BackgroundDiabetic polyneuropathy (DPN) is one of the most common complications of diabetes and can exist with or without neuropathic pain. We were interested in how neuropathic pain impairs the quality of life in diabetic patients and what is the role of comorbidities in this condition.MethodsThe study included 80 patients with painful DPN (group “P”) and 80 patients with DPN, but without neuropathic pain (group “D”). Visual analogue scale (VAS) and Leeds assessment of neuropathic symptoms and signs (LANSS) pain scale were used for assessment of neuropathic pain, SF-36 standardized questionnaire for assessment of the quality of life and BDI questionnaire for assessment of depression.ResultsSubjects in group P had statistically significantly lower values compared to group D in all 8 dimensions and both summary values of the SF-36 scale. We ascribe the extremely low results of all parameters of SF-36 scale in group P to painful diabetic polyneuropathy with its complications. The patients in group D showed higher average values in all dimension compared to group P, but also somewhat higher quality of life compared to general population of Croatia in 4 of 8 dimensions, namely vitality (VT), social functioning (SF), role-emotional (RE) and mental health (MH), which was unexpected result.Clinically, the most pronounced differences between two groups were noted in sleeping disorders and problems regarding micturition and defecation , which were significantly more expressed in group P. The similar situation was with walking distance and color-doppler sonography of carotid arteries, which were significantly worse in group P. Consequently, subjects in group P were more medicated than the patients in group D, particularly with tramadol, antiepileptics and antidepressants.ConclusionPainful DPN is a major factor that influences various aspects of quality of life in diabetic patients. Additionally, this study gives an overview of diabetic population in the Republic of Croatia, information that could prove useful in future studies.

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Adenosine monophosphate (AMP)-activated kinase (AMPK) modulators have been shown to exert cytotoxic activity in hematological malignancies, but their role in the differentiation of acute myeloid leukemia (AML) is less explored. In this study, the effects of AMPK agonists on all-trans retinoic acid (ATRA)-mediated differentiation of acute promyelocytic leukemia (APL) and non-APL AML cell lines were investigated. The results show that AMPK agonists inhibit the growth of myeloblastic HL-60, promyelocytic NB4 and monocytic U937 cells. 5-Aminoimidazole-4-carboxamide ribonucleoside (AICAR), an AMPK activator, enhances ATRA-mediated differentiation of NB4 cells. In U937 cells, AICAR alone induces the expression of cell surface markers associated with mature monocytes and macrophages. In both cell lines, AICAR increases the activity of mitogen-activated protein kinase (MAPK), and the presence of a MAPK inhibitor reduces the expression of differentiation markers. These results reveal beneficial effects of AICAR in AML, including differentiation of non-APL AML cells.

Phosphatidylinositol-specific phospholipase C (PI-PLC) is activated in cell nuclei during the cell cycle progression. We have previously demonstrated two peaks of an increase in the nuclear PI-PLC activities in nocodazole-synchronized HL-60 cells. In this study, the activity of nuclear PI-PLC was investigated in serum-stimulated HL-60 cells. In serum-starved HL-60 cells, two peaks of the activity of nuclear PI-PLC were detected at 30 min and 11 h after the re-addition of serum with no parallel increase in PLC activity in cytosol, postnuclear membranes or total cell lysates. An increase in the serine phosphorylation of b splicing variant of PI-PLCbeta(1) was detected with no change in the amount of PI-PLCbeta(1b) in nuclei isolated at 30 min and 11 h after the addition of serum. PI-PLC inhibitor ET-18-OCH(3) and MEK inhibitor PD 98059 completely abolished serum-mediated increase at both time-points. The addition of inhibitors either immediately or 6 h after the addition of serum had inhibitory effects on the number of cells entering S phase. These results demonstrate that two waves of nuclear PI-PLCbeta(1b) activity occur in serum-stimulated cells during G(1) phase of the cell cycle and that the later increase in the PLC activity is equally important for the progression into the S phase.

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