Absorption des médicaments lors de syndrome du grêle court

Short bowel syndrome (SBS) occurs when a patient is left with less than 200 cm of functional small intestine. Drug absorption is mostly a passive process and can be affected by the surface area of the remaining gastrointestinal tract. Oral medication absorption is often impaired and larger doses, or other administration routes may be required. Although patients with SBS do need pharmacotherapy for symptoms associated with their pathology or for other comorbidities, there are few published case reports on drug absorption, and few studies have been conducted in small patients’ samples. Moreover, due to the highly heterogeneous nature of this patient population, it is difficult to directly apply the findings of the published literature to specific patients. Drug dosages should be guided by the monitoring of clinical endpoints and/or of biomarkers.     

alpha- and epsilon-protein kinase C activity during smooth muscle cell apoptosis in response to gamma-radiation

The use of gamma-radiation in treatment of pelvic cancer is associated with injury of healthy surrounding tissues and disorders of intestinal motility; however, the cellular mechanisms involved are unclear. We tested the hypothesis that exposure of visceral smooth muscle cells (SMCs) to gamma-radiation induces apoptosis via activation of specific protein kinase C (PKC) isoforms. Cultured SMCs and slices from guinea pig ileum smooth muscle longitudinal layer (GPISMLL) were exposed to 10 to 50 Gy. Flow cytometry in gamma-radiated SMCs showed increased percentage of cells in the sub-G(0)/G(1) phase, a hallmark of apoptosis. gamma-Radiation-induced reduction in cell survival was partially but significantly alleviated with the PKC inhibitors. Sections of gamma-irradiated GPISMLL showed DNA fragmentation and apoptotic bodies analyzed by the terminal deoxynucleotidyl transferase dUTP nick-end labeling method, whereas the plasma and nuclear membranes were preserved. Confocal microscopy in gamma-radiated SMCs labeled with annexin V-fluorescein showed an increase in apoptotic cells and phosphatidylserine externalization. Contraction of GPISMLL strips in response to KCl and acetylcholine was reduced in tissues exposed to 30 and 50 Gy. gamma-Radiation of GPISMLL caused an increase in PKC activity in the particulate fraction, a decrease in the cytosolic fraction, and increased particulate/cytosolic PKC activity ratio. Western blot analysis revealed significant amounts of alpha- and epsilon-PKC in the cytosolic fraction of control GPISMLL. gamma-Radiation caused an increase in the amount of alpha- and epsilon-PKC in the particulate fraction and a decrease in the cytosolic fraction. Data suggest that gamma-radiation induces apoptosis, growth arrest, and contractile dysfunction in visceral SMCs of GPISMLL via activation and translocation of alpha- and epsilon-PKC isoforms.     

The link between dopamine function and apathy in cannabis users: an [18F]-DOPA PET imaging study

Rationale

Cannabis is the most widely used illicit drug in the world, and regular use has been associated with reduced motivation, i.e. apathy. Regular long-term cannabis use has been associated with reduced dopamine synthesis capacity. The mesolimbic dopaminergic system mediates the processing of incentive stimuli by modifying their motivational value, which in turn is modulated by endocannabinoid signalling. Thus, it has been proposed that dopaminergic dysfunction underlies the apathy associated with chronic cannabis use.

Objectives

The aim of this study was to examine the relationship between dopaminergic function and subjective apathy in cannabis users.

Methods

We measured dopamine synthesis capacity (indexed as the influx rate constant K _i ^cer ) via 3,4-dihydroxy-6-[¹⁸F]-fluoro-l-phenylalanine positron emission tomography and subjective apathy using the self-rated Apathy Evaluation Scale (AES-S) in 14 regular cannabis users.

Results

All subjects scored in excess of 34 points on the AES-S (median [interquartile range] 59.5 [7.5]), indicative of significant apathy based on normative data. K _i ^cer was inversely correlated to AES-S score in the whole striatum and its associative functional subdivision (Spearman’s rho?=??0.64, p?=?0.015 [whole striatum]; rho?=??0.69, p?=?0.006 [associative]) but not in the limbic or sensorimotor striatal subdivisions. There were no significant relationships between AES-S and current cannabis consumption (rho?=?0.28, p?=?0.34) or age of first cannabis use (rho?=?0.25, p?=?0.40).

Conclusions

These findings indicate that the reduction in striatal dopamine synthesis capacity associated with chronic cannabis use may underlie reduced reward sensitivity and amotivation associated with chronic cannabis use.     

Problem Drinking’s Associations with Social Structure and Mental Health Care: Race/Ethnicity Differences

This research used a nationally representative sample of 12,756 respondents self-identified as White, Black, Hispanic, or Asian to examine problem drinking in relationship to social structure and mental healthcare factors. Associations between problem drinking and particular factors varied by racial/ethnic group. Results also indicated that Whites’ problem-drinking rates were higher than those of Hispanics, Blacks, and Asians. Americans sometimes use alcohol to manage stress stemming from social disadvantage and inadequate material resources. Across racial/ethnic groups, drinking level was associated with the type and degree of such disadvantage. Additionally, the presence of a mental health problem was associated with problem drinking.     

Polydopamine nanoparticles kill cancer cells

Polydopamine (PD) is a synthetic melanin analogue of growing importance in the field of biomedicine, especially with respect to cancer research, due, in part, to its biocompatibility. But little is known about the cytotoxic effects of PD on cancer cell lines. PD is a UV-vis absorbing material whose absorbance overlaps with that of formazan salts, which are used to assess cell viability in MTT assays. In this study, a protocol has been established to eliminate the contributing absorbance of PD at 550 nm, and has been applied to characterize the cytotoxicity of PD nanoparticles in both healthy and breast cancer cell lines. Once the protocol is applied, it was found that PD is per se an antineoplastic system, meaning it selectively kills cancer cells, especially those of breast cancer, but it has no toxic effect on healthy cells. The mechanism of action could be related to the production of ROS and the alteration of iron homeostasis in lysosomes. To the best of our knowledge there are only a few examples of nanoparticle systems devoid of drugs that selectively kill cancer cells.

Polydopamine (PD) is a synthetic melanin analogue of growing importance in the field of biomedicine, especially with respect to cancer research, due, in part, to its biocompatibility.