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Tommaso Verdina,1 Purva Date,2 Caterina Benatti,1 Andrea Lazzerini,1 Elisa Fornasari,1 Michele De Maria,3 Elena Pellacani,1 Matteo Forlini,4 Gian Maria Cavallini11Institute of Ophthalmology, University of Modena and Reggio Emilia, Modena, Italy; 2Aditya Jyot Eye Hospital, Mumbai, India; 3Clinical and Experimental Medicine PhD Program, University of Modena and Reggio Emilia, Modena, Italy; 4Domus Nova Hospital, Ravenna, ItalyBackground: To evaluate macular pigment optical density (MPOD) after bimanual femtosecond laser-assisted cataract surgery (FLACS) compared to standard bimanual phacoemulsification (B-MICS).Methods: A prospective, case matched, comparative cohort study conducted at the Institute of Ophthalmology, University of Modena and Reggio Emilia (Italy); 30 eyes underwent bimanual FLACS with low-energy Ziemer LDV Z8 (FLACS) and 30 underwent B-MICS standard technique (B-MICS). All interventions were conducted by the same expert surgeon. MPOD using the Macular Pigment Screener II (MPS II) was evaluated at baseline, 7 and 30 days after surgery. As secondary outcomes, we considered best corrected visual acuity (BCVA) and central macular thickness (CMT) obtained using optical coherence tomography.Results: In all cases, a BunnyLens AF IOL was safely implanted in the capsular bag through a 1.4 mm incision. We found a significant reduction in MPOD in both groups at 7 and 30 days; 0.16±0.14 and 0.10±0.12 (FLACS) and 0.18±0.13 and 0.15±0.14 (B-MICS), respectively (P

Aim: To report a paediatric case of retinopathy-positive cerebral malaria, emphasizing the clinical significance of long-term neurological and ophthalmological follow-up (5,5 years)., Case Report: After a recent journey in Ghana, a 17-month-old African female child was admitted at the Paediatric Emergency Room with fever and vomiting. Blood smear confirmed a Plasmodium Falciparum parasitaemia. Iv quinine was promptly administered, but after a few hours, the child developed generalized seizures, requiring benzodiazepine therapy and assisted ventilation for severe desaturation. Brain imaging (CT and MRI), lumbar puncture and several electroencephalograms showed data compatible with cerebral involvement of malaria. Schepens ophthalmoscopy and Ret-Cam pictures acquisition revealed macular haemorrhages in the left eye with central whitening and bilateral capillary abnormalities, typical signs of malarial retinopathy. Antimalarial therapy and iv Levetiracetam allowed neurological improvement. Eleven days after the admission, the child was discharged, showing no neurological symptoms and with an improved EEG signal, a normalized fundus oculi and brain imaging. Neurological and ophthalmological long-term follow-up were conducted: EEG controls didn't reveal abnormalities and the complete ophthalmological assessment showed a regular visual acuity and fundus oculi, as well as a normal SD-OCT and electrophysiologic testing., Conclusion: Cerebral malaria is a severe complication, characterized by a high fatality rate and challenging diagnosis. A helpful instrument for diagnostic and prognostic evaluation is the ophthalmological detection of malarial retinopathy and its monitoring over time. In our patient the long term visual follow-up didn't reveal any adverse outcome., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

(1) Background: Obesity, a complex metabolic disease resulting from an imbalance between food consumption and energy expenditure, leads to an increase in adipocytes and chronic inflammatory conditions. The aim of this paper was to synthesize a small series of carvacrol derivatives ( CD1-3 ) that are able to reduce both adipogenesis and the inflammatory status often associated with the progression of the obesity disease. (2) Methods: The synthesis of CD1-3 was performed using classical procedures in a solution phase. Biological studies were performed on three cell lines: 3T3-L1, WJ-MSCs, and THP-1. The anti-adipogenic properties of CD1-3 were evaluated using western blotting and densitometric analysis by assessing the expression of obesity-related proteins, such as ChREBP. The anti-inflammatory effect was estimated by measuring the reduction in TNF-α expression in CD1-3 -treated THP-1 cells. (3) Results: CD1-3 -obtained through a direct linkage between the carboxylic moiety of anti-inflammatory drugs (Ibuprofen, Flurbiprofen, and Naproxen) and the hydroxyl group of carvacrol-have an inhibitory effect on the accumulation of lipids in both 3T3-L1 and WJ-MSCs cell cultures and an anti-inflammatory effect by reducing TNF- α levels in THP-1 cells. (4) Conclusions: Considering the physicochemical properties, stability, and biological data, the CD3 derivative-obtained by a direct linkage between carvacrol and naproxen-resulted in the best candidate, displaying anti-obesity and anti-inflammatory effects in vitro.

So far, there is no effective disease-modifying therapies for Alzheimer's Disease (AD) in clinical practice. In this context, glycine-L-proline-L-glutamate (GPE) and its analogs may open the way for developing a novel molecule for treating neurodegenerative disorders, including AD. In turn, this study was aimed to investigate the neuroprotective potentials exerted by three novel GPE peptidomimetics (GPE1, GPE2, and GPE3) using an in vitro AD model. Anti-Alzheimer potentials were determined using a wide array of techniques, such as measurements of mitochondrial viability (MTT) and lactate dehydrogenase (LDH) release assays, determination of acetylcholinesterase (AChE), α-secretase and β-secretase activities, comparisons of total antioxidant capacity (TAC) and total oxidative status (TOS) levels, flow cytometric and microscopic detection of apoptotic and necrotic neuronal death, and investigating gene expression responses via PCR arrays involving 64 critical genes related to 10 different pathways. Our analysis showed that GPE peptidomimetics modulate oxidative stress, ACh depletion, α-secretase inactivation, apoptotic, and necrotic cell death. In vitro results suggested that treatments with novel GPE analogs might be promising therapeutic agents for treatment and/or or prevention of AD.

Cyclic dipeptides administered by both parenteral and oral routes are suggested as promising candidates for the treatment of neurodegeneration-related pathologies. In this study, we tested Cyclo (His-Pro) isomers (cHP1-4) for their anti-Alzheimer potential using a differentiated human neuroblastoma cell line (SH-SY5Y) as an Alzheimer's disease (AD) experimental model. The SH-SY5Y cell line was differentiated by the application of all-trans retinoic acid (RA) to obtain mature neuron-like cells. Amyloid-beta 1-42 ( Aβ 1-42 ) peptides, the main effector in AD, were administered to the differentiated cell cultures to constitute the in vitro disease model. Next, we performed cell viability analyses 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) release assays) to investigate the neuroprotective concentrations of cyclodipeptides using the in vitro AD model. We evaluated acetylcholinesterase (AChE), α- and β-secretase activities (TACE and BACE1), antioxidant potency, and apoptotic/necrotic properties and performed global gene expression analysis to understand the main mechanism behind the neuroprotective features of cHP1-4. Moreover, we conducted sister chromatid exchange (SCE), micronucleus (MN), and 8-hydroxy-2'-deoxyguanosine (8-OHdG) analyses to evaluate the genotoxic damage potential after applications with cHP1-4 on cultured human lymphocytes. Our results revealed that cHP1-4 isomers provide a different degree of neuroprotection against Aβ 1-42 -induced cell death on the in vitro AD model. The applications with cHP1-4 isomers altered the activity of AChE but not the activity of TACE and BACE1. Our analysis indicated that the cHP1-4 increased the total antioxidant capacity without altering total oxidative status levels in the cellular AD model and that cHP1-4 modulated the alterations of gene expressions by Aβ 1-42 exposure. We also observed that cHP1-4 exhibited noncytotoxic and non-genotoxic features in cultured human whole blood cells. In conclusion, cHP1-4 isomers, especially cHP4, have been explored as novel promising therapeutics against AD.

Purpose: To evaluate the efficacy and safety of bimanual, low-energy femtosecond laser-assisted cataract surgery with 1.4-mm microincisions compared to standard bimanual phacoemulsification (bimanual microincision cataract surgery)., Design: Prospective, non-randomized comparative case series., Methods: Bimanual femtosecond laser-assisted cataract surgery with microincisions was performed on 80 eyes (Group A) with the low-energy Ziemer LDV Z8; a matched case-control series of 80 eyes performed with standard bimanual microincision cataract surgery technique was selected for comparison (Group B). All interventions were performed by the same experienced surgeon. Intraoperative parameters were recorded as well as intra- and postoperative complications. Best corrected visual acuity, surgically induced astigmatism, central corneal thickness and endothelial cell count were evaluated before surgery and at 1 and 3 months post intervention., Results: The mean effective phaco times were 3.79 ± 2.19 s (Group A) and 4.49 ± 1.84 s (Group B) (p = 0.041). No major intra- or postoperative complications occurred. An overall significant mean best corrected visual acuity improvement was noted at 3 months, but was not statistically different between the groups. No significant changes were observed for surgically induced astigmatism or corneal pachymetry. A significant loss of endothelial cell count in both groups was detected at 3 months, with Group A reporting a significantly lower endothelial cell count loss compared to Group B (p = 0.009)., Conclusion: Bimanual, low-energy femtosecond laser-assisted cataract surgery with 1.4-mm microincisions by an expert surgeon was proven to be safe and effective in this study. This technique has advantages compared with standard bimanual microincision cataract surgery in terms of endothelial preservation.

Carvacrol (CAR), a natural monoterpene particularly abundant in plants belonging to the Lamiaceae family, has recently attracted much attention for its many biological properties (antioxidant, anti-inflammatory, neuroprotective, antitumour, antibacterial, and several others). However, CAR has poor chemical-physical properties (low water solubility and high volatility), which hamper its potential pharmacological uses. In this paper, the synthesis and antimicrobial evaluation of 23 carvacrol derivatives (WSCP1-23) against a panel of selected gram-positive and gram-negative bacteria are reported. Using the prodrug approach, CAR hydrophilic (WSCP1-17) and lipophilic prodrugs (WSCP18-23) were prepared. Notably, CAR water solubility was increased by using polar neutral groups (such as natural amino acids) with the aim of improving oral drug delivery. On the other hand, CAR lipophilic prodrugs, obtained by prenylation of CAR hydroxyl group, were designed to promote membrane permeation and oral absorption. Our results revealed that WSCP1-3, showing the highest water solubility (>1700-fold compared to that of CAR), possessed good antibacterial activity against gram-negative bacteria with MIC values comparable to those of CAR and antifungal properties against different species of Candida. WSCP18-19 were the most promising prodrugs, showing good antibacterial profiles against gram-positive bacteria by interfering with the biofilm formation of Staphylococcus aureus and Staphylococcus epidermidis. Moreover, WSCP18-19 resulted more stable in simulated fluids and human plasma than WSCP1-3. Toxicity studies performed on human erythrocytes and HaCaT cells revealed that all WSCPs were not toxic at the tested concentrations., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

This study investigated the anti-inflammatory effects of novel pseudotripeptides (GPE 1-3) as potential candidates to counteract neuroinflammation processes in Alzheimer's disease. GPE 1-3 pseudotripeptides are synthetic derivatives of Gly-l-Pro-l-Glu (GPE), the N-terminal tripeptide of IGF-1, obtained through the introduction of isosteres of the amidic bond (aminomethylene unit) to increase the metabolic stability of the native tripeptide. The results showed that all synthetic derivatives possessed higher half-lives (t 1/2  > 4 h) than GPE (t 1/2  = 30 min) in human plasma and had good water solubility. The biological results demonstrated that GPE 1-3 had protective properties in several experimental models of treated THP-1 cells. Notably, the novel pseudotripeptides influenced inflammatory cytokine expression (IL-1β, IL-18, and TNF-α) in Aβ 25-35 -, PMA-, and LPS-treated THP-1 cells. In PMA-differentiated THP-1 macrophages, both GPE 1 and GPE 3 reduced the expression levels of all selected cyto-chemokines, even though GPE 3 showed the best neuroprotective properties., (Copyright © 2018. Published by Elsevier Ltd.)

Purpose: To describe the intraoperative complications and the learning curve of microincision cataract surgery assisted by femtosecond laser (FLACS) with bimanual technique performed by an experienced surgeon., Methods: It is a prospective, observational, comparative case series. A total of 120 eyes which underwent bimanual FLACS by the same experienced surgeon during his first experience were included in the study; we considered the first 60 cases as Group A and the second 60 cases as Group B. In both groups, only nuclear sclerosis of grade 2 or 3 was included; an intraocular lens was implanted through a 1.4-mm incision. Best-corrected visual acuity (BCVA), surgically induced astigmatism (SIA), central corneal thickness and endothelial cell loss (ECL) were evaluated before and at 1 and 3 months after surgery. Intraoperative parameters, and intra- and post-operative complications were recorded., Results: In Group A, we had femtosecond laser-related minor complications in 11 cases (18.3%) and post-operative complications in 2 cases (3.3%); in Group B, we recorded 2 cases (3.3%) of femtosecond laser-related minor complications with no post-operative complications. Mean effective phaco time (EPT) was 5.32 ± 3.68 s in Group A and 4.34 ± 2.39 s in Group B with a significant difference (p = 0.046). We recorded a significant mean BCVA improvement at 3 months in both groups (p < 0.05) and no significant SIA nor corneal pachymetry changes in the two groups during the follow-up (p > 0.05). Finally, we found significant ECL in both groups with a significant difference between the two groups (p = 0.042)., Conclusions: FLACS with bimanual technique and low-energy LDV Z8 is associated with a necessary initial learning curve. After the first adjustments in the surgical technique, this technology seems to be safe and effective with rapid visual recovery and it helps surgeons to standardize the crucial steps of cataract surgery.

Purpose: We describe the clinicopathological and ultrastructural features of an opaque single-piece hydrophilic acrylic intraocular lens (IOL) explanted from a patient., Method: The main outcome of this report is the documentation of calcium deposits confirmed by surface analysis. The decrease in visual acuity was due to the opacification of the IOL. The opacification involved both the optic plate and the haptics., Results: The analysis at the scansion electron microscope revealed that the opacity was caused by the deposition of calcium and phosphate within the lens optic and haptics., Conclusion: This is the first case about the opacification of an Oculentis L-313. The opacification was characterized by calcium and phosphate deposition probably due to a morphological alteration of the posterior surface of the IOL.

Purpose: Comparative evaluation of morphological features of anterior capsules and apoptosis induction in epithelial cells after femtosecond laser-assisted cataract surgery (FLACS) and standard phacoemulsification surgery., Methods: Group 1: 30 FLACS anterior capsulotomies and Group 2: 30 manual anterior continuous curvilinear capsulorhexes. All patients were operated on by the same experienced surgeon. Morphological features of the anterior capsules and apoptosis induction in epithelial cells were evaluated., Results: All patients revealed a significant mean best-corrected visual acuity (BCVA) improvement 3 months after surgery, and no major intraoperative nor postoperative complications occurred. The capsular epithelium appeared to be preserved in both groups. Scanning electron microscopy analysis revealed irregular saw-tooth shaped edges in capsules from Group 1 whereas capsules from Group 2 showed regular and smooth edges. A statistically significant higher expression of the downstream apoptotic effector cleaved caspase 3 was observed in Group 1., Conclusions: The saw-tooth appearance was likely due to the progressive sequence of laser pulses on the capsule. The low energy/high frequency properties of the laser pulse, combined with an overlapped pulse pattern, resulted in highly continuous morphology of capsule edges. The higher apoptosis induction in FLACS group might be due to photodisruption-dependent plasma generation and formation of cavitation bubbles.

In this study, effects of LA-GPE (R-α-Lipoyl-Gly-l-Pro-l-Glu dimethyl ester) and GPE (Gly-L-Pro-L-Glu) on the cytotoxic action of Aβ 1-42 were tested with differentiated human neuroblastoma SH-SY5Y cells as cellular Alzheimer model via measurements of mitochondrial viability (MTT assay) and lactate dehydrogenase release (LDH assay). Effects of LA-GPE and GPE on acetylcholinesterase (AChE) activity, total antioxidant capacity (TAC) and total oxidative status (TOS) levels, and neural cell apoptosis and necrosis were also determined. In addition, biological safety of these novel formulations was evaluated in human blood cells using different cytotoxicity and genotoxicity assays. Our results indicated that both compounds could block Aβ 1-42 induced cell death. LA-GPE reduced Aβ-induced AChE activity and oxidative stress, suggesting it as a multifunctional compound potentially valuable for the treatment of Alzheimer's disease (AD)., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Aim: To analyze the visual outcomes and the posterior capsule opacification (PCO) with the new Incise ® MJ14 intraocular lens (IOL) implanted through a 1.4 mm clear corneal incision (CCI) in patients who underwent bimanual microincision cataract surgery (B-MICS)., Methods: Eighty eyes which underwent cataract surgery using B-MICS technique performed by the same experienced surgeon were included in the study: 40 eyes were implanted with an Incise ® MJ14 IOL through a 1.4 mm CCI (group A) without enlargement of the main CCI, while 40 eyes were implanted with an Akreos ® MI60 IOL with enlargement of the main CCI to 1.8 mm (group B). Best corrected visual acuity (BCVA), astigmatism and endothelial cell loss were evaluated before and after surgery at 7, 30d and 6mo. Anterior segment-optical coherence tomography (AS-OCT) of CCI was performed at 1, 3, 7, 30d, 6 and 18mo. PCO incidence was evaluated at 18mo using EPCO 2000 Software., Results: Mean BCVA improvement and endothelial cell loss were statistically significant at 18mo in both groups with no difference between the two groups; no statistically significant difference in surgically induced astigmatism (SIA) was noticed in the two groups. At AS-OCT the only significant alterations in the CCI were endothelial gaping and local detachment of Descemet's membrane at 1 and 7d after surgery; no statistically significant alterations were found at 1, 6 and 18mo. PCO score at 18mo was 0.03±0.07 for group A and 0.08±0.18 for group B ( P =0.11) with no sign of central optic plate invasion in both groups., Conclusion: The implant of the new Incise ® MJ14 IOL through a 1.4 mm CCI and B-MICS technique appeared to be a safe and effective procedure with rapid visual recovery. PCO rate resulted very low and the CCI presented few morphological alterations which were only detectable in the first days postoperatively and achieved fast corneal healing during the long-term follow-up.

Glioblastoma is one of the most aggressive malignant primary brain cancer in adults. To date, surgery, radiotherapy and current pharmacological treatments are not sufficient to manage this pathology that has a high mortality rate (median survival 12-15months). Recently, anticancer multi-targeted compounds have attracted much attention with the aim to obtain new drugs able to hit different biological targets that are involved in the onset and progression of the disease. Here, we report the synthesis of novel memantine-derived drugs (MP1-10) and their potential antitumor activities in human U87MG glioblastoma cell line. MP1-10 were synthetized joining memantine, which is a NMDA antagonist, to different histone deacetylase inhibitors to obtain one molecule with improved therapeutic efficacy. Biological results indicated that MP1 and MP2 possessed more potent anti-proliferative effects on U87MG cells than MP3-10 in a dose-dependent manner. MP1 and MP2 induced significant cell death by apoptosis characterized by apoptotic morphological changes in Hoechst staining. Both drugs also exhibited non-genotoxic and only mild cytotoxic effects in human whole blood cells. However, only MP1, showing good chemico-physical properties (solubility, LogP) and enzymatic stabilities in gastric and intestinal fluids, can be considered a suitable candidate for in vivo pharmacokinetic studies., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Medicinal chemistry methodologies are presently used to develop multifunctional molecules which simultaneously reduce oxidative stress, excitotoxicity, metal dyshomeostasis, and neuroinflammation that characterize neuropathological conditions, such as Alzheimer's Disease., Results: Memantine (MEM) derivatives 1-6 were designed and synthesized as novel multifunctional entities with antioxidant and neuroprotective capabilities to manage neurodegenerative diseases, such as Alzheimer's Disease. In vitro neuroprotective studies were performed by using astroglial GL15 cell line to assess antioxidant capability of MEM derivatives 1-6., Conclusion: Our outcomes showed that compounds 1 and 5 (at the concentration of 10 μM), containing as antioxidant portion residues of N-acetyl-Cys-OH and N-acetyl-Cys(Allyl)-OH, respectively, revealed a significant neuroprotective activity against oxidative stress, as assessed by NBT assays., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Background: MRJF4, a novel haloperidol metabolite II prodrug, was obtained through the esterification of the secondary hydroxyl group of haloperidol metabolite II with 4-phenylbutyric acid. The activities of (±)-MRJF4 and its two enantiomers [(+)-MRJF4 and (-)-MRJF4] as tumor specific inducers of pro-apoptotic genes were evaluated on malignant C6 glioma cells. In particular, changes in Nf-κB signaling pathway, activity of nitric oxide synthases (NOS), metalloproteinases (MMPs), and membrane adhesion proteins were investigated., Results: IκBα reduced phosphorylation and iNOS lowered activity could be correlated with the previously demonstrated decreased proliferation and tumor progression of C6 cells upon 24 h of treatment with all the three compounds. Integrin β1 decreased expression, at the same experimental time, seems to support lower C6 cells migrative capability and the consequent reduced invasiveness of these cells upon treatment with (±)-MRJF4 and its enantiomers., Conclusion: These results suggest that this multi-target prodrug and its two enantiomers might be a valuable clinical tool for the treatment of metastatic glioblastoma., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Introduction: The failure of many molecules as CNS bioactive compounds is due to many restrictions: poor water solubility, intestinal absorption, in vivo stability, bioavailability, therapeutic effectiveness, side effects, plasma fluctuations, and difficulty crossing physiological barriers, like the brain blood barrier (BBB), to deliver the drug directly to the site of action., Area Covered: Nanotechnology-based approaches with the employment of liposomes, micelles, dendrimers, and solid lipid nanoparticles (SLN) as drug delivery systems, are used to overcome the above reported limitations. Here, we focus on the delivery of drugs based on SLN formulation to treat neurodegenerative diseases. Notably, SLN have the ability to protect drugs from chemical and enzymatic degradation, direct the active compound towards the target site with a substantial reduction of toxicity for the adjacent tissues, and pass physiological barriers increasing bioavailability without resorting to high dosage forms., Expert Opinion: We believe that SLN could represent a suitable tool to pass the BBB and permit drugs to reach damaged areas of the CNS in patients affected by neurodegenerative pathologies, such as Alzheimer's and Parkinson's diseases.

Nonsteroidal anti-inflammatory drugs (NSAIDs) have been suggested for the potential treatment of neurodegenerative diseases, such as Alzheimer's disease (AD). Prolonged use of NSAIDs, however, produces gastrointestinal (GI) toxicity. To overcome this serious limitation, the aim of this study was to develop novel NSAID-derived drug conjugates (Anti-inflammatory-Lipoyl derivatives, AL4-9) that preserve the beneficial effects of NSAIDS without causing GI problems. As such, we conjugated selected well-known NSAIDs, such as (S)-naproxen and (R)-flurbiprofen, with (R)-α-lipoic acid (LA) through alkylene diamine linkers. The selection of the antioxidant LA was based on the proposed role of oxidative stress in the development and/or progression of AD. Our exploratory studies revealed that AL7 containing the diaminoethylene linker between (R)-flurbiprofen and LA had the most favorable chemical and in vitro enzymatic stability profiles among the synthesized compounds. Upon pretreatment, this compound exhibited excellent antioxidant activity in phorbol 12-miristate 13-acetate (PMA)-stimulated U937 cells (lymphoblast lung from human) and Aβ(25-35)-treated THP-1 cells (leukemic monocytes). Furthermore, AL7 also modulated the expression of COX-2, IL-1β and TNF-α in these cell lines, suggesting anti-inflammatory activity. Taken together, AL7 has emerged as a potential lead worthy of further characterization and testing in suitable in vivo models of AD.

In staphylococci, quorum sensing regulates both biofilm formation and toxin production, moreover it has been demonstrated to be inhibited by RNAIII inhibiting peptide (RIP). Aim our study was to evaluate the in vitro activity and its in vivo efficacy of the combined administration of FS10, a novel RIP derivative, and tigecycline in an animal model of methicillin-resistant (MR) and methicillin-sensitive (MS) Staphylococcus aureus wound infection. Using a 1.x2 cm template, one full thickness wound was established through the panniculus carnosus on the back subcutaneous tissue of each animal. Infection was determined by inoculation of 5x107 CFU/ml of bacteria, that produced an abscess within 24 h, after this, treatment was initiated. The study included, for each strain, a control group without infection, a control infected group that did not receive any treatment and a control infected group with drug-free foam dressing, and three infected groups treated, respectively, with: FS10-soaked foam dressing (containing 20 μg FS10), daily intraperitoneal tigecycline (7 mg/Kg), FS10-soaked foam dressing (containing 20 μg FS10) and daily intraperitoneal injections of tigecycline (7 mg/Kg). The main outcome measures were quantitative culture and histological examination of tissue repair. The highest inhibition of infection was achieved in the group that received FS10-soaked and parenteral tigecycline reducing the bacterial load from 107 CFU/ml to about 103 CFU/g for MSSA and to about 104 CFU/g for MRSA. The group treated with FS10-soaked foam dressing associated with parenteral tigecycline showed, histologically, better overall healing with epithelialization and collagen scores significantly higher than those of the other groups in both strains. In conclusion, the combined use of topical FS10 with i.p. tigecycline induced positive interaction in vivo, resulting in an enhanced therapeutic benefit versus staphylococcal infections in murine wound models.

Herein is described the synthesis of novel glycine-α-methyl-proline-containing tripeptides (GP(Me)X tripeptides namely GP(Me)R, GP(Me)K, and GP(Me)H) with the aim of obtaining derivatives highly stable in human plasma and able to counteract neuroinflammatory processes that are distinctive of neurodegenerative pathologies. The syntheses of GP(Me)R, GP(Me)K, and GP(Me)H were all achieved both by introducing the Pro(Me) residue into the Gly-Pro-Arg (GPR) sequence in place of the native Pro in P2 position and replacing the basic amino acid Arg in P3 position by Lys or His. Results showed that all novel GP(Me)X tripeptides are stable in human plasma (t1/2 > 51 h) and that GP(Me)H - generating stable intramolecular H-bond in a C11-turn by interaction of His imidazole ring and Gly carbonyl group - restored physiological levels of nitric oxide deriving from neuronal NOS (nNOS) activity, thus preventing the inflammatory response by suppression of the NF-kB activity and, consequently, the expression of inflammatory genes such as inducibile NOS (iNOS). Therefore, GP(Me)H could be a lead compound for further development of peptidomimetics able to contrast neuroinflammatory processes., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)