P2X7 receptor inhibition improves recovery after spinal cord injury.

Secondary injury exacerbates the extent of spinal cord insults, yet the mechanistic basis of this phenomenon has largely been unexplored. Here we report that broad regions of the peritraumatic zone are characterized by a sustained process of pathologic, high ATP release. Spinal cord neurons expressed P2X7 purine receptors (P2X7R), and exposure to ATP led to high-frequency spiking, irreversible increases in cytosolic calcium and cell death. To assess the potential effect of P2X7R blockade in ameliorating acute spinal cord injury (SCI), we delivered P2X7R antagonists OxATP or PPADS to rats after acute impact injury. We found that both OxATP and PPADS significantly improved functional recovery and diminished cell death in the peritraumatic zone. These observations demonstrate that SCI is associated with prolonged purinergic receptor activation, which results in excitotoxicity-based neuronal degeneration. P2X7R antagonists inhibit this process, reducing both the histological extent and functional sequelae of acute SCI.

Astrocytic Ca2+ signaling evoked by sensory stimulation in vivo.

Although astrocytes are the most abundant cell type in the brain, evidence for their activation during physiological sensory activity is lacking. Here we show that whisker stimulation evokes increases in astrocytic cytosolic calcium (Ca(2+)) within the barrel cortex of adult mice. Increases in astrocytic Ca(2+) were a function of the frequency of stimulation, occurred within several seconds and were inhibited by metabotropic glutamate receptor antagonists. To distinguish between synaptic input and output, local synaptic activity in cortical layer 2 was silenced by iontophoresis of AMPA and NMDA receptor antagonists. The antagonists did not reduce astrocytic Ca(2+) responses despite a marked reduction in excitatory postsynaptic currents in response to whisker stimulation. These findings indicate that astrocytes respond to synaptic input, by means of spillover or ectopic release of glutamate, and that increases in astrocytic Ca(2+) occur independently of postsynaptic excitatory activity.

[Evaluation of the value of ultrasound-guided core needle biopsy in the diagnosis of breast lesions].

OBJECTIVE: To investigate the accuracy, consistency and related affecting factors in pathological results of breast lesions diagnosed by ultrasound-guided core needle biopsy (CNB) and conventional excision histopathology. METHODS: The clinical data of 177 consecutive cases of breast lesions examined by ultrasound-guided CNB and subsequently excised were reviewed from Jan. 2003 to Nov. 2009. The agreement of pathological diagnosis between the CNB and subsequent excision pathology was analyzed. RESULTS: There were 136 cancers in the final diagnosis after surgical excision among 386 breast lesions and 129 of them were diagnosed by CNB. The sensitivity (true positive) of CNB was 94.9%, false negative rate was 5.1%, specificity (true negative) was 100%, false positive rate 0, Youden's index was 0.949, and positive predictive value and negative predictive value were 100% and 85.4%, respectively. Condensation rate was 96.0% and Kappa value was 0.895. CONCLUSION: Ultrasound-guided CNB with histopathological assessment is accurate in diagnosis of breast lesions and has a great consistency with conventional excision pathology. It is a reliable method for the diagnosis of breast lesions to avoid an over-reliance on excision pathological examination.

Expression and role of the TRPC family in TGF-β1-induced calcium influx in podocytes / 生理学报

The TRPC family consists of multiple important cationic channels in mammals that participate in a variety of physiological and pathological processes. Our previous studies have shown that transforming growth factor-β1 (TGF-β1) increases the expression of TRPC6 in podocytes, but the roles of other members of the TRPC family in podocytes require further investigation. In this study, we investigated the effect of TGF-β1 on the expression of the TRPC family and the role of the TRPC family in the changes of the intracellular Ca2+ concentration ([Ca2+]i) in podocytes induced by TGF-β1. The model of podocyte injury was established by treatment with TGF-β1 in immortalized glomerular podocytes (MPC5) in vitro. qRT-PCR and Western blot were used to detect the effect of TGF-β1 on the mRNA and protein expression of each TRPC family member. After the expression of each TRPC family member was knocked down by a siRNA-based approach and blocked by SKF96365, respectively, free cytosolic Ca2+ was measured using the fluorescent Ca2+ indicator Fluo-3/AM, and the dynamic change of [Ca2+]i in podocytes was detected by a dynamic high-speed calcium imaging system. The results showed that TGF-β1 increased the protein expression of TRPC1/3/6 in podocytes, but had no effects on the protein expression of TRPC4. The protein expression levels of TRPC5/7 were only affected by 4 ng/mL and 8 ng/mL TGF-β1, respectively. TGF-β1 increased TRPC1/3/6 mRNA levels in podocytes, however had no effects on TRPC4/5/7 mRNA. TGF-β1 significantly increased [Ca2+]i in podocytes. Knockdown of TRPC1/4/5/7 in podocytes had no significant effect on the [Ca2+]i induced by TGF-β1, but TRPC3/6 knockdown significantly decreased the [Ca2+]i. There was no significant difference in the [Ca2+]i between the TRPC6 siRNA-treated group and SKF96365-treated group, but the [Ca2+]i of the TRPC3 siRNA-treated group was significantly higher than that of SKF96365-treated group. These results demonstrate that TGF-β1 increases the expression of the TRPC1/3/6 in podocytes. TGF-β1 increases [Ca2+]i in podocytes, which is dependent on the TRPC3/6 expression. Our results also suggest that the effect of TRPC6 on [Ca2+]i in podocytes may be greater than that of TRPC3.

T cell receptor constant alpha chain gene +1592C/T polymorphism may not be associated with IgA nephropathy / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the relationship between T cell receptor constant alpha chain (TCRCα) gene +1592C/T polymorphism and IgA nephropathy.</p><p><b>METHODS</b>TCRCα +1592C/T genotypes were identified by PCR-RFLP and direct sequencing in 244 Chinese Han patients with IgA nephropathy, who were classified according to their genotype into CC (188 cases), CT (54 cases) and TT (2 cases) groups. The clinical and pathological data of the patients were analyzed in relation to the TCRCα +1592C/T genotypes.</p><p><b>RESULTS</b>No significant differences in the clinical and biochemical indices were found in these patients with different TCRCα gene +1592C/T genotypes. TCRCα +1592C/T polymorphism was not found to contribute to severity or manifestations of renal pathology.</p><p><b>CONCLUSIONS</b>TCRCα+1592C/T polymorphism may not be associated with the susceptibility to IgA nephropathy in the Chinese Han population.</p>