CLINICAL AND PATHOLOGICAL MANIFESTATIONS OF BRAIN DAMAGE IN HIV INFECTION

A feature of the HIV epidemic is currently a large number of comorbid and severe forms of the disease, with frequent involvement in the pathological process of the brain. Methods of in vivo verification of brain damage in clinical practice is sufficient, but in some cases they are limited by financial availability and time factor. Correct and timely deciphering of the nature of brain damage is necessary for the choice of treatment tactics, and as a consequence, reducing mortality. Objective: to study the epidemiology, clinic and pathomorphology of brain damage in HIV infection in conditions of urgent and planned admission of patients to a specialized hospital. Materials and methods. Clinical and pathomorphological studies of HIV-infected patients (n=85) receiving specialized medical care were carried out. The final diagnosis was made taking into account clinical, laboratory and morphological data on the classification of ICD-10 in accordance with the domestic requirements of the formulation of comorbid diagnosis. Conclusion. Brain lesions are clinically and morphologically detected in most HIV-infected patients. Opportunistic and secondary diseases with brain damage have their clinical picture, but it is not specific. From the timely decoding of the nature of brain damage depends on the choice of treatment tactics and, as a consequence, reducing the risk of death. Therefore for verification of the etiological agent, you need to conduct a comprehensive examination: clinical (neurological, psychological distress) and laboratory (cellular composition of CSF protein level and glucose) and bacteriological (seeding of CSF on the flora, on Wednesday Saburo to identify mushrooms on medium Bactec and Lowenstein-Jensen medium for detection of M.tuberculesis); immunological (number of CD4-lymphocytes, at.gondii IgM, at.gondii IgG antibodies), molecular genetic (HIV RNA; DNA HSV1, 2; VZV DNA; DNA EBV; CMV DNA; DNA ВГЧ6; T.gondii DNA; DNA of M.tuberculesis; DNA Cr.neoformans; JC virus DNA) and radiological (MRI brain) research methods. The structure of brain damage in deceased patients was dominated by toxoplasmosis in 28,8% of cases; neuroinfection of unspecified etiology in 28,8% and herpesvirus lesion in 11,9%. Rarely met: tuberculosis 8,47%; candidiasis 8,47%; PML 3,39%; cryptococcosis 3,39%; b-cell lymphoma with brain metastases 3,39%.

Download Full-text

EPIDEMOILOGY, DIAGNOSIS, AND TREATMENT OF HIV-ASSOCIATED NON-HODGKIN LYMPHPOMAS

HIV Infection and Immunosuppressive Disorders ◽

10.22328/2077-9828-2018-10-3-17-29 ◽

2018 ◽

Vol 10 (3) ◽

pp. 17-29

Author(s):

V. V. Rassokhin ◽

A. V. Nekrasova ◽

V. V. Baikov ◽

N. V. Ilyin ◽

Yu. N. Vinogradova

Keyword(s):

Hiv Infection ◽

Opportunistic Infections ◽

Clinical Laboratory ◽

B Cell Lymphoma ◽

Current Treatment ◽

Infectious Complications ◽

Hospital Environment ◽

Team Approach ◽

Oncological Diseases ◽

Cd4 Lymphocyte

The objective of the study was to analyze clinical, immunological and morphological features of malignant non-Hodgkin lymphpomas (MNHL) in HIV-infected patients, evaluate the options and the results of the treatment for the patients in oncohematological hospital environment. Materials and methods. The study evaluated the data from Original Medical Records of 185 HIVinfected patients (mean age 36–40 years) with MNHL that was detected during the period from 1994 to 2017. The results of clinical, laboratory, morphological and immunohistochemical methods used for the study in HIV-infected patients with MNHL were represented. Results. During the period from 1994 to 2017, increasing in the number of HIV-infected patients with MNL, mean age of which was less than 40 years, had been marked. Duration of HIV-infection up to the time of detection the MNHL was 7 years but in 23% of cases the HIV-infection and tumor disease were diagnosed at the same time. Low number of CD4 lymphocyte cells (132 cells/μL) and high number of RNA HIV (more than 550 000 copies/μL) were detected in the blood of the patients. The following distribution was among morphological types of MNHL: diffuse large B-cell lymphoma (DLBCL) — 42%, Burkitt's lymphomas — 32%, plasmablastic lymphomas — 26%. Clinical lymphomas with the extranodal manifestations accompanied with large quantity of complications and opportunistic infections directly resulted from immunosuppression severity (p<0,05) were predominant (76%). Evaluation of combined chemoimmunotherapy effectiveness in HIV-infected patients and in the patients with MNHL showed comparable results in contrast with the population of seronegative HIV-infected patients under using standard polychemotherapy regimens with rituximab, antiretroviral therapy, prevention of infectious complications and immune reconstitution syndrome. Conclusion. Malignant non-Hodgkin lymphpomas represent the group of oncological diseases, which is predominant in HIV-infected patients. These diseases require team approach in early detection, current treatment, prevention of complications in the multidisciplinary team that will significantly improve disease outcome.

Download Full-text

Progressive Multifocal Leukoencephalopathy Associated with Rituximab Treatment of B-Cell Lymphoproliferative Disorders: A Report of 29 Cases from the RADAR Project.

Blood ◽

10.1182/blood.v110.11.370.370 ◽

2007 ◽

Vol 110 (11) ◽

pp. 370-370

Author(s):

Kenneth R. Carson ◽

Andrew M. Evens ◽

Steven T. Rosen ◽

Jane N. Winter ◽

Leo I. Gordon ◽

...

Keyword(s):

Progressive Multifocal Leukoencephalopathy ◽

Hiv Infection ◽

B Cell ◽

Active Surveillance ◽

Medical Literature ◽

Jc Virus ◽

Case Reports ◽

B Cell Lymphoma ◽

Lymphoproliferative Disorders ◽

Purine Analog

Abstract Background- Progressive multifocal leukoencephalopathy (PML) is a demyelinating disorder of the brain caused by the reactivation of latent JC polyoma virus. Rituximab (Rituxan, Mabthera) is a B-cell depleting, monoclonal antibody which has been linked to reactivation of the hepatitis B virus. HIV infection, purine analog therapy, hematopoietic transplant and lymphoma have previously been associated with PML. We evaluated the characteristics of patients with B-cell lymphoproliferative disorders who developed PML after exposure to rituximab, and the quality of case reports available in the medical literature and at the FDA. Methods- Data sources included 1 observation at Northwestern Memorial Hospital, 14 reports obtained from the FDA MedWatch database, 9 case reports from the medical literature, and 21 reports from the manufacturer, Genentech, that were submitted to the FDA. Reports that did not confirm the diagnosis of PML, were associated with HIV infection, or rituximab use for a rheumatologic indication were excluded. Results- Of 47 unique case reports screened, 3 were excluded for rituximab use in rheumatologic disease, 2 for pre-existing HIV, and 13 for inadequate confirmation of the PML diagnosis. In the 29 remaining cases, survival of PML was reported in only one patient. Diagnosis was made by brain biopsy (n=6), autopsy (n=6), or MRI of brain AND positive JC virus by PCR (n=17). Five cases were seen in hematopoietic transplant recipients, 4 autologous and 1 allogeneic. Of the 24 patients who were not transplanted, 10 had purine analog exposure. Thirteen of the 14 patients that did not receive transplant or a purine analog received an alkylating agent, with 7 receiving standard R-CHOP. The median age of the 29 patients was 63.5 years (range 32–89), 15 were female and 14 male. Indications for rituximab were: large B-cell lymphoma (n=6), follicular lymphoma (n=6), CLL (n=5), Waldenstrom (n=2) and other non-Hodgkin lymphomas (n=10). Median time to diagnosis of PML from first and last rituximab doses was 10 and 5 months respectively. The median number of rituximab doses was 6. Quality comparison of source data is contained in table 1. Overall completeness ratio for literature and observed reports vs. FDA and manufacturer reports was 1.48. Conclusions: We have found 29 cases of rituximab-associated PML, of which 14 were not associated with transplantation or purine analog exposure, suggesting an association of rituximab therapy independent of these other treatment related risk factors. FDA and manufacturer reports are inferior to those available in published case reports or through active surveillance. Further examination of the relationship of rituximab to PML, using an active surveillance strategy, is warranted. Type of Information Literature and Observed Cases (n=10) %Reporting FDA and Manufacturer Cases (n=19) %Reporting Completeness Ratio Outcome 90 63 1.42 Date of Lymph 80 68 1.18 Diagnosis Date of Death 78 53 1.47 HIV Status 60 16 3.75 Specific Lymphoma Type 100 84 1.19 Dose of Rituximab 80 63 1.27 Date of 1st Dose 70 94 .74 Date of Last Dose 70 84 .83

Download Full-text

Lesions of brain structures in HIV infection

Medical academic journal ◽

10.17816/maj19383-95 ◽

2019 ◽

Vol 19 (3) ◽

pp. 83-95 ◽

Cited By ~ 1

Author(s):

Tatyana Trofimova ◽

Vadim V. Rassokhin ◽

Olga N. Leonova ◽

Alexey S. Shelomov ◽

Aleksey A. Yakovlev ◽

...

Keyword(s):

Magnetic Resonance Imaging ◽

Magnetic Resonance ◽

Hiv Infection ◽

Brain Damage ◽

Clinical Laboratory ◽

Pathological Process ◽

Resonance Imaging ◽

Intravenous Contrast ◽

The Brain ◽

Secondary Diseases

A feature of the HIV epidemic is currently a large number of comorbid and severe forms of the disease, with frequent involvement in the pathological process of the brain. Brain lesions can be primary, caused by the human immunodeficiency virus itself and secondary, due to the development of opportunistic and secondary diseases and tumors. Correct and timely deciphering of the nature of brain damage is necessary for the choice of treatment tactics and as a consequence of reducing mortality. Objective. To study the radiological manifestations of brain damage in HIV infection in urgent and planned admission of patients to specialized hospitals. Materials and methods of research. In the work, studies were conducted to study the clinical and radiological manifestations of brain damage in HIV-infected patients admitted to various medical institutions with a diagnosis of HIV infection. Radiation examination of the brain was performed in adult HIV-infected patients (n = 410) using magnetic resonance imaging with intravenous contrast. The final diagnosis was made taking into account clinical, laboratory, radiological studies on the classification of ICD-10 in accordance with the domestic requirements of the formulation of comorbid diagnosis. Conclusion. To correctly decipher the nature of brain damage, it is necessary to use comprehensive studies including clinical, laboratory and radiation examination methods. Magnetic resonance imaging with intravenous contrast is the method of choice in the examination of the brain in HIV-infected patients. The structure of brain damage in HIV-infected patients had a different nature: in 54.4% there were signs of the presence of opportunistic and secondary diseases; in 24.9% signs of HIV encephalopathy; in 13.2% signs of nonspecific changes in small vessels of the brain, indicating premature aging or abnormal development; in 7.56% signs of involvement of the brain in the pathological process were not detected. Structure and opportunistic secondary diseases were presented: toxoplasmosis of the brain 18.3%; herpes lesions 12.2%; chief of 10.24%; neuroinfection unspecified etiology is 12.2%; cryptococcosis 4.39%; TB is 2.44%; lymphoma of the brain is 2.44%; MAC infection is 0.24%. Brain damage in HIV-infected patients is largely characterized by synchronicity (mixed infection in 8.52 %) and multifactorial lesions.

Download Full-text

SECONDARY DISEASES IN TANATOGENESIS IN HIV INFECTION

HIV Infection and Immunosuppressive Disorders ◽

10.22328/2077-9828-2019-11-1-46-55 ◽

2019 ◽

Vol 11 (1) ◽

pp. 46-55 ◽

Cited By ~ 2

Author(s):

E. G. Koshevaya ◽

V. A. Zinserling

Keyword(s):

Hiv Infection ◽

Clinical Laboratory ◽

Morphological Data ◽

Detailed Structure ◽

Histological Studies ◽

Associated Diseases ◽

Depth Study ◽

Time Periods ◽

Secondary Diseases

The problem of HIV infection has not lost its relevance, despite the progress and deepening of our knowledge about the disease over the years of study. The paper reflects the detailed structure of lethal outcomes and secondary diseases in HIV infection, taking into account in-depth histological studies in three time periods (1996/97, 2006, 2016) on the basis of these protocols of pathoanatomical autopsies in S.P.Botkin. Some of the data obtained confirms the facts known from the literature, while others are new and need further in-depth study. An important aspect of the work was the assessment of the significance of individual diseases in the tanatogenesis of each case, taking into account all clinical, laboratory and morphological data. The range of HIV-associated diseases varied in different time periods, although in many cases it was insignificant. In general, during the 20-year period of time HIV infection has undergone significant pathomorphosis.

Download Full-text

The Pattern of Ventricular Remodeling Influences the Level of Oxidative Stress in Heart Failure Patients

Revista de Chimie ◽

10.37358/rc.17.7.5705 ◽

2017 ◽

Vol 68 (7) ◽

pp. 1506-1511

Author(s):

Cerasela Mihaela Goidescu ◽

Anca Daniela Farcas ◽

Florin Petru Anton ◽

Luminita Animarie Vida Simiti

Keyword(s):

Oxidative Stress ◽

Heart Failure ◽

Ventricular Remodeling ◽

Clinical Laboratory ◽

Left Ventricular ◽

Control Group ◽

Reactive Protein ◽

Lv Mass ◽

Few Data

Oxidative stress (OS) is increased in chronic diseases, including cardiovascular (CV), but there are few data on its effects on the heart and vessels. The isoprostanes (IsoP) are bioactive compounds, with 8-iso-PGF25a being the most representative in vivo marker of OS. They correlate with the severity of heart failure (HF), but because data regarding OS levels in different types of HF are scarce, our study was aimed to evaluate it by assessing the urinary levels of 8-iso-PGF2aand its correlations with various biomarkers and parameters. Our prospective study included 53 consecutive patients with HF secondary to ischemic heart disease or dilative cardiomyopathy, divided according to the type of HF (acute, chronic decompensated or chronic compensated HF). The control group included 13 hypertensive patients, effectively treated. They underwent clinical, laboratory - serum NT-proBNP, creatinine, uric acid, lipids, C reactive protein (CRP) and urinary 8-iso-PGF2a and echocardiographic assessment. HF patients, regardless the type of HF, had higher 8-iso-PGF2a than controls (267.32pg/�mol vs. 19.82pg/�mol, p[0.001). The IsoP level was directly correlated with ejection fraction (EF) (r=-0.31, p=0.01) and NT-proBNP level (r=0.29, p=0.019). The relative wall thickness (RWT) was negatively correlated with IsoP (r=-0.55, p[0.001). Also 8-iso-PGF25a was higher by 213.59pg/�mol in the eccentric left ventricular (LV) hypertrophy subgroup comparing with the concentric subgroup (p=0.014), and the subgroups with severe mitral regurgitation (MR) and moderate/severe pulmonary hypertension (PAH) had the highest 8-iso-PGF2a levels. Male sex, severe MR, moderate/severe PAH, high LV mass and low RWT values were predictive for high OS level in HF patients.Eccentric cardiac remodeling, MR severity and PAH severity are independent predictors of OS in HF patients.

Download Full-text

B-cell–specific conditional expression of Myd88p.L252P leads to the development of diffuse large B-cell lymphoma in mice

Blood ◽

10.1182/blood-2015-11-684183 ◽

2016 ◽

Vol 127 (22) ◽

pp. 2732-2741 ◽

Cited By ~ 43

Author(s):

Gero Knittel ◽

Paul Liedgens ◽

Darya Korovkina ◽

Jens M. Seeger ◽

Yussor Al-Baldawi ◽

...

Keyword(s):

B Cell ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Specific Expression ◽

Large B Cell Lymphoma ◽

Key Points ◽

Conditional Expression ◽

Large B Cell

Key Points B-cell–specific expression of Myd88p.L252P leads to the development of DLBCL in mice. The Myd88p.L252P mutation cooperates with BCL2 amplifications in ABC-DLBCL lymphomagenesis in vivo.

Download Full-text

Anti-Cancer Properties of Theaflavins

Molecules ◽

10.3390/molecules26040987 ◽

2021 ◽

Vol 26 (4) ◽

pp. 987

Author(s):

Eric J. O’Neill ◽

Deborah Termini ◽

Alexandria Albano ◽

Evangelia Tsiani

Keyword(s):

Signaling Pathways ◽

Cancer Progression ◽

Treatment Strategies ◽

B Cell Lymphoma ◽

Black Tea ◽

Phosphorylated Akt ◽

Phenolic Components ◽

Anti Cancer

Cancer is a disease characterized by aberrant proliferative and apoptotic signaling pathways, leading to uncontrolled proliferation of cancer cells combined with enhanced survival and evasion of cell death. Current treatment strategies are sometimes ineffective in eradicating more aggressive, metastatic forms of cancer, indicating the need to develop novel therapeutics targeting signaling pathways which are essential for cancer progression. Historically, plant-derived compounds have been utilized in the production of pharmaceuticals and chemotherapeutic compounds for the treatment of cancer, including paclitaxel and docetaxel. Theaflavins, phenolic components present in black tea, have demonstrated anti-cancer potential in cell cultures in vitro and in animal studies in vivo. Theaflavins have been shown to inhibit proliferation, survival, and migration of many cancer cellswhile promoting apoptosis. Treatment with theaflavins has been associated with increased levels of cleaved poly (ADP-ribose) polymerase (PARP) and cleaved caspases-3, -7, -8, and -9, all markers of apoptosis, and increased expression of the proapoptotic marker Bcl-2-associated X protein (Bax) and concomitant reduction in the antiapoptotic marker B-cell lymphoma 2 (Bcl-2). Additionally, theaflavin treatment reduced phosphorylated Akt, phosphorylated mechanistic target of rapamycin (mTOR), phosphatidylinositol 3-kinase (PI3K), and c-Myc levels with increased expression of the tumour suppressor p53. This review summarizes the current in vitro and in vivo evidence available investigating the anti-cancer effects of theaflavins across various cancer cell lines and animal models.

Download Full-text

Development of a photochemical thrombosis investigation system to obtain a rabbit ischemic stroke model

Scientific Reports ◽

10.1038/s41598-021-85348-6 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Yoonhee Kim ◽

Yoon Bum Lee ◽

Seung Kuk Bae ◽

Sung Suk Oh ◽

Jong-ryul Choi

Keyword(s):

Ischemic Stroke ◽

Brain Damage ◽

Rabbit Model ◽

Specific Area ◽

Brain Atlas ◽

Rabbit Brain ◽

Stroke Model ◽

Triphenyltetrazolium Chloride ◽

Induction System

AbstractPhotochemical thrombosis is a method for the induction of ischemic stroke in the cerebral cortex. It can generate localized ischemic infarcts in the desired region; therefore, it has been actively employed in establishing an ischemic stroke animal model and in vivo assays of diagnostic and therapeutic techniques for stroke. To establish a rabbit ischemic stroke model and overcome the shortcoming of previous studies that were difficult to build a standardized photothrombotic rabbit model, we developed a photochemical thrombosis induction system that can produce consistent brain damage on a specific area. To verify the generation of photothrombotic brain damage using the system, longitudinal magnetic resonance imaging, 2,3,5-triphenyltetrazolium chloride staining, and histological staining were applied. These analytical methods have a high correlation for ischemic infarction and are appropriate for analyzing photothrombotic brain damage in the rabbit brain. The results indicated that the photothrombosis induction system has a main advantage of being accurately controlled a targeted region of photothrombosis and can produce cerebral hemisphere lesions on the target region of the rabbit brain. In conjugation with brain atlas, it can induce photochemical ischemic stroke locally in the part of the brain that is responsible for a particular brain function and the system can be used to develop animal models with degraded specific functions. Also, the photochemical thrombosis induction system and a standardized rabbit ischemic stroke model that uses this system have the potential to be used for verifications of biomedical techniques for ischemic stroke at a preclinical stage in parallel with further performance improvements.

Download Full-text

Imaging the mechanisms of anti-CD20 therapy in vivo uncovers spatiotemporal bottlenecks in antibody-dependent phagocytosis

Science Advances ◽

10.1126/sciadv.abd6167 ◽

2021 ◽

Vol 7 (8) ◽

pp. eabd6167

Author(s):

Capucine L. Grandjean ◽

Zacarias Garcia ◽

Fabrice Lemaître ◽

Béatrice Bréart ◽

Philippe Bousso

Keyword(s):

B Cell ◽

Cell Lymphoma ◽

Critical Path ◽

B Cell Lymphoma ◽

Antibody Dependent Cellular Cytotoxicity ◽

Fluorescent Reporter ◽

Cd20 Antibody ◽

Anti Cd20 ◽

Partial Depletion

Anti-CD20 antibody (mAb) represents an effective strategy for the treatment of B cell malignancies, possibly involving complement activity, antibody-dependent cellular cytotoxicity and phagocytosis (ADP). While ADP by Kupffer cells deplete circulating tumors, mechanisms targeting non-circulating tumors remain unclear. Using intravital imaging in a model of B cell lymphoma, we establish here the dominance and limitations of ADP in the bone marrow (BM). We found that tumor cells were stably residing in the BM with little evidence for recirculation. To elucidate the mechanism of depletion, we designed a dual fluorescent reporter to visualize phagocytosis and apoptosis. ADP by BM-associated macrophages was the primary mode of tumor elimination but was no longer active after one hour, resulting in partial depletion. Moreover, macrophages were present at low density in tumor-rich regions, targeting only neighboring tumors. Overcoming spatiotemporal bottlenecks in tumor-targeting Ab therapy thus represents a critical path towards the design of optimized therapies.

Download Full-text

TRIM41 is required to innate antiviral response by polyubiquitinating BCL10 and recruiting NEMO

Signal Transduction and Targeted Therapy ◽

10.1038/s41392-021-00477-8 ◽

2021 ◽

Vol 6 (1) ◽

Author(s):

Zhou Yu ◽

Xuelian Li ◽

Mingjin Yang ◽

Jiaying Huang ◽

Qian Fang ◽

...

Keyword(s):

Nucleic Acids ◽

Ubiquitin Ligase ◽

E3 Ubiquitin Ligase ◽

B Cell Lymphoma ◽

Antiviral Response ◽

Type I Interferons ◽

Type I ◽

Innate Response ◽

Innate Antiviral Response

AbstractSensing of pathogenic nucleic acids by pattern recognition receptors (PRR) not only initiates anti-microbe defense but causes inflammatory and autoimmune diseases. E3 ubiquitin ligase(s) critical in innate response need to be further identified. Here we report that the tripartite motif-containing E3 ubiquitin ligase TRIM41 is required to innate antiviral response through facilitating pathogenic nucleic acids-triggered signaling pathway. TRIM41 deficiency impairs the production of inflammatory cytokines and type I interferons in macrophages after transfection with nucleic acid-mimics and infection with both DNA and RNA viruses. In vivo, TRIM41 deficiency leads to impaired innate response against viruses. Mechanistically, TRIM41 directly interacts with BCL10 (B cell lymphoma 10), a core component of CARD proteins−BCL10 − MALT1 (CBM) complex, and modifies the Lys63-linked polyubiquitylation of BCL10, which, in turn, hubs NEMO for activation of NF-κB and TANK-binding kinase 1 (TBK1) − interferon regulatory factor 3 (IRF3) pathways. Our study suggests that TRIM41 is the potential universal E3 ubiquitin ligase responsible for Lys63 linkage of BCL10 during innate antiviral response, adding new insight into the molecular mechanism for the control of innate antiviral response.

Download Full-text