Daily magnesium supplementation effect on magnesium deficiency in rats during prolonged restriction of motor activity

The objective of this investigation was to evaluate the effect of magnesium (Mg) supplements in rats during prolonged restriction of motor activity (hypokinesia [HK]) and in the presence of Mg deficiency, which is characterized by increased rather than decreased plasma Mg concentration, as occurs in ambulatory conditions. The studies were performed during 98 days of HK on 100 13-week-old Sprague-Dawlay male rats weighing 360 to 390 g. They were equally divided into four groups: (1) unsupplemented control animals (UCA), (2) unsupplemented hypokinetic animals (UHA), (3) supplemented control animals (SCA), and (4) supplemented hypokinetic animals (SHA). For the simulation of the hypokinetic effect, SHA and UHA were kept for 98 days in small individual wood cages that restricted their movements in all directions without hindering food and water intake. The SCA and SHA took daily with their food an additional 0.35 mg of Mg. Before and during the hypokinetic period of 98 days, Mg in plasma, urine, and feces, balance of Mg, food intake of Mg, and body weight were determined at different intervals. In SHA and UHA, plasma Mg concentration and excretion of Mg in urine and feces increased significantly compared with SCA and UCA. Magnesium balance was negative in UHA and AHA throughout the hypokinetic period. Body weight and a food intake decreased significantly in SHA and UHA when compared with SCA and UCA. Significant losses of Mg in SHA and UHA occurred in the presence of Mg deficiency and suggest that prolonged HK induces another factor that influences Mg metabolism. We conclude that prolonged HK causes significant changes in Mg values of plasma, urine, and feces and a negative Mg balance in rats, despite Mg supplements leading to Mg deficiency.     

The fetal-pelvic index has minimal utility in predicting fetal-pelvic disproportion

OBJECTIVE: Our purpose was to evaluate the fetal-pelvic index in our patient population and to determine whether it would be predictive of route of delivery. STUDY DESIGN: One hundred seventy-six patients with a previous history or clinical findings in the current pregnancy suggestive of fetal-pelvic disproportion participated in this Human Investigation Committee-approved study. All underwent fetal ultrasonographic examinations and modified digital radiography before labor. Fetal head and abdominal circumferences and maternal inlet and midpelvic circumferences were determined, and the fetal-pelvic index was calculated. RESULTS: Ninety-one patients fulfilled all aspects of the study, including rigorous criteria pertaining to labor management. Thirty of these patients underwent cesarean delivery and 61 were delivered vaginally. The fetal-pelvic index value for the vaginal delivery group was -5.4 +/- 5.3, as opposed to -2.4 +/- 5.8 in the cesarean delivery group (P <.02). Notwithstanding this difference, the fetal-pelvic index had a low overall ability to predict fetal-pelvic disproportion (0.65) and had associated sensitivity and specificity of 0.27 and 0.84, respectively. Predictive thresholds other than zero were tested, but optimal predictive ability, at a fetal-pelvic index cutoff of 2, was only 70% (sensitivity 0.20, specificity 0.95). CONCLUSION: In our patient population the fetal-pelvic index was only moderately predictive of fetal-pelvic disproportion. Factors other than those assessed by the fetal-pelvic index are probably important in determining the route of delivery. Further studies are indicated.     

Molecular interaction of DNA with bisplatinum(II) complexes having bis(vicinal 1,2-diamines) as ligand

The interaction of novel, tetrafunctional bisplatinum compounds with DNA was investigated. These compounds have bis(vicinal 1,2-diamines) as ligand. The reactions' efficiency, types of cross-links, alterations of the global DNA structure, and sequence selectivity differ significantly from the corresponding features of cisplatin. In particular, they form multiple complexes with dsDNA, which include intrastrand, interstrand and interhelical cross-links and cross-links over sticky ends. The novel compounds are able to untwist but not shorten dsDNA. The reactivity and adduct-forming efficiency of these compounds is, depending on the spacer length, 100-200-fold higher than that of cisplatin. As a consequence, interstrand cross-links are also formed to a higher extent. The chemical stability of the interstrand cross-links against cyanide ions, however, is weaker than that of interstrand cross-links formed by cisplatin, suggesting that each platinum sphere of a bisplatinum compound forms intrastrand cross-links. With dsDNA, they show a preference toward purines, particularly guanines, but they apparently are also coordinated to other nucleobases. Their sequence selectivity toward dsDNA is higher than that of cisplatin. Thus, the novel compounds extend the spectrum of alternative platinum-based compounds with chemical features different from cisplatin.     

Cholinergic short-term conditioning and activation of ATP-sensitive K+ current in cat atrial myocytes

In atrial myocytes, an initial exposure to acetylcholine (ACh1) exerts a short-term conditioning effect such that a second ACh exposure (ACh2) activates ATP-sensitive K+ current (IK,ATP). The purpose of the present study was to determine the mechanism underlying the short-term conditioning induced by ACh that results in subsequent ACh-induced activation of IK.ATP. Cat atrial myocytes were studied using a nystatin-perforated patch whole cell recording method. Changes in L-type Ca2+ current (ICa,L) amplitude were used as an index of relative changes in cyclic AMP (cAMP). The results show that when atrial myocytes are treated with two consecutive exposures to 10 microM ACh separated by a recovery interval, ACh2 activates a larger increase in potassium conductance (gK+) than ACh1. The additional ACh2-induced increase in gK+ is selectively blocked by 10 microM glibenclamide, identifying the current as IK,ATP. Moreover, ICa,L activated immediately after the withdrawal of ACh1 exhibited a transient increase in amplitude above control (+ 76%), consistent with rebound stimulation of cAMP. Rp-cAMPs (50 microM), a selective antagonist of cAMP-dependent protein kinase A, blocked the rebound stimulation of ICa,L and abolished ACh2-induced activation of IK,ATP. Thapsigargin (5 microM), an inhibitor of Ca2+ ATPase in the sarcoplasmic reticulum (SR), abolished ACh2-induced activation of IK,ATP without decreasing rebound stimulation of ICa,L. Rebound stimulation of ICa,L and ACh2-induced activation of IK,ATP both varied as a function of ACh1 duration. We conclude that withdrawal of an initial ACh exposure elicits a rebound cAMP-mediated stimulation of SR Ca2+ uptake. This mechanism induces a short-term conditioning in atrial myocytes such that a subsequent ACh exposure activates IK,ATP. The present results demonstrate novel cholinergic signaling mechanisms in the regulation of IK,ATP.     

Tolerance induction for xenotransplantation

The transplantation of donor hematopoietic tissue prior to organ xenografting has the potential to induce lasting T cell tolerance and, possibly, tolerance of natural antibody-producing B cells. However, the development of specific and nontoxic methods of overcoming the immunologic and physiologic barriers to xenogeneic marrow engraftment is a major challenge that must be met before this goal can be achieved. A greater understanding of the species specificity of molecular interactions important for hematopoiesis and cell homing is a first step toward transcending these physiologic barriers. Perhaps most promising is the potential associated with the use of nonprimate xenogeneic donors genetically engineered to make donor tissues more readily capable of surviving and, in the case of hematopoietic cells, competing with host tissues for survival in a human environment.     

Ovarian steroid regulation of vascular endothelial growth factor in the human endometrium: implications for angiogenesis during the menstrual cycle and in the pathogenesis of endometriosis

The human endometrium undergoes a complex process of vascular and glandular proliferation, differentiation, and regeneration with each menstrual cycle in preparation for implantation. Vascular endothelial growth factor (VEGF) is an endothelial cell-specific angiogenic protein that appears to play an important role in both physiological and pathological neovascularization. To investigate whether VEGF may regulate human endometrial angiogenesis, we examined VEGF messenger ribonucleic acid (mRNA) and protein throughout the menstrual cycle and studied the regulation of VEGF by reproductive steroids in isolated human endometrial cells. By ribonuclease protection analysis, VEGF mRNA increased relative to early proliferative phase expression by 1.6-,2.0-, and 3.6-fold in midproliferative, late proliferative, and secretory endometrium, respectively. In histological sections, VEGF mRNA and protein were localized focally in glandular epithelial cells and more diffusely in surrounding stroma, with greatest VEGF expression in secretory endometrium. Consistent with these in vivo results, the treatment of isolated human endometrial cells with estradiol (E2), medroxyprogesterone acetate (MPA), or E2 plus MPA significantly increased VEGF mRNA expression over the control value by 3.1-, 2.8-, and 4.7-fold, respectively. The VEGF response to E2 was rapid, with steady state levels of VEGF mRNA reaching 85% maximum 1 h after the addition of steroid. E2 also caused a 46% increase in secreted VEGF protein, and the combination of E2 and MPA caused an 18% increase. VEGF expression in endometriosis, an angiogenesis-dependent, estrogen-sensitive disease was similar to that seen in eutopic endometrium. Peritoneal fluid concentrations of VEGF were significantly higher in women with moderate to severe endometriosis than in women with minimal to mild endometriosis or no disease. VEGF, therefore, may be important in both physiological and pathological angiogenesis of human endometrium, as it is an estrogen-responsive angiogenic factor that varies throughout the menstrual cycle and is elevated in women with endometriosis.