Evaluation of corneal hysteresis after pars plana vitrectomy combined phacoemulsification and intraocular lens implantation.

We evaluated the early effects of pars plana vitrectomy (PPV) on corneal biomechanics by comparing corneal hysteresis (CH) after cataract surgery (phacoemulsification and aspiration with intraocular lens implantation; PEA + IOL) alone and PPV combined with cataract surgery. This study included 20 eyes (18 patients), who underwent cataract surgery alone (PEA + IOL group), and 28 eyes (27 patients) who underwent PPV combined with cataract surgery (PPV triple group). The CH was 11.1 ± 1.1, 10.4 ± 1.1, and 11.0 ± 1.0 mmHg in the PEA + IOL group and 11.0 ± 1.4, 9.8 ± 1.4, and 10.6 ± 1.6 mmHg in the PPV triple group, preoperatively, at 2 weeks, and 3 months after surgery, respectively. The CH was not significantly different after surgery in the PEA + IOL group, but decreased significantly in the PPV triple group 2 weeks following surgery (p < 0.01). Intraocular pressure (IOP) and central corneal thickness (CCT) did not change significantly after surgery in either group. Preoperatively, there was a positive correlation between CH and CCT in the PPV triple group, but the correlation disappeared postoperatively. In PPV combined with cataract surgery, CH temporarily decreased postoperatively, independent of IOP and CCT. Removal of the vitreous may reduce the elasticity and rigidity of the entire eye.

Urinary metabolic fingerprinting for alpha-naphthylisothiocyanate-induced intrahepatic cholestasis in rats using Fourier transform-ion cyclotron resonance mass spectrometry.

Urinary metabolic fingerprinting with Fourier transform-ion cyclotron resonance mass spectrometry (FT-ICR MS) was performed to monitor metabolic changes in an alpha-naphthylisothiocyanate (ANIT)-induced rat model of intrahepatic cholestasis and to investigate the relationships among metabolic changes, histopathology, and blood chemistry. ANIT was administered orally as a single dose of 100 mg/kg. Urine samples were collected predose (-31 to -24 hours) and postdose at 0-7, 7-24, 24-31, 31-48, 48-55, 55-72, and 72-96 hours, and serum samples were collected on days 1, 2, and 4 postdose. Increased levels of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and total bilirubin were seen on day 2. The negative ion profiles for urine samples collected after 7-24, 24-31, 31-48, and 48-55 hours differed from the predose profile based on principal component analysis. Onset of recovery was observed after 24-31 hours, when the urinary composition reverted toward the predose position. In conclusion, it is possible to monitor the progression of and recovery from drug-induced hepatotoxicity by urinary metabolic fingerprinting with FT-ICR MS and to search for potential biomarkers involved in intrahepatic cholestasis.

Metabolic fingerprinting of amniotic fluid from the streptozotocin-induced diabetic pregnant rat using Fourier transform-ion cyclotron resonance mass spectrometry.

Metabolic fingerprinting of amniotic fluid from streptozotocin-induced diabetic pregnant rats was performed using Fourier transform-ion cyclotron resonance mass spectrometry. Some of the fetuses from the diabetic pregnant rats exhibited ventricular septal defect. The positive ion profiles of amniotic fluids from diabetes were different to those of the control rats. The alteration of biochemical composition in the diabetic amniotic fluid suggests the presence of potential biomarkers to indicate progression of malformation under the diabetic pregnancy.

Urinary metabolic fingerprinting for amiodarone-induced phospholipidosis in rats using FT-ICR MS.

In the research and development for new therapeutic compounds, there has been a focus on detecting the changes of metabolites induced by drug administration and finding surrogate markers to assess its toxicity. We examined the suitability of urinary metabolic fingerprinting using Fourier transform-ion cyclotron resonance mass spectrometry (FT-ICR MS) for toxicological assessment in the amiodarone (AMD)-induced phospholipidosis (PLD) rat model. There were more than 400 different ion peaks detected in the negative ion mode analysis with FT-ICR MS. About 20% of the detected ions were altered more than 1.5 fold by AMD-treatment. On the scores plot of principal component analysis (PCA), the ion profiles of the treated were separated time-dependently. The loading plot revealed that the metabolites causing PCA results were m/z 178.05101, 191.01979, 192.06676, 212.00239, 258.9944 and 283.0820. The ion at m/z 178.05101 is considered to be hippurate (HA), 192.06676 is phenylacetylglycine (PAG) and 212.00239 is indican (IDN). These results indicate that PAG, IDN and HA are biomarkers for AMD-induced PLD in urinary metabolic fingerprinting using FT-ICR MS. These markers may be useful for evaluation of chemicals, which have the potential to induce PLD.

Alternations of phospholipid profile in placenta of streptozotocin-induced diabetic rat.

Phospholipids have important roles in many biological processes, but their role in fetal malformation in pregnancy in diabetes is unclear. Metabolic fingerprinting of placental phospholipids in pregnant streptozotocin-induced type 1 diabetic rats was performed using Fourier transform-ion cyclotron resonance mass spectrometry. Some of the fetuses from the pregnant diabetic rats exhibited ventricular septal defects. Alterations of phospholipid compositions in the diabetic rat placenta were detected. We suggest that these changes in phospholipids in the diabetic placenta might be involved in development of fetal malformation in a type 1 diabetic pregnancy.

Metabolic Fingerprinting in Toxicological Assessment Using FT-ICR MS.

Detection of the toxicity of a candidate compound at an early stage of drug development is an emerging area of interest. It is difficult to determine all of the effects of metabolism of a compound using traditional approaches such as histopathology and serum biochemistry. The goal of a metabolomics approach is to determine all metabolites in a living system, with the potential to detect and identify biomarkers involved in toxicity onset. Here, we summarize the metabolic fingerprints for detection and identification of metabolic changes and biomarkers related to drug-induced toxicity using Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS).

Effects of Nanpao, a Kampo medicine, on the decline in estrous cyclicity with advancing age in female rats, as measured by vaginal impedance methods.

The present study was designed to evaluate the time-dependent effects of Nanpao, a kampo medicine, on age-related changes in the estrous cycle of female rats, and to investigate the utility of measuring electrical impedance in the vagina (EIV) for studying transitional changes in the estrous cycle. Rats were allocated to 3 groups: control, Nanpao 30 mg/kg/day, and 100 mg/kg/day groups. EIV measurements and cytology samples were taken for 14 days at the age of 6 months before the initial treatment. After the start of the treatment, these data were collected at about monthly intervals until the age of 10 months in the same manner. Observations at the ages of 7 (weeks 2-3 of dosing) and 8 months (weeks 6-7 of dosing) showed that loss of a regular estrous cycle in the 100 mg/kg/day group was inhibited as compared to the control group. Moreover, at the ages of 9 (weeks 11-12 of dosing) and 10 months (weeks 17-18 of dosing), these effects were identified not only in the 100 mg/kg/day group, but also in the 30 mg/kg/day group. Since vaginal cytology and EIV gave almost concordant results as indicators of estrous cyclicity, we concluded that the measurement of EIV was capable of detecting time-dependent changes in the estrous cycle as well as observations of vaginal smears. A short period of Nanpao administration inhibited loss of regular estrous cycles, and the EIV method is a worthwhile approach to a more precise study of estrous cyclicity in rats exhibiting abnormal estrous cycles.

Time-course changes of hematology and clinical chemistry values in pregnant rats.

The aim of this study is to report how pregnancy alters hematology and clinical chemistry values in rats. Female and male Sprague-Dawley rats were mated; the day of copulation was designated as Day 0. Hematology and clinical chemistry measurements were conducted on Days 7, 14, 17 and 21 in pregnant rats. Measurements were also conducted in non-pregnant rats. Red blood cells (RBC), hemoglobin (Hb), hematocrit (Ht), total protein and albumin decreased on Days 7, 14, 17 and 21; sodium, chloride and glucose decreased on Days 14, 17 and 21; iron decreased on Days 17 and 21; hemoglobin content of reticulocytes (CHr), calcium, inorganic phosphorus and the albumin/globulin ratio decreased on Day 21; and total cholesterol, phospholipid and high-density lipoprotein cholesterol decreased on Day 14 in pregnant rats compared with non-pregnant rats. Reticulocyte increased on Days 7, 14 and 17; mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, neutrophil count and rate increased on Days 14, 17 and 21; platelets, fibrinogen, triglyceride and free fatty acid increased on Days 17 and 21; and activated partial thromboplastin time was prolonged on Days 17 and 21 in pregnant rats compared with non-pregnant rats. The decreased RBC, Hb, Ht, CHr and iron in pregnant rats indicated that they suffered from iron deficiency anemia. These data can be used as background information for effective evaluation in reproductive toxicology studies.

Urinary metabolic fingerprinting for thioacetamide-induced rat acute hepatic injury using fourier transform-ion cyclotron resonance mass spectrometry (FT-ICR MS), with reference to detection of potential biomarkers for hepatotoxicity.

In this study, we performed urinary metabolic fingerprinting using Fourier transform-ion cyclotron resonance mass spectrometry (FT-ICR MS) in the thioacetamide (TAA)-induced rat model of acute hepatic injury to search for useful biomarkers involved in the acute hepatic toxicity. TAA was intraperitonealy administered a single dose of 300 mg/kg, and urine sample and livers were collected on predose, and days 1, 3, 5, and 7 postdose (Days 1, 3, 5, and 7). Histopathologically, infiltration of macrophages occurred in the TAA-induced centrilobular injured area on Days 1 and 3, and the injured liver recovered on Days 5 and 7. On the scores plot of principal component analysis (PCA), the ion profiles of Days 1 and 3 were different from those of the predose, Days 5 and 7. The loading plot revealed that the metabolites causing PCA results were m/z 266.05390, 401.20737, and 429.23882. The ion at m/z 266.05390 was identified as a potassium ion adduct of deoxycytidine (dCyt). Because the appearance of urinary dCyt was corresponding to macrophage infiltration in the rat-injured liver, it was considered that the urinary dCyt might be released from infiltrated macrophages. dCty might be a biomarker for the acute hepatotoxicity in rats.