Amelioration of intestinal disease severity in cystic fibrosis mice is associated with improved chloride secretory capacity

The variability in intestinal disease severity in patients with cystic fibrosis (CF) has been associated with the expression of secondary modifier genes. The locus containing these modifier genes in CF patients is syntenic with a modifier locus previously associated with survival in CF transmembrane conductance regulator-knockout mice. These previous studies showed that the proportion of CF mice that survive weaning (mildly affected mice) versus those that succumb to obstruction of the small intestine (severely affected) is related to their genetic background and the expression of modifier genes. In the present work, we show that the basal transepithelial chloride transport measured across jejuna obtained from mice of mixed genetic backgrounds segregates into two groups, some mice having low and others having high, near normal chloride transport. Further, we report that the segregation of mice with respect to intestinal chloride transport correlates with their predicted segregation on the basis of genotype at the "modifier locus." These findings support the hypothesis that intestinal disease modification in CF mice correlates with improved chloride transport through non-CF transmembrane conductance regulator chloride channels.     

Development of Immunosorbents for apoB-Containing Lipoproteins Apheresis

Abstract: Three types of sorbents were developed for the specific removal of atherogenic apoB-containing low-density lipoprotein (LDL) and lipoprotein LDL(a) (Lp[a])from human plasma. Two sorbents contained monospecific sheep polyclonal or mouse monoclonal antibodies against human apoprotein B-100. The third one was intended for specific removal of Lp(a) and contains sheep antibodies against human Lp(a). Thirty patients were treated for up to 9 years by LDL apheresis with anti-LDL immunosorbents. A pilot study of Lp(a) apheresis with 3 patients was conducted during 3 years. The results showed that extracorporeal immunosorption is safe and effective for lowering LDL and Lp(a). These procedures may be used both for metabolic investigations and for studies on possible regression of atherosclerosis.     

Self-Sustaining Status Epilepticus: A Condition Maintained by Potentiation of Glutamate Receptors and by Plastic Changes in Substance P and Other Peptide Neuromodulators

Summary: We describe a model of self-sustaining status epilepticus (SSSE) induced by stimulation of the perforant path in free-running rats. In this model, seizures can be transiently suppressed by intrahippocampal injection of a blocker of α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid/kainate synapses but return in the absence of further stimulation when the drug ceases to act. However, seizures are irreversibly abolished by blockers of N -methyl- d -aspartate receptors given locally or systemically. SSSE is enhanced by substance P and its agonists and blocked by its antagonists. SSSE induces novel expression of substance P-like immunoreactivity in hippocampal principal cells. These changes and those in other limbic peptides may contribute to the maintenance of SSSE and to the modulation of hippocampal excitability during epileptic seizures.     

Morphometric dual-energy X-ray absorptiometry of the spine: report of a large series and correlation with axial bone mineral density.

We studied vertebral morphometry and its relation to bone mineral density (BMD) in normal Brazilian women (n = 605). All women (age 22-97 years) were ambulatory and healthy. A lateral spine scan was done for morphometric X-ray absorptiometry using an imaging densitometer. In 429 of these women, BMD of the spine and proximal femur also were measured using dual-energy X-ray absorptiometry. All women were white with mean (+/- 1 SD) age of 53.7 (+/- 9.5) years. About 21% of the women over 50 years had a T score for spine BMD lower than -2.5 SD, and 7% had a femoral neck BMD below this osteoporosis threshold. Vertebral heights (anterior, HA; middle, HM; and posterior, HP) and ratios (HA/HP and HM/HP) were assessed. There was no systematic difference between younger (20-49 years) and older (50+ years) women in heights or ratios. The vertebral heights were normalized for those observed in each individual case for the L2-L4 sequence. This normalization was adequate for all vertebral heights; the Z score averaged about +0.1. The average Z score for HA/HP was +0.01, but that for the HM/HP was -0.72, indicating that the latter ratio might differ from the reference population used (white American and European women). We observed a small positive correlation between vertebral heights and spine or femur BMD, but this was due entirely to the influence of body size on BMD. On a group basis, the HM/HP showed a significant association with axial BMD; the 1 SD difference between the lowest and highest quartile was associated with a difference of 8-15% (0.5-1.0 SD) in axial BMD.     

Epidemiology of small intestinal bacterial overgrowth

Small intestinal bacterial overgrowth(SIBO) is defined as an increase in the bacterial content of the small intestine above normal values. The presence of SIBO is detected in 33.8% of patients with gastroenterological complaints who underwent a breath test, and is significantly associated with smoking, bloating, abdominal pain, and anemia. Proton pump inhibitor therapy is a significant risk factor for SIBO. The risk of SIBO increases with age and does not depend on gender or race. SIBO complicat...     

Mitochondrial Calcium Uptake Regulates Cold Preservation-Induced Bax Translocation and Early Reperfusion Apoptosis

Mitochondrial calcium (mCa + 2) overload occurs during cold preservation and is an integral part of mitochondrial-dependent apoptotic pathways. We investigated the role of mCa + 2 overload in cell death following hypothermic storage using HepG2 cells stored in normoxic-hypothermic (4 degrees C) or hypoxic (< 0.1% O2)-hypothermic Belzer storage solution. Cells were stored for 6 h, with or without 10 microM ruthenium red (mCa + 2 uniporter inhibitor) followed by rewarming in oxygenated media at 37 degrees C. Cytoplasmic cytochrome c levels were studied by Western analysis and by fluorescent microscopy after transfection of cytochrome c-GFP expression plasmid. Immunofluorescence determined the intracellular, spatio-temporal distribution of Bax, and TUNEL staining was used to evaluate cell death after 180 min of rewarming. Caspase activation was evaluated using Western analysis and a caspase 3 activity assay. Bax translocation, cytochrome c release, and early rewarming cell death occurred following hypothermic storage and were exacerbated by hypoxia. Caspase 3 activation did not occur following hypothermic storage. Blockade of mCa + 2 uptake prevented Bax translocation, cytochrome c release, and early rewarming cell death. These studies demonstrate that mCa + 2 uptake during hypothermic storage, both hypoxic and normoxic, contributes to early rewarming apoptosis by triggering Bax translocation to mitochondria and cytochrome c release.     

Postoperative pancreatitis after biliary and gastric operations

Based on review of the literature and on their own material, authors have established that pancreatitis, following biliary and gastric operations, develops mostly at interventions performed on the papilla of Vater and/or around its region. The characteristic signs of the early postoperative. (2nd-4th day) pancreatitis are essentially confined to the pancreas (i.e. necrosis, abscess, erosion, bleeding, fistula). The time of early surgical intervention and the type of solution vary by patients. Recognition of the spreading of autolysis is possible by sonographic or computer tomographic control which also help in diagnosing further complications and indicating additional operations. Prognosis is poor and lethality is high and, consequently, the gastric or biliary operations involving the papilla of Vater or its region should be performed with particular caution. Postoperative pancreatitis can be a specific risk-factor of these operations.     

Evaluation of the potential absorbed doses from patients based on whole-body 131I clearance in thyroid cancer therapy

The evaluation of the absorbed dose from radioactive patients during the treatment of thyroid disease is an important factor in establishing precautions in these procedures, and the I retention/excretion by patients' bodies provides additional information to medical and radioprotection service. In 94 patients, the measurement of exposure rates was performed over 7 d following NaI administration, and the rates permitted the study of the dynamics of excretion and the potential dose evaluation. The administered activities ranged from 3.7 GBq (100 mCi) to 16.65 GBq (450 mCi), and the results proved that the majority of the activity is excreted by patients in the first 3 d after NaI administration. The average (131)I activity excreted at 24, 48, 72, 96, and 120 h after oral administration was (72 +/- 10), (91 +/- 6), (97 +/- 3), (98.9 +/- 1.5), and (99.6 +/- 0.7)%, respectively. According to the administered activity, the evaluation of the accumulated absorbed dose from patients ranged from 3.0 +/- 0.7 to 8.4 +/- 1.1 mSv at 1 m and 1.2 +/- 0.4 to 3.2 +/- 0.4 mSv at 2 m. The data reported here are important to radioprotection policy and to add to and improve on the guidelines reported in U.S. NRC Regulatory Guide 8.39.