Effect of mitomycin C on the corneal endothelial cells of Saudi patients with myopia after transepithelial photorefractive keratectomy:a two-armed cohort study

AIM:To study the effect of mitomycin C(MMC)applied during transepithelial photorefractive keratectomy(TPRK)on the corneal endothelium one week(W1)and three months(M3)after surgery and its determinants.METHODS:In this two-armed cohort study conducted in 2022,eyes treated with MMC during TPRK(group 1)were compared with eyes not treated with MMC(group 2).The corneal endothelial cell(EC)count,EC density(ECD;cells/mm2),average(μm2),standard deviation(μm2),coefficient of variation(CV%),ECmax,ECmin,and EC percentage of hexagonality were estimated at W1 and M3.The postoperative changes in the EC count in the two groups were compared and correlated with the other independent variables.RESULTS:Group 1 had 26 eyes,and group 2 had 78 eyes.All TPRK indices were significantly higher for the eyes in group 1 than for those in group 2.The MMC usage was not a significant predictor of the change in ECD(P=0.644),change in CV(P=0.374),and change in the percentage of hexagonality of EC(P=0.164)at W1.However,the use of MMC was a significant predictor of changes in CV(P=0.014)and the change in the percentage of hexagonality of EC(P=0.039)at M3.The duration of laser exposure and the size of the optical zone influenced the correlation of MMC use with the changes in EC indices,postoperatively.CONCLUSION:The use of MMC doesn’t affect ECD,CV,and percentage of hexagonality at W1 if other surgical indices are considered.At M3 after operating myopic eyes by TPRK,MMC significantly influence the CV and percentage of hexagonality.The duration of the laser application and the size of the optical zone should be considered when determining the effect of MMC on the EC indices.

Clinical outcomes at one year following keratoconus treatment with accelerated transepithelial cross-linking

This study evaluated the clinical outcomes in keratoconus corneas following accelerated transepithelial corneal collagen cross-linking（CXL）（Avedro KXL system,Waltham,MA,USA） over one year of follow-up.The mean depth of the demarcation line measured by optical coherence tomography（OCT） was 205.19 μm.One month after surgery,a non-statistically significant change was noted in sphere（P= 0.18） and in spherical equivalent（P= 0.17）,whereas a significant improvement was observed in corrected distance visual acuity（P=0.04）.A significant change was observed in topographic astigmatism（P= 0.03） and posterior corneal a sphericity（P= 0.04）.Accelerated transepithelial CXL may be a useful technique for the management of progressive keratoconus.

Transepithelial photorefractive keratectomy mode using SCHWIND-ESIRIS excimer laser:initial clinical results

AIM: To evaluate postoperative pain, uncorrected visual acuity (UCVA), and cornea haze value after transepithelial photorefractive keratectomy (T-PRK) performed with aspherical ablation profile using SCHWIND ESIRIS excimer laser. METHODS: Retrospective case series. Fifty-nine eyes (32 patients) with myopia associated with or without astigmatism underwent phototherapeutic keratectomy (PTK) followed by photorefractive keratectomy (PRK) which performed by Optimized Refractive Keratecomy (ORK)-CAM software based on aspherical ablation profile using SCHWIND ESIRIS excimer laser. Postoperative pain scale was measured on a questionnaire through five levels. Haze was graded by five grades, and UCVA, manifest refraction spherical equivalent (MRSE) were analyzed. RESULTS: Mean pain level was (1.37 +/- 0.613) (range: 1 to 3), the mean time picking out the soft contact lens was (6.22 +/- 1.73) days, at 3 months, UCVA was 1.0 for 40 eyes (67.8%), 0.5 for all eyes (100.0%). The UCVA was significantly less than the preoperative best spectacle corrected visual acuity (BSCVA) (t=-2.84, P=0.006), haze value was (0.27 +/- 0.25), no patients had a haze grade up to 2. Mean MRSE was (0.76 +/- 0.96) diopter(D) by 3 months. CONCLUSION: The outcomes from this study show that using the SCHWIND ESIRIS aspherical ablation profile for transepithelial PRK has a good visual result. The primary advantage is related to a spherical ablation profile, automatically considers the ablation volume of the stroma and the accurate and smooth removal of the epithelium with PTK. Additional studies are needed to determine long-term outcomes.

Clinical outcomes of transepithelial photorefractive keratectomy versus femtosecond laser assisted keratomileusis for correction of high myopia in South Egyptian population

AIM: To evaluate the safety and efficacy of transepithelial photorefractive keratectomy(t-PRK) with adjuvant mitomycin C(MMC) versus femtosecond laser assisted keratomileusis(Femto-LASIK) in correction of high myopia.METHODS: Prospective randomized comparative study including 156 eyes of 156 patients with high myopia and a spherical equivalent refraction(SER) <-6.00 D. They were divided randomly into two groups: Group A included 72 eyes treated with t-PRK with adjuvant MMC and Group B included 84 eyes treated with Femto-LASIK. Visual acuity, SER, corneal topography, pachymetry and keratometry were assessed for 12 mo postoperatively.RESULTS: The preoperative mean SER was-8.86±1.81 and-9.25±1.70 D in t-PRK MMC group and Femto-LASIK respectively(P=0.99) which improved to-0.65±0.43 D and-0.69±0.50 D at 12 mo follow up. Mean SER remained stable during the 12 mo of follow-up, with no statistically significant difference between the two groups(P=0.64). In t-PRK MMC group, only six eyes needed retreatment after six months of follow up. And two eyes showed haze(one reversible haze grade 2, while the other had dense irreversible haze grade 4).CONCLUSION: t-PRK MMC provides safe and satisfactory visual outcomes and acceptable risk as Femto-LASIK in patients with high myopia.

Transepithelial photorefractive keratectomy for myopia:effect of age and keratometric values

AIM:To investigate demographic and preoperative factors increasing the risk of ametropia following transepithelial photorefractive keratectomy(trans PRK)in myopia and myopic astigmatism.METHODS:This retrospective cohort study included myopic eyes(-0.50 to-8.75 D)with or without astigmatism(up to 3.50 D)enrolled at Dr.Yap Eye Hospital Yogyakarta.Trans PRK was performed using Technolaz 217 z100 excimer laser.Subjects were clustered into ametropia and emmetropia group based on uncorrected distance visual acuities(UDVA)3 mo post-operatively.Multiple preoperative and intraoperative parameters were analyzed using Logistic regression to obtain their effect on ametropia risk following trans PRK.RESULTS:A total of 140 eyes of 87 consecutive subjects were studied.Prevalence of ametropia following trans PRK was 20(14.29%)eyes.Subjects in ametropia group were significantly older than the emmetropia group(31.80±14.23 vs 18.88±2.41,respectively;P<0.001).Bivariate Logistic regression analysis showed that older age(OR=1.23),higher preoperative spherical equivalent(>-6 D;OR=12.78),steeper anterior keratometric readings(Kmax>45 D and mean K>44 D;OR=4.28 and 4.35,respectively)increased the risk of ametropia following trans PRK.Adjusted multivariate Logistic regression analysis showed that age was the strongest predictor for the incidence of ametropia following trans PRK.Complications of trans PRK were overcorrection,suspected posterior keratoectasia and accommodation insuffiency.CONCLUSION:Older age can be the strongest factor for increasing ametropia risk following trans PRK.Cut-off points of Kmax and mean K at 45 and 44 D respectively are proposed as the predictors for ametropia following trans PRK.

Transepithelial leak in Barrett's esophagus patients: The role of proton pump inhibitors

AIM： To determine if the observed paracellular sucrose leak in Barrett＇s esophagus patients is due to their pro- ton pump inhibitor （PPI） use. METHODS： The in vivo sucrose permeability test was administered to healthy controls, to Barrett＇s patients and to non-Barrett＇s patients on continuous PPI thera- py. Degree of leak was tested for correlation with pres- ence of Barrett＇s, use of PPIs, and length of Barrett＇s segment and duration of PPI use. RESULTS： Barrett＇s patients manifested a near 3-fold greater, upper gastrointestinal sucrose leak than healthy controls. A decrease of sucrose leak was ob- served in Barrett＇s patients who ceased PPI use for 7 d.Although initial introduction of PPI use （in a PPI-na＇ive population） results in dramatic increase in sucrose leak, long-term, continuous PPI use manifested a slow spon- taneous decline in leak. The sucrose leak observed in Barrett＇s patients showed no correlation to the amount of Barrett＇s tissue present in the esophagus. CONCLUSION： Although future research is needed to determine the degree of paracellular leak in actual Barrett＇s mucosa, the relatively high degree of leak ob- served with in vivo sucrose permeability measurement of Barrett＇s patients reflects their PPI use and not their Barrett＇s tissue perse.

Comparison of corneal biological parameters between transepithelial and epithelium-off corneal cross-linking in keratoconus

AIM:To evaluate the differences in corneal biological parameters between transepithelial and epithelium-off corneal cross-linking in keratoconus.METHODS:In our prospective clinical trial,40 patients(60 eyes)with progressive keratoconus were randomized to undergo corneal cross-linking with transepithelial(TE group,n=30)or epithelium-off(EO group,n=30)keratoconus.Examinations comprised topography,corneal biomechanical analysis and specular microscopy at 6 mo postoperatively.RESULTS:The keratometer values were not significantly different between the TE and EO corneal cross-linked groups in different periods(each P>0.05).The corneal thickness of the EO group was greater than that of the TE group at 1 wk after the operation(each P<0.05).Regarding corneal biomechanical responses,the EO group showed a longer second applanation length than TE group(P=0.003).Regarding the corneal endothelial function,standard deviation of the endothelial cell size,and coefficient of variation in the cell area,the values of EO group were larger than those of TE group at 1 wk(P=0.011,0.026),and the percentage of hexagonal cells in EO group was lower than that in TE group at 1 and 6 mo(P=0.018,0.019).CONCLUSION:Epithelium-off corneal cross-linking may strengthen corneal biomechanics better than TE procedure can.However,the TE procedure with a lower ultraviolet-A irradiation intensity would be safer for corneal endothelial function.

Single-step transepithelial photorefractive keratectomy in high myopia：qualitative and quantitative visual functions

AIM：To investigate quantitative and qualitative optical outcomes of single-step transepithelial photorefractive keratectomy（Trans PRK）in high myopia.METHODS：In a prospective interventional case-series,30 eyes with high myopia（-6.00 to-8.75 D）with（up to-3.00 D）or without astigmatism were enrolled from Bina Eye Hospital,Tehran,Iran. One-step Trans PRK was performed with aberration-free aspherical optimized profile and SCHWIND AMARIS 500 laser. One-year follow-up results for refraction,visual acuities,vector analysis,ocular wavefront（OWF）and corneal wave-front（CWF）higher order aberrations（HOA）,contrast sensitivity（CS）,and postoperative haze were assessed.RESULTS：After the surgery,both photopic and mesopic CSs significantly improved（both P〈0.001）. We detected significant induction of OWF coma and trefoil（P〈0.001 for both）HOAs; CWF coma（P=0.002）,spherical（P〈0.001）,and tetrafoil（P=0.003）HOAs in 6 mm analysis diameter; and CWF trefoil（P=0.04）HOA in 4 mm analysis diameter. The range of mean induction observed for various HOAs was0.005-0.11 μm. The 86.7% of eyes reached an uncorrected distance visual acuity of 20/20 or better; 96.7% of eyes were within ±0.5 D of targeted spherical refraction. In vector analysis,mean correction index value was 1.03 and mean index of success was 0.22. By 12mo after the operation,no eye lost any number of corrected distancevisual acuity lines. We detected no corneal haze greater than 1~＋ throughout the follow-up.CONCLUSION：Our findings show promising effects of single-step Trans PRK on quality of vision in high myopic eyes. It also improves refraction and visual acuity.

A 3-month comparison study of subjective and objective visual quality of small incision lenticule extraction and transepithelial photorefractive keratectomy in patients with low and moderate myopia

AIM:To compare the subjective and objective visual quality between small incision lenticule extraction(SMILE)and transepithelial photorefractive keratectomy(t PRK)in patients with low and moderate myopia.METHODS:Patients undertaking SMILE or t PRK for the correction of low and moderate myopia were consecutively recruited in this prospective cohort study with a 3-month follow-up period.Objective evaluation[visual acuity test,manifest refraction,wavefront aberrations,the total cut-off value of the total modulation transfer function(MTFcut-off),and Strehl ratio(SR)]and subjective evaluation of visual quality(quality-of-life questionnaire)were conducted before surgery and at days 1,7,30,and 90 after surgery.RESULTS:A total of 47 patients(94 eyes)with SMILE and 22 patients(22 eyes)with t PRK were enrolled.The uncorrected visual acuity(UCVA)was better in SMILE patients on day 7 after surgery(1.13±0.13 vs 0.99±0.17,t=4.85,P<0.001)but was comparable at days 30 and 90.At day 90,the SMILE group had a lower spherical equivalent(SE)than the t PRK group(0.04±0.31 vs 0.19±0.43,t=2.08,P=0.042).Total higher order aberrations(HOAs)were induced in both surgical types,which were more evident in the t PRK group with 3-mm pupil diameter(0.16±0.07 vs0.11±0.05,t=4.27,P<0.001)and 5-mm pupil diameter(0.39±0.17 vs 0.36±0.11,t=2.33,P=0.022).The MTFcut-offand SR showed a trend of improvement in both SMILE and t PRK patients but were statistically better in the SMILE group with both pupil diameters.There was a significant improvement of contrast sensitivity(CS)over baseline levels at the spatial frequency of 18 cycles/degree(c/d)in the SMILE group(F=2.72,P=0.033)and at 3 c/d(F=3.03,P=0.031),12 c/d(F=3.72,P=0.013),and 18 c/d(F=4.62,P=0.004)in the t PRK group.The subjective quality of life questionnaire showed a steady improvement in the SMILE group(F=8.31,P<0.001)but not the t PRK group.CONCLUSION:SMILE and t PRK are both safe and effective ways to correct low and moderate myopia.A generally better and quicker recovery of visual quality favors the application of SMILE in qualified patients.

Changes in Antioxidant Activity of Alcalase-Hydrolyzed Soybean Hydrolysate under Simulated Gastrointestinal Digestion and Transepithelial Transport

Peptides from Alcalase-hydrolyzed soybean protein hydrolysate(SPH)may hold the potential as natural antioxidants.In addition,the effect of human gastrointestinal(GI)tract on peptide bioavailability needs to be explored.In this study,the impact of simulated GI digestion and transepithelial transport on various antioxidant properties of SPH were investigated.SPH displayed DPPH radical scavenging(IC50=4.22 mg/m L),ABTS·+radical scavenging(IC50=2.93 mg/m L),reducing power and metal ion-chelating activities(IC50=0.67 mg/m L).Furthermore,SPH significantly(P<0.05)inhibited the generation of intracellular reactive oxygen species(ROS)in Caco-2 cells.After simulated GI digestion,the antioxidant properties of SPH were enhanced,except for a decrease in ABTS·+radical scavenging activity.After transepithelial transport,the permeates maintained partial antioxidant activity and the LC-MS/MS data further identified the absorbed soybean peptides.These results suggest that SPH contains the antioxidant peptides that are potentially bioavailable and can be regarded as a promising source of functional food ingredients.

A histological study of rabbit corneas after transepithelial corneal crosslinking using partial epithelial photoablation or ethanol treatment

AIM: To evaluate the histological changes after transepithelial corneal crosslinking(CXL) using partial thickness excimer laser ablation or epithelial ethanol application in an experimental rabbit study.METHODS: Right eyes of twenty-four rabbits were studied. Four eyes received total epithelial debridement(group I). Four eyes received partial thickness epithelial ablation with excimer laser(group II). Twelve eyes were treated with different durations(30s and 60s) and concentrations(18% to 48%) of ethanol(group III).Riboflavin was applied for 30 min intervals along with topical proparacaine drops with benzalkonium chloride,and 370 nm irradiation was performed for 30 min, while riboflavin was instilled every 3min. Four eyes(group IV)received 48% ethanol for 30 s without riboflavin and irradiation. Eyes were collected after 24 h and examined histologically.RESULTS: All eyes in group I showed keratocyte loss in the superficial 300 μ of corneal storma. In group II, 1-4layers of epithelium were preserved and no keratocyte loss occurred. In group III, CXL after treatment with ethanol up to 24% concentration and up to 60 s revealed no keratocyte loss. CXL after treatment with 48% and higher ethanol concentrations yielded keratocyte loss in the superficial 200 μ to 300 μ of cornea.CONCLUSION: Incomplete excimer laser ablation of the epithelium or treatment with ethanol up to 24%concentration and up to 60 s duration yielded no stromal keratocyte loss. To get the same histological appearance seen in epithelial debridement group, partial thicknessexcimer laser epithelial ablation or ethanol application is not adequate for transepithelial CXL.

Transpalpebral intraocular pressure measurement by Diaton compared to Goldman applanation tonometer in myopic eyes before and after transepithelial photorefractive keratectomy in Saudi Arabia

AIM:To compare intraocular pressure(IOP)measured via the trans palpebral IOP(tp IOP)method using a Diaton or with a Goldman applanation tonometer(GAT)and study the determinants of IOP difference in eyes undergoing transepithelial photorefractive keratectomy(TPRK)for myopia.METHODS:This cross-sectional validation study was held in 2020 in an eye hospital in Saudi Arabia.IOP was measured by Diaton and GAT before treatment,after one week,and one month of TPRK.It is considered if IOP difference by Diaton and GAT was less than±2 mm Hg acceptable.The IOP difference was tested if correlated to spherical equivalent(SE),central corneal thickness(CCT),age,gender,or tp IOP.RESULTS:Totolly 200 myopic eyes of 100 patients were included in the study.The mean difference of IOP measured by two methods before TPRK,1wk,and 1mo after TPRK were 0.790,-0.790,and-0.920 mm Hg,respectively(P<0.001).Diaton could measure IOP effectively 89.5%eyes before TPRK and 82%and 84%at 1wk and 1mo after TPTK,respectively.At week 1,IOP differences were significantly correlated to baseline CCT(P=0.02)and tp IOP at week 1(P<0.001).One month after TPRK,only tp IOP was significantly correlated to the difference in IOP(P<0.001).CONCLUSION:Diaton is a good screening tool for IOP before TPRK.It helps in monitoring IOP after surgery.Although more practical,it is less efficient than GAT.In eyes with high myopia and low tp IOP before surgery,IOP post-TPRK by Diaton and GAT could differ.

Transepithelial transport of nanoparticles in oral drug delivery:From the perspective of surface and holistic property modulation

Despite the promising prospects of nanoparticles in oral drug delivery,the process of oral administration involves a complex transportation pathway that includes cellular uptake,intracellular trafficking,and exocytosis by intestinal epithelial cells,which are necessary steps for nanoparticles to enter the bloodstream and exert therapeutic effects.Current researchers have identified several crucial factors that regulate the interaction between nanoparticles and intestinal epithelial cells,including surface properties such as ligand modification,surface charge,hydrophilicity/hydrophobicity,intestinal protein corona formation,as well as holistic properties like particle size,shape,and rigidity.Understanding these properties is essential for enhancing transepithelial transport efficiency and designing effective oral drug delivery systems.Therefore,this review provides a comprehensive overview of the surface and holistic properties that influence the transepithelial transport of nanoparticles,elucidating the underlying principles governing their impact on transepithelial transport.The review also outlines the chosen of parameters to be considered for the subsequent design of oral drug delivery systems.

SmartSurf^(ACE)transepithelial photorefractive keratectomy with mitomycin C enhancement after small incision lenticule extraction

Background:To evaluate predictability,stability,efficacy,and safety of transepithelial photorefractive keratectomy(TPRK)using smart pulse technology(SPT)(SmartSurface procedure)of Schwind Amaris with mitomycin C for correction of post small incision lenticule extraction(SMILE)myopic residual refractive errors.Method:This study is a prospective,non-comparative case series conducted at a private eye centre in Ismailia,Egypt,on eyes with post-SMILE myopic residual refractive errors because of undercorrection or suction loss(suction loss occurred after the posterior lenticular cut and the creation of side-cuts;redocking was attempted,and the treatment was completed in the same session with the same parameters)with myopia or myopic astigmatism.The patients were followed up post-SMILE for six months before the SmartSurface procedure,and then they were followed up for one year after that.TPRK were performed using Amaris excimer laser at 500 kHz.The main outcomes included refractive predictability,stability,efficacy,safety and any reported complications.Results:This study included 68 eyes of 40 patients out of 1920 total eyes(3.5%)with post-SMILE technique myopic residual refractive errors.The average duration between the SMILE surgery and TPRK was 6.7±0.4 months(range 6 to 8 months).The mean refractive spherical equivalent(SE)was within±0.50 D of plano correction in 100%of the eyes at 12 months post-TPRK.Astigmatism of<0.50 D was achieved in 100%of the eyes.The mean of the residual SE error showed statistically significant improvement from preoperative−1.42±0.52 D to 0.23±0.10 D(P<0.0001).Uncorrected distance visual acuity(UDVA)(measured by Snellen’s chart and averaged in logMAR units)was improved significantly to 0.1±0.07(P<0.0001).UDVA was 0.2 logMAR or better in 100%of the eyes,0.1 logMAR or better in 91.2%of the eyes,and 0.0 logMAR in 20.6%of the eyes.Corrected distance visual acuity(CDVA)remained unchanged in 79.4%of eyes.14.7%of eyes gained one line of CDVA(Snellen).5.9%of eyes gained two lines of CDVA(Snellen).Conclusion:Transepithelial photorefractive keratectomy using smart pulse technology with mitomycin C enhancement after SMILE is a safe,predictable,stable,and effective technique.

Semaphorin 7A impairs barrier function in cultured human corneal epithelial cells in a manner dependent on nuclear factor-kappa B

●AIM:To evaluate the role of semaphorin 7A(Sema7A)and its associated regulatory mechanisms in modulating the barrier function of cultured human corneal epithelial cells(HCEs).●METHODS:Barrier models of HCEs were treated with recombinant human Sema7A at concentrations of 0,125,250,or 500 ng/mL for 24,48,or 72h in vitro.Transepithelial electrical resistance(TEER)as well as Dextran-fluorescein isothiocyanate(FITC)permeability assays were conducted to assess barrier function.To quantify tight junctions(TJs)such as occludin and zonula occludens-1(ZO-1)at the mRNA level,reverse transcriptionpolymerase chain reaction(RT-PCR)analysis was performed.Immunoblotting was used to examine the activity of the nuclear factor-kappa B(NF-κB)signaling pathway and the production of TJs proteins.Immunofluorescence analyses were employed to localize the TJs.Enzyme-linked immunosorbent assay(ELISA)and RT-PCR were utilized to observe changes in interleukin(IL)-1βlevels.To investigate the role of NF-κB signaling activation and IL^(-1)βin Sema7A’s anti-barrier mechanism,we employed 0.1μmol/L IκB kinase 2(IKK2)inhibitor IV or 500 ng/mL IL^(-1)receptor(IL-1R)antagonist.●RESULTS:Treatment with Sema7A resulted in decreased TEER and increased permeability of Dextran-FITC in HCEs through down-regulating mRNA and protein levels of TJs in a time-and dose-dependent manner,as well as altering the localization of TJs.Furthermore,Sema7A stimulated the activation of inhibitor of kappa B alpha(IκBα)and expression of IL-1β.The anti-barrier function of Sema7A was significantly suppressed by treatment with IKK2 inhibitor IV or IL-1R antagonists.●CONCLUSION:Sema7A disrupts barrier function through its influence on NF-κB-mediated expression of TJ proteins,as well as the expression of IL-1β.These findings suggest that Sema7A could be a potential therapeutic target for the diseases in corneal epithelium.

Omeprazole decreases magnesium transport across Caco-2 monolayers

AIM:To elucidate the effect and underlying mechanisms of omeprazole action on Mg 2+ transport across the intestinal epithelium.METHODS:Caco-2 monolayers were cultured in various dose omeprazole-containing media for 14 or 21 d before being inserted into a modified Ussing chamber apparatus to investigate the bi-directional Mg 2+ transport and electrical parameters.Paracellular permeability of the monolayer was also observed by the dilution potential technique and a cation permeability study.An Arrhenius plot was performed to elucidate the activation energy of passive Mg 2+ transport across the Caco-2 monolayers.RESULTS:Both apical to basolateral and basolateral to apical passive Mg 2+ fluxes of omeprazole-treated epithelium were decreased in a dose-and time-dependent manner.Omeprazole also decreased the paracellular cation selectivity and changed the paracellular selective permeability profile of Caco-2 epithelium to Li +,Na +,K +,Rb +,and Cs + from seriesⅦto seriesⅥof the Eisenman sequence.The Arrhenius plot revealed the higher activation energy for passive Mg 2+ transport in omeprazoletreated epithelium than that of control epithelium,indicating that omeprazole affected the paracellular channel of Caco-2 epithelium in such a way that Mg 2+ movement was impeded.CONCLUSION:Omeprazole decreased paracellular cation permeability and increased the activation energy for passive Mg 2+ transport of Caco-2 monolayers that led to the suppression of passive Mg 2+ absorption.

Omeprazole induces gastric transmucosal permeability to the peptide bradykinin

AIM:To investigate omeprazole-induced transepithelial gastric leak and its effects on the permeability of the peptides bradykinin and oxytocin.METHODS:Rat gastric corpus tissue was isolated and mounted in an Ussing chamber apparatus to evaluate the permeability of 3H-bradykinin,3H-oxytocin,and 14CEDTA in the presence or absence of omeprazole.Thinlayer chromatography was performed to identify any metabolic breakdown products of the peptides resulting from permeation through the gastric tissue,and thereby calculate the true flux of the peptide.RESULTS:The flux rate ofintact 3H-bradykinin increased substantially after omeprazole addition (109.5%) compared to the DMSO vehicle control (14%).No corresponding change in flux ofintact 3H-oxytocin was observed under the same conditions (11.9% and 6.4% in the DMSO-and omeprazole-treated conditions,respectively).After exposure to omeprazole,the flux rate of 14C-EDTA also increased dramatically (122.3%) compared to the DMSO condition (36.3%).CONCLUSION:The omeprazole-induced gastric leak allows for transmucosal permeability to charged molecules as well as non-electrolytes.This induced leak will allow certain peptides to permeate.

Clinical and microstructural changes with different iontophoresis-assisted corneal cross-linking methods for keratoconus

AIM: To compare the clinical and microstructural changes induced by different transepithelial iontophoresis-assisted corneal cross-linking(I-CXL) methods for keratoconus. METHODS: A total of 42 eyes of 42 patients with progressive keratoconus were divided into two groups. Group A received I-CXL for 5 min, while group B received I-CXL for 10 min. Visual acuity, optical coherence tomography(OCT), specular microscopy and confocal microscopy were evaluated preoperatively and at 1, 3, 6, and 12 mo postoperatively. RESULTS: Twelve months after the operation, uncorrected visual acuity(UCVA) and corrected distance visual acuity(CDVA) were improved in both groups, with a better outcome in the I-CXL 10 min group(P=0.025, 0.021, respectively). Kmax values decreased by 0.94±3.00 D in the I-CXL 10 min group(P=0.033) but increased by 1.87±3.29 D in the I-CXL 5 min group(P=0.012). OCT scans showed that the demarcation line was most visible and substantially deeper in the I-CXL 10 min group. Confocal microscopy showed greater anterior stromal keratocyte decreases in the I-CXL 10 min group than in the I-CXL 5 min group at 3 and 6 mo postoperatively(P<0.001); however, anterior stromal keratocytes and subbasal nerve density were not significantly different between the two groups at 12 mo postoperatively. CONCLUSION: I-CXL for 10 min more effectively halts the progression of keratoconus than I-CXL for 5 min after 12 mo of follow-up. However, long-term studies are needed to evaluate the efficacy and safety of I-CXL.

Increased paracellular permeability of tumor-adjacent areas in 1,2-dimethylhydrazine-induced colon carcinogenesis in rats

Objective: The morphology and functions of the proximal and distal large intestine are not the same. The incidence of colorectal cancer in these regions is also different, as tumors more often appear in the descending colon than in the ascending colon.Inflammatory bowel disease and colorectal cancer can increase transepithelial permeability, which is a sign of reduced intestinal barrier function. However, there is not enough evidence to establish a connection between the difference in colorectal cancer incidence in the proximal and distal colon and intestinal permeability or the effects of carcinogenesis on the barrier properties in various areas of the colon. The aim of the study was to assess the permeability of different segments of the large intestine according to a developed mapping methodology in healthy rats and rats with 1,2-dimethylhydrazine(DMH)-induced colon adenocarcinoma.Methods: The short circuit current, the transepithelial electrical resistance and the paracellular permeability to fluorescein of large intestine wall of male Wistar rats were examined in the Ussing chambers. The optical density of the solution from the serosa side to assess the concentration of the diffused fluorescein from mucosa to serosa was analyzed by spectrophotometry. The morphometric and histological studies were performed by optical microscopy.Results: Rats with DMH-induced colon adenocarcinomas showed elevated transepithelial electrical resistance in the areas of neoplasm development. In contrast, there was no change in the electrophysiological properties of tumor adjacent areas, however,the paracellular permeability of these areas to fluorescein was increased compared to the control rats and was characterized by sharply reduced barrier function.Conclusions: The barrier properties of the colon vary depending on tumor location. The tumors were less permeable than the intact intestinal wall and probably have a negative influence on tumor-adjacent tissues by disrupting their barrier function.

Trichomonas vaginalis perturbs the junctional complex in epithelial cells

Trichomonas vaginalis,a protist parasite of the urogenital tract in humans,is the causative agent of trichomonosis,which in recent years have been associated with the cervical cancer development.In the present study we analyzed the modifications at the junctional complex level of Caco-2 cells after interaction with two isolates of T.vaginalis and the influence of the iron concentration present in the parasite’s culture medium on the interaction effects.Our results show that T.vaginalis adheres to the epithelial cell causing alterations in the junctional complex,such as:(a)a decrease in transepithelial electrical resistance;(b)alteration in the pattern of junctional complex proteins distribution as observed for E-cadherin,occludin and ZO-1;and(c)enlargement of the spaces between epithelial cells.These effects were dependent on(a)the degree of the parasite virulence isolate,(b)the iron concentration in the culture medium,and(c)the expression of adhesin proteins on the parasite surface.