The hepatoprotective effect of lycopene on Con A-induced liver injury in mice.

Lycopene, the main fat-soluble pigment responsible for the red color of ripe tomatoes, is a symmetrical tetraterpene comprising eight isoprene units. In vitro and in vivo studies have shown that lycopene acts as a potent antioxidant; it is 100 times more effective than vitamin E and 125 times more effective than glutathione as an antioxidant. Here, we divided BALB/c male mice into three equal groups: control, Concanavalin A (Con A), and Con A and lycopene. The control group mice received only vehicle by intraperitoneal injection, the Con A group mice were given Con A, and the Con A and lycopene group mice received Con A and lycopene. The results showed that Con A administration increased histopathological damage, and the levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), interleukin (IL)-6, interferon (IFN)-γ and tumor necrosis factor (TNF)-α were increased in serum samples whereas the levels of these compounds were significantly decreased in the Con A and lycopene group compared to the Con A group. Furthermore, we observed that lycopene led to an increase in cell viability and cell growth. The results of this study revealed that lycopene might be a useful hepatoprotective agent for reducing increased proinflammatory cytokine levels, and for increasing cell viability and cell growth.

Effects of surface charge and palladium on hepatic and kidney injury induced by polystyrene nanoparticles co-administered to mice with paraquat and cisplatin.

Recently, with the advancement of nanotechnology, various nanoparticles have been developed and used in fields such as electronics, cosmetics, and foods. However, the toxicity of nanoparticles has yet to be fully investigated. In particular, the interactions between nanoparticles and therapeutic drugs require further study. We previously reported that unmodified polystyrene nanoparticles with a particle size of 50 nm (NPP50) co-administered with paraquat (PQ) or cisplatin (CDDP) induce hepatic and kidney injury. Here, we determined if NPP50 modified with the amino group (NPP50-NH2), carboxyl group (NPP50-COOH), or palladium (Pd-NPP50) caused liver or kidney injury when co-administered with PQ or CDDP. The results showed that when NPP50-NH2, NPP50-COOH, or Pd-NPP50 was administered alone via the mouse tail vein, serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and blood urea nitrogen (BUN) did not increase or cause injury. When NPP50, NPP50-NH2, NPP50-COOH, or Pd-NPP50 was co-administered with PQ, serum levels of ALT and AST increased in the NPP50 group but did not increase in the NPP50-NH2, NPP50-COOH, or Pd-NPP50 groups. When NPP50-NH2, NPP50-COOH, or Pd-NPP50 was co-administered with CDDP, ALT, AST, and BUN values did not increase. These data suggest that injury due to the interaction of polystyrene nanoparticles with CDDP or PQ can be suppressed by changes in the surface charge of nanoparticles or by Pd modification.

Helical Phase Structure of Radiation from an Electron in Circular Motion.

We theoretically show that a single free electron in circular motion radiates an electromagnetic wave possessing helical phase structure, which is closely related to orbital angular momentum carried by it. We experimentally demonstrate it by interference and double-slit diffraction experiments on radiation from relativistic electrons in spiral motion. Our results indicate that photons carrying orbital angular momentum should be created naturally by cyclotron/synchrotron radiations or Compton scatterings in various situations in cosmic space. We propose promising laboratory vortex photon sources in various wavelengths ranging from radio wave to gamma-rays.

Angular Momentum of Twisted Radiation from an Electron in Spiral Motion.

We theoretically demonstrate for the first time that a single free electron in circular or spiral motion emits twisted photons carrying well-defined orbital angular momentum along the axis of the electron circulation, in adding to spin angular momentum. We show that, when the electron velocity is relativistic, the radiation field contains harmonic components and the photons of lth harmonic carry lℏ total angular momentum for each. This work indicates that twisted photons are naturally emitted by free electrons and are more ubiquitous in laboratories and in nature than ever thought.

Hepatotoxicity, nephrotoxicity, and drug/chemical interaction toxicity of platinum nanoparticles in mice.

Nanomaterials are frequently used in microelectronics, cosmetics, and sunscreens. Platinum reagents are commonly used in disease diagnosis, cosmetics, and the food industry. Although research into the development of nanomaterialbased drug delivery systems has yielded promising results, the toxicity of these materials is not fully understood. We investigated the toxicity and drug interactions of 1- and 8-nm diameter platinum nanoparticles (nPt1 and nPt8, respectively) in mice. Acute hepato-renal toxicity of intravenously administered platinum nanoparticles was evaluated biochemically and histologically. Dose-dependent increases in serum markers of hepato-renal function (serum aminotransferases and blood urea nitrogen) were observed following administration of nPt1, whereas nPt8 had no effect, even at 20 mg/kg. Moreover, nPt1 induced interleukin (IL)-6 and IL-1ß production 3 and 6 hours after administration. The effect of nPts on drug-induced toxicity was evaluated in mice injected intraperitoneally with carbon tetrachloride or cisplatin, with or without intravenous administration of platinum nanoparticles. All treatments in the absence of nanoparticles were non-lethal and resulted in moderate toxicity. However, exacerbated toxicity was observed in mice injected with carbon tetrachloride or cisplatin together with nPt1, but not in mice co-injected with nPt8. We found that nPt1 cause hepato-renal damage, and the effect is enhanced by chemical inducers of hepatotoxicity and nephrotoxicity. This is the first report demonstrating that nPt1 not only are hepatotoxic and nephrotoxic but also exacerbate drug toxicity. These findings will be useful for future nanotechnology and nanoscience research.

Communicating Radiation Risk to the Population of Fukushima.

Radiological specialists from Nagasaki University have served on the medical relief team organized at Fukushima Medical University Hospital (Fukushima City) ever since the accident at the Fukushima Dai-ichi nuclear power plant. Furthermore, we have conducted the radiation crisis communication efforts by spreading correct information on the health effects of radiation as 'advisors on radiation health risk control'. Nagasaki University has been assisting the reconstruction efforts of Kawauchi Village in Fukushima Prefecture, which was the first village to declare that residents could safely return to their homes because radiation doses were found to be at comparatively low levels. In April 2013, Nagasaki University and the Kawauchi government office concluded an agreement concerning comprehensive cooperation toward reconstruction of the village. As a result, we established a satellite facility of the university in the village. In conclusion, training of specialists who can take responsibility for long-term risk communication regarding the health effects of radiation as well as crisis communication in the initial phase of the accident is an essential component of all such recovery efforts. Establishment of a training system for such specialists will be very important both for Japan and other countries worldwide.

Images created in a model eye during simulated cataract surgery can be the basis for images perceived by patients during cataract surgery.

PURPOSE: To evaluate the images created in a model eye during simulated cataract surgery. PATIENTS AND METHODS: This study was conducted as a laboratory investigation and interventional case series. An artificial opaque lens, a clear intraocular lens (IOL), or an irrigation/aspiration (I/A) tip was inserted into the 'anterior chamber' of a model eye with the frosted posterior surface corresponding to the retina. Video images were recorded of the posterior surface of the model eye from the rear during simulated cataract surgery. The video clips were shown to 20 patients before cataract surgery, and the similarity of their visual perceptions to these images was evaluated postoperatively. RESULTS: The images of the moving lens fragments and I/A tip and the insertion of the IOL were seen from the rear. The image through the opaque lens and the IOL without moving objects was the light of the surgical microscope from the rear. However, when the microscope light was turned off after IOL insertion, the images of the microscope and operating room were observed by the room illumination from the rear. Seventy percent of the patients answered that the visual perceptions of moving lens fragments were similar to the video clips and 55% reported similarity with the IOL insertion. Eighty percent of the patients recommended that patients watch the video clip before their scheduled cataract surgery. CONCLUSIONS: The patients' visual perceptions during cataract surgery can be reproduced in the model eye. Watching the video images preoperatively may help relax the patients during surgery.

Fecal steroid metabolites and reproductive monitoring in a female Tsushima leopard cat (Prionailurus bengalensis euptilurus).

Although the Tsushima leopard cat (Prionailurus bengalensis euptilurus) is one of the most endangered mammals in Japan, its reproductive physiology and endocrinology have been not elucidated. The objective was to establish the non-invasive monitoring of reproductive endocrinology in a female Tsushima leopard cat and to identify the types of fecal reproductive steroid metabolites in this species. Fecal concentrations of estrogen and progestin were determined by enzyme immunoassays, from 60 d before to 60 d after the last copulation, during three pregnancies. Fecal estrogen metabolite concentrations were increased before/around the mating period and after mid-pregnancy. Fecal progestin metabolite concentrations increased after the last copulation and remained high during pregnancy. The gestation period was 65.0 ± 0.6 d (mean ± SD). Fecal extracts were separated by high-performance liquid chromatography for identification of fecal metabolites. Fecal estrogens were identified as estradiol-17ß and estrone. Fecal progestins during pregnancy contained 5α-reduced pregnanes: 5α-pregnan-3α-ol-20-one, 5α-pregnan-3ß-ol-20-one and 5α-pregnan-3,20-dione, and nonmetabolized progesterone was barely detected in feces. In conclusion, measurement of fecal estrogen and progestin metabolites was effective for noninvasive reproductive monitoring in the Tsushima leopard cat. An immunoassay for fecal estradiol-17ß concentrations seemed useful to monitor follicular activity, whereas an immunoassay with high cross reactivity for 5α-reduced pregnanes was useful to monitor ovarian luteal activity and pregnancy.

Prospective randomized comparison of DisCoVisc and Healon5 in phacoemulsification and intraocular lens implantation.

PURPOSE: To compare two ophthalmic viscosurgical devices (OVDs), DisCoVisc (viscous dispersive) and Healon5 (viscoadaptive), in terms of their overall clinical performance during phacoemulsification and intraocular lens (IOL) implantation. METHODS: In 323 patients (DisCoVisc; 157, Healon5; 166), the surgeons evaluated on a three-point scale, the maintenance of anterior chamber (AC) during continuous curvilinear capsulorhexis (CCC), maintenance of AC during IOL implantation, retention during phacoemulsification, ease of injection, facilitation of CCC, transparency during surgery, and ease of removal from the eye. The time needed to completely remove OVDs after IOL implantation was measured. Masked examiners measured intraocular pressure (IOP), corneal thickness, and corneal endothelial cell count up to 90 days postoperatively. RESULTS: DisCoVisc was assessed to be significantly better than Healon5 in maintenance of AC during CCC (P=0.0008, Cochran-Mantel-Haenszel test) and IOL implantation (P=0.0055), retention during phacoemulsification (P=0.0009), ease of injection (P<0.0001), facilitation of CCC (P<0.0001), transparency (P<0.0001), and ease of removal (P<0.0001). The washout time was 29.6+/-13.4 and 36.2+/-17.5 s in the DisCoVisc and Healon5 groups, respectively (P=0.0002, unpaired t-test). The mean endothelial cell loss was 1.8+/-8.7% in the DisCoVisc group and 3.8+/-8.3% in the Healon5 group (P=0.0358). There were no statistically significant between-group differences in IOP and corneal thickness. CONCLUSION: DisCoVisc was better retained in the eye during phacoemulsification and was easier to remove after IOL implantation. The corneal endothelial cell loss was significantly less with DisCoVisc than with Healon5. It was indicated that the whole surgical process can be efficiently covered by DisCoVisc alone.

Implant-retained overdenture following hemiglossectomy: a 10-year clinical case report.

A clinical evaluation of an implant-supported overdenture placed in the edentulous mandible after hemiglossectomy is described. The deltopectoral flap covering the mandibular ridge was replaced with a free mucosal graft. Four Brånemark system implants were inserted into the anterior part of the mandible, but one of the four fixtures did not show osseointegration. The superstructure was designed as a spaced round bar-attachment supported by three implants so as to retain the complete overdenture. In addition to the metal clip, a silicone-based soft denture liner material was applied in the female portion of the attachment so as to prevent the attachment from making a clattering noise upon mastication. Although the overdenture required adjustment at regular intervals, the treatment was successful both aesthetically and functionally for up to at least 10 years.

Surface treatment of dentin with GLUMA and iron compounds for bonding indirect restorations.

The purpose of this study was to evaluate five dentin bonding systems simulating indirect restorations. The surface of bovine and human dentin was primed with a glutaraldehyde agent (GLUMA) and placed in a humidor at 37 degrees C for 168 h. In an experimental bonding system (GLUMA/CY/SB), the surfaces were etched with phosphoric acid, primed with cytochrome c, and then bonded to an acrylic rod with a self-curing resin (4-META/MMA-TBB). Specimens using two commercially available bonding systems [All-Bond 2 (AB2) and Super-Bond C & B (10-3/SB)] and two controls with and without GLUMA (GLUMA/10-3/SB and CY/SB) were also prepared. Tensile testing revealed that the bond strengths were influenced by the bonding system, 168 h dentin exposure and their interaction, but not by the tooth origin. AB2 showed the lowest bond strength. With the 10-3/SB system, exposing the dentin to humidity resulted in a decrease in bond strength. After 168 h of exposure, no significant differences were observed between 10-3/SB and CY/SB. The most effective bonding was obtained with the bonding systems of GLUMA/10-3/SB and GLUMA/CY/SB. Improved outcome is expected with these bonding systems when building up abutment teeth with indirect restorations.

Increased vascular endothelial growth factor peptide and gene expression in hypoplastic lung in nitrofen induced congenital diaphragmatic hernia in rats.

Persistent pulmonary hypertension (PPH) in congenital diaphragmatic hernia (CDH) lung has been shown to be associated with structural changes in the pulmonary vasculature, including medial and adventitial thickening. Vascular endothelial growth factor (VEGF) is a potent mitogenic and permeability factor targeting predominantly endothelial cells. mRNA encoding VEGF is detected in all fetal tissues and is most abundant in fetal lung, kidney, and liver. Recently, antenatal dexamethasone (Dex) treatment has been shown to prevent pulmonary-artery structural changes in experimentally-produced CDH. The aim of this study was to investigate mRNA and protein levels of VEGF in CDH lung and to determine whether antenatal Dex treatment has any effect on the production of VEGF. A CDH model was induced in pregnant rats following administration of 100 mg nitrofen on days 9.5 of gestation (term=22 days). Dex 0.25 mg/kg was given on day 18.5 and 19.5. Cesarean section was performed on day 21 of gestation. The fetuses were divided into three groups: normal controls (NC, n=8); nitrofen-induced CDH (CDH, n=8); and nitrofen-induced CDH with antenatal Dex treatment (CDH-Dex, n=8). Protein and mRNA were extracted from the whole lung. VEGF protein was measured by ELISA assay and mRNA expression was evaluated by reverse transcription-polymerase chain reaction. Immunohistochemistry using anti-rat VEGF antibody was also performed in each group. VEGF protein as well as mRNA expression were significantly increased in the CDH group compared to the NC group, which was not affected by antenatal Dex treatment. VEGF immunoreactivity in pulmonary vessel walls was increased in the CDH and CDH-Dex groups compared to the NC group. The enhanced VEGF protein and mRNA expression in CDH lung suggests that increased local synthesis of VEGF may be responsible for the structural changes in the pulmonary vasculature in CDH lung. VEGF expression in CDH lung is not downregulated by antenatal Dex treatment.

Adhesive bonding of titanium nitride-plated stainless steel for magnetic attachments.

The purpose of this study was to evaluate adhesive bonding of resin to titanium nitride ion-plated stainless steel in order for magnetic attachments to survive in the oral environment. Two primers, Cesead II Opaque Primer (CPII) and Metal Primer II (MPII), and one bonding agent, Super-Bond C&B (SB), were used. The surfaces of stainless steel disks were ground and then plated with titanium nitride. After the primer and SB resin were applied, a self-curing resin was bonded to the metal surfaces. Shear bond strengths were determined after 24 h of water storage and after 2,000 thermocycles. Titanium nitride ion-plated stainless steel showed bond strength comparable to the non-plated material. After thermocycling, all specimens of the group no primer/no SB were debonded. The bond strengths of groups CPII/no SB, MPII/no SB and no primer/SB were significantly lower bond strengths than groups CPII/SB and MPII/SB. An appropriate combination of primer and bonding agent should be selected when bonding a magnetic attachment to the denture base.

[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.

[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.

Antenatal dexamethasone administration inhibits smooth-muscle-cell DNA synthesis in pulmonary-arterial media in nitrofen-induced congenital diaphragmatic hernia in rats.

The aim of this study was to investigate the effect of antenatal glucocorticoid therapy on smooth-muscle-cell (SMC) DNA synthesis in the pulmonary arteries (PA) in a nitrofen-induced congenital diaphragmatic hernia (CDH) rat model following nitrofen administration on day 9.5 of gestation. Antenatal dexamethasone (DEX) was given intraperitoneally on days 18.5 and 19.5 of gestation. Bromodeoxyuridine (BrdU) was injected via a jugular vein into the dam 1 h before the fetuses were killed by cesarean section at term. The fetuses were divided into three groups: group I (n = 10): normal controls; group II (n = 10): nitrofen-induced CDH; group III (n = 10): nitrofen-induced CDH with antenatal DEX treatment. Immunostaining of the lungs with anti-BrdU antibody was obtained by a standard avidin-biotin complex method. The number of immunopositive cells in the PA media and adventitia were counted using an image analyzer and analyzed statistically. The number of BrdU-immunopositive cells in the media was significantly increased in group II (16.83 +/- 3.01) compared to groups I (9.16 +/- 2.20) and III (6.83 +/- 1.70) (P < 0.01). There was no significant difference between groups I and III. The number of BrdU-immunopositive cells in the adventitia was not significantly different between the three groups. Antenatal DEX treatment inhibits SMC DNA synthesis in PA media in CDH lungs. This may be a possible mechanism by which antenatal DEX prevents structural PA changes in nitrofen-induced CDH in rats.

[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.

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.

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).

Administration of antenatal glucocorticoids upregulates peptide growth factor gene expression in nitrofen-induced congenital diaphragmatic hernia in rats.

BACKGROUND/PURPOSE: There is increasing evidence to suggest that various growth factors play a crucial role in fetal lung growth and morphogenesis. An array of peptide growth factors regulate cell proliferation, differentiation, and various other cell functions in the developing lung. The aim of this study was to investigate the effect of antenatal glucocorticoids administration on gene expression of basic fibroblast growth factor (bFGF), platelet-derived growth factor (PDGF) and transforming growth factor (TGF)-beta1 in nitrofen-induced congenital diaphragmatic hernia (CDH) in rats. METHODS: A CDH model was induced in pregnant rats after administration of nitrofen. Dexamethasone (Dex; 0.25 mg/kg) was given intraperitoneally on day 18.5 and 19.5 of gestation (term, day 22). Cesarean section was performed on day 21 of gestation. mRNA was extracted from left lung and reverse transcription-polymerase chain reaction (RT-PCR) was performed to evaluate mRNA expression of each growth factors. Relative 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. RESULTS: Relative mRNA levels of bFGF and TGF-beta1 were decreased significantly in CDH lung compared with controls. Antenatal Dex treatment up-regulated gene expression of bFGF, PDGF, and TGF-beta1 in the hypoplastic CDH lung. CONCLUSIONS: The authors' findings suggest that decreased gene expression of bFGF, PDGF, and TGF-beta1 in the CDH lung may suppress lung growth and development. Increased gene expression of bFGF, PDGF, and TGF-beta1 in Dex-treated lung suggests that antenatal glucocorticoid administration may accelerate fetal lung growth by up-regulating these growth factors.