Dynamics of cellular immunity indicators in the complex treatment of acute optic neuritis

An increase in the incidence of optic neuritis among the working-age population, as well as an unpromising prognosis for vision due to the development of optic nerve atrophy, determines the high social significance of this problem. The aim of the work is to analyze the effect of Imunofan at the parameters of cellular immunity and clinical symptoms of the disease in the complex treatment of optic neuritis associated with herpes virus infection. The study involved 37 people (37 eyes) with acute optic neuritis associated with herpes infection. The treatment regimen included the appointment of a dexamethasone solution according to a decreasing scheme, a 1% solution of the drug Emoxipin 0.5 mL and a 12.5% solution of the drug Dicynone 0.5 mL through an irrigation system implanted in the retrobulbar space, in combination with the neuroprotection drugs (Pikamilon and Semax) for 10 days. All patients were divided into 2 groups. The main group consisted of 20 patients who received Imunofan to the treatment regimen in addition. The comparison group included 17 patients who were treated only according to the method described above. The course of treatment lasted 10 days. The analysis of the data showed a more significant positive dynamics of cellular immunity parameters in those who received immunotherapy. Our studies showed the effectiveness of this drug in the complex treatment of optic neuritis associated with herpes infection, what is confirmed by the acceleration of inflammation relief, a more significant increase in visual functions of patients treated with Imunofan, and a lower percentage of optic nerve atrophy. In this group of patients, changes in the parameters of the cellular link of immunity occurred earlier and remained stable throughout the entire period of observation. According to our data, an intergroup assessment of the immunoregulatory index showed its faster increase in patients of the comparison group who received Imunofan, and reached normal values already 6 months after treatment. The clinical effectiveness of Imunofan in the complex therapy of optic neuritis associated with herpes infection was characterized by a reduction in the period of relief of signs of inflammation in the optic nerve by 2 times or more, by an increase in the maximum corrected visual acuity by 4.5 times, and by a decrease in the incidence of recurrence of optic neuritis by 2 times over a 12 months observation period

Prospects of modern pharmacotherapy in postoperative rehabilitation of patients after endovitreal surgery of rhegmatogenous retinal detachment

Purpose. To assess increasing the functional effectiveness of the results of endovitreal surgery in patients with rhegmatogenous retinal detachment (RRD) by using modern pharmacotherapy drug in the postoperative rehabilitation.Material and methods. 108 people (108 eyes) with RRD. All patients underwent standard three-port vitrectomy, after which tamponade of the vitreous cavity with silicone oil with its removal 3 months after operation was performed. Patients were divided into 2 groups: the first – 60 people who received Cytoflavin on the background of standard therapy, and the second – 48 people with postoperative treatment only with standard therapy. Depending on the visual prognosis calculated before the operation, both groups were represented patients with satisfactory (A subgroup) and low (B subgroup) visual prognosis. Laser Doppler fluometry (LDF) was used to study chorioretinal microcirculation: microcirculation index and microcirculation efficiency index were recorded. Using OCT angiography (OCT-A), signs of macular ischemia were investigated: choroidal thickness, area nonperfusion of foveal avascular zone, density in the superficial capillary plexuses and density in the deep capillary plexuses in the macular area.Results. The inclusion of Cytoflavin in the postoperative rehabilitation of patients with RRD increases the possibility of a favorable functional outcome of the operation, affects the positive dynamics in the state of the capillary plexus in the macula. In the aggregate of patients of the 1st group, the increase in visual acuity was 2 times higher than in patients of the 2nd group 6 months after surgery. Also, in patients of the 1st group there was a more significant activation of chorioretinal blood flow according to LDF and OCT-A.Conclusion. The prescription of Cytoflavin in the postoperative treatment of patients underwent endovitreal surgery of RRD, regardless of the visual prognosis, increases the functional outcome of the operation. Improvement in visual functions in patients receiving Cytoflavin therapy is directly related to improved intraocular blood flow and macular perfusion

Intracellular zinc depletion induces caspase activation and p21Waf1/Cip1 cleavage in human epithelial cell lines

To better understand the mechanisms by which zinc deficiency induces epithelial cell death, studies were done of the effects of intracellular zinc depletion induced by the zinc chelator TPEN on apoptosis-related events in human malignant epithelial cell lines LIM1215 (colonic), NCI-H292 (bronchial), and A549 (alveolar type II). In TPEN-treated cells, depletion of zinc was followed by activation of caspase-3 (as demonstrated by enzymatic assay and Western blotting), DNA fragmentation, and morphologic changes. Increase in caspase-3 activity began 1–2 h after addition of TPEN, suggesting that zinc may suppress a step just before the activation of this caspase. Caspase-6, a mediator of caspase-3 processing, also increased, but later than caspase-3. Effects of TPEN on apoptosis were completely prevented by exogenous ZnSO4 and partially prevented by peptide caspase inhibitors. A critical substrate of caspase-3 may be the cell cycle regulator p21Waf1/Cip1, which was rapidly cleaved in TPEN-treated cells to a 15-kDa fragment before further degradation.F. Chai, A. Q. Truong-Tran, A. Evdokiou, G. P. Young and P. D. Zalewsk

Role of immunotherapy in complex treatment of acute optic neuritis associated with herpesvirus infection

Background. An increase in the incidence of optic neuritis (ON) among the workingage population, the complexity of etiological diagnosis and the choice of adequate etiotropic therapy, as well as a disappointing prognosis for vision due to the development of optic nerve atrophy determines the high social significance of this problem.The aim. Comprehensive clinical, functional, morphometric and laboratory-immunological evaluation of results of using the drug Imunofan® in combined treatment of ON associated with herpesvirus infection (HVI).Materials and methods. The study involved 39 people (39 eyes) with acute ON associated with HVI. The standard treatment regimen for the patients included the appointment of solutions: dexamethasone in a decreasing scheme, a 1 % Emoxypine® preparation 0.5 ml and 12.5 % Dicynone® preparation 0.5 ml through an irrigation system implanted into the retrobulbar space, with subsequent appointment of medicinal means of neuroprotection (Picamilon® and Semax®). All patients were divided into two groups. The main group – 22 patients, whose standard inpatient treatment was supplemented with intramuscular administration of the drug Imunofan®, 50 μg daily for 10 days. The control group consisted of 17 patients, who were treated only according to the standard method.Results. Analysis of obtained data showed that more significant positive dynamics was noted in patients of the main group.Conclusion. The clinical efficacy of the drug Imunofan® in the complex therapy of ON associated with HVI was characterized by relief of signs of inflammation in the optic nerve in the main group immediately after the end of the course of treatment, while in the control group – only after 3 months; an increase in the best corrected visual acuity by 1.3 times, a decrease in the incidence of postneuritic optic nerve atrophy at a follow-up period of 12 months

Nursing brain drain from India

In response to recent findings regarding migration of health workers out of Africa, we provide data from a survey of Indian nurses suggesting that up to one fifth of the nursing labour force may be lost to wealthier countries through circular migration

Tumor-Shed PGE2 Impairs IL2Rγc-Signaling to Inhibit CD4+ T Cell Survival: Regulation by Theaflavins

BACKGROUND:Many tumors are associated with decreased cellular immunity and elevated levels of prostaglandin E2 (PGE2), a known inhibitor of CD4+ T cell activation and inducer of type-2 cytokine bias. However, the role of this immunomodulator in the survival of T helper cells remained unclear. Since CD4+ T cells play critical roles in cell-mediated immunity, detail knowledge of the effect tumor-derived PGE2 might have on CD4+ T cell survival and the underlying mechanism may, therefore, help to overcome the overall immune deviation in cancer. METHODOLOGY/PRINCIPAL FINDINGS:By culturing purified human peripheral CD4+ T cells or Jurkat cells with spent media of theaflavin- or celecoxib-pre-treated MCF-7 cells, we show that tumor-shed PGE2 severely impairs interleukin 2 receptor gammac (IL2Rgammac)-mediated survival signaling in CD4+ T cells. Indeed, tumor-shed PGE2 down-regulates IL2Rgammac expression, reduces phosphorylation as well as activation of Janus kinase 3 (Jak-3)/signal transducer and activator of transcription 5 (Stat-5) and decreases Bcl-2/Bax ratio thereby leading to activation of intrinsic apoptotic pathway. Constitutively active Stat-5A (Stat-5A1 6) over-expression efficiently elevates Bcl-2 levels in CD4+ T cells and protects them from tumor-induced death while dominant-negative Stat-5A over-expression fails to do so, indicating the importance of Stat-5A-signaling in CD4+ T cell survival. Further support towards the involvement of PGE2 comes from the results that (a) purified synthetic PGE2 induces CD4+ T cell apoptosis, and (b) when knocked out by small interfering RNA, cyclooxygenase-2 (Cox-2)-defective tumor cells fail to initiate death. Interestingly, the entire phenomena could be reverted back by theaflavins that restore cytokine-dependent IL2Rgammac/Jak-3/Stat-5A signaling in CD4+ T cells thereby protecting them from tumor-shed PGE2-induced apoptosis. CONCLUSIONS/SIGNIFICANCE:These data strongly suggest that tumor-shed PGE2 is an important factor leading to CD4+ T cell apoptosis during cancer and raise the possibility that theaflavins may have the potential as an effective immunorestorer in cancer-bearer

Targeting and killing of glioblastoma with activated T cells armed with bispecific antibodies

Abstract Background Since most glioblastomas express both wild-type EGFR and EGFRvIII as well as HER2/neu, they are excellent targets for activated T cells (ATC) armed with bispecific antibodies (BiAbs) that target EGFR and HER2. Methods ATC were generated from PBMC activated for 14 days with anti-CD3 monoclonal antibody in the presence of interleukin-2 and armed with chemically heteroconjugated anti-CD3×anti-HER2/neu (HER2Bi) and/or anti-CD3×anti-EGFR (EGFRBi). HER2Bi- and/or EGFRBi-armed ATC were examined for in vitro cytotoxicity using MTT and 51Cr-release assays against malignant glioma lines (U87MG, U118MG, and U251MG) and primary glioblastoma lines. Results EGFRBi-armed ATC killed up to 85% of U87, U118, and U251 targets at effector:target ratios (E:T) ranging from 1:1 to 25:1. Engagement of tumor by EGFRBi-armed ATC induced Th1 and Th2 cytokine secretion by armed ATC. HER2Bi-armed ATC exhibited comparable cytotoxicity against U118 and U251, but did not kill HER2-negative U87 cells. HER2Bi- or EGFRBi-armed ATC exhibited 50—80% cytotoxicity against four primary glioblastoma lines as well as a temozolomide (TMZ)-resistant variant of U251. Both CD133– and CD133+ subpopulations were killed by armed ATC. Targeting both HER2Bi and EGFRBi simultaneously showed enhanced efficacy than arming with a single BiAb. Armed ATC maintained effectiveness after irradiation and in the presence of TMZ at a therapeutic concentration and were capable of killing multiple targets. Conclusion High-grade gliomas are suitable for specific targeting by armed ATC. These data, together with additional animal studies, may provide the preclinical support for the use of armed ATC as a valuable addition to current treatment regimens

Role of genetic mutations in development of immunological and clinical disorders in children with chronic pyelonephritis

At the present time, the study of mechanisms of recognition of foreign agents, which is realized by means of Toll-like receptors (TLR) of the innate immune system, has become one of the main tasks of clinical immunology. The aim of our study was to investigate the prevalence of polymorphism of Toll-like receptor 4 (Asp299Gly, Gly299Gly) among children with chronic pyelonephritis (CP) and determine the association of this TLR4 polymorphism with phenotypic features of chronic pyelonephritis and level of interleukin-6 (IL-6). Significantly higher frequency of the mutant allele 299Gly among children with CP was revealed. Significant correlation between the presence of 299Gly TLR4, association of U. urealyticum and M.hominis in lower sections of urinary tract and highest levels of IL-6 concentration was reflected. Sick children with polymorphous locus of TLR4 gene had higher risk of CP early manifestation and formation of its recurrent course with protracted urinary syndrome and unstable remission in comparison with the carriers of “wild” genotype. Obtained results prove the important role of TLR4 in the realization of innate immune response in children with CP and allow considering the TLR4 polymorphism as an additional prognostic indicator in this category of patients