in the 50% protein group. At 40 days the cortical DNA content, but not the protein/DNA ratio, was significantly increased in the 50% group. The glomerular filtration rate (GFR) was studied at 40 days. Total GFR as well as GFR/BW was significantly higher in the 50% group than in the 21% group. In one protocol the diet was discontinued at age 40 days and the rats were studied at age 80 days. In these rats all parameters of renal size and function were the same as in the rats that had had a normal (21%) protein intake from weaning. We conclude that in young rats high protein intake reversibly increases GFR out of proportion to BW and selectively and reversibly stimulates kidney growth by stimulating cell proliferation.