Effects of enteral feedback inhibition on motility,luminal flow,and absorption of nutrients in proximal gut of minipigs

We wanted to clarify whether the postprandial intestinal feedback control activated by nutrients in the distal gut exerts different effects on motility, transit of digesta, and absorption of nutrients in the proximal gut. Additionally, interrelationships among motility, transit, and absorption were to be elucidated because these relationships have only been investigated in the fasted state. In five minipigs, a 150-cm segment of the proximal jejunum was isolated by two cannulas. Motility of the jejunal segment was recorded by multiple strain gauges and analyzed by computerized methods. Markers (Cr- and Cu-EDTA) were used for the measurement of the flow rate, transit time, and absorption of nutrients. After a meal, the test segment was perfused with 2 kcal/min of an elemental diet over a period of 90 min. A feedback inhibition was activated by infusion of nutrients into the midgut at rates of 1–4 kcal/min. Saline was infused as control. With increasing energy loads infused into the midgut, the motility index and the length of contraction waves decreased, whereas the incidence of stationary contractions increased, ie, the motility changed from a propulsive to a segmenting pattern. These modulations of motility were associated with a linear decrease in the flow rate and a linear increase in transit time. Flow and transit were linearly correlated with each other. Additionally, the reduction in flow rate and the delay in luminal transit were associated with a linear increase in the absorption of nutrients. However, the increase in absorption induced by the feedback mechanism was small (7.3–13.4%) compared to the marked inhibition of the motility parameters (54–64%), the flow rate (59%), and the delay of transit (5.8-fold). Feedback control primarily modulated motor patterns and luminal flow, whereas the small increase in absorption was only a side effect due to the longer contact time of the nutrients with the mucosa.The study was supported by the Deutsche Forschungsgemeinschaft, grant Eh 64/6-3.     

Metabolism of aniline and 3-chloroaniline in Pseudomonas acidovorans CA28: Evidence of isofunctional muconate cycloisomerases

Two distinct muconate cycloisomerases are involved in the degradation of aniline and 3-chloroaniline (3-CA) proceeding via the ortho-cleavage pathways in Pseudomonas acidovorans CA28. After partial purification of these two enzymes kinetic investigations resulted in a clear differentiation of aniline-derived muconate cycloisomerase (MC) and 3-CA-derived chloromuconate cycloisomerase (CMC). A further result of this study revealed the simultaneous coexistence of MC and CMC in strain CA28 when grown on a mixture of aniline and 3-CA.     

Urinary oxalate and glycolate excretion in healthy infants and children

The molar ratios of oxalate and glycolate over creatinine were determined in single urine samples of 26 infants and 27 children aged 1–5 years. In 135 children aged 5–16 years, two urine specimens were collected, one before breakfast and one at noon. Oxalate was determined by oxalate oxidase, and glycolate was measured by a colorimetric method (improved chromatotropic acid-sulphuric acid assay after prior purification by cation and anion exchanger). Both ratios (expressed in mmol/mol creatinine and analysed on a log-normal basis) were highest in infants 0–6 months old [mean oxalate 147 (95% confidence interval: 60–360), mean glycolate 175 (72–425)]. The mean oxalate ratio was 72 mmol/mol (29–174) at the age of 7–24 months, 44 (19–101) at the age of 2–5 years and 22 (12–40) in adolescents aged 16 years. Molar glycolate ratios were higher, but disclosed the same pattern. Oxalate and glycolate ratios in fasting urines did not differ significantly from those in noon samples (except glycolate in the oldest age group). Oxalate ratios correlated well with glycolate ratios in children up to 5 years of age only. Random urine samples are thus suitable for screening. However, interpretation of data requires use of age-specific reference values that are based on comparable methods.     

Synthesis and Evaluation of Azole-Substituted Tetrahydronaphthalenes as Inhibitors of P450 arom,P450 17, and P450 TxA2

In search of potential drugs for the treatment of estrogen- and androgen-dependent cancer as well as the prophylaxis of metastases, tetralones, tetralins, and dihydronaphthalenes bearing a OCH₃ substituent at the benzene nucleus and an imidazol-4-yl, imidazol-1-yl, or 1,2,4-triazol-1-yl substituent in 2-position were synthesized with and without C₁-spacer between the rings (compounds 2 – 26 ). The compounds were tested in vitro for inhibition of the three target enzymes P450 arom (human placental microsomes), P450 17 (rat testicular microsomes), and P450 TxA₂ (citrated human whole blood). To examine selectivity, some compounds were further tested in vitro for inhibition of P450 18 (bovine adrenal mitochondria), P450 see (bovine adrenal mitochondria) and corticoid formation (aldosterone, corticosterone; ACTH stimulated rat adrenal tissue). In vivo, selected compounds were examined in Sprague Dawley rats regarding P450 TxA₂ inhibition, reduction of plasma testosterone concentration, antiuterotrophic activity (inhibition of the uterotrophic activity of androstenedione), reduction of plasma estradiol concentration (pregnant mares' serum gonadotropin-primed rats), and mammary tumor inhibiting activity (dimethylbenzanthracene-induced tumor; pre- and postmenopausal model). In the series of imidazol-4-yl compounds, which represent a novelty in the field of azole inhibitors of steroidogenic P450 enzymes, strong inhibitors of P450 arom and/or P450 17 were found: 7-OCH₃-2-(imidazol-4-ylmethylene)-1-tetralone ( 4 ) and 7-OCH₃-2-(imidazol-4-ylmethyl)-tetralin ( 12 ) are among the most potent inhibitors of P450 arom in vitro known so far. Compound 4 is a selective inhibitor, whereas 12 shows in addition strong inhibition of P450 17. In contrast to 12 , the 6-OCH₃ derivative (compound 11 ) is a selective inhibitor of P450 17, being 50 times more potent than ketoconazole. Some imidazol-1-yl compounds show a marked inhibition of P450 TxA₂: 2-(imidazol-1-ylmethyl)-1-tetralone ( 13 ) is a selective inhibitor of P450 TxA₂, whereas 7-OCH₃-2-(imidazol-1-ylmethyl)-tetralin ( 17 ) as well as 2-(imidazol-1-ylmethyl)-tetralin ( 16 ) and 7-OCH₃-2-imidazol-1-yl-3,4-dihydronaphthalene ( 25 ) additionally show strong inhibition of P450 arom and P450 17. Regarding the other steroidogenic P450 enzymes as well as corticosterone formation, the compounds show only little inhibitory activity. Aldosterone formation, however, is inhibited at low concentrations. Nevertheless, 4 and 12 are more selective, i.e. inhibit aldosterone synthesis less than the well known inhibitor of P450 arom fadrozole. The compounds show activity in the aforementioned in vivo tests.     

Emergency Treatment of Multiply Injured Patients with Unstable Disruption of the Posterior Pelvic Ring by Using the “C–Clamp”

Abstract Purpose: Evaluation of the therapeutic usefulness of the “pelvic C–clamp” (PCC) during emergency treatment of multiply injured patients with unstable disruption of the posterior pelvic ring. Patients and Methods: The data of 28 patients with polytrauma in combination with an unstable fracture of the posterior pelvic ring (average Injury Severity Score [ISS]: 49 points; average Polytrauma Score [PTS]: 41 points) were retrospectively analyzed from the moment they were admitted to the emergency room until 48 h after admittance. The PCC was used immediately for primary stabilization of the pelvis after clinical diagnosis of the unstable pelvic fracture. Main outcome measurements: development of mean blood pressure, development of oxygenation level, period of time until the PCC was placed, number of blood units needed, period of time until circulatory stabilization occurred. Results: The PCC was applied in all cases within an average of 64.7 min after trauma. Seven patients (25%) died within the first 45 min after admission. The surviving patients showed:• an increase in mean blood pressure of 25% 20 min after application of the PCC,• a hemodynamic stabilization 6 h after application of the PCC,• a stabilization of the oxygenation level 6 h after application of the PCC,• a decrease in the number of required blood units 6 h after application of the PCC. Conclusion: The present study shows, that the application of the PCC to critically injured patients with unstable pelvic fractures leads to stabilization of the vital parameters within a short period of time.     

Prof. Dr. Dr. Elmar Esser zum 65. Geburtstag

Ohne Zusammenfassung     

Optimized and combined T1 and B1 mapping technique for fast and accurate T1 quantification in contrast-enhanced abdominal MRI.

Fast T(1) mapping techniques are a valuable means of quantitatively assessing the distribution and dynamics of intravenously or orally applied paramagnetic contrast agents (CAs) by noninvasive imaging. In this study a fast T(1) mapping technique based on the variable flip angle (VFA) approach was optimized for accurate T(1) quantification in abdominal contrast-enhanced (CE) MRI. Optimization methods were developed to maximize the signal-to-noise ratio (SNR) and ensure effective RF and gradient spoiling, as well as a steady state, for a defined T(1) range of 100-800 ms and a limited acquisition time. We corrected B(1) field inhomogeneities by performing an additional measurement using an optimized fast B(1) mapping technique. High-precision in vitro and abdominal in vivo T(1) maps were successfully generated at a voxel size of 2.8 x 2.8 x 15 mm(3) and a temporal resolution of 2.3 s per T(1) map on 1.5T and 3T MRI systems. The application of the proposed fast T(1) mapping technique in abdominal CE-MRI enables noninvasive quantification of abdominal tissue perfusion and vascular permeability, and offers the possibility of quantitatively assessing dilution, distribution, and mixing processes of labeled solutions or drugs in the gastrointestinal tract.     

Anaphylaxis to isosulfan blue and cross-reactivity to patent blue V: case report and review of the nomenclature of vital blue dyes.

BACKGROUND: Blue dyes used for lymphatic mapping in sentinel lymph node biopsy cause intraoperative anaphylactic reactions in up to 2.7% of patients. With increasing implementation of this technique, the incidence of anaphylaxis to these dyes can be expected to increase. In the literature, the chemically often unrelated and inconsistently designated dyes have been confused, adding to other inconsistencies in the nomenclature. OBJECTIVE: To demonstrate the nomenclature, chemical and physiologic differences, and allergenicity of the various blue dyes used in a medical context. METHODS: We describe a patient with an intraoperative grade IV anaphylactic reaction to isosulfan blue. Immediate-type hypersensitivity was proved by positive skin test reactions and CD63 expression to isosulfan blue and cross-reactivity to patent blue V. RESULTS: A review of the literature clarified the exact nomenclature of the blue dyes and the possible pitfalls of confusing nomenclature in the context of structurally closely related dyes with different allergenic properties. For the detection of type I hypersensitivity, intracutaneous tests are valuable tools. An IgE-mediated mechanism has been shown recently. In most cases, sensitization exists without known previous exposure in a medical context. This may be due to the widespread use of such dyes in objects of everyday life. Preoperative antiallergic medication use does not prevent anaphylactic reactions but apparently reduces their severity. CONCLUSION: For better comparison and precision, the Chemical Abstracts Service number of the respective dye should always be given.