Threonine imbalance and the threonine requirement of the chicken

Experiments were conducted to determine the influence of dietary amino acids on the threonine requirement of chicks. A diet limiting in threonine and containing the equivalent of 20.6% crude protein was imbalanced by supplements of 0.9 to 1.5% L-tryptophan, 3.0% L-serine, a mixture of 2% each, leucine, isoleucine and valine or a 6.0% mixture of all essential amino acids but threonine. All amino acid supplements decreased the growth of chicks, and decreased food intake and/or efficiency of food utilization (P less than 0.05). Supplemental threonine prevented these effects in all cases except for 1.5% tryptophan in which the adverse effect of tryptophan was not prevented completely. The threonine requirement of Leghorn chicks was 0.69 to 0.72 percent of the diet when the diet did not contain the imbalancing amino acid supplements. We concluded that the threonine requirement of the chick is higher than previously reported, and is influenced by the amino acid content of the diet.     

Incidence of sexual dysfunction in neurologic disability

Patients and their families are frequently faced with changes in sexual behavior after the onset of a neurologic disability. Health professionals who familiarize themselves with the physical and psychological problems affecting sexuality can facilitate diagnosis and enhance the success of treatment programs. This article will review the available literature on the incidence of sexual dysfunction in neurologic disabilities frequently seen in the rehabilitation setting including stroke, brain injury, spinal cord injury and multiple sclerosis. Quality of life for survivors of these disorders may be improved through comprehensive rehabilitation programs that address the issues of sexuality.     

Taurine deficiency in the kitten: exchange and turnover of [35S] taurine in brain, retina, and other tissues

Kittens fed a purified diet containing partially-purified casein as the source of protein become taurine-deficient and develop retinal degeneration. The present studies report the exchange and turnover of taurine in different areas of brain, retina and other tissues and fluids of control and taurine-deficient kittens. The various tissues and fluids have different rates of exchange and different half-lives of taurine; taurine deficiency causes a range of changes in these parameters. Generally, tissues and fluids from taurine-deficient kittens accumulated more [35S] taurine and had a longer half-life of taurine than tissues and fluids from control kittens. Nine areas of brain were studied and, of these areas, olfactory bulb had the greatest concentration of taurine. Olfactory bulb resisted taurine depletion to a greater extent than other areas; and, in contrast to other areas of brain, in taurine-deficient kittens, it accumulated [35S] taurine for most of the experiment. Retina resisted taurine depletion and, in taurine-deficient kittens but not in control kittens, it accumulated [35S] taurine throughout the experiment. The amount of taurine conjugated to bile acids was unchanged by the taurine depletion, but the kinetic behavior was altered and was similar to that of retina. The results provide support for the suggestion that, in the kitten at least, taurine is most important for the functions of bile and retina and that taurine depletion affects retina before bile. Taurine may have special importance in olfactory bulb but not necessarily in other regions of brain.     

Family systems approach to sexual dysfunction in neurologic disability

The treatment of sexuality issues among the disabled is improved by the use of tools drawn from the Family Systems Model. The systems perspective lends an overview of the unique meaning of sex to the individual client as he or she has learned it in the context of the family. The construction of a genogram and an ecogram map the psychosexual patterns that are affected by the onset of a disability, suggesting treatment that exactly matches the needs of the persons involved. Use of the model is beneficial for many other reasons than the increased effectiveness of treatment, however. It is faster and more effective than many other modalities. It is a good tool for training teams to better understanding their own family sexuality messages. Lastly, picturing of the issues supports the development of research and therefore resources for the treatment of sexuality matters among the disabled.ACSW, BCD     

Association of pesticide exposure with neurologic dysfunction and disease

Poisoning by acute high-level exposure to certain pesticides has well-known neurotoxic effects, but whether chronic exposure to moderate levels of pesticides is also neurotoxic is more controversial. Most studies of moderate pesticide exposure have found increased prevalence of neurologic symptoms and changes in neurobehavioral performance, reflecting cognitive and psychomotor dysfunction. There is less evidence that moderate exposure is related to deficits in sensory or motor function or peripheral nerve conduction, but fewer studies have considered these outcomes. It is possible that the most sensitive manifestation of pesticide neurotoxicity is a general malaise lacking in specificity and related to mild cognitive dysfunction, similar to that described for Gulf War syndrome. Most studies have focused on organophosphate insecticides, but some found neurotoxic effects from other pesticides, including fungicides, fumigants, and organochlorine and carbamate insecticides. Pesticide exposure may also be associated with increased risk of Parkinson disease; several classes of pesticides, including insecticides, herbicides, and fungicides, have been implicated. Studies of other neurodegenerative diseases are limited and inconclusive. Future studies will need to improve assessment of pesticide exposure in individuals and consider the role of genetic susceptibility. More studies of pesticides other than organophosphates are needed. Major unresolved issues include the relative importance of acute and chronic exposure, the effect of moderate exposure in the absence of poisoning, and the relationship of pesticide-related neurotoxicity to neurodegenerative disease.     

Resveratrol prevents ammonia-induced mitochondrial dysfunction and cellular redox imbalance in C6 astroglial cells

Background: Resveratrol is a polyphenolic compound that presents several protective effects in the central nervous system, including gliotoxicity associated to hyperammonemia, a key element for the development of hepatic encephalopathy. In this condition, mitochondrial dysfunction leads to a reactive oxygen species (ROS) overproduction, which, in turn, exacerbates mitochondrial failure and causes cellular damage.

Objective: This study sought to determine whether prevention of mitochondrial dysfunction and the maintenance of cellular redox status by resveratrol contribute to its protective action toward ammonia toxicity.

Methods: C6 astrocyte cell line was pre-incubated in the presence or absence of resveratrol (100?μM) for 1 hour. After pre-incubation, resveratrol was maintained and 5?mM ammonia was added for 24 hours, followed by the evaluation of ROS production, mitochondrial functionality, antioxidant enzymatic and non-enzymatic defenses, energy metabolic parameters, and genotoxicity.

Results: We showed that resveratrol prevented the increase in ROS production, the decrease of mitochondrial membrane potential (ΔΨ_m), and bioenergetics deficit caused by ammonia in C6 astroglial cells. In addition, resveratrol avoided the ammonia-induced upregulation of NOX activity and impairment in enzymatic and non-enzymatic antioxidant defenses. Ammonia also induced DNA damage that was prevented by resveratrol, indicating its genoprotective effect.

Conclusions: In summary, our study demonstrates that resveratrol prevents ammonia-induced cytotoxicity, as well as supports the role of resveratrol on mitochondrial/cellular redox functionality.     

Threonine metabolism in sheep. 2. Threonine catabolism and gluconeogenesis in pregnant ewes

The irreversible loss rate (ILR) of glucose, bicarbonate and threonine were determined in six twin- and triplet-bearing ewes on three occasions during the last 6 weeks of gestation. Three of the ewes (group S) were given conventional rations of hay plus concentrates so that their blood ketone levels did not rise over this period. The other three ewes (group H) were given a fixed intake of hay throughout; their blood ketone levels rose, but remained at subclinical levels. The results are presented in the form of three-pool open-compartment models for each period. There was an increase in the glucose ILR for both groups over the 6-week period, but the over-all increase (mean +/- SE) was much greater (P less than 0.001) in group S (35.1 +/- 2.43 g carbon/d) than in group H (11.3 +/- 1.28 g C/d). Similarly, increases in bicarbonate ILR were also higher in group S (161 +/- 11.2 g C/d) than in group H (63 +/- 21.7 g C/d). However, whereas with group S ewes, receiving supplementary feed, this increase was progressive throughout the 6 weeks, with the group H ewes the increase which occurred over the last 3 weeks of gestation (56 +/- 26.3 g C/d) was much greater than that which occurred over the preceding 3 weeks (7 +/- 4.7 g C/d). This pattern was also evident in the oxidation of glucose to CO2. In contrast to the previously mentioned findings, neither threonine ILR nor the amount of threonine converted to glucose or catabolized to CO2 changed significantly over the 6-week period. The results are discussed in the light of findings presented in the previous paper that the amount of threonine used in catabolic processes can alter if a glucose-only sink is created in wether sheep.     

Leucine and isoleucine requirements of the kitten

In separate experiments the isoleucine and leucine requirements of the kitten were determined on the basis of growth and nitrogen retention. The dietary concentrations of isoleucine tested were (g/kg diet) 1.4, 2.2, 3.0, 3.8, 4.6 and 9.0 with adequate (12.0 g/kg diet) leucine. The levels of leucine tested were (g/kg diet) 5.0, 7.5, 9.0, 10.5, 12.0 and 20.0 in diets containing adequate (9.0 g/kg diet) isoleucine. In both experiments six male and six female kittens received each dietary level of isoleucine or leucine for periods of 10 d in a balanced 6 X 6 Latin-square experimental design. Asymptotic curves were fitted to the response relationships and the minimal dietary requirements for maximal response were estimated from the values at 0.95 of the asymptote. On this basis, the requirements for maximal growth were 6.2 g isoleucine/kg and 7.8 g leucine/kg diet. The requirements for maximal N retention were higher; 8.4 g isoleucine and 10.6 g leucine/kg diet. The isoleucine requirements suggested by this method are probably overestimations and might be slightly above 4.6 g/kg diet. Plasma isoleucine and leucine concentrations were not useful in estimating the requirements. Plasma leucine increased rectilinearly with increasing dietary leucine while the response of plasma isoleucine to increasing dietary isoleucine was non-rectilinear. Neither response relationship exhibited a breakpoint at the level of requirement. Below the suggested minimal requirement for leucine there were significant increases in the concentrations of isoleucine and valine in the plasma. Dietary isoleucine below the level of requirement had no effect on plasma valine and leucine. Dietary leucine had no effect on the plasma concentrations of methionine, phenylalanine and threonine, suggesting that the effect of decreasing dietary leucine on plasma isoleucine and valine is a result of decreased oxidation rather than decreased protein anabolism. In a separate experiment six kittens, presented a diet containing 2.2 g isoleucine/kg, developed crusty exudates around their eyes within 27 d and six kittens, presented diets containing 3.8 g isoleucine/kg, showed this clinical sign but with less severity within 47 d. Cultures of conjunctival swabs taken from the most severely affected kittens showed the presence of staphylococcal species, suggesting that in isoleucine-deficient kittens there was impaired resistance to these dermal microbes.     

Methionine requirement of the growing kitten, in the absence of dietary cystine

This study was conducted to determine the methionine requirement for maximal weight gain and nitrogen retention in growing kittens fed a 24% crystalline amino acid diet containing no cystine. Six male and six female kittens wee fed each of six levels of methionine, 0.45, 0.7, 0.8, 0.9, 1.0 and 1.5% of the diet, for 10 days in a 6 x 6 Latin square design. Diets were made isonitrogenous with alanine and were isocaloric with a calculated metabolizable energy of approximately 5.0 kcal/g. Food intake and body weights were recorded daily, and nitrogen balance for each cat in each 10-day period was determined. On the 7th day of each period, blood was drawn for subsequent analysis of plasma methionine concentrations. From growth response results, the methionine requirement in the absence of dietary cystine was estimated to be 0.07% of the diet for male and female kittens. On the basis of nitrogen balance results, the methionine requirement appeared to be slightly higher, at 0.75% of the diet for both sexes. Plasma methionine concentrations appear to increase exponentially with dietary methionine concentrations, and wee of limited usefulness in estimating the methionine requirement of the kitten in the context of the experimental protocol used here.     

Threonine, tryptophan and histidine requirements of immature beagle dogs

The threonine, tryptophan and histidine requirements of growing male Beagle dogs were determined using diets containing the equivalent of 14% protein as crystalline L-amino acids. For each amino acid the requirement was taken to be the minimum dietary quantity required for optimal growth, feed efficiency and nitrogen retention. In experiment 1 the threonine requirement was found to be provided by 0.52% or more dietary threonine. In experiments 2 and 3 the minimal dietary tryptophan and histidine requirements of immature dogs were estimated as 0.17 and 0.21%, respectively. The requirements for threonine and tryptophan are similar to those for growing rats. However, the histidine requirement of Beagles appears to be lower than that of rats.     

Vitamin E deficiency and psychomotor dysfunction in adults with primary biliary cirrhosis

The purpose of this study was to determine the prevalence of vitamin E deficiency in adults with chronic cholestatic liver disease and to quantify the association between their psychomotor performance and vitamin E status. In 42 female patients with primary biliary cirrhosis, 43.5% met two standard criteria for vitamin E deficiency. Vitamin E-deficient patients performed less well than did healthy control subjects on six of eight neuropsychologic tests of psychomotor capacity (p less than 0.01). Vitamin E-sufficient patients did not differ significantly from normal control subjects. Serum vitamin E concentrations were significantly lower in the group classified as significantly psychomotor-impaired by two independent neuropsychologists (blind to vitamin E status) whereas liver-injury measures failed to distinguish between these two groups. Patients with low serum vitamin E exhibited clinically evident neurologic abnormalities. These data suggest that vitamin E deficiency may, in part, underlie psychomotor and neurologic disturbance found in adult patients with chronic cholestatic liver disease.     

Acid-base imbalance and the skeleton

Summary Humans generally consume a diet that generates metabolic acids leading to a reduction in the concentration of systemic bicarbonate and a fall in pH. In vitro experiments indicate that this metabolic acidosis causes a release of calcium from bone that initially is simply due to physicochemical dissolution of the mineral. On a more chronic basis metabolic acidosis alters bone cell function; there is an increase in osteoclastic bone resorption and a decrease in osteoblastic bone formation. Concomitant with the dissolution and resorption of the bone mineral there is buffering of the addition protons by bone leading to restoration of the systemic pH. Interestingly respiratory acidosis, caused by an increase in the partial pressure of carbon dioxide induces far less bone dissolution and resorption and the additional hydrogen ions are not buffered by bone. As we age we are less able to excrete these metabolic acids due to the normal decline in renal function. We hypothesize that a slight, but significant, metabolic acidosis leads to greater loss of bone mineral and increase potential to fracture. Received: 13 September 2001, Accepted: 20 September 2001     

Threonine metabolism in sheep. I. Threonine catabolism and gluconeogenesis in mature Blackface wethers given poor quality hill herbage

In three experiments, mature Blackface wethers were given freeze-stored Agrostis festuca herbage by continuous feeder. In Expt 1, on separate occasions [U-14C]threonine, [U-14C]glucose and NaH14CO3 were infused over 12 h periods to obtain estimates of irreversible loss rate (ILR) of threonine, glucose and carbon dioxide in the plasma and of the exchange of C between these metabolites. In Expts 2 and 3, during periods when glucose and threonine metabolism were examined, glucose loss across the kidneys (23-29 g/d) was induced by infusion of phloridzin. Results from the four sheep used in Expts 1 and 3 are presented as three-pool models. They indicate that threonine ILR (7.8 g/d; 3.1 g C/d) was approximately three times the estimated rate of absorption of exogenous threonine (1 g C/d). Glucose ILR was approximately 76 g/d (mean +/- SE; 30.3 +/- 0.57 g C/d). Only 0.3% of the glucose-C (0.09 g/d) was derived directly from threonine-C (i.e. 3% of the threonine-C ILR). Bicarbonate ILR was 170 +/- 7.3 g C/d, and glucose contributed 11.1 +/- 3.52 g C/d to this, accounting for 51 +/- 4.4% of glucose-C ILR. Threonine contributed 0.20 +/- 0.026 g C/d to the bicarbonate-C ILR, accounting for only 6.4 +/- 0.87% of the threonine-C ILR. When, in Expts 2 and 3, phloridzin was infused, glucose ILR was increased by 28 +/- 1.5% and bicarbonate ILR was increased by 13 +/- 2.4%. Threonine ILR (3.1 g C/d) was not increased, but the metabolic distribution of threonine-C was altered. The transfer of threonine-C into glucose and CO2 was increased by 39 and 69% respectively to 0.125 and 0.45 g C/d, accounting for 4 and 13% of the threonine ILR respectively. Both technical and metabolic considerations which affect interpretation of these results in terms of rates of catabolism of threonine and of quantitative estimates of gluconeogenesis from threonine are discussed.     

Vitamin D deficiency in community older adults with falls of gait imbalance: an under-recognized problem in the inner city

INTRODUCTION: Recent reports suggest that vitamin D deficiency is both under-recognized and undertreated in the geriatric population. In particular, older adults with unexplained pain, falls, and gait disorders often may have osteomalacia from vitamin D deficiency. Currently, older adults are not screened for vitamin D status even when clinical skin suggest deficiency. Our pilot study determined the vitamin D status in older, inner city community adults with features suggestive of vitamin D deficiency. METHODS: The study was prospective and observational. Community-dwelling adults (> 60 years) from our ambulatory clinic or in-patient geriatric program, with features compatible with vitamin D deficiency (history of falls, gait imbalance, unexplained musculoskeletal pain, and/or fractures), were enrolled. IRB approval and signed informed consents were obtained. Following a history and physical exam, blood samples for vitamin D assay and routine chemistries were obtained. Additional information was collected on age, gender, race, dairy product intake, calcium and/or vitamin D supplement use, weekly sunlight exposure, season of exam (May-October vs. November-April), prior falls and fractures, musculoskeletal pain, and gait disturbances. RESULTS: Data were obtained from 48 patients (32F and 16M), mean age of 79 +/- 9 (SD) years (range 60-95). Seventy-seven percent of enrollees had gait disturbances, 77% had a history of falls, 29% had previous fractures and 6% had unexplained pain; 79% consumed milk daily, 25% took calcium supplements and 21% used vitamin D supplements (in a multivitamin or calcium supplement). Self-reported weekly exposure to sunlight ranged from 0 to 42 hours (clothing amount was highly variable). Fifty-four percent of this sample had sub-normal vitamin D status (serum vitamin D < 20 ng/mL). Patient age (P = 0.2287), gender (P=0.9270), exposure to sunlight (P=0.3493), season (P=0.573), and dairy intake (P = 0.735) were not associated with vitamin D status. However, 80% of vitamin D supplement users versus 37% of non-users had normal vitamin D status (P = 0.029) and 75% of calcium supplement users versus 36% of non-users had normal vitamin D status (P = 0.042). A logistic regression model determined that the use of vitamin D or calcium supplements decreased the risk of low vitamin D status by 94% and 93% (P = 0.009 and P = 0.010, respectively). CONCLUSION: In this pilot study of older adults with gait imbalance and falls, vitamin D deficiency (< 20 ng/mL) was observed in 54% of patients tested and previously unrecognized. Higher serum vitamin D levels appeared related to the use of vitamin D (in multivitamin or calcium supplements) suggesting that deficiency may be preventable and easily treated. As vitamin D deficiency is associated with substantial disability, the need for increased awareness to screen and prevent this disorder is evident.     

Threonine utilization is high in the intestine of piglets

The whole-body threonine requirement in parenterally fed piglets is substantially lower than that in enterally fed piglets, indicating that enteral nutrition induces intestinal processes in demand of threonine. We hypothesized that the percentage of threonine utilization for oxidation and intestinal protein synthesis by the portal-drained viscera (PDV) increases when dietary protein intake is reduced. Piglets (n = 18) received isocaloric normal or protein-restricted diets. After 7 h of enteral feeding, total threonine utilization, incorporation into intestinal tissue, and oxidation by the PDV, were determined with stable isotope methodology [U-(13)C threonine infusion]. Although the absolute amount of systemic and dietary threonine utilized by the PDV was reduced in protein-restricted piglets, the percentage of dietary threonine intake utilized by the PDV did not differ between groups (normal protein 91% vs. low protein 85%). The incorporation of dietary threonine into the proximal jejunum was significantly different compared with the other intestinal segments. Dietary, rather than systemic threonine was preferentially utilized for protein synthesis in the small intestinal mucosa in piglets that consumed the normal protein diet (P < 0.05). Threonine oxidation by the PDV was limited during normal protein feeding. In protein-restricted pigs, half of the total whole-body oxidation occurred in the PDV. We conclude that, in vivo, the PDV have a high obligatory visceral requirement for threonine. The high rate of intestinal threonine utilization is due mainly to incorporation into mucosal proteins.     

Early iron deficiency has brain and behavior effects consistent with dopaminergic dysfunction

To honor the late John Beard's many contributions regarding iron and dopamine biology, this review focuses on recent human studies that test specific hypotheses about effects of early iron deficiency on dopamine system functioning. Short- and long-term alterations associated with iron deficiency in infancy can be related to major dopamine pathways (mesocortical, mesolimbic, nigrostriatal, tuberohypophyseal). Children and young adults who had iron deficiency anemia in infancy show poorer inhibitory control and executive functioning as assessed by neurocognitive tasks where pharmacologic and neuroimaging studies implicate frontal-striatal circuits and the mesocortical dopamine pathway. Alterations in the mesolimbic pathway, where dopamine plays a major role in behavioral activation and inhibition, positive affect, and inherent reward, may help explain altered social-emotional behavior in iron-deficient infants, specifically wariness and hesitance, lack of positive affect, diminished social engagement, etc. Poorer motor sequencing and bimanual coordination and lower spontaneous eye blink rate in iron-deficient anemic infants are consistent with impaired function in the nigrostriatal pathway. Short- and long-term changes in serum prolactin point to dopamine dysfunction in the tuberohypophyseal pathway. These hypothesis-driven findings support the adverse effects of early iron deficiency on dopamine biology. Iron deficiency also has other effects, specifically on other neurotransmitters, myelination, dendritogenesis, neurometabolism in hippocampus and striatum, gene and protein profiles, and associated behaviors. The persistence of poorer cognitive, motor, affective, and sensory system functioning highlights the need to prevent iron deficiency in infancy and to find interventions that lessen the long-term effects of this widespread nutrient disorder.     

The utilization of ornithine and citrulline by the growing kitten.

Previous experiments have demonstrated that cats fed an arginine free purified amino acid diet (-Arg) could be protected from hyperammonemia by the inclusion of ornithine in the diet. Experiments reported here show that diets containing ornithine added at an equimolar (+Orn) or five times equimolar (+5 Orn) to replace arginine in the +Arg basal diet (2.0% Arg . HCl), were incapable of maintenance of body weight. Growing kittens fed a -Arg +Orn and -Arg +5 Orn diets had a daily rate of body weight loss of 6.5 +/- 0.6 and 7.9 +/- 2.2 g, respectively, which is somewhat less than the mean rate of weight loss of kittens fed diets devoid of most of the other amino acids indispensable for the kitten. When citrulline was added to a -Arg diet at an equimolar level to the arginine in the +Arg basal diet, growth rates were equivalent. The mean plasma free ornithine concentration of kittens receiving the -Arg +5 Orn diet was about 33 times higher than when they were fed the +Arg diet. For kittens fed the -Arg + Orn and -Arg +5 Orn diets the mean plasma free arginine was less (but significant only for the -Arg + Orn diet) than that observed for the basal diet. When the -Arg + Cit diet was fed, plasma free arginine concentration was similar and plasma free citrulline was about 18 times higher than when these cats were fed the basal diet.     

Estimation of the dietary iron requirement for the weanling puppy and kitten

An estimate of the dietary requirement for iron (Fe) has never been made for the growing canine or feline. Therefore, two assays were conducted in which weanling puppies or kittens were fed a casein-based, fiber-free diet containing 5, 30, 55, 80, 105, or 130 mg/kg Fe (supplied as FeSO4 X 7H2O) for 30 d. Blood samples were obtained and body weight measured at 10-d intervals. Hemoglobin concentration and hematocrit were determined and a one-slope broken-line model analysis of these two parameters was used to estimate the dietary Fe requirement for each species. For the puppy, 84 +/- 6.1 mg dietary Fe/kg was necessary to maximize hemoglobin concentration, whereas 81 +/- 5.0 mg dietary Fe/kg was the requirement estimate using hematocrit as the response criterion. For the kitten, requirement estimates were 77 +/- 8.1 and 80 +/- 7.2 mg dietary Fe/kg for maximizing hemoglobin concentration and hematocrit, respectively. We conclude that at least 80 mg dietary Fe/kg is required by growing dogs and cats fed a purified casein-dextrose diet.