A cloned frog vasoactive intestinal polypeptide/pituitary adenylate cyclase-activating polypeptide receptor exhibits pharmacological and tissue distribution characteristics of both VPAC1 and VPAC2 receptors in mammals

Three receptor subtypes for the neuropeptides vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) have been identified in mammals: the PAC1 receptor (PAC1-R) which is selectively activated by PACAP, and two VPAC receptors (VPAC1-R and VPAC2-R), which are equally stimulated by PACAP and VIP. The structures of PACAP and VIP have been well conserved during evolution, but little is known about VIP/PACAP receptors in nonmammalian species. An amphibian VIP/PACAP receptor complementary DNA (cDNA) has been cloned and characterized from a frog (Rana ridibunda) pituitary cDNA library. The predicted protein contains seven putative transmembrane domains and exhibits the highest sequence identity (65%) with the human VPAC1-R. The cloned cDNA was transiently expressed in LLC-PK1 cells, and its pharmacological profile was determined in comparison with the human VPAC1-R. Both PACAP and VIP stimulated cAMP accumulation through the cloned receptor with an EC50 of about 30 nM. In contrast, secretin, at concentrations that stimulate the human VPAC1-R, had no effect on cAMP production. RT-PCR analysis revealed the widespread distribution of this frog VIP/PACAP receptor in peripheral tissues. In situ hybridization histochemistry using a complementary RNA probe showed that the receptor gene is highly expressed in several hypothalamic and thalamic nuclei and to a lesser extent in the pallium and striatum. In the pituitary, the highest messenger RNA levels were detected in the distal lobe. Taken together, these data show that the cloned frog receptor shares several common features with both the VPAC1-R and VPAC2-R of mammals; the frog receptor exhibits the highest sequence identity with mammalian VPAC1-R, but the lack of effect of secretin and the brain distribution of the receptor are reminiscent of the characteristics of the mammalian VPAC2-R. The sequence of the frog receptor should thus prove useful to decipher the structure-activity relationships of the VIP/PACAP receptor family.     

Lipoprotein-Associated Phospholipase A2 (Lp-PLA2) in Acute Coronary Syndrome: Relationship With Low-Density Lipoprotein Cholesterol

Background

Lipoprotein-associated phospholipase A₂ (Lp-PLA₂) might play a role in the formation of vulnerable atherosclerotic plaques. Its plasma distribution and mass in subjects with acute coronary syndrome (ACS) has yet to be characterized.

Methods

We compared plasma levels of Lp-PLA₂ in 24 patients within 48 hours of an ACS (acute) and 12 weeks after (recovery), in 26 patients with stable coronary artery disease and in 10 normal healthy control subjects. Lp-PLA₂ mass was determined using enzyme-linked immunosorbent assay.

Results

The ACS patients (mean age 57 ± 8.7 years) had high-sensitivity C-reactive protein (hsCRP) levels of 30.46 ± 57.57 mg/L (ACS acute) vs 1.69 ± 1.32 mg/L (ACS recovery). Plasma Lp-PLA₂ levels were significantly higher in ACS acute subjects than in ACS recovery subjects (143.13 ± 60.88 ng/mL vs 88.74 ± 39.12 ng/mL; P < 0.0001). Interestingly, stable coronary artery disease patients had higher Lp-PLA₂ levels than ACS recovery patients (121.72 ± 31.11 ng/mL vs 88.74 ± 39.12 ng/mL; P = 0.0018). There was a strong correlation between Lp-PLA₂ and low-density lipoprotein (LDL) cholesterol (LDL-C) (r = 0.709; P < 0.0001) or changes in LDL (r = 0.449; P = 0.027), suggesting that the major determinant of plasma Lp-PLA₂ is LDL-C. No significant correlations were observed between Lp-PLA₂ and hsCRP or high-density lipoprotein (HDL) cholesterol. When separated using high-performance liquid chromatography, > 65%-70% of Lp-PLA₂ mass was within the apolipoprotein B-containing lipoprotein fraction, with approximately 30%-35% on HDL fraction, with no significant change in distribution between ACS acute and recovery.

Conclusions

Subjects with an ACS have markedly increased Lp-PLA₂ levels acutely related to LDL-C levels.     

Same wrist intervention via the cubital (ulnar) artery in case of radial puncture failure for percutaneous cardiac catheterization or intervention: The multicenter SWITCH registry

Aims

The radial approach is safer than the femoral for percutaneous coronary procedures. However its feasibility is lower, mainly for technical issues, often related to failure to puncture or cannulate the radial artery. The ulnar approach is a valid alternative to radial. We aimed to test the incidence, feasibility and safety of a direct homolateral ulnar approach in case of failed radial sheath insertion.

Methods and results

Five operators collected their 1-year activity (diagnostic and interventional) with focus on entry site. Entry site choice was left to operators' discretion. In case of failed radial sheath insertion, an attempt to cannulate the homolateral ulnar artery was mandated, if ulnar pulse was present. All patients in whom this attempt was performed were followed until discharge.Out of 2403 procedures (1271 interventions), the final successful entry site was radial in 66.5%, femoral in 31.0%, ulnar in 2.1% and brachial in 0.4%. Radial failure occurred in 117 patients (6.9%). In 75 patients, the radial failure was not due to sheath insertion (which was successful), but to lack of catheter support or to tortuosity of the subclavian/brachial arteries. In the remaining 42 (35.9% of all radial failures), a homolateral ulnar approach was attempted. A successful cannulation of the ulnar artery occurred in 36 patients (85.7%) with further performance of the complete procedure. Concerning local complications, 1 radial pseudo-aneurysm (treated with additional compression) occurred, while no cases of early hand ischemia were reported.

Conclusions

In this multicenter registry, in case of failed radial sheath insertion, switching directly to the homolateral ulnar artery for percutaneous coronary procedures is feasible and it appears to be safe, without cases of symptomatic hand ischemia.     

White matter tracts lesions and decline of verbal fluency after deep brain stimulation in Parkinson's disease

Decline of verbal fluency (VF) performance is one of the most systematically reported neuropsychological adverse effects after subthalamic nucleus deep brain stimulation (STN‐DBS). It has been suggested that this worsening of VF may be related to a microlesion due to the electrode trajectories. We describe the disruption of surrounding white matter tracts following electrode implantation in Parkinson's disease (PD) patients with STN‐DBS and assess whether damage of fiber pathways is associated with VF impairment after surgery. We retrospectively analyzed 48 PD patients undergoing bilateral STN DBS. The lesion mask along the electrode trajectory transformed into the MNI 152 coordinate system, was compared with white matter tract atlas in Tractotron software, which provides a probability and proportion of fibers disconnection. Combining tract‐ and atlas‐based analysis reveals that the trajectory of the electrodes intersected successively with the frontal aslant tract, anterior segment of arcuate tract, the long segment of arcuate tract, the inferior longitudinal fasciculus, the superior longitudinal fasciculus, the anterior thalamic radiation, and the fronto striatal tract. We found no association between the proportion fiber disconnection and the severity of VF impairment 6 months after surgery. Our findings demonstrated that microstructural injury associated with electrode trajectories involved white matter bundles implicated in VF networks.     

La maladie de Trevor: à propos de deux nouvelles observations

Trevor’s disease is a rare skeletal developmental disorder affecting the epiphysis in children. It usually affects a lower limb and involves one or more than one epiphysis. We report two new cases of Trevor’s disease of knee and ankle in 8 and 14 years old boys respectively. The treatment was surgical excision. We discuss the modalities of recognition and the treatment of this rare disease.     

Phytochemical,antioxidant and protective effect of cactus cladodes extract against lithium-induced liver injury in rats

Context: Opuntia ficus-indica (L.) Mill. (Castaceae) (cactus) is used in Tunisian medicine for the treatment of various diseases.

Objective: This study determines phytochemical composition of cactus cladode extract (CCE). It also investigates antioxidant activity and hepatoprotective potential of CCE against lithium carbonate (Li₂CO₃)-induced liver injury in rats.

Materials and methods: Twenty-four Wistar male rats were divided into four groups of six each: a control group given distilled water (0.5?mL/100?g b.w.; i.p.), a group injected with Li₂CO₃ (25?mg/kg b.w.; i.p.; corresponding to 30% of the LD₅₀) twice daily for 30 days, a group receiving only CCE at 100?mg/kg of b.w. for 60 days and then injected with distilled water during the last 30 days of CCE treatment, and a group receiving CCE and then injected with Li₂CO₃ during the last 30 days of CCE treatment. The bioactive components containing the CCE were identified using chemical assays.

Results: Treatment with Li₂CO₃ caused a significant change of some haematological parameters including red blood cells (RBC), white blood cells (WBC), haemoglobin content (Hb), haematocrit (Ht) and mean corpuscular volume (VCM) compared to the control group. Moreover, significant increases in the levels of glucose, cholesterol, triglycerides and of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) activities were observed in the blood of Li₂CO₃-treated rats. Furthermore, exposure to Li₂CO₃ significantly increased the LPO level and decreased superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) activities in the hepatic tissues.

Conclusion: CCE possesses a significant hepatoprotective effect.     

Osteotomy of the spine for multifocal deformities

Introduction

When a deformity involves more than one area of the spine, it becomes a multifocal deformity; such a deformity could either be extending on two adjacent segments, or be two separated deformities on two non-adjacent segments.

Materials and methods

The surgical management of multifocal spinal deformities is challenging and must be done through a thorough preoperative planning where spinal and pelvic parameters should accurately be determined. Different strategies should be applied depending on the type of the multifocal deformity, the area involved, the angulation and stiffness of the spine in that area, and the presence of either a pure sagittal malalignment or a combined coronal and sagittal malalignment. This paper discusses these strategies and gives guidelines regarding the use of the different osteotomy techniques depending on each different situation that the deformity spine surgeon may encounter. For instance, where is the ideal level to perform a pedicle subtraction osteotomy (PSO) in a multifocal deformity? How does one take advantage of the remaining high discs to increase the correction without the need for a second PSO? When and where does one perform an asymmetrical PSO? When and where does one perform two PSOs? How does navigation help the spine surgeon to push the surgical limits further in these complex cases?

Conclusion

All these questions about the management of multifocal deformities will be discussed and answered with technical details and concrete examples of the different situations that may be encountered.