Evidence that renal arginine transport is impaired in spontaneously hypertensive rats.

Low renal nitric oxide (NO) bioavailability contributes to the development and maintenance of chronic hypertension. We investigated whether impaired l-arginine transport contributes to low renal NO bioavailability in hypertension. Responses of renal medullary perfusion and NO concentration to renal arterial infusions of the l-arginine transport inhibitor l-lysine (10 µmol·kg(-1)·min(-1); 30 min) and subsequent superimposition of l-arginine (100 µmol·kg(-1)·min(-1); 30 min), the NO synthase inhibitor N(G)-nitro-l-arginine (2.4 mg/kg; iv bolus), and the NO donor sodium nitroprusside (0.24 µg·kg(-1)·min(-1)) were examined in Sprague-Dawley rats (SD) and spontaneously hypertensive rats (SHR). Renal medullary perfusion and NO concentration were measured by laser-Doppler flowmetry and polarographically, respectively, 5.5 mm below the kidney surface. Renal medullary NO concentration was less in SHR (53 ± 3 nM) compared with SD rats (108 ± 12 nM; P = 0.004). l-Lysine tended to reduce medullary perfusion (-15 ± 7%; P = 0.07) and reduced medullary NO concentration (-9 ± 3%; P = 0.03) while subsequent superimposition of l-arginine reversed these effects of l-lysine in SD rats. In SHR, l-lysine and subsequent superimposition of l-arginine did not significantly alter medullary perfusion or NO concentration. Collectively, these data suggest that renal l-arginine transport is impaired in SHR. Renal l-[(3)H]arginine transport was less in SHR compared with SD rats (P = 0.01). Accordingly, we conclude that impaired arginine transport contributes to low renal NO bioavailability observed in the SHR kidney.

Oligodendrocyte-specific expression and autoantigenicity of transaldolase in multiple sclerosis.

Although the etiology of multiple sclerosis (MS) is unknown, there is compelling evidence that its pathogenesis is mediated through the immune system. Molecular mimicry, i.e., crossreactivity between self-antigens and viral proteins, has been implicated in the initiation of autoimmunity and MS. Based on homology to human T cell lymphotropic virus type I (HTLV-I) a novel human retrotransposon was cloned and found to constitute an integral part of the coding sequence of the human transaldolase gene (TAL-H). TAL-H is a key enzyme of the nonoxidative pentose phosphate pathway (PPP) providing ribose-5-phosphate for nucleic acid synthesis and NADPH for lipid biosynthesis. Another fundamental function of the PPP is to maintain glutathione at a reduced state and, consequently, to protect sulfhydryl groups and cellular integrity from oxygen radicals. Immunohistochemical analyses of human brain sections and primary murine brain cell cultures demonstrated that TAL is expressed selectively in oligodendrocytes at high levels, possibly linked to production of large amounts of lipids as a major component of myelin, and to the protection of the vast network of myelin sheaths from oxygen radicals. High-affinity autoantibodies to recombinant TAL-H were detected in serum (25/87) and cerebrospinal fluid (15/20) of patients with MS. By contrast, TAL-H antibodies were absent in 145 normal individuals and patients with other autoimmune and neurological diseases. In addition, recombinant TAL-H stimulated proliferation and caused aggregate formation of peripheral blood lymphocytes from patients with MS. Remarkable amino acid sequence homologies were noted between TAL-H and core proteins of human retroviruses. Presence of crossreactive antigenic epitopes between recombinant TAL-H and HTLV-I/human immunodeficiency virus type 1 (HIV-1) gas proteins was demonstrated by Western blot analysis. The results suggest that molecular mimicry between viral core proteins and TAL-H may play a role in breaking immunological tolerance and leading to a selective destruction of oligodendrocytes in MS.

Nucleated assembly of Chlamydomonas and Volvox cell walls.

The Chlamydomonas reinhardtii cell wall is made up of hydroxyproline-rich glycoproteins, arranged in five distinct layers. The W6 (crystalline) layer contains three major glycoproteins (GP1, GP2, GP3), selectively extractable with chaotropic agents, that self-assemble into crystals in vitro. A system to study W6 assembly in a quantitative fashion was developed that employs perchlorate-extracted Chlamydomonas cells as nucleating agents. Wall reconstitution by biotinylated W6 monomers was monitored by FITC-streptavidin fluorescence and quick-freeze/deep-etch electron microscopy. Optimal reconstitution was obtained at monomer concentrations (0.2-0.3 mg/ml) well below those required for nonnucleated assembly. Assembly occurred from multiple nucleation sites, and faithfully reflected the structure of the intact W6 layer. Specificity of nucleated assembly was demonstrated using two cell-wall mutants (cw-2 and cw-15); neither served as a substrate for assembly of wild-type monomers. In addition, W6 sublayers were assembled from purified components: GP2 and GP3 coassembled to form the inner (W6A) sublayer; this then served as a substrate for self-assembly of GP1 into the outer (W6B) sublayer. Finally, evolutionary relationships between C. reinhardtii and two additional members of the Volvocales (Chlamydomonas eugametos and Volvox carteri) were explored by performing interspecific reconstitutions. Hybrid walls were obtained between C. reinhardtii and Volvox but not with C. eugametos, confirming taxonomic assignments based on structural criteria.

Neural nitric oxide synthase in the renal medulla and blood pressure regulation.

We studied the effect of selective inhibition of the neural isoform of nitric oxide synthase in the rat renal medulla in conscious Sprague-Dawley rats. Continuous renal medullar interstitial infusion of an antisense oligonucleotide complementary to the initiation region of the mRNA for neural nitric oxide synthase increased blood pressure 14 +/- 1 mm Hg in rats maintained on a high sodium intake. Medullary interstitial infusion of saline vehicle or a scrambled oligonucleotide probe failed to alter blood pressure in separate groups of high salt control rats. Renal medullary interstitial infusion of the antisense oligonucleotide significantly decreased the level of neural nitric oxide synthase in the renal medulla by 53 +/- 8% and decreased total renal medullary nitric oxide synthase activity by 28 +/- 8%. No alterations were detected in the levels of inducible nitric oxide synthase or beta-actin in the antisense oligonucleotide-infused rats. To confirm the antisense oligonucleotide data, we administered a mechanistically different inhibitor of neural nitric oxide synthase, 7-nitroindazole, to an additional group of rats maintained on a high salt diet. Direct renal medullary interstitial infusion of this selective enzyme inhibitor significantly increased mean arterial pressure (15 +/- 6 mm Hg) and decreased total renal medullary nitric oxide synthase activity by 37 +/- 12% in rats on a high sodium diet. The present experiments demonstrate a role for the neural isoform of nitric oxide synthase in the long-term control of blood pressure in the presence of a high salt diet.

Nitric oxide synthase activity and isoforms in rat renal vasculature.

Experiments were performed to quantify nitric oxide synthase (NOS) activity and identify the NOS isoforms present in the Sprague-Dawley rat renal vasculature. NOS enzymatic activity was measured by adding [(3)H]arginine to microdissected renal blood vessels and quantifying the conversion to [(3)H]citrulline by reverse-phase high-performance liquid chromatography. Total NOS activity was greatest in microdissected vasa recta (123+/-41 pmol. mg(-1). h(-1), n=5) and significantly less in glomeruli (46+/-9 pmol. mg(-1). h(-1), n=6) and afferent arterioles (42+/-10 pmol. mg(-1). h(-1), n=6) and averaged <5 pmol. mg(-1). h(-1) in arcuate (n=8) and interlobular (n=9) arteries. Addition of 1.0 mmol/L EDTA to the reaction decreased NOS activity to <5 pmol. mg(-1). h(-1) in afferent arterioles, glomeruli, and vasa recta (n=5 each), indicating that the NOS enzymatic activity in these segments is primarily a result of constitutive NOS. Both neuronal and endothelial NOS mRNA were identified in each vascular segment by reverse transcription-polymerase chain reaction, but inducible NOS mRNA was detected only in microdissected arcuate arteries. The present experiments indicate that the vasa recta, glomeruli, and afferent arterioles contain large amounts of calcium-dependent NOS enzymatic activity and that neuronal NOS and endothelial NOS mRNA are present in these segments.

Influence of dietary sodium intake on renal medullary nitric oxide synthase.

We previously reported that chronic systemic treatment of rats with a nitric oxide synthase inhibitor leads to a selective decrease in renal medullary blood flow, retention of sodium, and the development of hypertension. In the present studies, we used protein blotting techniques to determine the whole tissue distribution and relative quantitation of the different nitric oxide synthase isoforms in the renal cortex and medulla of Sprague-Dawley rats maintained on a low (0.4% NaCl) or high (4.0% NaCl) dietary salt intake. Neural, endothelial, and inducible nitric oxide synthase were readily detectable in homogenized renal inner and outer medullas. Only endothelial nitric oxide synthase was detectable in the renal cortex. Densitometric comparison of Western blots from equal amounts of total inner medullary tissue protein indicated that endothelial, inducible, and neural nitric oxide synthase were increased by 145%, 49%, and 119%, respectively, in rats maintained on a high NaCl diet compared with rats on a low NaCl diet. No significant differences in nitric oxide synthase levels were detected in the outer medulla, renal cortex, or aorta of rats maintained on low and high NaCl diets. In separate studies, continuous intravenous infusion of N(G)-nitro-L-arginine methyl ester (8.6 mg/kg per day) for 11 days in chronically instrumented rats increased mean arterial pressure 32 +/- 3 mm Hg in rats on a high NaCl diet (n=5) but only increased pressure 17 +/- 3 mm Hg in rats on a low NaCl diet (n=6). These data indicate that increased levels of renal medullary nitric oxide synthase may be important in the chronic adaptation to increased sodium intake.

Kinin actions on renal papillary blood flow and sodium excretion.

Infusion of bradykinin into the renal medullary interstitium (0.1 micrograms/min, n = 6) significantly increased renal papillary blood flow as measured by laser-Doppler flowmetry to 117 +/- 3% of control without altering cortical blood flow or blood pressure in anesthetized Munich-Wistar rats. In animals prepared for clearance studies, renal medullary bradykinin infusion did not alter total renal blood flow, glomerular filtration rate, or renal interstitial hydrostatic pressure but increased urine flow by 100%, sodium excretion by 111%, and fractional sodium excretion by 107%. No changes occurred in mean arterial pressure or contralateral kidney function during the interstitial bradykinin infusion. Blockade of endogenous kinin degradation by interstitial infusion of captopril (1 mg/hr) significantly increased papillary blood flow by 21 +/- 5% without altering cortical blood flow. Pretreatment with the nitric oxide inhibitor NG-nitro-L-arginine-methyl ester (2 micrograms/min, n = 7) eliminated the increase in papillary blood flow associated with either bradykinin or captopril infusion. We conclude that renal medullary interstitial infusion of bradykinin increases sodium and water excretion, which is associated with a selective increase in papillary blood flow by a nitric oxide-dependent mechanism.

Chronic sodium balance and blood pressure response to captopril in conscious mice.

The influence of chronic administration of the converting enzyme inhibitor captopril on blood pressure and sodium balance was evaluated in conscious Swiss Webster mice. Arterial pressure was measured with chronic indwelling catheters, and sodium balance was determined by infusing sodium intravenously in isotonic saline and collecting urine 24 h/d. Experiments to validate sodium balance measurements in mice demonstrated recovery of 100+/-3% of sodium intake under steady-state conditions (n=20 mice on 70 individual days, sodium intake range 160 to 1000 micromol/d). It was further demonstrated that mean arterial pressure, heart rate, and body weight were unaltered from 115+/-7 mm Hg, 646+/-12 bpm, and 34+/-0.6 g, respectively, as sodium intake was increased stepwise from 150 to 900 micromol NaCl per day. An additional validation group (n=7) demonstrated that daily and cumulative sodium balance can be accurately determined during and after the intravenous administration of an agent known to alter renal sodium handling (furosemide 50 mg. kg-1. d-1). Experiments were then performed to examine the influence of intravenous captopril infusion (40 mg. kg-1. d-1, n=7) in mice in which the daily sodium intake was fixed at approximately 200 micromol/d. This dose of captopril was determined to significantly decrease the pressor response to a 10-ng bolus of angiotensin I (Ang I) from 24+/-5 in the control state to 6+/-2 mm Hg (n=5). After 5 days of infusion of the converting enzyme inhibitor, mean arterial pressure significantly fell from 114+/-3 to 58+/-2 mm Hg, body weight significantly decreased from 36+/-1 to 33+/-1 g, and cumulative sodium balance significantly decreased to -270+/-55 micromol. These parameters returned toward control during 5 postcontrol days. Results of this study demonstrate that accurate sodium balance measurements can be obtained from individual conscious mice over a 5-fold range of sodium intake. The experiments also indicate that converting enzyme inhibition has a potent influence to lower blood pressure in normal mice; the hypotensive response appears to be due in part to increased urinary sodium excretion.

Renal medullary captopril delivery lowers blood pressure in spontaneously hypertensive rats.

We examined the contribution of renal medullary function to the maintenance of hypertension in spontaneously hypertensive rats by infusing captopril chronically into the renal medullary interstitial space of uninephrectomized rats. Changes in cortical and medullary blood flow were determined using a newly developed optical fiber implantation technique for laser-Doppler flowmetry. Renal medullary interstitial infusion of captopril (5 mg/kg per day) selectively increased medullary blood flow by 40% without altering renal cortical blood flow throughout the 5 days of captopril delivery. In association with the selective increase of medullary perfusion, a significant natriuresis was observed on the second day of the drug infusion, and urine osmolality was significantly reduced during the first 3 days of captopril infusion. Mean arterial pressure was significantly decreased by 20 mm Hg during 5 days of captopril infusion, and the chronic renal function curve was shifted to a lower level of arterial pressure compared with the control values when 0.9% sodium chloride saline vehicle was infused. Intravenously infused captopril at 5 mg/kg per day did not alter mean arterial pressure, excluding the possibility that the hypotensive effect of medullary captopril infusion was due to recirculation. In summary, chronic reduction of the elevated renal medullary vascular tone by medullary interstitial infusion of captopril reset the steady-state renal function curve and lowered arterial pressure in spontaneously hypertensive rats.

Role of nitric oxide in renal papillary blood flow and sodium excretion.

Renal medullary interstitial infusion of NG-nitro-L-arginine (120 micrograms/hr, n = 7) decreased papillary blood flow to 71 +/- 5% of control without altering outer cortical flow. Before NG-nitro-L-arginine infusion, interstitial acetylcholine administration (200 micrograms/hr) increased cortical and papillary blood flow to 134 +/- 6% and 113 +/- 2% of control, respectively. After NG-nitro-L-arginine administration, the vasodilator response to acetylcholine was abolished. In clearance experiments, renal medullary infusion of NG-nitro-L-arginine (120 micrograms/hr, n = 7) significantly decreased total renal blood flow by 10%, renal interstitial fluid pressure by 23%, sodium excretion by 34%, and urine flow by 39% without altering glomerular filtration rate, fractional sodium and water excretion, blood pressure, or urine osmolality. These data indicate that selective inhibition of nitric oxide in the renal medullary vasculature reduces papillary blood flow, which is associated with decreased sodium and water excretion. We conclude that nitric oxide exerts a tonic influence on the renal medullary circulation.

Inhibition of renal outer medullary 20-HETE production produces hypertension in Lewis rats.

Recent studies have indicated that a deficiency in the production of 20-hydroxyeicosatetraenoic acid (20-HETE) in the outer medulla of the kidney may contribute to the abnormalities in the renal handling of sodium and the development of hypertension in Dahl salt-sensitive rats. To determine whether a reduction in 20-HETE production in the outer medulla is sufficient to induce hypertension, an inhibitor of the renal metabolism of arachidonic acid by P450 enzymes, 17-octadecenoic acid (17-ODYA), was chronically infused directly into the outer medulla of the left kidney of uninephrectomized Lewis rats fed a high salt diet. Renal medullary interstitial infusion of 17-ODYA (400 pmol/min) reduced the formation of 20-HETE in the outer medulla of the infused kidney by 70% compared with values seen in the right kidney collected when the rat was uninephrectomized, but it had no effect on the production of 20-HETE in the renal cortex. After 5 days, mean arterial pressure rose from 115 +/- 2 to 142 +/- 2 mm Hg (n = 6) in the rats infused with 17-ODYA, while mean arterial pressure was not significantly altered in the rats infused with vehicle alone (116 +/- 1 versus 117 +/- 2 mm Hg, n = 6). These results suggest that inhibition of the renal metabolism of arachidonic acid by P450 enzymes in the outer medulla of the kidney is sufficient to induce the development of hypertension in Lewis rats fed a high salt diet and support the view that P450 metabolites of arachidonic acid play an important role in the regulation of renal function and the long-term control of arterial pressure.

The renal medulla and hypertension.

We review evidence supporting the conclusion that renal dysfunction underlies the development of all forms of hypertension in humans and experimental animals. Indexes of global renal function are generally normal in the early stages of most genetic forms of hypertension, but renal function is clearly impaired in long-established hypertension. Studies in our laboratory over the past decade summarized below have established that the renal medulla plays an important role in sodium and water homeostasis and in the long-term control of arterial pressure. Development of implanted optical fibers for measurement of cortical and medullary blood flows with laser-Doppler flowmetry and techniques for delivery of vasoactive compounds into the medullary interstitial space enabled us to examine determinants of medullary flow (nitric oxide, atrial natriuretic peptides, kinins, eicosanoids, vasopressin, renal sympathetic nerves, etc). We have shown in spontaneously hypertensive rats that the initial changes of renal function begin as a reduction of medullary blood flow in the absence of changes of cortical flow. Long-term medullary interstitial infusion of captopril, which preferentially increased medullary blood flow, resulted in a lowering of arterial pressure. In normal Sprague-Dawley rats, selective reduction of medullary flow with medullary interstitial or intravenous infusion of small amounts of NG-nitro-L-arginine methyl ester resulted in hypertension. These and other studies we review show that although blood flow to the inner renal medulla comprises less than 1% of the total renal blood flow, changes in flow to this region can have a major effect on sodium and water homeostasis and on the long-term control of arterial blood pressure.

Influence of eicosanoids on renal function of DOCA-salt hypertensive rats.

The present study examined the contribution of changes in the synthesis or degradation (or both) of renal eicosanoids to the alterations in renal hemodynamics observed in deoxycorticosterone acetate (DOCA)-salt hypertensive rats. Renal blood flow and glomerular filtration rate were markedly reduced in DOCA-salt hypertensive rats compared with values observed in control rats given water or saline to drink. The abnormalities in renal hemodynamics in the hypertensive rats were associated with an increase in the excretion of thromboxane B2, an increase in the release of thromboxane B2 from renal cortical tissue slices, and a diminished release of prostaglandin E2 (PGE2) from renal medullary tissue. Additionally, the urinary excretion of PGE2 and 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) and the release of 6-keto-PGF1 alpha from renal cortical and medullary tissue were elevated in rats with DOCA-salt hypertension. Since the excretion of PGE2 and 6-keto-PGF1 alpha and the release of 6-keto-PGF1 alpha by medullary tissue were also elevated in normotensive rats given 1% NaCl solution to drink, these latter changes probably were related to an elevation of sodium intake rather than to the development of hypertension. The functional significance of the alterations in the renal production of thromboxane in DOCA-salt hypertensive rats was evaluated by comparing the effects of a thromboxane synthesis inhibitor and a receptor antagonist on renal function in normotensive and DOCA-salt hypertensive rats. The administration of the thromboxane synthetase inhibitor furegrelate and the thromboxane receptor blocker SQ 29548 had no effect on renal hemodynamics in either group.(ABSTRACT TRUNCATED AT 250 WORDS)

Increase in renal medullary nitric oxide synthase activity protects from norepinephrine-induced hypertension.

Studies were performed in conscious Sprague-Dawley rats to determine the role of the alpha(2)-adrenergic receptor-mediated increase in the renal medullary nitric oxide synthase (NOS) activity as a counterregulatory mechanism of blood pressure control in response to increased renal adrenergic stimulation. A subpressor dose of norepinephrine (NE, 8 microg. kg(-1). h(-1)) was infused intravenously, and NOS activity was determined with arginine-citrulline conversion by high-performance liquid chromatography in renal cortical and outer and inner medullary tissues. It was found that after 7 days of intravenous NE infusion, NOS activity was significantly higher in both the outer and inner medullary tissues (158+/-45 versus 30+/-24 pmol. mg(-1). h(-1) [outer medulla] and 5.1+/-0.7 versus 2.0+/-0.5 nmol. mg(-1). h(-1) [inner medulla] for NE-treated versus control rats, respectively). To determine whether the increase of NOS activity was mediated through renal medullary alpha(2)-receptors, the receptor antagonist rauwolscine (RAU, 1 microg. kg(-1). min(-1)) was infused via an implanted renal medullary interstitial catheter, and the consequences of intravenous NE administration were evaluated. NOS activity was significantly lower in the RAU-infused animals and did not increase with infusion of NE. To determine the systemic effects of the renal medullary alpha(2)-receptors, studies were performed to determine the consequences of chronic intravenous infusion of subpressor amounts of NE in the presence and absence of renal medullary alpha(2)-receptor inhibition. Under conditions in which RAU was continuously infused into the renal medulla, the same subpressor dose of NE caused sustained and reversible hypertension (mean arterial pressure increased from 120+/-3 to 131+/-3 mm Hg). Chronic blunting of the renal medullary NOS activity with N(G)-nitro-L-arginine methyl ester (75 microg. kg(-1). h(-1)) also enabled NE to produce a significant rise in mean arterial pressure (from 117+/-2 to 134+/-4 mm Hg). We conclude that the hypertensive effects of moderate elevations of renal adrenergic activity were chronically buffered by the alpha(2)-receptor-mediated increase in NOS activity within the renal medulla.

Inducible nitric oxide synthase and blood pressure.

In the present studies, the influence of inducible nitric oxide synthase (NOS) inhibition with aminoguanidine on renal function and blood pressure was examined in rats. Intravenous aminoguanidine infusion (60 mg x kg-1 x hr-1) for 40 minutes to anesthetized Sprague-Dawley rats (n=7) resulted in no significant changes in mean arterial pressure or renal cortical blood flow, while medullary blood flow was slightly increased. Despite minimal effects on renal blood flow, urine flow was significantly decreased from 14.2+/-2.7 to 10.4+/-2.3 microL x min-1 x g kidney wt-1 during aminoguanidine infusion. To examine the possible effects of inducible NOS on blood pressure, aminoguanidine (10 mg x kg-1 x h-1 IV) was infused chronically into uninephrectomized rats maintained on a high salt (4.0% NaCl) diet. Mean arterial pressure significantly increased from 104+/-2 to 118+/-3 mm Hg after 6 days of aminoguanidine infusion (n=7) and returned to levels not different from those in the control group after 2 days of postcontrol infusion. Calcium-independent NOS activity in the renal medulla, a tissue that expresses inducible NOS in normal rats, was significantly decreased by 49% in the aminoguanidine-infused group (n=6) compared with that activity in the vehicle-infused control animals (n=6). In contrast, calcium-dependent NOS activity in the renal medulla was not significantly altered by aminoguanidine infusion, indicating specificity of aminoguanidine for inducible NOS in these experiments. In a final group of rats (n=5), oral L-arginine administration in drinking water (2% wt/vol) increased plasma arginine levels from 118+/-5 to 232+/-16 micromol/L and blocked the increase in arterial pressure after 6 days of aminoguanidine infusion. The present experiments provide evidence supporting a role for inducible NOS in the control of arterial pressure, possibly by renal tubular effects.

Iron attenuates nitric oxide level and iNOS expression in endotoxin-treated mice.

The effect of exogenous Fe-citrate complex (Fe doses of 120 and 240 micromol/kg) on nitric oxide (NO) production in vivo has been studied in blood and liver tissue of endotoxin-treated mice. Fe-citrate complex was administered to mice subcutaneously at the same time with intravenous injection of Escherichia coli lipopolysaccharide (LPS). Iron-dependent decrease in NO2-/NO3- and nitrosyl hemoglobin levels in blood of animals was detected at 6 h after LPS administration, suggesting systemic attenuation of NO generation. NO production in the liver tissue of LPS-treated mice was decreased after Fe administration judging from the amount of mononitrosyl-iron complexes formed in the tissue by diethyldithiocarbamate. The iNOS protein determination in the liver tissue of LPS-treated mice demonstrated iron-dependent inhibition of iNOS expression. We have found previously that exogenous iron does not affect systemic NO level when it is given at 6 h after LPS injection, i.e. after iNOS expression. This is a first report demonstrating iron-dependent iNOS down-regulation in endotoxin-treated mice.

Protein quality of two liquid-formula diets used in nursing homes.

The protein quality of the liquid diet Two Cal HN was evaluated by plasma amino acid (PAA) ratio and by chemical score. The PAA test was performed in young healthy men, elderly healthy men, and elderly institutionalized, tube-fed men. In all three groups the PAA ratio for tryptophan was negative, indicating a deficiency of this amino acid in the formula's protein. But the amino acid score for tryptophan based on the manufacturer's stated amino acid composition was adequate (0.90). To resolve the discrepancy between PAA test and amino acid score, the formula's protein was isolated and its amino acid composition analyzed. In three samples of Two Cal HN, the tryptophan content of the isolated protein averaged only 45% of the content stated in the manufacturer's product description. A similar discrepancy was then found for Isocal, another liquid diet used in nursing homes.

Osteopenia in the men of a Veterans Administration nursing home.

We measured by photon absorptiometry the bone density at six sites in 65 nursing home men aged 57-85 y and in 25 independent community men aged 57-80 y. Average bone density in the community men ranged from 97% to 105% of age-matched normal men. In the nursing home men these values ranged from 71% to 92% of age-matched normal men (p less than 0.05 for comparison with the community men). About 50% of the nursing home men but none of the community men had a value less than 70% of age-matched normal men at one or more sites. Among the institutionalized men bone densities at all six sites (in g/cm2) were significantly (p less than 0.05) and directly correlated with body weight but were not significantly correlated with height, age, principal or secondary diagnoses, continuing medications, or functional level.

Fasting plasma amino acids in elderly men.

The fasting amino acid profile in 22 healthy young men aged 25-35 y (group A) was compared with the fasting profile in 21 healthy independent men aged 65-85 y (group B), in 23 orally-fed nursing home men with dementia aged 65-92 y (group C), and in 17 tube-fed nursing home men with dementia aged 65-88 y (group D). Groups B, C, and D had significantly (p less than 0.05) lower levels of methionine and branched-chain amino acids than group A. Methionine was significantly lower in groups C and D than in group B. The ratio of essential to nonessential amino acids was significantly lower in groups B, C, and D than in group A. The data suggest that the intake of essential amino acids may often be suboptimal in both independent and institutionalized elderly men.

Intravenous lipid dose and incidence of bacteremia and fungemia in patients undergoing bone marrow transplantation.

Experimental data have implicated intravenous lipids as being immunosuppressive, yet evidence that lipids are associated with an increase in clinically documented infections is sparse. A prospective trial conducted in patients with hematologic malignancies who were undergoing bone marrow transplantation compared the incidence of bacteremia and fungemia during the first month after the transplant. Patients (n = 512) were randomly assigned to receive 6-8% (low dose) or 25-30% (standard dose) of total daily energy as a 20% lipid emulsion. An adaptive randomization scheme stratified for treatments that might influence infection outcome (hematopoietic growth factors, fluconazole, graft-versus-host disease prophylaxis with steroids, pentoxifylline, intravenous immunoglobulin, and total body irradiation). The transplant type (autologous, related family donor, or unrelated donor) did not differ in distribution between treatment groups. Of the evaluable patients (n = 482), 55 patients in the standard-dose lipid group developed bacteremia or fungemia compared with 54 in the low-dose lipid group. The log-rank test comparing the time to first infection found no association between the incidence of bacteremia or fungemia and intravenous lipid (P = 0.95). Similar results were found when analyzed as intent-to-treat (P = 0.98), when bacterial or fungal infections at all sites were included (P = 0.94), and when the observation period was extended to 60 d (P = 0.58 for blood infections, P = 0.77 for infections at all sites). These data indicate that moderate amounts of intravenous lipid rich in linoleic acid are not associated with an increased incidence of bacterial or fungal infections in patients undergoing bone marrow transplantation and receiving total parenteral nutrition.