Antibodies against cyclic citrullinated peptides in infectious diseases—a systematic review

Rheumatoid arthritis (RA) is a disease characterized by symmetrical polyarthritis of the large and small joints, and in the majority of patients, there is a presence of the rheumatoid factor and erosions in the X-ray of the joints. More recently, the presence of anti-cyclic citrullinated peptide antibodies (anti-CCP) in this disease has been described, with diagnostic and prognostic value. Nevertheless, these antibodies have also been described in infectious diseases. The aim of the present study was to make a systematic review of the presence of antibodies against citrullinated peptides in infectious diseases. Search was conducted in the MEDLINE (1966 to 2010), Cochrane, SCielo, and LILACS databases, using the terms: “anti-CCP, anti-MCV, and infectious diseases”; “anti-CCP, anti-MCV, and virus”; “anti-CCP, anti-MCV, and mycobacteria”; “anti-CCP, anti-MCV, and tuberculosis”; “anti-CCP, anti-MCV, and leprosy”; “anti-CCP, anti-MCV, and leishmaniasis”; “anti-CCP, anti-MCV, and HIV”; “anti-CCP and HTLV”; “anti-CCP, anti-MCV, and Chagas disease”; “anti-CCP, anti-MCV, and Lyme disease”, and the corresponding terms in Portuguese. Twenty-five publications were found, which dealt with anti-CCP and infection, and only one on anti-MCV and infection. Of these, 23 were cross-sectional and three cohort studies. Anti-CCP antibodies were found in various frequencies, reaching 37% in tuberculosis. In the other infections, it was a rare finding. In only one publication, anti-MCV was found in only one patient with hepatitis. Since infectious diseases are capable of running their course with osteoarticular symptoms, sometimes difficult to differentiate from RA, additional studies are necessary to define the performance of the test for the detection of anti-CCP antibodies in populations in which the frequency of such infections is high.     

Kidney and Hypertension—Causes

Renal disease is closely associated with hypertension. On the one hand, kidney disease provokes hypertension. On the other hand, hypertension aggravates the progression of renal dysfunction. The pathomechanisms through which the kidney raises blood pressure have been considerably clarified in recent years. In experimental and clinical studies, it could be shown that "hypertension goes with the kidney". This suggests that some renal anomalies predispose to hypertension. Recently, it could be shown that the kidneys of individuals with so-called essential hypertension have less glomeruli than the kidneys of control individuals. In renal patients the kidney raises blood pressure through several mechanisms. First, the pressure-natriuresis relationship is shifted to the right, i. e., sodium excretion requires higher renal perfusion pressures. Second, there is inappropriate activation of the renin-angiotensin system. Third, as only recently documented in detail, renal injury raises the sympathetic tone, even when whole kidney glomerular filtration rate (GFR) is unchanged. This results from stimulating afferent signals emanating from the kidney. Fourth, there is evidence of impaired endothelial cell dependent vasodilatation even in very early stages of renal dysfunction. Fifth, the pulse pressure profile is altered as a consequence of premature and accelerated aging causing stiffening of the aorta. Knowledge of these pathomechanisms is important for selection of appropriate antihypertensive treatment.     

Elevated nitric oxide and 3′,5′ cyclic guanosine monophosphate levels in patients with alcoholic cirrhosis

AIM： To evaluate whether serum levels of nitric oxide （NO^.） and plasma levels of cyclic guanosine monophosphate （cGMP） and total glutathione （GSH） are altered in patients with alcoholic cirrhosis and to examine their correlation with the severity of liver disease.
METHODS： Twenty-six patients with alcoholic liver cirrhosis were studied. Serum levels of NO^. and plasma levels of cGMP and GSH were measured in 7 patients with compensated alcoholic cirrhosis （Child-Pugh A） and 19 patients with advanced cirrhosis （Child-Pugh B and C）. The model for end-stage liver disease （MELD） score was evaluated. Sixteen healthy volunteers served as controls. Liver enzymes and creatinine levels were also tested.
RESULTS： NO^. and cGMP levels were higher in patients with Child-Pugh B and C cirrhosis than in Child-Pugh A cirrhosis or controls （NO^.： 21.70 ± 8.07 vs 11.70 ± 2.74; 21.70± 8.07 vs 7.26 ± 2.47 μmol/L, respectively; P 〈 0.001） and （cGMP： 20.12 ± 6.62 vs 10.14 ± 2.78; 20.12 ± 6.62 vs 4.95 ± 1.21 pmol/L, respectively; P 〈 0.001）. Total glutathione levels were lower in patients with Child-Pugh B and C cirrhosis than in patients with Child-Pugh A cirrhosis or controls （16.04 ± 6.06 vs 23.01 ± 4.38 or 16.04 ± 6.06 vs 66.57 ±26.23 μmol/L, respectively; P 〈 0.001）. There was a significant correlation between NO^. and cGMP levels in all patients with alcoholic cirrhosis. A significant negative correlation between reduced glutathione/glutathione disulfide and the MELD score was found in all cirrhotic patients.
CONCLUSION： Our results suggest a role for oxidative stress in alcoholic liver cirrhosis, which is more significant in decompensated patients with higher levels of NO^. and cGMP and lower GSH levels than in compensated and control patients. Altered mediator levels in decompensated patients may influence the hemodynamic changes in and progression of liver disease.     

Thromboelastography and recombinant factor VIIa—hemophilia and beyond

Thromboelastography (TEG), which records the continuous profiles of whole blood (WB) coagulation, can be used to evaluate the effects of hemostatic agents, such as recombinant factor VII (rFVIIa). Our group has developed a revised TEG model, involving activation with minute amounts of tissue factor and subsequent signal processing, and has used this method to evaluate the effects of rFVIIa both in patients with hemophilia and in those receiving vitamin K antagonist (VKA) thromboprophylaxis. We review the early results of our investigations, which suggest that, in clinical situations where rFVIIa has shown benefit, the changes in the profiles obtained by TEG recording appear to correlate with the clinical outcome.