Salivary gland derived peptides as a new class of anti-inflammatory agents: review of preclinical pharmacology of C-terminal peptides of SMR1 protein.

The limitations of steroidal and non steroidal anti-inflammatory drugs have prompted investigation into other biologically based therapeutics, and identification of immune selective anti-inflammatory agents of salivary origin. The traditional view of salivary glands as accessory digestive structures is changing as their importance as sources of systemically active immunoregulatory and anti-inflammatory factors is recognized. Salivary gland involvement in maintenance of whole body homeostasis is regulated by the nervous system and thus constitutes a "neuroendocrine axis". The potent anti-inflammatory activities, both in vivo and in vitro, of the tripeptide Phe-Glu-Gly (FEG) are reviewed. FEG is a carboxyl terminal peptide of the prohormone SMR1 identified in the rat submandibular salivary gland, The D-isomeric form (feG) mimics the activity of its L-isomer FEG. Macropharmacologically, feG attenuates the cardiovascular and inflammatory effects of endotoxemia and anaphylaxis, by inhibition of hypotension, leukocyte migration, vascular leak, and disruption of pulmonary function and intestinal motility. Mechanistically, feG affects activated inflammatory cells, especially neutrophils, by regulating integrins and inhibiting intracellular production of reactive oxygen species. Pharmacodynamically, feG is active at low doses (100 µg/kg) and has a long (9-12 hour) biological half life. As a therapeutic agent, feG shows promise in diseases characterized by over exuberant inflammatory responses such as systemic inflammatory response syndrome and other acute inflammatory diseases. Arthritis, sepsis, acute pancreatitis, asthma, acute respiratory inflammation, inflammatory bowel disease, and equine laminitis are potential targets for this promising therapeutic peptide. The term "Immune Selective Anti-Inflammatory Derivatives" (ImSAIDs) is proposed for salivary-derived peptides to distinguish this class of agents from corticosteroids and nonsteroidal anti-inflammatory drugs.

Effect of intraarticular injection of autologous adipose-derived mesenchymal stem and regenerative cells on clinical signs of chronic osteoarthritis of the elbow joint in dogs.

Autologous adipose-derived mesenchymal stem cell (AD-MSC) therapy involves harvesting fat from the patient, isolating the stem and regenerative cells, and administering the cells back to the patient. Autologous AD-MSC therapy in veterinary regenerative medicine has been commercially available since 2003. Previously reported results from a blinded, controlled trial in dogs with chronic osteoarthritis of the coxofemoral (hip) joint demonstrated efficacy of a single intraarticular injection of autologous AD-MSC therapy. The primary objective of the current study was to evaluate the effectiveness of this therapy in dogs with chronic osteoarthritis of the humeroradial (elbow) joints and to determine the duration of effect. Fourteen dogs were recruited. Veterinarians assessed each dog for lameness, pain on manipulation, range of motion, and functional disability using a numeric rating scale at baseline and specified intervals up to 180 days after treatment. Statistically significant improvement in outcome measures was demonstrated.

Effect of adipose-derived mesenchymal stem and regenerative cells on lameness in dogs with chronic osteoarthritis of the coxofemoral joints: a randomized, double-blinded, multicenter, controlled trial.

Autologous stem cell therapy in the field of regenerative veterinary medicine involves harvesting tissue, such as fat, from the patient, isolating the stem and regenerative cells, and administering the cells back to the patient. Autologous adipose-derived stem cell therapy has been commercially available since 2003, and the current study evaluated such therapy in dogs with chronic osteoarthritis of the hip. Dogs treated with adipose-derived stem cell therapy had significantly improved scores for lameness and the compiled scores for lameness, pain, and range of motion compared with control dogs. This is the first randomized, blinded, placebo-controlled clinical trial reporting on the effectiveness of stem cell therapy in dogs.

Use of client-specific outcome measures to assess treatment effects in geriatric, arthritic dogs: controlled clinical evaluation of a nutraceutical.

A questionnaire method was designed for dog owners to monitor the orthopedic disabilities of their pets for evaluation of a nutraceutical with joint health claims. Fifty large-breed dogs, 7 to 12 years of age, presenting with signs of osteoarthritis, were randomly allocated to placebo and active treatment groups. Degree of disability was assessed by physical examination, a standard questionnaire on daily activities, and a case-specific questionnaire that monitored specific impairments of each dog. The test product was a special milk protein concentrate (SMPC) from hyperimmunized cows, previously shown to express antiinflammatory and antiarthritic activity in humans. After a 1-week run-in period of dosing with placebo, each dog was randomly assigned to a treatment and given gelatin capsules containing either SMPC or a placebo twice daily for 8 weeks. Overall improvement was noted in 68% and 35% of the SMPC and placebo groups, respectively. Significant (P <.05) improvement in mean standardized and patient- specific questionnaire scores and in owner global assessments was detected in the SMPC group but not in the placebo group. Compared with the placebo group, the treatment response was significantly better in the SMPC group with regard to case-specific scores (P <.001) and owner global assessments (P =.004). The product was well tolerated and serum chemistry findings remained within normal limits.

Use of client-specific outcome measures to assess treatment effects in geriatric, arthritic dogs: controlled clinical evaluation of a nutraceutical.

A questionnaire method was designed for dog owners to monitor the orthopedic disabilities of their pets for evaluation of a nutraceutical with joint health claims. Fifty large-breed dogs, 7 to 12 years of age, presenting with signs of osteoarthritis, were randomly allocated to placebo and active treatment groups. Degree of disability was assessed by physical examination, a standard questionnaire on daily activities, and a case-specific questionnaire that monitored specific impairments of each dog. The test product was a special milk protein concentrate (SMPC) from hyperimmunized cows, previously shown to express antiinflammatory and antiarthritic activity in humans. After a 1-week run-in period of dosing with placebo, each dog was randomly assigned to a treatment and given gelatin capsules containing either SMPC or a placebo twice daily for 8 weeks. Overall improvement was noted in 68% and 35% of the SMPC and placebo groups, respectively. Significant (P <.05) improvement in mean standardized and patient-specific questionnaire scores and in owner global assessments was detected in the SMPC group but not in the placebo group. Compared with the placebo group, the treatment response was significantly better in the SMPC group with regard to case-specific scores (P lt;.001) and owner global assessments (P =.004). The product was well tolerated and serum chemistry findings remained within normal limits.

Effects of a milk-based bioactive micronutrient beverage on pain symptoms and activity of adults with osteoarthritis: a double-blind, placebo-controlled clinical evaluation.

OBJECTIVES: A 6 wk, double-blind, placebo-controlled study investigated the effects of a nutritional supplement beverage containing milk-based micronutrients and fortified with vitamins and minerals on pain symptoms and activity in adults with osteoarthritis. METHODS: Thirty-one subjects with osteoarthritis of both knees were randomized into two groups and given 12 oz daily of the micronutrient-containing beverage or a placebo for 6 wk. Subjects were instructed not to change their normal activities and diets. Body weights, vital signs, blood chemistries, and adverse events were monitored to assess safety. The principal outcome measurement for efficacy was the Western Ontario MacMaster Universities Osteoarthritis Index (WOMAC) derived from the Knee Injury and Osteoarthritis Outcome Score (KOOS) questionnaire administered weekly. RESULTS: Safety indicators remained unchanged in the test and placebo groups. All KOOS scores improved significantly (P < 0.03) over time in the micronutrient group, whereas scores only for sport function and knee-related quality of life improved in the placebo group. The overall treatment effect (based on changes in the WOMAC composite score) was significant (P = 0.016). The effect size was moderate at 0.555. CONCLUSIONS: Thus, daily consumption of the nutritional beverage containing milk-based micronutrients, vitamins, and minerals was beneficial in alleviating symptoms and dysfunction in subjects with osteoarthritis.