Neuroleptic malignant syndrome in the intensive therapy unit

A case of the neuroleptic malignant syndrome occurred in a 40-year-old male after administration of chlorpromazine while on an Intensive Therapy Unit. Treatment with dantrolene sodium was successful, and a muscle biopsy was examined in the recovery phase of the illness. The importance of this condition and the difficulties in establishing a diagnosis at an early stage in patients on an Intensive Therapy Unit are discussed, along with implications for treatment.     

Enrichment techniques and trace analysis with microbore columns in liquid chromatography

The advantages of microbore columns for trace analysis by liquid chromatography are identified, with reference to on-column enrichment techniques performed on analytical micro-columns. The selectivity and high sensitivity of the amperometric detector are utilized in combination with a microbore column for a number of pharmaceutical and bioanalytical analyses, including phenothiazines, parabens, sulphonamides, catecholamines, tetracyclines, vitamins, amino acids and dipeptides.     

A Review of Experimental Work on Radio-yttrium Comprising 1. The Tissue Distribution, 2. The Mechanism of Deposition in Bone,and 3. The State in the Blood

The author reviews the literature covering the deposition of injected radio-yttrium in soft tissues and bone. It is clear that when injected in a carrier-free form yttrium is a bone-seeking isotope. In the presence of carrier, aggregates of larger particle size are formed, and these show greater affinity for the soft tissues which have the highest proportion of reticulo-endothelial cells. The effect of chelating agents is to render the yttrium more soluble, thus increasing excretion; they reduce the extent of colloid formation and reduce the size of the colloidal particles formed. Contradictory reports as to the site of deposition of yttrium can be explained by the fact that the authors have not appreciated the radiocolloidal properties of yttrium and that insufficient attention has been paid to the form in which it is present in the blood-stream.     

“Tau Protein Targeting Via Radioiodinated Azure A For Brain Theranostics: Radiolabeling,Molecular Docking,in vitro And in vivo Biological Evaluation”

Azure-A is one of the phenothiazines (PTZs) derivatives which for decades have been used as antipsychotic drugs due to good lipophilic characteristics which enable them to pass through the blood brain barrier (BBB), besides the important property of enabeling investigation of the pathological forms of aggregated tau protein found in the neurons of the central nervous system. Radioiodination of Azure-A was carried out via an electrophilic substitution reaction using chloramine-T as oxidizing agent. The influence of various reaction parameters and conditions on radioiodination efficiency was investigated, and a high radiochemical yield of 92.07 ± 0.9 % was obtained. An in vitro cytotoxicity study of iodinated Azure-A on three cell lines (HCT-116, human colon carcinoma cell line; Hep-G2, liver carcinoma cell line and HFB-4, normal human melanocytes) was carried out, and the data revealed that ioiodinated Azure A has no to very low toxic effect. The in vivo biodistribution study of ¹³¹I-Azure A showed a high brain uptake of 6.15 ± 0.09 % injected dose/g tissue organ at 30 minutes post-injection, and its retention in brain remained high up to 2 hours, whereas the clearance from the body appeared to proceed via the renal system. The experimental data were confirmed by the molecular docking studies to predict the effect of radioiodination on the binding affinity of the parent molecule (Azure A) to tau paired helical filaments (PHFs). Both ligands showed better binding to S2 and S3 pockets of (PHFs). Consequently, radioiodinated Azure A seems to be a good candidate as an imaging agent for taupathies such as Alzheimer's disease, chronic traumatic encephalopathy, and corticobasal degeneration. Furthermore, it could be a very potent theranostics agent for brain tumors.     

Determination of threshold UV-A elicitation dose in photopatch testing

Photopatch testing, although widely used in the diagnosis of photosensitivity disorders, is not Standardized. We performed this study to determine the threshold ultraviolet tight A (UV-A) dose required to elicit photopatch test responses. 4 patients with previously positive tests were reexposed to the offending allergen, using an incremental dosage regime. Isopropyl dibenzoylmethane (Eusolex 8020), mexenone (benzophenone-10) and oxybeozone (benzophenone-3) produced positive responses at 1.0, 1.0 and 0.7 J/cm², respectively. Responses to phenothiazines were deemed phototoxic. These results demonstrate that high doses of UV-A (e.g., 10–15 J/cm²) are unnecessary, and that 5 J/cm² should become the current Standard.     

N-homolupinanoyl and N-(omega-lupinylthio)alkanoyl derivatives of some tricyclic systems as ligands for muscarinic M1 and M2 receptor subtypes

A set of N-homolupinanoyl- and N-(omega-lupinylthio)alkanoyl derivatives of tricyclic systems (as phenothiazine, iminodibenzyl and dihydropyridobenzodiazepinone) has been prepared and tested for affinity for rat muscarinic M(1) and M(2) receptor subtypes labeled with [3H]pirenzepine and [3H]AF-DX 384. Good affinity for both M(1) and M(2) subtypes was displayed by most compounds, often with nanomolar K(i) values, which for lupinylthiopropionyl- and lupinylthiobutyryl-phenothiazines (13-16) were comparable to those of pirenzepine and methoctramine, respectively. However, only moderate selectivity for one or the other subtype was seen.     

Cellular and molecular actions of Methylene Blue in the nervous system

Methylene Blue (MB), following its introduction to biology in the 19th century by Ehrlich, has found uses in various areas of medicine and biology. At present, MB is the first line of treatment in methemoglobinemias, is used frequently in the treatment of ifosfamide‐induced encephalopathy, and is routinely employed as a diagnostic tool in surgical procedures. Furthermore, recent studies suggest that MB has beneficial effects in Alzheimer's disease and memory improvement. Although the modulation of the cGMP pathway is considered the most significant effect of MB, mediating its pharmacological actions, recent studies indicate that it has multiple cellular and molecular targets. In the majority of cases, biological effects and clinical applications of MB are dictated by its unique physicochemical properties including its planar structure, redox chemistry, ionic charges, and light spectrum characteristics. In this review article, these physicochemical features and the actions of MB on multiple cellular and molecular targets are discussed with regard to their relevance to the nervous system. © 2009 Wiley Periodicals, Inc. Med Res Rev, 31, No. 1, 93–117, 2010     

Involvement of calmodulin in platelet reaction

Penothiazines, known as selective inhibitors of calmodulin, completely inhibited platelet aggregation and secretion induced by ADP, collagen, epinephrine, thrombin or calcium ionophore. They also completely inhibited aggregation induced by exogenous arachidonate (AA) or a mixture of thromboxane A₂ and prostaglandin endoperoxides (TxA₂/PG G₂,H₂). Also, in the presence of these calmodulin inhibitors, the release of AA from platelet phospholipids (PL) was dosedependently inhibited in stimulated platelets. These observations suggest that in platelet reaction, calmodulin is involved in at least two different steps of the reaction: activation of phospholipases and contraction of platelet actomyosin after the formation of TxA₂.     

酚噻嗪类药物引起角膜晶状体混浊90例观察

用随机抽样方法,对116例精神病患者进行观察,结果,服用酚噻嗪类药物90例180眼,角膜、晶状体发生改变58例116眼,占64.4％;服用氯氮平作对照组26例52眼,角膜、晶状体改变18例20眼,占38.4％,两组有非常显著性差异(P<0.01)。随着酚噻嗪类药物服用时间延长,其阳性率上升,提示:长期应用酚噻嗪类药物可致角膜、晶状体混浊,对视力有一定影响。