Adult reproductive functions after early postnatal inhibition by imatinib of the two receptor tyrosine kinases, c-kit and PDGFR, in the rat testis

Imatinib mesylate (Glivec, STI 571; Novartis), a small-molecular analog of ATP that potently inhibits the tyrosine kinase activities of Bcr-Abl, PDGFR-alpha, PDGFR-beta, c-Fms, Arg and c-kit, is one of the novel molecularly targeted agents being introduced into cancer therapy. Stem cell factor (SCF)/c-kit and platelet-derived growth factor (PDGF) signaling pathways regulate postnatal formation of the pools of spermatogonial stem cells and Leydig cells in the rat testis. The effect of short postnatal imatinib exposure on fertility of the male rats and offspring of these animals were investigated. Imatinib significantly reduced the litter size sired by the treated animals and led to permanently slightly elevated serum levels of the gonadotropins. Testicular morphology and mRNA levels of ligands and receptors involved in stem cell factor/c-kit and PDGF signaling returned to control levels, and the offsprings were born healthy. Our findings indicate that treatment of cancer with certain molecularly targeted drugs may have latent effects on testicular development by inhibiting specific physiological signaling pathways.     

Retinoic acid inhibits the infectivity and growth of Chlamydia pneumoniae in epithelial and endothelial cells through different receptors

Chlamydia pneumoniae is a human respiratory pathogen that has also been associated with cardiovascular disease. C. pneumoniae infection accelerates atherosclerotic plaque development in hyperlipidemic animals and promotes oxidation of low density lipoprotein in vitro. All-trans-retinoic acid (ATRA), an antioxidant, has been shown to inhibit C. pneumoniae infectivity for endothelial cells by preventing binding of the organism to the M6P/IGF2 receptor on the cell surface. This current study investigates whether ATRA similarly affects C. pneumoniae infectivity of epithelial cells, which are the primary site of infection in the respiratory tract, and the effects on intracellular growth in both endothelial and epithelial cells. Because ATRA binds to both the nuclear retinoid acid receptor (RAR) and the M6P/IGF2 receptor, 4-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)-1-propenyl]benzoic acid (TTNPB), an ATRA analog, which binds to the RAR but not the M6P/IGF2 receptor was used to differentiate the receptor mediating the effects of ATRA. The results of this study showed two separate effects of ATRA. The first effect is through interaction with the M6P/IGF2 receptor on the cell surface preventing attachment of the organism (inhibition by ATRA but not TTNPB) in endothelial cells and the second is through the nuclear receptor (inhibition by both ATRA and TTNPB) which inhibits growth in both epithelial and endothelial cells.     

Predicting microvascular obstruction with cardiac troponin T after acute myocardial infarction: a correlative study with contrast-enhanced magnetic resonance imaging

Background  

The presence of microvascular obstruction (MVO) is associated with more severely impaired left ventricular function and adverse prognosis. The aim of this study was to evaluate whether a single cardiac troponin T-value (cTnT) was able to predict the presence of MVO and whether cTnT is an independent predictor of MVO as compared to usual risk factors.     

Patient experience with hydrophilic catheters used in clean intermittent catheterization

ObjectiveTo evaluate patient experience of hydrophilic catheters used for clean intermittent catheterization (CIC).Patients and methodsOut of 107 consecutive patients on a CIC programme, 100 filled in a questionnaire concerning the hydrophilic catheters they were using for CIC.ResultsSixty-four out of 100 patients were females and 83 had a neurogenic reason for CIC. The programme was started at median age 4 (range 0–32) years. The handling and sliding properties of the catheters were usually good, although 26% felt that the hydrophilic catheters were too slippery in the hands and 11% felt some sticking during catheter removal. Catheter packages got the most criticism. Pain experiences were rare, although 87 performed CIC through the urethra. In general, there were no differences between brands of catheter (LoFric^® (Astratech) vs Easi/SpeediCath^® (Coloplast)), although the patients had preferences.ConclusionsPatients have individual preferences, although the technical properties of hydrophilic catheters are in general quite good and similar. As CIC treatment is demanding, the patient is justified in selecting the best catheter for them.     

Changes in physical activity and sedentary time in the Finnish Schools on the Move program: a quasi‐experimental study

The aim of the Finnish Schools on the Move program is to create a more active and pleasant school day through physical activity (PA). In this quasi‐experimental design, we compared changes in moderate‐to‐vigorous‐intensity physical activity (MVPA) and sedentary time (ST) during the school day and outside school hours for Grades 1–9 over two academic years in four program schools and two reference schools. Altogether 319 girls and boys aged 7–15 participated in the study between 2010 and 2012. MVPA and ST were measured four times over the 1.5‐year follow‐up period for seven consecutive days, using a hip‐worn ActiGraph accelerometer. Linear growth curve modeling was used to examine the effect of the program on MVPA and ST during follow‐up. School day MVPA increased (P = 0.010) and school day ST decreased (P = 0.008) in program primary schools (Grades 1–6) more compared with the reference schools. The effect sizes (Cohen's d) for the difference in change (from the first to the last measurement) were small (d = 0.18 and d = ?0.27, respectively). No differences in the changes of leisure‐time or whole‐day MVPA and ST between the program and reference schools were observed during follow‐up. In conclusion, the changes in school day MVPA and ST did not translate into positive effects across the whole day. More effective and longer promotion actions are needed for positive changes in PA and ST, especially in lower secondary schools and for all daily segments.     

Lifestyle Risk Factors Increase the Risk of Hospitalization for Sciatica: Findings of Four Prospective Cohort Studies

Background

The purpose of this study is to assess the effects of lifestyle risk factors on the risk of hospitalization for sciatica and to determine whether overweight or obesity modifies the effect of leisure-time physical activity on hospitalization for sciatica.

The effects of physical activity counseling on mood among 75- to 81-year-old people: a randomized controlled trial

OBJECTIVES: To examine the effects of physical activity counseling on mood among older people unselected for their depressive symptomatology. METHODS: Data are from "Screening and Counseling for Physical Activity and Mobility in Older People" project (SCAMOB), conducted in Finland during 2003-2005. SCAMOB was a 2-year single-blinded randomized controlled trial among 624 participants 75 years and older randomized into physical activity counseling group and control group. Depressive symptoms were assessed at baseline and after 24 months using Center for the Epidemiologic Studies Depression Scale. RESULTS: Among all the study participants, no effect of intervention was observed. However, among subgroup with minor depressive symptoms at baseline, a significant treatment effect was observed, where depressive symptoms decreased in the intervention group and increased in the control group. CONCLUSIONS: These findings suggest that physical activity counseling may reduce depression among those with minor depressive symptoms, which warrants for future studies.     

Analysis,storage stability and reference values for urinary chromium and nickel

Summary Simple direct dilution methods are described for the analysis of urinary chromium and nickel with electrothermal atomic absorption spectrometry. The day-to-day variation of the methods is in the order of 5%, and the detection limits 20 and 0.1 nmol/l (1.2 and 0.0052 g/l) for urinary nickel and chromium, respectively. At levels corresponding to occupational exposures, both metals are stable (within 20%) in urine specimens in the refrigerator for the least ten months. The stability does not require acidification. Geometric mean values for urinary nickel and chromium in the non exposed population in Finland (n = 299 and 155) are 70 and 1.5 nmol/l (4.8 and 0.078 g/l), and the upper 95% confidence limits from a log-normal distribution, are 170 and 11 nmol/l(10 and 0.57 g/l), respectively.     

Epilepsy and the Electroencephalogram in Progressive Encephalopathy with Edema, Hypsarrhythmia, and Optic Atrophy (the PEHO Syndrome)

Summary: Progressive encephalopathy with edema, hypsarrhythmia, and optic atrophy (PEHO syndrome) is an apparently autosomal recessive disorder manifested by infantile spasms, severe hypotonia, and early arrest of psychomotor development. Subcutaneous edema in the limbs, typical facial features, and blindness with optic atrophy are also present. Neuropathologic and radiographic studies show progressive brain atrophy, which is accentuated infratentorially. We recorded 85 EEGs from 10 patients between the ages of 3 weeks and 12.7 years; follow-up ranged from 7 months to 12.1 years. The infantile spasms were preceded by other neurological symp- toms in all patients. Seven of nine patients showed focal or generalized epileptiform activity or abnormal EEG background. All patients developed hypsarrhythmia, first recorded between 3 and 11 months of age, that was resistant to therapy with ACTH and antiepileptic drugs. After the hypsarrhythmia disappeared, five patients showed slow spike-wave activity generally seen in the Lennox-Gastaut syndrome, and three patients showed background EEG abnormality with generalized or diffuse paroxysmal activity. There were no specific EEG features that could help in the diagnosis of PEHO. The PEHO syndrome should be borne in mind in the diagnostic work-up of patients with infantile spasms, so that potentially harmful treatment can be avoided, and the parents can be counseled about the inheritability of the disorder.     

TNF-α, myocardial perfusion and function in patients with ST-segment elevation myocardial infarction and primary percutaneous coronary intervention

Aims

To characterize the time course of tumor necrosis factor-α (TNF-α) serum levels along with myocardial perfusion and contractile function in patients with ST-segment elevation myocardial infarction (STEMI) and successful primary percutaneous coronary intervention (PCI).

Methods

Serum levels of TNF-α, interleukin 6 (IL-6), and C-reactive protein (CRP) were measured in 42 patients with STEMI before, one and 6?days after successful PCI. Myocardial perfusion was assessed by contrast-enhanced echocardiography (ceEcho), contractile function by unenhanced two-dimensional (2DE) and real-time three-dimensional echocardiography. In a subset of 18 patients, infarct size was quantified by late gadolinium enhancement cardiovascular magnetic resonance imaging (LGE-CMR) on day six.

Results

TNF-α serum levels were in the upper normal range within the first 12?h from symptom onset and increased continuously until day six, while IL-6 and CRP increased subsequently with a peak on day one after STEMI. Serum TNF-α on day one after PCI correlated with perfusion defects, wall motion abnormalities, and infarct size (ceEcho: r?=?0.52, p?=?0.005; 2DE: r?=?0.56, p?=?0.002; LGE-CMR: r?=?0.83–0.86; p?p?=?0.006, adjusted R ² 0.638).

Conclusion

Our data reflect the clinical significance of early TNF-α elevation in patients with STEMI and primary PCI (Controlled Clinical Trials number, NCT00529607).