Caramel Standardization with Respect to 5-Hydroxymethylfurfurol

Pharmaceutical Chemistry Journal -     

The psychomodulatory action of subpyrogenic doses of interleukin-1β in conditions of chronic administration to rats

The effects of interleukin-1β at low, subpyrogenic doses on behavior were studied in rats. Signs of increased anxiety were evident by day 5 of treatment courses. These results provide evidence supporting the role of proinflammatory cytokines in the pathogenesis of emotional disorders. __________ Translated from Rossiiskii Fiziologicheskii Zhurnal imeni I. M. Sechenova, Vol. 92, No. 3, pp. 299–307, March, 2006.     

Synthesis and analgesic activity of new α-truxillic acid derivatives with monoterpenoid fragments

Novel derivatives of α-truxillic acid with a camphor framework were synthesized and evaluated for their in vivo analgesic activity. α-Truxillic acid derivatives were prepared via solvent-free photocatalyzed [2+2] cyclodimerization of (E)-cinnamic acid. Target compounds were obtained through the substitution of –Cl or –OH groups in α-truxillic acid. The chemical structures of the synthesized compounds were elucidated by ¹H, ¹³C-NMR, and mass spectrometry. Their analgesic activities were evaluated by the acetic acid-induced writhing test and the hot plate method. Compounds 7b and 7f containing the cyclobutane unit and natural fragments at 10 mg/kg exhibited analgesic activity in the acetic acid-induced writhing test, while α-truxillic acid (10 mg/kg, per os) did not show analgesic activity in the test. Intermediate 2 caused a decrease in the writhing with pain inhibition of 28 %. In the hot plate test, borneol showed high analgesic activity with pain inhibition of 60 %.     

Prothrombin/thrombin and the thrombin receptors PAR-1 and PAR-4 in the brain: localization, expression and participation in neurodegenerative diseases

Emerging evidence demonstrates that thrombin exerts physiological and pathological functions in the central nervous system. Both prothrombin and its active form thrombin have been detected locally in the brain. The cellular functions of thrombin are mainly regulated by G protein-coupled protease-activated receptors (PARs). Thrombin can signal via PAR-1, PAR-3 and PAR-4. Some neurological diseases (e.g. Alzheimer's disease or Parkinson's disease) are characterized by increased levels of both active thrombin and PAR-1. This indicates that thrombin and its receptor may be closely involved in the development of neurodegenerative processes. The role of thrombin in brain injury can be either protective or deleterious, depending on the concentration of thrombin. Thrombin at high concentrations exacerbates brain damage. In contrast, low concentrations of thrombin rescue neural cells from death after brain insults. Also thrombin preconditioning has neuroprotective effects. Therefore, thrombin and thrombin receptors represent novel therapeutic targets for treating neurodegenerative diseases.     

Choice of optimal respiratory therapy in patients operated for tumors of the posterior cranial fossa

The results of two different approaches to respiratory support after surgical intervention into the structures of the posterior cranial fossa (PCF) are analyzed in 74 neurosurgical patients, including 41 patients having synchronized pressure support ventilation and 50-80% spontaneous intermittent mandatory ventilation (SIMV + PSV) (Group 1) and 33 patients receiving continuous positive end-expiratory airway pressure (CPAP + PSV) (Group 2). Respiratory therapy has been ascertained to provide at least 50-80% of the minute ventilation volume in neurosurgical patients after interventions into PCF when respiratory failure develops in the postoperative period. Diminished respiratory support may be performed only after neurological stabilization and within 24 hours. Early transition to spontaneous respiration increases the duration of artificial ventilation and worsens neurological symptoms.     

Antiproliferative,proapoptotic, and tumor-suppressing effects of the novel anticancer agent alsevirone in prostate cancer cells and xenografts

The aim of this study was to explore the mechanisms of action of alsevirone in prostate cancer (PC) in vitro and in vivo: CYP17A1 inhibition, cytotoxic, apoptotic, and antitumor effects in comparison with abiraterone. The CYP17A1-inhibitory activity was investigated in rat testicular microsomes using high-performance liquid chromatography. Testosterone levels were evaluated using enzyme-linked immunoassay. IC₅₀ values were calculated for PC3, DU-145, LNCaP, and 22Rv1 cells using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) test. The antitumor effect in vivo was studied in DU-145 and 22Rv1 subcutaneous xenografts in Balb/c nude mice. Alsevirone reduced the CYP17A1-inhibitory activity by 98% ± 0.2%. A statistically significant reduction in the testosterone concentration in murine blood was recorded after the 7th administration of 300 mg/kg alsevirone at 0.31 ± 0.03 ng/ml (p < .001) versus 0.98 ± 0.22 ng/ml (p = .392) after abiraterone administration and 1.52 ± 0.49 ng/ml in control animals. Alsevirone was more cytotoxic than abiraterone in DU-145, LNCaP, and 22Rv1 cells, with IC₅₀ values of 23.80 ± 1.18 versus 151.43 ± 23.70 μM, 22.87 ± 0.54 versus 28.80 ± 1.61 μM, and 35.86 ± 5.63 versus 109.87 ± 35.15 μM, respectively. Alsevirone and abiraterone significantly increased annexin V-positive, caspase 3/7-positive, and activated Bcl-2-positive cells. In 22Rv1 xenografts, alsevirone 300 mg/kg × 10/24 h per os inhibited tumor growth: on Day 9 of treatment, tumor growth inhibition = 59% (p = .022). Thus, alsevirone demonstrated significant antitumor activity associated with CYP17A1 inhibition, apoptosis in PC cells, and testosterone reduction.     

A single amino acid substitution controls DAF-dependent phenotype of echovirus 11 in rhabdomyosarcoma cells

Decay accelerating factor (DAF, CD55) is used by DAF-dependent (Daf+) variants of echovirus 11 (EV11) as a primary cellular receptor. The interaction of EV11 with DAF is completely reversible, therefore DAF-dependent variants require an unidentified coreceptor to initiate uncoating. Daf- variants of EV11, which do not interact with DAF, use an alternative primary cellular receptor. The aim of this study was to test the hypothesis whether the coreceptor, which is necessary for the uncoating of DAF-dependent variants, may act as an alternative primary receptor for the Daf- variants of EV11. By using the model of the two closely related daf+ and daf- clones of EV11 in rhabdomyosarcoma (RD) cell line, it was shown that a single amino acid substitution in the capsid protein VP2 could control the expression of the DAF-dependent phenotype. Anti-DAF monoclonal antibody has blocked the infection of RD cells by the DAF-dependent daf+ clone, but not by the daf- clone of EV11. Since the structural proteins of the two clones differed only in the receptor binding site for DAF, the unidentified non-DAF primary receptor for the daf- clone might have the same conformation as the uncoating coreceptor required for the daf+ clone. Despite the difference in primary receptors, both daf+ and daf- clones were equally inhibited by a monoclonal antibody to beta2-microglobulin. The monoclonal antibody B9.12.1 to class I human leukocyte antigen molecules showed no inhibitory effect in regards to either clone. The hypothesis of convergent intracellular traffic of Daf+ and Daf- variants of EV11 is discussed.     

Normal and system lupus erythematosus red blood cell interactions studied by double trap optical tweezers: direct measurements of aggregation forces

Direct measurements of aggregation forces in piconewton range between two red blood cells in pair rouleau are performed under physiological conditions using double trap optical tweezers. Aggregation and disaggregation properties of healthy and pathologic (system lupus erythematosis) blood samples are analyzed. Strong difference in aggregation speed and behavior is revealed using the offered method which is proposed to be a promising tool for SLE monitoring at single cell level.     

Surveillance and control of communicable diseases related to passenger ships in Europe

This study was conducted within the European SHIPSAN (ship sanitation) project and aims at exploring the legislative framework and current practices related to surveillance of communicable diseases and response aboard passenger ships in Europe. A detailed questionnaire was disseminated and completed by 59 competent authorities in 27 European countries. The majority of competent authorities used national legislation without special provisions for passenger ships. Only 20% had specific provisions for ships regarding quarantine, while a smaller proportion of new Member States (MS) have specific legislation in comparison with old MS (p = 0.01). The Maritime Declaration of Health (MDH) was the main reporting tool used. About 30.5% of the competent authorities declared that they require submission of MDH by all arriving ships, but 28.8% only from affected areas, and 11.9% never require MDH. A total of 45 outbreaks or incidents (36 gastrointestinal, 1 incident of legionellosis, 3 respiratory, and 1 influenza-like illness outbreak, occupational tuberculosis, varicella, scabies, and meningitis) were reported to EU competent authorities during 2006. About 75% of the responders stated that there are gaps in the surveillance and control of communicable diseases. A diversity of approaches in EU countries, and gaps regarding surveillance and response and training needs of personnel were identified.