A study on combination of non-ablative local RFA with PD-1 and angiogenesis blocking to prolong survival through improvement of immune microenvironment in advanced Hepatocellular Carcinoma.

Radiofrequency ablation (RFA), an effective local treatment method for early-stage Hepatocellular Carcinoma (HCC), combined with PD-1 blocking and anti-angiogenic therapy is being extensively explored in advanced HCC, however, the definite results and underlying mechanisms still remain to be elucidated. Therefore, whether non-ablative RFA-based combined therapy can play a synergistic anti-tumor effect through improving tumor immune microenvironment was investigated by us in HCC mouse models. Our results showed that non-ablative RFA could regulate multilayered immunity, such as inducing immunogenic death of tumor cells, upregulating the secretion of inflammatory cytokines, mainly IFN-γ, TNF-α, and IL-10, and subsequently promoting the infiltration of CD8 + T cells. As a result, a significant synergistic anti-tumor effect was demonstrated in the combination therapy group. Similarly, in the real-world setting, non-curative RFA combined with PD-1 blocking and Lenvatinib for 12 patients with Barcelona Clinic Liver Cancer (BCLC) stage C achieve promising results, with 6.9 months (95 % CI: 3.23-15.73) median progression-free survival (mPFS) and 12.7 months (95 % CI: 7.40-19.73) median overall survival (mOS). The common treatment-related adverse reactions were pneumonia and thyroiditis with low prevalence, both less than grade 3 and manageable by symptomatic treatment. Summarily, local non-ablative RFA should be a clinically preferred strategy in combination with PD-1 blocking and anti-angiogenic therapy, because this more flexible scheme abandons its historical concept of tumor eradication, but fully utilizes the immune regulatory function by inducing immunogenic tumor death and has higher-level of safety. Therefore, this is a two-pronged and highly balanced approach to achieved favorable treatment outcomes, while conclusive evidence is still pending, it can be attempted in the real world anyway.

Management of intrascleral chestnut burr spines under ultrasound biomicroscopy guidance.

Purpose: To explore the efficacy of ultrasound biomicroscopy (UBM) as a tool for detecting and localizing intrascleral chestnut burr spines. Methods: Individuals who were diagnosed with definitive or suspected intrascleral chestnut burr injuries between 2019 and 2020 were retrospectively reviewed. All patients underwent UBM to detect potential intrascleral spines. UBM imaging features were recorded and analyzed. Intrascleral spines were removed based upon UBM-guided localization. Patient clinical profiles, management, and treatment outcomes were recorded. Results: A total of 10 eyes (10 patients; 6 males, 4 females) were diagnosed with intrascleral spines over the study period, with an average patient age of 55 years (range: 39-71). Three of these 10 eyes exhibited involvement of the palpebrae and cornea, whereas three exhibited corneal involvement, and the remaining four patients exhibited only intrascleral spine injuries owing to their having undergone previous intracorneal spine extraction procedures. UBM features consistent with chestnut burr spines manifest a hyperechoic spot with a shadow. UBM enabled the precise localization of these spines and thus ensured their successful removal via a single surgery. During follow-up, two patients experienced vitreous hemorrhage due to a penetrating injury into the ciliary body that was gradually absorbed. All patients with eye irritation and red eyes progressed favorably, and no surgical complications were recorded. Conclusion: A retained scleral chestnut burr spine should be suspected if a patient complains of persistent eye irritation following intracorneal spine removal. UBM may be a valuable tool for detecting spines retained in the sclera, enabling the successful removal thereof.

Amelioration of Endotoxin-Induced Inflammatory Toxic Response by a Metal Chelator in Rat Eyes.

Purpose: Metal ions play a key role in exacerbating toxicity associated with oxidative stress and inflammation. This study examines the effects of a formulation containing the metal chelator ethylenediaminetetraacetic acid (EDTA) and permeability enhancer methyl sulfonyl methane (MSM) on the early course of inflammation in endotoxin-induced uveitis (EIU). The proprietary MSM/EDTA formulation of Livionex, Inc., which was used for this study, is covered by several patents and pending patent applications. Methods: EIU was induced by using subcutaneous injection of lipopolysaccharide (LPS) into the thighs of Lewis rats. Treatment consisted of topical application to the eyes of either PBS or eye drops designated as ME that contain EDTA and MSM. Clinical signs of uveitis were monitored at 6 and 24 hours postinjection. Oxidative and inflammatory markers were evaluated by ELISA or immunohistochemistry. Results: Rats treated with ME showed fewer clinical signs of uveitis including reduced miosis, fibrinous exudates, and dilated blood vessels. The aqueous humor of treated rats contained fewer leukocytes, lower protein levels, and less PGE2. Formation of protein adducts with the lipid peroxidation end-product, 4-hydroxynonenal, expression of NF-κB, TNF-α, and MMP-9 were all reduced in rats treated with ME. Conclusions: Our results indicate that ME eye drops downregulate the ocular inflammatory response in LPS treated rats, suggesting that induction of EIU involves metal ions and chelation therapy with ME is a potential treatment for uveitis.

NUAK1 knockdown suppresses prostate cancer cell epithelial-mesenchymal transition, migration, and invasion through microRNA-30b-5p.

OBJECTIVE: Prostate cancer is one of the most diagnosed malignancies in men worldwide. Novel (nua) kinase family 1 (NUAK1) is a member of adenosine monophosphate (AMP)-related kinase which participates in varying cancers progression. However, the role of NUAK1 in prostate tumorigenesis has not been fully characterized. The aim of this study was to elucidate the potential biological role of NUAK1 in prostate cancer. METHODS: Quantitative real-time PCR (qRT-PCR) was performed to determine the expression levels of NUAK1 and microRNA-30b-5p (miRNA-30b-5p) in prostate cancer cell lines and samples. Western blot was conducted to explore the related protein levels of epithelial-mesenchymal transition (EMT) and NUAK1 expression in prostate cancer cells. Trans-well test was used to assay prostate cancer cell migration and invasion. Luciferase assays were employed to probe the interaction between NUAK1 and miR-30b-5p. RESULTS: NUAK1 abundance was enhanced in prostate cancer tissues and cell lines. The knockdown of NUAK1 may inhibit prostate cancer cells EMT, migration and invasion. Luciferase assays suggested NUAK1 was a target gene of miR-30b-5p. Furthermore, miR-30b-5p suppressed EMT, migration, and invasion in prostate cancer cells and introduction of NUAK1 abated the inhibitory effect. CONCLUSIONS: Both of NUAK1 and miR-30b-5p were required for prostate cancer progression. NUAK1 interference limited prostate cancer cell EMT, migration and invasion by miRNA-30b-5p modulating, providing a promising therapeutic approach for prostate cancer.

Knockdown of miR-572 suppresses cell proliferation and promotes apoptosis in renal cell carcinoma cells by targeting the NF2/Hippo signaling pathway.

Background: Renal cell carcinoma (RCC) is one of the most common types of cancer. miR-572 has been proposed to be implicated in a number of human cancers, including RCC. Nevertheless, the detailed functions and molecular mechanisms of miR-572 in RCC have not been well illustrated. Methods: qRT-PCR assay was used to assess the expression of miR-572 in RCC specimens and cell lines. Loss-of-function experiments were carried out to explore the effect of miR-572 on proliferation and apoptosis in 786-O cells. Predicted by TargetScan, the interaction between miR-572 and neurofibromin 2 (NF2) was explored by dual-luciferase reporter assay and western blot analysis. To investigate whether the regulatory effect of miR-572 was mediated by NF2, 786-O cells were transfected with anti-miR-572 alone, or together with si-NF2. After that, western blot assay was used to validate whethermiR-572 regulated proliferation and apoptosis of the RCC cell line through NF2/Hippo signaling. Results: miR-572 expression was upregulated in RCC specimens and cell lines, and miR-572 knockdown suppressed proliferation and enhanced apoptosis in 786-O cells. miR-572 repressed NF2 expression by binding to NF2 mRNA 3'-UTR. Moreover, the anti-miR-572-mediated regulatory effect on proliferation and apoptosis was abated by the restoration of NF2 expression in RCC cells. Furthermore, miR-572 knockdown activated NF2/Hippo signaling pathway in RCC cells. Conclusions: The regulatory effect of miR-572 on proliferation and apoptosis is mediated through modulating NF2/Hippo signaling in RCC cell lines, providing a novel potential strategy for RCC.

In Vivo and Cadaver Studies of the Canalicular/Lacrimal Sac Mucosal Folds.

Purpose. The study aimed to investigate canalicular/lacrimal sac mucosal folds (CLS-MFs) in vivo and in cadavers in order to explore their functional roles in the lacrimal drainage system. Method. The observations of CLS-MFs in vivo were performed on 16 patients with chronic dacryocystitis after undergoing an endonasal endoscopic dacryocystorhinostomy (EE-DCR). The lacrimal sacs and common canaliculi of 19 adult cadavers were dissected. The opening/closing of an orifice and mucosal fold was recorded. All of the specimens were subjected to a histological examination. Results. The upper and lower lacrimal canaliculi in all of the samples united to form a common canaliculus that opened to the lacrimal sac. CLS-MFs were observed in 10 of the 16 patients (62.5%) and 9 of the 19 cadavers (47.4%). The orifices or mucosal folds could be opened or closed when related muscles contracted or relaxed. Histological sections showed a mucosal fold at one side of an orifice. Conclusion. Common canaliculus is the most common type that the canaliculus opens to lacrimal sac. CLS-MFs exist in a certain ratio that can be opened/closed with the movement of the orifices. They may be involved in the drainage of tears or the pathogenesis of acute dacryocystitis or lacrimal sac mucocele.

Iris reconstruction combined with iris-claw intraocular lens implantation for the management of iris-lens injured patients.

AIM: To study the efficiency and safety of iris reconstruction combined with iris-claw intraocular lens (IOL) implantation in the patients with iris-lens injuries. SETTINGS AND DESIGN: Retrospective, noncomparable consecutive case series study. MATERIALS AND METHODS: Eleven patients (11 eyes) following iris-lens injuries underwent iris reconstructions combined with iris-claw IOL implantations. Clinical data, such as cause and time of injury, visual acuity (VA), iris and lens injuries, surgical intervention, follow-up period, corneal endothelial cell count, and optical coherence tomography, were collected. RESULTS: Uncorrected VA (UCVA) in all injured eyes before combined surgery was equal to or <20/1000. Within a 1.1-4.2-year follow-up period, a significant increase, equal to or better than 20/66, in UCVA was observed in six (55%) cases, and in best-corrected VA (BCVA) was observed in nine (82%) cases. Postoperative BCVA was 20/40 or better in seven cases (64%). After combined surgery, the iris returned to its natural round shape or smaller pupil, and the iris-claw IOLs in the 11 eyes were well-positioned on the anterior surface of reconstructed iris. No complications occurred in those patients. CONCLUSIONS: Iris reconstruction combined with iris-claw IOL implantation is a safe and efficient procedure for an eye with iris-lens injury in the absence of capsular support.

Association of DNMT3B -283 T > C and -579 G > T polymorphisms with decreased cancer risk: evidence from a meta-analysis.

Numerous studies have explored the association of polymorphisms in the DNA methyltransferase 3b (DNMT3B) gene with the risk of different types of cancer, but yielded controversial results. Therefore, we performed a meta-analysis to derive a more precise estimation of the association between three widely-studied DNMT3B polymorphisms and overall cancer susceptibility. Totally, 4 studies with 1234 cases and 1337 controls were eligible for DNMT3B -283 T > C (rs6087990), 19 studies with 5332 cases and 7407 controls for DNMT3B -149 C > T (rs2424913), and 14 studies with 3933 cases and 4436 controls for DNMT3B -579 G > T (rs1569686). Overall, DNMT3B -283 T > C was associated with a significantly reduced risk of overall cancer (T vs. C: OR = 0.84, 95% CI = 0.71-0.99, P = 0.039). Likewise, the association of DNMT3B -579 G > T with a decreased overall cancer risk was also observed (heterozygous: OR = 0.77, 95% CI = 0.65-0.91, P = 0.003 and dominant: OR = 0.80, 95% CI = 0.66-0.98, P = 0.029); in the subgroup analysis, the protective association was found for lung and colorectal cancer, but not for head and neck cancer. Finally, the pooled analysis showed no significant association between DNMT3B -149 C > T and overall cancer susceptibility, but stratification analysis indicated that this polymorphism decreased the risk of developing head and neck cancer (heterozygous: OR = 0.73, 95% CI = 0.59-0.90, P = 0.003 and dominant: OR = 0.76, 95% CI = 0.61-0.93, P = 0.009). In conclusion, our results suggested that DNMT3B -283 T > C and DNMT3B -579 G > T but DNMT3B -149 C > T might confer protection against overall cancer risk. In the future, large and well-designed case-control studies are needed to validate our findings.

A Lacrimal Sump Syndrome With a Large Intranasal Ostium.

Lacrimal sump syndrome is an uncommon cause of failed dacryocystorhinostomy. Small osteotomy was reported as the major cause of this syndrome. Here, the authors described the first case of a lacrimal sump syndrome with a large intranasal ostium following endoscopic endonasal dacryocystorhinostomy (EE-DCR). A 51-year-old women patient suffered recurrence of epiphora and dacryocystitis for 8 months following an EE-DCR. Examination showed a large intranasal ostium with a lot of purulent discharge and patent lacrimal irrigation. Lacrimal sump syndrome was diagnosed after passing a probe into the residual lacrimal sac under the aid of an endoscope. The residual sac was reopened and merogel was packed around the wound. The clinical symptoms disappeared after the surgery. It is indicated that lacrimal sump syndrome does happen not only in a small intranasal ostium, but also in a large intranasal ostium. Existing residual sac with bacterial infection may be related to this particular case.

Endoscopic endonasal dacryocystorhinostomy combined with canaliculus repair for the management of dacryocystitis with canalicular obstruction.

Purpose. The aim of this study is to propose a simple and efficient combination surgery for the management of dacryocystitis with canalicular obstruction. Methods. A retrospective noncomparative case series of dacryocystitis with canalicular obstruction has been studied. Twelve patients with dacryocystitis and canalicular obstruction underwent a conventional endoscopic endonasal dacryocystorhinostomy (EE-DCR) combined with a modified canalicular repair. Postoperative observations included slit lamp, fluorescein dye disappearance test, lacrimal syringing, lacrimal endoscopy, and nasal endoscopy. Results. After 6-18 months of postoperative follow-up, the symptoms of epiphora and mucopurulent discharge disappeared completely in 10 patients, and occasional or intermittent epiphora remained in 2 patients. All of the twelve patients showed an opened intranasal ostium and normal fluorescein dye disappearance test. Patent bicanalicular irrigation was achieved in 9 patients. One patient had a partial and the other two had a complete reobstruction by lacrimal irrigation to their repaired lower canaliculus; however, all of them had a patent lacrimal irrigation to upper canaliculus. The functional success rate for the combination surgery is 83% (10/12), and anatomical success rate is 75% (9/12). Conclusion. EE-DCR combined with modified canalicular repair is a simple and efficient method for the management of dacryocystitis with canalicular obstruction.

Quantitative analysis of the association between CRP rs2808630 and rs1417938 polymorphisms and cancer risk.

Accumulating evidence indicates that polymorphisms in the CRP gene are important in the development of cancer. The current meta-analysis was performed to investigate the association between CRP polymorphisms 3407 A>G (rs2808630) and 29 A>T (rs1417938), and the risk of developing cancer. A search of the relevant literature was conducted using the PubMed database to identify eligible studies published up until March 25, 2014. Five case-control studies involving 888 cases and 3,167 controls for the 3407 A>G polymorphism, and six case-control studies involving 3,110 cases and 5,951 controls for the 29 A>T polymorphism were included in the current meta-analysis. The pooled odds ratios with 95% confidence intervals were calculated using the fixed- or random-effects model. Meta-analysis identified no association between the CRP 3407 A>G and 29 A>T polymorphisms, and overall cancer risk. Additional stratified analysis by cancer type did not reveal any significant associations in the genetic models investigated. The findings of the present study indicated that CRP 3407 A>G and 29 A>T polymorphisms are not associated with cancer risk.

A novel method for the localization and management of traumatic cyclodialysis cleft.

Purpose. To propose a novel surgical method for the localization and management of traumatic cyclodialysis clefts. Methods. Five patients with traumatic cyclodialysis clefts who underwent the innovative surgery were retrospectively reviewed. The new method was introduced to repair a cyclodialysis cleft with two running sutures from the middle to each end of the cleft under the guidance of a probe. Preoperative and postoperative visual acuity (VA), intraocular pressure (IOP), slit lamp and gonioscopic results, ultrasound biomicroscopy (UBM), and optical coherence tomography (OCT) findings were recorded. Results. Cyclodialysis clefts were completely closed postoperatively in four patients (four eyes); this was confirmed by progressively improved VA, restoration into the normal range of the IOP, disappearance of suprachoroidal fluid, and reduced macular edema. Only one patient with multiple clefts had an incomplete reattachment. Conclusions. This clinical study offers a novel and efficient method to localize and repair the cyclodialysis clefts.

Anterior and pan-endophthalmitis caused by Candida albicans and Aspergillus fumigatus: report of two cases.

We report two posttraumatic fungal endophthalmitis cases with anterior and entire segment involvement caused, respectively, by Candida albicans and Aspergillus fumigatus. The anterior endophthalmitis induced by C. albicans presented multifocal lesions with hyphael structures in anterior chamber, but without involvement of posterior vitreous. The pan-endophthalmitis caused by A. fumigatus displayed significant hypopyon and vitritis. Treatment strategies are anterior chamber cleaning for anterior endophthalmitis and vitrectomy for pan-endophthalmitis, excepting systemic and topical antifungal drug applications including intravitreal injection for both types of endophthalmitis. There is a much better outcome in the case with anterior segment involvement than that with entire segment involvement. This case report provides evidence that the different types of posttraumatic fungal endophthalmitis related to different fungal infections indeed existed and should be managed with different strategies.

Combination surgery for management of perforating eye injury with retained magnetic intraorbital foreign body.

PURPOSE: The objective of this study was to evaluate the feasibility and safety of vitrectomy combined with magnetic intraorbital foreign body (IOrFB) removal in the patients with perforating eye injury and retained magnetic IOrFBs. METHODS: A consecutive series of 7 patients with perforating eye injury and retained magnetic IOrFBs were included to perform secondary combination surgery (vitrectomy combined with IOrFB removal) after primary repair. Clinical data such as age, sex, hours and cause of injury, site and size of penetrating wound and IOrFB, involved intraocular tissues, surgical intervention, interval between surgeries, length of follow-up, anatomic recovery, visual outcome, and so on were recorded. RESULTS: Except for an unsuccessful IOrFB removal in case 6 in which IOrFB was finally extracted after 3 months, the remaining 6 cases had been operated on successfully both in vitrectomy and IOrFB removal. All the cases resulted in not only anatomic recovery but also good visual outcomes. No complications occurred. Seven cases revealed flat retina after silicone oil removal at a 3- to 12-month follow-up. Final best correct visual acuity equal to or better than 0.05 and 0.2 were 6 (85.7%) and 4 (57%) cases, respectively, and only 1 case was without improvement because of macular involvement. CONCLUSIONS: A combination surgery of vitrectomy with IOrFB removal is a highly efficient and safe procedure for the management of perforating eye injury with magnetic IOrFB. Prompt and proper management, such as preoperative exact localization of IOrFB, thoroughly cleaning of vitreous hemorrhage, complete sealing of retinal hole, and so on, is crucial for the successful achievement.

Ocular and generalized myasthenia gravis induced by human acetylcholine receptor γ subunit immunization.

INTRODUCTION: HLA-DQ8 transgenic mice develop ocular myasthenia gravis (oMG), which then progresses to generalized MG (gMG) when immunized with the human acetylcholine receptor (H-AChR) α subunit. Because the fetal AChR γ subunit is expressed in adult extraocular muscles, we anticipated that γ subunit immunization would generate an immune response to mouse AChR and induce MG in mice. RESULTS: H-AChR γ subunit immunization in HLA-DQ8 mice induced an autoimmune response to mouse AChR and led to the destruction of AChR in the neuromuscular junction (NMJ) by anti-AChR antibody and complement activation, and it triggered upregulation of AChR gene transcription. CONCLUSION: Our findings indicate that oMG may be induced by immunity to the AChR γ subunit.

Topical metal chelation therapy ameliorates oxidation-induced toxicity in diabetic cataract.

Oxidative stress plays a critical role in cataractogenesis, the leading cause of blindness worldwide. Since transition metals generate reactive oxygen species (ROS) formation, metal chelation therapy has been proposed for treatment of cataracts. However, the effectiveness of most chelators is limited by low tissue penetrability. This study is the first to demonstrate that the topically applied divalent metal chelator ethylenediamine tetraacetic acid (EDTA) combined with the carrier and permeability enhancer methyl sulfonyl methane (MSM) ameliorates both oxidation-induced lens opacification and the associated toxic accumulation of protein-4-hydroxynonenal (HNE) adducts. Both in vitro (rat lens culture) and in vivo (diabetic rats), EDTA-MSM (1) significantly reduced lens opacification by about 40-50%, (2) significantly diminished lens epithelial cell proliferation and fiber cell swelling in early stages of cataract formation in vivo, and (3) notably decreased the levels of protein-HNE adducts. These findings have important implications specifically for the treatment of cataract and generally for other diseases in which oxidative stress plays a key pathogenic role.

Trochlear calcification and intraorbital foreign body in ocular trauma patients.

OBJECTIVE: To distinguish trochlear calcification and intraorbital foreign body after eye injury in order to avoid misdiagnosis as well as mistreatment. METHODS: The orbital CT images of 403 patients, who visited the Eye Hospital or the Second Affiliated Hospital of Wenzhou Medical College during May 2005-April 2007, were reviewed. The diagnosis of trochlear calcification and intraorbital foreign body was made together by a skilled radiologist as well as an ophthalmologist. General information and CT characteristics in the patients with trochlear calcification were collected. RESULTS: Using CT scan images, 27 among 403 patients (6.69%) were identified with trochlear calcification. Three patients (3/27, 11.11%) were misdiagnosed by radiologists as intraorbital foreign body. Among the 27 patients with trochlear calcification, 23 (85.19%) were male and 4 (14.81%) were female, with an unilateral calcification in 7 patients (7/27, 25.93%) and bilateral in 20 (74.07%) . The highest occurrence of trochlear calcification was in 31-40 years old group (13/403, 3.23%) which reached to 12.87% (13/101) after age-correction. There were 3 types of trochlear calcification on the basis of CT images: commas, dot and inverted "U". CONCLUSIONS: The trochlear calcification is not an uncommon phenomenon and should not be diagnosed as intraorbital foreign body, especially when it co-exists with eye injury in 31-40 years old group. Injury history and our classification method on the basis of CT images could help to avoid misdiagnosis.

[Metabolism and detoxification of the lipid derived aldehyde, 4-Hydroxynonenal in diabetic cataractogenesis in rat].

OBJECTIVE: To study the metabolism of 4-hydroxynonenal (HNE), one of lipid derived aldehydes (LDAs), in diabetic rat lens and its role in diabetic cataract formation. METHODS: Experimental research. A factor design was used to set up the experiment statistically upon two factors: diabetic and normal control as treatment factors; day 30, 45 and 70 as the time factors. Normal and diabetic rats' lenses were incubated with HNE for 2 hours. HNE metabolites in the culture media were studied by high performance liquid chromatography (HPLC). Aldehyde dehydrogenase (ALDH) activity in normal and diabetic rat lens (30, 45 and 70 d after inducing of cataract) was detected by a spectrophotometer, ALDH protein and HNE-protein were detected by Western Blot. All data were analyzed by the Bonferroni test using SAS 8.0 software. RESULTS: The major pathway for HNE metabolism in normal lens was conjugation with glutathione (GSH) to form GS-HNE (45%), followed by HNE's oxidation to 4-hydroxy-2-nonenoic acid (HNA) by ALDH, which accounted for approximately 9.1% of HNE. The conjugation of HNE with GSH in diabetic lens was decreased approximately 64% at day 30 compared with the controls (F = 49.59, P < 0.001). The pathway of HNE oxidation by ALDH in the diabetic lens was enhanced approximately 1.7 times at day 70 compared to day 30 (F = 11.51, P = 0.0442). A higher ALDH activity, greater amount of ALDH protein, and less amount of HNE-protein adduct were presented in diabetic rat lens. CONCLUSIONS: The pathway of conjugation of HNE with GSH is inhibited in diabetic lens which may play a role in the formation of diabetic cataract. The oxidation of HNE by ALDH is a compensation process for protecting the lens against diabetic damage.

Molecular cloning and oxidative modification of human lens ALDH1A1: implication in impaired detoxification of lipid aldehydes.

Earlier studies showed that human lens ALDH1A1 plays a critical role in protection against oxidative stress-induced cytotoxicity in human lens epithelial cells (HLEC), and opacification of rat and mouse lens. The complete coding sequence of ALDH1A1 was cloned from human lens cDNA library by using PCR methods and expressed it in Escherichia coli. The cloned human lens ALDH1A1 cDNA encodes a 501-amino-acid protein (molecular mass = 54.8 kD) that is 100% identical to human liver ALDH1A1 and shares significant identity with the same isozyme from other tissues and species. The purified recombinant human lens ALDH1A1 exhibited optimal catalytic activity at pH 8 and preferred NAD(+) as cofactor and specifically catalyzed the oxidation of toxic lipid aldehydes such as 4-hydroxynonenal (HNE; K(m) = 4.8 microM) and malonaldehyde (K(m) MDA = 3.5 microM). Citral, disulfiram, and cyanamide were found to inhibit human lens ALDH1A1 at IC50 values of 55, 101, and 22610 microM, respectively, whereas diethylstilbestrol (DES) was found to be an activator (EC(50), 1.3 microM). Further, modification of recombinant human lens ALDH1A1 with nitric oxide donors such as S-nitroso-N-acetylpenicillamine (SNAP) and S-nitrosoglutathione (GSNO) significantly inhibited the enzyme activity. It therefore appears that activation of ALDH1A1, which efficiently catalyzes the detoxification of lipid-derived toxic aldehydes, and/or prevention of its oxidative modification may be novel therapeutic interventions against oxidative stress-induced lens pathologies.

Primary treatment of acute dacryocystitis by endoscopic dacryocystorhinostomy with silicone intubation guided by a soft probe.

PURPOSE: To investigate the suitability of cold steel endonasal endoscopic dacryocystorhinostomy (EES-DCR) with circular bicanalicular intubation with silicone tubes (CBIST) guided by a soft probe for the primary treatment of acute purulent dacryocystitis (APD). DESIGN: Prospective, randomized, interventional case series. PARTICIPANTS: Seventy-two patients (59 females, 13 males) with a median presenting age of 55+/-12 years (range, 28-71 years). METHODS: Eighty-four patients with unilateral APD were equally and randomly divided into 2 groups. Cold steel EES-DCR was performed after the lacrimal abscess formation, and external dacryocystorhinostomy (E-DCR) was performed 1 to 2 weeks after resolution of the acute inflammation. In both groups, CBIST guided by a soft probe was performed and the silicone tubes were kept in the lacrimal passages for 3 months. Postoperative follow-up ranged from 12 to 24 months. Outcomes were compared between both groups, considering resolution time for external acute inflammation, success rate of free lacrimal passage reconstruction, and lack of complications as indicators of treatment suitability. MAIN OUTCOME MEASURES: Time for resolution of the external acute inflammation, success rate of free lacrimal passage reconstruction, and complications. RESULTS: In this study, complete postoperative data were acquired from 40 patients in the EES-DCR group and from 32 patients in the E-DCR group, and the outcomes were compared. Acute inflammation resolved more quickly in the EES-DCR group than in the E-DCR group (P<0.05). Ostium patency at 12 months after silicone tube removal was achieved in significantly more patients in the EES-DCR group (36/40 [90%]) than in the E-DCR group (21/32 [65.7%]; P<0.01). In the EES-DCR group, lacrimal passage reconstruction failed because of intranasal ostial closure in 3 patients and because of common canaliculus obstruction in 1 patient. In the E-DCR group, lacrimal passage reconstruction failed because of intranasal ostial closure in 3 patients, lacrimal sac fibrosis, granulation, or both in 6 patients, and common canaliculus obstruction in 2 patients. Other than the slight laceration of the inferior puncta, no significant complications arose from the treatments. CONCLUSIONS: Cold steel EES-DCR with CBIST guided by a soft probe is a promising alternative for the primary treatment of APD with abscess formation. FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial interest in any materials discussed in this article.