Tubular expression of angiotensin II receptors and their regulation in IgA nephropathy

Enhanced renal expression for the renin-angiotensin system (RAS) is detected in IgA nephropathy (IgAN). Previous data showed an altered glomerular expression of angiotensin II type 1 receptor (AT1R), suggesting a regulatory response to high intrarenal angiotensin II (Ang II) concentration in IgAN. In this study, the expression and regulation of Ang II receptors were examined in human proximal tubular epithelial cells (PTEC) in IgAN. Tubular expression of AT1R and Ang II type 2 receptor (AT2R) was increased in IgAN. In vitro culture experiment showed that the upregulation of Ang II receptors was not due to the direct effect of IgA but the indirect effect after IgA deposition on human mesangial cell. When PTEC were cultured with conditioned culture medium from human mesangial cells activated with IgA, Ang II production was upregulated, leading to inflammation and apoptosis via the AT1R and AT2R, respectively. Sequential expression of Ang II receptors determined the injury of PTEC induced by mediators in the conditioned medium. The initial interaction between Ang II and AT1R activated both protein kinase C and mitogen-activated protein kinase pathways, leading to inflammatory responses. This early AT1R-dependent event was followed by upregulation of AT2R expression and continued Ang II release. The interaction between Ang II and AT2R subsequently led to expression of cleaved poly[ADP-ribose] polymerase through downregulation of the mitogen-activated protein kinase pathway. The data suggest that appropriate control of Ang II receptor activities in PTEC may ameliorate tubulointerstitial injury in IgAN.     

Corticotropin-releasing hormone peptide and human first-trimester placental growth

The aim of this study was to determine whether corticotropin-releasing hormone (CRH) regulates human trophoblast cell growth. The results showed that exogenous CRH significantly stimulated human trophoblast proliferation in first-trimester primary cultures. In vivo, CRH was strongly immunolocalised to cytotrophoblastic cells in proliferative cell columns and in chorionic villi. We postulate that CRH may have an important role in early placental development and successful pregnancy.     

Investigating a possible cause of mesh migration during totally extraperitoneal (TEP) repair

Background In experienced hands, laparoscopic inguinal hernia repair has a low rate of recurrence, but it still can recur, and a number of reasons for this have been identified. In published studies, the majority of such cases seem to result from inadequate dissection leading to missed hernias or suboptimal mesh placement. But even with adequate dissection and proper placement of a sufficiently large mesh, recurrence sometimes happens. A number of investigators have cited mesh migration or dislocation as a possible cause, and this study examined how hip flexion affects the position of newly placed meshes and staples in totally extraperitoneal (TEP) repair of inguinal hernia.Methods After completion of the dissection and reduction of discovered hernias, a 15 × 15-cm polypropylene mesh was placed either unilaterally or bilaterally, as indicated. The preperitoneal space then was desufflated. The operating table, in an extended –20° position during surgery, was placed in a 90° position for approximately 15 s. After reinsufflation, the possibility of mesh migration and folding was investigated. Finally, the mesh was stapled, the table again extended and flexed, and the possibility of mesh migration and staple dislodgement investigated once more.Results The mesh did not migrate or become displaced from any potential hernia area, nor did any of the staples become dislodged.Conclusions Concern about mesh migration attributable to patients sitting up immediately after surgery appears to be unfounded, at least according to the findings for the current, small, simulated study group.     

Incidence and outcome of antiglomerular basement membrane disease in Chinese

Background: Antiglomerular basement membrane (anti‐GBM) disease is an uncommon disease, especially among Asian population. Many reports and studies on this condition in the Caucasian population are available, but little information exists on anti‐GBM disease in Asians. To study the incidence and clinical characteristics of anti‐GBM disease among Chinese patients, we reviewed our experience of anti‐GBM disease in our hospital (Queen Mary Hospital, Hong Kong) from 1992 to 2003. Methods: All patients who were admitted for acute renal impairment, which was caused by crescentic glomerulonephritis associated with linear immunoglobulin G (IgG) staining on immunofluorescence, were included in the analysis. Serum anti‐GBM antibodies were detected by either enzyme‐linked immunofluorescence or indirect immunofluorescence. Ten patients were treated for anti‐GBM disease during this 11‐year period, yielding an incidence of approximately 0.6 cases per million population per year. Results: In this cohort, anti‐GBM disease predominantly affected older patients (mean age: 58.6 ± 21.7 years). Eight patients were aged between 60 and 80 years and there was a female preponderance (M:F = 2:8). The 1‐year renal and patient survival was 15% (95% CI 0–40%) and 70% (95% CI 42–98%), respectively. Most patients presented with non‐specific symptoms as well as impaired renal function. Detection of anti‐GBM antibody provided a good screening test for the disease. Antiglomerular basement membrane antibodies were not detected in two patients. All but two patients received steroid, cyclophosphamide and intensive plasmapheresis therapy. Haemoptysis occurred in four patients (40%), and usually lagged behind the renal presentation and commencement of treatment. Six patients required long‐term dialysis after the acute disease. Three patients died from the disease, two died from pulmonary complications and one died suddenly after a partial recovery of renal function. Conclusion: Antiglomerular basement membrane disease is uncommon among the Chinese population. It predominantly affects older patients, and prognosis is poor. Long‐term preservation of renal function after the initial attack is unusual.     

Clinical experience with inhibition of interleukin-6

Rheumatoid arthritis (RA) is a systemic disease that is associated with increased mortality and morbidity. Prognosis depends on disease severity and response to treatment. Those patients whose diseases are refractory to treatment with disease-modifying antirheumatic drugs (DMARDs) and have persistent inflammation have reduced survival similar to patients with triple-vessel coronary artery disease and Hodgkin's lymphoma. Although DMARDs reduce inflammation and improve symptoms, they do not improve long-term prognosis. Chronic synovial inflammation results in damage to the articular cartilage and adjacent bone. Consequently,after 10 years of disease most patients develop significant disability due to joint damage. Interleukin-6 (IL-6) is a key mediator of inflammation in RA. Inhibition of IL-6 reduces synovitis and improves symptoms. Therapies targeting IL-6 are promising new treatments for RA.