Pronounced susceptibility to infection by Salmonella enterica serovar Typhimurium in mice chronically exposed to lead correlates with a shift to Th2-type immune responses

Persistent exposure to inorganic lead (Pb) is known to adversely affect the immune system. In the present study, we assessed the effect of chronic Pb exposure on susceptibility to infection by the facultative intracellular pathogen Salmonella enterica serovar Typhimurium. Mice were exposed to 10 mM Pb-acetate in drinking water for approximately 16 weeks, resulting in a significant level of Pb in the blood (106.2+/-8.9 microg/dl). Pb exposure rendered mice susceptible to Salmonella infection, manifested by increased bacterial burden in target organs and heightened mortality. Flow cytometric analysis of the splenic cellular composition in normal and Pb-exposed mice revealed no gross alteration in the ratios of B and T lymphocytes or myeloid cells. Similarly, the capacity of B and T cells to upregulate the expression of activation antigens in response to mitogenic or inflammatory stimuli was not hindered by Pb exposure. Analysis of the ability of ex vivo-cultured splenocytes to secrete cytokines demonstrated a marked reduction in IFN-gamma and IL-12p40 production associated with Pb exposure. In contrast, secretion of IL-4 by splenocytes of Pb-treated mice was 3- to 3.6-fold higher than in normal mice. The increased capacity to produce IL-4 correlated with a shift in the in vivo anti-Salmonella antibody response from the protective IgG2a isotype to the Th2-induced IgG1 isotype. We conclude that chronic exposure to high levels of Pb results in a state of immunodeficiency which is not due to an overt cytotoxic or immunosuppressive mechanism, but rather is largely caused by a shift in immune responsiveness to Th2-type reactions.     

Dentofacial development abnormalities in paediatric sleep-related breathing disorders

IntroductionThe recent interest in sleep-related breathing disorders has re-opened the old debate as to whether there is a causal relationship between upper respiratory obstruction and abnormalities in dentofacial development.ObjectiveTo establish the impact of dentofacial development on sleep-related breathing disorders in children.MethodThis is a prospective study in which the dentofacial studies of 30 children, diagnosed with a sleep-related breathing disorder using polysomnography, were compared with a control group of 30 healthy children. The ages of both groups were between 3 and 13 years.ResultsThe statistical analysis showed significant differences between the groups in the proportion of children with a narrow palate (83% of the problem group and 57% in the control; P = 0.024) and cross bite (40% and 13%; P = 0.020). On comparing the angles measured, the only statistically-significant difference was the skull base-mandibular plane angle: The problem children group had a mean of 37.59 ± 5.56 and the control group, a mean of 34.41 ± 4.62 (P = 0.023).ConclusionChildren with sleep-related breathing disorders have abnormalities in facial and dental development caused by upper respiratory obstruction. These anomalies, vertical growth of the face, narrow palate and dental occlusion changes should be taken into account when assessing the indication for a adenotonsillectomy.     

Congenital non-familial unilateral basaloid follicular hamartoma

Basaloid follicular hamartoma is not a well-recognized clinical entity and has often been diagnosed as trichoepithelioma or basal cell carcinoma. It is a unique benign follicular tumour which comprises a variety of clinical manifestations. We present the case of a 24-year-old male with unilateral basaloid follicular hamartoma present at birth and later misdiagnosed as basal cell carcinoma. Histological features of basaloid follicular hamartoma are not always diagnostic and clinico-pathological correlation is particularly important to distinguish this benign hamartoma from other basaloid tumours including basal cell carcinoma. Continuous follow-up of our patient did not reveal any clinical or histological malignant transformation.     

A Mysterious Crescent in the Heart: Ruptured Sinus of Valsalva Dissecting Interatrial Septum,Multimodality Imaging,and Full Recovery

A 59‐year‐old man who was admitted to the emergency department with new and spontaneous onset of fatigue, dyspnea, and palpitations. There was neither a history of trauma, chest pain, nor infection. Transthoracic two‐ and three‐dimensional echocardiography and computer tomography demonstrated sinus of Valsalva aneurysm rupture dissecting interatrial septum and leading to a huge thrombus formation in it. The diagnosis with multimodality imaging performed within hours, and urgent surgery saved the patient's life.     

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A novel anticholinesterase THB013: Biochemical and behavioural studies

Summary Clinical trials with tacrine (THA) have resulted in elevations of liver enzymes in Alzheimer patients that showed improvement. In an effort to minimize these side effects several THA analogues were synthesized. These analogues were compared to THA in biochemical as well as behavioural studies. In this study, the biochemical effects of THA and one of these analogs, THB 013, on plasma cholinesterase activity, cholinergic receptors as well as the effect of these drugs on spatial learning in adult rats were examined. THB 013 was, at lower concentration, more efficacious in inhibiting plasma cholinesterase as well as blocking the scopolamine induced disruption of spatial learning when administered 10 min before the scopolamine injection. It is possible that THB 013 with more potent cholinergic effects than THA might be useful in the treatment of Alzheimer's disease.     

Right ventricular function and its relationship with grade of hepatosteatosis in non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD) is increasingly recognised as the most common cause of chronic liver disease worldwide.1 NAFLD encompasses a spectrum of disorders, including variable degrees of simple hepatic steatosis (HS, fatty liver), non-alcoholic steatohepatitis (NASH) and cirrhosis.This disease is a common clinicopathological condition characterised by significant lipid deposition in the hepatocytes of the liver parenchyma in the absence of alcohol abuse, contributing medications and viral hepatitis. It is strongly associated with several cardiovascular risk factors such as obesity, insulin resistance, hypertension, hyperlipidaemia, coronary artery disease, obstructive sleep apnoea syndrome, oxidative stress, endothelial dysfunction and the metabolic syndrome.2-5 There are recent data suggesting that NAFLD is linked to increased cardiovascular risk independent from the broad spectrum of metabolic syndrome (MS) risk factors.6,7Multiple mechanisms contribute to left ventricular dysfunction in obesity, including lipotoxicity associated with cardiac steatosis and lipo-apoptosis, alterations in fatty acid metabolism, overproduction of cardio-inhibitory cytokines, up-regulation of some neurohormones (especially angiotensin II), myocardial fibrosis and chronic overload with left ventricular dilatation and hypertrophy, and increased oxygen consumption.8Evaluating the possible influence and correlation of metabolic, cardiovascular and liver biopsy parameters on cardiac left ventricular dysfunction, we found a positive correlation between left ventricular parameters and severity of liver damage (NAS score).9 Cardiac dysfunction determined by echocardiographic measurements in patients with NAFLD was also studied.10 Determination of myocardial velocity using tissue Doppler imaging (TDI) is a new technique that has recently been developed to analyse right ventricular function.11-14This study aimed to investigate the association between right ventricular function and grade of hepatosteatosis (HS grade) in NAFLD patients using transthoracic and tissue Doppler echocardiography.