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Rational Medical Therapy of Functional GI Disorders
Published in Kevin W. Olden, Handbook of Functional Gastrointestinal Disorders, 2020
Richard M. Sperling, Kenneth R. McQuaid
Sensitivity to other stimuli is also reported. Pain during blinded intragastic infusions of 0.1 NHC1, saline, and pancreaticobiliary secretions has been reported (120). Some NUD patients also experience pain after an intravenous injection of pentagastrin—even when an H2-antagonist is given to block the stimulated acid secretion (121). This may be analagous to the provocation of pain after edrophonium in patients with noncardiac chest pain.
Effects of Dopamine on The Digestive System
Published in M.D. Francesco Amenta, Peripheral Dopamine Pathophysiology, 2019
In healthy humans, DA (4 μg/kg/min i.v.) decreased basal as well as pentagastrin-stimulated gastric juice volume and acid output.119 Pretreatment with metoclopramide prevented these effects and an interaction with DA receptors was suggested. The inhibitory effect on pentagastrin-stimulated gastric acid secretion was also seen for DA 5 and 10 μg/ kg/min i.v. by Valenzuela et al.120 The effect of DA was abolished when the subjects received haloperidol before. Oral administration to healthy individuals of ibopamine, which quickly metabolizes to N-methyl-DA (epinine) in the organism, did not, however, influence basal or pentagastrin-stimulated gastric acid output and juice volume, and oral administration of bromocriptine to healthy subjects was reported to increase the gastric acid response to submaximal pentagastrin doses.121,122
Methods for the Analysis of Gastrointestinal Function
Published in Shayne C. Gad, Toxicology of the Gastrointestinal Tract, 2018
Gastric acid determination is a procedure to evaluate gastric secretion function by measuring the amount of acid secreted from the stomach [22]. This is the most widely practiced procedure in humans [23]. In humans, it is often done in conjunction with the gastric acid stimulation test, a procedure that measures gastric acid output after injection of a drug to stimulate gastric acid secretion. In fasted animals, a flexible tube is inserted through the mouth or nasogastrically to the stomach, with proper positioning confirmed by fluoroscopy or x-ray. After a short acclimation period, specimens are obtained every 15 minutes for a period of 90 minutes. The first two specimens are discarded to eliminate gastric contents that might be affected by the stress of the intubation process. The specimens are then analyzed for gastric acid. A gastric acid stimulation test may be conducted immediately after the last gastric sampling. Pentagastrin, or a similar drug that stimulates gastric acid output, is injected subcutaneously. Specimens are collected every 15 minutes for 1 hour and analyzed for gastric secretions.
A practical approach to the management of thyroid dysfunction during pregnancy
Published in Gynecological Endocrinology, 2022
Costanzo Moretti, Natalia Lazzarin, Elena Vaquero, Alessandro Dal Lago, Luisa Campagnolo, Herbert Valensise
Ultrasound scans represent the best approach for the diagnosis and characterization of thyroid nodules. Through this technique it is possible to evaluate their growth and risk, as well as excluding the presence of suspicious lymph nodes [59]. In addition, it is important to obtain the ultrasound characteristics of the nodules, and eventual cytological characterization, to facilitate the correct management. A nodule characterized by hypo echogenicity, blurred and irregular margins and micro calcifications should be considered as high risk. In contrast, mixed solid-cystic or spongiform nodules are generally considered as low risk lesions. During pregnancy scintigraphy and pentagastrin stimulation test are contraindicated. Moreover, various contradictory factors can interfere with a biochemical evaluation. For example, low TSH levels, generally associated with a functioning adenoma, are often found during the first trimester of pregnancy. Likewise, the evaluation of plasma thyroglobulin levels it is not recommended. Plasma calcitonin assessment, aimed at the diagnosis of medullary K, should be used in pregnancy only in women with a family history of medullary thyroid carcinoma, with MEN 2 or with RET gene mutations.
Human pharmacokinetics prediction with an in vitro–in vivo correction factor approach and in vitro drug-drug interaction profile of bictegravir, a potent integrase-strand transfer inhibitor component in approved biktarvy® for the treatment of HIV-1 infection
Published in Xenobiotica, 2022
Raju Subramanian, Jianhong Wang, Bernard Murray, Joseph Custodio, Jia Hao, Scott Lazerwith, Kelly MacLennan Staiger, Judy Mwangi, Hailing Sun, Jennifer Tang, Kelly Wang, Gerry Rhodes, Samantha Wijaya, Heather Zhang, Bill J. Smith
The in vitro hepatic metabolic clearance of BIC was assessed from the rates of metabolism of [3H]BIC in pooled hepatic microsomal fractions from rats, dogs, monkeys, and humans, as described previously. The stability of BIC in hepatic microsomal fractions, expressed as in vitro t1/2 values, was scaled using the well-stirred liver model (Obach et al. 1997) to predict hepatic metabolic clearance (without plasma protein binding restriction). To predict in vivo clearance, well-stirred model-based methods were applied to the in vitro predicted hepatic clearance in nonclinical species with and without consideration of binding to plasma and microsomal proteins. The human volume of distribution at steady state (Vss) was predicted from the Vss observed from all evaluated nonclinical species. The absorption rate constant (ka) was assessed following administration of BIC tablets in pentagastrin-pretreated fasted dogs, which is a standard nonclinical model to evaluate the pharmacokinetics of human oral formulations (Lentz, 2008; Kesisoglou, 2014). In pentagastrin-pretreated fasted dogs the stomach pH is similar to that in humans and PK comparator studies showed similar trends in changes of plasma exposure profiles of orally dosed drugs (Zane et al. 2014). These studies support the hypothesis that the ka in pentagastrin-pretreated dogs is an appropriate approach for predicting ka in fasted humans. The oral bioavailability was estimated from the observed bioavailability following oral administration of BIC solution to rat, dog, and monkey (Supplemental Table 1).
Pituitary-adrenal axis hormones in early-onset versus late-onset panic disorder
Published in International Journal of Psychiatry in Clinical Practice, 2022
Vasilios G. Masdrakis, Emilia-Maria Legaki, Charalambos Papageorgiou, Manolis Markianos
Contrary to depression, investigations regarding alterations of DHEA/DHEAS in anxiety disorders are rare. Few studies in PD patients (Fava et al. 1989; Tait et al. 2002; Brambilla et al. 2005) and healthy subjects (Dell'Osso et al. 2012; Brambilla et al. 2013) suggest a potential association between DHEA/DHEAS levels and panic manifestations, possibly due to the implication of this neurosteroid in the modulation of respiration (Klein 1993; Brambilla et al. 2003). Nevertheless, previous data are often contradictory. Thus, no alterations of DHEA levels could be determined in PD in the absence of panic attacks (Brambilla et al. 2003). However, the same group reported greater DHEA plasma levels in male PD patients compared to controls, which nevertheless were not reduced after pharmacotherapy (Brambilla et al. 2005). Pentagastrin-induced panic was associated with increases in DHEA plasma levels in both PD patients and controls (Tait et al. 2002). Likewise, we have previously reported greater increases in plasma DHEAS after caffeine-challenge compared to placebo administration in PD patients, which were yet unrelated to the occurrence or not of caffeine-induced panic attack (Masdrakis et al. 2015). The present study’s results in medication-free patients further suggest that the early-onset subtype of the disorder demonstrate significantly greater DHEAS plasma levels compared to the late-onset patients. Whether these increased levels of DHEAS are observed only in the acutely-ill patients (as were all study’s subjects), or precede and contribute to the early emergence of PD, due to the GABA-antagonistic properties that this neuroactive steroid exerts, is a hypothesis which might be explored in future studies.