Suchergebnisse

Neuromidin Attenuates Neuropathic Pain in the Streptozocin-Induced Diabetes Model in RatsDiabetic neuropathy, which affects all peripheral nerves and may cause dramatic pain, is one of the most severe pathologies associated with hyperglycaemia, damage in the blood vessels, and inflammation in nerves. Anticonvulsants and antidepressants are still the most commonly used options to manage diabetic neuropathy. However, to improve clinical benefit in the treatment of diabetic neuropathies, as well as to minimize side effects, search for a new type of drugs to protect/treat neuropathic pain is still important. The aim of this study was to investigate neuromidin (ipidacrine, amiridin, NIK-247), an anticholinesterase drug of tetrahydroaminoacridine series, in the streptozocin (STZ)-induced diabetic neuropathic pain model in rats. Neuromidin was administered per os at daily doses 0.3, 1.0 and 3.0 mg/kg for ten days. The dynamics in the development of hyperalgesia (pain threshold) was measured by algesimeter for five weeks. The data obtained show that neuromidin considerably protects the development of peripheral neuropathic pain caused by STZ. The most active dose was the lowest—0.3 mg/kg. Neuromidin did not affect STZ-hyperglycemia, nor the weight gain in animal groups. Neuromidin per se at the doses 0.3 and 1.0 mg/kg showed a short-term analgesic activity. The cholinergic mechanism of neuromidin may be considered as essential in attenuating of diabetic neuropathic pain; other mechanisms remain to be elucidated.

Protective effects of mildronate in indinavir- and efavirenz-induced toxicity in micePreviously we showed that mildronate effectively protected mice heart tissue against the toxic influence of anti-HIV drugs azidothymidine, stavudine and lamivudine, which belong to nucleosideanalogue reverse transcriptase inhibitor (NRTI) class. Recently we also demonstrated that mildronate protected isolated rat liver mitochondria against mitochondrial damage caused by azidothymidine. The present study was devoted to examine the possible protective effectiveness of mildronate in cardio-, hepato- and neurotoxicity models caused by anti-HIV drugs of other classes: indinavir, a representative of protease inhibitor (PI) class, and efavirenz, a non-nucleoside-analogue reverse transcriptase inhibitor (NNRTI). Drugs were administered intraperitoneally for two weeks, at the dose of 50 mg/kg of anti-HIV drugs and 100 mg/kg for mildronate. Afterwards, mice heart, liver and brain tissue were examined morphologically and immunohistochemically. The results showed that indinavir in heart tissue caused inflammatory and degenerative changes, manifested as increased expression of nuclear factor kappaBp65 (NF-kBp65), as well as cardiomyocyte necrosis and cellular infiltration. Efavirenz did not cause pathological changes in mice heart tissue, whereas it induced marked expression of caspase-3 and glial fibrillary acidic protein (GFAP) in mice brain tissue and small degenerative alterations in mice liver tissue. The data obtained show mildronate's protective properties in indinavir-induced cardiotoxicity and efavirenz-induced neurotoxicity.

Mildronate's protective effects in the peripheral nervous system: stavudine-induced neuropathy and formalin-induced inflammation
Mildronate, previously known as a cardioprotective drug, recently was found to normalise mitochondrial processes by preventing the dysfunction of complex I in rat liver mitochondria. Previously we have shown also the ability of mildronate to prevent pathologies in the central nervous system by normalizing the expression of different signalling molecules in brain tissue. This allowed us to suggest that mildronate may possess a beneficial role also in peripheral nervous system pathologies. The present study was designed to assess the peripheral tissue damage caused by anti-HIV drug stavudine, as well as pain and inflammation caused by formalin. For this demonstration, we investigated the influence of mildronate: (1) on decreased myelin expression and increased neuron degeneration in rat sciatic nerve tissue caused by stavudine; and (2) on formalin-induced inflammation in mice. We found that mildronate protected the stavudine-induced degeneration of neurons in rat peripheral sciatic nerve without a significant influence on demyelination. In a formalin test, mildronate showed anti-inflammatory action comparable to that of indomethacin, a reference drug. The present results show that mildronate is capable of regulating peripheral nerve damage and peripheral inflammatory responses. We suggest that the multifunctional effects of mildronate can be attributed to its ability to regulate mitochondrial processes. The obtained data indicate protective effects of mildronate in different peripheral neurological pathologies.

Evaluation of work conditions and occupational health risk factors in enterprises within a 10-year period in Latvia
The objective of the study was to conduct a survey in the field of occupational health and safety the results of which could be used in rational and effective decision making for elaboration of employment and social policy programmes and for ensuring occupational safety and health programme development. During the study the following groups of people were surveyed: employers, occupational health and safety specialists, and employees. The traditional work risk factors (physical, chemical, biological) have changed to new risks (psychosocial, ergonomic, microclimatic) in Latvia today. The study included objective assessment of occupational health and safety situation (analysis of work environment risk factors measurement data bases, information on occupational diseases, workplace accidents). Results of measurements showed that one-third of measured risk factors values exceeded mandatory or recommended limits but situation has been improved during the last years (2002 compared to 2006). The results of surveys reveal insufficient assessment of risk factors in workplaces and selection of most hazardous ones only. Awareness and understanding of employers and employees regarding occupational health and safety requirements was dissatisfactory. The results of the study reveal a low level of workplace accidents compared to other countries within EU, which may be the result of poor registration system in Latvia. Strengthening of occupational safety and health normative basis and improvement of qualification of occupational physicians has increased the number of occupational diseases and patients revealed for the first time from 1996 to 2006. Early diagnose of occupational diseases and effective rehabilitation is an important question to favour a more rapid return of workforce after occupational morbidity. Study showed that attention should further be paid to simplification of legal requirements, development of alternative methods for informing and educating people, as well as recurrent definition of national indicators to assess efficacy of implemented measures related to occupational health and safety.

Abstract
Polyprenols (PPs) have been identified in almost all living organisms. The richest source of PPs is the needles of conifer trees. Endogenously, PPs, similarly to cholesterol, are synthesised in human and animal cells via the mevalonate pathway. Previous studies have demonstrated the anti-oxidant properties of PPs. To our knowledge, no studies have been published on the influence of PPs on muscle strength. We hypothesised that administration of PPs could prevent changes in muscle functioning caused by statins (weakness, etc.). In the present study, atorvastatin (80 mg/kg) was used as a model compound. PPs at doses 1, 10 and 20 mg/kg were administered. Both drugs were given per os for 16 days. The influence of atorvastatin, PPs and their combination on behaviour, muscle strength, plasma cholesterol and creatine kinase activity was assessed in female Wistar rats. Our data demonstrated that atorvastatin considerably impaired muscle strength, whereas PPs protected that effect. Neither PPs, nor atorvastatin influenced plasma cholesterol levels, whereas PPs at dose 20 mg/kg elevated creatine kinase activity by about 25%. PPs at the tested doses did not alter behaviour, indicating safety of central nervous system functions. The obtained data suggest usefulness of PPs as a complement in statin therapy to reduce muscle-related side effects.