Nitric Oxide/Nitric Oxide Synthase System in the Pathogenesis of Neurodegenerative Disorders-An Overview.

Nitric oxide, a ubiquitous molecule found throughout the natural world, is a key molecule implicated in many central and benefic molecular pathways and has a well-established role in the function of the central nervous system, as numerous studies have previously shown. Dysregulation of its metabolism, mainly the upregulation of nitric oxide production, has been proposed as a trigger and/or aggravator for many neurological affections. Increasing evidence supports the implication of this molecule in prevalent neurodegenerative diseases, such as Parkinson's disease, Alzheimer's disease, or amyotrophic lateral sclerosis. The mechanisms proposed for its neurotoxicity mainly center around the increased quantities of nitric oxide that are produced in the brain, their cause, and, most importantly, the pathological metabolic cascades created. These cascades lead to the formation of neuronal toxic substances that impair the neurons' function and structure on multiple levels. The purpose of this review is to present the main causes of increased pathological production, as well as the most important pathophysiological mechanisms triggered by nitric oxide, mechanisms that could help explain a part of the complex picture of neurodegenerative diseases and help develop targeted therapies.

Performances of Corneal Topography and Tomography in the Diagnosis of Subclinical and Clinical Keratoconus.

Aim: The purpose of the study was to assess the efficacy of topographical and tomographical indices given by the Pentacam (pachymetric, tomopetric, and aberometric) in clinical and subclinical keratoconus (KCN) diagnosis. Material and Methods: In this observational analytic retrospective study, patients with abnormal findings in topography and tomography maps but with no signs on clinical examination (subclinical KCN group, sKCN), patients with clinical keratoconus (KCN group), and healthy subjects (Control group) were evaluated. Results: The KCN group proved significantly different (p < 0.001) values of the investigated parameters than the Control group. Eleven out of 28 investigated parameters proved significantly different in the sKCN group compared to controls (p < 0.001). Two topographic measurements, namely I-S (cut-off = 1.435, a large value indicates the presence of KCN) and CCT (cut-off = 537, a small value indicates the presence of KCN), showed AUCs equal to 1 [0.999 to 1]. Six other Pentacam measurements, including Back maximum keratometry (Back Kmax) proved to be excellent parameters for case-finding and screening. In distinguishing sKCN from normal eyes, Pentacam index of vertical asymmetry (IVA), inferior-superior difference (I-S) value, thinnest point (TP), Belin Ambrosio Enhanced Ectasia Display (BAD_D) and root mean square total (RMS total) performed best. Conclusions: In distinguishing sKCN from normal eyes, Back Kmax, IVA, I-S, and RMS total values demonstrated higher accuracy and utility. Six indices, namely ISV, IVA, KISA, PRC, RMS-HOA, and Back Kmax demonstrate excellent utility in case-finding and screening for clinical KCN.

Protective Effect of Liposomal Epigallocatechin-Gallate in Experimental Gentamicin-Induced Hepatotoxicity.

Our study aimed to assess the effect of liposomal epigallocatechin-gallate (LEGCG) compared with epigallocatechin-gallate (EGCG) solution on hepatic toxicity induced by gentamicin (G) administration in rats. Five groups were evaluated, a control group (no G administration) and four groups that received G (1 mL, i.p, 80 mg/kg b.w. (body weight/day), for 7 days) to which we associated daily administration 30 min before G of EGCG (G-EGCG, 2.5 mg/0.1 kg b.w.), LEGCG (G-LEGCG, 2.5 mg/0.1 kg b.w.) or silymarin (100 mg/kg b.w./day). The nitro-oxidative stress (NOx), catalase (CAT), TNF-α, transaminases, creatinine, urea, metalloproteinase (MMP) 2 and 9, and liver histopathological changes were evaluated. LEGCG exhibited better efficacy than EGCG, improving the oxidant/antioxidant balance (p = 0.0125 for NOx and 0.0032 for CAT), TNF-α (p < 0.0001), MMP-2 (p < 0.0001), aminotransferases (p = 0.0001 for AST and 0.0136 for ALT), creatinine (p < 0.0001), urea (p = 0.0006) and histopathologic liver changes induced by gentamicin. Our study demonstrated the beneficial effect of EGCG with superior results of the liposomal formulation for hepatoprotection in experimental hepatic toxicity induced by gentamicin.

Long term visual outcomes in cataract surgery with bilateral implantation of the Extended Depth of Focus Intraocular Lens - Mini Well Ready type.

Purpose: To evaluate the refractive results, visual outcomes and patients' satisfaction of a new extended depth-of-focus (EDOF) intraocular lens (IOL). Setting: Oculens Clinic, Cluj-Napoca, Romania. Design: Retrospective, single-center, observational study. Methods: 104 eyes of 52 patients undergoing cataract surgery with implantation of the Mini Well Ready EDOF-IOL (SIFI, Catania, Italy) were included in the study. Visual acuity at distance, intermediate and near was evaluated at 1, 6 and 12 months. Refractive results, contrast sensitivity, defocus curve and photic phenomena were also assessed. Results: The mean age of patients was 66.04±7.82. A significant reduction of the spherical equivalent and improvement of corrected distance visual acuity (CDVA) was observed (p<0.0001) after the surgery. All eyes obtained a CDVA of 0.5 or better at one month. All eyes achieved a corrected intermediate visual acuity (CIVA) of 0.5 or better and a corrected near visual acuity (CNVA) of 0.5 or better. At 12 months the spherical equivalent was within -0.5- +0.5 diopters (D). Conclusions: The EDOF-IOL offers good visual outcomes at distance, intermediate and near vision, providing an adequate contrast sensitivity and low rate of visual disturbances.

One year outcomes after small incision lenticule extraction ReLEX in the correction of myopia and myopic astigmatism.

PURPOSE: To report the visual and refractive outcomes of small incision lenticule extraction ReLEX (SMILE) technique using VisuMax femtosecond laser in myopia and myopic astigmatism patients. MATERIAL AND METHODS: A non-randomized clinical study has been conducted on patients with myopia and myopic astigmatism who underwent ReLEX SMILE technique, using the Zeiss VisuMax Laser system (Carl Zeiss Meditec AG, Jena, Germany) at Oculens Clinic, Cluj-Napoca, Romania. Patients older than 18 years, with ocular astigmatism up to -5 diopters (D), spherical equivalent up to -10.00 D, corrected distance visual acuity (CDVA) of 0.3 or better before the surgery, stable refraction for one year, and with a minimum calculated post operator residual stromal bed of 250µ were included in the study. RESULTS: The study involved a total of 25 myopic eyes (median of sphere diopters equal with -4D) and 67 myopic astigmatic eyes (median of cylinder diopters equal with -1.5 D). The mean refractive spherical equivalent (MRSE) on patients with myopic eyes reduced from -4.25D (median) to -0.5D at one month follow-up, -0.25 D at 6 and 12 months. The mean refractive spherical equivalent (MRSE) on patients with astigmatic myopic eyes reduced from-6.25 D to -0.67 D at one month, -0.62 D at six and twelve months. The value of sphere decreased postoperatively on myopic eyes with a median of -0.25D at one, six and twelve months. The value of cylinder decreased postoperatively on myopic astigmatic eyes with a median of -0.50 D at one month, -0.25 D at six months and -0.50 D at 12 months. At 6 and 12 months, 20 (80.0%) of myopic eyes were maintained within ±0.5 D and 22 (88.0%) with ±1D. On both groups (myopic eyes and myopic astigmatic eyes), statistically significant differences were observed when the keratometric baseline values were compared to each follow-up (P-values < 0.0001), without any significant differences between follow-ups (P-values>0.15). At 1-month follow-up, uncorrected distance visual acuity (UDVA) was better than or equal to 0.5 in 88.0% of myopic eyes and 82.1% of myopic astigmatic eyes. UDVA remained stable in all cases of myopic eyes at six months and the percentage increased at 92.0% in myopic eyes. UDVA slightly increased at 6-months (85.1%) and remained at the same value at 12-months in myopic astigmatism eyes. CONCLUSIONS: SMILE proved an effective and safe refractive corneal procedure and provided a predictable and stable correction of myopia and myopic astigmatism. SMILE technique demonstrated very good outcomes in terms of keratometric, cylinder, spherical measurements.

Comparative Results Between "Epi-Off" Accelerated and "Epi-Off" Standard Corneal Collagen Crosslinking-UVA in Progressive Keratoconus - 7 Years of Follow-Up.

PURPOSE: The purpose of the present study was to assess the long-term efficiency and safety of the "epi-off" accelerated CXL (9 mW/cm2 for 10 minutes) in comparison to the standard "epi-off" CXL (3 mW/cm2 for 30 minutes) in terms of topographical and keratometric parameters, refractive data and visual outcomes at 7 years of follow-up, in progressive keratoconus. MATERIAL AND METHOD: A retrospective and comparative study was performed. A total of 183 eyes from 183 patients with documented progressive keratoconus were included in the study. The patients were divided in two groups: 93 eyes from 93 patients underwent "epi-off" standard cross-linking technique (3 mW/cm2 for 30 minutes) (S-CXL group) and 90 eyes from 90 patients underwent accelerated "epi-off" corneal CXL technique (9 mW/cm2 for 10 minutes) (A-CXL group). RESULTS: Improvements in uncorrected distance visual acuity (UDVA) were statistically significant compared to baseline values in both groups at each time-point visit (p=0.0421 at 1 year, p=0.0411 at 7 years for A-CXL and p=0.0375 at 1 year, p=0.0389 at 7 years for S-CXL). At 7 years there was a statistically significant increase in CDVA (p=0.039 in the A-CXL group and p=0.0343 in the S-CXL group at 7 years). Statistically significant reduction was noticed in Ksteep (p=0.0411 in A-CXL group and p=0.0224 in S-CXL group), Kflat (p=0.0198 in A-CXL group and p=0.008 in S-CXL group), K mean (p=0.0106 in A-CXL group and p=0.0193 in S-CXL group) and Kmax (p=0.0413 in A-CXL group and p=0.054 in S-CXL group) at 7 years, compared to baseline values, in both groups, but without any statistically difference between the two procedures, at all time-point visits (p>0.05). CONCLUSION: The long-term outcomes of "epi-off" accelerated corneal collagen crosslinking-UVA (9 mW/cm2 for 10 minutes) are similar to standard "epi-off" corneal collagen crosslinking procedure in the treatment of progressive keratoconus.

Protective Effects of Liposomal Curcumin on Oxidative Stress/Antioxidant Imbalance, Metalloproteinases 2 and -9, Histological Changes and Renal Function in Experimental Nephrotoxicity Induced by Gentamicin.

BACKGROUND: Our study aimed to assess the efficiency of Curcumin nanoformulation (LCC) on experimental nephrotoxicity induced by Gentamicin in rats. METHODS: Six groups of seven rats were used: C-(control group) received saline solution i.p. (i.p. = intraperitoneal), G-gentamicin (G, 80 mg/kg body weight (b.w.)), GCC1 and GCC2-with G and CC solution (single dose of 10 mg/kg b.w.-CC1, or 20 mg/kg b.w.-CC2), GLCC1 (10 mg/kg b.w.) and GLCC2 (20 mg/kg b.w.) with G and LCC administration. Oxidative stress parameters (NOx = nitric oxide, MDA = malondialdehyde, TOS = total oxidative stress), antioxidant parameters (CAT = catalase, TAC = total antioxidant capacity), matrix metalloproteinases (MMP-2 and MMP-9), and renal function parameters (creatinine, blood urea nitrogen, and urea) were measured. Kidneys histopathologic examination was made for each group. RESULTS: Pretreatment with CC and LCC in both doses had significantly alleviating effects on assessed parameters (NOx, MDA, TOS, CAT, TAC, MMP-2, and -9) as compared with the untreated group (p < 0.006). Histopathological aspect and renal function were significantly improved in CC and LCC groups. Liposomal formulation (LCC) showed higher efficiency on all examined parameters compared to CC (p < 0.006). CONCLUSIONS: Our results demonstrated improving renal function and kidney cytoarchitecture, oxidative stress/antioxidant/balance, and MMPs plasma concentrations with better dose-related efficacity of LCC than CC.

Refractive Lens Exchange in Hyperopic Presbyopes with the Acrysof IQ Panoptix Intraocular Lens: One-Year Results and Analysis of the Literature.

PURPOSE: To assess the functional and refractive outcomes in hyperopia and presbyopia correction by clear lens exchange with the intraocular trifocal artificial lens (IOL) Acrysof IQ Panoptix implant at 1 year. MATERIALS AND METHODS: A number of 128 eyes (64 patients) underwent clear lens exchange with placement of the trifocal IOL Acrysof IQ Panoptix implant for hyperopia and presbyopia. Prior to the surgery the patients had a complete ocular examination. In all cases the artificial lens was implanted in the bag without any intraoperative complications. Visual acuity (VA) at distance, intermediate and near and ocular refraction were evaluated at 4 weeks, 6 and 12 months postoperatively. RESULTS: The mean age was 53.49 ±7.377 years old (range 40-73 years). As high as 51.57% of the patients were males and 48.43% were females. The mean achieved refraction was 0.26 ± 0.73D. Almost 60.93% of patients were within ±0.25D of the target refraction, with 82.03% eyes within ±0.50D of the planned correction. At 1 year after surgery, 96.45% of eyes had a stable refraction (p >0.05). At 1 year, a total of 92.25%, 89.92% and 91.47% achieved a monocular uncorrected distance, intermediate and near visual acuity of 0.2 logarithm of the minimum angle of resolution or better, respectively. At the same time point, a total of 95.35%, 91.47% and 93.80% achieved a binocular uncorrected distance, intermediate and near visual acuity of 0.2 logarithm of the minimum angle of resolution or better, respectively. There was no statistically significant difference (p>0.05) between the postoperative uncorrected and best corrected VA (distance, intermediate, near) at 6 months and postoperative uncorrected and best corrected VA (distance, intermediate, near) at 12 months. None of our patients had any intraoperative complications. Two cases (1.56%) developed posterior capsule opacification. Twelve patients (18.75%) complained about photic phenomena such as glare and haloes, but this symptom disappeared after 6 months postoperatively. As high as93.56% of patients had a high satisfaction with the outcomes of the surgery. Spectacle independence was obtained in 97.65% eyes. CONCLUSION: The Acrysof Panoptix trifocal artificial lens offers a good vision at distance, intermediate and near, with a good quality of vision and refraction.

The morphological characteristics of the physically abused child. Report of a case and literature review.

Child abuse remains a current problem, despite progress in the field of prevention and social assistance. The injuries produced by physical abuse have to be evaluated using scientific methods, in order to be considered as evidences later in Court, but also to ensure the physical and social security of the child. Among the morphological characteristics of the child (on which depends how the lesions are formed, differently in children from adults), there is the strong adherence of the dura mater to the skull bones, this fact preventing the formation of extradural hematomas. Another special aspect is the poor development of skeletal muscle before puberty, which confers poor protection of the internal organs against the traumatic physical agents. This paper presents the particular morphological and histological aspects that can be evidenced by forensic autopsy in children. The study was conducted on a female child, physically assaulted, arrived in the emergency department of the hospital. The death occurred shortly after hospitalization. The investigations revealed multiple external (on the whole body) and internal injuries. According to the statements of those who called the ambulance, the injuries occurred because of falling on the stairs and were considered by the family as being superficial, without requiring medical care. The forensic autopsy, through the external, internal and histopathological examination, highlighted the specific injuries that led to the death, thereby contributing to the elucidation of the tanatogenerative mechanism, of the way the lesions were produced and to the applying the law.

Comparative Results of "Epi-Off" Conventional versus "Epi-Off" Accelerated Cross-Linking Procedure at 5-year Follow-Up.

PURPOSE: The aim of our study was to compare the long-term efficacy and safety of "epi-off" conventional and "epi-off" accelerated corneal cross-linking (CXL) in patients with progressive keratoconus. METHODS: "Epithelial-off" ("Epi-off") CXL using the conventional technique (3 mW/cm2, 30 minutes) was performed in 93 eyes of 93 patients (S-CXL group) and "epi-off" accelerated method (9 mW/cm2, 10 minutes) in 76 eyes of 76 patients with progressive KCN (A-CXL group). Cases with different stages of keratoconus and topographic evidence of progression were included. Main outcomes comprised refraction, keratometry measurements, uncorrected (UCVA) and best-corrected visual acuity (BCVA), and topographical indices. Micromorphological analysis was assessed by anterior segment ocular coherence tomography (AS-OCT). The follow-up period was 5 years. RESULTS: In both groups, Kflat presented similar results: decrease at 1 year (p=0.465), at 2 years (p=0.672), at 3 years (p=0.198), at 4 years (p=0.32), and at 5 years (p=0.864). In both groups, Ksteep presented a similar decrease at 1 year (p=0.709), at 2 years (p=0.455), at 3 years (p=0.43), at 4 years (p=0.57), and at 5 years (p=0.494), with no statistically significant difference. Decrease in Kavg was similar in both groups at all analyzed time points (p=0.18 at 1 year, p=0.093 at 2 years, p=0.57 at 3 years, p=0.154 at 4 years, and p=0.247 at 5 years). Kmax had a similar decrease in both groups at 1 year (p=0.06), at 2 years (p=0.09), at 3 years (p=0.126), at 4 years (p=0.113), and at 5 years (p=0.114). There was no statistically significant difference between the cylinder decrease in both groups (p=0.349 at 1 year, p=0.6782 at 2 years, p=0.299 at 3 years, p=0.0943 at 4 years, and p=0.144 at 5 years). The BCVA values were statistically significantly higher than the preoperative values in both groups at all time points (p < 0.05). Topographical indices such as thinnest corneal point (TP), corneal volume (CV), index vertical asymmetry (IVA), index of vertical asymmetry (ISV), index of height asymmetry (IHA), index of height decentration (IHD), Belin/Ambrosio Enhanced Ectasia Display (BAD_D), and Ambrosio retinal thickness (ART Max) were significantly statistically decreased compared with baseline at all time points, in both groups. CONCLUSION: "Epi-off" accelerated and conventional CXL have the same efficacy in terms of improvement in visual and topographic outcomes.

The Effect of Nano-Epigallocatechin-Gallate on Oxidative Stress and Matrix Metalloproteinases in Experimental Diabetes Mellitus.

BACKGROUND: The antioxidant properties of epigallocatechin-gallate (EGCG), a green tea compound, have been already studied in various diseases. Improving the bioavailability of EGCG by nanoformulation may contribute to a more effective treatment of diabetes mellitus (DM) metabolic consequences and vascular complications. The aim of this study was to test the comparative effect of liposomal EGCG with EGCG solution in experimental DM induced by streptozotocin (STZ) in rats. METHOD: 28 Wistar-Bratislava rats were randomly divided into four groups (7 animals/group): group 1-control group, with intraperitoneal (i.p.) administration of 1 mL saline solution (C); group 2-STZ administration by i.p. route (60 mg/100 g body weight, bw) (STZ); group 3-STZ administration as before + i.p. administration of EGCG solution (EGCG), 2.5 mg/100 g b.w. as pretreatment; group 4-STZ administration as before + i.p. administration of liposomal EGCG, 2.5 mg/100 g b.w. (L-EGCG). The comparative effects of EGCG and L-EGCG were studied on: (i) oxidative stress parameters such as malondialdehyde (MDA), indirect nitric oxide (NOx) synthesis, and total oxidative status (TOS); (ii) antioxidant status assessed by total antioxidant capacity of plasma (TAC), thiols, and catalase; (iii) matrix-metalloproteinase-2 (MMP-2) and -9 (MMP-9). RESULTS: L-EGCG has a better efficiency regarding the improvement of oxidative stress parameters (highly statistically significant with p-values < 0.001 for MDA, NOx, and TOS) and for antioxidant capacity of plasma (highly significant p < 0.001 for thiols and significant for catalase and TAC with p < 0.05). MMP-2 and -9 were also significantly reduced in the L-EGCG-treated group compared with the EGCG group (p < 0.001). CONCLUSIONS: the liposomal nanoformulation of EGCG may serve as an adjuvant therapy in DM due to its unique modulatory effect on oxidative stress/antioxidant biomarkers and MMP-2 and -9.

Comparative Effect Of Curcumin Versus Liposomal Curcumin On Systemic Pro-Inflammatory Cytokines Profile, MCP-1 And RANTES In Experimental Diabetes Mellitus.

PURPOSE: Anti-inflammatory proprieties of curcumin were proved to be useful in various diseases, including diabetes mellitus. The aim of this study was to assess the anti-inflammatory comparative effect of curcumin solution with liposomal curcumin formula, regarding the improvement of serum levels of TNF-α (tumor necrosis factor-alpha), IL-6 (interleukin), IL-1α, IL-1ß, MCP-1 (monocyte chemoattractant protein-1) and RANTES in experimental diabetes, induced by streptozotocin (STZ), in rats. MATERIALS AND METHODS: Six groups of 7 rats were investigated regarding the effect of i.p. (intraperitoneal) administration of two concentrations of curcumin solution (CC1 and CC2) and two concentrations of liposomal curcumin (LCC1 and LCC2): group 1 - control group with i.p. administration of 1 mL saline solution, group 2 - i.p. STZ administration (60mg/kg bw, bw=body weight), group 3 - STZ+CC1 administration, group 4 - STZ+CC2 administration, group 5 - STZ+ LCC1 administration and group 6 - STZ+ LCC2 administration. The concentrations of curcumin formulas were 1 mg/0.1 kg bw for CC1 and LCC1 and 2 mg/0.1 kg bw for CC2 and LCC2, respectively. Serum levels of C-peptide (as an indicator of pancreatic function) and TNF-α, IL-6, IL-1α, IL-1ß, MCP-1, and RANTES (as biomarkers for systemic inflammation) were assessed for each group. RESULTS: The plasma level of C-peptide showed significant improvements when LCC was administrated, with better results for LCC2 when compared to LCC1 (P<0.003). LCC2 pretreatment proved to be more efficient in reducing the level of TNF-α (P<0.003) and RANTES (P<0.003) than CC2 pretreatment. Upon comparing LCC2 with LCC1 formulas, the differences were significant for TNF-α (P=0.004), IL-1ß (P=0.022), and RANTES (P=0.003) levels. CONCLUSION: Liposomal curcumin in a dose of 2 mg/0.1 kg bw proved to have an optimum therapeutic effect as a pretreatment in DM induced by STZ. This result can constitute a base for clinical studies for curcumin efficiency as adjuvant therapy in type 1 DM.

Comparative Results Between "Epi-Off" Conventional and Accelerated Corneal Collagen Crosslinking for Progressive Keratoconus in Pediatric Patients.

PURPOSE: The aim of our study was to evaluate the efficacy and safety of epi-off conventional and accelerated corneal collagen cross-linking in the treatment of progressive keratoconus in pediatric patients up to 4 years after treatment. PATIENTS AND METHODS: Conventional (standard) CXL epi-off technique was performed in 37 eyes (S-CXL group) and accelerated CXL in 27 eyes (A-CXL group). Refraction, keratometry, cylindrical equivalent, spherical equivalent, slit lamp examination, pachymetry, corneal tomography, anterior segment ocular coherence tomography and visual acuity were performed up to 4 years. RESULTS: In the S-CXL group: the flat K values decreased from 47.41±3.39 D to 45.36±3.62 D at 4 years (p=0.004); steep K decreased from 51.98±4.11 to 50.21±4.81 D at 4 years (p=0.0078); mean K decreased with 1.99 D at 4 years (p=0.009). In the A-CXL group: the flat K values decreased from 46.97±4.17 D to 44.97±4.24 D at 4 years (p=0.048); steep K decreased from 50.55±4.10 D to 48.75±4.17 D at 4 years (p=0.0287); mean K decreased from 48.79±3.86 D to 46.86±4.11 D at 4 years (p=0.0356). The preoperative mean UCVA in the S-CXL group was 0.8 ±0.23 logMar and improved during the follow-up reaching 0.65 ±0.24 logMar at 4 years (p=0.072). The baseline mean UCVA in A-CXL group was 0.77±0.25 logMar and increased during the follow-up to 0.63 ±0.25 logMar at 4 years (p=0.0039). A similar improvement of BCVA was observed during the follow-up. CONCLUSION: Epi-off conventional and accelerated CXL are efficient procedures for progressive keratoconus in pediatric patients. Accelerated and conventional CXL were comparable at all time points and both represent viable options for the therapy of KC in these patients.