Low extracellular Ca2+: a mediator of endothelial inflammation.

BACKGROUND: Recent studies have suggested that vitamin D and an imbalance in calcium homeostasis may have an impact on the cardiovascular system. The aim of this study was to assess the impact of different concentrations of extracellular Ca(2+) on human umbilical vein cord endothelial cells (HUVEC) by measuring its effect on parameters involved in the pathogenesis of vascular inflammatory responses. METHODS: HUVEC were grown in the 3.5, 4.5 or 5.8 mg/dL concentration of extracellular Ca(2+) for 2-3 weeks. Expression of adhesion molecules was analysed by flow cytometry. Endothelial nitric oxide synthase (eNOS), receptor of advanced glycation end-product (RAGE) and interleukin-6 (IL-6) mRNA expressions were determined by real-time PCR. eNOS, inhibitor kappa Balpha (IkappaBalpha) and phosphorylated IkappaBalpha protein levels by Western blot, eNOS activity by conversion of [(14)C]-arginine to [(14)C]-citrulline, IL-6 and osteoprotegerin (OPG) secretion by ELISA and DNA-binding activity of nuclear factor kappa B (NFkappaB)-p65 were assayed colorimetrically in nuclear extracts. RESULTS: In the presence of low Ca(2+) (3.5 mg/dL), protein expressions and activity of eNOS were diminished, while the protein expressions of intercellular adhesion molecule-1 (ICAM-1), as well as the mRNA expressions of RAGE and IL-6, were elevated. The protein secretions of IL-6 and OPG were also stimulated in low Ca(2+) concentration. At this concentration, the DNA-binding activity of NFkappaB was enhanced, probably due to the decreased level of IkappaBalpha. CONCLUSIONS: These results suggest that lower extracellular ionized Ca(2+) may play a relevant role in modifying endothelial cells functions.

[Long-term follow-up on the treatment of diffuse proliferative glomerulonephritis in patients with systemic lupus erythematosus].

BACKGROUND: Diffuse Proliferative Glomerulonephritis (DPGN) is the most ominous form of lupus nephritis. Treatment according to the "NIH Protocol" is considered by many physicians to be the treatment of choice for this form of disease, but this is not accepted exclusively. OUR AIM: To evaluate the outcome of SLE patients with biopsy proven DPGN diagnosed and treated in our department, between the years 1976-1996, and to compare the results achieved by using the "NIH Protocol" as opposed to other forms of treatment. PATIENTS AND METHODS: The archive of the Department of Pathology was screened for patients with SLE and DPGN. The specimens were re-examined to confirm the diagnosis and calculate the activity and chronicity scores. The pertinent data was extracted from the patients medical records. RESULTS: Twenty-six patients fulfilled the inclusion criteria, 22 females and 4 males. We followed-up on these patients for an average period of 89 +/- 74 months (range 9-255). More than 80% of the patients achieved remission, about a third experienced at least one relapse. Only one patient died during the follow-up period and 4 others developed end stage renal failure necessitating chronic renal replacement therapy. Sixteen patients were treated according to the NIH protocol, the other 10 were treated with high dose Prednisone, either alone or in combination with oral immunosuppressive drugs. At time of diagnosis there was no statistically significant difference between the two groups regarding the age and gender distribution, blood levels of creatinine and C3 and the level of proteinuria. We were unable to demonstrate any statistically significant difference between the two groups in any of the evaluated parameters, regarding neither patient and kidney survival nor the type and rate of complications. CONCLUSION: Following treatment, patient and kidney survival is good. The NIH protocol is the treatment of choice, but the use of high dose steroids for six months with or without oral immunosuppressive drugs may yield comparable results in selected cases.