A lymphoma patient with Cytomegalovirus retinitis and post‐autologous hematopoietic cell transplantation immune reconstitution uveitis: A case report and review of the literature

Cytomegalovirus (CMV) retinitis in hematologic malignancies in the absence of hematopoietic cell transplant (HCT) is uncommon. We report a case of a 54‐year‐old woman with peripheral T‐cell lymphoma who develops CMV retinitis and subsequently undergoes an autologous HCT, with eventual development of immune reconstitution uveitis. We further reviewed the PubMed literature on CMV retinitis in patients with lymphoma. We describe that CMV retinitis in patients with lymphoma has variable clinical presentations, may occur at any time during the course of the disease and chemotherapy, and is associated with significant morbidity.     

Effect of chloroquine on phagolysosomal fusion in cultured guinea pig alveolar macrophages: Implications in drug delivery

The aim of this study was to evaluate the effects of chloroquine on phagolysosomal fusion (PLF) in cultured guinea pig alveolar macrophages (AMs). This technique may be of significance for antitubercular drugs, because the survival of Mycobacterium tuberculosis is linked to evasion of PLF. Guinea pig AMs were obtained from anesthetized animals after exsanguination. The AMs were cultured at a density of 1×10⁶ cell/mL in 24-well plates after attachment to 13-mm coverslips. Culture conditions were at 37°C, with 95% air/5% C^O2 in Roswell Park Memorial Institute (RPMI) 1640 medium with 10% heat-inactivated fetal bovine serum. Rhodamine-dextran (70 kd) was incubated with the cells at 0.25 mg/mL for 24 hours to label the lysosomes. Chloroquine treatment where indicated was performed at 10–20 μ g/mL for 1 hour. Fluorescent BioParticles were then added, and PLF was monitored by formation of an organge-yellow fluorescence on fusion of green fluorescent BioParticles with rhodamine-labeled lysosomes. PLF endpoints were measured by scoring for the percentage of orange-yellow cells in the field of view. Image analysis to measure the intensity of the orange-yellow color was performed by obtaining a, b values for 5×5 pixel areas using the Photo Adobe program 4.0.1. The results indicated that the rate of PLF was enhanced by chloroquine. Thus, chloroquine may be used to potentiate the effects of rifampicin. This may be confirmed by studies involving similar dual fluorophore labeling techniques of fluorescein-labeled formulation in macrophages infected with M. tuberculosis. Preliminary studies with the rhodamine-labeled formulation confirmed cellular uptake and persistence for up to 7 days in culture.     

Hepatitis B vaccination in haemodialysis patients: A randomized clinical trial

Aim:   A short vaccination protocol against hepatitis B was compared to the standard approach in patients under haemodialysis who were primarily non-responsive to the vaccine.
Methods:   This randomized, controlled open trial included 51 chronic haemodialysis subjects previously vaccinated against hepatitis B and with anti-HBs levels of less than 10 IU/mol/L. Twenty-six patients received 20 µg i.m. once a week for 8 weeks (short protocol) and 25 subjects three doses of 40 µg i.m. at months 0, 1 and 6 (standard protocol). Clinical and laboratory data were compared between responders and non-responders. A logistic regression model included selected parameters to assess risk factors for non-seroconversion.
Results:   Seroconversion rates to vaccine at 2 months were 80% and 78% in the short and standard protocol groups, respectively ( P  = 0.99). Median of anti-HBs levels were similar up to 6 months of follow up, but patients in the standard protocol showed a trend to higher anti-HBs in month 3 and a more steady decline in antibody titres. Non-responders were older, had longer duration of dialysis and a higher prevalence of a prior renal transplant and hepatitis C. In multivariate analysis, only advanced age and hepatitis C remained independently associated with non-responsiveness to vaccination.
Conclusion:   In haemodialysis patients, a short vaccination protocol against hepatitis B did not provide any benefit compared to the standard approach with respect to peak anti-HBs titres or a higher rate of seroprotection at the end of follow up. Other strategies to increase seroconversion rates should be explored, especially in the elderly and in patients with hepatitis C.     

Expression of complement regulatory proteins on erythrocytes from patients with idiopathic focal segmental glomerulosclerosis

SUMMARY: Focal segmental glomerulosclerosis (FSGS) is a heterogeneous group of disorders with respect to aetiology, morphology, clinical course and response to treatment. The present study assessed the expression of complement receptor 1 (CR1), decay accelerating factor (DAF) and membrane inhibitor of reactive lysis (CD59) on the erythrocytes of FSGS patients using flow cytometry compared with their expression on the erythrocytes of minimal change nephrotic syndrome (MCNS) patients. Significantly reduced expression of CR1, DAF and CD59 was observed on the erythrocytes of FSGS patients compared with the reduced expression of CR1 and enhanced expression of DAF on the erythrocytes of MCNS patients. A significant inverse relationship was demonstrated between CR1 expression and proteinuria levels in FSGS patients ( r = 0.55, P < 0.01). A follow-up study of 12 patients with FSGS after immunosuppressive therapy showed that the levels of complement regulatory proteins are significantly increased when the disease goes into remission. However, in patients not responding to immunosuppressive therapy, levels of these proteins remained low. MCNS patients showed significant increases in CR1 and decreases in DAF expression during remission of the disease.     

Immunomodulatory effects of Premna tomentosa (L. Verbenaceae) extract in J 779 macrophage cell cultures under chromate (VI)-induced immunosuppression

OBJECTIVE: In the present study, the immunomodulatory effects of Premna tomentosa extract against chromate (VI)-induced toxicity was assessed in J 779 macrophage cell line. DESIGN: The cells were analyzed for cytotoxicity, phagocytosis, oxidant burst, antioxidant status, and cell proliferation. RESULT: Chromate treatment resulted in a significant increase in cytotoxicity and free radical production. Furthermore, there is a significant decrease in reduced glutathione (GSH) levels and glutathione peroxidase activity (GPx). There was an appreciable decrease in cell proliferation and phagocytosis by macrophages in the presence of chromate. However, pretreatment of the cells with P. tomentosa extract (500 microg concentration), 30 minutes prior to chromate (VI) treatment resulted in a significant inhibition of chromate-induced cytotoxicity and reactive oxygen species production. The extract also restored the antioxidant status, cell proliferation, and phagocytosis similar to that of control cells. CONCLUSION: The results confirm the cytoprotective and immunomodulatory effects of the leaves of P. tomentosa and its possible usage in immunosuppressed conditions.     

Current Allogeneic Hematopoietic Stem Cell Transplantation for Pediatric Acute Lymphocytic Leukemia: Success,Failure and Future Perspectives—A Single-Center Experience, 2008 to 2016

Hematopoietic stem cell transplantation (HSCT) is the only curative option for a subset of patients with high-risk or relapsed acute lymphoblastic leukemia (ALL). Given evolving practices, it is important to continually evaluate outcomes for pediatric ALL following HSCT. Outcomes after HSCT are influenced by the type of donor used as this determines the degree and method of T cell depletion used and, consequently, specific transplant-related morbidities. We retrospectively analyzed HSCT data from our center for transplants performed between January 2008 and May 2016, comparing outcomes among different donor types. One hundred and twenty-four pediatric patients underwent HSCT from a matched sibling donor (MSD; n?=?48), an unrelated matched donor (UMD; n?=?56), or a haploidentical donor (n?=?20). We observed a similar 3-year event-free survival (EFS) for MSD recipients (of .64) and for UMD recipients (.62), but a significantly lower EFS for recipients of haploidentical transplants (.35; P?=?.01). Relapse was the main cause of HSCT failure and was significantly higher in the haploidentical donor group (.47 versus .19 for MSD and .24 for UMD; P?=?.02). Treatment-related mortality was evenly distributed among the donor groups (.17, .16, and .15 for the MSD, UMD, and haploidentical groups, respectively). Rates of infection-related mortality were lower than previously reported. Relapse is the main obstacle for successful HSCT in the contemporary era, and this effect is most evident in recipients of haploidentical donor grafts. Newer methods to improve graft-versus-leukemia effect are being evaluated and will need to be incorporated into the management of high-risk patients.     

GABA interneurons mediate the rapid antidepressant-like effects of scopolamine

Major depressive disorder (MDD) is a recurring psychiatric illness that causes substantial health and socioeconomic burdens. Clinical reports have revealed that scopolamine, a nonselective muscarinic acetylcholine receptor antagonist, produces rapid antidepressant effects in individuals with MDD. Preclinical models suggest that these rapid antidepressant effects can be recapitulated with blockade of M1-type muscarinic acetylcholine receptors (M1-AChR); however, the cellular mechanisms underlying activity-dependent synaptic and behavioral responses to scopolamine have not been determined. Here, we demonstrate that the antidepressant-like effects of scopolamine are mediated by GABA interneurons in the medial prefrontal cortex (mPFC). Both GABAergic (GAD67⁺) interneurons and glutamatergic (CaMKII⁺) interneurons in the mPFC expressed M1-AChR. In mice, viral-mediated knockdown of M1-AChR specifically in GABAergic neurons, but not glutamatergic neurons, in the mPFC attenuated the antidepressant-like effects of scopolamine. Immunohistology and electrophysiology showed that somatostatin (SST) interneurons in the mPFC express M1-AChR at higher levels than parvalbumin interneurons. Moreover, knockdown of M1-AChR in SST interneurons in the mPFC demonstrated that M1-AChR expression in these neurons is required for the rapid antidepressant-like effects of scopolamine. These data indicate that SST interneurons in the mPFC are a promising pharmacological target for developing rapid-acting antidepressant therapies.