Centella asiatica extract selectively decreases amyloid β levels in hippocampus of Alzheimer's disease animal model

PSAPP mice expressing the ‘Swedish’ amyloid precursor protein and the M146L presenilin 1 mutations are a well‐characterized model for spontaneous amyloid β plaque formation. Centella asiatica has a long history of use in India as a memory enhancing drug in Ayurvedic literature. The study investigated whether Centella asiatica extract (CaE) can alter the amyloid pathology in PSAPP mice by administering CaE (2.5 or 5.0 g/kg/day) starting at 2 months of age prior to the onset of detectable amyloid deposition and continued for either 2 months or 8 months. A significant decrease in amyloid β 1–40 and 1–42 was detectable by ELISA following an 8 month treatment with 2.5 mg/kg of CaE. A reduction in Congo Red stained fibrillar amyloid plaques was detected with the 5.0 mg/kg CaE dose and long‐term treatment regimen. It was also confirmed that CaE functions as an antioxidant in vitro, scavenging free radicals, reducing lipid peroxidation and protecting against DNA damage. The data indicate that CaE can impact the amyloid cascade altering amyloid β pathology in the brains of PSAPP mice and modulating components of the oxidative stress response that has been implicated in the neurodegenerative changes that occur with Alzheimer's disease. Copyright © 2008 John Wiley & Sons, Ltd.     

Neuropsychological assessment, neuroimaging, and neuropsychiatric evaluation in pediatric and adult patients with sickle cell disease (SCD)

Traditionally, neuropsychological deficits due to Sickle Cell Disease (SCD) have been understudied in adults. We have begun to suspect, however, that symptomatic and asymptomatic Cerebrovascular Events (CVE) may account for an alarming number of deficits in this population. In the current brief review, we critically evaluated the pediatric and adult literatures on the neurocognitive effects of SCD. We highlighted the studies that have been published on this topic and posit that early detection of CVE via neurocognitive testing, neuropsychiatric evaluations, and neuroimaging may significantly reduce adult cognitive and functional morbidities.     

Comparison between two valsalva techniques for improvement of hypopharyngeal nasendoscopy: a preliminary communication

Objective: To compare the nasal valsalva with the trumpet manoeuvre and anterior neck skin traction as aids to nasendoscopic examination of the hypopharynx. Design: Randomised, controlled comparison of examination techniques. Setting: Single tertiary referral centre. Participants: Twenty‐six adult patients requiring hypopharyngeal nasendoscopic examination were recruited. Patients were examined with both techniques in a randomised order that was recorded to video cassette. Main Outcome Measures: Blinded assessment of the percentage visualisation of the pyriform fossae, post‐cricoid and upper oesophageal sphincter was carried out by three consultant otolaryngologists independently. Results: Mean percentage scores (and 95% confidence intervals) for nasal valsalva versus trumpet manoeuvre for the three consultants, respectively, were as follows: right pyriform fossa: 77(68, 87) versus 80(71, 91), 61(55, 66) versus 60(54, 66), 46(38, 54) versus 45(37, 54); left pyriform fossa: 76(65, 87) versus 80(69, 91), 59(53, 64) versus 55(49, 61), 42(35, 49) versus 42(35, 50); post‐cricoid: 55(44, 67) versus 59(47, 71), 53(46, 60) versus 53(46, 60), 32(25, 39) versus 32(25, 39); upper oesophageal sphincter: 11(1, 21) versus 21(11, 31), 15(9, 21) versus 20(14, 26), 4(0, 8) versus 7(3, 11). No significant difference was found between the two techniques at any subsite. Individual differences were noted in a minority of patients where one or other technique gave a clearly improved view. Conclusions: The nasal valsalva and the trumpet manoeuvre with anterior neck skin traction are complementary techniques for improving the view of the hypopharynx.     

Microarray analysis of healing rat Achilles tendon: evidence for glutamate signaling mechanisms and embryonic gene expression in healing tendon tissue.

Tendon healing is a complex process consisting of a large number of intricate pathways roughly divided into the phases of inflammation, proliferation, and remodeling. Although these processes have been extensively studied at a variety of levels in recent years, there is still much that remains unknown. This study used microarray analyses to investigate the process at a genetic level in healing rat Achilles tendon at 1, 7, and 21 days postinjury, roughly representing the inflammation, proliferation, and remodeling phases. An interesting temporal expression profile was demonstrated, identifying both known and novel genes and pathways involved in the progression of tendon healing. Both inflammatory response and pro-proliferative genes were shown to be significantly upregulated from 24 h postinjury through to 21 days. Day 7 showed the largest increase in genetic activity, particularly with the expression of collagens and other extracellular matrix genes. Interestingly, there was also evidence of central nervous system-like glutamate-based signaling machinery present in tendon cells, as has recently been shown in bone. This type of signaling mechanism has not previously been shown to exist in tendon. Another novel finding from these analyses is that there appears to be several genes upregulated during healing which have exclusively or primarily been characterized as key modulators of proliferation and patterning during embryonic development. This may suggest that similar pathways are employed in wound healing as in the tightly regulated progression of growth and development in the embryo. These results could be of use in designing novel gene-based therapies to increase the efficacy and efficiency of tendon healing.     

Cyclosporine A alleviates severe anaemia associated with refractory large granular lymphocytic leukaemia and chronic natural killer cell lymphocytosis

Large granular lymphocytic (LGL) leukaemia and chronic natural killer cell lymphocytosis (CNKL) are chronic indolent disorders often associated with neutropenia and constitutional symptoms. Severe anaemia occurs in about 20% of patients and is currently treated with corticosteroids followed by oral cyclophosphamide in non-responders. 30% of patients fail initial measures, and salvage therapy is inadequate. We describe three transfusion-dependent patients (two with T-LGL leukaemia, one with CNKL) refractory to corticosteroids, cyclophosphamide, and in one case fludarabine. Cyclosporine A (CSA) initiation resulted in prompt transfusion-independence and was well tolerated in all patients, making it an attractive alternative therapy for this disorder.     

Features of pediatric head injury in Hong Kong

Head injury in children causes special concern in most communities. From 1989 to 1994, 2,785 children younger than 16 years old were admitted to our neurosurgical service because of head injury. Fall from a height was the major cause of head injury leading to admission in infants and children in preschool age groups, whereas traffic-related or bicycle-related accidents were more likely to be the cause of head injury for those aged 11–15 years. In all age groups there was a male preponderance. The overall mortality was 0.6%. Traffic-ralated accidents caused more severe injury and accounted for 67% of all fatalities. For patients under 6 years old, about 40% of head injuries occurred at home. Preventive measures for pediatric head injury in Hong Kong are suggested.     

Memory following cholinergic (NBM) and noradrenergic (DNAB) lesions made singly or in combination: potentiation of disruption by scopolamine

Groups of rats were trained on either delayed matching or nonmatching to position tasks, then divided into four subgroups and given the following bilateral lesions: (a) SHAM [vehicle injection into the nucleus basalis magnocellularis (NBM) and dorsal noradrenergic bundle (DNAB)], (b) DNAB (6-hydroxydopamine lesion of the DNAB, vehicle into the NBM), (c) NBM (quisqualic acid lesion of the NBM, vehicle into the DNAB) and (d) DUAL (neurotoxin lesions of both DNAB and NBM). Following postoperative recovery, the DUAL lesion subjects were slightly impaired, but by the seventh day of testing all groups were performing at similar levels. This strongly suggests that quisqualate lesions of the NBM are not sufficient to produce severe and lasting mnemonic disorders resembling those seen in Alzheimer's disease (AD). These data also indicate that the noradrenergic system may not be of critical importance with respect to cognition. It was reasoned that an additional anticholinergic treatment might exacerbate an underlying deficiency. All groups were injected, peripherally, with the cholinergic antagonist scopolamine (0-0.5 mg/kg). This drug dose-dependently disrupted performance in all groups. Moreover, the highest dose had a marked effect in the DUAL group, impairing performance even when no mnemonic burden was present (at zero delay). The results suggest that cholinergic NBM and noradrenergic DNAB lesions produce only transient mnemonic deficiencies. A combination of the two can be disruptive, but longer term task (or reference) memory is the primary process affected, and only under certain conditions. The implication of these findings to research concerning animal models relating to Alzheimer's disease is discussed.     

Calcium Concentration-dependent Mechanisms through which Ketamine Relaxes Canine Airway Smooth Muscle

Background: Ketamine is a potent bronchodilator that, in clinically used concentrations, relaxes airway smooth muscle in part by a direct effect. This study explored the role of calcium concentration (Ca2+) in this relaxation.

Methods: Canine trachea smooth muscle strips were loaded with the fluorescent probe fura-2 and mounted in a spectrophotometric system to measure force and intracellular calcium concentration ([Ca2+]i) simultaneously. Calcium influx was estimated using a manganese quenching technique. Cyclic nucleotides in the airway smooth muscle strips were measured by radioimmunoassay.

Results: In smooth muscle strips stimulated with submaximal (0.1 micro Meter) and maximal (10 micro Meter) concentrations of acetylcholine, ketamine caused a concentration-dependent decrease in force and [Ca2+]i. The sensitivity of the force response to ketamine significantly decreased as the intensity of muscarinic receptor stimulation increased; the median effective concentration for relaxation induced by ketamine was 59 micro Meter and 850 micro Meter for tissue contracted by 0.1 micro Meter or 10 micro Meter acetylcholine, respectively (P < 0.05). In contrast, the sensitivity of the [Ca2+] sub i response did not depend on the intensity of muscarinic receptor stimulation. Ketamine at 1 mM significantly inhibited calcium influx. Ketamine did not significantly increase cyclic nucleotide concentrations.     

Infusion clearance of subcutaneous iothalamate versus standard renal clearance

 Accurate, timed urine collections for the measurement of glomerular filtration rate (GFR) may be impractical in infants or in patients with urological abnormalities. GFR may be measured without urine collection using a constant subcutaneous infusion of iothalamate. We compare the infusion clearance with conventional renal clearance in 14 children and young adults. The mean clearance ratio (infusion clearance/renal clearance ± 1 SD) was 0.99±0.1 and the mean discrepancy between the two methods was 8.5%±4.7%. The 95% limits of agreement for the ratio of the two methods are 0.83–1.23. These data indicate that subcutaneous infusion of iothalamate is a practical method for measuring GFR in children without a urine collection. Received March 18, 1996; received in revised form February 12, 1997; accepted March 26, 1997