Early stage of adjuvant arthritis alters behavioral responses in male but not female rats

Anxiety and depression commonly occur in the pathology of rheumatic diseases. Little is known about how inflammatory disease in its early stage, before any clinical manifestation, may affect general activity. The aim of this study was to compare the anxiety-like behaviour in the early stage of adjuvant arthritis (AA), and the paw edema, and corticosterone (CORT) levels in the developed stage of AA among male and female Long Evans rats. The behavioural activity was evaluated by elevated plus maze tests. These revealed significantly reduced number of entries into the open arm of the maze in arthritic males compared to controls or to females 4 days after AA induction. Arthrihtic and control females did not differ. The number of entries into the closed arm of the maze was the same across the genders and studied intervals. Time spent in the open arm was significantly lower in arthritic males against controls or arthitic females. Time spent in the closed arm showed inverse picture to the time spent in the open arm. Hind paw swelling measured on day 23 of AA was the same in males and females, as was the elevation of CORT levels in plasma. Male rats showed anxiety-like behaviour on day 4 of AA, while female rats did not show any change, indicating different brain sensitivity to early inflammation among the genders.     

The Preparation and Characterization of Chitosan-Based Hydrogels Cross-Linked by Glyoxal

In this study, hydrogels based on chitosan cross-linked by glyoxal have been investigated for potential medical applications. Hydrogels were loaded with tannic acid at different concentrations. The thermal stability and the polyphenol-releasing rate were determined. For a preliminary assessment of the clinical usefulness of the hydrogels, they were examined for blood compatibility and in the culture of human dental pulp cells (hDPC). The results showed that after immersion in a polyphenol solution, chitosan/glyoxal hydrogels remain nonhemolytic for erythrocytes, and we also did not observe the cytotoxic effect of hydrogels immersed in tannic acid (TA) solutions with different concentration. Tannic acid was successfully released from hydrogels, and its addition improved material thermal stability. Thus, the current findings open the possibility to consider such hydrogels in clinics.     

The relationship between angle kappa and astigmatism after phacoemulsification with implanting of spherical and aspheric intraocular lens

Purpose:To determine the significance of any association between either change in angle kappa (K°) or the rectilinear displacement (L, mm) of the first Purkinje image relative to the pupil center and unexpected changes in astigmatism after phacoemulsification.Methods:Orbscan II (Bausch and Lomb) measurements were taken at 1, 2, and 3 months after unremarkable phacoemulsification in patients implanted with spherical (group 1, SA60AT, Alcon) or aspheric (group 2, SN60WF, Alcon) nontoric IOLs. The outputs were used to calculate L. Astigmatism, measured by autorefractometry and subjective refraction, was subjected to vector analysis (polar and cartesian formats) to determine the actual change induced over the periods 1–2 and 2–3 months postop.Results:Chief findings were that the mean (n, ±SD, 95%CI) values for L over each period were as follows: Group 1, 0.407 (38, ±0.340, 0.299–0.521), 0.315 (23, ±0.184, 0.335–0.485); Group 2, 0.442 (45, ±0.423, 0.308–0.577), 0.372 (26, ±0.244, 0.335–0.485). Differences between groups were not significant. There was a significant linear relationship between (A) the change in K (ΔK = value at 1 month-value at 2 months) and K at 1 month (x), where ΔK =0.668-3.794X (r = 0.812, n = 38, P = <0.001) in group 1 and ΔK = 0.263x -1.462 (r = 0.494, n = 45, P = 0.002) in group 2, (B) L and the J₄₅ vector describing the actual change in astigmatism between 1 and 2 months in group 2, where J₄₅ (by autorefractometry) =0.287L-0.160 (r = 0.487, n = 38, P = 0.001) and J₄₅ (by subjective refraction) =0.281L-0.102 (r = 0.490, n = 38, P = 0.002), and (C) J₄₅ and ΔK between 2 and 3 months in group 2, where J₄₅ (by subjective refraction) =0.086ΔK-0.063 (r = 0.378, n = 26, P = 0.020).Conclusion:Changes in the location of the first Purkinje image relative to the pupil center after phacoemulsification contributes to changes in refractive astigmatism. However, the relationship between the induced change in astigmatism resulting from a change in L is not straightforward.     

The effect of corneal crosslinking on the rigidity of the cornea estimated using a modified algorithm for the Schiøtz tonometer

Purpose:The aim of this study was to test a method for estimating corneal rigidity before and after cross-linking (CXL) using a Schiøtz tonometer.Methods:The study was performed in the Kyiv City Clinical Ophthalmological Hospital “Eye Microsurgical Center”, Ukraine. This was a prospective, consecutive, randomized, masked, case-by-case, clinical study. Corneal rigidity, indicated by the gradient (G) between lg applied weight and corresponding lg scale reading during Schiøtz tonometry, were obtained by increasing (A-mode) then reducing (D-mode) weights by two operators [A] in keratoconus, post-CXL and control subjects for estimation of (i) interoperator and (ii) intersessional errors, (iii) intergroup differences; [B] before and after CXL. Central corneal thickness CCT was measured by scanning slit pachymetry. ANOVA, t tests, linear regression were the statistical tools used.Results:Average interoperator difference (ΔG) was –0.120 (SD = ±0.294, 95%CI = –0.175 to –0.066). A significant correlation between ΔG and the mean of each pair of G values was found (r = –0.196, n = 112, P = 0.038). Intersessional differences in mean G values were insignificant (P > 0.05). There was a significant correlation between G at first session (X₁) and difference between sessions (ΔG) [Operator 1, ΔG = 0.598x₁–0.461, r = 0.601, n = 27, P = 0.009]. Significant intergroup differences in G were found (Operator 1, one-way ANOVA, F = 4.489, P = 0.014). The difference (Δ) between the pre-(X₂) and post-CXL treatment G values was significantly associated with the pre-CXL treatment value (Operator 1, Δ = 1.970x₂-1.622, r = 0.642, n = 18, P = <.001). G values were correlated with CCT in keratoconus and post-CXL.Conclusion:Corneal rigidity (G) estimated using the Schiøtz tonometer can be useful for detecting changes after CXL. However, G values are linked to CCT, can vary from time-to-time and the procedure is operator dependent.     

The effect of potassium dichromate on free radical processes in goldfish: possible protective role of glutathione

The effects of 96 h exposure to Cr(6+) (added as potassium dichromate) on the status of antioxidant defenses and markers of oxidative damage were evaluated in three tissues of goldfish, Carassius auratus. Fish exposure to high dichromate concentrations, 10 and 50mg/l, increased protein carbonyl levels in brain and liver, but not in kidney. Chromium exposure also increased concentrations of lipid peroxides in brain (at 5mg/l) and liver (10mg/l), but not in kidney. The concentrations of reduced glutathione (GSH) were higher in the liver of goldfish treated with 5-50mg/l Cr(6+) than in controls, but in kidney only the 5mg/l-treated group showed increased GSH levels. Dichromate at 1mg/l increased the concentration of oxidized glutathione (GSSG) in liver and kidney by 80% and 60%, respectively, whereas at 10 and 50mg/l the levels of GSSG decreased by 50% in kidney. These results indicate that the dichromate concentrations used induced oxidation of lipids and proteins in goldfish tissues in a concentration- and tissue-specific manner. Also, the redox status of fish tissues was affected in a concentration- and tissue-specific manner. The activities of glutathione reductase increased in all three tissues in response to dichromate treatment, increasing by approximately 2-fold in brain and liver in goldfish treated with 50mg/l Cr(6+). Dichromate treatment did not change the activities of SOD, catalase or GST in brain, but reduced the activities of SOD in liver and kidney, and catalase in liver. The results suggest that the glutathione system may be responsible for protecting against the deleterious effects of dichromate in fish and indicate the possible development of an adaptive response during the 96 h treatment with the toxicant.     

A βIV-spectrin/CaMKII signaling complex is essential for membrane excitability in mice

Ion channel function is fundamental to the existence of life. In metazoans, the coordinate activities of voltage-gated Na⁺ channels underlie cellular excitability and control neuronal communication, cardiac excitation-contraction coupling, and skeletal muscle function. However, despite decades of research and linkage of Na⁺ channel dysfunction with arrhythmia, epilepsy, and myotonia, little progress has been made toward understanding the fundamental processes that regulate this family of proteins. Here, we have identified β_IV-spectrin as a multifunctional regulatory platform for Na⁺ channels in mice. We found that β_IV-spectrin targeted critical structural and regulatory proteins to excitable membranes in the heart and brain. Animal models harboring mutant β_IV-spectrin alleles displayed aberrant cellular excitability and whole animal physiology. Moreover, we identified a regulatory mechanism for Na⁺ channels, via direct phosphorylation by β_IV-spectrin–targeted calcium/calmodulin-dependent kinase II (CaMKII). Collectively, our data define an unexpected but indispensable molecular platform that determines membrane excitability in the mouse heart and brain.     

Identification of Nordic Berries with Beneficial Effects on Cognitive Outcomes and Gut Microbiota in High-Fat-Fed Middle-Aged C57BL/6J Mice

High-fat diets are associated with neuronal and memory dysfunction. Berries may be useful in improving age-related memory deficits in humans, as well as in mice receiving high-fat diets. Emerging research has also demonstrated that brain health and cognitive function may be related to the dynamic changes in the gut microbiota. In this study, the impact of Nordic berries on the brain and the gut microbiota was investigated in middle-aged C57BL/6J mice. The mice were fed high-fat diets (60%E fat) supplemented with freeze-dried powder (6% dwb) of bilberry, lingonberry, cloudberry, blueberry, blackcurrant, and sea buckthorn for 4 months. The results suggest that supplementation with bilberry, blackcurrant, blueberry, lingonberry, and (to some extent) cloudberry has beneficial effects on spatial cognition, as seen by the enhanced performance following the T-maze alternation test, as well as a greater proportion of DCX-expressing cells with prolongation in hippocampus. Furthermore, the proportion of the mucosa-associated symbiotic bacteria Akkermansia muciniphila increased by 4–14 times in the cecal microbiota of mice fed diets supplemented with lingonberry, bilberry, sea buckthorn, and blueberry. These findings demonstrate the potential of Nordic berries to preserve memory and cognitive function, and to induce alterations of the gut microbiota composition.     

Comparison of three chiral stationary phases with respect to their enantio- and diastereoselectivity for cyclic beta-substituted alpha-amino acids.

Three chiral stationary phases were examined for the enantio- and diastereoseparation of cycloaliphatic beta-substituted alpha-quaternary alpha-amino acids. Resolution of diastereomeric analytes is feasible with a chiral crown ether based column, whereas the separation of enantiomers, except for one pair of amino acids, could not be achieved. The two chiral stationary phases with the glycopeptide antibiotic teicoplanin and with the copper(II)-D-penicillamine complex, respectively, are, however, both very potent in the separation of the enantiomeric, as well as of the diastereomeric amino acids. A baseline separation of all four stereoisomeric forms in one chromatographic run was possible with the exception of one type of amino acid. The results of the method development are presented in this paper.     

βIV-Spectrin and CaMKII facilitate Kir6.2 regulation in pancreatic beta cells

Identified over a dozen years ago in the brain and pancreatic islet, β_IV-spectrin is critical for the local organization of protein complexes throughout the nervous system. β_IV-Spectrin targets ion channels and adapter proteins to axon initial segments and nodes of Ranvier in neurons, and β_IV-spectrin dysfunction underlies ataxia and early death in mice. Despite advances in β_IV-spectrin research in the nervous system, its role in pancreatic islet biology is unknown. Here, we report that β_IV-spectrin serves as a multifunctional structural and signaling platform in the pancreatic islet. We report that β_IV-spectrin directly associates with and targets the calcium/calmodulin-dependent protein kinase II (CaMKII) in pancreatic islets. In parallel, β_IV-spectrin targets ankyrin-B and the ATP-sensitive potassium channel. Consistent with these findings, β_IV-spectrin mutant mice lacking CaMKII- or ankyrin-binding motifs display selective loss of expression and targeting of key protein components, including CaMKIIδ. β_IV-Spectrin–targeted CaMKII directly phosphorylates the inwardly-rectifying potassium channel, Kir6.2 (alpha subunit of K_ATP channel complex), and we identify the specific residue, Kir6.2 T224, responsible for CaMKII-dependent regulation of K_ATP channel function. CaMKII-dependent phosphorylation alters channel regulation resulting in K_ATP channel inhibition, a cellular phenotype consistent with aberrant insulin regulation. Finally, we demonstrate aberrant K_ATP channel phosphorylation in β_IV-spectrin mutant mice. In summary, our findings establish a broader role for β_IV-spectrin in regulation of cell membrane excitability in the pancreatic islet, define the pathway for CaMKII local control in pancreatic beta cells, and identify the mechanism for CaMKII-dependent regulation of K_ATP channels.The coordinate expression, localization, and regulation of ion channels are critical for excitable cell biology, namely, neuronal transmission, cardiac excitation–contraction coupling, endocrine/exocrine secretory regulation, and skeletal muscle function. The spectrin family of polypeptides, originally discovered as a critical component of the erythrocyte plasma membrane over 30 y ago, is now known to play important structural roles in both nonexcitable and excitable cells (1, 2). Spectrin alpha (α) and beta (β) subunits form antiparallel dimers that self-associate to form tetramers, creating a submembranous scaffolding network anchored to actin filaments via β-spectrin (2). Whereas two genes encode α-spectrin polypeptides (α_I-, α_II-spectrin), spectrin family diversity is created through assembly of α-spectrin products with five β-spectrin genes (encoding β_I–β_V-spectrin) (2). Over a dozen years ago, β_IV-spectrin was identified in brain and pancreatic islets (3). Since these findings, a host of studies have identified β_IV-spectrin as a critical player for defining local membrane domains in the nervous system (4–6). Notably, β_IV-spectrin complexes serve essential roles in targeting ankyrin and associated membrane proteins, to axon initial segments and nodes of Ranvier. Dysfunction in β_IV-spectrin leads to aberrant membrane protein targeting, cell and animal phenotypes, and early death (6, 7). Despite these striking findings in brain, the role of β_IV-spectrin in pancreatic islets is unknown.Here, we define a role for β_IV-spectrin in regulating membrane excitability in islets. β_IV-spectrin directly associates with ankyrin-B and Ca²⁺/calmodulin-dependent protein kinase II (CaMKII). We define the structural requirements for these interactions and show that β_IV-spectrin associates with additional islet proteins, including actin and the ATP sensitive potassium channel (K_ATP channel). Notably, β_IV-spectrin mutant mice that lack ankyrin- or CaMKII-binding activity display coordinate loss of ankyrin, K_ATP channel, and CaMKII expression and targeting. Finally, we demonstrate that β_IV-spectrin is critical for CaMKII-dependent regulation of the K_ATP channel through Kir6.2 residue T224 and show that Kir6.2 T224 phosphorylation is altered in β_IV-spectrin mutant mice. In summary, our findings provide initial insight into the role of β_IV-spectrin in the expression, targeting, and regulation of critical membrane and signaling proteins in islets.     

Maternal Height and the Risk of Preterm Birth and Low Birth Weight: A Systematic Review and Meta-Analyses

ObjectivePreterm birth (PTB) and low birth weight (LBW) are the leading causes of neonatal morbidity and mortality, but the effect of maternal height on these outcomes continues to be debated. Our objective was to determine the relationships between maternal height and PTB and LBW.Data SourcesMedline and EMBASE were searched from their inceptions.Study SelectionStudies with a reference group that assessed the effect of maternal height on PTB (< 37 weeks) and LBW (< 2500 grams) in singletons were included.Data ExtractionData were extracted independently by two reviewers.Data SynthesisFifty-six studies were included involving 333 505 women. In the cohort studies, the unadjusted risk of PTB in short-statured women was increased (relative risk [RR] 1.23; 95% CI 1.11 to 1.37), as was the unadjusted risk of LBW (RR 1.81; 95% CI 1.47 to 2.23), although not all of the studies with adjusted data found the same association. Maternal tall stature was not associated with PTB (unadjusted RR 0.97; 95% CI 0.82 to 1.14), although LBW was decreased (unadjusted RR 0.56; 95% CI 0.46 to 0.69), but not in the adjusted data.ConclusionFrom our complete systematic review and metaanalyses, to our knowledge the first in this area, we conclude that short-statured women have higher unadjusted risks of PTB and LBW and tall women have approximately one half the unadjusted risk of LBW of women of reference height.