Can peripheral arterial disease be early screened for in a podiatric setting? A preliminary study in a cohort of asymptomatic adults.

BACKGROUND: Peripheral arterial disease (PAD) is a strong marker of cardiovascular disease but remains an under-diagnosed problem. Moreover, PAD frequently leads to foot problems requiring particular care and surveillance. AIM: The aims of this study were (1) to determine the prevalence of undiagnosed PAD in a cohort of asymptomatic subjects referred to a podiatric clinic and (2) to evaluate whether a four-item form assessing medical history for the presence of cardiovascular risk factors could identify subjects at high risk for asymptomatic PAD. PATIENTS AND METHODS: This study included 717 consecutive subjects (121 males, age 50.9±13.9 y) referring to a podiatric clinic who were asymptomatic for PAD and free of cardiovascular disease. The ankle brachial index (ABI) was measured in all subjects. Each subject also completed a self-administered form to identify cardiovascular risk factors. RESULTS: Among the entire cohort, the prevalence of PAD was 8.3% in males and 1.2% in females. Three subgroups were identified according to the number of risk factors reported (no risk factors, one risk factor, and two or more risk factors), and the prevalence of PAD differed between each subgroup (0.2%, 3.2%, and 18.9%, respectively; p < 0.001). CONCLUSIONS: In an unselected cohort of subjects referring to a podiatric clinic, who were asymptomatic for PAD and free from cardiovascular diseases, a remarkable prevalence of PAD was found among subjects reporting a minimum of two cardiovascular risk factors. In a podiatric setting, screening with a self-administered form for the presence of cardiovascular risk factors might lead to an early diagnosis of PAD.

Phenotypic expression of familial hypobetalipoproteinemia in three kindreds with mutations of apolipoprotein B gene.

We report the clinical phenotype in three kindreds with familial heterozygous hypobetalipoproteinemia (FHBL) carrying novel truncated apolipoprotein Bs (apoBs) of different sizes (apoB-8.15, apoB-33.4 and apoB-75.7). In D.A. kindred, we found three carriers of a C-deletion in exon 10 leading to the synthesis of apoB-8.15 not detectable in plasma. They showed steatorrhea and fatty liver. In N.L. kindred, the proband is heterozygous for a nonsense mutation in exon 26, leading to the formation of apoB-33.4. He had premature cerebrovascular disease and fatty liver; two apoB-33.4 carriers in this kindred showed only fatty liver. In B.E. kindred, the proband is heterozygous for a T-deletion in exon 26, which converts tyrosine at codon 3435 into a stop codon, resulting in apoB-75.7. The proband, a heavy alcohol drinker, had steatohepatitis, whereas his teetotaller daughter, an apoB-75.7 carrier, had no detectable fatty liver. This study suggests that: i) fatty liver invariably develops in FHBL carriers of short and medium-size truncated apoBs (< apoB-48), but its occurrence needs additional environmental factors in carriers of longer apoB forms; ii) intestinal lipid malabsorption develops only in carriers of short truncated apoBs, which are not secreted into the plasma; and iii) cerebrovascular disease due to premature atherosclerosis may occur even in FHBL subjects.

A study of fatty liver disease and plasma lipoproteins in a kindred with familial hypobetalipoproteinemia due to a novel truncated form of apolipoprotein B (APO B-54.5).

BACKGROUND/AIMS: Familial hypobetalipoproteinemia (FHBL) is a co-dominant disorder characterized by reduced plasma levels of low-density lipoproteins. It can be caused by mutations in the gene encoding apolipoprotein B-100 (apo B), leading to the formation of truncated apo Bs which have a reduced capacity to export lipids from the hepatocytes as lipoprotein constituents. Case reports suggest the occurrence of liver disease in FHBL, but there are no studies of liver involvement in FHBL with defined apo B gene mutations. The presence of fatty liver disease was investigated in a large FHBL kindred. METHODS: Plasma lipoprotein and apolipoprotein analysis, liver function tests, and apo B gene sequence were performed in 16 members of a FHBL kindred. The presence of fatty liver was assessed by ultrasound and computed tomography scanning. RESULTS: The proband, a non-obese heavy drinker male with hypobetalipoproteinemia, had steatohepatitis with fibrosis. He was heterozygous for a novel non-sense mutation of apo B gene producing a truncated apo B of 2745 amino acids (designated apo B-54.5, having half the size of normal apo B-100). Seven other members of his kindred carried apo B-54.5. Although all of them were hypolipidemic, their lipid levels showed a large inter-individual variability not accounted for by polymorphisms of genes involved in apo B metabolism. Four carriers (two heavy drinkers and two teetotallers), irrespective of their plasma lipid levels, had ultrasonographic evidence of fatty liver. In the other four carriers no evidence of fatty liver was found. CONCLUSIONS: In this kindred apo B-54.5 predisposes to fatty liver, which however may require some additional factors to become clinically relevant.

[The false myth of toxoplasmosis in salami]. / Il falso mito della toxoplasmosi nei salumi.

On the basis of available literature concerning Toxoplama gondii infection in swine (swine toxoplasmosis) and the resistance of parasite to heating, freezing, gamma-radiation, salting, seasoning and production processes of "cooked" and "fermented" salami, the possible risk of transmission of the disease from pig (where toxoplasmosis is widely diffuse) to man is discussed. No risk of transmission of the disease, even to children and pregnant women, can derive from the consumption of cooked meat, cooked or salted-fermented salami and ham. The only risk could be related to eating of even small amount of fresh sausages or chitterlings (especially heart, brain and other viscera) and consumption of not drinking water.

[Extra-nutritional and nutraceutical effects of traditional foods of Parma]. / Effetti extranutrizionali e nutraceutici degli alimenti tradizionali di Parma.

Territorial Products and food-culture relationship are described. On the basis of food extra-nutritional constituents and on the characteristics of functional food (nutraceutical food), traditional Parma products, i.e. Parma Ham and Parmigiano-Reggiano Cheese, are examined in their nutritional, extra-nutritional and functional consequences.

Secretion of apoB- and apoA-I-containing lipoproteins by chick kidney.

Previous studies showed that chick kidney is a site of synthesis of apolipoprotein (apo) B(B-100) and A-I. Aims of the present study were: a) to compare apoB and apoA-I production in chick kidney and liver; b) to investigate whether kidney apolipoproteins were secreted as constituents of lipoproteins; and c) to define the cellular sites of renal apolipoprotein synthesis. Kidney and liver slices taken from the same animals were incubated with 35S-labeled amino acids and radioactive apoB and apoA-I were immunoprecipitated from cell homogenate and incubation medium. The percentage of total protein radioactivity incorporated into cell plus medium apoB and apoA-I was 0.23+/-0.08 and 0.19+/-0.11 in kidney and 0.38+/-0.05 and 0.38+/-0.07 in liver, respectively (P < 0.05 kidney vs. liver). 35S-labeled medium lipoproteins were separated by density gradient ultracentrifugation and three major classes corresponding to VLDL + IDL, LDL, and HDL were identified. Most of the apoB secreted by the liver was found in VLDL, IDL, and LDL whereas kidney apoB was found in VLDL, LDL and "light" HDL (d 1.070-1.130 g/ml). In both hepatic and renal lipoproteins apoA-I was found not only in HDL but also in the other lipoproteins. Immunohistochemical analysis of kidney sections showed that apoB and apoA-I were present almost exclusively in the epithelial cells of proximal and distal convoluted tubules. Thus apoB and apoA-I synthesized by the epithelial cells of the proximal and distal convoluted tubules of chick kidneys are secreted as constituents of lipoprotein particles floating within the density range of plasma lipoproteins. These observations suggest that in the chick, the kidneys may contribute to the plasma lipoprotein pool.

Fatty liver in heterozygous hypobetalipoproteinemia caused by a novel truncated form of apolipoprotein B.

Fatty liver has been anecdotally associated with heterozygous hypobetalipoproteinemia. The aim of this study was to characterize the molecular defect in a subject with heterozygous hypobetalipoproteinemia (low-density lipoprotein cholesterol, 52 mg/dL; apolipoprotein [apo] B, 15 mg/dL) and otherwise unexplained fatty liver. Plasma lipoproteins were separated by ultracentrifugation, and apo B was analyzed by electrophoresis and immunoblotting. A fragment of genomic DNA corresponding to the 5' end of exon 26 of the apo B gene was amplified by polymerase chain reaction and sequenced. The plasma lipoproteins of the proband contained, besides normal apo B-100, a 200-kilodalton truncated apo B whose size suggested the presence of a mutation in exon 26 of the apo B gene. The nucleotide sequence of a fragment of the 5' end of exon 26 revealed that the proband was a heterozygote for a 14-nucleotide deletion, producing a frameshift resulting in a premature stop codon at residue 1768. This truncated apo B was named apo B-38.95. The proband's father was a carrier of the same mutation. Fatty liver in this subject with familial heterozygous hypobetalipoproteinemia most likely results from the inability of apo B-38.95 to export lipids from hepatocytes into the blood stream. Heterozygous hypobetalipoproteinemia should be considered in a hypolipidemic subject with an otherwise unexplained fatty liver.

Synthesis and secretion of B-100 and A-I apolipoproteins in response to the changes of intracellular cholesteryl ester content in chick liver.

We investigated in the chick whether the diet-induced changes of the hepatic content of cholesteryl esters (CE) influence the synthesis and the secretion of apoB- and apoA-I-containing lipoproteins. Control chicks received a low cholesterol diet for 2 (SD-1), 4 (SD-2), or 7 (SD-3) weeks; the chicks in the experimental groups received a cholesterol-rich diet for 2 weeks and were killed at the end of the cholesterol feeding (CH-F), and after 2 (CH-D) or 5 (CH-DD) weeks of a low cholesterol diet. Hepatic CE content in CH-F chicks was 30-fold that observed in controls, but returned to the control level after 5 weeks of cholesterol depletion (CH-DD). The incorporation of 35S-labeled amino acids into cell and medium apoB and apoA-I was measured in liver slices. Intracellular 35S-labeled apoB was similar in all groups whereas medium 35S-labeled apoB was 2-fold higher in CH-F than in controls (SD-1). Pulse-chase experiments showed that radioactive apoB secreted by CH-F chicks at 120 min of chase was 2 times that of SD-1 chicks. This increased secretion of apoB was not found in CH-D chicks. In CH-F chicks, the intracellular and medium 35S-labeled apoA-I were 2-fold the values found in controls (SD-1); apoA-I production returned to the control level only after 5 weeks of cholesterol depletion (CH-DD). The increased secretion of apoB and apoA-I in CH-F chicks was associated with an increased secretion of very low, intermediate, and low density lipoproteins containing newly synthesized apoB and apoA-I and of high density lipoproteins containing predominantly apoA-I. Thus, in response to hepatic CE accumulation induced by cholesterol feeding, a larger proportion of newly synthesized apoB is driven to the secretory pathway and more apoA-I is synthesized. This promotes an increased secretion of plasma lipoproteins that contribute to the removal of CE from the liver.

Apolipoprotein B-100 production and cholesteryl ester content in the liver of developing chick.

In the chick, the large cholesteryl ester (CE) store present in the liver during the last period of embryonic life increases at hatching and is rapidly depleted after 2-7 days of postnatal life. In this study we asked whether these changes were associated with variations in the hepatic production of apoB-containing lipoproteins. Liver slices taken from chicks at -3, 0 (hatching), 2, 4, 7, and 10 days of development were incubated with [35S]methionine in steady state incubations. ApoB production (cell + medium radioactivity) decreased from day -3 to day 0 (40%), increased at day 4 (54%), and decreased afterwards (45%). At day 4 the amount of 35S-labeled apoB-containing lipoproteins (VLDL-LDL) secreted into the medium was 1.7- and 1.5-times that found at days 0 and 7, respectively; the radioactivity incorporated into medium HDL (containing predominantly apoA-I) was 1.7-times that found at days 0 and 7. The incubation of liver slices with [3H]oleate showed that CE production at days 4 and 7 was 58% and 33%, respectively, of that found at day 0. The percentage of newly synthesized hepatic CE secreted into medium lipoproteins was 2.4%, 3.1%, and 2.2% at days 0, 4, and 7, respectively. The percentage of lipoprotein CE present in VLDL-LDL ranged from 38% at day 0 to 21% at day 7, and that present in HDL ranged from 62% at day 0 to 79% at day 7. To define whether the changes in the production of apoA-I- and apoB-containing lipoproteins were due to variations in apoB and apoA-I synthesis, the initial synthetic rate (pulse-labeling) and the mRNA content of these apolipoproteins were investigated. The initial apoB synthetic rate decreased 1.5-fold from day -3 to day 0, remained stable up to day 7, and decreased at day 10. Hepatic apoB mRNA followed a similar trend. The synthesis of apoA-I increased 2-fold from days -3/2 up to day 4 and did not change afterwards. In conclusion the increased hepatic CE content at hatching reflects a decreased production of apoB, while the depletion of CE observed from day 2 to day 7 is associated with an increased production of both apoB- and apoA-I-containing lipoproteins. The decreased apoB production at hatching is due to a decreased apoB synthesis whereas the increased apoB production at day 4 appears to be related to a post-translational event.

Hygienic aspects of the production and agricultural use of animal wastes.

Regarding the hygienic aspects of the production and use of animal wastes, further research on the following aspects is essential: pathogenic agents present in residues of animal production in the context of transmissible multifactorial diseases and the epidemiology of pathogens under different ecological conditions; recycling of toxic agents, e.g., copper, selenium and iodine, in animal wastes in the context of the food chain from soil to humans; hygienic effects of animal wastes on water as regards the standards required by medical authorities; effects of agents used to increase animal production, or used for medicinal purposes, which are present as residues in animal excreta and may be hazardous to public health; effects of animal excreta on microbiological processes in the soil; effects of dust and airborne microbial emissions from animal production, and finally, processes of self-disinfection of manure and livestock slurry during storage as a means of reducing the amounts of chemical disinfectants used, of reducing environmental pollution, and of studying the application of biotechnological methods to disinfect manure and livestock slurry, this study being of particular importance.

Current clinical problems of intensive husbandry.

The author performs an examination of the concept of pathocenosis, diseases of groups, and the consequences of the continually increasing unification of microbial populations on a world level. Then the current problems of veterinary assistance on intensive farms are examined and discussed with particular reference to the clinical and control aspects.