Decreased R-R variation: A criterium for overdosage of tricyclic psychotropic drugs

Objective Since intoxication with tricyclic antidepressants is common, a supplementary screening method for differentiation between therapeutic and supratherapeutic ranges would be a valuable diagnositc tool, particularly in delirious and unconscious patientsSetting 109 patients treated with amitriptyline, 8 patients treated with doxepin, 10 patients treated with clozapine, and 72 normal control subjects matched for age and sex were tested for heart rate variability while resting.Results Considering time and frequency derived measures, which are rather independent of heart rate, the patients showed significantly decreased heart rate variability parameters (p<0.0001), as compared with the normal subjects. Of the patients presenting delirious symptoms 6 showed coefficients of variation more than 4 standard deviations below the mean control value.Conclusions As heart rate variability can be easily calculated, this measurement is suggested as a useful tool to quickly exclude or support the diagnosis of chronic intoxication with tricyclic antidepressants or clozapine.     

Differences in protein synthesized in vivo and in vitro by cells associated with the cerebral microvasculature. A protein synthesized in response to trauma?

A protein of molecular weight 71,000 (P₇₁) was synthesized by cells associated with the cerebral microvasculature in telencephalon slices incubated in vitro. This protein, however, was not synthesized in vivo. There was a 30 min delay in the synthesis of P₇₁ by brain slices. During this lag period a new ribonucleic acid species which was required for P₇₁ synthesis was produced in the slices. After this delay P₇₁ became a major product of protein synthesis. P₇₁ was also produced by microvasculature enriched fractions isolated from telencephalon.This protein may be involved in the initial response of the vascular system to injury.     

Quantitative determination of anti-dsDNA antibodies and antibody/dsDNA stoichiometries in prepared,soluble complement-fixing antibody/dsDNA immune complexes

We have investigated quantitatively the complement-mediated binding of prepared, soluble ¹²⁵I-7S IgG antibody/³H-dsDNA immune complexes to human red blood cells (RBCs). We have performed these studies by using a detailed modification of the RBC-CF assay [Pedersen et al., J. Immun. Meth. 38, 2692–2280 (1980)] which now allows for the simultaneous measurement of both ³H-DNA and ¹²⁵I-binding to the cells. Our results indicate that, in the case of three SLE patients, their anti-dsDNA antibody titers are sufficiently high that a small fraction of their ¹²⁵I-7S IgG antibodies (ca 0.1–0.2%) can be identified as specifically anti-dsDNA. We have also used an indirect method (with ¹²⁵I-labelled rabbit anti-human IgG) for the determination of IgG anti-dsDNA antibodies in complement-fixing antibody/dsDNA immune complexes that bind to RBCs, and the results of these measurements are in reasonable agreement with the direct binding experiments. These studies have also allowed us to estimate the antibody/DNA stoichiometries in complement-fixing immune complexes. The results of these experiments may provide a useful standard for the analysis of monoclonal anti-dsDNA antibodies.     

Characterization of major histocompatibility antigens on trinitrophenyl-modified cells.

Cell membrane proteins encoded for by the major histocompatibility complex (MHC)¹ are associated with the antigenic determinant(s) recognized on trinitrophenyl (TNP)-modified cells by syngeneic murine cytotoxic T lymphocytes and by hapten-reactive guinea pig T cells. To investigate the relationship of the TNP moiety on TNP-modified cells to these major histocompatibility antigens, peritoneal exudate cells or splenocytes from two inbred guinea pig strains and one inbred murine strain were TNP-modified, radioiodinated and lysed in detergent. TNP-derivatized proteins were then isolated using an anti-TNP immunoabsorbent, and the presence on TNP-derivatized histocompatibility antigens in the eluted proteins was determined by immunoprecipitation experiments and SDS-polyacrylamide gel electrophoretic analysis. Whereas most of the various histocompatibility antigens examined were found to be TNP-derivatized in amounts proportional to the degree of membrane protein derivation as a whole, only small amounts of TNP-modified strain 2 guinea pig Ia antigens were found, and no hapten-modified strain 13 guinea pig Ia antigens were detected. It is concluded that, in contrast to most MHC gene products, strain 13 Ia antigens are not derivatized on TNP-modified cells and, thus, represent an important exception demonstrating that histocompatibility antigens need not be directly TNP-derivatized for T cell recognition and activation.     

Salvage of pyrimidine nucleosides by Trichomonas vaginalis

Trichomonas vaginalis is incapable of de novo pyrimidine biosynthesis because it cannot incorporate bicarbonate, aspartate or orotate into its pyrimidine nucleotides or nucleic acids. The organism can salvage exogenous cytidine greater than uridine greater than uracil and thymidine, and incorporate them into the nucleotide pool. A portion of cytidine is converted to CMP, CDP and CTP by cytidine phosphotransferase and nucleotide kinases. Some cytidine and most of uracil are, however, converted first to uridine by cytidine deaminase and uridine phosphorylase respectively; uridine is then incorporated into UMP, UDP and UTP by uridine phosphotransferase and nucleotide kinases. The two phosphotransferases, found mainly in the non-sedimentable fraction of T. vaginalis, provide the main avenue of pyrimidine salvage. No significant levels of pyrimidine phosphoribosyl transferase or nucleoside kinases can be detected in the extract. T. vaginalis has no appreciable dihydrofolate reductase or thymidylate synthetase; it grows normally in millimolar concentrations of methotrexate, pyrimethamine, or trimethoprim, and cannot incorporate labels from exogenous uracil or uridine into DNA. It has an enzyme thymidine phosphotransferase in the sedimentable fraction which converts thymidine to TMP. Thymidine salvage in T. vaginalis is thus totally isolated from the rest of the pyrimidine salvage.     

Tracheoesophageal fistula: New option in management

Tracheoesophageal fistula is a life threatening condition. Patients not managed surgically ultimately die of their disease. Surgical management is the treatment of choice. We present a case of a patient that developed a tracheoesophageal fistula after tracheostomy. Surgical repair was done which failed due to infection. The patient was managed with the help of an esophageal stent and Trichloroacetic Acid cautery. This approach can be used in selected patients, depending upon the size and site of TEE Larger fistulae and those situated lower down e.g. supra carinal cannot be managed by this technique.     

Early and repeated use of plasma for the management of Ebola patients: Reflection around a case

In December 2013, the most widespread epidemic of Ebola virus disease began in Guinea and continued for over 2 years. At the request of the Guinean state, France deployed a military field hospital to treat Ebola infected healthcare workers. From January to July 2015, our center supported 26 healthcare workers suffering from Ebola virus disease. Despite an individualized care and optimal treatment, the fatality rate remained high at 30.7%. Improved therapies are required to reduce mortality risk in Ebola virus disease. We report the case of a patient admitted to the hospital on the 4th day after onset, who survived despite several clinical and biological predictors of fatal outcome. We transfused plasma at a high dose and spread over time. This innovative therapeutic approach was based on our clinical experience of Ebola patients’ management, literature review and knowledge of plasma ability to restore coagulation disorders and endotheliopathy. Even without any bleeding sign, coagulopathy and endothelial permeability disorders participate in hypovolemia and fatal multi-system organ failure. Early intake of therapeutic plasma at repeated doses seems to reduce the endothelial permeability and coagulation disorders related to Ebola virus disease.     

Dynamics and regulation of glycolysis‐tricarboxylic acid metabolism in the midgut of Spodoptera litura during metamorphosis

Significant changes usually take place in the internal metabolism of insects during metamorphosis. The glycolysis‐tricarboxylic acid (glycolysis‐TCA) pathway is important for energy metabolism. To elucidate its dynamics, the mRNA levels of genes involved in this pathway were examined in the midgut of Spodoptera litura during metamorphosis, and the pyruvate content was quantified. The expression patterns of these genes in response to starvation were examined, and the interaction between protein phosphatase 1 (PP1) and phosphofructokinase (PFK) was studied. The results revealed that the expression or activities of most glycolytic enzymes was down‐regulated in prepupae and then recovered in some degree in pupae, and all TCA‐related genes were remarkably suppressed in both the prepupae and pupae. Pyruvate was enriched in the pupal midgut. Taken together, these results suggest that insects decrease both glycolysis and TCA in prepupae to save energy and then up‐regulate glycolysis but down‐regulate TCA in pupae to increase the supply of intermediates for construction of new organs. The expression of all these genes were down‐regulated by starvation, indicating that non‐feeding during metamorphosis may be a regulator of glycolysis‐TCA pathway in the midgut. Importantly, interaction between PP1 and PFK was identified and is suggested to be involved in the regulation of glycolysis.     

Psychopharmacology and Cardiovascular Disease

This review discusses common mental health disorders and their associations with cardiovascular disease risks. Commonly found mental health disorders include depression, anxiety, and personality types. The link between depression and cardiovascular disease mortality has been established. Depression is also common in patients with heart failure. In addition to discussing psychological disorders, a review of psychotropic drugs is also included. Drugs are described for therapy for depression and anxiety, as well as associations with cardiovascular drug-drug interactions. Drug-drug interactions are more common and potentially dangerous in elderly patients, in whom the conditions often coexist. The most common drug-drug interactions involve the P450 system of enzymes.     

Improved quantification of protein in vaccines containing aluminum hydroxide by simple modification of the Lowry method

Aluminum (Al) components in vaccines are known to act as adsorbents that interfere with accurate protein quantification by the Lowry method. Therefore, certain modifications based on the characteristics and compositions of the vaccine are required for determination of protein contents.We investigated the effects of an additional centrifugal separation and found that protein contents were overestimated by up to 238% without centrifugation through a collaborative study performed with hepatitis B vaccines containing Al. However, addition of a centrifugation step yielded protein concentrations that were similar to the actual values, with small coefficients of variation (CVs). Proficiency testing performed in 11 laboratories showed that four laboratories did not have satisfactory results for vaccines containing aluminum hydroxide, although all laboratories were proficient in protein analysis when samples did not contain aluminum hydroxide. Incomplete resuspension of aluminum hydroxide solution with alkaline copper solution was the major cause of insufficient proficiency in these laboratories.