Low-density lipoprotein profile changes during the neonatal period.

OBJECTIVE: To investigate natural change of low-density lipoprotein (LDL) profile during the neonatal period and the impact of gestational age and birth weight on those changes. STUDY DESIGN: We measured lipid composition in LDL fraction, LDL particle size and apolipoprotein B (apoB) concentration at birth, 5 days of age and 1 month of age in 63 healthy neonates that had 37 to 41-week gestational age. RESULT: Low-density lipoprotein cholesterol and apoB concentrations increased from birth to 5 days of age, and the concentration persisted at 1 month in breast-fed and mixed-fed infants. However, in formula-fed infants, the concentration decreased at 1 month. At 5 days of age, neonates had larger and more triglyceride (TG)-rich LDL particles than at birth. At 1 month of age, LDL particles were smaller and more cholesterol rich than at 5 days of age. Single regression analyses showed that gestational age had influenced the LDL profile at birth and 5 days of age, while at 1 month milk determined the profile. CONCLUSION: The number of LDL particles increased rapidly during the first 5 days of life, and the composition of LDL particles is modulated by TG content throughout the neonatal period. Gestational age and milk, rather than birth weight, determine postnatal changes in LDL profile.

Multiple activation of mitogen-activated protein kinases by purified independent CCN2 modules in vascular endothelial cells and chondrocytes in culture.

CCN2 consists of 4 distinct modules that are conserved among various CCN family protein members. From the N-terminus, insulin-like growth factor binding protein (IGFBP), von Willebrand factor type C repeat (VWC), thrombospondin type 1 repeat (TSP1) and C-terminal cysteine-knot (CT) modules are all aligned tandem therein. The multiple functionality of CCN2 is thought to be enabled by the differential use of these modules when interacting with other molecules. In this study, we independently prepared all 4 purified module proteins of human CCN2, utilizing a secretory production system with Brevibacillus choshinensis and thus evaluated the cell biological effects of such single modules. In human umbilical vascular endothelial cells (HUVECs), VWC, TSP and CT modules, as well as a full-length CCN2, were capable of efficiently activating the ERK signal transduction cascade, whereas IGFBP was not. In contrast, the IGFBP module was found to prominently activate JNK in human chondrocytic HCS-2/8 cells, while the others showed similar effects at lower levels. In addition, ERK1/2 was modestly, but significantly activated by IGFBP and VWC in those cells. No single module, but a mixture of the 4 modules provoked a significant activation of p38 MAPK in HCS-2/8 cells, which was activated by the full-length CCN2. Therefore, the signals emitted by CCN2 can be highly differential, depending upon the cell types, which are thus enabled by the tetramodular structure. Furthermore, the cell biological effects of each module on these cells were also evaluated to clarify the relationship among the modules, the signaling pathways and biological outcomes. Our present results not only demonstrate that single CCN2 modules were potent activators of the intracellular signaling cascade to yield a biological response per se, while also providing new insight into the module-wise structural and functional relationship of a prototypic CCN family member, CCN2.

Trace elements and mineral requirements for very low birth weight infants in rickets of prematurity.

To establish mineral and trace element requirements for very low birth it is important to prevent bone mineral disorder. Those infants fed mother's milk only are thought to be at higher risk of this disorder. Both calcium and phosphorus supplementation were thought to be needed to prevent it. Copper and zinc are important as cofactors of major enzymes involved in the synthesis of collagen. These trace elements especially zinc may not be enough for very low birth weight infants fed mother's milk. At present however the relationship between these trace elements and minerals, and bone metabolic disease in preterm infants is not completely clear.

[Improvement in the mechanical properties of artificial blood vessel suitable for the extracranial cerebral artery].

Saphenous vein interposition grafts have been commonly used for the reconstruction of occlusive lesions in the extracranial cerebral vessels, such as carotid or vertebral arteries. In contrast, cerebral revascularization using an artificial blood vessel has not been so common. This is due to the fact that conventional artificial blood vessels have been too firm or too rigid for use in the neurosurgery. Another reason is that the long term patency rate of small caliber artificial blood vessels has usually been inferior to that found in autologous vein grafts. The purpose of this study was to develop a soft and compliant artificial blood vessel suitable for cerebrovascular surgery. This new artificial blood vessel is made of polyurethane, porous in structure (porous polyurethane). Thus, multiple small-sized pores exist both in the inner and outer surfaces, and in the wall of the porous polyurethane graft. To test its mechanical properties, we evaluated stress-strain curves and compliance. In comparison to expanded polytetrafluoroethylene graft (Goretex), which has been one of the most commonly used artificial blood vessels in the cardiovascular surgery, the mechanical properties of the porous polyurethane graft more closely resembled those of the common carotid artery in dogs. Thus, porous polyurethane graft was shown to be a soft and compliant new artificial blood vessel. This means not only that it can be maneuvered with technical ease for anastomosis but also that there is a reduction of compliance-mismatch between the host vessel and the artificial vessel. Compliance mismatch has been documented as a major factor in the inducement of intimal hyperplasia, which causes a delayed occlusion.(ABSTRACT TRUNCATED AT 250 WORDS)

[A study of an autosomal recessive polycystic kidney disease with facial and skeletal abnormalities in rat].

Clinico-pathological studies were made on rats with polycystic kidney disease (PCK), a congenital renal disorder transmitted as an autosomal recessive trait and characterised by facial and skeletal anomalies, with the results summarised as follows: 1) Affected animals had a poor weight gain and slightly increased urinary excretion of low molecular weight protein from 2 months after birth, and developed polyuria and hypocalciuria 5 months postnatally. They had elevation of serum urea nitrogen, increased urinary excretion of urea nitrogen and hypoproteinemia 8 months postnatally though without showing elevated serum creatinine and died around 10 months of life. 2) Kidneys of chin rats appear granular in surface, enlarge little by little while preserving the entire kidney morphology; a small cyst is formed in the renal medulla 2 months postnatally, then enlarges gradually to encroach upon the cortex and grows to involve all cortical layers by 8 months of life. This cyst was revealed by lectin staining to be derived from the collecting ducts and was assumed to correspond, both morphologically and clinically, to the infantile or juvenile form of PCK in humans. Pathogenetic factors of the characteristic facies and skeletal abnormalities were also investigated.

Irreducible indirect inguinal hernia containing uterus, ovaries, and Fallopian tubes.

An indirect inguinal hernia containing the entire uterus, ovaries, and Fallopian tubes is extremely rare in pediatrics. The present report describes the very rare case of a 1-month-old girl with an irreducible indirect inguinal hernia containing the entire uterus, ovaries, and Fallopian tubes, and the successful surgical treatment of simple herniorraphy. We review the literature on this type of relationship between indirect inguinal hernia and hernial visceras of the uterus, ovaries, and Fallopian tubes and discuss the clinical features of this complication. Furthermore, the possible cause of indirect inguinal hernia containing the uterus, ovaries, and Fallopian tubes was explored.

Umbilical cord milking reduces the need for red cell transfusions and improves neonatal adaptation in infants born at less than 29 weeks' gestation: a randomised controlled trial.

OBJECTIVE: To investigate the effects of umbilical cord milking on the need for red blood cell (RBC) transfusion and morbidity in very preterm infants. PATIENTS AND METHODS: 40 singleton infants born between 24 and 28 weeks' gestation were randomly assigned to receive umbilical cord clamped either immediately (control group, n = 20) or after umbilical cord milking (milked group, n = 20). Primary outcome measures were the probability of not needing transfusion, determined by Kaplan-Meier analysis, and the total number of RBC transfusions. Secondary outcome variables were haemoglobin value and blood pressure at admission. RESULTS: There were no significant differences in gestational age and birth weight between the two groups. The milked group was more likely not to have needed red cell transfusion (p = 0.02) and had a decreased number (mean (SD)) of RBC transfusions (milked group 1.7 (3.0) vs controls 4.0 (4.2); p = 0.02). The initial mean (SD) haemoglobin value was higher in the milked group (165 (14) g/l) than in the controls (141 (16) g/l); p<0.01). Mean (SD) blood pressure at admission was significantly higher in the milked group (34 (9) mm Hg) than in the controls 28 (8) mm Hg; p = 0.03). There was no significant difference in mortality between the groups. The milked group had a shorter duration of ventilation or supplemental oxygen than the control group. CONCLUSION: Milking the umbilical cord is a safe procedure, reducing the need for RBC transfusions, and the need for circulatory and respiratory support in very preterm infants.

Why do we help a micropreemie to live?

UNLABELLED: Helping a "micropreemie" to live by aggressive interventions may sometimes seem unnatural. However, utilitarian assessment of benefits derived from lifesaving efforts for a micropreemie is considered inappropriate. The goal in treating premature infants has advanced from fetal salvage to achieving "intact survival", which represents a new therapeutic target. In this way, the record for lifesaving in extremely low-birthweight infants is continually being broken. Why do we help a micropreemie to live? Moral and ethical emotions are the underlying reasons for the aggressive care devoted to premature infants, including micropreemies. Such human feelings might even be considered the purpose of life. Human emotion is the impetus for aggressive efforts to improve the survival prospects of premature infants. The beautiful and delicate nature of a newborn is compelling. The high-order emotion of empathy for another's misfortune is also important. Most human emotions are related to an awareness of death, and micropreemies are near death. In Oriental thought, a human being is a growing product of nature. Forces of nature and changes in a living being follow nature's rules. First and foremost, an individual life is part of the long chain of existence beginning before the self and continuing beyond it. An immature human being, even a newborn, is simultaneously a complete entity and part of nature's long chain of being, which has a wholeness of its own that affirms a micropreemie's right to life. A fetus is a member of human society in the sense that there is an overall reverence for life as a quality that lives on. CONCLUSION: The limit that bioethics must not exceed is the sanctity of life. We believe that the birth of a micropreemie is an important and serious event. We profoundly wish that a micropreemie might live and thrive, because we on earth must live with the continual presence and imminence of death.

[A comparative study of C19 steroid-induced hypertension and deoxycorticosterone acetate (DOCA)-salt hypertension].

In order to evaluate the hypertensinogenic action of 19-hydroxyandrostenedione (19-OH-AD), which has been reported to be an amplifier of mineralocorticoid, the changes in several humoral factors were observed in 19-OH-AD treated rats as compared to those in DOCA hypertensive rats. Twenty-five male Wistar rats were castrated at 11 weeks of age, and the experiments were begun at 12 weeks of age. The rats were divided into 3 groups. The control group (n = 8) was given an s.c. injection of 0.2 ml of sesame oil. The 19-OH-AD group (n = 10) was injected s.c. with 10 mg of 19-OH-AD dissolved in 0.2 ml of sesame oil, and the DOCA group (n = 8) was injected s.c. with 10 mg of DOCA dissolved in 0.2 ml of sesame oil three time weekly. The urine was collected for a period of 24 hours, and the urine volume, and urinary excretions of electrolytes, prostaglandin E2 (PGE2), kinin and catecholamine were measured before and after the start of the experiment. The systolic blood pressure (S.B.P.) was measured by the tail-cuff method. The S.B.P. values before and at 9 weeks after the start of the experiments were 136.7 +/- 3.8 and 156.0 +/- 2.6 mmHg in the 19-OH-AD group, and 140.6 +/- 5.6 and 179.3 +/- 5.5 mmHg in the DOCA group, respectively. Body weight, which was elevated in both groups, was higher in the 19-OH-AD group than in the DOCA group. Water intake and urine volume were significantly (p less than 0.001) increased only in the DOCA group. The urinary Na/K ratio was significantly (p less than 0.001) elevated in the DOCA group as compared to that in the other two groups. However, there was no significant difference in urinary Na/K ratio between the control and 19-OH-AD groups. The urinary PGE2 and kinin excretions were significantly (p less than 0.01) increased in the DOCA group but did not change appreciably in the 19-OH-AD group. The urinary catecholamine excretion was significantly increased in the DOCA group. However, there were no differences in the catecholamine excretion between the control and 19-OH-AD groups.(ABSTRACT TRUNCATED AT 400 WORDS)

Platelet deposition onto polymeric surfaces during shunting.

In an attempt to develop blood-contacting tubes that can be applied for short-term uses with a reduced heparin concentration or, ideally, without heparinization, we evaluated the blood compatibility of polymeric materials with a rabbit ex vivo shunt model. The shunt tubes employed were made of silicone, plasticized poly(vinyl chloride) (PVC), and segmented poly(ether urethane) (PU). In addition, two kinds of surface-modified tube were used: poly(vinyl alcohol) (PVA)-coated PVC and poly(dimethylacrylamide) (PDMAA)-grafted PU. The ex vivo shunt results correlated well with protein adsorption and platelet adhesion in vitro. The following order for the extent of platelet deposition was given, irrespective of the blood-contacting duration: PDMAA-grafted PU < PVA-coated PVC < PU < silicone, PVC. It is likely that many platelet aggregates detached from the PVA-coated PVC surface. For PDMAA-grafted PU, no trace of detachment of aggregates could be detected on any of the SEM photographs. The number and morphology of blood cells adhered onto the tube surfaces during ex vivo shunting were dependent on the kind of polymer surfaces, the blood exposure time, and the flow rate of blood.

Low doses of endothelin-3 elicit endothelium dependent vasodilation which accompanies with elevation of cyclic GMP.

Low doses (10(-16)-10(-10) M) of endothelin-3 (ET-3) elicited continuous vasodilations of mesenteric arteries preconstricted with norepinephrine (NE) but not with KCl. In arteries perfused with Ca2+ free solution, ET-3 did not affect the perfusion pressure. In endothelium-denuded arteries preconstricted with NE, ET-3 significantly elevated the perfusion pressure in a dose-related manner. The levels of cyclic GMP and cyclic AMP from the intact arteries were significantly elevated by ET-3; the cyclic GMP elevasion disappeared with methylene blue. Following endothelium-denudation, cyclic GMP elevation was abolished, but cyclic AMP elevation was unaffected. Levels of 6-Keto-PGF1 alpha in the arteries were not changed appreciably by ET-3. These data indicate that the vasodilating effects of ET-3 depend on the presence of extracellular Ca2+ and the existence of endothelium. They are accompanied by elevations of cyclic nucleotides and the elevation of cyclic GMP depends on the endothelium. It is possible that the vasodilating effects of low doses of ET-3 are associated with endothelium-derived relaxing factor.

Cyclic GMP formation of resistance vessel in the development of hypertension in spontaneously hypertensive rats.

We investigated the basal levels and responses of cyclic GMP (cGMP) derived from perfused mesenteric arteries to acetylcholine (ACh) and sodium nitroprusside (SNP) in spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY) at different ages, in order to evaluate the basal and stimulated release of endothelium-derived relaxing factor (EDRF) from the resistance vessel during the development of hypertension. The mesenteric arteries were removed from 8-, 12- and 20-week-old WKY and SHR, and were perfused with Krebs-Henseleit solution containing 0.2 mM isobutyl methyl xanthine. The effluents from the perfused arteries were corrected before and after infusions of graded doses of ACh or SNP, and the levels of cGMP were measured. The basal levels of cGMP from the mesenteric arteries in the 12- and 20-week-old SHR were significantly lower than those in age-matched WKY. A negative correlation was observed between the basal levels of cGMP and the systolic blood pressure in SHR, but not in WKY, among all ages. On the other hand, there were no differences in the responses of cGMP to infusion of ACh between the WKY and SHR at each age. Moreover, the responsiveness of cGMP to infusion of SNP in the 12-week-old SHR was much higher than that in age-matched WKY. These data suggest that the basal cGMP formation in the arteries which may reflect the basal release of EDRF is reduced in older SHR and is associated with the development of hypertension, and that the stimulated release of EDRF is not associated with the development of hypertension.