Neuroprotective Effects of a Novel Demeclocycline Derivative Lacking Antibiotic Activity: From a Hit to a Promising Lead Compound.

The antibiotic tetracycline demeclocycline (DMC) was recently reported to rescue α-synuclein (α-Syn) fibril-induced pathology. However, the antimicrobial activity of DMC precludes its potential use in long-term neuroprotective treatments. Here, we synthesized a doubly reduced DMC (DDMC) derivative with residual antibiotic activity and improved neuroprotective effects.

Rescue of degenerating neurons and cells by stem cell released molecules: using a physiological renormalization strategy.

Evidence suggests that adult stem cell types and progenitor cells act collectively in a given tissue to maintain and heal organs, such as muscle, through a release of a multitude of molecules packaged into exosomes from the different cell types. Using this principle for the development of bioinspired therapeutics that induces homeostatic renormalization, here we show that the collection of molecules released from four cell types, including mesenchymal stem cells, fibroblast, neural stem cells, and astrocytes, rescues degenerating neurons and cells. Specifically, oxidative stress induced in a human recombinant TDP-43- or FUS-tGFP U2OS cell line by exposure to sodium arsenite was shown to be significantly reduced by our collection of molecules using in vitro imaging of FUS and TDP-43 stress granules.

Nomad Biosensors: A New Multiplexed Technology for the Screening of GPCR Ligands.

Nomad Technology (Innoprot [Innovative Technologies in Biological Systems], Derio, Spain), a novel tool for multiplexing high-throughput cell-based G protein-coupled receptor (GPCR) assays, is described in this work. This new technology comprises a family of fluorescent biosensors called Nomad Biosensors that allow for the measurement of responses mediated by G proteins through their interactions with second-messenger transduction proteins. GPCRs are one of the largest protein families of receptors in eukaryotes, and their signaling mediates important physiological processes within cells.

The Food Environment, Preference, and Experience Modulate the Effects of Exendin-4 on Food Intake and Reward.

Objective: The obesogenic food environment facilitates access to multiple palatable foods. Exendin-4 (EX4) is a glucagon-like peptide 1 receptor (GLP1R) agonist that inhibits food intake and has been proposed as an obesity therapy. This study tested whether the composition of the food environment and experience with palatable foods modulate the effects of EX4 on food intake and reward.

Fluorescent Parkin Cell-Based Assay Development for the Screening of Drugs against Parkinson Disease.

Parkinson disease (PD) is a prevalent neurodegenerative disease characterized by selective degeneration of dopaminergic neurons in the substantia nigra, causing tremor and motor impairment. Parkin protein, whose mutants are the cause of Parkinson disease type 2 (PARK2), has been mechanistically linked to the regulation of apoptosis and the turnover of damaged mitochondria. Several studies have implicated aberrant mitochondria as a key contributor to the development of PD.

First report of splenic rupture following deep enteroscopy.

Splenic rupture is a rare complication of diagnostic and therapeutic gastrointestinal endoscopy procedures. Herein, we report for the first time a case of splenic rupture following therapeutic retrograde double-balloon enteroscopy, which occurred in an 85-year-old man who was treated for recurrent mid-intestinal bleeding that resulted from ileal angioectasia. This patient promptly underwent an operation and eventually recovered.

Sulfonylureas and their use in clinical practice.

Many anti-diabetic drugs with different mechanisms of action are now available for treatment of type 2 diabetes mellitus. Sulfonylureas have been extensively used for treatment of type 2 diabetes for nearly 50 years and, even in our times, are widely used for treatment of this devastating chronic illness. Here, we review some of the available data on sulfonylureas, evaluating their mechanism of action and their effects on glycemic control.

Oral glucose tolerance test-based calculation identifies different glucose intolerance phenotypes within the impaired fasting glucose range.

Aims/introduction: The conventional oral glucose tolerance test (OGTT) cannot detect future diabetics among isolated impaired fasting glucose (is-IFG) nor normal glucose tolerant (NGT) groups. By analyzing the relationship between fasting (FPG) and 2-h plasma glucose (2hPG), the present study identifies is-IFG subjects liable to worsening glucose homeostasis.

Materials And Methods: Oral glucose tolerance test was carried out in 619 patients suffering from obesity, hypertension or dyslipidemia, whose FPG was in the 100-125 mg/dL range.

Sex differences in lipid profiles in relation to the progression of glucose abnormalities.

Background: In the present study, we investigated the role of changes in blood lipids in the abolition of the lower cardiovascular risk associated with the female gender in individuals with type 2 diabetes mellitus (T2DM).

Methods: An oral glucose tolerance test (OGTT) was performed in 1091 consecutive patients (478 men and 613 women) and patients were divided into groups as follows: (i) those with normal glucose tolerance (NGT; n = 589); (ii) those with pre-diabetes (pre-T2DM), who were further divided into those with impaired fasting glucose (IFG; n = 212), impaired glucose tolerance (IGT; n = 84), and both IFG and IGT (IFG/IGT; n = 102); and (iii) those with T2DM (n = 104). Total cholesterol, triglycerides, high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C), apolipoprotein (apo) A-I, apoB, and the apoB:apoA-I ratio were determined in each patient.

Expanding the clinical use of standard OGTT: the percentage increment of 2 h with respect to fasting glucose as an index of β-cell dysfunction.

Aims: Since glucose levels during oral glucose tolerance test (OGTT) are determined both by insulin sensitivity and insulin secretion, we investigated whether the percentage increment (PG%) of 2-h plasma glucose (2hPG) over fasting plasma glucose (FPG) is related to validated indexes of insulin sensitivity and insulin secretion.

Methods: Using Stumvoll's formulas we calculated estimated insulin sensitivity index and first-phase insulin secretion in 1281 subjects who underwent a standard OGTT. The ratio first-phase insulin secretion/(1/estimated insulin sensitivity index) was considered a surrogate index of β-cell function.

Renal function and volume of infants born with a very low birth-weight: a preliminary cross-sectional study.

Aim: The aim of our study was to compare the function and volumes of kidneys of very low birth-weight (VLBW) and of extremely low birth-weight (ELBW) infants at pre-school ages.

Patients And Methods: We did a revision of the neonatal records of infants born in our hospital that weighed < or =1500 g at birth. The children were divided into two groups according to their weight at birth: ELBW (<1000 g) and VLBW (1000-1500 g).

The Anabaena sp. strain PCC 7120 asr1734 gene encodes a negative regulator of heterocyst development.

The novel asr1734 gene of Anabaena (Nostoc) sp. strain PCC 7120 inhibited heterocyst development when present in extra copies. Overexpression of asr1734 inhibited heterocyst development in several strains including the wild type and two strains that form multiple contiguous heterocysts (Mch phenotype): a PatS null mutant and a hetR(R223W) mutant.

[Evaluation of mental and communication functions in mapuche and non mapuche elderly subjects in rural communities in Southern Chile].

Background: The main predictors of functional impairment in the elderly are alterations in mental or communication functions.

Aim: To study mental and communication functions in rural elderly subjects of Mapuche and non Mapuche origin.

Patients And Methods: Elderly subjects coming from a rural Mapuche community and a non Mapuche community were studied.

Vacuolar H(+)-ATPase is expressed in response to gibberellin during tomato seed germination.

Completion of germination (radicle emergence) by gibberellin (GA)-deficient (gib-1) mutant tomato (Lycopersicon esculentum Mill.) seeds is dependent upon exogenous GA, because weakening of the endosperm tissue enclosing the radicle tip requires GA. To investigate genes that may be involved in endosperm weakening or embryo growth, differential cDNA display was used to identify mRNAs differentially expressed in gib-1 seeds imbibed in the presence or absence of GA(4+7).

[Hemostasis in patients at high hemorrhagic risk].

Surgical treatment in patients with heavy coagulation disorders needs measures that minimize immediate and post-surgical hemorrhagic risk. Besides the subjects afflicted with constitutional coagulation pathologies such as haemophilia A, B, C, AB, Von Willebrand disease, platelet disorders and others, too many are the patients that need pharmacological therapy to impede the creation of intra-vascular coagula. Today, surgical treatment of these patients is possible with the use of human fibrin glue (Tissucol) that permits excellent surgical and post-surgical hemostasis without therapy suspension, independently of coagulation disorder.

Malignant fibrous histiocytoma of the gingiva. A clinicopathological study.

A case is reported of malignant fibrous histiocytoma (MFH) of the gingiva. The 65-year-old female presented with a fast-growing mass originating from the left lower gingiva. The tumor measured 15 cm in diameter, occupying the entire oral cavity, protruding outside, and causing a mechanical airway obstruction.