Apomorphine Reduces A53T α-Synuclein-Induced Microglial Reactivity Through Activation of NRF2 Signalling Pathway.

The chiral molecule, apomorphine, is currently used for the treatment of Parkinson's disease (PD). As a potent dopamine receptor agonist, this lipophilic compound is especially effective for treating motor fluctuations in advanced PD patients. In addition to its receptor-mediated actions, apomorphine has also antioxidant and free radical scavenger activities.

Bioimpedance analysis is not superior to clinical assessment in determining hydration status: A prospective randomized-controlled trial in a Western dialysis population.

Introduction: Fluid management is an important goal of dialysis treatment. The accurate assessment of fluid status is still a challenge for clinical nephrologists. Bioimpedance analysis (BIA) has been proposed as an objective tool to assess hydration.

Tumor suppressor miR-215 counteracts hypoxia-induced colon cancer stem cell activity.

Cancer stem cells, also known as tumor-initiating cells (TICs), are a population of aggressive and self-renewing cells that are responsible for the initiation and progression of many cancers, including colorectal carcinoma. Intratumoral hypoxia, i.e.

Kinase inhibitor library screening identifies synergistic drug combinations effective in sensitive and resistant melanoma cells.

Background: Melanoma is the most aggressive and deadly form of skin cancer with increasing case numbers worldwide. The development of inhibitors targeting mutated BRAF (found in around 60% of melanoma patients) has markedly improved overall survival of patients with late-stage tumors, even more so when combined with MEK inhibitors targeting the same signaling pathway. However, invariably patients become resistant to this targeted therapy resulting in rapid progression with treatment-refractory disease.

A new ALK isoform transported by extracellular vesicles confers drug resistance to melanoma cells.

Background: Drug resistance remains an unsolved clinical issue in oncology. Despite promising initial responses obtained with BRAF and MEK kinase inhibitors, resistance to treatment develops within months in virtually all melanoma patients.

Methods: Microarray analyses were performed in BRAF inhibitor-sensitive and resistant cell lines to identify changes in the transcriptome that might play a role in resistance.

The miR-371∼373 Cluster Represses Colon Cancer Initiation and Metastatic Colonization by Inhibiting the TGFBR2/ID1 Signaling Axis.

The vast majority of colorectal cancer-related deaths can be attributed to metastatic spreading of the disease. Therefore, deciphering molecular mechanisms of metastatic dissemination is a key prerequisite to improve future treatment options. With this aim, we took advantage of different colorectal cancer cell lines and recently established primary cultures enriched in colon cancer stem cells, also known as tumor-initiating cells (TIC), to identify genes and miRNAs with regulatory functions in colorectal cancer progression.

Alpha-Synuclein Proteins Promote Pro-Inflammatory Cascades in Microglia: Stronger Effects of the A53T Mutant.

Parkinson's disease (PD) is histologically described by the deposition of α-synuclein, whose accumulation in Lewy bodies causes dopaminergic neuronal death. Although most of PD cases are sporadic, point mutations of the gene encoding the α-synuclein protein cause inherited forms of PD. There are currently six known point mutations that result in familial PD.

NLRP3 Inflammasome Is Expressed and Functional in Mouse Brain Microglia but Not in Astrocytes.

Neuroinflammation is the local reaction of the brain to infection, trauma, toxic molecules or protein aggregates. The brain resident macrophages, microglia, are able to trigger an appropriate response involving secretion of cytokines and chemokines, resulting in the activation of astrocytes and recruitment of peripheral immune cells. IL-1β plays an important role in this response; yet its production and mode of action in the brain are not fully understood and its precise implication in neurodegenerative diseases needs further characterization.

Microglial activation depends on beta-amyloid conformation: role of the formylpeptide receptor 2.

Alzheimer's disease (AD) is characterized by the presence of extracellular deposits referred to beta-amyloid (Abeta) complexes or senile plaques. Abeta peptide is firstly produced as monomers, readily aggregating to form multimeric complexes, of which the smallest aggregates are known to be the most neurotoxic. In AD patients, abundant reactive microglia migrate to and surround the Abeta plaques.

Jagged1 regulates the activation of astrocytes via modulation of NFkappaB and JAK/STAT/SOCS pathways.

The Notch pathway is implicated in many aspects of the central nervous system (CNS) development and functions. Recently, we and others identified the Notch pathway to be involved in inflammatory events of the CNS. To understand the implication of this pathway on astrocytes, we have studied the Jagged-Notch-Hes pathway under inflammatory conditions.

Synergistic action of heparin and serum on basic fibroblast growth factor-modulated DNA synthesis and mitochondrial activity of cultured bovine corneal endothelial cells.

Basic fibroblast growth factor (bFGF) is a major mitogen and chemoattractant for many cell types. The synergistic role of fetal bovine serum (FBS) and heparin on the modulation of tissue-cultured bovine corneal endothelial cells by bFGF was studied. Cell modulation was assessed by DNA synthesis ([3H]thymidine incorporation), mitochondrial activity (MTT assay), mitochondrial volume (transmission electron microscope study), and cell shape in mitotically competent cells and cells mitotically inhibited by 5-fluorouracil, mitomycin C, and irradiation.

Histopathologic effects of mitomycin C after trabeculectomy in human glaucomatous eyes with persistent hypotony.

We evaluated the histopathologic findings in seven patients who underwent surgical revision of the filtration site after trabeculectomy with mitomycin C because of persistent hypotonous maculopathy. Light microscopic examination of subconjunctival tissue and sclera demonstrated hypocellularity of fibroblasts and disruption of the normal architecture. Tissue fragments at the margin of the bleb wall demonstrated scarring and contained multiple fibroblasts.

Platelet-derived growth factor: receptor expression in corneas and effects on corneal cells.

Purpose: Platelet-derived growth factor (PDGF), a major mitogen and chemoattractant, is a dimeric molecule of disulfide-bonded A and/or B polypeptide chains (PDGF-AA/AB/BB). Two PDGF receptors (PDGFR) exist, alpha and beta, which dimerize after ligand exposure. The alpha-receptor binds both A- and B-chains, whereas the beta-receptor preferentially binds the B-chain.

Quality assessment in worksite health promotion.

The rapid expansion of worksite health promotion programs and the proliferation of service providers have resulted in increased concern about the quality of such programs. And while employers may view health promotion programs as a service to be purchased, in general, quality standards, price, and outcomes are less well established for primary prevention programs than for other medical services. This trend creates substantial potential for inappropriate expenditures, undermining the general credibility of such programs.

Reducing tobacco consumption in California. Development of a statewide anti-tobacco use campaign.

Cigarette smoking continues to be the leading preventable cause of death in California and the United States. Although substantial progress has been made over the past 25 years, there is growing recognition of the need for large-scale efforts to reduce tobacco use. Given their central roles in implementing public health programs and their ability to reach many of the groups most at risk of tobacco use uptake and tobacco-related disease, state health agencies have an important challenge before them.

Solitary nonepidermotropic T cell pseudolymphoma of the skin.

A possibly new type of T cell pseudolymphoma is described in three cases. It presented as a small, solitary lesion on the trunk of 3 to 5 months' duration. It was slightly elevated, round, and erythematous, with a diameter of 1 to 2 cm.

Indices of relative body weight and ideal weight charts.

Established indices of relative body weight are reviewed and critically evaluated in terms of five criteria: (1) high correlation with obesity, (2) a conceptual interpretation, (3) universality, (4) simplicity of computation, and (5) zero correlation with height. Regression procedures are used to create standard weight charts which are distributed similarly to the body weight of 13,645 Americans, provided by the National Health Survey (NHS), and which have an arithmetic mean equal to the mean of the Metropolitan Life Insurance ( MLI ) table of desirable weights. A similar method is used to create a standard weight table based on body mass index (BMI).

California's approach to hypertension control: an overview.

California's Department of Health Services, recognizing the serious community health problem presented by uncontrolled hypertension, developed community-based programs of early detection and referral, follow-up and education. Special consideration was given to underserved populations at high risk. A statewide probability household survey was conducted and showed an improvement in control status during the past decade for definite and critical hypertension, but not for mild hypertension.

[Hyperthermia with acute rhabdomyolysis in a psychotic treated with neuroleptics].

A 36 year old psychotic man receiving treatment with slow-release pipotiazine and trihexyphenidyl developed nine days after addition of droperidol signs suggestive of a malignant neuroleptic syndrome: altered general condition, diffuse hypertonia, akinesia, fever and vomiting. Results of biologic tests and a muscle biopsy were suggestive of a severe rhabdomyolysis. Cessation of neuroleptic therapy and the administrative of nifedipine brought a gradual return return to normal conditions, and progressively increasing doses of neuroleptic could be given without complications 12 days later.

In vitro fertilizing capacity of fresh and cryopreserved human spermatozoa: a comparative study of freezing and thawing procedures.

The capacity of human spermatozoa to penetrate zona-free hamster ova was used to investigate several methods of freezing and thawing sperm. No differences in postthaw sperm viability were obtained after cooling spermatozoa either with a complex egg yolk cryoprotective medium or glycerol. The in vitro fertilizing capacity of postthaw spermatozoa frozen with a moderate freezing rate was similar to that of spermatozoa frozen with a slow freezing rate.