Pan-Asian adaptation of the EHNS-ESMO-ESTRO Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with squamous cell carcinoma of the head and neck.

The most recent version of the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of squamous cell carcinoma (SCC) of the oral cavity, larynx, oropharynx and hypopharynx was published in 2020. It was therefore decided by both the ESMO and the Korean Society of Medical Oncology (KSMO) to convene a special, virtual guidelines meeting in July 2021 to adapt the ESMO 2020 guidelines to consider the potential ethnic differences associated with the treatment of SCCs of the head and neck (SCCHN) in Asian patients. These guidelines represent the consensus opinions reached by experts in the treatment of patients with SCCHN (excluding nasopharyngeal carcinomas) representing the oncological societies of Korea (KSMO), China (CSCO), India (ISMPO), Japan (JSMO), Malaysia (MOS), Singapore (SSO) and Taiwan (TOS). The voting was based on scientific evidence and was independent of the current treatment practices and drug access restrictions in the different Asian countries. The latter was discussed when appropriate. This manuscript provides a series of expert recommendations (Clinical Practice Guidelines) which can be used to provide guidance to health care providers and clinicians for the optimisation of the diagnosis, treatment and management of patients with SCC of the oral cavity, larynx, oropharynx and hypopharynx across Asia.

PVX-tolerant potato development using a nucleic acid-hydrolyzing recombinant antibody.

3D8 scFv, a catalytic recombinant antibody developed in the MRL mouse, exhibits nucleic acid-hydrolyzing activity. Previous studies have demonstrated that tobacco plants harboring 3D8 scFv antibodies showed broad-spectrum resistance to infection by both DNA and RNA viruses. In this study, potatoes were transformed with the 3D8 scFv gene and screened by potato virus X (PVX) challenge. Starting with the T0 and T1 potato lines, PVX-tolerant T1 potatoes were identified in the field and characterized by ELISA and RT-PCR analysis. T2 potatoes were propagated for T3 generation and additional virus challenges in the field, and 44% of the 3D8 scFv T3 transgenic potatoes grown in GMO fields were found to be tolerant to PVX infection. Tubers from PVX-tolerant T3 lines were 60% bigger and 24% heavier, compared with tubers from PVX-susceptible transgenic lines and wild-type potatoes. Three-step virus challenge experiments and molecular characterization techniques were used for plants grown in growth chambers or fields to identify 3D8 scFv-transgenic, PVX-tolerant potatoes. These studies also revealed that the viral tolerance enabled by 3D8 scFv persisted during asexual propagation.

p47phox and reactive oxygen species production modulate expression of microRNA-451 in macrophages.

The production of microRNAs (miRNA) is influenced by various stimuli, including environmental stresses. We hypothesized that reactive oxygen species (ROS)-associated stress could regulate macrophage miRNA synthesis. miRNAs undergo unique steps of maturation processing through either one of two pathways of cytoplasmic processing. Unlike the canonical pathway, the regulation of alternative cytoplasmic processing of miRNA has not been fully elucidated yet. We cultured bone marrow derived macrophages (BMDM) from wild type (WT) and p47(phox-/-) mice and profiled miRNA expression using microarrays. We analyzed 375 miRNAs including four endogenous controls to normalize the data. At resting state, p47(phox-/-) BMDM has the markedly reduced expression of miR-451 compared to WT BMDM, without other significant differences. Unlike majority of miRNAs, miR-451 goes through the unique alternative processing pathway, in which Ago2 plays a key role. In spite of significant reduction of mature miR-451, however, its precursor form, pre-mir-451, was similar in both BMDMs, suggesting that the processing of pre-mir-451 is impaired in p47(phox-/-) BMDM. Moreover, p47(phox-/-) BMDM expressed significantly reduced level of Ago2. In contrast, Ago2 mRNA levels were similar in WT and p47(phox-/-) BMDM, suggesting a post-transcriptional defect of Ago2 production in p47(phox-/-) macrophages, which resulted in impaired processing of pre-miR-451. In order to examine the functional significance of miR-451 in macrophages, we cultured BMDMs from miR-451 knock-out mice. Of interest, miR-451-deficient BMDM exhibited reduced ROS generation upon zymosan stimulation, compared to WT BMDM. Our studies suggest functional crosstalk between ROS and miR-451 in the regulation of macrophage oxidant stress.

Aluminum based sulfide solid lithium ionic conductors for all solid state batteries.

The present work focuses on the synthesis of lithium ionic conductors based on a Li2S-Al2S3-GeS-P2S5 system due to the high ionic conductivity exhibited by the constituents of this system. Mechanical milling for a short duration and a single step heat treatment at a moderate temperature of 550 °C resulted in crystalline powders with high lithium ionic conductivity at room temperature that are comparable to the organic liquid electrolytes. The effect of various aluminum to germanium ratios was studied. Among the samples containing Al : Ge, the ratio of 30 : 70 was found to show high ionic conductivities of 1.7 × 10(-3) S cm(-1) at 25 °C and ∼ 6 × 10(-3) S cm(-1) at 100 °C equivalent. The activation energy of this material was significantly less (Ea = 17 kJ mol(-1)), which can be considered to be the best value among solid electrolytes. The electrochemical stability was analyzed using cyclic voltammetry between -0.3 and 5.0 V and it was found that the voltammetric profile was smooth without any additional current response, due to electrolyte decomposition, or any other side reaction, except a pair of lithium deposition and stripping peaks.

Sympathetic influence on biomechanical skin properties after spinal cord injury.

STUDY DESIGN: Case-control study. OBJECTIVES: To investigate changes of biomechanical skin properties and their relationship with paralysis following spinal cord injury (SCI). SETTING: South Korea. METHODS: A total of 48 male subjects with chronic SCI and 48 age-matched healthy controls were enrolled into this study. The C4 shoulder group and L2 thigh group were prescribed by two measured anatomical regions that represented the C4 and L2 American Spinal Injury Association sensory dermatomes. Each anatomical group was comprised of one control subgroup and three SCI subgroups determined by sympathetic paralysis at the measured region and somatic completeness. The following biomechanical skin properties were compared between the subgroups in each anatomical group by using Cutometer, a non-invasive suction device: distensibility (Uf), elasticity (Ua/Uf and Ur/Uf) and viscoelasticity (Uv/Ue and H). The impact of sympathetic and somatic sensory paralysis, somatic completeness, age, smoking, body mass index and duration of injury on the indices of skin properties were analyzed. RESULTS: In each anatomical group, sympathetic paralyzed subgroups regardless of somatic sensory completeness showed lower value of skin distensibility (Uf), and higher values of elasticity (Ua/Uf and Ur/Uf) and viscoelasticity (Uv/Ue and H), compared with other subgroups. Age and duration of injury had significant impact on biomechanical skin properties. CONCLUSION: The non-invasive suction method is useful for quantitative evaluation of skin affected by SCI. In chronic SCI patients, biomechanical skin properties are significantly altered in the skin with sympathetic paralysis rather than somatic sensory paralysis.

The incidence, risk factors and prognostic implications of venous thromboembolism in patients with gastric cancer.

BACKGROUND: Data on venous thromboembolism (VTE) in gastric cancer (GC) are very scarce. OBJECTIVE: To investigate the incidence, risk factors and prognostic implications of VTE in Asian GC patients. METHODS: Prospective databases containing clinical information on GC patients (n = 2,085) were used. RESULTS: The 2-year cumulative incidences of all VTE events were 0.5%, 3.5% and 24.4% in stages I, II-IV(M0) and IV(M1), respectively. Advanced stage, older age and no major surgery were independent risk factors for developing VTE. When the VTE cases were classified into extremity venous thrombosis (EVT), pulmonary thromboembolism (PTE) or intra-abdominal venous thrombosis (IVT), IVTs (62%) were more common than EVTs (21%) or PTEs (17%). Although peri-operative pharmacologic thromboprophylaxis was not routinely administered, the VTE incidence after major surgery was only 0.2%. During chemotherapy, EVT/PTE developed more frequently than IVT (54% vs. 19%); however, during untreated or treatment-refractory periods, IVT developed more frequently than EVT/PTE (69% vs. 36%). In multivariate models, the development of EVT/PTE was a significant predictor of early death when compared with no occurrence of VTE (P < 0.05). However, IVT did not affect survival. CONCLUSION: This is the largest study that specially focused on VTE in GC and the VTE incidence in Asian GC patients was first demonstrated. Considering the low incidence of post-operative VTE development, the necessity of peri-operative pharmacologic thromboprophylaxis should be evaluated separately in Asian patients. The clinical situation of the development of EVT/PTE and IVT differed. Only EVT/PTE had an adverse effect on survival and IVT had no prognostic significance.

Kinase activity-independent suppression of p73alpha by AMP-activated kinase alpha (AMPKalpha).

Although p73alpha induces many of the same cellular events as p53, it is structurally distinct from p53 in that it possesses a unique COOH-terminal domain. To dissect the function of this domain, we performed yeast two-hybrid screening of a HeLa cDNA library using residues 552-636 of p73alpha as bait. Among the clones that showed a specific interaction with p73alpha was AMP-activated protein kinase alpha (AMPKalpha). Additional yeast two-hybrid assays indicated that the betagamma-binding domain of AMPKalpha is critical for the interaction with p73alpha. The interaction was further confirmed in vitro by glutathione S-transferase pull-down, and in vivo by immunoprecipitation and immunofluorescence microscopy. Transient coexpression of AMPKalpha resulted in downregulation of the effect of p73alpha, but not of p53, on various p53-responsive promoters. Chromatin immunoprecipitation indicated p73alpha-dependent recruitment of AMPKalpha to the p21WAF1 promoter. Treatment with 5-aminoimidazole-4-carboxamide ribonucleotide, an agonist of AMPKalpha, and expression of dominant-negative versions of AMPKalpha revealed that the repression of p73alpha was independent of AMPKalpha kinase activity. In addition, cisplatin-induced growth repression was impaired when AMPKalpha was overexpressed. Upon the knock down of AMPKalpha by siRNA, the induction of p21WAF1 by p73alpha was significantly increased. Taken together, these data indicate that AMPKalpha specifically regulates p73alpha by a direct interaction without affecting its phosphorylation status. From these data, we speculate that AMPKalpha may provide a molecular clue to understand the repressive role of the C-terminus of p73alpha in transcription and DNA damage response.

Src kinase-targeted anti-inflammatory activity of davallialactone from Inonotus xeranticus in lipopolysaccharide-activated RAW264.7 cells.

BACKGROUND AND PURPOSE: Mushrooms are popular both as food and as a source of natural compounds of biopharmaceutical interest. Some mushroom-derived compounds such as beta-glucan have been shown to be immunostimulatory; this study explores the anti-inflammatory properties of hispidin analogues derived from the mushroom, Inonotus xeranticus. We sought to identify the molecular mechanism of action of these hispidin analogues by determining their effects on lipopolysaccharide (LPS)-mediated inflammatory responses in a macrophage cell line. EXPERIMENTAL APPROACH: The production of inflammatory mediators was determined by Griess assay, reverse transcription-PCR and ELISA. The inhibitory effect of davalliactone on LPS-induced activation of signalling cascades was assessed by western blotting, immunoprecipitation and direct kinase assay. KEY RESULTS: In activated RAW264.7 cells, davallialactone strongly downregulated LPS-mediated inflammatory responses, including NO production, prostaglandin E2 release, expression of proinflammatory cytokine genes and cell surface expression of co-stimulatory molecules. Davallialactone treatment did not alter cell viability or morphology. Davallialactone was found to exert its anti-inflammatory effects by inhibiting a signalling cascade that activates nuclear factor kappa B via PI3K, Akt and IKK, but not mitogen-activated protein kinases. Treatment with davallialactone affected the phosphorylation of these signalling proteins, but not their level of expression. These inhibitory effects were not due to the interruption of toll-like receptor 4 binding to CD14. In particular, davallialactone strongly inhibited the LPS-induced phosphorylation and kinase activity of Src, implying that Src may be a potential pharmacological target of davallialactone. CONCLUSIONS AND IMPLICATIONS: Our data suggest that davallialactone, a small molecule found in edible mushrooms, has anti-inflammatory activity. Davallialactone can be developed as a pharmaceutically valuable anti-Src kinase agent.

VCaP, a cell-based model system of human prostate cancer.

OBJECTIVES: We report the isolation and characterization of a novel prostate cancer cell line derived from a vertebral metastatic lesion, Vertebral-Cancer of the Prostate (VCaP). METHODS: Prostate cancer tissue was harvested at autopsy from a metastatic lesion to a lumbar vertebral body of a patient with hormone refractory prostate cancer. This tissue was aseptically xenografted into SCID mice and later harvested and plated on tissue culture dishes. For characterization, soft agar clonegenic assay, in vivo xenograft growth, in vitro doubling time, karyotype analysis, immunocytochemistry for cytokeratin-18 expression immunochemistry for PSA (prostate specific antigen), RT PCR for PAP (prostatic acid phosphatase) and northern blot and western blot analysis to determine expression of Rb and p53, were performed. Androgen receptor expression was measured by transient transfection with a luciferase reporter construct. RESULTS: VCaP cells are immortal in vitro and can be passaged serially in vivo. They express large quantities of prostate specific antigen (PSA). This cell line also expresses prostatic acid phosphatase (PAP), cytokeratin-18 and the androgen receptor, and is androgen sensitive in vitro and in vivo. CONCLUSIONS: This cell line was derived from a metastatic tumor to the vertebrae of a prostate cancer patient. It exhibits many of the characteristics of clinical prostate carcinoma, including expression of PSA, PAP, and AR. We believe that VCaP will be a useful addition to the existing models of prostate cancer, and enable more advanced study of the mechanisms of prostate cancer progression and metastasis.

Establishment and characterization of a new human prostatic cancer cell line: DuCaP.

BACKGROUND: The lack of appropriate, clinically relevant, cell-based model systems has limited prostate cancer research and the development of new therapeutic modalities. Here we report the isolation and characterization of a new adherent prostate cancer cell line, derived from the dura mater of a cancer patient. METHODS: Prostate cancer tissue was harvested at autopsy from a metastatic lesion to the dura mater of a patient with hormone refractory prostate cancer. This tissue was xenografted into SCID mice and later harvested and plated on tissue culture dishes. For characterization, soft agar clonegenic assay, in vivo xenograft growth, in vitro doubling time, karyotype analysis, immunocytochemistry for cytokeratin-18, androgen receptor, and PAP (prostatic acid phosphatase) expression, RT PCR for PAP, PSMA (prostate specific membrane antigen), expression and northern and western blot analysis to determine expression of Rb and p53, were performed. RESULTS: DuCap grows in vitro (passage 55), forms colonies in soft agar, produces tumors in SCID mice (xenograft passage 12), and is androgen sensitive. DNA content was hypertriploid. PSA was detected in mouse serum and media. Cells were AR, PAP and cytokeratin-18 positive by immunocytochemistry. PSMA and PAP were detected by RT-PCR. AR, P53, and Rb were expressed in Northern blot analysis. P53 protein was detected in Western blot analysis but Rb protein was not. CONCLUSIONS: This cell line exhibits many phenotypic characteristics of clinical prostate carcinoma, including expression of PSA, PSMA, PAP and AR.

Comparison of laser epithelial keratomileusis and photorefractive keratectomy for low to moderate myopia.

PURPOSE: To compare the effectiveness, safety, and stability of laser epithelial keratomileusis (LASEK), a modified photorefractive keratectomy (PRK) technique, with those of conventional PRK for low to moderate myopia. SETTING: Department of Ophthalmology, Yonsei University School of Medicine, Seoul, Korea. METHODS: In this prospective study, 27 patients with a manifest refraction of -3.00 to -6.50 diopters were treated and followed for 3 months. In each case, PRK was performed in 1 eye and LASEK in the other eye. The first eye treated and the surgical method used in the first eye were randomized. Postoperative pain, epithelial healing time, uncorrected visual acuity (UCVA), manifest refraction, corneal haze, and surgical preference were examined in PRK- and LASEK-treated eyes. RESULTS: During the 3 month follow-up, there were no significant between-eye differences in epithelial healing time, UCVA, or refractive error. However, LASEK-treated eyes had lower postoperative pain scores (P =.047) and corneal haze scores (1 month; P =.02) than PRK-treated eyes. Seventeen patients (63%) preferred the LASEK procedure. CONCLUSIONS: Laser epithelial keratomileusis safely and effectively treated eyes with low to moderate myopia. It reduced the incidence of significant postoperative pain and corneal haze and may prevent the flap- and interface-related problems of laser in situ keratomileusis.

Corneal haze after photorefractive keratectomy using different epithelial removal techniques: mechanical debridement versus laser scrape.

PURPOSE: To determine differences of corneal wound healing and haze after photorefractive keratectomy (PRK) using either mechanical epithelial debridement or laser-scrape epithelial removal in human subjects. DESIGN: A 6-month randomized, masked, prospective, paired-eye clinical study. PARTICIPANTS: Twenty eyes in 10 myopic patients treated between March 1999 and May 1999. INTERVENTION: Photorefractive keratectomy treatments with two different epithelial removal techniques. Continuous z-scan of confocal image, termed confocal microscopy through focusing (CMTF), was performed before surgery and at 3 weeks, 6 weeks, 3 months, and 6 months after surgery. MAIN OUTCOMES MEASURES: Epithelial and stromal thickness measurement, achieved stromal ablation depth, and objective assessment of corneal light-backscattering (corneal haze) were obtained from digital image analysis of the CMTF scans. Manifest refraction was also measured. Student's paired t test or two-way repeated-measures analysis of variance after rank transformation were performed to evaluate statistical differences between groups. RESULTS: Comparison of the mean posttreatment spherical equivalent between the two techniques showed no statistically significant difference. In preoperative corneas, mean epithelial thickness was 50.08+/-3.70 microm in the mechanical debridement group and 50.49+/-4.01 microm in laser-scrape group (not significant). For both groups, the epithelium was significantly thinner at 3 weeks, but returned to preoperative values by 6 months, with no difference between groups. Planned stromal ablation depth by PRK was 59.38+/-11.48 microm (39-73 microm; n = 8) in the mechanical group and 57.75 +/- 7.21 microm (48-70 microm; n = 8) in the laser-scrape group. Achieved stromal ablation depth was not significantly different between the two groups. Most importantly, in both groups CMTF-measured corneal haze increased significantly after surgery, peaked at 3 months, and then decreased at 6 months, with no significant difference between groups. (Power = 0.96). CONCLUSIONS: There is no significant difference in the corneal wound healing response between mechanical epithelial debridement versus laser-scrape technique in human myopic eyes undergoing PRK.

A [4 + 4] 2-pyridone approach to taxol. 3. Stereocontrol during elaboration of the cyclooctane.

Intramolecular photocycloaddition of 2-pyridones connected through a four-carbon tether (6-[4-(1,2-dihydro-1-methyl-2-oxo-3-pyridinyl)-4-[[(1,1-dimethylethyl)++ +dimethylsilyl]oxy]butyl]-4-methoxy-1,3-dimethyl-2(1H)-pyridinone) yields a single tetracyclic product with four new stereogenic centers. The diastereoselectivity of this [4 + 4] reaction is fully controlled by a stereogenic carbon of the tether. Treatment of the photoproduct with osmium tetraoxide transforms the alkene to a diol and the enol ether to an alpha-hydroxy ketone, with stereocontrol dictated by nearby lactams that block one face of each alkene. Allylmagnesium bromide addition to the ketone also yields a single diastereomer, but unexpectedly this product results from approach of the nucleophile to the most-hindered face of the ketone. Study of this reaction in a model system has found the allylic nucleophile to be unique, with nonallylic reagents approaching along the expected, least-hindered path. This contrasteric addition likely results from coordination of the allylic nucleophile to the nearby amide. The amide can therefore act either as a steric shield or as a directing group. The three steps of photocycloaddition, cis-hydroxylation, and nucleophilic addition constructs both quaternary carbons of the cyclooctane and four of the five stereogenic centers found in the eight-membered ring of Taxol.

Effect of 0.2% brimonidine in preventing intraocular pressure elevation after Nd:YAG laser posterior capsulotomy.

BACKGROUND AND OBJECTIVE: To determine the prophylactic effect of 0.2% brimonidine in reducing the elevated intraocular pressure (IOP) in patients undergoing Nd:YAG laser posterior capsulotomy. PATIENTS AND METHODS: The 81 patients (81 eyes), who underwent Nd:YAG laser posterior capsulotomy, were allocated to two treatment groups. One drop of 0.2% brimonidine or vehicle was instilled 1 hour preoperatively and one drop immediately after capsulotomy. IOPs were measured preoperatively and 1, 2, 3, and 24 hours postoperatively. RESULTS: Intraocular pressure decreased from the baseline in the brimonidine group by the third postoperative hour (P<0.05), while the vehicle group exhibited an increase. Intraocular pressure elevations of 5 mm Hg or greater occurred in 7.3% (3/41) in the brimonidine group compared to 20.0% (8/40) in the vehicle group. IOP elevations of 10 mm Hg or greater occurred in 2.4% (1/41) in the brimonidine group compared to 7.5% (3/40) in the vehicle group. CONCLUSIONS: One drop of 0.2% brimonidine instilled 1 hour preoperatively and immediately after capsulotomy was found to be efficacious and safe in preventing IOP elevations that frequently follow Nd:YAG laser posterior capsulotomy.

Nocardia keratitis after traumatic detachment of a laser in situ keratomileusis flap.

PURPOSE: Nocardia are gram-positive bacteria existing ubiquitously in the environment; they can cause keratitis. Nocardia asteroides keratitis occurred in the interface between the stromal bed and flap after traumatic detachment of the flap 4 months after an initially uncomplicated laser in situ keratomileusis (LASIK) procedure. METHODS: Nocardia asteroides keratitis was confirmed by culture. Therapy included topical and oral trimethoprim-sulfamethoxazole. RESULTS: Thirteen months after the trauma, the patient's spectacle-corrected visual acuity was 20/20 with a manifest refraction of -2.25 -1.00 x 30 degrees. CONCLUSIONS: The immediate steps of management consisting of surgically lifting the corneal flap, rapid microbial identification, and proper treatment with specific antibiotics resulted in the successful treatment of Nocardia asteroides keratitis in a traumatized eye after LASIK.

The effective concentration and exposure time of mitomycin-C for the inhibition of lens epithelial cell proliferation in rabbit eyes.

The proliferation of residual lens epithelial cells following cataract surgery is assumed to be a major cause of posterior capsular opacification. To assess the efficacy of mitomycin-C in preventing posterior capsular opacification, we determined the effective concentration and exposure time of mitomycin-C in inhibiting rabbit lens epithelial cell proliferation. The fourth-passaged rabbit lens epithelial cells were maintained for one day and then exposed to mitomycin-C for 1, 2, 3, and 5 minutes, respectively. There were 9 different plating concentrations of mitomycin-C with two-fold serial dilution. The maintenance of the phenotypic properties of lens epithelial cells was confirmed by continuous transcription of lambda-crystalline mRNA determined by reverse transcription-polymerase chain reaction and the polymorphism of the restriction fragment. Cell proliferation was assayed with 3H-thymidine incorporation into DNA. The fourth-passaged cells maintained the expression of lambda-crystalline mRNA, suggesting that they are phenotypically authentic lens epithelial cells. The effective concentrations and exposure time of mitomycin-C were 0.1 mg/ml for 1 minute and 2 minutes, and 0.025 mg/ml for 2 minutes. By these results, we postulated that mitomycin-C at relatively short incubation times could be clinically used for prevention of posterior capsular opacification after cataract surgery.

Prolonged exposure to cigarette smoke blocks the neurotoxicity induced by kainic acid in rats.

We examined the effects of cigarette smoke (CS) on three parameters associated with kainic acid (KA)-induced neurotoxicity: seizure activity, cell loss in the hippocampus, and increased Fos-related antigen (FRA) expression. Animals were exposed to the main stream of CS from 15 Kentucky 2R1F research cigarettes containing 28.6 mg tar and 1.74 mg nicotine per cigarette, for 10 min a day, 6 days per week, for 4 weeks, using an automatic smoking machine. KA administration (10 mg/kg, i.p.) produced robust behavioral convulsions lasting 4-5 h. Pre-exposure to CS significantly reduced the seizures, mortality, and severe loss of cells in regions CA1 and CA3 of the hippocampus after KA administration. Consistently, pre-exposure to CS significantly attenuated the KA-induced increased FRA immunoreactivity in the hippocampus. In contrast, pretreatment with central nicotinic antagonist, mecamylamine (2 or 10 mg/kg, i.p.) blocked the neuroprotective effects mediated by CS in a dose-dependent manner. These results indicate that CS exposure provides neuroprotection against the KA insult via nicotinic receptor activation.

The effect of mitomycin-C on postoperative corneal astigmatism in trabeculectomy and a triple procedure.

BACKGROUND AND OBJECTIVE: The authors attempted to determine the effect of mitomycin-C (MMC) on postoperative corneal astigmatism in patients who underwent trabeculectomy or a triple procedure (trabeculectomy, extracapsular cataract extraction, and intraocular lens implantation). PATIENTS AND METHODS: Using the vector analysis method, the authors measured the postoperative induced astigmatism of 76 eyes in 59 patients who underwent trabeculectomy or a triple procedure with or without the application of MMC. Postoperative induced astigmatism corresponding to the 180 degrees axis was compared between the two groups. RESULTS: The patients who underwent trabeculectomy with or without MMC showed a mean induced astigmatism of -1.01 D and -2.63 D, respectively, after 1 month (P < .05), and 0.34 D and -1.42 D after 12 months (P < .05). Those who underwent a triple procedure with or without MMC showed a mean induced astigmatism of -1.81 D and -4.50 D, respectively, after 7 days (P < .05), and 1.73 D and -0.13 D, respectively, after 12 months (P < .05). The entire amount of postoperative against-the-rule astigmatic shift was similar between the with-MMC group and the without-MMC group. The against-the-rule astigmatic shift of the group without MMC reached a plateau after 3 months. However, the group with MMC showed continuous against-the-rule astigmatic shift until 12 months. CONCLUSION: This study suggests that MMC induces less with-the-rule astigmatism in early postoperative periods and continuous against-the-rule shift after 3 months following a trabeculectomy or a triple procedure.

TGF-beta s stimulate cell proliferation via an autocrine production of FGF-2 in corneal stromal fibroblasts.

PURPOSE: Although transforming growth factor-betas (TGF-beta s) inhibit epithelial cell proliferation, these same substances stimulate cell proliferation of fibroblasts. In order to elucidate the mechanism of stimulatory activity of TGF-beta on fibroblast, the present study was performed to determine whether TGF-beta might be an indirect mitogen acting through induction of an endogenous growth factor(s) that then acts as the direct mitogen in an autocrine manner in corneal stromal fibroblasts (CSFs). METHODS: Cell proliferation was determined either by counting cell numbers or by analyzing the incorporation of [3H]-thymidine into DNA. The synthesis of TGF-beta, TGF-beta receptors, FGF-2 and p27 was analyzed by immunoprecipitation and immunoblotting. RESULTS: TGF-beta 1, TGF-beta 2, and TGF-beta 3 significantly stimulated cell proliferation of CSFs in a dose-dependent manner. The medium conditioned by CSFs and subsequently activated by acid-inhibited cell proliferation of corneal endothelial cells by 40%. When the acid-activated media conditioned by CSFs were immunoprecipitated with either combined anti-TGF-beta 1 and TGF-beta 2 antibodies or anti-TGF-beta 3 antibody, all three TGF-beta s, with an apparent molecular size of 25 kDa, were detected, whereas CSFs produced an 80-kDa latent form of TGF-beta 1. These cells can also express TGF-beta type II receptor and betaglycan. Interestingly, CSFs produced and secreted 18-kDa FGF-2, the synthesis of which is further stimulated by either TGF-beta 1 or TGF-beta 3, while both the neutralizing antibody to FGF-2 and the FGF-2 specific antisense oligonucleotide primers significantly inhibited the stimulatory activities of TGF-beta 1 in CSFs. The expression of p27, a negative regulator in cell cycle, was not altered by TGF-beta. CONCLUSIONS: These findings indicate that CSFs produce both TGF-beta s and FGF-2 and that FGF-2 appears to be a direct stimulator for TGF-beta-mediated cell proliferation in CSFs.

Effect of subchronic administration of antioxidants against cigarette smoke exposure in rats.

Effects of subchronic administration of antioxidants against pulmonary damage mediated by cigarette smoke were investigated in rats. Rats were continuously received ascorbic acid, N-acetylcysteine and ginseng extract together drinking water from day 25 after birth. After 30 days of antioxidant supplementation, rats were exposed to cigarette smoke generated from six cigarettes (11 mg tar) for 20 min per day throughout 30 days, and then several biochemical markers related to the redox status in vivo were analyzed in the respiratory system. The cigarette smoke induced mild histological changes in trachea and lungs. The activity of superoxide dismutase (SOD) in the lung was significantly increased, and catalase and glutathione peroxidase activities were increased less than SOD, but total sulfhydryl compounds (Total-SH) content was decreased by cigarette smoking. In spite of the increase in activities of antioxidant enzymes, the inhibitory capacity of lung preparations on in vitro lipid peroxidation using ox brain homogenates was decreased and the change in the capacity was not related to the changes of these intracellular enzymes activities, but with the content of Total-SH. On the other hand, the content of thiobarbituric acid reactive substances and the ratio of elastase to anti-protease in the lung homogenates were significantly increased. Supplementation of antioxidants, however, effectively attenuated all of such alterations induced by cigarette smoke. These results indicate that although cigarette smoking induces antioxidant enzymes in the lung as a self defense mechanism, it seems to be not sufficient to protect the pulmonary system, and that chronic antioxidant feeding could be effective to reduce pulmonary damage induced by free radicals.