Role of metabotropic glutamate receptor 5 in the procholinergic effects of neuropsychotherapeutic compounds

We investigated the participation of the metabotropic glutamate receptor type 5 (mGluR5) in mediating increases in cortical acetylcholine (ACh) efflux elicited by established or putative neuropsychotherapeutic compounds, using in vivo microdialysis in rats. The norepinephrine transporter inhibitor atomoxetine, the cannabinoid CB1 receptor antagonist SR141716A, the dopamine D1 receptor agonist dihydrexidine, and the atypical antipsychotic clozapine increased cortical ACh (by about 2-3 fold), whereas the mGluR5 antagonist 2-methyl-6-(phenylethynyl)-pyridine (MPEP) by itself had no effect. The stimulatory effects of atomoxetine, SR141716A and dihydrexidine on cortical ACh were abolished by pretreatment with MPEP. MPEP also attenuated the stimulatory effect of clozapine on ACh efflux. Thus, mGluR5 activation appears to be involved in the procholinergic effects of compounds that exhibit therapeutic properties or potential in neuropsychiatry.     

Feasibility of percutaneous nephrolithotomy under assisted local anaesthesia: a prospective study on selected patients with upper urinary tract obstruction

OBJECTIVE: To evaluate the feasibility of performing percutaneous nephrolithotomy (PCNL) under local anaesthesia in selected patients. METHODS: Twenty-four patients with unilateral renal obstruction due to pelvic stones > or =2.0 cm were enrolled in our study. First a percutaneous nephrostomy to decompress the obstructed kidney was performed using local anaesthesia (lignocaine). A 16-Fr nephrostomy tube was left in place for 1 wk, and then the second stage was carried out. After having infiltrated the tract and the renal parenchyma with lignocaine, dilatation of the nephrostomy tract was performed. Subsequently, PCNL was done using a 24-Fr rigid nephroscope and a ballistic lithotripter. All patients were premedicated with pethidine HCl intramuscularly 30 min before the beginning of both stages. Diazepam was given (0.1mg/kg orally) to patients before the second stage. Pain scores were collected using 10-cm linear visual analogue scale (VAS) after the completion of both procedures. RESULTS: The procedure was well tolerated. One patient needed further treatment with midazolam during PCNL. The mean VAS score was 38 mm (range: 17-60 mm) for the first stage and 36 mm (13-69 mm) for the second stage. The mean operative time, including both stages, was 127 min (85-155 min). No anaesthesia-related complications occurred. CONCLUSION: Our study indicates that PCNL under assisted local anaesthesia is safe and effective in selected patients.     

Metastatic renal clear cell carcinoma in the parotid gland: A study of immunohistochemical profile and cell adhesion molecules (CAMs) expression in two cases

Metastasis of renal cell carcinoma (RCC) may involve any organ, including the parotid salivary gland. While the definition of salivary gland neoplasms with clear cell transformation can be concluded by the synchronous presence of areas showing typical morphology, sometimes the definition of a metastatic RCC in the parotid is difficult and the application of immunohistochemistry may support the clinical and radiographic observations in the final diagnosis. The aim of this paper was to describe the heterogeneous immunohistochemical features and, furthermore, to characterize the pattern of expression of cell adhesion molecules (CAMs) E-cadherin, β4-integrin, desmoglein-2, ICAM-1 and CD44s (HCAM) in two cases of metastatic parotid RCC.     

Influence of GH substitution therapy in deficient adults on the recurrence rate of hormonally inactive pituitary adenomas: a case control study

OBJECTIVE: Several studies documented metabolic and psychological benefits of GH substitution in deficient adults, most of them suffering from benign pituitary adenomas. Since GH substitution is considered to promote tumour regrowth, adequate treatment is performed with some reservation. Therefore, we aimed to elucidate the effect of GH replacement therapy on tumour recurrence following surgery. METHODS: In patients with hormonally inactive pituitary adenomas undergoing tumour surgery, a retrospective case-control study was performed. Pre- and postoperative magnetic resonance (MR) images of GH-treated and untreated patients were matched for best fit by two independent observers. The treated patients were retrieved from the surveillance programme of the German KIMS database and the untreated from the database of the Department of Neurosurgery, University of Erlangen. A total of 55 matched pairs were followed for at least 5 years. Tumour recurrence and progression rates were determined according to the postoperative MR. RESULTS: There were 16 tumour progressions in the treatment group and 12 in the control group. Statistical analysis revealed no significant increase in either recurrence (P = 0.317) or progression (P = 0.617) within the follow-up period of 5 years when GH was adequately replaced. CONCLUSIONS: This study provides further observational data of substitution therapy in GH-deficient adults with pituitary adenomas. Comparing long-term surgical results, we found no evidence that GH substitution should be withheld in deficient patients. Even residual tumour does not constitute a contraindication to GH replacement. However, since pituitary tumours are slow growing, an observational period of 5 years may not have been long enough to verify any absolute influence on recurrence potential.     

Focal therapy for prostate cancer: patient selection and evaluation

Recent stage migration toward low-risk prostate cancer, overtreatment of biologically insignificant tumors with radical prostatectomy at the additional expense of a non-negligible morbidity and undertreatment of patients improperly selected for active surveillance are the main reasons that have fueled the concept of focal therapy. Optimal selection of patients is the key for the successful implementation of focal therapy. Selection criteria for focal therapy vary widely and depend on clinical, histological and imaging characteristics of the patients that are highlighted in this article. In addition, the rationales, merits and limitations of the available methods for the assessment of potential candidates, the evaluation of treatment efficacy and follow-up of these patients are discussed.     

Osteolytic lesions of the patella as an early manifestation of gout

We describe the case of a 60-year-old patient who presented a pre-patellar mass for a period of 2 months, which did not respond to NSAIDs and antibiotic treatment. At physical history, the patient mentioned a recent direct hit at the pre-patellar region. Moreover, he stated that the lesion was painful and fast progressing. Clinical examination revealed the presence of the pre-patellar mass. At palpation, the pre-patellar area was found solid, warm and swollen. No other signs of systemic inflammation were detected. Aspiration of the pre-patellar area with fine needle did not revealed the nature of the lesion. Therefore, we proceeded to a surgical resection of the mass, at healthy margins. Pathologoanatomic examination set the diagnosis of gout. Such an early manifestation of gout is extremely rare and should always be taken into account when one is dealing with painful syndromes of the pre-patellar region.      

Endocannabinoids activate transient receptor potential vanilloid 1 receptors to reduce hyperdopaminergia-related hyperactivity: therapeutic implications.

BACKGROUND: Knockout (KO) mice invalidated for the dopamine transporter (DAT) constitute a powerful animal model of neurobiological alterations associated with hyperdopaminergia relevant to schizophrenia and attention-deficit/hyperactivity disorder (ADHD). METHODS: Because of continuously increasing evidence for a neuromodulatory role of endocannabinoids in dopamine-related pathophysiological responses, we assessed endocannabinoid signaling in DAT KO mice and evaluated the ability of endocannabinoid ligands to normalize behavioral deficits, namely spontaneous hyperlocomotion in these mice. RESULTS: In DAT KO mice, we found markedly reduced anandamide levels, specifically in striatum, the dopamine nerve terminal region. Furthermore, three distinct indirect endocannabinoid agonists, the selective anandamide reuptake inhibitors AM404 and VDM11 and the fatty acid amidohydrolase inhibitor AA5HT, attenuated spontaneous hyperlocomotion in DAT KO mice. The hypolocomotor effects of AM404, VDM11, and AA5HT were significantly attenuated by co-administration of the transient receptor potential vanilloid 1 (TRPV1) antagonist capsazepine but not the selective cannabinoid type 1 (CB1)receptor antagonist AM251. Interestingly, TRPV1 binding was increased in the striatum of DAT KO mice, while CB1 receptor binding was unaffected. CONCLUSIONS: These data indicate a dysregulated striatal endocannabinoid neurotransmission associated with hyperdopaminergic state. Restoring endocannabinoid homeostasis in active synapses might constitute an alternative therapeutic strategy for disorders associated with hyperdopaminergia. In this process, TRPV1 receptors seem to play a key role and represent a novel promising pharmacological target.     

Effects of 6 vs 3 eucaloric meal patterns on glycaemic control and satiety in people with impaired glucose tolerance or overt type 2 diabetes: A randomized trial

Background/objectives

The study aimed to compare the effects of two eucaloric meal patterns (3 vs 6 meals/day) on glycaemic control and satiety in subjects with impaired glucose tolerance and plasma glucose (PG) levels 140–199 mg/dL at 120 min (IGT-A) or PG levels 140–199 mg/dL at 120 min and >200 mg/dL at 30/60/90 min post-oral glucose load on 75-g OGTT (IGT-B), or overt treatment-naïve type 2 diabetes (T2D).