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Biomedical subjects

I Seri

Publications and source records attributed to I Seri.

At least 19 recordsLinked to original sources
PubMed2001

Circulatory support of the sick preterm infant.

In the majority of preterm infants, especially during the immediate postnatal period, hypotension is primarily caused by abnormal peripheral vasoregulation and/or myocardial dysfunction and not by absolute hypovolemia. Therefore, aggressive volume resuscitation is not warranted and is potentially harmful. Volume support should be limited to 10-20 ml/kg of isotonic saline administration and, if sustained normalization of the blood pressure cannot be achieved, early initiation of cardiovascular pharmacological support is recommended. However, in preterm infants who present with an identifiable volume loss, the kind of fluid lost should first be replaced. Due to its beneficial cardiovascular and renal actions, dopamine is the drug of choice in the treatment of neonatal hypotension. Dobutamine may be added if myocardial dysfunction persists or develops during dopamine treatment. In some critically ill preterm infants, escalation of dopamine therapy or addition of epinephrine is necessary yet not always effective indicating the development of pressor resistant hypotension. Downregulation of cardiovascular adrenergic receptors and some degree of adrenal insufficiency may explain this phenomenon. In these patients, a brief course of steroid treatment may be successful in stabilizing the cardiovascular status and decreasing the requirement for pressor/inotrope support. However, well-designed randomized and controlled clinical trials are needed in the future to determine the effectiveness and potential short- and long-term side effects of steroid administration in preterm infants with pressor-resistant hypotension. In summary, management of the critically ill hypotensive preterm infant remains challenging and requires a better understanding of the pathophysiology of neonatal shock and improvements in our ability to evaluate cardiac output, organ blood flow, and tissue perfusion at the bedside.

Cardiotonic Agents↗
PubMed2001

Controversies in the diagnosis and management of hypotension in the newborn infant.

Although close to half of the newborns admitted to neonatal intensive care units receive treatment for "hypotension," the normal physiologic blood pressure range ensuring appropriate organ perfusion in the neonate is unknown. Thus, the decision to treat hypotension in the newborn is based on statistically defined gestational and postnatal age-dependent normative blood pressure values and physicians' beliefs rather than on data bearing physiologic reference. Dopamine is the most widely used sympathomimetic amine in the treatment of neonatal hypotension, and it is more effective than dobutamine in raising blood pressure. Volume administration is less effective in the immediate postnatal period, and its extensive use is associated with significant untoward effects, especially in preterm infants. During the course of their disease, some of the sickest hypotensive newborns become unresponsive to volume and pressor administration. This phenomenon is caused by the desensitization of the cardiovascular system to catecholamines by the critical illness and relative or absolute adrenal insufficiency. The findings that steroids rapidly up-regulate cardiovascular adrenergic receptor expression and serve as hormone substitution in cases of adrenal insufficiency explain their effectiveness in stabilizing the cardiovascular status and decreasing the requirement for pressor support in the critically ill newborn with volume-and pressor-resistant hypotension. Finally, despite recent advances in our understanding of the pathophysiology and management of neonatal hypotension, there are few data on the impact of the treatment on organ blood flow and tissue perfusion and on neonatal morbidity and mortality.

Blood Pressure↗
PubMed2001

Cardiovascular effects of hydrocortisone in preterm infants with pressor-resistant hypotension.

OBJECTIVE: To study the cardiovascular effects of hydrocortisone in preterm infants with hypotension unresponsive to volume and pressor administration. STUDY DESIGN: Retrospective review of the cardiovascular response to 23 courses of hydrocortisone administration during the first day of treatment in 21 preterm infants (gestational age: 26.9 +/- 3.9 weeks; postnatal age: 11.3 +/- 13.1 days). Hydrocortisone (2 mg/kg/d in 16 patients and 3-6 mg/kg/d in 5 patients) was administered when dopamine (22.2 +/- 11 microg/kg/min, range: 8-60) alone (n = 16) or in combination with dobutamine (8.4 +/- 4.9 microg/kg/min, range: 5-20, n = 7) and/or epinephrine (0.38 +/- 0.56 microg/kg/min, range: 0.01-1.2, n = 4) failed to normalize blood pressure. RESULTS: Mean blood pressure increased from 29.3 +/- 4.1 to 34.1 +/- 5.2, 38.0 +/- 8.0, and 41.8 +/- 6.6 mm Hg by 2, 4, and 6 hours of hydrocortisone administration, respectively, and remained stable thereafter. Urine output increased despite a decrease in fluid administration during the first day of hydrocortisone treatment. The dose of dopamine and the number of patients receiving dobutamine and/or epinephrine also decreased during the same period. Eighteen of the 21 patients survived. CONCLUSIONS: Preterm infants with volume- and pressor-resistant hypotension respond to hydrocortisone with rapid normalization of the cardiovascular status and sustained decreases in volume and pressor requirement.

Blood Glucose↗
PubMed2000

Developmental changes in erythrocyte Na(+),K(+)-ATPase subunit abundance and enzyme activity in neonates.

AIM: To study the relation between erythrocyte Na(+),K(+)-ATPase subunit isoform composition, Na(+),K(+)-ATPase activity, and cation pump function in preterm and term neonates. DESIGN: Erythrocyte Na(+),K(+)-ATPase subunit isoform abundance, Na(+),K(+)-ATPase activity, and cation pump function were studied in blood samples obtained from 56 preterm neonates of 28-32 weeks gestation (group 1), 58 preterm neonates of 33-36 weeks gestation (group 2), and 122 term neonates (group 3) during the first two postnatal days. RESULTS: alpha(1) isoform abundance was higher and beta(2) isoform abundance was lower in group 1 than in group 3 (p = 0.0002). alpha(2) and beta(1) isoform abundance did not change with maturation and there was no evidence for the presence of the alpha(3) isoform. Gestational age was inversely related to Na(+), K(+)-ATPase activity (p = 0.0001) and directly related to intracellular Na(+) concentration (p = 0.0025). CONCLUSIONS: Expression of the alpha(1) and beta(2) Na(+),K(+)-ATPase subunit isoforms is developmentally regulated. The increased abundance of alpha(1) isoforms of immature neonates translates to increased ATPase activity. The lower intracellular Na(+) concentration of immature neonates suggests that their erythrocyte Na(+),K(+)-ATPase cation pump function may also be increased.

Blotting, Western↗
PubMed1999

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Journal Article↗
PubMed1999

Changes in oxygenation with inhaled nitric oxide in severe bronchopulmonary dysplasia.

BACKGROUND: Severe bronchopulmonary dysplasia (BPD), which is associated with high mortality and morbidity, is thought to be the result of mechanical, inflammatory, and oxidant injury to the immature lung, and includes the development of pulmonary hypertension with vascular remodeling. METHODS: A phase II pilot study was conducted to determine the effect of inhaled nitric oxide (iNO) on oxygenation in severe BPD. This was an open-labeled, noncontrolled trial to evaluate safety and determine appropriate dosing for a future randomized controlled trial. Infants were eligible for enrollment if they were >/=4 weeks of age and ventilator dependent with a mean airway pressure of >/=10 cm H2O and an FIO2 of >/=0.45. Study infants received iNO (20 ppm) for 72 hours, and FIO2 was adjusted to maintain oxygen saturations of >92%. Infants who had a >/=15% reduction in FIO2 after 72 hours received prolonged treatment with low-dose iNO, weaning by 20% every 3 days as tolerated. FINDINGS: Sixteen preterm infants (23-29 weeks of gestation), age 1 to 7 months, were enrolled. Eleven of 16 infants had a significant increase in PaO2 after 1 hour of iNO (median change, 24 mm Hg; range, -15 to 59 mm Hg; P <.01), but there was no significant change in PaCO2. After 72 hours of iNO, 11 infants had >/=15% reduction in FIO2, and 7 of the 11 had >/=35% reduction (P <. 01). Among the 11 infants who responded to iNO after 72 hours, 10 had a sustained improvement in oxygenation throughout their course of treatment (duration, 8-90 days), and ventilator support could also be decreased. No adverse effects from iNO (increased methemoglobin, bleeding, or increased plasma 3-nitrotyrosine) were observed. Four of the 11 infants (36%) who responded to iNO ultimately weaned off mechanical ventilation and 4 died, whereas all the infants who failed to respond to iNO either died or continue to require mechanical ventilation. INTERPRETATION: We conclude that the use of low-dose iNO may improve oxygenation in some infants with severe BPD, allowing decreased FIO2 and ventilator support without evidence of adverse effects. Randomized clinical trials of low-dose iNO for BPD are warranted.

Administration, Inhalation↗
PubMed1998

Regional hemodynamic effects of dopamine in the sick preterm neonate.

OBJECTIVE: To study the effects of dopamine on renal, mesenteric, and cerebral blood flow in sick preterm neonates. STUDY DESIGN: The pulsatility index was used to assess the dopamine-induced changes in renal, mesenteric, and cerebral blood flow by means of color Doppler ultrasonography in 23 nonhypotensive preterm neonates (birth weight: 981 +/- 314 g; postnatal age: <2 days). Dopamine was given at a dose of 6.1 +/- 3.0 microgram/kg per minute to combat oliguria, impaired peripheral perfusion, or both. Blood flow velocity measurements were made before and during dopamine administration, with each patient serving as his or her own control subject. RESULTS: Dopamine significantly increased blood pressure and urine output. Dopamine decreased the pulsatility index in the renal artery (2.98 +/- 1.18 vs 1.68 +/- 0.45; P <.05) while the pulsatility index in the superior mesenteric and medial cerebral artery was not affected. Thus renal blood flow increased while mesenteric and cerebral blood flow remained unchanged during dopamine treatment. The increase in renal blood flow was independent of the blood pressure changes. CONCLUSIONS: These findings suggest a functionally mature renal, but not mesenteric, vasodilatory dopaminergic response in the preterm neonate. The observations also indicate the lack of an effect of low- to medium-dose dopamine on cerebral hemodynamics in the nonhypotensive preterm neonate.

Blood Flow Velocity↗
PubMed1998

Developmental regulation of the inhibitory effect of dopamine on prolactin release in the preterm neonate.

The secretion and release of prolactin from the anterior pituitary is under the tonic inhibitory control of endogenous dopamine produced in the central nervous system. Exogenous dopamine inhibits prolactin secretion by reaching the pituitary via the portal circulation, and the hypolactotropic effect of dopamine infusion has been documented in all age groups in humans. However, the maturation of lactotroph sensitivity to dopaminergic inhibition has not been studied. Therefore, we followed the changes in serum prolactin concentrations before, during, and after dopamine infusion in 19 sick preterm infants with a mean gestational age of 30.6+/-0.6 weeks during the first 3 days of life, and examined the relationship of the hypolactotropic effect of dopamine to gestational age and birth weight in this patient population. As expected, dopamine therapy resulted in a decrease in mean serum prolactin from 89.4+/-9.5 to 58.6+/-9.1 microg/l (p < 0.05) with a return of the serum prolactin concentration to the pretreatment level 2-6 h after discontinuation of drug administration (98.3+/-11.7 microg/l, p < 0.05). However, simple regression analysis of the individual data revealed that the magnitude of the dopamine-induced decrease in serum prolactin was significantly influenced by gestational age (p = 0.006) and birthweight (p = 0.037). Thus, our findings provide evidence for the maturation of pituitary lactotroph sensitivity to dopaminergic inhibition in the preterm human neonate.

Dopamine↗
PubMed1996

The p15 matrix protein of moloney murine leukemia virus is a phosphotyrosine protein.

Retroviruses have been etiologically implicated with leukemia in humans and animals. Understanding the virus life cycle, the proteins and enzymes involved in its replication, is essential for developing potent anti-viral drugs. Phosphorylation of retroviral proteins may alter their shape in such a way as to increase or inhibit their biological activities and thus influence the replication and pathogenic potential of the retroviruses. In our previous work, we demonstrated that non-cytotoxic doses of tyrphostins (protein tyrosine kinase blockers) inhibit moloney murine leukemia virus (Mo-MuLV) replication in acutely and chronically infected cells. In an attempt to understand their mode of action as anti-MoMuLV drugs, we examined the possibility that a viral protein is phosphorylated in tyrosine. Indeed, in our present work, we show that the p15 matrix protein (MA) of Mo-MuLV is a phosphotyrosine protein and is the only viral protein which is phosphorylated on tyrosine. Moreover, treatment of Mo-MuLV/NIH/3T3 chronically infected cells with tyrphostin AG-555 specifically inhibits the synthesis of p15 and other viral proteins but does not affect the synthesis of cellular proteins. Our results suggest that tyrosine phosphorylation of p15 MA protein may play a pivotal role in Mo-MuLV replication.

3T3 Cells↗
PubMed1995

DNA binding properties of the zinc-bound and zinc-free HIV nucleocapsid protein: supercoiled DNA unwinding and DNA-protein cleavable complex formation.

The HIV nucleocapsid (NC) protein contains, as those of other retroviruses, two Cys-His arrays which function as zinc finger binding domains. The nucleic acid binding properties of retroviral NC have been previously demonstrated. In this study, we characterized the DNA binding ability of the zinc-bound and zinc-free forms of HIV NC. We found that in addition to binding single-stranded DNA, both forms bind and unwind supercoiled plasmid DNA. The binding ability of the zinc-bound form was higher than the zinc-free form. In addition we showed the formation of NC protein-DNA cleavable complex which is the result of a presumably covalent bond formed between the protein and the phosphate moiety of the DNA backbone. The NC unwinding activity and the protein-DNA cleavable complex formation resembles the first step of the relaxing mechanism of DNA topoisomerase. Our results shed light on the possibility of a novel physiological function for the HIV NC protein in the viral life cycle.

Capsid↗
PubMed1993

Effects of low-dose dopamine infusion on cardiovascular and renal functions, cerebral blood flow, and plasma catecholamine levels in sick preterm neonates.

Effects of 2 and 4 micrograms/kg/min dopamine infusion on cardiovascular and renal functions, cerebral blood flow (CBF) and plasma catecholamine levels were studied in sick preterm neonates during the first four days of life. Preterm infants were found to have an enhanced responsiveness to the pressor effects of dopamine during this period. Comparison of the renal effects of 2 and 4 micrograms/kg/min dopamine in 61 preterm infants indicate that 2 micrograms/kg/min dopamine induces maximum diuresis and natriuresis during the first day of life provided that systemic blood pressure is within the predicted normal range. Although administration of 4 micrograms/kg/min dopamine induces further increases in blood pressure and glomerular filtration rate, urine output and sodium excretion remain similar to that on 2 micrograms/kg/min of the drug. These findings demonstrate that the direct tubular effects of dopamine play an important role in the diuretic and natriuretic action of the drug in the one-day old preterm infant. In five preterm neonates, changes in CBF transiently paralleled the dopamine-induced alterations in systemic blood pressure indicating that autoregulation of CBF is impaired but not completely ineffective in the one-day old preterm infant. In eight term neonates, increases in blood pressure had no effect on CBF. Measurements of plasma dopamine and norepinephrine levels in 14 preterm neonates and five children suggest that decreased metabolism of dopamine may contribute to the enhanced pressor responsiveness to dopamine in sick preterm infants.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Pressure↗
PubMed1990

The significance of L-amino acid decarboxylase and DARPP-32 in the kidney.

This study examines the role of endogenous dopamine (DA) for the regulation of renal tubular sodium (Na) transport. The enzyme L-amino acid decarboxylase (L-AADC) that converts L-dopa to DA has been localized to the proximal tubule cells with immunocytochemistry. Locally formed DA will inhibit the activity of Na-K-ATPase, the enzyme that yields energy to active Na transport. The effect is of physiological importance during high salt diet. The phosphoprotein DARPP-32, a DA1 receptor associated third messenger is abundant in the medullary thick ascending limb of Henle (mTAL). DARPP-32 is phosphorylated after activation of DA1 receptors. DARPP-32 is in its phosphorylated form a potent phosphatase inhibitor. Activation of the DA1 receptor in mTAL with the DA1 agonist SKF 82526 causes dose-dependent inhibition of Na-K-ATPase activity. The effect involves activation of cAMP protein kinase. It is likely that this effect is potentiated by DARPP-32.

Animals↗