Chloroquine Treatment (chloroquine + treatment)

Distribution by Scientific Domains
Medical Sciences57%
Life Sciences42%

Selected Abstracts

Does chloroquine therapy of porphyria cutanea tarda influence liver pathology?

INTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 11 2009
U Wollina MD
Background, Porphyria cutanea tarda (PCT) is regularly associated with changes in liver tissue. On the other hand, systematic investigations are lacking on whether there is a correlation between the severity of liver damage and chloroquine treatment. Patients and methods, During a 20-year period, liver biopsies were obtained in 89 patients with PCT confirmed by biochemical analysis of urine and feces and low-dose chloroquine therapy. Seventeen patients with alcohol-induced liver disease were excluded. In 8 of 63 patients, only a single biopsy was available. Classification of liver damage was performed according to the Riedel score. Electron microscopy was available from 24 patients. In a second group of patients, the HFE status was investigated and Berlin blue stains of liver biopsies were performed. Results, There was no correlation between the duration of cutaneous symptoms and liver pathology. After 12 months chloroquine treatment, 45 patients (81%) disclosed an improvement of liver pathology, nine (16%) had no change, and a worsening was observed in one patient (3%). All patients achieved a complete clinical and biochemical remission. In 13 of 16 patients with a relapse, there was again a deterioration of liver damage. Patients with HFE mutations had a significant higher risk (P < 0.05) for hepatic siderosis. Conclusions, The severity of liver damage was not correlated with the disease duration. Chloroquine treatment resulted in PCT remission (clinical and biochemical) and in 81% to an improvement of liver morphology. [source]

Accelerated release of exosome-associated GM1 ganglioside (GM1) by endocytic pathway abnormality: another putative pathway for GM1-induced amyloid fibril formation

JOURNAL OF NEUROCHEMISTRY, Issue 1 2008
Kohei Yuyama
Abstract Exosomes are extracellularly released small vesicles that are derived from multivesicular bodies formed via the endocytic pathway. We treated pheochromocytoma PC12 cells with chloroquine, an acidotropic agent, which potently perturbs membrane trafficking from endosomes to lysosomes. Chloroquine treatment increased the level of GM1 ganglioside in cell media only when the cells were exposed to KCl for depolarization, which is known to enhance exosome release from neurons. In the sucrose-density-gradient fractionation of cell media, GM1 ganglioside was exclusively recovered with Alix, a specific marker of exosomes, in the fractions with the density corrresponding to that of exosomes. Notably, amyloid-, assembly was markedly accelerated when incubated with the exosome fraction prepared from the culture media of PC12 cells treated with chloroquine and KCl. Furthermore, amyloid-, assembly was significantly suppressed by the co-incubation with an antibody specific to GM1-bound amyloid-,, an endogenous seed for amyloid formation of Alzheimer's disease. Together with our previous finding that chloroquine treatment induces the accumulation of GM1 ganglioside in early endosomes, results of this study suggest that endocytic pathway abnormality accelerates the release of exosome-associated GM1 ganglioside following its accumulation in early endosomes. Furthermore, this study also suggests that extracellular amyloid fibril formation is induced by not only GM1 gangliosides accumulated on the surface of the cells but also those released in association with exosomes. [source]

pH-dependent translocation of ,-tocopherol transfer protein (,-TTP) between hepatic cytosol and late endosomes

GENES TO CELLS, Issue 10 2003
Masakuni Horiguchi
Background:, ,-Tocopherol transfer protein (,-TTP), a member of the Sec14 protein family, plays an important role in transporting ,-tocopherol, a major lipid-soluble anti-oxidant, in the cytosolic compartment of hepatocytes and is known as a product of the causative gene for familial isolated vitamin E deficiency. It has been shown that the secretion of hepatocyte ,-tocopherol taken up with plasma lipoproteins is facilitated by ,-TTP. To explore the mechanism of ,-TTP mediated ,-tocopherol secretion, we investigated drugs which may affect this secretion. Results:, We found that, in a hepatocyte cell culture system, intracellular ,-tocopherol transport is impaired by chloroquine, an agent known for its function of elevating the pH in acidic compartments. Under chloroquine treatment, the diffuse cytosolic distribution of ,-TTP changes to a punctate pattern. Double-staining experiments with endocytosis markers revealed that ,-TTP accumulates transiently on the cytoplasmic surface of late endosomal membranes. This phenomenon is specific for hepatoma cell lines or primarily cultured hepatocytes. Other members of the Sec14 family, such as cellular retinaldehyde-binding protein (CRALBP) and supernatant protein factor (SPF), do not show this accumulation. Furthermore, we elucidate that the obligatory amino acid sequence for this function is located between amino acids 21 and 50, upstream of the N-terminal end of the lipid-binding domain. Conclusion:, We hypothesize that a liver-specific target molecule for ,-TTP exists on the late endosomal membrane surface. This transient binding may explain the mechanism of how ,-tocopherol is transferred from late endosomes to cytosolic ,-TTP. [source]

Does chloroquine therapy of porphyria cutanea tarda influence liver pathology?

INTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 11 2009
U Wollina MD
Background, Porphyria cutanea tarda (PCT) is regularly associated with changes in liver tissue. On the other hand, systematic investigations are lacking on whether there is a correlation between the severity of liver damage and chloroquine treatment. Patients and methods, During a 20-year period, liver biopsies were obtained in 89 patients with PCT confirmed by biochemical analysis of urine and feces and low-dose chloroquine therapy. Seventeen patients with alcohol-induced liver disease were excluded. In 8 of 63 patients, only a single biopsy was available. Classification of liver damage was performed according to the Riedel score. Electron microscopy was available from 24 patients. In a second group of patients, the HFE status was investigated and Berlin blue stains of liver biopsies were performed. Results, There was no correlation between the duration of cutaneous symptoms and liver pathology. After 12 months chloroquine treatment, 45 patients (81%) disclosed an improvement of liver pathology, nine (16%) had no change, and a worsening was observed in one patient (3%). All patients achieved a complete clinical and biochemical remission. In 13 of 16 patients with a relapse, there was again a deterioration of liver damage. Patients with HFE mutations had a significant higher risk (P < 0.05) for hepatic siderosis. Conclusions, The severity of liver damage was not correlated with the disease duration. Chloroquine treatment resulted in PCT remission (clinical and biochemical) and in 81% to an improvement of liver morphology. [source]

Accelerated release of exosome-associated GM1 ganglioside (GM1) by endocytic pathway abnormality: another putative pathway for GM1-induced amyloid fibril formation

JOURNAL OF NEUROCHEMISTRY, Issue 1 2008
Kohei Yuyama
Abstract Exosomes are extracellularly released small vesicles that are derived from multivesicular bodies formed via the endocytic pathway. We treated pheochromocytoma PC12 cells with chloroquine, an acidotropic agent, which potently perturbs membrane trafficking from endosomes to lysosomes. Chloroquine treatment increased the level of GM1 ganglioside in cell media only when the cells were exposed to KCl for depolarization, which is known to enhance exosome release from neurons. In the sucrose-density-gradient fractionation of cell media, GM1 ganglioside was exclusively recovered with Alix, a specific marker of exosomes, in the fractions with the density corrresponding to that of exosomes. Notably, amyloid-, assembly was markedly accelerated when incubated with the exosome fraction prepared from the culture media of PC12 cells treated with chloroquine and KCl. Furthermore, amyloid-, assembly was significantly suppressed by the co-incubation with an antibody specific to GM1-bound amyloid-,, an endogenous seed for amyloid formation of Alzheimer's disease. Together with our previous finding that chloroquine treatment induces the accumulation of GM1 ganglioside in early endosomes, results of this study suggest that endocytic pathway abnormality accelerates the release of exosome-associated GM1 ganglioside following its accumulation in early endosomes. Furthermore, this study also suggests that extracellular amyloid fibril formation is induced by not only GM1 gangliosides accumulated on the surface of the cells but also those released in association with exosomes. [source]

The influence of antimalarial treatment on IL-1,, IL-6 and TNF-, mRNA expression on UVB-irradiated skin in systemic lupus erythematosus

BRITISH JOURNAL OF DERMATOLOGY, Issue 5 2008
A. Wozniacka
Summary Background, There are very few data addressing the mechanisms of antimalarial treatment benefit locally within the skin of patients with lupus erythematosus, at the level of cytokine messenger RNA (mRNA) expression. Objectives, The aim of this study was to evaluate whether 3 months of monotherapy with chloroquine influences the mRNA skin expression of interleukin (IL)-1,, IL-6 and tumour necrosis factor-, (TNF-,) in nonirradiated and locally ultraviolet B (UVB) irradiated nondiseased skin of patients with systemic lupus erythematosus (SLE). Patients/Methods, Skin biopsies were collected from 14 patients with SLE 24 h after irradiation at one site and from an adjacent unirradiated site, before and after 3 months of chloroquine treatment. Messenger RNA levels for IL-1,, IL-6 and TNF-, were determined by relative quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). Results, There were no significant differences in the levels of mRNA cytokine expressions in the unirradiated sites before and after 3 months of chloroquine administration. In the irradiated sites, the expression of all three cytokine mRNA levels was significantly higher than in the unirradiated group, approximately 24 h after irradiation, before chloroquine treatment. Significantly lower expression of IL-1,, IL-6 and TNF-, mRNAs was noted in irradiated skin samples after 3 months of chloroquine treatment. Conclusions, These results demonstrate the local inhibitory effects of chloroquine on UVB-induced upregulation in the mRNA expression of proinflammatory cytokines in irradiated skin of SLE patients, and provide further insight into the apparent immunomodulatory, anti-inflammatory and photoprotective properties of chloroquine. [source]