Dosimetry to Electron Spin Resonance (ESR) using organic compounds (alanine and ammonium tartrate) for mixed neutron-gamma fields

Alongside with the development of Neutron Capture Therapy (NCT) and the use of thermal neutrons for radiotherapeutic purposes, many efforts have been devoted to the characterization of the beam in order to optimize therapy procedures. Reliable dose measurements should be able to determine the various (neutrons and photonic) components of the mixed beam usually employed for therapy. This paper studies the effect of additives such as Boric and Gadolinium nuclei on the sensitivity of neutron organic (alanine and ammonium tartrate) dosimeters analyzed through Electron Spin Resonance (ESR) technique. These dosimeters were exposed to a mixed (neutron-gamma) field mainly composed of thermal neutrons. The choice of 10B and 64Gd as nuclei additives is due to their very high capture cross section for thermal neutrons. Also, after the nuclear reaction with thermal neutrons are emitted particles, which in turn release their energy in the vicinity of the reaction site. The irradiation with mixed (neutron-gamma) field were performed within the thermal column of the TRIGA reactor, University of Pavia. Dosimeters readout was performed through the Electron Spin Resonance (ESR) spectrometer Bruker ECS106 located at the Laboratory of Dosimetry ESR / TL of the Department of Physics and Chemistry - University of Palermo. We found that the addition of Gadolinium allows to largely increase the sensitivity of the dosimeters for thermal neutrons. In particular, a low concentration (5% by weight) of gadolinium oxide leads to an improvement of the sensitivity of neutrons more than 10 times. In addition, for this low content of gadolinium the photon tissue equivalence is not heavily reduced. This experimental analyses are compared with computational analyses carried out by means of Monte Carlo simulations performed with the MCNP (Monte Carlo N-Particle) transport code. A good agreement was observed for alanine dosimeters

Lamivudine-Induced Liver Injury

BACKGROUND: Lamivudine is a nucleoside analogue antiretroviral drug, known for its low toxicity at clinically prescribed dose. However, the toxicity or mechanism of toxicity and target tissue effects during prolonged administration of higher doses were hardly given sufficient laboratory attention. AIM: The present work was designed to investigate the biochemical and histopathological changes in the liver of rat administered with prolonged doses of lamivudine. MATERIAL AND METHODS: Lamivudine in multiple doses of five ranging from 4 mg/kg to 2500 mg/kg were administered, in vitro, by injection into the air-sac of 10–day old fertile embryonated eggs of Gallus domesticus. Also, female rats of the Wistar strain received oral doses, up to 500 mg/kg singly or repeatedly for 15 or 45 days, respectively. Spectrophotometric techniques were employed to monitor activities of the aminotransferases (ALT and AST), γ–glutamyltransferase (GGT) and total protein concentration in serum while activities of glutathione S–transferase (GST), GGT and superoxide dismutase (SOD) as well as concentrations of malondialdehyde (MDA) and protein were determined in liver. Histopathological studies were carried out on liver. Data were analysed using ANOVA and were considered significant when p < 0.05. RESULTS: The LD50 for the drug calculated from the incubation experiment was 427 mg/kg. Total serum protein concentration significantly reduced while enzymes activities significantly increased at 500 mg/kg only among the repeat-dosed rats. Hepatic GGT, GST and SOD activities as well as MDA concentration were significantly elevated at 20 mg/kg. Histopathological studies showed multifocal lymphoid cell population in the liver sinusoid of the chicken and hydropic degeneration of hepatocytes were recorded among rats repeatedly exposed to the drug respectively at doses ≥ 100 mg/kg

White Matter Hyperintensities in Vascular Contributions to Cognitive Impairment and Dementia (VCID): Knowledge Gaps and Opportunities

White matter hyperintensities (WMHs) are frequently seen on brain magnetic resonance imaging scans of older people. Usually interpreted clinically as a surrogate for cerebral small vessel disease, WMHs are associated with increased likelihood of cognitive impairment and dementia (including Alzheimer\u27s disease [AD]). WMHs are also seen in cognitively healthy people. In this collaboration of academic, clinical, and pharmaceutical industry perspectives, we identify outstanding questions about WMHs and their relation to cognition, dementia, and AD. What molecular and cellular changes underlie WMHs? What are the neuropathological correlates of WMHs? To what extent are demyelination and inflammation present? Is it helpful to subdivide into periventricular and subcortical WMHs? What do WMHs signify in people diagnosed with AD? What are the risk factors for developing WMHs? What preventive and therapeutic strategies target WMHs? Answering these questions will improve prevention and treatment of WMHs and dementia

White matter hyperintensities in vascular contributions to cognitive impairment and dementia (VCID): Knowledge gaps and opportunities

White matter hyperintensities (WMHs) are frequently seen on brain magnetic resonance imaging scans of older people. Usually interpreted clinically as a surrogate for cerebral small vessel disease, WMHs are associated with increased likelihood of cognitive impairment and dementia (including Alzheimer's disease [AD]). WMHs are also seen in cognitively healthy people. In this collaboration of academic, clinical, and pharmaceutical industry perspectives, we identify outstanding questions about WMHs and their relation to cognition, dementia, and AD. What molecular and cellular changes underlie WMHs? What are the neuropathological correlates of WMHs? To what extent are demyelination and inflammation present? Is it helpful to subdivide into periventricular and subcortical WMHs? What do WMHs signify in people diagnosed with AD? What are the risk factors for developing WMHs? What preventive and therapeutic strategies target WMHs? Answering these questions will improve prevention and treatment of WMHs and dementia

aHUS caused by complement dysregulation: new therapies on the horizon

Atypical hemolytic uremic syndrome (aHUS) is a heterogeneous disease that is caused by defective complement regulation in over 50% of cases. Mutations have been identified in genes encoding both complement regulators [complement factor H (CFH), complement factor I (CFI), complement factor H-related proteins (CFHR), and membrane cofactor protein (MCP)], as well as complement activators [complement factor B (CFB) and C3]. More recently, mutations have also been identified in thrombomodulin (THBD), an anticoagulant glycoprotein that plays a role in the inactivation of C3a and C5a. Inhibitory autoantibodies to CFH account for an additional 5–10% of cases and can occur in isolation or in association with mutations in CFH, CFI, CFHR 1, 3, 4, and MCP. Plasma therapies are considered the mainstay of therapy in aHUS secondary to defective complement regulation and may be administered as plasma infusions or plasma exchange. However, in certain cases, despite initiation of plasma therapy, renal function continues to deteriorate with progression to end-stage renal disease and renal transplantation. Recently, eculizumab, a humanized monoclonal antibody against C5, has been described as an effective therapeutic strategy in the management of refractory aHUS that has failed to respond to plasma therapy. Clinical trials are now underway to further evaluate the efficacy of eculizumab in the management of both plasma-sensitive and plasma-resistant aHUS

ESR response of watch glasses to neutron irradiation

In this paper we report the results of the electron spin resonance (ESR) study of the radiation-induced signal of watch glasses exposed to neutrons. This work extends the series of analyses of the response of watch glasses to various radiation beams which our research group is carrying out for possible applications in retrospective dosimetry. We have considered fluences up to about 3x1011 cm 2. We evaluated the signal fading and we found that in the first hours after exposure the signal rapidly decreases. After about 1000 h, it decreases much more slowly. The signal was reduced by about 25% in about 5 months. The radiation induced signal is found to be linearly dependent on neutron fluence and an estimate of the lowest detectable fluence is provided

Nutrient based intervention to reduce malaria related morvidity and mortality in Nigeria

No Abstract. Journal of Malaria in Africa and the Tropics Vol. 1 (2) 2002: pp. 17-2

Comparative In - vitro Efficacy of Chloroquine, Fansidar, Cotecxin and Amalar in Human Plasmodium falciparum in Malaria

In vitro drugs test with WHO micro test method was used to compare the efficacy of four antimalarials: Chloroquine, Fansidarâ, Cotecxinâ and Amalarâ on isolates of plasmodium malaria. A three-day (72 hrs) incubation period for drugs-parasites interactions was used. Thirteen (13) patients with chloroquine treatment had no complete parasite clearance for the 72 hours incubation. However, total parasite clearance was observed in two (2) patients with Cotecxinâ and Fansidarâ treatment for the 72 hours incubation. A more total parasite clearance was found with only Cotecxinâ on the seventh (7) day of the treatment. There was treatment failure in nine (9) patients in Amalarâ group on the seventh day of the treatment, while Cotecxinâ had only four (4) patients and Fansidarâ in six (6) patients respectively on same day. There was a high therapeutic efficacy of Cotecxinâ in the treatment of Plasmodium falciparum malaria. Key Words: Chloroquine, Fansidarâ, Amalarâ, Cotecxinâ, in vitro efficacy, P. falciparum. Résumé le test de medicament invitro avec la methode microtest de l'OMS on été utilisés pour comparer l'efficacité de quatre antimalariales: chloroquine, Fansidar, Cotexin and Amalar sur des plasmodium malariae isolés. Une période de trios jous (72hrs) d'incubation pour interaction medicament-parasite était utilisé. Treize (13) patients traités à la chloroquine ont eu une asbsence parasitaire incomplète après 72heurs d'incubation. Néanmoins la clearance parasitaire total on été observé chez 2 patients utilisant comme traitement cotexin et fansidar après 72 hrs d'incubation. Une clearance total parasitaire avancée était vu avec l'utilisation exclusive du Cotexin au 7ème jour de traitement, alors que Cotexin a eu seleument 4 patients et fansidar 6 patients respectivement le même jour. Il ya une grande éfficacite therapeutique du cotexin dans le traitement du plasmodium falciparum malaria. Mot clés: Chloroquine,Fansidar, Amalar, Cotexin, efficacite invitro, P. falciparum. West Afr. J. Pharmacol. Drug Res. Vol.19 (1&2) 2003: 55-5