Seasonal cyclicity of secretogranin-II expression and its modulation by sex steroids and GnRH in the female goldfish pituitary

The secretory vesicle protein secretogranin-II (SgII), a precursor for the bioactive peptide secretoneurin, is expressed at all levels of the goldfish reproductive axis, including the hypothalamus, pituitary and ovaries. These findings led us to hypothesize that SgII is involved in reproduction and is physiologically regulated. We investigated the effects of different sex steroids on pituitary SgII expression throughout the seasonal reproductive cycle of the female goldfish, as well as the effects of GnRH and testosterone on pituitary LHbeta subunit, GH, and SgII expression in sexually recrudescent female fish using northern blot analysis. We demonstrated that SgII expression levels vary seasonally, with levels being highest in winter and lowest in spring. Sex steroids did not alter SgII expression at any of the time periods studied. In sexually mature goldfish, injection of a GnRH agonist stimulated the expression of LHbeta and SgII specifically in the pars distalis but not the neurointermediate lobe of the pituitary. Although testosterone alone did not alter the expression of either of these genes, it did abolish the stimulatory effects of GnRH on both LHbeta and SgII expression. This represents the first study where testosterone is shown to modulate SgII expression in the pituitary.     

Increased Contextual Fear Conditioning in iNOS Knockout Mice: Additional Evidence for the Involvement of Nitric Oxide in Stress-Related Disorders and Contribution of the Endocannabinoid System

Background:

Inducible or neuronal nitric oxide synthase gene deletion increases or decreases anxiety-like behavior in mice, respectively. Since nitric oxide and endocannabinoids interact to modulate defensive behavior, the former effect could involve a compensatory increase in basal brain nitric oxide synthase activity and/or changes in the endocannabinoid system. Thus, we investigated the expression and extinction of contextual fear conditioning of inducible nitric oxide knockout mice and possible involvement of endocannabinoids in these responses.

Methods:

We evaluated the effects of a preferential neuronal nitric oxide synthase inhibitor, 7-nitroindazol, nitric oxide synthase activity, and mRNA changes of nitrergic and endocannabinoid systems components in the medial prefrontal cortex and hippocampus of wild-type and knockout mice. The effects of URB597, an inhibitor of the fatty acid amide hydrolase enzyme, which metabolizes the endocannabinoid anandamide, WIN55,212-2, a nonselective cannabinoid agonist, and AM281, a selective CB1 antagonist, on contextual fear conditioning were also evaluated.

Results:

Contextual fear conditioning expression was similar in wild-type and knockout mice, but the latter presented extinction deficits and increased basal nitric oxide synthase activity in the medial prefrontal cortex. 7-Nitroindazol decreased fear expression and facilitated extinction in wild-type and knockout mice. URB597 decreased fear expression in wild-type and facilitated extinction in knockout mice, whereas WIN55,212-2 and AM281 increased it in wild-type mice. Nonconditioned knockout mice showed changes in the mRNA expression of nitrergic and endocannabinoid system components in the medial prefrontal cortex and hippocampus that were modified by fear conditioning.

Conclusion:

These data reinforce the involvement of the nitric oxide and endocannabinoids (anandamide) in stress-related disorders and point to a deregulation of the endocannabinoid system in situations where nitric oxide signaling is increased.     

Importance of specimen size in accurate needle liver biopsy evaluation of patients with chronic hepatitis C.

BACKGROUND & AIMS: In patients with chronic hepatitis C (CHC), percutaneous needle liver biopsy examination establishes the severity of necroinflammatory activity and fibrosis, thus guiding treatment decisions. Optimal biopsy specimen size remains controversial. We sought to determine how varying lengths of biopsy specimens influence the grading and staging of CHC. METHODS: We used 100 liver biopsy specimens from patients with CHC. The slides were evaluated blindly using the METAVIR scoring system, after being covered with paper, so that only specific specimen lengths (5 mm, 10 mm, 15 mm, and > or =20 mm) were visible. In each case, the scores obtained with biopsies 5 mm, 10 mm, or 15 mm long were compared with the scores at 20 mm or greater by weighted kappa statistics (kappa of >.75 signified excellent agreement). A subset of specimens 20 mm or greater was selected for a blinded repeat scoring to assess intraobserver agreement. The kappa statistics for the designated features and lengths were compared using analysis of variance. RESULTS: In assessing the stage of fibrosis, the weighted kappa statistics for agreement with the 20-mm or greater score at 5 mm, 10 mm, and 15 mm were .75, .85, and .92, respectively. In assessing the histologic activity score, the corresponding figures were .73, .81, and .77, respectively. Average kappa statistic comparisons showed that intraobserver agreement was significantly better than agreement between the 20-mm or greater scores and those at shorter lengths; the 5-mm kappa scores were significantly lower than the others; and there was no significant difference between the 10-mm and 15-mm kappa scores. CONCLUSIONS: Liver biopsy specimens measuring at least 10 mm usually reflect the grade and stage of CHC reliably. Relatively little improvement in diagnostic accuracy is obtained with longer specimens.     

Efficacy of different modes of fractional CO2 laser in the treatment of primary cutaneous amyloidosis: A randomized clinical trial

Background

Primary cutaneous amyloidosis (PCA) comprises three main forms: macular, lichen, and nodular amyloidosis. The current available treatments are quite disappointing.

Objectives

Assess and compare the clinical and histological changes induced by different modes of Fractional CO₂ laser in treatment of PCA.

Patients and Methods

Twenty five patients with PCA (16 macular and 9 lichen amyloidosis) were treated by fractional CO₂ using; superficial ablation (area A ) and deep rejuvenation (area B ). Each patient received 4 sessions with 4 weeks intervals. Skin biopsies were obtained from all patients at baseline and one month after the last session. Patients were assessed clinically and histologically (Congo red staining, polarized light). Patients were followed‐up for 3 months after treatment.

Results

Both modes yielded significant reduction of pigmentation, thickness, itching, and amyloid deposits (P‐value < 0.001). However, the percentage of reduction of pigmentation was significantly higher in area A (P‐value = 0.003). Pain was significantly higher in area B. Significant reduction in dermal amyloid deposits denotes their trans‐epidermal elimination induced by fractional photothermolysis.

Conclusion

Both superficial and deep modes of fractional CO₂ laser showed comparable efficacy in treatment of PCA. Superficial mode being better tolerated by patients, is recommended as a valid therapeutic option. Lasers Surg. Med. 47:388–395, 2015. © 2015 Wiley Periodicals, Inc.     

Significance of serum levels of vitamin D and some related minerals in breast cancer patients

Vitamin D and calcium are involved in a wide range of proliferation, apoptosis and cell signaling activities in the body. Suboptimal concentrations may lead to cancer development. The role of phosphate in cancer metabolism is particularly relevant in breast cancer while, magnesium deficiency favors DNA mutations leading to carcinogenesis. Objectives: To determine serum levels of vitamin D, calcium, phosphorus, magnesium, and parathormone in female breast cancer patients and to assess their association with some prognostic factors in breast cancer. Design and methods: This study is done on 98 newly diagnosed female breast cancer patients and 49 age matched apparently healthy female volunteers as controls. Serum samples from all patients and controls were subjected to 25-OH Vit D, calcium, phosphorus, magnesium, and parathormone measurements. Results: In the breast cancer group, the median serum levels of 25-OH Vit D were 15 ng/ml, while it was 21 ng/ml in the control group. Levels of 25-OH Vit D and other tested minerals were significantly lower while calcium:magnesium (Ca:Mg) ratio, and calcium:phosphorus (Ca:P) ratio were significantly higher in the breast cancer group. Significant negative correlation was detected between phosphorus and calcium, ionized calcium , calcium magnesium ratio, and calcium phosphorus ratio. Conclusion: It is not only the deficient levels of Vit D and other related minerals, but the combination of the abnormal levels of all the studied parameters that might contribute to the development of cancer. Further studies with larger number of patient are needed.     

A national interactive web-based physical activity intervention in women, evaluation of the american heart association choose to move program 2006-2007

Increased physical activity (PA) is associated with improvement of cardiac risk factors and prevention of cardiovascular disease, yet many women remain sedentary. With rising Internet use, Web-based interventions provide an alternative to improve PA, but their effectiveness for change in PA and quality of life (QOL) in a real-world setting is unknown. Participants were United States women ≥18 years old who received 12 weekly PA modules and completed surveys on PA, QOL, and readiness for PA at registration (registration cohort, n = 3,796) or registration and 12 weeks (evaluation cohort, n = 892). QOL was assessed with a modified Short Form-36 with subscores for energy and well-being. Participants showed significant (p <0.001) favorable changes in PA (baseline, median 240 kcal/week, interquartile range 62 to 667; 12 weeks, 343 kcal/week, 131 to 828), stage of readiness for PA, and body mass index (baseline, 29.3 kg/m(2), 24.9 to 34.7; 12 weeks, 28.9 kg/m(2), 24.6 to 34.2). Significant improvements (p <0.0001) were also found in composite scores for energy and well-being. Compliance with PA guideline recommendations increased from 15.8% to 21.4%. Program weeks completed (p = 0.03), energy (p = 0.04), and well-being (p = 0.002) were significantly associated with achieving guideline compliance. In women reporting no PA at baseline (n = 88), program participation resulted in 54.6% achieving some PA and another 9.1% achieving total compliance with recommendations. In conclusion, in this national cohort of women, a 12-week Web-based intervention improved PA and QOL measurements, resulting in higher short-term PA guideline compliance and better QOL. Increasing use of this simple Web-based tool could improve PA and promote disease prevention.