Effective sympathetic nerve block for chemotherapy-induced peripheral neuropathy: a case report.

Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most difficult-to-alleviate side effects of chemotherapy, impacting the patient's daily activities and quality of life and frequently necessitating the discontinuation or dose reduction of anticancer drugs. An effective treatment for CIPN is yet to be established. Herein, we report the case of a patient who developed CIPN after receiving paclitaxel as postoperative chemotherapy for breast cancer. The patient experienced difficulties in performing daily activities owing to pain in her fingers and toes despite attempts to treat these symptoms with medications. Stellate and lumbar sympathetic ganglion blocks improved CIPN-induced symptoms of numbness and pain in the extremities. Thereafter, lumbar sympathetic ganglion block was performed once every 6 months, markedly improving the patient's quality of life. Accordingly, sympathetic nerve block can facilitate pain control in patients with CIPN refractory to pharmacotherapy.

Lipid hydroperoxides in human plasma after ethanol consumption.

Oxidative stress contributes to the pathogenesis of alcoholic liver disease. The purpose of this study is to estimate the amount of oxidative stress that is present when healthy humans consume moderate amounts of ethanol. Blood was collected from healthy volunteers before, 1 h, and 3 h after drinking 400 ml of Japanese rice wine at the rate of 100 ml per 5 min. The aldehyde dehydrogenase 2 genotype and the concentrations of blood ethanol, total lipid hydroperoxides (LOOH), and cholesterol hydroperoxides were determined. The plasma LOOH was found to have significantly increased 1h after drinking. Cholesterol hydroperoxides were not detected in plasma, either before or after drinking. There was no relationship between the LOOH and the ethanol concentration. We showed that one-shot of moderate ethanol consumption temporarily increases the plasma LOOH in healthy volunteers but excessive plasma LOOH compounds were eliminated within a short time.

Adipocere formation via hydrogenation of linoleic acid in a victim kept under dry concealment.

Adipocere formation is well known as a later post-mortem change. We experienced a female victim who had been sealed up in a clothes box for approximately 4 years. We collected several subcutaneous fats as well as visceral fats from the victim to investigate adipocere formation. Fresh subcutaneous fats of one female and five male victims who suddenly died were used as the control. These samples were homogenized and the lipids were extracted with chloroform and methanol followed by injection into gas chromatography-mass spectrometry and gas chromatography. We detected a hydroxy fatty acid in the fat of the case, but not in the controls. Using standard synthetic hydroxy fatty acid, the lipid extract component was identified as 10-hydroxyoctadecanoic acid (10-OH 18:0) and this concentration was quantified. Consequently we confirmed that adipocere was formed much slowly in dry concealment. In addition, the fatty acid composition was compared with the control. Most of the linoleic acid (18:2) disappeared and a peak developed instead. Using standard synthetic fatty acid, this peak was identified as cis-12-octadecenoic acid (cis-12-18:1). This suggests that linoleic acid is hydrogenated to cis-12-octadecenoic acid in the process of adipocere formation.

Analysis of phosphatidylcholine oxidation products in human plasma using quadrupole time-of-flight mass spectrometry.

We report here an application of the previous method for the analysis of phosphatidylcholine (PC) and lysophosphatidylcholine (lysoPC) oxidation products in human plasma using quadrupole time of flight (Q-TOF) mass spectrometry with electrospray ionization. We separated these products using an HPLC C8 column with a gradient of methanol and 10 mM aqueous ammonium acetate. Monohydroperoxides, epoxyhydroxy derivatives, oxo derivatives, and trihydroxides of palmitoyl-linoleoyl (C16:0/C18:2) PC and stearoyl-linoleoyl (C18:0/C18:2) PC were detected mainly as MH+ and [M+Na]+ ions in the plasma of alcoholic patients. Using standard synthetic PC-OH (C16:0/C18:2-OH), the lipid extract component was identified as (C16:0/C18:2-OH) PC based on the product ions of ESI-MS-MS. Using standard synthetic PCOOH (C16:0/C18:2-OOH) as a reference, the PCOOH concentration in plasma was quantified. Two oxidatively modified lysoPCs were also detected. This is the first report showing the presence of epoxyhydroxy derivatives, monohydroperoxides, oxo derivatives, and trihydroxides of (C16:0/C18:2) PC and (C18:0/C18:2) PC, and PC-OH (C16:0/C18:0-OH) in human plasma.

Protective effect of daidzein against acute ethanol-induced lipid peroxidation in rat jejunum.

Ethanol causes extensive damage to the intestinal tract from the oropharynx to the rectum. The jejunum has also been shown to be particularly vulnerable to the deleterious effects of ethanol. We hypothesized that (I) the pathogenesis of acute alcohol-mediated injury in the small intestine involves generation of reactive oxygen species, and consequentially, enhanced lipid peroxidation; (II) the pathogenic changes due to alcohol can be ameliorated with daidzein pretreatment. To test these hypotheses male Wistar rats (n=24) were divided into four groups as follows (pretreatment followed by treatment): [A] carrier+saline (control); [B] daidzein+saline; [C] carrier+ethanol; [D] daidzein+ethanol. Daidzein (100 mg/kg) or carrier (Intralipid) pretreatment was twice administered as a single dose, whereas ethanol (75 mmol/kg) or saline (0.15 mol/l NaCl) treatment was administered once only. At 24 h after ethanol or saline was administered, rats were sacrificed. The analytes 7alpha-and 7beta-hydroperoxycholest-5-en-3beta-ol (7alpha-OOH and 7beta-OOH), 7alpha-and 7beta-hydroxycholesterol (7alpha-OH and 7beta-OH), and 7-ketocholesterol (7-keto) in jejunum were analyzed by HPLC. The data showed that daidzein per se did not affect levels of cholesterol hydroperoxides nor oxysterols. However, there were significant increases in 7alpha- and 7beta-OOHs, 7alpha- and 7beta-OHs, and 7-keto after ethanol dosage compared to controls. Daidzein ameliorated these effects, i.e., values in the daidzein+ethanol group were similar to those in the carrier+saline (control) group. This is the first report showing that (1) cholesterol-derived markers of oxidative stress are increased in the rat jejunum in response to ethanol, indicative of metabolic damage; (2) daidzein pretreatment has protective effects against ethanol-induced injury.

Enhanced lipid peroxidation in tourniquet-release mice.

BACKGROUND: The pathogenesis of ischemia-reperfusion involves generation of reactive oxygen and resulting lipid peroxidation. However, investigation that ischemia-reperfusion following tourniquet release enhances lipid peroxidation is insufficient. METHODS: Tourniquet was applied to a unilateral hind limb of mice for 3h followed by 5-, 15-, 30- and 60-min release. To examine superoxide production immunohistochemically in ischemia-reperfusion muscles, a primary antibody directed to 4-hydroxy-nonenal (HNE) was used. Furthermore, we analyzed 7alpha- and 7beta-hydroperoxycholest-5-en-3beta-ol, 7alpha- and 7beta-hydroxycholesterol, and 7-ketocholesterol by HPLC in the gastrocnemius muscles, kidneys, liver, heart and lungs of mice after 1-h reperfusion. RESULTS: Increased HNE immunoreactivitiy was observed in the tourniquet-applied side of gastrocnemius muscles of hind limb particularly after 5-min reperfusion. All the oxysterols were significantly higher in the gastrocnemius muscles of the tourniquet-applied side than of the contralateral muscles. Oxysterols were elevated in the kidneys and the liver. Together with the presence of high blood urea nitrogen, these data indicate that the kidney is vulnerable to ischemia-reperfusion. CONCLUSIONS: The enhanced oxidative stress due to ischemia-reperfusion appears to increase HNE in muscle and oxysterols by peroxidation not only in the gastrocnemius muscles but also in the kidneys and liver.

Skeletal muscle and liver oxysterols during fasting and alcohol exposure.

Oxysterols are cytotoxic agents that have a range of cellular actions, including impairment of albumin synthesis, cell differentiation, and induction of apoptosis. Their regulations by nutritional factors are poorly described. Our objective was to test the hypothesis that the imposition of food withdrawal and alcohol exposure increases tissue oxysterol concentrations. We measured the concentrations of the oxysterols 7alpha-hydroxycholest-5-en-3beta-ol (7alpha-OH), 7beta-hydroxycholest-5-en-3beta-ol (7beta-OH), and 3beta-hydroxycholest-5-en-7-one (7-keto) in liver and skeletal muscle of fed and fasted (food withdrawal for 1 and 2 days) male Wistar rats. Both oxidative (type I; soleus) and glycolytic (type II; plantaris) muscles were analyzed. We also investigated the effects of a nutritional perturbant induced by a short-term bolus of ethanol (75 mmol/kg weight IP administered 2.5 hours before sacrifice). The results showed that in response to fasting there were significant increases in 7alpha-OH, 7beta-OH, and 7-keto in liver and both type I and II skeletal muscle (P < .001 in all instances). For skeletal muscle, the increases were blunted or ameliorated after 2 days when compared with data from rats starved for 1 day. In contrast, the increases in liver after 1 day's fasting were relatively sustained at 2 days. Short-term ethanol increased 7alpha-OH, 7beta-OH, and 7-keto in type I muscle of fed animals only (P < .001 in all instances) with a significant interaction between fasting and alcohol (P < .001 in all instances). For the first time, we have shown that oxysterols can increase in muscle and liver in response to food withdrawal and in response to an immediately imposed nutritional perturbant (ie, alcohol). Increased oxysterols represent elevated oxidative stress and/or disturbances in their formation or clearance. Because of the reported cytotoxic properties of oxysterols, these data are important in understanding cellular pathology because episodic anorexia and/or oxidative stress occur in a variety of disease conditions including sepsis, cancer cachexia, ischemia, and hormonal imbalance.

Detection of phosphatidylcholine oxidation products in rat heart using quadrupole time-of-flight mass spectrometry.

An improved technique for the analysis of phosphatidylcholine (PC) and lyso-phosphatidylcholine (lyso-PC) oxidation products was developed using quadrupole time of flight (Q-TOF) mass spectrometry with electrospray ionization. We separated these products using an HPLC C(8) column with a gradient of methanol and 10mM aqueous ammonium acetate. Monohydroxides, oxo derivatives, and trihydroxides of palmitoyl-linoleoyl (C16:0/C18:2) PC, stearoyl-linoleoyl (C18:0/C18:2) PC, and oleoyl-linoleoyl (C18:1/C18:2) PC were detected mainly as MH(+) and [M+Na](+) ions in the heart of the intact rat. Using standard synthetic PC-OH (C16:0/C18:2-OH), the lipid extract component was identified as (C16:0/C18:2-OH) PC based on the product ions of ESI-MS-MS and, the PC-OH concentration was quantitated. Four oxidatively modified 1-lyso-phosphatidylcholines (lyso-PCs) were also detected. This is the first report showing the presence of monohydroxides, oxo derivatives, and trihydroxides of (C16:0/C18:2)PC, (C18:0/C18:2)PC, and (C18:1/C18:2) PC in the rat heart.

Oxysterols increase in diabetic rats.

To address whether diabetes enhances lipid peroxidation and attenuates nitric oxide (NO) generation resulting in tissue complications, we measured oxysterols and NO metabolites (NOx) in the tissues of diabetic Wistar rats. After 4 weeks of streptozotocin injection (STZ, 80 mg/kg, i.p.), we measured 7 alpha- and 7 beta-hydroperoxycholest-5-en-3 beta-ol (7 alpha-OOH and 7 beta-OOH), 7 alpha- and 7 beta-hydroxycholesterol (7 alpha-OH and 7 beta-OH) and 7-ketocholesterol (7-keto) by HPLC in the kidneys, heart, and liver. All the oxysterols were much higher in the diabetic than in sham rats, while the extent of the increase was higher in the order of the kidney, heart, and liver. Together with high blood urea nitrogen, the data indicate that the kidney is the predominant target of early diabetic complications. Plasma NOx were decreased by 20% in the STZ rats. The enhanced oxidative stress in diabetes would increase oxysterols by peroxidation, while superoxide is known to reduce NO by reaction to form another potent oxidant peroxynitrite.

Early differential gene expression of rat lung after exposure to paraquat.

Paraquat (PQ), a quaternary nitrogen herbicide, is highly toxic to humans and animals. Acute poisoning and death due to PQ exposure have been reported over the past few decades. Excessive production of oxygen free radicals has been proposed to play an important role in the pulmonary pathology. The aim of the present work was to evaluate the implications for genes that are regulated by oxidative stress at the early stage of PQ exposure in rat lungs. We performed differential display RT-PCR (DD-PCR) on total RNA extracted from rat lungs after injection of 20mg per kg body weight. The experimental DD-PCR conditions, primer length and annealing temperature, were adjusted to improve reproducibility, and 19 differentiated clones were isolated. Sequence analysis followed by conventional RT-PCR and real-time RT-PCR analyses were used to confirm the results. Four clones were finally determined to be significantly affected. These genes were mRNAs for plasma phospholipid transfer protein (PLTP), CL1BA protein, (latrophilin: LPH), and alphaII-spectrin as well as one unknown gene. We demonstrated the distribution of mRNA expression of one gene, LPH, in lung tissues. The present study suggests that 20mg per kg intraperitoneal PQ affects the expression of numerous genes in the lung at 3 h, the onset of pulmonary injury, and that the four genes specified may be major contributors to serious lung injury due to PQ exposure.

Determination of phosphatidylcholine monohydroperoxides using quadrupole time-of-flight mass spectrometry.

An improved technique for the analysis of phosphatidylcholine (PC) monohydroperoxides was developed using quadrupole time-of-flight (Q-TOF) mass spectrometry with electrospray ionization. Separation was obtained using an HPLC C8 column with a gradient of methanol and 10 mM aqueous ammonium acetate. Monohydroperoxides of palmitoyl-linoleoyl (C16:0/C18:2) PC, stearoyl-linoleoyl (C18:0/C18:2) PC, and oleoyl-linoleoyl (C18:1/C18:2) PC were detected mainly as MH(+) and [M+Na](+) ions in the heart of the intact rat. Using standard synthetic PCOOH (C16:0/C18:2-OOH), the lipid extract component was identified as (C16:0/C18:2-OOH) PC based on the product ions of ESI-MS-MS and, the PCOOH concentration was quantitated using HPLC with chemiluminescence detection. Two epoxyhydroxy derivatives of the three PCs mentioned above were also detected. This is the first report to show the presence of monohydroperoxides and epoxyhydroxy-derivatives of (C16:0/C18:2)PC, (C18:0/C18:2)PC, and (C18:1/C18:2) PC in the rat heart.

Plasma phosphatidylcholine hydroperoxide as a new marker of oxidative stress in alcoholic patients.

Quantitative analysis of plasma phosphatidylcholine hydroperoxide (PCOOH) is an important step in evaluating the biochemical processes leading to oxidative injury. However, secondary products of lipid peroxidation are now used as indices. One hundred nine alcoholic patients, aged 22-81 years (mean +/- SEM, 52.0 +/- 1.3 years), and 21 healthy volunteers, aged 41-79 years (51.2 +/- 2.2 years), participated in this study. Plasma PCOOH was measured by HPLC with chemiluminescence detection. Plasma PCOOH concentration was significantly higher in alcoholic patients (46.1 +/- 4.1 pmol/ml) than in controls (15.6 +/- 1.8 pmol/ml). It was significantly higher in patients with blood alcohol (88.0 +/- 10.5 pmol/ml) than in those without alcohol (32.6 +/- 3.1 pmol/ml). The patients with high levels of aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transpeptidase (gamma-GTP), and triglyceride (TG) showed significantly higher PCOOH concentrations than did patients with normal levels. The PCOOH level was positively correlated with levels of gamma-GTP, HDL, blood alcohol concentration, and TG. Plasma PCOOH levels in 29 alcoholic patients after a 6 week abstinence were decreased significantly (22.8 +/- 11.1 pmol/ml), which was associated with improvement on liver function tests. This is the first measurement of plasma PCOOH in alcoholic patients. These results suggest the involvement of lipid peroxidation in alcohol-induced liver damage and confirm that the PCOOH plasma concentration is a new marker of alcohol consumption as well as oxidative stress in alcoholic patients.

Phosphatidylcholine hydroperoxide levels in human plasma are lower than previously reported.

The quantification of PC hydroperoxide (PCOOH) in human plasma was studied by HPLC with chemiluminescence detection (HPLC-CL). We identified for the first time the monohydroperoxide of 1-palmitoyl-2-linoleoyl-PC hydroperoxide (PC 16:0/18:2-OOH) in plasma by LC-MS and HPLC-CL. The standard compound, PC 16:0/18:2-OOH (synthetic PCOOH), as well as PCOOH from egg yolk, was used. Comparison of the PCOOH concentration in each participant's plasma as determined by use of a Finepak SIL NH2 column with 2-propanol/methanol/water as the mobile phase (system A, the conventional method) gave a higher concentration than did an LC-18-DB column with methanol containing 0.01% triethylamine (system B). The mean PCOOH concentration for the 43 healthy volunteers was 55.1+/-30.4 pmol/mL (mean+/-SD) for system A and 16.3+/-9.9 pmol/mL for system B. Moreover, the main peak of the plasma extract appeared at a different time from that of synthetic PCOOH or egg yolk PCOOH in system A, whereas in system B plasma sample retention time practically corresponded to that of standard PCOOH. These findings confirm that the PCOOH plasma concentration is not so high as previously reported.

Alcoholic muscle disease and biomembrane perturbations (review).

Excessive alcohol ingestion is damaging and gives rise to a number of pathologies that influence nutritional status. Most organs of the body are affected such as the liver and gastrointestinal tract. However, skeletal muscle appears to be particularly susceptible, giving rise to the disease entity alcoholic myopathy. Alcoholic myopathy is far more common than overt liver disease such as cirrhosis or gastrointestinal tract pathologies. Alcohol myopathy is characterised by selective atrophy of Type II (anaerobic, white glycolic) muscle fibres: Type I (aerobic, red oxidative) muscle fibres are relatively protected. Affected patients have marked reductions in muscle mass and impaired muscle strength with subjective symptoms of cramps, myalgia and difficulty in gait. This affects 40-60% of chronic alcoholics (in contrast to cirrhosis, which only affects 15-20% of chronic alcohol misuers).Many, if not all, of these features of alcoholic myopathy can be reproduced in experimental animals, which are used to elucidate the pathological mechanisms responsible for the disease. However, membrane changes within these muscles are difficult to discern even under the normal light and electron microscope. Instead attention has focused on biochemical and other functional studies. In this review, we provide evidence from these models to show that alcohol-induced defects in the membrane occur, including the formation of acetaldehyde protein adducts and increases in sarcoplasmic-endoplasmic reticulum Ca(2+)-ATPase (protein and enzyme activity). Concomitant increases in cholesterol hydroperoxides and oxysterol also arise, possibly reflecting free radical-mediated damage to the membrane. Overall, changes within muscle membranes may reflect, contribute to, or initiate the disturbances in muscle function or reductions in muscle mass seen in alcoholic myopathy. Present evidence suggest that the changes in alcoholic muscle disease are not due to dietary deficiencies but rather the direct effect of ethanol or its ensuing metabolites.

Sexual asphyxia by hanging--a case report and a review of the literature.

A case of sexual asphyxial death by hanging is presented. A 35-year-old male, found dead lying on his face in a bed of a truck cab, had hanged himself from a window frame using a leather belt. He was completely naked. There were pornographic and sadomasochistic magazines beneath his face, opened to pages depicted nude photographs of a woman. Autopsy findings revealed a ligature mark on the neck and petechial hemorrhages in the conjunctivae, but there were no hemorrhages in the neck muscles or fractures of the hyoid bone or the thyroid cartilage. The alcohol levels in the blood and urine were 0.78 and 0.45 mg/ml, respectively. The circumstances suggested that his death was accidental, and due to asphyxia by hanging performed to enhance sexual gratification during masturbation. Sexual asphyxia is reviewed and discussed.

The importance of alcohol-induced muscle disease.

Alcohol-induced muscle disease (AIMD) is a composite term to describe any muscle pathology (molecular, biochemical, structural or physiological) resulting from either acute or chronic alcohol ingestion or a combination thereof. The chronic form of AIMD is arguably the most prevalent skeletal muscle disorder in the Western Hemisphere affecting more than 2000 subjects per 100,000 population and is thus much more common than hereditary disorders such as Becker or Duchenne muscular dystrophy. Paradoxically, most texts on skeletal myopathies or scientific meetings covering muscle disease have generally ignored chronic alcoholic myopathy. The chronic form of AIMDs affects 40-60% of alcoholics and is more common than other alcohol-induced diseases, for example, cirrhosis (15-20% of chronic alcoholics), peripheral neuropathy (15-20%), intestinal disease (30-50%) or cardiomyopathy (15-35%). In this article, we summarise the pathological features of alcoholic muscle disease, particularly biochemical changes related to protein metabolism and some of the putative underlying mechanisms. However, the intervening steps between the exposure of muscle to ethanol and the initiation of the cascade of responses leading to muscle weakness and loss of muscle bulk remain essentially unknown. We argue that alcoholic myopathy represents: (a) a model system in which both the causal agent and the target organ is known; (b) a myopathy involving free-radical mediated pathology to the whole body which may also target skeletal muscle and (c) a reversible myopathy, unlike many hereditary muscle diseases. A clearer understanding of the mechanisms responsible for alcoholic myopathy is important since some of the underlying pathways may be common to other myopathies.

7-hydroperoxycholesterol and oxysterols as indices of oxidative stress: chronic ethanol feeding and rat skeletal muscle.

The present study is undertaken to determine if ethanol affects 7-hydroperoxycholesterol or oxysterols in rat skeletal muscle after chronic ethanol feeding. Wistar rats were fed a liquid diet containing ethanol as 35% of total calories. After 6 weeks, soleus (Type I fibre-predominant) and plantaris (Type II fibre-predominant) skeletal muscles were dissected out. We measured 7alpha- and 7beta-hydroperoxycholest-5-en-3beta-ol (7alpha-OOH and 7beta-OOH) as well as 7alpha- and 7beta-hydroxycholesterol (7alpha-OH and 7beta-OH) and 3beta-hydroxycholest-5-en-7-one (7-keto). We found that in response to chronic alcohol feeding, there were significant increases in soleus 7alpha-OH (P=0.0005), 7beta-OH (P=0.0005) and 7-keto (P=0.0007), but in the plantaris, 7beta-OH increased (P=0.0418). Their elevation in chronic experimental alcoholism, together with increases in cholesterol hydroperoxides, may possibly represent evidence of increased oxidative stress.

Fatty acid profile in skeletal muscle of the rat in response to acute (2.5 hours) and prolonged (6 weeks) ethanol-dosage.

We tested the hypothesis that phospholipids are altered in skeletal muscles of rats exposed to ethanol for either acute (2.5 hours) or prolonged (6 weeks) periods. In acute studies, rats were dosed with saline (0.15 mmol/l; controls) or ethanol (75 mmol/kg body weight; treated). There were four groups: (A) saline (control); (B) cyanamide (an aldehyde dehydrogenase inhibitor); (C) ethanol; and (D) cyanamide + ethanol. In prolonged studies, two groups of rats were fed liquid diets containing 35% of total dietary energy as either glucose [group (E)] or ethanol [group (F)]. At the end of the treatments, membrane phospholipids were measured in soleus (Type I fibre-predominant) and plantaris (Type II fibre-predominant) muscle. In acute studies, ethanol alone [(A) vs. (C)] and cyanamide + ethanol [(A) vs. (D)] significantly increased 18 : 2 in plantaris (p < 0.05), whereas in soleus none of the treatments had any effect on the phospholipids. In prolonged studies [(E) vs. (F)], there were decreases in 16 : 0 (p < 0.05) and 18 : 1 (p < 0.01) and increases in 18 : 2 (p < 0.001) in plantaris. In soleus, decreases in 18 : 1 (p < 0.05) and increases in 18 : 2 (p < 0.01) occurred. In conclusion, alterations in the proportions of 16 : 0, 18 : 1 and 18 : 2 provide evidence of an altered membrane domain which may contribute to the pathogenesis of alcohol-induced muscle disease. Changes due to prolonged exposure are more profound than those in acute exposure and the preferential effects in Type II plantaris may reflect the greater susceptibility of this muscle to alcohol.

Consecutive administration of paraquat to rats induces enhanced cholesterol peroxidation and lung injury.

It is our hypothesis that as a consequence of increased oxidative stress, rats develop lung injury with increased cholesterol-derived hydroperoxides and oxysterols in lung after consecutive exposure of the rats to paraquat. To test this we administered 10 mg/kg of paraquat i.p. once or seven times (once a day) to Wistar rats. Rats were killed, and lung tissue was collected 24 h after the last paraquat injection. We found that in response to consecutive paraquat doses, there were significant increases in 7alpha- and 7beta-hydroperoxycholest-5-en-3beta-ol (7alpha-OOH and 7beta-OOH; P=0.01) as well as 7alpha- and 7beta-hydroxycholesterol (7alpha-OH and 7beta-OH; P=0.01), and 7-ketocholesterol (7-keto; P=0.03). In addition, pulmonary hemorrhage, thickening of alveolar septum, and inflammatory cell infiltration of macrophages were observed. This is the first report showing enhanced cholesterol peroxidation and lung injury of rats due to consecutive doses of paraquat.

Decreased arterial responses in WHHL rabbits, an animal model of spontaneous hypercholesterolemia and atherosclerosis.

We examined changes in blood pressure and blood flow of the arteries of WHHL and Japanese white rabbits after intravenous bolus injections of acetylcholine (3.0 micrograms/kg), bradykinin (0.5 microgram/kg), and sodium nitroprusside (3.0 micrograms/kg) under a condition of anesthesia. These vasodilators lowered the blood pressure and increased the blood flow in WHHL and Japanese white rabbits. The changes in the hemodynamic parameters of WHHL rabbits after injection of sodium nitroprusside were similar to those of Japanese white rabbits. This suggests that the relaxation response of the tunica media was not diminished in WHHL rabbits. In contrast, the changes in the hemodynamic parameters of WHHL rabbits after injection of acetylcholine or bradykinin were significantly lower than those in Japanese white rabbits. In the histopathological and immunohistological examination, atherosclerotic lesions were observed in the ascending aortas of WHHL rabbits. In the surface of the atheromatous plaques, CD31-positive endothelial cells disappeared partly and the accumulation of RAM-11-positive macrophages was observed in these regions. In addition, plasma NO2- and NO3- levels of WHHL rabbits were significantly lower than those of Japanese white rabbits. These findings suggest that relaxation responses derived from arterial endothelial cells were probably depressed in WHHL rabbits due to dysfunction or denudation of the arterial endothelial cells.