Inhibition of nitrergic neurotransmission in the bovine retractor penis muscle by an oxidant stress: effects of superoxide dismutase mimetics.

1. A number of superoxide dismutase (SOD) mimetics were examined both biochemically for their ability to inhibit the superoxide-catalyzed reduction of cytochrome c and nitro blue tetrazolium, and functionally for their ability to mimic authentic Cu/Zn SOD in restoring nitrergic neurotransmission in bovine retractor penis (BRP) muscle following its inhibition by oxidant stress. 2. The SOD mimetics investigated were CuSO4, MnCl2, CuDIPS (copper [II] [diisopropylsalicylate]2), MnTBAP (manganese [III] tetrakis 4-benzoic acid porphyrin), MnTMPyP (manganese [III] tetrakis 1-methyl-4-pyridyl porphyrin pentachloride), tiron (4,5-dihydroxy-1,3-benzene disulphonic acid), PTIYO (4-phenyl,2,2,5,5,-tetramethyl-3-imidazolin-1-yloxy-3-oxide) and tempol (4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl). 3. The rank order of potency in inhibiting the reduction of cytochrome c was: CuSO4 > or = MnCl2 > or = CuDIPS > or = MnTMPyP > MnTBAP > tempol > or = tiron > PTIYO. 4. The requirement for EDTA (0.1 mM) prevented assessment of the activity of CuSO4, MnCl2 and CuDIPS in the assay involving inhibition of reduction of nitro blue tetrazolium. However, the rank order of potency for those agents which could be examined (MnTMPyP > MnTBAP > tiron > or = tempol > PTIYO) was essentially similar to that seen in the cytochrome c assay. 5. Inhibition of endogenous Cu/Zn SOD with diethyldithiocarbamate (DETCA, 3 mM, 120 min) in BRP muscle strips, followed by addition of the superoxide anion generator, LY 83583 (1 microM), resulted in almost complete abolition of nitrergic relaxation (4 Hz, 10 s). 6. Authentic Cu/Zn SOD (1-300 u ml(-1)), CuSO4 (0.1-300 microM), MnCl2 (0.1-100 microM) and MnTMPyP (10-300 microM) each restored nitrergic transmission by around 50%. However, CuDIPS (0.1-30 microM), MnTBAP (0.1-100 microM), tempol (10 microM - 3 mM), PTIYO (1-300 microM) and tiron (10 microM - 10 mM) all failed to restore nitrergic transmission. 7. The ability of MnTMPyP to restore nitrergic neurotransmission may therefore provide a lead in the development of SOD mimetics as therapeutic agents in the treatment of neuropathies associated with oxidant stress.

Gray scale and power Doppler sonography in cases of Kimura disease.

SUMMARY: Kimura disease is a rare chronic inflammatory disorder mimicking malignancy. Nodes are present in the submental and submandibular regions, within the parotid gland, and in the upper cervical chain. On gray scale sonograms, they are hypoechoic and round, with normal hilar architecture and homogeneous internal echoes. On power Doppler sonograms, the nodes show prominent intranodal vessels with a hilar pattern and low intranodal resistance. The soft tissue and parotid lesions also show low-resistance vascularity within.

Cardiovascular responses in the normotensive rat produced by intravenous injection of gambirine isolated from Uncaria callophylla B1. ex Korth.

Among several alkaloids, including dimeric indoles, isolated from Uncaria callophylla, gambirine which is an alkaloid unique to this plant, has been found to be another hypotensive principle from the plant. Intravenous injections of gambirine in the dose range of 0.2 to 10.0 mg/kg caused a dose-related fall in both systolic and diastolic blood pressures as well as heart rate. At all doses gambirine showed a prompt onset of action and at the higher doses (5.0-10 mg/kg), marked persistence of hypotension accompanied by severe bradycardia were observed. In addition, higher doses of gambirine produced a more marked decrease in diastolic than systolic pressure while at lower doses both decreased equally. It is suggested that the hypotensive effect of gambirine may be peripheral in origin and is associated, at least in part, with a cardiac action.

Giant benign sinonasal squamous papilloma: report of a case.

We treated a patient with a giant squamous papilloma in the nasal cavity and maxillary sinus that extended through a bony defect into the oral cavity. The mass was excised with a combined endoscopic, Caldwell-Luc, and transoral approach. Lesions of this type are rare, but when they do occur, the rate of recurrence is high. Therefore, long-term followup, including endoscopic examination, is important.

Transforming growth factor-ß impairs glucocorticoid activity in the A549 lung adenocarcinoma cell line.

BACKGROUND AND PURPOSE: The lung adenocarcinoma cell line, A549, undergoes epithelial-mesenchymal cell transition (EMT) in response to TGF-ß. Glucocorticoids do not prevent the EMT response, but TGF-ß induced resistance to the cytokine-regulatory action of glucocorticoids. We sought to characterize the impairment of glucocorticoid response in A549 cells. EXPERIMENTAL APPROACH: A549 cells were exposed to TGF-ß for up to 96 h before glucocorticoid treatment and challenge with IL-1α to assess glucocorticoid regulation of IL-6 and CXCL8 production. Nuclear localization of the glucocorticoid receptor α (GRα) was ascertained by immunofluorescence and Western blotting. Transactivation of the glucocorticoid response element (GRE) was measured with a transfected GRE-secreted human placental alkaline phosphatase reporter. KEY RESULTS: TGF-ß (40-400 pM) reduced the maximum inhibitory effect of dexamethasone on IL-1α-induced IL-6 and CXCL8 production. The impaired glucocorticoid response was detected with 4 h of TGF-ß (40 pM) exposure (and 4 h IL-1α to induce CXCL8 expression) and therefore was not secondary to EMT, a process that requires longer incubation periods and higher concentrations of TGF-ß. TGF-ß also impaired dexamethasone regulation of granulocyte-macrophage colony-stimulating factor in thrombin-stimulated BEAS-2B epithelial cells. Impaired regulation of CXCL8 was associated with markedly reduced GRE transactivation and reduced induction of mRNA for IκBα, the glucocorticoid-inducible leucine zipper and the epithelial sodium channel (SCNN1A). The expression, cellular levels and nuclear localization of GRα were reduced by TGF-ß. CONCLUSIONS AND IMPLICATIONS: We have identified mechanisms underlying the impairment of responses to glucocorticoids by TGF-ß in the A549 and BEAS-2B cell lines.

The actions of dopamine on the blood pressure and heart rate of conscious hypertensive rats: evidence for reduced dopaminergic activity in rats of the Japanese strains.

The effects of intracerebroventricularly (icv) and intravenously (iv) administered dopamine (DA) on mean arterial pressure (MAP) and heart rate were investigated in conscious spontaneously hypertensive rat (SHR), stroke-prone SHR (spSHR) and normotensive Wistar-Kyoto (WKY) rat of Japanese strains, genetically hypertensive (GHR) and normotensive (NT-NZ) rat of New Zealand strains, Sprague-Dawley (SD) rat, and left renal artery stenosed hypertensive WKY (WKYLRAS) and SD (SDLRAS) rats. Icv DA (0.0125-0.4 mg/kg) caused a linear dose-related decrease in MAP, accompanied by bradycardia in all animals. By contrast, the same doses of DA given iv caused a linear dose-related increase in MAP, accompanied by reflex bradycardia in most groups (except the spSHR, SHR and WKYLRAS where tachycardia occurred to most of the doses employed), indicating that the decrease in MAP following icv DA is centrally-mediated. A "greater" relative hypotensive effect to icv DA was seen in the Japanese hypertensive strains SHR and spSHR compared to the WKY, but not between the New Zealand strains or the renal hypertensive animals. Our data also show that this marked hypotensive responsiveness is not related to the basal MAP, but appears to be strain-specific. It is thus possible that the alleged reduced central dopaminergic activity in the Japanese strains of hypertensive rats may be responsible for exaggerated hypotensive responses observed in these strains.

Neuropeptide abnormalities suggest a dopaminergic basis for high blood pressure in the spontaneously hypertensive rat.

The spontaneously hypertensive rat (SHR) and the stroke-prone substrain (sp-SHR) have been reported to have several abnormalities in levels of peptides both in tissue and in plasma (beta-endorphin, prolactin, thyroid stimulating hormone and vasopressin) when compared to the Wistar Kyoto (WKY) normotensive control rat. As the secretion of these peptides is under dopaminergic control and the abnormalities consistently suggest under-activity of the dopaminergic control system in the brain, injections of dopamine (0.4 mg/kg) were given i.c.v. to 10 SHR, 10 renal artery stenosis hypertensive rats (LRAS) and 10 genetically hypertensive rats of the New Zealand strain (GHR). Mean blood pressure fell from 205 +/- 6 (SEM) mmHg to 128 +/- 8 mmHg in the SHR (p less than 0.001), from 184 +/- 7 mmHg to 176 +/- 7 mmHg in the LRAS (p greater 0.05) and from 157 +/- 5 mmHg to 138 +/- 6 mmHg in he GHR (p less than 0.02). These effects were unlikely to be due to leakage of dopamine out into the periphery as i.v. dopamine (0.4 mg/kg) increased blood pressure in these animals.

Effects of dopamine on blood pressure and heart rate after microinjection into the hypothalamus of spontaneously hypertensive and normotensive Wistar-Kyoto rats.

In anaesthetized spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats, 0.0125-0.4 mg/kg dopamine (DA) given intracerebroventricularly (icv) produced dose-related decreases in mean arterial blood pressure (MAP) and heart rate (HR), whereas intravenous DA produced dose-related increases in MAP and HR. SHR was significantly more responsive to icv DA compared with the normotensive controls. DA (0.02 mg/kg) significantly reduced MAP in a biphasic manner, when microinjected into the arcuate nucleus or third ventricle of SHR, with no significant changes in HR. No such effect occurred in WKY rats. Metoclopramide given concurrently with DA into the third ventricle attenuated the hypotensive response to DA. Saline injection had no significant effect on MAP and HR. The hypotensive responses to DA were not confounded by the spread of injected DA into the adjacent hypothalamic areas. These results support the hypothesis that there exists an abnormal sensitivity in SHR to centrally administered DA and that the arcuate appears to be the brain site involved in this abnormality.

Unusual T- and T/NK- cell non-Hodgkin's lymphoma of the larynx: a diagnostic challenge for clinicians and pathologists.

BACKGROUND: Lymphomas of T-cell and T/natural killer (T/NK)-cell types rarely involve the larynx. Early symptoms are subtle and nonspecific, and confirmation of the diagnosis is often difficult. Because of the rarity of this disease entity, the optimal management remains controversial. METHODS: The case records of patients with the diagnosis of lymphoma involving the larynx were retrospectively reviewed. Details of the pathologic condition, the difficulties in diagnosis, and treatment were presented. RESULTS: One case of T-cell lymphoma (Lennert's lymphoma subtype) and two cases of T/NK-cell lymphomas involving the larynx were presented. The diagnoses were all difficult to establish. All three patients received either multiagent chemotherapy or radiotherapy as the first-line treatment. They all died of the disease within 32 months of diagnosis. CONCLUSIONS: T- and T/NK-cell non-Hodgkin's lymphoma of the larynx is a diagnostic challenge for clinicians and pathologists. Conventional chemotherapy or radiotherapy has not been effective. A more aggressive therapy should be considered.

Acute renal failure in a healthy young adult after dextran 40 infusion for external-ear reattachment surgery.

Dextran 40 is used to improve the microcirculation after certain surgical procedures. We report a rare case of acute anuric renal failure in a healthy young adult after administration of dextran 40 to improve the microcirculation following ear-reattachment surgery. The renal failure was subsequently reversed by plasmapheresis and intensive care support. Although rare in the young and fit, the risk of developing acute anuric renal failure exists with administration of dextran 40 and appropriate monitoring is essential.

Percutaneous embolization to control intractable epistaxis in nasopharyngeal carcinoma.

BACKGROUND: Epistaxis in patients with nasopharyngeal carcinoma (NPC) who have received radiotherapy can be difficult to control by conventional methods. The use of angiography and embolization to control problematic epistaxis has been well documented in other situations, but its use in severe or recurrent epistaxis following irradiation for NPC has not been described. METHODS: We retrospectively reviewed case notes of all patients with NPC initially seen with epistaxis over a 4-year period. Those patients with refractory epistaxis which could not be controlled by conventional methods and required angiography and embolization were assessed. RESULTS: Eight patients who underwent angiography were identified. Five patients showed hypervascularization and three patients had pseudoaneurysms or an aneurysm of the internal carotid artery seen on the angiogram. All these patients were successfully embolized. There were no significant complications after the procedure. CONCLUSION: We conclude that embolization is a safe and effective method of controlling refractory epistaxis in patients irradiated for NPC.