Efficient Production of Recombinant Human Brain-Derived Neurotrophic Factor in Through the Engineering of Its Pro-Region.

Thus far, no manufacturing process able to support industrialization has been reported for the recombinant human brain-derived neurotrophic factor (rhBDNF). Here, we described the setup of a new protocol for its production in () and its purification to homogeneity. A synthetic gene, codifying for the neurotrophin precursor, was inserted into an expression vector and transformed into BL21 (DE3) strain.

ProNGF processing in adult rat tissues and bioactivity of NGF prodomain peptides.

The neurotrophin nerve growth factor (NGF) and its precursor proNGF are both bioactive and exert similar or opposite actions depending on the cell target and its milieu. The balance between NGF and proNGF is crucial for cell and tissue homeostasis and it is considered an indicator of pathological conditions. Proteolytical cleavage of proNGF to the mature form results in different fragments, whose function and/or bioactivity is still unclear.

Intranasal delivery of NGF rescues hearing impairment in aged SAMP8 mice.

Hearing loss impacts the quality of life and affects communication resulting in social isolation and reduced well-being. Despite its impact on society and economy, no therapies for age-related hearing loss are available so far. Loss of mechanosensory hair cells of the cochlea is a common event of hearing loss in humans.

Stress-related testicular changes in Wistar and Sprague-Dawley rats following oral administration of an interleukin-8 inhibitor.

We describe testicular changes in Wistar and Sprague-Dawley rats following oral administration of DF2156A, a novel allosteric inhibitor of the CXCR1/CXCR2 receptors of interleukin-8. These testicular changes, which were associated with clinical signs, modifications of body weight parameters (decrease of body weight and weight gain) and a decrease of testosterone serum levels, were not considered to be a direct toxic effect of the test substance but secondary to a likely induced stress resulting from the oral administration of a high dose (200 mg/kg/day) of the test substance to male rats for a period of six weeks. Testicular changes consisted of seminiferous tubules atrophy and germinal cell degeneration and only occurred in animals presenting clinical signs of transient visible weight loss, ruffled fur and/or weakened condition, and/or decreased body weight and weight gain.

Ketoprofen lysine salt has a better gastrointestinal and renal tolerability than ketoprofen acid: A comparative tolerability study in the Beagle dog.

Due to the widespread use of non-steroidal anti-inflammatory drugs (NSAIDs), the incidence of NSAID-associated adverse events has increased exponentially over the past decades. Ketoprofen (ketoprofen acid, KA) is a widely used NSAID and, like with other NSAIDs, its use can be associated with adverse effects that especially involve the gastrointestinal tract and the kidney. The salification of KA with L-lysine has led to the synthesis of ketoprofen lysine salt (KLS), which is characterized by higher solubility and a more rapid gastrointestinal absorption compared to KA.

CXCL1-CXCR1/2 signaling is induced in human temporal lobe epilepsy and contributes to seizures in a murine model of acquired epilepsy.

CXCL1, a functional murine orthologue of the human chemokine CXCL8 (IL-8), and its CXCR1 and CXCR2 receptors were investigated in a murine model of acquired epilepsy developing following status epilepticus (SE) induced by intra-amygdala kainate. CXCL8 and its receptors were also studied in human temporal lobe epilepsy (TLE). The functional involvement of the chemokine in seizure generation and neuronal cell loss was assessed in mice using reparixin (formerly referred to as repertaxin), a non-competitive allosteric inhibitor of CXCR1/2 receptors.

Safety and pharmacokinetics of escalating doses of human recombinant nerve growth factor eye drops in a double-masked, randomized clinical trial.

Background And Objectives: Nerve growth factor (NGF) is a neurotrophin with therapeutic possibilities that extend from the nervous system to the eye. We tested the safety, maximal tolerated dose, pharmacokinetics, and antigenicity of a novel human recombinant NGF (rhNGF) eye-drop formulation in a phase I study.

Methods: This prospective, randomized, double-masked, vehicle-controlled trial, sponsored by Dompé SpA (registered as NCT01744704 at ClinicalTrials.

Crucial pathophysiological role of CXCR2 in experimental ulcerative colitis in mice.

Polymorphonuclear leukocyte infiltration and activation into colonic mucosa are believed to play a pivotal role in mediating tissue damage in human ulcerative colitis (UC). Ligands of human CXC chemokine receptor 1 and 2 (CXCR1/R2) are chemoattractants of PMN, and high levels were found in the mucosa of UC patients. To investigate the pathophysiological role played by CXCR2 in experimental UC, we induced chronic experimental colitis in WT and CXCR2(-/-) mice by two consecutive cycles of 4% dextran sulfate sodium administration in drinking water.

The role of CXCR2 activity in the contact hypersensitivity response in mice.

The recruitment of polymorphonuclear neutrophil leukocytes (PMN) into a challenge site, and their subsequent activation, are thought to play a role in the elicitation of the contact hypersensitivity (CHS) response. The present study investigated the role played by CXCR2 activity in tissue PMN infiltration and subsequent triggering of CHS. Our results show that the cutaneous infiltration by PMN, induced by hapten challenge was dramatically inhibited in sensitized, CXCR2-deficient (CXCR2(-/-)) mice.

Amphibian transition to the oxidant terrestrial environment affects the expression of glutathione S-transferases isoenzymatic pattern.

It has been postulated that glutathione S-transferases (GST; EC 2.5.1.

Scavenging system efficiency is crucial for cell resistance to ROS-mediated methylglyoxal injury.

Methylglyoxal is a reactive dicarbonyl compound endogenously produced mainly from glycolytic intermediates. Recent research indicates that methylglyoxal is a potent growth inhibitor and genotoxic agent. The antiproliferative activity of methylglyoxal has been investigated for pharmacological application in cancer chemotherapy.