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Andrea Fratter,Damiano Biagi,Isabella Giacomini,Monica Montopoli,Veronica Cocetta 한국식품영양과학회 2021 Journal of medicinal food Vol.24 No.12
Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most commonly prescribed and self-prescribed drugs to treat inflammation and pain associated with several conditions. Although their efficacy and overall safety have been recognized when used according to medical prescriptions and for a short period time, their acute impact on enteric physiology has rarely been studied. NSAIDs are known to cause gastrointestinal side effects due to their intrinsic mechanism of action, which involves prostaglandins synthesis, leading to impaired mucopolysaccharide layer production. Despite this well-known and investigated side effect, the short- and long-term influences of acute administration of these drugs on the biochemical environment of enteric cells are not well understood. This study investigates the rate of adenosine triphosphate (ATP) loss and permeability alterations occurring in a model of human enteric cells, as a consequence of acute administration of NSAIDs as major perpetrators of enteric toxicity. For the first time, we investigate the ability of a novel ATP-containing formulation to prevent ATP hydrolysis in the stomach and ensure its delivery at the proximal duodenal site.
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Surgical Management of Rhinosinusitis in Onco-Hematological Patients
Stefano Di Girolamo,Sara Mazzone,Roberta Di Mauro,Piergiorgio Giacomini,Maria Cantonetti 대한이비인후과학회 2014 Clinical and Experimental Otorhinolaryngology Vol.7 No.4
Objectives. In onco-hematological diseases, the incidence of paranasal sinuses infection dramatically increase and requires a combination of medical and surgical therapy. Balloon dilatation surgery (DS) is a minimally invasive, tissue preserv- ing procedure. The study evaluates the results of DS for rhinosinusitis in immunocompromised patients. Methods. A retrospective chart review was conducted in 110 hematologic patients with rhinosinusitis. Twenty-five patients were treated with DS technique and 85 patients with endoscopic sinus surgery (ESS). We considered the type of an- esthesia and the extent of intra- and postoperative bleeding. Patients underwent Sino-Nasal Outcome Test (SNOT-20) to evaluate changes in subjective symptoms and global patient assessment (GPA) questionnaire to value patient satis- faction. Results. Local anesthesia was employed in 8 cases of DS and in 15 of ESS. In 50 ESS patients, an anterior nasal packing was placed and in 12 cases a repacking was necessary. In the DS group, nasal packing was required in 8 cases and in 2 cases a repacking was placed (P=0.019 and P=0.422, respectively). The SNOT-20 change score showed significant improvement of health status in both groups. However the DS group showed a major improvement in 3 voices: need to blow nose, runny nose, and facial pain/pressure. The 3-month follow-up GPA questionnaire showed an higher sat- isfaction of DS group. Conclusion. Balloon DS represents a potentially low aggressive treatment and appears to be relatively safe and effective in onco-hematologic patients. All these remarks may lead the surgeon to consider a larger number of candidates for sur- gical procedure.
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Sodium Dependent Taurine Transport into the Choroid Plexus, the Blood-Cerebrospinal Fluid Barrier
Chung, Suk-Jae,Ramanathan, Vikram,Brett, Claire M.,Giacomini, Kathleen M. The Korean Society of Pharmaceutical Sciences and 1995 Journal of Pharmaceutical Investigation Vol.25 No.3
Taurine, a ${\beta}-amino$ acid, plays an important role as a neuromodulator and is necessary for the normal development of the brain. Since de novo synthesis of taurine in the brain is minimal and in vivo studies suggest that taurine dose not cross the blood-brain barrier, we examined whether the choroid plexus, the blood-cerebrospinal fluid (CSF) barrier, plays a role in taurine transport in the central nervous system. The uptake of $[^3H]-taurine$ into ATP depleted choroid plexus from rabbit was substantially greater in the presence of an inwardly directed $Na^+$ gradient taurine accumulation was negligible. A transient in side-negative potential gradient enhanced the $Na^+-driven$ uptake of taurine into the tissue slices, suggesting that the transport process is electrogenic, $Na^+-driven$ taurine uptake was saturable with an estimated $V_{max}$ of $111\;{\pm}\;20.2\;nmole/g/15\;min$ and a $K_M\;of\;99.8{\pm}29.9\;{\mu}M$. The estimated coupling ratio of $Na^+$ and taurine was $1.80\;{\pm}\;0.122.$ $Na^+-dependent$ taurine uptake was significantly inhibited by ${\beta}-amino$ acids, but not by ${\alpha}-amino$ acids, indicating that the transporter is selective for ${\beta}-amino$ acids. Since it is known that the physiological concentration of taurine in the CSF is lower than that in the plasma, the active transport system we characterized may face the brush border (i.e., CSF facing) side of the choroid plexus and actively transport taurine out of the CSF. Therefore, we examined in vivo elimination of taurine from the CSF in the rat to determine whether elimination kinetics of taurine from the CSF is consistent with the in vitro study. Using a stereotaxic device, cannulaes were placed into the lateral ventricle and the cisterna magna of the rat. Radio-labelled taurine and inulin (a marker of CSF flow) were injected into the lateral ventricle, and the concentrations of the labelled compounds in the CSF were monitored for upto 3 hrs in the cisterna magna. The apparent clearance of taurine from CSF was greater than the estimated CSF flow (p<0.005) indicating that there is a clearance process in addition to the CSF flow. Taurine distribution into the choroid plexus was at least 10 fold higher than that found in other brain areas (e. g., cerebellum, olfactory bulb and cortex). When unlabelled taurine was co-administered with radio-labelled taurine, the apparent clearance of taurine was reduced (p<0.0l), suggesting a saturable disposition of taurine from CSF. Distribution of taurine into the choroid plexus, cerebellum, olfactory bulb and cortex was similarly diminished, indicating that the saturable uptake of taurine into these tissues is responsible for the non-linear disposition. A pharmacokinetic model involving first order elimination and saturable distribution described these data adequately. The Michaelis-Menten rate constant estimated from in vivo elimination study is similar to that obtained in the in vitro uptake experiment. Collectively, our results demonstrate that taurine is transported in the choroid plexus via a $Na^+-dependent,saturable$ and apparently ${\beta}-amino$ acid selective mechanism. This process may be functionally relevant to taurine homeostasis in the brain.
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