Effect of fructo-oligosaccharides on nutrient digestibility and digesta retention time in adult guinea pigs.

A previous study suggested that addition of fructo-oligosaccharides (FOS) to the diet improved nitrogen (N) utilization and decreased acid detergent fiber (ADF) digestibility in guinea pigs. The present study was conducted to clarify the relationship between ADF digestibility and gastrointestinal mean retention time (MRT) in guinea pigs under FOS supplementation. Adult male guinea pigs were fed a commercial diet (50 g/day) with either 5% glucose (glucose group) or 5% FOS (FOS group) for 12 days in individual metabolism cages. Unlike the glucose group, N utilization improved, but ADF digestibility significantly (P < 0.05) decreased in the FOS group. MRT of solid digesta also significantly (P < 0.05) decreased in the FOS group compared with that in the glucose group. We concluded that reduction of MRT of solid digesta containing FOS decreased ADF digestibility in guinea pigs.

Embryonic and postnatal development of calcium-binding proteins immunoreactivity in the anterior thalamus of the guinea pig.

Our recent studies have shown that the distribution of calretinin (CR) in the anterior thalamic nuclei (ATN) changes significantly during the development of the guinea pig. The present study was designed to reveal the distribution pattern of calcium-binding proteins, i.e. calbindin (CB) and parvalbumin (PV), as well as the colocalization pattern of all three proteins, including CR, in the ATN of guinea pigs ranging from the 40th embryonic day (E40) to the 80th postnatal day (P80). According to these patterns, CB appears exclusively in the perikarya of the anteromedial nucleus (AM) not before P20 and always colocalizes with CR. Moreover, CB and CR colocalize in fibers of thin bundles traversing the anteroventral nucleus (AV) since E50. The ATN also display CB-positive neuropil in all studied stages, especially a strong one in the ventral part of the AV. PV was not observed in the perikarya of the ATN in all the stages, but was abundantly present in the neuropil of the anterodorsal nucleus (AD). No colocalizations exist between PV and the rest of the studied proteins. In conclusion, our study reveals that the distribution of the studied proteins differs greatly. Nevertheless, the postnatal coexistence of CB and CR in the AM perikarya may indicate the cooperation of both of the proteins in some functions of the nucleus. Parvalbumin is limited mostly to the neuropil of the AD, suggesting different functions in comparison to CB and CR.

Influence of sodium selenite on growth, nutrient utilization and selenium uptake in Cavia porcellus.

A 70 day experiment on forty guinea pigs (Cavia porcellus) was conducted to find the influence of different level of sodium selenite (inorganic selenium supplementation) on growth, nutrient utilization and selenium uptake. The sodium selenite was supplemented into a basal diet at 0, 0.1, 0.2 and 0.3 ppm, respectively and the basal diet comprised of 25% ground cowpea (Vigna unguiculata) hay, 30% ground maize (Zea mays) grain, 22% ground gram (Cicer arietinum) grain, 9.5% deoiled rice (Oryza sativa) bran, 6% soybean (Glycine max) meal, 6% fish meal, 1.5% mineral mixture (without Se), ascorbic acid (200 mg kg) and 0.1 ppm Se to meet their nutrient requirements. Daily feed intake and weekly body weights were recorded. Intake and digestibility of dry matter, organic matter, ether extract, crude fiber and nitrogen-free extract as well as uptake of calcium and phosphorus, total body weight and average daily gain were similar (p>0.05) among the four groups. However, there was a trend of increase in Se absorption of the guinea pigs with the increasing levels of Se, in the groups given 0.2 and 0.3 ppm of Se. It can be concluded that requirement of Se in guinea pigs is 0.1 ppm, as supplementation of > or =0.1 ppm sodium selenite in the diet (having 0.1 ppm Se) did not enhanced their growth rate and nutrient utilization.

Isolation and cloning of the K+-independent, ouabain-insensitive Na+-ATPase.

Primary Na+ transport has been essentially attributed to Na+/K+ pump. However, there are functional and biochemical evidences that suggest the existence of a K+-independent, ouabain-insensitive Na+ pump, associated to a Na+-ATPase with similar characteristics, located at basolateral plasma membrane of epithelial cells. Herein, membrane protein complex associated with this Na+-ATPase was identified. Basolateral membranes from guinea-pig enterocytes were solubilized with polyoxyethylene-9-lauryl ether and Na+-ATPase was purified by concanavalin A affinity and ion exchange chromatographies. Purified enzyme preserves its native biochemical characteristics: Mg2+ dependence, specific Na+ stimulation, K+ independence, ouabain insensitivity and inhibition by furosemide (IC50: 0.5 mM) and vanadate (IC50: 9.1 µM). IgY antibodies against purified Na+-ATPase did not recognize Na+/K+-ATPase and vice versa. Analysis of purified Na+-ATPase by SDS-PAGE and 2D-electrophoresis showed that is constituted by two subunits: 90 (α) and 50 (ß) kDa. Tandem mass spectrometry of α-subunit identified three peptides, also present in most Na+/K+-ATPase isoforms, which were used to design primers for cloning both ATPases by PCR from guinea-pig intestinal epithelial cells. A cDNA fragment of 1148 bp (atna) was cloned, in addition to Na+/K+-ATPase α1-isoform cDNA (1283 bp). In MDCK cells, which constitutively express Na+-ATPase, silencing of atna mRNA specifically suppressed Na+-ATPase α-subunit and ouabain-insensitive Na+-ATPase activity, demonstrating that atna transcript is linked to this enzyme. Guinea-pig atna mRNA sequence (2787 bp) was completed using RLM-RACE. It encodes a protein of 811 amino acids (88.9 kDa) with the nine structural motifs of P-type ATPases. It has 64% identity and 72% homology with guinea-pig Na+/K+-ATPase α1-isoform. These structural and biochemical evidences identify the K+-independent, ouabain-insensitive Na+-ATPase as a unique P-type ATPase.

Effect of organic selenium supplementation on growth, Se uptake, and nutrient utilization in guinea pigs.

Forty weaned male guinea pigs (Cavia porcellus) of 152.6 +/- 7.96 g mean body weight were divided into four equal groups and fed a common basal diet comprised of 25% ground cowpea (Vigna unguiculata) hay, 30% ground maize (Zea mays) grain, 22% ground gram (Cicer arietinum) grain, 9.5% deoiled rice (Oryza sativa) bran, 6% soybean (Glycine max) meal, 6% fish meal, 1.5% mineral mixture (without Se), and ascorbic acid at 200 mg/kg to meet their nutrient requirements along with 0, 0.1, 0.2, and 0.3 ppm of organic selenium (Se) in groups I, II, III, and IV, respectively. Experimental feeding lasted for a period of 10 weeks, during which, daily feed intake and weekly body weights were recorded. Intake and digestibility of dry matter, organic matter, ether extract, crude fiber, and nitrogen-free extract as well as uptake of calcium and phosphorus were similar (P > 0.05) among the four groups. Feed:gain ratio was also similar (P > 0.05) in the four groups. However, digestibility of crude protein was significantly (P < 0.001) higher in group II supplemented with 0.1 ppm organic Se as compared to other three group. Intake and absorption of Se was significantly (P < 0.001) higher in all the Se supplemented groups as compared to control group. Average daily gain (ADG) was significantly (P < 0.05) higher in group II (3.16 g/day) and III (3.38 g/day) as compared to group I (2.88 g/day). However, ADG in group IV (supplemented 0.3 ppm organic Se) was significantly (P < 0.05) lower (2.83 g/day) than group II and III, but comparable (P > 0.05) to group I. Findings of the present experiment suggests that Se requirements of guinea pigs are > or =0.2 ppm, as supplementation of 0.1 ppm organic Se in the diet (having 0.1 ppm Se) not only enhanced their growth rate but also improved the protein utilization.

Estimation of the selenium requirement of growing guinea pigs (Cavia porcellus).

The aim of the study was to determine the selenium (Se) requirement of guinea pigs as a species unable to synthesize ascorbic acid. Forty-nine male guinea pigs (average weight 208 +/- 3.5 g) were divided into an initial status group and six experimental groups. The animals received a Se deficient Torula yeast based basal diet (<0.02 mg Se and 26 mg alpha-tocopherol/kg) or a Se addition of 0.05, 0.10, 0.15, 0.20 and 0.25 mg/kg diet as sodium selenate for 10 weeks. There was no significant difference in weight gain (final weight 643 +/- 21 g) between the groups and no clinical symptoms of Se deficiency occurred. With the exception of the testes, there was an increasing Se concentration in liver, plasma and haemolysate dependent on supplementation level. Glutathione peroxidase was determined in the plasma and Se dependent glutathione peroxidase (GPx1) in haemolysate, liver, kidney, heart and lung. Thioredoxin reductase (TR) activity was measured in liver, kidney and heart and deiodinase activity in the liver. A phospholipid hydroperoxide reducing activity with Se influence was determined in liver, kidney, heart, testes and brain. With the exception of GPx1 activity in heart and haemolysate and TR activity in the kidney, all enzymes already reached their maximal activity at 0.05 mg Se/kg diet. The activities of GPx1 and TR were used as parameters for broken line analysis and a Se requirement of 0.080 mg Se/kg diet was derived as sufficient for growing guinea pigs adequately supplied with vitamin E.

The Guinea pig as a preclinical model for demonstrating the efficacy and safety of statins.

Statins, because of their excellent efficacy and manageable safety profile, represent a key component in the current armamentarium for the treatment of hypercholesterolemia. Nonetheless, myopathy remains a safety concern for this important drug class. Cerivastatin was withdrawn from the market for myotoxicity safety concerns. BMS-423526 [{(3R,5S)-7-[4-(4-fluorophenyl)-6,7-dihydro-2-(1-methylethyl)-5H-benzo[6,7]cyclohepta[1,2-b]pyridin-3-yl]-3,5-dihydroxy-heptenoic acid} sodium salt], similar to cerivastatin in potency and lipophilicity, was terminated in early clinical development due to an unacceptable myotoxicity profile. In this report, we describe the guinea pig as a model of statin-induced cholesterol lowering and myotoxicity and show that this model can distinguish statins with unacceptable myotoxicity profiles from statins with acceptable safety profiles. In our guinea pig model, both cerivastatin and BMS-423526 induced myotoxicity at doses near the ED(50) for total cholesterol (TC) lowering in plasma. In contrast, wide differences between myotoxic and TC-lowering doses were established for the currently marketed, more hydrophilic statins, pravastatin, rosuvastatin, and atorvastatin. This in vivo model compared favorably to an in vitro model, which used statin inhibition of cholesterol synthesis in rat hepatocytes and L6 myoblasts as surrogates of potential efficacy and toxicity, respectively. Our conclusion is that the guinea pig is a useful preclinical in vivo model for demonstrating whether a statin is likely to have an acceptable therapeutic safety margin.

Androgen-dependent expression, gene structure, and molecular evolution of guinea pig caltrin II, a WAP-motif protein.

We determined the cDNA and gene structures of guinea pig caltrin II, a unique member of the calcium transporter inhibitors containing a whey acidic protein (WAP) motif, and we established that it is a secretory protein with a potential 21-amino acid signal peptide in its N-terminus. Northern blot analysis and in situ hybridization histochemistry indicated that the expression of caltrin II is restricted to luminal epithelial cells in the seminal vesicles. Its message levels markedly decreased either after castration (and were restored by simultaneous administration of testosterone) or after treatment of the animals with estradiol, suggesting that the expression of caltrin II is androgen-dependent. Recombinant caltrin II had an elastase-inhibitor activity. Comparison of sequence between the caltrin II and related genes and their molecular evolutionary analyses revealed that caltrin II and seminal vesicle secretory proteins (SVPs) appear to be evolved from a common ancestor gene that is made by the fusion of semenogelin and trappin genes. Caltrin II and SVPs lost the transglutaminase substrate domain and the WAP motif, respectively, within a single exon, resulting in the exertion of different functions.

Investigation of the pharmaceutical and pharmacological equivalence of different Hawthorn extracts.

Seven Hawthorn extracts were tested in isolated guinea pig aorta rings. The effect on noradrenaline- (10 microM) induced contraction was investigated. The extracts were prepared using ethanol (40 to 70% v/v), methanol (40 to 70% v/v), and water as the extraction solvents. The aqueous-alcoholic extracts displayed similar spectra of constituents. They were characterised by similar procyanidin, flavonoid, total vitexin and total phenols content and by similar TLC fingerprint chromatograms. The aqueous extract, however, showed a different fingerprint and a noticeably lower concentration of procyanidins, flavonoids and total phenols but a similar total vitexin content. All 7 extracts had a relaxant effect on the aorta precontracted by noradrenaline and led to relaxations to 44 until 29% of the initial values. The EC50 values of the aqueous-alcoholic extracts varied between 4.16 and 9.8 mg/l. The aqueous extract produced a similarly strong maximal relaxation as the other extracts, but the EC50, at 22.39 mg/l, was markedly higher. The results show that Hawthorn extracts with comparable quality profiles were obtained by using aqueous-alcoholic extraction solvents (40 to 70% ethanol or methanol). The extracts exerted comparable pharmacological effects. When using water as the extraction solvent, both, the spectrum of constituents and the pharmacological effect, deviated remarkably. It is thus possible to obtain bioequivalent extracts with comparable effect profiles by using 40 to 70% ethanol or methanol as the extraction solvent.

Age- and sex-determined differences in the establishment of tetanus antitoxin production in guinea-pigs.

For lack of relevant data of the literature, the tetanus immunisation results obtained in the two sexes were compared in an animal model. Complete immunisation series of weaned, adult and aged guinea-pigs (20-25 animals/group) were performed with aluminium phosphate (AlPO4) adsorbed purified tetanus toxoid (PTAP) as well as with typhoid-tetanus vaccine (TY-TE) containing lipopolysaccharide (LPS). Both vaccines contained 5.0 Lf (limes flocculans, Ramon) per single dose of tetanus toxoid, purity degree: 1500 Lf/mg protein nitrogen (PN). Tetanus antitoxin titres (TAT) were measured after the first shot, and subsequently before and after booster. Compared to TAT of male animals, significantly lower titres were found in female animals after basic immunisation with PTAP in all the three age groups: 1.03 vs. 0.57, 8.75 vs. 5.64, and 0.27 vs. 0.15 IU (international units, related to the Copenhagen International Standard) per ml (sex-chromosome-dependent differences?), as well as in adult animals immunised with TY-TE, before booster: 0.07 vs. 0.02 IU/ml (hormone-dependent differences?). In the latter case the TAT results after booster were 14.49 vs. 12.89 IU/ml. Thus, the lower female prebooster titres were counterbalanced by a quick and effective increase of titres following booster. These results are in accordance with our previous observations in humans (Réthy and Réthy, 1986). From our observations with tetanus immunisation series on guinea-pigs it can be concluded that TAT may be influenced by the effects of sex chromosomes as well as of sexual hormones. During active anti-tetanus immunisation with LPS-containing vaccine (TY-TE) the lower adult female prebooster titres are presumably counterbalanced by the better functionality of the female immune memory.

Influence of 3,4-dihydroxybenzoic acid on metal ion concentrations in guinea pig tissues after copper intoxication.

3,4-Dihydroxybenzoic acid (3,4-dhbH3 or protocatechuic acid) is a copper chelator which has potential as an agent for the treatment of copper-overload disease (Wilson's disease). The present investigation describes the fluctuation in copper, magnesium, zinc and calcium (Cu, Mg, Zn, Ca) concentrations in tissues of guinea pigs intoxicated with Cu after the administration of 3,4-dhbH3. We investigated the efficacy of 3,4-dhbH3 to eliminate Cu from poisoned guinea pigs, as well as to assess the changes in concentrations of Zn, Ca and Mg which normally occur in the tissues of experimental animals. The results are in agreement with other experimental data when we administered drugs capable of forming complexes with metal ions. Although 3,4-dhbH3 is capable of forming in vitro complexes with Cu, it can not be used successfully for chelation therapy of Cu intoxication, but its effectiveness as a ligand for Ca, Zn and Mg mobilization is discussed.

Mice, hamsters and guinea pigs differ in efficiency of pyridoxine-5'-beta-D-glucoside utilization.

Mice, hamsters and guinea pigs were studied to assess species variation in utilization of pyridoxine-5'-D-glucoside (PN-glucoside), a form of vitamin B-6 found in plants. Animals fed vitamin B-6-deficient or marginally supplemented diets [1 mg pyridoxine (PN)/kg] were given an oral dose of [3H]PN-glucoside plus [14C]PN. Urinary and fecal isotopic excretion was measured over 24 h and the distribution of B-6 vitamins in liver determined at the end of the 24-h period. Intestinal absorption was nearly complete, as very little (< 6%) of each isotope was excreted in the feces. In mice, hamsters and guinea pigs, 31.3, 31.5 and 9.5%, respectively, of urinary 3H was present as intact PN-glucoside. Incorporation into liver was reflected by 3H/14C ratios of hepatic vitamin B-6 as follows: mice, 0.39; hamsters, 0.73; guinea pigs, 1.49 (means for both diets). The intake of dietary vitamin B-6 had little effect on [3H]PN-glucoside metabolism. Guinea pigs displayed greater utilization of PN-glucoside than did mice, hamsters or rats (seen previously), although they may not be the best animal model for the study of PN-glucoside metabolism. Because the bioavailability of PN-glucoside in humans has been estimated to be 58% relative to PN, mice or hamsters, rather than guinea pigs or rats, would be better species for quantitative studies of PN-glucoside bioavailability and associated enzymatic processes.

Distribution of estrogen receptor-immunoreactive cells in the forebrain of the female guinea pig.

We mapped the distribution of estrogen receptor-containing cells in the forebrain of the adult female guinea pig. Cellular estrogen receptor content was detected using monoclonal antibody H222, directed against the estrogen receptor, and the avidin-biotin method with nickel-intensified diaminobenzidine as the chromagen. A complete set of deletion, titration, and adsorption controls established the specificity of the staining. The most dense collections of estrogen receptor-immunoreactive cells were found in medial preoptic, medial hypothalamic, and limbic nuclei (amygdala, bed nucleus of the stria terminalis, lateral septum). Numerous estrogen receptor-immunoreactive cells were also found in additional, specific subregions of the remainder of the preoptic area, hypothalamus, and limbic system, and also in the midbrain (central gray). Elsewhere, estrogen receptor-immunoreactive cells were present in smaller numbers or were absent. This map confirms and extends previous maps based on estrogen binding. The majority of estrogen receptor-immunoreactive cells are found in areas known to be involved in some aspect of reproduction. In addition, many estrogen receptor-immunoreactive cells are found in areas not typically considered to have a primary role in reproductive behavior or neuroendocrine function.

Apoprotein E biosynthesis in the cholesterol-fed guinea pig.

Apoprotein E biosynthesis was evaluated in the livers of guinea pigs fed chow, 1% cholesterol plus 5% corn oil, or 1% cholesterol plus 5% coconut oil for a period of 12 weeks. Hypercholesterolemia was induced by both experimental diets, although the coconut-oil diet resulted in higher levels. The ratios of free cholesterol/cholesterol ester and of free cholesterol/total phospholipid increased in the plasma of these animals. Peak lipid levels were mostly achieved by 8 weeks of diet. Both cholesterol and triglyceride were substantially increased in the liver of animals fed the experimental diets, while phospholipid content was unchanged. The amount of apoprotein E mRNA in the guinea pig livers was evaluated by cell free translation assays and by membrane hybridization. The livers of animals fed corn oil with cholesterol for 4 weeks or 8 weeks contained 2 to 2.5 more apoprotein E mRNA compared to the control livers. With the diet containing coconut oil with cholesterol, the hepatic apoprotein E mRNA increased somewhat later, so that by 8 weeks it was 1.7- to 1.9-fold higher than in the control animals. We conclude that high cholesterol diets, when fed as part of a high saturated or polyunsaturated fat diet, lead to increased hepatic apo E mRNA abundance. The relationship between the increased apo E mRNA levels and the previously described increases in apo E synthesis and circulating apo E levels is discussed.

Comparative immunocytochemical study of the catecholaminergic and peptidergic afferent innervation to the dorsal vagal complex in rat and guinea pig.

Light and electron microscopic immunocytochemistry was used to study the fine structural organization of the catecholaminergic and hypothalamic peptidergic innervation of the dorsal vagal complex of the medulla oblongata in the rat and guinea pig, the latter of which is known to lack central adrenergic neurons. In the rat, adrenergic fibers immunoreactive to phenylethanolamine-N-methyltransferase were concentrated in the dorsal motor nucleus of the vagus, where they established frequent symmetric synapses with dendrites and perikarya. On the other hand, the density of both oxytocin- and corticotropin-immunoreactive fibers appeared far lower in this nucleus than in the dorsal regions of the nucleus of the tractus solitarius, where they formed asymmetric synapses with small dendrites. In tissue treated for the dual labeling of two neuronal antigens, oxytocin- or corticotropin-reactive fibers were in close contact with adrenergic neurons in this dorsal medullary region. In the guinea pig, unlike the rat, the dorsal motor nucleus of the vagus contained large amounts of oxytocin- and corticotropin-reactive fibers, which formed many symmetric synapses with perikarya and dendrites. Taken together, these data suggest that the control of vagal preganglionic neurons by hypothalamic peptidergic neurons involves a bisynaptic neuronal pathway including adrenergic medullary neurons in the rat, whereas it is direct in the guinea pig, which lacks this adrenergic relay.

Macrominerals in guinea pig milk during 21 days of lactation.

Milk samples were obtained daily from English short-hair albino guinea pigs for 21 d. Analyses included six macrominerals: Ca, P, K, chloride, Na, and Mg (in order of decreasing concentration). All minerals except K gradually increased in concentration from the beginning to the end of lactation. Calcium concentration began at 38 mM on d 1 and was 78 mM on d 21. The pattern of increase was quadratic: Y (mM) = 39 -.48X (day of lactation) + .11 X2. Phosphorus concentration was 38 mM on d 1 and highest at 51 mM on d 21. Chloride was 19 mM on d 1 and 68 mM on d 21. Sodium was 13 mM on d 1 and highest at 42 mM on d 21. Magnesium was 11 mM on d 1 and was highest on d 18 (13 mM). However, K was 31 mM on d 1, reached a high of 33 mM on d 3, and was lowest on d 19 (12 mM). These changes in concentration and previously reported volume changes suggest alterations in functional capacities of ionic transport mechanisms of secretory cell membranes in this species.

The antiscorbutic action of L-ascorbic acid and D-isoascorbic acid (erythorbic acid) in the guinea pig.

Female guinea pigs were fed a scorbutigenic diet supplemented with either L-ascorbic acid or D-isoascorbic acid or combinations of these. Their responses were judged by changes in body weight, serum alkaline phosphatase levels, wound healing, and tooth structure. Large additions (100 mg daily) of D-isoascorbic acid to the scorbutigenic diet resulted in normal growth over a 7-wk period and normal serum alkaline phosphatase levels, tooth structure development, and collagen formation after wounding. The addition of 0.5 or 5.0 mg of L-ascorbic acid to this high D-isoascorbic diet improved neither growth rate nor collagen deposition during wound healing. On the basis of changes in tooth structure, D-isoascorbic acid has 1/20 the potency of L-ascorbic acid. Its effect is additive to subminimal maintenance levels of L-ascorbic acid implying that there is no competitive inhibition in the utilization of the two compounds. The relatively weak activity of D-isoascorbic acid is probably due to poor transport to the tissues and ineffective binding to functional sites. This explains why the onset of scurvy is much more rapid after withdrawal of D-isoascorbic acid from the diet when it had been the sole antiscorbutic dietary constituent. It is concluded that D-isoascorbic acid is a "weakly" antiscorbutic agent on the basis that it is both poorly absorbed and retained by the tissue; that in fact it may, to the degree that it is taken up by the tissues and retained, be equal in antiscorbutic potency to L-ascorbic acid.

Regional brain ascorbic acid distribution: its functional relationship to appetite and leptazol-induced convulsions in guinea-pigs.

The distribution of ascorbic acid has been compared in the fore-, mid- and hind-brains of guinea-pigs maintained on a scorbutogenic diet alone, or the diet with supplementary Vitamin C, or the supplemented diet and a terminal convulsant dose of leptazol after 27 days. At the beginning of the investigation, mid-brain ascorbic acid concentrations were similar in both sexes and highest in the mid-brain. After 27 days on the supplemented diet, levels of ascorbic acid were raised in all three brain sections and were still highest in the mid-brains. In the scorbutic group, ascorbic acid concentrations had not changed from control levels in the mid-brain, but had fallen in the other two sections. In a dose-range of 40-60 mg/kg, leptazol caused an increase in convulsive index, and progressive depletion of brain ascorbic acid. No change occurred in fore-brain ascorbic acid, a reduction took place in the hindbrain, and the greatest fall occurred in the mid-brain. It is concluded that ascorbic acid plays an essential role in mid-brain metabolism, and that the convulsant effect of leptazol is influenced by an interaction with brain ascorbic acid.

Plasma cholesterol esterifying activity in guinea pigs.

Plasma cholesterol esterifying activity has been measured in guinea pigs fed either a control diet or the same diet supplemented with 1% cholesterol. The extent of esterification was found to be similar in the cholesterol-fed and control guinea pigs and somewhat lower than in rats. The initial rate of esterification was also of the same magnitude as that found in rats and humans, and unaffected by dietary cholesterol if autologous plasma was used as substrate. However, LCAT activity from cholesterol-fed guinea pigs was significantly higher than that of control plasma when acting on either control or cholesterol-fed substrate. This suggests that dietary cholesterol increases the amount (or activity) of LCAT but that the substrate is unsuitable or that a necessary cofactor is present in limiting amounts. Heat treatment of guinea pig plasma seems to alter substrate availability to varying degrees. The implications of these findings in relation to substrate specificity and cofactor requirements of guinea pig LCAT are discussed.