Association Between IL-6 Concentration and Diabetes-Related Variables in DM1 Patients with and without Microvascular Complications

Interleukin 6 (IL-6) plays an important role in the initiation and acceleration of chronic inflammation and could contribute to development of microvascular complications in patients with type 1 diabetes (DM1). Therefore, this study was aimed to investigate the association between concentration of IL-6 in relation to glucose control, lipid profile, and body mass index (BMI) in 69 DM1 patients subdivided according to the absence or presence of microvascular complications. BMI, level of fasting plasma glucose (FPG), and concentrations of total cholesterol (TCH), LDL cholesterol (LDL-C), and IL-6 were higher in DM1 patients compared to the control group. In DM1 patients, IL-6 concentration was positively correlated with level of FPG, LDL-C, TCH concentrations, and BMI. These correlations were stronger in the subgroup of patients with microvascular complications. In addition, BMI independently influences IL-6 concentration in DM1 patients. In conclusion, elevated IL-6 concentration is associated with diabetes-related variables which could accelerate progression of microvascular complications in DM1 patients.     

Low carbohydrate, high protein diet promotes atherosclerosis in apolipoprotein E/low-density lipoprotein receptor double knockout mice (apoE/LDLR(-/-))

Although in apoE/LDLR(-/-) mice atherosclerotic plaques develop spontaneously, various atherogenic diets (e.g. Western diet) are frequently used to accelerate the disease in this model. The objective of this study was to compare the effects on atherosclerosis of Western diet and other types of high-fat, high cholesterol, hypertriglyceridemic diets with the effects of the low carbohydrate, high protein (LCHP) diet. 16-18 week old mice with pre-established atherosclerosis were assigned to experimental groups and fed for the next 10 weeks with control diet, margarine diet (margarine 7%), hypertrigliceridemic diet (fructose 62%), high-fat diet (Western diet), high cholesterol diet (egg yolk diet) or with LCHP diet. No differences in body weight were observed among experimental groups. Plasma cholesterol concentration was significantly increased in egg yolk diet- and LCHP diet-fed apoE/LDLR(-/-) mice as compared to other types of diets. Plasma concentration of triacylglycerols was significantly elevated in egg yolk diet- and LCHP diet-fed apoE/LDLR(-/-) mice. The area of atherosclerotic plaques in the aortic root was substantially increased in LCHP diet-fed mice as compared to other types of diets. Furthermore, in brachiocephalic arteries of LCHP diet-fed mice there was evidence of plaque rupture. In conclusion, the LCHP diet promoted atherosclerosis in apoE/LDLR(-/-) mice more intensively than classical Western diet and favored the development of unstable lesions.     

Two common mutations in the CLN2 gene underlie late infantile neuronal ceroid lipoluscinosis

Zhong N, Wisniewski KE, Hartikainen J, Ju W, Moroziewicz DN, McLendon L, Sklower Brooks S, Brown WT. Two common mutations in the CLN2 gene underlie late infantile neuronal ceroid lipofuscinosis
Late infantile neuronal ceroid lipofuscinosis (LINCL) is one of the most common pediatric neuronal degenerative disorders. A candidate gene underlying this disease, designated CLN2, was recently cloned and the gene product was characterized as a lysosomal pepstatin-insensitive carboxypeptidase (LPIC). Four mutations were identified in CLN2 from three unrelated LINCL individuals. To investigate further the mutation frequency in LINCL, we screened 16 LINCL probands for these four mutations. The previously reported intronic mutation, T523–1 G°C, was found in 56% (9/16) of the cases, of which two were homozygous and accounted for 34% (11/32) of LINCL chromosomes. The previously reported nonsense mutation, 636 C→T leading to R208stop, was found in 31% (5/16) of the cases, including one ho-mozygote and accounted for 19% (6/32) of LINCL chromosomes. Two previously described missense mutations, 1107 T°C and 1108 G→A, were not detected in any of these 16 probands. In total, the two observed mutations, T523–1 G°C and 636 C→T, accounted for 53% (17/32) of LINCL alleles. Thus, one or both mutations were seen in 11 (69%) cases and no mutation has yet been identified in five. Our finding that these two mutations are common in LINCL cases adds further evidence in support of the idea that dysfunction of LPIC underlies LINCL. Positive molecular testing can now complement clinical diagnosis of LPIC and will allow for pre-natal diagnosis for subsequent pregnancies.     

Hybrid compound based on diethylenetriaminecopper(ii) cations and scarce V-monosubstituted β-octamolybdate as water oxidation catalyst

Herein, we report on a new hybrid compound (NH₄){[Cu(dien)(H₂O)₂]₂[β-VMo₇O₂₆]}·1.5H₂O (1), where dien = diethylenetriamine, containing an extremely rare mixed-metal pseudo-octamolybdate cluster. An ex situ EPR spectroscopy provided insights into the formation of paramagnetic species in reaction mixture and in solution of 1. The magneto-structural correlations revealed weak antiferromagnetic exchange interactions between the [Cu(dien)]²⁺ cations transmitted by intermolecular pathways. The cyclic voltammetry showed the one-electron process associated with the Cu³⁺/Cu²⁺ oxidation followed by the multi-electron catalytic wave due to water oxidation with a faradaic yield of 86%. The title compound was thus employed in homogeneous water oxidation catalysis using tris(bipyridine)ruthenium photosensitizer. At pH 8.0, efficiency of the catalytic system attained 0.19 turnovers per second supported by the relatively mild water oxidation overpotential of 0.54 V.

A new hybrid compound (NH₄){[Cu(dien)(H₂O)₂]₂[β-VMo₇O₂₆]}·1.5H₂O was employed in homogeneous water oxidation catalysis. At pH 8.0, its efficiency attains 0.19 turnovers per second, supported by the relatively mild water oxidation overpotential of 0.54 V.     

Percutaneous vertebroplasty in the treatment of diseases causing vertebral bone loss

Background. Percutaneous vertebroplasty involves the injection of acrylic surgical cement into the vertebral body. The basic principles of vertebroplasty and the authors' own clinical experiences are described. Material and methods. Between November 1999 and January 2005 the authors performed percutaneous vertebroplasty on 75 patients: 45 with osteoporotic compression fractures, 15 with angiomas of the vertebral bodies, and 12 patients with spinal neoplasms. There were also 3 patients with coexisting spinal angiomas and osteoporotic compression fractures. All these patients were treated under local anesthesia. Cement injections were realized by the transpedicular approach under fluoroscopic guidance; in certain cases a CT-guided approach was used. The clinical outcome was assessed based on follow-up examinations, the Oswestry questionnaire, and the Visual Analog Pain Scale. Plain x-rays or CT scans were made for purposes of radiological evaluation. Results. Follow-up examinations revealed pain relief or significant reduction of pain in 89% of the patients. In 2 cases (3%) vertebroplasty was complicated by intracanal leakage of cement. Conclusions. Percutaneous vertebroplasty is well tolerated by patients. Filling with cement is effective in the treatment of osteoporotic compression fractures and of vertebral angiomas.     

The hydrochemistry of peatland lakes as a result of the morphological characteristics of their basins

The physico-chemical water characteristics and basin morphology of 10 well-preserved Pomeranian peatland lakes were examined. These are acidic (pH 3.95–5.99), softwater (1.5 ±0.9 mg Ca dm^?3), and oligotrophic water bodies. Their hydrochemical conditions differentiate them into two groups: poor (3.04 ±2.77 mg C dm^?3) and rich (10.36 ±7.27 mg C dm^?3) in organic carbon compounds. They differ in water colour (p = 0.02), humic acid concentration (p<0.001), redox potential (p = 0.007), and irradiance (PAR; p = 0.03). The hydrochemistry of the lakes is determined by their basin morphology, which affects the water colour and the concentrations of humic acids and organic carbon compounds.     

A modeling approach for compounds affecting body composition

Body composition and body mass are pivotal clinical endpoints in studies of welfare diseases. We present a combined effort of established and new mathematical models based on rigorous monitoring of energy intake (EI) and body mass in mice. Specifically, we parameterize a mechanistic turnover model based on the law of energy conservation coupled to a drug mechanism model. Key model variables are fat-free mass (FFM) and fat mass (FM), governed by EI and energy expenditure (EE). An empirical Forbes curve relating FFM to FM was derived experimentally for female C57BL/6 mice. The Forbes curve differs from a previously reported curve for male C57BL/6 mice, and we thoroughly analyse how the choice of Forbes curve impacts model predictions. The drug mechanism function acts on EI or EE, or both. Drug mechanism parameters (two to three parameters) and system parameters (up to six free parameters) could be estimated with good precision (coefficients of variation typically <20 % and not greater than 40 % in our analyses). Model simulations were done to predict the EE and FM change at different drug provocations in mice. In addition, we simulated body mass and FM changes at different drug provocations using a similar model for man. Surprisingly, model simulations indicate that an increase in EI (e.g. 10 %) was more efficient than an equal lowering of EI. Also, the relative change in body mass and FM is greater in man than in mouse at the same relative change in either EI or EE. We acknowledge that this assumes the same drug mechanism impact across the two species. A set of recommendations regarding the Forbes curve, vehicle control groups, dual action on EI and loss, and translational aspects are discussed. This quantitative approach significantly improves data interpretation, disease system understanding, safety assessment and translation across species.