Transplantation of embryonic noradrenergic neurons in two models of adult rat spinal cord injury: ultrastructural immunocytochemical study

The synaptic connections established by grafted noradrenergic (NA) neurons into the lesioned adult rat spinal cord were analysed using immunocytochemistry at the electron microscopic level. An embryonic cell suspension of the locus coeruleus region from E-13 rat embryos was transplanted into the spinal cord following either: (1) spinal cord transection or (2), partial selective denervation by 6-hydroxy dopamine (6-OH DA). One month after grafting, the NA-neurons established, in the two models, an innervation pattern similar to that found in the intact spinal cord. In both models, the transplanted NA-immunoreactive neurons formed extensive synaptic contacts with dendrites, spines and perikarya. The proportion of axodendritic and axospinous contacts was inverse in the two models. The first model thus reproduced more closely the normal synaptic pattern prefering dendritic targets, which could correspond to a better integration of the graft. In the second model, a partially NA-denervated spinal cord, there existed a competition between residual intrinsic and grafted neuron-derived fibres, which presumably affects synaptogenesis. In conclusion, the present study illustrate the complexity of cell interations conducting to the formation of a specific circuitry. Recognition phenomenon are likely modulated by space constraints, which ultimately shape-up the geometry of synaptic contacts.     

Efficacy of continuous subcutaneous insulin infusion in Type 1 diabetes: a 2-year perspective using the established criteria for funding from a National Health Service.

AIM: To determine the 2-year efficacy of continuous subcutaneous insulin infusion (CSII) following the current established criteria for funding of a National Health Service. METHODS: Longitudinal, prospective, observational unicentre study. Included in the study were 153 Type 1 diabetes (T1D) subjects, previously treated with multiple daily injections (MDI) of insulin, in whom CSII was started in accordance with the criteria for reimbursement of the Catalan National Health Service. At baseline, we recorded data on age, gender, duration of the disease, body mass index (BMI), insulin dose and indications for CSII. Glycated haemoglobin (HbA(1c)) and the frequency of hypoglycaemic events were used to assess glycaemic control. Quality of life was assessed using three different self-report questionnaires. After 24 months, these same items were remeasured in all subjects. Serious adverse events and injection-site complications were also recorded. RESULTS: In 96% of subjects, CSII indication included less than optimal glycaemic control using MDI. HbA(1c) fell from 7.9 +/- 1.3 to 7.3 +/- 1.1% (P < or = 0.001) after 24 months of CSII. Insulin requirements were significantly lower at the end of follow-up (0.55 +/- 0.21 U/kg body weight) in comparison with before use of CSII (0.70 +/- 0.20, P < or = 0.001). BMI increased from 24.0 +/- 3.1 to 24.4 +/- 3.2 kg/m(2) after 24 months (P < or = 0.025). The rate of episodes of diabetic ketoacidosis per year remained unchanged. Mild and severe hypoglycaemic episodes were significantly reduced. The scores in all subsets of the Diabetes Quality-of-Life (DQoL) questionnaire significantly improved after 24 months of CSII. CONCLUSIONS: CSII, commenced according to the criteria for a nationally funded clinical programme, improves glycaemic control and quality-of-life outcomes with fewer hypoglycaemic episodes in T1D subjects previously conventionally treated with MDI.     

Endocrinology: Intravenous albumin does not prevent the development of severe ovarian hyperstimulation syndrome in an in-vitro fertilization programme

A cohort study was undertaken to compare the effect at the timeof oocyte retrieval of the i.v. administration of either 1000ml of lactated Ringer' solution or 1000 ml of a 5% solutionof human albumin on in-vitro fertilization patients at riskfor severe ovarian hyperstimulation syndrome (OHSS). A totalof 207 patients with an oestradiol concentration > 10 000pmol/l and/or > 15 follicles (>10 mm diameter) on theday of human chorionic gonadotrophin (HCG) injection were reviewed.Of these, 158 women received 500 ml of lactated Ringer’ssolution both before and after egg retrieval, and 49 women receivedtwo infusions of 500 ml of 5% human albumin in normal salineat the time of egg retrieval. Severe OHSS developed in two patientswho received human albumin and in 10 women who did not receivethe albumin. This difference was not statistically significant.There were no differences between the two groups in terms ofage, number of follicles punctured at transvaginal oocyte retrievalor oestradiol concentration at the time of HCG injection. Theadministration of a 5% human albumin solution does not preventthe development of severe OHSS in at risk patients. It doesappear to blunt the severity of the condition.     

A cystic fibrosis patient homozygous for the new frameshift mutation 936delTA: description and clinical data.

We report the identification of a new frameshift mutation (936delTA) in exon 6b of the CFTR gene. In the screening of 486 unrelated Spanish CF patients we found a patient homozygous for 936delTA (with consanguineous parents) and a patient heterozygous for delta F508 and 936delTA. Genotype-phenotype correlation studies showed that 936delTA is associated with pancreatic insufficiency and chronic pulmonary colonisation.     

Ultrastructural changes associated with the inhibition of monocyte chemotaxis caused by products of axenically grown Entamoeba histolytica

The supernatant fluid of axenically grown Entamoeba histolytica-HM1 significantly modifies the ultrastructural features associated with monocyte chemotaxis as assayed in Boyden chambers. This morphological evidence supports the existence of a factor, monocyte locomotion inhibitory factor (MLIF), produced by E. histolytica that inhibits the in vitro locomotion of human monocytes. None of the leucocyte-locomotion modifying drugs included in this study (i.e., cytochalasin-B, colchicine, vinblastine, and hydrocortisone) caused changes totally comparable with those induced by MLIF. The most striking feature was the increase of centriole-associated microtubules induced by MLIF and by cytochalasin-B. MLIF may inhibit monocyte locomotion by directly inducing excessive microtubule assembly, although a direct, if somewhat weak effect upon microfilaments cannot be excluded. The increase in microtubules could then represent a perhaps futile attempt of the microtubule organizing center to overcome the locomotion blockade that has occurred elsewhere in the cell. If active in vivo, MLIF may contribute to the paucity of inflammation in the advanced stages of invasive amebiasis, and consequently to the lack of scar tissue formation upon recovery from such lesions, as monocytes constitute an essential link to the healing process.     

Age-dependent changes of gene expression in the Drosophila head

Previous gene expression profiling studies in Drosophila have provided clues for understanding the aging process at the gene expression level. For a detailed understanding, studies of specific regions of the body are necessary. We therefore employed microarray analysis to examine gene expression changes in the Drosophila head during aging. Six hundred and eighty-four of the 5405 genes present in the microarray showed significant age-dependent changes as determined by significance analysis of microarray (SAM) (q < 0.05). The biological significance of the changes was analyzed using the gene annotations provided by the Gene Ontology Consortium. Major changes involved genes affecting energy metabolism (proton transport, energy pathways, oxidative phosphorylation) and neuronal function, especially responses to light. Genes involved in protein catabolism and several other metabolic processes also showed age-dependent changes. Most of the changes were reductions in gene expression and occurred before day 13 of adult life. After day 13, the age-dependent gene expression changes were relatively smaller than earlier life. Interestingly, the two biological processes of major gene expression changes are related to the two known environmental changes that increase life span in Drosophila: caloric restriction and light reduction. Our findings suggest that light signaling and energy metabolism may be important biological processes affected by aging and be interesting targets for the further investigation related to the longevity in Drosophila.