The Spectrum of Uveitis in Southern Vietnam.

PURPOSE: To describe the pattern of uveitis among Vietnamese at two eye hospitals in Southern Vietnam. METHODS: We retrospectively reviewed the charts of 212 consecutive uveitis cases that presented to two eye hospitals in Ho Chi Minh City, Vietnam, from July 2011 to February 2015. The patients were identified from a database maintained by the hospitals. Patients with keratitis, episcleritis, orbital inflammation, post-surgical endophthalmitis, traumatic iritis, and corneal graft rejection were excluded. Data collected included demographic, clinical, and laboratory findings. RESULTS: Uveitis was seen most commonly in the 21-60-year-old age group. Gender distribution was not significantly different among the various age groups. Anterior uveitis was the most common (46%), followed by posterior uveitis (22%), panuveitis (18%), and intermediate uveitis (14%). Infectious etiologies were observed in 27%. Idiopathic uveitis (36%) was the most common non-infectious uveitis, followed by Vogt-Koyanagi-Harada disease (14%) and Behçet disease (7%). Tuberculous uveitis was the most common infectious etiology (9%), followed by toxocariasis (6%) and herpetic uveitis (6%), and cytomegalovirus anterior uveitis (4%). CONCLUSIONS: In southern Vietnam, infectious uveitis, such as tuberculosis, toxocariasis, and herpetic infection, are common but toxoplasmosis is rare. Idiopathic uveitis, Vogt-Koyanagi-Harada disease, and Behçet disease are the most common non-infectious uveitis, with a notable absence of birdshot retinochoroidopathy.

Elevated intraocular pressure is a common complication during active microbial keratitis.

PURPOSE: To determine the incidence, risk factor, and outcomes of elevated intraocular pressure (IOP) during active microbial keratitis. DESIGN: Retrospective cohort study. METHODS: One hundred eighty-four patients with culture-proven microbial keratitis examined from January 2003 through December 2007 were included. High IOP was defined as IOP of 22 mm Hg or higher measured during the episode of active keratitis. The control group consisted of eyes with microbial keratitis whose IOP remained less than 22 mm Hg. Twelve factors were evaluated by univariate and multivariate analyses to determine whether any were associated with increased IOP. The incidence, risk factors, microbial profile, the necessity of therapeutic surgery, time to resolution, and final visual acuity were compared between the high IOP group and the control group. RESULTS: High IOP (mean, 29.1 mm Hg; range, 22 to 51 mm Hg) occurred in 52 (28%) of 184 patients with active corneal infection. Prior ocular surgery, diabetes mellitus, and ulcer size of 4.0 mm or larger were associated with IOP elevation (P ≤ .013). Surgical interventions were necessary in 19 (39%) of 49 patients in the high IOP group and in 14 (11%) of 129 patients in the control group (P < .0001). Time to ulcer resolution was longer in the high IOP group (mean, 50.1 ± 53.2 days) than in the control (mean, 31.6 ± 42.0 days; P = .005). Final visual acuity of 20/40 or better was achieved by more patients in the control group (47%) than in the high IOP group (20%; P < .001). CONCLUSIONS: Elevated IOP was detected in a significant proportion of patients with active microbial keratitis and was associated with poorer outcomes. Routine IOP check should be performed to avoid possible optic nerve damage.

Corneal biomechanical properties in normal, forme fruste keratoconus, and manifest keratoconus after statistical correction for potentially confounding factors.

PURPOSE: To evaluate the difference in corneal biomechanical properties, after controlling for potentially confounding factors, along the spectrum of keratoconic disease as measured by the keratoconus severity score. METHODS: The corneal biomechanical properties of 73 keratoconic (KCN) eyes of 54 patients, 42 forme fruste keratoconic (FFKCN) eyes of 32 patients, and 115 healthy eyes of 115 age- and sex-matched patients were reviewed retrospectively. The main outcome measures were corneal hysteresis (CH) and corneal resistance factor (CRF). RESULTS: In the normal group, the mean CH was 11.0 ± 1.4 mm Hg and mean CRF was 11.1 ± 1.6 mm Hg. The FFKCN mean CH was 8.8 ± 1.4 mm Hg and mean CRF was 8.6 ± 1.3 mm Hg. The KCN mean CH was 7.9 ± 1.3 mm Hg and mean CRF was 7.3 ± 1.4 mm Hg. There were statistically significant differences in the mean CH and CRF in the normal group compared with the FFKCN and the KCN groups (P < 0.001) after statistically controlling for differences in central corneal thickness, age, and sex. CONCLUSIONS: There is a significant difference in the mean CH and CRF between normal and FFKCN corneas after controlling for differences in age, sex, and central corneal thickness. However, there is a significant overlap in the distribution of CH and CRF values among all groups. The biomechanical parameters CH and CRF cannot be used alone but may be a useful clinical adjunct to other diagnostic tools, such as corneal tomography, in distinguishing normal from subclinical keratoconic corneas.

Corneal ectasia after laser in situ keratomileusis after laser thermal keratoplasty.

PURPOSE: To report a case of corneal ectasia following hyperopic laser in situ keratomileusis in a patient who had previous laser thermal keratoplasty. METHODS: Case report. RESULTS: We report a case of a 66-year-old emmetropic man initially presented with complaint of difficulty reading without correction. Laser thermal keratoplasty (LTK) was performed on the non-dominant right eye, resulting in successful monovision. Three years later, the patient presented with decreased unaided near vision caused by hyperopic regression of the LTK. Conventional hyperopic laser in situ keratomileusis (LASIK) was performed, again resulting in successful monovision. More than three years later, the patient returned with worsening near vision. A focal corneal ectasia was noted in the same location as the 6 o'clock LTK leukoma. CONCLUSIONS: To our knowledge, this is the first report of ectasia occuring after LASIK following LTK. Consideration should be given to performing photorefractive keratectomy (PRK) instead of LASIK following thermal keratoplasty.

Effect of Ca2+ on cardiac mitochondrial energy production is modulated by Na+ and H+ dynamics.

The energy production of mitochondria in heart increases during exercise. Several works have suggested that calcium acts at multiple control points to activate net ATP production in what is termed "parallel activation". To study this, a computational model of mitochondrial energy metabolism in the heart has been developed that integrates the Dudycha-Jafri model for the tricarboxylic acid cycle with the Magnus-Keizer model for mitochondrial energy metabolism and calcium dynamics. The model improves upon the previous formulation by including an updated formulation for calcium dynamics, and new descriptions of sodium, hydrogen, phosphate, and ATP balance. To this end, it incorporates new formulations for the calcium uniporter, sodium-calcium exchange, sodium-hydrogen exchange, the F(1)F(0)-ATPase, and potassium-hydrogen exchange. The model simulates a wide range of experimental data, including steady-state and simulated pacing protocols. The model suggests that calcium is a potent activator of net ATP production and that as pacing increases energy production due to calcium goes up almost linearly. Furthermore, it suggests that during an extramitochondrial calcium transient, calcium entry and extrusion cause a transient depolarization that serve to increase NADH production by the tricarboxylic acid cycle and NADH consumption by the respiration driven proton pumps. The model suggests that activation of the F(1)F(0)-ATPase by calcium is essential to increase ATP production. In mitochondria very close to the release sites, the depolarization is more severe causing a temporary loss of ATP production. However, due to the short duration of the depolarization the net ATP production is also increased.

Mitochondrial calcium signaling and energy metabolism.

A computational model of energy metabolism in the mammalian ventricular myocyte is developed to study the effect of cytosolic calcium (Ca(2+)) transients on adenosine triphosphate (ATP) production. The model couples the Jafri-Dudycha model for tricarboxylic acid cycle regulation to a modified version of the Magnus-Keizer model for the mitochondria. The fluxes associated with Ca(2+) uptake and efflux (i.e., the Ca(2+) uniporter and Na(+)-Ca(2+) exchanger) and the F(1)F(0)-ATPase were modified to better model heart mitochondria. Simulations were performed at steady state and with Ca(2+) transients at various pacing frequencies generated by the Rice-Jafri-Winslow model for the guinea pig ventricular myocyte. The effects of the Ca(2+) transients for mitochondria both adjacent to the dyadic space and in the bulk myoplasm were studied. The model shows that Ca(2+) activation of both the tricarboxylic acid cycle and the F(1)F(0)-ATPase are necessary to produce increases in ATP production. The model also shows that in mitochondria located near the subspace, the large Ca(2+) transients can depolarize the mitochondrial membrane potential sufficiently to cause a transient decline in ATP production. However, this transient is of short duration, minimizing its impact on overall ATP production.

Effects of cisplatin on expression of DNA ligases in MiaPaCa human pancreatic cancer cells.

The effect of the broad-spectrum anticancer agent, cisplatin, on the expression of DNA ligase I in human pancreatic carcinoma MiaPaCa cells was examined in this study, since DNA ligase I is known to be involved in various DNA repair pathways. Upon exposure of MiaPaCa cells to cisplatin at near IC(50) value (2.5-5 microM), about 2-3-fold increase of DNA ligase I levels was observed within 24h, while levels of other DNA ligases (III and IV) remained unchanged or slightly decreased. The same fold-increase in DNA ligase I levels was also observed in MiaPaCa cells exposed to cytostatic concentrations, but not cytotoxic concentrations of cisplatin, which significantly reduced the number of cells. Flow cytometric analysis revealed that normal cell cycle progression was disrupted in the cells treated with cisplatin, resulting in an initial arrest of the cells in the S-phase, concomitant with a decrease of cells in G0/G1-phase. With time elapsing, the transition from S- to G2 + M-phase was observed, but further progression into G0/G1-phase was blocked. Overall, the increase of DNA ligase I expression seems to correlate well with the arrest of the cell cycle between the S- and G2-phases in response to cisplatin treatment. Interestingly, the cisplatin-induced DNA ligase I increase was abrogated by caffeine treatment in MiaPaCa cells, suggesting that caffeine sensitive kinases might be important mediators in the pathway, leading to the increase of DNA ligase I levels in response to cisplatin. We propose that the increase of DNA ligase I expression after exposure to cisplatin might be required for aiding the cells to recover from the damage by facilitating the repair process.

Induction of DNA ligase I by 1-beta-D-arabinosylcytosine and aphidicolin in MiaPaCa human pancreatic cancer cells.

Exposure of MiaPaCa cells to 1-beta-D-arabinosylcytosine (ara-C) resulted in an increase in DNA ligase levels up to threefold compared to that in the untreated control cells, despite significant growth inhibition. Increased levels of DNA ligase I protein appear to correlate with the appearance of increased mRNA levels. The [(3)H]thymidine incorporation experiment and the biochemical assay of total polymerase activity revealed that an increase in DNA ligase I levels after treatment with ara-C was not accompanied by an increase of DNA synthesis or an increased presence of DNA polymerase activity inside cells. When cells resumed DNA synthesis after drug treatment, DNA ligase I levels began to drop, indicating that increased DNA ligase I is not required for DNA synthesis. An increase in DNA ligase I was also observed in cells treated with aphidicolin, another inhibitor of DNA synthesis that inhibits DNA polymerases without incorporating itself into DNA, indicating that an increase in DNA ligase I levels could be caused by the arrest of DNA replication by these agents. Interestingly, caffeine, which is a well-known inhibitor of DNA damage checkpoint kinases, abrogated the increase in DNA ligase I in MiaPaCa cells treated with ara-C and aphidicolin, suggesting that caffeine-sensitive kinases might be important mediators in the pathway leading to the increase in DNA ligase I levels in response to anticancer drugs, including ara-C and aphidicolin. We propose that ara-C and aphidicolin induce damage to the DNA strand by arresting DNA replication forks and subsequently increase DNA ligase I levels to facilitate repair of DNA damage.

Enhancement of DNA ligase I level by gemcitabine in human cancer cells.

PURPOSE: DNA ligase I is an essential enzyme for completing DNA replication and DNA repair by ligating Okazaki fragments and by joining single-strand breaks formed either directly by DNA-damaging agents or indirectly by DNA repair enzymes, respectively. In this study, we examined whether the DNA ligase I level could be modulated in human tumor cell lines by treatment with gemcitabine (2', 2'-difluoro-2'-deoxycytidine), which is a nucleoside analogue of cytidine with proven antitumor activity against a broad spectrum of human cancers in clinical studies. EXPERIMENTAL DESIGN: To determine the effect of gemcitabine on DNA ligase I expression, Western blot analysis was used to measure the DNA ligase I levels in MiaPaCa, NGP, and SK-N-BE cells treated with different concentrations of gemcitabine and harvested at different time intervals. Cell cycle analysis was also performed to determine the underlying mechanism of DNA ligase I level enhancement in response to gemcitabine. In addition, other agents that share the same mechanism of action with gemcitabine were used to elucidate further details. RESULTS: When different types of tumor cell lines, including MiaPaCa, NGP, and SK-N-BE, were treated with gemcitabine, the level of DNA ligase I increased severalfold despite significant cell growth inhibition. In contrast, other DNA ligases (III and IV) either remained unchanged or decreased with treatment. Cell cycle analysis showed that arrest in S-phase corresponded to an increase of DNA ligase I levels in gemcitabine treated cells. Other agents, such as 1-beta-D-arabinofuranosylcytosine and hydroxyurea, which partly share mechanisms of action with gemcitabine by targeting DNA polymerases and ribonucleotide reductase, respectively, also caused an increase of DNA ligase I levels. However, 5-fluorouracil, which predominantly targets thymidylate synthase, did not cause an increase of DNA ligase I level. CONCLUSIONS: Our results suggest that an arrest of DNA replication caused by gemcitabine treatment through incorporation of gemcitabine triphosphate into replicating DNA and inhibition of ribonucleotide reductase would trigger an increase in DNA ligase I levels in cancer cells. The elevated presence of DNA ligase I in S-phase-arrested cells leads us to speculate that DNA ligase I might have an important role in repairing DNA damage caused by stalled replication forks.