Relationship Between Osteoporosis and Marginal Bone Loss in Osseointegrated Implants: A 2‐Year Retrospective Study

Background: Fitting implants in osteoporotic patients has traditionally been controversial, and there is little scientific evidence relating osteoporosis to marginal bone loss (MBL). The aims of this study are as follows: 1) to evaluate the possibility of a correlation between osteoporosis, as measured by the mandibular cortical index (MCI), and MBL and 2) to assess how various systemic diseases, periodontitis, and placement of implants in regenerated bone are correlated with MBL and MCI. Methods: This retrospective study examines 212 implants inserted in 67 patients. To take a possible cluster failure into account, an implant for each patient was selected (n = 67 implants). MBL was assessed. Osteoporosis was evaluated using the MCI. Both MBL and MCI were assessed from panoramic radiographs. χ² test was performed (Haberman post hoc test). Significance was P <0.05. Results: When the total sample implant (N = 212) was evaluated, a significant association was found between the presence of osteoporosis and MCI (P <0.001) and between the presence of diabetes mellitus and MCI (P <0.01). Significant associations were also found between MBL and placement of implants in regenerated sites (P <0.001) and between MBL and a previous history of periodontitis (P <0.05). When the sample is evaluated only in selected implants (one per patient, n = 67), significant differences appear to relate only to the MBL with the placement of implants in regenerated bone sites (P <0.001). Conclusions: Osteoporosis (as evaluated by MCI) does not pose a risk for the development of greater MBL. Parameters adversely affecting the development of increased MBL are a previous history of periodontitis and especially the placement of implants at sites of bone regeneration.     

Effect of erythromycin on antroduodenal motility in children with chronic functional gastrointestinal symptoms

To evaluate the effects of erythromycin on antroduodenal motility in children with chronic functional gastrointestinal symptoms, we studied 35 consecutive subjects referred for diagnostic motility studies. We recorded fasting motility for >4 hr, then infused in random order either 1 or 3 mg/kg erythromycin intravenously over 1 hr and continued the study for another hour. Erythromycin induced phase III in 18 of 20 children who had phase III during fasting compared to only one of 15 who did not (P<0.001). The antral motility index increased after erythromycin (1596±323 vs 436±242 mm Hg/30 min before erythromycin,P<0.005) but the duodenal motility index did not change. The antral motility index was greater in children receiving 3 mg/kg than in those receiving 1 mg/kg (1968±391 vs 1226±285 mm Hg/30 min,P<0.01), but duodenal motility indices did not differ. Only one child receiving the lower dose erythromycin complained of abdominal pain, nausea, or vomiting vs 9 of 19 the children receiving the higher dose (P<0.02). In summary, in children with chronic functional gastrointestinal disorders, erythromycin rarely induced phase III in patients who did not have it during fasting. When different doses erythromycin are compared, 1 and 3 mg/kg are equally efficacious in inducing phase III episodes; the lower dose is associated with fewer side effects and the higher dose produces a higher antral motility index.     

Properties of a cell-free system for synthesis of citrus exocortis viroid

Partially purified nuclei from citrus exocortis viroid (CEV)-infected Gynura aurantiaca are able to synthesize linear and circular viroid molecules. Pretreatment of the nuclei with actinomycin D or deoxyribonuclease did not affect viroid synthesis, whereas the synthesis of other cellular RNAs was severely reduced. These observations support the essential role of CEV complementary RNA sequences in viroid replication. However, when α-amanitin was included in this in vitro synthesis system, CEV replication was markedly reduced by concentrations of 10 nM or greater. Taken together, these data support the proposition that viroid synthesis is catalyzed by a DNA-dependent RNA polymerase acting on a RNA template.     

Susceptibility of murine periportal hepatocytes to hypoxia-reoxygenation: role for NO and Kupffer cell-derived oxidants

Ischemia/reperfusion (I/R) is an important problem in liver resection and transplantation that is associated with hepatocellular dysfunction and injury. This study was designed to investigate whether a difference in hepatocyte susceptibility occurs in the periportal (PP) and/or perivenous (PV) zones in response to hypoxia/reoxygenation (H/R), and to delineate the mechanisms underlying this susceptibility. H/R was induced in an in situ perfused mouse liver model with deoxygenated Krebs-Henseleit buffer followed by oxygenated buffer. Selective destruction of PP or PV sites was achieved by digitonin perfusion into the portal or inferior vena cava, and was confirmed by histological evaluations and zone-specific enzymes. Hepatocellular injury was assessed by alanine aminotransferase (ALT) release. In whole liver, H/R significantly increased perfusate ALT. H/R of PP-enriched zones caused ALT release that was similar to that of whole liver (80 + 10 vs. 70 + 12 U/mg protein), consistent with significant PP hepatocyte injury. Minimal ALT release occurred in PV zones (10 + 5 U/mg protein). Administration of N-acetyl L-cysteine or a chimeric superoxide dismutase (SOD)-SOD2/3, a genetically engineered SOD-abrogated ALT release in H/R-perfused PP zones, implicating a role for superoxide (O(2) (-)). This elevated ALT release was attenuated by gadolinium chloride pretreatment, indicating that Kupffer cells are the O(2) (-) source. Enzymatic inhibition of cellular nitric oxide synthase (NOS) or genetic depletion of endothelial nitric oxide synthase (eNOS) aggravated hypoxia injury while exogenous NO and inducible nitric oxide synthase (iNOS) deficiency abolished reoxygenation injury. In conclusion, PP hepatocytes are more vulnerable to H/R; this injury is mediated directly or indirectly by Kupffer cell derived O(2) (-) and is limited by eNOS-derived NO.     

Exercise training improves baroreflex sensitivity associated with oxidative stress reduction in ovariectomized rats

The protection from coronary events that young women have is sharply reduced at menopause. Oxidative stress and baroreflex sensitivity impairment of the circulation have been demonstrated to increase cardiovascular risk. On the other hand, exercise training has been indicated as a nonpharmacological treatment for many diseases. The aim of the present study was to test the hypothesis that exercise training can improve baroreflex sensitivity associated with reduction in oxidative stress in ovariectomized rats, an experimental model of menopause. Exercise training was performed on a treadmill for 8 weeks. Arterial pressure and baroreflex sensitivity, which were evaluated by tachycardic and bradycardic responses to changes in arterial pressure, were monitored. Oxidative stress was evaluated by chemiluminescence and superoxide dismutase and catalase antioxidant enzyme activities. Exercise training reduced resting mean arterial pressure (112+/-2 vs 122+/-3 mm Hg in the sedentary group) and heart rate (325+/-4 vs 356+/-12 bpm in the sedentary group) and also improved baroreflex sensitivity (tachycardic response, 63% and bradycardic response, 58%). Myocardium (25%) and gastrocnemius muscle (48%) chemiluminescence were reduced, and myocardial superoxide dismutase (44%) and gastrocnemius catalase (97%) activities were enhanced in trained rats in comparison with sedentary rats. Myocardium chemiluminescence was positively correlated with systolic arterial pressure (r=0.6) and inversely correlated with baroreflex sensitivity (tachycardic response, r=-0.8 and bradycardic response, r=-0.7). These results indicate that exercise training in ovariectomized rats improves resting hemodynamic status and reflex control of the circulation, probably associated with oxidative stress reduction, suggesting a homeostatic role for exercise training in reducing cardiovascular risk in postmenopausal women.     

Peripheral nerve abnormalities in newly-diagnosed diabetic children

Summary The prevalence of clinical and subclinical peripheral neuropathy was evaluated in 51 unselected children at the time of onset of type I diabetes. Twenty-eight patients were followed for one year in order to establish the influence of metabolic control on peripheral nerve function. Twenty-two % of the diabetic children showed nerve conduction abnormalities at the onset and 11.7% had clinical features of peripheral neuropathy. After one year of disease, these figures had changed to 14.3% and 7.1%. Five of 7 children with altered electrophysiological tests in the baseline assessment had had normalization of all parameters one year later. No correlations between insulin requirement and nerve conduction were found. The M value was significantly correlated only with median sensory conduction velocity (p<0.005). Significant correlations were demonstrated between HbA₁ concentration and both peroneal motor conduction velocity (p<0.025) and median sensory conduction velocity (p<0.005); these correlations were still present after one year of disease. In the first period of diabetic disease there is functional rather than structural damage of the nerves. The pathogenetic role of hyperglycemia is confirmed; however individual susceptibility to nerve dysfunction may play an important role in the nerve impairment in diabetes. This study was supported by the C.N.R. Project ‘Preventive and Rehabilitative Medicine’, Subproject ‘Degenerative Diseases of the Nervous System’; Project N. 84.02472.56.115.10324.     

Activation of the anti‐inflammatory reflex blocks lipopolysaccharide‐induced decrease in synaptic inhibition in the temporal cortex of the rat

Stress is a potential trigger for a number of neuropsychiatric conditions, including anxiety syndromes and schizophrenic psychoses. The temporal neocortex is a stress‐sensitive area involved in the development of such conditions. We have recently shown that aseptic inflammation and mild electric shock shift the balance between synaptic excitation and synaptic inhibition in favor of the former in this brain area (Garcia‐Oscos et al., 2012), as well as in the prefrontal cortex (Garcia‐Oscos et al., 2014). Given the potential clinical importance of this phenomenon in the etiology of hyperexcitable neuropsychiatric illness, this study investigates whether inactivation of the peripheral immune system by the “anti‐inflammatory reflex” would reduce the central response to aseptic inflammation. For a model of aseptic inflammation, this study used i.p. injections of the bacterial toxin lipopolysaccharide (LPS; 5 µM) and activated the anti‐inflammatory reflex either pharmacologically by i.p. injections of the nicotinic α₇ receptor agonist PHA543613 or physiologically through electrical stimulation of the left vagal nerve (VNS). Patch‐clamp recording was used to monitor synaptic function. Recordings from LPS‐injected Sprague Dawley rats show that activation of the anti‐inflammatory reflex either pharmacologically or by VNS blocks or greatly reduces the LPS‐induced decrease of the synaptic inhibitory‐to‐excitatory ratio and the saturation level of inhibitory current input–output curves. Given the ample variety of pharmacologically available α₇ nicotinic receptor agonists as well as the relative safety of clinical VNS already approved by the FDA for the treatment of epilepsy and depression, our findings suggest a new therapeutic avenue in the treatment of stress‐induced hyperexcitable conditions mediated by a decrease in synaptic inhibition in the temporal cortex. © 2015 Wiley Periodicals, Inc.     

Differential contributions of microglial and neuronal IKKβ to synaptic plasticity and associative learning in alert behaving mice

Microglia are CNS resident immune cells and a rich source of neuroactive mediators, but their contribution to physiological brain processes such as synaptic plasticity, learning, and memory is not fully understood. In this study, we used mice with partial depletion of IκB kinase β, the main activating kinase in the inducible NF‐κB pathway, selectively in myeloid lineage cells (mIKKβKO) or excitatory neurons (nIKKβKO) to measure synaptic strength at hippocampal Schaffer collaterals during long‐term potentiation (LTP) and instrumental conditioning in alert behaving individuals. Resting microglial cells in mIKKβKO mice showed less Iba1‐immunoreactivity, and brain IL‐1β mRNA levels were selectively reduced compared with controls. Measurement of field excitatory postsynaptic potentials (fEPSPs) evoked by stimulation of the CA3‐CA1 synapse in mIKKβKO mice showed higher facilitation in response to paired pulses and enhanced LTP following high frequency stimulation. In contrast, nIKKβKO mice showed normal basic synaptic transmission and LTP induction but impairments in late LTP. To understand the consequences of such impairments in synaptic plasticity for learning and memory, we measured CA1 fEPSPs in behaving mice during instrumental conditioning. IKKβ was not necessary in either microglia or neurons for mice to learn lever‐pressing (appetitive behavior) to obtain food (consummatory behavior) but was required in both for modification of their hippocampus‐dependent appetitive, not consummatory behavior. Our results show that microglia, through IKKβ and therefore NF‐κB activity, regulate hippocampal synaptic plasticity and that both microglia and neurons, through IKKβ, are necessary for animals to modify hippocampus‐driven behavior during associative learning. GLIA 2015;63:549–566     

Neurobiological and Clinical Variables Associated with Alcohol Abuse in Bulimia Nervosa

The study was aimed at analysing the reciprocal relationships of several clinical and neurobiological items in order to predict alcohol misuse in patients with bulimia nervosa (BN). Seventy BN patients and 70 healthy controls were assessed for depression, impulsivity, borderline personality traits and self‐defeating behaviours using specific scales; serum cortisol and 24‐hour urinary excretion of serotonin and 5‐hydroxiindolacetic acid were also assessed. The study confirmed the implications of these clinical factors for alcohol misuse in BN patients, but the results suggested that depressive symptoms and hypercortisolism could lie behind these relationships. Copyright © 2015 John Wiley & Sons, Ltd and Eating Disorders Association.