26 research outputs found
Influence of S-adenosyl-L-methionine on chronic mild stress-induced anhedonia in castrated rats
No full text1 S-adenosyl-L-methionine (SAMe) is the most important methyl donor in the brain and is essential for polyamine synthesis. Methyl group deficiency in the brain has been implicated in depression; on the other hand, polyamines enhance phosphorylation processes, and phosphorylation of functional proteins in neurons is involved in the therapeutic mechanisms of antidepressants. 2 The effect of SAMe in an animal model of 'depression', the chronic mild stress-induced anhedonia, was studied using long-term castrated male and female Lister hooded rats. 3 Chronic daily exposure to an unpredictable sequence of mild stressors produced, within 3 weeks, a significant reduction of the consumption of a sucrose solution. SAMe (100, 200 or 300 mg kg(-1) daily i.m.) while having no influence on sucrose intake in non-stressed animals, dose-dependently reinstated sucrose consumption within the first week of treatment, both in male and in female stressed rats. Imipramine (10 mg kg(-1) daily i.p.) produced a similar effect after a 3 week treatment. 4 Similarly, a palatable food reward-induced place preference conditioning was developed in SAMe (200 or 300 mg kg(-1) daily i.m.)- and in imipramine (10 mg kg(-1) daily i.p.)-treated chronically stressed animals (males and females), whilst it could not be obtained in vehicle-treated rats. 5 Moreover, the same doses of SAMe (but not of imipramine) restored the exploratory activity and curiosity for the environment (rearing), in the open-field test. 6 While imipramine caused a blockade of the growth throughout the treatment, SAMe produced only a transient growth arrest during the first week of treatment. 7 These results show that SAMe reverses an experimental condition of 'depression-like' behaviour in rats, the effect being more rapid and complete than that of imipramine, and without apparent side effects
Characterization of Walnut Oil and Evaluation of Its Neuroprotective Effects in an In Vitro Model of Parkinson’s Disease
No full textParkinson’s disease (PD) is a common neurodegenerative disorder marked by the degeneration of dopaminergic neurons and the buildup of α-synuclein aggregates. The current treatments focus on symptom relief, with no drugs available to halt disease progression. This has prompted interest in plant-based extracts as alternative therapies. This study examines the neuroprotective and antioxidant effects of walnut oil (WO), extracted from Juglans regia L., in an in vitro PD model using the neurotoxin rotenone (ROT). WO, rich in polyunsaturated fatty acids (PUFAs), including linoleic acid (LA) and α-linolenic acid (ALA), together with minor bioactive components, is known for its neuroprotective properties. Using human HMC3 microglial and SH-SY5Y neuroblastoma cells, we tested WO’s effects on ROT-induced toxicity. The experiments were performed at different time points. The results showed that the co-administration of WO with ROT significantly improved cell viability and reduced reactive oxygen species (ROS) levels. Additionally, conditioned media from WO-treated HMC3 cells enhanced SH-SY5Y cell survival, indicating positive microglia–neuron interactions. Cell viability appeared to be concentration- and time-dependent. These findings highlight WO’s potential, mainly due to its PUFA content, as a promising candidate for preventing neurodegenerative diseases like PD; they underscore the potential of WO content in food for the prevention of neurodegenerative diseases such as PD
Influence of SAMe on the modifications of brain poliamine levels in an animal model of depression
No full textThe mechanism(s) of the antidepressant activity of S-adenosyl-L-methionine (SAMe) have not yet been elucidated. SAMe is essential for the synthesis of polyamines, which have a key role in protein synthesis, cell proliferation, and neuronal plasticity. On the other hand, accumulating data indicate that depression is associated with a reduction in regional brain volume and that antidepressants increase neurogenesis in defined brain regions and also influence neuronal plasticity. Here we show that in a validated rat model of depression (chronic unpredictable mild stress-induced anhedonia) there is a significant reduction of putrescine, spermidine and spermine in the hippocampus, and of only putrescine in the nucleus accumbens septi. SAMe, at a fully antidepressant dose (300 mg/kg i.m., daily for 7 days), completely restores the levels of putrescine in the nucleus accumbens, and restores in part the levels of both spermidine and spermine in the hippocampus. These results may suggest (i) a role for brain polyamines in depression and in reward processes, and (ii) that the antidepressant effect of SAMe may be due, at least in part, to a normalization of putrescine levels in the nucleus accumbens septi
Single center experience with the Sorin Bicarbon prosthesis. A 17-year follow-up
No full textObjective: To evaluate the long-term results of aortic valve replacement (AVR) and mitral valve replacement
(MVR) with the Sorin Bicarbon prosthesis (SBP).
Methods: Five hundred seven patients (306 men, 201 women), mean age 62 10 years (range, 21-86 years),
received an SBP between 1994 and 2000; AVR was performed in 344 (67%) and MVR in 163 (33%). The main
concomitant procedure was coronary artery grafting in 79 patients (16%). Follow-up was 99%complete; mean
follow-up was 12.7 4.0 years with a cumulative duration of follow-up of 6475 patient-years in the entire group
(4348 patient-years for AVR and 2124 patient-years for MVR).
Results: Hospital mortality was 2.7% (AVR, 2.03%; MVR, 4.3%). There were 169 late deaths (AVR, 128;
MVR, 41). Actuarial survival at 17 years is 49.7% 5.3% for AVR and 62.0% 6.1% for MVR. At the
last follow-up, 310 survivors (199 AVR, 111 MVR) are in New York Heart Association functional class I or
II. At 17 years, actuarial freedom from valve-related deaths, embolism, and bleeding is 89.8% 4.8%,
85.8% 5.4%, and 96.2% 1.2% after AVR, and 91.9% 3.9%, 96.3% 1.8%, 95.0% 2.9% after
MVR. Reoperation was required in 5 patients with AVR (thrombosis in 4 and perivalvular leak in 1). Actuarial
freedom from reoperation is 98.1% 0.8% after AVR and 100% after MVR; freedom from endocarditis is
100% after AVR and 99.2% 0.7% after MVR. No cases of intrinsic structural valve failure were observed.
Conclusions: The SBP has shown excellent results in terms of clinical improvement and freedom from
valve-related complications, even up to 17 years after AVR and MVR. It therefore seems to be a safe option
whenever a mechanical prosthesis is needed. (J Thorac Cardiovasc Surg 2014;148:2039-44
Single center experience with the Sorin Bicarbon prosthesis: A 17-year clinical follow-up
No full textObjectiveTo evaluate the long-term results of aortic valve replacement (AVR) and mitral valve replacement (MVR) with the Sorin Bicarbon prosthesis (SBP).MethodsFive hundred seven patients (306 men, 201 women), mean age 62 ± 10 years (range, 21-86 years), received an SBP between 1994 and 2000; AVR was performed in 344 (67%) and MVR in 163 (33%). The main concomitant procedure was coronary artery grafting in 79 patients (16%). Follow-up was 99% complete; mean follow-up was 12.7 ± 4.0 years with a cumulative duration of follow-up of 6475 patient-years in the entire group (4348 patient-years for AVR and 2124 patient-years for MVR).ResultsHospital mortality was 2.7% (AVR, 2.03%; MVR, 4.3%). There were 169 late deaths (AVR, 128; MVR, 41). Actuarial survival at 17 years is 49.7% ± 5.3% for AVR and 62.0% ± 6.1% for MVR. At the last follow-up, 310 survivors (199 AVR, 111 MVR) are in New York Heart Association functional class I or II. At 17 years, actuarial freedom from valve-related deaths, embolism, and bleeding is 89.8% ± 4.8%, 85.8% ± 5.4%, and 96.2% ± 1.2% after AVR, and 91.9% ± 3.9%, 96.3% ± 1.8%, 95.0% ± 2.9% after MVR. Reoperation was required in 5 patients with AVR (thrombosis in 4 and perivalvular leak in 1). Actuarial freedom from reoperation is 98.1% ± 0.8% after AVR and 100% after MVR; freedom from endocarditis is 100% after AVR and 99.2% ± 0.7% after MVR. No cases of intrinsic structural valve failure were observed.ConclusionsThe SBP has shown excellent results in terms of clinical improvement and freedom from valve-related complications, even up to 17 years after AVR and MVR. It therefore seems to be a safe option whenever a mechanical prosthesis is needed
Influence of f-MLP, ACTH(1-24) and CRH on in vitro chemotaxis of monocytes from centenarians
No full textOBJECTIVE: The lifelong exposure to a variety of stressors activates a plethora of defense mechanisms, including the hypothalamic-pituitary-adrenal axis which releases neuropeptides affecting the immune responses. Here, we report data on the capability of monocytes from young subjects and centenarians to migrate towards chemotactic stimuli (formyl-methionyl-leucyl-phenylalanine, f-MLP; adrenocorticotropic hormone, ACTH, and corticotrophin-releasing hormone, CRH). Plasma levels of ACTH, CRH and cortisol were measured as an index of ongoing stress response. METHODS: Monocyte chemotaxis towards f-MLP (10(-8)M), ACTH(1-24) (10(-14) and 10(-8)M) and CRH (10(-14) and 10(-8)M) was evaluated in vitro in young subjects (n = 8, age range 25-35 years) and centenarians (n = 9, age >100 years) and expressed as chemotactic index. In 9 young subjects and 6 centenarians, plasma levels of cortisol, ACTH and CRH were measured. RESULTS: Monocyte chemotaxis towards f-MLP, ACTH(1-24) and CRH (10(-8)M) was well preserved in centenarians, except when the lowest concentration of CRH was used. CRH, ACTH and cortisol plasma levels were significantly higher in centenarians than in young subjects. CONCLUSIONS: The capability of monocytes from centenarians to respond to chemotactic neuropeptides is well preserved. The decreased responsiveness to the lowest concentration of CRH might be due to downregulation of CRH receptors or to defects in the intracellular signal transduction pathway. The high plasma levels of cortisol, CRH and ACTH in centenarians indicate an activation of the entire stress axis, likely counteracting the systemic inflammatory process occurring with age. This activation fits with the hypothesis that lifelong low-intensity stressors activate ancient, hormetic defense mechanisms, favoring healthy aging and longevity
Influence of f-MLP, ACTH(1-24) and CRH on in vitro chemotaxis of monocytes from centenarians.
No full textDisclosing the Antioxidant and Neuroprotective Activity of an Anthocyanin-Rich Extract from Sweet Cherry (Prunus avium L.) Using In Vitro and In Vivo Models
No full textIn this study, an autochthonous variety of sweet cherry (Prunus avium L.), namely “Moretta di Vignola”, was processed to prepare extracts rich in polyphenols, which were characterized by high-performance liquid chromatography (HPLC) separation coupled to UV/DAD and ESI-MSn analysis. Then, a sweet cherry anthocyanin-rich extract (ACE) was prepared, fully characterized and tested for its activity against Parkinson’s disease (PD) in cellular (BV2 microglia and SH-SY5Y neuroblastoma) and in Drosophila melanogaster rotenone (ROT)-induced model. The extract was also evaluated for its antioxidant activity on Caenorhabditis elegans by assessing nematode resistance to thermal stress. In both cell lines, ACE reduced ROT-induced cell death and it decreased, alone, cellular reactive oxygen species (ROS) content while reinstating control-like ROS values after ROT-induced ROS rise, albeit at different concentrations of both compounds. Moreover, ACE mitigated SH-SY5Y cell cytotoxicity in a non-contact co-culture assay with cell-free supernatants from ROT-treated BV-2 cells. ACE, at 50 μg/mL, ameliorated ROT (250 μM)-provoked spontaneous (24 h duration) and induced (after 3 and 7 days) locomotor activity impairment in D. melanogaster and it also increased survival and counteracted the decrease in fly lifespan registered after exposure to the ROT. Moreover, heads from flies treated with ACE showed a non-significant decrease in ROS levels, while those exposed to ROT markedly increased ROS levels if compared to controls. ACE + ROT significantly placed the ROS content to intermediate values between those of controls and ROT alone. Finally, ACE at 25 μg/mL produced a significant increase in the survival rate of nematodes submitted to thermal stress (35 °C, 6–8 h), at the 2nd and 9th day of adulthood. All in all, ACE from Moretta cherries can be an attractive candidate to formulate a nutraceutical product to be used for the prevention of oxidative stress-induced disorders and related neurodegenerative diseases
Live-cell imaging and in vitro assays study of macrophage phagocytosis of mineral fibers
No full textThe interaction between inhaled mineral fibres and alveolar macrophage provokes many adverse effects including cell damage. The mechanisms by which macrophage phagocytosis of mineral fibres exert cytotoxic activity are not fully understood. Our work focuses on the monitoring of the early steps of the interaction between chrysotile, crocidolite and erionite fibres and M0-THP-1 macrophages (8 h of exposure to 25 μg/mL of fibres) using time-lapse video microscopy (TLM) coupled with in vitro assays. TLM movies showed that macrophages easily phagocytose erionite fibres (mean L<10 μm) while numerous chrysotile and crocidolite fibres are partially phagocytosed due to their extreme length (mean L> 10 μm). The cytotoxic action of fibrous erionite occurs rapidly (2 h) while that of asbestos increases gradually. Asbestos fibres trigger significant apoptotic phenomena while fibrous erionite is associated with a necrotic-like effect. Asbestos toxicity is linked to their ability to stimulate production of Reactive Oxygen Species (ROS). ROS are generated by iron on the fibre surface (primary) or by M0-THP-1 cells as a result of frustrated phagocytosis induced by the long asbestos fibres (secondary). An alternative mechanism by which fibrous erionite can induce cytotoxicity may occur during phagocytosis due to the absorption of ions present in the cytosol of cells leading to dysregulation of ion homeostasis, swelling and cell lysis. At the same time, engulfed erionite fibres can reduce the level of cytosolic Ca2+ and interfere with endoplasmic reticulum-mitochondria crosstalk causing failure of M0-THP-1 cells apoptosis
Studies on the effects of homocysteine (hcy) and Aβ peptides on human glioma cells
No full textStudies on the effects of homocysteine (hcy) and Aβ peptides on human glioma cell
