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.

OBJECTIVE: To compare the immunogenicity, safety, and efficacy of Gan & Lee insulin glargine (GL Glargine) with that of the originator insulin glargine (Lantus) in patients with type 1 diabetes mellitus (T1DM). METHODS: This was a phase 3, multicenter, randomized, open-label, equivalence study. Five hundred seventy-six subjects with T1DM were randomized 1:1 to receive either GL Glargine or Lantus treatment for 26 weeks. The primary end point was the percentage of subjects in each treatment group who developed treatment-induced anti-insulin antibody 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, and adverse events including hypoglycemia. RESULTS: The percentage of subjects positive for treatment-induced anti-insulin antibody 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 (-5.4, 6.5) of the difference in proportions that fell completely between the similarity margins (-11.3, 11.3). The least squares mean difference between treatment groups for changes in glycated hemoglobin was -0.08 (90% confidence interval: -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.

Rigid Body Dynamics Algorithm for Modeling Random Packing Structures of Nonspherical and Nonconvex Pellets.

Despite the common use of nonspherical catalyst pellets in chemical engineering applications, the packing structures of such pellets have not been as systematically studied and characterized as spherical packings. We propose a packing algorithm based on rigid body dynamics to simulate packing of nonspherical and possibly nonconvex pellets. The algorithm exerts a hard-body approach to model collision phenomena. The novelty is that the transition between moving and resting particles is controlled by a cutoff on the relative contact velocities, instead of artificially damping linear and angular velocities to stabilize the algorithm. The algorithm is used to synthesize packings of spheres, cylinders, and Raschig rings with tube-to-pellet diameter ratios 3-9.16. The packings are validated in terms of bulk porosity and radial void fraction distribution, finding satisfactory agreement with literature data. Denser packing structures are generated with high restitution coefficients and low friction coefficients. The confining tube walls play an important role, with highly fluctuating bulk porosities in narrow tubes.

Complexity and Challenges in Noncontact High Temperature Measurements in Microwave-Assisted Catalytic Reactors.

The complexity and challenges in noncontact temperature measurements inside microwave-heated catalytic reactors are presented in this paper. A custom-designed microwave cavity has been used to focus the microwave field on the catalyst and enable monitoring of the temperature field in 2D. A methodology to study the temperature distribution in the catalytic bed by using a thermal camera in combination with a thermocouple for a heterogeneous catalytic reaction (methane dry reforming) under microwave heating has been demonstrated. The effects of various variables that affect the accuracy of temperature recordings are discussed in detail. The necessity of having at least one contact sensor, such as a thermocouple, or some other microwave transparent sensor, is recommended to keep track of the temperature changes occurring in the catalytic bed during the reaction under microwave heating.

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.

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.

Typha latifolia (broadleaf cattail) as bioindicator of different types of pollution in aquatic ecosystems-application of self-organizing feature map (neural network).

The contents of Cd, Cu, Fe, Mn, Ni, Pb, and Zn in leaves of Typha latifolia (broadleaf cattail), water and bottom sediment from 72 study sites designated in different regions of Poland were determined using atomic absorption spectrometry. The aim of the study was to evaluate potential use of T. latifolia in biomonitoring of trace metal pollution. The self-organizing feature map (SOFM) identifying groups of sampling sites with similar concentrations of metals in cattail leaves was able to classify study sites according to similar use and potential sources of pollution. Maps prepared for water and bottom sediment showed corresponding groups of sampling sites which suggested similarity of samples features. High concentrations of Fe, Cd, Cu, and Ni were characteristic for industrial areas. Elevated Pb concentrations were noted in regions with intensive vehicle traffic, while high Mn and Zn contents were reported in leaves from the agricultural area. Manganese content in leaves of T. latifolia was high irrespectively of the concentrations in bottom sediments and water so cattail can be considered the leaf accumulator of Mn. Once trained, SOFMs can be applied in ecological investigations and could form a future basis for recognizing the type of pollution in aquatic environments by analyzing the concentrations of elements in T. latifolia.

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.

Cardiac autonomic dysfunction in patients with normal tension glaucoma: 24-h heart rate and blood pressure variability analysis.

AIMS: To define parameters of autonomic nervous system activity in patients with normal tension glaucoma (NTG). METHODS: Ambulatory 24-h ECG (Lifecard CF) and 24-h blood pressure (BP) monitoring (SpaceLab 90207-30) were carried out in 54 patients with NTG (44 women, mean age 59.7) and 43 matched control subjects (34 women, mean age 57.0). Heart rate variability time and frequency domain parameters (low frequency (LF), high frequency (HF) and LF/HF ratio), BP variability (BPV), diurnal and nocturnal BP variables were compared between study groups. RESULTS: Patients with NTG demonstrated higher LF, LF/HF and lower HF values than control subjects for the 24-h, daytime and night-time periods. The mean 24-h, daytime and night-time LF/HF ratios were statistically higher in patients with glaucoma as compared to control subjects ((3.2±1.5 vs 2.2±0.8, p=0.0009), (3.5±1.7 vs 2.7±1.0, p=0.0173) and (2.6±1.7 vs 1.4±0.6, p=0.0001), respectively). There were no statistical differences in the mean BP during the whole day, daytime and night-time, and in BPV (10.4±1.9 vs 10.5±2.1, p=0.790) between study groups. No difference was also found in the percentage decrease in night-time mean BP (12.3% vs 13.6%, p=0.720). 'Dippers', 'non-dippers' and 'overdippers' with NTG showed significantly higher LF/HF ratio as compared to the same subgroups of control subjects. CONCLUSIONS: The sympathovagal balance of autonomic nervous system in patients with NTG shifted towards sympathetic activity however with no change of 24-h pattern of BPV as compared to controls.

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.

[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.

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.

Intraocular pressure and ocular hemodynamics in patients with primary open-angle glaucoma treated with the combination of morning dosing of bimatoprost and dorzolamide hydrochloride.

AIMS: This prospective, multicenter, single-masked study evaluated the additive effect of dorzolamide hydrochloride 2% on the diurnal intraocular pressure (IOP) curve and retinal and retrobulbar hemodynamics in patients with primary open-angle glaucoma (POAG) treated with morning-dosed bimatoprost 0.03%. METHODS: Eighty-nine patients (aged, 60.7 ± 11.8 years, range 33-80; 68 women) with POAG received bimatoprost dosed once in the morning for 1 month, after which dorzolamide was added twice daily for 2 months. IOP (Goldmann) and arterial blood pressure (BP) and diurnal ocular perfusion pressures (OPP) were measured every 2 hr for 24 hr. Heidelberg retina flowmetry of the retinal microcirculation was recorded four times daily in 64 patients and colour Doppler imaging of the ophthalmic and central retinal arteries was recorded five times daily in 25 patients. All measurements were taken after the two phases of treatment and compared using anova analysis with Bonferroni adjustment. RESULTS: Mean baseline IOP was 16.5 ± 3.4 mmHg. Mean diurnal IOP with dorzolamide adjunctive therapy (12.9 ± 2.1 mmHg) was significantly lower compared to mean IOP with bimatoprost monotherapy (13.6 ± 2.2 mmHg) (p = 0.03). Adjunctive dorzolamide therapy significantly decreased vascular resistance in the ophthalmic artery (p = 0.02). Mean diastolic BP and OPP were significantly lower after adjunctive therapy. There were no changes in retinal microcirculation between the two phases of treatment. CONCLUSIONS: Adjunctive dorzolamide therapy to morning-dosed bimatoprost 0.03% reduced diurnal IOP and vascular resistance in the ophthalmic artery but did not alter retinal circulation in this group of patients with POAG.

Intensified reaction and separation systems.

Process intensification follows four main goals: to maximize the effectiveness of intra- and intermolecular events, to give each molecule the same processing experience, to optimize the driving forces/maximize specific interfacial areas, and to maximize the synergistic effects of partial processes. This paper shows how these goals can be reached in reaction and separation systems at all relevant time and length scales and is focused on the structuring of reactors and separation units, on the use of different energy forms to improve the reaction and separation, on combining and superimposing of different phenomena in one integrated unit or reactor, and on the application of oscillations for intensification of reaction and separation processes.

[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.

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.