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In his endeavor to promote a “rational medicine”, Leibniz endorsed the accomplishments of a group of physiologists, some of whom he had developed close relationship with during his sojourn in Italy (1688-1690). One of the main figures of that network, Bernardino Ramazzini is well known for having elaborated and implemented a model to analyze “epidemic constitutions”, which received Leibniz’s full approval. Our present task is to analyze the epistemic features of Ramazzini’s model and the assessment Leibniz made of it from both theoretical and practical viewpoints. Visant à promouvoir une « médecine rationnelle », Leibniz soutenait les réalisations d’un groupe de physiologistes, avec certains desquels il avait noué des relations étroites lors de son séjour en Italie (1688-1690). L’un des principaux participants de ce réseau, Bernardino Ramazzini, est reconnu pour avoir développé et implanté un modèle d’analyse des « constitutions épidémiques » qui reçut le plein aval de Leibniz. Nous entreprenons ici d’analyser les caractéristiques épistémologiques du modèle de Ramazzini et l’évaluation qu’en fit Leibniz, tant du point de vue théorique que pratique. In seinem Bestreben, eine „rationale Medizin“ zu fördern, unterstützte Leibniz die Errungenschaften einer Gruppe von Physiologen, zu denen er während seines Italienaufenthalts (1688-1690) zum Teil enge Beziehungen aufgebaut hatte. Eine der Hauptfiguren dieses Netzwerkes, Bernardino Ramazzini, wurde besonders dadurch bekannt, ein Modell zur Analyse „epidemischer Lagen“ entwickelt und implementiert zu haben, welches Leibniz’ volle Zustimmung erfuhr. Unser Ansatz in diesem Artikel besteht nun darin, die epistemischen Merkmale von Ramazzinis Modell zu analysieren sowie die Beurteilung, die Leibniz dazu sowohl aus theoretischer als auch aus praktischer Sicht getroffen hat.

In his endeavor to promote a “rational medicine”, Leibniz endorsed the accomplishments of a group of physiologists, some of whom he had developed close relationship with during his sojourn in Italy (1688-1690). One of the main figures of that network, Bernardino Ramazzini is well known for having elaborated and implemented a model to analyze “epidemic constitutions”, which received Leibniz’s full approval. Our present task is to analyze the epistemic features of Ramazzini’s model and the assessment Leibniz made of it from both theoretical and practical viewpoints. Visant à promouvoir une « médecine rationnelle », Leibniz soutenait les réalisations d’un groupe de physiologistes, avec certains desquels il avait noué des relations étroites lors de son séjour en Italie (1688-1690). L’un des principaux participants de ce réseau, Bernardino Ramazzini, est reconnu pour avoir développé et implanté un modèle d’analyse des « constitutions épidémiques » qui reçut le plein aval de Leibniz. Nous entreprenons ici d’analyser les caractéristiques épistémologiques du modèle de Ramazzini et l’évaluation qu’en fit Leibniz, tant du point de vue théorique que pratique. In seinem Bestreben, eine „rationale Medizin“ zu fördern, unterstützte Leibniz die Errungenschaften einer Gruppe von Physiologen, zu denen er während seines Italienaufenthalts (1688-1690) zum Teil enge Beziehungen aufgebaut hatte. Eine der Hauptfiguren dieses Netzwerkes, Bernardino Ramazzini, wurde besonders dadurch bekannt, ein Modell zur Analyse „epidemischer Lagen“ entwickelt und implementiert zu haben, welches Leibniz’ volle Zustimmung erfuhr. Unser Ansatz in diesem Artikel besteht nun darin, die epistemischen Merkmale von Ramazzinis Modell zu analysieren sowie die Beurteilung, die Leibniz dazu sowohl aus theoretischer als auch aus praktischer Sicht getroffen hat.

Impaired endothelium-mediated relaxation contributes to vasospasm and myocardial ischemia in patients with coronary artery disease. We hypothesized that cholesterol-lowering therapy with the 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor lovastatin could improve endothelium-mediated responses in patients with coronary atherosclerosis. In a randomized, double-blind, placebo-controlled trial, we studied coronary endothelial responses in 23 patients randomly assigned to either lovastatin (40 mg twice daily; 11 patients) or placebo (12 patients) plus a lipid-lowering diet (American Heart Association Step 1 diet). Patients were studied 12 days after randomization and again at 5 1/2 months. These patients had total cholesterol levels ranging from 160 to 300 mg per deciliter (4.1 to 7.8 mmol per liter) and were undergoing coronary angioplasty. At the initial and follow-up studies, patients received serial intracoronary infusions (in a coronary artery not undergoing angioplasty) of acetylcholine to assess endothelium-mediated vasodilatation. The responses of the coronary vessels were analyzed with quantitative angiography. The patients in the placebo and lovastatin groups had similar responses to acetylcholine at a mean of 12 days of therapy (expressed as the percentage of change in diameter in response to acetylcholine doses of 10(-9) M, 10(-8) M, 10(-7) M, and 10(-6) M). In the placebo group, the respective mean (+/-SE) changes were 1 +/- 2, 0 +/- 2, -2 +/- 4, and -19 +/- 4 percent; in the lovastatin group, they were -2 +/- 2, -4 +/- 4, -12 +/- 5, and -16 +/- 7 percent (P = 0.32). (Coronary-artery constriction is reflected by negative numbers.) The responses to acetylcholine in the placebo group after a mean of 5.5 months of therapy were -3 +/- 3, -1 +/- 2, -8 +/- 4, and -18 +/- 5 percent, respectively; there was significant improvement in the lovastatin group, which had responses of 3 +/- 3, 3 +/- 3, 0 +/- 2, and 0 +/-3 percent (P = 0.004)

Patients with coronary artery disease and abnormalities of serum lipid levels often have endothelial vasodilator dysfunction, which may contribute to ischemic cardiac events. Whether cholesterol-lowering or antioxidant therapy can restore endothelium-dependent coronary vasodilatation is unknown. We randomly assigned 49 patients (mean [+/-SD) serum cholesterol level, 209 +/- 33 mg per deciliter 5.40 +/- 0.85 mmol per liter]) to receive one of three treatments: an American Heart Association Step 1 diet (the diet group, 11 patients); lovastatin and cholestyramine (the low-density lipoprotein [LDL]-lowering group, 21 patients); or lovastatin and probucol (the LDL-lowering-antioxidant group, 17 patients). Endothelium-dependent coronary-artery vasomotion in response to an intracoronary infusion of acetylcholine (10(-8) to 10(-6) M) was assessed at base line and after one year of therapy. Vasoconstrictor responses to these doses of acetylcholine are considered to be abnormal. Treatment resulted in significant reductions in LDL cholesterol levels of 41 +/- 22 percent in the LDL-lowering-antioxidant group and 38 +/- 20 percent in the LDL-lowering group (P 0.001 vs. the diet group). The maximal changes in coronary-artery diameter with acetylcholine at base line and at follow-up were -19 and -2 percent, respectively, in the LDL-lowering-antioxidant group, -15 and -6 percent in the LDL-lowering group, and -14 and -19 percent in the diet group (P 0.01 for the LDL-lowering-antioxidant group vs. the diet group P

Transition metals such as iron, copper, manganese, and zinc are essential nutrients. The yeast Saccharomyces cerevisiae is an ideal organism for deciphering the mechanism and regulation of metal ion transport. Recent studies of yeast have shown that accumulation of any single metal ion is mediated by two or more substrate-specific transport systems. High-affinity systems are active in metal-limited cells, whereas low-affinity systems play the predominant roles when the substrate is more abundant. Metal ion uptake systems of cells are tightly controlled, and both transcriptional and posttranscriptional regulatory mechanisms have been identified. Most importantly, studies of S. cerevisiae have identified a large number of genes that function in metal ion transport and have illuminated the existence and importance of gene families that play related roles in these processes in mammals

The aim of our study was to investigate the changes in uric acid, leukocytes, plasma biochemical parameters and heart rate in metabolic endurance horses. Thirty Arabian endurance horses were physically examined and blood samples were collected pre and post-race. After physical examination, the successfully completed (n = 10) and metabolic disordered (n = 20) endurance horses were identified. Blood samples in heparinised vacutainer tubes were used for the determination of uric acid, triglycerides, creatine kinase, aspartate transaminase, packed cell volume, lactate, total protein and plasma protein. Blood samples in ethyl diaminotetra-acetic acid vacutainer tubes were used for the analysis of leukocytes. The age, body weight, heart rate, humidity and ambient temperature were also recorded. One way analysis of variance and pairwise correlations were used for the analysis. The mean values of uric acid, lactate, leukocytes, packed cell volume, plasma protein, total protein, heart rate, creatine kinase, aspartate transaminase and triglycerides were significantly different between the successful and matabolic disordered endurance horses. There were significant positive correlations between uric acid and lactate (r = 0.5196; P less than 0.0271), between uric acid and plasma protein (r = 0.6025; P less than 0.0175), between uric acid and packed cell volume (r = 0.5206; P less than 0.0268), between uric acid and triglycerides (r = 0.5541; P less than 0.0170) and between uric acid and heart rate (r = 0.5629; P less than 0.0150) in the metabolic disordered endurance horses. In conclusion, heart rate, triglycerides, blood lactate and packed cell volume were significantly associated with uric acid, a biomarker of oxidative stress. Therefore, uric acid could be used to evaluate performance and health status in endurance horses during training and endurance events.

The large docking protein IRS-1 is a major substrate for the insulin receptor and other tyrosine kinases. It plays a key role in eliciting many of insulin's actions, including binding and activation of phosphatidylinositol (PI) 3-kinase and the subsequent increase in glucose transport. Gene disruption of IRS-1 in mice is associated with an impaired insulin-stimulated glucose disposal in vivo and glucose transport in vitro, but the survival of the animals and residual insulin sensitivity is dependent on the presence of the alternative docking protein IRS-2. We examined the expression and function of IRS-1 and IRS-2 in adipocytes from healthy and diabetic individuals. Cells from subjects with non-insulin-dependent diabetes mellitus (NIDDM), but not with insulin-dependent diabetes mellitus, had an impaired insulin effect and a marked reduction (70 +/- 6%) in the expression of IRS-1 protein, whereas IRS-2 was unchanged. In normal cells, IRS-1 was the main docking protein for the binding and activation of insulin-stimulated PI 3-kinase; IRS-2 was also functional but required a higher insulin concentration for a similar binding and activation of PI 3-kinase. In contrast in NIDDM cells with a low IRS-1 content, IRS-2 became the main docking protein. These findings may provide important reasons for the insulin resistance in NIDDM

Despite its abundance in the earth's crust, iron deficiency is a serious health issue in many parts of the world. Although fundamental observations about iron metabolism and the significance of iron nutriture were first noted some time ago, the molecular mechanisms involved in iron metabolism are just now being defined

This paper describes the course and variation in the brain base arteries in fallow deer. The metrical features of the brain base arteries were determined with an image analysis system. The main sources of blood supply to the brain in fallow deer are internal carotid arteries; vertebral arteries rarely participate in blood supply. The brain base arteries in fallow deer show variation both in their course and in the way of descent of particular vessels. The highest variation was observed in the way of the opening of caudal cerebral arteries. The volume of the arterial circle of brain in fallow deer is similar to the volume of the basilar artery. Considering the correlation between specific parameters, it can be concluded that the volume of the basilar artery is highly correlated with the volume of the posterior part of the arterial circle of the brain, i.e., the volume of the caudal communicating arteries.