Neurotransmitter-mediated regulation of CNS myelination: a review

In addition to treatments aimed at preventing or limiting damage to myelin and oligodendrocytes, there is a crucial need for repair strategies in human demyelinating disorders. There is increasing evidence that besides growth factors, neurotransmitters can regulate different steps of the oligodendrogliogenesis. The present review on neurotransmitter receptor expression and function in the oligodendrocyte lineage emphasizes the concept that in this lineage cell proliferation and differentiation can be controlled through the modulation of the functional state of channel proteins and receptors, such as the delayed K+ rectifier, the AMPA/kainate, dopamine or muscarinic receptors, and, most likely, others yet to be found. We anticipate that a better understanding of the neurotransmitter-mediated neuronal oligodendroglial communication network opens prospects in the field of central nervous system (CNS) myelin repair, allowing the recruitment of the myelinating machinery that is known to remain present but quiescent in the CNS of multiple sclerosis patients.     

Gallstone disease in a teaching hospital, Addis Ababa: a 5-year review

There are not many studies of gallbladder disease in Africa. The disease appears to be not uncommon in Ethiopia. To determine the prevalence and evaluate the management of gallstone disease in a central teaching hospital, a 5-year retrospective study was undertaken in 747 patients surgically treated for gallbladder disease in the period 1995-99 in Tikur Anbessa Hospital, Addis Ababa. The sex ratio (M:F) was 1:5, narrower ratio in complicated cholelithiasis. The mean age was 42 years. About 80% of patients were in the age group between 30 and 60 years. The median duration of symptoms at admission was 2 years. Abdominal pain, in 96% of cases situated in the right upper quadrant (RUQ) and usually aching type, was the most frequent presenting symptom; RUQ tenderness was the most common sign. Clinically, 29.4% of patients were categorized obese. Gallstone detection rate by ultrasound was about 96% but cholecystitis appeared to be overlooked. At operation, about 77% of cases had features of chronic cholecystitis, 2% acalculous cholecystitis. Majority of the stones were grossly cholesterol stones. Cholecystectomy was performed in 99% of cases, most often through the oblique subcostal and transverse routes. The overall in-hospital mortality rate was 0.4%. Nearly 87% of cases had postoperative course without incident. The etiologic factors and the type of gallstones, we believe, are not different from that of the developed world. Cholecystectomy is a safe and most effective procedure that provides ultimate cure for symptomatic gallstone disease.     

Overexpression of delta-like (Dlk) in a subset of myelodysplastic syndrome bone marrow trephines

The mRNA expression level of the gene delta-like (Dlk), coding for a signal transducer related to the Delta-Notch family, was measured using real-time PCR methodology in a large series of control biopsies (n = 61) and bone marrow trephines from patients with myelodysplastic syndrome (MDS) (n = 93) and related myeloid disorders (AML, n = 16 and chronic myeloproliferative disease (CMPD), n = 38). It turned out that dlk is strongly overexpressed in a subset of MDS (16%) cases, however with higher frequency in blast rich MDS cases. Therefore, the quantitative detection of dlk mRNA can support the morphological diagnosis of MDS in selected cases.     

Prevalence of symptoms of asthma and allergies in schoolchildren in Gondar town and its vicinity,northwest Ethiopia

A low level of allergic disorders has been generally reported in children from developing countries. A survey was conducted to determine the prevalence of symptoms of asthma and allergies among schoolchildren in Gondar, northwest Ethiopia. A standardized self-administered questionnaire developed by the International Study of Asthma and Allergies in Children (ISAAC) was used. In total, 3,365 children aged 13-14 years were surveyed at school, with a response rate of 98.4%. The female to male ratio was 1.5:1. The 12-month-period prevalences of wheeze (16.2%), rhino-conjunctivitis (14.5%), and eczema (10.9%) were comparable to findings from Addis Ababa, but significantly higher than reported from Jimma. A striking seasonal pattern of rhinitis symptoms is observed during the months of September-December with a peak in November, corresponding with the main pollen season of the area. Overall, about 36% of the children reported symptoms of atopic disorders. However, the prevalence of diagnosed atopic diseases (8.6%) is less than a quarter of the symptom prevalence rate. This may reflect a generally poor awareness and low health service utilization, or underdiagnosis by health facilities. In conclusion, it appears that the prevalence of atopic diseases in Gondar area is high, and there is also wide variation within the country. This calls for further epidemiological studies with more objective assessments of atopy, such as allergen and bronchial hyperresponsiveness tests and ecological analysis.     

Long-term results of laparoscopic adjustable gastric banding for the treatment of morbid obesity

Background: Since the first laparoscopic adjustable gastric banding (LAGB) operation on September 1, 1993, there have been important publications related to this procedure. The majority of the articles reported surgical technique and short-term results. Long-term results of LAGB are lacking. The authors report long-term data (at least 4 years) from 3 major bariatric centers in Belgium that perform LAGB routinely. Methods: The 3 centers applied the same patient selection criteria, the same standard surgical technique, the same laparoscopic band (Lap-Band?) and the same follow-up program. 763 patients have been enrolled. Sex ratio was 22% male/78% female. Mean age was 34 years, and mean preoperative BMI was 42 kg/m². Results:The follow-up rate was 90%, and the minimum follow-up time was 4 years. The average BMI after 4 years was 30 kg/m². Early complications were: gastric perforation 4 (0.5%); large bowel perforation 1 (0.1%); bleeding 1 (0.1%); and conversion to open 10 (1.3%). Late complications were: erosion 7 (0.9%); total food intolerance 59 (8%); access port problems 20 (2.5%); re-operations 80 (11.1%); death 1 (0.1%). Conclusion: Long-term results of LAGB have been rarely reported, although publications on the procedure are copious. Our long-term data found that BMI evolution is good, the complication and re-operation rates are acceptable and the overall long-term results of the Lap-Band? system are good.     

Cell cycle and no end

Our knowledge about the molecular circuits regulating the duplication of the genetic material and the subsequent division of a cell into two daughter cells has exploded over the last decade. Aberrations in the regulation of the cell cycle belong to the hallmarks of malignant transformation, leading, in turn, to the development of tumours. After introducing the basics of eukaryotic cell-cycle regulation and describing the four phases of the cell cycle (namely, G1, S, G2 and M) in more detail, alterations of key components of the cell-cycle machinery in human malignancies and their functional consequences are presented. Principally, deregulation of the cell cycle can be caused by unrestricted activity of cell-cycle promoting factors (many oncogenes fall into this class) or by inactivation of inhibitory factors (many tumour suppressor genes belong to this class). Both types of deregulation have been described in human tumours and are discussed in detail. Perspectives concerning the translation of this knowledge into daily routine practice and future applications are discussed at the end. The molecular mechanisms of actual cell division (sister chromatid segregation and cytokinesis) are mentioned only briefly.     

Identification of PSF, the polypyrimidine tract-binding protein-associated splicing factor, as a developmentally regulated neuronal protein.

The polypyrimidine tract-binding protein-associated splicing factor (PSF), which plays an essential role in mammalian spliceosomes, has been found to be expressed by differentiating neurons in developing mouse brain. The sequence of a fragment of mouse PSF was found to be remarkably similar to that of human PSF. Both the expression of PSF mRNA in cortex and cerebellum and PSF immunoreactivity in all brain areas were high during embryonic and early postnatal life and almost disappeared in adult tissue, except in the hippocampus and olfactory bulb where various neuronal populations remained PSF-immunopositive. Double-labeling experiments with anti-PSF antibody and anti-neurofilaments or anti-glial fibrillary acidic protein antibodies on sections of cortex, hippocampus, and cerebellum indicate that PSF is expressed by differentiating neurons but not by astrocytic cells. In vitro, mouse PSF was found to be expressed by differentiating cortical and cerebellar neurons. Radial glia or astrocyte nuclei were not immunopositive; however, oligodendrocytes differentiating in vitro were found to express PSF. The restricted expression of PSF suggests that this splicing factor could be involved in the control of neuronal-specific splicing events occurring at particular stages of neuronal differentiation and maturation.     

Maternal nutritional status mediates the association between maternal age and birth outcomes

Young maternal age during pregnancy is linked with adverse birth outcomes. This study examined the role of maternal nutritional status in the association between maternal age and small for gestational age (SGA) delivery and birth length. We used data from a birth cohort study in Ethiopia, involving women who were 15–24 years of age and their newborns. A mediation analysis was fitted in a sample of 1,422 mother infant dyads for whom data on birth length were available, and 777 dyads for whom gestational age and birth weight was measured. We used commands, medeff for the mediation analysis and medsens for sensitivity analysis in STATA 14. Maternal nutritional status, measured by mid‐upper arm circumference, mediated 21% of the association between maternal age and birth length and 14% of the association with SGA delivery. The average direct effect (ADE) of maternal age on birth length was (β = 0.45, 95% CI [0.17, 0.99]) and the average causal mediated effect (ACME) was (β = 0.12, 95% CI [0.02, 0.15]). We also found an ADE (β = 0.31, 95% CI [0.09, 0.47]) and an ACME of (β = 0.05, 95% CI [0.003, 0.205]) of maternal age on SGA delivery. The sensitivity analysis suggests an unmeasured confounder with a positive correlation of 0.15 and 0.20 between the mediator and the outcome could explain the observed ACME for birth length and SGA, respectively. We cannot make strong causal assertions as the findings suggest the mediator partly explained the total effect of maternal age on both outcomes.