Diets rich in n-9, n-6 and n-3 fatty acids differentially affect the generation of inositol phosphates and of thromboxane by stimulated platelets, in the rabbit

We have studied the effects of semi-synthetic diets rich in either n-9 (olive oil, OO) or n-6 (corn oil, CO), or n-3 (fish oil, FO, as MaxEPA) fatty acids on the levels of major PUFA in platelet lipids, on the generation of inositol phosphates by [3H]inositol labelled platelets after stimulation with thrombin and of thromboxane B2 (TxB2) by platelet rich plasma (PRP) after stimulation with collagen. The predicted elevations of oleic (OA), linoleic (LA) and eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids were observed in platelet lipids of each animal group, but in the MaxEPA fed group accumulation of EPA was associated with depletion of linoleic acid (LA) rather than of arachidonic acid (AA). Basal levels of inositol-tris-phosphate (IP3) in platelets were lowest in the OO group and highest in the CO group, whereas the increment after thrombin stimulation (1 unit/ml NIH) was maximal in the OO group and minimal in the FO group. Instead, when generation of TxB2 by stimulated platelets was evaluated, no appreciable difference among the various groups could be detected, in accordance with the limited modifications of platelet AA content induced by the diets. The overall data indicate that dietary fatty acids modulate the pathway of inositol phosphate generation in rabbit platelets, independently of modifications of TxB2 production.     

Immunochemical characterization of multiple forms of cytochrome P-450 in rabbit nasal microsomes and evidence for tissue-specific expression of P-450s NMa and NMb

Two unique forms of cytochrome P-450 (P-450), designated NMa and NMb, were recently isolated in this laboratory from nasal microsomes of rabbits. In the present study, polyclonal antibodies to the purified nasal cytochromes were prepared. Immunochemical analysis with specific rabbit anti-NMa and sheep anti-NMb antibodies indicated that P-450 isozymes identical to or having a high structural homology with NMa are present in both olfactory and respiratory mucosa, as well as in liver, but NMb was detected only in the olfactory mucosa. Neither form was detected in other tissues examined, including brain, esophageal mucosa, heart, intestinal mucosa, kidney, and lung. The specific occurrence of NMb in the olfactory mucosa was further substantiated by the detection and specific inhibition by anti-NMb of the formation of unique NMb-dependent metabolites of testosterone in olfactory microsomes but not in microsomes from liver or respiratory mucosa. Similar experiments with antibodies to previously purified rabbit hepatic P-450 isozymes indicated that not all of the hepatic cytochromes are expressed in the nasal tissues. Thus, P-450 isozymes structurally homologous to hepatic forms 2, 3a, and 4, but not 3b and 6, were found in the olfactory mucosa. On the other hand, only form 2 was detected in the respiratory mucosa. Immunoquantitation experiments revealed that NMa and NMb are the major P-450 forms in olfactory microsomes, whereas NMa and P-450 form 2 (or its homolog) constitute the major portion of the respiratory nasal microsomal P-450. The level of NMa in the liver is relatively low, accounting for less than 3% of total microsomal P-450 in this tissue. In addition, evidence is provided that NMa is the major catalyst in the dealkylation of two nasal carcinogens, hexamethylphosphoramide and phenacetin, in both olfactory and respiratory nasal microsomes.     

A modified algorithm for the management of ureteral calculi: 100 consecutive cases

We treated 100 consecutive ureteral calculi requiring intervention with a previously described algorithm. There were 16 ureteropelvic junction, and 18 upper, 22 mid and 44 lower ureteral calculi. Treatment was by a stent and extracorporeal shock wave lithotripsy in 10 ureteropelvic junction, 10 upper ureteral and 3 mid ureteral calculi, ureteroscopy and extracorporeal shock wave lithotripsy in 6 upper and 6 mid ureteral calculi, and ureteroscopy alone in 5 ureteropelvic junction, 2 upper and 12 mid ureteral calculi. All 44 lower ureteral calculi were treated successfully by ureteroscopy. Of the 100 patients studied 98 were treated by endourological methods (extracorporeal shock wave lithotripsy or ureteroscopy), while 2 required an operation (1 with a ureteropelvic junction calculus and 1 with a mid ureteral calculus). Over-all, 100 patients required a total of 125 procedures to accomplish successful stone removal. An algorithm is developed in which lower ureteral calculi are treated by ureteroscopy, mid ureteral calculi (large and dense) by stent bypass and extracorporeal shock wave lithotripsy or (lucent and fragile) by ureteroscopy, upper ureteral calculi by stent bypass and extracorporeal shock wave lithotripsy without manipulation, and impacted ureteral stones initially by ureteroscopy and, if necessary, then by extracorporeal shock wave lithotripsy.     

Giant hydronephrosis presenting as unilateral iliofemoral vein thrombosis

We report a case of left iliofemoral vein thrombosis with extension to the inferior vena cava associated with giant right hydronephrosis secondary to ureteropelvic junction obstruction. Surgery revealed marked infrarenal vena caval compression and deviation to the left side caused by the dilated right renal pelvis, with resultant kinking of the origin of the left iliac vein. It is postulated that the reduction in blood flow caused by this compression and distortion predisposed this patient to venous thrombosis.     

Increased (L+)-lactic acid production in lysozyme-inactivated suspensions of human dental plaque

The effect of lysozyme-inactivation on L(+)-lactic acid (LA) production in dental plaque suspensions was evaluated. From 10 children 24-h plaque was collected and lysozyme activity inhibited by addition of goat antiserum to human lysozyme. Acid production was stimulated by addition of glucose. The results showed significantly increased LA levels (50-150%) in lysozyme-inactivated plaque suspensions from 8 of the subjects compared to untreated controls. The increase in acid production activity was not related to plaque lysozyme levels. The findings indicate that the presence of lysozyme may be limiting on acid production in the early dental plaque.     

Pharmacological studies of 6-amidino-2-naphthyl 4-[(4,5-dihydro-1H-imidazol-2-yl)amino]benzoate dimethanesulfonate. Effects on experimental pancreatitis

The effects of FUT-187 (6-amidino-2-naphthyl 4-[(4,5-dihydro-1H-imidazol-2-yl)amino]benzoate dimethanesulfonate, CAS 103926-82-5), a novel synthetic protease inhibitor, were examined in experimental rat and canine models of pancreatitis. 1. FUT-187 significantly increased the survival of rats with trypsin- and phospholipase A2-induced pancreatitis in a dose-dependent manner (10-100 mg/kg, p.o.). 2. FUT-187 decreased plasma enzymatic activity reflecting the degree of pancreatitis in rats with ethionine-induced pancreatitis, and showed a tendency to ameliorate histopathological changes in the pancreas (10-100 mg/kg p.o.). 3. FUT-187 (10 mg/kg) produced an obvious improvement of various biochemical parameters of pancreatitis and also reduced histopathological changes in the pancreas in animals with experimental pancreatitis produced by the closed duodenal loop method. In addition, FUT-187 significantly increased the survival of dogs when given by direct administration into the lumen of the closed duodenal loop. The therapeutic effects of FUT-187 in experimental pancreatitis were nearly equal in most instances to those of camostat mesilate. Thus, FUT-187 would appear to be an effective new agent for the treatment of pancreatitis.     

Mycenon, a new metabolite from a Mycena species TA 87202 (basidiomycetes) as an inhibitor of isocitrate lyase

Mycenon (C11H5Cl3O3), a new inhibitor of isocitrate lyase (EC 4.1.3.1) was isolated from the culture broth of a basidiomycete, Mycena sp. Mycenon is a novel chlorinated benzoquinone derivative which is also active against bacteria and fungi. Malate synthase (EC 4.1.3.2) the second key enzyme of the glyoxylate cycle was not affected by mycenon. Isocitrate lyase preparations from plants, bacteria and fungi were sensitive. The following Ki-values for mycenon have been determined: Ricinus communis, 5.2 microM; Acinetobacter calcoaceticus, 11 microM; Neurospora crassa, 7.4 microM. The structure of mycenon has been determined by a single crystal X-ray analysis.     

Levodopa up-regulates platelet alpha 2-adrenoceptors

Treatment of dogs for 21 days with oral levodopa (100 mg b.i.d.) plus benserazide (25 mg b.i.d.) induced a significant increase in the number of platelet alpha 2-adrenoceptors labelled by [3H] yohimbine with no change in Kd. The rise was maximal at the end of the treatment and remained significant during the month following the cessation of treatment. Plasma catecholamine levels did not vary. Competition experiments showed a low affinity of both dopamine and levodopa for platelet alpha 2-adrenoceptors. These results suggest that levodopa treatment regulates alpha 2-adrenoceptor number in dog platelets.