Local anesthetics inhibit glutamate release from rat cerebral cortex synaptosomes

Local anesthetics have been widely used for regional anesthesia and the treatment of cardiac arrhythmias. Recent studies have also demonstrated that low‐dose systemic local anesthetic infusion has neuroprotective properties. Considering the fact that excessive glutamate release can cause neuronal excitotoxicity, we investigated whether local anesthetics might influence glutamate release from rat cerebral cortex nerve terminals (synaptosomes). Results showed that two commonly used local anesthetics, lidocaine and bupivacaine, exhibited a dose‐dependent inhibition of 4‐AP‐evoked release of glutamate. The effects of lidocaine or bupivacaine on the evoked glutamate release were prevented by the chelation of extracellular Ca²⁺ ions and the vesicular transporter inhibitor bafilomycin A1. However, the glutamate transporter inhibitor dl ‐threo‐beta‐benzyl‐oxyaspartate did not have any effect on the action of lidocaine or bupivacaine. Both lidocaine and bupivacaine reduced the depolarization‐induced increase in [Ca²⁺]_C but did not alter 4‐AP‐mediated depolarization. Furthermore, the inhibitory effect of lidocaine or bupivacaine on evoked glutamate release was prevented by blocking the Ca_v2.2 (N‐type) and Ca_v2.1 (P/Q‐type) channels, but it was not affected by blocking of the ryanodine receptors or the mitochondrial Na⁺/Ca²⁺ exchange. Inhibition of protein kinase C (PKC) and protein kinase A (PKA) also prevented the action of lidocaine or bupivacaine. These results show that local anesthetics inhibit glutamate release from rat cortical nerve terminals. This effect is linked to a decrease in [Ca²⁺]_C caused by Ca²⁺ entry through presynaptic voltage‐dependent Ca²⁺ channels and the suppression of the PKA and PKC signaling cascades. Synapse 67:568–579, 2013 . © 2013 Wiley Periodicals, Inc.     

Acoustic characteristics of vowels and plosives/affricates of Mandarin-speaking hearing-impaired children

This article presents the results of an acoustic analysis of vowels and plosives/affricates produced by 45 Mandarin-speaking children with hearing impairment. Vowel production is represented and categorized into three groups by vowel space size calculated with normalized F1 and F2 values of corner vowels. The correlation between speech intelligibility and language abilities assessed by the level of word comprehension and the complexity of sentence structure is statistically significant. Vowel space grouping is correlated with speech intelligibility and spike percentage of plosives/affricates production. The generalized linear model analysis also shows that the level of word comprehension and the degree of hearing loss are the two most significant factors in predicting speech intelligibility. The statistical results suggest that the interplay of acoustic characteristic and speech ability is complex.     

Articular cartilage deformation following experimental synovitis in the rabbit hip

The development of transient synovitis in the hips of young children occurs quite frequently. This experiment examined the effects of a model synovitis on the deformability of articular cartilage of the immature rabbit hip. At 1, 2, 3, and 4 weeks following synovitis, there was an increase of cartilage deformability on both the acetabular and femoral sides of the joint. This increased deformability may alter force transmission to the underlying bone and its contained vascular structures.     

Successful pregnancy in a woman with symptomatic fibroids who underwent laparoscopic bipolar coagulation of uterine vessels

OBJECTIVE: To report a case of successful pregnancy after laparoscopic bipolar coagulation of uterine vessels (LBCUV). DESIGN: Case report. SETTING: University-affiliated tertiary referral center. PATIENT(S): One woman, treated with LBCUV for symptomatic fibroids, who subsequently had a successful pregnancy. INTERVENTION(S): Laparoscopic bipolar coagulation of uterine arteries and anastomotic sites of uterine arteries with ovarian arteries. MAIN OUTCOME MEASURE(S): Patient evaluation by physical and ultrasound examinations. RESULT(S): Complete resolution of menorrhagia and dysmenorrhea was found after LBCUV. Reduction in fibroid size was seen by ultrasound. Two months later, the patient conceived a singleton pregnancy without the use of assisted reproductive technologies. The woman delivered by cesarean section. Neither myoma recurrence nor abnormality in uterine function was observed. CONCLUSION(S): Although fecundity- and pregnancy-related complications after LBCUV for managing uterine fibroids are still unclear, this first case report of successful pregnancy after LBCUV is promising. LBCUV might be a safe and effective alternative to myomectomy and hysterectomy.     

Dopamine Modulation of GABAergic Function Enables Network Stability and Input Selectivity for Sustaining Working Memory in a Computational Model of the Prefrontal Cortex

Dopamine modulation of GABAergic transmission in the prefrontal cortex (PFC) is thought to be critical for sustaining cognitive processes such as working memory and decision-making. Here, we developed a neurocomputational model of the PFC that includes physiological features of the facilitatory action of dopamine on fast-spiking interneurons to assess how a GABAergic dysregulation impacts on the prefrontal network stability and working memory. We found that a particular non-linear relationship between dopamine transmission and GABA function is required to enable input selectivity in the PFC for the formation and retention of working memory. Either degradation of the dopamine signal or the GABAergic function is sufficient to elicit hyperexcitability in pyramidal neurons and working memory impairments. The simulations also revealed an inverted U-shape relationship between working memory and dopamine, a function that is maintained even at high levels of GABA degradation. In fact, the working memory deficits resulting from reduced GABAergic transmission can be rescued by increasing dopamine tone and vice versa. We also examined the role of this dopamine–GABA interaction for the termination of working memory and found that the extent of GABAergic excitation needed to reset the PFC network begins to occur when the activity of fast-spiking interneurons surpasses 40 Hz. Together, these results indicate that the capability of the PFC to sustain working memory and network stability depends on a robust interplay of compensatory mechanisms between dopamine tone and the activity of local GABAergic interneurons.     

Andrographolide mitigates cardiac apoptosis to provide cardio‐protection in high‐fat‐diet‐induced obese mice

Excessive intake of high fat diet (HFD) and associated obese conditions are critical contributors of cardiac diseases. In this study, an active metabolite andrographolide from Andrographis paniculata was found to ameliorate HFD‐induced cardiac apoptosis. C57/BL6 mouse were grouped as control (n = 9), obese (n = 8), low dose (25 mg/kg/d) andrographolide treatment (n = 9), and high dose (50 mg/kg/d) andrographolide treatment (n = 9). The control group was provided with standard laboratory chow and the other groups were fed with HFD. Andrographolide was administered through oral gavage for 1 week. Histopathological analysis showed increase in apoptotic nuclei and considerable cardiac‐damages in the obese group signifying cardiac remodeling effects. Further, Western blot results showed increase in pro‐apoptotic proteins and decrease in the proteins of IGF‐1R‐survival signaling. However, feeding of andrographolide significantly reduced the cardiac effects of HFD. The results strongly suggest that andrographolide supplementation can be used for prevention and treatment of cardiovascular disease in obese patients.     

Stepping test in mice: A reliable approach in determining forelimb akinesia in MPTP-induced Parkinsonism

Currently existing behavioral measures for motor impairments in rodent models with bilateral dopamine depletion have demonstrated to be difficult to assess due to the degree of task complexity. There is clearly a need for a behavioral test that is simplistic in design and does not require the animal to learn a specific task, in particular for mice. Here we adapted the stepping test, originally designed for assessing asymmetric motor deficits in rats (Olsson, M., Nikkhah, G., Bentlage, C., Bjorklund, A., 1995. Forelimb akinesia in the rat Parkinson model: differential effects of dopamine agonists and nigral transplants as assessed by a new stepping test. J. Neurosci. 15, 3863–3875; Schallert, T., De Ryck, M., Whishaw, I.Q., Ramirez, V.D., Teitelbaum, P., 1979. Excessive bracing reactions and their control by atropine and l-DOPA in an animal analog of Parkinsonism. Exp. Neurol. 64, 33–43), into a mouse-friendly version for bilateral dopamine lesion induced by subacute MPTP injection. We found that MPTP-treated mice exhibit a significant and persistent reduction in the number of adjusting steps when compared to saline-treated animals. Typically, MPTP-induced stepping deficit becomes apparent by the fourth MPTP injection. The number of adjusting steps continues to decline throughout the injections, and by day 10 from the last MPTP injection, the stepping deficit observed is associated with  65% TH positive cells loss in the SN. Importantly, l-DOPA administration significantly improved stepping performance in MPTP-treated mice. Thus, stepping test in mice is a reliable and simple behavioral measure for assessing forelimb akinesia induced by systemic MPTP.