Search PubMed⌕ Search

Biomedical subjects

Y Taira

Publications and source records attributed to Y Taira.

At least 37 records · Page 2Linked to original sources
PubMed2000

Antenatal dexamethasone enhances endothelin receptorB expression in hypoplastic lung in nitrofen-induced diaphragmatic hernia in rats.

BACKGROUND/PURPOSE: The hypoplastic lung and persistent pulmonary hypertension (PPH) are the principle causes of high mortality and morbidity in infants with congenital diaphragmatic hernia (CDH). Endothelin-1 (ET-1), which is produced by vascular endothelial cells and some leukocytes, plays a key role in modulating pulmonary vascular tone in PPH. Two different receptors (ET(A) and ET(B)) for ET-1 have been characterized. Binding of ET-1 to ET(A), which is present on smooth muscle cells in fetal lung, results in vasoconstriction. However, binding of ET-1 to ET(B), which is present on endothelial cells results in vasodilation mediated by endogenous nitric oxide. Antenatal glucocorticoid therapy has been shown to prevent abnormal pulmonary arterial structural changes in animal model with CDH. The aim of this study was to investigate the effect of antenatal glucocorticoid administration on ET-1 system in nitrofen-induced CDH hypoplastic lung in rats. METHODS: A CDH model was induced in pregnant rats after administration of nitrofen on day 9.5 of gestation. Dexamethasone (Dex) was given intraperitoneally on days 18.5 and 19.5 of gestation. Cesarean section was performed on day 21 of gestation. Rat ET-1 protein expression was measured in solubilized lung tissue extracts, by sandwich type enzyme-linked immunosorbent assay (ELISA) analysis. Reverse transcription polymerase chain reaction was performed to evaluate the relative amount of ET-1, ET(A), and ET(B) mRNA expression. RESULTS: The ET-1 protein and mRNA expression of ET-1 and both receptors were increased significantly in CDH lung compared with controls. Although there was no significant difference in ET(A) mRNA expression between CDH lung with Dex treatment and without Dex treatment, ET(B) mRNA expression was elevated significantly in CDH lung with Dex treatment compared with CDH lung without Dex treatment. CONCLUSION: These findings suggest that antenatal glucocorticoid therapy may modulate pulmonary vascular tone in CDH hypoplastic lung by selectively upregulating local expression of ET(B).

Animals↗
PubMed2000

Incipient cauda equina syndrome as a model of somatovisceral pain in dogs: spinal cord structures involved as revealed by the expression of c-fos and NADPH diaphorase activity.

Segmental and laminar distribution of Fos-like immunoreactive, reduced nicotinamide adenine dinucleotide phosphate diaphorase (NADPHd)-exhibiting and double-labeled (Fos-like immunoreactive and NADPHd-exhibiting) neurons was examined in lower lumbar and sacral segments of the dog spinal cord using the model of multiple cauda equina constrictions. NADPHd histochemistry was used as marker of nitric oxide synthase-containing neurons. The appearance and the time-course of Fos-like immunoreactive, NADPHd and double-labeled neurons was studied at 2 h and 8 h postconstriction characterized as the incipient phase of cauda equina syndrome. The occurrence of Fos-like immunoreactive and NADPHd-exhibiting neurons in fully developed cauda equina syndrome was studied at five days postconstriction. An increase in Fos-like immunoreactivity in superficial laminae (I-II) and an enhanced NADPHd staining of lamina VIII neurons were found. A statistically significant increase in Fos-like immunoreactive neurons was found in laminae I-II and VIII-X 8 h postconstriction, and in contrast, a prominent decrease in Fos-like immunoreactive neurons was found in laminae I-II, accompanied by a statistically significant increase in Fos-like immunoreactive neurons in more ventrally located laminae VII-X at five days postconstriction. Quantitative analysis of laminar distribution of constriction-induced NADPHd-exhibiting neurons revealed a considerable increase in these neurons in laminae VIII-IX 8 h postconstriction and a statistically highly significant increase in NADPHd-exhibiting neurons in laminae VII-X five days postconstriction. Concurrently, the number of NADPHd-exhibiting neurons in laminae I-II was greatly reduced. While a low number of double-labeled neurons was found throughout the gray matter of lower lumbar and sacral segments at 2 h postconstriction, a statistically significant number of double-labeled neurons was found in lamina X 8 h and in laminae VII-X five days postconstriction. The course and distribution of anterograde degeneration resulting five days after multiple cauda equina constrictions are compared with segmental and laminar distribution of Fos-like immunoreactive and NADPHd-exhibiting neurons. Prominent involvement of the spinal cord neurons appearing in the lumbosacral segments at the early beginning and in fully developed cauda equina syndrome results in a Fos-like immunoreactivity and strongly enhanced NADPHd staining of some neuronal pools. Under such circumstances, an early cauda equina decompression surgery is advisable aimed at decreasing or preventing the derangement of the neural circuits in the lumbosacral segments.

Animals↗
PubMed2000

Adhesive bonding of titanium with a thione-phosphate dual functional primer and self-curing luting agents.

A consistent bond between the metal framework and the luting agent is desired when resin-bonded prostheses are constructed with titanium. The purpose of this study was to evaluate three different metal primers on titanium bonding. Two sources of titanium (machined 99.9% titanium and cast Titan Ingot JS2) were used. Disk specimens were bonded with eight combinations of three primers and two luting agents (Panavia 21 and Super-Bond C&B), including two controls. Shear bond strengths were determined after 24-h water storage and after 10,000 cycles of thermocycling. Bond strengths were influenced by thermocycling, primer, luting agent and their combinations, but no significant differences were found between the machined 99.9% titanium and the cast ingot. The thione-phosphate dual functional primer (Alloy Primer) was comparable to the phosphate primer (Cesead II Opaque Primer) and the thiophosphate primer (Metal Primer II) for bonding the titanium metals examined. The most durable bond was obtained in three combinations of these primers and one luting agent (Super-Bond C&B).

Analysis of Variance↗
PubMed2000

Influence of formaline cresol on bond strength of adhesive luting agents to dentin.

The present study investigates the influence of the pulpotomy agent formaline cresol (FC) on bond strength between dentin and five adhesive systems (Super-Bond C&B, Bistite II, Imperva Dual Set, Panavia 21, and Panavia 21 with AD Gel). After the dentin surfaces of 75 bovine teeth (including 25 control samples) were exposed by grinding, 25 of the samples were soaked in FC for 2 days, and 25 samples were soaked for 7 days. Samples were bonded to acrylic rods using five adhesive systems, and tensile bond strengths were determined after 1-day immersion in water. Data were analysed by analysis of variance and Duncan's new multiple range test, and the fractured surfaces were observed through a scanning electron microscope. The bond strengths were found to be influenced by the type of system, soaking period, and their combination. The bond strength values of three adhesive systems (Super-Bond C&B, Imperva Dual Set Bistite II, and Panavia 21 with AD Gel) decreased after soaking in FC. After 7 days of FC exposure, the highest bond strength (9.8+/-2.9 MPa) was obtained with the Super-Bond C&B system.

Analysis of Variance↗
PubMed2000

Spinal and supraspinal midazolam potentiates antinociceptive effects of isoflurane.

The effects of lumbar intrathecal (i.t.) and intracerebroventricular (i.c.v.) midazolam on nociception during isoflurane anaesthesia were studied in rats using the tail-flick test. Rats received i.t. midazolam 2 and 4 microg or i.c.v. midazolam 4 and 8 microg during 1.1, 1.2 and 1.3% isoflurane or without isoflurane. Neither i.t. nor i.c.v. midazolam alone at doses studied influenced nociceptive responses. 1.1% isoflurane showed a minimum antinociceptive effect which was not influenced by i.t. or i.c.v. midazolam. 1.2 and 1.3% isoflurane produced moderate antinociception which was markedly potentiated by both i.t. and i.c.v. midazolam. The effects of midazolam shown in the present study are different from the reported effects of midazolam on opioid-induced antinociception; where spinally administered midazolam potentiates and supraspinal midazolam inhibits the antinociceptive effects of morphine. The present results suggest that midazolam potentiates isoflurane-induced antinociception at doses where no effect is seen alone.

Adjuvants, Anesthesia↗
PubMed2000

[A case of pulmonary actinomycosis radiologically mimicking a lung cancer].

A 59-year-old male clerk consulted in general practitioner due to cough and hemoptysis. A mass shadow was pointed out in the left upper lung field on a chest radiograph. Patient was referred to our hospital for further treatment. Any definitive daiagnosis could not be made after examinations including sputum culture, cytology and TBLB. Because a lung cancer was strongly suspected, an exploratory thoracotomy was performed. Actinomyces was detected by pathological study of excised specimen, with no evidence of cancer. ABPC was administered for two months postoperatively. The patient is doing well without recurrence of actinomycosis 2.5 years after the surgery. Pulmonary actinomycosis presenting a mass shadow on a radiograph may mimick a pulmonary tumor, especially a lung cancer. Pulmonary actinomycosis should be considered in a differential diagnosis of pulmonary lesion thought to be malignant.

Actinomycosis↗
PubMed2000

[The effects of intravenous anesthetics, propofol, fentanyl and ketamine on the excitability of spinal motoneuron in human: an F-wave study].

We have investigated the effects of various intravenous anesthetics, propofol, fentanyl and ketamine on the excitability of spinal motoneuron using an F-wave analysis in a total of 28 patients. All patients were divided randomly into three groups as follows; 2 mg.kg-1 intravenous bolus injection followed by 6 mg.kg-1.h-1 infusion of propofol (P group), 1 mg.kg-1 intravenous bolus injection followed by 1 mg.kg-1.h-1 infusion of ketamine (K group), and 5 micrograms.kg-1 injection of fentanyl (F group). The F-wave was determined after supramaximal electrostimulation of the median nerve in distal point. After establishing stable baseline values, intravenous injection of one of the three anesthetics was applied. The F-wave was recorded 3 minutes after the time of bolus administration. We found a significant (P = 0.018) reduction of the persistence from 77.5 +/- 15.2 to 40.9 +/- 16.8% in the propofol group. On the other hand, no significant changes in F-wave parameters were found in ketamine, or fentanyl group. These results suggested that motoneuron excitability in spinal cord could be inhibited by anesthetic dose of propofol, but not by ketamine or fentanyl.

Adult↗
PubMed2000

[Pre-emptive analgesia with intravenous ketamine reduces postoperative pain in young patients after appendicectomy: a randomized control study].

Thirty-six young patients (12-17 years old) for appendicectomy were randomly allocated to receive ketamine 0.5 mg.kg-1 (K 0.5 group; n = 12), ketamine 1.0 mg.kg-1 (K 1.0 group; n = 12), or lactated Ringer's solution 5 ml (control group; n = 12), which was administered intravenously before incision. After the surgery, all patients received a nonsteroidal anti-inflammatory drug (NSAID) without limitation as requested by the patient. Pain scores at rest and on movement were assessed at 6-10 hr, 24 hr, and 48 hr post-operatively using a visual analogue scale. The frequency at which NSAID was given for postoperative analgesia in the first 48 hr after the surgery was recorded. The patients in the K 0.5 and K 1.0 groups had significantly lower pain scores at rest 6-10 hr postoperatively than the patients in the control group (P < 0.05). Additionally, the patients in the K 1.0 group had a significantly lower pain score on movement 6-10 and 48 hr postoperatively than those in the control group (P < 0.05). The K 0.5 and K 1.0 groups each used significantly less NSAID during the 48-hr postoperative period than the control group (P < 0.05). Intravenous administration of ketamine before incision was associated with decreases in pain at rest 6-10 hr postoperatively and a reduction in NSAID requirement after appendicectomy. Administration of ketamine 1.0 mg.kg-1 prior to incision was superior to administration of 0.5 mg.kg-1 in relief of pain on movement after the surgical procedure.

Adolescent↗
PubMed2000

[Continuous hepatic arterial infusion of 5-fluorouracil with leucovorin for unresectable liver metastases from colorectal cancer].

Twenty-three patients with liver metastases from colorectal cancer were treated by continuous hepatic arterial infusion chemotherapy with 5-FU and Leucovorin. The regimen was that 500 mg/body of 5-FU with 30 mg/body of Leucovorin was administered continuously for 5 days, followed by no medication for 16 days. The effect of this therapy was evaluated and the relationship between this therapy and the overexpression of vascular endothelial growth factor (VEGF) or microvessel density (MVD) was also studied. Complete response was obtained in 4 patients and partial response in 3 patients; the response rate was 32%. The response rate was 60% in patients who underwent more than 7 courses. The response rate was 44% in patients with positive VEGF and 33% in patients with negative VEGF. The response rate was 50% in patients with an MVD of more than 30 and 33% in patients with an MVD of less than 30. The 3-year survival rate for patients who underwent more than 7 courses was 37.5%. This therapy had to be abandoned in 6 patients due to occlusion of the catheter. Skillful maintenance of the catheter is necessary for a high response rate and satisfactory prognosis using this therapy.

Aged↗
PubMed2000

Bond strength of prosthodontic luting materials to titanium after localized cyclic loading.

PURPOSE: To establish an in vitro analysis system to evaluate the effect of cyclic loading on the bond strengths and durability of luting materials bonded to titanium. MATERIALS AND METHODS: Machine-milled titanium disks were finished with 600 grit silicon-carbide paper and pairs of disks were bonded together using the five different luting materials. A stainless steel stylus was vertically loaded at a center position (Model 1) or at the border (Model 2) of the specimens with a force of 75.6 N at 7500 cycles/hr. When the stylus contacted the specimen surface through the water slurry of poly(methyl methacrylate) beads, it rotated clockwise up to 15 degrees and counter-rotated. Shear bond strengths were determined 1 hr after bonding, after storage in water at room temperature for 24 hr, and after the loading for 100,000 cycles. RESULTS: The bond strengths of the unfilled adhesive resin and resin-based composite cement (RBC) were significantly higher than those of the glass-ionomer cements. Zinc phosphate cement demonstrated no bonding ability to titanium. After 100,000 cycles, peripheral loading in Model 2 significantly reduced the bond strength of the RBC and glass-ionomer cements, while Model 1 loading did not. The highest and the most durable bonds were obtained with the unfilled adhesive resin in both models.

Adhesiveness↗
PubMed1999

Localization of NADPHd-exhibiting neurons in the spinal cord of the rabbit.

Segmental and laminar distributions of nicotinamide adenine dinucleotide phosphate diaphorase (NADPHd)-exhibiting neurons were examined in the rabbit spinal cord by using horizontal, sagittal, and transverse sections. A large number of NADPHd-positive neurons in the spinal cord of rabbit appeared to fall into six categories (N1-N6), but others could not be classified. Major cell groups of NADPHd-exhibiting neurons were identified in the superficial dorsal horn and around the central canal at all spinal levels and in the intermediolateral cell column at thoracic and upper lumbar levels. NADPHd-exhibiting neurons of the pericentral region were divided into a thin subependymal cell column containing longitudinally arranged, small bipolar neurons with processes penetrating deeply into the intermediolateral cell column and/or running rostrocaudally in the subependymal layer. The second pericentral cell column located more laterally in lamina X contains large, intensely stained NADPHd-exhibiting neurons with long dendrites radiating in the transverse plane. In the pericentral region (lamina X), close association of NADPHd-exhibiting somata and fibers and mostly longitudinally oriented blood vessels were detected. Neurons of the sacral parasympathetic nucleus, seen in segments S1-S3, exhibited prominent NADPHd cellular staining accompanied by heavily stained fibers extending from Lissauer's tract through lamina I along the lateral edge of the dorsal horn to lamina V. A massive dorsal gray commissure, highly positive in NADPHd staining, was found in segments S1-S3. Scattered positive cells were also found in the deeper dorsal horn, ventral horn, and white matter. Fiberlike NADPHd staining was found in the superficial dorsal horn and pericentral region in all the segments studied. Dense, punctate, nonsomatic NADPHd staining was detected in the superficial dorsal horn, in the pericentral region all along the rostrocaudal axis, and in the nucleus phrenicus (segments C4-C5), nucleus dorsalis (segments Th2-L2), Onuf's nucleus (segments S1-S3), and the dorsal part of the dorsal gray commissure (S1-S3).

Animals↗
PubMed1999

A study on cytochrome c oxidoreductase for bonding a tri-n-butylborane-initiated luting agent to dentin.

The purpose of this study was to investigate the effectiveness of cytochrome c, an oxidoreductase, in terms of initiation of polymerization in dentin bonding. The efficacy of experimental dentin primers was evaluated via the bonding of a luting agent to dentin. The eight primers evaluated were cytochrome c aqueous solutions, four with 35 wt% 2-hydroxyethyl methacrylate (HEMA) and four without. The concentrations of cytochrome c in the primers were 0, 0.01, 0.1, and 1[corrected] micromol/g. The luting agent (Super-Bond C&B) consisted of methyl methacrylate (MMA), 4-methacryloyloxyethyl trimellitate anhydride (4-META), and tri-n-butylborane (TBB) initiator. Bovine dentin surfaces were flattened, etched with an aqueous solution of 10 wt% phosphoric acid, primed, and then bonded with stainless steel rods. After 1-day immersion in water, tensile testing revealed that the bond strength was influenced by the application of cytochrome c and HEMA. The maximum bond strength of 24.6 MPa was recorded with aqueous HEMA primer containing 10 micromol/g cytochrome c. This bonding technique, combining oxidoreductase with Super-Bond C&B, may potentially be applied for seating resin-bonded restorations.

Animals↗
PubMed1999

Effect of antenatal glucocorticoid administration on insulin-like growth factor I and II levels in hypoplastic lung in nitrofen-induced congenital diaphragmatic hernia in rats.

There is increasing evidence to suggest that insulin-like growth factors (IGF) I and II play a crucial role in fetal lung development. Expression of IGF-I and II has been demonstrated to be predominant during fetal life and decreases prior to birth. Antenatal glucocorticoids are reported to improve lung immaturity. The aim of this study was to investigate the effect of antenatal glucocorticoid administration on IGF-I and II expression in nitrofen-induced congenital diaphragmatic hernia (CDH) in rats. A CDH model was induced in pregnant rats following administration of 100 mg nitrofen on day 9.5 of gestation (term = 22 days). Dexamethasone (0.25 mg/kg) was given intraperitoneally on days 18.5 and 19.5 of gestation. Cesarean section was performed on day 21. The fetuses were divided into three groups: I, normal controls; II, nitrofen-induced CDH; and III, nitrogen-induced CDH with antenatal dexamethasone treatment. mRNA was extracted from whole lung and a reverse transcription-polymerase chain reaction (RT-PCR) was performed to evaluate the relative amounts of IGF I and II mRNA. Levels of mRNA were expressed as a ratio of the band density divided by that of beta-actin, a housekeeping gene known to be expressed at a constant level. Immunohistochemistry using anti-rat IGF I and II antibody was also performed in each group. Levels of IGF I mRNA were significantly increased in group II (0.50 +/- 0.08) compared to group I (0.34 +/- 0.10) or group III (0.32 +/- 0.06) (P < 0.05). Levels of IGF II mRNA were also significantly increased in group II (0.95 +/- 0.20) compared to group I (0.42 +/- 0.07) or group III (0. 31 +/- 0.09) (P < 0.05). Strong IGF I and II expression was observed in the hypoplastic CDH lung (group II), mainly in the bronchiolar epithelium. IGF I and II expression in group I and III lungs was either absent or weak. The finding of significant reductions in IGF I and II mRNA and protein levels in dexamethasone-treated CDH lung suggest that dexamethasone may accelerate the fetal stage of lung development.

Animals↗
PubMed1999

Increased tropoelastin and procollagen expression in the lung of nitrofen-induced diaphragmatic hernia in rats.

BACKGROUND/PURPOSE: Collagen and elastin, the predominant components of the lung connective tissue network, have been suggested to have an important influence on lung compliance and maximal expansion. Decrease in lung compliance and distensibility often is seen in human congenital diaphragmatic hernia (CDH) lung as well as in experimentally produced CDH lung. The aim of this study was to investigate mRNA levels of tropoelastin and alpha1 (I) procollagen, the precursors of elastin, and type I collagen, respectively, in CDH lung and to determine whether antenatal dexamethasone treatment has any effect on the production of these extracellular matrix proteins. METHODS: CDH model was induced in pregnant rats after administration of 100 mg nitrofen on day 9.5 of gestation (term, 22 days). Dexamethasone (0.25 mg/kg) was given on day 18.5 and 19.5. Cesarean section was performed on day 21. The fetuses were divided into three groups: group I, normal controls; group II, nitrofen-induced CDH; and group III, nitrofen-induced CDH with antenatal dexamethasone treatment. Reverse transcription-polymerase chain reaction (RT-PCR) was performed to evaluate relative amounts of tropoelastin and alpha1 (I) procollagen mRNA. RESULTS: Levels of both tropoelastin and alpha1 (I) procollagen mRNA were significantly increased in group II compared with group I (P< .05). Neither tropoelastin nor alpha1 (I) procollagen mRNA levels were significantly different between group II and III. CONCLUSIONS: The increased local synthesis of tropoelastin and type I procollagen in CDH lung may be responsible for the increased rigidity and decreased compliance observed in the CDH hypoplastic lung. Glucocorticoids have no effect on pulmonary tropoelastin and alpha1 (I) procollagen gene expression in CDH lungs.

Animals↗
PubMed1999

Adhesive bonding of noble metal alloys with a triazine dithiol derivative primer and an adhesive resin.

The purpose of this study was to evaluate the bond strength and durability of a metal adhesive system bonded to noble metal alloys. Disc specimens were cast from type IV gold (type IV, Casting Gold M. C., metal-ceramic gold (Au-Pt-Pd, Degudent Universal, metal-ceramic palladium (Pd-Ga-Co, PTM 88 silver-indium (Ag-In-Zn, Salivan Hard and silver-palladium-copper-gold (Ag-Pd-Cu, S12) alloys and pure silver (pure Ag). The specimens were air-abraded with 50 micron alumina, conditioned with a thiol-based primer designed for noble alloys (V-Primer), and then bonded with an adhesive resin (Super-Bond Opaque Ivory). Shear bond strengths were determined after repeated thermocycling (4-60 degrees C, 1 min each, 100 000 cycles). The average bond strengths in MPa (n=8) were 30.9 for the type IV alloy, 29.0 for the Ag-Pd-Cu alloy, 28.0 for the Au-Pt-Pd alloy, 26.3 for the pure Ag, 26.0 for the Pd-Ga-Co alloy and 9.3 for the Ag-In-Zn alloy. The Ag-In-Zn alloy exhibited significantly lower bond strength than the other alloys, whereas the bond strengths of the other four alloys and pure Ag were comparable (P<0.05). It is concluded that the combined use of the thiol derivative primer and the adhesive resin is effective for bonding the noble metal alloys examined, with the exception of the Ag-In-Zn alloy.

Adhesives↗
PubMed1999

The effect of graded postischemic spinal cord hypothermia on neurological outcome and histopathology after transient spinal ischemia in rat.

BACKGROUND: Previous data have shown that postischemic brain hypothermia is protective. The authors evaluated the effect of postischemic spinal hypothermia on neurologic function and spinal histopathologic indices after aortic occlusion in the rat. METHODS: Spinal ischemia was induced by aortic occlusion lasting 10 min. After ischemia, spinal hypothermia was induced using a subcutaneous heat exchanger. Three studies were conducted. In the first study, the intrathecal temperature was decreased to 34, 30, or 27 degrees C for 2 h beginning with initial reperfusion. In the second study, hypothermia (target intrathecal temperature 27 degrees C) was initiated with reflow and maintained for 15 or 120 min. In the third study, the intrathecal temperature was decreased to 27 degrees C for 2 h starting 5, 60, or 120 min after normothermic reperfusion. Animals survived for 2 or 3 days, at which time they were examined and perfusion fixed with 4% paraformaldehyde. RESULTS: Normothermic ischemia followed by normothermic reflow resulted in spastic paraplegia and spinal neuronal degeneration. Immediate postischemic hypothermia (27 degrees C for 2 h) resulted in decreasing motor dysfunction. Incomplete protection was noted at 34 degrees C. Fifteen minutes of immediate cooling (27 degrees C) also provided significant protection. Delay of onset of post-reflow hypothermia (27 degrees C) by 5 min or more failed to provide protection. Histopathologic analysis revealed temperature-dependent suppression of spinal neurodegeneration, with no effect of delayed cooling. CONCLUSIONS: These findings indicate that the immediate period of reperfusion (0-15 min) represents a critical period that ultimately defines the degree of spinal neuronal degeneration. Hypothermia, when initiated during this period, showed significant protection, with the highest efficacy observed at 27 degrees C.

Animals↗
PubMed1999

Antenatal dexamethasone suppresses tumor necrosis factor-alpha expression in hypoplastic lung in nitrofen-induced diaphragmatic hernia in rats.

The hypoplastic lung in congenital diaphragmatic hernia (CDH) has both a quantitative and qualitative reduction in surfactant. Tumor necrosis factor-alpha (TNF-alpha) drastically decreases surfactant phospholipids synthesis by isolated human type II pneumocytes. Recently, it was shown that TNF-alpha mRNA expression is increased in human hypoplastic CDH lung. Antenatal glucocorticoid therapy demonstrates improved surfactant biochemical immaturity in an animal CDH model. The aim of this study was to investigate the effect of antenatal dexamethasone (Dex) on TNF-alpha protein and gene expression in nitrofen-induced CDH hypoplastic lung in rats. A CDH model was induced in pregnant rats after the administration of nitrofen on d 9.5 of gestation. Dex was given intraperitoneally on d 18.5 and 19.5. Cesarean section was performed on d 21. In situ hybridization was performed with a rat TNF-alpha-specific and digoxigenin-labeled oligonucleotide probe. TNF-alpha level was measured in solubilized lung tissue extracts by ELISA. In control lung, TNF-alpha mRNA expression was weak or absent. In contrast, strong TNF-alpha mRNA expression was demonstrated in type II pneumocytes and bronchiolar epithelium in CDH lung. In Dex-treated CDH lung, TNF-alpha mRNA expression was weak in both type II pneumocytes and the bronchiolar epithelium. The level of TNF-alpha was elevated significantly in CDH lung compared with levels in control lung extracts (p < 0.01). In Dex-treated CDH lung, TNF-alpha protein was significantly decreased compared with CDH lung (p < 0.05). Our findings suggest that the reduction in the local production of TNF-alpha may be one contributing mechanism by which antenatal glucocorticoid therapy improves pulmonary parenchymal immaturity, including surfactant.

Abnormalities, Drug-Induced↗