Therapeutic ultrasound after sciatic nerve compression of Wistar rats

Objectives: The present study analyzed the effect of therapy with therapeutic ultrasound on the sciatic nerve after compression injury, comparing two similar doses of SATA.

Methods: In total, 32 Wistar rats were used, divided into the following groups: CG — control; IG — compression injury of the sciatic nerve; IGCU — injury and continuous ultrasound; and IGPU — injury and 20% pulsed ultrasound. The treatment with ultrasound started on the 3rd postoperative day, with a frequency of 1 MHz, 0.4 W/cm² (SATA) for IGCU. IGPU received 2.0 W/cm² (SATP), with 20% of the active cycle, for 3 minutes. The treatment was performed on a daily basis, totaling 15 days of therapy. Evaluations were performed for functional, histological, and morphometric forms.

Results: Both the Sciatic Functional Index and the withdrawal threshold and grip strength failed to show an advantage of using therapeutic ultrasound. For the morphometric evaluations of nerve fiber diameter and axons, myelin sheath thickness, and G quotient and nerve fiber estimates, IGPU values were estimated to be significantly lower. The morphological analysis revealed intense inflammatory response and neovascularization, as well as degeneration of axons and the myelin sheath, for the injury group and IGCU; however, IGPU showed greater tissue disorganization.

Conclusion: There were no significant differences, showing functional or nocicepitive recovery of the treated groups, including with characteristics pointing to the pulsed group with worse results.     

Systematic autistic-like behavioral phenotyping of 4 mouse strains using a novel wheel-running assay

Three core symptoms of autistic spectrum disorders are stereotypic movements, resistance to change in routines and deficits in social interaction. In order to understand their neuronal mechanisms, there is a dire need for behavioral paradigms to assess those symptoms in rodents. Here we present a novel method which is based on positive reward in a customized wheel-running apparatus to assess these symptoms. As a proof of concept, 4 mouse strains were tested in the new behavioral paradigm; 2 control lines (C57BL/6 and ICR) and 2 mouse-models of autism (BTBR T+ tf/J and Nlgn3(tm1Sud)). We found that the C57BL/6, ICR and Nlgn3(tm1Sud) mice showed a significant reduction in stereotypical behavior in the presence of the running wheel, ability to forfeit the running habit when the running-wheel was jammed, and preference of interacting with a social stimulus over the jammed running-wheel. No difference was found between genotypes of the Nlgn3(tm1Sud) mice. On the other hand, the BTBR mice exhibited persistent, elevated levels of stereotypical behavior. In addition, they presented a deficit in their ability to adjust to a changing environment, as manifested in persistence to interact with the wheel even when it was jammed. Lastly, the BTBR mice exhibited no significant preference to interact with the stranger mouse over the jammed running-wheel. These results were validated by a set of commonly used behavioral tests. Overall, our novel behavioral paradigm detects multiple components of autistic-like phenotypes, including cognitive rigidity, stereotypic behavior and social deficiency.     

Correction to: Expression of O-glycosylated oncofetal fibronectin in alternatively activated human macrophages

Immunologic Research -     

The treatment of choroidal melanoma with 198 Au plaque brachytherapy.

BACKGROUND: Seventy-nine consecutive patients with primary choroidal melanoma were treated with 198 Au plaque brachytherapy at the British Columbia Cancer Agency (BCCA) between 1992 and 1998 with perioperative ultrasound to confirm plaque placement. Seventy-seven of the 79 patients were analyzable for this study. RESULTS: Five year actuarial disease specific survival, enucleation free survival, and local control are 95, 94, and 98%, respectively. There were four melanoma related deaths, all secondary to liver metastases. CONCLUSIONS: The BCCA experience in selected patients with choroidal melanomas treated with 198Au plaque brachytherapy has resulted in excellent survival and local control with minimal significant toxicity while preserving the globe. Our results using 198 Au seeds are comparable to other series using 125I, 60Co, and 106Ru at other centers.     

Acetylcholine Elevation Relieves Cognitive Rigidity and Social Deficiency in a Mouse Model of Autism

Autism spectrum disorders (ASD) are defined by behavioral deficits in social interaction and communication, repetitive stereotyped behaviors, and restricted interests/cognitive rigidity. Recent studies in humans and animal-models suggest that dysfunction of the cholinergic system may underlie autism-related behavioral symptoms. Here we tested the hypothesis that augmentation of acetylcholine (ACh) in the synaptic cleft by inhibiting acetylcholinesterase may ameliorate autistic phenotypes. We first administered the acetylcholinesterase inhibitor (AChEI) Donepezil systemically by intraperitoneal (i.p.) injections. Second, the drug was injected directly into the rodent homolog of the caudate nucleus, the dorsomedial striatum (DMS), of the inbred mouse strain BTBR T+tf/J (BTBR), a commonly-used model presenting all core autism-related phenotypes and expressing low brain ACh levels. We found that i.p. injection of AChEI to BTBR mice significantly relieved autism-relevant phenotypes, including decreasing cognitive rigidity, improving social preference, and enhancing social interaction, in a dose-dependent manner. Microinjection of the drug directly into the DMS, but not into the ventromedial striatum, led to significant amelioration of the cognitive-rigidity and social-deficiency phenotypes. Taken together, these findings provide evidence of the key role of the cholinergic system and the DMS in the etiology of ASD, and suggest that elevated cognitive flexibility may result in enhanced social attention. The potential therapeutic effect of AChEIs in ASD patients is discussed.     

Relation of insulin-like growth factor-1 and insulin-like growth factor binding protein-3 levels to growth retardation in extrahepatic portal vein obstruction

Background  Growth retardation has been described in patients with extrahepatic portal vein obstruction (EHPVO). An abnormal growth hormone (GH)–insulin-like growth factor (IGF) axis has been postulated as a possible etiology. We compared anthropometric parameters and IGF-1 and insulin-like growth factor binding protein-3 (IGFBP-3) levels in patients with EHPVO with their siblings as controls. Methods and patients  Consecutive patients diagnosed with EHPVO who presented to out-patient clinic in Department of Gastroenterology between February 2005 and February 2006 were enrolled along with their siblings whenever possible. After detailed history and clinical examination, anthropometric parameters such as age, height, weight, and mid-parental height were measured in patients and controls. IGF-1 and IGFBP-3 levels were also estimated. Results  Fifty-two patients (40 males, 32 adults) were enrolled. Sibling controls were available for 28 patients. Variceal bleeding was the presenting symptom in 41 of 52 (78.8%) patients. Target height was not achieved in 7 of 32 (22.6%) adults and 6 of 20 (30%) children, showing evidence of growth retardation. The mean IGF-1 levels in patients and controls were 124.71 ± 65.49 ng/ml and 233 ± 76.98 ng/ml (P < 0.01), respectively. The mean IGFBP-3 levels in patients and controls were 2.90 ± 1.07 μg/ml and 4.22 ± 0.77 μg/ml (P < 0.01), respectively. Hormonal levels between those with and without evidence of growth retardation did not differ significantly. Duration of symptoms, spleen size, platelet count, and age of presentation did not correlate with anthropometry and hormonal levels. Conclusions  Growth retardation by anthropometry was documented in a quarter of patients with EHPVO. All patients had significantly low IGF-1 and IGFBP-3 levels in comparison with controls despite normal anthropometry in majority of patients (75%).     

Bone mineral density and disorders of mineral metabolism in chronic liver disease

AIM： To estimate the prevalence and identify the risk factors for metabolic bone disease in patients with cirrhosis. METHODS： The study was performed on 72 Indian patients with cirrhosis （63 male, 9 female; aged 〈 50 years）. Etiology of cirrhosis was alcoholism （n = 37）, hepatitis B （n = 25） and hepatitis C （n = 10）. Twenty-three patients belonged to Child class A, while 39 were in class B and 10 in class C. Secondary causes for metabolic bone disease and osteoporosis were ruled out. Sunlight exposure, physical activity and dietary constituents were calculated. Complete metabolic profiles were derived, and bone mineral density （BMD） was measured using dual energy X ray absorptiometry. Low BMD was defined as a Z score below -2. RESULTS： Low BMD was found in 68% of patients. Lumbar spine was the most frequently and severely affected site. Risk factors for low BMD included low physical activity, decreased sunlight exposure, and low lean body mass. Calcium intake was adequate, with unfavorable calcium： protein ratio and calcium： phosphorus ratio. Vitamin D deficiency was highly prevalent （92%）. There was a high incidence of hypogonadism （41%）. Serum estradiol level was elevated significantly in patients with normal BMD. Insulin-like growth factor （IGF） 1 and IGF binding protein 3 levels were below the age-related normal range in both groups. IGF-1 was significantly lower in patients with low BMD. Serum osteocalcin level was low （68%） and urinary deoxypyridinoline to creatinine ratio was high （79%）, which demonstrated low bone formation with high resorption. CONCLUSION： Patients with cirrhosis have low BMD. Contributory factors are reduced physical activity, low lean body mass, vitamin D deficiency and hypogonadism and low IGF-1 level.     

Spontaneous activity competes with externally evoked responses in sensory cortex

The interaction between spontaneous and externally evoked neuronal activity is fundamental for a functional brain. Increasing evidence suggests that bursts of high-power oscillations in the 15- to 30-Hz beta-band represent activation of internally generated events and mask perception of external cues. Yet demonstration of the effect of beta-power modulation on perception in real time is missing, and little is known about the underlying mechanism. Here, we used a closed-loop stimulus-intensity adjustment system based on online burst-occupancy analyses in rats involved in a forepaw vibrotactile detection task. We found that the masking influence of burst occupancy on perception can be counterbalanced in real time by adjusting the vibration amplitude. Offline analysis of firing rates (FRs) and local field potentials across cortical layers and frequency bands confirmed that beta-power in the somatosensory cortex anticorrelated with sensory evoked responses. Mechanistically, bursts in all bands were accompanied by transient synchronization of cell assemblies, but only beta-bursts were followed by a reduction of FR. Our closed loop approach reveals that spontaneous beta-bursts reflect a dynamic state that competes with external stimuli.

The brain is constantly active, even at resting states in the absence of external stimuli (1). Spontaneously active resting-state networks (RSNs) were found in memory, visual, auditory, tactile, and sensorimotor regions, with activity patterns similar to task-evoked responses (2, 3). Functional connectivity studies in humans suggest that a default network, spontaneously activated at resting states and deactivated upon increased cognitive demands, antagonizes a network involved in active attention to external sensory input (4–8). However, whether the activity in different networks is anticorrelated is under debate, and their antagonizing mechanisms and influence on local circuits remain unknown (9).Here, we utilized the occupancy of high-power bursts in the beta-band (15 to 30 Hz) of local field potentials (LFPs) as an indicator of spontaneous activity to investigate its influence on detection in real time. Several lines of evidence relate the RSN to beta-bursts. First, spontaneous correlated oscillatory activity in beta (termed “beta-connectome”) (10) was reported in anatomical regions corresponding to the RSN (11, 12). A recent study derived this beta-connectome from burst occupancy (10). Second, beta-oscillations are dominant during the resting state (13) and bursts are responsible for virtually all beta-band power modulation (14). Third, task-dependent desynchronization of beta was observed in the somatosensory (15, 16), visual (17), auditory (18), and motor (19) cortices, resembling RSN deactivation (4, 7). The task-dependent averaged power modulation was attributed to changes in burst rates in rodents, nonhuman primates, and humans (14, 20, 21). Fourth, the burst duration (50 to a few hundred milliseconds) (22) is similar to “packets” of neural activity, which are conceived as messages initiated in a particular cortical region and spread as a wave over the cortex. Most of these packets are generated spontaneously, and spontaneous and sensory-evoked packets are remarkably similar (23).We found that bursts in all bands indicate transient synchronization of flexible neuronal networks, but only beta-bursts were followed by a reduction in population firing rate (FR). High occupancies of beta-bursts predicted reduced detection, and this effect can be counterbalanced bidirectionally in real time by adjusting the stimulus intensity according to burst occupancy.