The Methylazoxymethanol Acetate (MAM-E17) Rat Model: Molecular and Functional Effects in the Hippocampus

Administration of the DNA-alkylating agent methylazoxymethanol acetate (MAM) on embryonic day 17 (E17) produces behavioral and anatomical brain abnormalities, which model some aspects of schizophrenia. This has lead to the premise that MAM rats are a neurodevelopmental model for schizophrenia. However, the underlying molecular pathways affected in this model have not been elucidated. In this study, we investigated the molecular phenotype of adult MAM rats by focusing on the frontal cortex and hippocampal areas, as these are known to be affected in schizophrenia. Proteomic and metabonomic analyses showed that the MAM treatment on E17 resulted primarily in deficits in hippocampal glutamatergic neurotransmission, as seen in some schizophrenia patients. Most importantly, these results were consistent with our finding of functional deficits in glutamatergic neurotransmission, as identified using electrophysiological recordings. Thus, this study provides the first molecular evidence, combined with functional validation, that the MAM-E17 rat model reproduces hippocampal deficits relevant to the pathology of schizophrenia.     

An in vivo [18F]MK-9470 microPET study of type 1 cannabinoid receptor binding in Wistar rats after chronic administration of valproate and levetiracetam

There is substantial evidence that the endocannabinoid system and in particular the type 1 cannabinoid receptor (CB1R) is involved in epilepsy. We evaluated the in vivo effect of chronic administration of the anti-epileptic drugs valproate (VPA) and levetiracetam (LEV) on rat brain CB1 receptors using the positron emission tomography (PET) tracer [¹⁸F]MK-9470.

Six Wistar rats were treated with VPA (200 mg/kg) or LEV (50 mg/kg) IP daily for 2 weeks. Dynamic imaging after intravenous injection of 18 MBq [¹⁸F]MK-9470 was performed on a FOCUS 220 microPET at baseline and after chronic treatment. Six animals were used as controls and were injected with saline, using the same protocol. Parametric images based on standardized uptake values (SUV) were generated and were spatially normalized to Paxinos space. These CB1R images were analyzed using a predefined volume of interest (VOI)-based analysis. Differences in SUV values between chronic and baseline scans in each condition (saline, VPA and LEV treatment) were calculated in each VOI. Direct binding affinity of the drugs at CB1R was assessed by competitive binding assay in Chinese hamster ovarian cells expressing human CB1R.

Chronic injections of saline did not produce significant changes in global [¹⁸F]MK-9470 binding (p = 0.43), nor in tracer binding in individual VOIs. We found a significant increase in global cerebral [¹⁸F]MK-9470 binding after chronic VPA administration compared to sham treated animals (+32.5%, p < 0.001), as well as in tracer binding in all individual VOIs. After chronic administration of LEV, there was no significant change in global cerebral CB1R binding (+6.9%, p = 0.81), nor in tracer binding in individual VOIs. As VPA does not exhibit high affinity for CB1R (displacement of [³H]-SR141716A 1.3 ± 14.0%), such upregulation is most likely caused by an indirect effect on the endocannabinoid system.

This increase in CB1R tracer binding and possibly signaling may represent a supplementary and new mechanism of VPA, but not LEV, since activation of CB1Rs has been shown to decrease excitability and excitotoxicity on-demand.     

Effect of immobilization on myocardial mitochondrial energy metabolism and ultrastructure in rats of different zoosocial ranks

I. M. Sechenov First Moscow Medical Institute. P. K. Anokhin Institute of Normal Physiology, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR K. V. Sudakov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 110, No. 9, pp. 318–321, September, 1990.     

The use of an electrolytic solution of sodium hypochlorite in acute suppurative diseases of the soft tissues]

The effect of electrolysis sodium hypochlorite solution (ENaClO) on the course of an inflammatory process in 233 patients with purulent pathology of different etiology was studied. ENaClO was obtained by means of electrolysis of the isotonic sodium chloride solution in the electrochemical cell. It was established that ENaClO had a pronounced bactericidal action contributing to acceleration of an inflammatory focus clearance of purulent-necrotic masses, stimulation of local immunity, activation of reparative processes.     

Indium-111 labeled platelet deposition following transfemoral angiography

The incidence of thromboembolitic events in patients undergoing transfemoral angiography was examined using indium-111 labeled platelets. Twenty-seven patients received approximately 300 muCi of autologous labeled platelets at least 3 hours before angiography and were scanned with a gamma camera immediately before and after angiography. All patients were free of clinically obvious complications in the 1-2 day period after angiography. Our results showed evidence of platelet deposition at 21 sites other than the puncture site in 12 (44%) patients. Most platelet deposition (54%) occurred along the region between the puncture site and the aortic bifurcation; 24% occurred at sites not traversed by the catheter. At the puncture site itself, there was substantial platelet uptake in 44% of patients. This study indicates the need for further work in determining the most suitable catheter material and in assessing the efficacy of other measures such as anticoagulant or antiplatelet therapy.     

Morphometry error due to non-perpendicular section of microvessel characterized by two-dimensional isotropic arrangement

Formulas for calculation of the section non-perpendicularity error in estimation of the perimeter and cross-sectional area of microvessel profiles are proposed for the two-dimensional isotropic approximation. A relationship was established between the bias and random error associated with non-perpendicularity corresponding to θ_min for microvessel profiles meeting the condition θ_min⩽B/C,, where B and C are the minimum and maximum axes of the microvessel profile, respectively. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 130, No. 10, pp. 478–480, October, 2000     

Long-term use of antecubital veins for plasma exchange. The Canadian Cooperative Multiple Sclerosis Study Group

True or sham plasma exchange was done weekly for 20 weeks in patients in two of the randomization groups in a prospective, blind clinical trial of experimental treatments for multiple sclerosis. Because patients could be randomized to receive sham plasma exchange and placebo medications, it was decided when the trial was designed that the use of fistulae, arteriovenous shunts, venous cutdowns, or other aggressive forms of venous access would not be permitted for any patient. Accordingly, patients judged to have inadequate superficial antecubital veins were ineligible for the trial. To date, only 13 (4.4%) of 294 patients considered for entry into the trial have been rejected on these grounds. In only 4 of the 93 patients undergoing exchange was it necessary to discontinue plasma exchange because of inadequate venous access. In 79.3 percent of the 1207 exchanges done in these patients, there were no problems of any kind with venous access. In 5.4 percent of these 1207 exchanges, it was necessary to terminate the procedure prematurely because of difficulties with patients' veins. Thus, the great majority of patients free of serious systemic illness (other than chronic progressive multiple sclerosis) can undergo weekly plasma exchange for up to 20 weeks using superficial antecubital veins without the need to resort to more invasive methods of venous access.     

The Mechanism of the Development of Macrophage Tolerance in Tumor Microenvironment

Bulletin of Experimental Biology and Medicine - Bacteria forming the resident microbiome of the tumor are an integral component of its microenvironment. The interaction of the tumor microbiome with...