Intraocular inflammation after Ultrasound Cyclo Plasty for the treatment of glaucoma

This is a prospective interventional clinical study evaluating intraocular inflammation developed after Ultrasound Cyclo Plasty (UCP) for the treatment of glaucoma. Eighteen eyes of 18 patients were treated with UCP second-generation probes (Eye OP1). After treatment, the mean intraocular pressure (IOP) significantly decreased from 26.8±7.2 to 18.8±6.1 mm Hg at day 1 and to 14.7±3.4 mm Hg at month 6 (all P<0.001). Mean laser flare-cell photometry value steeply increased after surgery from 12.1±7.5 to 64.1±53.9 ph/ms (P=0.001) at day 1, and then progressively decreased to respectively 60.6±49.7 at day 7, 43.5±38.5 at day 14 and 28.2±18.3 at month 1 (all P<0.05), returning at levels similar to baseline ones at month 3 and month 6 (respectively 16.7±6.2 and 12.8±10.2, both P>0.05). A significant negative correlation was found between postoperative increase of aqueous flare values and anterior chamber depth (R=-0.568, P=0.014). This timeframe may be considered reasonable for repeating UCP treatment, when required.     

Parental loss of family members within two years of offspring birth predicts elevated absorption scores in college

Liotti proposed that interactions during infancy with a parent suffering unresolved loss could lead to vulnerabilities to altered states of consciousness. Hesse and van IJzendoorn provided initial support for Liotti’s hypothesis, finding elevated scores on Tellegen’s Absorption Scale - a normative form of dissociation - for undergraduates reporting that their parents had experienced the loss of family members within two years of their birth. Here, we replicated the above findings in a large undergraduate sample (N = 927). Additionally, we investigated mother’s and father’s losses separately. Perinatal losses, including miscarriage, were also considered. Participants reporting that the mother or both parents had experienced loss within two years of their birth scored significantly higher on absorption than those reporting only perinatal, only father, or no losses. While not applicable to the assessment of individuals, the brief loss questionnaire utilized here could provide a useful addition to selected large-scale studies.     

Use of a semi-physiological pharmacokinetic model to investigate the influence of itraconazole on tacrolimus absorption,distribution and metabolism in mice

1.?The aim of this study was to investigate the influence of itraconazole (ITCZ) on tacrolimus absorption, distribution and metabolism by developing a semi-physiological pharmacokinetic model of tacrolimus in mice.

2.?Mice were randomly divided into four groups, namely control group (CG, taking 3?mg kg^?1 tacrolimus only), low-dose group (LDG, taking tacrolimus with 12.5?mg kg^?1 ITCZ), medium-dose group (MDG, taking tacrolimus with 25?mg kg^?1 ITCZ) and high-dose group (HDG, taking tacrolimus with 50?mg kg^?1 ITCZ).

3.?Liver clearance (CL_li) decreased significantly (**p?<?0.01) in LDG (35.3%), MDG (45.2%) and HDG (58.7%) mice compared to CG mice. With respect to gut clearance (CL_gu), significant (**p?<?0.01) decrease was also revealed in LDG (35.9%), MDG (50.2%) and HDG (64.6%) mice. A significant (**p?<?0.01) higher tacrolimus brain-to-blood partition coefficient (K_t,br) was found in MDG (25.3%) and HDG (55.9%) mice than in CG mice. Moreover, a significant (*p?<?0.05) increase (16.3%) was found in the absorption rate constant (K_a) in HDG mice compared to CG mice. There was a significant (**p?<?0.01) association between ITCZ dose and the change in CL_gu (ΔCL_gu, r=??0.790), the change in CL_li (ΔCL_li, r=??0.787) and the change in K_t,br (ΔK_t,br, r?=?0.727), while the association between ITCZ dose and the change in K_a (ΔK_a) was not significant (p?>?0.05).

4.?These findings could be useful in predicting the efficacy and toxicity of tacrolimus, and drug–drug interaction of ITCZ and tarcolimus in human.     

Measurement of pulse oximetry,capnography and pH

The measurement of arterial oxygen saturations, end-tidal carbon dioxide and pH are all key to modern anaesthetic practice. They can all be measured in a variety of ways, but the most common are discussed in this article. The understanding of the underlying physical principles and how the anaesthetist monitors function to measure these variables is discussed in this article, including limitations and inaccuracies of each technique.     

In vitro and in vivo correlation for lipid-based formulations: Current status and future perspectives

Lipid-based formulations (LBFs) have demonstrated a great potential in enhancing the oral absorption of poorly water-soluble drugs. However, construction of in vitro and in vivo correlations (IVIVCs) for LBFs is quite challenging, owing to a complex in vivo processing of these formulations. In this paper, we start with a brief introduction on the gastrointestinal digestion of lipid/LBFs and its relation to enhanced oral drug absorption; based on the concept of IVIVCs, the current status of in vitro models to establish IVIVCs for LBFs is reviewed, while future perspectives in this field are discussed. In vitro tests, which facilitate the understanding and prediction of the in vivo performance of solid dosage forms, frequently fail to mimic the in vivo processing of LBFs, leading to inconsistent results. In vitro digestion models, which more closely simulate gastrointestinal physiology, are a more promising option. Despite some successes in IVIVC modeling, the accuracy and consistency of these models are yet to be validated, particularly for human data. A reliable IVIVC model can not only reduce the risk, time, and cost of formulation development but can also contribute to the formulation design and optimization, thus promoting the clinical translation of LBFs.     

在体单向肠灌流法研究细叶远志皂苷的大鼠肠吸收特性

目的：研究细叶远志皂苷在大鼠四个肠段的吸收状况。方法运用大鼠在体单向肠灌流模型,采用重量法,研究细叶远志皂苷在不同肠段的吸收情况。结果在体小肠吸收实验中,细叶远志皂苷可被大鼠全肠段吸收,在十二指肠、空肠、回肠及结肠各肠段的药物吸收速率常数（Ka）分别是0．05922,0．06387,0．06345,0．06409s－1;药物表观吸收系数（Papp）分别是0．03322,0．03751,0．03733,0．04830cm? s－1,结肠段吸收最好（P＜0．001）。结论细叶远志皂苷为全肠道吸收的药物,且结肠部位吸收最好。     

Effects of Ethanol on Intestinal Absorption of Drugs.

The effect of chronic alcohol intake on the intestinal absorption of seven compounds belonging to a homologous series (ciprofloxacin derivatives) was evaluated using an in situ rat gut technique that measures the intrinsic absorption rates of the compounds both in control and chronic alcohol-fed rats. For chronic alcohol treatment, the animals were fed a liquid diet containing ethanol (36% of calories), whereas an isocaloric diet was given to the pair-fed control animals. The biophysical absorption model, relating the intestinal absorption rate constants and partition indexes of the tested compounds, was then established either for control or alcohol-fed animals. Differences were analyzed and tentatively interpreted on the basis of general diffusion principles. Results revealed that, in chronic alcohol-fed animals, hydrophilic homologs are absorbed at a significantly faster rate than in control ones, whereas lipophilic homologs do not change their absorption rate relative to controls. Results demonstrate that the bulk polarity of the microvillous lipoidal membrane is enhanced by chronic ethanol intake, whereas basic features of the aqueous boundary layer are not altered. These observations suggest that the physicochemical properties of the compounds are an important factor in explaining the influence of chronic alcohol intake on passive intestinal absorption of xenobiotics. The possible practical implications of our results are discussed from a speculative viewpoint     

Effects of Insulin-like Growth Factor-I and its Analogue,Long-R 3 -IGF-I,on Intestinal Absorption of 3- O -methyl- d -glucose are Less Pronounced than Gut Mucosal Growth Responses

The relationship between insulin-like growth factor-I (IGF-I) peptide-induced increases in bowel mass and functional improvement is unclear. We utilised three independent methods to investigate the effects of IGF-I peptides on intestinal absorption of the glucose analogue, 3- O -methyl- d -glucose (3MG) in rats. Rats received vehicle, IGF-I or the more potent analogue, long-R 3 -IGF-I via subcutaneously implanted mini-pump, for 7 days, at which time intestinal absorption was assessed by: (1) plasma 3MG appearance following oral gavage, (2) single-pass- or (3) recirculating-perfusion of a jejunal segment. 3MG (320 or 800 &#117 mg) was gavaged on day 7 to rats treated with vehicle, IGR-I or long-R 3 -IGF-I. With the lower 3MG dose, only long-R 3 -IGF-I increased (40%) the initial rate of 3MG appearance in plasma. IGF-I had no significant effect, whilst at the higher 3MG dose neither peptide was effective. Utilising perfusion techniques, long-R 3 -IGF-I, but not IGF-I, significantly increased 3MG uptake per cm of jejunum by up to 69%, although significance was lost when expressed as a function of tissue weight. Long-R 3 -IGF-I, but not native IGF-I, enhanced 3MG absorption from the intestinal lumen, presumably reflecting an increased mucosal mass rather than an up-regulation of specific epithelial glucose transporters.     

Dorsal Raphe Dopamine Neurons Signal Motivational Salience Dependent on Internal State,Expectation, and Behavioral Context

The ability to recognize motivationally salient events and adaptively respond to them is critical for survival. Here, we tested whether dopamine (DA) neurons in the dorsal raphe nucleus (DRN) contribute to this process in both male and female mice. Population recordings of DRN^DA neurons during associative learning tasks showed that their activity dynamically tracks the motivational salience, developing excitation to both reward-paired and shock-paired cues. The DRN^DA response to reward-predicting cues was diminished after satiety, suggesting modulation by internal states. DRN^DA activity was also greater for unexpected outcomes than for expected outcomes. Two-photon imaging of DRN^DA neurons demonstrated that the majority of individual neurons developed activation to reward-predicting cues and reward but not to shock-predicting cues, which was surprising and qualitatively distinct from the population results. Performing the same fear learning procedures in freely-moving and head-fixed groups revealed that head-fixation itself abolished the neural response to aversive cues, indicating its modulation by behavioral context. Overall, these results suggest that DRN^DA neurons encode motivational salience, dependent on internal and external factors.SIGNIFICANCE STATEMENT Dopamine (DA) contributes to motivational control, composed of at least two functional cell types, one signaling for motivational value and another for motivational salience. Here, we demonstrate that DA neurons in the dorsal raphe nucleus (DRN) encode the motivational salience in associative learning tasks. Neural responses were dynamic and modulated by the animal''s internal state. The majority of single-cells developed responses to reward or paired cues, but not to shock-predicting cues. Additional experiments with freely-moving and head-fixed mice showed that head-fixation abolished the development of cue responses during fear learning. This work provides further characterization on the functional roles of overlooked DRN^DA populations and an example that neural responses can be altered by head-fixation, which is commonly used in neuroscience.     

L’insuline par voie inhalée : un modèle pour l’absorption systémique pulmonaire ?

European Union has recently approved a form of insulin intended to be inhaled. This innovative presentation has the potential to partially or completely replace the injections and thus facilitate starting insulin therapy which is considered with apprehension and too often differed. On this occasion, we reviewed the issues raised by this pulmonary route for systemic absorption (anatomical and cytological limits, cellular mechanisms, relevant physical parameters, facilitating chemical cofactors, role of tobacco smoking and of common respiratory diseases). The pharmacokinetics of inhaled and injectable insulins are comparable, apart from an appreciably faster absorption of the former and both show the same intra-individual variability. The total biodisponibility is definitely lower with the inhaled way but it is notably increased in smokers. These characteristics can vary according to the inhalation system used. A frequent induced cough, the increase in circulating anti-insulin antibodies and a potentially higher cost are not really determining obstacles. The indications will have to be clearly specified and the long-term inocuity of long term inhalation of such a mitogene especially in children and former smokers remains to be formally proven.