Preoperative [11C]methionine PET to personalize treatment decisions in patients with lower-grade gliomas

BackgroundPET with radiolabeled amino acids is used in the preoperative evaluation of patients with glial neoplasms. This study aimed to assess the role of [¹¹C]methionine (MET) PET in assessing molecular features, tumor extent, and prognosis in newly diagnosed lower-grade gliomas (LGGs) surgically treated.MethodsOne hundred and fifty-three patients with a new diagnosis of grade 2/3 glioma who underwent surgery at our Institution and were imaged preoperatively using [¹¹C]MET PET/CT were retrospectively included. [¹¹C]MET PET images were qualitatively and semi-quantitatively analyzed using tumor-to-background ratio (TBR). Progression-free survival (PFS) rates were estimated using the Kaplan-Meier method and Cox proportional-hazards regression was used to test the association of clinicopathological and imaging data to PFS.ResultsOverall, 111 lesions (73%) were positive, while thirty-two (21%) and ten (6%) were isometabolic and hypometabolic at [¹¹C]MET PET, respectively. [¹¹C]MET uptake was more common in oligodendrogliomas than IDH-mutant astrocytomas (87% vs 50% of cases, respectively). Among [¹¹C]MET-positive gliomas, grade 3 oligodendrogliomas had the highest median TBR_max (3.22). In 25% of patients, PET helped to better delineate tumor margins compared to MRI only. In IDH-mutant astrocytomas, higher TBR_max values at [¹¹C]MET PET were independent predictors of shorter PFS.ConclusionsThis work highlights the role of preoperative [¹¹C]MET PET in estimating the type of suspected LGGs, assessing tumor extent, and predicting biological behavior and prognosis of histologically confirmed LGGs. Our findings support the implementation of [¹¹C]MET PET in routine clinical practice to better manage these neoplasms.     

Effect of Two-Step Sintering on Properties of Alumina Ceramics Containing Waste Alumina Powder

This study aims to evaluate the recycling potential of solid waste alumina powder (WAP) by utilization of the two-step sintering (TSS) process. For the study, WAP was collected as an industrial scrap after the machining process for the formation of green alumina compacts. The alumina samples were prepared according to the slip casting method by preparing suspensions containing commercial alumina with 0.8 μm average particle size and by adding up to 20 dwb. % (i.e., expressed on a dry weight basis) of WAP with 3.4 μm average particle size. The samples were sintered at optimized TSS conditions and compared with conventional one-step sintering (OSS) by conducting morphological analyses. The average grain size (AGS) was determined from the obtained field emission scanning electron microscopy (FESEM) images, while the sample porosity was calculated based on apparent densities. The obtained micrographs after TSS implementation revealed a partially textured microstructure. Furthermore, a comparison of the mechanical properties of alumina samples lacking or containing 20 dwb. % of WAP obtained after sintering is presented. The indentation fracture toughness (~3.2 MPa m^1/2) and Vickers hardness data (~14.5 GPa) showed a positive effect of adding WAP to alumina samples. The slightly improved mechanical properties of ceramic samples containing waste alumina are a consequence of lower porosity, which is due to the remaining sintering additives in WAP. The collected results demonstrate the possibility of using TSS for sintering ceramic materials that contain WAP.     

Magnetic and Electrical Behaviors of the Homo- and Heterometallic 1D and 3D Coordination Polymers Based on the Partial Decomposition of the [Cr(C2O4)3]3− Building Block

One-dimensional (1D) oxalate-bridged homometallic {[Mn(bpy)(C₂O₄)]·1.5H₂O}_n (1) (bpy = 2,2’-bipyridine) and heterodimetallic {[CrCu₃(bpy)₃(CH₃OH)(H₂O)(C₂O₄)₄][Cu(bpy)Cr(C₂O₄)₃]·CH₂Cl₂·CH₃OH·H₂O}_n (2) coordination polymers, as well as the three-dimensional (3D) heterotrimetallic {[CaCr₂Cu₂(phen)₄(C₂O₄)₆]·4CH₃CN·2H₂O}_n (3) (1,10-phenanthroline) network, have been synthesized by a building block approach using a layering technique, and characterized by single-crystal X-ray diffraction, infrared (IR) and impedance spectroscopies and magnetization measurements. During the crystallization process partial decomposition of the tris(oxalato)chromate(III) happened and 1D polymers 1 and 2 were formed. The antiferromagnetic interactions between the manganese(II) ions were mediated by oxalate ligands in the chain [Mn(bpy)(C₂O₄)]_n of 1, with intra-chain super-exchange interaction 𝐽 = (−3.134 ± 0.004) K; magnetic interaction between neighbouring chains is negligible making this system closer than other known Mn-chains to the ideal 1D Heisenberg antiferromagnet. Compound 2 comprises a 1D coordination anion [Cu(bpy)Cr(C₂O₄)₃]_nⁿ⁻ (Cr2–Cu4) with alternating [Cr(C₂O₄)₃]³⁻ and [Cu(bpy)]²⁺ units mutually bridged through the oxalate group. Another chain (Cr1–Cu3) is similar, but involves a homodinuclear unit [Cu(bpy)(H₂O)(µ-C₂O₄)Cu(bpy)(CH₃OH)]²⁺ (Cu1–Cu2) coordinated as a pendant group to a terminal oxalate oxygen. Magnetic measurements showed that the Cu1−Cu2 cationic unit is a strongly coupled antiferromagnetic dimer, independent from the other magnetic ions within ferromagnetic chains Cr1–Cu3 and Cr2–Cu4. A 3D polymer {[CaCr₂Cu₂(phen)₄(C₂O₄)₆]·4CH₃CN·2H₂O}_n (3) comprising three different metal centers (Ca²⁺, Cr³⁺ and Cu²⁺) oxalate-bridged, contains Ca²⁺ atoms as nodes connected with four Cr³⁺ atoms through oxalate ligands. The network thus formed can be reduced to an underlying graph of diamondoid (dia) or (6⁶) topology. Magnetization of 3 shows the ferromagnetic oxalate-bridged dimers [Cu^IICr^III], whose mutual interaction could possibly originate through the spin polarization of Ca²⁺ orbitals. Compounds 1 and 3 exhibit lower electrical conductivity at room temperature (RT) in comparison to compound 2.     

Proinflammatory cytokine levels in patients with diastolic heart failure

BACKGROUND: The role of cytokines in the pathogenesis of systolic heart failure (HF) has been well established whereas in diastolic HF it remains uncertain. AIM: To define levels of Tumor Necrosis Factor-a (TNFa) and Interleukin-6 (IL-6) in patients with diastolic HF and to reveal their association with functional class and types of left ventricular (LV) diastolic dysfunction. METHODS: We examined 26 patients with diastolic HF. The control group consisted of 10 healthy persons. Commonly used echocardiographic parameters of systolic and diastolic function of the LV, thickness of the interventricular septum (IVS), posterior LV wall thickness (PWLV), end-diastolic size of the LV (EDSLV) and left atrial (LA) volume were assessed. Serum levels of TNFa and IL-6 were measured with highly sensitive enzyme-linked immunosorbent assay. RESULTS: The TNFa and IL-6 levels were significantly higher in the group with diastolic HF than in the control group. TNFa and IL-6 levels in groups with impaired LV relaxation and restriction/pseudonormalisation were significantly higher than in the control group. TNFa level was significantly higher in the restriction/pseudonormalisation group than in the group with impaired relaxation, whereas the IL-6 level was similar. The TNFa level was significantly higher in the group with NYHA class III-IV in comparison to the group with NYHA class II. The IL-6 level in these groups was similar. Of the echocardiographic parameters, only LA volume significantly correlated with the TNF+/- level. No relationship between the IL-6 level and echocardiographic parameters was found. CONCLUSIONS: In diastolic HF, serum levels of TNFa and IL-6 are elevated. The magnitude of TNF+/- elevation is associated with the severity of HF, assessed by NYHA classification, LV diastolic dysfunction level or LA volume.     

Lungs: remote inflammatory target of systemic cadmium administration in rats

Pulmonary inflammation is a biological response to cadmium entering the body via the respiratory route. Systemic administration of this metal revealed the lungs as a significant site of its disposition. In this study, the presence of basic indicators of lung inflammation (leukocyte infiltration and activity of cells recovered from lungs by enzyme digestion) was analyzed in the rat model of acute systemic cadmium intoxication.Intraperitoneal administration of both cadmium doses (0.5 mg/kg and 1.0 mg/kg) resulted in increased numbers of neutrophils. Signs of spontaneous activation of lung cells including the capacity of reduction of nitroblue tetrazolium (NBT), increase in myeloperoxidase (MPO) intracellular content and increase in interleukin-6 (IL-6) production were noted at both cadmium doses. Increased lung cell responsiveness to stimulation in vitro was noted at the higher cadmium dose. The presence of pulmonary inflammatory parameters in rats administered intraperitoneally with cadmium revealed the lungs as remote inflammatory targets of this metal.     

Lack of anti-inflammatory effect of botulinum toxin type A in experimental models of inflammation

Botulinum toxin type A (BTX-A) has a long-lasting antinociceptive activity and less clear effect on inflammation. It was proposed that these two effects share the same mechanism--the inhibition of neurotransmitter exocytosis from peripheral nerve endings. However, till now possible anti-inflammatory action of BTX-A did not evoke much attention. In the present paper, we investigate possible anti-inflammatory action of the toxin in carrageenan and capsaicin models of inflammation in rats. BTX-A (5 and 10 U/kg) was injected into the plantar surface of the rat right hind-paw pad 5 days before the injection of the carrageenan (1%) or capsaicin (0.1%) at the same site. Carrageenan-induced paw oedema and capsaicin-induced protein extravasation were measured. Control, inflamed and BTX-A pretreated inflamed paws were photographed and histopathological analysis (haematoxylin & eosin) was performed. Pretreatment with BTX-A had no effect on the size of carrageenan-induced paw oedema, measured as paw volume and weight or capsaicin-induced plasma extravasations, measured by Evans blue as a marker of protein leakage. Neither macroscopic nor microscopic analysis showed a significant difference between BTX-A pretreated and control inflamed tissue. Results show dissociation between the effect of BTX-A on pain and inflammation thus questioning the validity of the suggested assumption about the common peripheral mechanism of action.     

Synthesis and antiviral and cytostatic evaluations of the new C-5 substituted pyrimidine and furo[2,3-d]pyrimidine 4',5'-didehydro-L-ascorbic acid derivatives

The novel C-5 alkynyl substituted pyrimidine (1-11) and furo[2,3-d]pyrimidine derivatives (12-22) of l-ascorbic acid were synthesized by coupling of 5-iodouracil-4',5'-didehydro-5',6'-dideoxy-l-ascorbic acid with terminal alkynes by using Sonogashira cross-coupling reaction conditions. The new compounds were evaluated for their cytostatic and antiviral activities. Among all evaluated compounds, the octynyl-substituted uracil derivative of l-ascorbic acid (3) exhibited the most pronounced cytostatic activities against all examined tumor cell lines (IC50 = 2-12 microM). Pyrimidine derivatives of l-ascorbic acid containing p-substituted phenylacetylene groups (8-11) displayed also a rather pronounced (IC50 = 3-37 microM) inhibitory effect toward all tumor cell lines. From the bicyclic series of compounds, 6-butylfuro[2,3-d]pyrimidine derivative (12) and 6-p-bromophenylfuro[2,3-d]pyrimidine derivative (19) showed the highest cytostatic activity (IC50 = 4.5-20 microM), particularly against malignant leukemia (L1210) and T-lymphocyte (Molt4/C8 and CEM) cells. Compounds 3 and 9 showed specific albeit moderate activity against cytomegalovirus (CMV, Davis strain, EC50 = 1.8 and 3.8 microM, respectively, for compounds 3 and 9) at a approximately 5-fold lower concentration than that required to show cytotoxicity.     

Temporal Patterns of Soluble Adhesion Molecules in Cerebrospinal Fluid and Plasma in Patients with the Acute Brain Infraction

The aim of this study was to define concentration changes of soluble adhesion molecules (sICAM-1, sVCAM-1 and sE-Selectin) in cerebrospinal fluid and plasma, as well as, number of peripheral blood leukocytes and the albumin coefficient in the patients with the acute brain infarction. We also, analyzed the correlation between the measured levels, the infarct volume and the degree of neurological and the functional deficit. The study included 50 patients with the acute cerebral infarction and the control group consisted of 16 patients, age and sex matched. Obtained results showed significant increase in number of leukocytes, the albumin coefficient and the level of soluble adhesion molecules within the first seven days in patients. The highest values of measured parameters were noted within the third and the fourth day after the insult, which is the suggested period of maximal intensity of inflammatory reactions. Significant correlation was found between measured parameters and the infarct volume, the degree of neurological and the functional deficit. The results suggest that investigated parameters in CSF and blood represent a dynamic index of inflammatory events as one of the fundametal mechanisms responsible for neuron damage during acute phase of brain infarction.