Regulation of interleukin-12 expression in human monocytes: selective priming by interferon-gamma of lipopolysaccharide-inducible p35 and p40 genes

Interleukin-12 (IL-12) is a monocyte/macrophage-derived cytokine that is critical for T lymphocyte and natural killer cell activities and functions. In this study, we examined the regulation of IL-12 expression by human monocytes in response to bacterial lipopolysaccharide (LPS). Several novel aspects of IL-12 induction from monocytes were shown. Optimal expression of IL-12 mRNA and bioactivity required specific priming of monocytes by interferon-gamma (IFN-gamma) before LPS stimulation. Granulocyte-macrophage colony-stimulating factor (GM-CSF) provided an equivalent priming stimulus for LPS-induced tumor necrosis factor (TNF) and IL-12 p40 mRNA, but primed poorly for LPS-inducible p35 message and secreted IL-12 activity. Macrophage colony-stimulating factor (M-CSF), although a potent survival factor for monocytes, showed no priming activity for IL-12 production. Time course experiments demonstrated independent regulation of p40 and p35 by IFN-gamma and LPS. LPS inducibility of p40 expression required only a brief exposure to IFN-gamma (2 hours), while prolonged exposure (+/- 24 hours) to IFN-gamma resulted in diminishing levels of p40 mRNA. p35 inducibility (by LPS) required a longer exposure to IFN-gamma (8 to 16 hours), and continued to be inducible up to 40 hours following IFN- gamma priming. Both mRNAs were rapidly induced (1 to 2 hours) in IFN- gamma-primed monocytes; p35 message reached a plateau by 2 hours, while p40 continued to accumulate. Finally, both p40 and p35 were directly induced by LPS in the presence of cycloheximide. These results indicated that both p40 and p35 are LPS-inducible in monocytes following IFN-gamma pretreatment, and that the regulated expression of p35 controls the level of active IL-12 protein in purified human monocytes. The selectivity of priming by IFN-gamma is in accord with a putative role for IL-12 in the initiation and amplification of TH1-type responses.     

Evaluation of residual hearing in cochlear implants candidates using auditory steady-state response

Conclusion: The correlations between behavioral and auditory steady-state response (ASSR) thresholds were significant at 500, 1000, 2000, and 4000 Hz. ASSR presented high sensitivity and specificity in the detection of residual hearing in cochlear implant candidates when compared with warble-tone audiometry. Objectives: To assess residual hearing in cochlear implant candidates by comparing the electrophysiological thresholds obtained in dichotic single-frequency ASSR with behavioral thresholds at 500, 1000, 2000, and 4000 Hz. Methods: This was a comparative study between ASSR and warble-tone audiometry thresholds in 40 cochlear implant candidates (80 ears) before cochlear implantation with bilateral severe-to-profound sensorineural hearing loss. Results: Thresholds were obtained in 62.5% of all frequencies evaluated in warble-tone audiometry and in 63.1% in the ASSR. ASSR sensitivity was 96% and specificity was 91.6%. Mean differences between behavioral and ASSR thresholds did not reach significance at any frequencies. Strong correlations between behavioral and ASSR thresholds were observed in 500, 1000, and 2000 Hz and moderate in 4000 Hz, with correlation coefficients varying from 0.65 to 0.81. On 90% of occasions, ASSR thresholds were acquired within 10 dB of behavioral thresholds.     

Perforated duodenal diverticulum: Surgical treatment and literature review

INTRODUCTION

Duodenum is the second most frequent location for a diverticulum in the digestive tract. Complications are rare and perforation was only reported in less than 200 cases.

PRESENTATION OF CASE

A 79-year-old female was admitted to Emergency Department with abdominal pain and vomiting for the last 24 h. A CT scan was performed and moderated extra-luminal air was identified. During surgery a fourth portion perforated duodenal diverticulum was diagnosed and duodenal resection was performed.

DISCUSSION

First reported in 1710, the incidence of duodenal diverticula can be as high as 22%. Nevertheless complications are extremely rare and include haemorrhage, inflammation, compression of surrounding organs, neoplastic progression, cholestasis and perforation.As perforations are often retroperitoneal, symptoms are nonspecific and rarely include peritoneal irritation, making clinical diagnose a challenge.CT scan will usually present extra-luminal retroperitoneal air and mesenteric fat stranding, providing clues for the diagnosis.Although non-operative treatment has been reported in selected patients, standard treatment is surgery and alternatives are diverse including diverticulectomy or duodenopancreatectomy.

CONCLUSION

Perforated diverticula of the fourth portion of the duodenum are extremely rare and current evidence still supports surgery as the primary treatment modality.