Trans-fat supplementation over two generations of rats exacerbates behavioral and biochemical damages in a model of mania: Co-treatment with lithium.

AIMS: We investigated whether trans-fat supplemented over two generations of rats could alter neuronal membranes and influence mania-like behaviors, as well as the effects of lithium (Li). MAIN METHODS: Two generations of female rats were supplemented with soybean oil (SO-C, rich in n-6 fatty acids - FA) or hydrogenated vegetable fat (HVF, rich in trans-fatty acids - TFA). Male rats born from the 1st and 2nd generations were maintained in the same supplementation until adulthood, when they were exposed to an amphetamine (AMPH)-induced model of mania and co-treated with Li or not. KEY FINDINGS: AMPH increased locomotion of both generations and this influence was higher in the HVF than in the SO-C group. Conversely, AMPH increased long-term memory in SO-C group of the 2nd generation. HVF supplementation allowed hippocampal TFA incorporation in rats of both generations (0.1 and 0.2%, respectively). Oxidative parameters indicated higher levels of protein carbonyl (PC) in the HVF group with no changes in catalase (CAT) activity in the 1st generation. In the 2nd generation, AMPH increased PC levels of both experimental groups, whereas CAT activity was lower per se in the HVF group only. The co-treatment with Li leveled out all behavioral parameters, PC levels and CAT activity indicating a significant neuroprotective role. SIGNIFICANCE: These findings suggest that chronic HVF consumption allows a rising incorporation of TFA in the brain, which may be reflected on the neuropsychiatric conditions related to mania, whereas the effects of Li are not modified in the course of this harmful dietary habit.

Chronic consumption of trans fat can facilitate the development of hyperactive behavior in rats.

In recent decades, the increased consumption of processed foods, which are rich in hydrogenated vegetable fat (HVF), has led to a decreased consumption of fish and oilseed, rich in omega-3 fatty acids. This eating habit provides an increased intake of trans fatty acids (TFA), which may be related to neuropsychiatric conditions, including inattention and hyperactivity. In this study, we evaluated the potential connection between prolonged trans fat consumption and development of hyperactivity-like symptoms in rats using different behavioral paradigms. Trans fat intake for 10 months (Experiment 1), as well as during pregnancy and lactation across two sequential generations of rats, (Experiment 4) induced active coping in the forced swimming task (FST). In addition, HVF supplementation was associated with increased locomotion before and after amphetamine (AMPH) administration (Experiment 2). Similarly, HVF supplementation during pregnancy and lactation were associated with increased locomotion in both young and adult rats (Experiment 3). Furthermore, trans fat intake across two sequential generations increased locomotor and exploratory activities following stressors (Experiment 4). From these results, we suggest that chronic consumption of trans fat is able to enhance impulsiveness and reactivity to novelty, facilitating hyperactive behaviors.

Cross-generational trans fat intake facilitates mania-like behavior: oxidative and molecular markers in brain cortex.

Since that fast food consumption have raised concerns about people's health, we evaluated the influence of trans fat consumption on behavioral, biochemical and molecular changes in the brain-cortex of second generation rats exposed to a model of mania. Two successive generations of female rats were supplemented with soybean oil (SO, rich in n-6 FA, control group), fish oil (FO, rich in n-3 FA) and hydrogenated vegetable fat (HVF, rich in trans FA) from pregnancy, lactation to adulthood, when male rats from 2nd generation received amphetamine (AMPH-4 mg/kg-i.p., once a day, for 14 days) treatment. AMPH increased locomotor index in all animals, which was higher in the HVF group. While the FO group showed increased n-3 polyunsaturated fatty acid (PUFA) incorporation and reduced n-6/n-3 PUFA ratio, HVF allowed trans fatty acid (TFA) incorporation and increased n-6/n-3 PUFA ratio in the brain-cortex. In fact, the FO group showed minor AMPH-induced hyperactivity, decreased reactive species (RS) generation per se, causing no changes in protein carbonyl (PC) levels and dopamine transporter (DAT). FO supplementation showed molecular changes, since proBDNF was increased per se and reduced by AMPH, decreasing the brain-derived neurotrophic factor (BDNF) level following drug treatment. Conversely, HVF was related to increased hyperactivity, higher PC level per se and higher AMPH-induced PC level, reflecting on DAT, whose levels were decreased per se as well as in AMPH-treated groups. In addition, while HVF increased BDNF-mRNA per se, AMPH reduced this value, acting on BDNF, whose level was lower in the same AMPH-treated experimental group. ProBDNF level was influenced by HVF supplementation, but it was not sufficient to modify BDNF level. These findings reinforce that prolonged consumption of trans fat allows TFA incorporation in the cortex, facilitating hyperactive behavior, oxidative damages and molecular changes. Our study is a warning about cross-generational consumption of processed food, since high trans fat may facilitate the development of neuropsychiatric conditions, including bipolar disorder (BD).

Cross-generational trans fat intake exacerbates UV radiation-induced damage in rat skin.

We evaluated the influence of dietary fats on ultraviolet radiation (UVR)-induced oxidative damage in skin of rats. Animals from two consecutive generations born of dams supplemented with fats during pregnancy and breastfeeding were maintained in the same supplementation: soybean-oil (SO, rich in n-6 FA, control group), fish-oil (FO, rich in n-3 FA) or hydrogenated-vegetable-fat (HVF, rich in TFA). At 90 days of age, half the animals from the 2nd generation were exposed to UVR (0.25 J/cm(2)) 3×/week for 12 weeks. The FO group presented higher incorporation of n-3 FA in dorsal skin, while the HVF group incorporated TFA. Biochemical changes per se were observed in skin of the HVF group: greater generation of reactive oxygen species (ROS), lower mitochondrial integrity and increased Na(+)K(+)-ATPase activity. UVR exposure increased skin wrinkles scores and ROS generation and decreased mitochondrial integrity and reduced-glutathione levels in the HVF group. In FO, UVR exposure was associated with smaller skin thickness and reduced levels of protein-carbonyl, together with increased catalase activity and preserved Na(+)K(+)-ATPase function. In conclusion, while FO may be protective, trans fat may be harmful to skin health by making it more vulnerable to UVR injury and thus more prone to develop photoaging and skin cancer.

Influence of lifelong dietary fats on the brain fatty acids and amphetamine-induced behavioral responses in adult rat.

The influence of dietary fatty acids (FA) on mania-like behavior and brain oxidative damage were evaluated in rats. First generation of rats born and maintained under supplementation with soybean-oil (SO), fish-oil (FO) or hydrogenated-vegetable-fat (HVF), which are rich in n-6, n-3 and trans (TFA) FA, respectively, until adulthood, were exposed to an amphetamine (AMPH)-induced mania animal model to behavioral and biochemical evaluations. While AMPH caused hyperlocomotion in HVF and, to a less extent, in SO- and FO-groups, a better memory performance was observed in FO group. Among vehicle-groups, HVF increased reactive species (RS) generation and protein-carbonyl (PC) levels in cortex; FO reduced RS generation in hippocampus and decreased PC levels in hippocampus and striatum. Among AMPH-treated animals, HVF exacerbated RS generation in all evaluated brain areas and increased PC levels in cortex and striatum; FO reduced RS generation in hippocampus and decreased PC levels in hippocampus and striatum. FO was related to higher percentage of polyunsaturated fatty acids (PUFA) and docosahexaenoic acid (DHA) in cortex and striatum, while HVF was associated to higher incorporation of TFA in cortex, hippocampus and striatum, besides increased n-6/n-3 FA ratio in striatum. While a continuous exposure to TFA may intensify oxidative events in brain, a prolonged FO consumption may prevent mania-like-behavior; enhance memory besides decreasing brain oxidative markers. A substantial inclusion of processed foods, instead of foods rich in omega-3, in the long term is able to influence the functionality of brain structures related to behavioral disturbances and weaker neuroprotection, whose impact should be considered by food safety authorities and psychiatry experts.

[Balloon dacryocystoplasty: interventional radiological therapy of congenital dacryostenosis]. / Ballondakryozystoplastie: Interventionell-radiologische Therapie konnataler Dakryostenosen.

PURPOSE: To evaluate the results of balloon dacryocystoplasty in the treatment of complicated development of connatal obstructed nasolacrimal duct system. MATERIALS AND METHODS: Dacryocystography under general anaesthesia was performed on 46 children with epiphora from birth and recurrent infection of the nasolacrimal duct system. 54 nasolacrimal ducts (8 children bilaterally) were treated with balloon catheter dilatation and antibiotic irrigation of the nasolacrimal sac. In all cases previous conservative treatment with eye drops and superficial massage of the lacrimal sac had failed. 11 children without clinical improvement were irrigated before catheter dilatation by an ophthalmologist. The ages ranged from 6 weeks to 7.5 years (mean 23.5 months). 39 dilatations were carried out as an out-patient procedure. The clinical results were confirmed by a questionnaire filled in by the parents. RESULTS: 15 incomplete obstructions and 39 occlusions of the Hasner valve (n = 45) or of the nasolacrimal duct system (n = 9) were demonstrated with dacryocystography. Dilatation with a 2.5 mm ballon was successfully performed in all cases and the mean radiation time was 2.1 minutes. No relevant complications occurred. The mean follow up time was 18.4 months (3 - 41 months). 39 of 46 children showed no symptoms, 6 children seldomly experienced onset of epiphora. The symptoms did not improve in only one child. The cumulative clinical success rate is 98 %. CONCLUSION: Following diagnostic dacryocystography, balloon catheter dilatation is a low risk and very successful treatment of complicated connatal obstructed nasolacrimal duct system.

Cefotaxime acts synergistically with levofloxacin in experimental meningitis due to penicillin-resistant pneumococci and prevents selection of levofloxacin-resistant mutants in vitro.

Cefotaxime, given in two doses (each 100 mg/kg of body weight), produced a good bactericidal activity (-0.47 Deltalog(10) CFU/ml. h) which was comparable to that of levofloxacin (-0.49 Deltalog(10) CFU/ml. h) against a penicillin-resistant pneumococcal strain WB4 in experimental meningitis. Cefotaxime combined with levofloxacin acted synergistically (-1.04 Deltalog(10) CFU/ml. h). Synergy between cefotaxime and levofloxacin was also demonstrated in vitro in time killing assays and with the checkerboard method for two penicillin-resistant strains (WB4 and KR4). Using in vitro cycling experiments, the addition of cefotaxime in sub-MIC concentrations (one-eighth of the MIC) drastically reduced levofloxacin-induced resistance in the same two strains (64-fold increase of the MIC of levofloxacin after 12 cycles versus 2-fold increase of the MIC of levofloxacin combined with cefotaxime). Mutations detected in the genes encoding topoisomerase IV (parC and parE) and gyrase (gyrA and gyrB) confirmed the levofloxacin-induced resistance in both strains. Addition of cefotaxime in low doses was able to suppress levofloxacin-induced resistance.

Quantitative determination and structure elucidation of type A- and B-trichothecenes by HPLC/ion trap multiple mass spectrometry.

A method is presented for the quantification and structure confirmation of trichothecenes in wheat by high-performance liquid chromatography combined with multiple mass spectrometry (MS(n)()). Nine type A- and B-trichothecenes were determined (nivalenol, deoxynivalenol, fusarenon-X, 3-acetyldeoxynivalenol, 15-acetyldeoxynivalenol, neosolaniol, diacetoxyscirpenol, HT-2 toxin, and T-2 toxin). Extraction was carried out with acetonitrile/water. The extract was purified on a MycoSep column. Quantification was based on an internal standard and atmospheric pressure chemical ionization in the positive ion mode. Recoveries from spiked wheat were in the range of 80-106% at levels of 500 ppb. The limits of quantification for the whole method were between 10 and 100 ppb. Ion adduct formation with ammonium and acetate ions and MS(n) experiments provided information about substitution and fragmentation behavior of the mycotoxins. A scheme has been established for the partial structure elucidation of type A- and B-trichothecenes in fungal cultures.

The continuous-injection technique to reduce complications during retrobulbar anesthesia.

Retrobulbar as well as peribulbar anesthesia remain relatively risky procedures; retrobulbar hemorrhage and especially globe penetration or perforation can have blinding consequences. Our continuous-injection-technique greatly reduces these risks whether used for retrobulbar or peribulbar anesthesia. If the ophthalmologist starts injecting the agent while advancing the needle, the fluid pushes tissues away, possibly preventing a hemorrhage. Since resistance against the plunger is instantaneously experienced if the needle impacts the sclera, the ophthalmologist is adequately warned before actual perforation of the sclera occurs.

Capsaicin's effect on rat nasal mucosa substance P release: experimental basis for vasomotor rhinitis treatment.

Substance P (SP) is one of several neuropeptides found in nasal mucosa. It exists primarily in sensory afferent neurons, which are best demonstrated by immunohistochemical staining. These substance P-like immunoreactive (SPLI) nerve fibers are unmyelinated C fibers, which connect to the trigeminal ganglion and the spinal trigeminal nucleus. They are found around vessels and seromucinous glands in the submucosa. When the nasal mucosa receives a noxious stimulus, SP is released and acts orthodromically as a comediator of nasal pain, while antidromically it induces vasodilatation, plasma extravasation, mucosal edema, and rhinorrhea. Its antidromic effects have been implicated in vasomotor rhinitis and can be blocked by topical intranasal capsaicin application. Wolf and others have demonstrated in human subjects that vasomotor rhinitis can be blocked up to 1 year by a series of intranasal capsaicin applications. It has not yet been demonstrated that nasal mucous SP levels following noxious nasal stimulus change after intranasal capsaicin pretreatment. Consequently a project was designed to determine whether intranasal capsaicin pretreatment would affect nasal substance P release measured in nasal secretion. Nasal secretion SP levels were measured before and after noxious nasal stimulus in controls and in capsaicin pretreated rats. The difference in measured nasal secretion SP levels were significant (p < 0.05).

Intraarterial 5-FU-infusion and simultaneous radiotherapy as palliative treatment of recurrent rectal cancer.

Palliative treatment of recurrent rectal cancer remains to be a challenge. From 1989 to 1991 13 patients with recurrent rectal cancer were treated with intraarterial infusion of 5-Fluorouracil and simultaneous radiotherapy in a palliative intent. Seven patients had received postoperative adjuvant radiotherapy with 56 to 60 Gy. Three patients had been treated with systemic chemotherapy. Radiotherapy of the recurrence was performed with 19.8 to 30.6 Gy in the pre-irradiated patients and with 50.4 to 59.4 Gy in the others. One complete remission, three partial remissions and nine minor responses were observed. Three patients had complete pain relief after the treatment, in the remaining patients major pain reduction was achieved. Palliation lasted from three to twelve months (median: five months). Our results indicate that locoregional chemo- and radiotherapy are a effective modality in recurrent rectal cancer.

Antiemotional and anticonvulsant activity of brotizolam and its effects on motor performance in animals.

Brotizolam (2-bromo-4-(2-chlorophenyl)-9-methyl-6H-thieno[3,2-f]-1,2,4-triazolo [4,3-a]-1,4-diazepine, We 941, Lendormin) is a thienotriazolo diazepine with predominantly sleep-inducing properties. Additionally, brotizolam, attenuated conflict behavior in rats and inhibited aggressive behavior in mice and cats. Brotizolam prevented audiogenic seizures in mice, seizures provoked by electroshock in rats and inhibited convulsions elicited by electrical stimulation in the limbic system of cats. Furthermore, brotizolam antagonized seizures induced by the convulsant drugs pentetrazol, bicuculline and strychnine in mice. Motocoordination was not impaired within the effective dose range. Muscle relaxant effects appeared at higher doses only. The onset of effect of brotizolam occurred in the different experiments within 15-30 min, thus indicating a fast enteral absorption and penetration of the blood-brain barrier. The duration of action within the therapeutic dose range was between 2-6 h. The effect of brotizolam was compared with other diazepine derivatives. Brotizolam was more active than diazepam, nitrazepam, estazolam, flurazepam and clonazepam and nearly as active as triazolam.

Cromolyn sodium nasal solution in the prophylactic treatment of pollen-induced seasonal allergic rhinitis.

A large-scale multicenter investigation was undertaken in 3 cities with comparable pollen seasons and atmospheric pollen concentrations in order to obtain more definite information about the safety and efficacy of cromolyn sodium in the treatment of pollen-induced seasonal rhinitis. The 9-wk double-blind study was conducted in 104 patiets in Pittsburgh, Pa., Cleveland, Ohio, and Louisville, Ky., during the 1975 ragweed season. It indicated that a nebulized 4% aqueous solution of cromolyn sodium is effective in reducing sneezing, rhinorrhea, nasal congestion, and ocular irritation in ragweed hay fever patients. The efficacy of the drug was notable despite the fact that patients used an average of 52 mg instead of the recommended 62.4 mg daily. Cromolyn sodium did not appear to have a significant effect on transseasonal antiragweed IgE (IgEAR) levels. Patients acceptance of the cromolyn nasal solution was good, and there were no significant adverse reactions. The side effects, which were distributed equally between the drug and placebo groups, were mild and of limited duration.