Dietary essential fatty acids and gender-specific behavioral responses in cranially irradiated rats

Specific memory deficits, reduced intellectual processing speed, and a variety of social and behavioral problems have been implicated as long-term effects of cranial radiation therapy (CRT). These deficits are thought to be related to changes in brain cytology and structure associated with microvascular aberrations. N-3 fatty acids may serve as protectants in pediatric patients who receive CRT for brain tumors. Timed-pregnant rat dams were fed one of four diets that were identical in all respects, except for their essential fatty acid content. The dams were placed on these diets at the beginning of the third trimester of gestation and their pups remained on them throughout the study. The rats’ behavioral response as judged by acoustic startle response (ASR) and neurocognitive response (performance in a radial maze, RM) were evaluated in relation to diet, gender, and CRT. The following hypotheses were tested: (1) female rats will show greater CRT-induced neurocognitive and behavioral deficits; (2) dietary n-3 fatty acids will diminish CRT-induced neurocognitive and behavioral deficits; (3) gender-specific differences would be dampened by n-3 fatty acids in the diet. All three hypotheses were partially supported. These findings are discussed in light of the potential neuroprotective effects of n-3 fatty acids.     

Narrowband UVB phototherapy for small plaque parapsoriasis

BACKGROUND: Narrowband UVB (NB-UVB) phototherapy has been shown to be effective for the treatment of various dermatoses. OBJECTIVE: To analyze the effects of NB-UVB phototherapy for small plaque parapsoriasis (SPP). METHODS: The response of 45 patients (24 females, 21 males, age range 20-58 years) with histologically confirmed SPP were assessed. NB-UVB therapy was given 3-4 times weekly. The initial treatment dose was 70% of the minimal erythema dose. The doses were increased gradually with a standard increment of 20/10/0. Clinical response was determined as follows: complete response (CR), at least 90% clearing of skin lesions; partial response (PR), at least 50% but less than 90% clearing and no response (NR), less than 50% clearing. The follow-up period was 6-24 months after the treatment. RESULTS: NB-UVB treatment led to CR in 33 of 45 patients (73.3%) with a mean cumulative dose of 14.3 J/cm(2) (range 3.2-24.1 J/cm(2)) after a mean number of 29 exposures (range 16-51 sessions); PR in 12 of 45 (26.6%) with a cumulative dose of 15.6 J/cm(2) (range 10.4-23.3 J/cm(2)) after a mean number of 29.4 exposures (range 25-50 sessions). Nineteen patients with CR had skin phototype II, 13 had type III and 1 had type I. Among the patients with PR, 7 had skin phototype II and 5 had type III. Postinflammatory hyperpigmentation was observed in 51% of the patients. Relapses occurred in six patients within a mean time of 7.5 months (2-12 months). CONCLUSION: NB-UVB phototherapy has several advantages over treatment with broadband UVB and PUVA. NB-UVB therapy for patients with SPP is an effective, safe and practical alternative treatment modality. Further larger studies with longer follow-up periods are necessary to determine the proper clinical response and long-term complications of NB-UVB therapy in this disease.     

Molecular and clinical characterization of a patient with duplication of 1p36.3 and metopic synostosis

Chromosome 1p duplications are rare. There have been only 11 reported cases of isolated 1p duplication, all of which were proximal, interstitial duplications. We present a patient with a terminal duplication of 1p (1p36.3). To our knowledge, this is the first such reported case. Our patient presented with metopic synostosis, rectal stenosis, atrial septal defect, and mildly delayed gross motor development. Molecular characterization using microsatellite marker analysis and fluorescence in situ hybridization (FISH) revealed an area of duplication between p58 and D1S2893, approximately 13 cM in size. We compare our patient's clinical findings with the clinical phenotype found in patients with the corresponding deletion of 1p36.3 and discuss the role of gene dosage in other deletion/duplication syndromes.     

Inhibition of heparanase activity and tumor metastasis by laminarin sulfate and synthetic phosphorothioate oligodeoxynucleotides.

Heparanase activity correlates with the metastatic potential of tumor cells. Moreover, the anti-metastatic effect of non-anti-coagulant species of heparin and certain sulfated polysaccharides was attributed to their heparanase-inhibiting activity. We investigated the effect of a chemically sulfated polysaccharide (laminarin), consisting primarily of beta-1,3 glucan (sodium laminarin), and of synthetic phosphorothioate oligodeoxynucleotides, primarily phosphorothioate homopolymer of cytidine (SdC28), on heparanase activity and tumor metastasis. Investigation of the ability of tumor cells to degrade heparan sulfate in intact extracellular matrix revealed that heparanase activity expressed by B16-BL6 mouse melanoma cells and 13762 MAT rat mammary adenocarcinoma cells was effectively inhibited by LS (50% inhibition at 0.2-1 microgram/ml), but there was no inhibition by sodium laminarin up to a concentration of 50 microgram/ml. Complete inhibition of the melanoma heparanase was obtained in the presence of 0.1 microM SdC28. A single i.p. injection of laminarin sulfate, but not of sodium laminarin, before i.v. inoculation of the melanoma or breast-carcinoma cells inhibited the extent of lung colonization by the tumor cells by 80 to 90%. Similar inhibition was exerted by 0.1 microM SdC28. At the effective concentrations, both compounds had a small effect on proliferation of the tumor cells and on growth of the primary tumors in vivo. These results further emphasize the involvement of heparanase in tumor metastasis and the potential clinical application of diverse heparanase-inhibiting molecules such as sulfated polysaccharides and synthetic polyanionic molecules.