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IntroductionBipolar Affective Disorder(BAPD) is characterized by variations in mood from elation and/or irritability to depression.Valproic acid(VPA) is indicated for the treatment of acute manic episodes in BPAD.The use of VPA can be limited by either loss or lack of efficacy or by adverse drug reactions. Stevens-Johnson syndrome(SJS) toxic epidermal necrolysis(TEN) are the rare but fatal cutaneous adverse drug reactions for VPA.ObjectivesWe wanted to draw attention that drug induced bullous lesions which has been seen rarely in the literature caused by valproic acid in bipolar disorder.MethodsWe examined the side effects of valproic acid in one of our patients with bipolar affective disorder using our observations and laboratory tests.ResultsA 41 year old man was admitted to the our hospital with complaints of decreased amount of sleep, increased amount of speech, skepticism,irritability and dysphoric mood.The patient who was followed up with a diagnosis of BPAD for about 10 months,attempted suicide by taking lithium 2 days before his hospitalization.Considering that it was a mixed episode and the prophylactic effect of lithium was insufficient,VPA 1000 mg/day and Risperidone 2 mg/day treatment were started.Risperidone was increased to 4 mg/day because psychotic symptoms persisted.Valproic acid dose was increased to 1000 to 1500mg/day after the Valproic acid blood level reached 55.28 in the follow-ups.After 5 days 2 bullous lesions developed on the lower extremity of the patient.Routine laboratory investigations were within normal limits.When we consult the patient with the dermatologist;the dermatologist recommended that the lesion be fixed drug eruption and that valproic acid should be discontinued if possible.It was thought that the lesions of the patient who did not have dermatological disorders and did not describe insect bites,might be due to valproic acid. In addition to all these,the patient’s mother had pemphigus vulgaris.The patient’s valproic acid drug was discontinued and lithium was started.Risperidone treatment was continued.In the follow-ups,the patient’s bullous lesions regressed and no new lesion formation was observed.Image:ConclusionsThe differential diagnosis of bullous lesions at first may appear overwhelming.In this case traumatic bulla,Pemphigus vulgaris,drug induced bulla,Fixed drug eruption,Steven Johnson Syndrome were among our prediagnosis.Cutaneous drug eruptions associated with VPA can range from maculopapular eruption to severe Stevens-Johnson syndrome or toxic epidermal necrolysis.We were worried that the patient had SJS, but it remained only bullous lesions.We could not biopsy the patient lesions to understand the underlying cause but development of bullous lesions with the initiation of valproate and subsequent remission of the lesions with the discontinuation of the drug and subsequent course clearly suggests a causal relation between valproate and skin lesions.Disclosure of InterestNone Declared

With its excellent biocompatibility, biodegradability, and antimicrobial activity, chitosan is a promising scaffold material for hard-tissue engineering. Yet, pristine chitosan foams typically lack the strength and porosity required for such use. Here we present a simple emulsion-templating approach to fabricate pristine chitosan foams with optimized strength and porosity. Sodium dodecyl sulfate (SDS), a widely used biocompatible anionic surfactant, was employed at trace levels to aid polymerization. The foams display a dual-scale pore morphology. Cavities of 150–300 μm are separated by around 50 μm thick chitosan walls containing large interconnecting openings. The walls are further populated with meso- and macropores of 50–500 nm. This architecture should support cell attachment and growth, facilitate proliferation, and enhance nutrient transport and metabolic exchange. The structure yields high surface area (up to 10 m2 g−1). Mechanically, the thick-walled cavities impart both elastic recovery and high compressive resistance (255 kPa at 40% strain from foams polymerized with 4% chitosan). A preliminary drug-release study using vancomycin confirmed excellent loading and sustained release.

The preparation of materials with high attenuation performance is one of the major issues in the radiation shielding applications. This study is based on the investigation of gamma-shielding performances of various polyester composites reinforced with Zn. Utilizing gamma spectrometer based on HPGe detector, the mass attenuation coefficient ( μ / ρ ) of the present composites was measured at various photon energies between 59.5–1408 keV. The obtained experimental data were confirmed with those of MCNPX code as well as XCOM program. It is found that the attenuation coefficient values of the studied composites are in good agreement with the results of other approaches at the investigated energies. The best photon-shielding effectiveness was observed in the composite tagged with Zn (10%). The shielding characteristics of composite enhances with the addition of Zn as filler.

This research aims to increase the solubility of Dexamethasone (Dex) using cyclodextrin and develop a temperature-triggered in situ gelling system for the ocular application. The solubility of Dex was increased with SBE-β-CD. Dex- SBE-β-CD inclusion complex was prepared with kneading and freeze-drying method. Structural characterization was carried out using DSC and FT-IR. When in situ gel formulations were prepared, Pluronic F127 (PF127), a thermosensitive polymer, and Chitosan (CH), a natural, biodegradable, and mucoadhesive hydrophilic polymer, were used together. When the solubility diagrams of the drug-cyclodextrin inclusion complex were examined, it was determined that SBE-β CD showed a linear increase, and AL-type diagram was selected in consequence. The formulations were produced using different amounts of PF127 and a fixed ratio of CH. In situ gels were evaluated for clarity, pH, gelation temperature, and rheological behaviors and selected one formulation. It was established that the formulations were clear, their pH was 6, their gelation temperature decreased with increasing PF127, and was between 22-34 °C. For the selected formulation, 0.1% Dex and Dex/ SBE-β-CD were transferred to in situ gelling systems. As a result of in vitro release studies, it was observed that the release of the Dex/SBE-β-CD inclusion complex containing BRN formulation showed a higher burst effect than the other and was released for 6 hours. The results exhibited that the combination of PF127 and CH has potential as an in situ gelling systems for ocular delivery of Dex and Dex/ SBE-β-CD.

Corneal neovascularization (CNV) is a serious ocular surface disease that causes the cornea to lose its transparent structure. It is a difficult disease to treat, so different drugs and different carrier systems are tried in the treatment of the disease. One of these methods is the combined application of metformin HCl (MHL) with a fluoroquinolone group antibiotic. The aim of this study is to load MHL with low permeability into a drug delivery system that can prolong the residence time on the ocular surface. In this context, different in situ gel formulations were produced by using poloxamer, a thermosensitive polymer, together with hydroxypropylmethylcellulose, a natural viscosity increaser. In situ gels were evaluated for clarity, pH, gelation temperature, and rheological behaviors and selected two formulation. After loading MHL and moxifloxacin HCl (MOX) into these two formulations, it was determined that they were clear, had a pH of around 7, a gelling temperature of 34-35 °C, and showed pseudoplastic flow. However, drug loading capacities were found to be over 97%.When in vitro release studies were examined, it was determined that both MHL and MOX released for at least six hours. The results showed that the combination of PF127 and HPMC has potential as an in situ gelling systems for ocular delivery of MHL and MOX.

Design spectrum shape in many recent standards and codes is defined by spectral accelerations for two periods, Ts,(~0.2s) and T1,(~1 s), modified by multiplicative factors that account for the site class and strength of the ground shaking. This article draws attention to apparent discord between spectra from actual recordings at a number of stations of the national strong motion network of Turkey with the design spectra for the same location and site characteristics as given by the national seismic hazard map. We find that, for deep basins with Site Class D or E profiles, the design spectrum seems not to recognize consistently the constant velocity and longer period demand. If this conjecture is true, it may foreshadow unsafe designs for the building stock in Turkey in similar environments. Many more earthquake recordings than are currently at hand are needed to verify the applicability of using the two-point design spectrum that is embedded in the regulation. This is not a unique problem only to the Turkey Building Earthquake Regulation (TBER 2018). The recently recorded strong ground motion records from the 06 February 2023, M 7.7 and M 7.5 Kahramanmaraş, earthquakes support the conjecture of this study and provide strong evidence for a need to revise the corner periods of the design spectrum in the Regulation.

In this study, photon interaction parameters such as radiation protection efficiency ( RPE ), total mass attenuation coefficient ( μ/ρ ), linear attenuation coefficients ( μ ), half value layers ( HVL ), tenth value layers ( TVL ), mean free paths ( MFP ), effective atomic numbers ( Z Eff ) and effective electron densities ( N Eff ) were experimentally investigated for the BCZrB-0, BCZrB-10, BCZrB-20, BCZrB-30, BCZrB-40 and BCZrB-50 in the energy range from 59.5 keV to 1332.5 keV. In the experiment, HPGe detector and 241 Am (59.5 keV), 133 Ba (81 keV, 276.4 keV, 302.9 keV, 356 keV and 383.9 keV), 22 Na (511 keV and 1274.5 keV), 137 Cs (661.7 keV), and 60 Co (1173.2 keV and 1332.5 keV) radioactive point sources were used. Experimental results compared with results of the WinXCOM, GEANT4 simulation code and FLUKA simulation code. Energy absorption build-up factors ( EABF ) and exposure build-up factors ( EBF ) were calculated with G-P fitting method in the energy region 0.015 MeV ≤ E ≤ 15 MeV. Kerma relative to air values were investigated in the energy region 0.001 MeV ≤ E ≤ 20 MeV. Effective removal cross section, total macroscopic cross section and number of transmitted neutron values were defined for composites. The agreement between experimental and WinXCOM program, between experimental and GEANT 4 simulation codes and between experimental and FLUKA simulation codes of gamma-ray interaction parameters are < 5.1%, < 6.5% and < 5%, respectively. All of the results are compatible with each other and BCZrB-50 is a good gamma-ray radiation absorber in the studied composites and BCZrB-0 is the best neutron absorber in the studied composites.

This paper investigates the radiation shielding properties, such as linear and mass attenuation coefficients, half and tenth value layers, effective atomic number and electron density, and radiation protection efficiency as a function of photon energy, of a new composite, PbI 2 -doped polyester. The mentioned polyester composite was prepared with different proportions of lead(II) iodide (5% increments between 5 and 20%) so that impact of the dopant amount on radiation shielding could be properly analyzed. The prepared composites were tested in 22 different energies in the energy range of 59.5–1408.0 keV with the use of HPGe detector and eight radioactive point sources. The obtained results were further validated by comparing the results of XCOM computer program, and negligible discrepancies were observed. It was observed that PbI 2 (20%) composite is more effective gamma radiation shielding material than other produced composites. In light of this information, it can be said that the shielding efficiency increases with increasing lead(II) iodide amount.

The pentose phosphate pathway (PPP) plays an essential role in the metabolism of breast cancer cells for the management of oxidative stress and the synthesis of nucleotides. 6-phosphogluconate dehydrogenase (6PGD) is one of the key enzymes of the oxidative branch of PPP and is involved in nucleotide biosynthesis and redox maintenance status. Here, we aimed to analyze the functional importance of 6PGD in a breast cancer cell model. Inhibition of 6PGD in MCF7 reduced cell proliferation and showed a significant decrease in glucose consumption and an increase in glutamine consumption, resulting in an important alteration in the metabolism of these cells. No difference in reactive oxygen species (ROS) production levels was observed after 6PGD inhibition, indicating that 6PGD, in contrast to glucose 6-phosphate dehydrogenase, is not involved in redox balance. We found that 6PGD inhibition also altered the stem cell characteristics and mammosphere formation capabilities of MCF7 cells, opening new avenues to prevent cancer recurrance after surgery or chemotherapy. Moreover, inhibition of 6PGD via chemical inhibitor S3 resulted in an induction of senescence, which, together with the cell cycle arrest and apoptosis induction, might be orchestrated by p53 activation. Therefore, we postulate 6PGD as a novel therapeutic target to treat breast cancer.

Nucleotide pools need to be constantly replenished in cancer cells to support cell proliferation. The synthesis of nucleotides requires glutamine and 5-phosphoribosyl-1-pyrophosphate produced from ribose-5-phosphate via the oxidative branch of the pentose phosphate pathway (ox-PPP). Both PPP and glutamine also play a key role in maintaining the redox status of cancer cells. Enhanced glutamine metabolism and increased glucose 6-phosphate dehydrogenase (G6PD) expression have been related to a malignant phenotype in tumors. However, the association between G6PD overexpression and glutamine consumption in cancer cell proliferation is still incompletely understood. In this study, we demonstrated that both inhibition of G6PD and glutamine deprivation decrease the proliferation of colon cancer cells and induce cell cycle arrest and apoptosis. Moreover, we unveiled that glutamine deprivation induce an increase of G6PD expression that is mediated through the activation of the nuclear factor (erythroid-derived 2)-like 2 (NRF2). This crosstalk between G6PD and glutamine points out the potential of combined therapies targeting oxidative PPP enzymes and glutamine catabolism to combat colon cancer.