The microheterogeneities of thyroxine-binding globulin and alpha 1 protease inhibitor (alpha 1-antitrypsin) are interrelated.

Addition of 125I-thyroxine to serum allows autoradiography for thyroxine-binding globulin microheterogeneity to be carried out after isoelectric focusing has been performed to display (by protein stain) the heterogeneous bands of the alpha 1-antitrypsin (PI) system. Comparison of the protein stain for PI with the autoradiograph for thyroxine-binding globulin indicates that these two systems are interrelated with the major bands of the PI system corresponding to the bands on the autoradiograph. This correspondence holds for PI variants other than the common M type and in particular it holds for the deficient Z type in which the autoradiograph for thyroxine-binding globulin is strikingly different from normal. We conclude that the major cause of microheterogeneity of TBG is due to an association with the PI system under the conditions of isoelectric focusing as normally performed. Precipitation experiments with antisera to PI and TBG suggest that the complex between these biologically important globulins may occur under conditions other than isoelectric focusing, but further work will be needed to examine this possibility.

Endogenous opiates modulate release of growth hormone in response to electroacupuncture.

The effect of electroacupuncture on serum growth hormone levels was investigated in 5 normal subjects and in 10 patients with chronic musculoskeletal pain. Serum growth hormone did not change in the normal subjects but there was an approximate 5-fold increase in the chronic pain subjects. This effect was partially inhibited by prior administration of the opiate antagonist naloxone, suggesting that the rise in growth hormone was mediated via release of central nervous system opioids.

Fermentation--a traditional anti-diarrhoeal practice lost? The use of fermented foods in urban and rural Kenya.

Whereas modern dietary advice emphasizes the importance of freshly preparing food, many African communities leave food to ferment. Fermentation of cereals is a traditional method of reducing the microbial contamination of porridges. Beliefs and consumption patterns of fermented food were examined among mothers of children aged under five and health workers in a rural and urban community in Kenya. The majority (83%) of rural mothers reported that their families regularly consumed fermented food and over half (66%) gave their young children fermented food. In the urban area, fewer mothers (56%) reported that their families ate fermented food and only (40%) gave their children some kind of fermented food. Several reasons for the declining uses of fermented food were given including education by health workers that fermented foods were bad, declining production and availability, and substitution of traditional foods by commercial products such as soft drinks. Health educators need to consider that mothers may be missing out on a potentially useful means of preventing diarrhoea in their children.

An evaluation of a project to improve child nutrition in Tanzania.

Dietary bulk has been cited as an important factor influencing the nutritional intake of young children in developing countries. In Tanzania, a potential solution to the problem of dietary bulk in weaning foods, has been the promotion of 'kimea' or 'power flour' which is a cereal grain that has been sprouted (germinated). Flour made from this germinated grain contains amylase and has a thinning effect when added in small quantities to thick porridge thus allowing small children to consume a greater quantity of porridge. Alternatively, the effect of adding kimea to porridge can be seen as improving energy density because more flour can be added to the mixture whilst the same consistency is maintained. The frequency of use of kimea and mothers' perceptions about its value for young child feeding were evaluated in eight villages of Kyela district, Mbeya region, Tanzania. In four villages kimea had been promoted (project villages) and in the other four villages there had been no special programme of promotion (nonproject). A total of 131 mothers attending MCH clinics and 37 dispensary staff were interviewed. Forty two per cent of project village mothers and 18% of nonproject village mothers had heard about the use of kimea for young child feeding but only 45% of these mothers used kimea when preparing porridge for their young children. Reasons for low adoption rates are discussed. Thirty seven per cent of mothers who had heard about kimea were unable to describe correctly how to use it to thin porridge.(ABSTRACT TRUNCATED AT 250 WORDS)

Crystallographic studies of reduced bond inhibitors complexed with an aspartic proteinase.

To aid in the design of an effective inhibitor to human renin, it is essential to have a detailed knowledge of how this aspartic proteinase interacts with its substrate, angiotensinogen. Human renin shows a stringent specificity toward the Leu-Val bond in its natural substrate. The minimal length for an effective substrate has been characterised as an octapeptide sequence derived from the amino terminal portion of angiotensinogen (residues 6----13): His-Pro-Phe-His-Leu-Val-Ile-His (Leu-Val is the scissile bond). This suggests that renin has a fairly extensive active site cleft, as has been observed in homologous enzymes whose three-dimensional structures have been solved using x-ray diffraction methods. The homologous fungal aspartic proteinase, endothiapepsin, has been cocrystallised with human renin inhibitors of the type His-Pro-Phe-His-Leu-R-Val-Ile-His, where R indicates a reduced carbonyl analogue of the scissile peptide bond. The three-dimensional crystallographic structures of two complexes of endothiapepsin with an inhibitor have been solved. The details of inhibitor binding at the active site cleft of endothiapepsin are described. These data allow a rational approach to the design of novel renin inhibitors, through studies of these inhibitors in a three-dimensional model of human renin constructed in our laboratory.

High resolution X-ray analyses of renin inhibitor-aspartic proteinase complexes.

Inhibitors of the conversion of angiotensinogen to the vasoconstrictor angiotensin II have considerable value as antihypertensive agents. For example, captopril and enalapril are clinically useful as inhibitors of angiotensin-converting enzyme. This has encouraged intense activity in the development of inhibitors of kidney renin, which is a very specific aspartic proteinase catalysing the first and rate limiting step in the conversion of angiotensinogen to angiotensin II. The most effective inhibitors such as H-142 and L-363,564 have used non-hydrolysable analogues of the proposed transition state, and partial sequences of angiotensinogen (Table 1). H-142 is effective in lowering blood pressure in humans but has no significant effect on other aspartic proteinases such as pepsin in the human body (Table 1). At present there are no crystal structures available for human or mouse renins although three-dimensional models demonstrate close structural similarity to other spartic proteinases. We have therefore determined by X-ray analysis the three-dimensional structures of H-142 and L-363,564 complexed with the aspartic proteinase endothiapepsin, which binds these inhibitors with affinities not greatly different from those measured against human renin (Table 1). The structures of these complexes and of that between endothiapepsin and the general aspartic proteinase inhibitor, H-256 (Table 1) define the common hydrogen bonding schemes that allow subtle differences in side-chain orientations and in the positions of the transition state analogues with respect to the active-site aspartates.