Periodontitis, Dental Procedures, and Young-Onset Cryptogenic Stroke.

Periodontitis is associated with an increased risk of ischemic stroke, and the risk may be particularly high among young people with unexplained stroke etiology. Thus, we investigated in a case-control study whether periodontitis or recent invasive dental treatments are associated with young-onset cryptogenic ischemic stroke (CIS). We enrolled participants from a multicenter case-control SECRETO study including adults aged 18 to 49 y presenting with an imaging-positive first-ever CIS and stroke-free age- and sex-matched controls. Thorough clinical and radiographic oral examination was performed. Furthermore, we measured serum lipopolysaccharide (LPS) and lipotechoic acid (LTA) levels. Multivariate conditional regression models were adjusted for stroke risk factors, regular dentist visits, and patent foramen ovale (PFO) status. We enrolled 146 case-control pairs (median age 41.9 y; 58.2% males). Periodontitis was diagnosed in 27.5% of CIS patients and 20.1% of controls (P < 0.001). In the fully adjusted models, CIS was associated with high periodontal inflammation burden (odds ratio [OR], 95% confidence interval) with an OR of 10.48 (3.18-34.5) and severe periodontitis with an OR of 7.48 (1.24-44.9). Stroke severity increased with the severity of periodontitis, having an OR of 6.43 (1.87-23.0) in stage III to IV, grade C. Invasive dental treatments performed within 3 mo prestroke were associated with CIS, with an OR of 2.54 (1.01-6.39). Association between CIS and invasive dental treatments was especially strong among those with PFO showing an OR of 6.26 (1.72-40.2). LPS/LTA did not differ between CIS patients and controls but displayed an increasing trend with periodontitis severity. Periodontitis and recent invasive dental procedures were associated with CIS after controlling for multiple confounders. However, the role of bacteremia as a mediator of this risk was not confirmed.

Monitoring of Insecticides resistance against cotton Jassid (Amrasca biguttutla biguttutla) under laboratory conditions / Monitoramento da resistência de inseticidas contra o algodão Jassid (Amrasca biguttutla biguttutla) em condições laboratoriais

Abstract Development of insecticides resistance mainly hinge with managements techniques for the control of Jassid, Amrasca biguttutla biguttutla. Five insecticides were applied against field collected and laboratory rared jassid populations during the years of 2017 to 2019 to profile their resistance level against field population of jassid through leaf dip method. Very low resistance level was found in jassid against confidor whereas high level of resistance was observed by pyriproxyfen against other test insecticides. Gradual resistance was observed against diafenthiuron. It is concluded that for the management of Jassid repetition of same insecticide should be avoided. The use of confidor may be reduced to overcome resistance against Jassid.

Resumo Desenvolvimento da resistência a inseticidas principalmente em dobradiça com técnicas de manejo para o controle de jassid, Amrasca biguttutla biguttutla. Cinco inseticidas foram aplicados contra populações de jassídeos coletados em campo e em laboratório durante os anos de 2017 a 2019 para traçar o perfil de seu nível de resistência contra populações de jassídeos em campo através do método de imersão nas folhas. Nível de resistência muito baixo foi encontrado em jassid contra confidor, enquanto alto nível de resistência foi observado por piriproxifeno contra outros inseticidas de teste. Resistência gradual foi observada contra o diafenthiuron. Conclui-se que, para o manejo do jassid, a repetição do mesmo inseticida deve ser evitada. O uso de confidor pode ser reduzido para superar a resistência contra jassid.

Monitoring of Insecticides resistance against cotton Jassid (Amrasca biguttutla biguttutla) under laboratory conditions / Monitoramento da resistência de inseticidas contra o algodão Jassid (Amrasca biguttutla biguttutla) em condições laboratoriais

Development of insecticides resistance mainly hinge with managements techniques for the control of Jassid, Amrasca biguttutla biguttutla. Five insecticides were applied against field collected and laboratory rared jassid populations during the years of 2017 to 2019 to profile their resistance level against field population of jassid through leaf dip method. Very low resistance level was found in jassid against confidor whereas high level of resistance was observed by pyriproxyfen against other test insecticides. Gradual resistance was observed against diafenthiuron. It is concluded that for the management of Jassid repetition of same insecticide should be avoided. The use of confidor may be reduced to overcome resistance against Jassid.

Desenvolvimento da resistência a inseticidas principalmente em dobradiça com técnicas de manejo para o controle de jassid, Amrasca biguttutla biguttutla. Cinco inseticidas foram aplicados contra populações de jassídeos coletados em campo e em laboratório durante os anos de 2017 a 2019 para traçar o perfil de seu nível de resistência contra populações de jassídeos em campo através do método de imersão nas folhas. Nível de resistência muito baixo foi encontrado em jassid contra confidor, enquanto alto nível de resistência foi observado por piriproxifeno contra outros inseticidas de teste. Resistência gradual foi observada contra o diafenthiuron. Conclui-se que, para o manejo do jassid, a repetição do mesmo inseticida deve ser evitada. O uso de confidor pode ser reduzido para superar a resistência contra jassid.

Monitoring of Insecticides resistance against cotton Jassid (Amrasca biguttutla biguttutla) under laboratory conditions

Abstract Development of insecticides resistance mainly hinge with managements techniques for the control of Jassid, Amrasca biguttutla biguttutla. Five insecticides were applied against field collected and laboratory rared jassid populations during the years of 2017 to 2019 to profile their resistance level against field population of jassid through leaf dip method. Very low resistance level was found in jassid against confidor whereas high level of resistance was observed by pyriproxyfen against other test insecticides. Gradual resistance was observed against diafenthiuron. It is concluded that for the management of Jassid repetition of same insecticide should be avoided. The use of confidor may be reduced to overcome resistance against Jassid.

Resumo Desenvolvimento da resistência a inseticidas principalmente em dobradiça com técnicas de manejo para o controle de jassid, Amrasca biguttutla biguttutla. Cinco inseticidas foram aplicados contra populações de jassídeos coletados em campo e em laboratório durante os anos de 2017 a 2019 para traçar o perfil de seu nível de resistência contra populações de jassídeos em campo através do método de imersão nas folhas. Nível de resistência muito baixo foi encontrado em jassid contra confidor, enquanto alto nível de resistência foi observado por piriproxifeno contra outros inseticidas de teste. Resistência gradual foi observada contra o diafenthiuron. Conclui-se que, para o manejo do jassid, a repetição do mesmo inseticida deve ser evitada. O uso de confidor pode ser reduzido para superar a resistência contra jassid.

Prospect of microbial food borne diseases in Pakistan: a review / Perspectiva de doenças microbianas transmitidas por alimentos no Paquistão: uma revisão

Abstract Nowadays food borne illness is most common in people due to their epidemic nature. These diseases affect the human digestive system through bacteria, viruses and parasites. The agents of illness are transmitted in our body through various types of food items, water and uncooked. Pathogens show drastic changes in immunosuppressant people. This review gives general insights to harmful microbial life. Pakistan is a developed country and because of its improper food management, a lot of gastrointestinal problems are noted in many patients. Bacteria are most common agents to spread diarrhoea, villi infection, constipation and dysenteric disease in human and induce the rejection of organ transplant. Enhancement of their lifestyle, properly cooked food should be used and to overcome the outbreak of the diseases.

Resumo Hoje em dia, as doenças transmitidas por alimentos são mais comuns em pessoas devido à sua natureza epidêmica. Essas doenças afetam o sistema digestivo humano por meio de bactérias, vírus e parasitas. Os agentes das doenças são transmitidos em nosso corpo por meio de diversos tipos de alimentos, água e crus. Os patógenos mostram mudanças drásticas em pessoas imunossupressoras. Esta revisão fornece uma visão geral da vida microbiana prejudicial. O Paquistão é um país desenvolvido e, devido ao seu manejo alimentar inadequado, muitos problemas gastrointestinais são observados em muitos pacientes. As bactérias são os agentes mais comuns para espalhar diarreia, infecção de vilosidades, obstipação e doença disentérica em humanos e induzem a rejeição de transplantes de órgãos. Melhoria de seu estilo de vida, alimentos devidamente cozidos devem ser utilizados e para superar o aparecimento de doenças.

Prospect of microbial food borne diseases in Pakistan: a review / Perspectiva de doenças microbianas transmitidas por alimentos no Paquistão: uma revisão

Abstract Nowadays food borne illness is most common in people due to their epidemic nature. These diseases affect the human digestive system through bacteria, viruses and parasites. The agents of illness are transmitted in our body through various types of food items, water and uncooked. Pathogens show drastic changes in immunosuppressant people. This review gives general insights to harmful microbial life. Pakistan is a developed country and because of its improper food management, a lot of gastrointestinal problems are noted in many patients. Bacteria are most common agents to spread diarrhoea, villi infection, constipation and dysenteric disease in human and induce the rejection of organ transplant. Enhancement of their lifestyle, properly cooked food should be used and to overcome the outbreak of the diseases.

Resumo Hoje em dia, as doenças transmitidas por alimentos são mais comuns em pessoas devido à sua natureza epidêmica. Essas doenças afetam o sistema digestivo humano por meio de bactérias, vírus e parasitas. Os agentes das doenças são transmitidos em nosso corpo por meio de diversos tipos de alimentos, água e crus. Os patógenos mostram mudanças drásticas em pessoas imunossupressoras. Esta revisão fornece uma visão geral da vida microbiana prejudicial. O Paquistão é um país desenvolvido e, devido ao seu manejo alimentar inadequado, muitos problemas gastrointestinais são observados em muitos pacientes. As bactérias são os agentes mais comuns para espalhar diarreia, infecção de vilosidades, obstipação e doença disentérica em humanos e induzem a rejeição de transplantes de órgãos. Melhoria de seu estilo de vida, alimentos devidamente cozidos devem ser utilizados e para superar o aparecimento de doenças.

Monitoring of Insecticides resistance against cotton Jassid (Amrasca biguttutla biguttutla) under laboratory conditions.

Development of insecticides resistance mainly hinge with managements techniques for the control of Jassid, Amrasca biguttutla biguttutla. Five insecticides were applied against field collected and laboratory rared jassid populations during the years of 2017 to 2019 to profile their resistance level against field population of jassid through leaf dip method. Very low resistance level was found in jassid against confidor whereas high level of resistance was observed by pyriproxyfen against other test insecticides. Gradual resistance was observed against diafenthiuron. It is concluded that for the management of Jassid repetition of same insecticide should be avoided. The use of confidor may be reduced to overcome resistance against Jassid.

Prospect of microbial food borne diseases in Pakistan: a review.

Nowadays food borne illness is most common in people due to their epidemic nature. These diseases affect the human digestive system through bacteria, viruses and parasites. The agents of illness are transmitted in our body through various types of food items, water and uncooked. Pathogens show drastic changes in immunosuppressant people. This review gives general insights to harmful microbial life. Pakistan is a developed country and because of its improper food management, a lot of gastrointestinal problems are noted in many patients. Bacteria are most common agents to spread diarrhoea, villi infection, constipation and dysenteric disease in human and induce the rejection of organ transplant. Enhancement of their lifestyle, properly cooked food should be used and to overcome the outbreak of the diseases.

Characterization of a virulent ranavirus isolated from marine ornamental fish in India.

A viral agent implicated in the mortality of marine ornamental "Similar Damselfish" (Pomacentrus similis Allen, 1991) was isolated and characterized. The virus grew well in marine and freshwater fish cell lines from seabass and snakehead. The virus was sensitive to chloroform, acidic pH (3.0) and heat treatment at 56 °C. Biochemical characterisation indicated that the virus had double stranded DNA genome. Transmission electron microscopic analysis of ultrathin sections of infected cell pellets showed iridovirus-like icosahedral virus particles of 120-130 nm. Purified virus had six structural protein bands that ranged from of 44 to 132 kDa. PCR analysis confirmed the presence of viral DNA in infected cell cultures and sequence analysis of the major capsid protein gene showed an identity of 99.82% to that of largemouth bass virus. Serum neutralization studies involving the viral agent and koi ranavirus (KIRV) indicated partial homogeneity between the two isolates. Experimental infection of seabass (Lates calcarifer) and similar damselfish (P. similis) fingerlings with the similar damselfish virus showed cumulative mortalities of 68.75 and 93.33%. The biophysical and biochemical properties of the viral agent isolated, serological characteristics, size of major capsid proteins and the sequence similarity of the MCP gene proved that the virus belongs to the genus Ranavirus of the family Iridoviridae. Ability of the virus to grow in marine and freshwater fish cell lines and its pathogenicity to one of the cultivable marine fish shows the wide host range of the virus. This is the first report of ranavirus induced mortality in marine fish in India.

Synthesis, characterization and antibacterial studies on mixed ligand copper complexes with polydentate ligands.

Mixed ligand Cu(II) complexes of the type [M(Q)(L)]-2H2O have been synthesized using 8-hydroxyquinoline (HQ) as a primary ligand and N- and/or O-donor amino acids (HL) such as L-threonine, L-proline, L-hydroxyproline, L-isoleucine and L-serine as secondary ligands. The metal complexes have been characterized on the basis of elemental analysis, electrical conductance, room temperature magnetic susceptibility measurements, spectral and thermal studies. The electrical conductance studies of the complexes in DMSO (dimethyl sulfoxide) in 10(-3) M concentration indicate their non-electrolytic nature. Room temperature magnetic susceptibility measurements revealed paramagnetic nature of the complexes. Electronic absorption spectra of the complexes show intra-ligand, charge transfer transitions and d-d transitions. The thermal analysis data of the complexes indicate the presence of crystallized water molecules. The agar cup method and tube dilution method have been used to study the antibacterial activity of the complexes against the pathogenic bacteria S. aureus, C. diphtheriae, P. aeruginosa and E. coli. The results have been compared with those of tetracycline, which was screened simultaneously and indicated mild antibacterial activity of the complexes.

Synthesis, characterization and antibacterial activity of mixed ligand dioxouranium complexes of 8-hydroxyquinoline and some amino acids.

Mixed ligand complexes of dioxouranium(VI) of the type [UO2(Q)(L)-2H2O] have been synthesized using 8-hydroxyquinoline (HQ) as a primary ligand and N- and/or O- donor amino acids (HL) such as L-lysine, L-aspartic acid and L-cysteine as secondary ligands. The metal complexes have been characterized on the basis of elemental analysis, electrical conductance, room temperature magnetic susceptibility measurements, spectral and thermal studies. The electrical conductance studies of the complexes in DMF in 10(-3) M concentration indicate their non-electrolytic nature. Room temperature magnetic susceptibility measurements revealed diamagnetic nature of the complexes. Electronic absorption spectra of the complexes show intra-ligand and charge transfer transitions, respectively. Bonding of the metal ion through N- and O- donor atoms of the ligands is revealed by IR studies and the chemical environment of the protons is also confirmed by NMR studies. The thermal analysis data of the complexes indicate the presence of coordinated water molecules. The agar cup and tube dilution methods have been used to study the antibacterial activity of the complexes against the pathogenic bacteria S. aureus, C. diphtherinae, S. typhi and E. coli.

Involvement of histamine receptors in SAPK/JNK phosphorylation.

Histamine is a mediator of inflammation in allergic disease and asthma. Stress activated protein kinases/c-jun N-terminal kinases (SAPK/JNK) are involved in asthma. This study examined the role of histamine receptors on the phosphorylation of SAPK/JNK in splenocytes. C57BL/6 mice splenocytes were treated with histamine (10⁻4 M to 10⁻¹¹ M), and its selective receptor agonists, phorbol 12 myristate 13-acetate (PMA) was used as a positive control, and phosphorylation of SAPK/JNK was determined. Histamine (10⁻4 M-10⁻8 M) inhibited phosphorylation of SAPK/JNK. H1R agonist betahistine (10⁻5 M) decreased SAPK/JNK phosphorylation and H2R agonist amthamine (10⁻5 M) did not show any significant effect. However, H3R agonist methimepip (10⁻6 M) and H4R agonist 4-methyl histamine (10⁻6 M), increased SAPK/JNK phosphorylation. We used TNFα knockout mice to determine if histamine regulated SAPK/JNK phosphorylation via TNFα. While the effects of histamine and H1 agonists were similar to that of wild type mice in inhibiting the phosphorylation of SAPK/JNK, the effects of H3 and H4 agonists differed in TNFα knockout mice splenocytes. Activation of H3 receptors decreased SAPK/JNK phosphorylation in TNFα knockout mice, as opposed to an increase in wild type mice, whereas H4 agonist did not show any significant effect on the phosphorylation of SAPK/JNK. This data showed that histamine acting through H4 receptors caused the phosphorylation of SAPK/JNK via TNFα. The role of H4 receptors in pro-inflammatory response is intriguing.

Synthesis, spectral, thermal and antibacterial investigations of mixed ligand complexes of thorium(IV) derived from 8-hydroxyquinoline and some amino acids.

Mixed ligand Th(IV) complexes of the type [M(Q)(L)(NO3)2] x 2 H2O have been synthesized using 8-hydroxyquinoline (HQ) as a primary ligand and N- and/or O- donor amino acids (HL) such as L-lysine, L-aspartic acid and L-cysteine as secondary ligands. The metal complexes have been characterized on the basis of elemental analysis, electrical conductance, room temperature magnetic susceptibility measurements,spectral and thermal studies. The electrical conductance studies of the complexes in DMF in 10(-3) M concentration indicate their non-electrolytic nature. Room temperature magnetic susceptibility measurements revealed diamagnetic nature of the complexes. Electronic absorption spectra of the complexes show intra-ligand and charge transfer transitions, respectively. Bonding of the metal ion through N- and O- donor atoms of the ligands revealed by IR studies and the chemical environment of the protons is also confirmed by NMR studies. The thermal analysis data of the complexes indicate the presence of crystallized water molecules. The agar cup and tube dilution method have been used to study the antibacterial activity of the complexes against the pathogenic bacteria S. aureus, C. diphtheriae, S. typhi and E. coli.

Synthesis, characterization and antibacterial studies on some mixed ligand thorium complexes with N- and O-donor ligands.

Mixed ligand Th(IV) complexes of the type [M(Q)(L)(NO3)2] x 2H2O have been synthesized using 8-hydroxyquinoline (HQ) as a primary ligand and N- and/or O- donor amino acids (HL) such as L-threonine, L-tryptophan and L-isoleucine as secondary ligands. The metal complexes have been characterized on the basis of elemental analysis, electrical conductance, room temperature magnetic susceptibility measurements, spectral and thermal studies. The electrical conductance studies of the complexes in DMF in 10(-3). M concentration indicate their non-electrolytic nature. Room temperature magnetic susceptibility measurements revealed diamagnetic nature of the complexes. Electronic absorption spectra of the complexes show intra-ligand and charge transfer transitions, respectively. Bonding of the metal ion through N- and O-donor atoms of the ligands revealed by IR studies and the chemical environment of the protons is also confirmed by NMR studies. The thermal analysis data of the complexes indicate the presence of crystalline water molecules. The tube dilution method has been used to study the antibacterial activity of the complexes against the pathogenic bacteria S. aureus, C. diphtheriae, S. typhi and E. coli.

Regulation of ERK2 phosphorylation by histamine in splenocytes.

Histamine is implicated in allergic disease and asthma and ERK1/2 is involved in allergic inflammation including Th2 differentiation and proliferation. This study was designed to study the effects of histamine on ERK1/2 phosphorylation in splenocytes. C57/BL6 splenocytes were treated with different concentrations of histamine (10(-4) to 10(-11) M). Histamine (10(-4) M) increased ERK2 phosphorylation. There was, however, no significant effect seen at other concentrations (10(-11) to 10(-6) M). Surprisingly, H1 receptor agonist ß-histine (10(-5) M), H2 agonist amthamine (10(-5) M), H3 agonist methimepip (10(-6) M), and H4 agonist 4-methyl histamine (10(-6) M), all increased ERK2 phosphorylation. H1R antagonist pyrilamine (10(-6) M), H2R antagonist ranitidine (10(-5) M), H3/H4R antagonist thioperamide (10(-6) M), and H3R antagonist clobenpropit (10(-5) M) inhibited histamine-mediated ERK2 phosphorylation suggesting that all four histamine receptor subtypes played some role in this phosphorylation. Because tumor necrosis factor-α (TNF-α) causes phosphorylation of ERK1/2, we investigated whether histamine acted via secretion of TNF-α to affect ERK1/2 phosphorylation. As a consequence, TNF-α knockout mice were used and we found that there was inhibition of ERK1 and ERK2 phosphorylation by H2, H3, and H4 agonists. This was in contrast to the wild-type splenocytes where histamine augmented the phosphorylation of ERK2 via H2, H3, and H4 receptors. In TNF-α knockout mice histamine did not affect the phosphorylation of ERK2 via H1 receptors. The results suggested that histamine indirectly caused the ERK2 phosphorylation via its effects on the secretion of TNF-α and these effects were mediated via H1, H2, H3, and H4 receptors.

Synthesis, characterization, and antibacterial studies of mixed ligand dioxouranium complexes with 8-hydroxyquinoline and some amino acids.

Mixed ligand complexes of dioxouranium (VI) of the type [UO(2)(Q)(L)·2H(2)O] have been synthesized using 8-hydroxyquinoline (HQ) as a primary ligand and amino acids (HL) such as L-threonine, L-tryptophan, and L-isoleucine as secondary ligands. The metal complexes have been characterized by elemental analysis, electrical conductance, magnetic susceptibility measurements, and spectral and thermal studies. The electrical conductance studies of the complexes indicate their nonelectrolytic nature. Magnetic susceptibility measurements revealed diamagnetic nature of the complexes. Electronic absorption spectra of the complexes show intraligand and charge transfer transitions, respectively. Bonding of the metal ion through N- and O-donor atoms of the ligands is revealed by IR studies, and the chemical environment of the protons is confirmed by NMR studies. The thermal analysis data of the complexes indicate the presence of coordinated water molecules. The agar cup and tube dilution methods have been used to study the antibacterial activity of the complexes against the pathogenic bacteria S. aureus, C. diphtheriae, S. typhi, and E. coli.

Aspergilloma complicating newly diagnosed pulmonary echinococcal (hydatid) cyst: a rare occurrence.

Aspergilloma is a saprophytic infection that colonizes pre-existing lung cavities. Typically, aspergilloma develops in cavities formed as a result of diseases such as tuberculosis, sarcoidosis, bronchiectasis, lung abscess and cavitatory neoplasia. Coexistence of fungi with a pulmonary echinococcal (hydatid) cyst is seen more commonly in immunocompromised patients. Although aspergilloma has occasionally been described in operated hydatid cyst cavities, only one case has been reported previously in an unoperated case. We report on the case of a 40-year-old man with normal immune status and histologically proven concurrent infection of aspergillus in a previously unoperated pulmonary hydatid cyst.

Synthesis and biological activity of mixed ligand dioxouranium(VI) and thorium(IV) complexes.

Mixed ligand complexes of dioxouranium(VI) and thorium(IV) in the proportion 1:1:1 and 1:2:1 have been synthesized using 8-hydroxyquinoline as a primary ligand and L-proline and 4-hydroxy-L-proline as secondary ligands, respectively. The metal complexes have been characterized on the basis of elemental analysis, molar conductance, magnetic, spectral and thermal studies. The molar conductance studies of the complexes in DMF at 10(-3) M concentrations indicate their non-electrolytic nature. Room temperature magnetic susceptibility measurements revealed diamagnetic nature of the complexes. Electronic absorption spectra of the complexes show intra-ligand and charge transfer transitions, respectively. The thermal analysis data of the complexes indicates the presence of a coordinated water molecule/molecules. The tube dilution method has been used to study the antibacterial activity of the complexes against the pathogenic bacteria Staphylococcus aureus and Escherichia coli. The results have been compared against those of control tetracycline, which was screened simultaneously. The complexes have been screened for in vitro cytotoxicity (IC50) studies against Ehrlich ascites cells and Dalton's lymphoma ascites cells, respectively.

Histamine affects STAT6 phosphorylation via its effects on IL-4 secretion: role of H1 receptors in the regulation of IL-4 production.

Signal Transducer and Activator of Transcription (STAT)-6 is a transcriptional factor activated mainly through the cytokines IL-4 and IL-13 leading to the Th2 cell differentiation. Th2 cells play a role in the etiology and pathogenesis of allergic disease. Histamine alters the Th1/Th2 cytokine balance towards the Th2 cytokine profile and consequently plays a role in allergic diseases and asthma. This study was designed to investigate the effects of histamine on the STAT6 phosphorylation. C57/BL6 splenocytes were pretreated with different concentrations of histamine (10(-)(4) M to 10(-)(13) M) followed by stimulation with PMA+ionomycin or IL-4. The phosphorylated and total basal STAT6 levels were assessed by employing the immunoblotting technique. Histamine caused the hyper-phosphorylation of STAT6. H1 receptor antagonist pyrilamine reversed the effect of histamine on STAT6 phosphorylation. However, H2 receptor antagonist ranitidine and H3/H4 receptor antagonist thioperamide did not affect the histamine mediated hyper-phosphorylation of STAT6. Furthermore, H1 receptor agonist betahistine enhanced the phosphorylation of STAT6 whereas H2 receptor agonist amthamine did not affect the phosphorylation STAT6. Furthermore, tyrosine kinase inhibitor, tyrphostin, inhibited the histamine mediated phosphorylation of STAT6 when stimulated with PMA+ionomycin. The effects of histamine on the STAT6 phosphorylation were indirect since they were blocked either by the antibodies to IL-4 and IL-13 or in IL-4 knock out mice in the presence of IL-13 antibody. These observations suggest that histamine indirectly affected the STAT6 phosphorylation via its effects on the secretion of cytokines (IL-4) and H1 receptor played a role in this process.

Role of H1 receptors in histamine-mediated up-regulation of STAT4 phosphorylation.

Histamine shifts TH1/TH2 cytokine balance from TH1 to TH2 cytokines and regulates the function of lymphocytes after binding to histamine receptors. The phosphorylation of STAT factors and the translocation to the nucleus are important steps in the regulation of TH1/TH2 cytokine balance. This study was designed to investigate the effects of histamine on the phosphorylation of STAT4. C57BL/6 splenocytes were isolated and treated with histamine (10(-4) to 10(-9) M) after activation with either PMA (phorbol 12 myristate 13-acetate) plus ionomycin or IL-12. The phosphorylated STAT4 levels were analyzed by Western Blot Analysis. Unstimulated splenocytes expressed both STAT4 and phosphorylated STAT4. However, phosphorylated STAT4 gradually declined within 24 h. Histamine increased the phosphorylation of STAT4 at lower concentrations (10(-6) to 10(-9) M), and had no effect at higher concentrations (10(-4) and 10(-5) M) after the cells were stimulated with PMA + ionomycin. Histamine did not affect IL-12-induced phosphorylation of STAT4. To characterize the histamine receptor subtypes involved in the up-regulation of STAT4 phosphorylation, various H1, H2 and H3/H4 receptor antagonists and/or agonists were employed. H1 receptor agonist (betahistine), but not H2 receptor agonist (amthamine), induced phosphorylation of STAT4. H1 receptor antagonist (pyrilamine) inhibited histamine-mediated phosphorylation of STAT4. However, H2 receptor antagonist (ranitidine) and H3/H4 receptor antagonist (thioperamide) did not alter this effect. Tyrosine kinase inhibitor (tyrphostin) failed to block histamine-mediated phosphorylation of STAT4. These observations suggest that histamine up-regulated the phosphorylation of STAT4 via H1 receptors, and that the Ca2+-PKC pathway, but not the tyrosine kinase pathway, was involved in this effect.