Seasonal proteome variation in intertidal shrimps under a natural setting: Connecting molecular networks with environmental fluctuations.

The ability of intertidal organisms to maintain their performance via molecular and physiological adjustments under low tide, seasonal fluctuations and extreme events ultimately determines population viability. Analyzing this capacity in the wild is extremely relevant since intertidal communities are under increased climate variability owing to global changes. We addressed the seasonal proteome signatures of a key intertidal species, the shrimp Palaemon elegans, in a natural setting. Shrimps were collected during spring and summer seasons at low tides and were euthanized in situ. Environmental variability was also assessed using hand-held devices and data loggers. Muscle samples were taken for 2D gel electrophoresis and protein identification through mass spectrometry. Proteome data revealed that 55 proteins (10.6% of the proteome) significantly changed between spring and summer collected shrimps, 24 of which were identified. These proteins were mostly involved in cytoskeleton remodelling, energy metabolism and transcription regulation. Overall, shrimps modulate gene expression leading to metabolic and structural adjustments related to seasonal differences in the wild (i.e. abiotic variation and possibly intrinsic cycles of reproduction and growth). This potentially promotes performance and fitness as suggested by the higher condition index in summer-collected shrimps. However, inter-individual variation (% coefficient of variation) in protein levels was quite low (min-max ranges were 0.6-8.3% in spring and 1.2-4.8% in summer), possibly suggesting reduced genetic diversity or physiological canalization. Protein plasticity is relevant to cope with present and upcoming environmental variation related to anthropogenic forcing (e.g. global change, pollution) but low inter-individual variation may limit evolutionary potential of shrimp populations.

Ocean warming alters cellular metabolism and induces mortality in fish early life stages: A proteomic approach.

Climate change has pervasive effects on marine ecosystems, altering biodiversity patterns, abundance and distribution of species, biological interactions, phenology, and organisms' physiology, performance and fitness. Fish early life stages have narrow thermal windows and are thus more vulnerable to further changes in water temperature. The aim of this study was to address the sensitivity and underlying molecular changes of larvae of a key fisheries species, the sea bream Sparus aurata, towards ocean warming. Larvae were exposed to three temperatures: 18°C (control), 24°C (warm) and 30°C (heat wave) for seven days. At the end of the assay, i) survival curves were plotted for each temperature treatment and ii) entire larvae were collected for proteomic analysis via 2D gel electrophoresis, image analysis and mass spectrometry. Survival decreased with increasing temperature, with no larvae surviving at 30°C. Therefore, proteomic analysis was only carried out for 18°C and 24°C. Larvae up-regulated protein folding and degradation, cytoskeletal re-organization, transcriptional regulation and the growth hormone while mostly down-regulating cargo transporting and porphyrin metabolism upon exposure to heat stress. No changes were detected in proteins related to energetic metabolism suggesting that larval fish may not have the energetic plasticity needed to sustain cellular protection in the long-term. These results indicate that despite proteome modulation, S. aurata larvae do not seem able to fully acclimate to higher temperatures as shown by the low survival rates. Consequently, elevated temperatures seem to have bottleneck effects during fish early life stages, and future ocean warming can potentially compromise recruitment's success of key fisheries species.

Influence of temperature in thermal and oxidative stress responses in estuarine fish.

The influence of increasing temperatures in thermal and oxidative stress responses were studied in the muscle of several estuarine fish species (Diplodus vulgaris, Diplodus sargus, Dicentrarchus labrax, Gobius niger and Liza ramada). Selected fish were collected in July at the Tagus estuary (24±0.9°C; salinity of 30±4‰; pH=8). Fish were subjected to a temperature increase of 1°C.h(-1) until they reached their Critical Thermal Maximum (CTMax), starting at 24°C (control temperature). Muscle samples were collected during the trial and results showed that oxidative stress biomarkers are highly sensitive to temperature. Results from stress oxidative enzymes show alterations with increasing temperature in all tested species. Catalase (CAT; EC 1.11.1.6) activity significantly increased in L. ramada, D. labrax and decreased in D. vulgaris. Glutathione S-transferase (GST; EC 2.5.1.18) activity increased in L. ramada, D. sargus, D. vulgaris, and D. labrax. In G. niger it showed a cycle of increase-decrease. Lipid peroxidation (LPO) increased in L. ramada, D. sargus and D. labrax. With respect to correlation analysis (Pearson; Spearman r), the results showed that oxidation products and antioxidant defenses were correlated in L. ramada (LPO-CAT and LPO-GST, D. sargus (LPO-CAT), and D. labrax (LPO-CAT). Oxidative biomarkers were correlated with thermal stress biomarker (Hsp70) in L. ramada (CAT-Hsp70), D. vulgaris (LPO-Hsp70), D. labrax (GST-Hsp70) and G. niger (LPO-Hsp70). In conclusion, oxidative stress does occur with increasing temperatures and there seems to be a relation between thermal stress response and oxidative stress response. The results suggest that oxidative stress biomarkers should be applied with caution, particularly in field multi-species/multi-environment studies.

Metabolism of triglyceride-rich lipoproteins and transfer of lipids to high-density lipoproteins (HDL) in vegan and omnivore subjects.

BACKGROUND AND AIMS: Vegan diet excludes all foodstuffs of animal origin and leads to cholesterol lowering and possibly reduction of cardiovascular disease risk. The aim was to investigate whether vegan diet improves the metabolic pathway of triglyceride-rich lipoproteins, consisting in lipoprotein lipolysis and removal from circulation of the resulting remnants and to verify whether the diet alters HDL metabolism by changing lipid transfers to this lipoprotein. METHODS AND RESULTS: 21 vegan and 29 omnivores eutrophic and normolipidemic subjects were intravenously injected triglyceride-rich emulsions labeled with (14)C-cholesterol oleate and (3)H-triolein: fractional clearance rates (FCR, in min(-1)) were calculated from samples collected during 60 min for radioactive counting. Lipid transfer to HDL was assayed by incubating plasma samples with a donor nanoemulsion labeled with radioactive lipids; % lipids transferred to HDL were quantified in supernatant after chemical precipitation of non-HDL fractions and nanoemulsion. Serum LDL cholesterol was lower in vegans than in omnivores (2.1 ± 0.8, 2.7 ± 0.7 mmol/L, respectively, p < 0,05), but HDL cholesterol and triglycerides were equal. Cholesteryl ester FCR was greater in vegans than in omnivores (0.016 ± 0.012, 0.003 ± 0.003, p < 0.01), whereas triglyceride FCR was equal (0.024 ± 0.014, 0.030 ± 0.016, N.S.). Cholesteryl ester transfer to HDL was lower in vegans than in omnivores (2.7 ± 0.6, 3.5 ± 1.5%, p < 0,05). Free-cholesterol, triglyceride and phospholipid transfer were equal, as well as HDL size. CONCLUSION: Remnant removal from circulation, estimated by cholesteryl oleate FCR was faster in vegans, but the lipolysis process, estimated by triglyceride FCR was equal. Increased removal of atherogenic remnants and diminution of cholesteryl ester transfer may favor atherosclerosis prevention by vegan diet.

Thermal tolerance of the crab Pachygrapsus marmoratus: intraspecific differences at a physiological (CTMax) and molecular level (Hsp70).

Temperature is one of the most important variables influencing organisms, especially in the intertidal zone. This work aimed to test physiological and molecular intraspecific differences in thermal tolerance of the crab Pachygrapsus marmoratus (Fabricius, 1787). The comparisons made focused on sex, size, and habitat (estuary and coast) differences. The physiological parameter was upper thermal limit, tested via the critical thermal maximum (CTMax) and the molecular parameter was total heat shock protein 70 (Hsp70 and Hsp70 plus Hsc70) production, quantified via an enzyme-linked imunosorbent assay. Results showed that CTMax values and Hsp70 production are higher in females probably due to different microhabitat use and potentially due to different hormonal regulation in males and females. Among females, non-reproducing ones showed a higher CTMax value, but no differences were found in Hsp70, even though reproducing females showed higher variability in Hsp70 amounts. As reproduction takes up a lot of energy, its allocation for other activities, including stress responses, is lower. Juveniles also showed higher CTMax and Hsp70 expression because they occur in greater shore heights and ageing leads to alterations in protein synthesis. Comparing estuarine and coastal crabs, no differences were found in CTMax but coastal crabs produce more Hsp70 than estuarine crabs because they occur in drier and hotter areas than estuarine ones, which occur in moister environments. This work shows the importance of addressing intraspecific differences in the stress response at different organizational levels. This study shows that these differences are key factors in stress research, climate research, and environmental monitoring.

Diet and niche overlap of southern populations of brill Scophthalmus rhombus and turbot Scophthalmus maximus.

The diets of adult brill Scophthalmus rhombus and turbot Scophthalmus maximus from the Portuguese coast relied mostly on fishes. There was a higher diversity of food items compared to their northern counterparts, and several of the identified prey are the first records of these species, including a brown alga, echinoderms, nematodes, oligochaetes, gastropods, bivalves and various fish species. The diet of the two species was significantly different and niche overlap was low.

Chloroquine increases low-density lipoprotein removal from plasma in systemic lupus patients.

Low-density lipoprotein (LDL) pathway in systemic lupus erythematosus (SLE) patients taking chloroquine diphosphate (CDP) was evaluated through the kinetic behavior of a radioactive cholesterol-rich nanoemulsion (LDE) that resembles the LDL lipidic structure. LDE was labeled with (14)C-cholesteryl ester ((14)C-CE), then IV injected in inactive female SLE patients: 10 taking CDP (CDP), 10 without therapy (NO THERAPY); and 10 normal subjects (CONTROL). Groups were age-matched and followed rigorous selection criteria of conditions that interfere in the lipid profile. Blood samples were collected in pre-established intervals after infusion for radioactivity measurement. Fasting lipoproteins were determined in the beginning of kinetic studies. Fractional clearance rate (FCR) of (14)C-CE was significantly different in the three groups (P = 0.03). In fact, a greater FCR of (14)C-CE was observed in CDP compared to NO THERAPY (0.076 +/- 0.037 versus 0.046 +/- 0.021 h(-1); P < 0.05) and to CONTROL (0.0516 +/- 0.0125 h(-1); P < 0.05). Accordingly, a significant lower total and LDL cholesterol were observed in CDP (156 +/- 16 and 88 +/- 16 mg/dl) compared to NO THERAPY (174 +/- 15 and 108 +/- 17 mg/dl; P < 0.05) and to CONTROL (200 +/- 24 and 118 +/- 23 mg/dl; P < 0.05). In contrast, no difference in (FCR) of (14)C-CE of NO THERAPY and CONTROL groups was observed. This is the first in vivo demonstration that LDE removal by LDL receptor from plasma is increased in SLE patients taking CDP with a consequent beneficial decrease in LDL-c levels.

Lipolysis of emulsion models of triglyceride-rich lipoproteins is altered in male patients with abdominal aorta aneurysm.

Disorders of the lipid metabolism may play a role in the genesis of abdominal aorta aneurysm. The present study examined the intravascular catabolism of chylomicrons, the lipoproteins that carry the dietary lipids absorbed by the intestine in the circulation in patients with abdominal aorta aneurysm. Thirteen male patients (72 +/- 5 years) with abdominal aorta aneurysm with normal plasma lipid profile and 13 healthy male control subjects (73 +/- 5 years) participated in the study. The method of chylomicron-like emulsions was used to evaluate this metabolism. The emulsion labeled with 14C-cholesteryl oleate and (3)H-triolein was injected intravenously in both groups. Blood samples were taken at regular intervals over 60 min to determine the decay curves. The fractional clearance rate (FCR) of the radioactive labels was calculated by compartmental analysis. The FCR of the emulsion with (3)H-triolein was smaller in the aortic aneurysm patients than in controls (0.025 +/- 0.017 vs 0.039 +/- 0.019 min-1; P < 0.05), but the FCR of 14C-cholesteryl oleate of both groups did not differ. In conclusion, as indicated by the triglyceride FCR, chylomicron lipolysis is diminished in male patients with aortic aneurysm, whereas the remnant removal which is traced by the cholesteryl oleate FCR is not altered. The results suggest that defects in the chylomicron metabolism may represent a risk factor for development of abdominal aortic aneurysm.

Lipolysis of emulsion models of triglyceride-rich lipoproteins is altered in male patients with abdominal aorta aneurysm

Disorders of the lipid metabolism may play a role in the genesis of abdominal aorta aneurysm. The present study examined the intravascular catabolism of chylomicrons, the lipoproteins that carry the dietary lipids absorbed by the intestine in the circulation in patients with abdominal aorta aneurysm. Thirteen male patients (72 ± 5 years) with abdominal aorta aneurysm with normal plasma lipid profile and 13 healthy male control subjects (73 ± 5 years) participated in the study. The method of chylomicron-like emulsions was used to evaluate this metabolism. The emulsion labeled with 14C-cholesteryl oleate and ³H-triolein was injected intravenously in both groups. Blood samples were taken at regular intervals over 60 min to determine the decay curves. The fractional clearance rate (FCR) of the radioactive labels was calculated by compartmental analysis. The FCR of the emulsion with ³H-triolein was smaller in the aortic aneurysm patients than in controls (0.025 ± 0.017 vs 0.039 ± 0.019 min-1; P < 0.05), but the FCR of14C-cholesteryl oleate of both groups did not differ. In conclusion, as indicated by the triglyceride FCR, chylomicron lipolysis is diminished in male patients with aortic aneurysm, whereas the remnant removal which is traced by the cholesteryl oleate FCR is not altered. The results suggest that defects in the chylomicron metabolism may represent a risk factor for development of abdominal aortic aneurysm.

Assessing anthropogenic pressures on estuarine fish nurseries along the Portuguese coast: a multi-metric index and conceptual approach.

Estuaries are among the most productive ecosystems and simultaneously among the most threatened by conflicting human activities which damage their ecological functions, namely their nursery role for many fish species. A thorough assessment of the anthropogenic pressures in Portuguese estuarine systems (Douro, Ria de Aveiro, Mondego, Tejo, Sado, Mira, Ria Formosa and Guadiana) was made applying an aggregating multi-metric index, which quantitatively evaluates influences from key components: dams, population and industry, port activities and resource exploitation. Estuaries were ranked from most (Tejo) to least pressured (Mira), and the most influential types of pressure identified. In most estuaries overall pressure was generated by a dominant group of pressure components, with several systems being afflicted by similar problematic sources. An evaluation of the influence of anthropogenic pressures on the most important sparidae, soleidae, pleuronectidae, moronidae and clupeidae species that use these estuaries as nurseries was also performed. To consolidate information and promote management an ecological conceptual model was built to identify potential problems for the nursery function played by these estuaries, identifying pressure agents, ecological impacts and endpoints for the anthropogenic sources quantified in the assessment. This will be important baseline information to safeguard these vital areas, articulating information and forecasting the potential efficacy of future management options.

[Role of Herpes simplex virus in the immune stromal keratitis]. / Rol del virus Herpes simplex en la queratitis inmune estromal.

BACKGROUND: Herpes simplex virus (HSV) infection of the cornea is a leading cause of blindness in occidental countries and a common recurrent manifestation of it is the immune stromal keratitis (ISK). However, it is not known whether active viral replication occurs during the acute phase of the disease, because isolation of the virus by conventional culture techniques has not been accomplished. AIM: To establish the presence of HSV in patients with ISK. MATERIAL AND METHODS: Fourteen corneal swabbing samples, from active diseased eyes of patients with clinical diagnosis of ISK, were submitted to Herpchek and PCR for the identification of HSV antigens and genome. RESULTS: All ISK samples were negative by both techniques. CONCLUSIONS: It was not possible to identify HSV antigens nor their genome by the methodology used. It is likely that, they can't be detected in corneal superficial layers or probably there is no viral replication at this stage of the disease, so antiviral therapy should be reconsidered.

Effects of etofibrate upon the metabolism of chylomicron-like emulsions in patients with coronary artery disease.

Slow chylomicron intravascular catabolism has been associated with coronary artery disease and screening for drugs that can speed-up this process can be important. In this study, the effects of etofibrate upon chylomicron metabolism was tested by determination of the plasma kinetics of a chylomicron-like emulsion model in 12 patients with coronary artery disease, aged 59+/-11 years, (total cholesterol: 240+/-41 mg/dl; triglycerides: 188+/-42 mg/dl) submitted to a randomized, crossover, double-blind, placebo-controlled study with administration of 1 g per day etofibrate or placebo for 1-month. A 1-month washout period was inserted between the treatment periods. Patients were intravenously injected a chylomicron-like emulsion doubly labeled with 14C-cholesteryl oleate and 3H-triolein at baseline and after treatments. After etofibrate treatment, there was decrease of total cholesterol and triglyceride plasma levels and a trend to increase high-density lipoprotein cholesterol plasma levels. Etofibrate elicited 62% enhancement of post-heparin lipolytic activity and 100% increase of 3H-triglyceride fractional clearance rate compared with placebo treatment. 14C-cholesterol ester fractional clearance rate was 260% greater after etofibrate than after placebo. Therefore, a potent effect of etofibrate on both chylomicron lipolysis and remnant removal was achieved, indicating that this drug can be used to improve this metabolism in future prospective studies.

Plasma kinetics of a cholesterol-rich emulsion in young, middle-aged, and elderly subjects.

Low density lipoprotein (LDL) plasma concentration is increased in the elderly. In this group, the incidence of coronary artery disease (CAD) is greater and LDL remains an important risk factor for CAD development. In this study, the plasma kinetics of a cholesterol-rich emulsion that binds to LDL receptors was studied in 10-subject groups of the elderly (70 +/- 4 yr), middle-aged (42 +/- 5 yr) and young (23 +/- 2 yr). All were normolipidemic, nonobese, nondiabetic subjects who did not have CAD. The emulsion was labeled with 14C-cholesteryl oleate and injected intravenously into the subjects. Blood samples were drawn at regular intervals over 24 h to determine the plasma decay curve of the emulsion radioactive label and to estimate its plasma fractional clearance rate (FCR, in h(-1)). FCR of the emulsion label was smaller in elderly compared to young subjects (0.032 +/- 0.035 and 0.071 +/- 0.049 h(-1), respectively; mean +/- SD, P< 0.05). FCR of the middle-aged subjects (0.050 +/- 0.071 h(-1)) was intermediate between the values of the elderly and young subjects, although not statistically different from them. A negative correlation was found betweeen the emulsion FCR and subjects' age (r = -0.47, P = 0.008). We conclude that aging is accompanied by progressively diminished clearance of the emulsion cholesterol esters and, by analogy, of the native LDL.

Chylomicron metabolism is markedly altered in systemic lupus erythematosus.

OBJECTIVE: To verify the in vivo status of chylomicron metabolism in systemic lupus erythematosus (SLE) since there is a high incidence of atherosclerosis in this disease and chylomicrons may have an important role in atherogenesis. METHODS: A chylomicron-like emulsion labeled with 14C-cholesteryl esters and 3H-triglycerides was injected intravenously into 10 female patients with inactive SLE and 10 healthy age- and sex-matched control subjects to determine the plasma kinetics of the emulsion lipids from consecutive plasma samples taken at regular intervals for 1 hour. Lipolytic activity was determined in vitro after incubation of the labeled emulsion with postheparin plasma. RESULTS: The decay curves for the emulsion were markedly slowed in SLE. Chylomicron lipolysis, indicated by the fractional clearance rate (FCR) of emulsion 3H-triglyceride, was 2-fold smaller in SLE patients than in controls (mean +/- SD 0.023 +/- 0.011 versus 0.047 +/-0.015 minute(-1); P = 0.010). Chylomicron removal, indicated by emulsion 14C-cholesteryl ester FCR, was 3-fold smaller in SLE patients than in controls (0.007 +/-0.007 versus 0.023 +/- 0.011 minute(-1); P = 0.009). In vitro lipolysis in SLE patients was nearly half that of the controls (mean +/- SD 10,199 +/- 2,959 versus 6,598 +/-2,215; P = 0.014). Higher levels of very-low-density lipoprotein cholesterol and triglycerides and lower levels of high-density lipoprotein cholesterol and apolipoprotein A-I were also observed in the SLE patients. CONCLUSION: SLE patients have disturbances in chylomicron metabolism that are characterized by decreased lipolysis and chylomicron remnant removal from the plasma. This finding, together with other alterations in lipid profiles that were confirmed in the present study, is largely accountable for the accelerated atherosclerotic process of the disease.

Chylomicron metabolism in patients submitted to cardiac transplantation.

BACKGROUND: Development of coronary graft disease is the most important cause of late heart graft failure. Alterations in plasma lipid profile are frequent in heart transplant (HT) patients, but they seem not to be prominent. Currently, the metabolism of chylomicrons, the lipoproteins that carry dietary lipids absorbed by the intestine, was evaluated because chylomicron remnants are considered atherogenic. METHODS: An emulsion labeled with 3H-triolein and 14C-cholesteryl oleate and known to mimic the metabolic behavior of chylomicrons was injected intravenously after a 12-hr fast into 34 HT patients, 24 patients with end-stage heart failure (ESHF), and 30 healthy normolipidemic subjects. The plasma disappearance curves of the radioisotopes were determined from blood samples collected over 1 hr. In some of the patients and in controls, in vitro postheparin lipolytic activity was measured and an oral fat load test with postprandial measurement of triglyceridemia was performed. RESULTS: Fractional clearance rate (in m(-1), median [25%; 75%]) of both emulsion 3H-triolein and 14C-cholesteryl oleate was extremely diminished in HT patients (HT: 0.0114 [0.0114; 0.0179] and 0.2x10(-8) [0.2x10(-8); 0.0041, respectively]; ESHF: 0.0226 [0.0223; 0.0568] and 0.0160 [0.0055; 0.0189]; control subjects: 0.0270 [0.0226; 0.0392] and 0.0090 [0.0042; 0.0180], respectively, P<0.05). HT patients also had reduced postheparin lipolysis and marked elevation of postprandial triglyceridemia compared with the controls. CONCLUSIONS: HT patients develop accumulation in the plasma of chylomicrons and their remnants. The observed alterations were so intense that they may suggest an important involvement of atherogenic chylomicron remnants in coronary graft disease.

Increased apolipoprotein B serum concentration in Alzheimer's disease.

OBJECTIVE: To investigate the lipoprotein profile in a group of Alzheimer's disease (AD) patients. PATIENTS AND METHODS: Twenty-four patients with AD and 32 elderly controls were evaluated. Fasting blood samples were obtained for determination of total VLDL, HDL and LDL cholesterol, lipoprotein (a), triglycerides, apolipoprotein A1 and apolipoprotein B. RESULTS: Significantly higher levels of apolipoprotein B were found in AD patients (P = 0.004), whereas the concentration of lipoprotein (a) and plasma lipids was not statistically different. Apo B levels were similar between AD patients with or without leukoaraiosis on CT scan. CONCLUSION: AD patients had high serum concentration of apolipoprotein B. This finding suggests that apolipoprotein E may not be the single factor in lipid metabolism to play a role in AD pathogenesis.

[Emergence of resistance to macrolides in Streptococcus pyogenes]. / Emergencia de resistencia a macrólidos en Streptococcus pyogenes.

BACKGROUND: Diseases produced by Streptoccocus pyogenes are still a problem in Chile, as in the rest of the world. It exhibits in vitro susceptibility to different antimicrobials, but penicillin continues to be the treatment of choice. Alternative drugs have been developed for allergic patients, such as erythromycin, new macrolides and cephalosporins. Nevertheless, resistant strains are appearing due to the indiscriminate use of macrolides. AIM: To assess present antimicrobial susceptibility of S Pyogenes strains isolated from chilean patients. MATERIAL AND METHODS: The susceptibility to penicillin, macrolides, clindamycin, cephalotin and vancomycin of 153 S Pyogenes strains, obtained from different health centers of the Metropolitan Region and isolated between 1996 and 1998, was assessed using the Kirby-Bauer method. Agar dilution minimal inhibitory concentration was then determined to macrolide resistant strains. RESULTS: All strains were susceptible to penicillin. There was a 7.2% cross-resistance to macrolides. CONCLUSIONS: These results confirm that S Pyogenes resistance to macrolides has increased considerably in the Metropolitan Region of Chile during the last years.

Apolipoprotein and lipid abnormalities in chronic liver failure

Total serum lipids, as well as apolipoproteins A-I (apo A-I) and B (apo B), were determined in 74 patients with chronic liver failure without cholestasis and in 82 normal subjects. The VLDL, LDL and HDL lipid fractions were reduced in the liver failure group by 36 percent, 24 percent and 46 percent, respectively (P<0.001). Apolipoproteins A-I and B were also reduced by 26 percent and 25 percent, respectively (P<0.001). However, the reduction of HDL cholesterol (HDLc) was more pronounced than that of apo A-I and HDLc:apo A-I ratio was significantly lower in the liver failure group. After separating these patients into groups with plasma albumin lower than 3.0, between 3.0 and 3.5, and higher than 3.5 g/dl, the HDLc:apo A-I ratio was proportional to plasma albumin, but the correlation was not statistically significant. When these patients were separated by the Child classification of liver function, there was a correlation between the HDLc:apo A-I ratio and liver function. The differences in the HDLc:apo A-I ratio between the Child groups B and C, and A and C were statistically significant (P<0.05). We conclude that there is a more pronounced reduction in HDL cholesterol than in apo A-I in liver failure patients. Therefore, the HDLc:apo A-I ratio is a marker of liver function, probably because there is a decreased lecithin-cholesterol acyltransferase production by the diseased liver.

Apolipoprotein and lipid abnormalities in chronic liver failure.

Total serum lipids, as well as apolipoproteins A-I (apo A-I) and B (apo B), were determined in 74 patients with chronic liver failure without cholestasis and in 82 normal subjects. The VLDL, LDL and HDL lipid fractions were reduced in the liver failure group by 36%, 24% and 46%, respectively (P < 0.001). Apolipoproteins A-I and B were also reduced by 26% and 25%, respectively (P < 0.001). However, the reduction of HDL cholesterol (HDLc) was more pronounced than that of apo A-I and the HDLc:apo A-I ratio was significantly lower in the liver failure group. After separating these patients into groups with plasma albumin lower than 3.0, between 3.0 and 3.5, and higher than 3.5 g/dl, the HDLc:apo A-I ratio was proportional to plasma albumin, but the correlation was not statistically significant. When these patients were separated by the Child classification of liver function, there was a correlation between the HDLc:apo A-I ratio and liver function. The differences in the HDLc:apo A-I ratio between the Child groups B and C, and A and C were statistically significant (P < 0.05). We conclude that there is a more pronounced reduction in HDL cholesterol than in apo A-I in liver failure patients. Therefore, the HDLc:apo A-I ratio is a marker of liver function, probably because there is a decreased lecithin-cholesterol acyltransferase production by the diseased liver.