Novel multi-marker proteomics in phenotypically matched patients with ST-segment myocardial infarction: association with clinical outcomes

Journal of Thrombosis and Thrombolysis - Early prediction of significant morbidity or mortality in patients with acute ST-segment elevation myocardial infarction (STEMI) represents an unmet...     

Transcriptional regulation of left ventricular beta-adrenergic receptors during chronic hypoxia.

beta-Adrenergic receptor downregulation is the end result of cellular adaptation to prolonged agonist exposure. The factors mediating receptor downregulation include receptor phosphorylation, receptor movement from the plasma membrane to intracellular sites, and alterations in nascent receptor synthesis. We have previously demonstrated a downregulation of the left ventricular beta-receptor during chronic hypoxia in vivo. To determine the mechanism of this downregulation, we produced chronic hypoxia in seven newborn lambs by creating right ventricular outflow obstruction and an atrial septal defect. Oxygen saturation was reduced to 65-74% for 2 weeks. Six lambs served as normoxic controls. Sarcolemmal membrane and cytosolic fractions were prepared from left ventricular free wall samples. beta-Receptor density in each fraction was determined with the radioligand [125I]iodocyanopindolol. Steady-state levels of beta-receptor mRNA were determined by Northern blot analysis using a beta 1-adrenergic receptor cDNA probe. During chronic hypoxia, left ventricular membrane beta-adrenergic receptor density decreased by 55% (153 +/- 28 fmol/mg for hypoxic lambs versus 342 +/- 79 fmol/mg for control lambs, p < 0.05). There was no corresponding increase in beta-receptor density in the cytosolic fraction (23 +/- 3 fmol/mg for hypoxic lambs versus 33 +/- 9 fmol/mg for control lambs, p = NS), nor was there a significant change in the ratio of beta 1-receptor/beta 2-receptor subtypes as assessed by radioligand binding (beta 1 subtype, 84.1 +/- 10.1% for hypoxic lambs versus 93.2 +/- 8.8% for control lambs; p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)     

Improving oral cavity cancer diagnosis and treatment with fluorescence molecular imaging

Early diagnosis and radical surgical excision of oral squamous cell carcinomas are essential for achieving optimal treatment outcomes. To date, diagnostic tools that rely on anatomical anomalies provide limited information and resolution in clinical practice. As a result, oral cancer is often detected in an advanced stage. Also, no reliable real‐time intraoperative tools are readily available for the evaluation of surgical resection margins. Fluorescence imaging visualises biological processes that occur in early carcinogenesis and could, therefore, enable detection of small tumours in early stages. Furthermore, due to the high sensitivity and spatial resolution, fluorescence imaging could assist in resection margin assessment during surgery. In this review, we discuss several techniques that employ fluorescence for early diagnosis and surgical guidance in oral squamous cell carcinoma and present future perspectives on the potential of fluorescence imaging in oral cancer in the near future.     

Pharmacokinetics of rituximab in a pediatric patient with therapy-resistant nephrotic syndrome

Background

Rituximab (RTX) has recently been introduced as a second-line therapy for nephrotic syndrome in children. Studies show that RTX given during the nephrotic state may be less effective than treatment during a non-nephrotic state, possibly due to loss of RTX in the urine.

Case-Diagnosis/Treatment

We describe a 10-year-old boy with steroid-resistant nephrotic syndrome (SRNS) treated with RTX during a phase of active non-selective proteinuria. The serum half-life of RTX in this patient was less than 1 day compared to 20 days in patients without protein losses. Urinary clearance was at least 25 %, compared to approximately 0 % in control patients. However, RTX loss in the urine, as well as in pleural effusion and ascites, only partly explains the rapid drop in the serum RTX concentration of this patient.

Conclusions

Serum half-life of RTX can be extremely short, partly due to excessive urinary losses in therapy-resistant nephrotic syndrome with non-selective proteinuria, as seen in our patient. These findings may help to explain the poor results of RTX treatment in patients with active proteinuria.

     

The effect of light-emitting diode and laser on mandibular growth in rats

Objective:To evaluate the effect of a light-emitting diode (LED) and/or low-level laser (LLL) with or without the use of anterior bite jumping appliances (also known as functional appliances [FAs]) on mandibular growth in rats.Materials and Methods:Thirty-six 8-week-old male Sprague-Dawley rats weighing 200 g were obtained from Charles River Canada (St. Constant, QC, Canada) and were divided into six groups of six animals each. Groups were as follows: group 1: LLL; group 2: LLL + FA; group 3: LED; group 4: LED + FA; group 5: FA; and group 6: control (no treatment). Mandibular growth was evaluated by histomorphometric and micro computed tomographic (microCT) analyses.Results:The LED and LED + FA groups showed an increase in all condylar tissue parameters compared with other groups.Conclusion:The LED-treated groups showed more mandibular growth stimulation compared with the laser groups.     

Longitudinal control of blood pressure among a cohort of Ghanaians with hypertension: A multicenter,hospital‐based study

There are limited data on factors associated with longitudinal control of blood pressure (BP) among Ghanaians on antihypertensive treatment. We sought to evaluate associations between prospective BP control and 24 putative factors within socio‐demographic, biological, and organizational domains. This is a cohort study involving 1867 (65%) adults with hypertension and 1006 (35%) with both hypertension and diabetes mellitus at five public hospitals. Clinic BP was measured every 2 months for 18 months of follow‐up. A multivariate logistic regression analysis was fitted via generalized linear mixed models to identify factors associated with clinic BP ≥ 140/90 mm Hg at each clinic visit during follow‐up. Mean age of study participants was 58.9 ± 16.6 years and 76.8% were females. Proportions with controlled BP increased from 46.3% at baseline to 59.8% at month 18, P < .0001. Eight factors with adjusted OR (95% CI) associated prospectively with uncontrolled BP were male gender: 1.37 (1.09‐1.72), secondary education: 1.32 (1.00‐1.74), non‐adherence to antihypertensive treatment: 1.03 (1.00‐1.06), fruit intake: 0.94 (0.89‐1.00), duration of hypertension diagnosis: 1.01 (1.00‐1.02), hypertension with diabetes mellitus: 2.05 (1.72‐2.46), number of antihypertensive medications: 1.63 (1.49‐1.79), and estimated glomerular filtration rate (mL/min rise): 0.82 (0.76‐0.89). Interventions aimed at addressing modifiable factors associated with poorly controlled BP would be critical in prevention of cardiovascular diseases among Ghanaians.     

Two surfaces on the histone chaperone Rtt106 mediate histone binding, replication, and silencing

The histone chaperone Rtt106 binds histone H3 acetylated at lysine 56 (H3K56ac) and facilitates nucleosome assembly during several molecular processes. Both the structural basis of this modification-specific recognition and how this recognition informs Rtt106 function are presently unclear. Guided by our crystal structure of Rtt106, we identified two regions on its double-pleckstrin homology domain architecture that mediated histone binding. When histone binding was compromised, Rtt106 localized properly to chromatin but failed to deliver H3K56ac, leading to replication and silencing defects. By mutating analogous regions in the structurally homologous chromatin-reorganizer Pob3, we revealed a conserved histone-binding function for a basic patch found on both proteins. In contrast, a loop connecting two β-strands was required for histone binding by Rtt106 but was dispensable for Pob3 function. Unlike Rtt106, Pob3 histone binding was modification-independent, implicating the loop of Rtt106 in H3K56ac-specific recognition in vivo. Our studies described the structural origins of Rtt106 function, identified a conserved histone-binding surface, and defined a critical role for Rtt106:H3K56ac-binding specificity in silencing and replication-coupled nucleosome turnover.