Prediction of early (30-day) and late (30-90-day) mortality after radical cystectomy in a comprehensive cancer centre over two decades.

BACKGROUND: Radical cystectomy (RC) is associated with substantial postoperative mortality. In this study, we analyzed early (30-day; 30 M) and late (30-90-day; 30-90 M) mortality after RC in a Dutch tertiary referral center and determined factors associated with 30 M, 30-90 M and 90-day mortality (90 M). PATIENTS AND METHODS: We identified 823 patients who underwent RC for bladder cancer in the Netherlands Cancer Institute between 1997 and 2017. Predictive factors for mortality were analyzed to identify patients with a higher mortality risk. Multivariate logistic regression analysis was performed to examine the influence of patient, surgical and histopathological variables on 30 M, 30-90 M and 90 M. RESULTS: Thirty-day mortality was 1.9% and 90 M was 6.0%. Multivariable analysis showed that age (OR 1.08, 95% CI 1.01-1.1, p = 0.002) and ASA 3-4 (OR 3.57, 95% CI 1.25-10.16, p = 0.002) were significant predictors of 30 M while higher ASA score (OR 2.9, 95% CI 1.31-6.5, p = 0.009) and higher pathological T stage (OR 8.8, 95% CI 1.9-40.4, p = 0.005) were associated with 30-90 M. Risk of 90 M was increased in patients with ASA 3-4 (OR 2.4, 95% CI 1.2-4.9, p = 0.01), pT3-4 (OR 3.1, 95% CI 1.27-7.57, p = 0.01) and positive LNs (OR 2.5, 95% CI 1.25-4.98, p = 0.009). CONCLUSIONS: Patient-related factors predicted 30 M whereas both patient-related and cancer-related factors predicted 30-90 M. This suggests that patient mix, i.e. patient- vs. cancer-related factors for 30 M and 30-90 M, should be taken into account if mortality rates are to be compared between hospitals.

[Sacral neuromodulation in under- and overactive detrusor-quo vadis? : Principles and developments]. / Sakrale Neuromodulation bei unter- und überaktivem Detrusor ­ quo vadis? : Prinzipien und Entwicklungen.

BACKGROUND: Sacral neuromodulation (SNM) has been used in the treatment of refractory overactive bladder syndrome, nonobstructive urinary retention and faecal incontinence for almost 40 years now. It is not to be confused with the sacral anterior root stimulation which is exclusively used for bladder dysfunction due to spinal paraplegia. MECHANISM OF ACTION: The principles of SNM are yet to be fully understood. Nevertheless, there is proof of modulating the activity of several micturition-associated, afferent neurons in the spine, brainstem and cerebrum. Thus, premature detrusor contractions are suppressed, the desire to void is delayed and detrusor-sphincter coordination improves. TECHNIQUES OF IMPLANTATION AND STIMULATION: Motor reactions are an important indicator of correct electrode placement. The implantation procedure consists of two stages with an initial trial phase to determine the best possible treatment response through an external generator before implanting the whole stimulating device. Yearly check-up examinations are recommended; wireless adjustments allow for long-lasting symptom reduction. INDICATION AND OUTCOME: Success rates in the treatment of the refractory overactive bladder syndrome and the non-obstructive urinary retention lie above 70% and can still be perceived as sufficient after 5 years of ongoing SNM therapy. There is also profound evidence of SNM being an effective option for patients with faecal incontinence or chronic obstipation. CONTRAINDICATIONS AND RISKS: Children, pregnant women and patients in need of frequent MRI examinations are usually not eligible for SNM therapy. Infection of the implant, technical failure (including lead displacement and battery depletion) and pain in the implantation site are important adverse effects which might require surgical revision. CONCLUSIONS: The indications for SNM in the German health care system can be expected to be expanded upon the chronic pelvic pain syndrome, erectile dysfunction and additional gastrointestinal conditions. Technical progress will continue to improve the risk-benefit ratio of SNM.

Influence of physical activity on addiction parameters of rats exposed to amphetamine which were previously supplemented with hydrogenated vegetable fat.

Amphetamine (AMPH) and its derivatives are addictive drugs used to promote and enhance alertness, motivation, willingness, courage and wellbeing. However, their chronic use is related to memory loss, emotional instability, insomnia, psychosis and paranoia. In the last decades, modern society has included processed foods, rich in trans fatty acids (TFA), in their diet, what has been related to several health problems including increased AMPH preference and self-administration. In this scenario, physical activity appears to be useful to attenuate rewarding symptoms related to addictive drugs mainly by affecting brain neuroplasticity and neurotransmission. The current study has been developed to assess the influence of physical activity on addiction parameters of rats exposed to AMPH which were previously supplemented with hydrogenated vegetable fat (HVF), rich in TFA. After six weeks of HVF or soybean oil (SO, control group) supplementation, adult rats were conditioned with d,l-AMPH or vehicle for 14 days. Then, half of each experimental group was submitted to physical activity in treadmill running sessions (60min/day, 5 days/week) for 5 weeks. Animals were re-conditioned with AMPH or vehicle for 3 more days, to observe drug relapse. Locomotor activity and anxiety-like symptoms were observed 24h after the last AMPH reconditioning, and fatty acids composition was quantified in the ventral tegmental area, striatum and prefrontal cortex. All animals showed AMPH preference, but only SO sedentary showed drug relapse. No differences were observed in locomotor activity among groups, while HVF-supplemented group showed decreased exploration per se, and physical activity prevented this. Moreover, AMPH-HVF group showed increased anxiety-like symptoms, which were prevented by physical activity. These results indicate that HVF supplementation modifies AMPH addiction, whereas regular physical activity could be protective against both AMPH and TFA damages.

Role of the adjunctive antimicrobial photodynamic therapy to periodontal treatment at plasmatic oxidative stress and vascular behavior.

BACKGROUND: To evaluate for the first time in vivo the effects of methylene blue (MB) photosensitizer dissolved in ethanol in antimicrobial photodynamic therapy (aPDT) as adjuvant periodontal treatment, at plasmatic oxidative stress and vascular behavior in rat model. METHODS: Wistar rats were divided into negative control (NC, no periodontitis) and positive control (PC, with periodontitis, without any treatment). The other groups had periodontitis and were treated with scaling and root planing (SRP); SRP+aPDT+MB dissolved in water (aPDT I); SRP+aPDT+MB dissolved in ethanol (aPDT II). The periodontitis was induced by ligature at the mandibular right first molar. At 7/15/30days, rats were euthanized, the plasma was used to determine oxidative stress parameters and gingival tissue for histomorphometric analysis. RESULTS: PC showed higher thiobarbituric acid reactive substances levels in 7/15/30days. aPDT II was able to block the lipid peroxidation, especially between 15th and 30th days. Glutathione reduced levels were consumed in PC, aPDT I and II groups throughout the experiment. aPDT II increased the vitamin C levels which were restored in this group in the 30th day. aPDT II group showed the highest number of blood vessels. CONCLUSION: In summary, the aPDT with MB dissolved in ethanol provides better therapeutic responses in periodontitis treatment.

Effect of (+)-dehydrofukinone on GABAA receptors and stress response in fish model.

(+)-Dehydrofukinone (DHF) is a major component of the essential oil of Nectandra grandiflora (Lauraceae), and exerts a depressant effect on the central nervous system of fish. However, the neuronal mechanism underlying DHF action remains unknown. This study aimed to investigate the action of DHF on GABAA receptors using a silver catfish (Rhamdia quelen) model. Additionally, we investigated the effect of DHF exposure on stress-induced cortisol modulation. Chemical identification was performed using gas chromatography-mass spectrometry and purity was evaluated using gas chromatography with a flame ionization detector. To an aquarium, we applied between 2.5 and 50 mg/L DHF diluted in ethanol, in combination with 42.7 mg/L diazepam. DHF within the range of 10-20 mg/L acted collaboratively in combination with diazepam, but the sedative action of DHF was reversed by 3 mg/L flumazenil. Additionally, fish exposed for 24 h to 2.5-20 mg/L DHF showed no side effects and there was sustained sedation during the first 12 h of drug exposure with 10-20 mg/L DHF. DHF pretreatment did not increase plasma cortisol levels in fish subjected to a stress protocol. Moreover, the stress-induced cortisol peak was absent following pretreatment with 20 mg/L DHF. DHF proved to be a relatively safe sedative or anesthetic, which interacts with GABAergic and cortisol pathways in fish.

Effect of (+)-dehydrofukinone on GABAA receptors and stress response in fish model

(+)-Dehydrofukinone (DHF) is a major component of the essential oil of Nectandra grandiflora (Lauraceae), and exerts a depressant effect on the central nervous system of fish. However, the neuronal mechanism underlying DHF action remains unknown. This study aimed to investigate the action of DHF on GABAA receptors using a silver catfish (Rhamdia quelen) model. Additionally, we investigated the effect of DHF exposure on stress-induced cortisol modulation. Chemical identification was performed using gas chromatography-mass spectrometry and purity was evaluated using gas chromatography with a flame ionization detector. To an aquarium, we applied between 2.5 and 50 mg/L DHF diluted in ethanol, in combination with 42.7 mg/L diazepam. DHF within the range of 10-20 mg/L acted collaboratively in combination with diazepam, but the sedative action of DHF was reversed by 3 mg/L flumazenil. Additionally, fish exposed for 24 h to 2.5-20 mg/L DHF showed no side effects and there was sustained sedation during the first 12 h of drug exposure with 10-20 mg/L DHF. DHF pretreatment did not increase plasma cortisol levels in fish subjected to a stress protocol. Moreover, the stress-induced cortisol peak was absent following pretreatment with 20 mg/L DHF. DHF proved to be a relatively safe sedative or anesthetic, which interacts with GABAergic and cortisol pathways in fish.

Impact of perioperative chemotherapy on survival in patients with advanced primary urethral cancer: results of the international collaboration on primary urethral carcinoma.

BACKGROUND: To investigate the impact of perioperative chemo(radio)therapy in advanced primary urethral carcinoma (PUC). PATIENTS AND METHODS: A series of 124 patients (86 men, 38 women) were diagnosed with and underwent surgery for PUC in 10 referral centers between 1993 and 2012. Kaplan-Meier analysis with log-rank testing was used to investigate the impact of perioperative chemo(radio)therapy on overall survival (OS). The median follow-up was 21 months (mean: 32 months; interquartile range: 5-48). RESULTS: Neoadjuvant chemotherapy (NAC), neoadjuvant chemoradiotherapy (N-CRT) plus adjuvant chemotherapy (ACH), and ACH was delivered in 12 (31%), 6 (15%) and 21 (54%) of these patients, respectively. Receipt of NAC/N-CRT was associated with clinically node-positive disease (cN+; P = 0.033) and lower utilization of cystectomy at surgery (P = 0.015). The objective response rate to NAC and N-CRT was 25% and 33%, respectively. The 3-year OS for patients with objective response to neoadjuvant treatment (complete/partial response) was 100% and 58.3% for those with stable or progressive disease (P = 0.30). Of the 26 patients staged ≥cT3 and/or cN+ disease, 16 (62%) received perioperative chemo(radio)therapy and 10 upfront surgery without perioperative chemotherapy (38%). The 3-year OS for this locally advanced subset of patients (≥cT3 and/or cN+) who received NAC (N = 5), N-CRT (N = 3), surgery-only (N = 10) and surgery plus ACH (N = 8) was 100%, 100%, 50% and 20%, respectively (P = 0.016). Among these 26 patients, receipt of neoadjuvant treatment was significantly associated with improved 3-year relapse-free survival (RFS) (P = 0.022) and OS (P = 0.022). Proximal tumor location correlated with inferior 3-year RFS and OS (P = 0.056/0.005). CONCLUSION: In this series, patients who received NAC/N-CRT for cT3 and/or cN+ PUC appeared to demonstrate improved survival compared with those who underwent upfront surgery with or without ACH.

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.

Trans fat supplementation increases UV-radiation-induced oxidative damage on skin of mice.

We evaluated the influence of fish oil (FO, rich in n-3 FA), soybean oil (SO, rich in n-6 FA) and hydrogenated vegetable fat (HVF, rich in trans FA) on the oxidative status and viability of skin cells of mice exposed to ultraviolet radiation (UVR). Mice were supplemented with FO, SO or HVF for three months and exposed to UVR (2.72 mJ/cm(2)) for 2 days. One day after the last UVR session, the FO group showed higher levels of n-3 fatty acids (FA), while the HVF showed higher incorporation of trans FA (TFA) in dorsal skin. UVR increased lipid peroxidation and protein carbonyl levels of the HVF and to a lesser extent of the control and SO groups. Although all irradiated groups showed increased skin thickness, this increase was slighter in FO mice. UVR exposure reduced skin cell viability of the control, SO and HVF groups, while FO prevented this. Catalase activity was reduced independently of the supplementation and SOD level was increased in C and FO groups after UVR exposure; FO prevented the UVR-induced increase in glutathione levels, which was observed in skin of the control, SO and HVF mice. Our results showed the beneficial effects of FO supplementation, as well as the harmful effects of trans FA, whose intensity can increase vulnerability to skin diseases.

[Sacral neuromodulation as second-line treatment strategy for lower urinary tract symptoms of various aetiologies: experience of a German high-volume clinic]. / Sakrale Neuromodulation als Zweitlinien-Therapie bei therapierefraktären irritativen Symptomen des unteren Harntrakts verschiedener Ätiologie: Erfahrungen einer deutschen Anwender-Klinik.

INTRODUCTION: Lower urinary tract symptoms (LUTS) are a common and multiform micturition disorder of various possible origins. Several second-line techniques are available in the event of first-line medicinal treatment failure. These include the intravesical injection of Botulinum toxin, bladder augmentation and sacral neuromodulation (SNM). This study presents current data and results from a prospective study of patients with LUTS of various aetiologies. MATERIAL AND METHODS: Clinical success was investigated for all patients who underwent SNM for LUTS with or without urge incontinence caused by chronic pelvic pain syndrome, multiple sclerosis and idiopathic disease between May 2007 and December 2010. The preoperatively determined symptoms were compared with current follow-up data. Median follow-up time was 11 months (1 - 43). RESULTS: A total of 47 patients were indicated for SNM over the investigated period. 80.9 % were female, median patient age was 67 years (19 - 84). The testing phase was successful in 38 cases (80.9 %) with 9 electrodes being explanted (19.1 %). In the case of idiopathic LUTS we could show a statistically significant increase of micturition volume and reduction of incontinence pad use. There was no statistically significant improvement of any micturition parameter for patients with multiple sclerosis, patients with chronic pelvic pain syndrome showed a statistically significant reduction of micturition frequency and a subjective improvement of symptoms in 75 %. CONCLUSIONS: In the selected patient groups SNM is a promising and, in experienced hands, a low-complication second-line therapy for the treatment of LUTS of idiopathic aetiology. However, the general recommendation of SNM for multiple sclerosis and chronic pelvic pain syndrome patients cannot be given on the basis of our results. Further prospective, randomised multicentre studies are need to further refine the indications for SNM in LUTS of neurogenic and non-neurogenic origins.

Exercise affects memory acquisition, anxiety-like symptoms and activity of membrane-bound enzyme in brain of rats fed with different dietary fats: impairments of trans fat.

Here we evaluated the influence of physical exercise on behavior parameters and enzymatic status of rats supplemented with different dietary fatty acids (FA). Male Wistar rats fed diets enriched with soybean oil (SO), lard (L), or hydrogenated vegetable fat (HVF) for 48 weeks were submitted to swimming (30 min/d, five times per week) for 90 days. Dietary FA per se did not cause anxiety-like symptoms in the animals, but after physical exercise, SO group showed a better behavioral performance than L and the HVF groups in elevated plus maze (EPM). In Barnes maze, HVF group showed impaired memory acquisition as compared to L group, and exercise reversed this effect. SO-fed rats showed an improvement in memory acquisition after 1 day of training, whereas lard caused an improvement of memory only from day 4. HVF-fed rats showed no improvement of memory acquisition, but this effect was reversed by exercise in all training days. A lower activity of the Na(+)K(+)-ATPase in brain cortex of rats fed lard and HVF was observed, and this effect was maintained after exercise. Similarly, the HVF diet was related to lower activity of hippocampal Na(+)K(+)-ATPase, and exercise reduced activity of this enzyme in the SO and L groups. Our findings show influences of dietary FA on memory acquisition, whereas regular exercise improved this function and was beneficial on anxiety-like symptoms. As FA are present in neuronal membrane phospholipids and play a critical role in brain function, our results suggest that low incorporation of trans FA in neuronal membranes may act on cortical and hippocampal Na(+)K(+)-ATPase activity, but this change appears to be unrelated to the behavioral parameters primarily harmed by consumption of trans and less so by saturated FA, which were reversed by exercise.

Oxidative stress and anxiety-like symptoms related to withdrawal of passive cigarette smoke in mice: beneficial effects of pecan nut shells extract, a by-product of the nut industry.

The present study evaluated the role of pecan nut (Carya illinoensis) shells aqueous extract (AE) against oxidative damage induced by cigarette smoke exposure (CSE) and behavioral parameters of smoking withdrawal. Mice were passively exposed to cigarette smoke for 3 weeks (6, 10, and 14 cigarettes/day) and orally treated with AE (25 g/L). CSE induced lipid peroxidation in brain and red blood cells (RBC), increased catalase (CAT) activity in RBC, and decreased plasma ascorbic acid levels. AE prevented oxidative damage and increased antioxidant defenses of mice exposed to cigarette smoke. In addition, AE reduced the locomotor activity and anxiety symptoms induced by smoking withdrawal, and these behavioral parameters showed a positive correlation with RBC lipid peroxidation. Our results showed the beneficial effects of this by-product of the pecan industry, indicating its usefulness in smoking cessation.

Protective effects of a by-product of the pecan nut industry (Carya illinoensis) on the toxicity induced by cyclophosphamide in rats Carya illinoensis protects against cyclophosphamide-induced toxicity.

This study investigated the antioxidant effects of pecan nut (Carya illinoensis) shell aqueous extract (AE) on toxicity induced by cyclophosphamide (CP) in the heart, kidney, liver, bladder, plasma and erythrocytes of rats. Rats were treated with water or pecan shell AE (5%) ad libitum, replacing drinking water for 37 days up to the end of the experiment. On day 30, half of each group received a single administration of vehicle or CP 200 mg/kg-ip. After 7 days, the organs were removed. Rats treated with CP showed an increase in lipid peroxidation (LP) and decrease in reduced glutathione (GSH) levels in all structures. Catalase (CAT) activity was increased in the heart and decreased in liver and kidney. Besides, CP treatment decreased plasmatic vitamin C (VIT C) levels and induced bladder macroscopical and microscopical damages. In contrast, co-treatment with pecan shell AE prevented the LP development and the GSH depletion in all structures, except in the heart and plasma, respectively. CAT activity in the heart and liver as well as the plasmatic VIT C levels remained unchanged. Finally, AE prevented CP-induced bladder injury. These findings revealed the protective role of pecan shell AE in CP-induced multiple organ toxicity.

Ilex paraguariensis has antioxidant potential and attenuates haloperidol-induced orofacial dyskinesia and memory dysfunction in rats.

Tardive dyskinesia (TD) is a syndrome associated with administration of antipsychotics drugs and may be a consequence of a free radical increase. Ilex paraguariensis (IP), rich in polyphenols, is used to prepare a tea-like beverage, the "mate", and has been investigated for its antioxidant action. Here, we examined the aqueous extract of IP on in vitro TBARS production and in vivo study, using two behavioral models, i.e., haloperidol-induced orofacial dyskinesia (evaluated measuring vacuous chewing movements, VCMs) and memory dysfunction, evaluated in a water-maze task. In vitro, we examine different concentrations of IP against the basal, Fe(II) and sodium nitruproside-induced TBARS production in rat brain homogenate. IP extract was able to prevent the basal formation of TBARS (IC50 = 6.6 mg/ml) and TBARS induced by SNP (IC50 = 3.7 mg/ml) and Fe(II) (IC50= 4.8 mg/ml). Haloperidol administration (12 mg/kg/week, im, x4 weeks) increased VCMs (p <0.001). Rats treated with mate (50 g/l, ad libitum, 60 days) did not exhibit the increase in VCMs observed in control rats treated with haloperidol (p <0.001). In the water maze task, haloperidol treated animals displayed an impairment in memory acquisition (p <0.05) compared to rats treated with vehicle. The "mate" prevented the effects of haloperidol in this behavioral paradigm. Our results indicate that IP exhibits an antioxidant role probably related to the presence of polyphenols. The benefit of IP is possibly related to an indirect modulation of oxidative stress.

Accumulation in marine sponge grafts of the mRNA encoding the main proteins of the cell adhesion system.

Specific cell adhesion in the marine sponge Microciona prolifera is mediated by an extracellular aggregation factor complex, whose main protein component, termed MAFp3, is highly polymorphic. We have now identified MAFp4, an approximately 400-kDa protein, from the aggregation factor that is translated from the same mRNA as MAFp3. The existence of multiple potential sites for N-glycosylation and calcium binding suggests a direct involvement of MAFp4 in the species-specific aggregation of sponge cells. The deduced partial polypeptide consists of a 16-fold reiterated motif that shows significant similarity to a repeat in an endoglucanase from the symbiontic bacterium Azorhizobium caulinodans and to the intracellular loop of mammalian Na+-Ca2+ exchangers. Restriction fragment length polymorphism analysis indicated that the genomic variability of MAFp4 is high and comparable to that of MAFp3. Their combined polymorphism correlates with allogeneic responses studied in a population of 23 sponge individuals. Peptide mass fingerprinting of tryptic digests of the polymorphic MAFp3 bands observed on polyacrylamide gels after chemical deglycosylation of the Microciona aggregation factor revealed that the variability detected on Southern blots at least partially reflects the individual variability of aggregation factor protein components. Polyclonal antibodies raised against MAFp3 strongly cross-reacted with a 68-kDa protein localized in sponge cell membranes. Immunohistochemical use of the anti-MAFp3 antibodies strongly stained a cell layer along the line of contact in allogeneic grafts. We show that the transcription level of the MAFp3/MAFp4 mRNA in sponge allo- and isografts is clearly increased in comparison with non-grafted tissue. These data are discussed with respect to a possible evolutionary relationship between cell adhesion and histocompatibility systems.

A 35-kDa protein is the basic unit of the core from the 2 x 10(4)-kDa aggregation factor responsible for species-specific cell adhesion in the marine sponge Microciona prolifera.

Dissociated sponge cells quickly reaggregate in a species-specific manner, differentiate, and reconstruct tissue, providing a very handy system to investigate the molecular basis of more complex intercellular recognition processes. Species-specific cell adhesion in the marine sponge Microciona prolifera is mediated by a supramolecular complex with a Mr = 2 x 10(7), termed aggregation factor. Guanidinium hydrochloride/cesium chloride dissociative gradients and rhodamine B isothiocyanate staining indicated the presence of several proteins with different degrees of glycosylation. Hyaluronate has been found to be associated with the aggregation factor. Chemical deglycosylation revealed a main component accounting for nearly 90% of the total protein. The cDNA-deduced amino acid sequence predicts a 35-kDa protein (MAFp3), the first sponge aggregation factor core protein ever described. The open reading frame is uninterrupted upstream from the amino terminus of the mature protein, and the deduced amino acid sequence for this region has been found to contain a long stretch sharing homology with the Na+-Ca2+ exchanger protein. A putative hyaluronic acid binding domain and several putative N- and O-glycosylation signals are present in MAFp3, as well as eight cysteines, some of them involved in intermolecular disulfide bridges. Northern blot data suggest variable expression, and Southern blot analysis reveals the presence of other related gene sequences. According to the respective molecular masses, one aggregation factor molecule would contain about 300 MAFp3 units, suggesting that sponge cell adhesion might be based on the assembly of multiple small glycosylated protein subunits.