Degradation of human articular cartilage by neutrophils in synovial fluid

Objective. To determine whether surface-adherent immunoglobulins are capable of mediating synovial fluid (SF) neutrophil degradation of proteoglycan and collagen in intact, normal human articular cartilage, and to define the respective roles of neutrophil serine proteases and metalloproteases in degrading these cartilage constituents. Methods. Pellet explants of normal human articular cartilage pretreated with bovine serum albumin (BSA) or IgG were incubated with polymorphonuclear cells suspended in SF (PMN-SF), or with supernatants derived from neutrophils stimulated with surface-associated IgG. Proteoglycan degradation was measured by assaying release of ³⁵S-proteoglycan fragments from cartilage explants prelabeled with ³⁵S-sulfate. Collagen degradation was measured by assaying hydroxyproline content in the PMN-SF preparations or neutrophil supernatants following their incubation with unlabeled explants. Results. Significant release of both ³⁵S fragments and hydroxyproline was noted following incubation of PMN-SF with IgG-treated pellets, compared with pellets treated with BSA. IgG preparations derived from pooled normal serum or rheumatoid arthritis SF were equally efficacious in mediating PMN degradation of cartilage collagens. Explant release of ³⁵S fragments during incubation with PMN supernatant was completely inhibited when serine proteases were inactivated by diisopropyl fluorophosphate (DFP); however, release of ³⁵S fragments was enhanced when metalloprotease activity was present in the supernatant. Release of hydroxyproline during incubation of explants with PMN supernatant was comparable in the presence of DFP or EDTA, but was markedly enhanced when both serine and metalloprotease activity were present in the supernatant. Conclusion. Neutrophils in SF are capable of degrading both proteoglycans and collagens in intact human articular cartilage. Degradation of these cartilage constituents is facilitated by immunoglobulins adherent to the cartilage surface and by the synergistic action of PMN serine and metalloproteases released during activation of neutrophils with surface-associated immunoglobulin.     

Carbohydrate craving in obese people: Suppression by treatments affecting serotoninergic transmission

We examined the existence of carbohydrate cravings, and the effects on such cravings of treatments that enhance serotonin release, among 24 obese subjects who claimed to have excessive appetites for carbohydrates. Subjects living in a college dormitory for four weeks were given three fixed meals daily and allowed to choose at will among five protein-rich or five carbohydrate-rich isocaloric snack foods, provided via a vending machine. For two weeks, they received no treatment (study 1) or a placebo (study 2); for the next two weeks, they received placebo, d-1 fenfluramine or 1-tryptophan. All but one of the subjects exhibited a marked preference for carbohydrate-rich over protein-rich snacks during the first two weeks of the study. The average daily intake of carbohydrate-rich snacks was 4.1 ± 0.4 and of protein-rich snacks 0.8 ± 0.3. Seventeen of the subjects failed to consume any protein snacks on most days during the baseline or test periods, thus it was not possible for us to examine the effect of test treatments on protein snack intake. Fenfluramine administration significantly reduced carbohydrate snacking in six of nine test subjects, as well as in the group as a whole (2.4 ± 0.6 snacks/day vs 4.2 ± 0.6 during the two-week baseline period). Tryptophan significantly diminished carbohydrate intake in three of the eight treated subjects, and increased it in one subject; it did not significantly modify snacking patterns in the group as a whole. Placebo administration did not affect carbohydrate intake in any of the seven test subjects. These observations show that some obese people do consume carbohydrate-rich snacks frequently and preferentially, and that this behavior can sometimes be diminished by treatments thought to enhance serotonin's release (fenfluramine) or synthesis (tryptophan).     

Acute Metabolic Effects of Nitrogen Mustard and Thiotepa on Rabbit Articular Cartilage and Synovium

Metabolic alterations in immature rabbit joint tissues were examined following in vitro and in vivo exposure to the alkylating agents Thiotepa and nitrogen mustard. Brief exposure in vitro to either agent resulted in marked suppression of incorporation of radiolabeled precursors of protein, RNA, and glycosaminoglycan synthesis in articular cartilage, which was partially reversible after Thiotepa exposure. In vivo, nitrogen mustard had little effect on synovium and transient inhibitory effects on cartilage vital processes, whereas Thiotepa caused a prolonged inhibition of synovial metabolism with little effect on cartilage. Autoradiographic localization of labeled agents indicated that synovial tissue and cartilage were readily penetrated by nitrogen mustard, but only a few synovial lining cells and superficial chondrocytes were labeled with ³⁵S-Thiotepa. Furthermore, trypsin significantly reduced labeling of cartilage with ¹⁴C-nitrogen mustard. These data suggest that alkylating agents differentially affect metabolic processes in joint tissues in vivo and that with Thiotepa, this interference occurs primarily in the synovium. The degree of interference is apparently dependent upon time of exposure to the agents and the relative DNA-RNA synthetic activity of the joint tissue.     

Complications of total hip arthroplasty: periprosthetic fractures of the acetabulum

Periprosthetic fractures of the acetabulum are a rare but potentially disastrous complication of total hip arthroplasty. Such fractures occur either as early perioperative complications or late complications when they are associated with either significant trauma or as a result of the loss of the structural integrity of the bone supporting the prosthesis, such as aseptic osteolysis. The incidence of such fractures appears to be increasing with the increased use of uncemented acetabular components. This article explores the current literature on the epidemiology, etiology, and classification of periprosthetic acetabular fractures as well as offering potential treatment strategies.     

Prenatal Stress Increases the Hypothalamo-Pituitary-Adrenal Axis Response in Young and Adult Rats

Prenatal stress is considered as an early epigenetic factor able to induce long-lasting alterations in brain structures and functions. It is still unclear whether prenatal stress can induce long-lasting modifications in the hypothalamo-pituitary-adrenal axis. To test this possibility the effects of restraint stress in pregnant rats during the third week of gestation were investigated in the functional properties of the hypothalamo-pituitary-adrenal axis and hippocampal type I and type II corticosteroid receptors in the male offspring at 3, 21 and 90 days of age. Plasma corticosterone was significantly elevated in prenatally-stressed rats at 3 and 21 days after exposure to novelty. At 90 days of age, prenatally-stressed rats showed a longer duration of corticosterone secretion after exposure to novelty. No change was observed for type I and type II receptor densities 3 days after birth, but both receptor subtypes were decreased in the hippocampus of prenatally-stressed offspring at 21 and 90 days of life. These findings suggest that prenatal stress produces long term changes in the hypothalamo-pituitary-adrenal axis in the offspring.     

Effects of cholinergic stimulation on pituitary hormone release

Physostigmine was infused into human volunteers to assess the effect of central cholinergic stimulation on memory and on neuroendocrine function. Methscopolamine bromide, a peripheral anticholinergic agent, was given simultaneously. The lower dose of physostigmine (1.0 mg) produced no change in AVP, cortisol, melatonin, GH or LH in those subjects without unpleasant cholinergic side effects. Larger doses of physostigmine usually produced nausea, and were associated with marked elevations of AVP, cortisol and prolactin, but no change in GH, LH or melatonin. Thus, cholinergic agents easily induce a stress response, but the GH component of this response can be suppressed by peripheral cholinergic blockade.     

Diagnostic criteria for multiple sclerosis: 2005 revisions to the "McDonald Criteria"

New diagnostic criteria for multiple sclerosis integrating magnetic resonance image assessment with clinical and other paraclinical methods were introduced in 2001. The "McDonald Criteria" have been extensively assessed and used since 2001. New evidence and consensus now strengthen the role of these criteria in the multiple sclerosis diagnostic workup to demonstrate dissemination of lesions in time, to clarify the use of spinal cord lesions, and to simplify diagnosis of primary progressive disease. The 2005 Revisions to the McDonald Diagnostic Criteria for MS should simplify and speed diagnosis, whereas maintaining adequate sensitivity and specificity.