A Comparison of Oral and Rectal Absorption of L-Dopa Esters in Rats and Mice

Short-chain alkyl esters of L-dopa were administered to rats and mice via oral and rectal routes. Plasma L-dopa esters and L-dopa were determined in the systemic and portal circulation by HPLC. A comparison of isopropyl, butyl, and 4-hydroxybutyl esters of L-dopa demonstrated significantly higher levels of the esters in both systemic and portal blood samples following rectal administration than following oral administration. In most cases, oral administration resulted in nondetectable (<0.01 µg/ml) levels of the esters in plasma. Correspondingly, the plasma levels of L-dopa itself were consistently higher following rectal administration. At very high oral doses (500 mg L-dopa equivalents/kg body weight), systemic plasma levels of the butyl ester could be detected (1.25 µg/ml at 10 min), which might indicate saturation of the esterase activity of the small intestine. These studies indicate that the systemic availability of L-dopa from short-chain alkyl esters of L-dopa may be best optimized by rectal administration, which avoids the relatively high esterase activity characteristic of the small intestine.     

Inhaled allergen-driven CD1c up-regulation and enhanced antigen uptake by activated human respiratory-tract dendritic cells in atopic asthma

Background Dendritic cells (DC) mediate inflammation in rodent models of allergic airway disease, but the role played by human respiratory‐tract DC (hRTDC) in atopic asthma remains poorly defined. Recent data suggest that CD1 antigen presentation by hRTDC may contribute to asthma pathogenesis. Objective To investigate the influence of hRTDC on the balance between atopy and allergic asthma in human subjects and to determine whether CD1 expression by hRTDC is modulated during asthmatic inflammation. Methods Sputum cells were induced from steroid‐naïve, allergen‐challenged and allergen‐naïve subjects (atopic asthmatics, atopic non‐asthmatics and non‐atopic controls). hRTDC were identified using monoclonal antibody labelling and analysis by flow cytometry. Results hRTDC stained HLA‐DR⁺ (negative for markers of other cell lineages) were predominantly myeloid and comprised ∼0.5% of viable sputum cells. Sputum cells were potent stimulators of allogeneic CD4⁺ naïve T cells and enrichment/depletion experiments correlated stimulatory potency with DC numbers. Sputum contained cells that exhibited typical dendritic morphology when analysed by electron microscopy. Myeloid hRTDC were endocytically active, but uptake of FITC‐dextran was enhanced in cells from asthmatics (P<0.001). Despite their increased endocytic capacity, asthmatic myeloid hRTDC appeared mature and expressed increased levels of maturation markers (P<0.05–P<0.001), CD1c, CD1d and langerin (P<0.05). CD1c expression by asthmatic myeloid hRTDC was enhanced upon in vivo allergen challenge (three to ninefold within 24 h; P<0.05). CD11c⁻CD123^high hRTDC were only detected in asthmatic sputum and were increased in number following allergen challenge. Conclusion Despite limited cell numbers, it proved possible to analyse human RTDC in induced sputum, providing evidence that increased antigen uptake and enhanced CD1 presentation by activated hRTDC may contribute to allergic airway disease. CD1 presentation by hRTDC in atopic asthma may therefore constitute a novel target for future intervention strategies.     

Image fusion of bone SPECT and CT - a specific diagnostic method in oral and maxillofacial surgery]

OBJECTIVE: The aim of this study was to evaluate the benefit of image fusion of CT (computertomography) and bone SPECT (single photon emission computed tomography) in diagnosis of head and neck cancer. METHODS AND PATIENTS: Computer based image fusion has been applied in 39 patients with suspected cancer in the oromaxillofacial region following CT and SPECT without any further hazard for the patients. Afterwards image fusion was set in comparision to simultaneously evaluation of CT and SPECT and histological findings. RESULTS: In 5 out of 39 patients SPECT/CT image fusion obtained more precise anatomical findings in tumour expansion than simultaneously evaluation of CT and SPECT. CONCLUSION: For planning of surgical and radiation therapy of oral and maxillofacial cancer, image fusion of CT/SPECT provides efficient and plastical diagnostic imaging. Particularly in complex anatomical regions like maxilla or base of the skull image fusion could be an additional device, if simultaneous evaluation of CT and SPECT is not clear.     

Effects of food restriction and refeeding on adipocyte glucose metabolism in Zucker rats

Chronic food restriction has been shown to enhance glucose metabolism in adipocytes from lean Zucker rats at 10, 26, and 52 weeks of age compared to ad libitum-fed lean rats. Only adipocytes from food restricted 10-week-old obese rats demonstrated this response. In this study, lean and obese rats were food restricted from 5 until 14 weeks of age to determine the age at which adipocytes from obese rats were no longer affected by this intervention. Effects of 1 week of refeeding were also determined. When the rats were killed, body weights were highest in control rats followed by restricted/refed and then restricted rats within each genotype. Epididymal pad weights of lean rats were resistant to dietary intervention, while those of obese-restricted and obese-restricted/refed rats weighed less than pads of obese-control rats. Retroperitoneal pad weight was lowered by food restriction in both genotypes; but only that of lean-restricted/refed rats totally recovered with refeeding. Adipocytes of lean-restricted rats had the highest conversion of glucose to CO₂. Glyceride-glycerol production was higher in obese compared to lean rats, but restricted rats had elevated conversion of glucose to fatty acids. In general, these results indicate that by 14 weeks of age obese Zucker rats no longer respond to food restriction with an elevated rate of glucose metabolism in adipocytes.     

Side reactions during the initiation step in oligomerization of methacrylic esters by electron transfer reaction

Anionic oligomerization of methacrylic esters (methyl (MMA), ethyl (EMA), butyl (n-BMA), tert-butyl (t-BMA) methacrylates) was conducted in a one-step process by mixing, in tetrahydrofuran, the monomer, an alkali metal (sodium) and a deactivating agent (sulfur or tert-butyl alcohol). The formation of alcohol due to a nucleophilic attack of the ester group by the methacrylic carbanion was quantified and related to the monomer structure, temperature and nature of the living ends. It was shown that this side reaction is not limited to the propagation step but can occur during the initiation step. From mass spectra and nuclear magnetic resonance (NMR) spectroscopy of the protonated oligomers (tert-butyl alcohol as deactivating agent), it was concluded that this side reaction led to five-membered cyclic β-keto esters during the initiation step of MMA, EMA and n-BMA monomers only. This implies an intramolecular reaction between one carbanion of the dianionic dimer and the penultimate ester group. It was found that this reaction involves primarily dianionic tail-to-tail dimer, even though head-to-tail dimer was also formed.     

The optimal procedure for the great arteries and left ventricular outflow tract obstruction. An anatomical study.

OBJECTIVE: To describe the optimal surgical strategy in heart specimens with transposition of the great arteries (TGA) and left ventricular outflow tract obstruction (LVOTO). METHODS: Thirty-three specimens with LVOTO were selected: TGA with intact ventricular septum (TGA/IVS) (10), TGA/VSD (21), and Taussig-Bing (2). RESULTS: LVOTO in TGA/IVS consisted of combinations of bicuspid pulmonary valve (four), subpulmonary fibrous ridge (four), obstructive muscular conus (two) and bulging muscular septum (four). Arterial switch operation (ASO) with LVOTO resection/valvotomy was feasible in nine hearts. Obstructive anterior papillary muscle prohibited LVOTO relief in one specimen. In TGA/VSD and Taussig-Bing LVOTO consisted of combinations of bicuspid (nine) or unicommissural (one) pulmonary valve, fibrous ridge (three), obstructive muscular conus (five), malaligned outlet septum (six), accessory mitral valve tissue (two), straddling mitral valve (two) and anterior mitral valve rotation (four). VSDs were subpulmonary in 13 (9 perimembranous, 4 muscular), subaortic in 3 (2 perimembranous, 1 anterior muscular), doubly committed in 2, inlet in 3 (2 perimembranous, 1 muscular), non-committed and anterior in 1, and finally 1 VSD extended both into inlet and subpulmonary outlet septum. LVOTO resection and ASO with VSD closure was possible in 10. In six specimens, both a Rastelli and a Nikaidoh operation were feasible. For two hearts, a Nikaidoh procedure was the only option, while Rastelli was considered optimal in another specimen. Mitral valve anomalies prevented LVOTO relief in four, only permitting for Senning/VSD closure (one) or univentricular palliation (three). CONCLUSIONS: LVOTO resection and pulmonary valvotomy frequently permits an ASO. Inlet VSD, impossibility of VSD enlargement, straddling mitral valve, distant aorta and small right ventricle make the Nikaidoh procedure the best option. Mitral anomalies preventing LVOTO relief can make biventricular repair impossible.     

Lack of Nonshivering Thermogenesis in Infants Anesthetized with Fentanyl and Propofol

Background: Sweating, vasoconstriction, and shivering have been observed during general anesthesia. Among these, vasoconstriction is especially important because-once triggered-it minimizes further hypothermia. Surprisingly, the core-temperature plateau associated with vasoconstriction appears to preserve core temperature better in infants and children than adults. This observation suggests that vasoconstriction in anesthetized infants may be accompanied by hypermetabolism. Consistent with this theory, unanesthetized infants rely on nonshivering thermogenesis to double heat production when vasoconstriction alone is insufficient. Accordingly, the authors tested the hypothesis that intraoperative core hypothermia triggers nonshivering thermogenesis in infants.

Methods: With Ethics Committee approval and written parental consent, the authors studied six infants undergoing abdominal surgery. All were aged 1 day to 9 months and weighed 2.4-9 kg. Anesthesia was maintained with propofol and fentanyl. The infants were mechanically ventilated and allowed to cool passively until core (distal esophageal) temperatures reached 34-34.5 degrees Celsius. Oxygen consumption-the authors' index of metabolic rate- was recorded throughout cooling. Because nonshivering thermogenesis triples circulating norepinephrine concentrations, arterial blood was analyzed for plasma catecholamines at [nearly equal] 0.5 degrees Celsius intervals. Thermoregulatory vasoconstriction was evaluated using forearm - fingertip, skin-surface gradients, with gradients exceeding 4 degrees Celsius, indicating intense vasoconstriction. The patients were subsequently rapidly rewarmed to 37 degrees Celsius. Regression analysis was used to correlate changes in oxygen consumption and plasma catecholamine concentrations with core temperature.

Results: All patients were vasoconstricted by the time core temperature reached 36 degrees Celsius. Further reduction in core temperature to 34-34.5 degrees Celsius did not increase oxygen consumption. Instead, oxygen consumption decreased linearly. Hypothermia also failed to increase plasma catecholamine concentrations.