Regularizing firing patterns of rat subthalamic neurons ameliorates parkinsonian motor deficits.

The subthalamic nucleus (STN) is an effective therapeutic target for deep brain stimulation (DBS) for Parkinson's disease (PD), and histamine levels are elevated in the basal ganglia in PD patients. However, the effect of endogenous histaminergic modulation on STN neuronal activities and the neuronal mechanism underlying STN-DBS are unknown. Here, we report that STN neuronal firing patterns are more crucial than firing rates for motor control. Histamine excited STN neurons, but paradoxically ameliorated parkinsonian motor deficits, which we attributed to regularizing firing patterns of STN neurons via the hyperpolarization-activated cyclic nucleotide-gated channel 2 (HCN2) channel coupled to the H2 receptor. Intriguingly, DBS increased histamine release in the STN and regularized STN neuronal firing patterns under parkinsonian conditions. HCN2 contributed to the DBS-induced regularization of neuronal firing patterns, suppression of excessive ß oscillations, and alleviation of motor deficits in PD. The results reveal an indispensable role for regularizing STN neuronal firing patterns in amelioration of parkinsonian motor dysfunction and a functional compensation for histamine in parkinsonian basal ganglia circuitry. The findings provide insights into mechanisms of STN-DBS as well as potential therapeutic targets and STN-DBS strategies for PD.

[Establishment of a penile transplantation model in beagle dogs].

OBJECTIVE: To investigate the feasibility of establishing a model of allograft penile transplantation in adult beagle dogs and explore the conditions for constructing a stable animal model of penis transplant. METHODS: Following the principles of similarity, repeatability, feasibility, applicability, and controllability in the construction of experimental animal models, we compared the major anatomic features of the penis of 20 adult beagle dogs with those of 10 adult men. Using microsurgical techniques, we performed cross-transplantation of the penis in the 20 (10 pairs) beagle dogs and observed the survival rate of the transplanted penises by FK506+MMF+MP immune induction. We compared the relevant indexes with those of the 10 cases of microsurgical replantation of the amputated penis. RESULTS: High similarities but no statistically significant differences were observed in penile anatomic features between the 20 beagle dogs and 10 men. All the 10 cases of cross-transplantation of the penis were successfully completed in the 20 beagle dogs, of which the transplanted glans survived with normal micturition in 12 but developed necrosis in the other 8; the success rate of one-time venous anastomosis was 95.0% (38/40) and that of one-time arterial anastomosis was 87.5% (35/40), with an average vascular anastomosis time of (71.0±9.0) minutes, a mean operation time of (133.0±10.3) minutes, and a mean blood loss of (135.8±41.4) ml. In the 10 cases of penile replantation, the success rate of one-time venous anastomosis was 100% (20/20) and that of one-time arterial anastomosis was 90.0% (18/20), with an average vascular anastomosis time of (65.0±7.9) minutes, a mean operation time of (117.4±10.0) minutes, and a mean blood loss of (85.0±10.8) ml. In the 12 cases of replantation of the amputated penis, the success rate of one-time venous anastomosis was 100% (24/24) and that of one-time arterial anastomosis was 95.8% (23/24), with an average vascular anastomosis time of (79.0±17.6) minutes, a mean operation time of (125.0±20.6) minutes, and a mean blood loss of (140.0±44.3) ml. No statistically significant differences were found in the relevant indexes among the three groups. CONCLUSIONS: The anatomic structure of the corpus cavernosum penis of beagle dogs is highly similar to that of men, almost the same in cross-section anatomy. Microsurgical replantation and allograft transplantation of the penis were both successfully performed in beagle dogs, which showed similar operative indexes to those of human penile replantation. The construction of the allograft penile transplantation model in adult beagle dogs is feasible clinically, with the advantages of operability and repeatability.

5-HT2A receptor-mediated excitation on cerebellar fastigial nucleus neurons and promotion of motor behaviors in rats.

It has long been known that serotonergic afferent inputs are the third largest afferent population in the cerebellum after mossy fibers and climbing fibers. However, the role of serotonergic inputs in cerebellar-mediated motor behaviors is still largely unknown. Here, we show that only 5-HT2A receptors among the 5-HT2 receptor subfamily are expressed and localized in the rat cerebellar fastigial nucleus (FN), one of the ultimate outputs of the spinocerebellum precisely regulating trunk and limb movements. Remarkably, selective activation of 5-HT2A receptors evokes a postsynaptic excitatory effect on FN neurons in a concentration-dependent manner in vitro, which is in accord with the 5-HT-elicited excitation on the same tested neurons. Furthermore, selective 5-HT2A receptor antagonist M100907 concentration-dependently blocks the excitatory effects of 5-HT and TCB-2, a 5-HT2A receptor agonist, on FN neurons. Consequently, microinjection of 5-HT into bilateral FNs significantly promotes rat motor performances on accelerating rota-rod and balance beam and narrows stride width rather than stride length in locomotion gait. All these motor behavioral effects are highly consistent with those of selective activation of 5-HT2A receptors in FNs, and blockage of the component of 5-HT2A receptor-mediated endogenous serotonergic inputs in FNs markedly attenuates these motor performances. All these results demonstrate that postsynaptic 5-HT2A receptors greatly contribute to the 5-HT-mediated excitatory effect on cerebellar FN neurons and promotion of the FN-related motor behaviors, suggesting that serotonergic afferent inputs may actively participate in cerebellar motor control through their direct modulation on the final output of the spinocerebellum.

[Clinical value of ATP determination in CD4+ cells of patients with cytomegaloviral pneumonia after kidney transplantation].

OBJECTIVE: To explore the clinical value of determination of ATP levels in CD4(+) cells of patients with cytomegaloviral pneumonia after kidney transplantation. METHODS: Twenty-eight patients with cytomegaloviral pneumonia following kidney transplantation and 30 healthy volunteers were enrolled in this study. ATP-bioluminescence assay (ATP-CVA) was used to assess the immune response of CD4(+) cells to phytohemagglutinin (PHA) stimulation in the normal volunteers and the recipients (before and at 1, 2, and 4 weeks after renal transplantation, before and at 2 and 4 week after the treatment). RESULTS: ATP concentration in CD4(+) cells of the recipients was 402-/+58 ng/ml before the operation, significantly lower than that in normal volunteers (458-/+196 ng/ml, P<0.05), and reached the lowest level in the first week after operation especially in the recipients with antibody-inducing therapy; ATP level increased slowly since week 2 post-operation, but still remained significantly lower than the preoperative by the fourth week (266-/+87 ng/ml, P<0.05), especially in the recipients receiving antibody-inducing therapy. In the event of cytomegaloviral pneumonia, ATP level underwent a mild reduction to 152-/+78 ng/ml in comparison with the postoperative level at the first week (P>0.05), and was significantly lower than preoperative level (P<0.01); the decrease was especially obvious during the exacerbation of the condition. ATP level then increased slowly after effective treatment, but was still lower than the preoperative level at 4 weeks after the operation (336-/+92 ng/ml, P<0.05). CONCLUSION: The determination of ATP level in CD4(+) cells allows more accurate assessment of the cellular immunity in the renal transplant recipients with cytomegaloviral pneumonia to help in the clinical treatment of the patients.

[Effects of antibiotic and anti-inflammatory treatment on serum PSA and free PSA levels in patients with chronic prostatitis IIIA].

OBJECTIVE: To investigate the effect of antibiotics and a nonsteroidal anti-inflammatory agent on the level of total prostate specific antigen (PSA) and free PSA ratio (F-PSAR) in patients with chronic prostatitis IIIA. METHODS: A total of 228 outpatients diagnosed as with chronic prostatitis III A received 4-week antibiotic and anti-inflammatory treatment. The PSA level and F-PSAR were determined before and after the treatment, and the changes analyzed. RESULTS: Significant variations were observed in the median PSA concentrations (3.51 microg/L and 2.75 microg/L) and F-PSAR (0.25% and 0.27%) 4 weeks after the treatment. Sixty-five of the patients (28.5%) presented with serum PSA greater than 4 ng/ml, the mean PSA decreased by 32.9%, from 6.24 microg/L before the treatment to 4.58 microg/L 4 weeks after the treatment (P < 0.05), and the serum PSA was normalized in 18 of the 65 patients (27.7%). The median variation of F-PSAR (0.16% and 0.22%) was greater than that of PSA. The variation indexes obtained 4 weeks after the treatment showed no statistical difference from those observed 8 weeks after the treatment. CONCLUSION: Chronic prostatitis IIIA appears to contribute to increased serum PSA levels in some men. Antibiotic and anti-inflammatory treatment could significantly reduce the PSA level and increase F-PSAR.