Pharmacological validation of a mouse model of l-DOPA-induced dyskinesia

Dyskinesia (abnormal involuntary movements) is a common complication of l-DOPA pharmacotherapy in Parkinson's disease, and is thought to depend on abnormal cell signaling in the basal ganglia. Dopamine (DA) denervated mice can exhibit behavioral and cellular signs of dyskinesia when they are treated with l-DOPA, but the clinical relevance of this animal model remains to be established. In this study, we have examined the pharmacological profile of l-DOPA-induced abnormal involuntary movements (AIMs) in the mouse. C57BL/6 mice sustained unilateral injections of 6-hydroxydopamine (6-OHDA) in the striatum. The animals were treated chronically with daily doses of l-DOPA that were sufficient to ameliorate akinetic features without inducing overt signs of dyskinesia upon their first administration. In parallel, other groups of mice were treated with antiparkinsonian agents that do not induce dyskinesia when administered de novo, that is, the D2/D3 agonist ropinirole, and the adenosine A2a antagonist KW-6002. During 3 weeks of treatment, l-DOPA-treated mice developed AIMs affecting the head, trunk and forelimb on the side contralateral to the lesion. These movements were not expressed by animals treated with ropinirole or KW-6002 at doses that improved forelimb akinesia. The severity of l-DOPA-induced rodent AIMs was significantly reduced by the acute administration of compounds that have been shown to alleviate l-DOPA-induced dyskinesia both in parkinsonian patients and in rat and monkey models of Parkinson's disease (amantadine, -47%; buspirone, -46%; riluzole, -33%). The present data indicate that the mouse AIMs are indeed a functional equivalent of l-DOPA-induced dyskinesia.     

Primary liver cancer and occupation in men: a case-control study in a high-incidence area in Northern Italy.

The objective of our study was to evaluate the association between occupation and risk of liver cancer. A hospital-based case-control study was carried out during 1997-1999 in the Province of Brescia, a highly industrialized area in Northern Italy with a high incidence of this neoplasm. The cases were 144 male patients with incident liver cancer (96% hepatocellular carcinoma). Controls were 283 male patients, matched to cases on age (+/-5 years), period and hospital of admission. Information on lifetime occupational history and alcohol consumption was obtained via interview. Specific occupational exposures to pesticides, solvents and other suspected hepatocarcinogens were evaluated. A blood sample was collected to detect hepatitis B and C infections. Odds ratios (OR) of occupational exposure and 95% confidence intervals (CI), adjusted for age, residence, education, heavy alcohol intake, hepatitis B surface antigen and hepatitis C virus antibodies positivity were computed. A statistically significant increased OR was observed for employment in repair of motor vehicles (OR 3.7; 95% CI 1.1-12.3; 9 exposed cases, 10 exposed controls). Increased ORs, although not statistically significant, were found for field-crop farm workers, food and beverage processors, blacksmiths and machine-tool operators, electrical fitters, clerical workers, manufacture of industrial machinery and personal and household services. A slightly increased OR was noted in workers exposed to toluene and xylene (OR 1.4; 95% CI 0.7-3.0, 23 cases, 36 controls); the OR was 2.8 (95% CI 1.0-7.6, 11 cases, 12 controls) for 20 or more years of exposure and 2.0 (95% CI 0.9-4.1, 21 cases, 28 controls) for 30 or more years of time since first exposure. The increase in OR seemed to be independent from that of alcohol or viral infections. Our study showed that the role of occupational exposures in liver carcinogenesis is limited. However, prolonged exposure to organic solvents such as toluene and xylene may represent a risk factor for liver cancer.     

Job fitness definitions in workers exposed to biological risks in a health care environment: highlights of a case report]

The definition of the specific job fitness for individual clinical cases often requires significant detailed investigation by the occupational physician. Such professional commitment is particularly important when biological risks in health care personnel are concerned. In fact, besides correct diagnostic procedures and the specific risk assessment implications, the level of competence of the worker, the safety of patients, work organization, risk perception and health education are also especially relevant. The aim of this paper is to report the case of a young nurse employed in the haematology section of the division of internal medicine, who was in charge of preparing and administering antineoplastic drugs. Risk assessment and a thorough clinical evaluation were performed in order to make a job fitness decision, with specific reference to biological risks. The nurse was suffering from membranous glomerulonephritis and was therefore being treated with various immunosuppressant agents. When she came to occupational physician, risk assessment showed that the preparation and administration of the antineoplastic drugs was not safely performed; the clinical picture showed moderate leukopenia while the kidney disease was functionally controlled. The worker was judged unfit to manipulate antineoplastic or perform activities in divisions at high biological risk. Recommendations were given to follow standard precautions and to follow up the case after cessation of immunosuppressant therapy. The case dealt with a specific biological risk assessment in health care settings and with the need to obtain through knowledge of the clinical state of the subject. Such information is necessary to assess job fitness, also giving recommendations related to employer's and employee's responsibility. The case report also provided the opportunity of underlining the role of the occupational physician in the management of cases of particular clinical relevance and of stressing the necessity of continuing scientific updating in order to reach sound conclusions.     

Neuronal activity in macaque supplementary eye field during planning of saccades in response to pattern and spatial cues

The aim of this study was to determine whether neuronal activity in the macaque supplementary eye field (SEF) is influenced by the rule used for saccadic target selection. Two monkeys were trained to perform a variant of the memory-guided saccade task in which any of four visible dots (rightward, upward, leftward, and downward) could be the target. On each trial, the cue identifying the target was either a spot flashed in superimposition on the target (spatial condition) or a foveally presented digitized image associated with the target (pattern condition). Trials conforming to the two conditions were interleaved randomly. On recording from 439 SEF neurons, we found that two aspects of neuronal activity were influenced by the nature of the cue. 1) Activity reflecting the direction of the impending response developed more rapidly following spatial than following pattern cues. 2) Activity throughout the delay period tended to be higher following pattern than following spatial cues. We consider these findings in relation to the possible involvement of the SEF in processes underlying attention, arousal, response-selection, and motor preparation.     

Txt u ltr: using cellular phone technology to enhance a parenting intervention for families at risk for neglect

One of the biggest challenges facing home visiting programs aimed at high-risk families is keeping families involved in the intervention. Cellular phones afford the opportunity for home visitors to maintain regular communication with parents between intervention visits and thus retain high-risk families in parenting interventions. The use of cellular phones may also increase the dosage of intervention provided to families and the fidelity with which parents implement the intervention, thus resulting in improved outcomes for parents and children. This brief report describes the development and initial testing of a parenting program, Planned Activities Training (PAT), which was enhanced through the use of cellular phones to promote the active engagement of parents. PAT is a five-session intervention aimed at improving parent-child interactions, increasing child engagement in daily activities, and reducing challenging child behaviors. To date, 19 parents have completed PAT and cell phone-enhanced PAT, and all have met the 90% correct mastery criterion and demonstrated improvements in their parenting behaviors. Parents have rated PAT and the text messaging and cellular phone call enhancements very positively.     

Long-term outcome after conservative treatment of indirect traumatic optic neuropathy

PURPOSE: To report the long-term outcome of patients with indirect traumatic optic neuropathy (TON) which showed useful vision for a short period after trauma. METHODS: A cohort of 12 TON patients treated with steroids megadose immediately after trauma was followed every 6 months for an overall period of 5 years. Other than a full neuro-ophthalmologic examination, each visit included quantitative Goldmann perimetry and pattern reversal visual evoked potentials. The results of each examination were compared with the visual function at baseline. The main outcome measures were visual acuity and visual field. Data were analyzed using the Wilcoxon signed-rank test. A p value of less than 0.05 was considered statistically significant. RESULTS: All patients showed a stable visual function 5 years after optic nerve trauma. There was no difference in visual acuity levels (p=0.65) and no visual field surface area between the visit at baseline and the last follow-up. However, a significant improvement in visual field extension (p=0.036) was observed after perimetry evaluation. CONCLUSIONS: This cohort of patients clearly demonstrates that the residual visual function found in the short term after TON is maintained for at least 5 years. These findings add further important clinical information for patients with TON. Furthermore, these data may be helpful to better quantify morbidity related to optic nerve trauma and its permanent sequelae.     

Chemistry, biological properties and SAR analysis of quinoxalinones

Quinoxaline derivatives have received much attention in recent years owing to their both biological properties and pharmaceutical applications. In this review we focus the attention on quinoxalin-2(3)-ones and quinoxalin-2,3-diones. These derivatives are particularly interesting since some of them showed antimicrobial (against several bacteria, viruses, fungi, etc), or anticancer activities. Furthermore, others are reported to be potent no-NMDA glutamate receptor antagonists, endowed with anxiolytic, deconditioning, analgesic, antispastic, antiallergic, antithrombotic activities. In this article we also report SAR studies and the most important methods of synthesis of the quinoxalin-2(3)-(di)ones.