Idazoxan down-regulates beta-adrenoceptors on C6 glioma cells in vitro.

Incubation of the C6 cells with 10 microM idazoxan (an alpha 2-adrenoceptor antagonist and putative antidepressant) for 5 days in vitro resulted in a 23% reduction of beta-adrenoceptor number and a 37% decrease in isoproterenol-induced cyclic AMP accumulation. In contrast, post-receptor stimulated cyclic AMP accumulation (by the use of forskolin or cholera toxin) was unaffected. The desensitization of the beta-adrenoceptor was accompanied by an increase in the KL/KH ratio for this receptor. Chronic in vitro treatment of C6 glioma cells with idazoxan did not significantly affect cholera or pertussis toxin catalyzed ribosylation of Gs and Gi/Go in these cells. Similarly, idazoxan did not alter either the basal levels of protein kinase C (PKC) alpha, or its cytoplasm to membrane translocation. These results suggest that idazoxan may have direct postsynaptic effects, the site of which may be at the level of receptor/G protein interaction.     

Progressive multifocal leucoencephalopathy isolated to the posterior fossa in a patient with systemic lupus erythematosus

SIR, Progressive multifocal leucoencephalopathy (PML) may complicateimmunosuppressive states other than HIV infection. Its presentationas an isolated posterior fossa lesion is uncommon. We describehere ante-mortem diagnosis on cerebellar biopsy of PML in apatient with systemic lupus erythematosus (SLE) immunosuppressedwith prednisolone and azathioprine. The case illustrates boththat immunosuppression, other than that induced by HIV, maybe complicated by PML and that this devastating opportunisticviral infection should be considered in the differential diagnosisof isolated progressive posterior fossa white matter disease. A 41-yr-old Asian     

Randomized trial of vitamin supplements in relation to transmission of HIV-1 through breastfeeding and early child mortality

BACKGROUND: HIV-1 transmission through breastfeeding is a global problem and has been associated with poor maternal micronutrient status. METHODS: A total of 1078 HIV-infected pregnant women from Tanzania were randomly assigned to vitamin A or multivitamins excluding A from approximately 20 weeks' gestation and throughout lactation. RESULTS: Multivitamins excluding A had no effect on the total risk of HIV-1 transmission (RR 1.04, 95% CI 0.82-1.32, P= 0.76). Vitamin A increased the risk of transmission (RR 1.38, 95% CI 1.09-1.76, P = 0.009). Multivitamins were associated with non-statistically significant reductions in transmission through breastfeeding, and mortality by 24 months among those alive and not infected at 6 weeks. Multivitamins significantly reduced breastfeeding transmission in infants of mothers with low baseline lymphocyte counts (RR 0.37; 95% CI 0.16-0.85, P = 0.02) compared with infants of mothers with higher counts (RR 0.99, 95% CI 0.68-1.45, P = 0.97; -for-interaction 0.03). Multivitamins also protected against transmission among mothers with a high erythrocyte sedimentation rate (P-for-interaction 0.06), low hemoglobin (P-for-interaction 0.06), and low birthweight babies (P-for-interaction 0.04). Multivitamins reduced death and prolonged HIV-free survival significantly among children born to women with low maternal immunological or nutritional status. Vitamin A alone increased breastfeeding transmission but had no effect on mortality by 24 months. CONCLUSION: Vitamin A increased the risk of HIV-1 transmission. Multivitamin (B, C, and E) supplementation of breastfeeding mothers reduced child mortality and HIV-1 transmission through breastfeeding among immunologically and nutritionally compromised women. The provision of these supplements to HIV-infected lactating women should be considered.     

Seizures following cardiac surgery: the impact of tranexamic acid and other risk factors

Background

Seizures after cardiac surgery are a serious complication. The antifibrinolytic agent tranexamic acid (TA), which has known proconvulsant properties, may be associated with postoperative seizures. We sought to determine the association between TA and other risk factors for seizures after cardiac surgery.

Methods and results

We analyzed a database of consecutive cardiac surgery patients (April 2003 to December 2009) using multivariable logistic regression analysis to assess for seizure risk factors. Seizures occurred in 56 of 5,958 patients (0.94%). TA use was associated with an increased risk of seizures (odds ratio 7.4, 95% confidence interval 2.8?C19.3; P??20; preoperative cardiac arrest; preoperative neurological disease; open chamber surgery; cardiopulmonary bypass time?>?150?min; and previous cardiac surgery. Seizures occurred at a median of 5.3 hr (interquartile range 2.4?C15.1 hr) after the end of surgery. In all, 58.1% were grand mal, 14.5% were associated with a stroke, and 58.1% recurred in hospital. Altogether, 48.3% of the patients were able to discontinue anticonvulsant medications prior to discharge. Compared to the non-seizure group, seizure patients had an increased rate of postoperative neurological complications, defined as delirium and/or stroke (3.2% vs 19.6%, P?vs 4.7?days, P?<?0.001), and increased ICU mortality (1.4 % vs 9.7 %, P?=?0.001).

Conclusions

Our data suggest that multiple risk factors, including TA, are associated with seizures after cardiac surgery. Thus, the TA dose may be a readily modifiable risk factor for postoperative seizures.     

Chronic exposure of C6 glioma cells to desipramine desensitizes beta-adrenoceptors, but increases KL/KH ratio.

Incubation of rat glioma C6 cells with 10 microM desipramine for five days in vitro resulted in a 31% reduction of beta-adrenoceptors and a 38% reduction in isoproterenol-stimulated cyclic AMP accumulation. In contrast, forskolin or cholera toxin-stimulated cyclic AMP was unaffected by desipramine. Surprisingly, the beta-adrenoceptor desensitization was accompanied by an increase in the ratio of dissociation constants (KL/KH) for the low and high affinity states of the beta-adrenoceptor respectively and supports the concept of a complex interaction between the receptor and Gs protein.     

The mechanisms of action of lithium. II. Effects on adenylate cyclase activity and beta-adrenergic receptor binding in normal subjects.

As part of a study of the effects of lithium carbonate on neurochemical function in man, platelet and lymphocyte adenylate cyclase activity and lymphocyte beta-adrenergic receptor binding characteristics were determined before and after 2 weeks of lithium treatment in 10 normal volunteers. Lithium had differential effects on platelet and lymphocyte adenylate cyclase activity. In platelets, basal and stimulated (guanyl imidodiphosphate [Gpp[NH]p] or cesium fluoride) adenylate cyclase activity was significantly augmented by lithium treatment. By contrast, in lymphocytes, Gpp(NH)p- and cesium fluoride-stimulated adenylate cyclase activity was unaffected, while basal activity was decreased modestly after lithium. These results are consistent with preclinical studies that suggest that lithium's effects on adenylate cyclase activity are specific with respect to tissue and brain region and that lithium may interfere with guanine nucleotide binding (G) protein function. Lithium treatment significantly increased the ratio of low- to high-affinity dissociation constants for agonist displacement of antagonist binding to lymphocyte beta-adrenergic receptors (thought to reflect coupling between the beta-adrenergic receptor and stimulatory G protein). Lithium had significant effects on measures associated with signal transduction that might be contrasted to its more subtle effects on neuronal function (norepinephrine release) and neuroendocrine systems (responses to serotoninergic challenge) in these same subjects (reported in a companion article). Lithium's primary site of action may be on signal transduction mechanisms. These effects subsequently may be manifested in changes in neurotransmitter function that may be important to lithium's mood-stabilizing actions.     

Designing better dentistry: the ergonomic approach.

The ergonomic dental office is designed around the people who work there on a daily basis as well as the patients it serves. Because it is attractive, functional, esthetic and comfortable, it cultivates happy, productive dental teams and relaxed, contented patients. An ergonomic office enables people to move about freely, with easy access to the materials and equipment they need. And it encourages staff to take pride in their jobs, an activity that occupies more than half of their waking hours. In other words, the ergonomic office is not a luxury; it's an essential.     

Cellular plasticity cascades in the pathophysiology and treatment of bipolar disorder.

Bipolar disorder (BPD) is characterized by recurrent episodes of disturbed affect including mania and depression as well as changes in psychovegetative function, cognitive performance, and general health. A growing body of data suggests that BPD arises from abnormalities in synaptic and neuronal plasticity cascades, leading to aberrant information processing in critical synapses and circuits. Thus, these illnesses can best be conceptualized as genetically influenced disorders of synapses and circuits rather than simply as deficits or excesses in individual neurotransmitters. In addition, commonly used mood-stabilizing drugs that are effective in treating BPD have been shown to target intracellular signaling pathways that control synaptic plasticity and cellular resilience. In this article we draw on clinical, preclinical, neuroimaging, and post-mortem data to discuss the neurobiology of BPD within a conceptual framework while highlighting the role of neuroplasticity in the pathophysiology and treatment of this disorder.     

Profiles of destructive periodontal disease in different populations

In this study we evaluated the traditional view that the severity of periodontal disease varies between populations in that African and Asian populations are more severely affected than other populations. Our data on periodontal destruction in two random samples of a Kenyan and a Chinese adult population were recalculated to conform with the methods of examination and data presentation utilized in each of 6 other studies of attachment loss levels in different populations. The adult Kenyan and the adult Chinese group, who had very poor oral hygiene conditions and massive gingival inflammation, had attachment loss levels which were quite similar to those in a Japanese population (31), in a Norwegian population (27) and in a New Mexico group of adults (30). Attachment losses were similar in a population of young US adults (26) aged between 35 and 60 years relative to the corresponding Kenyan and Chinese groups while young US citizens had higher and elderly US citizens had lower mean attachment levels than either Kenyans or Chinese. Higher attachment loss levels beyond the age of 27 years were reported for a population of Sri Lankan tamil tea workers (27) and across all ages in two South Pacific island populations (29). Overall, the analysis indicates that the periodontal attachment loss profiles may differ between populations, but that these differences do not conform with the traditional generalization that African and Asian populations suffer more severe periodontal breakdown than other populations.