Failure of eruption of first permanent molar teeth: a diagnostic challenge

Ankylosis, mechanical and primary failure of eruption of molar teeth are rare and often difficult to distinguish between. All may have significant repercussions on the occlusion and successful management may involve invasive procedures. We present a case where an initial presentation characteristic of mechanical failure of eruption (ankylosis) of a first permanent molar tooth was excluded following a period of monitoring. Subsequent relief of crowding using a removable and then sectional fixed orthodontic appliance allowed spontaneous eruption of the tooth obviating the need for surgical intervention. This case highlights the utilisation of conservative treatment options until a diagnosis was confirmed to minimise the risk of iatrogenic damage and unnecessary treatment.     

The hemochromatosis protein HFE inhibits iron export from macrophages

Hereditary hemochromatosis (HH) is a disorder of iron metabolism caused by common mutations in the gene HFE. The HFE protein binds to transferrin receptor-1 (TfR1) in competition with transferrin, and in vitro, reduces cellular iron by reducing iron uptake. However, in vivo, HFE is strongly expressed by liver macrophages and intestinal crypt cells, which behave as though they are relatively iron-deficient in HH. These latter observations suggest, paradoxically, that expression of wild-type HFE may lead to iron accumulation in these specialized cell types. Here we show that wild-type HFE protein raises cellular iron by inhibiting iron efflux from the monocytemacrophage cell line THP-1, and extend these results to macrophages derived from healthy individuals and HH patients. In addition, we find that the HH-associated mutant H41D has lost the ability to inhibit iron release despite binding to TfR1 as well as wild-type HFE. Finally, we show that the ability of HFE to block iron release is not competitively inhibited by transferrin. We conclude that HFE has two mutually exclusive functions, binding to TfR1 in competition with Tf, or inhibition of iron release.     

Carbetocin at elective Cesarean delivery: a sequential allocation trial to determine the minimum effective dose

Purpose

The purpose of this study was to determine the intravenous dose of carbetocin required to produce effective uterine contraction in 90% of females (ED₉₀) undergoing elective Cesarean delivery (CD) under spinal anesthesia.

Methods

We conducted a double-blind dose-finding study of carbetocin. Forty females undergoing elective CD received carbetocin intravenously upon delivery of the fetus. The dose of carbetocin for each patient was determined according to a biased-coin up-and-down sequential allocation scheme designed to cluster doses close to ED₉₀. The initial dose was 10 μg, with increments/decrements of 5 μg. The anesthesiologist, obstetrician, and patient were blinded to the dose. The obstetrician assessed the uterine tone at one-minute intervals for five minutes after carbetocin administration. In case of unsatisfactory tone, additional uterotonics were administered. The primary outcome was requirement for additional intraoperative uterotonics. Secondary outcomes were postoperative requirement for additional uterotonics within 24 hr of delivery, estimated blood loss and side effects.

Results

The ED₉₀ of carbetocin was 14.8 μg (95% confidence interval 13.7 to 15.8). Thirty-seven patients (92.5%) had adequate uterine tone with no requirement of additional intraoperative uterotonics. Two patients (5%) required postoperative uterotonics within 24 hr. The overall mean (SD) estimated blood loss was 786 (403) mL and the overall incidence of hypotension (decrease in systolic blood pressure ≥ 20% baseline) was 37.5%.

Conclusion

Based on our study, the ED₉₀ of carbetocin at elective CD is less than one-fifth the currently recommended dose of 100 μg. This study was registered at clinicaltrials.gov (NCT-01651130).     

Age-related changes in mitochondrial respiration and oxidative damage in the cerebral cortex of the Fischer 344 rat

This study probed possible age-related changes in mitochondrial bioenergetics in naïve Fischer 344 rats. Synaptic and extrasynaptic mitochondria were isolated from the cortex of one hemisphere of young (3-5 months), middle (12-14 months), or aged (22-24 months) rats. Respiration parameters were obtained using a Clarke-type electrode. Aged rats displayed no significant alterations in respiration, indicating mitochondria must be more resilient to the aging process than previously thought. Synaptic mitochondria displayed lower respiration capacities than the extrasynaptic fraction. Aged F344 rats appear capable of normal electron transport chain function without declines in ability to produce ATP. Markers of cortical oxidative damage (3-nitrotyrosine [3-NT], 4-hydroxynonenal [4-HNE], and protein carbonyls [PC]) were collected from the post-mitochondrial supernatant (PMS) from the contralateral hemisphere, and from mitochondrial samples following respiration analysis. Age-related increases in PC and 3-NT levels were found in synaptic mitochondria, whereas significant extrasynaptic elevations were only found in middle aged rats. These findings support an age-related increase in oxidative damage in the cortex, while proposing the two fractions of mitochondria are differentially affected by the aging process. Levels of oxidative damage that accumulates in the cortex with age does not appear to significantly impair cortical mitochondrial respiration of F344 rats.     

Dietary iron status has little effect on expression of ceruloplasmin but alters that of ferritin in rats

Evidence supports a role for ceruloplasmin (ferroxidase I) in the release of iron to the blood from mammalian cells. However, recent studies with cultured cells have suggested that it has the opposite effect, and that iron deficiency enhances expression of ceruloplasmin. We therefore examined in rats how nutritional iron status would affect expression of ceruloplasmin. Groups of male Sprague-Dawley rats were reared on a low iron, starch-based diet for 6-8 wk; half were supplemented by injection of iron dextran. At killing, hematocrits of deficient rats were half normal. Supplemented rats had normal liver concentrations of ferritin and ferritin iron. No ferritin was detected in the livers of the deficient rats. Northern analysis showed that ferritin L and H mRNAs were present in the deficient livers, but expression was half that of the normal rats. There was also twice as much copper. Levels of circulating ceruloplasmin (measured by rocket immunoelectrophoresis) were not altered by iron deficiency, although p-phenylenediamine oxidase activity and plasma copper were reduced approximately 30%. In repeated studies, no differences in the expression of hepatic ceruloplasmin mRNA were detected. Treatment of rats of both sexes with additional iron (25 mg as iron dextran) 5-14 d before killing increased liver ferritin but did not alter liver ceruloplasmin mRNA expression or levels of circulating ceruloplasmin. We conclude that iron status is not an important factor in the expression of plasma ceruloplasmin made by the liver. However, it does have modest effects on steady-state levels of liver ferritin mRNA.     

Oxidative stress and toxicity induced by the nucleoside reverse transcriptase inhibitor (NRTI)--2',3'-dideoxycytidine (ddC): relevance to HIV-dementia

Human immunodeficiency virus dementia (HIVD) is the most common form of dementia occurring among young adults. In HIVD, neuronal cell loss occurs in the absence of neuronal infection. With the advent of highly active anti-retroviral therapy (HAART), the incidence of HIVD has drastically reduced, though prevalence of milder forms of HIVD continues to rise. Though these agents have been used successfully in suppressing viral production, they have also been associated with a number of side effects. Here we examine the possible role of NRTIs, in particular 2',3'-dideoxycytidine (ddC), in the neuropathology of HIVD. Synaptosomes and isolated mitochondria treated and incubated for 6 h with CSF-achievable concentrations of ddC, i.e., 6-11 ng/ml, were found to show a significant increase in oxidative stress with 40 nM ddC as measured by protein carbonyls and 3-nitrotyrosine (3NT), effects that were not observed in the more tolerable NRTI, 3TC. Protection against protein oxidation induced by ddC was observed when brain mitochondria were isolated from gerbils 1 h after injection i.p. with the brain accessible antioxidant and glutathione mimetic, tricyclodecan-9-yl-xanthogenate (D609). In addition, there is a significant reduction in the levels of anti-apoptotic protein Bcl-2 and a significant increase in cytochrome c release and also a significant increase in the expression of pro-apoptotic protein caspase-3 after mitochondria were treated with 40 nM ddC. The results reported here show that ddC at 40 nM can induce oxidative stress, cause the release of cytochrome c, and in addition, reduce the levels of anti-apoptotic proteins, increase the levels of pro-apoptotic proteins, thereby increasing the possibility for induction of apoptosis. These findings are consistent with the notion of a possible role of the NRTIs, and in particular, ddC, in the mechanisms involved in HIVD.     

Post-Tonsillectomy Pain and Vomiting:Role of Pre-operative Steroids

Objective: To evaluate the effects of a single pre-operative dose of dexamethasone with the frequency of postoperative vomiting and severity of throat pain in children undergoing electrocautery tonsillectomy under standard general anaesthesia. Study Design: Randomised controlled trial. Place and Duration of Study: ENT Department, Combined Military Hospital, Kharian, from January to December 2010. Methodology: Children of either gender aged between 4 - 12 years, undergoing tonsillectomy were divided into two groups of 50 each. One group was selected to receive dexamethasone 0.5 mg/kg (maximum of 8 mg); the second group was given equivalent volume of saline, pre-operatively. The frequency of early and late vomiting was assessed postextubation. Mean time of first oral intake in minutes after extubation and mean score of postoperative throat pain were compared in both groups. Severity of throat pain was monitored by Visual Analogue Scale (VAS) score 0-10 after 4,8,12 and 24 hours of extubation. Results: Dexamethasone group showed significantly less postoperative early vomiting (12%, n = 6) as compared to placebo (30%, n = 15) group (p < 0.05). The mean time of first oral intake was earlier in the dexamethasone group (4 hours and 16 minutes postextubation), while in saline group it was 5 hours and 20 minutes (p < 0.001). Pain score was also significantly lower and swallowing was less painful in patients after 4,8,12 and 24 hours in dexamethasone group. Pain score on the average was 0.8 - 1.2 factors less in dexamethasone group than in saline group in first 24 hours on a VAS score of 1 -10. Conclusion: Pre-operative intravenous dexamethasone reduced postoperative vomiting and pain significantly in children undergoing electrocautery tonsillectomy.     

Inhibition of NF-κB activation by 5-lipoxygenase inhibitors protects brain against injury in a rat model of focal cerebral ischemia

Background  

Stroke is one of the leading causes of death worldwide and a major cause of morbidity and mortality in the United States of America. Brain ischemia-reperfusion (IR) triggers a complex series of biochemical events including inflammation. Leukotrienes derived from 5-lipoxygenase (5-LOX) cause inflammation and are thus involved in the pathobiology of stroke injury.