Dual Fatty Acid Amide Hydrolase and Monoacylglycerol Lipase Blockade Produces THC-Like Morris Water Maze Deficits in Mice

Acute administration of Δ(9)-tetrahydrocannabinol (THC) or exposure to marijuana smoke impairs short-term spatial memory in water maze tasks through a CB(1) receptor mechanism of action. N-Arachidonoylethanolamine (anandamide; AEA) and 2-arachidonoylglycerol (2-AG) are endogenous cannabinoids that are predominantly metabolized by the respective enzymes fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL). Although the MAGL inhibitor JZL184 enhances short-term synaptic plasticity, it has yet to be evaluated in the Morris water maze. Previous research demonstrated that simultaneous, complete blockade of FAAH and MAGL produces full blown THC-like effects. Thus, in the following studies we tested whether dual blockade of FAAH and MAGL would impair learning in a repeated acquisition Morris water maze task. Mice treated with the dual FAAH/MAGL inhibitor JZL195 (20 mg/kg) as well as JZL184-treated FAAH -/- mice displayed robust deficits in Morris water maze performance that were similar in magnitude to THC-treated mice. While 20 or 40 mg/kg impaired water maze performance in FAAH -/- mice, only the high dose of JZL184 disrupted performance in FAAH +/+ mice. The memory impairing effects of JZL184 were blocked by the CB(1) receptor antagonist rimonabant. Neither JZL184 nor JZL195 impaired performance in a cued version of the water maze task, arguing against the notion that sensorimotor or motivational deficits accounted for the impaired acquisition performance. JZL184 increased 2-AG levels in the hippocampus, prefrontal cortex, and cerebellum to a similar degree in FAAH -/- and +/+ mice. FAAH -/- mice, regardless of drug treatment, possessed elevated AEA levels in each brain region assessed. The results of this study reveal that concomitant increases in AEA and 2-AG disrupt short-term spatial memory performance in a manner similar to that of THC.     

The extended ocular hypotensive effect of positive liposomal cholesterol bound timolol maleate in glaucomatous rabbits

Increased intraocular pressure (IOP) is a significant risk factor for the development of glaucoma. Timolol maleate is a beta-adrenergic receptor blocking agent and it is used for the treatment of glaucoma in order to reduce the elevated IOP that is characteristic of this eye disease. Systemic toxicity from topical timolol occurs more frequently than local toxicity and can affect the pulmonary, cardiac and central nervous systems. The objective of the present study, therefore, was to formulate multilamellar vesicles (MLVs) liposomal preparations of timolol maleate using their advantage of being less toxic compared with non-liposome-based drugs to be applied topically and to evaluate the in vivo performance of the prepared liposomes to extend the time of reduced IOP of glaucomatous rabbit's eye measured using a standard Shiotz tonometer. The encapsulation efficiency of MLVs was measured using a spectrophotometric technique. Differential scanning calorimetry (DSC) was used to monitor the effects of timolol maleate in the absence and presence of cholesterol on liposome thermal behaviour. Positively charged MLVs of timolol in the presence of a lower amount of cholesterol (DPPC(7):Chol(2):Timolol(2):SA(1) molar ratio) were found to be superior compared with other formulations in extending the ocular hypotensive effect approximately for 1 week (160 h) which encourages its physiological effectiveness. The increase of the cholesterol molar ratio in the prepared liposomal formulations serves to decrease the permeability of the lipid bilayer that is manifested by a low rate of drug release, an increased percentage of entrapment efficiency and a consequently lower bioavailability.     

Postoperative cognitive dysfunction and the possible underlying neurodegenerative effect of anaesthesia

Introduction: There is alarming evidence about the involvement of general anaesthesia in the development of postoperative cognitive dysfunction.

Aim: To clarify the impact of general anaesthesia on cognitive function and to study the possible effect of general anaesthesia on serum S100B, the marker of neuronal degeneration.

Methods: This is a prospective randomised controlled study carried out on 50 patients undergoing elective laparoscopic cholecystectomy under conventional general anaesthesia. Cognitive assessment for selected patients was done preoperative and 1?week postoperative using Paired Associate Learning test (PALT) for assessment of verbal memory and Benton Visual Retention test (BVRT) for assessment of visual memory. Quantitative determination of serum S100B was done for all patients in the basal sample and postoperative sample by applying an enzyme- linked immunoabsorbent assay technique on am automated ELISA platform.

Results: Regarding cognitive tests, there was a statistically significant difference between the mean value of preoperative PALT and postoperative PALT (p-value?=?.012). There was also a statistically significant difference between the mean value of preoperative BVRT and postoperative BVRT (p-value?=?.011). Regarding S100B, there was a statistically significant difference between preoperative and postoperative serum level (p-value?=?.002). There was also a statistically significant negative correlation between postoperative S100B serum level and the postoperative scores of both PALT and BVRT.

Conclusion: General anaesthesia is incriminated in the development of postoperative verbal and visual memory impairment and in the postoperative increase in serum S100B, the markers of neuronal degeneration.     

An Analysis of Overweight and Obesity Status among Childhood Cancer Survivors in Saudi Arabia: A Single Center Study

Overweight and obesity in the pediatric population remains a growing worldwide health burden. The extent to which this trend extends to childhood cancer survivors (CCS) remains less well explored. We conducted a retrospective observational study from a single institution in Saudi Arabia to estimate the prevalence of overweight and obese status among CCS over a five-year period. A total of 91 CCS patients were identified, 63 of whom had complete weight data from their treatment to the time of the study. Of these patients, 29 (46.0%) were found to be overweight or obese [body mass index (BMI) ≥85th percentile] at the time of the study. Of these patients, this rate was particularly high for patients who were female, older at the time of diagnosis (>6?years) (72.8%) and among pubescent patients (Tanner 3–5 at diagnosis). The rate of overweight and obesity increased from 31.7% immediately after the end of treatment (average age of 7.1?years) to 36.5% one year after. Thereafter, these percentages increased to approximately 38% over the 5-year follow-up period and increased beyond that up to 46%. A high prevalence of overweight and obesity among CCS was found at the end of their treatment with an observed increasing trend towards overweight and obesity in the following years, suggesting the need for early and continuous intensive intervention and frequent dietary evaluation.     

A novel side-chain liquid crystal polymer of 5-substituted cis-cyclooctene via ring-opening metathesis polymerization

In this communication, we report the synthesis and ring-opening metathesis polymerisation (ROMP) of a 5-substituted cyclooctene-derivative, (±)-cis-[11-(4′-cyanobiphenyl-4-yloxy)undecyl]cyclooct-4-enecarboxylate. A highly active molybdenum-carbene was used as initiator. The prepared polymer is liquid crystalline and shows a nematic phase between ?5 and 53°C.     

Observations on the swelling behaviour of copolymeric hydrogels containing N-vinyl-2-pyrrolidone

Polymer-water interaction parameters, sequence length distributions and contents of total, freezing and non-freezing water have been discussed for a family of hydrogels. The xerogel precursors contained N-vinyl-2-pyrrolidone (VP) with several co-monomers of different levels of hydrophobicity present in the xerogel over a wide range of composition. Common trends in the behaviour of these systems have been noted and rationalised. In particular the findings indicate that (i) in the poly-VP hydrogel ther are ca. 8–10 molecules of non-freezing water per VP unit and (ii) in the copolymeric hydrogels the maximum occurring in the variation of mole fraction of VP versus mole fraction of water is due substantially to the sharp increase in uptake of freezing (or bulk) water by copolymers rich in VP.