Clinical variability in mucolipidosis III (pseudo-Hurler polydystrophy)

Mucolipidosis III (MLIII) is caused by a deficiency of UDP-N-acetylglucosamine:lysosomal enzyme N-acetylglucosamine 1-phosphotransferase (phosphotransferase) activity, an enzyme responsible for the formation of the recognition marker on most lysosomal enzymes. The consequences of this defect are impairment of many lysosomal catabolic processes. A deficiency of phosphotransferase activity causes two phenotypically different diseases: mucolipidosis II and a rare form, mucolipidosis III (pseudo-Hurler polydystrophy). The purpose of this article is to report three patients with ML III, presenting quite different clinical courses: Patient 1 is a 13-year-old girl in whom the only symptoms of ML III were joint stiffness of the hands. Patients 2 and 3 are sibs: a 5-year-old boy with a severe form of ML III and his 2-year-old sister, who is less affected than her brother at the same age. A comparison of biochemical results and the clinical picture of our patients with cases in the literature is presented.     

Atorvastatin affects several angiogenic mediators in human endothelial cells.

The pleiotropic effects of statins, inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, have been recently extended to the modulation of angiogenesis. Here, to get more insight into the statins action, the authors have investigated the effect of atorvastatin on the expression of several angiogenic and inflammatory genes in human umbilical endothelial cells (HUVECs). Atorvastatin was proangiogenic at the dose of 10 nM, and antiangiogenic at the concentrations of 1 to 10 micro M. Moreover, these higher concentrations inhibited also the proliferation of HUVECs induced by vascular endothelial growth factor (VEGF). Lower doses of atorvastatin did not influence endothelial cell proliferation. Importantly, atorvastatin at the micromolar concentrations diminished the production of interleukin (IL)-8, a proinflammatory and proangiogenic chemokine, and inhibited the synthesis of urokinase plasminogen activator (uPA), a potent proinflammatory mediator. However, it decreased also the expression of plasminogen activator inhibitor-1 (PAI-1) and thrombospondin-1 (TSP-1), the inhibitors of angiogenesis. Atorvastatin stimulated the expression of angiopoietin (Ang)-2 and moderately enhanced the expression of endothelial nitric oxide synthase (eNOS), whereas heme oxygenase-1 (HO-1) was not significantly affected. In conclusion, the present findings points to other angiogenesis-related effects of atorvastatin, which may be of relevance to the beneficial influence of statins in cardiovascular system.     

Dopamine, serotonin and noradrenaline changes in the striatum of C57BL mice following myelin oligodendrocyte glycoprotein (MOG) 35-55 and complete Freund adjuvant (CFA) administration.

Many data suggest involvement of inflammation in neurodegeneration. However, the exact mechanisms of this cooperation are poorly understood. We have previously shown that induction of inflammatory reaction, both before and after injury of the striatum, affects regeneration of dopaminergic neurons. In the present research we studied the role of inflammatory reaction in non-injured striatum. We used myelin oligodendrocyte glycoprotein (MOG) 35-55 in complete Freund's adjuvant (CFA) to elicit experimental autoimmune encephalomyelitis (EAE) mice model. As determined by HPLC, striatal dopamine (DA) and serotonin levels in mice treated with either MOG 35-55 in CFA or CFA alone were significantly higher compared to vehicle-treated controls on 13th day after induction. The ratio of homovanilic acid/dopamine (HVA/DA) and 3, 4 dihydroxyphenylacetic acid/dopamine (DOPAC/DA) were significantly lower in the MOG and CFA groups on 13th day, indicating decreased DA metabolism. Noradrenaline (NA) concentration did not differ between groups. Moreover, the striatal mRNA IL-1beta and TNF-alpha levels were elevated during induction phase of EAE in both groups, as determined by RT-PCR. Our data indicate regulatory connection between dopaminergic and immune systems.     

Involvement of the RE V3 gene in the methylated base-excision repair system. Co-operation of two DNA polymerases, δ and Rev3p, in the repair of MMS-induced lesions in the DNA of Saccharomyces cerevisiae

The ability of four yeast DNA polymerase mutant strains to carry out the repair of DNA treated with MMS was studied. Mutation in DNA polymerase Rev3, as well as the already known mutation in the catalytic subunit of DNA polymerase δ, were both found to lead to the accumulation of single-strand breaks, which indicates defective repair. A double-mutant strain carrying mutations in DNA polymerase δ and a deletion in the REV3 gene had a complete repair defect, both at permissive (23°C) and restrictive (38°C) temperatures, which was not observed in other pairwise combinations of tested polymerase mutants. Other polymerases are not involved in the repair of exogenous DNA methylation damage, since neither mutation in the DNA polymerase ɛ, nor deletion in the DNA polymerase IV (β₇₀) gene, caused defective repair. The data obtained suggest that DNA polymerases δ and Rev3p are both necessary to perform repair synthesis in the base-excision repair of methylation damage. The results are discussed in the light of current concepts on the role of DNA polymerase Rev3 in mutagenesis. Received: 18 November / 10 December 1996     

Does Drinking Coffee and Tea Affect Bone Metabolism in Patients with Inflammatory Bowel Diseases?

Patients suffering from Crohn’s disease and ulcerative colitis are at higher risk of osteoporosis due to lower bone mineral density. Risk factors of osteoporosis are divided into unmodifiable, namely, age, gender, genetic factors, as well as modifiable, including diet, level of physical activity, and the use of stimulants. Coffee and tea contain numerous compounds affecting bone metabolism. Certain substances such as antioxidants may protect bones; other substances may increase bone resorption. Nevertheless, the influence of coffee and tea on the development and course of inflammatory bowel diseases is contradictory.     

A Vicious Cycle of Osteosarcopenia in Inflammatory Bowel Diseases—Aetiology,Clinical Implications and Therapeutic Perspectives

Sarcopenia is a disorder characterized by a loss of muscle mass which leads to the reduction of muscle strength and a decrease in the quality and quantity of muscle. It was previously thought that sarcopenia was specific to ageing. However, sarcopenia may affect patients suffering from chronic diseases throughout their entire lives. A decreased mass of muscle and bone is common among patients with inflammatory bowel disease (IBD). Since sarcopenia and osteoporosis are closely linked, they should be diagnosed as mutual consequences of IBD. Additionally, multidirectional treatment of sarcopenia and osteoporosis including nutrition, physical activity, and pharmacotherapy should include both disorders, referred to as osteosarcopenia.     

What Role Does the Endocannabinoid System Play in the Pathogenesis of Obesity?

The endocannabinoid system (ECS) is an endogenous signaling system formed by specific receptors (cannabinoid type 1 and type 2 (CB₁ and CB₂)), their endogenous ligands (endocannabinoids), and enzymes involved in their synthesis and degradation. The ECS, centrally and peripherally, is involved in various physiological processes, including regulation of energy balance, promotion of metabolic process, food intake, weight gain, promotion of fat accumulation in adipocytes, and regulation of body homeostasis; thus, its overactivity may be related to obesity. In this review, we try to explain the role of the ECS and the impact of genetic factors on endocannabinoid system modulation in the pathogenesis of obesity, which is a global and civilizational problem affecting the entire world population regardless of age. We also emphasize that the search for potential new targets for health assessment, treatment, and the development of possible therapies in obesity is of great importance.     

Asprosin—A Fasting-Induced,Glucogenic, and Orexigenic Adipokine as a New Promising Player. Will It Be a New Factor in the Treatment of Obesity,Diabetes, or Infertility? A Review of the Literature

Asprosin is a recently discovered protein released during fasting conditions mainly by adipocytes from white adipose tissue. As a glucogenic peptide, it stimulates the release of glucose from hepatic cells by binding to the OLFR734 receptor and leading to the activation of the G protein-cAMP-PKA pathway. As it crosses the blood–brain barrier, it also acts as an orexigenic peptide that stimulates food intake through activation of AgRP neurons in the hypothalamus; thus, asprosin participates in maintaining the body’s energy homeostasis. Moreover, studies have shown that asprosin levels are pathologically elevated in obesity and related diseases. However, the administration of anti-asprosin antibodies can both normalize its concentration and reduce food intake in obese mice, which makes it an interesting factor to combat obesity and related diseases. Current research also draws attention to the relationship between asprosin and fertility, especially in men. Asprosin improves age- and obesity-related decrease in fertility potential by improving sperm motility. It should also be mentioned that plasma asprosin levels can be differentially modulated by physical activity; intense anaerobic exercise increases asprosin level, while aerobic exercise decreases it. However, further research is necessary to confirm the exact mechanisms of asprosin activity and its potential as a therapeutic target.     

Potential Immunomodulatory Effects from Consumption of Nutrients in Whole Foods and Supplements on the Frequency and Course of Infection: Preliminary Results

A diet rich in nutrients should be implemented in order to boost the immune system and prevent infections. To investigate which nutrients are commonly consumed, an anonymous survey was given to 120 individuals and their responses were collected. The respondents answered questions relating to their health status, and their consumption of nutrients and supplements that produce immunomodulating effects. The participants were also asked about any prior viral, bacterial or fungal infections experienced, and in particular, infection frequency, course, and duration. The data collected were subjected to a statistical analyses to assess the relationship between the reported frequency of infections and nutrients consumed including vitamins D3, A, C, E, selenium, zinc, iron, β-carotene, omega-3 fatty acids as well as live active probiotic bacteria. The findings show that vitamin and mineral supplementation did not positively affect the duration, frequency, or course of infections in the surveyed sample. An exception was vitamin D3 supplementation that was correlated to sporadic incidence of viral infections. Conversely, immunity was positively affected by consumption of natural nutrients contained in whole food (vitamin C, iron, selenium, omega-3 fatty acids), evidenced by lower incidences and milder courses of infection.