The neurotransmitter serotonin (5-HT) is involved in the regulation of mouse intermale aggression. Previously, it was shown that intensity of mouse intermale aggression was positively associated with activity of the key enzyme of 5-HT synthesis - tryptophan hydroxylase 2 (TPH2) in mouse brain. The aim of the present study was ...

Paclitaxel produces a sensory neuropathy, characterized by mechanical and cold hypersensitivity, which are abated by antioxidants. The transient receptor potential vanilloid 4 (TRPV4) channel has been reported to contribute to paclitaxel-evoked allodynia in rodents. We recently showed that TRP ankyrin 1 (TRPA1) channel mediates oxaliplatin-evoked cold and mechanical allodynia, and ...

The objective of this study was to analyze the clinical, laboratorial, and therapeutical response of polymyalgia rheumatica (PMR) to anti-tumor necrosis factor (anti-TNF) treatment. We systematically searched English articles on the subjects of PMR who were treated with TNF blockers in Pubmed from 1994 to 2010. In addition, we reported ...

Leishmaniasis is one of the most serious worldwide diseases caused by protozoan parasites of the Leishmania genus, affecting millions of people around the world. All currently available treatments present severe toxic side effects, require long-term compliance, cause serious side effects and are uncomfortable for patients. Leishmania amazonensis, a species endemic ...

Salmonella typhimurium double leu-arg auxotrophs have been shown to be highly effective as antitumor agents in nude mouse models of human metastatic cancer.  In order to proceed to clinical development of the S. typhimurium double auxotroph, termed A1-R, it is necessary to evaluate antitumor efficacy in immunocompetent mice.  In the ...

Fabry disease (FD) is an X-linked inherited disease due to alpha-galactosidase A (alpha-Gal A) deficiency and characterized by lysosomal storage of globotriaosylceramide (Gb3) and related neutral glycosphingolipids. Storage of these substrates results in multisystem manifestations, including renal failure, cardiomyopathy, premature myocardial infarctions, stroke, chronic neuronopathic pain, gastrointestinal disturbances, and skin ...

PURPOSE: Dexrazoxane is an established treatment option in extravasation of the classic anthracyclines such as doxorubicin, epirubicin, and daunorubicin. However, it is not known whether the protection against the devastating tissue injuries extends into extravasation with new types of anthracyclines, the anthracenediones, or the liposomal pegylated anthracycline formulations. We therefore ...

Scant information exists about pegylated interferons (PEG-IFNs) use for treating hypereosinophilic syndrome (HES). We describe 6 patients with HES-1 patient with a newly identified chromosomal abnormality-who received PEG-IFNs. PEG-IFN alpha-2b replaced interferon (IFN) alpha-2b for 4 patients and was initial treatment of 2 patients. PEG-IFN alpha-2a was substituted when PEG-IFN ...

The pathogenesis of angiostrongyliasis, resulting from Angiostrongylus cantonensis invasion of the human central nervous system, remains elusive. Anthelmintics are usually used to kill worms, although dead worms in the brain may cause severe inflammation which will lead to central nervous system damage. Therefore, combination therapy with anthelmintics and anti-inflammatory drugs ...

Summary.  Haemophilia A is a life long bleeding disorder caused by an inherited deficiency of factor VIII (FVIII). About 30% of haemophilia A patients develop neutralizing antibodies as a consequence of treatment with FVIII concentrates. Immune tolerance protocols for the eradication of inhibitors require daily delivery of intravenous FVIII. We ...

Allylnitrile, cis-crotononitrile, and 3,3'-iminodipropionitrile are known to cause vestibular toxicity in rodents, and evidence is available indicating that cis-2-pentenenitrile shares this effect. We evaluated nineteen nitriles for vestibular toxicity in wild type (129S1) and CYP2E1-null mice, including all the above, several neurotoxic nitriles, and structurally similar nitriles. A new acute ...

In this study, we evaluated the effect of ketamine on exploratory locomotion behaviours in the Balb/c and C57BL/6 strains of mice, which differ in their locomotion behaviours. Intraperitoneal administration of ketamine at three different doses (1, 5 or 10mg/kg, 0.1ml/10 gr body weight) was performed on adult male Balb/c and ...

Abrogation of uridine phosphorylase (UPase) leads to abnormalities in pyrimidine metabolism and host protection against 5-fluorouracil (5-FU) toxicity. We elucidated the effects on the metabolism and antitumor efficacy of 5-FU and Capecitabine in our UPase knockout (UPase -/-) model. Treatment with 5-FU (85 mg/kg) or Capecitabine (1000 mg/kg) 5 days ...

Increased use of ketamine as a recreational drug in rave party has raised lots of social concerns. Although its toxicity on the central nervous system (CNS) and urinary system had been reported, its potential adverse effects on the heart is still not addressed. Using our long term ketamine addiction model ...

ETHNOPHARMACOLOGICAL RELEVANCE: Rhizoma coptidis is used as an antidysenteric in clinics in China. However, patients suffering from dysentery are susceptible to the acute toxicity of Rhizoma coptidis. The current study investigates the effects of lipopolysaccharide (LPS), which are a key pathogenic factor in dysentery, on the acute toxicity of a ...

BACKGROUND: The response to pegylated interferon (peg-IFN) plus ribavirin therapy remains less than ideal with 40-50% of treated subjects failing to clear the virus. Moreover, retreatment is only minimally effective. Consensus interferon (c-IFN) has been shown to be efficacious in HCV genotype 1 patients who have failed therapy with peg-IFN. ...

To investigate whether the enhancement of joint lymphangiogenesis by injection of vascular endothelial growth factor C (VEGF-C) adeno-associated virus (AAV) into the affected joints has therapeutic efficacy in chronic inflammatory arthritis in mice. Tumor necrosis factor-transgenic (TNF-Tg) mice were used as a model of chronic inflammatory arthritis. Human VEGF-C was ...

BACKGROUND: Cancer cachexia is characterised by the loss of body mass and directly compromises immune response and the quality of life of cancer patients. In the present study, we set out to investigate the role of Chinese herbs as anticancer medicines and/or chemotherapeutic adjuvants to increase therapeutic efficacy and/or ameliorate ...

Angiotensin II (AngII) infusion initiates abdominal aortic aneurysm (AAA) development due to medial disruption and results in luminal dilation and thrombus formation. The objective of this study was to determine whether AAA progressed during protracted AngII infusion. Male apoE(-/-) mice were infused with AngII using miniosmotic pumps. On day 27, ...

Cisplatin is chemotherapeutic drug used in treatment of malignancies. However, its clinical utility is limited by nephrotoxicity. The purpose of present study is to investigate biochemical and molecular effects of alpha lipoic acid (ALA) to protect against cisplatin-induced nephrotoxicity in mice. Cisplatin (12mg/kg/day) was administered i.p. for 4days. Group of ...

The taxane chemotherapeutic paclitaxel frequently produces peripheral neuropathy in humans. Rodent models to investigate mechanisms and treatments are largely restricted to male rats, whereas female mouse studies are lacking. We characterized a range of paclitaxel doses on cold and mechanical allodynia in male and female C57Bl/6 mice. Because the nonpsychoactive ...

1 Levels of IL-13, IL-1β and TNF-α are increased in bronchial lavage fluid of asthmatics and induce certain significant features of bronchial asthma including airway hyper-responsiveness (AHR). In this study, we have investigated the effect of these cytokines in naïve mice and those sensitized to ovalbumin (OVA) on bronchoconstrictions to ...

Chemotherapy induced intestinal mucositis is still an unmet medical problem. 5-fluorouracil (5-Fu), a chemotherapy drug, was used to create the animal model of mucositis. Global gene expression array was applied to identify genetic signals involved in the pathogenesis of mucositis. Interleukin 1 receptor antagonist (IL-1Ra) was one of the candidates ...

Emerging evidence suggests that adenomyosis, like endometriosis, may also be an epigenetic disease. In this study, we evaluated the effect of valproic acid (VPA) in ICR mice with adenomyosis, induced by neonatal dosing with tamoxifen. For all mice, we evaluated the bodyweight and the response to thermal stimuli by hotplate ...

The aim of this study was to assess, based on observational data from the Finnish Register of Biological Treatment, the outcomes of switching an initial tumor necrosis factor (TNF) blocker to another in the treatment of rheumatoid arthritis (RA). RA patients, who started biological therapy with a TNF blocker between ...

Objective It has been reported that D-galactose (D-gal) can model subacute aging, and aluminum (Al) acts as a neurotoxin, but combined effects of them have not been reported. The present work aimed to reveal the effect of combined administration of D-gal and Al in mice and compare the effect of ...

Intravenous nicotine self-administration is the most direct measure of nicotine reinforcement in laboratory animals, but this procedure has proven difficult to establish in mice. We found that stable responding for nicotine in C57BL6/J mice was facilitated by prior instrumental training for food reward, initial exposure of mice to a lower ...

Pretargeted radioimmunotherapy (PRIT) using an anti-CD45 antibody (Ab)-streptavidin (SA) conjugate and DOTA-biotin labeled with β-emitting radionuclides has been explored as a strategy to decrease relapse and toxicity. α-emitting radionuclides exhibit high cytotoxicity coupled with a short path length, potentially increasing the therapeutic index and making them an attractive alternative to ...

Circadian disruption accelerates malignant growth; thus, it should be avoided in anticancer therapy. The circadian disruptive effects of irinotecan, a topoisomerase I inhibitor, was investigated according to dosing time and sex. In previous work, irinotecan achieved best tolerability following dosing at zeitgeber time (ZT) 11 in male and ZT15 in ...

OBJECTIVE.: To examine whether synovial IL-17 expression promotes TNF-induced joint pathology in vivo. Furthermore, to analyze the surplus value of neutralizing IL-17 in addition to TNF during collagen-induced arthritis (CIA). METHODS.: Using adenoviral vectors, IL-17 and/or TNF were overexpressed in murine knee joints. In addition, mice with CIA were treated ...

Aseptic joint loosening is a key factor that reduces the life span of arthroplasty. There are currently few effective treatments for joint loosening except surgical revision. We explored the inhibitory effects of tumor necrosis factor (TNF)-alpha-targeted small interfering RNA (siRNA) on particle-induced inflammatory cytokine expression in the murine macrophage cell ...

OBJECTIVE: Clinical and preclinical evidence suggests that somatostatin exhibits potent antiinflammatory and antinociceptive properties. However, it is not known which of the five somatostatin receptor subtypes (ssts) is involved in these actions. METHODS: We have therefore assessed the effects of the stable somatostatin analogs octreotide and pasireotide (SOM230) in a ...

Wear debris is believed to cause periprosthetic osteolysis and loosening of total joint arthroplasties. We investigated the wear debris-mediated osteolysis in wild-type mice and macrophage-deficient Csf1op/Csf1op (op/op) mice using high density polyethylene (HDP) particles transplanted on the parietal bone surface. Four weeks after surgery, phagocytosis of the HDP particles by ...

Objective Human chondrocytes and annulus fibrosus cells of intervertebral disc (IVD) express osteoprotegerin (OPG), but the effect of OPG on the pathogenesis of IVD degeneration remains unknown. Here we assessed the phenotype change of IVD in OPG(-/-) mice. METHODS: The IVDs from 12-, 20-, and 28-week-old OPG(-/-) mice and WT ...

Deficiencies in either growth hormone (GH) or insulin-like growth factor 1 (IGF-1) are associated with reductions in bone size during growth in humans and animal models. Liver-specific IGF-1-deficient (LID) mice, which have 75% reductions in serum IGF-1, were created previously to separate the effects of endocrine (serum) IGF-1 from autocrine/paracrine ...

The pharmacological mechanisms focusing on chiral isomer of ibuprofen are not fully understood. Only the (S)-isomer of ibuprofen inhibits cyclooxygenases, which mediates the generation of prostanoids and thromboxanes. Consequently, (S)-isomers represent a major promoter of the anti-inflammatory effect, and the effects of the (R)-isomers have not been widely discussed. However, ...

Thrombin is a positive mediator of thrombus formation through the proteolytic activation of protease-activated receptors (PARs), fibrinogen, factor XI (fXI), and other substrates, and a negative regulator through activation of protein C, a natural anticoagulant with anti-inflammatory/cytoprotective properties. Protease-engineering studies have established that 2 active-site substitutions, W215A and E217A (fII(WE)), ...

Although oxidative stress participates in the etiopathogenesis of rheumatoid arthritis, its importance in this inflammatory disease has not been fully elucidated. In this study we analyzed the relevance of the transcription factor Nrf2, master regulator of redox homeostasis, in the effector phase of an animal model of rheumatoid arthritis using ...

While maintaining cardiac performance, chronic β-adrenoceptor activation eventually exacerbates the progression of cardiac remodelling and failure. We examined the adverse signalling pathways mediated by nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and reactive oxygen species (ROS) after chronic β₂-adrenoceptor activation. Mice with transgenic β₂-adrenoceptor overexpression (β₂-TG) and non-transgenic littermates were either ...

Although rheumatoid arthritis (RA) is an autoimmune disease of unknown etiology, the role of IL-1β and IL-18 in the pathophysiology of RA has been well established. IL-1β and IL-18 are generated via cleavage of their pro-forms in the presence of the apoptosis-associated speck-like protein containing a caspase recruit domain (ASC), ...

OBJECTIVE: Evidence indicates that proteinase-activated receptor (PAR)-2 participates in the degradative processes of human osteoarthritis (OA). We evaluated the in vivo effect of PAR-2 on articular lesions in a PAR-2-knockout (KO) mouse model of OA. METHODS: OA was surgically induced by destabilization of the medial meniscus of the right knee ...

Few animal model studies have been conducted in order to evaluate the impact of androgenic anabolic steroids (AAS) supraphysiological doses on the cardiovascular system and myocardial injury. Twenty-five male CD1 mice (8-10 weeks old; 35g initial body weight) were randomized into three AAS treated groups and two control groups. The ...

To determine the mechanisms involved in inflammatory responses to octacalcium phosphate (OCP) crystals in vivo. OCP crystal-induced inflammation was monitored using a peritoneal model of inflammation in mice with different deficiencies affecting interleukin-1 (IL-1) secretion (IL-1α(-/-) , IL-1β(-/-) , ASC(-/-) , and NLRP3(-/-) mice) or in mice pretreated with IL-1 ...

Synovial joints enable smooth articulations between different skeletal elements and are essential for the motility of vertebrates. Despite decades of extensive studies of the molecular and cellular mechanisms of limb and skeletal development, the molecular mechanisms governing synovial joint formation are still poorly understood. In particular, whereas several signaling pathways ...

To study temporomandibular joint (TMJ) involvement in an autoimmune murine model of rheumatoid arthritis (RA), a disease characterized by inflammatory destruction of the synovial joints. Although TMJ dysfunction is frequently found in RA, TMJ involvement in RA remains unclear, and TMJ pathology has not been studied in systemic autoimmune animal ...

There has been a consistent gap in understanding how TNF-α neutralization affects the disease state of arthritis patients so rapidly, considering that joint inflammation in rheumatoid arthritis is a chronic condition with structural changes. We thus hypothesized that neutralization of TNF-α acts through the CNS before directly affecting joint inflammation. ...

OBJECTIVE: /st> Aggrecan is a critical component of cartilage extracellular matrix. Several members of the 'a disintegrin and metalloproteinase with thrombospondin motifs' (ADAMTS) family have been characterised as aggrecanases by their ability to generate fragments containing the NITEGE neoepitope from aggrecan. Increased NITEGE fragments in synovial fluid and articular cartilage ...

We investigated a small-molecule modulator of tumor necrosis factor alpha (TNF-alpha), UTL-5g (also referred to as GBL-5g), as a potential chemoprotective agent against cisplatin-induced side effects including nephrotoxicity, hepatotoxicity and hematotoxicity. Pretreatment of UTL-5g i.p. in BDF1 mice reduced the levels of blood urea nitrogen (BUN) and creatinine induced by ...

Leishmaniasis is a protozoan disease, affecting 12 million people in different regions of the world with a wide spectrum of diseases. Although several chemotherapeutic agents have been used for treating the disease, long-term therapy, limited efficacy and the development of drug-resistant parasites remain the major limitations. To develop a new ...

Chagas disease caused by Trypanosoma cruzi is an important cause of mortality and morbidity in Latin America but no vaccines or safe chemotherapeutic agents are available. Combined therapy is envisioned as an ideal approach since it may enhance efficacy by acting upon different cellular targets, may reduce toxicity and minimize ...