Relative exercise intensity of long-distance marching (120 km in 4 days) in 153 subjects aged 69-87 years.

The aim of this study was to determine the relative exercise intensity (oxygen uptake during the march/maximal oxygen uptake, VO2march/VO2max) during a long-distance march in subjects or over 70 years of age. Secondly, the effect of hypertension, cardiovascular and pulmonary diseases on the relative exercise intensity was evaluated. One hundred and fifty-three subjects, 97 men aged 76.7 (4.6) years and 56 women aged 72.8 (3.6) years who completed the 1993 Nijmegen day long-distance march (30 km x day(-1) on 4 consecutive days) participated in the study. Oxygen uptake (VO2) during walking at different velocities (v) was measured in a subgroup of nine men and nine women, selected randomly from the population under study. With these data, regression equations describing the relationship between VO2 and v were made. VO2march was estimated with the obtained regression equations from an average of the v(march) measured in all participants. VO2max was determined using incremental cycle ergometry in all subjects. VO2march was 13.7 (1.8) ml x kg(-1) x min(-1) in men and 15.2 (1.3) ml x kg x min(-1) in women at a mean v of 5 km x h(-1) in both sexes. This corresponded to 52% of VO2max in men and 63% in women. In both sexes subjects with cardiovascular and/or pulmonary diseases walked at a slower v and thus lower VO2march compared to subjects without these diseases. Due to the lower VO2max in subjects with these diseases there was no difference in the relative exercise intensity between the groups. A multiple linear regression analysis showed that and not age on the prevalence of hypertension, cardiovascular and/or pulmonary that VO2max was the most important predictor of the variance in self-selected v(march). This study demonstrates that these active people aged over 70 years could maintain a high relative exercise intensity during endurance walking on 4 subsequent days. Furthermore, it shows that the relative exercise intensity of marching is within the range recommended for improving fitness and reducing the risk of cardiovascular diseases. Finally, these results demonstrate that VO2max has a more important influence on performance than does age or chronic diseases in active elderly people.

Dietary intakes of energy and water-soluble vitamins in different categories of aging.

The dietary intakes of energy and the vitamins thiamin, riboflavin, B6, and C were assessed in four groups of elderly people, using the same modified dietary history method. The groups consisted of female nursing home residents (n = 40), people at admission to a nursing home (n = 21), free-living elderly people with a sedentary life style (n = 120), and physically active free-living elderly people (n = 66). Mean energy intake varied from 6.5 +/- 1.2 Megajoule (MJ)/day (nursing home residents) to 8.8 +/- 2.2 MJ/day (physically very active persons) in females and from 8.8 +/- 2.5 MJ/day (admission to nursing home) to 10.1 +/- 2.3 MJ/day (physically very active persons) in males. Dietary intakes of the selected vitamins were below the minimum requirements in almost half of the nursing home residents. However, the relative contribution of the various food groups to the dietary intake of these vitamins was similar in the four groups of elderly people. Stimulation of physical activity to increase energy requirements and use of foods with a high nutrient density may result in an improvement of dietary adequacy.

Maximal oxygen uptake in 153 elderly Dutch people (69-87 years) who participated in the 1993 Nijmegen 4-day march.

There are no studies on oxygen uptake of groups of physically active subjects aged over 70. This study describes the maximal oxygen uptake (VO2max) of 153 elderly people who completed the Nijmegen annual 4-day march (at least 30 km.day-1) in 1993. A total of 97 men with a mean age of 76.7 (SD 4.6) and 56 women with a mean age of 72.8 (SD 3.6) years participated in the study. The VO2max was determined using incremental cycle ergometry; 91 men and 49 women completed a maximal exercise test. Criteria for maximal performance were respiratory exchange ratio equal to or greater than 1.00, vertilatory equivalent for oxygen equal to or greater than 30.00 and maximal heart rate equal to or greater than (beats.min-1) 210 minus age (years). Mean maximal power output was 148.2 (SD 27.2) W and 120.4 (SD 20.5) W, mean VO2max.body mass-1 was 26.8 (SD 4.9) ml.kg-1.min-1 and 24.6 (SD 4.7) ml.kg-1.min-1, mean maximal heart rate was 152 (SD 18), and 157 (SD 14) beats.min-1 in men and women respectively. The mean VO2max.body mass-1 was about 20% higher than reported in other studies on subjects over 70 years of age. Mean maximal heart rate was about 10 beats.min-1 higher than predicted from the equation 220-age. The negative effect of chronic disease on VO2max.body mass-1 was smaller than in a sedentary reference population. The mean decline in VO2max.body mass-1 with age was 0.46 and 0.38 ml.kg-1.min-1 per year in the men and women respectively, which is the same rate as found in younger subjects. It was concluded that regular exercise might substantially increase aerobic power in the physically active elderly, even when they have chronic disease, and that it is unlikely that there is an accelerated loss of aerobic power in physically active elderly people aged over 70 year.

Biosynthesis of the macrolide antibiotic tylosin. A preferred pathway from tylactone to tylosin.

The efficiencies of bioconversion of twenty-three potential intermediates in the biosynthesis of tylosin were determined with a mutant strain blocked only in tylactone biosynthesis. The results indicated that tylactone, the first intermediate excreted by Streptomyces fradiae, is converted to tylosin by a preferred sequence of reactions which include: (1) addition of mycaminose to the C-5 hydroxyl position of the lactone; (2) hydroxylation of the C-20 methyl group to a hydroxymethyl group; (3) dehydrogenation of the C-20 hydroxymethyl group to a formyl group; (4) hydroxylation of the C-23 methyl group to a hydroxymethyl; (5) addition of 6-deoxy-D-allose to the C-23 hydroxymethyl group; (6) addition of mycarose to the 4'-hydroxyl group of mycaminose; (7) addition of a methyl group to the 2"'-hydroxyl position of demethylmacrocin, and (8) addition of a methyl group to the 3"'-hydroxyl position of macrocin to produce tylosin. The intermediates which lacked both neutral sugars (mycarose and 6-deoxy-D-allose) were biologically unstable, and substantial quantities of these compounds were degraded during standard bioconversion experiments. However, the amount of one such intermediate (O-mycaminosyltylonolide) degraded was substantially reduced when low concentrations of the compound were used for bioconversion, and under these conditions, much higher efficiencies of bioconversion to tylosin were obtained. We have shown that a mutant blocked in hydroxylation of the C-20 methyl group is also blocked in the further dehydrogenation of the C-20 hydroxymethyl group to a formyl group, and have confirmed in in vitro studies that the 2"'-O-methylation of demethylmacrocin must proceed the 3"'-O-methylation of macrocin to produce tylosin.

Structure-activity studies among 16-membered macrolide antibiotics related to tylosin.

Although a substantial number of 16-membered macrolides related to tylosin have now been isolated and evaluated as antibiotics, none appeared to be superior to tylosin in treating bacterial or mycoplasmal infections caused by sensitive organisms. Nevertheless, this comparison of the antibiotic activity of 16-membered macrolides clearly indicates that novel antibiotics with potentially useful activity can be obtained from mutant strains which have been blocked at various steps in their biosynthesis of antimicrobial agents. The novel compounds thus produced may also be used as starting materials for additional chemical and microbiological modification. Furthermore, the mutant strains which produced these novel compounds should be useful recipients for interspecific genetic recombination by protoplast fusion or gene cloning to yield hybrid antibiotics. Even greater exploitation of these methods will be required in the continuing search for new antibiotics and improved methods for producing them.

Novel fermentation products from Streptomyces fradiae: X-ray crystal structure of 5-O-mycarosyltylactone and proof of the absolute configuration of tylosin.

5-O-Mycarosyltylactone has been isolated as a predominant factor from fermentation broths of a Streptomyces fradiae mutant. The relative configurations of mycarose and tylactone (protylonolide) have been determined by X-ray crystal structure analysis. Hydrolysis of 5-O-mycarosyltylactone yielded (-)-tylactone and L-(-)-mycarose. Taken together, these two experiments establish the absolute configuration of (-)-tylactone. Bioconversion of (-)-tylactone to tylosin by tyl G mutants of S. fradiae proves the absolute configuration of tylosin. Physicochemical data for tylactone and a unique component piece of tylactone are also reported.