Cytoprotective actions of 2,4-dimethoxybenzylidene anabaseine in differentiated PC12 cells and septal cholinergic neurons

The potential cytoprotective actions of a novel nicotinic agent 2,4-dimethoxybenzilidene anabaseine (DMXB) were investigated in differentiated PC12 cells and transected rat septal cholinergic neurons in vivo. In NGF-differentiated PC12 cells, removal of both NGF and serum led to cell loss, a reduced % of cells expressing neurites, the release of lactate dehydrogenase, and a decrease in total cellular protein. Cell loss was apparent within 24 h, and remained constant between 4–8 days post-NGF removal. NGF alone (100 ng/ml), DMXB (10 μM), but not nicotine (10 μM), prevented these cell and neurite losses. DMXB-induced cytoprotection was blocked by 1 μM mecamylamine. DMXB (1 mg/kg, ip) injected twice but not once per day protected cholinesterase-staining septal neurons from retrograde degeneration following unilateral fimbrial transections. The twice per day DMXB injection-protocol also decreased cell roundness among cholinesterase-staining cells in the lesioned septal hemisphere compared to saline-injected animals. These studies suggest that DMXB may exert cytoprotective activity in NGF-sensitive neuronal populations. © 1994 Wiley-Liss, Inc.     

Structure and Spectral Properties of β-Carbolines,I: 13C-NMR and Mass Spectra of Decahydro-5H-pyrido[1′,2′;5,1]-imidazo[3,4-a]-β-carbolines

¹³C-NMR and the electron impact mass spectra of the β-carboline derivatives 1 – 18 were examined. The structure of the possible diastereomers is discussed. A quantitative relationship between the relative intensity of ions a in the mass spectra of 1 – 18 and the structure of substituents R was found.     

Morphometric insights into nephrotic syndrome in children: Are we any wiser?

Summary: The present study was undertaken in the hope that conflicting opinions concerning interrelationships among minimal change disease (MCD), mesangial proliferative glomerulonephritis (MPG) and focal segmental glomeruloscierosis (FSGS) might be elucidated by morphometric methods performed by image analysis, as well as to study whether serum creatinine and changes in quantitatively analysed glomeruli could correlate with the interstitial fibrosis in these glomerulopathies. Fifteen renal biopsy specimens from children with MCD, 10 with primary MPG and 12 with FSGS for whom both light and electron microscopy as well as immunofluorescence microscopy and full clinical data were available, were examined quantitatively. As a control five biopsy and 10 autopsy specimens of the normal kidneys were used. Our quantitative study showed that in MCD, MPG and FSGS glomerular and interstitial values differed from normal. Morphometric differences between MPG and both MCD and FSGS groups were also shown. Although the mean values of total glomerular area and relative interstitial volume were increased in FSGS patients, in total glomerular cells per unit of glomerular area and mesangium (% of total glomerular area) were similar in both MCD and FSGS groups. In MPG strong positive correlations existed between interstitial volume and serum creatinine, interstitial volume and total glomerular cells per unit of glomerular area as well as between interstitial volume and glomerular mesangium (% of total glomerular area). In FSGS there was significant positive correlation between interstitial volume and serum creatinine. In the MCD group all correlations were weak and not significant. In conclusion, our morphometric studies suggest a close relationship between MCD and FSGS, and indicate that MPG is a separate morphologic entity in children.     

A case of Prader – Willi syndrome arising as a result of familial unbalanced translocation t(11;15)(q25;q13)

We report on a case of Prader-Willi syndrome (PWS) with a true reciprocal unbalanced translocation, 45,XX,-15,der(11)t(11;15)pat. The proposita was diagnosed clinically as having severe PWS. Molecular studies revealed loss of the paternal methylation pattern at locus D15S63 and a deletion encompassing the loci from at least D15S10 to D15S97 of paternal chromosome 15. FISH studies confirmed the deletion of 15q11-q13 region and the presence of two telomeres on all chromosomes. The proposita's father, the father's sister and their mother are all carriers of the same balanced translocation t(11;15)(q25;q13). By genomic imprinting we would expect that if the father's sister were to give birth to a child with the same unbalanced translocation as the proband, it would be affected by Angelman syndrome.
To date, a similar familial unbalanced translocation due to loss of the small chromosome 15 derivative has not been described.     

Stimulation of the hamster ventral lateral geniculate nucleus induces Fos-like immunoreactivity in suprachiasmatic nucleus cells.

The suprachiasmatic nucleus (SCN) functions as a pacemaker for circadian rhythms in rodents. Its activity and, therefore, circadian rhythms, are synchronized by light information from both a direct retinal projection and an indirect projection from the thalamic intergeniculate leaflet (IGL) and ventral lateral geniculate nucleus (vLGN) (geniculohypothalamic tract; GHT). The GHT also appears to be important for synchronizing circadian rhythms to non-photic cues. Light can activate expression of several immediate-early genes in the SCN, including c-fos. We examined whether electrical stimulation of the IGL/vLGN region would induce Fos-like immunoreactivity (lir) in the hamster SCN. Electrical stimulation was given for one hour during the dark period of the lighting cycle. Stimulation at night of the IGL and adjacent LGN regions induced Fos-lir in cells in the SCN. Labeled cells were found in the dorsolateral part of the caudal SCN, and not in rostral or central regions of the SCN, nor in the ventral part of the caudal SCN. These results indicate that activation of cells contributing to the hamster GHT can induce Fos-lir in a restricted region of the caudal SCN.     

IL-8 and IFN-gamma in tear fluid of patients with cystic fibrosis.

Cystic fibrosis (CF) is inherited as an autosomal recessive disorder. It is caused by mutations in the protein-coding gene of chromosome 7, resulting in chronic pulmonary disease and pancreatic insufficiency. The disease affects all secretory epithelia, including the eye. The pathogenesis of ocular changes in CF is still unknown, but the involvement of immunologic processes in patients with CF has been studied in recent years. We measured interleukin-8 (IL-8) and interferon-gamma (IFN-gamma) levels in tears in a group of patients and a group of normal controls to determine if the levels of these cytokines are elevated in CF. The levels of these cytokines in tears and the clinical severity of CF and eye disease were compared. Tear samples were collected from 24 patients with CF at the department of pediatric diseases, Medical University of Bialystok, Poland. Cytokine levels were determined by ELISA. Ophthalmic examinations, including tests for keratoconjunctivitis sicca (dry eye), were used to study the ocular surface. The tear levels of IL-8 and IFN-gamma in the CF patients were significantly higher than those in controls. The clinical severity of CF correlated significantly with the IL-8 and IFN-gamma levels. We found positive correlation between the tear levels of IFN-gamma and dry eye findings in CF patients. Our results suggest that the inflammatory cytokines IL-8 and IFN-gamma may play key roles in the regulation of ocular surface inflammation and the immunologic reaction in patients with CF. The tear levels of IL-8 and IFN-gamma may be candidate markers for evaluation of the clinical status of CF and eye disease. These findings help to provide a new insight into the pathogenesis of dry eye in patients with CF and provide potential targets for therapy.     

Evidence that orexins A and B stimulate insulin secretion from rat pancreatic islets via both receptor subtypes

Orexins are recently identified neuropeptides that appear to play a role in the regulation of energy homeostasis and arousal. They bind to and activate two closely related G protein-coupled receptors (OXR1 and OXR2), previously described as orphans. In this study we examined involvement of orexins in regulation of insulin secretion from rat pancreatic islets utilizing an in situ perfused pancreas and isolated pancreatic islet models. By means of RT-PCR we found that both OXR1 and OXR2 are expressed in rat pancreatic islets. Furthermore, the expression levels of OXR1 were higher than OXR2. In both experimental models applied, orexins A and B (1, 10 and 100 nmol/l) concentration dependently stimulated insulin secretion at two different glucose concentrations (6.66 or 26.4 mmol/l), with orexin A being more potent than orexin B. This study demonstrates that orexins A and B modulate insulin secretion in vitro.