Biomedical subjects

Koji Okada

Publications and source records attributed to Koji Okada.

18 recordsLinked to original sources

PubMed2006

Mineralocorticoid receptor antagonist spironolactone prevents pig serum-induced hepatic fibrosis in rats.

Mineralocorticoid receptor (MR) antagonist spironolactone (SPL) is an effective agent for prevention of cardiovascular injury. However, whether and how SPL ameliorates hepatic fibrosis in rats is unknown. Pig serum (PS) (0.5 mL, twice a week, ip) or vehicle-administered rats for 12 weeks were used as rats with hepatic fibrosis or control rats, respectively. Rats given PS were treated with SPL (50 mg/kg/day, sc) for 12 weeks. Hepatic fibrosis, using picro-sirius red staining and determination of hydroxyproline content, immunohistochemistries of alpha-smooth muscle actin (alpha-SMA)-positive hepatic stellate cells (HSCs), Na/H exchange isoform-1 (NHE-1) protein, CYP11B2 aldosterone synthase protein for liver tissues, and plasma aldosterone concentrations were compared among the 3 groups of rats. Rats given PS alone exhibited hepatic fibrosis as well as increases in the number of the alpha-SMA-positive HSCs and NHE-1 protein expression in HSCs and hepatocytes, all of which were suppressed by SPL. Rats given PS alone revealed increased CYP11B2 protein expression in HSCs and hepatocytes, which was not inhibited by SPL. Plasma aldosterone concentrations were significantly greater in rats given PS and SPL than in control rats and rats given PS alone, although they were not different between control rats and rats given PS alone. PS-induced hepatic fibrosis together with HSC activation and NHE-1 protein expression occurs via MRs, and SPL ameliorates hepatic fibrosis presumably via the inhibition of HSC activation and NHE-1 protein expression in PS-induced liver injuries. The aldosterone produced in the injured liver contributes to the PS-induced hepatic fibrosis.

Actins↗

PubMed2006

The soluble form of human leukocyte antigen class I antigen causes apoptosis on hepatocellular carcinoma cell lines.

A soluble form of human leukocyte antigen class I antigen (sHLA-I) has been reported to cause apoptosis on cytotoxic T cells and inhibit killer activity of natural killer cells via killer-cell inhibitory receptors. However, its effect on cancer cells has not yet been elucidated. We examined the direct effect of sHLA-I on human liver cancer cell lines, HepG2, HLE and HLF. The effects of sHLA-I on cell growth, DNA synthesis, and apoptosis induction were evaluated. To elucidate the mechanisms, cDNA expression arrays were also examined. sHLA-I caused cell growth inhibition, resulting in apoptosis on human hepatocellular carcinoma, dose-dependently. In this process, caspase-3 was activated. sHLA-I also inhibited in vivo growth of hepatocellular carcinoma in severe combined immunodeficient mice. sHLA-I caused apoptosis on human hepatocellular carcinoma.

Alternative Splicing↗

PubMed2005

Diabetic lipemia with eruptive xanthomatosis in a lean young female with apolipoprotein E4/4.

Eruptive xanthomas in adults are usually indicative of chylomicronemia. Although diabetes mellitus is the most common secondary cause of chylomicronemia, which is designated as diabetic lipemia, the clinical characteristics of diabetes with regard to development of xanthomas are not well defined. In this paper, we describe a young female who displayed eruptive xanthomas as an initial manifestation of diabetic lipemia. The patient was a 20-year-old female with a body mass index of 18.9 kg/m2 and Marfanoid appearance. Her past history was unremarkable, except for patent ductus arteriosus and mild mental retardation. She was admitted to our division for eruptive xanthomas on the extremities and marked hyperglycemia (random glucose, 520 mg/dl) and hypertriglyceridemia (6880 mg/dl). She was diagnosed with Type 2 diabetes based on the positive family history of diabetes, residual secretory capacity of insulin, and absence of autoantibodies related to Type 1 diabetes. Based on the increase in the concentrations of both chylomicrons and very low density lipoproteins, type V hyperlipoproteinemia was diagnosed. After the initiation of insulin therapy, both hypertriglyceridemia and eruptive xanthomas subsided, without administering any hypolipidemic agents. Minimal model analysis of a frequently sampled intravenous glucose tolerance test revealed severe insulin resistance, despite the absence of obesity. Post-heparin lipoprotein lipase (LPL) activity was moderately decreased, and common mutations in the LPL gene were not demonstrated by genetic screening. The apolipoprotein E phenotype was E4/4, which is known to be associated with type V hyperlipoproteinemia. Hypoadiponectinemia of 1.7 microg/ml was also revealed, which may, in part, account for the insulin resistance and decreased LPL activity. In conclusion, the clustering of apolipoprotein E4/4 and hypoadiponectinemia, in addition to insulin resistance and poor glycemic control, might have resulted in hypertriglyceridemia with eruptive xanthomatosis in this subject.

Adult↗

PubMed2005

Clinical features and course of patients with glaucoma with the E50K mutation in the optineurin gene.

PURPOSE: To investigate the clinical features of subjects with glaucoma with the E50K mutation in the optineurin (OPTN) gene and to compare the onset, severity, and clinical course of these patients with a control group of subjects with glaucoma without this mutation. METHODS: The phenotype of well-characterized subjects from Moorfields Eye Hospital, London, who had been identified as carrying the OPTN E50K mutation was examined. A wide range of structural, psychophysical, and demographic factors were then compared with those in a control group of subjects with glaucoma without this mutation. RESULTS: Eleven subjects with glaucoma with the E50K mutation (nine in two families and two sporadic cases) were studied. All 11 subjects had normal tension glaucoma (NTG), with presenting and highest IOP of 15.3 +/- 3.0 and 16.5 +/- 2.5 mm Hg (+/-SD) on diurnal testing. Compared with 87 NTG control subjects who did not have this mutation, subjects with E50K presented at a younger age (40.8 +/- 15 years, P = 0.0001) and had more advanced optic disc cupping (mean cup-disc ratio +/- SD 0.86 +/- 0.1, P = 0.001) and smaller neuroretinal rim area (+/-SD; 0.5 +/- 0.28 mm2, P = 0.001) at diagnosis. The rate of filtration surgery performed for progressive visual field loss in those with and without the E50K mutation was 72.7% and 25.3%, respectively (P = 0.003), and all subjects with E50K were found to have progressing visual fields. In addition, seven E50K mutation-carrying individuals in two families (age range, 23-58 years) presented with normal optic discs and visual fields and, as yet, no signs of glaucoma. CONCLUSIONS: In this study, subjects with glaucoma who had the OPTN E50K mutation were found to have NTG that appeared to be more severe than that in a control group of subjects with NTG without this mutation. The findings emphasize the importance of early detection and treatment of glaucoma in such individuals, to minimize visual loss.

Adult↗

PubMed2004

Spironolactone prevents early renal injury in streptozotocin-induced diabetic rats.

BACKGROUND: Glomerular and tubulointerstitial injury leads to chronic impairment of renal function, and thus, reversal of the injury may improve renal function and survival. The present study investigated whether and how mineralocorticoid receptor antagonist spironolactone ameliorates early renal injury in streptozotocin-induced diabetic rats. METHODS: Streptozotocin (65 mg/kg, single intraperitoneal injection)- or vehicle-administered rats were used as diabetic or control rats, respectively. The streptozotocin-administered rats were treated with spironolactone (50 mg/kg/day sc) for 3 weeks. Among the 3 groups of rats, we compared renal fibrosis and renal hypertrophy, using picro-sirius red staining and immunohistochemistry of ED-1 macrophage marker, plasminogen activator inhibitor-1 (PAI-1), and transforming growth factor (TGF)-beta1. RESULTS: Three weeks after administration of streptozotocin, rats exhibited increased collagen deposition in glomerular, tubulointerstitial, and perivascular areas in the kidney, which was completely attenuated by spironolactone treatment. In rats given streptozotocin alone, there were increases in ED-1-positive cell, PAI-1 expression, and TGF-beta1 expression in glomeruli and tubulointerstitiums, which were also suppressed by spironolactone treatment. Maximal glomerular and proximal tubular areas were not significantly different among the 3 groups. Rats given streptozotocin alone revealed an increase in proximal tubule wall-to-lumen ratio that was not influenced by treatment with spironolactone. CONCLUSION: Streptozotocin-induced renal fibrosis, PAI-1 expression, TGF-beta1 expression, and macrophage infiltration occur via mineralocorticoid receptor, and spironolactone ameliorates renal fibrosis presumably via the inhibition of macrophage infiltration, PAI-1 expression, and TGF-beta1 expression in streptozotocin-induced early diabetic injury.

Animals↗

PubMed2003

Na/H exchange isoform 1 is involved in mineralocorticoid/salt-induced cardiac injury.

Long-term exposure of uninephrectomized rats to desoxycorticosterone acetate (DOCA)/salt induces cardiac fibrosis and hypertrophy through mineralocorticoid receptors (MRs). However, the underlying cellular mechanisms remain unclear. To determine whether Na/H exchange isoform 1 (NHE1) is involved in the cellular mechanisms, we examined the effects of a specific NHE1 inhibitor, cariporide, and an MR antagonist, spironolactone, on DOCA/salt-induced cardiac fibrosis and hypertrophy. Uninephrectomized rats were given 20 mg of DOCA (single subcutaneous injection) plus 0.9% NaCl/0.3% KCl to drink and were killed at 8 days. Two groups of rats given DOCA/salt were treated with either spironolactone (50 mg/kg per day SC) or cariporide (30 mg/kg per day PO) for 8 days. Control rats were treated with only high salt after the operation. The DOCA/salt-induced perivascular collagen deposition was completely abolished by cariporide and spironolactone. DOCA/salt-induced interstitial collagen deposition was partially and completely suppressed by spironolactone and cariporide, respectively. The rats exposed to DOCA/salt had cardiocyte hypertrophy in the subendocardial and subepicardial regions, a finding that was completely inhibited by cariporide but not by spironolactone. In rats given DOCA/salt, NHE1 protein expression was markedly increased. This was partially and completely reversed by spironolactone and cariporide, respectively. We concluded that cardiac NHE1 contributes to DOCA/salt-induced cardiac fibrosis and hypertrophy and that the NHE1 inhibitor cariporide completely prevents the detrimental effects of DOCA/salt on the heart. We also demonstrated that DOCA/salt-induced cardiac injury through the MRs partly occurs through NHE1 activation.

Animals↗

PubMed2003

Efficient gene transfer of a simian immuno-deficiency viral vector into cardiomyocytes derived from primate embryonic stem cells.

BACKGROUND: Embryonic stem (ES) cells continually proliferate and can generate large numbers of differentiated cells. Genetic manipulation of transplantable cells derived from primate ES cells offers considerable potential for development research and regenerative cell therapy. However, protocols for efficient gene transfer into primate ES-cell-derived cells have not yet been established. METHODS: Spontaneously contracting areas were derived from cynomolgus monkey ES cells. Features of cardiomyocytes in the area were analyzed according to gene expression (RT-PCR), morphology (immunostaining and electron microscopy), and function (intracellular calcium transience). Beating cells were transduced using a simian immunodeficiency virus (SIV) vector expressing enhanced green fluorescence protein (EGFP), then transplanted into ischemic rat myocardium. RESULTS: Beating cells derived from monkey ES cells displayed gene expression, ultrastructural and functional properties of early-stage cardiomyocytes. Highly efficient (97% cardiac phenotype) and stable transduction of these ES-cell-derived cardiomyocytes was achieved using SIV vector without altering contractile function. In addition, transduced cardiomyocytes survived in the myocardium of a rat myocardial infarction model. CONCLUSIONS: A lentiviral vector system based on SIV represents a useful vehicle for genetic modification of cardiomyocytes derived from primate ES cells, and can extend the application of primate ES cells to gene therapy.

Animals↗

PubMed2002

The negative correlation between age and intraocular pressures measured nyctohemerally in elderly normal-tension glaucoma patients.

PURPOSE: To evaluate the correlation between age and intraocular pressure (IOP) measured every 3 h for 24 h in older normal-tension glaucoma (NTG) patients. METHODS: Ninety consecutive patients suspected of having NTG on the basis of both visual field defect and disc appearance were hospitalized for measurement of nyctohemeral IOP every 3 h over a 24-h period with a Goldmann tonometer after a 4-week wash-out of any existing medication. Sixty-nine patients (76.7%) were diagnosed as having NTG. Sixty-nine eyes of 69 subjects were enrolled for this prospective, cross-sectional study. They were divided into two groups by age (cut-off between 59 and 60 years: group 1, under 60 years; group 2, over 60 years). The correlations between age and the mean, maximum and minimum IOP and IOP variation of the eight nyctohemeral IOP measurements nyctohemerally were evaluated for each group. The times of day at which the maximum and minimum IOPs were observed were recorded. RESULTS: Groups 1 and 2 consisted of 28 patients (age: 50.2+/-6.1 years) and 42 patients (age: 70.3+/-6.1 years) ( P<0.0001), respectively. Neither mean, maximum or minimum IOP nor the IOP variation was significantly different between the groups (all P values > or =0.115). The mean, maximum and minimum IOP in group 2 were all correlated with age ( n=41; r=-0.516, P=0.0004; r=-0.434, P=0.004; r=-0.522, P=0.0004, respectively), while none of those in group 1 was correlated with age (all P values > or =0.303). CONCLUSION: The IOPs of the elder NTG patients have a negative correlation with age while those of the younger ones have no relation to age.

Adult↗

PubMed2002

Severe ocular and orbital toxicity after intracarotid injection of carboplatin for recurrent glioblastomas.

BACKGROUND: Glioblastoma is a malignant tumor that occurs in the cerebrum during adulthood. With current treatment regimens including combined surgery, radiation and chemotherapy, the average life expectancy of the patients is limited to approximately 1 year. Therefore, patients with glioblastoma sometimes have intracarotid injection of carcinostatics added to the treatment regimen. Generally, carboplatin is said to have milder side effects than cisplatin, whose ocular and orbital toxicity are well known. However, we experienced a case of severe ocular and orbital toxicity after intracarotid injection of carboplatin, which is infrequently reported. CASE: A 58-year-old man received an intracarotid injection of carboplatin for recurrent glioblastomas in his left temporal lobe. He complained of pain and visual disturbance in the ipsilateral eye 30 h after the injection. Various ocular symptoms and findings caused by carboplatin toxicity were seen. RESULTS: He was treated with intravenous administration of corticosteroids and glycerin for 6 days after the injection. Although the intraocular pressure elevation caused by secondary acute angle-closure glaucoma decreased and ocular pain diminished, inexorable papilledema and exudative retinal detachment continued for 3 weeks. Finally, 6 weeks later, diffuse chorioretinal atrophy with optic atrophy occurred and the vision in his left eye was lost. CONCLUSION: When performing intracarotid injection of carboplatin, we must be aware of its potentially blinding ocular toxicity. It is recommended that further studies and investigations are undertaken in the effort to minimize such severe side effects.

Antineoplastic Agents↗

PubMed2002

Hyperglycemia enhances VSMC proliferation with NF-kappaB activation by angiotensin II and E2F-1 augmentation by growth factors.

To clarify the mechanisms of hyperglycemia-induced proliferation of vascular smooth muscle cells (VSMC), we examined the effects of high glucose (HG) on nuclear factor (NF)-kappaB and E2F-1. Angiotensin II (Ang II) significantly enhanced DNA binding activity of NF-kappaB under HG (25.6 mM) conditions with an increase in p65 subunit of NF-kappaB, and did it slightly under normal glucose (NG; 5.6 mM) conditions. Ang II failed to induce E2F-1 expression, or its binding to the cdc2 promoter, even under HG conditions. HG greatly augmented the cdc2 inducibility of fetal calf serum (FCS), through the increase in E2F-1 activity. These data indicate that hyperglycemia contributes to abnormal proliferation of VSMC by two mechanisms; the induction of NF-kappaB activation by Ang II, which facilitates transcription of certain growth factors, and the augmentation of E2F-1 in response to growth factors.

Angiotensin II↗

PubMed2002

In situ localization of nitric oxide synthase and direct evidence of NO production in rat retinal ganglion cells.

The expression of isoforms of nitric oxide synthase (NOS), enzymes responsible for NO production, and the synthesis of nitric oxide (NO) in rat retinal ganglion cells (RGCs) during synaptogenesis for various phases of the pre- and postnatal developmental periods were investigated. The retinas from prenatal, lactating, young, and adult rats were fixed in paraformaldehyde. The cryosections or paraformaldehyde-fixed ganglion cells purified from rat pups were immunostained for constitutive isoforms of NOS (n and eNOS) and observed with a confocal laser scanning microscope. Synthesis of NO in the RGCs was achieved by in vitro stimulation with glutamate. The intracellular NO levels were measured in real time using diaminofluorescein-2 diacetate, a fluorescence indicator of NO. Immunohistochemical analysis revealed nNOS and eNOS expressed in retinal ganglion cells during the first 2 postnatal weeks. Cultured RGCs also expressed nNOS and eNOS in vitro. Intracellular NO levels in cultured RGCs showed spontaneous fluctuation during a 20-min observation. The presence of both a non-specific NOS inhibitor, L-NAME, and a specific nNOS inhibitor, 7-NI, significantly inhibited (P<0.001) the increase of intracellular NO 6 and 8 min after the introduction of L-arginine and glutamate to the medium. This study revealed that all constitutive NOS isoforms are expressed in RGCs and demonstrated that NO is produced by nNOS mainly through stimulation by glutamate in cultured RGCs.

Aging↗

PubMed2002

Myopia and advanced-stage open-angle glaucoma.

OBJECTIVE: To investigate the effect of myopic refraction on the central visual field in patients with advanced open-angle glaucoma (OAG). DESIGN: Multicenter cross-sectional study. PARTICIPANTS: Three hundred thirteen OAG eyes (176 eyes of 176 primary open-angle glaucoma [POAG] patients and 137 eyes of 137 normal-tension glaucoma [NTG] patients) with clear ocular media and a mean deviation (MD) <-15 dB. Patients with a recorded maximum intraocular pressure (IOP) of 22 mmHg or greater were classified as POAG, and those with an IOP of 21 mmHg or less were classified as NTG. METHODS: Multiple regression analysis was used to study the influence of refraction on 12 central test points of the C30-2 Humphrey program, and the differences in visual field defects between POAG and NTG eyes were examined using logistic discriminant analysis. In the multiple regression analysis, total deviation (TD) of the 12 test points was graded and used as the dependent variable, and MD and the spherical equivalent refraction were the explanatory variables. In the logistic discrimination analysis, TD, MD, and refraction were covariants that determined the OAG subtypes. MAIN OUTCOME MEASURES: TD values of the 12 central test points (C30-2 program). RESULTS: Higher myopic refraction was significantly associated with more damage at a point just temporal and inferior to the fixation point in POAG eyes, whereas it was significantly associated with less damage at test points just temporal and superior to the fixation point in NTG eyes. After correcting for the influence of refraction, POAG eyes had significantly more damage at a test point just temporal and inferior to the fixation point, whereas NTG eyes had significantly more damage at those test points nasal and inferior to the fixation point. CONCLUSIONS: High myopia constitutes a threat to the remaining lower cecocentral visual field and is one of the factors that interfere with the quality of vision in advanced OAG with high IOP but not low IOP.

Cross-Sectional Studies↗

PubMed2002

Differences in E2F subunit expression in quiescent and proliferating vascular smooth muscle cells.

E2F is a family of transcriptional factors that control G(1)/S transition. We investigated how the E2F family participates in the biological responses of vascular smooth muscle cells (VSMC) to vasoconstrictive hormones compared with fetal bovine serum (FBS). FBS induced upregulation of E2F-1 and E2F-5 at both mRNA and protein levels and slightly reduced E2F-3 protein. Angiotensin II (ANG II) and arginine vasopressin increased E2F-3 protein, but not E2F-1 and E2F-5, without upregulating its mRNA level. FBS transactivated the E2F-1 gene through the induction of free E2F-1 binding onto its promoter, whereas ANG II-induced binding of E2F-3 did not result in activation of the E2F-1 promoter. These changes are responsible for hypertrophic or hyperplastic response of VSMC to different growth factors or stimulants. In contrast, both FBS and vasoconstrictive hormones drove transcription of the cdc6 gene by downregulating p130 and recruiting free E2F-3 in the latter, which underlies the progression of VSMC into S phase.

Angiotensin II↗

PubMed2002

P-gp-induced modulation of regulatory volume increase occurs via PKC in mouse proximal tubule.

The present study examined the role of protein kinase C (PKC) in the P-glycoprotein (P-gp)-induced modulation of regulatory volume increase (RVI) in the isolated nonperfused proximal tubule S2 segments from mice lacking both mdr1a and mdr1b genes (KO) and wild-type (WT) mice. The hyperosmotic solution (500 mosmol/kgH(2)O) involving 200 mM mannitol activated PKC and elicited RVI in the tubules from KO mice but not from WT mice. The addition of the hyperosmotic solution including the PKC activator phorbol 12-myristate 13-acetate (PMA) to the tubules of the WT mice activated PKC and elicited RVI. The hyperosmotic solution in the presence of the P-gp inhibitors (verapamil or cyclosporin A) elicited RVI in the tubules from the WT mice but not from the KO mice. The PMA- and the P-gp inhibitors-induced RVI was abolished by cotreatment with the PKC inhibitors (staurosporine or calphostin C). In the tubules of the KO mice, the PKC inhibitors abolished RVI, but PMA did not. In the tubules of the WT mice, the microtubule disruptor (colchicine), the microfilament disruptor (cytochalasin B), the phosphatidylinositol 3-kinase (PI 3-kinase) blocker (wortmannin), but not another PI 3-kinase blocker (LY-294002), inhibited the PMA-induced RVI. In the tubules of the KO mice, colchicine, cytochalsin B, and wortmannin abolished RVI, but LY-294002 did not. We conclude that 1) in the mouse proximal tubule, P-gp-induced modulation of RVI occurs via PKC; and 2) the microtubule, microfilament, and wortmannin-sensitive, LY-294002-insensitive PI 3-kinase contribute to the PKC-induced RVI.

ATP Binding Cassette Transporter, Subfamily B↗

PubMed2002

Effect of a single drop of latanoprost on intraocular pressure and blood-aqueous barrier permeability in patients with uveitis.

The purpose of our study is to evaluate the effect of a single drop of latanoprost on the intraocular pressure and blood-aqueous barrier permeability in 8 patients with uveitis. The degree of inflammation was determined by the intensity of aqueous flare measured with a laser flare cell meter every 2 hours from 11:00 to 17:00 hours for 2 days. Intraocular pressure was measured at 11:00 and 17:00 hours with a Goldmann applanation tonometer on both days. Patients were given one drop of 0.005% latanoprost at 11:00 hours on day 2 and results were compared with day 1 when latanoprost was not administered. There was no significant difference in the intensity of aqueous flare or intraocular pressure between day 1 and day 2. A single drop of latanoprost had little effect on intraocular pressure and aqueous flare intensity in patients with uveitis.

Administration, Topical↗

PubMedDate not supplied

Alternative method of evaluating visual field deterioration in very advanced glaucomatous eye by microperimetry.

PURPOSE: To report an alternative method of evaluating visual field deterioration in very advanced glaucomatous eyes. METHODS: This prospective, comparative study included 24 eyes of 24 consecutive patients with very advanced glaucoma. The eyes were divided into two groups based on their visual field measurements by Goldmann perimetry: Group 1 had a central island with or without a detached temporal island (n = 13), and Group 2 had a central island with a temporal island connected by only a thin isthmus (n = 11). The size of the central island was determined by Goldmann perimetry, and microperimetry plots were determined around the disc margin. The angle formed between a line passing from the disc center to the "seen" points and a second line passing to the "not seen" points at the superior temporal or the inferior temporal sites was used for the analyses. RESULTS: The mean size of the island was 6.3 +/- 1.9 in Group 1 and was 7.0 +/- 2.0 in Group 2 (P =.38). The mean angle between the "seen" and "not seen" points in Groups 1 and 2 was 56.1 +/- 6.9 and 76.1 +/- 11.8, respectively (P =.0002). The reduction in the angle correlated with the visual field loss (P =.018), but the reduction in the size of the central island was not significantly associated with the visual field loss (P =.29). CONCLUSION: Microperimetry may be an alternative method of evaluating advanced glaucoma.

Aged↗

PubMedDate not supplied

Additive effect of bunazosin on intraocular pressure when topically added to treatment with latanoprost in patients with glaucoma.

PURPOSE: To investigate whether an alpha-1 blocker, bunazosin, has an additive effect on lowering intraocular pressure (IOP) when topically added to latanoprost treatment in patients with glaucoma. METHODS: Bunazosin twice a day was added topically to the treatment for 12 patients with glaucoma who had been instilling latanoprost once a day for more than 1 month. IOP was measured and adverse events were checked 2, 4 and 8 weeks after the addition of bunazosin to their treatment. RESULTS: One of the 12 patients dropped out in the course of the study. Therefore, 11 patients were included for the analysis of IOP, and 12 for the analysis of adverse events. IOPs were decreased significantly (P=.008, Wilcoxon signed rank test) from 18.2+/-3.4 mm Hg to 16.6+/-3.5 mm Hg 8 weeks after the addition of bunazosin. Adverse events were seen in 5 of the 12 patients. CONCLUSION: Bunazosin has an additive effect on lowering IOP when topically added to latanoprost treatment in glaucoma patients.

Administration, Topical↗

PubMedDate not supplied

Lack of circadian change of concentration of C-type natriuretic peptide in rabbit aqueous humor.

PURPOSE: To determine whether there is a circadian change of the concentration of C-type natriuretic peptide (CNP) in rabbit aqueous humor. METHODS: Forty-one male white New Zealand rabbits were submitted to a 12 h light and 12 dark lighting schedule; lights on was at 0 h, lights off at 12 h. C-type natriuretic peptide was assayed at 3 light (2 h, 6 h and 10 h) and 3 dark (14,18 and 22 h) times. All groups consisted of four animals but two had more animals to increase the power of tests (6 h, n = 12; 22 h, n = 13). Dependence between the two eyes was tested by Pearson's correlation. The mean of two eyes was considered for analysis. Differences in concentration in pg/200 ml were evaluated by one-way ANOVA, t test and COSINOR analysis. RESULTS: There were no significant differences between the 6 analyzed groups (one-way ANOVA p = 0.157). Pooled into two groups (light and dark), the C-type natriuretic peptide concentration of the light group was lower, 2.626 +/- 0.92 pg/200 ml compared with the dark group 3.02 +/- 1.16 pg/200 ml but did not reach a significant difference (t test; p = 0.23). COSINOR analysis was not statistically significant (R% = 7.72 p = 0.209). CONCLUSION: These data demonstrate that the concentration of CNP in aqueous humor did not show a statistically significant circadian change in rabbits entrained to a 12 h light: 12 h dark lighting schedule.

Analysis of Variance↗