Fusion of <Emphasis Type="Italic">Gaussia</Emphasis> Luciferase to an Engineered Anti-carcinoembryonic Antigen (CEA) Antibody for <Emphasis Type="Italic">In Vivo</Emphasis> Optical Imaging

The bioluminescent protein Gaussia luciferase (GLuc) was fused to an anti-carcinoembryonic antigen (CEA) antibody fragment, the diabody, for in vivo optical tumor imaging. A 15-amino acid N-terminal truncation (GLΔ15) resulted in a brighter protein. Fusions of the anti-CEA diabody to full-length GLuc and GLΔ15 retained high affinity for the antigen, emitted light, and exhibited excellent enzymatic stability. In vivo optical imaging of tumor-bearing mice demonstrated specific targeting of diabody-GLΔ15 to CEA-positive xenografts, with a tumor/background ratio of 3.8 ± 0.4 at four hours after tail-vein injection, compared to antigen-negative tumors at 1.3 ± 0.1 (p = 0.001). MicroPET imaging using ¹²⁴I-diabody-GLΔ15 demonstrated specific uptake in the CEA-positive tumor (2.6% ID [injected dose]/g) compared to the CEA-negative tumor (0.4% ID/g) at 21 hours. Although further optimization of this fusion protein may be needed to improve in vivo performance, the diabody-GLΔ15 is a promising optical imaging probe for tumor detection in vivo.     

Utilization of serology for the diagnosis of suspected Lyme borreliosis in Denmark: Survey of patients seen in general practice

Background  

Serological testing for Lyme borreliosis (LB) is frequently requested by general practitioners for patients with a wide variety of symptoms.     

A small molecule accelerates neuronal differentiation in the adult rat

Adult neurogenesis occurs in mammals and provides a mechanism for continuous neural plasticity in the brain. However, little is known about the molecular mechanisms regulating hippocampal neural progenitor cells (NPCs) and whether their fate can be pharmacologically modulated to improve neural plasticity and regeneration. Here, we report the characterization of a small molecule (KHS101) that selectively induces a neuronal differentiation phenotype. Mechanism of action studies revealed a link of KHS101 to cell cycle exit and specific binding to the TACC3 protein, whose knockdown in NPCs recapitulates the KHS101-induced phenotype. Upon systemic administration, KHS101 distributed to the brain and resulted in a significant increase in neuronal differentiation in vivo. Our findings indicate that KHS101 accelerates neuronal differentiation by interaction with TACC3 and may provide a basis for pharmacological intervention directed at endogenous NPCs.     

Serological and molecular evidence of Rickettsia helvetica in Denmark

Recent seroepidemiological studies and examinations of Ixodes ricinus ticks in Europe have demonstrated the presence of an emerging tick-borne infection with Rickettsia helvetica. We conducted a serosurvey in 168 Danish patients seropositive for borreliosis reflecting their exposure to I. ricinus ticks. A total of 21 patients (12.5%) had positive antibody titres to R. helvetica including 4 cases of seroconversion. None of the samples were positive for antibodies to Ehrlichia. We conclude that in humans exposed to I. ricinus ticks in Denmark the risk of acquiring rickettsial infection is for the first time demonstrated. In the same region of Denmark we collected 570 I. ricinus ticks from various sources, and examinations by PCR for Rickettsia were performed. Positive reactions were obtained in 23 ticks (4%), and R. helvetica was identified in all 13 of those for which sequencing was performed.     

Does sports participation during adolescence prevent later alcohol,tobacco and cannabis use?

Aims   To study whether participation in organized sports during adolescence predicts increased smoking of tobacco, alcohol intoxication and cannabis use from late adolescence to adulthood when controlling for potential confounders. Moreover, to study whether such increased drug use varies according to type of sport (team versus individual), main skills needed (endurance, strength or technical) and level of competition.
Design, setting and participants   Survey of national sample of Norwegian high school students (aged 13–19 years) in 1992 (T1) followed-up in 1994 (T2), 1999 (T3) and 2006 (T4) ( n  = 3251).
Measurements   Outcome measures included smoking of tobacco and 12-month prevalences of alcohol intoxication and cannabis use, respectively. Confounders included pubertal timing, friends' drug use, perceived social acceptance, grades and parental socio-economic status.
Findings   Latent growth curve analyses showed that initial level of participation in organized sports predicted growth in alcohol intoxication. Those involved initially in team sports had greater growth in alcohol intoxication, but lower growth in tobacco use and cannabis use, during the adolescent and early adult years compared to those involved in technical or strength sports. Practising endurance sports, as opposed to technical or strength sports, predicted reduced growth in alcohol intoxication and tobacco use.
Conclusions   Sports participation in adolescence, and participation in team sports in particular, may increase the growth in alcohol intoxication during late adolescent and early adult years, whereas participation in team sports and endurance sports may reduce later increase in tobacco and cannabis use.     

Modulation of Volitional Ethanol Intake in the Rat by Central δ-Opioid Receptors

The acute effect of opioid antagonists on volitional ethanol intake was studied in unselected Sprague-Dawley rats using a two-bottle, free-choice model. The total daily intake of ethanol during saline treatment was 1.79 ± 0.4 g/kg/day ( n = 136). The rats were deprived of fluids for the last 4 hr of the light period. Saline or drug was given intraperitoneally 20 to 30 min before the onset of dark, and the ethanol and water intakes were measured during the following hour. The ethanol intake during this hour was 0.75 ± 0.06 g/kg ( n = 136). Naltrexone significantly reduced ethanol intake. There was also a signiflcant reduction in ethanol Intake following administration of ICI-174,864. Naloxonazine and naloxone methiodide lacked effect. None of the treatments had any effect on the water or food intake. The resutts suggest that central bopioid receptors modulate volitional ethanol intake in the rat.     

Ketogenic diet in pyruvate dehydrogenase complex deficiency: short- and long-term outcomes

Objectives

Our aime was to study the short- and long-term effects of ketogenic diet on the disease course and disease-related outcomes in patients with pyruvate dehydrogenase complex deficiency, the metabolic factors implicated in treatment outcomes, and potential safety and compliance issues.

Methods

Pediatric patients diagnosed with pyruvate dehydrogenase complex deficiency in Sweden and treated with ketogenic diet were evaluated. Study assessments at specific time points included developmental and neurocognitive testing, patient log books, and investigator and parental questionnaires. A systematic literature review was also performed.

Results

Nineteen patients were assessed, the majority having prenatal disease onset. Patients were treated with ketogenic diet for a median of 2.9 years. All patients alive at the time of data registration at a median age of 6 years. The treatment had a positive effect mainly in the areas of epilepsy, ataxia, sleep disturbance, speech/language development, social functioning, and frequency of hospitalizations. It was also safe—except in one patient who discontinued because of acute pancreatitis. The median plasma concentration of ketone bodies (3-hydroxybutyric acid) was 3.3 mmol/l. Poor dietary compliance was associated with relapsing ataxia and stagnation of motor and neurocognitive development. Results of neurocognitive testing are reported for 12 of 19 patients.

Conclusion

Ketogenic diet was an effective and safe treatment for the majority of patients. Treatment effect was mainly determined by disease phenotype and attainment and maintenance of ketosis.