Repeated sessions of PACK-CXL WA for the treatment of resistant bacterial keratitis: a retrospective study.

OBJECTIVE: The aim of this work is to evaluate the safety and efficacy of repeated sessions of photo-activated chromophore for keratitis-cross linking (PACK-CXL) window absorption (WA) for the treatment of resistant bacterial keratitis (BK). PATIENTS AND METHODS: This is a retrospective clinical cohort study. Thirty eyes with clinically suspected and lab-confirmed bacterial keratitis, resistant to appropriate antibiotic therapy- which was modified by sensitivity reports- for 2 weeks with failure of epithelialization for 4 weeks after the standard anti-microbial therapy (SAT) together with one setting of PACK-CXL WA were included. If after the first session of PACK-CXL, there is a start of improvement in the form of reduction of the size of corneal ulcer and stromal infiltrates together with the start of epithelialization on clinical examination and AS-OCT, another session of PACK-CXL WA was performed after one week, and so on, till the complete healing and resolution of bacterial keratitis and confirmation by negative bacterial culture. Identification of the micro-organisms was done by lab study before and after treatment. Corneal healing was evaluated by corneal examination and anterior segment OCT (AS-OCT). RESULTS: Thirty eyes of 30 patients were recruited in this study. They were 16 males and 14 females, their mean age was 44.3 ± 5.38 years. The mean ulcer size was 3.96 ± 1.87 (mm3), while the mean size of stromal infiltrates was 4.52 ± 2.24 (mm3). PACK-CXL WA treatment was performed an average of 2.87 times for the 30 eyes. Complete healing and resolution (Successful treatment) was observed in 27 eyes (90%) of cases and failure of epithelialization was observed only in 3 eyes (10%). Complete corneal healing was reported in the second month postoperatively in 90% of eyes. CONCLUSION AND RECOMMENDATION: PACK-CXL WA may be a promising, non-invasive treatment option for resistant bacterial keratitis. It may have a synergistic effect with standard antimicrobial treatment (SAT). Also, it can overcome the antibiotics resistance that has become rapidly spreading worldwide. Repeated sessions of PACK-CXL WA may be more effective for the treatment of resistant bacterial keratitis till complete epithelialization and resolution of BK than a single session with few complications. However, further prospective and comparative studies to support the results are needed.

SMILE lenticule versus amniotic membrane graft (AMG) augmented with platelet-rich plasma (PRP) for the treatment of perforated corneal ulcer.

PURPOSE: To evaluate the safety and efficacy of stromal lenticule obtained from small-incision lenticule extraction (SMILE) surgery versus amniotic membrane graft (AMG) augmented with platelet-rich plasma (PRP) for the treatment of perforated corneal ulcers and compare the results between the two groups. PATIENTS AND METHODS: This is a comparative retrospective study that included 40 eyes with medium-sized corneal perforations, which were classified into two equal groups of 20 eyes each; group (A) was treated with SMILE lenticule graft and group (B) was treated with AMG augmented with PRP. Pre- and postoperative evaluations were carried out using both slit-lamp (SL) examination and anterior segment optical coherence tomography (AS-OCT), including closure of perforation, complete healing, and best corrected visual acuity (BCVA). RESULTS: Complete closure of the perforation was achieved in both groups. However, healing was faster in the SMILE lenticule group than in the AMG with PRP group (P < 0.05). Complete healing was achieved in both groups: 100% in SMILE lenticule group and 95% in AMG with PRP group (P > 0.05). Both groups had few insignificant complications (30% in each), which were managed. CONCLUSION: Both methods achieved adequate healing of corneal perforations within few weeks without significant complications. However, the stromal lenticule obtained from small-incision lenticule extraction (SMILE) surgery tended to be safer with faster healing than AMG with PRP.

Combined Photoactivated Chromophore for Infectious Keratitis-Corneal Collagen Cross-Linking (PACK-CXL) and Therapeutic Penetrating Keratoplasty for Resistant Bacterial Keratitis.

PURPOSE: To report the results of treating resistant bacterial keratitis by corneal collagen cross-linking followed by therapeutic penetrating keratoplasty and to compare with those of therapeutic penetrating keratoplasty alone. METHODS: Retrospective analysis of the medical records of 33 eyes of 33 patients diagnosed with resistant bacterial keratitis. Fourteen eyes (14 patients) were treated with photoactivated chromophore for infectious keratitis corneal collagen cross-linking (PACK-CXL) followed by therapeutic penetrating keratoplasty (TPK) (group I) and 19 eyes (19 patients) were treated by TPK alone (group II). The main outcome measures were graft clarity and the mean best corrected visual acuity at 1, 3, 6, 12 and 18 months after penetrating keratoplasty. RESULTS: The mean age of the patients was 53.6 ± 1.9 years and 52.3 ± 1.8 years in group I and group II, respectively (p = 0.374), the mean ulcer size was 49.9 ± 16.2 mm2 and 54.7.1 ± 15.1 mm2 in group I and group II, respectively (p = 0.239), the mean corneal infiltrate size was 58.2 ± 17mm2 and 59.9 ± 15.7 mm2 in group I and group II, respectively (p = 0.384). Hypopyon was seen in 6 eyes (41.7%) in group I and in 8 eyes (42.1%) in group II. At the last follow-up visit, 12 corneal grafts (85.7%) maintained their clarity in group I while 13 corneal grafts (68.4%) maintained their clarity in group II (p = 0.037) and the mean best corrected visual acuity was 0.84 ± 0.63 log MAR in group I and 1.27 ± 0.81 log MAR in group II (p = 0.024). Postoperatively, one eye (7%) showed graft reinfection in group I that was controlled medically while 5 eyes (26.3%) showed resistant graft reinfection and ended in graft opacification in group II (p = 0.042). CONCLUSION: In resistant bacterial keratitis, priming infected corneas with PACK-CXL before performing TPK improve the results in such cases.

Drain fluid cryo-explant technique for treatment of superior bullous rhegmatogenous retinal detachment in young adults.

PURPOSE: To evaluate the efficacy of the drain fluid cryo-explant (DFCE) technique for the management of uncomplicated superior bullous rhegmatogenous retinal detachment (RRD) in young adults. PATIENTS AND METHODS: A retrospective study that included eyes with uncomplicated superior bullous RRD in patients ⩽40 years old. DFCE technique consists of sequential drainage of subretinal fluid, intravitreal fluid injection, cryotherapy, and placement of a scleral explant(s). The primary outcome measure was anatomical reposition of the retina after a single surgery. Secondary outcome measures included improvement in best corrected visual acuity (BCVA) and any reported complication related to the procedure. RESULTS: The study included 51 eyes which met the study eligibility criteria. The mean duration of detachment was 19.7 ± 6.4 days. A single retinal break was found in 31 eyes (60.8%), and more than one break were found in 20 eyes (39.2%). The mean number of breaks per eye was 1.72 ± 1.04. The mean detached area per eye was 7.21 ± 3.19 clock hours, and the macula was detached in 22 eyes (43.1%). Flattening of the retina and closure of all retinal breaks was achieved in all eyes after a single surgery. Late recurrence of retinal detachment occurred in two eyes (3.9%) due to proliferative vitreoretinopathy (PVR). No complicated cataract or iatrogenic retinal breaks were detected in all eyes. CONCLUSION: DFCE technique could be effectively used for treatment of uncomplicated superior bullous RRD in adults ⩽40 years. It is safe and provides good visualization during surgery with no iatrogenic retinal breaks or complicated cataract.

A Mitomycin C-Sparing Novel Technique for Subscleral Trabeculectomy in Primary Congenital Glaucoma.

PURPOSE: To evaluate the safety and efficacy of a novel modified subscleral trabeculectomy technique in management of primary congenital glaucoma. METHODS: This study included 25 infants diagnosed of having bilateral primary congenital glaucoma. For each patient, one eye was assigned to undergo subscleral trabeculectomy with trimming of the edges of the scleral bed (group I), while the contralateral eye underwent subscleral trabeculectomy with application of mitomycin C (0.4 mg/ml for 3 min) (group II). All the patients were followed up for a period of 14 ± 3 months (range 13-22 months). RESULTS: 25 eyes were included in each group. Patients' mean age was 2.5 ± 0.5 months (range 1.8-6.5 months). The mean preoperative intraocular pressure was 31 ± 4.9 mmHg and 32.1 ± 4.0 mmHg in group I and II, respectively. The mean postoperative intraocular pressure was 9.0 ± 1.0, 11.0 ± 3.2, 12.5 ± 0.9, 13.0 ± 2.9, and 15.5 ± 1.5 mm Hg in group I and was 10.3 ± 1.2, 12.0 ± 2.5, 13.5 ± 1.7, 15.0 ± 1.5, and 17.1 ± 2.8 mm Hg in group II at the first week and 1, 3, 6, and 12 months, respectively. There was no statistically significant difference between the mean intraocular pressure values recorded at both groups preoperatively and at each follow-up visit. Failure necessitating further surgical interventions was recorded in 4 eyes (16%) in group I as compared to 3 eyes (12%) in group II (P > 0.05). Postoperative complications included mild hyphema, which occurred in one eye (4%) in group I and 2 eyes (8%) in group II, and shallow anterior chamber in 3 eyes (12%) in group I and in 2 eyes (8%) in group II. One eye (4%) in group I developed drawn-up pupil. Choroidal effusion developed in one eye (4%) at each group. CONCLUSION: Trimming the edges of the scleral bed adjacent to the sclera flap is a safe and effective surgical step which can be added to the subscleral trabeculectomy procedure to effectively control the intraocular pressure in patients with primary congenital glaucoma, sparing them the hazards associated with mitomycin C application.

Intravitreal Clindamycin and Dexamethasone Combined with Systemic Oral Antitoxoplasma Therapy versus Intravitreal Therapy Alone in the Management of Toxoplasma Retinochoroiditis: A Retrospective Study.

PURPOSE: To compare clinical outcome of IVCD combined with oral therapy with IVCD alone in patients with toxoplasmic retinochoroiditis. PATIENTS AND METHODS: Thirty eyes were reviewed. Two equal groups were identified (15 eyes each). Clinical outcome measures were resolution of active inflammation, changes in BCVA and CMT, adverse drug reactions, and rate of recurrence. RESULTS: Mean baseline of BCVA 1.08 ± 0.17 and 1.03 ± 0.15 improved to 0.64 ± 0.18 and 0.69 ± 0.17 at the end of follow-up in group I and II, respectively. No statistically significant difference was observed. CMT was 392.6 ± 33.16 µm and 397.3 ± 14.6 µm significantly decreased to 314.7 ± 4.43 µm and 319.6 ± 7.8 µm. Resolution of acute inflammation was achieved in all cases in both groups. There were no recurrent cases in group I, and only one out of 15 (6.7%) in group II. No ocular or systemic adverse events were recorded. CONCLUSION: IVCD is an effective route of treatment for active toxoplasmic retinochoroiditis that can be used solely without the need to use systemic medications..

Pomegranate protective effect on experimental ischemia/reperfusion retinal injury in rats (histological and biochemical study).

Oxidative stress is one mechanism involved in the pathogenesis of ischemia/reperfusion (/R) retinal injury. The histological, biochemical, and functional changes associated with pomegranate (PMG) treatment prior to retinal I/R were analyzed using 40 adult male albino rats. Rats were divided into four groups: Groups I and II (sham operated and received saline or PMG, respectively); Groups III and IV (I/R rat models with prior administration of saline or 250 mg/kg/day PMG, respectively). Electroretinogram (ERG) results were recorded and eye specimens were taken and processed for light and electron microscopic examinations and for assessment of oxidative status in retinal homogenate. I/R lead to degenerative changes in retinal layers with a significant reduction in nuclear factor erythroid 2-related factor 2 (Nrf2) immunoreactivity in concomitant with significant oxidant-antioxidant disturbance and decreased a- and b-wave amplitude in the ERG. These alterations were ameliorated with prior PMG treatment. In conclusion, PMG treatment, as an antioxidant, attenuated retinal structural and functional I/R injury through activation of Nrf2 which could be a base for future therapy designs.

Pars Plana Vitrectomy with Internal Limiting Membrane Peeling in Traumatic Macular Hole: 14% Perfluoropropane (C3F8) versus Silicone Oil Tamponade.

PURPOSE: To evaluate the outcome of 23 G PPV and ILM peeling with 14% C3F8 compared with silicone oil tamponade in cases of TMHs without spontaneous closure. METHODS: A retrospective comparative study included 33 eyes with TMHs; 7 eyes healed spontaneously, and the remaining 26 eyes have been treated with PPV and ILM peeling. Silicone oil was used as a tamponade for children or adults who refused to adopt face-down position (10 cases). In all other cases (16 cases), 14% C3F8 was used. These cases were followed up for 6 months postoperatively. RESULTS: 26 cases (22 males and 4 females) were reviewed, including 10 cases treated with silicone oil and 16 cases treated with 14% C3F8. Patients' age ranged from 9 to 54 years. The success rate was 90% in the silicone-filled (9/10) and 94% in the gas-filled (15/16) eyes. At 6 months, the mean BCVA was 0.3 ± 0.25 in the silicone group and 0.2 ± 0.13 in the gas group (p < 0.05). CONCLUSIONS: Cases of TMHs should be observed for spontaneous closure. PPV with ILM peeling should be conducted for nonclosing cases. Gas and silicone oil tamponades are equally successful in anatomical and visual outcomes. This trial is registered with CTRI/2017/06/008765.

Photorefractive Keratectomy for Residual Myopia after Myopic Laser In Situ Keratomileusis.

Purpose. To evaluate the safety, efficacy, and predictability of photorefractive keratectomy (PRK) on the corneal flap for correction of residual myopia following myopic laser in situ keratomileusis (LASIK). Patients and Methods. A retrospective study on eyes retreated by PRK on the corneal flap for residual myopia after LASIK. All eyes had no enough stroma after LASIK sufficient for LASIK enhancement. Data included spherical equivalent (SE), uncorrected and best corrected visual acuity (UCVA and BCVA), central pachymetry, corneal higher order aberrations (HOAs), corneal hysteresis (CH), corneal resistance factor (CRF), and corneal haze. Results. The study included 64 eyes. Before PRK, the mean central pachymetry was 400.21 ± 7.8 µm, the mean SE was -1.74 ± 0.51 D, and the mean UCVA and BCVA were 0.35 ± 0.18 and 0.91 ± 0.07, respectively. 12 months postoperatively, the mean central corneal thickness was 382.41 ± 2.61 µm, the mean SE was -0.18 ± 0.32 D (P < 0.01), and the mean UCVA and BCVA were 0.78 ± 0.14 (P = 0.01) and 0.92 ± 0.13 (P > 0.5), respectively. The safety index was 1.01 and the efficacy index was 0.86. No significant change was observed in corneal HOAs. Conclusions. Residual myopia less than 3 D after LASIK could be safely and effectively treated by PRK and mitomycin C with a high predictability. This prevents postoperative ectasia and avoids the flap related complications but has no significant effect on HOAs.

Evaluation the adjunctive use of combined bevacizumab and mitomycinc to trabeculectomy in management of recurrent pediatric glaucoma.

PURPOSETO evaluate the efficacy and safety of combined bevacizumab-mitomycin c (MMC) in recurrent cases of pediatric glaucoma.METHODSA prospective non-masked controlled study that included bilateral cases of 12 patients (24 eyes) with recurrent (had previous glaucoma surgery before) pediatric glaucoma. One eye in each patient (12 eyes) was assigned to trabeculectomy operation with combined application of MMC (0.4 mg/ml for 3 min) under and around the scleral flap before trabeculectomy and bevacizumab (avastin) (2.5 mg in 0.2 ml) injected subconjunctivally around the bleb after completing the surgery (group I). The other eye of each patient (12 eyes) was assigned to trabeculectomy operation with application of MMC (0.4 mg/ml for 3 min) only (group II). The mean follow-up period was 13±1 months.ResultsThe mean age was 2.16±1.5 (range 7 months to 4.1 years). No significant difference in preoperative intraoperative pressure (IOP) was observed between the groups (P>0.05). Recurrent primary congenital glaucoma represents 66.7% of the cases. Other cases included were recurrent aphakic and pseudophakic glaucoma 25% and recurrent post uveitic glaucoma 8.3%. The mean IOP was 12.1±4.2, 12.6±5.4, and 12.8±5.2 mm Hg in group I at 3, 6, and 12 months, respectively, and was 12.8±5.3, 13.7±6.7 and 15.6±5.9 mm Hg in group II at 3, 6, and 12 months, respectively. There was a statistically significant difference in the mean IOP between the studied groups at the 1-year follow-up visit (P<0.05). In addition, group I showed a higher statistically significant difference in absolute and total success (75 and 91.7%, respectively) compared with group II (58.3 and 75%, respectively) (P<0.05). The encountered complications included mild hyphema, which occurred in 8.33% in group 1, wound leakage, which occurred in 8.33% in each group, and shallow anterior chamber (AC), which occurred in 16.7% in each group and was the most common encountered complication in the study. One case of shallow AC in group I led to choroidal effusion (8.33%). One case in group II developed late bleb-related endophthalmitis after 3 months, which resulted in phthisis bulbi (8.33%).ConclusionThe additive effect of subconjunctival bevacizumab to MMC-augmented trabeculectomy in the case of recurrent pediatric glaucoma was beneficial in improving the success rate. Better IOP control and prolonging the bleb survivalvia reducing the long-term need of using anti-glaucoma drugs postoperatively without adding complications had also been achieved with this technique. This offers a promising alternative for the treatment of this type of glaucoma.

Predictability of Sirius dual-scanning corneal tomography in the measurement of corneal power after photorefractive surgery.

Determining an accurate central corneal power (K) measurement is crucial for calculating the intraocular lens power in patients who are undergoing cataract extraction. The ideal method for measuring K is to use a device that works independently of the refractive surgery information. The Scheimpflug camera system offers a promising means of measuring the true corneal power after keratorefractive surgery. In this study, we investigated the accuracy of this system in measuring central corneal power after photorefractive corneal surgery by comparing it to the theoretically derived central corneal power by history method. A total of 120 eyes of 65 (35 females and 30 males) patients were included in this study. The mean change of refraction at the spectacle plane was 3.75 D, whereas the mean change of refraction at the corneal plane was 3.37 D. Using the Sirius dual-scanning corneal tomography, the mean change in corneal power was 3.96 D. No significant differences were detected between the mean post-operative corneal power measured by the Sirius tomographer and the mean change in refraction at the corneal plane calculated clinically (P = 0.076) and the correlation was found to be high (0.913). This study suggests that Sirius dual-scanning corneal tomography offers high predictability when measuring the central 5 mm corneal power in patients who have had myopic corneal photorefractive surgery.

Rehabilitación del ictus: modelo asistencial. Recomendaciones de la Sociedad Española de Rehabilitación y Medicina Física, 2009 / Stroke rehabilitation: Care model. Recommendations of the Spanish Society of Physical Medicine and Rehabilitation, 2009

Objetivos: La Sociedad Española de Medicina Física y Rehabilitación elabora un documento de recomendaciones de buena práctica clínica sobre el modelo asistencial en la rehabilitación (RHB) del ictus basadas en la experiencia clínica y el consenso de los autores y las guías de práctica clínica de referencia. Estrategia de búsqueda: La búsqueda se centra en guías de práctica clínica y artículos relevantes sobre el modelo asistencial en la RHB del ictus en las bases de datos MEDLINE, Embase y Cochrane Databases desde enero de 2004 hasta enero de 2009.Selección de estudios: Se seleccionan ensayos clínicos aleatorizados, metaanálisis, revisiones sistemáticas y artículos de revisión sobre el modelo asistencial en la RHB del ictus. Síntesis de resultados: El programa rehabilitador del ictus es un proceso complejo que requiere un abordaje multidisciplinario, siendo elementos claves el inicio precoz, la intensidad adecuada, la evaluación periódica y la participación activa de pacientes y cuidadores. Conclusiones: En todos los niveles de atención sanitaria y sociosanitaria, hospitalaria o comunitaria se debe asegurar la atención de RHB a cargo de un equipo multidisciplinario, coordinada por un médico especialista en RHB con adecuados niveles de organización y experiencia de los profesionales (AU)

Objectives: The Spanish Society of Physical Medicine and Rehabilitation has elaborated a document of good clinical practice recommendations on the care model in stroke rehabilitation based on the clinical experience and consensus of the authors and reference clinical practice guides. Search strategy: The search was focused on clinical practice guides and articles related with the care model in stroke rehabilitation in the MEDLINE, EMBASE and COCHRANE DATABASES from January 2004 to January 2009.Selection of studies Randomized clinical trials, meta-analyses, systematic reviews and review articles on the care model in stroke rehabilitation were selected. Synthesis of results: The stroke rehabilitation program is a complex procedure that requires a multidisciplinary approach. Its key elements are early initiation, adequate intensity, periodic evaluation and active participation of the patients and caregivers. Conclusions: Rehabilitation care under the responsibility of a multidisciplinary team, coordinated by a medical specialist in rehabilitation with adequate levels of organization and experience of the professionals should be assured on all health a and socio-health care, hospital or community levels (AU)

Antiproliferative actions of 7-substituted 1,3-dihydroxyacridones; possible involvement of DNA topoisomerase II and protein kinase C as biochemical targets.

7-Chloro-1,3-dihydroxyacridone (1) reversibly inhibited growth of KB and vero cell lines with IC50's of 35 and 40 microM, respectively, and a topoisomerase II-mediated multidrug resistant KB sub-clone was found to be about three-fold more susceptible to 1. In contrast, two cell lines of lymphoid origin were killed following treatments with 60 microM and at higher concentrations of 1. KB cell growth inhibition correlated with a rapid, reversible suppression of thymidine incorporation. Uridine but not leucine incorporation was also rapidly suppressed. The in vitro activities of DNA topoisomerase II and novel protein kinase C-subtype delta were inhibited at effective concentrations in tissue-culture, but 1 did not stimulate intracellular protein-associated DNA breaks nor interfere initially with topoisomerase II-mediated DNA cleavage in KB cells. In addition to antiproliferative effects against cells, the compound was weakly virustatic for herpes simplex virus type I with an IC50 of 8 microM. Limited studies comparing three 1-congeners and citpressine-I, an acridone alkaloid with reported antiherpes activity, demonstrated that 7-substituted 1,3-dihydroxyacridones are novel antiproliferative agents which share similar biological and biochemical properties.

Inhibition of DNA topoisomerases by sanguiin H-6, a cytotoxic dimeric ellagitannin from Sanguisorba officinalis.

Many tannins were previously identified as candidate topoisomerase poisons. Here we report further studies on sanguiin H-6, a dimeric ellagitannin isolated from Sanguisorba officinalis as an inhibitor of DNA topoisomerases. Catalytic strand-passing activities of topoisomerases I and II were inhibited in vitro with IC50 values of 1 microM and 0.01 microM, respectively. This inhibition was not associated with stabilization of covalent enzyme-DNA complexes but rather by a mechanism preventing formation of such covalent intermediates, as measured by interference with drug-induced cleavage in vitro. The IC50 values for topoisomerase I-DNA complexes induced by camptothecin and with topoisomerase II-DNA complexes induced by VP-16 were 0.02 microM and 0.16 microM, respectively. Pre-incubation studies followed by drug-dilution revealed that the in vitro inhibitory effects of sanguiin H-6 were irreversible, and for topoisomerase I, the test compound prevented enzyme-DNA interaction as seen by shifts in mobility on agarose gels. By measuring interference with drug-induced protein-linked DNA breaks in isolated HeLa nuclei, inhibition of topoisomerases I and II on a natural chromatin template was demonstrated with IC50 values of 5 microM and > 10 microM, respectively. Sanguiin H-6 inhibited HeLa cell growth with an ED50 of 12 microM and also interfered in a dose-dependent fashion with intracellular topoisomerase activities but with lower potencies than those observed using subcellular assay systems. Based on these studies, sanguiin H-6 could be broadly classified as a type of poison which does not stimulate the formation of cleavable-complexes, with intracellular activity but without any marked selectivity.(ABSTRACT TRUNCATED AT 250 WORDS)

Tannins as potent inhibitors of DNA topoisomerase II in vitro.

Fifty-two out of 60 tannins, including gallo-, ellagi-, condensed, and complex tannins, are inhibitors of human DNA topoisomerase II in vitro. Thirty-six compounds that completely inhibited enzyme activity at a concentration of 500 nM or less, as assessed by ATP-dependent unknotting of P4 phage DNA, were at least 100-fold more potent than the clinically useful antitumor agent etoposide (VP-16). Relative inhibitory activity was primarily related to the number of phenolic hydroxyl groups (galloyl and hexahydroxydiphenoyl moieties) found in the active structures, with more groups generally conferring increased potencies. Unlike VP-16 and some DNA intercalative agents that stabilize the topoisomerase II-DNA cleavage intermediate, none of the active compounds induced protein-linked DNA breaks in cultured cells. Some of the tannins reduced VP-16-induced protein-linked DNA breaks by 20% or more, but one of these compounds, (-)-epicatechin, was not an inhibitor in vitro. Our data suggest that some tannins, such as sangiin H-6, that are potent inhibitors of catalytic double DNA-strand passage in vitro may target intracellular enzyme activity in a similar fashion to known poisons that interfere with formation of the enzyme-DNA covalent intermediate.