Fumiko Yamato

Intracellular Magnesium and Adipokines in Umbilical Cord Plasma and Infant Birth Size

Many epidemiologic studies have disclosed that restricted fetal growth has been associated with an increased risk of insulin resistance in adulthood. We studied the relationship of intracellular magnesium ([Mg2+]i) in cord blood platelets to adipocytokine and birth size. The subjects were 20 infants with small for gestational age (SGA) and 45 infants with appropriate for gestational age (AGA). By using a fluorescent probe, we examined [Mg2+]i of platelets in the cord blood. Cord plasma insulin, IGF-I, ghrelin, adiponectin, plasminogen activator inhibitor-1 (PAI-1), and leptin levels were determined with the use of ELISA. Mean [Mg2+]i was lower in the SGA than in the AGA groups (p < 0.001). Adiponectin and IGF-I were also lower in the SGA than in the AGA, whereas PAI-1 was higher in the SGA. [Mg2+]i was significantly correlated with birth weight, birth length, and adiponectin. Birth weight was also correlated with cord plasma IGF-I, adiponectin, and leptin. Quantitative insulin sensitivity check index (QUICKI) was lower in the SGA group than in the AGA group. [Mg2+]i and adiponectin were correlated with QUICKI in all subjects. [Mg2+]i, as well as leptin and IGF-I, reflect the extent of fetal growth. Decreased [Mg2+]i may be involved in the underlying processes to insulin resistance.

Elevated intracellular calcium in neutrophils in patients with Down syndrome.

Background:  Neutrophils of patients with Down syndrome (DS) are known to have numerous abnormalities associated with diminished resistance to infection. The intracellular calcium (Ca2+i) acts as a second messenger and regulates diverse functions in many cell types. The purpose of the present study was to compare the intracellular calcium concentration ([Ca2+]i) at baseline and stimulated conditions in DS patients and in normal subjects to investigate [Ca2+]i regulation in neutrophils.

Slipped capital femoral epiphysis during the treatment of precocious puberty with a gonadotropin-releasing hormone-agonist: aetiological considerations

Slipped capital femoral epiphysis (SCFE) remains one of the most common hip disorders during adolescence, 78% of cases occurring in puberty, a period characterised by hormonal changes and the pubertal growth spurt [1,4]. Its aetiology is still unknown but appears to be multifactorial. Central precocious puberty(CPP)was reported in some patients with suprasellar arachnoid cysts (SAC) [3], and SCFE occurs in patients with CPP because of rapid growth and changes of growth hormone secretion. We describe a case of SCFE in a patient with CPP treated with a gonadotropin-releasing hormone (GnRH) analogue. A 7-year and 11-month-old boy, who was treated with endoscopic ventriculocisternostomy because of a SAC at 4 years of age, was referred to us with a 1-year history of rapid progression of precocious puberty. Physical examination at that time disclosed CPP and an enlarged penile size (70 mm) and testicular volume (12 ml) as well as pubic hair (Tanner stages III and IV, respectively). His bone age was 10 years and 11 months. Height, body weight and height velocity were 137 cm (+2.3SD), 34.0 kg (+1.7SD) and 13.5 cm/year, respectively (Fig. 1). Serum testosterone level was 212 ng/dl (reference range 3–13 ng/dl) and IGF-1 was 330 ng/ml (reference range 50–250 ng/ml). Peak levels of LH and FSH after an LHRH loading were 21.4 and 6.7 mIU/ml, respectively. After CPP was diagnosed,

Low calcium diet increases radical production of polymorphonuclear leukocytes from mice.

Although calcium is an essential mineral for bones, little is known about its effect on inflammatory or oxidative regulation. We hypothesize that calcium plays the role in the production of reactive oxygen species (ROS) and nitric oxide (NO) from polymorphonuclear leukocytes (PMNs). Our purpose was to determine the relationship of NO and ROS produced from PMNs, taking into account the role of calcium and magnesium in diet. Using flow cytometry, we compared ROS and NO production from PMNs after the stimulation by S. aureus or phorbol myristate acetate (PMA). PMNs taken from three murine groups were analyzed: C57BL/6 wild-type mice, low-calcium diet (Low Ca Group), or low-magnesium diet fed for 2 weeks. ROS production at baseline in the Low Ca Group was highest among the groups. PMA- and S. aureus-stimulated ROS production was also highest in the Low Ca Group. On the contrary, NO production at baseline in the Low Ca Group was lowest among the groups, while there was no significant difference among the groups in S. aureus-stimulated PMNs. A low-calcium diet increases ROS production from stimulated PMNs and decreases NO production at baseline. This finding suggests that calcium regulates ROS production from PMNs.

Intracellular magnesium of obese and type 2 diabetes mellitus children

IntroductionMagnesium is a critical cofactor in numerous enzymatic reactions. Diabetic patients and obese subjects are often reported to have intracellular magnesium ([Mg2+]i) deficiency. We studied the change of [Mg2+]i in obese children and children with type 2 diabetes mellitus (DM2) after educational intervention or treatment.MethodsA total of 25 subjects were included: 13 with simple obesity (10 male, 3 female; mean age 16±8 years, intervention period 1.0±0.6 years), 12 with DM2 (8 male, 4 female; mean age 15±3 years, medication period 1.1±0.7 years), and 16 controls (8 male, 8 female; mean age 17±7 years). By using a fluorescent probe, mag-fura-2, we examined the basal and insulin-stimulated [Mg2+]i of platelets in the blood. Plasma leptin, ghrelin, adiponectin, and resistin levels were determined with the use of enzyme-linked immunosorbent assay (ELISA).ResultsMean basal [Mg2+]i was lower in the obesity (160±65 μmol/L) and DM2 groups (140±30 μmol/L) compared with the control group (330±28 μmol/L). The elevated [Mg2+]i after insulin stimulation was also lower in these two groups (420±140 μmol/L, and 330±70 μmol/L, respectively) compared with the control group (690±270 μmol/L). In the DM2 group, the basal [Mg2+]i was significantly increased after treatment, while in the obesity group, stimulated [Mg2+]i was increased after intervention.ConclusionPlatelet [Mg2+]i increased after intervention in children with obesity or DM2.

Cerebral edema in a child with diabetic ketoacidosis before initial treatment

Cerebral edema is the most frequent and serious complication of diabetic ketoacidosis (DKA) in children. Cerebral edema occurs in approximately 1% of childhood DKA and is associated with high mortality and neurological morbidity. 1 – 3 The pathogenesis of the cerebral edema, however, is not understood fully. It is generally considered that the development of cerebral edema may be the result of an inappropriate treatment for DKA, a major factor of which is believed to be cellular swelling as a result of rapid osmolar changes occurring during i.v. infusion, 4 although there have been several contradictory studies. 2,5 We here report the case of a boy with newly diagnosed type-1 diabetes mellitus with cerebral edema before initiation of DKA therapy.

Angiotensin Type 1a Receptor Signaling Is Not Necessary for the Production of Reactive Oxygen Species in Polymorphonuclear Leukocytes

Background. Although angiotensin II (Ang II) has inflammatory effects, little is known about its role in polymorphonuclear leucocytes (PMLs). To elucidate the role of Ang II in PMLs ROS production, we examined hydrogen peroxide (H2O2), one of the ROS, and NO production in AT1a receptor knockout (AT1KO) mice. Methods and Results. PMLs were analyzed from Ang II type 1a receptor knockout mice (AT1KO) and C57BL/6 wild type mice. Using flow cytometry, we studied hydrogen peroxide (H2O2) production from PMLs after Staphylococcus aureus phagocytosis or phorbol myristate acetate (PMA) stimulation. Nitric oxide (NO) production in the AT1KO was low at basal and after phagocytosis. In the AT1KO, basal H2O2 production was low. After PMA or phagocytosis stimulation, however, H2O2 production was comparable to wild type mice. Next we studied the H2O2 production in C57BL/6 mice exposed to Ang II or saline. H2O2 production stimulated by PMA or phagocytosis did not differ between the two groups. Conclusions. AT1a pathway is not necessary for PMLs H2O2 production but for NO production. There was a compensatory pathway for H2O2 production other than the AT1a receptor.

Turner syndrome associated with ulcerative colitis.

We report the case of a 7-yr-old girl with Turner syndrome, ulcerative colitis (UC) and coarctation of the aorta. The diagnosis of Turner syndrome was made in early infancy (karyotype analysis 45, X). Growth hormone treatment was started at 3 yr and 2 mo of age. From the age of 4 yr and 5 mo, the patient suffered from persistent diarrhea with traces of blood and intermittent abdominal discomfort. As these symptoms gradually deteriorated, she was referred to our clinic at the age of 7 yr for further evaluation. Barium enema showed aphtha and loss of the fine network pattern in the descending colon and rectum. An endoscopic examination showed ulceration, edema, friability, and erythema beginning in the rectum and extending up to the splenic flexure of the descending colon. The histology of the descending colon area showed severe stromal infiltration of inflammatory cells. These endoscopic findings and the histological findings were consistent with UC. Thus, based on these findings, the patient was diagnosed as having UC. Mesalazine therapy was initiated at this time. The patient is currently being treated with mesalazine (1,000 mg/day) and abdominal symptoms and bloody diarrhea have disappeared. GH therapy was not interrupted during the therapy for UC. Retrospectively, growth hormone improved growth velocity (9 cm/year) during the first year of treatment, however from the age of 4 yr, growth velocity decreased (4–5 cm/yr) in spite of the GH treatment. Conclusion: Patients with Turner syndrome and gastrointestinal symptoms should be investigated for inflammatory bowel diseases. Growth velocity is useful for evaluating the presence of inflammatory bowel diseases and other systemic diseases.