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- Berg, Staffan, et al.
(författare)
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Impact of Intestinal Concentration and Colloidal Structure on the Permeation-Enhancing Efficiency of Sodium Caprate in the Rat
- 2022
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Ingår i: Molecular Pharmaceutics. - : American Chemical Society (ACS). - 1543-8384 .- 1543-8392. ; 19:1, s. 200-212
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Tidskriftsartikel (refereegranskat)abstract
- In this work, we set out to better understand how the permeation enhancer sodium caprate (C10) influences the intestinal absorption of macromolecules. FITC-dextran 4000 (FD4) was selected as a model compound and formulated with 50-300 mM C10. Absorption was studied after bolus instillation of liquid formulation to the duodenum of anesthetized rats and intravenously as a reference, whereafter plasma samples were taken and analyzed for FD4 content. It was found that the AUC and C-max of FD4 increased with increasing C10 concentration. Higher C10 concentrations were associated with an increased and extended absorption but also increased epithelial damage. Depending on the C10 concentration, the intestinal epithelium showed significant recovery already at 60-120 min after administration. At the highest studied C10 concentrations (100 and 300 mM), the absorption of FD4 was not affected by the colloidal structures of C10, with similar absorption obtained when C10 was administered as micelles (pH 8.5) and as vesicles (pH 6.5). In contrast, the FD4 absorption was lower when C10 was administered at 50 mM formulated as micelles as compared to vesicles. Intestinal dilution of C10 and FD4 revealed a trend of decreasing FD4 absorption with increasing intestinal dilution. However, the effect was smaller than that of altering the total administered C10 dose. Absorption was similar when the formulations were prepared in simulated intestinal fluids containing mixed micelles of bile salts and phospholipids and in simple buffer solution. The findings in this study suggest that in order to optimally enhance the absorption of macromolecules, high (>= 100 mM) initial intestinal C10 concentrations are likely needed and that both the concentration and total dose of C10 are important parameters.
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- González-Bueso, Vega, et al.
(författare)
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Compulsive Sexual Behavior Online and Non-online in Adult Male Patients and Healthy Controls : Comparison in Sociodemographic, Clinical, and Personality Variables
- 2022
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Ingår i: Frontiers in Psychiatry. - : Frontiers Media SA. - 1664-0640. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Background and Aims: Compulsive sexual behavior (CSB) is characterized by a persistent pattern of failure to control sexual impulses, resulting in repetitive sexual behavior over a prolonged period that causes marked discomfort in personal, family, social, school, work or in other functional areas. The evolution of the worldwide incidence of this disorder warrants further studies focused on examining the characteristics of the affected people. The purpose of this study was to compare online compulsive sexual behavior (when the problematic sexual practices were online) and non-online compulsive sexual behavior (when the problematic sexual practices were in-person) patients (OCSB and non-OCSB, respectively), and healthy controls in terms of sexual behavior, sociodemographic variables and psychopathology and personality characteristics. Method: A sample of 80 CSB male patients consecutively admitted to our Behavioral Addictions Unit and 25 healthy male controls, participated in the study. The CSB group was comprised by 36 online CSB patients (mean age 42.25, SD: 10.0) and 44 non-online CSB patients (mean age 43.5, SD: 11.9). Scores on the Sexual Compulsivity Scale, Temperament and Character Inventory-Revised, Symptom CheckList-90 Items-Revised, State-Trait Anxiety Index, and additional demographic, clinical, and social/family variables related to sexual behaviors between the three groups were compared. Results: When compared with healthy controls, both clinical groups showed higher psychopathology in all measures as well as higher harm avoidance and self-transcendence and lower self-directness and cooperativeness. When comparing OCSB and non-OCSB patients, results showed that non-OCSB patients exhibited higher prevalence of sexually transmitted diseases, higher percentage of homosexual and bisexual orientation and higher scores in anxiety and in sexual impulse control failure. Conclusion: Both online and non-online CSB patients may experience a variety of comorbid psychological and medical problems. Patients with non-OCSB may suffer more consequences that are negative. Therefore, these results should be considered when designing the most convenient therapeutic approach. Whether sexual orientation plays a role in treatment needs and treatment response in CSB, should be further explored in future studies.
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- Morud, Julia, 1984, et al.
(författare)
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Nicotine produces chronic behavioral sensitization with changes in accumbal neurotransmission and increased sensitivity to re-exposure
- 2016
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Ingår i: Addiction Biology. - : Wiley. - 1355-6215. ; 21:2, s. 397-406
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Tidskriftsartikel (refereegranskat)abstract
- Tobacco use is often associated with long-term addiction as well as high risk of relapse following cessation. This is suggestive of persistent neural adaptations, but little is known about the long-lasting effects of nicotine on neural circuits. In order to investigate the long-term effects of nicotine exposure, Wistar rats were treated for 3 weeks with nicotine (0.36mg/kg), and the duration of behavioral and neurophysiological adaptations was evaluated 7 months later. We found that increased drug-induced locomotion persisted 7 months after the initial behavioral sensitization. In vitro analysis of synaptic activity in the core and shell of the nucleus accumbens (nAc) revealed a decrease in input/output function in both regions of nicotine-treated rats as compared to vehicle-treated control rats. In addition, administration of the dopamine D2 receptor agonist quinpirole (5M) significantly increased evoked population spike amplitude in the nAc shell of nicotine-treated rats as compared to vehicle-treated control rats. To test whether nicotine exposure creates long-lasting malleable circuits, animals were re-exposed to nicotine 7 months after the initial exposure. This treatment revealed an increased sensitivity to nicotine among animals previously exposed to nicotine, with higher nicotine-induced locomotion responses than observed initially. In vitro electrophysiological recordings in re-exposed rats detected an increased sensitivity to dopamine D2 receptor activation. These results suggest that nicotine produces persistent neural adaptations that make the system sensitive and receptive to future nicotine re-exposure.
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- Perez-Alcazar, Marta, et al.
(författare)
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Altered cognitive performance and synaptic function in the hippocampus of mice lacking C3.
- 2014
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Ingår i: Experimental neurology. - : Elsevier BV. - 1090-2430 .- 0014-4886. ; 253C, s. 154-164
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Tidskriftsartikel (refereegranskat)abstract
- Previous work implicated the complement system in adult neurogenesis as well as elimination of synapses in the developing and injured CNS. In the present study, we used mice lacking the third complement component (C3) to elucidate the role the complement system plays in hippocampus-dependent learning and synaptic function. We found that the constitutive absence of C3 is associated with enhanced place and reversal learning in adult mice. Our findings of lower release probability at CA3-CA1 glutamatergic synapses in combination with unaltered overall efficacy of these synapses in C3 deficient mice implicate C3 as a negative regulator of the number of functional glutamatergic synapses in the hippocampus. The C3 deficient mice showed no signs of spontaneous epileptiform activity in the hippocampus. We conclude that C3 plays a role in the regulation of the number and function of glutamatergic synapses in the hippocampus and exerts negative effects on hippocampus-dependent cognitive performance.
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- Perez-Alcazar, Marta, et al.
(författare)
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Human Cerebrospinal Fluid Promotes Neuronal Viability and Activity of Hippocampal Neuronal Circuits In Vitro
- 2016
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Ingår i: Frontiers in Cellular Neuroscience. - : Frontiers Media SA. - 1662-5102. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- For decades it has been hypothesized that molecules within the cerebrospinal fluid (CSF) diffuse into the brain parenchyma and influence the function of neurons. However, the functional consequences of CSF on neuronal circuits are largely unexplored and unknown. A major reason for this is the absence of appropriate neuronal in vitro model systems, and it is uncertain if neurons cultured in pure CSF survive and preserve electrophysiological functionality in vitro. In this article, we present an approach to address how human CSF (hCSF) influences neuronal circuits in vitro. We validate our approach by comparing the morphology, viability, and electrophysiological function of single neurons and at the network level in rat organotypic slice and primary neuronal cultures cultivated either in hCSF or in defined standard culture media. Our results demonstrate that rodent hippocampal slices and primary neurons cultured in hCSF maintain neuronal morphology and preserve synaptic transmission. Importantly, we show that hCSF increases neuronal viability and the number of electrophysiologically active neurons in comparison to the culture media. In summary, our data indicate that hCSF represents a physiological environment for neurons in vitro and a superior culture condition compared to the defined standard media. Moreover, this experimental approach paves the way to assess the functional consequences of CSF on neuronal circuits as well as suggesting a novel strategy for central nervous system (CNS) disease modeling.
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