Immunogenicity, Efficacy, and Safety of Biosimilar Insulin Glargine (Gan & Lee Glargine) Compared with Originator Insulin Glargine (Lantus®) in Patients with Type 1 Diabetes after 26 Weeks Treatment.

OBJECTIVES: To compare the immunogenicity, safety, and efficacy of GL Glargine with that of the reference product (Lantus®) in patients with type 1 diabetes mellitus (T1DM). METHODS: This was a Phase 3, multicenter, randomized, open-label, equivalence study. 576 subjects with T1DM were randomized 1:1 to receive either GL Glargine or Lantus® treatment for 26 weeks. The primary endpoint was the percentage of subjects in each treatment group who developed treatment-induced anti-insulin antibody (AIA) after baseline and up to visit Week 26, which was evaluated using a country-adjusted logistic regression model. The study also compared the changes in glycated hemoglobin (HbA1c), and adverse events (AEs) including hypoglycemia. RESULTS: The percentage of subjects positive for treatment-induced AIA by Week 26 was 25.8% in the GL Glargine treatment group and 25.3% in the Lantus® treatment group, with a 90% confidence interval [CI] (-5.4, 6.5) of the difference in proportions that fell completely between the similarity margins (-11.3, 11.3). The least squares (LS) mean difference between treatment groups for changes in HbA1c was -0.08 (90% CI: -0.23, 0.06), and the other immunogenicity and safety profiles were comparable. CONCLUSION: GL Glargine demonstrated similar immunogenicity, efficacy, and safety compared to Lantus® over 26 weeks in patients with T1DM.

Perspectives of Microwaves-Enhanced Heterogeneous Catalytic Gas-Phase Processes in Flow Systems.

The paper discusses the currents status and future perspectives of the utilization of microwaves, as a selective and locally controlled heating method, in heterogeneous catalytic flow reactors. Various factors related to the microwave-catalyst interaction and the design of microwave-assisted catalytic reactor systems are analyzed. The analysis clearly shows the superiority of the traveling-wave systems over the mono-mode and multi-mode cavity-based systems when it comes to the design and application of microwave flow reactors at relevant production scales.

Subtle Microwave-Induced Overheating Effects in an Industrial Demethylation Reaction and Their Direct Use in the Development of an Innovative Microwave Reactor.

A systematic study of the conventional and microwave (MW) kinetics of an industrially relevant demethylation reaction is presented. In using industrially relevant reaction conditions the dominant influence of the solvent on the MW energy dissipation is avoided. Below the boiling point, the effect of MWs on the activation energy Ea and k0 is found nonexistent. Interestingly, under reflux conditions, the microwave-heated (MWH) reaction displays very pronounced zero-order kinetics, displaying a much higher reaction rate than observed for the conventionally thermal-heated (CTH) reaction. This is related to a different gas product (methyl bromide, MeBr) removal mechanism, changing from classic nucleation into gaseous bubbles to a facilitated removal through escaping gases/vapors. Additionally, the use of MWs compensates better for the strong heat losses in this reaction, associated with the boiling of HBr/water and the loss of MeBr, than under CTH. Through modeling, MWH was shown to occur inhomogeneously around gas/liquid interfaces, resulting in localized overheating in the very near vicinity of the bubbles, overall increasing the average heating rate in the bubble vicinity vis-à-vis the bulk of the liquid. Based on these observations and findings, a novel continuous reactor concept is proposed in which the escaping MeBr and the generated HBr/water vapors are the main driving forces for circulation. This reactor concept is generic in that it offers a viable and low cost option for the use of very strong acids and the managed removal/quenching of gaseous byproducts.

Penrose triangles of the fossil-to-bio-based transition.

Transition within the chemical industry from fossil to green feedstocks is a complex process characterized by the generation of commercially viable feedstock-process-product triangles. The research in this area encompasses a great diversity of relevant topics. A number of those topics have been addressed within this volume of Faraday Discussions and are summarized in this paper. They are categorized and discussed along with seven general questions arising from the feedstock-process-product triangles. Opportunities are identified that should make more of these triangles technically and economically feasible. The future role of renewable electricity as the primary energy source for the bio-based industry is emphasized.

Macro- and microelement distribution in organs of Glyceria maxima and biomonitoring applications.

The content of nutrients (N, P, K, Ca and Mg) and of trace metals (Fe, Cu, Mn, Zn, Pb, Cd, Co and Ni) in water, bottom sediments and various organs of Glyceria maxima from 19 study sites selected in the Jeziorka River was determined. In general, the concentrations of nutrients recorded in the plant material decreased in the following order: leaf>root>rhizome>stem, while the concentrations of the trace elements showed the following accumulation scheme: root>rhizome>leaf>stem. The bioaccumulation and transfer factors for nutrients were significantly higher than for trace metals. G. maxima from agricultural fields was characterised by the highest P and K concentrations in leaves, and plants from forested land contained high Zn and Ni amounts. However, the manna grass from small localities showed high accumulation of Ca, Mg and Mn. Positive significant correlations between Fe, Cu, Zn, Cd, Co and Ni concentrations in water or sediments and their concentrations in plant indicate that G. maxima may be employed as a biomonitor of trace element contamination. Moreover, a high degree of similarity was noted between self-organizing feature map (SOFM)-grouped sites of comparable quantities of elements in the water and sediments and sites where G. maxima had a corresponding content of the same elements in its leaves. Therefore, SOFM could be recommended in analysing ecological conditions of the environment from the perspective of nutrients and trace element content in different plant species and their surroundings.

Triple therapy: Phaco-vitrectomy with ILM peeling, retinal endophotocoagulation, and intraoperative use of bevacizumab for diffuse diabetic macular edema.

BACKGROUND: The aim of this study was to evaluate the visual acuity and structural outcomes of combined phacovitrectomy with ILM peeling, retinal endophotocoagulation and use of bevacizumab in patients with diffuse diabetic macular edema (DDME). MATERIAL/METHODS: In this prospective, nonrandomized, interventional study we included 29 eyes of 26 patients with DDME. The best-corrected visual acuity (BCVA) and central retinal thickness and volume (CRT and CRV) were recorded at 4, 8, 12, and 16 months after surgery. RESULTS: The mean preoperative BCVA was 0.74±0.36 logMAR (0.3-1.5) and improved finally to 0.4±0.24 logMAR (-0.1-1.0) p=0.000006. The mean preoperative CRT in the 1mm zone was 516±184 microm (256-950) and decreased postoperatively at the last control to 237±75 microm (117-489) p=0.000003. The mean preoperative CRV in the 1mm zone was 0.39±0.14 microL (0.19-0.74) and decreased postoperatively at the last control to 0.17±0.06 microL (0.09-0.36) p=0.000003. The mean preoperative CRT in the 6 mm zone was 407±105 microm (279-640) and decreased postoperatively at the last control to 282±40 µm (212-380) p=0.000004. The mean preoperative CRV in the 6 mm zone was 11.4±2.9 microL (7.85-17.93) and decreased postoperatively at the last control to 7.92±1.0 microL (5.62-10.97) p=0.000003. The 23 (79.3%) eyes showed improvement in BCVA ≥0.2 logMAR, 5 (17.2%) eyes improvement or stabilization of BCVA and 1(3.5%) eye deterioration. Preoperative BCVA was a positive factor for prognosis of BCVA at 12th month follow-up (b=0.42; p=0.006), while the negative factors were: previous panretinal photocoagulation (b=-0.24; p=0.04), presence of vitreomacular traction (b=-0.29; p=0.02) and preoperative CRT in the 1000 microm zone (b=-0.24; p=0.07). A greater visual acuity improvement occurred in eyes with worse baseline visual acuity (b=-1.01; p=0.00001). The presentation of vitreomacular traction (b=-0.38; p=0.02), previous panretinal photocoagulation (b=-0.31, p=0.04) and greater preoperative CRT in the 1000 µm zone (b=-0.31; p=0.07) were negative factors for visual improvement. CONCLUSIONS: This combined treatment resulted in improvement or stabilization of BCVA and decrease of CRT and CRV. Larger comparative studies are necessary to establish the real impact of this therapeutic approach.

Athyrium distentifolium used for bioindication at different altitudes in the Tatra National Park (South Poland).

This research is a continuation of investigations on the biogeochemistry of metal accumulation of the fern Athyrium distentifolium in the Tatra National Park in Poland. This species, abundantly growing throughout the Tatra mountains, was sampled from sites with identical type of bedrocks (granites/gneisses) at various altitudes between 1000 and 2050 m a.s.l. Concentrations of the elements Cd, Cr, Cu, Fe, Mn, Ni, Pb and Zn were measured in the fern. This investigation was done to verify the hypothesis that differences in the elemental composition of A. distentifolium (growing on the same type of substrate) reflect the differences of the atmospheric metal deposition at various altitudes. We verified this hypothesis using the Market Basket Analysis technique. MBA revealed that at low altitude (1000-1500 m a.s.l.) A. distentifolium contains very low concentrations of Cd, Fe, Mn, Ni, Pb and Zn. At a medium altitude (1501-1700 m a.s.l.) the fern contains a very high concentration of Pb and at a high altitude (1701-2050 m a.s.l.) the fern contains very high concentrations of Cd, Cr, Mn, Ni and Zn. The different altitudes on which A. distentifolium grew influenced the concentrations of elements accumulated in this species. Our investigation pointed out that A. distentifolium is able to accumulate elevated levels of metals and therefore may be used in controlling metal pollution. In addition A. distentifolium gives comparable bioindicative results as the moss P. schreberi in the same Tatra mountains. As the investigated species has a wide circumpolar distribution in mountains of the Northern hemisphere therefore it may be used in controlling long range metal pollution in such mountainous areas.

[Ocular complications of the diabetes--diagnostic and therapeutic implications]. / Cukrzycowe powiklania narzadu wzroku--uwarunkowania diagnostyczno-terapeutyczne.

Author describe actual knowledge about diabetes epidemiology and ocular complications in course of diabetes. More information about innovation diabetic macular edema treatment is done.

Effectiveness of ranibizumab intravitreal injections for exudative age-related macular degeneration treatment: 12-month outcomes.

BACKGROUND: The aim of this paper was to evaluate functional and anatomical results of intravitreal ranibizumab injections and the course of exudative age-related macular degeneration (AMD) treatment over a 12-month observation period. MATERIAL/METHODS: In 25 patients with active dominantly classic exudative AMD, treatment was performed according to the following schedule: 3 intravitreal injections of 0.5 mg ranibizumab at monthly intervals (saturation phase); further injections were based on activity of the neovascular process. Changes in VA and central retinal thickness (CRT) during treatment were evaluated with ANOVA testing. RESULTS: Mean pre-treatment best corrected visual acuity was 0.73±0.27 logMAR. After the third ranibizumab injection the best results, 0.54±0.27 logMAR, were seen; 12-month results were 0.58±0.26 logMAR. Patients had a mean improvement of 10.6 letters at 12 months. In 92% of patients stabilization or improvement of vision was observed. The mean number of injections in the 12-month period was 6. Baseline mean CRT was 351.12±74.15 µm. After the first ranibizumab injection it decreased significantly to 221.96±60.85 µm, after the third injection it was 200.80±47.63 µm, and after 12 months it was 213.16±44.37 µm. Mean correlations between baseline average CRT and baseline average VA measured in ETDRS letters (p=0.017) and in logMAR scale (p=0.033) and between average CRT after the third injection and average VA in logMAR scale after the third injection (p=0.047) were noted. CONCLUSIONS: Treatment with intravitreal ranibizumab injections according to the presented scheme provides AMD patients with a chance of stabilization and improvement of the topical state, with a lower number of injections and preserved topical and general safety. Our results suggest that regular monthly controls are necessary to be able react rapidly to the smallest signs of deterioration, not only in visual acuity, but also in OCT images.

[Age-related macular degeneration (AMD)--primary results "Bus-Tour'2011" action]. / Zwyrodnienie plamki zwiazane z wiekiem (AMD) --wstepne wyniki akcji "Bus-Tour'2011".

PURPOSE: The aim of article is to sum up "Bus-Tour'2011" action concerning age-related macular degeneration (AMD). MATERIAL AND METHODS: Between March 29 to May 28.2011 in 10 polish cities 7292 persons were examined. The ophthalmological examination were done in special bus with diagnostic equipment (Bausch & Lomb owner). RESULTS: In almost 19% (1355 persons), changes in eye fundus as age-related macular degeneration were found. Additionally in 324 persons (4,4%), ophthalmologists found some high suspicious AMD changes. CONCLUSIONS: Knowledge about AMD in polish population is very poor.

[Pharmacological treatment of recurrent idiopathic anterior uveitis]. / Leczenie farmakologiczne chorych na nawrotowe idiopatyczne zapalenie przedniego odcinka blony naczyniowej oka.

Recurrent anterior uveitis (AU) is an autoimmune disease that in 20% of patients leads to severe visual loss or blindness, thereby a severe disability and significant quality of life impairment. That is why, it is important to conduct a long term treatment after an acute phase of the disease, to keep the remission as long as possible. Up to 50% of patients with recurrent AU have no additional symptoms of systemic disease. This situation, classified as idiopathic AU (IAU), causes a lot of problems when a therapeutic strategy has to be chosen. Nevertheless, IAU is considered to be a first symptom of spondylarthropathy (SpA), even several dozen years prior to other typical manifestations of SpA. There have been published few papers concerning only small groups of patients with IAU, treated with disease modifying anti-rheumatic drugs. The authors present the recommendations for systemic treatment of IAU, based on their own clinical experience, and systematic review of the literature.

Market Basket Analysis: a new tool in ecology to describe chemical relations in the environment--a case study of the fern Athyrium distentifolium in the Tatra National Park in Poland.

In this study, the novel data mining technique Market Basket Analysis (MBA) was applied for the first time in biogeochemical and ecological investigations. The method was tested on the fern Athyrium distentifolium, in which we measured concentrations of the elements Ca, Cd, Cr, Cu, Fe, K, Mg, Mn, Na, Ni, Pb, and Zn. Plants were sampled from sites with different types of bedrock in the Tatra National Park in Poland. MBA was used to investigate whether specimens of Athyrium distentifolium that contain elevated levels of certain elements occur more frequently on a specific type of bedrock and to identify relationships between the type of bedrock and the concentrations of the elements in this fern. The results were compared with those of the commonly used principal component and classification analysis (PCCA) technique. MBA and PCCA ordination both yielded distinct groups of ferns growing on different types of bedrock. Although the results of MBA and PCCA were similar, MBA has the advantage of being independent of the size of the data set. In addition, MBA revealed not only dominant elements but, in the case of limestone bedrock, also showed very low concentrations of Cd, Fe, Mn, and Pb in ferns growing on this type of parent material. MBA, thus, appeared to be a promising data mining method to reveal chemical relations in the environment as well as the accumulation of chemical elements in bioindicators. This technique can be used to reveal associations and correlations among items in large data sets collected on a national or even larger scale.

Future possibilities in glaucoma therapy.

Glaucoma is a group of eye diseases causing irreversible optic nerve damage. This review presents 4 elements of future glaucoma treatment strategies: baroprotection, vasoprotection, neuroprotection and gene therapy. New baroprotection includes compounds that alter the actin cytoskeleton (rho-kinase inhibitors, latrunculin, cytochalasin), new drugs that enhance aqueous outflow via the trabecular meshwork (statins, steroid antagonists) and via the uveoscleral route (EP2 agonists, 5-HT2 agonists), as well as new classes of components that suppress aqueous humor formation (cannabinoids). Vasoprotection includes blocking reperfusion injury (NOS-2 inhibitors, endothelin blockers, MMP-9 inhibitors). Concerning neuroprotection antiamyloids antibodies, erythropoietin and caspase inhibitors are discussed. Gene therapy may target various effectors: the trabecular meshwork (cytoskeleton regulatory proteins, miocyllin, MMPs), the ciliary body epithelium (genes modifying aqueous humor production, neuropeptides), the ciliary body cells (MMPs, genes of local PGs biosynthesis, ciliary muscle relaxants), the retinal ganglion cells (neurotrophin genes, anti-apoptotic genes), Müller cells (neurotrophins, GLAST) and conjunctiva (gene of chloramphenicol acetyltransferase, inhibitor p21). Experimental studies on the graft mesenchymal stem cells and mature retinal cells to replace the dead retinal ganglion cells are advanced. Immunotherapy, offering a vaccination, providing protection against loss of retinal ganglion cells, has been investigated.

Lens epithelial cell damage after exposure to deionized water to prevent posterior capsule opacification after phacoemulsification: an in vitro study.

BACKGROUND: The aim was to study the effects of distilled deionized water (DDW) on lens epithelial cells (LECs) after two different exposure times in the context of preventing posterior capsule opacification (PCO) after phacoemulsification. MATERIAL/METHODS: Twenty-one subjects (21 eyes) (12 women, 9 men), with a mean age of 74.5 + or - 7.1 years, were in this study. Anterior capsulotomy specimens obtained during cataract phacoemulsification were immersed in a hypotonic solution of DDW. In group I (10 eyes) the anterior capsule fragments were exposed to DDW for 1 minute and in group II (11 eyes) for 3 minutes. The fragments then underwent histological examination; photographic documentation was made and measurements were done with an image analysis system. Log-linear analysis was performed to determine the odds ratio (OR). The significance of particular histological findings was evaluated with Fisher's exact test and Kendall's tau b coefficient was determined by analyzing contingency tables. RESULTS: Basement membrane and LECs showing different degrees of damage, from vacuolar degeneration to epithelial detachment and from karyorrhexis to total cytolysis, were detected in the microscopic specimens. The probability of lens epithelial cell cytolysis after 3-minute exposure was 3.5 times higher than after 1-minute exposure to DDW. CONCLUSIONS: Exposure to DDW causes different degrees of damage to LECs, ranging from reversible changes to total cell death. The changes seen in LECs are dependent on the duration of their exposure to DDW.

Müller glial cells--the mediators of vascular disorders with vitreomacular interface pathology in diabetic maculopathy.

The key to identifying the type of diabetic maculopathy is determining the status of posterior vitreous adhesion. In the pathological state, the breakdown of the internal and external blood-retina barrier is evident, however the mechanism is usually complex. The common denominator for these disorders are Müller glial cells, which mediate in maintaining the blood-retina barrier by linking the vessels, neurons and the vitreous in anatomical network and into functional dependence. The breakdown of the blood-retina barrier results in proliferation of Müller cells. Molecular changes in these cells increase endothelial barrier properties, but also induce pathological processes on the vitreo-retinal junction, resulting in increased adhesiveness of the collagen fibers of vitreous to retinal internal limiting membrane. The ability of Müller cells to reactive gliosis is influenced by the healthy functioning of the retinal pigment epithelium, which is a source of trophic factors necessary for appropriate Müller cells morphogenesis. Vitrectomy with the removal of ILM eliminates the vitreofoveal interface pathology, additionally provoking reactive gliosis within the macula. Intraoperative use of anti-VEGF supports short-term tightness of the blood-retina barrier in the perioperative neuralgic period. In the future, supplying astrocytes may be a strategy that will allow not only the inhibition of pathological neovascularization but also the restoration of the physiological network of capillaries in avascular retina areas. The delivery of recombinant PEDF allows for the recovery of Müller cells, and thus creates the conditions favourable for the survival of nerve cells in loss of retinal homeostasis.

[Combined surgical and pharmacological treatment of diabetic maculopathy]. / Skojarzone chirurgiczno-farmakologiczne leczenie makulopatii cukrzycowej.

There are at least three avenues of investigation that support the theoretical value of vitrectomy for the treatment of DME, based on (1) vitrectomy with ILM peeling for the relief of traction on the macula, (2) vitrectomy to improve oxygenation of the macula leading to decreased vascular permeability with subsequent resolution or decrease in DME, and (3) ILM peeling to remove a part of the Müller cell endfeet and the horizontal gliosis. Visual improvement could be due to the induction of a higher overexpression of GFAP at the Müller cells level. It is likely that the proliferation of GFAP-stained gliofibrils, observed in these cells, preserves the blood-retinal barrier, reinforces architectural cohesion, and opposes the installation of the edema. In addition, the search for a specific pharmacological treatment is ongoing on the basis of new findings regarding the involvement of cytokines and growth factors in the formation of macular edema. Vascular endothelial growth factor (VEGF), inhibitors are currently being investigated in clinical studies. However, endogenous VEGF is required for visual function. Growing body evidence indicates that VEGF acts also on nonvascular cells, it plays survival role on Müller cells and photoreceptors. Therefore anti-VEGF therapies should be administered with caution.

[Sealed-capsule irrigation during cataract surgery to prevent posterior capsule opacification]. / Zastosowanie systemu szczelnej irygacji w czasie operacji zacmy w zapobieganiu rozwojowi zmetnienia torebki tylnej.

The possibility of isolated use of pharmacological agents to selectively destroy anterior capsule epithelial cells and avoid toxic side effects on other tissues has become the aim of numerous research studies. Creation of a precise, tight, safe system which would allow delivery of pharmaceutical agents into the lens capsule following cataract extraction seems to be a solution. Thus, the aim of our study is to present a surgical technique preventing the development of posterior capsule opacification (PCO) after cataract surgery with the use of sealed-capsule irrigation system (SCI)--Perfect Capsule device.

[Autonomic nervous system and primary open angle glaucoma--pathogenetic and clinical correlations]. / Autonomiczny uklad nerwowy i jaskra pierwotnie otwartego kata--korelacje patogenetyczne i kliniczne.

Primary open angle glaucoma is linked to autonomic nervous system dysfunction. In a review the role of autonomic nervous system as an important determinant of systemic hemodynamic parameters such as heart rate and blood pressure, was presented. Human circadian clock and its impact on autonomic nervous system was emphasized. Finally some autonomic function tests and therapeutical implications were described.