Biomedical subjects

M Takada

Publications and source records attributed to M Takada.

At least 73 records · Page 4Linked to original sources

PubMed2001

[A role of visiting nurses in providing the terminal patients with their desirable life-discussion regarding the place of death of the patients who were registered for visiting nurse system].

AIM: To evaluate the prognosis of the patients who had visiting nurse service and discuss the place of death (life at the terminal stage). To determine the roles of visiting nurses in providing the patients at a terminal stage with their desirable life till death. METHODS: A total of 180 patients, who were registered for their home healthcare service in our Shonan Kamakura General Hospital and died between January 2000 and February 2001, were subjected to the study. All the subjects were classified into 3 groups according to the places of their death, 1) death at home, 2) death in the hospital and 3) death upon arrival after the admission to the hospital. Moreover, the following items were also surveyed and analyzed: 1) diagnosis (name of diseases), 2) cause of death, 3) age, 4) family structure, 5) whether their primary care physicians explained the prognosis and possible expected conditions to the patients and their family before hand, and 6) how the visiting nurses interact with the patients and their family members. RESULTS: Sixty-six patients died at home, 105 in the hospital and 9 upon arrival at the hospital. During this survey period, there were a total of 5,274 and 5,574 visits by primary care physicians and visiting nurses, respectively. The patients who died at home were more often observed in the patients whose primary care physicians explained their conditions to them and whose visiting nurses closely related to them. Moreover, the patients with malignant tumor also more often died at home. On the contrary, there were very few patients with chronic diseases, with whom death at home was accepted and agreed before hand, and there were some cases with chronic diseases who died inside of the ambulance transported on the way to the hospital after a sudden change in their conditions. DISCUSSION AND CONCLUSION: In order to have the patients live their desirable life till their death, it is required for the caretakers to prepare their mind for the day of the patient's death in addition to the patient's own wishes. For the patients with malignant tumor, it is easy to predict their prognosis, thus the caretakers can get prepared for the day of the patient's death. On the contrary, in case of the patients with chronic diseases, it is more difficult for the caretakers to experience an indefinite time with the patients since their prognosis is generally longer but the sudden change in their conditions may give the caretakers a high anxiety. Thus, it is essential for the visiting nurses to play a role as a mediator to interact between the patients and their family members, and their primary care physicians, and to establish a trustful relationship with the patients while their conditions are still stable. Moreover, similar to the malignant patients, the visiting nurses should explain the situations to the patients with chronic diseases, that they can choose the place of their own death and specific medical treatment at emergency and can decide the detail for their terminal stage with their family members. Thus, it was considered to be very important that the visiting nurses should frequently confirm these issues with the patients and their family according to their conditions.

Aged↗

PubMed2000

Definition of crucial structural factors of acetogenins, potent inhibitors of mitochondrial complex I.

Some natural acetogenins are the most potent inhibitors of bovine heart mitochondrial complex I. These compounds are characterized by two functional units (i.e. hydroxylated tetrahydrofuran (THF) and alpha,beta-unsaturated gamma-lactone ring moieties) separated by a long alkyl spacer. To elucidate which structural factors of acetogenins including their active conformation are crucial for the potent inhibitory effect, we synthesized a series of novel acetogenin analogues possessing bis-THF rings. The present study clearly demonstrated that the natural gamma-lactone ring is not crucial for the potent inhibition, although this moiety is the most common structural unit among a large number of natural acetogenins and has been suggested to be the only reactive species that directly interacts with the enzyme (Shimada et al., Biochemistry 37 (1998) 854-866). The presence of free hydroxy group(s) in the adjacent bis-THF rings was favorable, but not essential, for the potent activity. This was probably because high polarity (or hydrophilicity), rather than hydrogen bond-donating ability, around the bis-THF rings is required to retain the inhibitor in the active conformation. Interestingly, length of the alkyl spacer proved to be a very important structural factor for the potent activity, the optimal length being approximately 13 carbon atoms. The present study provided further strong evidence for the previous proposal (Kuwabara et al., Eur. J. Biochem. 267 (2000) 2538-2546) that the gamma-lactone and THF ring moieties act in a cooperative manner on complex I with the support of some specific conformation of the spacer.

Binding Sites↗

PubMed2000

Endogenous AP-1 levels necessary for oncogenic activity are higher than those sufficient to support normal growth.

We investigated the role of endogenous AP-1 in human tumor cell lines by introducing SupJunD-1, a dominant-negative mutant of AP-1, using vesicular stomatitis virus G protein (VSV-G)-pseudotyped retrovirus vectors. Single inoculation of six human tumor cell lines, originating from osteosarcomas, non-small cell lung carcinomas or cervical carcinomas, with recombinant SupJunD-1 virus at a high multiplicity of infection readily inhibited colony formation in soft agar. We detected no significant changes in expression levels of AP-1 components c-Jun or Fra-1, adhesion molecules CD44 or E-cadherin, or cell cycle regulator p53, which are encoded by genes previously reported to be under the control of AP-1 in some mouse or human cell lines. By varying the dosage of VSV-G-pseudotyped retrovirus, we were able to change the proviral copy number of supjunD-1 from 1 to approximately 10 and monitor suppression of endogenous AP-1 function as assessed by growth characteristics of the tumor cell lines, we found a SupJunD-1 dosage which significantly suppressed anchorage-independent growth without affecting the cellular growth in monolayer cultures at all. We conclude that endogenous AP-1 levels necessary for oncogenic activity are much higher than those sufficient to support normal growth.

3T3 Cells↗

PubMed2000

Involvement of protein kinase C-regulated ceramide generation in inostamycin-induced apoptosis.

Activation of caspases is commonly involved in the apoptosis induced by various anticancer drugs. However, the upstream events leading to the activation of caspases seem to be specific to each anticancer drug. In the present study, we examined the possible involvement of protein kinase C (PKC) and ceramide generation in caspase-3(-like) protease activation induced by inostamycin, a phosphatidylinositol synthesis inhibitor. Treatment of cells with 12-O-tetradecanoyl phorbol-13-acetate (TPA), an activator of PKC, suppressed the release of cytochrome c from mitochondria and the activation of caspase-3(-like) proteases in inostamycin-treated cells, but not in other anticancer drug-treated cells. Inostamycin induced the elevation of intracellular ceramide levels, and fumonisin B1, an inhibitor of ceramide synthase, inhibited inostamycin-induced cytochrome c release, caspase-3(-like) protease activation, and apoptosis. Moreover, TPA also inhibited inostamycin-induced ceramide synthesis. Taken together, our results suggest that inostamycin-induced apoptosis is mediated by PKC-regulated ceramide generation, leading to the activation of a caspase cascade.

Anti-Bacterial Agents↗

PubMed2000

Gravitational Lensing Effect on the Two-Point Correlation of Hot Spots in the Cosmic Microwave Background.

We investigate the weak gravitational lensing effect that is due to the large-scale structure of the universe on two-point correlations of local maxima (hot spots) in the two-dimensional sky map of the cosmic microwave background (CMB) anisotropy. According to the Gaussian random statistics, as most inflationary scenarios predict, the hot spots are discretely distributed, with some characteristic angular separations on the last scattering surface that are due to oscillations of the CMB angular power spectrum. The weak lensing then causes pairs of hot spots, which are separated with the characteristic scale, to be observed with various separations. We found that the lensing fairly smooths out the oscillatory features of the two-point correlation function of hot spots. This indicates that the hot spot correlations can be a new statistical tool for measuring the shape and normalization of the power spectrum of matter fluctuations from the lensing signatures.

Journal Article↗

PubMed2000

A cortical motor region that represents the cutaneous back muscles in the macaque monkey.

A cortical motor region that represented the cutaneous muscles on the back was identified on the medial wall of the frontal lobe in the macaque monkey. In this region, neurons responded to somatosensory stimuli such as light touch or squeezing of the back skin, and intracortical microstimulation elicited contraction of the back skin. Such a region was located primarily on the dorsal bank of the cingulate sulcus, corresponding to the dorsal cingulate motor area.

Animals↗

PubMed2000

4-Dimethylaminobenzylamine as a sensitive chemiluminescence derivatization reagent for 5-hydroxyindoles and its application to their quantification in human platelet-poor plasma.

A selective and sensitive high-performance liquid chromatographic method with chemiluminescence detection for the determination of 5-hydroxyindoles is described, based on the reaction of 5-hydroxyindoles with 4-dimethylaminobenzylamine. Serotonin, 5-hydroxyindole-3-acetic acid, 5-hydroxytryptophol, 5-hydroxyindole-3-acetamide and N-acetyl-5-hydroxytryptamine were used as model compounds to optimize the derivatization and chemiluminescent reaction. The reagent reacts with 5-hydroxyindoles in slightly alkaline media in the presence of potassium hexacyanoferrate(III) to give the corresponding derivatives, which can be separated on a reversed-phase column, Wakosil-II 5C18RS, with aqueous acetonitrile as an eluent. The derivatives were detected by peroxyoxalate chemiluminescence detection. The detection limits are in the range of 0.5-1.2 fmol per 100-microl injection. The method was applied to the simultaneous determination of serotonin and 5-hydroxyindole-3-acetic acid in human platelet-poor plasma.

Aniline Compounds↗

PubMed2000

Direct projections from the magnocellular division of the basal nucleus of the amygdala to the principal part of the cortical masticatory area in the macaque monkey.

Direct projections from the amygdala to the cortical masticatory area were found in the macaque monkey. Under the guidance of intracortical microstimulation, retrograde tracers were injected into multiple jaw movement-related regions of the frontal lobe. The cortical masticatory area, especially its principal part, stimulation of which elicited rhythmic jaw movement, was the only site of injection that produced neuronal labeling in the amygdala. The cells of origin of such projections were localized in the medial aspect of the magnocellular division of the basal nucleus through its rostral level. No labeled neurons were observed in the amygdala after tracer injection into any other cortical jaw movement-related region. The present results suggest that the amygdaloid input to the cortical masticatory area may exert some modulatory influence on the generation of masticatory rhythm.

Amygdala↗

PubMed2000

The relationship between risk of hypoglycemia and use of cibenzoline and disopyramide.

OBJECTIVE: A case-control study was carried out to compare the risks of hypoglycemia caused by disopyramide and cibenzoline. METHODS: We selected 91 subjects with hypoglycemia from among 14,156 outpatients who consulted the National Cardiovascular Center (NCVC) and received drug therapy between September 1997 and February 1998. We used the fasting blood sugar (FBS) level of 75 mg/dl or less as the cut-off level to screen for hypoglycemia. For each case, five controls matched for gender and age were selected from the clinical division consulted by relevant subjects. RESULTS: Ninety-one cases and 455 controls were enrolled in this study. Of 91 cases with hypoglycemia, 8 (8.8%) were treated with cibenzoline and 3 (3.3%) with disopyramide. The percentage of cases treated with cibenzoline was greater than that in the controls (1.5%), and the prescription frequency of cibenzoline during the study period was 2%. With adjustment for potential confounding factors using conditional logistic regression, hypoglycemia was significantly correlated with the use of cibenzoline [OR 8.0 (95% CI 1.7-36.8)], insulin [OR 48.4 (95% CI 8.8-267.2)], and thyroid agents [OR 13.0 (95% CI 1.1-160.4)]. An increased risk of hypoglycemia associated with the use of sulfonylureas was not detected. In additional logistic regression analysis, including the variables with individual sulfonylureas, glibenclamide but not gliclazide significantly increased the risk of hypoglycemia. The use of disopyramide did not affect the risk of hypoglycemia. In separate analyses for diabetic and non-diabetic patients, the risks of hypoglycemia associated with the use of drugs other than beta-blocking agents in non-diabetic patients were estimated to be lower than those in diabetic patients. CONCLUSION: The use of cibenzoline was significantly correlated with an increased risk of hypoglycemia.

Adult↗

PubMed2000

Viral serostatus and coexisting inflammatory activity affect metachronous carcinogenesis after hepatectomy for hepatocellular carcinoma. A further report.

Little data are available regarding the effects of hepatitis virus serostatus and the severity of coexisting chronic inflammation on intrahepatic recurrence after hepatectomy for hepatocellular carcinoma (HCC). We investigated the extent to which these factors modified the prognosis of hepatectomized patients. A total of 274 patients treated in the period January 1981 to December 1996 were divided into three groups: antihepatitis C-positive (HCV; n = 144), hepatitis B surface antigen-positive and HCV antibody (Ab)-negative (HBsAg; n = 106), and HBsAg-negative and HCV Ab-negative (NBNC; n = 20). Positivity for HBV-related antibody in the HCV group was 76%. Histologic grading of inflammatory activity from coexisting hepatitis was determined according to Knodel's histological activity index (HAI) scoring system. Post-hepatectomy crude survival rates and disease-free survival (DFS) rates were compared, according to tumor characteristics, between the three groups. In the patients overall and also in the patients with a single nodular HCC, the HCV group had significantly higher HAI scores and preoperative serum aspartate aminotransaminase (AST) levels than the other two groups. When the patients were limited to those with a single nodular HCC, the crude survival was similar in the three groups with comparable tumor characteristics; however, the DFS was different (NBNC > HBsAg > HCV). When the patients were further limited to those with a single nodular HCC without microscopic extracapsular spread, in whom removal of the tumor was expected to be microscopically complete, the difference in the DFS became more marked. Irrespective of the viral serostatus, better crude and disease-free survivals were observed in the patients with lower AST levels (< or =50 IU/ 1) than in those with higher AST levels (>50IU/l). In contrast, there were no differences in survivals and HAI scores according to the presence or absence of HBV-related antibody in the HCV group. From our univariate analysis, we can conclude that the severity of virally induced inflammation, which was well correlated with viral serostatus, may be a factor that affects intrahepatic recurrence, which is more likely to originate from metachronous carcinogenesis. Prior co-infection of HBV in HCV patients may not be an adverse risk factor for intrahepatic recurrence.

Carcinoma, Hepatocellular↗

PubMed2000

Comparison of various biochemical measurements with bone mineral densitometry and quantitative ultrasound for the assessment of vertebral fracture.

We have retrospectively studied postmenopausal elderly Japanese women (n = 288; age range, 60-75 years, 65.8 +/- 4.5 [mean +/- SD]) for the evaluation of biochemical measurements in assessment of bone mass and vertebral fracture, comparing with several bone mineral measurements and quantitative ultrasound (QUS) measurement. Several biochemical parameters [red cell count (RBC), hemoglobin (HB), albumin (ALB), and cholesterol (CHO)] positively correlated with bone mass parameters, but only serum cholesterol showed association with the presence of vertebral fracture. Urinary deoxypyridinoline (DPYD) and n-telopeptide (NTx) showed moderate negative correlation with bone mass parameters, and DPYD showed association with vertebral fracture. All bone mineral measurements (lumbar spine, total body, femoral neck by DXA, calcaneal bone by SXA, distal radius by pQCT) and QUS measurement (os calcaneus by two different QUS machines) showed a higher odds ratio and high chi2 value in logistic regression analysis for association with vertebral fracture. Thus, bone mass measurement is the principal method for assessment of fracture risk, and biochemical measurement should be used for motivation of further bone mass measurement. In biochemical measurements, measurement of serum cholesterol is cheap and easy, and thus might have an advantage, although further study is necessary.

Absorptiometry, Photon↗

PubMed2000

B-mode and color Doppler ultrasound imaging for localization of microelectrode in monkey brain.

Using alert monkeys, we attempted ultrasound imaging after partial craniotomy to localize a metal microelectrode in the brain. B-mode ultrasonography provided images of sulcus and gyrus patterns of the cerebral cortex, and locations of the ventricles and subarachnoid cisterns. As the microelectrode proceeded in the brain, the position of the microelectrode was clearly identified. Electrolytic microlesions generated by delivering direct currents via the microelectrode could also be detected. Color Doppler imaging of blood vessels of the brain was helpful to demarcate deep brain structures and to avoid accidental injury of the blood vessels by the microelectrode. The ultrasonography will make it possible to place recording microelectrodes or injection needles accurately in target regions of the brain in physiological, anatomical or behavioral experiments.

Animals↗

PubMed2000

Organization of somatic motor inputs from the frontal lobe to the pedunculopontine tegmental nucleus in the macaque monkey.

To reveal the somatotopy of the pedunculopontine tegmental nucleus that functions as a brainstem motor center, we examined the distribution patterns of corticotegmental inputs from the somatic motor areas of the frontal lobe in the macaque monkey. Based on the somatotopical map prepared by intracortical microstimulation, injections of the anterograde tracers, biotinylated dextran amine and wheat germ agglutinin-conjugated horseradish peroxidase, were made into the following motor-related areas: the primary motor cortex, the supplementary and presupplementary motor areas, the dorsal and ventral divisions of the premotor cortex, and the frontal eye field. Data obtained from the present experiments were as follows: (i) Corticotegmental inputs from orofacial, forelimb, and hindlimb representations of the primary motor cortex tended to be arranged orderly from medial to lateral in the pedunculopontine tegmental nucleus. However, the distribution areas of these inputs considerably overlapped; (ii) The major input zones from distal representations of the forelimb and hindlimb regions of the primary motor cortex were located medial to those from their proximal representations, although there was a substantial overlap between the distribution areas of distal versus proximal limb inputs; (iii) The main terminal zones from the forelimb regions of the primary motor cortex, the supplementary and presupplementary motor areas, and the dorsal and ventral divisions of the premotor cortex appeared to overlap largely in the mediolaterally middle aspect of the pedunculopontine tegmental nucleus; and (iv) Corticotegmental input from the frontal eye field was scattered over the pedunculopontine tegmental nucleus.Thus, the present results indicate that the pedunculopontine tegmental nucleus is likely to receive partly separate but essentially convergent cortical inputs not only from multiple motor-related areas representing the same body part, but also from multiple regions representing diverse body parts. This suggests that somatotopical representations are intermingled rather than segregated in the pedunculopontine tegmental nucleus.

Animals↗

PubMed2000

3D-CT diagnosis for ingested foreign bodies.

Ingested foreign bodies can be hard to diagnose but cannot be missed. We report two cases where helical computed tomography (three-dimensional computed tomography) was used for the effective preoperative diagnosis (swallowed fish bone-induced perforation of sigmoid colon and a case of ileus caused by ingested PTP [press-through package]). Other traditional diagnostic methods could not identify the foreign bodies. Three-dimensional computed tomography is useful for the diagnosis of foreign body ingestion and should be used for the difficult cases.

Abdominal Pain↗

PubMed2000

The effects of an angiotensin-converting enzyme inhibitor and an angiotensin II receptor antagonist on insulin resistance in fructose-fed rats.

The aim of this study was to compare the effects of an angiotensin-converting enzyme (ACE) inhibitor and an angiotensin II receptor (AT) antagonist on insulin resistance, especially on muscle fiber composition in fructose-induced insulin-resistant and hypertensive rats. Six-week-old male Sprague-Dawley rats were fed either normal rat chow (control) or a fructose-rich diet (FFR). For the last two weeks of a six-week period of either diet, the rats were treated with gum arabic solution as a vehicle (control or FFR), angiotensin-converting enzyme inhibitor (FFR+ACE), temocapril (1 mg/kg/ day) or an angiotensin II receptor antagonist (FFR+AT), CS-866 (0.3 mg/kg/day), by gavage, and then the euglycemic hyperinsulinemic glucose clamp technique was performed to evaluate insulin sensitivity. At the end of the glucose clamp, the soleus muscle was dissected for determination of the muscle fiber composition by ATPase methods. Blood pressure at the glucose clamp in the FFR group was significantly higher than that of the control group, and both temocapril and CS-866 significantly lowered the blood pressure of the FFR group. The average rate of glucose infusion during the glucose clamp, as a measure of insulin sensitivity (M value), was significantly lower in the FFR rats compared to the controls (15.4 +/- 0.4, 10.9 +/- 0.6 mg/kg/min, for control and FFR, respectively, P < .01). Both temocapril and CS-866 partially improved the M values compared to FFR (13.2 +/- 0.7, 12.8 +/- 0.5 mg/kg/min, for FFR+ACE, FFR+AT, respectively, P < .01 compared with FFR, P < .05 compared with control). The composite ratio of type I fibers of the soleus muscle was decreased significantly in the FFR rats compared with the controls (82% +/- 2%, 75% +/- 2%, for control and FFR, respectively, P < .01), and both temocapril and CS-866 restored a composite ratio of type I fibers to the same level as that of the controls (81% +/- 1%, 80% +/- 1% for FFR+ACE and FFR+AT, respectively). The M value was significantly correlated with the composition of type I and type II fibers. These results suggest that the fiber composition of skeletal muscle is correlated to insulin resistance, and that both ACE inhibitors and AT antagonists may modulate the muscle fiber composition in a hypertensive and insulin-resistant animal model, fructose-fed rats, to the same extent.

Angiotensin Receptor Antagonists↗

PubMed2000

Region-dependent disappearance of vinblastine in rat small intestine and characterization of its P-glycoprotein-mediated efflux system.

This study was aimed to characterize the absorption behavior of vinblastine (VLB), a well-known substrate of P-glycoprotein (P-gp), from rat small intestine, especially focusing on the regional-dependence of its efflux mediated by P-gp. VLB disappeared from duodenal and ileal loops of male Wistar rats fairly rapidly (30-60% in 30 min). In contrast, its disappearance from the jejunal loop was almost negligible and in some rats >100% of the jejunal dose was recovered. The radioactivity derived from [3H]VLB, which was absorbed from duodenum and ileum, was detected in the jejunal region. The jejunal appearance of radioactivity was increased when unlabeled VLB was present in the region in advance. The basolateral-to-apical transport of [3H]VLB across Caco-2 cell monolayers was greater when unlabeled VLB was added to the apical medium than when VLB-free buffer was applied to the apical side. When verapamil or cyclosporin A, potent modulators of P-gp, was added to the apical medium together with unlabeled VLB, enhanced basolateral-to-apical transport of [3H]VLB was disappeared. It is suggested that VLB absorption is strongly restricted by P-gp, especially in the jejunal region of the rat small intestine, and that the secretory transport via intestinal P-gp may be subject to trans-stimulation. Moreover, intravenously administered methylprednisolone and intramuscularly administered progesterone significantly enhanced the absorption of VLB, suggesting that parenterally administered P-gp modulators could influence the intestinal absorption of P-gp substrates.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2000

Design syntheses and mitochondrial complex I inhibitory activity of novel acetogenin mimics.

Some natural acetogenins are the most potent inhibitors of mitochondrial complex I. These compounds are characterized by two functional units [i.e. hydroxylated tetrahydrofuran (THF) and alpha, beta-unsaturated gamma-lactone ring moieties] separated by a long alkyl spacer. To elucidate which structural factors of acetogenins, including their active conformation, are crucial for the potent inhibitory activity we synthesized a novel bis-acetogenin and its analogues possessing two gamma-lactone rings connected to bis-THF rings by flexible alkyl spacers. The inhibitory potency of the bis-acetogenin with bovine heart mitochondrial complex I was identical to that of bullatacin, one of the most potent natural acetogenins. This result indicated that one molecule of the bis-acetogenin does not work as two reactive inhibitors, suggesting that a gamma-lactone and the THF ring moieties act in a cooperative manner on the enzyme. In support of this, either of the two ring moieties synthesized individually showed no or very weak inhibitory effects. Moreover, combined use of the two ring moieties at various molar ratios exhibited no synergistic enhancement of the inhibitory potency. These observations indicate that both functional units work efficiently only when they are directly linked by a flexible alkyl spacer. Therefore, some specific conformation of the spacer must be important for optimal positioning of the two units in the enzyme. Furthermore, the alpha,beta-unsaturated gamma-lactone, the 4-OH group in the spacer region, the long alkyl tail attached to the THF unit and the stereochemistry surrounding the hydroxylated bis-THF rings were not crucial for the activity, although these are the most common structural features of natural acetogenins. The present study provided useful guiding principles not only for simplification of complicated acetogenin structure, but also for further wide structural modifications of these molecules.

Animals↗

PubMed2000

Physiologic significance of nitric oxide and endothelin-1 in circulatory adaptation.

BACKGROUND: The purpose of the present paper was to evaluate the physiologic significance of nitric oxide (NO) and endothelin (ET)-1 in circulatory adaptation in the neonate. METHODS: The serum levels of NO metabolites (NOx; the sum of nitrites and nitrates) and the plasma level of ET-1 were determined in 14 healthy full-term infants at 0-6 h, 24 h and 5 days after birth. We measured the heart rate, the mean systemic blood pressure and the mean pulmonary arterial pressure, estimated by pulsed Doppler echocardiography, at each time point. RESULTS: The serum concentration of NOx was lowest at birth and increased with age. The plasma concentration of ET-1 was highest at birth and decreased with age. The ratio of NOx to ET-1 was inversely related to the estimated mean pulmonary arterial pressure in the early neonatal period. The ratio of NOx to ET-1 was not correlated with the systemic blood pressure. CONCLUSION: Increased NO synthesis and decreased production of ET-1 during the early neonatal period may contribute to the decrease in pulmonary arterial pressure.

Adaptation, Physiological↗