Antigen location contributes to the pathological features of a transplanted heart graft

Organ-specific injury after transplantation presents with a variety of clinical and pathological phenotypes, yet the factors influencing development of each outcome are poorly understood. Because primed T lymphocytes must re-encounter their antigen within the target organ to engage effector functions, we postulated that the cellular location of antigen within that organ could significantly impact the induced pathology. We challenged female Marilyn CD4 T-cell receptor transgenic mice, in which all T cells are specific for the male minor transplantation antigen, with male heart transplants expressing the relevant peptide: major histocompatibility complex on either graft parenchymal/vascular cells or alternatively, on graft-infiltrating mononuclear cells. The two different graft donors led to equivalent activation of recipient T cells as assessed by frequency, cell surface marker expression, cytokine production, and the ability to traffic to the graft. Nonetheless, if the target antigen was expressed on graft vascular and/or parenchymal cells, the outcome was acute graft destruction. In contrast, if the antigen was expressed only on graft-infiltrating mononuclear cells the same effector T-cell repertoire caused chronic rejection and vasculopathy. This unique result, that target antigen location can influence pathological outcome, has significant implications for understanding the pathogenesis of chronic allograft injury in humans.     

The prevalence of hereditary thrombophilia in the Trakya region of Turkey

The prevalences of deficiencies in antithrombin III (AT III), protein C (PC), protein S (PS) and in the activated protein C (APC) resistance in the thrombotic population of the Trakya region, Turkey were investigated. 37 patients with venous thrombosis (VT) and 17 patients with arterial thrombosis (ArT) were included in this study. The mean ages of the patients with VT and ArT were 46 years (range 20-70) and 38 years (range 32-40), respectively. The activity of AT III was measured by commercially available immuno-turbidimetric assay. The activities of PC and PS were determined by coagulometric assay. The APC resistance was measured using a modified APTT-based clotting assay. Among the VT patients, there were 2 cases (5.4%) with AT III, 5 (13.51%) with PC deficiency, 5 (13.51%) with PS deficiency and 2 (5.4%) with APC resistance. In the ArT patient group, there was 1 patient (5.88%) with AT III, 3 (17.64%) with PC deficiency, 1 (5.88%) with PS deficiency and no APC resistant patients, while there was one (2.08%) with PC deficiency and one (2.08%) with APC resistance in the control group (49 persons, mean age 41 years). The relative risk of thrombosis (odds ratio) was 1.7 in the deficiency of PC and 5.6 in the deficiency of PS. The data presented suggests that the prevalences of AT III, PC and PS deficiencies causing thrombophilia in the Trakya region of Turkey are higher than in other reported studies while the APC resistance is lower than in others. Further studies including more patients would be required to clarify these discrepancies.     

Effects of green tea polyphenols on murine transplant-reactive T cell immunity

Green tea polyphenols (GrTP), the active ingredient of green tea, may have immunosuppressive properties, but whether and how GrTP affect transplant-reactive T cells is unknown. To address this, we tested the effects of GrTP on in vitro and in vivo transplant-reactive T cell immunity. GrTP inhibited IFNgamma secretion by cultured monoclonal T cells and by alloreactive T cells in mixed lymphocyte reactions. Oral GrTP significantly prolonged minor antigen-disparate skin graft survival and decreased the frequency of donor-reactive interferon gamma-producing T cells in recipient secondary lymphoid organs compared to controls. In contrast to other hypothesized actions, oral GrTP did not alter dendritic cell trafficking to lymph nodes or affect metalloproteinase activity in the graft. This is the first report of an immunosuppressive effect of GrTP on transplant-reactive T cell immunity. The results suggest that oral intake of green tea could act as an adjunctive therapy for prevention of transplant rejection in humans.     

Impact of anxiety,stress and depression related to COVID-19 pandemic on the course of hereditary angioedema with C1-inhibitor deficiency

Background

Hereditary angioedema (HAE) attacks can be provoked with psychological factors. The aim of this study was to assess the effects of anxiety, depression and stress related to COVID-19 pandemic on disease activity of HAE patients during the quarantine period (QP) and the return to normal period (RTNP).

Methods

This study was conducted between March 2020 and September 2020 in four allergy centres. Demographic, clinical features and mental health status were evaluated in QP (from March to the beginning of June) and RTNP (from June to the beginning of September) applied by the government. The 10-point visual analogue scale (VAS10) was used to define the severity of HAE attacks. Depression, Anxiety and Stress Scales-21 (DASS-21) and Fear of COVID-19 (FC-19) scale were performed to assess mental health status.

Results

139 HAE patients were included in the study. In QP, median attack numbers and median VAS10 scores were 5 (min-max: 0–45) and 6 (min-max: 0–10), respectively. HAE attack numbers, DASS-21 stress, anxiety, depression and total DASS-21 scores, and FC-19 scores were higher in QP than RTNP (p = 0.001, p < 0.001, p = 0.001, p < 0.001, p < 0.001, p < 0.001, respectively). However, there was no difference in attack severity scores between the two periods (p > 0.05).

Conclusions

This study revealed that the restriction measures during COVID-19 outbreak cause an increase in the number of HAE attacks in relation to anxiety, depression, stress and fear of COVID-19 pandemic. Therefore, it is important to provide psychological support to HAE patients during the pandemic.

     

Morphological changes in mesothelial cells induced by shed menstrual endometrium in vitro are not primarily due to apoptosis or necrosis

In a previous study on the pathogenesis of endometriosis, we observed that constituents of menstrual effluent induce morphological alterations in human mesothelial cells. In this study, we investigated whether these alterations were associated with apoptosis or necrosis or were the result of cellular remodelling. After overnight incubation of confluent monolayers of human omental mesothelial cells (HOMEC) with conditioned media prepared from menstrual effluent shed anterogradely, severe alterations in morphology were observed. Typical polygonal mesothelial cell cultures at confluency acquired elongated spindle morphology, resulting in gaps between the cells. In contrast, mesothelial cells from the control groups receiving culture medium only, retained a normal morphology. Immunofluorescence staining revealed that cytokeratin, vimentin and actin filaments were still present, homogeneously distributed in the cell cytoplasm following changes in morphology. To evaluate whether the morphological alterations were associated with apoptosis and/or necrosis, the cells were stained with the M30 CytoDeath antibody or annexin V with propidium iodide and analysed using flow cytometry. The results showed that only a small percentage (1-7%) of the affected HOMEC were undergoing apoptosis or necrosis. We conclude that the profoundly altered morphology of HOMEC is a result of cellular remodelling and that the role of apoptosis and necrosis is negligible. Soluble paracrine factors released by cells isolated from menstrual effluent shed anterogradely may induce a reorganization of the cytoskeleton. As a result, the underlying basement membrane will be exposed and the mesothelium may no longer prevent implantation of endometrium shed retrogradely into the peritoneum, thus facilitating the development of endometriosis.     

The effects of vitamin B12, vitamin D,ferritin level,neutrophil/monocyte ratio and some blood parameters on genital warts presence,the number of lesions,and recurrence rates

The relationships between cancer caused by HPV and some vitamins, as well as leucocytes and their ratios, have been investigated in the literature. Our aim is to evaluate these relationships at the level of genital wart in terms of the investigated parameters and lesion numbers. Data were obtained from 98 and 94 patients for groups one and two, including warts patients and healthy people respectively. The Neutrophil/Monocyte ratio and lesion numbers in the warts patients were reported and analysed in terms of vitamin B12 and D, ferritin and leucocytes. A correlation was established between lesion numbers, age and midcorpuscular volume (p <0.05). There was no correlation between lesion numbers and recurrence. According to the comparative analysis, there were differences in terms of ferritin, neutrophil, monocyte, haemoglobin, midcorpuscular volume and neutrophil/monocyte ratio between groups. The cut-off values for neutrophil, monocyte and N/M ratios were 56.45, 4.91 and 7.825 respectively. While our study showed that wart development may be affected by blood ferritin levels and in this situation, midcorpuscular volume, neutrophil, monocyte and N/M ratios may change, a relation was found between lesion numbers and age and mean midcorpsucular volume values only. However, further studies are needed to clarify this issue.     

An independent indicator of erectile dysfunction is C-reactive protein/albumin ratio

Research has found that, instead of passive lipid-accumulated vascular damage, atherosclerosis which is the primary cause of erectile dysfunction (ED) can be seen as an active inflammatory cycle and that inflammation has a central role in the entire atherosclerotic process. As an inflammatory marker, serum C-reactive protein (CRP)/albumin ratio (CAR) may link to ED and ED severity. The CAR, demographic features and other criteria of 198 patients with ED who visited our outpatient clinic during March 2019–April 2020 were prospectively evaluated. The research also included healthy control subjects without systemic or infectious diseases. The mean difference of CAR between ED and no ED was statistically significant (0.55 ± 0.27 and 0.79 ± 0.49, p = .002 respectively). On the basis of the ROC analysis, CAR has a good ED diagnostic value with an area under the curve (AUC) of 0.63 (95% CI:0.541–0.714) and better diagnostic performance to distinguish ED severity (AUC:0.73, 95% CI:0.620–0.842). Additionally, mean CAR gradually increased with increasing severity of ED (for all p < .001). The CAR has been described as an independent ED indicator in the multivariate analysis (p = .001OR = 8.934; 95% CI:2.449–32.583). Increased CAR is associated with ED severity and increased ED risk. For CAR predicting ED and ED severity, a considerable cut-off point was identified.     

Recurrent priapism in spinal cord injury: A case report

Context: Recurrent priapism is characterized by repetitive episodes of erections which are unrelated to sexual interest or stimulation. It is extremely rare in patients with spinal cord injury (SCI). There are a number of conservative agents used in the treatment.Findings: We describe the case of a 20-year-old male with cervical-5 American Spinal Injury Association (ASIA) Impairment Scale (AIS) grade A tetraplegia as a result of a diving accident 2 years ago. He declared that the recurrent penile erections occurred up to 15–20 times day and night every day and lasted up to 20 min each time unrelated to sexual interest or stimulation. He was prescribed baclofen 10 mg, twice daily. The frequency and duration of erections decreased to 3–5 times/day lasting for about 5 min each and the patient reported a high treatment satisfaction.Conclusion: The presentation of this case is to remind clinicians this rare but distressing condition of recurrent priapism seen in men with complete spinal cord lesions and to summarize the use of medications, most commonly baclofen, to alleviate the condition.     

A method to evaluate microcirculatory vascular patency of full thickness burn in an animal model

BACKGROUND: In cases of thermal injuries it is always difficult to predict the extent of necrosis to the peripheral ischemic zone. Practically, full-thickness skin burn also affects the underlying muscle, panniculus carnosus, which adheres tightly to the skin. In this proposed model, the muscle which was always partly damaged also covers the ischemic zone of full-thickness burn injury. To evaluate the deeper levels of injury, the status of the micro circulation of thermally affected muscle was evaluated by counting the accumulated radioactive agent, 99mTc methoxyisobutylisonitril (MIBI) in the muscle cells. METHODS: 370 MBq/kg (10 mCi/kg) MIBI was administered intravenously to the animals having burn injuries by a comb device as described in previous literature. Then, 20 minutes after injection, whole burned areas were excised and placed under a gamma camera. Each thermally injured area showed four rectangular defects with lower tracer uptakes than the three adjacent interspaces. The tracer uptake of the burned sites and interspaces was analyzed from the acquired images on a computer, and the degree of injury could be assessed quantitatively. Additionally, specimen counts were obtained from selected burned stripes, interspaces and normal tissue for comparison. RESULTS: Burned sites were evident with lower tracer uptakes whereas interspaces with higher uptakes. Captured activity in interspaces indicated that capillary patency mostly maintained and it permitted the arrival of the radiopharmaceutical to the muscle cells. CONCLUSIONS: Muscle layer, where just below the burn area and tightly attached to the skin, could be assessed as a representative of the extension of the injury.     

Severe constricting ring syndrome: case report

This report presents a case of a male newborn with a severe circumferential amniotic band, treated by single-stage excision of the ring, and microvascular venous anastomosis between the proximal and distal parts of the affected site. No complications were encountered. A microsurgical approach to improve the circulation may be useful in some cases.