Taste reactivity alterations after IL-1beta microinjection into the ventromedial hypothalamic nucleus of the rat

The ventromedial hypothalamic nucleus (VMH) is a central site of action of interleukin-1beta (IL-1beta) induced feeding disturbances. This study was designed to elucidate taste-related perceptual and motivational processes potentially contributing to the anorexia and adipsia seen after bilateral IL-1beta microinjection into the VMH. A saccharin conditioned taste aversion (CTA) paradigm was tested after the central IL-1beta administration. To further investigate whether gustatory deficits are involved in development of the feeding alterations, IL-1beta induced changes of taste responsiveness were also studied in taste reactivity tests. Administration of the cytokine into the VMH did not cause the development of CTA. During taste reactivity tests, however, IL-1beta treated rats displayed significantly poorer ingestive reactions to pleasant taste stimuli than did animals of the control group. In addition, the aversive responses of IL-1beta injected rats to pleasant tastes were significantly more robust than those of control animals. The cytokine treated animals also showed stronger aversion than ingestion to hedonically positive tastes. The present findings indicate that (1) anorexigenic and adipsogenic consequences of IL-1beta microinjection into the VMH are not due to development of cytokine induced CTA; and (2) hedonic responsiveness to palatable tastes is processed by IL-1beta mediated neural mechanisms in the VMH.     

The Transplantation of hBM-MSCs Increases Bone Neo-Formation and Preserves Hearing Function in the Treatment of Temporal Bone Defects – on the Experience of Two Month Follow Up

Temporal bone reconstruction is a persisting problem following middle ear cholesteatoma surgery. Seeking to advance the clinical transfer of stem cell therapy we attempted the reconstruction of temporal bone using a composite bioartificial graft based on a hydroxyapatite bone scaffold combined with human bone marrow-derived mesenchymal stromal cells (hBM-MSCs). The aim of this study was to evaluate the effect of the combined biomaterial on the healing of postoperative temporal bone defects and the preservation of physiological hearing functions in a guinea pig model. The treatment’s effect could be observed at 1 and 2 months after implantation of the biomaterial, as opposed to the control group. The clinical evaluation of our results included animal survival, clinical signs of an inflammatory response, and exploration of the tympanic bulla. Osteogenesis, angiogenesis, and inflammation were evaluated by histopathological analyses, whereas hBM-MSCs survival was evaluated by immunofluorescence assays. Hearing capacity was evaluated by objective audiometric methods, i.e. auditory brainstem responses and otoacoustic emission. Our study shows that hBM-MSCs, in combination with hydroxyapatite scaffolds, improves the repair of bone defects providing a safe and effective alternative in their treatment following middle ear surgery due to cholesteatoma.     

Galectin-3 deficiency enhances type 2 immune cell-mediated myocarditis in mice

Experimental autoimmune myocarditis (EAM) is a mouse model of immune-mediated myocarditis and cardiomyopathy. The role of Galectin-3 (Gal-3), a β-galactoside-binding lectin, in autoimmune myocarditis has not been studied. Therefore, the aim of this study was to delineate the role of Gal-3 in myosin peptide-induced autoimmune myocarditis in mice. EAM was induced in relatively resistant C57BL/6J mice (wild type, WT) and in mice with a targeted deletion of Gal-3 gene (Gal-3KO) by immunization with myosin peptide MyHCα_334–352. Gal-3KO mice developed more severe myocarditis and more pronounced heart hypertrophy than WT mice. Increased infiltration of CD45⁺ leucocytes, CD3⁺ T cells, F4/80⁺ macrophages, and eosinophils was observed in hearts of Gal-3KO mice compared to WT mice on day 21 after EAM induction. Moreover, hearts of Gal-3KO mice had more T helper type 2 (Th2) cells, alternatively activated M2 macrophages, higher amounts of IgG deposits, and higher serum levels of IL-4 and IL-33 than WT mice. Ablation of Gal-3 in Th1-dominant C57BL/6J mice that are relatively resistant to EAM resulted in more severe disease characterized by type 2 cardiac inflammation. The complex effects of Gal-3 on EAM progression might be important in the consideration of therapeutic options for the treatment of EAM.     

1,4‐Bisbenzil: Visible‐Light‐ and Heat‐Assisted Crosslinking of Polystyrene Films

Polystyrene (PS) film containing 1,4‐bisbenzil is efficiently crosslinked in two steps. In the first step, visible light (λ > 400 nm) causes molecular oxygen to insert between two carbonyl groups of one of the 1,2‐dicarbonyl groups. The peroxide is subsequently decomposed by absorption of another photon, forming acyloxy radicals, which add to the aromatic ring of the PS chain. The remaining 1,2‐dicarbonyl group is then photoperoxidized to form PS with pendant benzoyl peroxide moieties. In the second step, pendant benzoyl peroxide groups are decomposed thermally to form acyloxy macroradicals responsible for the crosslinking. Crosslinking proceeds simultaneously with degradation. Finally, the gel content in the film may exceed 80 wt%.

     

Nickel release behavior and surface characteristics of porous NiTi shape memory alloy modified by different chemical processes

As a non-line-of-sight surface modification technique, chemical treatment is an effective method to treat porous NiTi with complex surface morphologies and large exposed areas due to its liquidity and low temperature. In the work described here, three different chemical processes are used to treat porous NiTi alloys. Our results show that H(2)O(2) treatment, NaOH treatment, and H(2)O(2) pre-treatment plus subsequent NaOH treatment can mitigate leaching of nickel from the alloy. The porous NiTi samples modified by the two latter processes favor deposition of a layer composed of Ca and P due to the formation of bioactive Na(2)TiO(3) on the surface. Among the three processes, H(2)O(2) pre-treatment plus subsequent NaOH modification is the most effective in suppressing nickel release. Small area X-ray photoelectron spectroscopy reveals that the surfaces treated by different chemical processes have different structures and compositions. The sample modified by the H(2)O(2) treatment is composed of rough TiO(2) on the outer surface and an oxide transition layer underneath whereas the sample treated by NaOH comprises a surface layer of titanium oxide and Na(2)TiO(3) together with a transition layer. The sample processed by the H(2)O(2) and NaOH treatment has a pure Na(2)TiO(3) layer on the surface and a transition layer underneath. These results help to elucidate the different nickel release behavior and bioactivity of porous NiTi alloys processed by different methods.     

Clinical and pathological features of an Alzheimer's disease patient with the MAPT Delta K280 mutation

We identified a case of Alzheimer's disease with a deletion of the lysine residue at codon 280 (DeltaK280) in exon 10-encoded microtubule-binding repeat domain of the tau gene (MAPT). This mutation was originally identified in a sporadic case of frontotemporal dementia (FTD) with a family history of Parkinson's disease. In the original report, the authors were careful in their assessment of the pathogenicity and suggested one could not be sure whether the mutation was pathogenic or not. The mutation has always presented a conundrum because it is the only known mutation, of assumed pathogenicity, which increases the proportion of 3-repeat tau mRNA in in vitro assays. Here we present the clinical and pathological features of a new case with this mutation and discuss whether the mutation is indeed pathogenic.     

Analysis of biennial outbreak pattern of respiratory syncytial virus according to subtype (A and B) in the Zagreb region

Background: The epidemic pattern of respiratory syncytial virus (RSV) in Croatia is biennial. In order to determine if the circulation of different RSV subtypes affects the outbreak cycle, the aim of the present study was to analyze the epidemic pattern of RSV in children in Croatia (Zagreb region) over a period of 3 consecutive years. Methods: The study group consisted of 696 inpatients, aged 0–5 years, who were hospitalized with acute respiratory tract infections caused by RSV, in Zagreb, in the period 1 January 2006–31 December 2008. The virus was identified in nasopharyngeal secretions using direct immunofluorescence. The virus subtype was determined on real‐time polymerase chain reaction. Results: Of 696 RSV infections identified in children, subtype A virus caused 374 infections, and subtype B, 318. Four patients had a dual RSV infection (subtypes A and B). The period of study was characterized by four epidemic waves of RSV infections: the first, smaller, in the spring of 2006; the second, larger, in December 2006/January 2007; the third in spring 2008, followed by a fourth outbreak beginning in November of 2008. The biennial virus cycles were persistent although the predominant RSV subtype in the first two epidemic waves was subtype B, and in the second two it was subtype A. Conclusion: Over a 3 year period of observation, the biennial RSV cycle in Croatia cannot be explained by a difference in the predominant circulating subtype of RSV. Other unknown factors account for the biennial cycle of RSV epidemics in Croatia.     

Improved spectral resolution and high reliability of in vivo 1H MRS at 7 T allow the characterization of the effect of acute exercise on carnosine in skeletal muscle

The aims of this study were to observe the behavior of carnosine peaks in human soleus (SOL) and gastrocnemius (GM) muscles following acute exercise, to determine the relaxation times and to assess the repeatability of carnosine quantification by ¹H MRS at 7 T. Relaxation constants in GM and SOL were measured by a stimulated echo acquisition mode (STEAM) localization sequence. For T₁ measurement, an inversion recovery sequence was used. The repeatability of the measurement and the absolute quantification of carnosine were determined in both muscles in five healthy volunteers. For absolute quantification, an internal water reference signal was used. The effect of acute exercise on carnosine levels and resonance lines was tested in eight recreational runners/cyclists. The defined carnosine measurement protocol was applied three times – before and twice after (approximately 20 and 40 min) a 1‐h submaximal street run and additional toe‐hopping. The measured T₁ relaxation times for the C2‐H carnosine peak at 7 T were 2002 ± 94 and 1997 ± 259 ms for GM and SOL, respectively, and the T₂ times were 95.8 ± 9.4 and 81.0 ± 21.8 ms for GM and SOL, respectively. The coefficient of variation of the carnosine quantification measurement was 9.1% for GM and 6.3% for SOL, showing high repeatability, and the intraclass correlation coefficients (ICCs) of 0.93 for GM and 0.98 for SOL indicate the high reliability of the measurement. Acute exercise did not change the concentration of carnosine in the muscle, but affected the shape of the resonance lines, in terms of the shifting and splitting into doublets. Carnosine measurement by ¹H MRS at 7 T in skeletal muscle exhibits high repeatability and reliability. The observed effects of acute exercise were more prominent in GM, probably as a result of the larger portion of glycolytic fibers in this muscle and the more pronounced exercise‐induced change in pH. Our results support the application of the MRS‐based assessment of carnosine for pH measurement in muscle compartments. © 2015 The Authors. NMR in Biomedicine published by John Wiley & Sons Ltd.     

Novel mutations in the PATCHED gene in basal cell nevus syndrome

Basal cell nevus syndrome (BCNS) is an autosomal dominant disease characterized by the presence of multiple basal cell carcinomas, odontogenic keratocysts, palmoplantar pits, and calcification in the falx cerebri caused by mutational inactivation of the PTCH gene. To investigate the molecular basis of BCNS in Chinese, we did a mutational analysis of the PTCH gene by performing denaturing high-performance liquid chromatography in three BCNS families. In this study, three novel mutations, two 1-bp frameshift insertions, i.e., 1468insA and 2392insC, and one 8-bp deletion, i.e., IVS5 + 1delGTAAGTGT, affecting a donor splice site, were identified. All the mutations cause a shift of the open reading frames and lead to premature termination of PTCH protein translation. Our results showed that mutational inactivation of the PTCH gene causes BCNS in Chinese.