Effects of exercise and n-3 fatty acids on postprandial lipemia.

Because n-3 fatty acid ingestion and aerobic exercise each has been associated with diminished postprandial lipemia (PPL), the purpose of this study was to evaluate the effect of a combination of these two factors on PPL. Sedentary men underwent a standard dietary preparation, including a 12-h fast before each trial. Six subjects performed a control trial (fat meal, 100 g fat) and an n-3 fatty acid trial (fat meal after 3 wk of n-3 fatty acid supplementation at 4 g/day). In a parallel experiment, six different subjects underwent a control trial and n-3 fatty acid supplementation + 60 min of exercise before ingestion of the fat meal. Supplementation with n-3 fatty acid significantly decreased baseline triglyceride (TG) concentrations but did not significantly affect PPL. The combination of n-3 fatty acid and exercise had no effect on the postprandial TG response. The present study suggests that n-3 fatty acid supplementation lowers resting TG concentrations but inhibits the beneficial effect of aerobic exercise on the postprandial TG response.

Voltage-gated sodium channels in human aortic smooth muscle cells.

Whole-cell, voltage clamp methods were used to study inward currents in human aortic smooth muscle cells in culture. Cells were plated on glass coverslips, cultured in supplemented M-199 media with 5% serum and studied as primary cells and at passages 2-5. Inward currents were measured with a pipette solution containing Cs+ and TEA+ to block K+ currents and with 2.5 mM [Ca2+]0 in the perfusate. Inward currents activated at about -50 mV, peaked at about -15 mV and reversed at about +30 mV. Values of peak inward current averaged 14. 7 +/- 3.3 pA/pF and cell capacitance averaged 124 +/- 10 pF (n = 35). These currents activated rapidly with a time-to-peak current of 2.4 +/- 0.3 ms at a test potential of -10 mV from a holding potential of -80 mV. The current also inactivated rapidly with a time course that could be described by two components with time constants of 1.8 +/- 0.2 and 17.8 +/- 3.5 ms at -10 mV. The currents decreased when extracellular Na+ was reduced and were completely inhibited by 50 nM tetrodotoxin (TTX), suggesting that they represented voltage-gated Na+ currents (INa). Activation curves were characterized with a V0.5 = -16.6 +/- 2.4 mV and a slope factor k = -5.2 +/- 0.2 mV while inactivation curves were characterized with a V0.5 = -60.9 +/- 1.7 mV and a slope factor k = 8.8 +/- 0.4 mV. Lowering external [Ca2+] to zero increased the maximum INa, shifted its voltage dependence in the hyperpolarizing direction and increased the rate of INa inactivation. Increasing external [Ca2+] or [Mg2+]decreased INa and slowed its rate of inactivation. These studies demonstrate the presence of voltage-gated Na+ channels with high TTX sensitivity that are modulated by extracellular divalent cations in human aortic smooth muscle cells maintained in cell culture. Window currents were found in the voltage range of -50 to -20 mV, suggesting that these channels could contribute to the resting membrane potential.

Transcendence and imminence in psychotherapy.

The traditional dilemma of the compatibility of religion and psychotherapy is discussed within the context of maturing beyond the language and behavior of the imminent, i.e., the here-and-now. Transcendence is presented as a model for therapist and therapeutic methodology.

Prevention of fluvastatin-induced toxicity, mortality, and cardiac myopathy in pregnant rats by mevalonic acid supplementation.

Mevalonic acid is a product of the enzyme HMG-CoA reductase which is essential for cholesterol biosynthesis. Fluvastatin (Sandoz compound XU 62-320) is a potent inhibitor of this enzyme and, hence, mevalonic acid production. In three separate studies, oral administration of fluvastatin at 12 and 24 mg/kg/day to mated rats from day 15 of gestation through weaning resulted in unanticipated maternal mortality at the time of parturition and during lactation. Microscopic evaluations performed in two studies revealed significant cardiac myopathy in the dying animals. Drug-related clinical signs, significant maternal body weight loss, and an increase in stillborn pups and neonatal mortality were also noted at one or both dose levels. Supplementation of fluvastatin administration with 500 mg/kg b.i.d. of mevalonic acid completely blocked and/or ameliorated the mortality, cardiac myopathy, and other adverse effects. These studies indicate that the adverse maternal effects observed with fluvastatin before or following parturition resulted from exaggerated pharmacologic activity at the dose levels administered, i.e., inhibition of the enzyme HMG-CoA reductase, its immediate product mevalonic acid, and cholesterol biosynthesis.

The borderline hypertensive rat: a model for studying the mechanisms of environmentally induced hypertension.

The borderline hypertensive rat (BHR) is a first-generation cross between the spontaneously hypertensive rat and the normotensive Wistar-Kyoto rat. The BHR develops frank hypertension when chronically stressed or when fed a high-sodium diet. Stress-induced hypertension can be blocked by exercise. The role of the central nervous system and kidney in hypertension development in this model is discussed.

The metabolism and excretion of 14C-styrene oxide-glutathione adducts administered to the winter flounder, Pseudopleuronectes americanus, a marine teleost. Identification of the corresponding S-cysteine derivatives as major urinary metabolites.

The metabolism and excretion of intramuscularly administered 14C-glutathione conjugates of styrene oxide (Ia and IIa) were studied in the winter flounder at three dose levels. The various radiolabeled thioether metabolites excreted were separated by reverse-phase high pressure liquid chromatography, and identified and quantitated by cochromatography with synthetic standards. The urine was the major excretion route for radioactivity derived from the glutathione conjugates (up to 90%) at each dose level (1.0, 3.9, and 24.4 mg/fish) studied. The corresponding cysteine derivatives (Ic, IIc) were the major urinary metabolites although the N-acetylcysteine derivatives (Id, IId), or mercapturic acids, were also present in significant amounts at each dose and excretion interval examined. Unchanged glutathione conjugates of styrene oxide were the major radioactive constituents of 24-hr bile samples from the treated flounder, although significant amounts of the cysteinylglycine (Ib, IIb), cysteine, and N-acetylcysteine derivatives were also present in bile. Bile was a minor excretory route relative to urine. The oxidation of 14C-styrene to styrene 7,8-oxide by the cytochrome P-450-dependent monooxygenase system of hepatic microsomes of winter flounder was also demonstrated; likewise, styrene was converted to the diastereomeric glutathione conjugates of styrene 7,8-oxide by 9,000g supernatant fractions of flounder liver supplemented with glutathione. This study demonstrated that flounder liver can convert styrene to glutathione conjugates to styrene oxide and that mercapturic acid biosynthesis occurs after parenteral administration of a xenobiotic-glutathione adduct to this marine species, although the major urinary metabolites were the cysteine conjugates rather than the anticipated mercapturic acid derivatives.

An approach to the anesthetic requirements for a chronic animal preparation.

The general anesthetic requirements for the preparation of a chronic experimental animal are discussed with respect to the implantation of an electromagnetic flow probe around the ascending aorta of the dog. After preanesthetic management and induction, several techniques for the maintenance of anesthesia are briefly considered. A technique is emphasized that combines a light general anesthetic with a regional nerve block and best fulfills the general anesthetic requirements.

Intrastrain difference in serotonin and norepinephrine in discrete areas of rat brain.

Determination of levels of serotonin and norepinephrine in various brain areas of male Sprague-Dawley rats obtained from four different breeder-suppliers showed considerably different basal levels among the various groups, as well as differences in response to monoamine oxidase inhibitors.