Effect of Glucagon-like Peptide-2 (GLP-2) on Diurnal SGLT1 Expression

Glucagon-like peptide 2 (GLP-2) is a 33-amino acid gut peptide that leads to villus hyperplasia and altered gene expression. We examined the effect of chronically administered GLP-2 on diurnal gene expression rhythms using the Na+/glucose cotransporter 1 (SGLT1) as the index. Animals were treated with [Gly2]GLP-2 (twice daily; 1microg/g body weight) or vehicle (control) for 10 days. Rats were killed at either 3 hr or 9 hr after light onset (ZT3 and ZT9, respectively), an interval during which SGLT1 expression exhibits a robust induction. SGLT1 mRNA expression was assessed by Northern blotting and in situ hybridization. SGLT1 protein was examined by immunofluorescence and Western blotting. Tissues from GLP-2-treated rats had increased villus height, crypt depth, and proliferation index (P < 0.05). GLP-2 administration did not alter the diurnal increase in mRNA levels of SGLT1, GLUT2, or GLUT5. However, in GLP-2-treated rats, the SGLT1 protein amount increased at both ZT3 and ZT9. Moreover, SGLT1 was preferentially localized to the apical membranes in this group. GLP-2 does not adversely affect the diurnal expression rhythm of SGLT1 and appears to increase membrane expression of the protein. These biological actions of GLP-2 may contribute to its therapeutic value in intestinal diseases.     

Transvaginal cholecystectomy without laparoscopic support using prototype flexible endoscopic instruments in a porcine model

Background

Transvaginal cholecystectomy with laparoscopic assistance has been performed safely in humans. The next goal was to develop a natural orifice transluminal endoscopic surgery (NOTES) technique to perform cholecystectomy without laparoscopic instruments using one flexible endoscope and flexible accessories. The aim of the study was to test the feasibility of the procedure in a survival porcine model.

Methods

Cholecystectomies were attempted in five 88–130-lb. pigs with a planned 2-week survival. Prototype flexible instruments (NOTES Toolbox, Ethicon Endo-Surgery, Inc.) were used to aid in access, dissection, and removal of the gallbladder via the transvaginal route.

Results

Cholecystectomy could be completed without abdominal incision using prototype instruments in four out of five pigs. The cystic duct could be exposed with a flexible hook knife and clips applied. The steerable trocar improved stability and the precision of the dissection. The critical view was established in all five pigs. Dissection of the gallbladder off the liver bed was imprecise resulting in gallbladder perforation in all pigs and liver hemorrhage in two. At necropsy, all clips on the cystic duct were secure and no bile leak, bowel injury, or adhesions were present.

Conclusions

NOTES cholecystectomy without laparoscopic support is feasible but challenging using prototype flexible endoscopic devices. A prototype clip applier was effective in controlling the cystic duct. Further improvements in instrument design to ensure precision and safety are needed before flexible devices should be used for pure NOTES procedures in humans.     

Incidence of hypohydration when consuming carbohydrate-electrolyte solutions during field training

Carbohydrate-electrolyte solutions (CE1, CE2) were evaluated for their ability to reduce the incidence of hypohydration during field training in hot weather (max Tamb = 88 degrees-100 degrees F). Hydration status was monitored twice daily in Army reservists who consumed ad libitum CE1, or CE2, or water, or a flavored water placebo. The water group had the highest percentage incidence of urine specific gravity greater than or equal to 1.030 (22%), whereas CE2 and flavored water placebo groups had the lowest (6% and 8%, respectively). Average total fluid intake was greatest in CE2 and lowest in CE1. CE2 and flavored water placebo were more effective than CE1 and water in reducing the overall incidence of hypohydration during this field exercise.     

A case of giant congenital nevocytic nevus with neurotization and onset of vitiligo

The authors report the case of a 21-year-old woman with a giant congenital nevocytic nevus (GCNN) who developed vitiligo at the age of 16 years on skin areas remote from the GCNN. This is the first reported case of GCNN developing neurotization combined with vitiliginous changes within the GCNN lesion. Treatment with PUVA achieved repigmentation of the vitiligo lesions, except for the hypochromic areas within the area of the nevus that were shielded from UVA radiation.     

Saponins from the fructus ofKochia scoparia

Two new triterpenoidal saponins,B(1) andC(2) were isolated from the fruccus ofKochia scoparia. On the basis of chemico-spectral evidences, the structures of1 and2 were elucidated as oleanolic acid 3-O-β-D-ribopyranosyl-(1→2)-β-D-glucuronopyranoside and 3-O-β-D-xylopyranosyl-(1→3)-β-D-glucuronopyranosyl-olean-12-en-28-O-β-D-glucopyranosyl ester, respectively.     

Biologische Halbwertzeit und Umsatzrate des Eisens im Gesamtk?rper des Menschen; ein Beitrag zur Frage des Gesamtk?rper-Eisenbedarfs

Zusammenfassung Mit einem 4-Großraum-Radioaktivitäts-Detektor wurde die⁵⁹Fe-Gesamtkörperretention des intestinal resorbierten⁵⁹Fe⁺⁺ bei gesunden Männern gemessen. Aus der bestimmten⁵⁹Fe-Gesamtkörperretention wurden eine konstant bleibende biologische Halbwertzeit von 510±221 ( ±s) Tagen und Umsatzrate von 0,136±0,059 ( ±s) %/Tag für die Zeit vom 20. bis 120. Tag nach der⁵⁹Fe⁺⁺-Resorption berechnet.Unter der Annahme, daß das⁵⁹Fe aus dem Gesamtkörper-Eisenpool des Mannes (4000 mg Fe) entsprechend der Umsatzrate mit 0,136%/Tag ausgeschieden wird, würden sich für den erwachsenen Mann eine Gesamtkörper-Eisenumsatzrate und ein optimaler Eisenbedarf von 5,5 mg/Tag ergeben.

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Biological halt life and tumover rate of iron in the human whole body a contribution to the problem of the whole body iron requirement

Summary The whole body retention of absorbed⁵⁹Fe was measured in normal male volunteers using a 4 large volume radioactivity detector with liquid organic scintillator.A biological half life of 510±221 ( ±s) days and a turnover rate of 0.136±0.059 (m±s) %/day were calculated from the estimated whole body retention of the absorbed⁵⁹Fe. If the⁵⁹Fe is excreted from the whole body iron pool of adult men (4000 mg Fe) with a turnover rate of 0.136%/day, it will be necessary to accept an absolute whole body iron turnover rate and optimum iron requirement of about 5.5 mg/day.

     

Die intestinale Resorption des Nahrungs-Eisens aus dem Hämoglobin,der Leber und Muskulatur bei Menschen mit normalen Eisenreserven und Personen mit prälatentem/latentem Eisenmangel

Zusammenfassung Die intestinale Resorption des in Kaninchen-Hämoglobin, Muskulatur und Leber biosynthetisch inkorporierten Nahrungseisens wurde mit dem⁵⁹Fe-Resorptions-Gesamtkörperretentions-Test bei Personen mit normalen Eisenreserven und Personen mit prälatentem/latentem Eisenmangel nach oraler Verabfolgung von jeweils 10 µMol (0,558 mg)⁵⁹Fe⁺⁺,⁵⁹Fe-Hämoglobin,⁵⁹Fe-Muskulatur und⁵⁹Fe-Leber untersucht.Personen mit normalen Eisenreserven resorbierten 23,3 ± 10,2 % des⁵⁹Fe⁺⁺ und 20,1 ± 10,3% des Hämoglobin-⁵⁹Fe (p>0,10). Bei prälatenten/latenten Eisenmangelzuständen war die Resorption des⁵⁹Fe⁺⁺ auf 81,1 ± 18,2% (=348% der Kontrollgruppe,p<0,001) und die Resorption des Hämoglobin-⁵⁹Fe auf 30,2±13,1% (=150% der Kontrollgruppe,p<0,005) angestiegen. Das Muskulatur-⁵⁹Fe und Leber-⁵⁹Fe wurden von der Kontrollgruppe mit 12,3±3,9% (p<0,05) bzw. 12,3±5,4% (p<0,02) in geringerem Umfange als Hämoglobin-⁵⁹Fe resorbiert. Im prälatenten/latenten Eisenmangel wurde ein Anstieg der Resorption des Muskel-Fe auf 23,5±8,5% (=191% der Kontrollgruppe,p<0,005) und beim Leber-Fe auf 25,7 ± 6,0 (=195% der Kontrollgruppe,p<0,001) gemessen. Zwischen der Resorbierbarkeit des Hämoglobineisens und des Muskulatur- bzw. Lebereisens besteht bei Personen mit prälatentem/latentem Eisenmangel kein signifikanter Unterschied (p<0,20 bzw. <0,40).Aus der bei Männern und Frauen mit normalen Eisenreserven durch Messung der biologischen Halbwertzeit des Gesamtkörper-Eisenpools ermittelten Gesamtkörper-Eisenumsatzrate (=Eisenbedarf) von 1,03–1,37 mg Fe/Tag (Männer) bzw. 0,99–1,39 mg Fe/Tag (Frauen) und der gemessenen Resorbierbarkeit des Hämoglobin-, Muskulatur- bzw. Lebereisens wurde berechnet, daß für die diätetische Eisenprophylaxe 3657–5133 g Muskulatur/Tag, 328–461 g Leber/Tag oder 3,5–4,8 g Hämoglobin/Tag erforderlich wären. Eine diätetische Eisenprophylaxe mit Fleisch oder Leber ist somit aus ökonomischen und praktisch diätetischen Gründen nicht durchführbar. Die berechnete tägliche Zufuhr von 3,5–4,8 g Hämoglobin wäre jedoch möglicherweise eine geeignete Grundlage für eine diätetische Eisenprophylaxe. Trotzdem dürfte eine gut resorbierbare und gut verträgliche orale Eisenpräparation am besten für die Prophylaxe und Therapie der weltweit verbreiteten prälateralen, latenten und manifesten Eisenmangelzustände geeignet sein.

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Summary The intestinal absorption of⁵⁹Fe which was incorporated into rabbit hemoglobin, muscle and liver by biosynthesis was measured with the⁵⁹Fe-absorption-whole body-retention test in human subjects with normal iron stores and individuals with prelatent/latent iron deficiency using an oral test dose of 10 µMol (0.558 mg)⁵⁹Fe.Persons with normal iron stores absorbed 23.3±10.2 % of⁵⁹Fe⁺⁺ and 20.1 ± 10.3% of the hemoglobin⁵⁹Fe (p>0.10). The absorption of⁵⁹Fe⁺⁺ was increased to 81.1±18.2% (=348% of control group,p<0.001) in prelatent/latent iron deficiency whereas the absorption of hemoglobin-⁵⁹Fe was augmented only to 30.2±13.1% (=150% of control group;p<0.005). In persons with normal iron stores muscle-⁵⁹Fe and liver-⁵⁹Fe is less available than hemoglobin-⁵⁹Fe, since an absorption of only 12.3±3.9% (p<0.05) and 13.2±5.4% (p<0.02) was observed for muscle-⁵⁹Fe and liver-⁵⁹Fe resp. Prelatent/latent iron deficiency caused an increase of the absorption of muscle-⁵⁹Fe to 23.5±8.5% (=191% of normal control group;p<0.005) and an increase of the absorbability of liver-⁵⁹Fe to 25.7±6.0 (=195% of normal control group;p<0.001), so that there is no more significant difference between the absorption of hemoglobin-⁵⁹Fe, muscle-⁵⁹Fe and liver-⁵⁹Fe in persons with prelatent/latent iron deficiency (p<0.20 and <0.40 resp.).The amount of dietary muscle-Fe, liver-Fe or hemoglobin-Fe required for covering the daily whole body iron turnover (=requirement) of 1.03–1.37 mg for men and 0.99–1.39 mg in females was calculated from the measured absorbability of muscle-, liver- and hemoglobin-iron. The calculation resulted in daily uptake requirements of 3657–5133 g muscle or 328 to 461 g liver which are completely unrealistic both from an economical and a dietary point of view. The calculated amount of 3.5 to 4.8 g of hemoglobin/day however could be a reasonable basis for a dietary prophylaxis of iron deficiency. Nevertheless a well-absorbable and tolerated oral iron preparation seems to be the best solution to the world-wide problem of necessary iron prophylaxis and therapy.

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Auszugsweise vorgetragen auf dem Western Hemisphere Nutrition Congress II, Research Forum, p.36, San Juan/Puerto Rico, 26.–29. August 1968.     

最小二乘法求算药物动力学参数标准差的研究

本文提出利用血药浓度的平均值拟合血药浓度和时间的关系。应用最小二乘法把血药浓度的标准差分配给曲线参数,再由误差传递原理将曲线参数的标准差传给药物动力学参数,从而使药物动力学参数既能表现出药物在生物体内的一般规律,又能反映出生物体的个体差异。文中介绍了本方法的数学原理及头孢羟氨苄在狗体内的药物动力学计算实例。结果表明,本方法计算量小,结果可靠。