Coordination of fingertip forces during precision grip in premanifest Huntington's disease

Precision grip control is important for accurate object manipulation and requires coordination between horizontal (grip) and vertical (load) fingertip forces. Manifest Huntington's disease (HD) subjects demonstrate excessive and highly variable grip force and delayed coordination between grip and load forces. Because the onset of these impairments is unknown, we examined precision grip control in premanifest HD (pre‐HD) subjects. Fifteen pre‐HD and 15 age‐ and sex‐matched controls performed the precision grip task in a seated position. Subjects grasped and lifted an object instrumented with a force transducer that measured horizontal grip and vertical load forces. Outcomes were preload time, loading time, maximum grip force, mean static grip force, and variability for all measures. We compared outcomes across groups and correlated grip measures with the Unified Huntington's Disease Rating Scale and predicted age of onset. Variability of maximum grip force (P < .0001) and variability of static grip force (P < .00001) were higher for pre‐HD subjects. Preload time (P < .007) and variability of preload time (P < .006) were higher in pre‐HD subjects. No differences were seen in loading time across groups. Variability of static grip force (r² = 0.23) and variability of preload time (r² = 0.59) increased with predicted onset and were correlated with tests of cognitive function. Our results indicate that pre‐HD patients have poor regulation of the transition between reach and grasp and higher variability in force application and temporal coordination during the precision grip task. Force and temporal variability may be good markers of disease severity because they were correlated with predicted onset of disease. © 2011 Movement Disorder Society     

Synovial sarcoma of anterior abdominal wall

Sarcomas are connective tissue tumours, and can arise in any part of the body, more commonly in the extremities. Histological types and clinical presentation of truncal sarcomas are similar to those seen in any other anatomic locations. Radiological investigations may be contributory, but biopsy is conclusive. Surgical resection with wide margins is the initial standard treatment, however a multimodal approach including radiotherapy and chemotherapy is often favoured. Because of the high recurrence rate regardless of therapy, close follow-up is imperative. We present a case of synovial sarcoma of the anterior abdominal wall.     

Simultaneous determination of Levetiracetam and its acid metabolite (ucb L057) in serum/plasma by liquid chromatography tandem mass spectrometry

ObjectiveLevetiracetam and its acid metabolite have almost identical MRMs. They therefore need to be separated chromatographically prior to quantitation.Research design and methodsThe sample is deproteinized with acetonitrile containing Ritonavir as internal standard, centrifuged and the supernatant diluted with water (1:2 v/v). Sixty microliters of the supernatant is injected into the LC–MS/MS and Levetiracetam (LEV) and LEV metabolite separated chromatographically at room temperature employing a Supelco C₁₈ column and a 0.1% formic acid methanol gradient at pH of 2.5.ResultsThe retention times for LEV metabolite, LEV and Ritonavir were 4.50, 5.38 and 9.18 min, respectively. Calibration curves in spiked plasma were linear over the concentration range of 0–50 μg/mL for LEV and 0.0–5.0 µg/mL for LEV metabolite. Intra- and inter-run imprecision (n = 10) gave CVs of 2.3–4.7%, 3.4–8.9% for LEV and 2.9–3.9%, 3.3–7.4% for LEV metabolite. Recoveries of both LEV and LEV metabolite were close to 100%. Results for LEV were compared with those obtained by a commercial reference laboratory (r = 0.974).ConclusionThe procedure is reliable, quick, and inexpensive. LEV and LEV metabolite co-elute using C-18 columns at pHs > 3.0 and previously published methods employing these conditions could therefore be subject to metabolite interference. In this method LEV and LEV metabolite are separated at pH 2.5. The total run time including the washing step is 10 min/sample, making this method suitable when moderate throughput is needed such as in clinical or commercial reference laboratories.     

Downregulation of cyclin D1 is associated with decreased levels of p38 MAP kinases,Akt/PKB and Pak1 during chemopreventive effects of resveratrol in liver cancer cells

Resveratrol is a naturally occurring phytoalexin with antioxidant activity. The chemopreventive effects of resveratrol against various types of cancer are well known, though the underlying molecular mechanisms of its action are still not identified. Hepatocellular carcinoma (HCC) is a one of the most lethal malignancies and there is no effective treatment till date. It is known that cyclin D1 is overexpressed in liver cancers. Accordingly we have studied the chemopreventive effects of resveratrol on cyclin D1 expression and the signaling pathways that regulate cyclin D1 in HepG2 cells. Flow cytometry and PCNA western blot data showed that resveratrol inhibits proliferation of HepG2 cells. Also, resveratrol treatment downregulated cyclin D1 as well as p38 MAP kinase, Akt and Pak1 expression and activity in HepG2 cells, suggesting that growth inhibitory activity of resveratrol is associated with the downregulation of cell proliferation and survival pathways. Furthermore, resveratrol treated cells showed increase in ERK activity suggesting possible sensitization to apoptosis. Thus in the present study, we report a three-dimensional relationship between the growth inhibitory effects of resveratrol – decrease in the levels of cyclin D1 – and downregulation of cell proliferation and survival pathways in HepG2 cells leading to cellular degenerative changes. These observations suggest that resveratrol has good potential as effective chemopreventive agent against liver cancer and warrant further studies.