Attenuation of postoperative adhesions using a modeled manual therapy.

Postoperative adhesions are pathological attachments that develop between abdominopelvic structures following surgery. Considered unavoidable and ubiquitous, postoperative adhesions lead to bowel obstructions, infertility, pain, and reoperations. As such, they represent a substantial health care challenge.

Modulation of breast cancer cell viability by a cannabinoid receptor 2 agonist, JWH-015, is calcium dependent.

Introduction: Cannabinoid compounds, both nonspecific as well as agonists selective for either cannabinoid receptor 1 (CB1) or cannabinoid receptor 2 (CB2), have been shown to modulate the tumor microenvironment by inducing apoptosis in tumor cells in several model systems. The mechanism of this modulation remains only partially delineated, and activity induced via the CB1 and CB2 receptors may be distinct despite significant sequence homology and structural similarity of ligands.

Methods: The CB2-selective agonist JWH-015 was used to investigate mechanisms downstream of CB2 activation in mouse and human breast cancer cell lines in vitro and in a murine mammary tumor model.

Immunosuppressive effects of erythropoietin on human alloreactive T cells.

Correction of anemia with erythropoietin (EPO) is associated with improved kidney transplant outcomes. Emerging evidence, predominantly from animal models, indicates that these observations may be erythropoiesis-independent and that EPO exhibits immunosuppressive properties. We examined the effects of EPO on human T-cell alloimmunity by first documenting that CD4(+) and CD8(+) T cells express EPO receptor (EPO-R) on their surfaces.

Disease modification of breast cancer-induced bone remodeling by cannabinoid 2 receptor agonists.

Most commonly originating from breast malignancies, metastatic bone cancer causes bone destruction and severe pain. Although novel chemotherapeutic agents have increased life expectancy, patients are experiencing higher incidences of fracture, pain, and drug-induced side effects; furthermore, recent findings suggest that patients are severely undertreated for their cancer pain. Strong analgesics, namely opiates, are first-line therapy in alleviating cancer-related pain despite the severe side effects, including enhanced bone destruction with sustained administration.

Novel peptide ligands with dual acting pharmacophores designed for the pathophysiology of neuropathic pain.

The conventional design of high affinity drugs targeted to a single molecule has not resulted in clinically useful therapies for pain relief. Recent reviews have suggested that newly designed analgesic drugs should incorporate multiple targets. The distributions of cholecystokinin (CCK) and CCK receptors in the central nervous system (CNS) overlap significantly with endogenous opioid systems and can be dually targeted.

Development of potent μ and δ opioid agonists with high lipophilicity.

An SAR study on the Dmt-substituted enkephalin-like tetrapeptide with a N-phenyl-N-piperidin-4-ylpropionamide moiety at the C-terminal was performed and has resulted in highly potent ligands at μ and δ opioid receptors. In general, ligands with the substitution of D-Nle(2) and halogenation of the aromatic ring of Phe(4) showed highly increased opioid activities. Ligand 6 with good biological activities in vitro demonstrated potent in vivo antihyperalgesic and antiallodynic effects in the tail-flick assay.

Constitutive activity at the cannabinoid CB(1) receptor and behavioral responses.

The cannabinoid receptor type 1, found mainly on cells of the central and peripheral nervous system, is a major component of the endogenous cannabinoid system. Constitutive and endogenous activity at cannabinoid receptor type 1 regulates a diverse subset of biological processes including appetite, mood, motor function, learning and memory, and pain. The complexity of cannabinoid receptor type 1 activity is not limited to the constitutive activity of the receptor: promiscuity of ligands associated with and the capability of this receptor to instigate G protein sequestration also complicates the activity of cannabinoid receptor type 1.