Nitric oxide synthase inhibition exaggerates the hypotensive response to ghrelin: role of calcium-activated potassium channels

OBJECTIVE: To investigate the mechanism underlying the observation that infusion of the growth hormone secretagogue peptide, ghrelin, produces a decrease in mean arterial pressure (MAP) with no change in heart rate. METHOD: The effect of a single bolus infusion of ghrelin (12 nmol/kg intravenously) on the changes in MAP and heart rate was determined in 12-week-old male anaesthetized Sprague-Dawley rats subjected to pretreatment with either the nitric oxide synthase (NOS) inhibitor, N-nitro-L-arginine methyl ester (L-NAME; 0.7 mg/ml by mouth for 5 days), or vehicle (control). RESULTS: Ghrelin produced a significant decrease in MAP at 20 min (P < 0.05) after infusion in the control group, without any change in heart rate. The MAP recovered partially over 1 h. The ghrelin-evoked decrease in MAP was much greater (P < 0.01) and was sustained for 1 h in rats subjected to NOS inhibition. Pretreatment with the cyclo-oxygenase inhibitor, indomethacin, failed to affect the responses in either group. Intravenous infusion of 50 mug/kg each of apamin and charybdotoxin (ChTX), a combination that is known to block Ca-activated K channels or the endothelium-derived hyperpolarization process, attenuated the decrease in MAP evoked by ghrelin in both control and NOS-inhibited rats. A sodium nitroprusside-induced decrease in MAP was unaffected in the presence of apamin-ChTX, but acetylcholine-evoked hypotension was significantly reduced in both groups. CONCLUSION: These data suggest that the Ca-activated, K-channel-mediated, ghrelin-evoked decrease in MAP may be significant in states of endothelial dysfunction associated with reduced nitric oxide availability.     

Norlignans, acylphloroglucinols, and a dimeric xanthone from Hypericum chinense

Two new norlignans, hyperiones A (1) and B (2), three new acylphloroglucinols, aspidinol C (3) and hyperaspidinols A (5) and B (6), the known compound aspidinol D (4), and the symmetrical dimeric xanthone hyperidixanthone (7) were isolated from Hypericum chinense. Their structures were established by spectroscopic analysis. In an antibacterial assay using a panel of multidrug-resistant (MDR) strains, compounds 3 and 4 exhibited promising activity against the NorA efflux protein overexpressing MDR Staphylococcus aureus strain SA-1199B with a minimum inhibitory concentration (MIC) of 2 μg/mL (8.4 μM) and 4 μg/mL (16.8 μM), respectively. The positive control antibiotic norfloxacin showed activity at MIC 32 μg/mL (100 μM).     

Furan metabolites from the sponge-derived yeast Pichia membranifaciens

Five new compounds, pichiafurans A-C (1-3) and pichiacins A and B (4 and 5), along with five known compounds (6-10), have been isolated from the yeast Pichia membranifaciens derived from a marine sponge Petrosia sp. Their structures were elucidated by 1D and 2D NMR and mass spectrometry techniques. Pichiafurans are rare examples of monofurano metabolites isolated from yeast.     

Interpectoral nodes in carcinoma of the breast: Requiem or resurrection

Fifty-eight consecutive patients undergoing a modified radical mastectomy were subjected to complete dissection and pathological assessment of the interpectoral fascia and the group of lymph nodes it contains. The dissection was carried out in all patients, irrespective of whether they were palpable or not. Interpectoral nodes (IPNs) were anatomically present in 28 patients (48%) and were completely absent in 30 patients (52%). Ten patients were Stage I, 18 were Stage II, and 30 were Stage III. Of the 25% (15/58) of patients with microscopic metastasis, only 12/15 had palpable nodes; 66% (10/15) of patients had axillary and apical nodes positive. Significantly, two patients with negative nodes in the axillary and apical group had metastatic Rotter's nodes. Of the 15 patients with positive IPNs, nine had primary tumors located within the upper quadrants of the breast, whereas only five had tumors in lower quadrants and one had a centrally located tumor. The neurovascular bundle to the pectoralis major could be safely preserved in 93% (54/58) of patients. The incidence of impalpable nodes with microscopic metastasis and the evidence of exclusively metastatic interpectoral nodes with uninvolved axillary and apical nodes prompt the following conclusions: (1) interpectoral fascia and nodes should be mandatorily dissected in all patients irrespective of the nodes being palpable or not; (2) the dissection is anatomic and is associated with almost no additional morbidity; (3) the group of patients with IPNs positive and the axillary group negative, would benefit maximally from the IPN dissection. Similarly, this dissection in all other groups of patients would enable a more accurate staging and selection of therapeutic strategies. © 1996 Wiley-Liss, Inc.     

Synthesis of new series of 1-Aryl-1,4-dihydro-4-oxo-6-methyl pyridazine-3-carboxylic acid as potential antibacterial agents

New series of 1-aryl-1,4-dihydro-4-oxo-6-methyl pyridazine-3-carboxylic acid has been synthesized and the structures of the new compounds were established on the basis of 1H-NMR, mass (ES/MS), elemental analysis and IR spectral data. In vitro antibacterial activity (MIC activity) was evaluated and compared with standard drugs ciprofloxacin, sparfloxacin and trovafloxacin. Most of the compounds in the series have shown very interesting antibacterial activity against both gram-positive and gram-negative organisms. In this paper, we describe studies leading to identification of antibacterial agents incorporating novel pyridazine ring surrogate. In a gratifying result, the initial pyridazine-3-carboxylic acid analogues prepared were found to exhibit in vitro antibacterial activity approaching that of corresponding fluoroquinolone progenitor.     

Aleukemic leukemia cutis

Aleukemic leukemia cutis has always been a dermatological curiosity. It is a rare condition characterized by the infiltration of skin by leukemic cells before their appearance in the peripheral blood or bone marrow. A 20 year old man had presented with nodular swelling on the scalp of 6 months duration along with cervical lymphadenopathy. Biopsy and immunohistochemistry revealed myeloid sarcoma. The initial presentation was aleukemic and repeated peripheral blood counts and marrow examinations were normal. However, the outcome was fatal within 3 months of diagnosis of cutaneous lesions.