In vivo PET study of 5HT(2A) serotonin and D(2) dopamine dysfunction in drug-naive obsessive-compulsive disorder

There are several lines of evidence, the majority indirect, suggesting that changes in serotonergic or dopaminergic neurotransmission may contribute to the pathogenesis of obsessive-compulsive disorder (OCD). We evaluated the co-occurrence of serotonergic and dopaminergic dysfunctions in OCD subjects, all drug-naive, with no co-morbidity and homogeneous for symptoms. Each subject underwent two positron emission tomography (PET) scans to measure in vivo both serotonin (5-HT(2A)) and dopamine (D(2)) receptor distribution. For this, we used [11C]MDL and [11C]Raclopride, highly selective antagonists of 5-HT(2A) and D(2) receptors, respectively. The comparison with a control group was carried out using both voxel-wise (SPM2) and regions of interest (ROI) approaches. There was a significant reduction of 5-HT(2A) receptor availability in frontal polar, dorsolateral, and medial frontal cortex, as well as in parietal and temporal associative cortex of OCD patients. We also found a significant correlation between 5-HT(2A) receptor availability in orbitofrontal and dorsolateral frontal cortex and clinical severity, suggesting a specific role for serotonin in determining the OCD symptoms. There was also a significant reduction of [11C]Raclopride uptake in the whole striatum, particularly in the ventral portion, possibly reflecting endogenous dopaminergic hyperactivity. The co-existence of serotonergic and dopaminergic dysfunction in the same homogeneous group of drug-naive OCD patients provides in vivo evidence for the complex molecular mechanisms of OCD, and represents the basis for further studies on the effect of therapeutic agents with specific modulatory effects on these neurotransmission systems.     

Phenylephrine versus norepinephrine for initial hemodynamic support of patients with septic shock: a randomized, controlled trial

Introduction

Previous findings suggest that a delayed administration of phenylephrine replacing norepinephrine in septic shock patients causes a more pronounced hepatosplanchnic vasoconstriction as compared with norepinephrine. Nevertheless, a direct comparison between the two study drugs has not yet been performed. The aim of the present study was, therefore, to investigate the effects of a first-line therapy with either phenylephrine or norepinephrine on systemic and regional hemodynamics in patients with septic shock.

Methods

We performed a prospective, randomized, controlled trial in a multidisciplinary intensive care unit in a university hospital. We enrolled septic shock patients (n = 32) with a mean arterial pressure below 65 mmHg despite adequate volume resuscitation. Patients were randomly allocated to treatment with either norepinephrine or phenylephrine infusion (n = 16 each) titrated to achieve a mean arterial pressure between 65 and 75 mmHg. Data from right heart catheterization, a thermodye dilution catheter, gastric tonometry, acid-base homeostasis, as well as creatinine clearance and cardiac troponin were obtained at baseline and after 12 hours. Differences within and between groups were analyzed using a two-way analysis of variance for repeated measurements with group and time as factors. Time-independent variables were compared with one-way analysis of variance.

Results

No differences were found in any of the investigated parameters.

Conclusions

The present study suggests there are no differences in terms of cardiopulmonary performance, global oxygen transport, and regional hemodynamics when phenylephrine was administered instead of norepinephrine in the initial hemodynamic support of septic shock.

Trial registration

ClinicalTrial.gov NCT00639015     

Reduced serum level of THDOC, an anticonvulsant steroid, in women with perimenstrual catamenial epilepsy

Purpose: Seizure exacerbation in catamenial epilepsy (CE) is associated with the decrease in progesterone secretion and increase in estradiol secretion during the premenstrual period. Moreover, experimental evidence suggests that tetrahydrodeoxycorticosterone (THDOC), a positive modulator of the type A receptor for γ-aminobutyric acid (GABA), and dehydroepiandrosterone sulfate (DHEAS), a negative modulator of this receptor, might play a crucial role in modulating seizure frequency during the menstrual cycle. Following these studies it seems of interest to investigate possible variations, among other hormonal parameters, of THDOC and DHEAS in CE patients.
Methods: The serum concentrations of progesterone (P4), pregnenolone, allopregnanolone (AP), THDOC, DHEAS, cortisol, and DHEAS/cortisol ratio were measured throughout the menstrual cycle at the 7th, 11th, 15th, 19th, 23rd, and 27th day from the onset of spontaneous menstrual blood loss in young premenopausal women with CE (n = 17) and age-matched controls (n = 13).
Results: At each time of the study, the serum concentration of THDOC and the DHEAS/cortisol ratio were lower (p < 0.05) in women with CE than in control women. The concentrations of P4, pregnenolone, and AP did not differ between the two groups of subjects.
Conclusions: The reduced serum concentration of THDOC and the reduced DHEAS/cortisol ratio detected throughout the menstrual cycle in women with CE might play a role in CE. Moreover, the peculiar pattern of CE seizure exacerbation might suggest that these neuroendocrine variations are worth investigating in other epileptic syndromes, particularly in those characterized by relevant and uncontrolled variations in seizure frequency.     

Gray-scale median of the atherosclerotic plaque can predict success of lumen re-entry during subintimal femoral-popliteal angioplasty

OBJECTIVE: This study assessed whether the duplex ultrasound (DUS)-derived gray-scale median (GSM) of the most six distal portion of the occluded femoral-popliteal arterial segment can predict success of lumen re-entry for subintimal angioplasty. METHODS: During the last 3 years, 108 patients (62% men) with a mean age of 73 +/- 10 years underwent 116 primary attempted DUS-guided subintimal angioplasties of the femoral-popliteal segment. Preprocedural B-mode DUS images of the plaque at the most distal occlusion segment were digitalized and normalized using Photoshop (Adobe, San Jose, Calif) software and standard criteria (gray level, 0 to 5 for lumen blood and 185 to 190 for the adventitia on a linear scale of 0 to 255). Overall GSM of the plaque segment about 2 cm long, immediately before the planned re-entry point to the true arterial lumen, was used for retrospective correlation with procedure success and other clinical indicators. RESULTS: Mean plaque GSM for all cases was 22.5 +/- 12.6 (range, 3 to 60). The overall success rate of subintimal angioplasty procedures was 85%. Mean plaque GSM for 99 successful cases (18.4 +/- 7.8) was significantly lower than for 17 cases (46.4 +/- 8.1) where we failed (P < .0001). We failed in 90% of 19 cases with GSM >35, in 71% of 24 cases with GSM >20, and in 50% of 34 cases with GSM >25. There was no statistically significant difference (P = .45) between plaque GSM in 64 patients with diabetes (23.3 +/- 13.5) compared with 52 nondiabetic patients (21.5 +/- 11.4). Similarly, plaque GSM was not statistically different (P = .9) in 52 patients with renal insufficiency (22.7 +/- 13.2) compared with 64 patients with normal creatinine levels (22.4 +/- 12.2). At the 6-month follow-up, no statistically significant difference was found between mean GSM (17.8 +/- 7.8) in 47 stenosis-free cases compared with mean GSM (18 +/- 6.8) in 22 cases where severe restenosis (>70%) or reocclusion was identified by DUS scan (P = .4). CONCLUSIONS: Plaque echogenicity represented by DUS-derived GSM can be used to predict the success of primary subintimal femoral-popliteal angioplasties.     

Comparative efficacy of topical versus systemic teicoplanin in experimental model of wound infections

INTRODUCTION: Surgical site infections are the second most common cause of nosocomial infections and, typically, gram-positive pathogens are involved. MATERIALS AND METHODS: A mouse model was used to investigate the efficacy of different methods for the treatment of wound infections. A full thickness wound was established on the back subcutaneous tissue of adult male BALB/c mice. A small gauze was placed over each wound and then inoculated with 5 x 10(7) colony-forming units of Staphylococcus aureus. The study included a control group that did not receive any treatment and four contaminated groups treated, respectively, with: (1) drug-free Allevyn (Smith and Nephew Healthcare, Yorkshire, United Kingdom), (2) teicoplanin-soaked Allevyn, (3) drug-free Allevyn and daily intraperitoneal teicoplanin (7 mg/kg) and, finally, (4) teicoplanin-soaked Allevyn and daily intraperitoneal teicoplanin (7 mg/kg). Main outcome measures were quantitative bacterial culture, assessment of vascular endothelial growth factor (VEGF) plasma levels, histological examination with assessment of microvessel density, and of VEGF expression in tissue sections. RESULTS: Data analysis showed that strong inhibition of bacterial growth was achieved in any group treated with intraperitoneal teicoplanin. However, the highest inhibition of bacterial growth was obtained in the group that received teicoplanin-soaked Allevyn and intraperitoneal teicoplanin. Histological examination showed that each treatment modality was able to reduce the delay in wound repair. The most effective treatment appeared to be the local application of teicoplanin-soaked hydro gel foam. The tissue effects were associated with an increase in neovascularization and VEGF expression by endothelial cells and fibroblasts in the granulation tissue. Bacterial colonies also were reduced, especially when teicoplanin was given parenterally. CONCLUSIONS: Soaking a hydro cellular foam with an antistaphylococcal agents, such as teicoplanin, may be useful for the management of infected wounds.