Dendritic Cells Are the Intriguing Players in the Puzzle of Idiopathic Pulmonary Fibrosis Pathogenesis

Idiopathic pulmonary fibrosis (IPF) is the most devastating progressive interstitial lung disease that remains refractory to treatment. Pathogenesis of IPF relies on the aberrant cross-talk between injured alveolar cells and myofibroblasts, which ultimately leads to an aberrant fibrous reaction. The contribution of the immune system to IPF remains not fully explored. Recent evidence suggests that both innate and adaptive immune responses may participate in the fibrotic process. Dendritic cells (DCs) are the most potent professional antigen-presenting cells that bridge innate and adaptive immunity. Also, they exert a crucial role in the immune surveillance of the lung, where they are strategically placed in the airway epithelium and interstitium. Immature DCs accumulate in the IPF lung close to areas of epithelial hyperplasia and fibrosis. Conversely, mature DCs are concentrated in well-organized lymphoid follicles along with T and B cells and bronchoalveolar lavage of IPF patients. We have recently shown that all sub-types of peripheral blood DCs (including conventional and plasmacytoid DCs) are severely depleted in therapy naïve IPF patients. Also, the low frequency of conventional CD1c+ DCs is predictive of a worse prognosis. The purpose of this mini-review is to focus on the main evidence on DC involvement in IPF pathogenesis. Unanswered questions and opportunities for future research ranging from a better understanding of their contribution to diagnosis and prognosis to personalized DC-based therapies will be explored.

Percutaneous Needle Electrolysis Reverses Neurographic Signs of Nerve Entrapment by Induced Fibrosis in Mice

Nerve entrapments such as carpal tunnel syndrome are the most common mononeuropathies. The lesional mechanism includes a scarring reaction that causes a vascular compromise. The most effective treatment is surgery, which consists of removing the scarred area, thus reverting the vascular impairment. In the present study, a more conservative therapeutic approach has been undertaken to release the nerve by means of galvanic current (GC) applied with a needle: percutaneous needle electrolysis (PNE). For this purpose, a mouse model of sciatic nerve entrapment has been created using albumin coagulated by glutaraldehyde (albumin 35% and glutaraldehyde 2% volume applied, 10 μl). After two weeks, a fibrous reaction was obtained which entrapped the nerve to the extent of causing atrophy of the leg musculature (14.7%, P < 0.05 compared to the control leg). Ultrasound imaging confirmed that the model’s image was compatible with that of nerve entrapment in patients. To quantify the degree of entrapment, nerve conduction recordings were made. The amplitude (peak-to-peak) of the compound muscle action potential (CMAPs) decreased by 32.2% ( P < 0.05 ), and the proximal latency increases by 17.7% ( P < 0.05 , in both cases). In order to release the sciatic nerve, PNE was applied (1.5 mA for 3 seconds and 3 repetitions; 1.5/3/3) by means of a solid needle in the immediacy of perineural fibrosis before and 5 minutes after the application of GC, and the proximal latency shows a decrease of 16% ( P < 0.05 ). The recovery of CMAPs amplitude was about 48.7% ( P < 0.05 ). Three weeks later, the CMAPs amplitude was almost completely recovered (94.64%). Therefore, with the application of GC by means of a solid needle, the sciatic nerve was definitively released from its fibrous entrapment.

MORPHOLOGY OF GRAFTED TENDON

This is the first research done to explore the morphologic changes in two stage tendon grafting as compared to one stage tendon grafting. AIMS: To compare morphology of grafted tendons with and with out first stage silicon rubber rod implantation. STUDY DESIGN: Comparative experimental study. PERIOD: 1994-2007. MATERIAL AND METHODS: 30 patients were included in this study. They was divided into 3 groups. Group 1 underwent 2 stage tendon grafting group 3 was used as control morphological study of tendons. RESULTS: Group 1 (1-stage) tendon grafting showed degeneration and fibrous reaction as morphological changes. Group 2. (2 Stage) appeared as normal tendons morphologically. CONCLUSION: This study concludes that instead of direct tendon grafting, two stage tendon grafting is recommended.

Assessment of the Efficacy of the Bio-Absorbable Oxidized Regenerated Cellulose for Prevention of Post-Operative Pericardial Adhesion in the Rabbit Model

Pericardial adhesions complicate re-operative cardiac surgery and several attempts have been made to reduce adhesion formation. The efficacy of bio-absorbable oxidized regenerated cellulose in preventing post-operative pericardial adhesions was evaluated in the present study. Forty New Zealand white rabbits were divided into four groups of 10. In all rabbits an area of pericardium (2 × 2 cm) was excised. The wound was left open in groups 1 and 2 but replaced with bio-absorbable oxidized regenerated cellulose in groups 3 and 4. Rabbits in groups 1 and 3 were killed 3 weeks after surgery and those in groups 2 and 4 were killed at 6 weeks. Groups 1 and 2 showed more severe pericardial adhesions, more fibrous reaction and increased visibility of coronary vessels than groups 3 and 4, although there was no difference in inflammation. Light microscopy showed a mesothelium-like cell layer in groups 3 and 4. It is concluded that bio-absorbable oxidized regenerated cellulose may be suitable in patients receiving staged cardiac surgery and in those with a high probability of re-operation.

A COMPARISON OF TOPICAL HAEMOSTATIC AGENTS IN EXPERIMENTAL LIVER RESECTION

Bleeding from lacerated paranchymal organs such as the liver and spleen may be profuse and difficult to control. The haemostatic agent, calcium alginate (Kaltostat), which acts as a source of chelateable calcium ions has been compared with oxidised cellulose (Surgicel) and porcine collagen (Medistat) in experimental liver resection.Under general anaesthesia, a standard 3cm2 piece of liver was excised in 42 NZW rabbits and the haemostatic agent immediately applied. Bleeding was assessed at 3-minute intervals and blood loss precisely measured by haemolysis and a haemoglobinometer. Macroscopic and histological examinations of the liver were performed at 2 and 6 weeks.Calcium alginate stopped bleeding within 3 minutes with minimal blood loss in every animal and was significantly better than the other materials by both criteria. At 2 weeks the macroscopic appearances were similar for the 3 implants with inflammation on microscopy. Oxidised cellulose had absorbed by 6 weeks with calcium alginate having only minimal residual material surrounded by a fibrous reaction. Porcine collagen remained intact with a vigorous foreign body reaction and granuloma formation.Calcium alginate is significantly more effective than the haemostatic materials currently used in surgical practice.

Fibrous Mass Complicating Epidural Morphine Infusion

The benefits of continuous epidural morphine infusion using an implanted pump delivery system to control intractable cancer pain have recently been described. Most articles on this subject relate to dosage, technique, degree of pain relief, and tolerance. There are some anticipated complications of the treatment related to the surgical implantation of the system and drug toxicity. We present a complication presumably related to the epidural catheter. A fibrous reaction that developed around the catheter tip progressed into a mass. This caused a significant displacement of the spinal cord with the development of long tract symptoms. Identification of this abnormality using myelography and computed tomography led to prompt surgical decompression resulting in improvement of the patient's condition. (Neurosurgery 16:68–70, 1985)

Cyanoacrylate encasement of intracranial aneurysms

✓ Some intracranial aneurysms, because of their broad base or incorporation of essential nutritive vessels, must be treated by adhesive reinforcement. The authors report successful results with cyanoacrylate adhesives in five patients. The unique quality of this material permits maximum adhesion in a moist operative field. This adhesive is nonviscous and will coat the entire aneurysm, obviating problems related to incomplete coating. Excellent long-term results are apparently due to the biological effect of this adhesive in which a proliferative fibrous reaction occurs and counteracts recognized erosive properties.