Production of angiotensin-I-converting enzyme inhibitory peptides from ß-lactoglobulin- and casein-derived peptides: an integrative approach.

Angiotensin I-converting enzyme (ACE) inhibition is one of the mechanisms by which reduction in blood pressure is exerted. Whey proteins are a rich source of ACE inhibitory peptides and have shown a blood pressure reduction effect i.e. antihypertensive activity. The aim of this work was to develop a simplified process using a combination of adsorption and microfiltration steps for the production of hydrolysates from whey with high ACE inhibitory activity and potency; the latter was measured as the IC50, which is the peptide concentration required to reduce ACE activity by half. This process integrates the selective separation of ß-lactoglobulin- and casein-derived peptides (CDP) from rennet whey and their hydrolysis, which results in partially pure, less complex hydrolysates with high bioactive potency. Hydrolysis was carried out with protease N "Amano" in a thermostatically controlled membrane reactor operated in a batch mode. By applying the integrative approach it was possible to produce from the same feedstock two different hydrolysates that exhibited high ACE inhibition. One hydrolysate was mainly composed of casein-derived peptides with IC50=285 µg/mL. In this hydrolysate we identified the well-known potent ACE-inhibitor and antihypertensive tripeptide Ile-Pro-Pro (IPP) and another novel octapeptide Gln-Asp-Lys-Thr-Glu-Ile-Pro-Thr (QDKTEIPT). The second hydrolysate was mainly composed of ß-lactoglobulin derived peptides with IC50=28 µg/mL. This hydrolysate contained a tetrapeptide (Ile-Ile-Ala-Glu) IIAE as one of the two major peptides. A further advantage to this process is that enzyme activity was substantially increased as enzyme product inhibition was reduced.

Vitamin A deficiency: a serious threat in Dodota district in central Ethiopia.

A total of 147 children, aged from six months to six years were examined for signs of xerophthalmia in a village in Arsi zone of Ethiopia. Night blindness, Bitot's spots, corneal ulceration and corneal scars were observed in 17.0%, 26.5%, 2.7% and 0.7% of the children respectively. The concentration of serum retinol was measured in all children with xerophthalmia and every twentieth of the remaining children. Serum retinol levels were in the deficient range (< 0.35 mumol/I) in 31.9% and low (0.35-0.69 mumol/I) in 48.9% of the children. There was a higher prevalence of stunting (24.5%) than wasting (18.4%) with an additional 10.2% of children being both stunted and wasted. The prevalence of diarrhoea was twice as high in children with xerophthalmia than children without (p < 0.01).

PIP: Vitamin A deficiency is a major public health problem in Ethiopia. Clinical examination of 147 children 6 months-6 years of age from Ouda Dodota village in Ethiopia's Arsi zone revealed that 40.6% of boys and 30.8% of girls had at least 1 recognizable symptom of vitamin A deficiency. As a result of drought, consumption of beta carotene is very low in this grain-farming zone. Only 13% of children with clinical manifestations of vitamin A deficiency were under 3 years of age, presumably reflecting the protective effect of prolonged breast feeding. Night blindness, Bitit's spots, corneal ulceration, and corneal scars were present in 17.0%, 26.5%, 2.7%, and 0.7% of children, respectively. The concentration of serum retinol was measured in all children with xerophthalmia and 1 in every 20 remaining children. These levels were deficient (0.35 mcgmol/l) in 31.9% and low (0.35-0.69 mcgmol/l) in 48.9% of children. There was no association between retinol levels and clinical signs of vitamin A deficiency. 18.4% of children were wasted, 24.5% were stunted, and 10.2% were both wasted and stunted. Again, there was no significant association with signs of vitamin A deficiency. Finally, the risk of diarrhea was 2.17 times higher among children with xerophthalmia, confirming observations that repeated, prolonged diarrhea is a risk factor for vitamin A deficiency.

Interrelationship between vitamin A, iodine and iron status in schoolchildren in Shoa Region, central Ethiopia.

A total of 14,740 schoolchildren in seven provinces of Shoa Administrative Region in Central Ethiopia were surveyed for the prevalence of goitre, xerophthalmia and anaemia. Haemoglobin and packed cell volume were assessed in 966 children in one province while an in-depth study was conducted on 344 children in the same province and two others. Goitre, xerophthalmia (Bitot's spots) and clinical anaemia were observed in 34.2, 0.91 and 18.6% respectively of the children. Most biochemical variables were within the normal range while those of haemoglobin (Hb), mean corpuscular Hb concentration (MCHC) and urinary I excretion were lower, and mean corpuscular volume, mean corpuscular Hb (MCH), and immunoglobulins G and M were higher. Hb was strongly correlated with retinol, ferritin, MCHC, MCH, packed cell volume and erythrocyte count while retinol formed a triad with transthyretin (TTR) and retinol-binding protein (RBP) which were all correlated with one another. Total and free thyroxin and total and free triiodothyronine were positively correlated as were the concentrations of the total and free hormones. Thyrotropin (TSH) was negatively correlated with total and free thyroxin and positively correlated with free triiodothyronine. Thyroxin and triiodothyronine in both free and combined forms were all correlated with thyroxin-binding globulin which in turn was negatively correlated with the triad retinol, RBP and TTR. The triad was also negatively correlated with C-reactive protein. Urinary I excretion was positively associated with total thyroxin and negatively associated with TSH. The anaemia found was not nutritional in origin but due to the effect of infestation with intestinal parasites and malaria.

Severe vitamin A deficiency in a rural village in the Hararge region of Ethiopia.

A total of 240 children were examined for vitamin A deficiency in a village in Hararge region of Ethiopia. Night blindness, Bitot's spots, corneal xerosis, corneal ulceration and corneal scars were observed in 69, 16, 2, 15 and 14 children, respectively, based on the most severe eye signs. Blood was collected from 76 children with eye signs and 9 other children selected at random. The concentration of retinol (vitamin A) in serum was < 0.35 mumol/l in 30.2% of children and the median serum retinol-binding protein, iron, transferrin saturation and ferritin levels were low while the parameters of iodine status, total triiodothyronine, total thyroxine and thyrotropin, were all within the normal range. Levels of IgG and IgM were elevated in 78.8% and 82.4% children, respectively, while C-reactive protein levels were elevated in 42.4% of children. There was a higher prevalence of wasting (33%) than stunting (10%) with an additional 8% of children being both stunted and wasted. In the 2 years prior to the study, there were 74 deaths of which 17 were reported to be associated with ruptured corneas. The community had been dependent on relief food aid for the previous 6 years.

PIP: In late 1988 in Ethiopia, a physician and a nutritionist examined 240 registered children in the village of Melkaye (Farmers' Association No. 34) in Darolobo District of Habro Province for vitamin A deficiency. These children had been dependent on food aid because of consistent drought and crop failures since, at least, 1982. The food aid, which was the main food source, included food deficient in vitamin A and beta-carotene: wheat flour, vegetable oil, butter-oil, and beans. 53.2% of the boys and 43.1% of the girls had at least 1 sign of vitamin A deficiency, especially night blindness, an early manifestation of vitamin A deficiency. 28.8% of all children had night blindness without signs of xerophthalmia compared with the WHO cut-off point of 1%. (The cut-off point is used to determine the public health significance of vitamin A deficiency.) 6.7% had Bitot's spots compared with a cut-off point of 0.5%. 7.1% had corneal xerosis/ulceration compared with a cut-off point of .01%. 5.8% had corneal scars compared with a cut-off point of .05%. 30.2% had a serum retinol level less than .35 mcmol/l compared with a cut-off point of 5%. 17 of 70 children (24.3%) who had died in the last 2 years had ruptured or damaged eye(s). The median levels of serum retinol-binding protein, iron, transferrin saturation, and ferritin were lower than normal levels. On the other hand, parameters of iodine status, total triiodothyronine, and total thyroxine and thyrotropin were all normal. 78.8% and 82.4% of the children experienced high levels of IgG and IgM, respectively. 42.4% had high C-reactive protein levels. Wasting was more common than stunting (33% vs. 10%). 8% suffered from both stunting and wasting. The severity of xerophthalmia was perhaps the most severe ever recorded and prompted health workers to distribute vitamin A capsules to all children in Melkaye and nearby villages.