Biomedical subjects

A Kharazmi

Publications and source records attributed to A Kharazmi.

At least 19 recordsLinked to original sources

PubMed2006

Increased serum concentration of G-CSF in cystic fibrosis patients with chronic Pseudomonas aeruginosa pneumonia.

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.

Adolescent↗

PubMed2004

A herbal remedy, Hyben Vital (stand. powder of a subspecies of Rosa canina fruits), reduces pain and improves general wellbeing in patients with osteoarthritis--a double-blind, placebo-controlled, randomised trial.

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.

Adult↗

PubMed2004

Faster activation of polymorphonuclear neutrophils in resistant mice during early innate response to Pseudomonas aeruginosa lung infection.

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.

Animals↗

PubMed2002

Improved outcome of chronic Pseudomonas aeruginosa lung infection is associated with induction of a Th1-dominated cytokine response.

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.

Agar↗

PubMed2001

A description of parasite-harbouring cells in localized lymphadenitis in dry type cutaneous leishmaniasis.

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.

Adolescent↗

PubMed2001

Pseudomonas aeruginosa and the in vitro and in vivo biofilm mode of growth.

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.

Animals↗

PubMed2001

Leishmanicidal, antiplasmodial, and cytotoxic activity of novel diterpenoid 1,2-quinones from Perovskia abrotanoides: new source of tanshinones.

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.

Abietanes↗

PubMed2001

Purification and enzymatic activity of an NADH-fumarate reductase and other mitochondrial activities of Leishmania parasites.

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.

Animals↗

PubMed2001

N-acetylcysteine attenuates oxidative burst by neutrophils in response to ergometer rowing with no effect on pulmonary gas exchange.

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.

Acetylcysteine↗

PubMed2001

Inhibition of fumarate reductase in Leishmania major and L. donovani by chalcones.

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.

Animals↗

PubMed2000

Intralesional autotherapy of cutaneous leishmaniasis with buffy coat cells: cytological findings.

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.

Adolescent↗

PubMed2000

Molecular characterization of a Leishmania donovanii cDNA clone with similarity to human 20S proteasome a-type subunit.

Using plasma from patients infected or previously infected with Leishmania donovanii, we isolated a L. donovanii cDNA clone with similarity to the proteasome a-type subunit from humans and other eukaryotes. The cDNA clone, designated LePa, was DNA sequenced and Northern blot analysis of L. donovanii poly(A(+))mRNA indicated the isolation of a full length cDNA clone with a transcript size of 1.9 kb. The expressed recombinant LePa fusion protein induced proliferation of peripheral blood mononuclear cells in one out of seven patients who had suffered from visceral leishmaniasis. Plasma from 16 out of 25 patients with visceral leishmaniasis and four out of 18 patients with cutaneous leishmaniasis contained IgG antibodies which reacted with the purified LePa fusion protein as evaluated in an ELISA. The LePa DNA sequence was inserted into an eukaryotic expression vector and Balb/c mice were vaccinated. DNA vaccination of Balb/c mice with LePa generated an initial significant reduction in lesion size after challenge.

Animals↗

PubMed2000

Absolute configuration and antiprotozoal activity of minquartynoic acid.

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.

Alkynes↗

PubMed2000

The immune response to chronic Pseudomonas aeruginosa lung infection in cystic fibrosis patients is predominantly of the Th2 type.

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.

Adult↗

PubMed2000

The development of post-kala-azar dermal leishmaniasis (PKDL) is associated with acquisition of Leishmania reactivity by peripheral blood mononuclear cells (PBMC).

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.

Adolescent↗

PubMed2000

Treatment with a monocolonal antibody to IL-8 attenuates the pleocytosis in experimental pneumococcal meningitis in rabbits when given intravenously, but not intracisternally.

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.

Animals↗

PubMed2000

Leishmanicidal, antiplasmodial and cytotoxic activity of indole alkaloids from Corynanthe pachyceras.

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.

Alkaloids↗

PubMed2000

Comparison of the immune profile of nonhealing cutaneous Leishmaniasis patients with those with active lesions and those who have recovered from infection.

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.

Adolescent↗