Drug and Alcohol Rehabilitation: G Protein-Coupled Receptors – Recent Advances.
G protein-coupled receptors – recent advances.
Filed under: Drug and Alcohol Rehabilitation
Acta Biochim Pol. 2012 Dec 18;
Latek D, Modzelewska A, Trzaskowski B, Palczewski K, Filipek S
The years 2000 and 2007 witnessed milestones in current understanding of G protein-coupled receptor (GPCR) structural biology. In 2000 the first GPCR, bovine rhodopsin, was crystallized and the structure was solved, while in 2007 the structure of ?(2)-adrenergic receptor, the first GPCR with diffusible ligands, was determined owing to advances in microcrystallization and an insertion of the fast-folding lysozyme into the receptor. In parallel with those crystallographic studies, the biological and biochemical characterization of GPCRs has advanced considerably because those receptors are molecular targets for many of currently used drugs. Therefore, the mechanisms of activation and signal transduction to the cell interior deduced from known GPCRs structures are of the highest importance for drug discovery. These proteins are the most diversified membrane receptors encoded by hundreds of genes in our genome. They participate in processes responsible for vision, smell, taste and neuronal transmission in response to photons or binding of ions, hormones, peptides, chemokines and other factors. Although the GPCRs share a common seven-transmembrane ?-helical bundle structure their binding sites can accommodate thousands of different ligands. The ligands, including agonists, antagonists or inverse agonists change the structure of the receptor. With bound agonists they can form a complex with a suitable G protein, be phosphorylated by kinases or bind arrestin. The discovered signaling cascades invoked by arrestin independently of G proteins makes the GPCR activating scheme more complex such that a ligand acting as an antagonist for G protein signaling can also act as an agonist in arrestin-dependent signaling. Additionally, the existence of multiple ligand-dependent partial activation states as well as dimerization of GPCRs result in a ‘microprocessor-like’ action of these receptors rather than an ‘on-off’ switch as was commonly believed only a decade ago.
HubMed – drug
The growing problem of illicit substance abuse in the elderly: a review.
Filed under: Drug and Alcohol Rehabilitation
Prim Care Companion CNS Disord. 2012; 14(4):
Taylor MH, Grossberg GT
Objective: To explore and integrate the extant data on the subject of illicit substance use and abuse in the elderly and to determine shortcomings in the current understanding of the problem and potential topics of future research.Data Sources: Ovid MEDLINE was searched (1960-2011) using the keywords substance use disorders and geriatrics; PsycINFO was searched (1967-2011) using the keywords drug abuse and geriatrics.Data Extraction: The searches of Ovid MEDLINE and PsycINFO returned 35 and 85 results, respectively. Other relevant articles were identified by checking reference lists of the identified studies. A total of 26 articles with a focus on use of illicit substances, excluding alcohol, over-the-counter drugs, and prescription drugs, in the elderly were determined to be applicable to the review.Data Synthesis: Limited data were available to combine between studies, but certain conclusions could be generalized among separate sources.Results: Geriatric substance abuse is a topic of growing interest, importance, and research; however, most of the existing literature has focused on licit substances. Illicit substance abuse has been incorrectly assumed to end as patients age, whereas in reality, elderly drug users are increasingly common and have a unique profile quite different from that of their younger counterparts.Conclusions: Geriatric substance abuse is a common problem and includes both licit and illicit substances. There are not yet reliable screening instruments or treatment methods for identification and treatment of illicit substance abuse in the elderly. A high index of suspicion and consideration of illicit substance use as a real possibility are vital for early recognition and diagnosis of such abuse in the elderly.
HubMed – drug
The Toxic Effects of Polychemotherapy onto the Liver Are Accelerated by the Upregulated MDR of Lymphosarcoma.
Filed under: Drug and Alcohol Rehabilitation
ISRN Oncol. 2012; 2012: 721612
Sen’kova AV, Mironova NL, Patutina OA, Ageeva TA, Zenkova MA
Antitumor therapy of hematological malignancies is impeded due to the high toxicity of polychemotherapy toward liver and increasing multiple drug resistance (MDR) of tumor cells under the pressure of polychemotherapy. These two problems can augment each other and significantly reduce the efficiency of antineoplastic therapy. We studied the combined effect of polychemotherapy and upregulated MDR of lymphosarcoma RLS(40) onto the liver of experimental mice using two treatment schemes. Scheme 1 is artificial: the tumor was subjected to four courses of polychemotherapy while the liver of the tumor-bearing mice was exposed to only one. This was achieved by threefold tumor retransplantation taken from animals subjected to chemotherapy into intact animals. Scheme 2 displays “real-life” status of patients with MDR malignancies: both the tumor and the liver of tumor-bearing mice were subjected to three sequential courses of polychemotherapy. Our data show that the strengthening of MDR phenotype of RLS(40) under polychemotherapy and toxic pressure of polychemotherapy itself has a synergistic damaging effect on the liver that is expressed in the accumulation of destructive changes in the liver tissue, the reduction of the regeneration capacity of the liver, and increasing of Pgp expression on the surface of hepatocytes.
HubMed – drug
Wound healing with medications for rheumatoid arthritis in hand surgery.
Filed under: Drug and Alcohol Rehabilitation
ISRN Rheumatol. 2012; 2012: 251962
Barnard AR, Regan M, Burke FD, Chung KC, Wilgis EF
Introduction. Medications used to treat rheumatoid arthritis, such as corticosteroids, disease-modifying agents (DMARDs), and injectable biological agents (anti-TNF?), may have widespread effects on wound healing. In hand surgery, it is important to balance the risks of poor wound healing from continuing a medication against the risks of a flare of rheumatoid arthritis if a drug is temporarily discontinued. Materials and Methods. A United Kingdom (UK) group of 28 patients had metacarpophalangeal joint replacement surgery in 35 hands (140 wounds). All medication for rheumatoid arthritis was continued perioperatively, except for the injectable biological agents. Results. There were no instances of wound dehiscence or deep infection and only one episode of minor superficial infection. Conclusions. We conclude that provided care is taken to identify and treat any problems promptly, it is appropriate to continue most antirheumatoid medications in the perioperative period during hand surgery to reduce the risk of destabilising the patients’ overall rheumatoid disease control.
HubMed – drug
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