Spontaneous intraocular pressure reduction in normal-tension glaucoma and associated clinical factors

PURPOSE: To investigate the intraocular pressure (IOP) reduction in certain normal-tension glaucoma (NTG) patients and clinical factors associated with this reduction. METHODS: Fifty-four NTG patients who met the following enrollment criteria were selected: IOP <21 mm Hg during a 24-hour pressure curve and throughout the subsequent 12 months; examined every 1 to 4 months for at least 3 years with no ocular hypotensive therapy. For each patient, the eye with the higher mean IOP during the 24-hour pressure curve was selected for this study. RESULTS: Six patients had an IOP reduction which was defined as a significant decrease (P <.05) of IOP over time, determined by the Spearman rank correlation coefficient method. These 6 eyes were rated positive for subsequent IOP reduction. The IOP reduction was correlated to clinical factors by means of a logistic multiple regression analysis (LOGIST procedure using PC-SAS), which demonstrated that the larger difference between the maximum IOP and the minimum IOP during the initial 24-hour pressure curve and the absence of disc hemorrhage showed significant correlation with IOP reduction (P =.026 and P =.013, respectively). The odds ratios were 2.05 per 1 mm Hg increase of difference between the maximum IOP and the minimum IOP during the initial 24-hour pressure curve and 1.13 for the absence of disc hemorrhage. CONCLUSIONS: The current study demonstrated that a significant reduction of IOP over time is not uncommon in NTG patients. One ninth of the NTG patients in this study showed a significant IOP reduction during a 3-year follow-up period.     

Disk hemorrhage is a significantly negative prognostic factor in normal-tension glaucoma

PURPOSE: We investigated the relationship between disk hemorrhage in normal-tension glaucoma and the progression of visual field defects and, additionally, whether hemorrhage plays a role in the pathogenic process of the chronic disease.METHODS: We retrospectively reviewed the charts of 70 patients with normal-tension glaucoma (mean follow-up, 5.6 years) who were not medicated for glaucoma, and we applied a regression analysis of survival data based on the Cox proportional hazards model. Several clinical factors were investigated to find a possible association with the progression of glaucomatous visual field defined by two different definitions: one by mean deviation change and the other by glaucoma change probability analysis.RESULTS: Disk hemorrhage, corrected-pattern standard deviation, age, systolic blood pressure, and pulse rate had a significant influence on the visual field defect. The cumulative probability of progression of visual field loss was significantly greater for patients with disk hemorrhage than for patients without disk hemorrhage by either criterion for progression (P 相似文献   

The effect of phosphodiesterase type 3 inhibitor on chorio-retinal blood flow in rabbits eyes

PURPOSE: To investigate the ocular effect of intravenous administration of a phosphodiesterase type 3 inhibitor (NSP-805) and to compare the effect of NSP-805 with that of a calcium antagonist (nicardipine hydrochloride) on chorio-retinal blood flow in anesthetized albino rabbits. METHODS: Twenty-four female albino rabbits (weighting 2.0-4.0 kg) were anesthetized with intravenous injection. NSP-805(40 micrograms/kg and 100 micrograms/kg) and nicardipine of 40 micrograms/kg were intravenously administrated to the anesthetized rabbits. Intravenously administration of 20% dimethyl sulfoxide (DMSO) was used as a vehicle. Chorio-retinal blood flow was measured with a laser Doppler flowmeter at baseline and every 20 minutes after intravenous administration for 120 minutes. Heart rates and systemic blood pressure were monitored. Baseline measurements were compared with every 10 minutes after intravenous administration. Differences between the drug groups and vehicle group were analyzed. RESULTS: After administration of a low dose of NSP--805 (40 micrograms/kg) and nicardipine (40 micrograms/kg), the chorio-retinal blood flow was significantly increased (p < 0.05). A high dose NSP-805(100 micrograms/kg) reduced systemic blood pressure significantly, but the increase of chorio-retinal blood flow was less than that at the low dose of NSP-805(40 micrograms/kg) and nicardipine (40 micrograms/kg). Chorio-retinal blood flow in the NSP 805(40 micrograms/kg) and nicardipine (40 micrograms/kg) groups was significantly increased over that in the control group (20% DMSO) (p < 0.05). CONCLUSION: The results suggest that the NSP-805 has the potential of increasing chorio-retinal blood flow in rabbit eyes.     

Medical treatment of normal tension glaucoma

Normal-tension glaucoma was previously thought to be pressure insensitive, as medical treatment hardly reduced intraocular pressure and it did not prevent visual field loss. In the last decade, however, evidence has shown that the treatment of normal-tension glaucoma by lowering intraocular pressure can slow the deterioration of visual fields, hence the glaucomatous process. It was shown that a reduction of IOP of at least 30% is needed to induce a favorable alteration in the course of normal-tension glaucoma. New agents, such as prostaglandin analogs, the alpha(2)-adrenoceptor agonist brimonidine, and carbonic anhydrase inhibitors, have become available and may be of use in the treatment of normal-tension glaucoma. Monotherapy with prostaglandin analogs may meet the target of a reduction of IOP with 30%, but combination therapy will be needed in many cases. Few studies have been performed with brimonidine, travoprost, and bimatoprost, and it is suggested that more attention should be given to studies with these agents, as about 30% of patients with open angles and glaucomatous visual field defects have normal-tension glaucoma. Although neuroprotection is the goal of the future, no hard data are available yet which demonstrate that treatment with these agents will indeed result in preservation of visual fields.     

Prohormone convertase furin has a role in gastric cancer cell proliferation with parathyroid hormone-related peptide in a reciprocal manner

We investigated the expression of parathyroid hormone-related peptide (PTHrP) and the relationship between PTHrP and its endoprotease furin in gastric cancer. PTHrP was colocalized with furin in 75% of gastric cancer tissues (six of eight) from patients with high serum PTHrP levels. PTHrP mRNA expression was confirmed in 67% of gastric cancer cell lines (four of six), whereas furin mRNA was detected in all six gastric cancer cell lines. In a cultured gastric cancer cell line, MKN28, mature PTHrP protein expression was markedly increased by transfection of furin cDNA. Furin cDNA-transfected MKN28 cells grew faster than did the mock controls. Moreover, furin mRNA expression in cultured gastric cancer cells was enhanced when PTHrP was added to the culture medium. These results suggest a link between PTHrP and furin in the regulation of gastric cancer cell growth. Furin might be involved not only in the production of the mature form of PTHrP, but also in promoting growth in gastric cancer cells.     

Enhancement of intestinal absorption of poorly absorbed hydrophilic compounds by simultaneous use of mucolytic agent and non-ionic surfactant.

The effect of co-administration of a mucolytic agent with a penetration enhancer was assessed on the intestinal absorption of poorly absorbed hydrophilic compounds. Fluorescein isothiocyanate-labeled dextran with average molecular weight of ca. 4.4 kDa (FD-4) was used as a model compound, and N-acetylcysteine (NAC) was used as a mucolytic agent. Sodium caprate (C10), tartaric acid (TA), sodium taurodeoxycholate (TDC), sodium dodecyl sulfate (SDS), p-t-octyl phenol polyoxyethylene-9.5 (Triton X-100, TX-100) were selected as penetration enhancers with different mechanisms of action. Various dosing solutions containing a penetration enhancer in the absence or in the presence of NAC were directly administered into the exposed rat jejunum, and the bioavailability of FD-4 up to 2 h was determined. The extent of improvement by co-administration was highly dependent on the penetration enhancer species applied. The observed enhancement was thought to result from the mucolytic activity of NAC, which can reduce the mucus viscosity and facilitate the penetration of FD-4 to mucosal membrane. Among the combinations tested, the simultaneous administration of NAC and TX-100 provided the highest enhancement (22.5-fold) of intestinal FD-4 absorption compared to the control. Although the detailed mechanism for the observed drastic improvement is unclear, one possible reason was thought to be due to the improved diffusivity of TX-100 micellar system in the mucus layer. All these results suggest that the combination of a mucolytic agent and a non-ionic surfactant may have potential as an enhancing system for peroral delivery of poorly absorbed hydrophilic compounds like protein and peptide drugs.     

Induction of S100A4 gene expression inhibits in vitro invasiveness of human squamous cell carcinoma, KOSC-3 cells

S100A4 is considered functionally involved in metastasis and invasiveness of rodent and human mammary tumors. We screened the expression of S100A4 in human squamous cell carcinoma cell lines, and found 2 cell lines which were highly invasive, but did not express any noticeable extent of S100A4. To examine whether the expression of S100A4 regulated invasiveness of squamous cell carcinoma, we transfected S100A4 cDNA into KOCS-3 and HSC-4 squamous cell carcinoma cells. The transfectants from KOSC-3 cells expressing sense S100A4 decreased invasiveness by 80% compared with cells of the wild type or those with the vector only.     

Surgery for refractory glaucoma

Purpose: To determine the surgical outcome of mitomycin trabeculectomy in patients with refractory glaucoma.
Methods: Sixty-six eyes of 52 patients with refractory glaucoma underwent mitomycin trabeculectomy. Mitomycin was applied for five minutes only once during trabeculectomy. The follow-up period was six to 61 months.
Results: Cumulative success probability was calculated using Kaplan-Meier life-table analysis assuming the cut-off postoperative IOP to be 20 mmHg or IOP reduction by at least 20% in eyes with preoperative IOP 24mmHg. At the end of 61-month follow-up the success probability was 80%± 6% without postoperative ocular hypotensive medication (complete success) and was 95%± 3% regardless of postoperative antiglaucoma medication (overall success), respectively.
Conclusion: The data suggest that mitomycin trabeculectomy is efficacious in reducing IOP in patients with refractory glaucoma.