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Neurotoxicity of herpes 2

Li Shao, Shasha Wang, Haitao Meng, Wenbin Qian, Wenyuan Mai, Wenjuan Yu, Hongyan Tong, Liping Mao, Juying Wei, Jiejing Qian, Jie Jin
OBJECTIVE: To describe the side effects of bortezomib in treatment of multiple myeloma (MM), especially the incidence of peripheral neuropathy (PN). METHODS: Information of 107 patients with MM who were treated with bortezomib in the First Affiliated Hospital of Zhejiang University from 2009 to 2014, were collected and analyzed retrospectively, to analyze the occurrence of adverse events during the treatment, especially the incidences of PN in each cycle and in different patients...
October 2015: Zhonghua Yi Xue za Zhi [Chinese medical journal]
Jean-Marc G Guedon, Shaogen Wu, Xuexing Zheng, Caroline C Churchill, Joseph C Glorioso, Ching-Hang Liu, Shue Liu, Lucy Vulchanova, Alex Bekker, Yuan-Xiang Tao, Paul R Kinchington, William F Goins, Carolyn A Fairbanks, Shuanglin Hao
The complexity of chronic pain and the challenges of pharmacotherapy highlight the importance of development of new approaches to pain management. Gene therapy approaches may be complementary to pharmacotherapy for several advantages. Gene therapy strategies may target specific chronic pain mechanisms in a tissue-specific manner. The present collection of articles features distinct gene therapy approaches targeting specific mechanisms identified as important in the specific pain conditions. Dr. Fairbanks group describes commonly used gene therapeutics (herpes simplex viral vector (HSV) and adeno-associated viral vector (AAV)), and addresses biodistribution and potential neurotoxicity in pre-clinical models of vector delivery...
2015: Molecular Pain
Naoko Sagawa, Yuya Tsurutani, Kazushi Nomura, Tomoko Okuyama, Mai Kondo, Akira Sata, Mariko Miyao, Yuzo Mizuno
An 83-year-old Japanese man had a 29-year history of well-controlled diabetes mellitus. His HbA1c level was approximately 6.0%, with no microalbuminuria and a serum creatinine level seven days before admission of 0.8 mg/dl (eGFR: 69.67 ml/min/1.73 m(2)). Five days before admission, he visited an ophthalmologist with inflammation of the right palpebra and conjunctiva and began taking valacyclovir at a dose of 3,000 mg for the treatment of herpes zoster. Two days before admission, he was prescribed loxoprofen at a dose of 180 mg for a headache...
2014: Nihon Ronen Igakkai Zasshi. Japanese Journal of Geriatrics
Daniel J Knapp
OBJECTIVE: Postherpetic neuralgia (PHN) is a neuropathic sequelae in 8% to 27% of individuals with prior varicella zoster virus infection and herpes zoster resulting in retrograde demyelination, neurotoxic reactive oxygen species levels, and proinflammatory cytokine activation of microglia. Pain management strategies are well documented, but not always effective. Laser therapy has shown utility in nerve injury-related pain disorders and was considered a potentially efficacious intervention...
October 2013: Clinical Journal of Pain
Sumedh S Hoskote, Narender Annapureddy, Atul K Ramesh, Keith Rose, James P Jones
We present the case of a 52-year-old man with hypertension, diastolic congestive heart failure, end-stage renal disease on hemodialysis 3 times a week and a remote history of a hemorrhagic stroke who presented to the emergency department with a vesicular rash on his left arm. The rash was observed to be in a dermatomal distribution, and a diagnosis of herpes zoster was made. The patient was discharged home on valacyclovir 1 g 3 times a day for a duration of 7 days. The patient took 2 doses of valacyclovir before presenting to the hospital again with irritability and hallucinations...
January 2016: American Journal of Therapeutics
Scott J Schachtele, Shuxian Hu, James R Lokensgard
Reactive oxygen species (ROS) produced by brain-infiltrating macrophages and neutrophils, as well as resident microglia, are pivotal to pathogen clearance during viral brain infection. However, unchecked free radical generation is also responsible for damage to and cytotoxicity of critical host tissue bystander to primary infection. These unwanted effects of excessive ROS are combated by local cellular production of antioxidant enzymes, including heme oxygenase-1 (HO-1) and glutathione peroxidase 1 (Gpx1). In this study, we showed that experimental murine herpes encephalitis triggered robust ROS production, as well as an opposing upregulation of the antioxidants HO-1 and Gpx1...
2012: PloS One
Heezoo Kim, Yoon-La Choi, Dong Kyu Lee, Sang Sik Choi, Il Ok Lee, Myoung Hoon Kong, Nan Sook Kim, Sang Ho Lim, Mikyoung Lee
BACKGROUND: Effective early antiviral treatments reduce both acute zoster pain and the risk of postherpetic neuralgia. The authors hypothesized that the direct neuraxial administration of acyclovir could provide superior drug application to the spinal neural structures with a higher viral burden and have various advantages over the other routes of drug administration in terms of required doses, side effects, and efficacy. OBJECTIVE: To know whether intrathecal acyclovir injection is neurologically and histopathologically safe or not...
January 2012: Pain Physician
Akio Takayanagi, Takeshi Maehana, Yuuki Kyoda, Masahiro Yanase
The patient was a 67-year-old man with a 2-year history of peritoneal dialysis for end-stage renal disease due to hypertensive nephropathy. He presented to a dermatologist with a complaint of pain in the right femoral region. He was diagnosed as having herpes zoster and valacyclovir, 1,000 mg/day, was prescribed. After 5 days of taking valacyclovir orally, he felt fretful and hallucinations appeared. He was admitted to our hospital and was hospitalized in our urology ward. We diagnosed his condition as neurotoxicity caused by an overdose of valacyclovir...
November 2010: Hinyokika Kiyo. Acta Urologica Japonica
Scott J Schachtele, Shuxian Hu, Morgan R Little, James R Lokensgard
BACKGROUND: Using a murine model of herpes simplex virus (HSV)-1 encephalitis, our laboratory has determined that induction of proinflammatory mediators in response to viral infection is largely mediated through a Toll-like receptor-2 (TLR2)-dependent mechanism. Published studies have shown that, like other inflammatory mediators, reactive oxygen species (ROS) are generated during viral brain infection. It is increasingly clear that ROS are responsible for facilitating secondary tissue damage during central nervous system infection and may contribute to neurotoxicity associated with herpes encephalitis...
June 28, 2010: Journal of Neuroinflammation
Angela L Lee, Laura B Campbell, Robert M Sapolsky
Viral vectors bearing protective transgenes can decrease neurotoxicity after varied necrotic insults. A neuron that dies necrotically releases glutamate, calcium and reactive oxygen species, thereby potentially damaging neighboring neurons. This raises the possibility that preventing such neuron death via gene therapy can secondarily protect neighboring neurons that, themselves, do not express a protective transgene. We determined whether such "good neighbor" effects occur, by characterizing neurons that, while uninfected themselves, are in close proximity to a transgene-bearing neuron...
June 21, 2010: Brain Research
K Ullah, P Ahmed, S Raza, T Satti, Q Nisa, S Mirza, F Akhtar, M K Kamal, F M Akhtar
One hundred and fifty-four patients received allogeneic stem cell transplantations from HLA-matched siblings for various hematological disorders from July 2001 to September 2006. Indications for transplantation included aplastic anemia (n=66), beta-thalassemia major (n=40), CML (n=33), acute leukemia (n=8), and miscellaneous disorders (n=7). One hundred and twenty patients were males and 34 were females. Median patient age was 14 years (range, 1(1/4)-54 years). All patients achieved successful engraftment. Median time to engraftment (ANC>0...
December 2007: Transplantation Proceedings
Hung-Hsu Yang, Yu-Ping Hsiao, Hung-Chun Shih, Jen-Hung Yang
A 70-year-old man developed herpes zoster over the right L5-S2 region for 3 days and was admitted for acyclovir therapy. He had a medical history of rectal cancer status post-colostomy and end-stage renal disease undergoing thrice weekly hemodialysis. Without a prior loading dose, acyclovir 500 mg (7.7 mg/kg) daily was given intravenously in two divided doses. On the third dosage, the patient became confused and agitated and developed insomnia. Within the following 24 h, delirium, visual and auditory hallucinations, disorientation to place and time, as well as impaired recent memory occurred...
August 2007: International Journal of Dermatology
Adrienne C Müller, Amichand Dairam, Janice L Limson, Santy Daya
The concentration of the endogenous neurotoxin quinolinic acid (QA) is increased in the central nervous system of mice with herpes simplex encephalitis. We have previously shown that the antiherpetic agent acyclovir (AC) has the ability to reduce QA-induced neuronal damage in rat brain, by attenuating lipid peroxidation. The mechanism by which QA induces lipid peroxidation includes the enhancement of the iron (Fe)-mediated Fenton reaction and the generation of free radicals, such as the superoxide anion (O(2)(-))...
February 13, 2007: Life Sciences
Nicolaus Kröger, Tatjana Zabelina, Francis Ayuk, Djordje Atanackovic, Heike Schieder, Helmut Renges, Axel Zander
OBJECTIVE: We investigated the effect of at least two cycles of bortezomib (1.3 mg/m(2) intravenously, days 1, 4, 8, and 11) after dose-reduced allogeneic stem cell transplantation (SCT) on toxicity, CD3(+) cells, graft-versus-host disease (GvHD), and response in patients with multiple myeloma. METHODS: Eighteen patients with multiple myeloma without progressive disease were included. The proteasome inhibitor was given at median of 8 months after allografting to enhance or maintain remission status...
June 2006: Experimental Hematology
Anders Helldén, Jan Lycke, Tatiana Vander, Jan-Olof Svensson, Ingegerd Odar-Cederlöf, Lars Ståhle
OBJECTIVES: Neuropsychiatric symptoms related to aciclovir or valaciclovir treatment have been a problem since aciclovir was introduced in the early 1980s. We have previously found that subjects with aciclovir-related neuropsychiatric symptoms have increased serum concentrations of aciclovir's main metabolite, 9-carboxymethoxymethylguanine (CMMG). The aim of this study was to investigate whether CMMG was present in the CSF of aciclovir- or valaciclovir-treated subjects with or without neuropsychiatric side effects that appeared during therapy...
May 2006: Journal of Antimicrobial Chemotherapy
Koji Tomori, Kazuo Isozumi, Sachiko Motohashi, Satoru Komatsumoto, Yasuo Fukuuchi
A previously healthy 30-year-old woman was admitted to our hospital because of impaired consciousness after convulsion. A temporary diagnosis of herpes simplex encephalitis was made, and intravenous acyclovir (ACV) therapy (250 mg four times daily in normal saline over 2 hours) was started. Three days later, she became confused, and was having hallucinations, dysarthria and generalized painful seizures occurred without focal neurologic deficit. Whether the neuropsychiatric symptoms were related to herpes simplex encephalitis or acyclovir neurotoxity was initially unclear...
August 2003: Rinshō Shinkeigaku, Clinical Neurology
Ryan Hagglund, Bernard Roizman
Herpes simplex virus type 1 (HSV-1) infected cell protein 0 (ICP0) is a multifunctional protein that functions as a promiscuous transactivator and promotes the degradation of multiple cellular proteins. In vitro studies indicated that it encodes two physically separated functional E3 ubiquitin ligase domains. One, designated herpesvirus ubiquitin ligase 1 (HUL-1), maps to a region encoded by exon 3 and is contained between residues 543 and 680. Deletion of amino acids 621 to 625 abolishes this activity. The second, designated HUL-2, maps to the RING finger domain present in ICP0 encoded by exon 2...
December 2003: Journal of Virology
M Roy, J Hom, R M Sapolsky
A large body of literature dealing with neurotoxicity has focused on trying to define the exact nature of cell death following a neurological insult. While there is some debate in the field, it has been shown that a number of neurons in a given population can respond to an acute insult stimulus by activating the apoptotic cascade. To what extent, however, these insults result in the classical manifestations of either apoptosis or necrosis, or whether a mixture of the two results, is highly controversial, in part dependent on the particular system utilized...
May 18, 2001: Brain Research
H Izzedine, L Mercadal, G Aymard, V Launay-Vacher, V Martinez, B Issad, G Deray
Valacyclovir is an effective oral agent for the treatment of herpes virus infection, however, the pharmacokinetics of the drug are altered in renal failure. It is increasingly recognized that dose adjustment of oral valacyclovir in renal failure is necessary to avoid neurotoxicity. We studied this drug in a continuous ambulatory peritoneal dialysis (CAPD) and immunocompromised patient. She developed neurotoxicity with an adjustment dosage of valacyclovir for a cutaneous zoster infection. The elimination half-time (15 h) was similar to that reported for end-stage renal disease patients, while the steady-state volume of distribution (85 l) and the area under the curve concentration (127 mg/l...
March 2001: American Journal of Nephrology
J McLaughlin, B Roozendaal, T Dumas, A Gupta, O Ajilore, J Hsieh, D Ho, M Lawrence, J L McGaugh, R Sapolsky
Numerous studies have demonstrated that gene therapy interventions can protect neurons from death after neurological insults. In nearly all such studies, however, "protection" consists of reduced neurotoxicity, with no demonstrated preservation of neuronal function. We used a herpes simplex virus-1 system to overexpress either the Glut-1 glucose transporter (GT) (to buffer energetics), or the apoptosis inhibitor Bcl-2. Both decreased hippocampal neuron loss to similar extents during excitotoxic insults in vitro and in vivo...
November 7, 2000: Proceedings of the National Academy of Sciences of the United States of America
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