Effect of maternal cadmium exposure on postnatal development and tissue cadmium,copper and zinc concentrations in rats

Administration of 60 ppm cadmium (Cd) in drinking water from the 1^st to the 20^th day of gestation to female rats did not affect the viability, body weight gain, food, and water consumption of offspring. The blood hemoglobin level was reduced in 2-week-old females and males but not in 16-week-old offspring. Hematocrit and serum glucose level were not affected at either age. Cadmium concentration in the intestinal wall was increased in both age groups, with marginal uptake in other organs. A decrease in copper (Cu) concentration was found in the brain of 2-week-old offspring of both sexes and of 16-week-old females. The brain zinc (Zn) concentration was decreased only in 16-week-old animals. The physical and neuromuscular development of offspring before weaning was not impaired by maternal Cd treatment. The alterations in Cu and Zn metabolism were associated with reduced locomotor activity and affected open-field behavior in adult offspring of either sex and with decreased avoidance acquisition in adult female offspring.The results obtained suggest a relationship between the reduced brain Cu and Zn levels and CNS dysfunction in adult offspring of female rats exposed to Cd during gestation.     

In vivo imaging of system xc- as a novel approach to monitor multiple sclerosis

Purpose

Glutamate excitotoxicity contributes to oligodendroglial and axonal damage in multiple sclerosis pathology. Extracellular glutamate concentration in the brain is controlled by cystine/glutamate antiporter (system xc-), a membrane antiporter that imports cystine and releases glutamate. Despite this, the system xc^? activity and its connection to the inflammatory reaction in multiple sclerosis (MS) is largely unknown.

Methods

Longitudinal in vivo magnetic resonance (MRI) and positron emission tomography (PET) imaging studies with 2-[¹⁸F]Fluoro-2-deoxy-D-glucose ([¹⁸F]FDG), [¹¹C]-(R)-(1-(2-chlorophenyl)-N-methyl-N-1(1-methylpropyl)-3-isoquinolinecarboxamide ([¹¹C]PK11195) and (4S)-4-(3-¹⁸F-fluoropropyl)-L-glutamate ([¹⁸F]FSPG) were carried out during the course of experimental autoimmune encephalomyelitis (EAE) induction in rats.

Results

[¹⁸F]FSPG showed a significant increase of system xc^? function in the lumbar section of the spinal cord at 14 days post immunization (dpi) that stands in agreement with the neurological symptoms and ventricle edema formation at this time point. Likewise, [¹⁸F]FDG did not show significant changes in glucose metabolism throughout central nervous system and [¹¹C]PK11195 evidenced a significant increase of microglial/macrophage activation in spinal cord and cerebellum 2 weeks after EAE induction. Therefore, [¹⁸F]FSPG showed a major capacity to discriminate regions of the central nervous system affected by the MS in comparison to [¹⁸F]FDG and [¹¹C]PK11195. Additionally, clodronate-treated rats showed a depletion in microglial population and [¹⁸F]FSPG PET signal in spinal cord confirming a link between neuroinflammatory reaction and cystine/glutamate antiporter activity in EAE rats.

Conclusions

Altogether, these results suggest that in vivo PET imaging of system xc^? could become a valuable tool for the diagnosis and treatment evaluation of MS.

     

Stable expression of Cryptosporidium parvum glycoprotein gp40/15 in Toxoplasma gondii

Cryptosporidium is a cause of diarrheal disease worldwide. Parasite glycoproteins involved in invasion of Cryptosporidium into host cells have been investigated as possible targets for effective interventions against this parasite. One of these, Cpgp40/15, is expressed as a precursor protein that is cleaved by a parasite-derived furin-like protease activity into gp15, a glycophosphatidyl inositol anchored surface protein, and gp40, that associates with gp15 and binds to host cells. Investigation of the functions of these glycoproteins requires an expression system that can produce similar glycosylation patterns to the native antigens. Previous work demonstrated that Cpgp40/15 transiently expressed in Toxoplasma gondii was appropriately localized and glycosylated. In this study, T. gondii stable transfectants expressing gp40/15, gp15, gp40 and hemagglutinin (HA) tagged gp40 were generated. T. gondii recombinant gp40HA and gp40/15 (recTggp40HA and recTggp40/15) were isolated from infected cells by HA affinity chromatography and Helix pomatia lectin affinity chromatography, respectively. Mass spectrometry confirmed that recTggp40-HA and native Cpgp40 were similarly glycosylated. Like native Cpgp40/15, recTggp40/15 could be cleaved into the gp40 and gp15 products by human furin or by a furin-like protease activity in T. gondii tachyzoite lysates. However, processing was inefficient in intact tachyzoites. Unlike the N-terminus of native Cpgp40/15, which appears to be processed following signal peptide cleavage, the N-terminus of recTggp40/15 began at the predicted signal sequence cleavage site, 11 amino acids upstream of the N-terminus of native Cpgp40. The ability to express and isolate appropriately glycosylated Cryptosporidium glycoproteins will enable further investigations into host-parasite interactions of this important pathogen.     

Outcomes from the International Survey Informing Greater Insights in Opioid Dependence Treatment (INSIGHT) project

Aims: The International Survey Informing Greater Insights in Opioid Dependence Treatment (INSIGHT) study evaluated the implementation of opioid dependence treatment across different countries to assess treatment delivery, quality of care and outcomes. Methods: A questionnaire-based survey was used to gather data in nine countries across Central and Eastern Europe, South Africa and South-East Asia, from patients with opioid dependence receiving medication-assisted treatment (MAT), healthcare professionals (HCPs) who cared for opioid-dependent patients and opioid users not receiving MAT. Findings: There was substantial variation between countries, but overall results suggest that several aspects of MAT can be improved, such as access to treatment (conditions to start or remain in treatment), quality of care (availability/awareness of treatment options and appropriate medication dosing) and treatment outcomes (on-top use, misuse and diversion). Conclusions: This analysis highlights key priorities that should improve the quality of opioid dependence care and access to treatment. These priorities include: acknowledging opioid dependence as a chronic medical condition requiring long-term treatment; recognition by policymakers of the cost-effectiveness of treatment; making available, to those who want them, psychosocial interventions and educating HCPs to prescribe the safest, least divertible forms of medications available at optimal doses in order to reduce opioid use, misuse and diversion.