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1.
Appl Opt ; 54(33): 9925-9, 2015 Nov 20.
Article in English | MEDLINE | ID: mdl-26836559

ABSTRACT

Willemite-based glass-ceramic was prepared from waste material using a conventional melt and quenching method. The crystalline willemite-based glass-ceramic was doped with Er2O3 (1-5 wt.%) followed by sintering at different temperatures (500°C-1100°C). Density and linear shrinkage were increased with the increase of the sintering temperature. Ultraviolet-visible spectroscopy (UV-Vis) confirmed an optimum optical absorption for sample doped with 3 wt.% of Er2O3 and sintered at 900°C. Photoluminescence measurements further confirmed 3 wt.% of Er2O3 as the optimum percentage of dopant. Results suggested that the obtained glass-ceramic could be a promising material for use as fiber amplifiers.

2.
Thorax ; 65(1): 57-62, 2010 Jan.
Article in English | MEDLINE | ID: mdl-19846469

ABSTRACT

BACKGROUND: Chronic lung infection with Pseudomonas aeruginosa is the most severe complication for patients with cystic fibrosis (CF). This infection is characterised by endobronchial mucoid biofilms surrounded by numerous polymorphonuclear leucocytes (PMNs). The mucoid phenotype offers protection against the PMNs, which are in general assumed to mount an active respiratory burst leading to lung tissue deterioration. An ongoing respiratory burst by the PMNs has, however, not been demonstrated previously in endobronchial secretions from chronically infected patients with CF. OBJECTIVE: Based on the accumulating evidence for depletion of molecular oxygen (O(2)) in the mucus in infected CF bronchi, it was hypothesised that the O(2) depletion in the mucus in infected CF bronchi may be accelerated by the respiratory burst of the PMNs due to the reduction of O(2) to the superoxide anion (O(-)(2)) by the phagocyte NADPH oxidase (Phox). METHODS: Methods were established to isolate the O(2) consumption by the respiratory burst from aerobic respiration in freshly expectorated sputum from chronically infected patients with CF. RESULTS: Inhibition of the Phox with diphenylene iodonium (DPI) delayed O(2) depletion, nearly abolished staining of O(-)(2)-producing PMNs with hydroethidine and inhibited the rapid luminol-enhanced chemiluminescence in sputum. Furthermore, the total O(2) consumption was correlated to the concentration of PMNs in the sputum samples. CONCLUSION: The results demonstrate that CF sputum contains PMNs with an active consumption of O(2) for O(-)(2) production and suggest that the respiratory burst is ongoing and causes accelerated O(2) depletion due to formation of O(-)(2) in the lungs of chronically infected patients with CF.


Subject(s)
Cystic Fibrosis/microbiology , Neutrophils/metabolism , Oxygen Consumption/physiology , Pseudomonas Infections/microbiology , Pseudomonas aeruginosa , Sputum , Adult , Bronchi/immunology , Bronchi/microbiology , Chronic Disease , Female , Humans , Male , Middle Aged , NADPH Oxidases/metabolism , Neutrophils/microbiology , Phagocytosis , Reactive Oxygen Species/metabolism , Respiratory Burst/physiology , Sputum/cytology , Sputum/microbiology , Superoxides/metabolism , Young Adult
3.
Phytomedicine ; 17(2): 87-93, 2010 Feb.
Article in English | MEDLINE | ID: mdl-19818588

ABSTRACT

OBJECTIVE: To investigate if standardised powder made from rose-hip (Rosa canina) can reduce the symptom score in patients with rheumatoid arthritis. METHODS: In a double-blind placebo-controlled trial, patients with rheumatoid arthritis (RA) according to ARA/ACR criteria were randomised to treatment with capsulated rose-hip powder 5g daily or matching placebo for 6 months at two outpatient clinics in Berlin and Copenhagen. Primary outcome variable was Health Assessment Questionnaire (HAQ) at 6 months, secondary outcome included DAS-28, physician's global evaluation of disease activity, RAQoL, SF-12 and concomitant pain medication. RESULTS: In a total of 89 patients (90% female, mean age 56.6+11.3 years, mean disease duration 12.8+9.6 years) HAQ-DI in the rose-hip group improved by 0.105+/-0.346, whereas in the placebo group it worsened by 0.039+/-0.253 (p adjusted=0.032). In the HAQ Patient Pain Scale no significant differences were observed between both groups. In the HAQ Patient Global Scale a trend was seen favouring rose-hip (p=0.078). The DAS-28 score yielded improvement in the rose-hip group of 0.89+/-1.32 and in the placebo group of 0.34+/-1.27 (p=0.056) indicating moderate clinical relevance. The Physicians Global Scale demonstrated more improvement in the rose-hip compared to the placebo group (p=0.012). RAQoL and SF-12 physical score improved significantly in the rose-hip group compared to placebo, whereas SF-12 mental score remained unchanged. Intake of pain medication was not different between the groups. Per-protocol analysis confirmed these results. CONCLUSION: The results indicate that patients with RA may benefit from additional treatment with rose hip powder.


Subject(s)
Arthritis, Rheumatoid/drug therapy , Pain/drug therapy , Phytotherapy , Plant Preparations/therapeutic use , Rosa , Aged , Arthritis, Rheumatoid/complications , Double-Blind Method , Female , Fruit , Humans , Male , Middle Aged , Pain/etiology , Powders
4.
J Cyst Fibros ; 5(3): 145-51, 2006 Aug.
Article in English | MEDLINE | ID: mdl-16503423

ABSTRACT

BACKGROUND: Chronic Pseudomonas aeruginosa lung infection is the major reason for premature death in patients with cystic fibrosis (CF). Infected patients experience a progressive deterioration of the lung tissue caused by a persistent accumulation of PMNs. We investigated if the pulmonary accumulation of PMNs is reflected as a migration of PMNs through the blood in chronically infected CF patients. METHODS: Blood and sputum samples from 37 stable, chronically (CF+P) and 6 non-infected (CF-P) CF patients without exacerbations were compared using FACS, leukocyte counting, and ELISA. Within the CF+P patients, the blood parameters were compared to the lung function (FEV1 and FVC) and to the sputum. Similar measurements were performed on 15 chronically infected CF patients before and after elective antibiotic treatment. RESULTS: In the CF+P patients the concentration of G-CSF in the sera and PMNs in the blood was increased and correlated to poor lung function. However, only the concentration of G-CSF in the sera was correlated to the concentration of TNF-alpha in the sputum. After the antibiotic treatment, the lung function was improved and the concentration of PMNs in the blood and G-CSF in the sera was reduced. CONCLUSION: G-CSF in the sera may contribute to the pulmonary inflammation in CF patients with chronic P. aeruginosa lung infection by regulating the number of PMNs available for migration and may be considered as an indicator of clinical status.


Subject(s)
Cystic Fibrosis/microbiology , Granulocyte Colony-Stimulating Factor/blood , Neutrophils/metabolism , Pneumonia/microbiology , Pseudomonas Infections/blood , Adolescent , Adult , Blood Cell Count , Cell Movement , Female , Flow Cytometry , Humans , Inflammation , Interleukin-8/blood , Male , Middle Aged , Tumor Necrosis Factor-alpha/analysis
5.
Phytomedicine ; 11(5): 383-91, 2004 Jul.
Article in English | MEDLINE | ID: mdl-15330493

ABSTRACT

The treatment of osteoarthritis, a disease that eventually affects the majority of the older population, involves the alleviation of symptoms such as pain and stiffness, and the reduction of inflammation. The double-blind, placebo-controlled, crossover study reported here examined the effect of Hyben Vital, a herbal remedy made from a subtype of Rosa canina and recently reported to have anti-inflammatory properties, on the symptoms of osteoarthritis. One hundred and twelve patients with osteoarthritis were randomly allocated to treatment with either Hyben Vital 5 g daily or an identical placebo for 3 months, followed immediately by the alternative treatment. The patients assessed changes in joint pain and stiffness after each treatment period on a 5-point categorical scale. General wellbeing, including mood, sleep quality and energy were also assessed and recorded in a personal diary. The results in the two arms of the crossover differed markedly. Group A (placebo first) showed significantly more improvement from Hyben Vital than from placebo, p < 0.0078 for pain and < 0.0025 for stiffness. But Group B (Hyben Vital first) revealed a positive effect of the same order as for Hyben Vital in group A, not only from the active drug, but also from placebo (difference not significant). An identical pattern was observed when we evaluated general wellbeing from the diary records. When patients, on the basis of reduction in joint pain, were divided into responders and non-responders, the first 3 months of active treatment (group A) showed a response rate of 31/47 (66%) compared to that of placebo (group B) 18/50 (36%), p < 0.0185. No major side effects occurred in either group. The data indicate that Hyben Vital reduces the symptoms of osteoarthritis. We interpret the marked differences in the responses of the two groups as indicating a strong "carryover" effect of Hyben Vital.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Osteoarthritis/drug therapy , Pain/drug therapy , Phytotherapy , Plant Extracts/therapeutic use , Rosa , Adult , Aged , Aged, 80 and over , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Cross-Over Studies , Double-Blind Method , Drug Administration Schedule , Female , Fruit , Humans , Male , Middle Aged , Osteoarthritis/pathology , Pain/pathology , Pain Measurement/drug effects , Plant Extracts/administration & dosage , Treatment Outcome
6.
Clin Exp Immunol ; 137(3): 478-85, 2004 Sep.
Article in English | MEDLINE | ID: mdl-15320896

ABSTRACT

Polymorphonuclear neutrophils (PMNs) are crucial for the outcome of Pseudomonas aeruginosa lung infection in patients with cystic fibrosis. We compared PMNs and inflammatory cytokines in the lungs and blood from susceptible BALB/c and resistant C3H/HeN mice 1 and 2 days after intratracheal challenge with alginate embedded P. aeruginosa. These parameters were correlated with the quantitative bacteriology and histopathology of the lungs. After challenge, the content of granulocyte colony-stimulating factor (G-CSF) and macrophage inflammatory protein-2 (MIP-2) was increased in the lungs and the sera and the percentage of PMNs was increased in the blood. However, 2 days after challenge the concentration of G-CSF and MIP-2 was higher in the lungs and sera of BALB/c mice. CD11b expression was higher on the PMNs of the C3H/HeN mice. The expression of CD62L on PMNs of both strains of mice was decreased 1 day after bacterial challenge, whereas the expression was increased after 2 days of challenge on PMNs of C3H/HeN mice only. These changes were accompanied by a more severe lung inflammation in BALB/c mice and faster clearance of the bacteria in C3H/HeN mice. In conclusion, the rapid early bacterial clearance in the lungs of C3H/HeN mice could be explained by faster activation of the PMNs, as indicated by the higher up-regulation of CD11b. The severe lung inflammation in BALB/c mice may be caused by the early higher content of G-CSF in the sera mobilizing PMNs from the bone marrow and the persistent chemotactic gradient provided by MIP-2 in the lungs.


Subject(s)
Lung/immunology , Neutrophil Activation , Neutrophils/immunology , Pseudomonas Infections/immunology , Animals , Bronchoalveolar Lavage Fluid/immunology , CD11b Antigen/analysis , Chemokine CXCL2 , Female , Granulocyte Colony-Stimulating Factor/analysis , Immunity, Innate , L-Selectin/analysis , Leukocyte Count , Mice , Mice, Inbred BALB C , Mice, Inbred C3H , Monokines/analysis
7.
Clin Exp Immunol ; 127(2): 206-13, 2002 Feb.
Article in English | MEDLINE | ID: mdl-11876741

ABSTRACT

Repeated challenge with antigen is involved in the pathogenesis of a variety of pulmonary diseases. Patients with cystic fibrosis (CF) experience recurrent pulmonary colonization with Pseudomonas aeruginosa before establishment of chronic lung infection. To mimic recurrent lung infections in CF patients, the lungs of susceptible BALB/c mice were re-infected with P. aeruginosa 14 days after the initial infection. Singly-infected BALB/c mice, as well as non-infected mice, were used as controls. Decreased mortality and milder lung inflammation in re-infected BALB/c mice, as well as a tendency for improved clearance of bacteria, was observed when compared with singly-infected mice. The improved outcome in re-infected mice correlated with changes in CD4 cell numbers. Surface expression of LFA-1 on pulmonary CD4 cells was increased in re-infected compared with singly-infected mice. Moreover, resistance to re-infection was paralleled by a shift towards a Th1-dominated response and increased IL-12 production. No significant increase in serum IgG was observed in the re-infected mice. In conclusion, these results indicate a protective role for a Th1-dominated response, independent of antibody production, in chronic P. aeruginosa lung infection in CF.


Subject(s)
Cytokines/biosynthesis , Pneumonia, Bacterial/immunology , Pseudomonas Infections/immunology , Th1 Cells/immunology , Agar , Alginates , Animals , Antibodies, Bacterial/biosynthesis , Antibodies, Bacterial/blood , Bronchoalveolar Lavage Fluid , CD4 Lymphocyte Count , Chronic Disease , Female , Glucuronic Acid , Hexuronic Acids , Immunoglobulin G/biosynthesis , Immunoglobulin G/blood , Interferon-gamma/biosynthesis , Interleukin-12/biosynthesis , Interleukin-4/biosynthesis , Lymphocyte Function-Associated Antigen-1/biosynthesis , Mice , Mice, Inbred BALB C , Models, Animal , Pseudomonas aeruginosa , Recurrence , Th1 Cells/metabolism
8.
J Nat Prod ; 64(11): 1398-403, 2001 Nov.
Article in English | MEDLINE | ID: mdl-11720520

ABSTRACT

Cryptotanshinone (1), a quinoid diterpene with a nor-abietane skeleton, and three new natural products, 1beta-hydroxycryptotanshinone (2), 1-oxocryptotanshinone (3), and 1-oxomiltirone (4), were isolated from roots of the Iranian medicinal plant Perovskia abrotanoides. Their structures were established using homo- and heteronuclear two-dimensional NMR experiments, supported by HRMS. The total amount of tanshinones isolated from dry roots of Perovskia abrotanoides was about 1.5%. The compounds exhibited leishmanicidal activity in vitro (IC(50) values in the range 18-47 microM). These findings provide a rationale for traditional use of the roots in Iran as a constituent of poultices for treatment of cutaneous leishmaniasis. The isolated tanshinones also inhibited growth of cultured malaria parasites (3D7 strain of Plasmodium falciparum), drug-sensitive KB-3-1 human carcinoma cell line, multidrug-resistant KB-V1 cell line, and human lymphocytes activated with phytohaemagglutinin A (IC(50) values in the range 5-45 microM). The toxicity of tanshinones toward the drug-sensitive KB-3-1 and the multidrug-resistant KB-V1 cells was the same, indicating that the compounds are not substrates for the P-glycoprotein drug efflux pump.


Subject(s)
Anti-Infective Agents/isolation & purification , Antineoplastic Agents, Phytogenic/isolation & purification , Antiprotozoal Agents/isolation & purification , Diterpenes/isolation & purification , Lamiaceae/chemistry , Phenanthrenes/chemistry , Phenanthrenes/isolation & purification , Abietanes , Animals , Anti-Infective Agents/chemistry , Anti-Infective Agents/pharmacology , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/pharmacology , Antiprotozoal Agents/chemistry , Antiprotozoal Agents/pharmacology , Chromatography, Thin Layer , Diterpenes/chemistry , Diterpenes/pharmacology , Drug Resistance/physiology , Humans , Iran , Leishmania major/drug effects , Lymphocytes/blood , Lymphocytes/drug effects , Nuclear Magnetic Resonance, Biomolecular , Phenanthrenes/pharmacology , Phytohemagglutinins/pharmacology , Plant Lectins , Plant Roots/chemistry , Plants, Medicinal/chemistry , Plasmodium falciparum/drug effects , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization , Tumor Cells, Cultured/drug effects
9.
Int J Sports Med ; 22(4): 256-60, 2001 May.
Article in English | MEDLINE | ID: mdl-11414666

ABSTRACT

This study evaluated whether the reduction of the neutrophil oxidative burst by N-acetylcysteine improves pulmonary gas exchange during a six minute maximal ergometer row. Healthy trained oarsmen were double-blinded randomized to either N-acetylcysteine (6 g daily for three days) or placebo groups. As determined by the relative changes of the zymosan-stimulated luminol-enhanced chemiluminescence response, N-acetylcysteine suppressed the exercise-induced enhanced neutrophil oxidative burst response to rowing (-7 +/- 6% vs. 17 +/- 8%; P < 0.05). This was the case although the concentration of neutrophils remained similarly elevated above the pre-exercise level in both trials (to 5.4+/-0.5 vs. 5.9+/-0.6 x 10(9) cells x l(-1), respectively, P>0.05). In the placebo and N-acetylcysteine groups, pulmonary ventilation increased and the arterial CO2 partial pressure decreased to the same extent during exercise. Also, at the end of exercise the arterial O2 partial pressure (77 1 vs. 78+/-1 mmHg), haemoglobin O2 saturation (92 +/- 1% vs. 93 +/- 1%) and O2 uptake (5.0 +/- 0.2 vs. 4.9 +/- 0.21 x min(-1)) were not significantly affected by N-acetylcysteine. Equally, two hours after exercise, the pulmonary diffusion capacity was reduced by 7 +/- 2% below the pre-exercise with no significant influence of N-acetylcysteine. We conclude that the neutrophil oxidative burst to exercise does not influence pulmonary gas exchange during and after maximal rowing.


Subject(s)
Acetylcysteine/pharmacology , Free Radical Scavengers/pharmacology , Neutrophils/drug effects , Pulmonary Gas Exchange/drug effects , Sports/physiology , Acetylcysteine/metabolism , Adult , Ergometry , Free Radical Scavengers/metabolism , Humans , Male , Neutrophils/physiology , Pulmonary Gas Exchange/physiology , Respiratory Burst/physiology
10.
Antimicrob Agents Chemother ; 45(7): 2023-9, 2001 Jul.
Article in English | MEDLINE | ID: mdl-11408218

ABSTRACT

Our previous studies have shown that chalcones exhibit potent antileishmanial and antimalarial activities in vitro and in vivo. Preliminary studies showed that these compounds destroyed the ultrastructure of Leishmania parasite mitochondria and inhibited the respiration and the activity of mitochondrial dehydrogenases of Leishmania parasites. The present study was designed to further investigate the mechanism of action of chalcones, focusing on the parasite respiratory chain. The data show that licochalcone A inhibited the activity of fumarate reductase (FRD) in the permeabilized Leishmania major promastigote and in the parasite mitochondria, and it also inhibited solubilized FRD and a purified FRD from L. donovani. Two other chalcones, 2,4-dimethoxy-4'-allyloxychalcone (24m4ac) and 2,4-dimethoxy-4'-butoxychalcone (24mbc), also exhibited inhibitory effects on the activity of solubilized FRD in L. major promastigotes. Although licochalcone A inhibited the activities of succinate dehydrogenase (SDH), NADH dehydrogenase (NDH), and succinate- and NADH-cytochrome c reductases in the parasite mitochondria, the 50% inhibitory concentrations (IC(50)) of licochalcone A for these enzymes were at least 20 times higher than that for FRD. The IC(50) of licochalcone A for SDH and NDH in human peripheral blood mononuclear cells were at least 70 times higher than that for FRD. These findings indicate that FRD, one of the enzymes of the parasite respiratory chain, might be the specific target for the chalcones tested. Since FRD exists in the Leishmania parasite and does not exist in mammalian cells, it could be an excellent target for antiprotozoal drugs.


Subject(s)
Chalcone/pharmacology , Leishmania donovani/drug effects , Leishmania major/drug effects , Succinate Dehydrogenase/antagonists & inhibitors , Animals , Antiprotozoal Agents/pharmacology , Chalcone/analogs & derivatives , Chalcones , Electron Transport/drug effects , Enzyme Inhibitors/pharmacology , Leishmania donovani/enzymology , Leishmania major/enzymology , Mitochondria/drug effects , Mitochondria/enzymology , NADH Dehydrogenase/metabolism , Permeability/drug effects , Phenylacetates/pharmacology , Succinate Cytochrome c Oxidoreductase/metabolism , Succinate Dehydrogenase/drug effects , Succinate Dehydrogenase/metabolism
11.
Acta Trop ; 79(2): 129-33, 2001 May 25.
Article in English | MEDLINE | ID: mdl-11369305

ABSTRACT

Lymphadenitis with or without dry-type cutaneous leishmaniasis is rare. The lesion might self heal or show excellent response to antimonial therapy. Routine histopathological changes of localized leishmaniasis lymphadenitis are non-caseating to suppurative granulomata mostly in paracortical areas, some with extension to germinal centres, medullary cords and/or pericapsular spaces which have to be distinguished from other causes of lymphadenitis such as tuberculosis, cat-scratch disease and toxoplasmosis. Dense lymphoplasmocytic infiltrate was observed surrounding the necrotizing granuloma together with dense capsular fibrosis with multiple granulomata in subcapsular and pericapsular areas. Immunostaining of lymph nodes showed that a few macrophages were harbouring Leishman bodies. Dispersed Langerhans cells were also harbouring Leishman bodies in the parasitophorous vacuoles between their cytoplasmic pseudopods. In conclusion multiple noncaseating to suppurative granulomata with dense pericapsular and capsular granulomo-sclerotic changes should be considered in the differential diagnosis of leishmaniasis lymphadenitis.


Subject(s)
Leishmania tropica/isolation & purification , Leishmaniasis, Cutaneous/pathology , Lymphadenitis/pathology , Adolescent , Adult , Animals , Case-Control Studies , Child , Diagnosis, Differential , Female , Humans , Leishmaniasis, Cutaneous/complications , Leishmaniasis, Cutaneous/diagnosis , Lymphadenitis/complications , Lymphadenitis/diagnosis , Male
12.
Microbes Infect ; 3(1): 23-35, 2001 Jan.
Article in English | MEDLINE | ID: mdl-11226851

ABSTRACT

The biofilm mode of growth is the survival strategy of environmental bacteria like Pseudomonas aeruginosa. Such P. aeruginosa biofilms also occur in the lungs of chronically infected cystic fibrosis patients, where they protect the bacteria against antibiotics and the immune response. The lung tissue damage is due to immune complex mediated chronic inflammation dominated by polymorphonuclear leukocytes releasing proteases and oxygen radicals.


Subject(s)
Cystic Fibrosis/microbiology , Pseudomonas Infections/microbiology , Pseudomonas aeruginosa/physiology , Animals , Anti-Bacterial Agents/pharmacology , Biofilms , Chronic Disease , Cystic Fibrosis/immunology , Drug Resistance, Microbial , Endopeptidases/metabolism , Humans , Inflammation/immunology , Lung/microbiology , Lung/pathology , Neutrophils/metabolism , Pseudomonas aeruginosa/drug effects
13.
APMIS ; 109(12): 801-8, 2001 Dec.
Article in English | MEDLINE | ID: mdl-11846720

ABSTRACT

A 65 kD membrane-associated NADH-fumarate reductase subunit, which has a molecular weight similar to that of one of the enzyme subunits from bacteria, was purified from Leishmania donovani promastigotes. NADH-fumarate reductase and other mitochondrial enzymatic activities of L. major and L. donovani promastigotes and amastigotes were investigated. The presence of NADH-fumarate reductase was demonstrated in digitonin-permeabilized L. major promastigotes and mitochondria of L. major and L. donovani promastigotes and amastigotes. The activity of solubilized NADH-fumarate reductase was measured in L. major and L. donovani promastigotes. Succinate exhibited a clear concentration-dependent inhibitory effect on fumarate reductase, whereas fumarate also exhibited a clear concentration-dependent inhibitory effect on succinate dehydrogenase. The data indicate that fumarate reductase is an obligatory component of the respiratory chain of the parasite. Since the enzyme is an important component in the intermediate metabolism in the Leishmania parasite and is absent in mammalian cells, it could be a potential target for antileishmanial drugs.


Subject(s)
Leishmania/enzymology , Mitochondria/enzymology , Oxidoreductases Acting on CH-CH Group Donors , Oxidoreductases/isolation & purification , Animals , Calcium/pharmacology , Cell Line , Magnesium/pharmacology , Mice , NAD/metabolism , Oxidoreductases/antagonists & inhibitors , Oxidoreductases/metabolism
14.
Clin Exp Immunol ; 122(2): 207-11, 2000 Nov.
Article in English | MEDLINE | ID: mdl-11091276

ABSTRACT

The role of interleukin (IL)-8 as mediator in the recruitment of leucocytes into the CSF was investigated during experimental pneumococcal meningitis. Rabbits were inoculated intracisternally with approximately 10(6) CFU Streptococcus pneumoniae, and treated (i) intravenously with 5 mg of a monoclonal antibody to IL-8 (n = 7) or 5 mg of an isotype control antibody (n = 6); (ii) intracisternally with anti-IL-8, 100 microg (n = 5), 10 microg (n = 4), 1 microg (n = 4), 0.1 microg (n = 2). Ten rabbits served as untreated control group. Intravenous treatment with anti-IL-8 attenuated the pleocytosis significantly compared to untreated rabbits (P < 0.04) or rabbits treated with an isotype control antibody (P < 0.02). In contrast, intracisternal treatment with anti-IL-8 failed to attenuate the pleocytosis (P > 0.05). These results show, that IL-8 plays an important role in the recruitment of leucocytes during experimental pneumococcal meningitis, and that the functional activity of IL-8 in this process appears to be on the bloodstream side of the microvascular endothelium of the brain.


Subject(s)
Antibodies, Monoclonal/administration & dosage , Interleukin-8/antagonists & inhibitors , Leukocytosis/therapy , Meningitis, Pneumococcal/therapy , Animals , Brain/blood supply , Brain/immunology , Cisterna Magna , Endothelium, Vascular/immunology , Injections , Injections, Intravenous , Leukocytosis/etiology , Leukocytosis/immunology , Meningitis, Pneumococcal/cerebrospinal fluid , Meningitis, Pneumococcal/complications , Meningitis, Pneumococcal/immunology , Rabbits
15.
Planta Med ; 66(6): 531-6, 2000 Aug.
Article in English | MEDLINE | ID: mdl-10985079

ABSTRACT

Five indole alkaloids, corynantheidine, corynantheine, dihydrocorynantheine, alpha-yohimbine and corynanthine were isolated from bark of Corynanthe pachyceras K. Schum. (Rubiaceae). The structures were established by spectroscopic methods, including previously unreported assignment of all 1H-NMR resonances by COSY and NOESY experiments. These and related alkaloids showed pronounced activity against Leishmania major promastigotes (IC50 at the micromolar level) but no significant in vitro antiplasmodial activity (against chloroquine-sensitive Plasmodium falciparum). Cytotoxicity assessed with drug sensitive KB-3-1 and multidrug-resistant KB-V1 cell lines was low; the alkaloids are apparently not substrates for the P-glycoprotein (P-170) efflux pump.


Subject(s)
Alkaloids/pharmacology , Antineoplastic Agents, Phytogenic/pharmacology , Antiprotozoal Agents/pharmacology , Indoles/chemistry , Plants, Medicinal/chemistry , Alkaloids/chemistry , Alkaloids/isolation & purification , Animals , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/isolation & purification , Antiprotozoal Agents/chemistry , Antiprotozoal Agents/isolation & purification , Humans , Leishmania major/drug effects , Plasmodium falciparum/drug effects , Tumor Cells, Cultured
16.
J Nat Prod ; 63(9): 1295-6, 2000 Sep.
Article in English | MEDLINE | ID: mdl-11000043

ABSTRACT

Minquartynoic acid (1) was isolated as an antimalarial and antileishmanial constituent of the Peruvian tree Minquartia guianensis and its absolute configuration at C-17 established to be (+)-S through conversion to the known (+)-(S)-17-hydroxystearic acid (2) and confirmed using Mosher's method.


Subject(s)
Alkynes , Antiprotozoal Agents/chemistry , Antiprotozoal Agents/pharmacology , Fatty Acids, Unsaturated/pharmacology , Animals , Cell Division/drug effects , Fatty Acids, Unsaturated/chemistry , Humans , Leishmania major/drug effects , Lymphocytes/cytology , Lymphocytes/drug effects , Molecular Structure , Plasmodium falciparum/drug effects , Polyynes
17.
APMIS ; 108(5): 329-35, 2000 May.
Article in English | MEDLINE | ID: mdl-10937769

ABSTRACT

Most cystic fibrosis (CF) patients with chronic Pseudomonas aeruginosa lung infection have a persistent acute type lung inflammation dominated by polymorphonuclear neutrophils (PMN) and a pronounced antibody response against P. aeruginosa. We speculated whether this immune response in CF is of the Th2 type and whether a change to a Th1 type immune response could improve the prognosis. Therefore, we studied 14 CF patients with (CF +P) and 14 CF patients without (CF -P) chronic P. aeruginosa lung infection. The specific production of interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) by peripheral blood mononuclear cells was determined. Cells from CF +P patients had lower IFN-gamma (p<0.05) and higher IL-4 (p<0.005) production as compared to cells from CF -P patients. Furthermore, a positive correlation between IFN-gamma production and lung function was found (FVC: Rho = 0.637; p<0.03; FEV1: Rho=0.524; p<0.07). We conclude that a Th2 type immune response is most frequent in CF patients with chronic P. aeruginosa lung infection, and the patients with a Th1-dominated immune response had the best lung function. The clinical implication is that a change to a Th1 type immune response might improve the prognosis in these patients.


Subject(s)
Cystic Fibrosis/immunology , Lung Diseases/immunology , Pseudomonas Infections/immunology , Th2 Cells/immunology , Adult , Anti-Bacterial Agents/therapeutic use , Chronic Disease , Female , Humans , Interferon-gamma/biosynthesis , Interleukin-4/biosynthesis , Lung Diseases/drug therapy , Male , Pseudomonas Infections/drug therapy
18.
Acta Trop ; 75(1): 1-7, 2000 Feb 25.
Article in English | MEDLINE | ID: mdl-10708001

ABSTRACT

The skin lesions of five patient volunteers with dry-type cutaneous leishmaniasis were treated by intralesional injection of auto-leukocytes prepared from buffy coat of the patient's own blood. Giemsa stained, air-dried cytological smear preparations were prepared from scrapings taken from the margins of the lesions. The cellular interaction between the organism and the inflammatory response of the host was studied. All lesions showed clinical evidence of regression. The cytological findings suggested progressive degradation of the Leishman donovan (LD) bodies within the parasitophorous vacuoles of the activated macrophages. The parasiticidal effect appeared to be induced by synergistic action of the injected neutrophils and lymphocytes. Due to lack of placebo controls in this study the possibility that, healing might not be related to therapy can not be excluded. This study illustrates the potential for intralesional autotherapy with buffy coat in dry-type cutaneous leishmaniasis.


Subject(s)
Immunotherapy , Leishmaniasis, Cutaneous/therapy , Leukocytes/immunology , Adolescent , Adult , Female , Humans , Injections, Intralesional , Leishmaniasis, Cutaneous/immunology , Leishmaniasis, Cutaneous/parasitology , Leishmaniasis, Cutaneous/pathology , Macrophages/parasitology , Male , Middle Aged , Skin/parasitology , Skin/pathology
19.
Infect Immun ; 68(4): 1760-4, 2000 Apr.
Article in English | MEDLINE | ID: mdl-10722561

ABSTRACT

Th1-type cellular immune responses play a critical role in protection against infection with Leishmania parasites, whereas activation of Th2-type cells results in progressive disease. Cutaneous leishmaniasis caused by Leishmania major is often a self-healing disease; however, persistent nonhealing forms are also known. In the present study, we have described cell-mediated immune responses in nonhealing patients by measuring T-cell proliferation, cytokine production, and phenotypic characterization of these cells. The responses were compared with those of patients with active lesions, patients who had recovered from infection, and healthy controls. Peripheral blood mononuclear cells from patients with active lesions and recovered donors proliferated vigorously and produced Th1-type cytokine when stimulated with L. major antigens, whereas in nonhealing patients the proliferative responses were significantly lower and showed a Th2-type response to Leishmania antigens. Interleukin-10 (IL-10) production was not a feature of L. major stimulation. Flow cytometric analysis revealed that L. major antigen induced proliferation of the CD4-positive population and that these cells were the major source of gamma interferon and IL-4. These results show a distinct dichotomy in the cytokine response to L. major infection.


Subject(s)
Leishmania major/immunology , Leishmaniasis, Cutaneous/immunology , T-Lymphocytes/immunology , Adolescent , Adult , Aged , Animals , CD4 Antigens/immunology , CD8 Antigens/immunology , Cell Division , Female , Flow Cytometry , Humans , Immunoglobulin G/immunology , Immunophenotyping , Interferon-gamma/biosynthesis , Interleukin-10/biosynthesis , Interleukin-4/biosynthesis , Leukocytes, Mononuclear/immunology , Lymphocyte Subsets/immunology , Male , Middle Aged , Th1 Cells/immunology
20.
Clin Exp Immunol ; 119(3): 523-9, 2000 Mar.
Article in English | MEDLINE | ID: mdl-10691926

ABSTRACT

PKDL develops in about 50% of Sudanese patients treated for visceral leishmaniasis (kala-azar). Patients with kala-azar were entered into this study and followed for a period of up to 2 years. During follow up 12 patients developed PKDL and eight did not. Proliferative responses and cytokine production to Leishmania donovani and control antigens were measured in vitro using PBMC isolated at the time of diagnosis of kala-azar, after treatment of visceral leishmaniasis, during follow up, and at the time of diagnosis of PKDL. Proliferative responses and interferon-gamma (IFN-gamma) production were low at diagnosis and increased after treatment of kala-azar in both patients who developed (group 1) and those who did not develop PKDL later (group 2). In group 1, development of PKDL was always associated by an increased PBMC response to Leishmania antigen in proliferation and IFN-gamma production assays. There were no differences in Leishmania antigen-induced production of IL-4, IL-5 and IL-10 between or within the two groups. We have previously shown that Leishmania parasites spread to the skin during visceral leishmaniasis and proposed that PKDL was the result of an immunological attack on parasites, which have survived in the skin despite the drug treatment. The finding that PKDL develops after treatment of kala-azar as Leishmania-reactive T cells start to circulate in peripheral blood in sufficient numbers to be detected in in vitro assays supports this hypothesis.


Subject(s)
Interferon-gamma/immunology , Leishmania/isolation & purification , Leishmaniasis, Visceral/immunology , Leishmaniasis, Visceral/parasitology , Leukocytes, Mononuclear/immunology , Leukocytes, Mononuclear/parasitology , Adolescent , Adult , Animals , Antigens, Protozoan/immunology , Cell Differentiation/immunology , Cell Division/immunology , Female , Humans , Leishmania/immunology , Leishmaniasis, Visceral/blood , Male , Middle Aged
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