Enantioselective rhodium(I)-catalyzed hydrogenation of trifluoromethyl ketones.

[figure: see text] The asymmetric hydrogenation of trifluoromethyl ketones to yield chiral alpha-trifluoromethyl alcohols with enantiomeric excesses up to 98% was achieved in the presence of chiral rhodium-(amidephosphine-phosphinite) complexes.

Mediastinal liposarcoma appearing as a tumor arising in the esophageal wall.

We report a case of mediastinal liposarcoma, a relatively uncommon neoplasm, in which the mass also appeared as a tumor arising in the esophageal wall. A 76-year-old man diagnosed with a posterior mediastinal mass had the tumor extirpated in local esophageal myectomy due to its unclear margin on the esophageal wall. The resected specimen was diagnosed as well-differentiated liposarcoma. Preoperative angiography showed the tumor received its blood supply from a branch of the left gastric artery, suggesting it arose in the lower esophageal segment close to the hiatus and extended to the mediastinum. Since this tumor's growth pattern differed completely from esophageal liposarcoma described in previous case reports, we concluded that it was mediastinal liposarcoma.

A comparison of the new preservation solution Celsior to Euro-Collins and University of Wisconsin solutions in lung reperfusion injury.

BACKGROUND: The lung is particularly susceptible to reperfusion injury, both experimentally and clinically after transplantation. The extracellular-type preservation solution Celsior, which has been predominantly studied in cardiac preservation, has components designed to prevent cell swelling, free radical injury, energy depletion, and calcium overload. Using an isolated blood-perfused rat lung model, we investigated whether Celsior would decrease preservation injury and improve lung function after cold ischemic storage and reperfusion compared to Euro-Collins (EC) and University of Wisconsin (UW) solutions. METHODS: Lewis rat lungs were isolated, flushed with the respective cold preservation solution, and then stored at 4 degrees C for 6 or 12 hr. After ischemic storage, the lung block was suspended from a force transducer, ventilated with 100% O2, and reperfused for 90 min with fresh blood via a cannula in the pulmonary artery. Lung compliance, alveolar-arterial oxygen difference, and outflow oxygen tension were all measured. The capillary filtration coefficient (Kf), a sensitive measure of changes in microvascular permeability, was determined. RESULTS: For 6 hr of cold storage, lungs stored in Celsior had lower Kf values than those stored in EC, indicating decreased microvascular permeability. No other significant differences were noted between Celsior and EC or UW. For 12 hr of cold storage, Celsior provided increased oxygenation, decreased alveolar-arterial O2 differences, increased compliance, and decreased Kf values as compared to both EC and UW. CONCLUSIONS: Celsior provides better lung preservation than EC or UW as demonstrated by increased oxygenation, decreased capillary permeability, and improved lung compliance, particularly at 12-hr storage times. These results are highly relevant, inasmuch as EC and UW are the most common clinically used lung preservation solutions. Further studies of Celsior in experimental and clinical lung transplantation, as well as in other solid organs, are indicated.

[Effect of unilateral superior cervical sympathetic ganglionectomy on the contralateral ganglion in rat].

The effect of unilateral superior cervical sympathetic ganglionectomy on the contralateral ganglion was investigated in Sprague-Dawley male rats employing histological and morphometrical procedures. Neuronal cells showed cell enlargement and no change in the nuclear size and the cell number. Neuronal hypertrophy was due to innervation by some fibers of the contralateral half of organs which had been innervated by the ipsilateral ganglion.

[Pathohistological changes of the superior cervical ganglion after 99.5% ethyl alcohol injection].

The authors attempted to clarify the histological changes of superior cervical ganglion (SCG) cells in chronological order. Adult rat SCGs were injected with ethyl alcohol and were examined under light microscopy after fixation and histological processes. All neurons showed the so-called coagulation necrosis. Inflammatory reactions characterized by cellular invasion were delayed in contrast to ethyl alcohol exposure from outside of the ganglion capsule.

Addition of aprotinin to organ preservation solutions decreases lung reperfusion injury.

BACKGROUND: Organ preservation injury is associated with endothelial cell damage, destabilization of mitochondrial and cell membranes, and the release of proteolytic enzymes. In addition to its well-known clinical effect of reducing perioperative blood loss, aprotinin has antiproteolytic and membrane-stabilizing properties. We hypothesized that adding aprotinin to Euro-Collins (EC) and University of Wisconsin (UW) solutions would decrease preservation injury in cultured endothelial cells and a whole organ rat lung model. METHODS: Bovine aortic endothelial cells were cultured and stored in the respective solution at 4 degrees C for 12 or 48 hours. Endothelial cell viability after storage was assessed by dimethylthiazole tetrazolium cytotoxicity assay. In the whole organ model, rat lungs were isolated, flushed with the respective solution, and stored at 4 degrees C for 6 or 12 hours. The lungs were ventilated with 100% O2 and reperfused with fresh blood. Alveolar-arterial O2 difference, O2 tension, capillary filtration coefficient, and compliance were determined. RESULTS: Endothelial cell viability was optimized with the addition of aprotinin to EC and UW at a dose of 150 KIU/mL (0.02 mg/mL). In the isolated perfused lung model, after 6 hours of ischemic storage, aprotinin-enhanced (100 KIU/mL [0.014 mg/mL]) EC and UW decreased alveolar-arterial O2 difference, increased O2 tension, and decreased capillary filtration coefficient compared with EC and UW alone. After 12 hours of ischemic storage, aprotinin-enhanced EC and UW decreased alveolar-arterial O2 difference, increased O2 tension, decreased capillary filtration coefficient, and increased compliance compared with EC and UW alone. CONCLUSIONS: The addition of aprotinin to EC and UW solutions increases endothelial cell viability in hypoxic cold storage conditions. In terms of whole organ function, aprotinin improves lung preservation as demonstrated by increased oxygenation and compliance, and decreased capillary permeability. This study is clinically applicable as there is already extensive experience with the use of aprotinin in heart and lung transplant recipients, in addition to its routine use in conventional cardiac operations.

Addition of a mast cell stabilizing compound to organ preservation solutions decreases lung reperfusion injury.

OBJECTIVE: Research in lung transplant preservation has generally focused on free radicals and enzyme release from neutrophils, parenchymal cells, macrophages, and endothelium. The lung has a large resident population of mast cells that, when activated, release potent inflammatory mediators. We hypothesized that adding an inhibitor of mast cell degranulation, lodoxamide tromethamine (10 micromol/L), to Euro-Collins and University of Wisconsin preservation solutions, would decrease lung preservation injury. METHODS: Rat lungs were isolated, flushed with the respective solution, and stored at 4 degrees C for 6 or 12 hours. The lungs were reperfused with fresh blood and ventilated with 100% oxygen. Alveolar-arterial oxygen difference, oxygen tension, capillary filtration coefficient, and compliance were determined. RESULTS: After 6 hours of ischemic storage: lodoxamide tromethamine-enhanced Euro-Collins solution decreased alveolar-arterial oxygen difference from 539 to 457 (p = 0.004), increased oxygen tension from 119 to 205 mm Hg (p = 0.006), and decreased capillary filtration coefficient from 3.9 to 2.0 (p < 0.001); lodoxamide tromethamine-enhanced University of Wisconsin solution decreased alveolar-arterial oxygen difference from 546 to 317 (p < 0.001), increased oxygen tension from 166 to 335 mm Hg (p < 0.001), and decreased capillary filtration coefficient from 3.0 to 1.7 (p < 0.001). After 12 hours of ischemic storage, lodoxamide tromethamine-enhanced Euro-Collins solution decreased alveolar-arterial oxygen difference from 588 to 485 (p < 0.001), increased oxygen tension from 100 to 161 mm Hg (p = 0.012), decreased capillary filtration coefficient from 6.2 to 2.6 (p < 0.001), and increased compliance from 0.12 to 0.21 (p < 0.001); lodoxamide tromethamine-enhanced University of Wisconsin solution decreased alveolar-arterial oxygen difference from 478 to 322 (p < 0.001), increased oxygen tension from 214 to 335 mm Hg (p < 0.001), decreased capillary filtration constant from 4.2 to 2.0 (p < 0.001), and increased compliance from 0.20 to 0.25 (p < 0.001). CONCLUSIONS: Addition of lodoxamide tromethamine to Euro-Collins or University of Wisconsin solution results in a marked decrease in lung reperfusion injury as demonstrated by increased oxygenation, decreased microvascular permeability, and increased compliance. These results are relevant as Euro-Collins and University of Wisconsin solutions are the most common clinically used lung preservation solutions. This study also highlights the deleterious role of resident mast cells in preservation injury.

Thoracoscopic parasternal lymph node dissection for the staging of breast cancer.

With the advent of advanced thoracoscopic techniques, new applications have been expanding their roles in thoracic surgery. The aim of this paper is to introduce our new thoracoscopic approach in performing parasternal lymph node dissection of advanced breast cancer for its staging. This technique does not need the removal of any costal cartilage which is usually done in the conventional classical technique after radical mastectomy. Thoracoscopic procedure, in which wide and complete parasternal lymph node dissection is done, is minimally invasive and easy to perform. Therefore, the thoracoscopic technique may be a suitable alternative to the conventional approach in the future.

Histopathological study on bone changes induced by recombinant granulocyte colony-stimulating factor in rats.

Histopathological bone changes were examined in growing rats intravenously administered with high doses (100 and 1000 micrograms/kg/day) of recombinant human granulocyte colony-stimulating factor (rG-CSF) for 28 days. The changes were observed in the region where physiological bone resorption actively occurs in the growth phase, that is the trabeculae of metaphyseal spongy bone and the endosteum region of diaphyseal compact bone. Histologically, the changes involved accelerated osteoclastic bone resorption and osteogenesis due to intramembranous ossification. While osteoclastic bone resorption was observed in almost all lesions, about half of which were accompanied by osteogenesis. Bone changes which appeared after administration of rG-CSF were characterized by frequent occurrence at the site of highly osteoclastic activity and by initial osteoclastic resorption followed by osteogenesis due to intramembranous ossification. These results suggest that the main action of rG-CSF on bone may be an acceleration of osteoclastic bone resorption.

The age-related difference in bone changes in rats induced by recombinant human granulocyte colony-stimulating factor.

We examined the bone changes in recombinant granulocyte colon-stimulating factor (rhG-CSF)-treated young and young adult rats in order to investigate the effect of age-related conditions of bone growth on the bone changes induced by rhG-CSF. Recombinant human G-CSF (100 and 1,000 micrograms/kg/day) was given to rats by daily intravenous injection for 28 days starting at the age of either 6 or 14 wk, and the hindlimb bones were evaluated histopathologically. In the young rats, bone lesions were observed in the 100- and 1,000-micrograms/k groups. In the young adult rats, lesions were found only in the 1,000-micrograms/kg group. The lesions involved accelerated osteoclastic bone resorption and osteogenesis due to intramembranous ossification and there was no age-related difference in these histopathological findings. However, both the incidence of bone involvement and the severity of lesions were greater in the young rats than in the dose-matched young adult rats. The results suggest that the higher dose of rhG-CSF may intrinsically induce bone lesions of a particular histopathological nature in rats regardless of their age, and the action of rhG-CSF on bone may be stronger in young growing rats than in young adults.

Thoracoscopic surgery combined with a supraclavicular approach for removing superior mediastinal tumor.

This report introduces our new technique of thoracoscopic surgery combined with a supraclavicular approach for removing superior mediastinal tumor. A 68-year-old woman noticed a tumor palpable in the left supraclavicular fossa. The patient had no pain around the neck and shoulder. A radio-opaque shadow 6 cm in diameter was detected in her left apical lung field on chest roentgenogram. Chest CT and MRI showed that the tumor was located in the superior mediastinum, extending up to the thoracic inlet, and there was no invasion of the surroundings. At first, a thoracoscopic examination was performed to assess the possibility of the excision. After dissecting the tumor from the mediastinal tissue and the first costovertebrae as far as possible by thoracoscopic surgery, a supraclavicular approach was used to enter the thoracic cavity. Complete resection of the tumor was successfully performed by thoracoscopic surgery combined with a supraclavicular approach. The tumor was removed in a plastic bag through the supraclavicular defect. Postoperative histopathology revealed that the tumor was a benign neurogenic one. A satisfactory follow-up of 5 postoperative days was observed without any complications, and the patient was discharged. The procedure was safe, easy, and minimally invasive to perform. Moreover, the supraclavicular approach could be used to add trocar port if needed.

Thoracoscopic treatment of esophagobronchial fistula with esophageal diverticulum.

Thoracoscopic fistulectomy and diverticulectomy for esophagobronchial fistula with esophageal diverticulum were performed on a 49-year-old-woman. The neck of the diverticulum and the fistula were divided with endo-stapling technique. Intraoperative esophagoscopy was found to be useful for the definite localization and complete excision of the fistula and the diverticulum and the avoidance of stenosis of the esophagus. To avoid the recurrence of fistula, a pedicle of viable mediastinal pleura was interposed between esophageal and bronchial closures. Postoperative course was uneventful, and the complete relief of symptom was experienced for a period of 10 months after the operation. It is to be considered that the present thoracoscopic procedure with intraoperative esophagoscopy can be used as a standard operative procedure for esophagobronchial fistula with esophageal diverticulum.

Rapid induction of more malignant tumors by various genotoxic carcinogens in transgenic mice harboring a human prototype c-Ha-ras gene than in control non-transgenic mice.

In this study, we investigated the carcinogenic response of transgenic mice carrying the human prototype c-Ha-ras gene, namely Tg rasH2/CB6F1 mice, to various genotoxic carcinogens and compared it with that of control non-transgenic CB6F1 mice (non-Tg mice). The present studies were conducted as the first step in the evaluation of the Tg rasH2/CB6F1 mouse as a model for the rapid carcinogenicity testing system. Short-term (< or = 6 months) rapid carcinogenicity tests of various genotoxic carcinogens, 4-nitroquinoline-1-oxide, cyclophosphamide, N,N-diethylnitrosamine, N-methyl-N-nitrosourea, N-methyl-N'-nitro-N-nitrosoguanidine and methylazoxymethanol, revealed that Tg rasH2/CB6F1 mice are more susceptible to these genotoxic carcinogens than control non-Tg mice. Tg rasH2/CB6F1 mice developed tumors more rapidly compared with non-Tg mice. Malignant tumors were observed only in the carcinogen-treated Tg rasH2/CB6F1 mice, but not in non-Tg mice treated with the same carcinogens. Each carcinogen induced tumors in corresponding target tissues of the Tg rasH2/CB6F1 mice. Only a very few lung adenomas but no other tumors were seen as spontaneous tumors during the 6 months of carcinogenicity tests. These results demonstrate that more rapid onset and higher incidence of more malignant tumors can be expected with high probability after treatment with various genotoxic carcinogens in the Tg rasH2/CB6F1 mice than in control non-Tg mice. The Tg rasH2/CB6F1 mouse seems to be a promising candidate as an animal model for the development of a rapid carcinogenicity testing system.

Effects of a calcium channel blocker, nicardipine, on pressure-natriuresis in Dahl salt-sensitive rats.

The effects of a calcium channel blocker, nicardipine, on pressure-natriuresis responses were studied in Dahl salt sensitive (DS) and resistant (DR) rats. Differences in the neural and endocrine background were minimized by renal denervation and by holding plasma vasopressin, aldosterone, corticosterone, and norepinephrine levels constant by intravenous infusion. The renal plasma flow (RPF) and glomerular filtration rate (GFR) of DS rats were disautoregulated in the low renal perfusion pressure range, while those of DR rats were autoregulated. Administration of nicardipine (0.3 microgram/kg/min) into the renal artery significantly increased RPF and GFR and abolished the autoregulation in both strains of rats. Nicardipine also sharpened the pressure-natriuresis responses in both strains without changes in fractional excretion of sodium. These findings suggest that nicardipine increased GFR and thereby improved the pressure-natriuresis responses of DS rats.

Contribution of prostaglandins to pressure natriuresis in Dahl salt-sensitive rats.

To examine the role of prostaglandins on pressure natriuresis in Dahl salt-sensitive (DS) rat, the pressure-natriuresis relationships in DS and Dahl salt-resistant (DR) rats were characterized with or without indomethacin (2 mg/kg/h) by utilizing an in vivo renal perfusion study. When untreated, in the DS rat the pressure-natriuresis curve was blunted (P less than .05) and excretion of prostaglandin E2 (38 +/- 11 to 109 +/- 43 pg/min) was decreased in comparison to the DR rat. With indomethacin, the pressure-natriuresis curve in the DR rat was blunted, while no significant changes were observed in the DS rat. Plasma renin activity and concentration of atrial natriuretic peptide were not changed by the treatment of indomethacin in both strains. These results suggest that the decrease in renal prostaglandins, at least in prostaglandin E2, plays some role in blunting pressure natriuresis in DS rat.

Different effects of low and high doses of endothelin on haemodynamics and hormones in the normotensive conscious dog.

The effects of low-dose endothelin on systemic haemodynamics and vasoactive hormones were examined in conscious dogs. In addition, we examined the effects of endothelin on pressor responses to noradrenaline and angiotensin II and the baroreflex regulation of heart rate in conscious dogs. Continuous infusion of 40 fmol/kg per min endothelin for 40 min induced a mild but significant reduction in mean arterial pressure from 89.1 +/- 1.7 to 82.7 +/- 2.0 mmHg (P less than 0.05), associated with decreases in total peripheral resistance 20 min later. A 400 fmol/kg per min dose of endothelin, on the other hand, induced a gradual elevation of mean arterial pressure from 89.2 +/- 2.3 to 96.8 +/- 2.0 mmHg (P less than 0.05), associated with increases in total peripheral resistance over 30 min. The 40 fmol/kg per min dose of endothelin infusion induced a significant reduction in plasma arginine vasopressin (AVP; P less than 0.05) and elevations of plasma atrial natriuretic peptide (ANP; P less than 0.05), plasma prostaglandin E2 (PGE2; P less than 0.05) and plasma 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha; P less than 0.05). The 400 fmol/kg per min dose produced elevations of AVP, ANP, PGE2 and 6-keto-PGF1 alpha (P less than 0.05). Pressor responses to noradrenaline and angiotensin II were significantly attenuated during continuous infusion of 40 fmol/kg per min endothelin, whereas 400 fmol/kg per min endothelin did not induce any significant changes compared with the control. Furthermore, baroreflex sensitivity was attenuated with 40 fmol/kg per min endothelin but did not show any significant changes at 400 fmol/kg per min.(ABSTRACT TRUNCATED AT 250 WORDS)

Calcitonin gene-related peptide modulates adrenal hormones in conscious dogs.

The effects of a small dose (2 pmol/kg) of human calcitonin gene-related peptide I on plasma renin activity and hormones, including, aldosterone, ACTH, cortisol, AVP and ANH, were investigated in 14 conscious dogs. In addition, we studied the effects of calcitonin gene-related peptide on aldosterone secretion when it is stimulated by angiotensin II and ACTH. An intravenous bolus injection of 2 pmol/kg of calcitonin gene-related peptide raised plasma renin activity (by 216%, p less than 0.05), ACTH (by 85%, p less than 0.05), AVP (by 89%, p less than 0.05), and ANH (by 36%, p less than 0.05). Despite the elevation of plasma renin activity, aldosterone was decreased (by 52%, p less than 0.05). Cortisol did not change significantly. Infusion of 1 pmol.kg-1.min-1 of angiotensin II produced an elevation of aldosterone (by 186%, p less than 0.01), which was completely inhibited by pretreatment with an injection of 2 pmol/kg of calcitonin gene-related peptide. On the other hand, aldosterone secretion stimulated by ACTH was not altered significantly by pretreatment with an injection of 2 pmol/kg of calcitonin gene-related peptide. These results suggest that calcitonin gene-related peptide inhibits aldosterone secretion, especially when aldosterone is stimulated by angiotensin II. In addition, calcitonin gene-related peptide may be involved as an endocrine modulator in the physiological control of other several hormones closely related to the hemodynamics.

[Six-month intraperitoneal toxicity study of cefpirome sulfate in rats].

A six-month intraperitoneal chronic toxicity study of cefpirome sulfate (CPR) in rats as well as a two-month recovery study were carried out at dose levels of 51.2, 128, 320 and 800 mg/kg/day. The results are as follows. 1. CPR caused no remarkable clinical signs in the general condition of the animals. 2. Body weight gain was depressed in males and females given 800 mg/kg/day. Food consumption, however, was not afected at any dose level. Water consumption increased in males and females at dose of greater than or equal to 320 mg/kg/day. 3. Except an increase in urine volume in males at 800 mg/kg/day, no abnormalities in urinary parameters were found. 4. Frequent decreases in erythrocyte count, hematocrit and hemoglobin concentration were seen in males and females of the 800 mg/kg/day group. At this dose, certain males and females also showed an increase in the reticulocyte count. 5. The serum-biochemical examinations showed a very slight or slight decrease in total cholesterol in males and females given 320 mg/kg/day or more, and increases in uric acid and inorganic phosphorus concentration in some males and females given 800 mg/kg/day. 6. Very slight or slight increases in spleen weight in males and females at a dose of greater than or equal to 320 mg/kg/day, in thyroid weight in females at a dose of greater than or equal to 320 mg/kg/day and in kidney weight in males given 320 mg/kg/day or more as well as in females at 800 mg/kg/day were measured. Further, a decrease in thymus weight was seen in females of the 800 mg/kg/day group. 7. At autopsy, very slight or slight reddish browning of the thyroid was seen in males given 320 mg/kg/day or more and in females given 800 mg/kg/day.(ABSTRACT TRUNCATED AT 400 WORDS)

A case of pseudotumor cerebri following glucocorticoid therapy in which warfarin prevented recurrence.

A patient with nephrotic syndrome developed pseudotumor cerebri following glucocorticoid therapy. Diagnosis of pseudotumor cerebri was based on satisfaction of four criteria proposed by Ahlskog and O'Neill. The symptoms of pseudotumor cerebri disappeared within 10 days. After a three-week interval of remission, relapse occurred. Glycerol and urokinase produced rapid resolution of the symptoms and warfarin prevented further recurrence of pseudotumor cerebri for one year. These results suggest that the pathogenesis of pseudotumor cerebri might be associated with the hypercoagulable state which was induced by glucocorticoid therapy and nephrotic syndrome.