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Biomedical subjects

K Chou

Publications and source records attributed to K Chou.

At least 19 recordsLinked to original sources

Orally administered RDP58 reduces the severity of dextran sodium sulphate induced colitis.

Oral administration of the novel anti-inflammatory peptide RDP58 markedly reduced the severity of dextran sulphate sodium (DSS) colitis as determined by clinical and quantitative histological criteria. The architecture of the colonic epithelium in DSS treated mice receiving RDP58 remained relatively normal compared with that of control DSS treated animals. 5-Bromo-2'-deoxyuridine (BrdU) labelling studies showed a pronounced inhibition of colonic epithelial cell proliferation during DSS treatment, which was partially reversed by RDP58 therapy. Remarkably, RDP58 almost completely prevented colonic epithelial cell death induced by DSS treatment. RDP58 therapy also inhibited the accumulation of neutrophils in the colon of DSS treated mice and effectively down regulated tumour necrosis factor (TNF) expression. Preservation of the intestinal mucosa by RDP58 may thus derive from its influence on TNF expression as well as additional anti-inflammatory properties. These findings indicate that RDP58 represents a new, orally available agent potentially useful in the treatment of inflammatory bowel disease.

Acute Disease↗

The anti-anginal drug fendiline increases intracellular Ca(2+) levels in MG63 human osteosarcoma cells.

The effect of fendiline, an anti-anginal drug, on cytosolic free Ca(2+) levels ([Ca(2+)](i)) in MG63 human osteosarcoma cells was explored by using fura-2 as a Ca(2+) indicator. Fendiline at concentrations between 1 and 200 microM increased [Ca(2+)](i) in a concentration-dependent manner and the signal saturated at 100 microM. The Ca(2+) signal was inhibited by 65+/-5% by Ca(2+) removal and by 38+/-5% by 10 microM nifedipine, but was unchanged by 10 microM La(3+) or verapamil. In Ca(2+)-free medium, pre-treatment with 1 microM thapsigargin (an endoplasmic reticulum Ca(2+) pump inhibitor) to deplete the endoplasmic reticulum Ca(2+) store inhibited fendiline-induced intracellular Ca(2+) release. The Ca(2+) release induced by 50 microM fendiline appeared to be independent of IP(3) because the [Ca(2+)](i) increase was unaltered by inhibiting phospholipase C with 2 microM U73122. Collectively, the results suggest that in MG63 cells fendiline caused an increase in [Ca(2+)](i) by inducing Ca(2+) influx and Ca(2+) release in an IP(3)-independent manner.

Calcium↗

Geochemistry of Bulgarian soils in villages affected and not affected by Balkan endemic nephropathy: a pilot study.

Balkan endemic nephropathy (BEN) is a chronic tubulointerstitial disease whose mosaic-like distribution throughout the Balkans has not changed significantly since its initial description. In this study, we explored the hypothesis that the occurrence of BEN is linked with the environmental geochemistry of villages. Soil samples were collected from BEN and non-BEN villages in the Vratza region of Bulgaria. Samples were digested in nitric acid and analyzed for 22 elements by hexapole, inductively coupled plasma, and mass spectrometry. Selected results are that: 1) absolute concentrations from both types of villages were not enriched above "background" concentrations; and 2) copper, molybdenum, lead, and cadmium concentrations were higher in BEN than in non-BEN soils, while selenium concentrations were lower. Although geochemical differences between BEN and non-BEN villages were found, not all differences were statistically significant, in part due to a limited number of samples.

Balkan Nephropathy↗

Color Doppler imaging of retrobulbar hemodynamics after topical carteolol in normal tension glaucoma.

BACKGROUND: Carteolol is a nonselective adrenergic blocking agent. The aim of this study was to evaluate the effect of topical carteolol on retrobulbar hemodynamics in patients with normal tension glaucoma (NTG). METHODS: Twelve NTG patients received twelve-week topical treatment of 2% carteolol. Color Doppler imaging (CDI) was used to evaluate the hemodynamic effects before and after drug therapy. Measurements were obtained from the central retinal artery (CRA), the lateral posterior ciliary artery (LPCA) and the medial posterior ciliary artery (MPCA). From each vessel, peak systolic velocity (PSV), end-diastolic velocity (EDV), resistance index (RI) and Gosling's pulsatility index (PI) were collected and analyzed. RESULTS: After topical carteolol treatment for twelve weeks, mean resistance index reduced significantly from 0.83 to 0.74 in the CRA (p = 0.03), from 0.74 to 0.68 in the LPCA (p = 0.09). Moreover, mean pulsatility index of the LPCA decreased from 1.45 to 1.26 (p = 0.08). CONCLUSIONS: Twelve weeks of 2% carteoiol treatment may decrease the vascular resistance in NTG patients possibly due to the intrinsic sympathomimetic activity (ISA) of carteolol.

Administration, Topical↗

Epilepsy and Cortical Dysplasias.

Focal cortical dysplasias (FCD) and diffuse cortical dysplasias (DCD) are a heterogeneous group of disorders defined by abnormal cerebral cortical cytoarchitecture that are associated with epilepsy. Patients with either DCD or FCD may suffer from a variety of epilepsy subtypes and these are often refractory to most anti-epileptic drugs (AEDs) despite polytherapy. The etiologies of cortical dysplasias (CD) are diverse, and include inherited genetic syndromes such as Miller-Dieker or X-linked lissencephaly, subcortical band heterotopia, and the tuberous sclerosis complex, as well as nongenetic exogenous insults such as hypoxic-ischemic injury, viral or other type of central nervous system infection, or traumatic injury. A large number of FCD cases are idiopathic and very small regions of FCD (microdysgenesis) are now being identified in resected epilepsy specimens. Recent data suggests that nearly 30% of epilepsy specimens evaluated histologically will contain regions of overt or microscopic CD. The mainstay of appropriate therapy for CD remains the standard AEDs or epilepsy surgery. In too few disorders, specific AEDs provide therapeutic advantage in the setting of individual forms of CD. The ketogenic diet may provide seizure control in a subpopulation of patients. In both DCD and FCD, surgical resection can be curative in the appropriately selected patients. Surgical approaches include focal neocortical resections, temporal lobectomy, or larger hemispheric resection procedures.

Journal Article↗

Pre- and postnatal exposure to 3,3',4,4'-tetrachlorobiphenyl: I. Effects on breeding ability and sperm fertilizing ability in male mice.

This study investigated the effects of 3,3',4,4'-tetrachlorobiphenyl (TCB) on the reproductive performance and in vitro sperm fertilizing ability of male mice. C57BL/6J female mice (F-0) were fed diets containing 0, 3, or 30 ppm TCB for 2 weeks before pairing with nontreated males for a 10-day breeding period. Females were continued on their treatment diet throughout mating, gestation, and lactation. Male offspring (F-1) were given the same diet as their dams throughout this study. F-1 males at 7 and 17 weeks of age were mated to nontreated B6D2-F1 female mice. Body weight, litter size, and survival indices of offspring sired by F-1 males were recorded. Sperm fertilizing ability of F-1 males at 9 and 19 weeks of age was examined in vitro using eggs collected from nontreated B6D2-F1 females. Sperm motion analysis was performed at the same time. When 7- and 17-week-old F-1 males were mated to nontreated females, no differences in fecundity, litter size, sex ratio, or survival indices among any of the treatments were observed. However, sperm fertilizing ability of 30 ppm-treated F-1 males at 19 weeks of age was less than that of the control mice. Testes weights were greater in 3-week-old, 30 ppm-treated mice.

Animals↗

Pre- and postnatal exposure to 3,3',4,4'-tetrachlorobiphenyl: II. Effects on the reproductive capacity and fertilizing ability of eggs in female mice.

This study investigated the effects of 3,3',4,4'-tetrachlorobiphenyl (TCB) on the reproductive capacity of female mice. Female C57BL/6J mice (F-0) were fed diets containing 0, 3, or 30 ppm TCB for 2 weeks before pairing with nontreated C57BL/6J males for a 10-day breeding period. Females were continued on their treatment diet throughout mating, gestation, and lactation. Female offspring (F-1) were fed the same diet as their dams throughout the study. The reproductive capacity of F-1 females was examined by mating with non-treated B6D2-F1 males. In addition, the fertilizing ability of eggs from F-1 females was examined in vitro by insemination with sperm from nontreated B6D2-F1 males. Fecundity in F-0 females after mating was 80%, 71%, and 47% in the 0, 3, and 30 ppm treatment groups, respectively. Four-day and 21-day survival indices were lower for offspring of 30 ppm TCB-treated F-0 females than for offspring of the control females. Fecundity in F-1 females was the same among all treatment groups, however, all offspring born to 3- and 30-ppm TCB-treated F-1 females died before 4 days of age. Although the litter size at birth was not affected, the in vitro fertilizing ability of eggs in the 3- and 30-ppm treatment groups was lower than in the control group. This decrease in fertilizing ability was associated with an increase in degenerated eggs. F-0 females treated with 30 ppm TCB had enlarged livers during pregnancy and lactation. At 5 and 6 weeks, liver enlargement and thymus atrophy were apparent in F-1 females exposed to 30 ppm TCB. This study demonstrated impaired reproductive capacity and decreased egg fertilizing ability in TCB-treated female mice.

Animals↗

Altered biologic activities of commercial polychlorinated biphenyl mixtures after microbial reductive dechlorination.

The reductive dechlorination of polychlorinated biphenyls (PCBs) by anaerobic bacteria has recently been established as an important environmental fate of these compounds. This process removes chlorines directly from the biphenyl ring with replacement by hydrogen, resulting in a product mixture in which the average number of chlorines per biphenyl is reduced. In this study, dechlorination of commercial PCB mixtures (Aroclors 1242 and 1254) by microorganisms eluted from PCB-contaminated sediments of the River Raisin (Michigan) and Silver Lake (Massachusetts) caused a depletion in the proportion of highly chlorinated PCB congeners and an accumulation of lesser-chlorinated congeners. Dechlorination occurred primarily at the meta and, to a much lesser extent, para positions of biphenyl. The concentrations of the coplanar congeners including 3,3',4,4',5-pentachlorobiphenyl, the most potent dioxinlike congener, were significantly lowered by reductive dechlorination. Microbial reductive dechlorination of commercial PCB mixtures caused a substantial reduction in biologic activities in several instances. It significantly lowered or eliminated the inhibitory effects of Aroclors on fertilization of mouse gametes in vitro. Similarly, the dechlorinated product mixtures had substantially lower ethoxyresorufin-O-deethylase induction potencies and showed less ability to induce activating protein 1 transcription factor activity as compared to the unaltered Aroclors. In other assays the same dechlorinated product mixtures demonstrated biologic activities similar to the nondechlorinated Aroclors, including the ability of PCB mixtures to stimulate insulin secretion and cause neutrophil activation. The data presented here establish that the biologic activities of commercial PCB mixtures are altered by microbial reductive dechlorination and that an assessment of their toxic potential requires an array of tests that include the different mechanisms associated with PCBs.

Animals↗

Maternal serum uric acid levels in preeclamptic women with multiple gestations.

Our study was designed to determine serum uric acid levels and establish clinically useful cutoff values for the diagnosis of preeclampsia in twin and triplet gestations. We reviewed the medical records of 129 multiple gestations with serum uric acid levels available. Fifty-five twin gestations were complicated by preeclampsia, 51 were not. Fifteen triplet gestations were complicated by preeclampsia, and 8 were not. Preeclampsia was defined as a persistent blood pressure > or =140/90 mmHg, and proteinuria, or elevated liver enzymes, thrombocytopenia, or eclamptic seizure. Receiver operating characteristic curves were generated for twin and triplet gestations. Serum uric acid levels at different stages of gestation in twin gestations were determined. Maternal serum uric acid levels in preeclamptic twin and triplet gestations were significantly higher than those in nonpreeclamptics. Serum uric acid levels at varying gestational ages were significantly higher in preeclamptic twin gestations than in nonpreeclamptics. Maternal serum uric acid levels of 6.3 mg/dL and 6.8 mg/dL were found to be the most useful cutoff values for the diagnosis of preeclampsia in twin and triplet gestations, respectively. We conclude that compared to nonpreeclamptics, preeclamptic women with multiple gestations had significantly higher serum uric acid levels. Mean serum uric acid levels based on gestational age should be justified for the diagnosis of preeclampsia in multiple gestations.

Adult↗

Human T cell leukemia virus type I (HTLV-I) molecular genotypes and disease outcome.

The approach taken in our laboratory to determine viral markers associated with human T cell leukemia virus type I (HTLV-I) disease induction was to compare viral genomes and host immune responses from HTLV-I-infected patients from two geographical areas with significant differences in the incidence rate of tropical spastic paraparesis/HTLV-I-associated myelopathy (TSP/HAM), Tumaco, Colombia, and Kyushu Island, Japan. These studies showed that TSP/HAM patients have higher antibody levels against viral antigens and a higher proviral load compared to asymptomatic carriers and adult T cell leukemia (ATL) patients. A mutation in the tax gene was found to be associated with TSP/HAM, which in turn correlates with a higher transactivation activity of Tax. In addition, we found that HTLV-I-infected individuals contain infected cells that are clonally expanded. The genomic structure of these expanded clones shows that defective proviruses are present in asymptomatic carriers. A predilection in the defectiveness, however, was found to correlate with the presence (Cosmopolitan molecular genotype) or absence of the tax mutation (Japanese molecular genotype). Our results suggest that defective proviruses retaining structural genes might be a risk factor for TSP/HAM development. Contrary, defective proviruses retaining regulatory genes in the pX region could be a risk factor for ATL development. The molecular mechanism by which these defective proviruses is generated and expressed should give new insight into HTLV-I pathogenesis.

Clone Cells↗

Female reproductive and developmental toxicology: overview and current approaches.

In recent years, concern about possible female reproductive and developmental toxicity due to environmental contaminants, such as PCBs, has been growing. Because this area of toxicology had not been emphasized prior to this time, there are many gaps in current knowledge about female developmental and reproductive toxicology and only a limited number of validated tests to assay effects of toxicants on various parts of the reproductive and developmental cycle. This article reviews the current state of knowledge on this topic and also explores a variety of techniques for assessing female reproductive and developmental toxicity. These include an assay of the state of intercellular communication among the embryo, fetus and placenta; protocols for assessing toxicity in early pregnancy; and techniques for evaluating the role of glutathione in protecting the conceptus from xenobiotics.

Embryonic and Fetal Development↗

Aluminium impacts elements of the phosphoinositide signalling pathway in neuroblastoma cells.

Inositol phosphate formation was examined in aluminium-treated murine neuroblastoma cells labelled with [3H]-myoinositol. Employing fluoride-stimulated intact cells, aluminium (0.2 microM to 1 mM) reduced inositol phosphate formation in a dose-dependent manner. In digitonin-permeabilized cells, stimulated with nonhydrolyzable GTP[S], inositol phosphate formation was also inhibited by increasing aluminium doses; the IC50 value was about 20 microM aluminium, while the inositol phosphate level was reduced 2.5 to 3 fold by 50 microM aluminium. The inhibitory effect of aluminium (50 microM) could not be reversed by increasing GTP[S] concentrations up to 500 microM. Prechelation of aluminium to citrate or EGTA completely abolished the aluminium-triggered inhibition of fluoride-stimulated inositol phosphate formation in intact cells, but had little effect on the inhibition of permeabilized cells stimulated with GTP[S]. In neuroblastoma cells phosphoinositide hydrolysis could be evoked either through a pathway involving the Mg2+/guanine nucleotide binding (Gp) protein, or via a pathway operative in the presence of high intracellular Ca2+ concentrations. In the Mg2+/Gp protein-mediated pathway, formation of inositol triphosphate, IP3, inositol diphosphate, IP2, and inositol monophosphate, IP, was apparently inhibited by aluminium in an interdependent manner. As to the Ca(2+)-mediated pathway, aluminium application mainly diminished the release of IP3. Following interiorization, aluminium thus acts upon elements critical for phosphoinositide-associated signal transduction. An aluminium target apparently resides on the Gp protein. Phosphatidylinositol-4,5-diphosphate-specific phospholipase C probably harbours a second aluminium target.

Aluminum↗

[A case of primary pulmonary artery sarcoma].

A 39-year-old male was admitted with persistent cough, palpitations and dyspnea on exertion. Chest X-ray showed cardiomegaly, left pleural effusion and left hilar mass shadow. Echocardiogram revealed dilatation and hypertrophy of the right atrium and ventricle. Perfusion lung scintigram disclosed a complete defect of the left lung and a partial defect of the right upper lobe. CT scan showed an intravascular tumor mass in the bilateral main pulmonary arteries. Digital subtraction angiography of the pulmonary artery revealed complete obstruction of the left pulmonary artery and stenosis of the right pulmonary artery. MR image showed intravascular tumor infiltrating the mediastinum and surrounding tissue. Sarcoma was highly suspected, but a histopathological diagnosis could not be made. The patient died of heart failure two months after admission to our hospital. Postmortem examination showed that the pulmonary trunk and left main pulmonary artery were markedly dilated and completely occluded by the tumor. Tumor infiltrated into the left upper lobe and mediastinal lymph nodes. The tumor was histologically diagnosed as undifferentiated sarcoma.

Adult↗

Elevation of intracellular free calcium levels in sperm in response to long-term feeding of fungicides to mice.

To assess the impact of long-term feeding of fungicides on sperm quality, mice were fed a daily diet containing a mixture of maneb and zineb, at concentrations of 30, 300, and 3000 ppm, respectively. Employing epididymal sperm suspended in a medium permitting in vitro capacitation, the intracellular free Ca2+ concentration, [Ca2+]i, was determined with a fluorescent Ca2+ indicator, Fura-2. Regardless of the fungicide dosages applied, [Ca2+]i was about 50 percent higher in treated animals relative to a value of 123 nM [Ca2+]i in the control group. Fungicide-treated mice were mated to mature, non-treated females; as in the control, the litter sizes were the same. In conclusion, the observed elevation in [Ca2+]i seems to reflect cellular adaptation responses to toxic stress at moderate fungicide doses.

Animals↗