Fish oil supplementation in obese rats ameliorates metabolic syndrome response.

Accumulation of visceral adipose tissue is associated with metabolic syndrome (MS), insulin resistance, and dyslipidemia. Here we examined several morphometric and biochemical parameters linked to MS in a rodent litter size reduction model, and how a 30-day fish oil (FO) supplementation affected these parameters. On day 3 post-birth, pups were divided into groups of ten or three. On day 22, rats were split into control (C) and small litter (SL) until 60 days old. Then, after metabolic disturbance and obesity were confirmed, FO supplementation started for 30 days and the new groups were named control (C), FO supplemented (FO), obese (Ob), and obese FO supplemented (ObFO). Comparison was performed by Student t-test or 2-way ANOVA followed by Tukey post hoc test. At the end of the 60-day period, SL rats were hyperphagic, obese, hypoinsulinemic, normoglycemic, and had high visceral fat depot and high interleukin (IL)-6 plasma concentration. Obese rats at 90 days of age were fatter, hyperphagic, hyperglycemic, hypertriacylgliceromic, hipoinsulinemic, with low innate immune response. IL-6 production ex vivo was higher, but in plasma it was not different from the control group. FO supplementation brought all biochemical changes to normal values, normalized food intake, and reduced body weight and fat mass in obese rats. The innate immune response was improved but still not as efficient as in lean animals. Our results suggested that as soon MS appears, FO supplementation must be used to ameliorate the morpho- and biochemical effects caused by MS and improve the innate immune response.

Fish oil supplementation in obese rats ameliorates metabolic syndrome response

Accumulation of visceral adipose tissue is associated with metabolic syndrome (MS), insulin resistance, and dyslipidemia. Here we examined several morphometric and biochemical parameters linked to MS in a rodent litter size reduction model, and how a 30-day fish oil (FO) supplementation affected these parameters. On day 3 post-birth, pups were divided into groups of ten or three. On day 22, rats were split into control (C) and small litter (SL) until 60 days old. Then, after metabolic disturbance and obesity were confirmed, FO supplementation started for 30 days and the new groups were named control (C), FO supplemented (FO), obese (Ob), and obese FO supplemented (ObFO). Comparison was performed by Student t-test or 2-way ANOVA followed by Tukey post hoc test. At the end of the 60-day period, SL rats were hyperphagic, obese, hypoinsulinemic, normoglycemic, and had high visceral fat depot and high interleukin (IL)-6 plasma concentration. Obese rats at 90 days of age were fatter, hyperphagic, hyperglycemic, hypertriacylgliceromic, hipoinsulinemic, with low innate immune response. IL-6 production ex vivo was higher, but in plasma it was not different from the control group. FO supplementation brought all biochemical changes to normal values, normalized food intake, and reduced body weight and fat mass in obese rats. The innate immune response was improved but still not as efficient as in lean animals. Our results suggested that as soon MS appears, FO supplementation must be used to ameliorate the morpho- and biochemical effects caused by MS and improve the innate immune response.

The relationship between gastric cancer cells circulating in the blood and microsatellite instability positive gastric carcinomas.

BACKGROUND: Cancers characterized by microsatellite instability may be biologically different from their counterparts with stable microsatellite sequences. Circulating cancers cell present in blood prior to surgery may constitute an adverse prognostic finding. AIM: To correlate these two phenomena with morphological features and survival in advanced gastric cancer. METHODS: We examined 76 cases of resected sporadic, advanced gastric cancer by means of routine morphology and a panel of microsatellite markers. Sixty-six cases were screened for presence of cancer cells circulating in blood prior to the surgery using combined morphological and immunocytochemical approach. RESULTS: Twenty-one (27.6%) cases demonstrated microsatellite instability in at least one locus. Among them 11 (14.5%) showed microsatellite instability in more than 30% (4/12) examined loci, and they were therefore designated as replication error positive (RER+). Circulating cancer cells were detected in 2/19 microsatellite instability and in 11/47 remaining cases (difference not significant). The survival of the microsatellite instability cases was significantly better. The presence of circulating cancer cells did not correlate with survival. CONCLUSION: It is possible that the microsatellite instability status, but not circulating cancer cells, constitutes a prognostic predictive factor in advanced gastric carcinoma. Confirmation of this hypothesis requires continuation of patient follow-up.

A technical note on microsatellite DNA instability studied in archival paraffin-embedded tissues.

The authors present brief overview of problems associated with analysis of microsatellite sequences in DNA from archival paraffin-embedded tissue. This methodology can serve several diagnostic and research purposes provided appropriate precautions are taken to extract DNA of acceptable quality with small admixture of contaminants. Also PCR amplification step requires some modifications compared to routine reactions involving DNA from fresh or freshly-frozen tissues.

A moderate and unspecific release of cysteinyl leukotrienes by aspirin from peripheral blood leucocytes precludes its value for aspirin sensitivity testing in asthma.

Aspirin-induced asthma (AIA) is a clinical syndrome related to cysteinyl leukotriene overproduction in airways. The confirmation of the diagnosis requires inconvenient provocation tests with acetyl salicylic acid (ASA). A study was performed to evaluate whether measurement in vitro of cysteinyl leukotrienes (cys-LTs) release by isolated peripheral blood leucocytes, stimulated with ASA, can be of use for diagnosis of AIA. A cellular allergen stimulation test, CAST, was adapted to measure leukotriene release from leucocytes of 32 aspirin-tolerant and 26 aspirin-intolerant asthmatics. The cells were stimulated with Lys-ASA, N-formyl-methionyl-leucyl-phenylalanine (fMLP), or both fMLP and Lys-ASA, in a buffer containing IL-3, and results compared with human leukaemia cell line (Hl-60) response to Lys-ASA. Cys-LTs were measured in cell supernatant fluids by ELISA. ASA had a rather week stimulatory effect on cys-LTs release in both groups of patients. Contrary to some previous studies, no significant differences were found between cys-LTs release by leucocytes from AIA and ATA, or by differentiated Hl-60 cells. Measurement of cysteinyl-leukotriene release by peripheral blood leucocytes pre-treated with aspirin has no value for diagnosis of AIA.

Differential effects of CGP 37849 and MK-801, competitive and noncompetitive NMDA antagonists, with respect to the modulation of sensorimotor gating and dopamine outflow in the prefrontal cortex of rats.

In the present study we compared effects of the competitive and non-competitive NMDA antagonists CGP 37849 and MK-801, respectively, on sensorimotor gating in rats, measured as prepulse-induced inhibition of the acoustic startle response, and the outflow of dopamine in the rat prefrontal cortex. CGP 37849 (10, 20 mg/kg), decreased the amplitude of the acoustic startle response, but was without effect on the prepulse-induced inhibition of the acoustic startle response. MK-801 (0.4 but not 0.2 mg/kg) enhanced the amplitude of the acoustic startle response and its doses of 0.2 and 0.4 mg/kg markedly attenuated the prepulse-induced inhibition of the acoustic startle response. The effects of MK-801 (0.4 mg/kg) on the prepulse-induced inhibition of the acoustic startle response were not antagonized by the selective antagonists of D-2 and D-1 dopaminergic receptors, S(-)sulpiride (25 mg/kg) and SCH 23390 (0.1 mg/kg), respectively. When given alone, S(-)sulpiride attenuated the amplitude of the acoustic startle response and failed to altered the prepulse-induced inhibition of the acoustic startle response. SCH 23390 (0.1 mg/kg) failed to alter the amplitude and prepulse-induced inhibition of the acoustic startle response. The effects of CGP 37849 and MK-801 also differed with respect to dopamine outflow. MK-801 (0.2 and 0.4 mg/kg) enhanced the outflow of dopamine in the rat prefrontal cortex, while CGP 37849 (10 and 20 mg/kg) was without any effect on the extracellular concentration of dopamine.(ABSTRACT TRUNCATED AT 250 WORDS)

The influence of repeated treatment with imipramine, (+)- and (-)-oxaprotiline on behavioural effects of dopamine D-1 and D-2 agonists.

The paper examined the action of imipramine, (+)- and (-)-oxaprotiline, administered repeatedly to rats, on the behavioural effects of the dopamine D-1 and D-2 agonists, SKF 38393 and quinpirole, respectively. The three antidepressants studied, given in the single dose or repeatedly, attenuate the enhanced grooming evoked by SKF 38393. The locomotor hyperactivity, evoked by quinpirole administered s.c., is increased by repeated but not single-dose treatment with imipramine and (+)-oxaprotiline [but not with (-)-oxaprotiline]. Quinpirole at a low dose produces the locomotor hypoactivity which is attenuated by repeated, but not single-dose, treatment with the anti-depressants studied here. Repeated imipramine and (+)-oxaprotiline [but not (-)-oxaprotiline] increase the locomotor activity effect of quinpirole injected into the nucleus accumbens. The results indicate that the enhanced responsiveness of the dopamine system, observed previously after repeated treatment with antidepressants, may be mediated by the dopamine D-2 receptors.

Functional supersensitivity to the alpha 1-adrenoceptor agonist after repeated treatment with antidepressant drugs is not conditioned by beta-down-regulation.

The effect of repeated administration of desipramine, and the (+)- and (-)-enantiomers of oxaprotiline (10 mg/kg i.p., twice daily for 14 days) on the binding of beta- and alpha 1-adrenoceptors in the cortex of the rat brain were studied. The functional consequences of such treatment were measured in a behavioural model, involving the exploratory activity of rats in response to administration of the alpha 1-agonist phenylephrine. Desipramine and (+)-oxaprotiline decreased the binding of [3H]dihydroalprenolol ([3H]DHA) to beta-adrenoceptors in the cortex, did not change the binding of [3H]prazosin to alpha 1-adrenoceptors, but enhanced behavioural responses to phenylephrine. A behavioural facilitation was also observed after administration of (-)-oxaprotiline, a substance which does not change the binding of [3H]DHA. These results indicate that a functional supersensitivity to the alpha 1-adrenoceptor agonist, after repeated treatment with antidepressants is not conditioned by beta-down-regulation.

Central beta- and alpha-adrenolytic activities of adimolol.

The central adrenergic blocking activity of adimolol (ADL) was studied in rats and mice in the tests which can differentiate beta-, alpha 1-, and alpha 2-adrenolytic effects. Clenbuterol- and salbutamol-induced sedation in rats (open field test) and clenbuterol-induced hyperthermia (at high ambient temperature) were antagonized by low doses of ADL (0.1-1.0 mg/kg ip). ADL (10 mg/kg ip) attenuated the clonidine-induced aggression in mice, and its higher doses (20 and 40 mg/kg ip) depressed the hind limb flexor reflex of the spinal rat and counteracted the stimulatory action of clonidine. ADL at doses from 2.5 to 40 mg/kg ip affected neither the clonidine-induced sedation in rats and mice (locomotor activity, open field test), nor the hyperthermia (at high temperature). The hypothermia (at a room temperature of 21 degrees C) induced by clonidine was partially antagonized. The Ki values for ADL displacement of 3H-dihydroalprenolol and 3H-prazosin binding in the rat cerebral cortex were 1.2 nM and 951 nM respectively. These results indicate that ADL is a potent antagonist of central beta-adrenoceptors and has a weaker alpha 1-adrenolytic action. The central alpha 2-antagonistic effect is either very weak or absent.

Interaction between beta-adrenoceptor agonists and alpha 1-adrenergic system. A behavioral study with the clonidine-induced aggression test.

The effects of beta-adrenoceptor agonists on the clonidine-induced aggression in mice were studied. Clenbuterol (0.05-2 mg/kg ip), salbutamol (5-20 mg/kg ip) and terbutaline (10, 20 mg/kg ip) significantly potentiated the effect of clonidine. The enhancement of clonidine aggressiveness induced by clenbuterol (0.5 mg/kg) was prevented by propranolol (2.5, 5 mg/kg) and reduced by prazosin (1 mg/kg). The obtained results provide evidence that stimulation of beta-adrenoceptors facilitates the alpha 1-adrenoceptor-mediated behavior.