Pharmacokinetics of ximedone

Optimum conditions for the spectrophotometric determination of pyrimidine derivatives in biological fluids of humans are determined. This method has been used for the investigation of the pharmacokinetics of the new immunomodulant ximedone in humans, dogs, and rats upon administration of the drug in different ways. Interspecific relationships of the key parameters of ximedone pharmacokinetics are established. __________ Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 40, No. 7, pp. 5–8, July, 2006.     

Effect of the immunomodulant ximedone on the pharmacokinetics of isonicotinic acid hydrazide in the human organism

The pharmacokinetics of isonicotinic acid hydrazide upon joint administration with the immunomodulant ximedone has been investigated. Ximedone influences the genetically determined parameters of the isonicotinic acid hydrazide pharmacokinetics. The dose-dependent and temporal schedules of ximedone administration in humans are established, which favor the induction of acetylation processes in patients. __________ Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 40, No. 3, pp. 3–6, March, 2006.     

Comparison of a Web-Based Dietary Assessment Tool with Software for the Evaluation of Dietary Records

Background

Dietary assessment in clinical practice is performed by means of computer support, either in the form of a web-based tool or software. The aim of the paper is to present the results of the comparison of a Slovenian web-based tool with German software for the evaluation of four-day weighted paper-and-pencil-based dietary records (paper-DRs) in pregnant women.

Methods

A volunteer group of pregnant women (n=63) completed paper-DRs. These records were entered by an experienced research dietitian into a web-based application (Open Platform for Clinical Nutrition, OPEN, http://opkp.si/en, Ljubljana, Slovenia) and software application (Prodi 5.7 Expert plus, Nutri-Science, Stuttgart, Germany, 2011). The results for calculated energy intake, as well as 45 macro- and micronutrient intakes, were statistically compared by using the non-parametric Spearman’s rank correlation coefficient. The cut-off for Spearman’s rho was set at >0.600.

Results

12 nutritional parameters (energy, carbohydrates, fat, protein, water, potassium, calcium, phosphorus, dietary fiber, vitamin C, folic acid, and stearic acid) were in high correlation (>0.800), 18 in moderate (0.600–0.799), 11 in weak correlation (0.400–0.599), while 5 (arachidonic acid, niacin, alpha-linolenic acid, fluoride, total sugars) did not show any statistical correlation.

Conclusion

Comparison of the results of the evaluation of dietary records using a web-based dietary assessment tool with those using software shows that there is a high correlation for energy and macronutrient content.     

Reactions after pneumococcal vaccine alone or in combination with influenza vaccine

We studied adverse reactions to immunisation in 541 individuals receiving simultaneous pneumococcal and influenza vaccination, and in 320 recipients of pneumococcal vaccine alone. Five days after immunisation, the participants completed a questionnaire covering systemic and local reactions to vaccination. Adverse effects were rated as mild if they did not interfere with the participant's daily activities, and moderate or serious if they moderately or markedly restricted these activities. There were no differences between the groups regarding general malaise, headache, myalgias and elevated body temperature. Redness at the injection site, but not soreness or swelling, occurred more frequently in individuals immunised simultaneously with both vaccines. Except for fever and local swelling, adverse reactions were significantly more frequent in women than in men in study groups. The rate of adverse reactions was higher in individuals less then 65 years of age than in older participants. Local reactions were reported by 358 (41.6%) participants, but they were mild and soon subsided. No serious reactions were reported. pneumococcal and influenza vaccine can be safely administered simultaneously.     

Exogenous Hsp70 delays senescence and improves cognitive function in aging mice

Molecular chaperone Heat Shock Protein 70 (Hsp70) plays an important protective role in various neurodegenerative disorders often associated with aging, but its activity and availability in neuronal tissue decrease with age. Here we explored the effects of intranasal administration of exogenous recombinant human Hsp70 (eHsp70) on lifespan and neurological parameters in middle-aged and old mice. Long-term administration of eHsp70 significantly enhanced the lifespan of animals of different age groups. Behavioral assessment after 5 and 9 mo of chronic eHsp70 administration demonstrated improved learning and memory in old mice. Likewise, the investigation of locomotor and exploratory activities after eHsp70 treatment demonstrated a significant therapeutic effect of this chaperone. Measurements of synaptophysin show that eHsp70 treatment in old mice resulted in larger synaptophysin-immunopositive areas and higher neuron density compared with control animals. Furthermore, eHsp70 treatment decreased accumulation of lipofuscin, an aging-related marker, in the brain and enhanced proteasome activity. The potential of eHsp70 intranasal treatment to protect synaptic machinery in old animals offers a unique pharmacological approach for various neurodegenerative disorders associated with human aging.Heat shock proteins (HSPs) serve to maintain intracellular protein homeostasis and have been shown to prevent protein damage during aging in different animal models (1). HSPs are required for longevity (2, 3), and a number of studies suggest that longer-lived species have higher constitutive expression of HSPs (4–7). Consistent with this finding, overexpression of HSP genes increased longevity in Drosophila, Caenorhabditis elegans, and vertebrates (1, 8, 9). Hsp70 is the major cytoprotective molecular chaperone with many different functions in the cell (10–12). Observations suggest that genetic variants of the Hsp70 family contribute to longevity in a wide range of organisms (9, 13, 14). Its defensive role in multiple neurodegenerative disorders (15, 16) can be explained by the multifaceted action of this protein. Indeed, the induction of Hsp70 has been shown to diminish oxidative stress damage (17, 18), suppress apoptosis (19), support proteasomal and lysosomal functioning (20), suppress toxic protein aggregation such as Aβ (21), inhibit proinflammatory signaling (22), and increase survival of endogenous neural progenitor cells (21). Notwithstanding Hsp70’s importance, its chaperone activity, as well as the rate of its synthesis and induction in response to stimuli, decreases in neurons with age (3, 6, 21, 22), suggesting that a pharmacological approach aiming to recover this chaperone in the aging brain may counter neurodegeneration.To our knowledge, the effect of exogenous HSPs on longevity has not yet been investigated. We previously showed that intranasally injected Hsp70 rapidly entered the brain of wild-type mice and was transported within neurons (23, 24). Furthermore, chronic Hsp70 treatment ameliorated multiple behavioral and molecular disturbances in two models of Alzheimer’s disease (AD)-type neurodegeneration (23). In this study, we explored the geroprotection potential of recombinant exogenous Hsp70 (eHsp70) in healthy mice. For all of the described experiments, we used highly pure LPS-free human eHsp70 (25), which rules out a possibility of confounding inflammatory responses associated with contaminated Hsp70. Our results demonstrate that long-term intranasal administration of human eHsp70 improves longevity and ameliorates aging-related behavioral deficits and molecular alterations to synaptic structure in the brains of aging mice.     

Coagulation factor activity and clinical bleeding severity in rare bleeding disorders: results from the European Network of Rare Bleeding Disorders

Summary. Background: The European Network of Rare Bleeding Disorders (EN‐RBD) was established to bridge the gap between knowledge and practise in the care of patients with RBDs. Objectives: To explore the relationship between coagulation factor activity level and bleeding severity in patients with RBDs. Patients/Methods: Cross‐sectional study using data from 489 patients registered in the EN‐RBD. Coagulation factor activity levels were retrieved. Clinical bleeding episodes were classified into four categories according to severity. Results: The mean age of patients at data collection was 31 years (range, 7 months to 95 years), with an equal sex distribution. On linear regression analysis, there was a strong association between coagulation factor activity level and clinical bleeding severity for fibrinogen, factor (F) X, FXIII, and combined FV and FVIII deficiencies. A weaker association was present for FV and FVII deficiencies. There was no association between coagulation factor activity level and clinical bleeding severity for FXI. The coagulation factor activity levels that were necessary for patients to remain asymptomatic were: fibrinogen, > 100 mg dL^?1; FV, 12 U dL^?1; combined FV + VIII, 43 U dL^?1; FVII, 25 U dL^?1; FX, 56 U dL^?1; FXI, 26 U dL^?1; FXIII, 31 U dL^?1. Moreover, coagulation factor activity levels that corresponded with Grade III bleeding were: undetectable levels for fibrinogen, FV and FXIII, < 15 U dL^?1 for combined FV + VIII; < 8 U dL^?1 for FVI; < 10 U dL^?1 for FX; and < 25 U dL^?1 for FXI. Conclusions: There is a heterogeneous association between coagulation factor activity level and clinical bleeding severity in different RBDs. A strong association is only observed in fibrinogen, FX and FXIII deficiencies.     

A Systematic Review of Vitamin D Status and Dietary Intake in Various Slovenian Populations

AimVitamin D (VitD) is involved in calcium and phosphate homeostasis, bone health, and normal functioning of the immune system. VitD status is monitored using serum 25-hydroxy-vitamin D (25(OH)D) as a biomarker. Serum 25(OH)D concentrations below 30 nmol/L indicate VitD deficiency and below 50 nmol/L indicate insufficiency. VitD can be synthesised endogenously in human skin when exposed to ultraviolet B (UVB) radiation. In the absence of sufficient UVB-light exposure, VitD intake becomes the main source of VitD, with a recommended daily intake of 20 μg. The aim of this study was to conduct a review and meta-analysis on the abovementioned topics, focusing on scientific studies in various Slovenian populations.MethodsWe conducted a systematic review and meta-analysis of published scientific papers, academic theses, or conference contributions reporting serum 25(OH)D status and VitD intake across various Slovenian populations. A search was carried out using Web of Science, Scopus, Medline, and the Slovenian library database.ResultsWe identified 43 pertinent studies that addressed 25(OH)D status and 16 that addressed VitD intake. Serum 25(OH)D status was generally low across all populations, and notable seasonal variability was observed. VitD intakes were below 5 μg in all studies.ConclusionsA general observation is that various population groups across Slovenia are at high risk of vitamin D insufficiency and deficiency, particularly during wintertime. Regarding vitamin D intake, all included studies reported daily intakes below the recommended level. We also identified key research gaps that need to be addressed to support further public health decision-making.