Uropathogenic Escherichia coli Induces Serum Amyloid A in Mice following Urinary Tract and Systemic Inoculation

Serum amyloid A (SAA) is an acute phase protein involved in the homeostasis of inflammatory responses and appears to be a vital host defense component with protective anti-infective properties. SAA expression remains poorly defined in many tissues, including the urinary tract which often faces bacterial challenge. Urinary tract infections (UTIs) are usually caused by strains of uropathogenic Escherichia coli (UPEC) and frequently occur among otherwise healthy individuals, many of whom experience bouts of recurrent and relapsing infections despite the use of antibiotics. To date, whether SAA is present in the infected urothelium and whether or not the induction of SAA can protect the host against UPEC is unclear. Here we show, using mouse models coupled with immunofluorescence microscopy and quantitative RT-PCR, that delivery of UPEC either directly into the urinary tract via catheterization or systemically via intraperitoneal injection triggers the expression of SAA. As measured by ELISA, serum levels of SAA1/2 were also transiently elevated in response to UTI, but circulating SAA3 levels were only up-regulated substantially following intraperitoneal inoculation of UPEC. In in vitro assays, physiological relevant levels of SAA1/2 did not affect the growth or viability of UPEC, but were able to block biofilm formation by the uropathogens. We suggest that SAA functions as a critical host defense against UTIs, preventing the formation of biofilms both upon and within the urothelium and possibly providing clinicians with a sensitive serological marker for UTI

Antibodies against carbonic anhydrase in patients with aplastic anemia

BACKGROUND/AIMS: Antibodies against carbonic anhydrase (CA) have been detected in patients with an aplastic anemia (AA)-like syndrome after autologous stem cell transplantation. METHODS: We analyzed sera of 53 bona fide AA patients before and after treatment with anti-thymocyte globulin (ATG) or bone marrow transplantation for the presence of anti-CA antibodies. RESULTS: Anti-CA antibodies were detected in 20 patients (38%) and were associated with older age at diagnosis of AA. Antibody-positive patients showed poor response to ATG treatment (complete response 14%) and inferior long-term survival (36% at 10 years), when compared to antibody-negative patients (complete response and 10-year survival both 64%). Two thirds of patients with antibodies at diagnosis of AA became antibody negative after treatment with ATG. Clearance of the antibody did not appear to be associated with hematological improvement. CONCLUSION: Antibodies against CA are detected frequently at diagnosis of AA, and their presence identifies a subset of patients with poor response to immunosuppressive treatment

BLOOD PARAMETERS, NONSPECIFIC RESISTANCE, AND PRODUCTIVITY OF FINE-WOOL SHEEP OF DIFFERENT GENOTYPES

Long-term studies carried out in the south-east of Saratov Oblast prove that the introductive crossing of the Stavropol wool breed to rams of the wool–meat double purpose increases the offspring live weight, wool yield, and meat productivity, as well as their adaptive capacity and preservation. The experimental data have been obtained in research farms of Saratov Oblast on the base of breeding farms “Krasnyi Partizan” and “Novouzensk”. The breeding involves wool–meat breeds: Caucasian and Transbaikalian. The results show that the mating of rock wool Stavropol sheep to Caucasian and Transbaikalian rams increases body weight and wool clip. It also strengthens the physique and the viability of the young. Along with these indications for selection, the level of natural resistance and adaptive potential of animals are of great importance. Assays of biochemical and hematological indices, humoral factors have shown that the hybrids, as compared to purebred peers, are more productive and have a higher adaptive capacity, which is a significant economic indicator in the modern sheep industry

A significance of additional chromosomal aberrations and other variables on post transplantation outcome of patients with CML

Chronic myeloic leukemia (CML) is a malignant disease of hematopoietic stem cell characterized by the bcr/abl gene rearrangement. Allogeneic transplantation of stem cells (SCT) is a routinely used treatment method of patients with this diagnosis and remains the only curative mode of treatment. From January 1990 to December 2002, 78 patients with CML underwent allogeneic transplantation and were examined at the Department of Genetics in the National Cancer Institute in Bratislava. Using conventional cytogenetic and FISH 6 patients (7.7%) showed additional chromosomal changes before SCT. These patients had statistically worse post transplantation prognosis compared to the patients without additional changes before SCT (mean survival in month+/-standard error (58.08 (+/-6.70) vs. 5.17 (+/-0.98), p-value=0.001), patient mortality (67% vs. 31%)). In addition five other variables were evaluated for transplant outcome, namely, patient's age at the time of transplantation, sibling or non-sibling donor, higher than 1st chronic phase CML, time from diagnosis to transplantation and sex of donor and recipient. Only the comparison of HLA-identical sibling transplantation to unrelated donor transplantation was statistically significant (mean survival in month- 56.6 (+/-7.2) vs. 13 (+/-0.0), patient mortality 31% vs. 67%)

High Avidity Anti-β2-Glycoprotein i Antibodies Activate Human Coronary Artery Endothelial Cells and Trigger Peripheral Blood Mononuclear Cell Migration

Anti-β2-glycoprotein I antibodies (aβ2GPI) represent a potential pathogenic candidate for coronary artery diseases. High avidity aβ2GPI (HAv aβ2GPI) are known to be associated with thrombotic and obstetric manifestations in patients with antiphospholipid syndrome, who are also susceptible to the development of premature atherosclerosis. However, there is little information about how human coronary artery endothelial cells (HCAEC) are affected by HAv aβ2GPI. The purpose of our study was to evaluate the pathophysiological effects of HAv aβ2GPI on HCAEC and determine their influence on cytokine expression and migration of peripheral blood mononuclear cells. Following the two hit hypothesis, we co-stimulated HAv aβ2GPI-treated HCAEC in the presence and absence of the acute phase protein serum amyloid A (SAA). HAv aβ2GPI induced in vitro HCAEC dysfunction, through the ERK1/2 signaling pathway, promoted the expression of chemokines (MCP-1, GROα and IL-8) and IL-6, which led to the attraction and migration of peripheral blood mononuclear cells. These effects were potentiated and intensified in conditions with SAA, indicating that HAv aβ2GPI, in the presence of physiological concentrations of acute-phase proteins represent pathogenic autoantibodies, which could lead to the development of premature atherosclerosis and/or thrombosis development

Anti‐COVID‐19 measurements for hidradenitis suppurativa patients

The reported incidence of COVID‐19 among cohorts of patients with inflammatory bowel and skin diseases under treatment with biologicals is low. Treatment may further modify disease severity as some biological modifiers, such as anakinra, are also proposed for the management of COVID‐19 patients potentially providing HS patients with an advantage. The above preliminary evidence suggests that hidradenitis suppurativa (HS) does probably not provide an increased susceptibility for COVID‐19 and that any susceptibility is unlikely to be modified negatively by treatment with biologicals. On the occasion of its 10th International Conference, experts of the European Hidradenitis Suppurativa Foundation e.V. have prepared a consensus statement regarding anti‐COVID‐19 measurements for HS patients. Based on the available knowledge, patients with HS may be vaccinated against SARS‐CoV2 and patients affected by metabolic syndrome constitute a high‐risk group for COVID‐19 and should be vaccinated at the earliest convenient point in time. HS patients on treatment with adalimumab can be vaccinated with non‐living virus anti‐SARS‐CoV2 vaccines. A possible suboptimal effect of the vaccine may be suspected but might not be expected universally. The management of the biological treatment in HS patients is at the discretion of the dermatologist / responsible physician

Supplementary Material for: Antibodies against Carbonic Anhydrase in Patients with Aplastic Anemia

<b><i>Background/Aims:</i></b> Antibodies against carbonic anhydrase (CA) have been detected in patients with an aplastic anemia (AA)-like syndrome after autologous stem cell transplantation. <b><i>Methods:</i></b> We analyzed sera of 53 bona fide AA patients before and after treatment with anti-thymocyte globulin (ATG) or bone marrow transplantation for the presence of anti-CA antibodies. <b><i>Results:</i></b> Anti-CA antibodies were detected in 20 patients (38%) and were associated with older age at diagnosis of AA. Antibody-positive patients showed poor response to ATG treatment (complete response 14%) and inferior long-term survival (36% at 10 years), when compared to antibody-negative patients (complete response and 10-year survival both 64%). Two thirds of patients with antibodies at diagnosis of AA became antibody negative after treatment with ATG. Clearance of the antibody did not appear to be associated with hematological improvement. <b><i>Conclusion:</i></b> Antibodies against CA are detected frequently at diagnosis of AA, and their presence identifies a subset of patients with poor response to immunosuppressive treatment