Kinetic analysis of the humoral immune response against 3 Toxoplasma gondii-recombinant proteins in infants with suspected congenital toxoplasmosis

The reactivity values of Toxoplasma gondii ROP2, GRA4, and GRA7 recombinant antigens (rAgs) were analyzed by immunoglobulin G (IgG) enzyme-linked immunosorbent assay (ELISA) in 23 congenitally infected (I) and 36 noninfected (NI) infants. The reactivity values observed from the serum samples of I versus NI infants for each recombinant protein were 91% versus 67% for rROP2 (P = .05), 86% versus 29% for rGRA4 (P < .001), and 56% versus 11% for rGRA7 (P = .003). The follow-up showed that serum samples from NI infants became negative for specific IgG at 5.8 months (95% confidence interval [CI], 4.9-6.7) using a commercial assay; meanwhile, by specific recombinant protein ELISA, the samples became negative at 3.7 months with rROP2 (95% CI, 2.8-4.6), at 1.3 months with rGRA4 (95% CI, 0.8-1.8), and at 0.9 months with rGRA7 (95% CI, 0.5-1.3). Kinetic analysis also showed that serum samples from group I presented different IgG-profiles among rAgs. The rROP2 IgG profile was similar to that of the commercial assay, whereas rGRA4 and rGRA7 profiles showed a gradual decrease along the period of the study. The potential of the utility of rAgs to develop a diagnostic system that discriminates congenitally I infants from NI is discussed.     

Association between Helicobacter pylori concentration and the combining frequency of histopathological findings in gastric biopsies specimens

BACKGROUND: Helicobacter pylori is the most prevalent infectious agent worldwide. About 90% of patients with chronic gastritis are infected with this bacterium. Some studies have shown a association between the H. pylori concentration and the scores of gastritis activity and severity. AIM: To evaluate the association between H. pylori concentration and the combining frequency of findings on histopathological examination. METHODS: Two hundred consecutive gastric endoscopic biopsies diagnosed as chronic gastritis were retrospectively investigated. The Warthin-Starry silver stain was used to study H. pylori and the following parameters were assessed (according to the Sydney system): 1. infiltration by polymorphonuclear cells in chorio and epithelium (activity) graded as mild, moderate and marked; 2. presence of lymphoid follicles; 3. presence of intestinal metaplasia; 4. presence of regenerative cell atypias, graded as mild, moderate and marked; and 5. H. pylori concentration on the mucous covering the foveolar epithelium. RESULTS: The most frequent association was chronic gastritis and activity, regardless of H. pylori concentration. The association of five histopathological findings in the same biopsy has not occurred in the cases of higher concentration of H. pylori. CONCLUSION: Our study has not revealed any association between H. pylori concentration and an increasing in the number of histopathological findings found in the gastric mucosa. Since referring to its presence is much more important than to its concentration.     

Idiopathic dilated cardiomyopathy exhibits defective vascularization and vessel formation

BACKGROUND: Ultrastructural findings of idiopathic dilated cardiomyopathy (IDCM) include myocyte atrophy and myofilament loss, yet little is known about the vascular abnormalities present in IDCM. METHODS AND RESULTS: Patients with IDCM and controls underwent multi-slice CT to examine length and diameter of epicardial vasculature. The levels of mobilizing cytokines and circulating EPCs were assessed by endothelial colony formation assay and flow cytometry. Immunohistochemistry and Western blot were used to examine microvessel density and expression of HIF-1alpha and beta-catenin. Main epicardial coronary arteries were shorter and smaller, and microvascular density was reduced in the epicardium in IDCM. Epicardial vessel paucity was associated with increased numbers of HIF-1alpha(+) cells (46.8+/-13.1% vs. 19.4+/-9.4%, p=0.006) indicating local epicardial hypoxia and elevation of circulating VEGF-A (394 pg/mL vs. 22 pg/mL, p=0.001). The number of mobilized progenitors CD133(+)/VEGF-R2(+) was 21-fold higher in IDCM compared with controls (6.5+/-3.3% vs. 0.3+/-0.2%; p<0.001). Moreover, this defective vascularization was associated with reduced myocardial expression of vascular beta-catenin, an important angiogenic regulator. CONCLUSIONS: This study shows defective vascularization and impaired vasculogenesis (the de novo vascular organization of mobilized endothelial progenitors) and angiogenesis (by which new blood vessels are formed from pre-existing mature endothelial cells) in human IDCM.     

Proxy‐reported health‐related quality of life of patients with juvenile idiopathic arthritis: The pediatric rheumatology international trials organization multinational quality of life cohort study

Objective

To investigate the proxy‐reported health‐related quality of life (HRQOL) and its determinants in patients with juvenile idiopathic arthritis (JIA).

Methods

In this multinational, multicenter, cross‐sectional study, HRQOL of patients with JIA was assessed through the Child Health Questionnaire (CHQ) and was compared with that of healthy children of similar age from the same geographic area. Potential determinants of HRQOL included demographic data, physician's and parent's global assessments, measures of joint inflammation, Childhood Health Assessment Questionnaire (CHAQ), and erythrocyte sedimentation rate.

Results

A total of 6,639 participants (3,324 with JIA and 3,315 healthy) were enrolled from 32 countries. The mean ± SD physical and psychosocial summary scores of the CHQ were significantly lower in patients with JIA than in healthy children (physical: 44.5 ± 10.6 versus 54.6 ± 4.0, P < 0.0001; psychosocial: 47.6 ± 8.7 versus 51.9 ± 7.5, P < 0.0001), with the physical well‐being domain being most impaired. Patients with persistent oligoarthritis had better HRQOL compared with other subtypes, whereas HRQOL was similar across patients with systemic arthritis, polyarthritis, and extended oligoarthritis. A CHAQ score >1 and a pain intensity rating >3.4 cm on a 10‐cm visual analog scale were the strongest determinants of poorer HRQOL in the physical and psychosocial domains, respectively.

Conclusion

We found that patients with JIA have a significant impairment of their HRQOL compared with healthy peers, particularly in the physical domain. Physical well‐being was mostly affected by the level of functional impairment, whereas the intensity of pain had the greatest influence on psychosocial health.     

Phosphodiesterase 5A inhibition induces Na+/H+ exchanger blockade and protection against myocardial infarction

Acute phosphodiesterase 5A inhibition by sildenafil or EMD360527/5 promoted profound inhibition of the cardiac Na(+)/H(+) exchanger (NHE-1), detected by the almost null intracellular pH recovery from an acute acid load (ammonium prepulse) in isolated papillary muscles from Wistar rats. Inhibition of phosphoglycerate kinase-1 (KT5823) restored normal NHE-1 activity, suggesting a causal link between phosphoglycerate kinase-1 increase and NHE-1 inhibition. We then tested whether the beneficial effects of NHE-1 inhibitors against the deleterious postmyocardial infarction (MI) remodeling can be detected after sildenafil-mediated NHE-1 inhibition. MI was induced by left anterior descending coronary artery ligation in Wistar rats, which were randomized to placebo or sildenafil (100 mg kg(-1) day(-1)) for 6 weeks. Sildenafil significantly increased left ventricular phosphoglycerate kinase-1 activity in the post-MI group without affecting its expression. MI increased heart weight/body weight ratio, left ventricular myocyte cross-sectional area, interstitial fibrosis, and brain natriuretic peptide and NHE-1 expression. Sildenafil blunted these effects. Neither a significant change in infarct size nor a change in arterial or left ventricular systolic pressure was detected after sildenafil. MI decreased fractional shortening and the ratio of the maximum rate of rise of LVP divided by the pressure at the moment such maximum occurs, effects that were prevented by sildenafil. Intracellular pH recovery after an acid load was faster in papillary muscles from post-MI hearts (versus sham), whereas sildenafil significantly inhibited NHE-1 activity in both post-MI and sildenafil-treated sham groups. We conclude that increased phosphoglycerate kinase-1 activity after acute phosphodiesterase 5A inhibition blunts NHE-1 activity and protects the heart against post-MI remodeling and dysfunction.     

Angiotensin II chronic infusion induces B1 receptor expression in aorta of rats

We investigated whether angiotensin II infusion modulates in vivo the kinin B1 receptor expression and the mechanisms involved in this process. We also evaluated the role of the B1 receptor activation in aorta. Wistar rats received 400 ng/kg per minute of angiotensin II or saline (control rats) infusion during 14 days through an osmotic minipump. To investigate the role of superoxide anion in B1 receptor expression, rats received a reduced nicotinamide-adenine dinucleotide phosphate oxidase inhibitor in the drinking water during 14 days (60 mg/L of apocynin) simultaneously with angiotensin II infusion. Angiotensin II induced B1 receptor expression in the aorta and increased significantly systolic blood pressure, superoxide anion, and the nuclear factor kappaB activity. Apocynin treatment did not alter the blood pressure levels of angiotensin II rats and reduced the B1 receptor expression, superoxide anion generation, and nuclear factor kappaB activity to similar levels of the control rats. Vascular reactivity studies in isolated aorta reveal that B1 receptor agonist promoted endothelium-dependent dilation and increased the NO generation in aorta of angiotensin II rats. NO synthase inhibitor and B1 receptor antagonist inhibited the vasodilation and NO generation, which were not affected by B2 receptor antagonist or indomethacin. These results provide evidence that angiotensin II induces B1 receptor expression in aorta by superoxide anion generation, via reduced nicotinamide-adenine dinucleotide phosphate oxidase, concomitant to nuclear factor kappaB activation. We have also shown that B1 receptor agonist causes endothelium-dependent vasodilation through NO production in aortic rings, suggesting that the B1 receptor expression could be related with the vascular tonus control of angiotensin II rats.     

Rapid, real-time detection of acute HIV infection in patients in Africa

BACKGROUND: We conducted a prospective study to evaluate methods of detecting clients with sexually transmitted diseases (STDs) who were acutely coinfected with human immunodeficiency virus (HIV) in Lilongwe, Malawi. METHODS: After informed consent was obtained, all clients with acute STDs were offered voluntary HIV counseling and testing by 2 rapid antibody tests. Samples from rapid test-negative or -discordant subjects were pooled (50 : 5 : 1) and tested for HIV RNA. Western blots were performed on all rapid test-discordant specimens with detectable HIV RNA. A subset of specimens received p24 antigen testing with standard and/or ultrasensitive methods. Patients with possible acute HIV infection were followed to confirm seroconversion. RESULTS: A total of 1450 clients (34% female and 66% male) agreed to testing, of whom 588 (40.55%) had established HIV infection and 21 (1.45%) had acute infection. Discordant rapid antibody tests identified 7 of 21 (33.3% sensitivity), standard p24 antigen identified 12 of 16 (75% sensitivity), and ultrasensitive p24 antigen identified 15 of 17 (88% sensitivity) acute cases. By definition, the sensitivity of the RNA assay was 100%. CONCLUSIONS: Real-time pooled RNA testing for the detection of acute HIV infection is feasible in resource-limited settings. However, parallel rapid testing and p24 antigen testing are technologically simpler and together may detect approximately 90% of acute cases.     

Leukocytoclastic vasculitis caused by hepatitis C virus in a liver transplant recipient: A case report

BACKGROUND Infection by the hepatitis C virus(HCV) is currently considered to be a global health issue, with a high worldwide prevalence and causing chronic disease in afflicted individuals. The disease largely involves the liver but it can affect other organs, including the skin. While leukocytoclastic vasculitis has been reported as one of the dermatologic manifestations of HCV infection, there are no reports of this condition as the first symptom of HCV recurrence after liver transplantation.CASE SUMMARY We report here a case of leukocytoclastic vasculitis in a liver transplant recipient on maintenance immunosuppression. The condition presented as a palpable purpura in both lower extremities. Blood and urine cultures were negative and all biochemical tests were normal, excepting evidence of anemia and hypocomplementemia. Imaging examination by computed tomography showed a small volume of ascites, diffuse thickening of bowel walls, and a small bilateral pleural effusion. Skin biopsy showed leukocytoclasia and fibrinoid necrosis.Liver biopsy was suggestive of HCV recurrence in the graft, and HCV polymerase chain reaction yielded 11460 copies/mL and identified the genotype as 1 A. Treatment of the virus with a 12-wk direct-acting antiviral regimen of ribavirin, sofosbuvir and daclatasvir led to regression of the symptoms within the first 10 d and subsequent complete resolution of the symptoms.CONCLUSION This case highlights the difficulties of diagnosing skin lesions caused by HCVinfection in immunosuppressed patients.