1. To test the mode of functional connectivity in the basal ganglia circuitry, we studied the activity of simultaneously recorded neurons in the globus pallidus (GP) of a behaving rhesus monkey. The cross-correlograms of pairs of neurons in the GP were compared with those of neurons in the thalamus and frontal cortex and to the cross-correlograms of pallidal pairs after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treatment. 2. In contrast with cortical and thalamic neuronal activity, almost all pairs (n = 76/81 pairs; 93.8%, 1,629/1,651 histograms; 98.7%) of GP neurons in the normal monkey were not driven by a common input. 3. The monkey was systemically treated with MPTP until the appearance of parkinsonian signs and an intermittent 7- to 11-Hz action/postural tremor. After the MPTP treatment, many pallidal neurons (49/140; 35%) became oscillatory, and 19% (n = 31/162) of pallidal pairs had oscillatory cross-correlograms. 4. These results support the model of parallel processing in the basal ganglia of normal monkeys and suggest a breakdown of the independent activity in the parkinsonian state.
Summary: Rhesus and vervet monkeys respond differently to treatment with I -methyl-4-phenyl-I ,2,3,6-tetrahydropyridine hydrochloride neurotoxin (MPTP). Both species develop akinesia. rigidity, and severe postural instability. However, rhesus monkeys only develop infrequent. short episodes of highfrequency tremor. whereas vervet monkeys have many prolonged episodes of low-frequency tremor. After MPTP treatment. the spiking activity of many pallidal neurons became oscillatory and highly correlated. Oscillatory autocorrelation functions were dominated by lower frequencies, crosscorrelograms by higher frequencies. The phase shift distribution of the oscillatory cross-correlograms of pallidal cells in MPTP-treated vcrvet monkey were clustered around 0 phase shift. unlike the oscillatory correlograms in the MPTP-treated rhesus monkey, which were widely distributed between 0" and Low-frequency resting tremor is frequently reported as the initial symptom of idiopathic Parkinson's disease (PD). Most patients (70-100%) manifest rest tremor during the course of the disease.' The typical frequency is 4-5 Hz; however, in several patients with early-onset parkinsonism, higher frequencies have been observed.' Posturalhction tremor of smaller amplitude and higher (6-12 Hz) frequency may be seen in most parkinsonian patients.3,4Understanding of the basic mechanisms of PD was enhanced by the discovery of I -methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride neurotoxin (MPTP). ',6 In people, MPTP can produce all major parkinsonian symptoms, including typical parkinsonian rest tremor.'.' The experimental study of tremor in parkinsonism was further advanced by the introduction of the MPTP- treated primate as a reliable animal model for PD."-" However, most primates develop akinesiahradykinesia, flexed posture, and rigidity but usually fail to develop low-frequency Short episodes of highfrequency (10-16 Hz) tremor have been described in MPTP-treated rhesus monkeys, possibly corresponding to postural/action tremor of human parkinsonian patients. In contrast, vervet (African green) monkeys develop prolonged episodes of low-frequency (4-6 Hz) tremor. 13. '4 This article summarizes the authors' electrophysiologic studies on the globus pallidus of MPTP-treated rhesus and vervet monkeys. These studies indicate that transient synchronization of neural activity is the hallmark of the spiking activity of neurons in the pallidum of MPTP-treated monkeys. If the tremor phenomenon is caused by these neural events, transient episodes of tremor coherency between different muscle groups or body segments should be observed. Testing for such episodes of synchronization of tremor was performed between different extremities of MPTP-treated monkeys and human parkinsonian patients.
Background Erectile dysfunction is a common multi-factorial complication of diabetes mellitus. Numerous strategies have been tried to overcome this diabetic complication. In recent years, phosphodiesterase type 5 (PDE-5) inhibitors have been introduced in the management of erectile dysfunction. Objectives The objective of this review was to assess the effect of PDE-5 inhibitors on the management of erectile dysfunction in diabetic men. Search methods Studies were obtained from computerised searches of MEDLINE, EMBASE and The Cochrane Library. Selection criteria Randomised controlled trials, in which treatment with PDE-5 inhibitors was compared to control, in diabetic patients with erectile dysfunction. Data collection and analysis Two reviewers independently extracted data and assessed trial quality. Main results Eight randomised controlled trials were identified. A total 976 men were allocated to receive a PDE-5 inhibitor and 741 were randomised to the control groups. Overall, 80% of the participants suffered from type 2 diabetes mellitus. The weighted mean difference (WMD) for the International Index of Erectile Function (IIEF) questions 3 and 4 (frequency of penetration during and maintaining erection to completion of intercourse) was 0.9 (95% CI 0.8 to 1.1) and 1.1 (95% CI 1.0 to 1.2) at the end of the study period, in favour of the intervention group. The WMD for the IIEF erectile dysfunction domain at the end of the study period was 6.6 (95% CI 5.2 to 7.9) in favour of the PDE-5 inhibitors arm. The relative risk (RR) for answering "yes" to a global efficacy question ("did the treatment improve your erections?") was 3.8 (CI 95% 3.1 to 4.5) in the PDE-5 inhibitors compared with the control arm. The WMD between the percentage of successful attempts in the PDE-5 inhibitors and in the control arm was 26.7 (95% CI 23.1 to 30.3). Mortality was not reported in any of the included trials. Adverse cardiovascular effects were reported in one study. Headache was the most frequent adverse event reported, flushing was the second most common event, with upper respiratory tract complaints and flu like syndromes, dyspepsia, myalgia, abnormal vision and back pain also reported in a descending order of frequency. The overall risk ratio for developing any adverse reaction was 4.8 (CI 95% 3.74 to 6.16) in the PDE-5 inhibitors arm as compared to the control. Phosphodiesterase inhibitors for erectile dysfunction in patients with diabetes mellitus (Review)
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