Bilateral optic disc pit with maculopathy in a patient with cleft lip and cleft palate

Optic disc pit (ODP) is small, gray-white, oval depression found at the optic nerve head. It is a congenital defect that occurs due to imperfect closure of superior edge of the embryonic fissure. Cleft lip and palate are also congenital midline abnormalities occurring due to defect in the fusion of frontonasal prominence, maxillary prominence and mandibular prominence. There is only one case report describing the occurrence of ODP in a young patient with cleft lip and palate who also had basal encephalocele. We describe a 52-year-old patient with congenital cleft lip and palate with bilateral ODP with maculopathy but without any other midline abnormality.     

Different mechanisms of homologous and heterologous μ-opioid receptor phosphorylation

The efficiency of μ-opioid receptor signalling is tightly regulated and ultimately limited by the coordinated phosphorylation of intracellular serine and threonine residues. Here, we review and discuss recent progress in the generation and application of phosphosite-specific μ-opioid receptor antibodies, which have proved to be excellent tools for monitoring the spatial and temporal dynamics of receptor phosphorylation and dephosphorylation. Agonist-induced phosphorylation of μ-opioid receptors occurs at a conserved 10 residue sequence ³⁷⁰TREHPSTANT³⁷⁹ in the receptor''s carboxyl-terminal cytoplasmic tail. Diverse opioids induce receptor phosphorylation at S375, present in the middle of this sequence, but only high-efficacy opioids have the ability to drive higher order phosphorylation on flanking residues (T370, T376 and T379). S375 is the initiating residue in a hierarchical phosphorylation cascade. In contrast, agonist-independent heterologous μ-opioid receptor phosphorylation occurs primarily at T370. The combination of phosphosite-specific antibodies and siRNA knockdown screening also facilitated the identification of relevant kinases and phosphatases. In fact, morphine induces a selective S375 phosphorylation that is predominantly catalysed by GPCR kinase 5 (GRK5), whereas multisite phosphorylation induced by high-efficacy opioids specifically requires GRK2/3. By contrast, T370 phosphorylation stimulated by phorbol esters or heterologous activation of G_q-coupled receptors is mediated by PKCα. Rapid μ-opioid receptor dephosphorylation occurs at or near the plasma membrane and is catalysed by protein phosphatase 1γ (PP1γ). These findings suggest that there are distinct phosphorylation motifs for homologous and heterologous regulation of μ-opioid receptor phosphorylation. However, it remains to be seen to what extent different μ-opioid receptor phosphorylation patterns contribute to the development of tolerance and dependence in vivo.

LINKED ARTICLES

This article is part of a themed section on Opioids: New Pathways to Functional Selectivity. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-2     

Volatile compounds reveal age: a study of volatile organic compounds released by Chrysomya rufifacies immatures

International Journal of Legal Medicine - Age determination of insects collected from vertebrate remains is an essential step in estimating time since colonization as related to the post-mortem...     

Encapsulation of In Situ Nanoprecipitated Inorganic Materials in Confined Geometries Into a Polymer Shell Using Inverse Miniemulsion

Highly insoluble inorganic nanoparticles can be prepared in situ by precipitation inside of aqueous nanodroplets of cosonicated inverse miniemulsions containing salts, which are readily soluble in water. If the different salt droplets are fused, a hardly soluble salt is formed in the dispersed phase with a size considerably smaller than the size of the droplets. Subsequent encapsulation of the nanoparticles into a polymer shell is achieved by an interfacial polyaddition reaction between a polyol present in the aqueous phase and a (second) monomer (2,4‐toluene diisocyanate (TDI)) in the continuous phase. The materials are studied by transmission electron microscopy, X‐ray diffraction, dynamic light scattering (DLS), and TGA.     

Multidimensional ultrasound imaging of the wrist: Changes of shape and displacement of the median nerve and tendons in carpal tunnel syndrome

Dynamics of structures within the carpal tunnel may alter in carpal tunnel syndrome (CTS) due to fibrotic changes and increased carpal tunnel pressure. Ultrasound can visualize these potential changes, making ultrasound potentially an accurate diagnostic tool. To study this, we imaged the carpal tunnel of 113 patients and 42 controls. CTS severity was classified according to validated clinical and nerve conduction study (NCS) classifications. Transversal and longitudinal displacement and shape (changes) were calculated for the median nerve, tendons and surrounding tissue. To predict diagnostic value binary logistic regression modeling was applied. Reduced longitudinal nerve displacement (p≤ 0.019), increased nerve cross‐sectional area (p≤ 0.006) and perimeter (p≤ 0.007), and a trend of relatively changed tendon displacements were seen in patients. Changes were more convincing when CTS was classified as more severe. Binary logistic modeling to diagnose CTS using ultrasound showed a sensitivity of 70–71% and specificity of 80–84%. In conclusion, CTS patients have altered dynamics of structures within the carpal tunnel. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:1332–1340, 2015.     

The relationship between serum cortisol,adrenaline, blood glucose and lipid profile of undergraduate students under examination stress

BackgroundStress is an extremely adaptive phenomenon in human beings and cortisol is a known stress hormone. Examination has been described as a naturalistic stressor capable of affecting human health.ObjectivesTo estimate the relationship between serum cortisol, adrenaline, fasting blood glucose (FBG) and lipid profile during examination stress.MethodsTwo hundred and eight (208) apparently-healthy undergraduate students (aged, 24 ± 6 years) were involved in the study. Exactly 5 mls of venous blood was collected from each subject 1–3 hours before a major examination. A second assessment was done on the same students 3–4 weeks before any examination (control samples). Cortisol and adrenaline were assayed using ELISA techniques, FBG was assayed using enzymatic method while lipid parameters were assayed using standard enzymatic-spectrophotometric methods.ResultsThere was statistically significant increase in serum cortisol, adrenaline, Total cholesterol, HDL-cholesterol and LDL-cholesterol levels in students under examination stress compared to the non examination period (p=0.001, 0.013, 0.0001, 0.0001 and 0.0001, respectively). FBG showed no significant increase. There was also significant positive correlation (r=0.297, p=0.032) between serum cortisol and TC/HDL ratio (cardiac risk factor) before examination stress but not during the stress period.ConclusionsSignificant positive correlation was observed between cortisol and TC/HDL ratio before examination stress.     

Increased afterload induces pathological cardiac hypertrophy: a new in vitro model

Increased afterload results in ‘pathological’ cardiac hypertrophy, the most important risk factor for the development of heart failure. Current in vitro models fall short in deciphering the mechanisms of hypertrophy induced by afterload enhancement. The aim of this study was to develop an experimental model that allows investigating the impact of afterload enhancement (AE) on work-performing heart muscles in vitro. Fibrin-based engineered heart tissue (EHT) was cast between two hollow elastic silicone posts in a 24-well cell culture format. After 2?weeks, the posts were reinforced with metal braces, which markedly increased afterload of the spontaneously beating EHTs. Serum-free, triiodothyronine-, and hydrocortisone-supplemented medium conditions were established to prevent undefined serum effects. Control EHTs were handled identically without reinforcement. Endothelin-1 (ET-1)- or phenylephrine (PE)-stimulated EHTs served as positive control for hypertrophy. Cardiomyocytes in EHTs enlarged by 28.4?% under AE and to a similar extent by ET-1- or PE-stimulation (40.6 or 23.6?%), as determined by dystrophin staining. Cardiomyocyte hypertrophy was accompanied by activation of the fetal gene program, increased glucose consumption, and increased mRNA levels and extracellular deposition of collagen-1. Importantly, afterload-enhanced EHTs exhibited reduced contractile force and impaired diastolic relaxation directly after release of the metal braces. These deleterious effects of afterload enhancement were preventable by endothelin-A, but not endothelin-B receptor blockade. Sustained afterload enhancement of EHTs alone is sufficient to induce pathological cardiac remodeling with reduced contractile function and increased glucose consumption. The model will be useful to investigate novel therapeutic approaches in a simple and fast manner.