Multidentate 2-pyridyl-phosphine ligands - towards ligand tuning and chirality.

In the current work a range of multidentate pyridyl-phosphine ligands are synthesised with tuneable electronic and steric character, through the incorporation of a variety of alcohols into (amino)pyridyl-phosphine frameworks. The stoichiometric reactions of compounds of the type (R2N)xP(2-py)3-x (2-py = 2-pyridyl) with alkyl as well as aryl alcohols result in the formation of (alkoxy)pyridyl-phosphines (RO)xP(2-py)3-x (R = Me, 2-Bu, Ph). This synthetic procedure also allows the introduction of enantiomerically pure alcohols, like (R)-(-)-2-BuOH and (S)-(+)-2-BuOH, and as such provides a very convenient two-step route to chiral multidentate pyridyl-phosphine ligand sets. Using the bis-amino-phosphine (Et2N)2P(2-py), the stepwise introduction of alcohols enables the synthesis of racemic alkoxy-amino-phosphines (R2N)(RO)P(2-py), as well as alkoxy-phosphines (RO)2P(2-py) and therefore offers easy access to a library of different pyridyl-phosphine ligands. Coordination studies of the (amino)pyridyl-phosphines and (alkoxy)pyridyl-phosphines with copper(i) reveal that ligands with two N donor atoms form dimeric arrangements, while (PhO)2P(2-py), in-corporating only one N donor atom, shows completely different coordination behaviour.

The influence of apolipoprotein E polymorphism on plasma concentrations of apolipoprotein B and A-I during the first year of life.

Apolipoprotein (apo)E polymorphism has been shown to be associated with different serum levels of cholesterol, apoB, and apoE. In clarifying the degree of influence of the apoE isoforms, investigations in an early stage of life are useful. The aim of the study was to investigate the plasma levels of apoB and apoA-I as structural proteins of low and high density lipoproteins, in relation to apoE phenotypes during the first year of life. Conclusions about the relationship between apoE phenotype and the development of the lipoprotein patterns can be drawn. The concentrations of apoB and apoA-I in capillary plasma as well as the apoE phenotype were estimated in 199 newborns (7 days old) and in follow-up investigations of a subgroup of 45 at 1, 4, 12, 24, and 52 weeks. The phenotype frequencies were as follows: 70% apoE 3/3, 16% apoE 3/4, 10% apoE 2/3, 2.5% apoE 2/2, and 1.5% apoE 4/2. The plasma concentrations of apoB and apoA-I in the newborns (7 days old) averaged 55% of the adult value and increased toward the end of the first year of life up to approximately 85%. The course of the plasma concentrations of apoB and apoA-I in relation to the apoE phenotype showed that, beginning at 24 weeks, the apoB levels were significantly lower for the phenotype E 2/2 and in tendency also for the phenotype E 2/3 in comparison with E 3/3. At the end of the first year of life, the apoB levels in infants with apoE phenotype 2/2 increased only by 50% and yielded 0.59 g/L.(ABSTRACT TRUNCATED AT 250 WORDS)

[Lipoproteins as coronary risk or non-risk indicators in elderly people]. / Lipoproteine als koronare Risiko- oder Antirisikoindikatoren bei alten Menschen.

Lipid and apolipoprotein (apo) levels were investigated in 98 (68 female, 30 male) subjects older than 85 years and 86 (59 female, 27 male) subjects aged 65-75 years. The mean cholesterol level of the long-lived persons who were free from overt degenerative arterial disease was 5.2 mmol/l and ranged markedly below the mean level of the population. Comparing both age groups, the triglyceride level of the high-age subjects was at 0.3 mmol/l, significantly lower; HDL-cholesterol and apo A-I at 0.15 mmol/l or 0.3 g/l were higher. Cholesterol, LDL-cholesterol, and apo B only tended to be lower in the higher age. Subjects suffering from degenerative arterial disease (circulatory disturbance, hypertonia, diabetes mellitus), especially the long-lived group, had a more marked unfavorable lipoprotein profile. Subjects over 85 years (13%) had markedly less disturbance in lipoprotein metabolism of high atherogenic potency (hyper-beta-, hypo-alpha-lipoproteinemia) than did subjects 65-75 years old (23%). Hypertriglyceridemia is with 38% or rather 21% very frequent and seems to be of less atherogenic potency. Hyper-alpha-lipoproteinemia as anti-risk factor for coronary heart diseases was established more frequently in the long-lived group with 13% in comparison to 3.5% in those 65-75 years of age.

[Diagnostic value of lipids and apolipoproteins for assessment of atherogenic risk]. / Zur diagnostischen Wertigkeit von Lipiden und Apolipoproteinen für die Beschreibung des atherogenen Risikos.

In 242 coronarographed male patients (51.7 +/- 7.6 years) with 0-, 1-, 2- or 3-vessel diseases as well as a clinically healthy control group (n = 68, 50.6 +/- 8.5 years) the lipoprotein pattern was investigated: total-, LDL-, HDL-, HDL2-, HDL3-, beta-, pre-beta-alpha-cholesterol, triglycerides, apolipoproteins (Apo) A-I, A-II, B, (A-I)HDL, Lp(a). With regard to the separation of patients with diseases of the coronary vessels and healthy persons out of the individual parameters Apo A-I (turbidimetrically), HDL3 and HDL cholesterol had the greatest significance (maximal diagnostic efficiency: 0.81, 0.76, 0.72). For the assessment of the severity of the change of the coronary vessels the quotient total/HDL cholesterol was most suitable (efficiency: 0.67). Differences in the diagnostic significance were established in the determination of a parameter by means of different methods. The intake of beta-receptor blockers increased the concentration of the triglycerides and pre-beta-cholesterol.

[An eicosapentaenoic acid-rich diet in relation to a reducing diet and physical training]. / Eikosapentaensäurereiche Diät in Verbindung mit Reduktionskost und physischem Training.

The effect of a mackerel diet alone or in connection with reducing diet and physical training has been tested during 4 weeks in 49 male patients with cardiovascular diseases undergoing a cure and in 45 males with healthy metabolism. 1st group: 15 persons with healthy metabolism, 240 g/die supplementary mackerel diet, no physical training; 2nd group: 16 cure patients with reducing diet (5,000 kJ/d), no mackerel diet, no physical training; 3rd group: 14 cure patients with reducing diet and a proportion of mackerels of 125 g/d, no physical training; 4th group: 19 cure patients with reducing diet and mackerel diet 125 g/d as well as daily swimming training (20 to 30 min). The decrease of beta-C and Apo B was most distinct in groups 3 and 4 and lay between 21 and 35%. The combination reducing diet with proportion of mackerels proved to be most effectively for the decrease of the atherogenic LDL and was superior to the monotherapies. A significant increase of the HDL (measured in alpha-C and Apo A) took place only in group 4 with simultaneous performance of physical training, alpha-C increased by 31 and Apo A by 8%.

[Lipids and apolipoproteins in relation to the degree of coronary sclerosis]. / Lipide und Apolipoproteine in Abhängigkeit vom Grad der Koronarsklerose.

86 male patients with 0-, 1-, 2- or 3 vascular disease who underwent coronary angiography as well as a control group were examined with regard to their lipoprotein constellation: total (TC-), LDL-, HDL-, beta- and alpha-cholesterol (C); triglycerides; apolipoproteins A, AI and B. Significant differences between the mean values of the control group and the patients with coronary disease were found for the groups with 2- and 3-vascular disease for the following parameters: TC, HDLC, TC/HDLC, LDLC/HDLC, alpha-C, TC/alpha-C, beta-C, alpha-C. The quotients TC/HDLC and TC/alpha-C most closely correlate with the degree of the coronary sclerosis. In the apolipoproteins A, B and the index Apo B/A the patients with coronary disease of the groups 0-3 possess equally lowered or increased serum levels and number values, respectively, in comparison to the control group. The apolipoproteins do not show any relationship to the degree of severity of the coronary sclerosis. By means of the parameters combination (Apo A + TC/alpha-C) with a diagnostic sensitiveness of 0.83 and a specificity of 0.87 a coordination coronary disease--healthy could be performed. The classification according to risks should then be performed by means of a cholesterol quotient (TC/alpha-C or TC/HDLC).

[Long-term oil therapy in elderly patients with peripheral arterial occlusive disease]. / Ollangzeittherapie bei älteren Patienten mit peripherer arterieller Verschlusskrankheit.

3-years dietetic application of polyenic fatty acids in 41 patients with peripheral arterial occlusion disease evoked significantly alterations of total and LDL-cholesterol level and of the serum fatty acid spectrum. These alterations must be valued as "antiatherogenic" although the HDL-cholesterol was not influenced. Linolenic acid enriched linseed oil seems to be more efficient than linolenic acid enriched sun flowers oil.

[Direct quantitative determination of LDL cholesterol and HDL cholesterol using agarose gel electrophoresis]. / Zur direkten quantitativen Bestimmung von LDL- und HDL-Cholesterol mittels Agarosegelelektrophorese.

The direct and quantitative determination of the main classes of the serum lipoproteins by means of a simple and reliable method is an urgent necessity for answering the numerous clinical questions. By precipitation of polyanions of the lipoproteins after electrophoretic separation in the agarosegel it is possible to determine sufficiently exactly and reproducibly their concentration without ultracentrifugation. For HDL- and LDL-cholesterol (beta-und alpha-lipoprotein cholesterol) a serial precision of 3 and 4%, respectively, and day,/day of 4 and 6%, respectively, was found. The methodology is described in detail and the problems of the establishment of the reference curves are particularly entered. In addition to this the determination of LDL- and HDL-cholesterol and beta- and alpha-lipoprotein cholesterol, respectively, was performed in sera of patients according to 3 and 4 variants, respectively, and these results were correlated with the densitometer surfaces of the beta- and alpha-lipoproteins. The correlation coefficients were between 0.94 and 0.99.

[Change in the concentration of lipoprotein parameters following swimming training in health resort patients]. / Die Veränderung der Konzentration von Lipoproteinparametern nach Schwimmtraining bei Kurpatienten.

On 197 patients who were admitted to a sanatorium for the purpose of a heart and circulation cure the influence of a daily swimming training, 20-30 minutes 6 times a week with intensities of about 50-60% VO2 max, on the lipid and lipoprotein spectre, respectively was investigated. In the whole group of patients HDL-cholesterol (HDL-C) did not change. In patients with increased risk n = 40 (initial HDL-C: lower than 0.91 mmol/l) HDL-C significantly increased in the course of the cure. In group I n = 157 (without increase of HDL-C) as well as in group II n = 40 (with increase of HDL-C) LDL-cholesterol significantly decreased. The lipid index after Klimov and the quotient LDL-C/HDL-C decreased at the end of the treatment and they showed the most distinct change in group II. The separation of the lipoproteins by disc electrophoresis and the establishment of their percental distribution resulted in a decrease of the beta-lipoproteins and an increase of the alpha-lipoproteins for the two groups (I and II). The quotient beta-lipoprotein/alpha-lipoprotein also significantly decreased in the two groups. For the apolipoproteins A and B in group II no statistically ascertained changes of concentration were established. At the end of the treatment in group I apolipoprotein B highly significantly decreased, while apolipoprotein A did not change. In accordance with the cholesterol index also the reduction of the apolipoprotein index apo B/A was significant.(ABSTRACT TRUNCATED AT 250 WORDS)

[Modification of lipoprotein parameters in the initial phase of physical exercise in middle-aged cardiovascular patients]. / Zur Beeinflussung von Lipoproteinparametern in der Anfangsphase körperlichen Trainings bei Herz-Kreislaufpatienten mittleren Alters.

The effect of a daily swimming-training of 20--30 minutes for four weeks (six times a week with intensities of 50--60% VO2 max) on the lipid and lipoprotein spectrum, respectively, was investigated in 40 elderly male patients in a heart-circulatory cure (on an average 48,7 years old). At the beginning all patients had an HDL-cholesterol level lower than 0.91 mmol/l which rose significantly towards the end of the cure. LDL-cholesterol dropped significantly. The lipid index by Klimov and the quotient LDL-C/HDL-C descended at the end cure. The separation of the lipoproteine (Lp) by discelectrophoresis and the evaluation of their percentage showed a reduction of the beta-Lp and an increase of the alpha-Lp coinciding with the lipid-data. The quotient beta-Lp/alpha-Lp also decreased significantly. In the apolipoproteins A and B statistically ensured alterations in concentrations could not be determined. The disproportional changes of the lipid- and protein-portions were referred to in the discussion. According to our results the lipid-portion of the Lp (especially LDL- and HDL-cholesterol) indicated the changes more sensitively than the apolipoproteins A and B. The data demonstrate the possibility of raising the HDL-cholesterol-level of elderly men by physical training.

[Clinical significance of arteriosclerosis indices of lipid metabolism and age dependence]. / Klinische Bedeutung von Arteriosklerose-Indizes des Lipidstoffwechsels und Altersabhängigkeit.

Age, arteriosclerosis indices, HDL-cholesterol, hyperlipoproteinemia, lipoproteins In 193 normal persons, 86 patients with arteriosclerosis obliterans of the lower extremities, 170 HLP patients, 87 adiposity patients and 22 chronic alcoholics were determined the arteriosclerosis indices (formula; see text) The arteriosclerosis indices increase in healthy males from the age of 30 and healthy females from the age of 45. In case of peripheral arterial occlusion HLP and adiposity the arteriosclerosis indices are elevated and give diagnostic and prognostic hints as to increased arteriosclerotic risk for these diseases.

[Effect of physical conditioning on fat metabolism--examinations performed on middle-aged long distance runners]. / Einfluss physischer Konditionierung auf den Fettstoffwechsel--Untersuchungen an Langstreckenläufern im mittleren Lebensalter.

The lipid and lipoprotein metabolism was examined in fortyfour long distance runners and in a cohort of sixty-five untrained subjects as well as in thirty-two runners before and immediately after 38- and 40-kilometer runs respectively. There was observed a significant increase of high density lipoprotein cholesterol in the runners, whereas very low density lipoprotein cholesterol showed a marked decrease. The low density lipoprotein cholesterol/high density lipoprotein cholesterol quotient (arteriosclerotic quotient) was found to be markedly reduced in the runners. There was no statistical difference in total cholesterol and low density lipoprotein cholesterol between long distance runners following sports as a pastime and untrained subjects. Post-heparin lipase and the rate of lipolysis were markedly increased in subjects following sports as a recreation. Parallelisms were observable between lipid values and lipoprotein percentages determined by disk electrophoresis. The proportions of alpha-lipoprotein, beta-lipoprotein, and pre-beta-lipoprotein in runners were found to be increased, unchanged, and reduced respectively. The increase in alpha-lipoprotein was accompanied by a shift in the spectrum of alpha-lipoprotein subfractions. After the 38- and 40-kilometer run, respectively, there were determined an increase in TGL and very low density lipoprotein cholesterol and a decrease in both post-heparin lipase and rate of lipolysis. The other cholesterol parameters showed no significant variations after straining. Whereas Apo A, like high density lipoprotein cholesterol, did not change during running, Apo B showed a marked increase. The results were discussed with due consideration of those reported by other authors.

[Modification of special blood-level forming lipid metabolites by long-distance running in men 20-60 years of age]. / Beeinflussung spezieller blutspiegelbildender Lipidmetaboliten bei Männern im Alter von 20-60 Jahren durch Langstreckenlauf.

The lipid metabolism and the lipoprotein metabolism was examined in 44 long-distance runners (people's athletics) and a group of 65 untrained persons as well as in 32 runners before and immediately after a 38-km and a 40-km-run, respectively. High density lipoprotein cholesterol (HDLC) was significantly increased in the runners, whereas very low density lipoprotein cholesterol (VLDLC) was found decreased. The quotient LDLC/HDLC (quotient of arteriosclerosis) is clearly decreased in runners. Total cholesterol and low density lipoprotein cholesterol (LDLC) of runners (people's athletics) and untrained persons were statistically not different. The post-heparin-lipase (pHL) and the rate of lipolysis pHL appeared clearly increased in persons participating in people's athletics. There were parallelities between the lipid values and the disc-electrophoretically established percental proportions of lipoproteins. The proportion of alpha-lipoprotein (Lp) of the runners was increased, the beta-Lp unchanged and the pre-beta-Lp decreased. The increase of the alpha-Lp was concomitant with a shift of the spectre of the alpha-Lp-subfractions. After the running (38 and 40 km) the triglycerides and VLDLC were increased, the pHL-activity and the rate of lipolysis pHL were decreased. In the other cholesterol parameters no significant shifts appeared after load. While Apo A does not change under the influence of the running, like HDLC, Apo B clearly increased. The results were discussed, taking into consideration the results of other authors.