Achilles Tendon ; Citric Acid ; administration & dosage ; Humans ; Organometallic Compounds ; administration & dosage ; Tendinopathy ; drug therapy ; Vitamin E ; administration & dosage

The toxic effects of lead on normal rat kidney epithelial cells (NRK cells) may occur via various pathways. However, the role of intrinsic mitochondrial pathway in Lead-induced apoptosis in NRK cells has not been investigated. The purpose of our study was to investigate cytotoxic responses and cell apoptosis mediated by lead in NRK cells. NRK cells were treated with different concentrations of Lead acetate for 12 h to determine the cytotoxicity of lead. Mitochondrial transmembrane potential was also analyzed using a fluorescence spectrophotometer. Moreover, the activities of caspase-3 and caspase-9 were detected in the presence of lead. Finally, the lead-induced cell apoptosis was evaluated by flow cytometry in the present of caspase inhibitors Z-VAD-FMK and Ac-LEHD-FMK, respectively. The results would contribute to clarify the role of Lead in proliferation and apoptosis of NRK cells, and help to understand the underlying mechanism responsible for lead-induced cell apoptosis.
Animals ; Apoptosis ; drug effects ; Cell Line ; Cell Survival ; drug effects ; Dose-Response Relationship, Drug ; Epithelial Cells ; drug effects ; Gene Expression Regulation ; drug effects ; Kidney ; cytology ; Organometallic Compounds ; administration & dosage ; toxicity ; Rats

Acute respiratory distress syndrome (ARDS) is a medical emergency that threatens life. To this day, ARDS is very rarely reported by iodine contrast media, and there is no reported case of ARDS induced by gadolinium contrast media. Here, we present a case with ARDS after the use of gadobutrol (Gadovist) as a magnetic resonance imaging (MRI) contrast medium. A 26 years old female without any medical history, including allergic diseases and without current use of drugs, visited the emergency room for abdominal pain. Her abdominopelvic computed tomography with iodine contrast media showed a right ovarian cyst and possible infective colitis. Eighty-three hours later, she underwent pelvis MRI after injection of 7.5 mL (0.1 mL/kg body weight) of gadobutrol (Gadovist) to evaluate the ovarian cyst. She soon presented respiratory difficulty, edema of the lips, nausea, and vomiting, and we could hear wheezing upon auscultation. She was treated with dexamethasone, epinephrine, and norepinephrine. Her chest X-ray showed bilateral central bat-wing consolidative appearance. Managed with mechanical ventilation, she was extubated 3 days later and discharged without complications.
Adult ; Animals ; Contrast Media/administration & dosage/*adverse effects ; Female ; Gadolinium ; Humans ; Magnetic Resonance Imaging/*methods ; *Organometallic Compounds/adverse effects ; Respiratory Distress Syndrome, Adult/*chemically induced ; Tomography, X-Ray Computed

OBJECTIVE: To evaluate the utility of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) using macromolecular contrast agent (P792) for assessment of vascular disrupting drug effect in rabbit VX2 liver tumor models. MATERIALS AND METHODS: This study was approved by our Institutional Animal Care and Use Committee. DCE-MRI was performed with 3-T scanner in 13 VX2 liver tumor-bearing rabbits, before, 4 hours after, and 24 hours after administration of vascular disrupting agent (VDA), using gadomelitol (P792, n = 7) or low molecular weight contrast agent (gadoterate meglumine [Gd-DOTA], n = 6). P792 was injected at a of dose 0.05 mmol/kg, while that of Gd-DOTA was 0.2 mmol/kg. DCE-MRI parameters including volume transfer coefficient (K(trans)) and initial area under the gadolinium concentration-time curve until 60 seconds (iAUC) of tumors were compared between the 2 groups at each time point. DCE-MRI parameters were correlated with tumor histopathology. Reproducibility in measurement of DCE-MRI parameters and image quality of source MR were compared between groups. RESULTS: P792 group showed a more prominent decrease in K(trans) and iAUC at 4 hours and 24 hours, as compared to the Gd-DOTA group. Changes in DCE-MRI parameters showed a weak correlation with histologic parameters (necrotic fraction and microvessel density) in both groups. Reproducibility of DCE-MRI parameters and overall image quality was not significantly better in the P792 group, as compared to the Gd-DOTA group. CONCLUSION: Dynamic contrast-enhanced magnetic resonance imaging using a macromolecular contrast agent shows changes of hepatic perfusion more clearly after administration of the VDA. Gadolinium was required at smaller doses than a low molecular contrast agent.
Animals ; Antineoplastic Agents/therapeutic use ; Benzophenones/therapeutic use ; Disease Models, Animal ; Heterocyclic Compounds/administration & dosage/*chemistry ; Liver Neoplasms/drug therapy/pathology/*radiography ; *Magnetic Resonance Imaging ; Male ; Organometallic Compounds/administration & dosage/*chemistry ; Rabbits ; Reproducibility of Results ; Valine/analogs & derivatives/therapeutic use

BACKGROUND/AIMS: We investigated whether sodium picosulfate with magnesium citrate (SPMC) plus bisacodyl compares favorably with conventional polyethylene glycol (PEG) with respect to bowel cleansing adequacy, compliance, and safety. METHODS: We performed a multicenter, prospective, single-blinded study in outpatients undergoing daytime colonoscopies. Patients were randomized into a split preparation SPMC/bisacodyl group and a conventional split PEG group. We compared preparation adequacy using the Boston bowel preparation scale (BBPS), ease of use using a modified Likert scale (LS), compliance/satisfaction level using a visual analogue scale (VAS), and safety by monitoring adverse events during the colonoscopy between the two groups. RESULTS: A total of 365 patients were evaluated by intention to treat (ITT) analysis, and 319 were evaluated by per protocol (PP) population analysis (153 for SPMC/bisacodyl, 166 for PEG). The mean total BBPS score was not different between the two groups in both the ITT and PP analyses (p>0.05). The mean VAS score for satisfaction and LS score for the ease of use were higher in the SPMC/bisacodyl group (p<0.001). The adverse event rate was lower in the SPMC/bisacodyl group than in the PEG group (p<0.05). CONCLUSIONS: The SPMC/bisacodyl treatment was comparable to conventional PEG with respect to bowel preparation adequacy and superior with respect to compliance, satisfaction, and safety.
Adult ; Aged ; Cathartics/*administration & dosage ; Citrates/*administration & dosage ; Citric Acid/*administration & dosage ; Colon/*drug effects/surgery ; *Colonoscopy ; Drug Combinations ; Drug Therapy, Combination/methods ; Female ; Humans ; Intention to Treat Analysis ; Laxatives/*administration & dosage ; Male ; Middle Aged ; Organometallic Compounds/*administration & dosage ; Patient Compliance ; Patient Satisfaction ; Picolines/*administration & dosage ; Polyethylene Glycols/*administration & dosage ; Preoperative Care/methods/psychology ; Single-Blind Method ; Young Adult

Bowel preparation is essential for successful colonoscopy examination, and the most important factor is the bowel preparation agent used. However, selection of a bowel preparation agent invariably involves compromise. Originally, bowel preparation was performed for radiologic and surgical purposes, when the process involved dietary limitations, cathartics, and enemas, which had many side effects. Development of polyethylene glycol (PEG) solution led to substantive advancement of bowel preparation; however, despite its effectiveness and safety, the large volume involved, and its salty taste and unpleasant odor reduce compliance. Accordingly, modified PEG solutions requiring consumption of lower volumes and sulfate-free solutions were developed. Aqueous sodium phosphate is more effective and better tolerated than PEG solutions; however, fatal complications have occurred due to water and electrolyte shifts. Therefore, aqueous sodium phosphate was withdrawn by the US Food and Drug Administration, and currently, only sodium phosphate tablets remain available. In addition, oral sulfate solution and sodium picosulfate/magnesium citrate are also available, and various studies have reported on adjunctive preparations, such as hyperosmolar or stimulant laxatives, antiemetics, and prokinetics, which are now in various stages of development.
Administration, Oral ; Cathartics/*administration & dosage ; Citrates/administration & dosage ; Citric Acid/administration & dosage ; Colonic Diseases/diagnosis ; Colonoscopy ; Humans ; Organometallic Compounds/administration & dosage ; Phosphates/administration & dosage ; Picolines/administration & dosage ; Polyethylene Glycols/administration & dosage

OBJECTIVE: To compare the effect of imaging time delay on the MR detection of intracerebral metastases using single dose gadobutrol. MATERIALS AND METHODS: Twenty-one patients with intracerebral metastases underwent contrast-enhanced MR with three-dimensional T1-weighted sequence at 1 minute, 5 minutes and 10 minutes after a single dose injection of gadobutrol. One hundred index metastatic lesions (1 to 30 mm; median, 7 mm) were chosen for the analysis. For the qualitative analysis, lesion conspicuity were assessed on a 1 (worst) to 5 (best) scale of the index lesions by an expert reader. For the quantitative analysis, signal intensity (SI) of enhancing lesions and normal parenchyma was measured to determine the contrast rate (CR, %) ([postcontrast SI lesion - postcontrast SI white matter] x 100 / postcontrast SI white matter) and the enhancement rate (ER, %) ([postcontrast SI lesion - baseline SI gray matter] x 100 / baseline SI gray matter). Statistical comparisons were made between three different time delays. RESULTS: Lesion conspicuity did not differ significantly among the three time delays (p = 0.097). Although the SI, CR and ER of lesions did not reveal any significant difference between 1 minute and 5 minutes delayed images, both the 1 minute and 5 minutes delayed images showed significantly higher CRs of lesions compared with the 10 minutes delayed images (p = 0.004 and p = 0.001, respectively). CONCLUSION: With single dose gadobutrol, imaging time delay did not have an effect on lesion conspicuity. Both 1-minute and 5-minute-delayed imaging after gadobutrol injection appears to be effective for the detection of intracerebral metastases.
Adult ; Aged ; Aged, 80 and over ; Brain Neoplasms/*diagnosis/*secondary ; Contrast Media/administration & dosage/*diagnostic use ; Female ; Humans ; Image Enhancement/methods ; Magnetic Resonance Imaging/*methods ; Male ; Middle Aged ; Observer Variation ; Organometallic Compounds/administration & dosage/*diagnostic use ; Time Factors

OBJECTIVETo investigate the impact of sub-chronic Aluminium-maltolate [Al(mal)3] exposure on the catabolism of amyloid precursor protein (APP) in rats.

METHODSForty adult male Sprague-Dawley (SD) rats were randomly divided into five groups: the control group, the maltolate group (7.56 mg/kg BW), and the Al(mal)3 groups (0.27, 0.54, and 1.08 mg/kg BW, respectively). Control rats were administered with 0.9% normal saline through intraperitoneal (i.p.) injection. Maltolate and Al(mal)3 were administered to the rats also through i.p. injections. Administration was conducted daily for two months. Rat neural behavior was examined using open field tests (OFT). And the protein expressions and their mRNAs transcription related with APP catabolism were studied using enzyme-linked immunosorbent assay (ELISA) and real-time polymerase chain reaction (RT-PCR).

RESULTSThe expressions of APP, β-site APP cleaving enzyme 1 (BACE1) and presenilin-1 (PS1) proteins and their mRNAs transcription increased gradually with the increase of Al(mal)3 doses (P<0.05). The enzyme activity of BACE1 in the 0.54 and 1.08 mg/kg Al(mal)3 groups increased significantly (P<0.05). The expression of β-amyloid protein (Aβ) 1-40 gradually decreased while the protein expression of Aβ1-42 increased gradually with the increase of Al(mal)3 doses (P<0.05).

CONCLUSIONResult from our study suggested that one of the possible mechanisms that Al(mal)3 can cause neurotoxicity is that Al(mal)3 can increase the generation of Aβ1-42 by facilitating the expressions of APP, β-, and γ-secretase.

Amyloidogenic Proteins ; genetics ; metabolism ; Animals ; Drug Administration Schedule ; Environmental Pollutants ; administration & dosage ; toxicity ; Gene Expression Regulation ; drug effects ; Male ; Organometallic Compounds ; administration & dosage ; toxicity ; Pyrones ; administration & dosage ; toxicity ; Random Allocation ; Rats ; Rats, Sprague-Dawley

This study is to assess the efficacy of BPCBG on the decorporation of uranium (VI) and protecting human renal proximal tubular epithelial cells (HK-2) against uranium-induced damage. BPCBG at different doses was injected intramuscularly to male SD rats immediately after a single intraperitoneal injection of UO2(CH3COO)2. Twenty-four hours later uranium contents in urine, kidneys and femurs were measured by ICP-MS. After HK-2 cells were exposed to UO2(CH3COO)2 immediately or for 24 h followed by BPCBG treatment at different doses for another 24 or 48 h, the uranium contents in HK-2 cells were measured by ICP-MS, the cell survival was assayed by cell counting kit-8 assay, formation of micronuclei was determined by the cytokinesis-block (CB) micronucleus assay and the production of intracellular reactive oxygen species (ROS) was detected by 2',7'-dichlorofluorescin diacetate (DCFH-DA) oxidation. DTPA-CaNa3 was used as control. It was found that BPCBG at dosages of 60, 120, and 600 micromol kg(-1) resulted in 37%-61% increase in 24 h-urinary uranium excretion, and significantly decreased the amount of uranium retention in kidney and bone to 41%-31% and 86%-42% of uranium-treated group, respectively. After HK-2 cells that had been pre-treated with UO2(CH3COO)2 for 24 h were treated with the chelators for another 24 h, 55%-60% of the intracellular uranium was removed by 10-250 micromol L(-1) of BPCBG. Treatment of uranium-treated HK-2 cells with BPCBG significantly enhanced the cell survival, decreased the formation of micronuclei and inhibited the production of intracellular ROS. Although DTPA-CaNa3 markedly reduced the uranium retention in kidney of rats and HK-2 cells, its efficacy of uranium removal from body was significantly lower than that of BPCBG and it could not protect uranium-induced cell damage. It can be concluded that BPCBG effectively decorporated the uranium from UO2(CH3COO)2-treated rats and HK-2 cells, which was better than DTPA-CaNa3. It could also scavenge the uranium-induced intracellular ROS and protect against the uranium-induced cell damage. BPCBG is worth further investigation.
Animals ; Cell Line ; Cell Survival ; drug effects ; Chelating Agents ; administration & dosage ; chemistry ; pharmacology ; Dose-Response Relationship, Drug ; Epithelial Cells ; cytology ; metabolism ; Humans ; Kidney ; metabolism ; Kidney Tubules, Proximal ; cytology ; Male ; Micronucleus Tests ; Molecular Structure ; Organometallic Compounds ; toxicity ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Reactive Oxygen Species ; metabolism ; Uranium ; metabolism ; urine

Leishmaniasis is a parasitic disease caused by Leishmania species and is classified into three forms; cutaneous, mucocutaneous, and visceral. The eyelid is a rare site involved by leishmaniasis and only makes up 2.5% of cases with cutaneous leishmaniasis (CL). Although CL can affect both upper and lower lids on either their outer or inner aspects, the lateral canthus is most often affected. The most common aspect of lid leishmaniasis is chalazion-like lesions but ulcerous, phagedenic, cancer-like forms, and unilateral chronic granulomatous blepharitis may be observed. When the lid is involved, the disease is usually self-limiting; healing usually takes up to one year, hence early diagnosis and treatment are important. The diagnosis is based on a high index of suspicion regarding the endemicity of the disease in the region. Response to treatment in lid CL cases is quite satisfactory. In this article, we report nine cases of lid leishmaniasis with satisfactory responses to intralesional meglumine antimoniate.
Adolescent ; Adult ; Child ; Eyelid Diseases/*parasitology ; Eyelids/*parasitology ; Female ; Humans ; Infant ; Injections, Intralesional ; Leishmaniasis, Cutaneous/*drug therapy ; Male ; Meglumine/*administration & dosage ; Organometallic Compounds/*administration & dosage ; Treatment Outcome