Antinociceptive effects of ceftriaxone in formalin-induced nociception

Ceftriaxone (CFX) is a β-lactam antibiotic with analgesic properties. However, its role in the formalin-induced nociception remains unknown. The purpose of this study was to investigate the antinociceptive effect of CFX in the 1% formalin test in rats. Formalin induced a typical nociceptive response (flinching behavior) of two phases. Local peripheral pretreatment (20 min) with CFX (400–800 μg/paw) slightly attenuated the flinching behavior in phase 2, but not phase 1. Acute intraperitoneal pretreatment (20 min) also reduced phase 2 of the formalin test. In both cases, CFX induced a dose-dependent antinociception. We also tested the effect of CFX 1 day after its administration and in two schedules of repeated administration. One-day pretreatment with CFX (50–400 mg/kg, ip) induced a dose-dependent antinociceptive effect in formalin-treated rats. Repeated administration (daily during 3 or 7 days) with CFX (50–400 mg/kg, ip) diminished formalin-induced nociception. Results suggest that local or systemic as well as single or repeated administration of CFX reduces formalin-induced nociception.     

Recycled Mortars with Ceramic Aggregates. Pore Network Transmutation and Its Relationship with Physical and Mechanical Properties

The porosity of mortars with recycled ceramic aggregates (10, 20, 30, 50, and 100% as a replacement of natural aggregate) was evaluated and analyzed using three different techniques. The results of gas adsorption (N₂), Scanning Electron Microscopy (SEM) image analysis and open porosity allowed establishing the relationship between the recycled aggregate content and the porosity of these mortars, as well as the relationship between porosity and the physical and mechanical properties of the mortars: absorption, density, compressive strength, modulus of elasticity, and drying shrinkage. Using the R² coefficient and the equation typology as criteria, additional data such as Brunauer, Emmett, and Teller (BET) surface area (N₂ adsorption) established significant correlations with the mentioned properties; with SEM image analysis, no explanatory relationships could be established; and with open porosity, revealing relationships were established (R² > 0.9). With the three techniques, it was confirmed that the increase in porosity is related to the increase in the amount of ceramic aggregate; in particular with gas adsorption (N₂) and open porosity. It was concluded that the open porosity technique can explain the behavior of these recycled mortars with more reliable data, in a simple and direct way, linked to its establishment with a more representative sample of the mortar matrix.     

Epidemiological and molecular evidence of two events of father-to-child HIV type 1 horizontal transmission

HIV-1 infection in children less than 15 years of age is mainly due to mother-to-child transmission. The aim of this work was to investigate molecular evidence to prove father-to-be horizontal transmission in two possible events of transmission. In the first event a boy was identified as HIV infected at 2-3 years of age. At the same time infection was confirmed in the father, while mother and siblings were negative. In the second event a girl was negative for HIV at age 1 and identified as HIV-1 infected at age 6. The father's HIV infection was diagnosed in the same period while the mother was repeatedly negative. No evidence of sexual assault or transfusion was recorded in any case. Peripheral blood mononuclear cells were obtained from both fathers and children. After PCR amplification, the C2V3 region of the envelope gene and the region coding for amino acid 132 of p24 up to amino acid 40 of p7 of the gag gene were sequenced. Genetic distance measurements and phylogenetic tree analysis showed that in both cases the father's and child's viral sequences were closely related. They were distinct when compared to Argentina sequences including sequences from the same geographic region. Epidemiological and molecular data strongly suggest that horizontal transmission had occurred, probably related to the close father-to-child contact.     

The role of socioeconomic status in the susceptibility to develop systemic lupus erythematosus in Mexican patients

Clinical Rheumatology - Systemic lupus erythematosus (SLE) is an autoimmune inflammatory disorder for which Major Histocompatibility Complex (MHC) genes are well-identified as risk factors. SLE...     

Synthesis of phenylazonaphtol-β-<Emphasis Type="SmallCaps">D</Emphasis>-<Emphasis Type="Italic">O</Emphasis>-glycosides,evaluation as substrates for beta-glycosidase activity and molecular studies

Background

Phenylazonaphtol-β-D-O-glycosides are alternative substrates for the detection of enzymatic activity of β-glycosidases which are involved in various important processes. These azoic compounds are currently exploited as prodrugs for colonic disease due the presence of β-glycosidase activity in the gut flora and therefore allowing the release of the drug at the specific site.

Results

Phenylazonaphtol-β-D-O-glucoside 3a and galactoside 3b were prepared via diazonium salt conditions under weak acidic conditions which do not compromise the O-glycosidic bond stability, by coupling reaction between 2-naphtol sodium salt with aminoglycosides 1a and 1b. The resulting phenylazonaphtol glycosides 2a and 2b were deprotected affording the phenylazonaphtol glycosides 3a and 3b in quantitative yield. The galactoside glycoside 3b was assayed as substrate for in vitro β-galactosidase enzymatic activity showing strong absorbance after releasing of the azoic chromophore. Also, docking studies were performed to determine the best pose as well as the interactions between the ligand and the residues located at the active site.

Conclusions

The methodology developed for synthesizing the phenylazonaphtol glycosides described proved to be convenient for generating azoic functionalities in the presence of glycosidic bonds and the glycosides suitable as alternative substrates and potentially useful prodrugs in the treatment of colonic diseases.

Open image in new window

     

Rescue of hypogonadotropic hypogonadism-causing and manufactured GnRH receptor mutants by a specific protein-folding template: misrouted proteins as a novel disease etiology and therapeutic target

In the present study, we demonstrate pharmacological rescue (assessed by ligand binding and restoration of receptor coupling to effector) of five naturally occurring GnRH receptor (GnRHR) mutants (T(32)I, E(90)K, C(200)Y, C(279)Y, and L(266)R), identified from patients with hypogonadotropic hypogonadism, as well as rescue of other defective receptors intentionally manufactured with internal or terminal deletions or substitutions at sites expected to be involved in establishment of tertiary receptor structure. The pharmacological agent used is a small, membrane-permeant molecule, originally designed as an orally active, nonpeptide receptor antagonist, but is believed to function as a folding template, capable of correcting the structural defects caused by the mutations and thereby restoring function. After rescue, this agent can be demonstrably removed. The rescued receptor, now stabilized in the plasma membrane, couples ligand binding to activation of the appropriate effector system. For comparison, low-, intermediate-, or high-affinity peptide antagonists of GnRHR (that do not penetrate the cell) were unable to effect rescue, as was a nonbinding peptidomimetic congener of the rescue agent; this latter effect demonstrates specificity of the rescue agent. Our findings, taken in concert with an earlier study showing rescue of a mutant by modifications to the receptor structure that enhance plasma membrane expression of the GnRHR, suggest that mutant GnRHRs have frequently not lost intrinsic functionality and are subject to rescue by techniques that enhance membrane expression. The present findings demonstrate the efficacy of an approach based on pharmacological rescue and suggest the basis of new approaches for intervention in this and similar diseases.