Influence of TNF-α and biomechanical stress on matrix metalloproteinases and lysyl oxidases expressions in human knee synovial fibroblasts

Purpose

It was reported that not only ACL but also the synovium may be the major regulator of matrix metalloproteinases (MMPs) in synovial fluids after ACL injury. In order to further confirm whether synovium is capable of regulating the microenvironment in the process of ACL injury, the complicated microenvironment of joint cavity after ACL injury was mimicked and the combined effects of mechanical injury and inflammatory factor [tumour necrosis factor-α (TNF-α)] on expressions of lysyl oxidases (LOXs) and MMPs in synovial fibroblasts derived from normal human synovium were studied.

Methods

Human normal knee joint synovial fibroblasts were stimulated for 1–6 h with mechanical stretch and inflammatory factor (TNF-α). Total RNA was harvested, reverse transcribed and assessed by real-time polymerase chain reaction for the expression of LOXs and MMP-1, 2, 3 messenger RNAs. MMP-2 activity was assayed from the collected culture media samples using zymography.

Results

Compared to control group, our results showed that 6 % physiological stretch increased MMP-2 and LOXs (except LOXL-3), decreased MMP-1 and MMP-3; injurious stretch (12 %) decreased LOXs (except LOXL-2)and increased MMP-1, 2 and 3; the combination of injurious stretch and TNF-α decreased LOXs and increased MMP-1, 2 and 3 in synovial fibroblasts in a synergistical manner.

Conclusion

This study demonstrated that combination of mechanical injury and inflammatory factors up-regulated the expressions of MMPs and down-regulated the expressions of LOXs in synovial fibroblasts, eventually alter the balance of tissue healing. Thus, synovium may be involved in regulating the microenvironment of joint cavity. Based on the mechanism, early interventions to inhibit the production of MMPs or promote the production of LOXs in the synovial fibroblasts should be performed to facilitate the healing of tissue.     

Ankle: surface coil MR imaging at 1.5 T

High-field surface coil magnetic resonance (MR) images were obtained of 12 ankles: two from healthy volunteers, seven from patients, and three from fresh cadavers. The cadaver ankles were sectioned in the coronal, sagittal, and axial planes for direct comparison with the MR images. Plain film confirmation of pathologic conditions was obtained in all patients, and five underwent arthroscopy or surgery, or both. MR imaging provided excellent delineation of ligaments and cartilaginous structures in all cases.     

Platelet transfusion from donors mismatched for crossreactive HLA antigens

Increments in platelet counts following the transfusion of platelets mismatched for crossreactive antigens were evaluated in 67 patients with broad alloimmunization to HLA antigens. The corrected increments following 100 HLA, A-matched and B1U- or B2U-matched transfusions were compared with the increments following 307 B1X- or B2X-matched transfusions. HLA-A3 platelets were tolerated poorly by A1 and A11 recipients, as were A1 and A11 by A3 recipients, B17 and BW21 by recipients in the B7 crossreactive group, B5 by B15 and B17 recipients, and B27 by recipients in the B5 crossreactive group. B12 and BW21, and B8 and B14 platelets were not tolerated bidirectionally. Antigens associated with good increments included A28 in A2 recipients, B18 and BW16 (C match) in recipients in the B5 crossreactive group, B5 in B18 recipients, BW22 and B7 in recipients in the B7 crossreactive group. A1 and A11 were transfused successfully bidirectionally. These observations suggest that some private antigens within crossreactive groups are more immunogenic than others and support the observation of others than B17 and BW21 are not in the B5 crossreactive group.     

The Hong Kong Society of Rheumatology consensus recommendations for the management of gout

Clinical Rheumatology - Gout is one of the most common noncommunicable diseases in Hong Kong. Although effective treatment options are readily available, the management of gout in Hong Kong remains...     

Vasodilator agents and supracollicular transection fail to inhibit cortical spreading depression in the cat

It remains an open question as to whether cortical spreading depression (CSD) is the pathophysiological correlate of the neurological symptoms in migraine with aura. In the experimental animal, CSD is an electrophysiological phenomenon mainly mediated via NMDA receptors. However, according to case reports in humans, visual aura in migraine can be alleviated by vasodilator substances, such as amyl nitrite and isoprenaline. There is also circumstantial evidence that brainstem nuclei (dorsal raphe nucleus and locus coeruleus) may play a pivotal role in the initiation of aura. In this study, CSD was elicited in alpha-chloralose anesthetized cats by cortical needle stab injury and monitored by means of laser Doppler flowmetry. Topical application of isoprenaline (0.1-1%) and amyl nitrite (0.05%) onto the exposed cortex had no effect on the elicitation or propagation of CSD. Also, after supracollicular transection, subsequent CSDs showed no differences in the speed of propagation and associated flow changes. We conclude from these data that--given CSD probably exists in humans during migraine--spreading neurological deficits during migraine aura are independent of brainstem influence and have a primarily neuronal rather than vascular mechanism of generation.     

Erythromycin treatment for gastrointestinal dysmotility in preterm infants

To report our clinical experience on the use of oral erythromycin for the treatment of severe gastrointestinal dysmotility in preterm infants.

Methodology:

A case series study of seven preterm infants (six were very low birthweight) with severe intestinal dysmotility in a tertiary neonatal centre.

Results:

All responded favourably without adverse effects and tolerated full enteral feeding within 1–2 weeks of the commencement of the drug.

Conclusions:

As prolonged total parenteral nutrition carries significant risk of complications, this therapy could be considered in selected preterm infants who fail to establish enteral feeding after an extended period, and in whom an anatomically obstructive lesion of the gastrointestinal tract has been excluded. Meanwhile, we would caution against the widespread implementation of this therapeutic approach until formal evaluation by randomized controlled trials have established the exact role of erythromycin, or its analogues, in the treatment of intestinal dysmotility in preterm infants.