60 research outputs found
Systemic Immune Responses in Alzheimerβs Disease: In Vitro Mononuclear Cell Activation and Cytokine Production
To investigate the systemic signs of immune-inflammatory responses in Alzheimerβs disease (AD), in the present study
we have analyzed blood lymphocyte subsets and the expression of activation markers on peripheral blood mononuclear cells
(PBMCs) fromADpatients and age-matched healthy controls (HC) activated in vitro by recombinant amyloid-Ξ² peptide (rAΞ²42).
Our study of AD lymphocyte subpopulations confirms the already described decrease of the absolute number and percentage of
B cells when compared to HC lymphocytes, whereas the other subsets are not significantly different in patients and controls.
We report the increased expression of the activation marker CD69 and of the chemokine receptors CCR2 and CCR5 on T cells
but no changes of CD25 after activation. B cells are also activated by rAΞ²42 as demonstrated by the enhanced expression of
CCR5. Moreover, rAΞ²42 induces an increased expression of the scavenger receptor CD36 on monocytes. Some activation
markers and chemokine receptors are overexpressed in unstimulated AD cells when compared to controls. This is evidence of
the pro-inflammatory status of AD. Stimulation by rAΞ²42 also induces the production of the pro-inflammatory cytokines IL-1Ξ²,
IL-6, IFN-Ξ³, and TNF-Ξ±, and of the anti-inflammatory cytokines IL-10 and IL-1Ra. The chemokines RANTES, MIP-1Ξ², and
eotaxin as well as some growth factors (GM-CSF, G-CSF) are also overproduced by AD-derived PBMC activated by rAΞ²42.
These results support the involvement of systemic immunity in AD patients. However, our study is an observational one so we
cannot draw a conclusion about its contribution to the pathophysiology of the disease
Facile Preparation of N-Glycosylated 10-Piperazinyl Artemisinin Derivatives and Evaluation of Their Antimalarial and Cytotoxic Activities
According to the precepts that C-10 amino-artemisinins display optimum biological
activities for the artemisinin drug class, and that attachment of a sugar enhances specificity of drug
delivery, polarity and solubility so as to attenuate toxicity, we assessed the effects of attaching sugars
to N-4 of the dihydroartemisinin (DHA)-piperazine derivative prepared in one step from DHA and
piperazine. N-Glycosylated DHA-piperazine derivatives were obtained according to the Kotchetkov
reaction by heating the DHA-piperazine with the sugar in a polar solvent. Structure of the D-glucose
derivative is secured by X-ray crystallography. The D-galactose, L-rhamnose and D-xylose derivatives
displayed IC50 values of 0.58\u20130.87 nM against different strains of Plasmodium falciparum (Pf ) and
selectivity indices (SI) >195, on average, with respect to the mouse fibroblast WEHI-164 cell line.
These activities are higher than those of the amino-artemisinin, artemisone (IC50 0.9\u20131.1 nM). Notably,
the D-glucose, D-maltose and D-ribose derivatives were the most active against the myelogenous
leukemia K562 cell line with IC50 values of 0.78\u20130.87 M and SI > 380 with respect to the human
dermal fibroblasts (HDF). In comparison, artemisone has an IC50 of 0.26 M, and a SI of 88 with
the same cell lines. Overall, the N-glycosylated DHA-piperazine derivatives display antimalarial
activities that are greatly superior to O-glycosides previously obtained from DHA
Salinomycin and Other Ionophores as a New Class of Antimalarial Drugs with Transmission-Blocking Activity
The drug target profile proposed by the Medicines for Malaria Venture for a malaria elimination/eradication policy focuses on molecules active on both asexual and sexual stages of Plasmodium, thus with both curative and transmission-blocking activities. The aim of the present work was to investigate whether the class of monovalent ionophores, which includes drugs used in veterinary medicine and that were recently proposed as human anticancer agents, meets these requirements. The activity of salinomycin, monensin, and nigericin on Plasmodium falciparum asexual and sexual erythrocytic stages and on the development of the Plasmodium berghei and P. falciparum mosquito stages is reported here. Gametocytogenesis of the P. falciparum strain 3D7 was induced in vitro, and gametocytes at stage II and III or stage IV and V of development were treated for different lengths of time with the ionophores and their viability measured with the parasite lactate dehydrogenase (pLDH) assay. The monovalent ionophores efficiently killed both asexual parasites and gametocytes with a nanomolar 50% inhibitory concentration (IC50). Salinomycin showed a fast speed of kill compared to that of standard drugs, and the potency was higher on stage IV and V than on stage II and III gametocytes. The ionophores inhibited ookinete development and subsequent oocyst formation in the mosquito midgut, confirming their transmission-blocking activity. Potential toxicity due to hemolysis was excluded, since only infected and not normal erythrocytes were damaged by ionophores. Our data strongly support the downstream exploration of monovalent ionophores for repositioning as new antimalarial and transmission-blocking leads
Salinomycin and other ionophores as a new class of antimalarial drugs with transmission-blocking activity
The drug target profile proposed by the Medicines for Malaria Venture for a malaria elimination/eradication policy focuses on molecules active on both asexual and sexual stages of Plasmodium, thus with both curative and transmission-blocking activities. The aim of the present work was to investigate whether the class of monovalent ionophores, which includes drugs used in veterinary medicine and that were recently proposed as human anticancer agents, meets these requirements. The activity of salinomycin, monensin, and nigericin on Plasmodium falciparum asexual and sexual erythrocytic stages and on the development of the Plasmodium berghei and P. falciparum mosquito stages is reported here. Gametocytogenesis of the P. falciparum strain 3D7 was induced in vitro, and gametocytes at stage II and III or stage IV and V of development were treated for different lengths of time with the ionophores and their viability measured with the parasite lactate dehydrogenase (pLDH) assay. The monovalent ionophores efficiently killed both asexual parasites and gametocytes with a nanomolar 50% inhibitory concentration (IC50). Salinomycin showed a fast speed of kill compared to that of standard drugs, and the potency was higher on stage IV and V than on stage II and III gametocytes. The ionophores inhibited ookinete development and subsequent oocyst formation in the mosquito midgut, confirming their transmission-blocking activity. Potential toxicity due to hemolysis was excluded, since only infected and not normal erythrocytes were damaged by ionophores. Our data strongly support the downstream exploration of monovalent ionophores for repositioning as new antimalarial and transmission-blocking leads
The T.O.S.C.A. Project: Research, Education and Care
Despite recent and exponential improvements in diagnostic-
therapeutic pathways, an existing βGAPβ has been revealed
between the βreal world careβ and the βoptimal careβ
of patients with chronic heart failure (CHF). We present the
T.O.S.CA. Project (Trattamento Ormonale dello Scompenso
CArdiaco), an Italian multicenter initiative involving different
health care professionals and services aiming to explore the
CHF βmetabolic pathophysiological modelβ and to improve
the quality of care of HF patients through research and continuing
medical education
ΠΠΎΡΠ»Π΅Π΄ΠΎΠ²Π°ΡΠ΅Π»ΡΠ½ΠΎΡΡΡ Π΄Π΅ΠΉΡΡΠ²ΠΈΠΉ ΠΏΡΠΈ Π²ΠΈΠ·ΡΠ°Π»ΠΈΠ·Π°ΡΠΈΠΈ ΠΊΡΠΎΠ²ΠΎΠΈΠ·Π»ΠΈΡΠ½ΠΈΠΉ/Π³Π΅ΠΌΠ°ΡΠΎΠΌ ΠΌΡΠ³ΠΊΠΈΡ ΡΠΊΠ°Π½Π΅ΠΉ Ρ ΠΏΠΎΠΆΠΈΠ»ΡΡ Π±ΠΎΠ»ΡΠ½ΡΡ , ΠΈΠ½ΡΠΈΡΠΈΡΠΎΠ²Π°Π½Π½ΡΡ SARS-CoV-2
Aim. To determine ultrasound, computed tomography and angiographic image characteristics for soft tissue hemorrhages/hematomas, the sequence of using imaging methods in patients infected with SARS-CoV-2, to study the morphology of changes in soft tissues, to determine the essence of the concept and to develop treatment tactics for this complication of COVID-19.Material and methods. During 4 months of treatment of elderly patients (+60) infected with SARS-CoV-2, 40 patients were identified with soft tissue hemorrhages/hematomas, of which 26 (65%) patients with large hematomas (>10 cm in size and > 1000 ml in volume). The analysis of clinical and laboratory parameters, methods of instrumental diagnostics (ultrasound β 26 patients, CT β 10 patients, angiography β 9 patients, punctures β 6 patients) was carried out; autopsy material was studied in 11 cases.Results. Image characteristics of hemorrhages/hematomas of soft tissue density were obtained using modern instrumental methods, and the sequence of application of visualization methods was determined. A tactic for managing a patient with stopped and ongoing bleeding has been developed. The morphological substrate of hemorrhagic complications in a new viral infection was studied. All patients were treated with conservative and minimally invasive procedures (embolization, puncture with pressure bandage). 15 patients (57.7%) recovered, 11 patients (42.3%) died from the progression of COVID-19 complications.Conclusion. Comprehensive clinical and laboratory sequential instrumental diagnosis of soft tissue hemorrhages in COVID-19. Treatment should be conservative and significantly invasive. The use of the term βsoft tissue hematomaβ in SARS-CoV-2 infected patients is not a natural quality of the normal pathological process and should not be observed from our point of view.Π¦Π΅Π»Ρ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡ: ΠΎΠΏΡΠ΅Π΄Π΅Π»ΠΈΡΡ Π²ΠΈΠ·ΡΠ°Π»ΡΠ½ΡΠ΅ ΡΠ»ΡΡΡΠ°Π·Π²ΡΠΊΠΎΠ²ΡΠ΅, ΠΊΠΎΠΌΠΏΡΡΡΠ΅ΡΠ½ΠΎ-ΡΠΎΠΌΠΎΠ³ΡΠ°ΡΠΈΡΠ΅ΡΠΊΠΈΠ΅ ΠΈ Π°Π½Π³ΠΈΠΎΠ³ΡΠ°ΡΠΈΡΠ΅ΡΠΊΠΈΠ΅ ΠΊΡΠΈΡΠ΅ΡΠΈΠΈ ΠΌΡΠ³ΠΊΠΎΡΠΊΠ°Π½Π½ΡΡ
ΠΊΡΠΎΠ²ΠΎΠΈΠ·Π»ΠΈΡΠ½ΠΈΠΉ/Π³Π΅ΠΌΠ°ΡΠΎΠΌ, ΠΏΠΎΡΠ»Π΅Π΄ΠΎΠ²Π°ΡΠ΅Π»ΡΠ½ΠΎΡΡΡ ΠΈΡΠΏΠΎΠ»ΡΠ·ΠΎΠ²Π°Π½ΠΈΡ ΠΌΠ΅ΡΠΎΠ΄ΠΎΠ² Π²ΠΈΠ·ΡΠ°Π»ΠΈΠ·Π°ΡΠΈΠΈ Ρ Π±ΠΎΠ»ΡΠ½ΡΡ
, ΠΈΠ½ΡΠΈΡΠΈΡΠΎΠ²Π°Π½Π½ΡΡ
SARS-CoV-2, ΠΈΠ·ΡΡΠΈΡΡ ΠΌΠΎΡΡΠΎΠ»ΠΎΠ³ΠΈΡ ΠΈΠ·ΠΌΠ΅Π½Π΅Π½ΠΈΠΉ Π² ΠΌΡΠ³ΠΊΠΈΡ
ΡΠΊΠ°Π½ΡΡ
, ΠΎΠΏΡΠ΅Π΄Π΅Π»ΠΈΡΡ ΡΡΡΡ ΠΏΠΎΠ½ΡΡΠΈΡ ΠΈ Π²ΡΡΠ°Π±ΠΎΡΠ°ΡΡ Π»Π΅ΡΠ΅Π±Π½ΡΡ ΡΠ°ΠΊΡΠΈΠΊΡ ΠΏΡΠΈ ΡΠ°ΠΊΠΎΠΌ ΠΎΡΠ»ΠΎΠΆΠ½Π΅Π½ΠΈΠΈ COVID-19.ΠΠ°ΡΠ΅ΡΠΈΠ°Π» ΠΈ ΠΌΠ΅ΡΠΎΠ΄Ρ. ΠΠ° 4 ΠΌΠ΅Ρ Π»Π΅ΡΠ΅Π½ΠΈΡ ΠΏΠΎΠΆΠΈΠ»ΡΡ
Π±ΠΎΠ»ΡΠ½ΡΡ
(+60), ΠΈΠ½ΡΠΈΡΠΈΡΠΎΠ²Π°Π½Π½ΡΡ
SARS-CoV-2, Π²ΡΡΠ²Π»Π΅Π½ΠΎ 40 ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠ² Ρ ΠΌΡΠ³ΠΊΠΎΡΠΊΠ°Π½Π½ΡΠΌΠΈ ΠΊΡΠΎΠ²ΠΎΠΈΠ·Π»ΠΈΡΠ½ΠΈΡΠΌΠΈ/Π³Π΅ΠΌΠ°ΡΠΎΠΌΠ°ΠΌΠΈ, ΠΈΠ· Π½ΠΈΡ
26 (65%) ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠ² Ρ Π±ΠΎΠ»ΡΡΠΈΠΌΠΈ Π³Π΅ΠΌΠ°ΡΠΎΠΌΠ°ΠΌΠΈ (ΡΠ°Π·ΠΌΠ΅Ρ >10 ΡΠΌ ΠΈ ΠΎΠ±ΡΠ΅ΠΌ> 1000 ΠΌΠ»). ΠΡΠΎΠ²Π΅Π΄Π΅Π½ Π°Π½Π°Π»ΠΈΠ· ΠΊΠ»ΠΈΠ½ΠΈΠΊΠΎ-Π»Π°Π±ΠΎΡΠ°ΡΠΎΡΠ½ΡΡ
ΠΏΠΎΠΊΠ°Π·Π°ΡΠ΅Π»Π΅ΠΉ, ΠΌΠ΅ΡΠΎΠ΄ΠΎΠ² ΠΈΠ½ΡΡΡΡΠΌΠ΅Π½ΡΠ°Π»ΡΠ½ΠΎΠΉ Π΄ΠΈΠ°Π³Π½ΠΎΡΡΠΈΠΊΠΈ (Π£ΠΠ β 26 ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠ², ΠΠ’ β 10 ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠ², Π°Π½Π³ΠΈΠΎΠ³ΡΠ°ΡΠΈΡ β 9 Π±ΠΎΠ»ΡΠ½ΡΡ
, ΠΏΡΠ½ΠΊΡΠΈΠΈ β 6 ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠ²), Π² 11 ΡΠ»ΡΡΠ°ΡΡ
ΠΈΠ·ΡΡΠ΅Π½ ΠΌΠ°ΡΠ΅ΡΠΈΠ°Π» Π°ΡΡΠΎΠΏΡΠΈΠΈ.Π Π΅Π·ΡΠ»ΡΡΠ°ΡΡ. Π‘ΠΎΠ²ΡΠ΅ΠΌΠ΅Π½Π½ΡΠΌΠΈ ΠΈΠ½ΡΡΡΡΠΌΠ΅Π½ΡΠ°Π»ΡΠ½ΡΠΌΠΈ ΠΌΠ΅ΡΠΎΠ΄Π°ΠΌΠΈ ΠΏΠΎΠ»ΡΡΠ΅Π½Π° Π²ΠΈΠ·ΡΠ°Π»ΡΠ½Π°Ρ Ρ
Π°ΡΠ°ΠΊΡΠ΅ΡΠΈΡΡΠΈΠΊΠ° ΠΊΡΠΎΠ²ΠΎ ΠΈΠ·Π»ΠΈΡΠ½ΠΈΠΉ/Π³Π΅ΠΌΠ°ΡΠΎΠΌ ΠΌΡΠ³ΠΊΠΎΡΠΊΠ°Π½Π½ΠΎΠΉ ΠΏΠ»ΠΎΡΠ½ΠΎΡΡΠΈ, ΠΎΠΏΡΠ΅Π΄Π΅Π»Π΅Π½Π° ΠΏΠΎΡΠ»Π΅Π΄ΠΎΠ²Π°ΡΠ΅Π»ΡΠ½ΠΎΡΡΡ ΠΏΡΠΈΠΌΠ΅Π½Π΅Π½ΠΈΡ ΠΌΠ΅ΡΠΎΠ΄ΠΎΠ² Π²ΠΈΠ·ΡΠ°Π»ΠΈΠ·Π°ΡΠΈΠΈ. Π Π°Π·ΡΠ°Π±ΠΎΡΠ°Π½Π° ΡΠ°ΠΊΡΠΈΠΊΠ° Π²Π΅Π΄Π΅Π½ΠΈΡ ΠΏΠ°ΡΠΈΠ΅Π½ΡΠ° ΠΏΡΠΈ ΠΎΡΡΠ°Π½ΠΎΠ²ΠΈΠ²ΡΠ΅ΠΌΡΡ ΠΈ ΠΏΡΠΎΠ΄ΠΎΠ»ΠΆΠ°ΡΡΠ΅ΠΌΡΡ ΠΊΡΠΎΠ²ΠΎΡΠ΅ΡΠ΅Π½ΠΈΠΈ. ΠΠ·ΡΡΠ΅Π½ ΠΌΠΎΡΡΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΈΠΉ ΡΡΠ±ΡΡΡΠ°Ρ Π³Π΅ΠΌΠΎΡΡΠ°Π³ΠΈΡΠ΅ΡΠΊΠΎΠ³ΠΎ ΠΎΡΠ»ΠΎΠΆΠ½Π΅Π½ΠΈΡ ΠΏΡΠΈ Π½ΠΎΠ²ΠΎΠΉ Π²ΠΈΡΡΡΠ½ΠΎΠΉ ΠΈΠ½ΡΠ΅ΠΊΡΠΈΠΈ. ΠΡΠ΅ Π±ΠΎΠ»ΡΠ½ΡΠ΅ ΠΏΡΠΎΠ»Π΅ΡΠ΅Π½Ρ ΠΊΠΎΠ½ΡΠ΅ΡΠ²Π°ΡΠΈΠ²Π½ΡΠΌΠΈ ΠΈ ΠΌΠΈΠ½ΠΈΠΌΠ°Π»ΡΠ½ΠΎ ΠΈΠ½Π²Π°Π·ΠΈΠ²Π½ΡΠΌΠΈ ΠΏΡΠΎΡΠ΅Π΄ΡΡΠ°ΠΌΠΈ (ΡΠΌΠ±ΠΎΠ»ΠΈΠ·Π°ΡΠΈΡ, ΠΏΡΠ½ΠΊΡΠΈΡ Ρ Π΄Π°Π²ΡΡΠ΅ΠΉ ΠΏΠΎΠ²ΡΠ·ΠΊΠΎΠΉ). ΠΡΠ·Π΄ΠΎΡΠΎΠ²Π΅Π»ΠΈ 15 (57,7%) ΠΏΠ°ΡΠΈΠ΅Π½ΡΠΎΠ², ΡΠΌΠ΅ΡΠ»ΠΈ ΠΎΡ ΠΏΡΠΎΠ³ΡΠ΅ΡΡΠΈΡΠΎΠ²Π°Π½ΠΈΡ ΠΎΡΠ»ΠΎΠΆΠ½Π΅Π½ΠΈΠΉ COVID-19 11 (42,3%) Π±ΠΎΠ»ΡΠ½ΡΡ
.ΠΠ°ΠΊΠ»ΡΡΠ΅Π½ΠΈΠ΅. ΠΠΎΠΌΠΏΠ»Π΅ΠΊΡΠ½Π°Ρ ΠΊΠ»ΠΈΠ½ΠΈΠΊΠΎ-Π»Π°Π±ΠΎΡΠ°ΡΠΎΡΠ½Π°Ρ ΠΏΠΎΡΠ»Π΅Π΄ΠΎΠ²Π°ΡΠ΅Π»ΡΠ½Π°Ρ ΠΈΠ½ΡΡΡΡΠΌΠ΅Π½ΡΠ°Π»ΡΠ½Π°Ρ Π΄ΠΈΠ°Π³Π½ΠΎΡΡΠΈΠΊΠ° ΠΌΡΠ³ΠΊΠΎΡΠΊΠ°Π½Π½ΡΡ
ΠΊΡΠΎΠ²ΠΎΠΈΠ·Π»ΠΈΡΠ½ΠΈΠΉ ΠΏΡΠΈ COVID-19-ΠΈΠ½ΡΠ΅ΠΊΡΠΈΠΈ ΠΏΠΎΠ·Π²ΠΎΠ»ΡΠ΅Ρ ΡΠ²ΠΎΠ΅Π²ΡΠ΅ΠΌΠ΅Π½Π½ΠΎ ΡΡΡΠ°Π½ΠΎΠ²ΠΈΡΡ ΡΠΎΠΏΠΈΡΠ΅ΡΠΊΠΈΠΉ Π΄ΠΈΠ°Π³Π½ΠΎΠ·, ΠΎΡΠ΅Π½ΠΈΡΡ ΡΡΠΆΠ΅ΡΡΡ ΠΊΡΠΎΠ²ΠΎΠΏΠΎΡΠ΅ΡΠΈ, Π΅Π΅ ΠΎΡΡΠ°Π½ΠΎΠ²ΠΊΡ ΠΈΠ»ΠΈ ΠΏΡΠΎΠ΄ΠΎΠ»ΠΆΠ΅Π½ΠΈΠ΅ ΠΊΡΠΎΠ²ΠΎΡΠ΅ΡΠ΅Π½ΠΈΡ. ΠΠ΅ΡΠ΅Π½ΠΈΠ΅ Π΄ΠΎΠ»ΠΆΠ½ΠΎ Π½ΠΎΡΠΈΡΡ ΠΊΠΎΠ½ΡΠ΅ΡΠ²Π°ΡΠΈΠ²Π½ΡΠΉ ΠΈ ΠΌΠΈΠ½ΠΈΠΌΠ°Π»ΡΠ½ΠΎ ΠΈΠ½Π²Π°Π·ΠΈΠ²Π½ΡΠΉ Ρ
Π°ΡΠ°ΠΊΡΠ΅Ρ. ΠΡΠΏΠΎΠ»ΡΠ·ΠΎΠ²Π°Π½ΠΈΠ΅ ΡΠ΅ΡΠΌΠΈΠ½Π° βΠ³Π΅ΠΌΠ°ΡΠΎΠΌΠ°β ΠΌΡΠ³ΠΊΠΈΡ
ΡΠΊΠ°Π½Π΅ΠΉ Ρ ΠΈΠ½ΡΠΈΡΠΈΡΠΎΠ²Π°Π½Π½ΡΡ
SARS-CoV-2 Π±ΠΎΠ»ΡΠ½ΡΡ
Π½Π΅ ΠΎΡΡΠ°ΠΆΠ°Π΅Ρ ΡΡΡΡ ΠΏΡΠΎΠΈΡΡ
ΠΎΠ΄ΡΡΠ΅Π³ΠΎ ΠΏΠ°ΡΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΎΠ³ΠΎ ΠΏΡΠΎΡΠ΅ΡΡΠ° ΠΈ, Ρ Π½Π°ΡΠ΅ΠΉ ΡΠΎΡΠΊΠΈ Π·ΡΠ΅Π½ΠΈΡ, Π½Π΅ Π΄ΠΎΠ»ΠΆΠ½ΠΎ ΠΈΡΠΏΠΎΠ»ΡΠ·ΠΎΠ²Π°ΡΡΡΡ
Indole derivatives useful for treating resistance to antitumor agents
The use of a group of indole compounds of formula (I) is described for treating tumours which have developed resistance to antitumour drugs. The compounds of formula (I) can be used in monotherapy, to treat tumours affected by drug resistance, or in co-therapy, as synergistic enhancers of the action of the aforesaid antitumour drugs. In addition, pharmaceutical compositions are described which comprise the indole derivatives of formula (I) in association with antitumour drugs the activity of which is to be enhance
Indole and Azaindole Derivatives For the Treatment of Inflammatory and Autoimmune Diseases
The use is described of compounds of formula (I) wherein A is chosen from a phenyl or a heterocyclic ring with 5 or 6 members containing up to two heteroatoms chosen from nitrogen, oxygen and sulfur, X and Y represent carbon or nitrogen, and R1-R6 are as described in the specification, in the prevention and/or treatment of inflammatory and autoimmune diseases
- β¦