Palmoplantar Pustulosis: Recent Advances in Etiopathogenesis and Emerging Treatments.

Palmoplantar pustulosis (PPP) is a chronic, recurrent skin disease belonging to the spectrum of psoriasis. It is characterized by an eruption of sterile pustules on the palms and soles. Recent studies in PPP have focused on genetic differences between pustular phenotypes and the role of the innate immunological system and the microbiome in the etiopathogenesis of the disease. Mutations in IL36RN (a major predisposing factor for generalized pustular psoriasis) were found in selected patients with PPP and were associated with earlier disease onset. Studies have shown that the interleukin (IL)-17 and IL-36 pathways might be involved in the pathogenesis of PPP. A microbiome has been demonstrated in the vesicopustules of PPP, and an abundance of Staphylococcus appears to be increased by smoking. Improved understanding of the underlying etiopathogenesis of PPP has led to advances in treatment options, and targeted therapies for PPP have been evaluated or are under evaluation against more than 12 molecules in ongoing clinical trials. These targets include CXCR2 (IL-8 receptor type B), granulocyte colony-stimulating factor receptor, IL-1 receptor, IL-8, IL-12, IL-23, IL-17A, IL-17 receptor, IL-36 receptor, phosphodiesterase-4, and tumor necrosis factor-α.

The upper-airway microbiota and loss of asthma control among asthmatic children.

The airway microbiome has an important role in asthma pathophysiology. However, little is known on the relationships between the airway microbiome of asthmatic children, loss of asthma control, and severe exacerbations. Here we report that the microbiota's dynamic patterns and compositions are related to asthma exacerbations. We collected nasal blow samples (n = 319) longitudinally during a clinical trial at 2 time-points within one year: randomization when asthma is under control, and at time of early loss of asthma control (yellow zone (YZ)). We report that participants whose microbiota was dominated by the commensal Corynebacterium + Dolosigranulum cluster at RD experience the lowest rates of YZs (p = 0.005) and have longer time to develop at least 2 episodes of YZ (p = 0.03). The airway microbiota have changed from randomization to YZ. A switch from the Corynebacterium + Dolosigranulum cluster at randomization to the Moraxella- cluster at YZ poses the highest risk of severe asthma exacerbation (p = 0.04). Corynebacterium's relative abundance at YZ is inversely associated with severe exacerbation (p = 0.002).

Atividade antimicrobiana do oleorresina de copaíba (Copaifera reticulata) frente a Staphylococcus coagulase positiva isolados de casos de otite em cães / Antimicrobial activity of copaiba oil (Copaifera reticulata) against coagulase positive Staphylococcus of canine otitis

The aim of this study was to investigate the antimicrobial activity of the oleoresin Copaifera reticulata Ducke against Staphylococcus coagulase positive (SCP) isolated from otitis externa in dogs. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of the oleoresin were determined by broth microdilution method. In addition, we verified the antimicrobial susceptibility profile of the isolates of SCP by agar diffusion method. Eight classes of antimicrobial were used to calculate the multidrug resistance. The chemical composition of the oleoresin was performed by gas chromatography coupled to the mass spectrometry (GC/MS), and β-caryophyllene, β-bisabolene, and (E)-α-bergamotene were the main compounds found. The copaiba oleoresin showed a MIC90 of 0.164mg/mL and a CBM90 of 1.3mg/mL. The multidrug resistance was found in 27% of the strains tested. The results suggest that copaiba oleoresin has bacteriostatic and bactericidal activity even in multidrug-resistant coagulase-positive strains.

O objetivo do presente trabalho foi investigar o potencial antimicrobiano do oleorresina de Copaifera reticulata Ducke em isolados de Staphylococcus coagulase positiva (SCP) provenientes de casos de otite externa em cães. O método de microdiluição em caldo foi utilizado para determinação da concentração inibitória mínima (CIM) e concentração bactericida mínima (CBM) de oleorresina de copaíba. Em adição, foi determinado o perfil de suscetibilidade aos antimicrobianos dos isolados de SCP pelo método de difusão em ágar. Oito classes de antimicrobianos foram usadas para o cálculo de multirresistência antimicrobiana. A determinação da composição química do oleorresina de copaíba foi realizada por cromatografia em fase gasosa acoplada à espectrometria de massas (GC/MS), sendo que β-cariofileno, β-bisaboleno e (E)-α-bergamoteno foram os compostos majoritários. O oleorresina de copaíba demonstrou CIM90 de 0,164mg/mL e CBM90 de 1,31mg/mL. A multirresistência foi verificada em 27% das cepas testadas. Os resultados sugerem que o oleorresina de copaíba exerceu atividade bacteriostática e bactericida mesmo em cepas multirresistentes de Staphylococcus coagulase-positiva.

Veronate (Inhibitex).

Inhibitex, under license from BioResearch, is developing Veronate, an antibody-based immunotherapy for the potential prevention of Staphylococcus epidermidis, Staphylococcus aureus and Candida infections in very-low-birth-weight infants. Phase III clinical trials of Veronate are ongoing.

Presence of glutamine at position 74 of pocket 4 in the BoLA-DR antigen binding groove is associated with occurrence of clinical mastitis caused by Staphylococcus species.

Potential relationships between amino acid motifs in the antigen binding groove of various alleles of the bovine major histocompatibility complex DR (BoLA-DR) molecule and occurrence of clinical mastitis caused by Staphylococcus species (non-Staphylococcus aureus) were investigated in a case-control study. A significant association (P< or =0.05) was detected between the presence of glutamic acid at position beta 74 and occurrence of mastitis caused by Staphylococcus spp. with a relative risk of 11. This motif is present in BoLA-DRB3.2*22, *23 and *24 alleles. Presence of a positively charged residue (arginine or lysine) at position 13 also showed a tendency (P< o r=0.1) towards an association with a higher risk of clinical mastitis caused by the same bacteria. This motif is present in BoLA-DRB3.2*23 and *8 alleles. Similarly, presence of arginine at position beta 71 (present in alleles *23 and *22) was associated with occurrence of this disease. These positions (beta 13, beta 71 and beta 74) form pocket 4 of the antigen binding groove, which plays an instrumental role in antigen binding and recognition by T-lymphocytes. Thus, it can be concluded that pocket 4 of the BoLA-DR molecule is involved in conferring susceptibility to clinical mastitis caused by Staphylococcus spp.

[The use of plasma from donor convalescent patients in the combined treatment of peritonitis]. / Primenenie plazmy donorov-rekonvalestsentov v kompleksnom lechenii peritonita.

The article analyses the treatment of 12 patients with diffuse purulent peritonitis in whom the titers of specific antibodies against microflora causing peritonitis were corrected in the period of secondary immunodeficiency. The authors suggest a new method for the treatment of peritonitis which is based on inclusion of convalescents' plasma after peritonitis in the therapeutic complex. This plasma contains specific antibodies against the cultured microflora in high titers and is a polyvalent hyperimmune medium which makes it possible to cause an effect on the level of humoral immunity. This improved the results of treatment: the titres of specific antibodies against the cultured microflora grew, such complications of diffuse peritonitis as the formation of circumscribed abscesses in the abdominal cavity and suppuration of the postoperative wound were encountered less frequently, mortality reduced by 16.6% as compared to the control group. The efficacy of the suggested methods was also proved in experiments on 164 animals.

[Effect of terrilytin on the activity of nonspecific resistance factors during immunization with staphylococcal anatoxin and staphylococcal infection]. / Vliianie terrilitina na aktivnost' faktorov nespetsificheskoi rezistentnosti pri immunizatsii stafilokokkovom anatoksinom i infitsirovanii stafilokokkom.

Terrilytin and immobilized terrilytin enhance the activity and intensity of phagocytosis and increase the concentration of lysozyme in nonimmunized animals. Both preparations increase the production of antibodies to staphylococcal alpha-hemolysin, the titers of beta-lysins, the activity and intensity of the phagocytosis of bacterial cells by peripheral blood leukocytes in animals immunized with staphylococcal toxoid and challenged with live staphylococcal culture. In healthy animals terrilytin and immobilized terrilytin induce an increase in total proteolytic activity and in the activity of alpha-1-antitrypsin and alpha-2-macroglobulin, decreased as the result of staphylococcal infection.

[Enhancement of antitoxic immunity in newborn infants by peroral administration of donor antistaphylococcal immunoglobulin]. / Povyshenie antitoksicheskogo immuniteta u novorozhdennykh detei putem peroral'nogo vvedeniia donorskogo antistafilokokkovogo immunoglobulina.

The possibility of enhancing specific immunity by the oral administration of homologous antistaphylococcal immunoglobulin in a dose of 50 I. U./kg b. w. before the first feeding was shown in 75 newborn infants with a high risk of staphylococcal infection. 24 hours after the first administration of Ig the titer of staphylococcal anti-alpha toxin in the blood rose from 0.68 +/- 0.05 I. U./ml to 2.9 +/- 0.14 I. U/ml, on day 7 this titer persisted at the level of 2.86 +/- 0.12 I. U./ml, and 3 months later the titer was 1.5 +/- 0.05 I. U./ml. No side effects were observed. In the reference group (50 infants) antitoxic titers remained low. No suppurative-septic diseases were observed in the test group within 3 months, while in the controls, focal forms of staphylococcal infection (12 cases) and sepsis (1 case) were registered.

[Experimental study of the immunological activity of a preparation made from the antigenic complexes of opportunistic microorganisms administered by different routes]. / Eksperimental'noe izuchenie immunologicheskoi aktivnosti preparata iz antigennykh kompleksov uslovno-patogennykh mikroorganizmov pri razlichnykh sposobakh vvedeniia.

The data obtained in the experimental study of the humoral factors of local and systemic immunity, as well as the morphofunctional changes of internal organs, after multiple subcutaneous and aerosol immunization with the combined preparation of Proteus, Staphylococcus, Klebsiella pneumoniae and Escherichia coli antigens (preparation nC-4) are presented. The subcutaneous and aerosol administration of preparation nC-4 has been found to induce an increase in the levels of antibodies to all components of the preparation in the blood serum and in respiratory tract secretions. The introduction of the preparation through the respiratory tract resulted in an earlier intensive accumulation of specific antibodies and IgA in respiratory tract secretions. The results of the quantitative cytological study of respiratory tract secretions and the morphofunctional changes of the lymphoid tissue associated with the lungs are indicative of an important role played by cell-mediated immunity factors in the formation of local postvaccinal immunity.

[Development and trial of a heterogenous antistaphylococcal gamma-globulin]. / Razrabotka i ispytaniie geterogennogo protivostafilokokkogo gamma-globulina.

Antitoxic and antibacterial equine gamma globulin for the treatment of staphylococcal infection has been developed and introduced into medical practice. The pronounced effectiveness of the preparation has been demonstrated in comparison with the ineffectiveness of traditional therapeutic measures. The development of mild forms of the serum disease in 33% of cases indicates that further investigations on the purification of gamma globulin preparations are necessary.

[Elimination of Klebsiella pneumoniae and humoral immunity in immunization with the IS-4 immunostimulating mixture]. / Eliminatsiia klebsielly pnevmonii i gumoral'nyi immunitet pri immunizatsii immunostimuliruiushchei smesi IS-4.

The present investigation has revealed that in mice, immunized with preparation HC-4 (an immunostimulating agent consisting of water-soluble antigenic complexes obtained from 4 opportunistic microorganisms: Klebsiella pneumoniae, staphylococcus, Proteus and Escherichia coli K-100 having a common antigen with Haemophilus influenzae) and challenged with K. pneumoniae culture on day 7 after immunization, the complete elimination of K. pneumoniae from the blood occurs within 24 hours. The subcutaneous immunization of rabbits with the above preparation leads to a significant increase in antibody titers, determined in the passive hemagglutination test with Klebsiella diagnosticum. The test of the passive protection of mice from Klebsiella sepsis has revealed a rise in the preventive activity of the sera of rabbits immunized with this preparation.

[Immunological status and the condition of local defense factors in patients with various forms of chronic bronchitis treated by using performed physical factors]. / Immunnyi status i sostoianie mestnykh faktorov zashchity u bol'nykh s razlichnymi formami khronicheskogo bronkhita, lechennykh s ispol'zovaniem performirovannykh fizicheskikh faktorov.

Physiotherapeutic and other methods were employed for the treatment of patients with chronic nonobstructive bronchitis (CNB), chronic bronchitis with transient obstruction of the small bronchi of inflammatory genesis, chronic asthmatic bronchitis (CAB) and chronic obstructive bronchitis (COB). The level of secretory IgA and relative E-RFC number in the bronchial wash off, lysozyme concentration, the level of IgA and titer of heterophilic normal antibodies in the saliva were assessed. The content of T- and B-lymphocytes in the blood was studied. The results were assessed with a method of discrete-dynamic analysis. It was established that the incorporation of inductothermia with ethonium-electrophoresis and the magnetic field effect on the thyroid in CAB and inductothermia with ethonium-electrophoresis in COB in the complex of therapeutic measures produced a positive effect. In CNB (inactive phase) and COB patients inductothermia resulted in restoration of some interrelationships in the immune system whereas in CAB patients in their dysbalance. Different changes in the levels of interrelationships of certain parameters of the immune system were observed in the incorporation of sinusoidal modulated currents in the therapeutic complexes.

[Effect of hyperbaric oxygenation on delayed hypersensitivity and antibody formation in patients with peritonitis]. / Vliianie giperbaricheskoi oksigenatsii na giperchuvstvitel'nost zamedlennogo tipa i antiteloobrazovanie u bol'nykh peritonitom.

The inhibition of the formation of hypersensitivity of delayed type to staphylococcus, Proteus, blue pus bacillus and Escherichia coli was found in patients with peritonitis given complex treatment including hyperbaric oxygenation, against the background of stimulation of the antibody formation to these bacteria. The level of staphylococcal alfa-antitoxin in the blood serum remained substantially lower than that of healthy people whether the treatment included HBO or not. The data obtained show the expediency of early use of HBO in patients with peritonitis.

[Experimental study of the immunogenicity of a monopreparation of Klebsiella pneumoniae antigen complex and its association with Staphylococcus, Proteus and Escherichia coli antigens]. / Eksperimental'noe izuchenie immunogennosti monopreparata antigennogo kompleksa klebsielly pnevmonii i ego assotsiatsiei s antigenami stafilokokka, proteia i kishechnoi palochki.

The study carried out in mice with experimental Klebsiella sepsis has revealed that Staphylococcus, Proteus and E. coli antigenic complexes used as monovaccines ensure the protection of a definite percentage of the animals from K. pneumoniae infection. The mixture of these 3 preparations possesses a higher protective potency. The immunogenic potency of K. pneumoniae antigenic complex used as a component of combined vaccines with 2 or 4 components has proved to be sufficiently high and not inferior to the potency of K. pneumoniae monovaccine.

[Experimental study of the therapeutic action of the surface antigenic complex of Staphylococcus]. / Eksperimental'noe izuchenie lechebnogo deistviia poverkhnostnogo antigennogo kompleksa stafilokokka.

The comparative experimental study of the therapeutic action of staphylococcal antigenic complex obtained by the method of aqueous extraction, corpuscular formalinized vaccine and commercial staphylococcal preparations (native toxoid and antiphagin) revealed the statistically significant difference in the process of the healing of local dermatonecrotic inflammation in the rabbits treated with staphylococcal antigenic complex in comparison with the untreated rabbits.

[Secretory antibodies to homologous and heterologous strains of staphylococci in rabbit colostrum]. / Sekretornye antitela k gomologichnomu i geterologichnym shtammam stafilokokka v molozive krolikov.

The titers of agglutinins to homologous and heterologous staphylococcal strains in the colostric sera of female rabbits immunized into the mammary gland tissue and in the colostric and blood sera of the control female rabbits were studied. Immunization into the mammary gland tissue induced an increase in the titers of colostric antibodies to both homologous and heterologous staphylococcal strains (1:320 and 1:160, respectively). Secretory IgA were predominant among antistaphylococcal antibodies in rabbit colostrum.

[Effect of lincomycin, chymotrypsin and their combinations on the splenic plasmacytic reaction and the antibody titer in experimental staphylococcal infection]. / Vliianie linkomitsina i khimotripsina i ikh sochetanii na plazmotsitarnuiu reaktsiiu selezenki i titr antitel pri eksperimental'noi stafilokokkovoi infektsii.

The effect of lincomycin, chymotrypsin and their combinations on the plasmocytic reaction of the spleen and agglutinin titer in mice with experimental staphylococcal infection was studied. The infected mice were divided into 4 groups: the 1st group included untreated infected animals, the 2nd, 3rd and 4th groups consisted of the mice treated with lincomycin, chymotrypsin and their combinations respectively. Lincomycin and chymotrypsin were used in doses of 150 and 2 mg/kg respectively. By the 3rd, 7th, 14th and 21st day of the infection and treatment the animals were decapitated, th blood was collected for determination of the staphylococcal agglutinin titers in the serum, the spleens were removed for investigation of the plasmocytic reaction. It was shown that the treatment of the experimental staphylococcal infection with lincomycin resulted in decreased proliferation of the plasmatic cells and antibody formation. The use of chymotrypsin resulted in increased proliferation of the plasmatic cells and specific antibody titer. The use of chymotrypsin in conjunction with lincomycin lowered the suppressing effect of the latter on the above indices.