In Vitro Interaction of Lithium on Phospholipids in Human Erythrocytes

Lithium salts are used in the treatment of mania and as prophylaxis against manic depressive disorder. The aim of these studies was the in vitro investigation of the effect of lithium on phospholipids of human erythrocyte membranes. Erythrocytes were treated with lithium for 1 h. Phospholipids phosphatidylinositol (PI), phosphatidylserine (PS), phosphatidylethanolamine (PE), and phosphatidylocholine (PC) were separated from erythrocyte ghosts and determined by HPLC. Blood samples from healthy adults were investigated. A very strong decrease in PC content in erythrocyte membranes due to lithium in vitro treatment was found, as well as a statistically significant increase in PI content

Late onset of development of natural anti-nonGal antibodies in infant humans and baboons:implications for xenotransplantation in infants

If an ABO-incompatible heart is transplanted into an infant before natural antibodies have developed to the specific donor carbohydrate A/B antigen(s), then B-cell tolerance to the donor A/B antigen is achieved, and these antibodies never develop. Anti-carbohydrate antibodies play a role in the rejection of wild type (WT) and alpha1,3-galactosyltransferase gene-knockout (GT-KO) pig xenografts. We investigated development of these antibodies in infant baboons and humans. Serum samples from infant baboons (n = 42) and humans (n = 42) were tested by flow cytometry for immunoglobulin M and immunoglobulin G binding to peripheral blood mononuclear cells from WT and GT-KO pigs, and for complement-dependent cytotoxicity. The presence of anti-blood group antibodies was tested in baboon serum. In infant baboons and humans, cytotoxic anti-Galalpha1,3Gal antibodies develop during the first 3 months, and steadily increase with age, whereas cytotoxic anti-nonGal antibodies are either absent or minimal in the majority of cases throughout the first year of life. Anti-blood group antibodies were not detected before 16 weeks of age. Our data suggest GT-KO pig organ/cell transplants could be carried out in early infancy in the absence of preformed cytotoxic anti-nonGalalpha1,3Gal antibodies.</p

Maternal oral health status and preterm low birth weight at Muhimbili National Hospital, Tanzania: a case-control study

The study examined the relationship between oral health status (periodontal disease and carious pulpal exposure (CPE)) and preterm low-birth-weight (PTLBW) infant deliveries among Tanzanian-African mothers at Muhimbili National Hospital (MNH), Tanzania. A retrospective case-control study was conducted, involving 373 postpartum mothers aged 14-44 years (PTLBW--150 cases) and at term normal-birth-weight (TNBW)--223 controls), using structured questionnaire and full-mouth examination for periodontal and dentition status. The mean number of sites with gingival bleeding was higher in PTLBW than in TNBW (P = 0.026). No significant differences were observed for sites with plaque, calculus, teeth with decay, missing, filling (DMFT) between PTLBW and TNBW. Controlling for known risk factors in all post-partum (n = 373), and primiparaous (n = 206) mothers, no significant differences were found regarding periodontal disease diagnosis threshold (PDT) (four sites or more that had probing periodontal pocket depth 4+mm and gingival bleeding > or = 30% sites), and CPE between cases and controls. Significant risk factors for PTLBW among primi- and multiparous mothers together were age < or = 19 years (adjusted Odds Ratio (aOR) = 2.09, 95% Confidence interval (95% CI): 1.18-3.67, P = 0.011), hypertension (aOR = 2.44, (95% CI): 1.20-4.93, P = 0.013) and being un-married (aOR = 1.59, (95% CI): 1.00-2.53, P = 0.049). For primiparous mothers significant risk factors for PTLBW were age < or = 19 years (aOR = 2.07, 95% CI: 1.13 - 3.81, P = 0.019), and being un-married (aOR = 2.58, 95% CI: 1.42-4.67, P = 0.002). These clinical findings show no evidence for periodontal disease or carious pulpal exposure being significant risk factors in PTLBW infant delivery among Tanzanian-Africans mothers at MNH, except for young age, hypertension, and being unmarried. Further research incorporating periodontal pathogens is recommended

Evaluation of Nod-Like Receptor (NLR) Effector Domain Interactions

Members of the Nod-like receptor (NLR) family recognize intracellular pathogens and recruit a variety of effector molecules, including pro-caspases and kinases, which in turn are implicated in cytokine processing and NF-κB activation

Will early detection of non-axillary sentinel nodes affect treatment decisions?

Axillary lymph node involvement is the best prognostic factor for breast cancer survival. Staging breast cancers by axillary dissection remains standard management and is part of the UK national guidelines for breast cancer treatment. In the presence of involved axillary lymph nodes best treatment has been shown to be axillary clearance (Fentiman and Mansell, 1991), but clearly for women whose nodes are uninvolved avoidance of morbidity is optimal and this will be achieved by minimal dissection of the axilla. Thus, for node-negative women the introduction of the sentinel node biopsy technique may revolutionise the approach to the axilla. These will be women with mammographic screen detected small well and moderately differentiated tumours (Hadjiloucas and Bundred, 2000). The impact of sentinel node biopsy in women who have symptomatic large tumours is unproven, and around half of these women will require a second procedure to clear their axilla or radiotherapy as treatment. Even for those women found to have involved sentinel lymph nodes the ability to use early systemic chemotherapy followed by axillary clearance or radiotherapy may provide long-term survival gains. Sentinel node biopsy should not, however, become routine practice until randomised controlled trials have proven its benefit and safety in reducing morbidity. Several randomised controlled trials (including ALMANAC) are currently underway

A double-blind placebo-controlled trial of azithromycin to reduce mortality and improve growth in high-risk young children with non-bloody diarrhoea in low resource settings: the Antibiotics for Children with Diarrhoea (ABCD) trial protocol

Background Acute diarrhoea is a common cause of illness and death among children in low- to middle-income settings. World Health Organization guidelines for the clinical management of acute watery diarrhoea in children focus on oral rehydration, supplemental zinc and feeding advice. Routine use of antibiotics is not recommended except when diarrhoea is bloody or cholera is suspected. Young children who are undernourished or have a dehydrating diarrhoea are more susceptible to death at 90 days after onset of diarrhoea. Given the mortality risk associated with diarrhoea in children with malnutrition or dehydrating diarrhoea, expanding the use of antibiotics for this subset of children could be an important intervention to reduce diarrhoea-associated mortality and morbidity. We designed the Antibiotics for Childhood Diarrhoea (ABCD) trial to test this intervention. Methods ABCD is a double-blind, randomised trial recruiting 11,500 children aged 2–23 months presenting with acute non-bloody diarrhoea who are dehydrated and/or undernourished (i.e. have a high risk for mortality). Enrolled children in Bangladesh, India, Kenya, Malawi, Mali, Pakistan and Tanzania are randomised (1:1) to oral azithromycin 10 mg/kg or placebo once daily for 3 days and followed-up for 180 days. Primary efficacy endpoints are all-cause mortality during the 180 days post-enrolment and change in linear growth 90 days post-enrolment. Discussion Expanding the treatment of acute watery diarrhoea in high-risk children to include an antibiotic may offer an opportunity to reduce deaths. These benefits may result from direct antimicrobial effects on pathogens or other incompletely understood mechanisms including improved nutrition, alterations in immune responsiveness or improved enteric function. The expansion of indications for antibiotic use raises concerns about the emergence of antimicrobial resistance both within treated children and the communities in which they live. ABCD will monitor antimicrobial resistance. The ABCD trial has important policy implications. If the trial shows significant benefits of azithromycin use, this may provide evidence to support reconsideration of antibiotic indications in the present World Health Organization diarrhoea management guidelines. Conversely, if there is no evidence of benefit, these results will support the current avoidance of antibiotics except in dysentery or cholera, thereby avoiding inappropriate use of antibiotics and reaffirming the current guidelines. Trial registration Clinicaltrials.gov, NCT03130114. Registered on April 26 2017

Clinical and socio-behavioral correlates of tooth loss: a study of older adults in Tanzania

BACKGROUND: Focusing 50 year olds and above, this study assessed the frequency, extent and correlates of tooth loss due to various reasons. Frequency and correlates of posterior occluding support was also investigated. METHOD: A cross-sectional household survey was conducted in Pwani region and in Dar es Salaam in 2004/2005. One thousand and thirty-one subjects, mean age 62.9 years participated in a clinical examination and completed interviews. RESULTS: The prevalence of tooth loss due to any reason was 83.5 %, due to caries 63.4% and due to other reasons than caries, 32.5%. A total of 74.9% had reduced number of posterior occluding units. Compared to subjects having less than 5 teeth lost due to caries, those with 5 or more lost teeth were more likely to be females, having decayed teeth, confirming dental attendance and to be among the least poor residents. Compared to subjects who had lost less than 5 teeth due to reasons other than caries, those who had lost 5 or more teeth were more likely to be of higher age, having mobile teeth, being males, being very poor and to disconfirm dental attendance when having problems. Predictors of prevalence of tooth loss (1 or more lost tooth) due to various reasons and reduced number of occluding units followed similar patterns of relationships. CONCLUSION: The results are consistent with prevalence and extent of tooth loss due to caries and due to reasons other than caries being differently related to disease- and socio- behavioral risk indicators. Caries was the principle cause of tooth loss and molar teeth were the teeth most commonly lost

Lithium and GSK3-β promoter gene variants influence white matter microstructure in bipolar disorder

Lithium is the mainstay for the treatment of bipolar disorder (BD) and inhibits glycogen synthase kinase 3-β (GSK3-β). The less active GSK3-β promoter gene variants have been associated with less detrimental clinical features of BD. GSK3-β gene variants and lithium can influence brain gray matter structure in psychiatric conditions. Diffusion tensor imaging (DTI) measures of white matter (WM) integrity showed widespred disruption of WM structure in BD. In a sample of 70 patients affected by a major depressive episode in course of BD, we investigated the effect of ongoing long-term lithium treatment and GSK3-β promoter rs334558 polymorphism on WM microstructure, using DTI and tract-based spatial statistics with threshold-free cluster enhancement. We report that the less active GSK3-β rs334558*C gene-promoter variants, and the long-term administration of the GSK3-β inhibitor lithium, were associated with increases of DTI measures of axial diffusivity (AD) in several WM fiber tracts, including corpus callosum, forceps major, anterior and posterior cingulum bundle (bilaterally including its hippocampal part), left superior and inferior longitudinal fasciculus, left inferior fronto-occipital fasciculus, left posterior thalamic radiation, bilateral superior and posterior corona radiata, and bilateral corticospinal tract. AD reflects the integrity of axons and myelin sheaths. We suggest that GSK3-β inhibition and lithium could counteract the detrimental influences of BD on WM structure, with specific benefits resulting from effects on specific WM tracts contributing to the functional integrity of the brain and involving interhemispheric, limbic, and large frontal, parietal, and fronto-occipital connections

Dendritic Morphology of Hippocampal and Amygdalar Neurons in Adolescent Mice Is Resilient to Genetic Differences in Stress Reactivity

Many studies have shown that chronic stress or corticosterone over-exposure in rodents leads to extensive dendritic remodeling, particularly of principal neurons in the CA3 hippocampal area and the basolateral amygdala. We here investigated to what extent genetic predisposition of mice to high versus low stress reactivity, achieved through selective breeding of CD-1 mice, is also associated with structural plasticity in Golgi-stained neurons. Earlier, it was shown that the highly stress reactive (HR) compared to the intermediate (IR) and low (LR) stress reactive mice line presents a phenotype, with respect to neuroendocrine parameters, sleep architecture, emotional behavior and cognition, that recapitulates some of the features observed in patients suffering from major depression. In late adolescent males of the HR, IR, and LR mouse lines, we observed no significant differences in total dendritic length, number of branch points and branch tips, summated tip order, number of primary dendrites or dendritic complexity of either CA3 pyramidal neurons (apical as well as basal dendrites) or principal neurons in the basolateral amygdala. Apical dendrites of CA1 pyramidal neurons were also unaffected by the differences in stress reactivity of the animals; marginally higher length and complexity of the basal dendrites were found in LR compared to IR but not HR mice. In the same CA1 pyramidal neurons, spine density of distal apical tertiary dendrites was significantly higher in LR compared to IR or HR animals. We tentatively conclude that the dendritic complexity of principal hippocampal and amygdala neurons is remarkably stable in the light of a genetic predisposition to high versus low stress reactivity, while spine density seems more plastic. The latter possibly contributes to the behavioral phenotype of LR versus HR animals