The inositol monophosphatase inhibitor L-690,330 affects pilocarpine-behavior and the forced swim test

Rationale

Lithium has been a standard pharmacological treatment for bipolar disorder over the last 60 years; however, the molecular targets through which lithium exerts its therapeutic effects are still not defined. Attenuation of the phosphatidylinositol signal transduction pathway as a consequence of inhibition of inositol monophosphatase (IMPase) has been proposed as one of the possible mechanisms for lithium-induced mood stabilization.

Objectives

The objective was to study the behavioral effect of the specific competitive IMPase inhibitor L-690,330 in mice in the lithium-sensitive pilocarpine-induced seizures paradigm and the forced swim test (FST).

Methods

The inhibitor was administered intracerebroventricularly in liposomes.

Results

L-690,330 increased the sensitivity to subconvulsive doses of pilocarpine and decreased immobility time in the FST.

Conclusions

It is possible that the behavioral effects of lithium in the pilocarpine-induced seizures and in the FST are mediated through the inhibition of IMPase, but reversal of the inhibitor’s effect with intracerebroventricular inositol would be an important further step in proof.     

Less efficient elementary visuomotor processes in 7- to 10-year-old preterm-born children without cerebral palsy: an indication of impaired dorsal stream processes

Follow-up studies of preterm children without serious neurological complications have consistently found deficits in visuomotor skills. To determine whether these deficits may be related to impaired elementary visuomotor processes, we investigated movement programming and execution of simple pointing movements in 7- to 10-year-old preterm (<34 weeks g.a. and/or b.w. <1800 g) and full-term children. Such detailed analysis of simple pointing movements provides information on the extent to which processes associated with dorsal and/or cerebellar functions are impaired. Multi-level analysis showed that movement programming and execution were slowed in the 7-, 9-, and 10-year-old preterm groups. This indicates impaired dorsal visual stream functioning in preterm children, but do not rule out impaired cerebellar functioning. At 8 years of age, there were no differences between the two groups in movement execution time. This could have reflected a transition in the development of movement control in the control group, which has been associated in typically developing children with a decrease in motor speed. Interestingly, a similar decrease was not found in the preterm group at 8 years of age.     

The Next Wave: Confexting

Radiology conferences enable participants the opportunity to ask experts questions through question and answer (Q and A) sessions or individually. Given the time limitations and intimidating circumstances, we incorporated conference text messaging (confexting) as a method of increasing interactivity between the audience and speakers. During a 5-day radiology conference, text messaging was utilized for anonymous interactivity between the audience and speakers during Q and A sessions. There were 324 text messages; 76 of these were either follow-up statements or questions related to earlier text messages. Forty-two questions were submitted via paper notes. There was a general trend of an increasing number of text messages and a decreasing number of paper notes. The anonymous text messaging system was found to be an effective method for interactivity between the audience and the speakers. The questions and answers could be presented in a PowerPoint format at the formal Q and A sessions. Questions texted to the authors during their talks could be immediately answered or addressed in subsequent talks. Although difficult for some individuals to embrace technology, confexting allows for interactivity and prompts discussion. Confexting is an effective method for interactivity between the audience and speakers not previously utilized in a conference setting. The anonymity and asynchronous communication enable conference participants to submit more questions than in the traditional setting. The speakers may be able to explain more thoroughly difficult concepts more thoroughly with additional slides at Q and A sessions or may immediately answer texted questions during their talks.     

Electron microscopic study of phagocytosis of Escherichia coli by human polymorphonuclear leukocytes.

The fate of Escherichia coli strains within the polymorphonuclear leukocytes was studied by determining the killing of bacteria, measuring the release of degradation products, and examining the phagocytic bacteria by electron microscopy. When sufficiently opsonized, both unencapsulated and encapsulated E. coli strains were rapidly phagocytized by polymorphonuclear leukocytes. Once phagocytized, the two unencapsulated E. coli strains (K-12 and O111) were rapidly killed (99% of the bacteria were killed during the first 5 min of phagocytosis) and extensively degraded (about 40% of the radiolabeled material was released from bacteria after 15 min of phagocytosis). Electron micrographs taken after 15 min of phagocytosis revealed extensive structural changes in most of the internalized bacteria. In contrast to the rapid killing and extensive breakdown of these strains, encapsulated E. coli O78:K80 was more resistant to killing and withstood degradation by polymorphonuclear leukocytes (only 5% of the radioactivity was released from the radiolabeled bacteria after 1 h of phagocytosis). Electron micrographs of thin sections taken after 1 h of phagocytosis revealed virtually no structural changes. Most of the internalized bacteria were still surrounded by thick capsular material.     

Morphology of the hemostatic plug in human skin wounds: transformation of the plug.

The transformation of hemostatic plugs in human skin wounds was studied in vivo after bleeding had stopped. Standardized bleeding time incisions were made on the dorsal side of the forearm of four normal male volunteers. The wounds were excised by punch biopsy 10 minutes, 30 minutes, or 2 hours after they had been made and studied by light and electron microscopy. The wounds were filled with red blood cells, and a network of fibrin strands was found in the wound, particularly near transected vessels. Polymorphonuclear leukocytes were encountered within transected vessels and at 2 hours also in the wounds and in concentric rings around the vessels up to 0.5 mm. from the wound. On top of the wounds a superficial scab, consisting of red blood cells and presumably air-dried proteins, had formed. Hemostatic plugs were found at the ends of transected blood vessels. At 10 minutes the plugs consisted of largely degranulated platelets which showed strong interdigitation. Fibrin was still absent from the center of the plugs. At 30 minutes the platelets became less densely packed, and small fibrin fibers were deposited between the platelets in large peripheral areas of the plugs. At 2 hours some of the platelets had assumed rounded shapes with few interdigitations and larger spaces between them. Areas in the plug with platelets that had lost their integrity alternated with areas where platelets still had their cytoplasmic matrix and were interdigitated. Fibrin fibers were especially demonstrable between the degenerated platelet vesicles. This occurred everywhere in small hemostatic plugs and in the periphery of larger plugs. In one individual it was also observed in the center of large hemostatic plugs. In the other individuals fibrin was present centrally as amorphous dark staining material which was fibrillar in tangential sections.     

Valnoctamide as a valproate substitute with low teratogenic potential in mania: a double‐blind,controlled, add‐on clinical trial

Bersudsky Y, Applebaum J, Gaiduk Y, Sharony L, Mishory A, Podberezsky A, Agam G, Belmaker RH. Valnoctamide as a valproate substitute with low teratogenic potential in mania: a double‐blind, controlled, add‐on clinical trial.
Bipolar Disord 2010: 12: 376–382. © 2010 The Authors. Journal compilation © 2010 John Wiley & Sons A/S. Objectives: Valproic acid’s well‐known teratogenicity limits its use in women of childbearing age. Valnoctamide is an analog of valproate that does not undergo biotransformation to the corresponding free acid. In mice, valnoctamide has been shown to be distinctly less teratogenic than valproate. Valnoctamide is an anticonvulsant, and we hypothesized that valnoctamide is antimanic. Methods: We performed a double‐blind, five‐week, add‐on, controlled trial of valnoctamide in mania. Patients were treated with risperidone at doses of the physician’s discretion. Valnoctamide or placebo was begun at doses of 600 mg/day and increased to 1200 mg after four days. Weekly ratings by a psychiatrist blind to the study drug were conducted using the Brief Psychiatric Rating Scale (BPRS), the Young Mania Rating Scale (YMRS), and the Clinical Global Impression (CGI). Results: Fifteen valnoctamide patients and 17 placebo patients completed at least one post‐baseline week and were included in data analysis. In all efficacy measures valnoctamide was more effective than placebo as an add‐on to risperidone, using two‐way analysis of variance (ANOVA) with time as the within‐subject factor. Two‐way ANOVA showed a significant effect of time (p < 0.001) and significant interaction between treatment and time (YMRS: p = 0.012; BPRS: p = 0.007; CGI: p = 0.003). Differences between valnoctamide and placebo were significant from week 3 to week 5. Conclusion: Valnoctamide could be an important valproate substitute for women of childbearing age with bipolar disorder who may become pregnant.     

Perinatal outcomes in inflammatory bowel disease

Objective: To determine whether inflammatory bowel disease (IBD) is associated with increased risk for adverse perinatal outcome.

Methods: A case–control study of 116 singleton pregnancies with IBD compared to 56?398 singleton controls delivered between 1986 and 2001.

Results: Patients with IBD were slightly older (32.8 vs. 30.6 years, p <?0.001), more likely to be Caucasian or Asian than Black or Latino (92% vs. 57%, p <?0.001) and have private health insurance (33% vs. 3%, p <?0.001). IBD was associated with an increased risk for labor induction (32% vs. 24%, p?=?0.002), chorioamnionitis (7% vs. 3%, p?=?0.04) and Cesarean section (32% vs. 22%, p?=?0.007), but there were no differences in neonatal outcomes. Subgroup analysis demonstrated an increased risk for low birth weight (LBW) in the ulcerative colitis group vs. the Crohn's disease group (19% vs. 0%, p?=?0.002). Patients with prior surgery for IBD had a lower incidence of LBW (0% vs. 12%, p?=?0.03). Flares during pregnancy were associated with an increased risk for preterm delivery (27% vs. 8%, p?=?0.02) and LBW (32% vs. 3%, p?=?0.003).

Conclusion: IBD was an independent risk factor for Cesarean section but there was no increase in adverse perinatal outcome. Crohn's disease, prior IBD surgery and quiescent disease were associated with a lower risk for LBW.