Effect of l-arginine on metabolism of polyamines in rat’s brain with extrahepatic cholestasis

Cholestatic encephalopathy results from accumulation of unconjugated bilirubin and hydrophobic bile acids in the brain. The aim of this study was to determine disturbances of polyamine metabolism in the brains of rats with experimental extrahepatic cholestasis and the effects of l-arginine administration. Wister rats were divided into groups: I: sham-operated, II: rats treated with l-arginine, III: animals with bile-duct ligation (BDL), and IV: cholestatic-BDL rats treated with l-arginine. Increased plasma γ-glutamyltransferase and alkaline phosphatase activity and increased bile-acids and bilirubin levels in BDL rats were reduced by administration of l-arginine (P < 0.001). Cholestasis increased the brain’s putrescine (P < 0.001) and decreased spermidine and spermine concentration (P < 0.05). The activity of polyamine oxidase was increased (P < 0.001) and diamine oxidase was decreased (P < 0.001) in the brains of BDL rats. Cholestasis increased the activity of arginase (P < 0.05) and decreased the level of citrulline (P < 0.001). Administration of l-arginine in BDL rats prevents metabolic disorders of polyamines and establishs a neuroprotective role in the brain during cholestasis.     

Carbon partitioning to cellulose synthesis

This article discusses the importance and implications of regulating carbon partitioning to cellulose synthesis, the characteristics of cells that serve as major sinks for cellulose deposition, and enzymes that participate in the conversion of supplied carbon to cellulose. Cotton fibers, which deposit almost pure cellulose into their secondary cell walls, are referred to as a primary model system. For sucrose synthase, we discuss its proposed role in channeling UDP-Glc to cellulose synthase during secondary wall deposition, its gene family, its manipulation in transgenic plants, and mechanisms that may regulate its association with sites of polysaccharide synthesis. For cellulose synthase, we discuss the organization of the gene family and how protein diversity could relate to control of carbon partitioning to cellulose synthesis. Other enzymes emphasized include UDP-Glc pyrophosphorylase and sucrose phosphate synthase. New data are included on phosphorylation of cotton fiber sucrose synthase, possible regulation by Ca²⁺ of sucrose synthase localization, electron microscopic immunolocalization of sucrose synthase in cotton fibers, and phylogenetic relationships between cellulose synthase proteins, including three new ones identified in differentiating tracheary elements of Zinnia elegans. We develop a model for metabolism related to cellulose synthesis that implicates the changing intracellular localization of sucrose synthase as a molecular switch between survival metabolism and growth and/or differentiation processes involving cellulose synthesis. Abbreviations: CesA, cellulose synthase; Csl, cellulose-like synthase (genes); DCB, dichlobenil; DPA, days after anthesis; SPS, sucrose phosphate synthase; SuSy, sucrose synthase; P-SuSy, particulate SuSy; S-SuSy, soluble SuSy     

Population variability of nonacosan-10-ol and n-alkanes in needle cuticular waxes of Macedonian pine (Pinus peuce GRISEB.)

This is the first report on population variability of nonacosan-10-ol and n-alkanes in needle epicuticular waxes of Macedonian pine (Pinus peuce GRISEB.) Hexane extracts of needle samples, originating from two natural populations in Montenegro (Zeletin and Sjekirica) and from one population in Serbia (Mokra Gora) were analyzed by gas chromatography (GC) and gas chromatography/mass spectrometry (GC/MS). The amount of nonacosan-10-ol varied individually from 41.3 to 72.31% (average 55.9%), with the Sjekirica population being statistically divergent (64.4% on average). The results showed n-alkanes in epicuticular waxes ranging from C?? to C??. The most abundant alkanes were C??, C??, C??, and C?? (15.5, 11.1, 10.6, and 10.5% on average, resp.). The carbon preference index of Pinus peuce ranged from 1.0 to 4.3 (1.9 on average). Average chain length ranged from 18.4 to 27.7 (average 25.7). A high level of inidividual quantitative variation in all of these hydrocarbon parameters was also detected. These results were compared with published data on other species from the Pinus genus.     

Cardiac autotransplantation and ex vivo surgical repair of giant left atrium: a case presentation

Background

Chronic Mitral Valve disease is strongly associated with Left atrial enlargement; the condition has a high mortality risk. Clinical manifestations include atrial fibrillation, pulmonary hypertension, thromboembolic events, and in cases of Giant Left Atrium (GLA) and a distorted cardiac silhouette. Full sternotomy, conventional open-heart surgery, reductive atrioplasty and atrioventricular valve repair are required to resolve symptoms. However, these procedures can be complicated due to the posterior location of the GLA and concomitant right lateral protrusion.Cardiac autotransplantation is superior under these conditions; it provides improved visual access to the posterior atrial wall and mitral valve, hence, facilitates corrective surgical procedures.We aimed to assess the clinical outcome of patients undergoing cardiac autotransplantation as the primary treatment modality to resolve GLA. Moreover, we evaluated the procedural safety profile and technical feasibility.

Case presentation

Four patients, mean EuroSCORE II of 23.7%?±?7.7%, presented with heart failure, atrial fibrillation, left atrial diameter?>?6.5?cm and a severe distorted cardiac silhouette; X-ray showed prominent right lateral protrusion.We performed cardiac autotransplantation using continuous retrograde perfusion with warm blood supplemented with glucose followed by atrioplasty, atrial plication, valve annuloplasty and valve repair on the explanted beating heart. The surgical approach reduced the left atrial area, mean reduction was ??90.71?cm² [CI95% -153.3?cm² to ??28.8?cm², p?=?0.02], and normalized pulmonary arterial pressure, mean decrease ??11.25?mmHg [CI95% -15.23?mmHg to ??7.272?mmHg, p?=?0.003]. 3 out of 4 patients experienced an uneventful postoperative course; 2 out of 4 patients experienced a transient return to sinus rhythm following surgery. One was operated on in 2017 and is still in good condition; two other patients survived for more than 10 years; Kaplan-Meier determined median survival is 10.5?years.

Conclusions

Cardiac autotransplantation is an elegant surgical procedure that facilitates the surgical remodelling of Giant Left Atrium. Surgical repair on the ex vivo beating heart, under continuous warm blood perfusion, is a safe procedure applicable also to high-risk patients.

     

Studies in the genus Capsicum

Meiotic chromosomes in the P.M.C.'s of cultivated peppers regularly show pycnotic degeneration and stickiness together with defective spindle movement and cytokinesis. These irregularities are held to follow from the genotypic unbalance which results from the inbreeding which has accompanied cultivation.This paper was prepared in the Department of Genetics, University of Birmingham while the author was a recipient of a British Council Scholarship.     

Glutamine Synthetase in Muscle Is Required for Glutamine Production during Fasting and Extrahepatic Ammonia Detoxification

The main endogenous source of glutamine is de novo synthesis in striated muscle via the enzyme glutamine synthetase (GS). The mice in which GS is selectively but completely eliminated from striated muscle with the Cre-loxP strategy (GS-KO/M mice) are, nevertheless, healthy and fertile. Compared with controls, the circulating concentration and net production of glutamine across the hindquarter were not different in fed GS-KO/M mice. Only a ∼3-fold higher escape of ammonia revealed the absence of GS in muscle. However, after 20 h of fasting, GS-KO/M mice were not able to mount the ∼4-fold increase in glutamine production across the hindquarter that was observed in control mice. Instead, muscle ammonia production was ∼5-fold higher than in control mice. The fasting-induced metabolic changes were transient and had returned to fed levels at 36 h of fasting. Glucose consumption and lactate and ketone-body production were similar in GS-KO/M and control mice. Challenging GS-KO/M and control mice with intravenous ammonia in stepwise increments revealed that normal muscle can detoxify ∼2.5 μmol ammonia/g muscle·h in a muscle GS-dependent manner, with simultaneous accumulation of urea, whereas GS-KO/M mice responded with accumulation of glutamine and other amino acids but not urea. These findings demonstrate that GS in muscle is dispensable in fed mice but plays a key role in mounting the adaptive response to fasting by transiently facilitating the production of glutamine. Furthermore, muscle GS contributes to ammonia detoxification and urea synthesis. These functions are apparently not vital as long as other organs function normally.     

A New Computational Method for Membrane Compressibility: Bilayer Mechanical Thickness Revisited

Because lipid bilayers can bend and stretch in ways similar to thin elastic sheets, physical models of bilayer deformation have utilized mechanical constants such as the moduli for bending rigidity $\left({\kappa }_C\right)$ and area compressibility (K_A). However, the use of these models to quantify the energetics of membrane deformation associated with protein-membrane interactions, and the membrane response to stress is often hampered by the shortage of experimental data suitable for the estimation of the mechanical constants of various lipid mixtures. Although computational tools such as molecular dynamics simulations can provide alternative means to estimate K_A values, current approaches suffer significant technical limitations. Here, we present a novel, to our knowledge, computational framework that allows for a direct estimation of K_A values for individual bilayer leaflets. The theory is based on the concept of elasticity and derives K_A from real-space analysis of local thickness fluctuations sampled in molecular dynamics simulations. We explore and validate the model on a large set of single and multicomponent bilayers of different lipid compositions and sizes, simulated at different temperatures. The calculated bilayer compressibility moduli agree with values estimated previously from experiments and those obtained from a standard computational method based on a series of constrained tension simulations. We further validate our framework in a comparison with an existing polymer brush model and confirm the polymer brush model’s predicted linear relationship with proportionality coefficient of 24, using elastic parameters calculated from the simulation trajectories. The robustness of the results that emerge from the method allows us to revisit the origins of the bilayer mechanical (compressible) thickness and in particular its dependence on acyl-chain unsaturation and the presence of cholesterol.     

Circulating nucleic acids in type 1 diabetes may modulate the thymocyte turnover rate

The autoimmunity of type 1 diabetes is associated with T-cell hyperactivity. Current study was designed to examine the effect of circulating ribonucleic acids (RNAs), isolated from type 1 diabetic patients on proliferative, apoptotic and inflammatory potential of rat thymocytes. Rat thymocytes were assayed for proliferating nuclear cell antigen (PCNA), Bcl-2, Bax and NF-κB level, using the flow cytometric and fluorometric assays. Cells were allocated into groups, treated with RNAs purified from plasma of juvenile diabetics, adult type 1 diabetic patients, control healthy children, healthy adult persons, nucleic acids and polynucleotide standards (RNA, polyC, PolyA, PolyIC, and CpG). The upregulation of PCNA and Bcl-2 protein and downregulation of Bax protein and NF-κB was shown when the thymocytes where incubated with RNA purified from plasma of juvenile type 1 diabetic patients. The dysregulation of inflammatory cascade and central tolerance may be a defect in autoimmune diseases related to innate immunity leading to corresponding alteration in adaptive immune response.     

Sesquiterpene lactones from Achillea collina J. Becker ex Reichenb

The flower heads of Achillea collina afforded 31 individual sesquiterpene lactones, among which nine guaianolides (1, 16, 20, 21, 23, 27-30), a germacranolide (18) and a dimeric guaianolide (31) were found to be new natural products. The lactones 2-4, 12, 14, 15, 17, 19 and 25 were isolated for the first time from the investigated species. Their structures were established by spectral methods.