Biochemical characterization of glucosaminylmuramyldipeptide binding sites of murine macrophages

AbstractBy using radioligand analysis, murine peritoneal macrophages were shown to express several hundred high-affinity cell surface GMDP-binding sites (Ka 350 pM). Photoaffinity labeling followed by SDS-PAGE enabled us to identify 32–34 and 38 kDa proteins inside these cells that bound GMDP specifically

A case of Guillain — Barre syndrome associated with ixodes tick borreliosis and listeriosis

Guillain — Barre syndrome (GBS) is an acute inflammatory demyelinating polyneuropathy, with the autoimmune character of the peripheral nervous system disorder. More than 2/3 of the patients indicate a previous infection caused by Campylobacter jejuni (35 %), Cytomegalovirus (15 %), Epstein — Barr virus (10 %), Mycoplasma pneumoniae (5 %). Acute inflammatory polyneuropathy with listeriosis, which is based on an autoimmune response to infection, is rare; it has an extremely severe course with brain stem structures damage. An immunocompetent patient aged 20 admitted. The disease debuted with a body temperature raised to 38.5 °C, progressive weakness in the legs which reached the umbilical region within 2 days. To the third day of the disease muscular weakness in the hands and pelvic disorders were added in the form of flatal incontinence. On the 4th day of the disease the patient was hospitalized to the neurological (rehanimation) unit. At admission, the consciousness was clear. The examination showed eye slits D = S, pupils D = S, weakness of ocular convergence on both sides, weakness of abduction in all directions, nasolabial asymmetry, medial tongue. The pharyngeal reflex was preserved, the soft palate was movable. Hand tendon reflexes were alive, D = S. Knee jerk and Achilles reflexes were absent on both sides. Muscular strength was reduced to the level of pronounced lower paraparesis in the limbs, and down to 4 points in the hands. Conductive hypoesthesia was revealed from the Th10 level. Meningeal signs were negative. Neurological symptoms increased quickly within 5 days: there was a pronounced upper paraparesis, ophthalmoplegic and bulbar syndromes, respiratory muscle paralysis. A tracheotomy was performed, followed by a transfer to APV. HIV EIA test as of 09.11.2016 showed negative result. SCT revealed no signs of volumetric and focal brain lesions. Cerebral spinal fluid analysis as of 07.11.2016 showed that CSF is clear and transparent, colorless, contains protein 0.71g/l, cytosis makes 1 cell per mcl (lymphocyte), red cell count was 1–3 per mcl, positive Pandy’s test, and glucose ratio of 3.9 mmol/l. IIFT (IgM, liquor) as of 07.11.2016 indentified: negative Rubella virus; measles, mumps, Varicella zoster virus, adenovirus type 3; EBV, capsid antigen; Treponema pallidum; Toxoplasma gondii; HSV type I; negative HSV type II; Coxsackie virus type B1; Coxsackie virus type А7; Echo virus type 7; positive Borrelia afzelii; Borrelia burgdorferi sensu stricto; Borrelia garinii; Listeria monocytogenes 1/2а; Listeria monocytogenes 4b; СМV; negative Hemophilus influenza. PCR (liquor) as of 07.11.2016 showed: no Toxoplasma gondii, Human herpes virus type 6, СМV. IgM antibodies profile to Borrelia antigens in the immunoblotting reaction (blood) as of 09.11.2016 revealed specific antibodies of IgM class to Borrelia garinii (Flagellin, OspC); OspC to Borrelia afzelii — negative; OspC to Borrelia burgdorferi — negative. There was diagnosed Guillain — Barre acute inflammatory-allergic polyneuropathy (Landry type) with pronounced quadriparesis, bulbar syndrome, oculomotor dysfunctions, associated with ixodes tick borreliosis and listeriosis, which were confirmed by IgM revealed to Borrelia garinii (IIFT in the liquor and Western blot reaction in the blood), IgM to Listeria monocytogenes 1/2а, 4b (IIFT in the liquor). The therapy included immunovenin, 5 sessions of plasmapheresis, cefepime, retarpen, cytoflavinum, cycloferonum, ceraxon, actovegin, neuromidin, proserinum, combilipen, diclophenacum, nucleo CMP, mexidol, fluconazole, probiotics, glucose solution, panangin, insulin, L-lysine aescinat, berlithion, suprastin, lasix, berlipril, bisoprololum, tube feeding, APV, microclysters. Since the 48th day of the disease the state of the patient started improving and the rapid recovery of neurological status was observed. Independent breathing restored. The laryngeal-pharyngeal reflexes, sensitive and motor activity in the upper extremities, the function of the pelvic organs restored as well. Legs began moving and became sensitive. The patient was transferred to the neurological department for community-base further care. The described clinical case demonstrated the complexity of etiological diagnosing severe form of acute polyneuropathy with bulbar syndrome. The absence of clinical and epidemiological data enables to suspect ITB and listeriosis as the cause of the disease that emphasizes the role of modern methods of examination of patients suffering from neuroinfection (IIFT, immunoblotting technique, PCR, etc.), with mandatory cerebrospinal fluid testing. The absence of glucocorticosteroid hormones in therapy was a peculiarity of the patient’s treatment

Histoire mondiale

International audienc

Histoire mondiale

International audienc

The synthetic fluorinated tetracarboranylchlorin as a versatile antitumor photoradiosensitizer

Tetrapyrrolic macrocycles are suitable for a variety of chemical modifications aimed at new agents for binary antitumor treatment and diagnosis. Previously we have reported that the conjugation of one single carborane cage to the chlorin e6 macrocycle, a modification designed for tumor sensitization in photodynamic (PDT) and boron neutron capture (BNCT) therapies, yielded the derivative with a higher photosensitizing potency in the models of transplanted rodent tumors. This effect was mechanistically linked to the localization of the carboranylchlorin in membrane organelles due to the carborane moiety. Further exploring the potential of modified tetrapyrrolic compounds as photoradiosensitizers we synthesized the chlorin derivative carrying four closo-carborane cages (44 boron atoms) and 16 fluorine atoms at the periphery of the macrocycle (fluorinated tetracarboranylchlorin, compound 1). For comparison of the properties of 1, its fluorine free congener (tetracarboranylchlorin 6) was obtained. The water soluble 1 and 6 accumulated preferentially in cells selected for resistance to chemotherapeutic drugs (multidrug resistance and cisplatin resistance) than in the parental non-selected counterparts. Compounds 1 and 6 showed a negligible dark cytotoxicity. In contrast, a monochromatic light illumination of cells loaded with low micromolar concentrations of 1 or 6 triggered rapid (within minutes) photonecrosis as determined by the entry of propidium iodide or SYTOX dyes into the parental as well as into resistant cells. In vivo 1 or 6 (up to 80 mg/kg i.p.) caused no general toxicity in Balb/c or C57BL6 mice. Illumination with a monochromatic light of B16 melanoma transplants in mice injected with 5 mg/kg 1 or 6 caused a significant shrinkage of tumor foci, with no re-growth in 77.8% animals by day 21 post PDT. BNCT on C6 rat glioma xenografts in Balb/c nu/nu mice injected i.p. with 5 mg/kg 1 led to a decrease of tumor foci and cure of animals by day 29 whereas the radiosensitizing potency of 6 was less pronounced. This difference was attributable to a limited intratumoral accumulation of 6. Altogether, an extensive modification of the chlorin macrocycle periphery with polyfluorines and polycarboranes yielded potent and well tolerable compounds for PDT and BNCT. © 2020 Elsevier Lt