We have investigated the pathophysiology and optimum treatment of PCM in Northern Thai children over the past 10 years and have developed what we consider to be an improved scoring system for the diagnosis of the three major forms of severe protein calorie malnutrition, namely: marasmus, marasmic kwashiorkor, and kwashiorkor. We feel that it gives a more definitive classification of these subgroups of PCM than any other system. It takes into account anthropometric and laboratory parameters, as well as clinical ones, and permits hospitals and metabolic units in various parts of the world to make better comparisons of their results.
Various aspects of the pathophysiology of PCM have been studied, including hematopoietic, endocrine, and metabolic aspects. We have developed a plan of therapy which has reduced mortality to 6-7%. In support of our plan of treatment, we have presented the clinical and biochemical data, and have demonstrated the protein and calorie requirements for the optimum treatment of severe protein calorie malnutrition.
The distribution of the three forms of protein calorie malnutrition clearly differs widely in affected countries throughout the world. In some, marasmus is more prevalent; in others, kwashiorkor. Investigators not familiar with the global distribution of the types of the disease may be regarding their particular population of children in a special way.

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A γ-carboxyglutamic acid (Gla)-containing protein was purified from rat femur cortical bone. The presence of 4 Gla residues in the rat protein was shown by amino acid analysis on alkaline and acid hydrolysates. The protein was extracted from rat cortical bone with 0.5 M EDTA (pH 7.6) and purified from the EDTA extracts by gel filtration on Sephadex G-100 and ion-exchange chromatography on DEAE-Sephadex A-25. The protein has a molecular weight of about 6, 000 on the basis of amino acid composition. The protein had 56 amino acid residues containing significant amounts of Asp, Glu, and Gla (acidic amino acids). The protein showed calcium-binding activity with K_d=0.2 mM and calcium-dependent electrophoretic mobility.

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A re-investigation of the use of the transketolase-TPP-effect for the assessment of the thiamine status of chronic alcoholics with various degrees of liver cirrhosis was carried out on 36 alcoholics. The extent of the liver damage in these patients was established by clinical examinations and biochemical tests.
Fourteen persons showed no significant hepatic abnormalities, 5 patients had compensated liver cirrhosis, 7 slightly decompensated, and 10 patients suffered from severely decompensated liver cirrhosis.
This investigation shows that the transketolase-TPP-effect is also present in patients even with severe liver cirrhosis and that a decrease of the TPPeffect can be observed after oral thiamine administration in these subjects. The TPP-effect of patients with compensated liver cirrhosis was markedly smaller than that of the subjects with slightly or severely decompensated cirrhosis. Accordingly a relationship exists between the TPP-effect and the degree of liver damage. No other correlations however could be established in this respect.

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Hydrolysis of FAD and FMN by rabbit blood was studied. The whole blood hydrolyzed both FAD and FMN to riboflavin. Blood plasma hydrolyzed FAD rapidly to FMN, but hydrolyzed FMN slowly to riboflavin. On the other hand, red cells hydrolyzed FAD slowly to FMN, but hydrolyzed FMN rapidly to riboflavin. These facts are explained by the localization of respective enzymes in blood plasma and cells.

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Some marketed vitamin tablets induce defects and fusion of body segments and appendages in the developing horseshoe crab.
α-Lipoic amide may be responsible for the induction, and the other vitamins are probably not directly responsible. α-Lipoic acid also induces the same malformations.
It is presumed that α-Lipoic amide and α-lipoic acid inhibit thioldisulphide exchange and this inhibition disturbs the morphogenetic movement. As a result, the monsters may be induced by treatment with vitamin tablets.

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In an attempt to clarify the nutritional enigma of the healthy strong physique of Papua New Guinea (PNG) highlanders who have a protein-deficient diet mainly composed of sweet potato, a pilot study was performed as follows with 10 volunteers of PNG highlanders, and with 8 Japanese controls, one group of whom took an experimental protein-deficient diet in Japan.
1. In 4 groups of subjects, i.e. adults of PNG highlanders, their children, Japanese controls who were having standard Japanese food (SPD), and those who were having a low protein diet (0.5g/kg) for 2 weeks (LPD), urea metabolism was investigated after oral administration of 15N urea. By tracing the cumulative excretion of ¹⁵N in urine successively for about 10 days after 15N urea administration, it was found that children of PNG highlanders can retain a large amount of ¹⁵N in the body, Japanese controls of LPD fairly well, PNG adult slightly and the Japanese controls of SPD the least of the four groups. It was demonstrated that the ¹⁵N atom% excess in the plasma protein of PNG adults, children, and Japanese control of LPD is maintained in the range of 0.02-0.05% fluctuating for 10 days after 15N urea administration. On the other hand, 15N atom% excess in plasma protein of Japanese control of SPD was within the scope of error (0.01%). ¹⁵N atom% excess in the lysine fraction of the hydrolysate of plasma protein was found in the range of 0.01-0.05% in a large number of cases of PNG subjects, and Japanese control of LPD, while it was not significantly detectable in Japanese controls of SPD. ¹⁵N atom% excess in essential and nonessential amino acids of the hydrolysate was significantly detectable in most cases of PNG subjects and Japanese controls of LPD, while not in the case of Japanese controls of SPD.
From discussions on the above findings it is presumed that 15N urea may be utilized in PNG highlanders and Japanese controls of LPD to produce amino acids, especially lysine in the intestine where the bacterial species are changed by a long-continued protein-deficient diet from those of Japanese controls of SPD. The possibility of urea recycling was thus verified.

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Time-courses of changes in the activities of liver and kidney glucose-6-phosphatase [EC 3. 1. 3. 9] and hepatic tryptophan pyrrolase [EC 1. 13. 1. 12; TPO] in rats pre-fed high-protein diets for 5 days and then shifted to zero-protein diets were studied. Liver glucose-6-phosphatase activity decreased 1 day after the dietary shift but then increased and remained significantly higher than the O day value for the next 2 days. Changes in liver glycogen were found to be intimately and inversely related to liver glucose-6-phosphatase activity. Changes in kidney glucose-6-phosphatase activity paralleled the pattern of changes observed in liver activity. An initial decrease in TPO activity was followed by increased enzyme activity up to the 3rd day of the dietary shift. Later there was a rapid fall in tryptophan pyrrolase activity. Changes observed in these specific enzyme proteins differed from those observed in total tissue proteins. Alterations in the activities of these enzymes and changes in other parameters are compared with those observed earlier with the reverse type of dietary shift.

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The effects of fasting and refeeding on hepatic Z protein were investigated in rats. When [U-¹⁴C]palmityl-CoA was added to the liver cytosol fraction from fat-free refed rats, more binding of labeled palmityl-CoA to the Z-protein region was found than in the case of fasted rats. Also the radioactivities in specific precipitations of the palmityl-CoA binding protein with anti-Z immunoglobulin G were higher in the refed rats. The Z protein which stimulated diacylglycerol acyltransferase may be involved in the change of triacylglycerol synthesis in fasted and refed rat livers.

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The effect of postnatal undernutrition on the catecholamine and serotonin contents of various parts of the brain of suckling rats was examined. Undernourishment was induced by increasing the litter size to 18 pups from day 1 to 21 after birth. In control pups, the total amounts of norepinephrine and dopamine in the whole brain increased greatly during the suckling period (norepinephrine: 17.7 ng at birth, 154 ng on day 10, and 420 ng on day 21; dopamine: 12.6 ng at birth, 269 ng on day 10, and 1, 022 ng on day 21). Similar, but less marked increases in the norepinephrine and dopamine contents of the brain were observed in malnourished pups. The norepinephrine contents of the forebrain, cerebellum, and brain stem of malnourished pups were comparable with those of normal pups on day 10 but the contents of the cerebellum and brain stem were significantly less than those of normal pups on day 21. Postnatal malnutrition also led to a significant decrease in the dopamine content of the forebrain. In contrast, the serotonin content of the brain of undernourished pups was significantly higher than that of controls. The activities of tyrosine hydroxylase in the forebrain and brain stem of control pups at the end of suckling period were significantly higher than those of undernourished pups (forebrain: 18.3 pmol in controls and 11.5 pmol in malnourished pups; brain stem: 12.3 pmol in controls and 9.8 pmol in malnourished pups). The tyrosine hydroxylase activity (pmol/g) correlated more closely with the norepinephrine content than with the dopamine or norepinephrine plus dopamine content. The tyrosine and phenylalanine contents of the brain were similar in the two groups. It is concluded from these findings that the catecholamine content of the brain is regulated by the enzyme activity rather than the levels of precursor amino acids.

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The influences of early changes in essential fatty acid deficiency on the structure and metabolism of lung phosphatidylcholine were studied.
In addition to general characteristics observed due to essential fatty acid deficiency such as significant decreases in linoleate and arachidonate, and concomitant increases in oleate and eicosatrienoate, a pronounced decrease in palmitate was noted in lung phosphatidylcholine, particularly in the 2-position. The decrease of palmitate in lung phosphatidylcholine was due to a similar decrease in disaturated classes, particularly in the dipalmitoyl species. These structural changes in phosphatidylcholine were found to be more significant in alveolar wash than in lung parenchyma and lamellar body fractions.
The specific activities of phosphatidylcholine and its disaturated classes in lung parenchyma and alveolar wash were significantly lower in the deficient state than in the controls at 2, 6, and 12 hr after the injection of [9, 10-3H]palmitate. However, relatively more of the phosphatidylcholine in the deficient state appeared in the alveolar space, disappearing more rapidly from the alveolar space than did the phosphatidylcholine in the controls. These results suggest that dietary linoleate may be a factor in regulating the amount of disaturated phosphatidylcholine in the lung, a principal component of lung surfactant, and also a factor in controlling the metabolism of alveolar phosphatidylcholine.

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To determine the effect of several oxidation stages of autoxidized methyl linoleate (AOML) on glutathione peroxidase (GSHPx), several experiments were carried out. In the first experiment, GSHPx was prepared from gastrointestinal tract and liver which were excised from mice, and the effects of AOML rich in hydroperoxides (HP) and that rich in the decomposition products of HP on the activity of GSH-Px were compared. The results indicate that GSH-Px indiscriminately metabolized both types of AOML without strict recognition of the specificity of the substrate. In the second experiment, it was noted that the inhibitory rate of GSH-Px by in vitro incubation with various AOML closely correlated with POV of the sample esters, but did not correspond with the toxicity revealed by intraperitoneal injection or intragastric feeding. In the next experiment, mice were given AOML with a low vitamin E diet for 45 days, and an increase of GSH-Px activity in gastrointestinal tract in proportion to the POV of the administered oil occurred, but the level in liver remained unchanged. On the contrary, the increase of GSH-Px activity by intraperitoneal injection of AOML in mice was marked in liver, but not in gastrointestinal tract. From these results, most of the orally administered AOML seemed to be reduced in the mucosa of the gastrointestinal tract. However, the marked increase of fluorescence in the lipid fraction of heart and kidney by oral administration of AOML suggested that the damage caused by it was not limited to gastrointestinal tract, but was spread through the whole body.

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