A Novel Small Molecule Supports the Survival of Cultured Dopamine Neurons and May Restore the Dopaminergic Innervation of the Brain in the MPTP Mouse Model of Parkinson's Disease.

We previously showed that monoterpenoid (1R,2R,6S)-3-methyl-6-(prop-1-en-2-yl)cyclohex-3-ene-1,2-diol 1 alleviates motor manifestations of Parkinson's disease in animal models. In the present study, we designed and synthesized monoepoxides of (1R,2R,6S)-3-methyl-6-(prop-1-en-2-yl)cyclohex-3-ene-1,2-diol 1 and evaluated their biological activity in the MPTP mouse model of Parkinson's disease. We also assessed the ability of these compounds to penetrate the blood-brain barrier (BBB). According to these data, we chose epoxide 4, which potently restored the locomotor activity in MPTP-treated mice and efficiently penetrated the BBB, to further explore its potential mechanism of action. Epoxide 4 was found to robustly promote the survival of cultured dopamine neurons, protect dopamine neurons against toxin-induced degeneration, and trigger the mitogen-activated protein kinase (MAPK) signaling cascade in cells of neuronal origin. Meanwhile, neither the survival-promoting effect nor MAPK activation was observed in non-neuronal cells treated with epoxide 4. In the MPTP mouse model of Parkinson's disease, compound 4 increased the density of dopamine neuron fibers in the striatum, which can highlight its potential to stimulate striatal reinnervation and thus halt disease progression. Taken together, these data indicate that epoxide 4 can be a promising compound for further development, not only as a symptomatic but also as a neuroprotective and neurorestorative drug for Parkinson's disease.

Whole-genome sequencing of a pandoravirus isolated from keratitis-inducing acanthamoeba.

Following the recent discovery of two Pandoravirus species in 2013, a previously described endocytobiont isolated from the inflamed eye of a patient with keratitis was subjected to whole-genome sequencing (WGS). Here, we present the complete genome sequence of a new Pandoravirus isolate.

Instruments for disease-specific quality-of-life measurement in patients with type 2 diabetes mellitus--a systematic review.

UNLABELLED: Diabetes mellitus is a disease which carries a considerable social impact in Bulgaria and across the world because of its high prevalence. Research literature has recently included lots of studies investigating the effects of diabetes mellitus on the quality of life of diabetic patients and also many instruments to assess these effects. Quality of life is a concept that encompasses an individual's subjective perception of physical, emotional and social wellbeing, including both a cognitive component (satisfaction) and an emotional component (happiness). We review and analyse in the present article major determinants of disease-specific quality of life in patients with type 2 diabetes mellitus and the tools used for assessment. RESULTS: Fourteen instruments for measuring quality of life in type 2 diabetes mellitus (T2DM) met our search criteria. Their contents covered different quality-of-life domains or indicators-- typical diabetes symptoms, general health and quality of life, personality traits, physical functioning, mental and social well-being, treatment and quality of life. Most of the disease-specific tools had been field tested and data about their reliability and validity have been reported. Few tools had been subjected to formal assessment of their adaptability to changes. CONCLUSIONS: Of the instruments we assessed the most promising approaches for measuring the diabetes-specific quality of life are offered by ADDQoL, DCP and WBQ. Patients were involved in the development of these tools which have been shown by a number of studies to have good internal reliability, external and construct validity. Efforts are being continually made worldwide to develop a standard ensuring valid, reliable, easy to use tool for assessing quality of life in patients with type 2 diabetes mellitus in order to promote patients integration into society.

Phenol biodegradation by fungal cells immobilized in sol-gel hybrids.

The capability of cells of the fungus Aspergillus awamori, either free or immobilized in hybrid sol-gel material cells, for phenol biodegradation was demonstrated. Phenol was present in the reaction mixture as the sole carbon and energy source, and its decomposition was followed in repeated batch degradation experiments. Atomic force microscopy provided information on the development of self-organizing structures in the materials synthesized by the sol-gel method. Phenol biodegradation was mediated only by the fungal cells, and no absorption by the hybrid matrix was observed. Ten cycles of phenol biodegradation using the immobilized cells system were conducted during which up to 2000 mg l(-1) phenol was completely decomposed. Immobilized cells degraded phenol at 8.33 mg h(-1), twice as fast as free cells. The good performance of the immobilized fungal cell system is promising for the development of an efficient technology for treating phenol-containing waste waters.

Long-term decrease of CD4+CD45RA+ T cells and impaired primary immune response after post-traumatic splenectomy.

Congenital or acquired absence of the spleen and functional hyposplenism are associated with abnormalities of host defence such as an increased susceptibility to infection with encapsulated bacteria. The effects of the lack of the spleen on cell-mediated immunity are largely unknown. In the present study we have investigated peripheral blood lymphocyte subpopulations in healthy adults who had undergone splenectomy because of severe abdominal trauma > 4 years before the study. The results show a significant reduction in the percentage of CD4+ T cells due to a selective and long-term decrease in the percentage of CD4+CD45RA+ lymphocytes, the CD4+ T-cell subset mainly involved in primary immune responses to newly encountered antigens. Levels of the reciprocal CD45RO+CD4+ T-cell subset were comparable between splenectomized and control individuals, as were lymphoproliferative responses and IFN-gamma production to recall antigens. Decreased levels of CD4+CD45RA+ cells were accompanied by an impairment in primary immune responsiveness, as assessed by investigating T-cell proliferation to stimulation with keyhole limpet haemocyanin and by measuring antibody responses following primary immunization with a clinically relevant T-dependent antigen, hepatitis A vaccine, in vivo. These findings suggest a possible role of the spleen in the generation, maintenance and/or differentiation of naive, unprimed T cells or their precursors, which might have a possible functional relevance for primary immune responses following splenectomy.

[Thumb reconstruction with free neurovascular wrap-around flap (bit-toe skin-nail flap) after traumatic amputation]. / Daumenrekonstruktion mit freiem, neurovaskulärem "Wrap-around"-Lappen (Big-toe Skin-Nail Flap) nach traumatischer Amputation.

From November 1993 until May 1995 there were three cases of traumatic loss of the thumb reconstructed, using the above mentioned method. In two cases, the thumbs were amputated in the region of the first phalanx, in one case in the region of the metacarpophalangeal joint. Thumb reconstruction in the technique described by Morrison et al. (1980) involved the neurovascular wrap-around flap from the ipsilateral greater toe. The flap consisted of 4/5 of the soft-tissue including the nail of the big toe and parts of the distal phalanx as well as the fibular nerve of the toe. The vessels of the flap included the first dorsal metatarsal artery and two branches of the vena saphena magna. This paper details surgical technique, pointing out its advantages and disadvantages and compares it with other procedures.