Toshiro Nakamura

Mild to moderate zinc deficiency in short children: Effect of zinc supplementation on linear growth velocity

Twenty-one prepubertal, short Japanese children (11 boys) without endocrine abnormalities were identified as having mild-to-moderate zinc deficiency by zinc kinetics studies (zinc body clearance > or = 20 ml/kg per hour). Only one child had a serum zinc level < 65 micrograms/dl (cutoff level). A total of 10 children (5 boys) received 5 mg/kg per day of zinc sulfate for 6 months; 11 untreated children (6 boys) served as control subjects. During treatment, calorie intake (p < 0.01), growth velocity (p < 0.01), serum zinc, calcium, and phosphorus concentrations, alkaline phosphatase activity (p < 0.001), percentage of tubular reabsorption of phosphorus (p < 0.05), ratio of maximal tubular reabsorption rate for phosphorus to the glomerular filtration rate (p < 0.05), serum osteocalcin level (p < 0.01), and plasma insulin-like growth factor 1 (p < 0.05) were significantly increased, but urinary excretion of growth hormone was unchanged in the zinc-supplemented group. All these values were unchanged in the untreated children. We conclude that zinc supplementation is effective for inducing growth in short children with zinc deficiency, and that body zinc clearance tests facilitate detection of marginal zinc deficiency.

Kinetics of Zinc Status in Children With IDDM

Objective To ascertain zinc deficiency in patients with insulin-dependent diabetes mellitus (IDDM) and evaluate the relationship between zinc clearance and body height velocity. Research Design and Methods Six boys and 11 girls with IDDM and zincuria and glycosuria were studied. Study quality and specific descriptive information concerning relationship and outcome measurement were assessed. Results The values of total-body zinc clearance in IDDM patients were higher than in the control subjects (24.6 ± 1.8 vs. 15.1 ± 0.6 ml · kg−1.h−1, P < 0.01). There was a negative correlation between body zinc clearance values and height velocity in IDDM patients. Conclusions Patients with IDDM have a secondary zinc deficiency, and normal growth may be stunted.

Zinc kinetics in patients with bone demineralization due to physical immobilization.

To examine the relationship between zinc (Zn) status and bone demineralization, a body Zn kinetics study was performed with 74 (37 male, 37 female) disabled persons ranging in age from 16 to 45 years. Three groups were classified according to degree of limited mobility: group 1 (n = 23), capable of walking; group 2 (n = 20), capable of crawling; group 3 (n = 31), bed-ridden, Serum Zn levels were similar in the three groups, whereas body Zn clearance and the distribution of Zn showed a pattern [group 1 < group 2 < group 3 (p < 0.01, p < 0.05)], with the reverse in cases of bone mineral density (BMD) [group 1 > group 2 > group 3 (p < 0.01)]. Renal handling of Zn did not different among the three groups. There was a negative correlation between Zn distribution volume and values of BMD (p < 0.005, gamma = 0.387). Thus, various organs, as well as the skeleton, are Zn deficient in immobilized patients.

Nutritional Copper Deficiency in Severely Handicapped Patients on a Low Copper Enteral Diet for a Prolonged Period: Estimation of the Required Dose of Dietary Copper

Six cases of nutritional copper deficiency were identified in a nursery institute for severely handicapped patients. All had been on prolonged enteral feeding of a copper-deficient diet and all had abnormalities related to the copper deficiency. Two of them had leukopenia, with or without macrocytic and normochromic anemia. After the oral administration of copper, the clinical and laboratory observations including neutrophil counts and serum copper and ceruloplasmin levels showed a complete recovery. The dietary copper requirement was estimated to be approximately 20 micrograms/kg/day for these patients, based on the correlation between the dietary copper intake and the levels of copper in the serum.

Zinc clearance correlates with clinical severity of Crohn's disease

After peroral and intravenous loading of zinc in 10 patients with Crohns disease, a kinetic analysis of serum zinc was carried out. The patients were divided into two groups depending on the clinical activity indices (group A: five with active form and group B: five with inactive form). The mean level of serum zinc was significantly reduced in group A patients, but not in group B, when compared to findings in control subjects. A significant reduction in AUCpo (area under the concentration vs time curve by peroral administration), accompanied by increased zinc clearance (ClZn) was also found in group A but not in group B. The ClZn significantly correlated with clinical activity indices. Absorption efficiency, the ratio of AUCpo/AUCiv (area under the concentration vs time curve by intravenous administration), was similar in group A, group B, and the control. Therefore, the absorption of zinc in patients with the disease seems to be intact, regardless of whether they have the active or inactive form of Crohns disease. The hypozincemia seen in patients with Crohns disease is presumably related to an accelerated turnover rather than to a malabsorption of zinc.

Zinc status relates to hematological deficits in women endurance runners.

OBJECTIVE We investigated zinc (Zn) status and effect of Zn supplementation in relation to iron deficiency anemia in Japanese female endurance runners in an attempt to define the role of Zn in hematologic abnormalities. METHODS After estimating zinc status based on total body zinc clearance (ClZn), 21 women runners were divided into two groups: one group was of normal Zn status (group A), and the other was a Zn deficient group (group B). We then compared the hematological status in both groups, before and after iron or iron plus Zn supplementation. RESULTS Number of red blood cells (RBC), serum concentrations of hemoglobin (Hb), iron and total protein in Group A were significantly higher than those in Group B, while serum Zn levels were similar in both groups. There was a significantly positive correlation between ClZn and total protein, and hemoglobin in all subjects. After combined treatment with ferrous citrate and zinc sulfate, the concentrations of total protein, iron, RBC, and Hb were significantly increased in the four Zn deficient runners. CONCLUSION Zn status to some extent can account for hematological abnormalities in female endurance runners.

Anti-neutrophil antibodies in patients with nutritional copper deficiency

Ten patients with nutritional copper deficiency were studied in terms of neutrophil counts and anti-neutrophil antibodies (ANA). In four patients with severe or moderate copper deficiency, the production of ANA was positive and two patients with a severe deficiency had neutropenia. After copper supplementation, ANA titres became negative or were reduced in all patients and neutrophil counts reverted to normal in two patients. It thus appears that copper deficiency is linked to the production of ANA, a condition which partly responsible for neutropenia.

A missense mutation (GGC[435Gly]-->AGC[Ser]) in exon 8 of the CYP11B2 gene inherited in Japanese patients with congenital hypoaldosteronism.

Objectives: To clarify the underlying molecular mechanism of corticosterone methyl oxidase type II (CMO II) deficiency, Japanese patients newly diagnosed with CMO II deficiency were investigated. Methods: We analyzed the patients’ genomic DNA sequence on all 9 exons of the CYP11B2 gene. In addition, restriction fragment length polymorphism (RFLP) analysis and expression studies were performed. Results: The analysis showed that the patients homozygously retained a missense mutation, GGC[435Gly]→AGC[Ser], in the CYP11B2 gene. Expression studies indicated that the steroid 18-hydroxylase/oxidase activities of the mutant enzyme were substantially reduced. Conclusion: These results support the hypothesis that this mutation causes CMO II deficiency in the patients, and are in accordance with our theory that the partial loss of P-450C18 activities causes CMO II deficiency.

Sex-determining region Y (SRY) in a patient with 46,XX true hermaphroditism

SummaryUsing a polymerase chain reaction method, a search for Y-specific DNA sequences was made in samples derived from tissues of a 46,XX true hermaphrodite. We found a sequence of SRY in the ovotestis, skin and leukocytes. Other DNA sequences, which covered the pseudoautosomal boundary region, amelogenin gene and DYZ1 locus of Y-chromosome were not detected. The SRY gene detected in the patient by the polymerase chain reaction was not detected by Southern blot analysis, using the SRY fragment as a probe. These findings suggest that in the patient there is a mosaicism of cells with and without part of the Y chromosome, including the SRY sequence. As the SRY sequence was responsible for the development of the gonadal primordium to the ovotestis, SRY seems essential for gonadal differentiation in testis development.

Infusion of zinc inhibits serum calcitonin levels in patients with various zinc status.

SummarySerum concentrations of ionized calcium, parathyroid hormone, and calcitonin were measured during zinc infusion in patients of short stature (n=15); those with insulin-dependent diabetes mellitus (n=13); and agematched controls (n=10). The increase in serum zinc concentrations after zinc infusion resulted in a decrease in the serum calcitonin concentrations but not in concentrations of ionized calcium and parathyroid hormone. A significant negative correlation was obtained between body zinc clearances and decreases in serum calcitonin levels at 60 minutes after the infusion of zinc. Thus, we found a relationship between infusion of zinc and the regulation of calcitonin secretion. We propose that an increase in the serum zinc pool plays a definite role in inhibiting calcitonin secretion from thyroid tissue.