Ultrastructural localization and function of dopamine D1‐like receptors in the substantia nigra pars reticulata and the internal segment of the globus pallidus of parkinsonian monkeys

The motor symptoms of Parkinson’s disease (PD) are commonly attributed to striatal dopamine loss, but reduced dopamine innervation of basal ganglia output nuclei, the internal globus pallidus (GPi) and the substantia nigra pars reticulata (SNr) may also contribute to symptoms and signs of PD. Both structures express dopamine D1 and D5 receptors under normal conditions, and we have recently demonstrated that their local activation reduces neuronal discharge rates and enhances bursts and oscillatory activity in both nuclei of normal monkeys [M.A. Kliem et al. (2007) J. Neurophysiol., 89, 1489–1500]. Here, we determined the ultrastructural localization and function of D1‐like receptors in 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP)‐treated parkinsonian monkeys. In both normal and MPTP‐treated monkeys, most of the D1 and D5 receptor immunoreactivity was associated with unmyelinated axons, but we also found significant postsynaptic D5 receptor immunostaining in dendrites of GPi and SNr neurons. A significant proportion of axonal D1 immunostaining was bound to the plasma membrane in both normal and MPTP‐treated monkeys. Local microinjections of the D1/D5 receptor agonist SKF82958 significantly reduced discharge rates in GPi and SNr neurons, while they increased burst firing and oscillatory activity in the 3–15‐Hz band in SNr, but not in GPi, of parkinsonian monkeys. Together with our recent findings from normal monkeys, these data provide evidence that functional D1/D5 receptors are expressed in GPi and SNr in both normal and parkinsonian states, and that their activation by endogenous dopamine (under normal conditions) or dopamine receptor agonists (in parkinsonism) may regulate basal ganglia outflow.     

精油对5-氟脲嘧啶渗透大鼠皮肤的促进作用

以月桂氮艹卓酮为参照研究了桉叶油、薄荷油和松节油3种精油对5-氟脲嘧啶渗透大鼠皮肤的促进作用及其机理。3种精油均具有促渗效果,其中桉叶油的增渗约60倍,而薄荷油和松节油分别引起46倍和28倍的增加,通过蒸馏分级将桉叶油按沸点高低分为5个部分,随着沸点升高,促渗效果也提高。在真空条件下140℃时的组分增渗倍数为83倍,略低于月桂氮艹卓酮(89倍)。精油的促渗作用可能与改进药物在组织中的分配和改进药物在皮肤中的扩散有关,但以改善扩散为主。3种精油改善扩散的程度与月桂氮艹卓酮相近。高沸点的桉叶油组分有类似的促渗机理。     

The management of benign salivary disease: a case series

There are many causes for benign salivary gland disease but the most common relate to inflammation and infection. This usually revolves around duct obstruction and a reduction in the normal salivary flow from the gland into the mouth. This leads to retention of saliva, proximal to the obstruction and ascending infection from the mouth, usually because of the decrease in salivary flow. The increase in tension behind the obstruction causes significant pain and swelling, along with the inevitable infection if the obstruction is not relieved. This paper discusses the various treatments available for benign salivary gland disease, the traditional methods of treatment through to the use of endoscopic techniques which are currently available, including a discussion about the use of sialoendoscopy.     

Clinical spectrum and frequency of Charcot–Marie–Tooth disease in Italy: Data from the National CMT Registry

Background and purpose

Data are reported from the Italian CMT Registry.

Methods

The Italian CMT Registry is a dual registry where the patient registers and chooses a reference center where the attending clinician collects a minimal dataset of information and administers the Charcot–Marie–Tooth (CMT) Examination/Neuropathy Score. Entered data are encrypted.

Results

Overall, 1012 patients had registered (535 females) and 711 had received a genetic diagnosis. Demyelinating CMT (65.3%) was more common than axonal CMT2 (24.6%) and intermediate CMT (9.0%). The PMP22 duplication was the most frequent mutation (45.2%), followed by variants in GJB1 and MPZ (both ~10%) and MFN2 (3.3%) genes. A relatively high mutation rate in some “rare” genes (HSPB1 1.6%, NEFL 1.5%, SH3TC2 1.5%) and the presence of multiple mutation clusters across Italy was observed. CMT4A was the most disabling type, followed by CMT4C and CMT1E. Disease progression rate differed depending on the CMT subtype. Foot deformities and walking difficulties were the main features. Shoe inserts and orthotic aids were used by almost one-half of all patients. Scoliosis was present in 20% of patients, especially in CMT4C. Recessive forms had more frequently walking delay, walking support need and wheelchair use. Hip dysplasia occurred in early-onset CMT.

Conclusions

The Italian CMT Registry has proven to be a powerful data source to collect information about epidemiology and genetic distribution, clinical features and disease progression of CMT in Italy and is a useful tool for recruiting patients in forthcoming clinical trials.