The Association of Essential Metals with APOE Genotype in Alzheimer's Disease.

Background: The major confirmed genetic risk factor for late-onset, sporadic Alzheimer's disease (AD) is variant ɛ4 of apolipoprotein E gene (APOE). It is proposed that ApoE, a protein involved in transport of cholesterol to neurons can cause neurodegeneration in AD through interaction with metals. Previous studies mostly associated copper, iron, zinc, and calcium with ApoE4-mediated toxicity.

Mixed vitiligo of Blaschko lines: a newly discovered presentation of vitiligo responsive to combination treatment.

Vitiligo, depigmenting disorder of the skin and mucous membranes, affects up to 1% of the population worldwide. It is classified into four major types: segmental, non-segmental, mixed, and unclassified type. Non-segmental vitiligo refers to non-dermatomal distribution of lesions, while dermatomal distribution of lesions is present in patients with segmental vitiligo.

Inositol pyrophosphates modulate cell cycle independently of alteration in telomere length.

Synthesis of inositol pyrophosphates through activation of Kcs1 plays an important role in the signalling response required for cell cycle progression after mating pheromone arrest. Overexpression of Kcs1 doubled the level of inositol pyrophosphates when compared to wild type cells and 30 min following the release from α-factor block further increase in inositol pyrophosphates was observed, which resulted that cells overexpressing Kcs1 reached G2/M phase earlier than wild type cells. Similar effect was observed in ipk1Δ cells, which are unable to synthesize IP6-derived inositol pyrophosphates (IP7 and IP8) but will synthesize IP5-derived inositol pyrophosphates (PP-IP4 and (PP)2-IP3).

Topical propranolol cream in treatment of superficial infantile hemangiomas: a literature review and 4 years of clinical experience.

The clinical efficacy and safety profile of propranolol 1% cream in treatment of superficial infantile hemangiomas (IHs) were determined in a preliminary randomized group of eight infants. Five boys and three girls, 3 to 12 months old, with an IHs superficial capillary type on the forehead, posterior side of the neck, forearm, abdomen, or posterior side of the trunk were examined at our outpatient clinic between 2011 and 2014. Topical propranolol was applied twice daily for 10 months with clinical evaluation and photographic documentation performed every 1 to 2 months.

The impact of neuropathic pain and other comorbidities on the quality of life in patients with diabetes.

Background: Diabetic 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.

Methods: The study included 80 patients with painful DPN (group "P") and 80 patients with DPN, but without neuropathic pain (group "D").

5-Aminoimidazole-4-carboxamide ribonucleoside induces differentiation of acute myeloid leukemia cells.

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.

Rapamycin enhances dimethyl sulfoxide-mediated growth arrest in human myelogenous leukemia cells.

Rapamycin and its derivatives have been proposed in the treatment of leukemia based on their cytostatic effects, but their possible role in differentiation therapy is less explored. The aim of the present study was to investigate the possible beneficial effects of the combination of rapamycin and dimethyl sulfoxide (DMSO) on growth arrest and differentiation of acute myelogenous leukemia (AML) cells. In myeloblastic HL-60, promyelocytic NB4, monocytic U937, immature KG-1 and erythro-megakaryocytic K562 cell lines, rapamycin alone had modest inhibitory effects, DMSO inhibited proliferation in a dose-dependent manner, and the combination of rapamycin and DMSO reduced the number of viable cells significantly more than either agent alone.

The activity of extracellular signal-regulated kinase is required during G2/M phase before metaphase-anaphase transition in synchronized leukemia cell lines.

The pharmacological inhibitors of extracellular signal-regulated kinase (ERK) have been suggested as a novel molecular target-based therapy for acute myeloid leukemia. Several studies have established the role of ERK in cell cycle progression from G(1) to S phase in response to mitogen, but the role of ERK after the restriction point is less clarified. In this study, we used models of aphidicolin and nocodazole-synchronized HL-60 and NB4 leukemia cell lines to determine the kinetics of ERK activity during the progression of the cell cycle and to test the effects of commercially available inhibitors on G(2)/M progression of synchronized leukemia cells.

Two waves of the nuclear phospholipase C activity in serum-stimulated HL-60 cells during G(1) phase of the cell cycle.

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.

Activation of phosphoinositide 3-kinase C2 beta in the nuclear matrix during compensatory liver growth.

In the nuclear matrix harvested 20 h after partial hepatectomy, an increase in immunoprecipitable PI3K-C2beta activity is observed, which is sensitive to wortmannin (10 Mm) and shows strong preference for PtdIns over PtdIns(4)P as a substrate. On western blots PI3K-C2beta revealed a single immunoreactive band of 180 kD, whereas 20 h after partial hepatectomy gel shift of 18kDa was noticed in the nuclear matrix, suggesting that observed activation of enzyme is achieved by proteolysis. As it is know that PI3K-C2alpha is associated with nuclear speckles [Didichenko SA, Thelen M.

Nuclear phospholipase C-beta1b activation during G2/M and late G1 phase in nocodazole-synchronized HL-60 cells.

In this study, the activity of nuclear phosphatidylinositol-specific phosholipase C (PI-PLC) was investigated in HL-60 cells blocked at G(2)/M phase by the addition of nocodazole, and released into medium as synchronously progressing cells. Two peaks of an increase in the nuclear PI-PLC activities were detected; an early peak reached a maximum at 1 h after release from the nocodazole block, and a second increase was detected at 8.5 h after the release.