Molecular Imaging of Membrane Transporters’ Activity in Cancer: a Picture is Worth a Thousand Tubes

Molecular imaging allows the non-invasive assessment of membrane transporter expression and function in living subjects. Such technologies have the potential to become diagnostic and prognostic tools, allowing detection, localization, and prediction of response of tumors and their metastases to therapy. Beyond tumors, imaging can also help understand the role of transporters in adverse drug effects and drug clearance. Here, we review molecular imaging technologies that monitor transporter-mediated processes. We emphasize emerging probe substrates and potential clinical applications of imaging the function of membrane transporters in cancer.KEY WORDS: membrane transporters, molecular imaging, multidrug resistance, near infrared, optical imaging     

<Emphasis Type="Italic">Rickettsia</Emphasis> species in fleas collected from small mammals in Slovakia

Epidemiological and epizootiological studies of Rickettsia felis and other Rickettsia spp. are very important, because their natural cycle has not yet been established completely. In total, 315 fleas (Siphonaptera) of 11 species of Ceratophyllidae, Hystrichopsyllidae and Leptopsyllidae families were tested for the presence of Rickettsia species and Coxiella burnetii with conventional and specific quantitative real-time PCR assays. Fleas were collected from five rodent hosts (Myodes glareolus, Apodemus flavicollis, Apodemus agrarius, Microtus subterraneus, Microtus arvalis) and three shrew species (Sorex araneus, Neomys fodiens, Crocidura suaveolens) captured in Eastern and Southern Slovakia. Overall, Rickettsia spp. was found in 10.8 % (34/315) of the tested fleas of Ctenophthalmus agyrtes, Ctenophthalmus solutus, Ctenophthalmus uncinatus and Nosopsyllus fasciatus species. Infected fleas were coming from A. flavicollis, A. agrarius, and M. glareolus captured in Eastern Slovakia. C. burnetii was not found in any fleas. R. felis, Rickettsia helvetica, unidentified Rickettsia, and rickettsial endosymbionts were identified in fleas infesting small mammals in the Ko?ice region, Eastern Slovakia. This study is the first report of R. felis infection in C. solutus male flea collected from A. agrarius in Slovakia.     

Effect of Matrix Metalloproteinase Inhibition by Doxycycline on Myocardial Healing and Remodeling after Myocardial Infarction

Summary The aim of conducting this study was to assess the clinical relevance of matrix metalloproteinase (MMP) inhibition by doxycycline, an effective MMP inhibitor, in a rat model of extensive myocardial infarction (MI) and left ventricular (LV) dysfunction. Rats (n = 22) were subjected to extensive anterior MI. Doxycycline (25 mg SC, daily) or saline (control) injections were started for nine days thereafter. The effect of doxycycline on MMP activity in the infarcted and remote myocardium was measured by zymography, in another subgroup (n = 8), nine days after MI. Echocardiography and magnetic resonance imaging (MRI) studies were performed at one and thirty days after MI to assess LV remodeling and function. After 4 weeks, hearts were fixed, and subjected to morphometric and histological analysis. Compared with control, doxycycline treatment attenuated MMP-9 and -2 activity in both infarcted and remote myocardium. Serial echocardiography studies showed that doxycycline failed to attenuate scar thinning, LV dilatation and dysfunction. MRI study showed that doxycycline impaired LV compensatory hypertrophy. Furthermore, compared with control, doxycycline reduced vessel density (/mm² ± SEM) in the infarcted myocardium (84 ± 16 vs. 46 ± 9/mm², respectively; p < 0.05). Our work suggest that effective MMPs’ inhibition in the infarcted and remote myocardium by doxycycline does not prevent LV remodeling and dysfunction but impairs angiogenesis and compensatory LV hypertrophy. Our findings caution against aggressive, non-selective inhibition of MMPs in the early healing phase after MI.     

Dynamics of the heart rate variability and oxygen saturation response to acute normobaric hypoxia within the first 10 min of exposure

Although the heart rate variability (HRV) response to hypoxia has been studied, little is known about the dynamics of HRV after hypoxia exposure. The purpose of this study was to assess the HRV and oxygen saturation (SpO₂) responses to normobaric hypoxia (FiO₂ = 9·6%) comparing 1 min segments to baseline (normoxia). Electrocardiogram and SpO₂ were recorded during a 10‐min hypoxia exposure in 29 healthy male subjects aged 26·0 ± 4·9 years. Baseline HRV values were obtained from a 5‐min recording period prior to hypoxia. The hypoxia period was split into 10 non‐overlapping 1‐min segments and time domain HRV indexes (RMSSD and SDNN) were calculated for each segment. Differences (Δ) from baseline values were calculated and transformed using natural logarithm (Ln). This study revealed that the decrease in ΔSpO₂ became significant (P<0·001) in the first minute of hypoxia, the decrease in ΔLn RMSSD became significant (P = 0·002) in the second minute, and the decrease in ΔLn SDNN became significant (P = 0·001) in the third minute. Between the second and fifth minute of hypoxia, ΔSpO₂ correlated with ΔLn RMSSD (r = 0·57, P<0·001) and ΔLn SDNN (r = 0·44, P<0·001). Five min after the onset of hypoxia, ΔSpO₂ was significantly (P = 0·002) decreased but changes in ΔLn RMSSD (P = 0·344) and ΔLn SDNN (P = 0·558) were not significant. In conclusion, the decrease in HRV was proportional to desaturation but only during the first 5 min of hypoxia.     

Concern and death anxiety during an ongoing terror wave: The moderating role of direct vs. indirect exposure

ABSTRACT

The current study examined whether emotional concern over one’s security situation is connected with death anxiety during an ongoing terror wave, and whether type of exposure (media exposure vs. contact with witnesses) moderates this connection. A total of 345 individuals, aged 18–70, were sampled during an ongoing wave of terror in Israel and filled out scales measuring death anxiety, concern over security situation, and type of exposure. Results indicated that increased concern was connected with enhanced death anxiety. Moreover, this connection was more pronounced among individuals exposed to the events through the media, in comparison with individuals who had first-hand contact with witnesses.     

Independence in self-care activities in children with myelomeningocele: exploring factors based on the International Classification of Function model

Purpose: To investigate the relationship between disease factors, body functions and structures, activities, personal and environmental factors with independence in self-care activities in children with myelomeningocele (MMC), utilizing the International Classification of Function model.

Method: 113 children with MMC, aged 3–18 years were assessed during an annual MMC-clinic visit. Data on the personal and environmental factors, disease factors, hand function, mobility, visual perception, cognition, and communication were assessed in relation to the Pediatric Evaluation of Disability Inventory (PEDI) self-care domain.

Results: The mean PEDI caregiver assistance score was 22.1 (ranged between <10 and 62) well below the norms. The most significant determinant of dependence in self-care activities was the presence of hydrocephalus, a child with hydrocephalus scored a mean of 9.2 points less on the PEDI caregiver scale (p?=?0.02). By using a linear regression, the most significant factors associated with the PEDI scores among children with hydrocephalus were the age of the child, function of the non-dominant hand, ambulation, and cognitive function.

Conclusion: In children with MMC the presence of hydrocephalus appears to be more significantly associated with functional independence than the neurological level. The International Classification of Function model provides an in-depth multidisciplinary model that facilitates in investigating independence in self-care activities in children with MMC. It is important to take personal factors and various functional impairments into account when working with these children to promote independence.

• Implications for Rehabilitation

• When working with children with myelomeningocele on independence in daily living activities, it is necessary that health professionals demonstrate a holistic view of the child and his/her disability.

• Health professionals should take into account information on all factors of the International Classification of Function, in order to help the children, achieve maximal independence.

• It is important for health professionals to consider presence or lack of hydrocephalus when working with children with myelomeningocele to achieve functional gains.

• Improving upper extremity function and cognitive ability in children with myelomeningocele may help promote independence in activities of daily living.

• It is necessary for health professionals to continue to work with children with myelomeningocele on maximizing independence as they get older, for it is possible for them to achieve independence at a later age.

• While this study did not explore participation, this is an essential part of the International Classification of Function and is generally related to function. Participation allows a child to be involved in life situations, contributes to life satisfaction and prepares children for critical adult roles. It is therefore important to assess and monitor this measure. Further studies should examine associations between independence in self-care activities and participation.