Clinical, urodynamic, and histologic effects of urethral intussusception in clinically normal dogs

OBJECTIVE: To evaluate clinical and histologic effects of surgically created urethral intussusception and determine whether it creates a high-pressure zone that resists passive urine flow in clinically normal dogs. ANIMALS: 8 healthy adult sexually intact female dogs. PROCEDURE: Urethral pressure profilometry was used to measure maximal urethral closure pressure (MUCP) and functional profile length (FPL) in dogs sedated with xylazine hydrochloride and atropine before and 2, 4, 7, 14, 28, 60, and 90 days after surgery. Cystourethral leak point pressure (CLPP) and cystourethral leak point volume (CLPV) were determined in anesthetized dogs immediately before and after surgery. Dogs were assigned to 4 groups of 2 dogs each; groups were euthanatized 4, 14, 28, and 90 days later, and representative tissues were examined. RESULTS: Dog 1 developed complete postoperative urethral obstruction. The procedure was altered, and all dogs recovered without complication. Mild inflammation attributable to surgical manipulation, but not ischemic damage or reduction of the intussusception, was evident. Comparison of preoperative MUCP and FPL with postoperative values did not yield significant differences. Immediate postoperative CLPP and CLPV were significantly higher than preoperative values, but were not significantly increased at euthanasia. A distinct but nonsignificant pressure spike was observed in postoperative urethral pressure profiles and persisted in 7 of 8 dogs. CONCLUSIONS: Urethral intussusception does not have deleterious effects when performed as described. Urodynamic data do not support the premise that urethral intussusception will create a high-pressure zone in the urethra that will resist passive urine flow long term in clinically normal dogs.     

Models to evaluate the role of stress in periodontal disease

We evaluated the association of stress,distress, and coping behaviors with periodontal disease in 1,426 subjects, aged 25 to 74, in Erie County, NY, Demographic characteristics, medical and dental history, and tobacco and alcohol consumption, as well as clinical assessments of supragingival plaque, subgingival flora, gingival bleeding, calculus, probing depth, clinical attachment level (CAL), and radiographic alveolar bone loss (ABL) were obtained for each subject. Subjects also completed a set of 5 psychosocial instruments that measured life events, daily strains, hassles and uplifts, distress, and coping behaviors. Internal consistencies of all subscales on the instruments were high, with Cronbach's alpha ranging from 0.88 to 0.99. Logistic regression indicated that financial strain was significantly associated with greater attachment and alveolar bone loss (OR 1.70; 95% CI, 1.09-2.65; and 1.68; 95% CI, 1.20-2.37, respectively) after adjusting for age, gender, and smoking. When those with financial strain were stratified with respect to coping behaviors, it was found that those who exhibited high emotion-focused coping (inadequate coping) had and even higher risk of having more severe attachment loss (OR 2.24; 95% CI, 1.15-4.38) and alveolar bone loss (OR 1.91; 95% CI, 1.15-3.17) than those with low levels of financial strain within the same coping group, after adjustment for age, gender, and cigarette smoking. After further adjusting for number of visits to the dentist, those with financial strain who were high emotion-focused copers still had higher levels of periodontal disease based on CAL (OR 2.12; 95% CI, 1.07-4.18). In contrast, subjects with high levels of financial strain who reported high levels of problem-based coping (good coping) had no more periodontal disease than those with low levels of financial strain. Salivary cortisol levels were higher in a test group exhibiting severe periodontitis, a high level of financial strain, and high emotion-focused coping, as compared to a control group consisting of those with little or no periodontal disease, low financial strain, and low levels of emotion-focused coping (11.04 +/-4.4 vs/ 8.6 +/- 4.1 nmol/L salivary cortisol, respectively). These findings suggest that psychosocial measures of stress associated with financial strain are significant risk indicators for periodontal disease in adults. Further prospective studies are needed to help establish the time course of stress, distress, and inadequate coping on the onset and progression of periodontal disease, as well as to evaluate the mechanisms by which stress exerts its effects on periodontal infections.     

Effect of different levels of hyperoxia on breathing in healthy subjects

We have recently shown that breathing 50% O2 markedly stimulates ventilation in healthy subjects if end-tidal PCO2 (PETCO2) is maintained. The aim of this study was to investigate a possible dose-dependent stimulation of ventilation by O2 and to examine possible mechanisms of hyperoxic hyperventilation. In eight normal subjects ventilation was measured while they were breathing 30 and 75% O2 for 30 min, with PETCO2 being held constant. Acute hypercapnic ventilatory responses were also tested in these subjects. The 75% O2 experiment was repeated without controlling PETCO2 in 14 subjects, and in 6 subjects arterial blood gases were taken at baseline and at the end of the hyperoxia period. Minute ventilation (VI) increased by 21 and 115% with 30 and 75% isocapnic hyperoxia, respectively. The 75% O2 without any control on PETCO2 led to 16% increase in VI, but PETCO2 decreased by 3.6 Torr (9%). There was a linear correlation (r = 0.83) between the hypercapnic and the hyperoxic ventilatory response. In conclusion, isocapnic hyperoxia stimulates ventilation in a dose-dependent way, with VI more than doubling after 30 min of 75% O2. If isocapnia is not maintained, hyperventilation is attenuated by a decrease in arterial PCO2. There is a correlation between hyperoxic and hypercapnic ventilatory responses. On the basis of data from the literature, we concluded that the Haldane effect seems to be the major cause of hyperventilation during both isocapnic and poikilocapnic hyperoxia.     

Cloning, sequencing and functional expression of a guinea pig lung bradykinin B2 receptor

Kinin receptors are classified as B1 and B2 based upon agonist and antagonist potencies and cloning and expression studies. Using sequences from human and rat bradykinin B2 receptors, polymerase chain reaction (PCR) was utilized to isolate cDNA from guinea pig lung. The receptor obtained is predicted to have 372 amino acids and shares > 80% sequence homology with human, rat, rabbit and mouse B2 receptors. In competition binding experiments in Chinese hamster ovary (CHO-K1) cells in which the guinea pig cDNA was expressed, [3H]bradykinin was displaced by kinin receptor ligands with an order of potency consistent with a B2 subtype. In CHO cells expressing the guinea pig receptor, bradykinin caused a concentration 45Ca2+ efflux. A B1 receptor agonist, desArg9-bradykinin, also caused 45Ca2+ efflux but with a potency several orders of magnitude lower than bradykinin. Curiously, several B1 and B2 receptor antagonists induced 45Ca2+ efflux, indicating that this receptor may be coupled differently in CHO cells than in native tissues.     

Epidemiology of interstitial cystitis: a population based study

Mycobacterium sp. strain CH1 was isolated from polycyclic aromatic hydrocarbon (PAH)-contaminated freshwater sediments and identified by analysis of 16S rDNA sequences. Strain CH1 was capable of mineralizing three- and four-ring PAHs including phenanthrene, pyrene, and fluoranthene. In addition, strain CH1 could utilize phenanthrene or pyrene as a sole carbon and energy source. A lag phase of at least 3 days was observed during pyrene mineralization. This lag phase decreased to less than 1 day when strain CH1 was grown in the presence of phenanthrene or fluoranthene. Strain CH1 also was capable of using a wide range of alkanes as sole carbon and energy sources. No DNA hybridization was detected with the nahAc gene probe, indicating that enzymes involved in PAH metabolism are not related to the well-characterized naphthalene dioxygenase gene. DNA hybridization was not detected when the alkB gene from Pseudomonas oleovorans was used under high-stringency conditions. However, there was slight but detectable hybridization under low-stringency conditions. This suggests a distant relationship between genes involved in alkane oxidation.     

Molecular and functional remodeling of electrogenic membrane of hypothalamic neurons in response to changes in their input

Neurons respond to stimuli by integrating generator and synaptic potentials and generating action potentials. However, whether the underlying electrogenic machinery within neurons itself changes, in response to alterations in input, is not known. To determine whether there are changes in Na+ channel expression and function within neurons in response to altered input, we exposed magnocellular neurosecretory cells (MNCs) in the rat supraoptic nucleus to different osmotic milieus by salt-loading and studied Na+ channel mRNA and protein, and Na+ currents, in these cells. In situ hybridization demonstrated significantly increased mRNA levels for alpha-II, Na6, beta1 and beta2 Na+ channel subunits, and immunohistochemistry/immunoblotting showed increased Na+ channel protein after salt-loading. Using patch-clamp recordings to examine the deployment of functional Na+ channels in the membranes of MNCs, we observed an increase in the amplitude of the transient Na+ current after salt-loading and an even greater increase in amplitude and density of the persistent Na+ current evoked at subthreshold potentials by slow ramp depolarizations. These results demonstrate that MNCs respond to salt-loading by selectively synthesizing additional, functional Na+ channel subtypes whose deployment in the membrane changes its electrogenic properties. Thus, neurons may respond to changes in their input not only by producing different patterns of electrical activity, but also by remodeling the electrogenic machinery that underlies this activity.     

Patterning of the R7 and R8 photoreceptor cells of Drosophila: evidence for induced and default cell-fate specification

Opsin gene expression in the R7 and R8 photoreceptor cells of the Drosophila compound eye is highly coordinated. We have found that the R8 cell specific Rh5 and Rh6 opsins are expressed in non-overlapping sets of R8 cells, in a precise pairwise fashion with Rh3 and Rh4 in the R7 cells of individual ommatidia. Removal of the R7 cells in sevenless, boss or sina mutants, disrupts Rh5 expression and dramatically increases the number of Rh6-expressing R8 cells. This suggests that the expression of Rh5 may be induced by an Rh3-expressing R7 cell, whereas Rh6 expression is most likely a default state of the R8 cell. We found that the paired expression of opsin genes in the R7 and R8 cells occurs in a sevenless and boss independent manner. Furthermore, we found that the generation of both Rh3- and Rh4-expressing R7 cells can occur in the absence of an R8 cell. These results suggest that the specification of opsin expression in the R7 cells may occur autonomously, whereas the R7 photoreceptor cell may be responsible for regulating a binary developmental switch between induced and default cell-fates in the R8 cell.