A gravity-based three-dimensional compass in the mouse brain.

Gravity sensing provides a robust verticality signal for three-dimensional navigation. Head direction cells in the mammalian limbic system implement an allocentric neuronal compass. Here we show that head-direction cells in the rodent thalamus, retrosplenial cortex and cingulum fiber bundle are tuned to conjunctive combinations of azimuth and tilt, i.e. pitch or roll. Pitch and roll orientation tuning is anchored to gravity and independent of visual landmarks. When the head tilts, azimuth tuning is affixed to the head-horizontal plane, but also uses gravity to remain anchored to the allocentric bearings in the earth-horizontal plane. Collectively, these results demonstrate that a three-dimensional, gravity-based, neural compass is likely a ubiquitous property of mammalian species, including ground-dwelling animals.

Altered activity of xenobiotic detoxifying enzymes at menopause - A cross-sectional study.

Xenobiotic metabolism at menopause is an under-investigated topic, albeit women spend one-third of their life in the postmenopausal period. The present study examined the effect of menopause on the in vivo activities of CYP1A2, CYP2A6, xanthine oxidase (XO) and N-acetyltransferase-2 (NAT2) xenobiotic metabolizing enzymes. Enzyme activity was determined in 152 non-smoking volunteers following oral intake of a single dose of 200 mg caffeine and subsequent determination of caffeine metabolite ratios (CMRs) in a 6-h urine sample as follows: CYP1A2: (AFMU+1U+1X)/17U, CYP2A6: 17U/(17U + 17X), XO: 1U/(1U+1X) and NAT2: AFMU/(AFMU+1U+1X). CMRs among groups were analyzed using one-way ANOVA. Significantly lower CYP1A2 and higher CYP2A6 CMRs were observed in postmenopausal compared to premenopausal women and age-matched men. These changes could be attributed to menopause rather than chronological aging since an age-related effect was not observed in premenopausal women or men of any age group. XO CMRs were higher in postmenopausal women and men>50 compared to premenopausal women and men<50, respectively, suggesting an age-related increase in XO activity. No significant alterations were discerned in NAT2 CMRs, in either slow- or rapid-acetylators, indicating that menopause exerts minimal modulation of xenobiotics metabolized by this enzyme. This study provides evidence that the transition to menopause induces significant alterations in xenobiotic-metabolizing enzymes independent of chronological aging suggesting altered metabolism of pharmaceutical and environmental agents.

Effects of short-term saffron (Crocus sativus L.) intake on the in vivo activities of xenobiotic metabolizing enzymes in healthy volunteers.

Crocus sativus L., a perennial plant grown mainly around the Mediterranean and Iran, has many medicinal properties including anti-inflammatory, anti-depressive and cancer preventing properties. Aqueous herbal extracts may affect the activity of Phase I and II enzymes involved in xenobiotic metabolism. The present study was designed to determine whether C. sativus infusion alters the activity of CYP1A2, CYP2A6, XO and NAT2 enzymes in humans. Thirty-four healthy volunteers consumed infusion prepared from C. sativus stigmata for six days. Enzyme phenotyping was assessed in saliva and urine using caffeine metabolite ratios as follows: CYP1A2: 17X/137Χ (saliva) and CYP1A2: (AFMU+1U+1X)/17U, CYP2A6: 17U/(17U + 17X), XO: 1U/(1U+1X) and NAT2: AFMU/(AFMU+1U+1X) (urine). Following C. sativus intake, CYP1A2 index was reduced by ∼13.7% in saliva (before: 0.51 ±â€¯0.22, after: 0.44 ±â€¯0.14; p = 0.002) and ∼6.0% in urine (before: 3.81 ±â€¯1.20, after: 3.58 ±â€¯0.92; p = 0.054). CYP1A2 index was significantly reduced only in males (saliva, before: 0.65 ±â€¯0.22, after: 0.51 ±â€¯0.16; p = 0.0001; urine, before: 4.53 ±â€¯1.19, after: 4.03 ±â€¯0.87; p = 0.017) suggesting sexual dimorphism in CYP1A2 inhibition. There was no effect of C. sativus intake on CYP2A6, XO or NAT2 indices. Short-term consumption of C. sativus infusion is unlikely to result in significant herb-drug interactions involving the enzymes studied, with the exception of potential herb-CYP1A2 substrate interaction in males.

Dietary effects of Sideritis scardica "mountain tea" on human in vivo activities of xenobiotic metabolizing enzymes in healthy subjects.

Sideritis scardica(S. scardica) is an endemic plant of the Balkan Peninsula traditionally used as herbal tea for inflammation and gastric disorders. Aqueous herbal extracts may affect the activity of Phase I and II enzymes involved in xenobiotic metabolism. The purpose of the present study was to determine whether S. scardica decoction alters the activity of CYP1A2, CYP2A6, XO, NAT2 and UGT1A1/1A6 enzymes in humans. Fourteen healthy subjects consumed S. scardica decoction for six days. Enzyme phenotyping was assessed in saliva and urine using caffeine and paracetamol metabolite ratios as follows: CYP1A2: 17X/137X (saliva) and (AFMU+1U+1X)/17U, CYP2A6: 17U/(17U + 17X), XO: 1U/(1U+1X), NAT2: AFMU/(AFMU+1U+1X) and UGT1A1/1A6: glucuronidated/total paracetamol (urine). After S. scardica intake, CYP1A2 index was reduced by ∼16% and ∼8% in saliva (before: 0.54 ±â€¯0.18, after: 0.46 ±â€¯0.09; p = 0.08) and urine (before: 3.59 ±â€¯0.52, after: 3.67 ±â€¯0.78; p = 0.12), respectively. CYP2A6 index was significantly reduced only in males (before: 0.76 ±â€¯0.08, after: 0.67 ±â€¯0.07; p = 0.004), suggesting sexual dimorphism in CYP2A6 inhibition. There was no effect of Sideritis scardica treatment on XO, NAT2 or UGT1A1/1A6 indices. Usual consumption of the aerial parts of S. scardica decoction is unlikely to result in herb-drug interactions involving the enzymes studied, with the exception of potential herb-CYP2A6 substrate interaction in males.

Tumor-treating fields as a fourth treating modality for glioblastoma: a meta-analysis.

BACKGROUND: We aim to review the available literature on patients suffering from glioblastoma treated with tumor-treating fields (TTFields) plus radio chemotherapy or conventional radio chemotherapy alone, to compare the efficacy and safety of the two methods. METHODS: A systematic literature search was performed in PubMed, Cochrane library, and Scopus databases, in accordance with the PRISMA guidelines. Six studies met the inclusion criteria incorporating 1806 patients for the qualitative analysis and 1769 for the quantitative analysis. RESULTS: This study reveals increased median overall survival (weighted mean difference (WMD) 3.29 [95% confidence interval (CI) 2.37, 4.21]; p < 0.00001), survival at 1 year (odds ratio (OR) 1.81 [95% CI 1.41, 2.32]; p < 0.00001) and 2 years (OR 2.33 [95% CI 1.73, 3.14]; p < 0.00001), and median progression-free survival (WMD 2.35 [95% CI 1.76, 2.93]; p < 0.00001) along with progression-free survival at 6 months (WMD 6.86 [95% CI 5.91, 7.81]; p < 0.00001) for the patients treated with TTFields. Survival at 3 years was comparable between the two groups. TTFields were associated with fewer adverse events compared to chemotherapy along with similar incidence of skin irritation. CONCLUSIONS: TTFields are a safe and efficient novel treatment modality. More randomized controlled studies, with longer follow-up, are necessary to further assess the clinical outcomes of TTFields.