Sugar-sweetened beverages, weight gain, and incidence of type 2 diabetes in young and middle-aged women

Context  Sugar-sweetened beverages like soft drinks and fruit punches contain large amounts of readily absorbable sugars and may contribute to weight gain and an increased risk of type 2 diabetes, but these relationships have been minimally addressed in adults. Objective  To examine the association between consumption of sugar-sweetened beverages and weight change and risk of type 2 diabetes in women. Design, Setting, and Participants  Prospective cohort analyses conducted from 1991 to 1999 among women in the Nurses' Health Study II. The diabetes analysis included 91 249 women free of diabetes and other major chronic diseases at baseline in 1991. The weight change analysis included 51 603 women for whom complete dietary information and body weight were ascertained in 1991, 1995, and 1999. We identified 741 incident cases of confirmed type 2 diabetes during 716 300 person-years of follow-up. Main Outcome Measures  Weight gain and incidence of type 2 diabetes. Results  Those with stable consumption patterns had no difference in weight gain, but weight gain over a 4-year period was highest among women who increased their sugar-sweetened soft drink consumption from 1 or fewer drinks per week to 1 or more drinks per day (multivariate-adjusted means, 4.69 kg for 1991 to 1995 and 4.20 kg for 1995 to 1999) and was smallest among women who decreased their intake (1.34 and 0.15 kg for the 2 periods, respectively) after adjusting for lifestyle and dietary confounders. Increased consumption of fruit punch was also associated with greater weight gain compared with decreased consumption. After adjustment for potential confounders, women consuming 1 or more sugar-sweetened soft drinks per day had a relative risk [RR] of type 2 diabetes of 1.83 (95% confidence interval [CI], 1.42-2.36; P<.001 for trend) compared with those who consumed less than 1 of these beverages per month. Similarly, consumption of fruit punch was associated with increased diabetes risk (RR for 1 drink per day compared with <1 drink per month, 2.00; 95% CI, 1.33-3.03; P = .001). Conclusion  Higher consumption of sugar-sweetened beverages is associated with a greater magnitude of weight gain and an increased risk for development of type 2 diabetes in women, possibly by providing excessive calories and large amounts of rapidly absorbable sugars.      

Low dose quetiapine for drug induced dyskinesias in Parkinson's disease: a double blind cross over study

OBJECTIVE: Drug induced dyskinesias remain a challenging problem in the long term management of Parkinson's disease (PD). We have assessed the effect of quetiapine on dyskinesias in a double blind placebo controlled cross over study. METHODS: Nine patients with PD were enrolled and received 25 mg of quetiapine or placebo at night for two weeks in prerandomised order, with one week of wash out between treatment periods. Assessments were made using on-off diaries, self assessment of dyskinesias, and L-dopa challenges at baseline and after each treatment period. Videotapes were rated blindly by two raters using modified Abnormal Involuntary Movement Scale and Goetz scores. Patients subsequently went on open label quetiapine at 50 mg/day, for a mean duration of 30 days, and completed the same self assessment forms. RESULTS: During the double blind phase, no significant change in dyskinesias was found on either 25 mg of quetiapine or placebo. Duration of off states and Unified PD Rating Scale motor scores also remained unchanged. Moderate tiredness and daytime sleepiness occurred in two patients on quetiapine. One patient dropped out early for unrelated reasons. Eight patients completed the open label phase. On 50 mg/day of quetiapine, a slight reduction in dyskinesias occurred on some scales. Reduction in dyskinesia severity on visual analogue scales was by 50.1%. Off time was not significantly increased. This improvement was not strongly reflected in patients' overall impression of treatment effect. Drowsiness and daytime sleep episodes led to discontinuation in four patients, after completion of the study, and two additional patients stopped treatment after the study because of lack of effect. CONCLUSION: Our study failed to demonstrate an antidyskinetic effect of low dose (25 mg) quetiapine. The absence of an increase in parkinsonism combined with a possible antidyskinetic effect on higher doses warrants further investigation.     

Mucuna pruriens in Parkinson's disease: a double blind clinical and pharmacological study

BACKGROUND: The seed powder of the leguminous plant, Mucuna pruriens has long been used in traditional Ayurvedic Indian medicine for diseases including parkinsonism. We have assessed the clinical effects and levodopa (L-dopa) pharmacokinetics following two different doses of mucuna preparation and compared them with standard L-dopa/carbidopa (LD/CD). METHODS: Eight Parkinson's disease patients with a short duration L-dopa response and on period dyskinesias completed a randomised, controlled, double blind crossover trial. Patients were challenged with single doses of 200/50 mg LD/CD, and 15 and 30 g of mucuna preparation in randomised order at weekly intervals. L-dopa pharmacokinetics were determined, and Unified Parkinson's Disease Rating Scale and tapping speed were obtained at baseline and repeatedly during the 4 h following drug ingestion. Dyskinesias were assessed using modified AIMS and Goetz scales. RESULTS: Compared with standard LD/CD, the 30 g mucuna preparation led to a considerably faster onset of effect (34.6 v 68.5 min; p = 0.021), reflected in shorter latencies to peak L-dopa plasma concentrations. Mean on time was 21.9% (37 min) longer with 30 g mucuna than with LD/CD (p = 0.021); peak L-dopa plasma concentrations were 110% higher and the area under the plasma concentration v time curve (area under curve) was 165.3% larger (p = 0.012). No significant differences in dyskinesias or tolerability occurred. CONCLUSIONS: The rapid onset of action and longer on time without concomitant increase in dyskinesias on mucuna seed powder formulation suggest that this natural source of L-dopa might possess advantages over conventional L-dopa preparations in the long term management of PD. Assessment of long term efficacy and tolerability in a randomised, controlled study is warranted.     

Sentinel lymph node biopsy for the T1 (thin) melanoma: is it necessary?

The use of sentinel lymph node biopsy for the T1 melanoma is controversial. Recent reports have demonstrated that certain T1 melanomas are at increased risk for early regional metastases and late recurrence when compared with all thin melanomas. The purpose of this study was to review the authors' experience with wide excision and sentinel lymph node biopsy for certain patients with T1 melanoma. A retrospective analysis of 34 patients with T1 melanoma was completed over a 3-year period. Indications for sentinel lymph node biopsy included a Breslow thickness of less than or equal to 1 mm a Clark level of III or IV tumor ulceration, or tumor regression. Twenty-four patients met these criteria (13 men and 11 women). Mean age was 47.6 years (range, 23-88 years). Mean tumor thickness for all patients was 0.69 mm (range, 0.3-1.0 mm), 0.61 mm for the Clark level III patients (N = 15), and 0.72 mm for the Clark level IV patients (N = 9). Tumor ulceration was present in 1 patient and histological regression was present in 2 patients. Regional lymph node metastases were confirmed histologically in 2 of 24 patients (8.3%) in whom the thickness of the melanoma was 0.9 mm and 1 mm. Both patients have died of metastatic melanoma. No recurrence has been demonstrated in the remaining 22 patients at the 2 to 5-year follow-up. Current indications for sentinel lymph node biopsy for patients with T1 melanoma include tumors associated with Clark level IV or V invasion, ulceration, regression, a positive deep margin on initial biopsy, or previous melanoma. Acral lentiginous melanoma associated with at least a Clark level III invasion warrant sentinel lymph node biopsy. Superficial spreading or nodular melanoma larger than 0.9 mm should include sentinel lymph node biopsy regardless of other associated histological factors.     

The association between magnesium intake and fasting insulin concentration in healthy middle-aged women

OBJECTIVE: We assessed the association between magnesium intake and fasting insulin levels in a large cohort of women. METHODS: Female nurses free of diabetes, cardiovascular diseases and cancer from the Nurses Health Study provided blood samples between 1989-1990. We selected a sub-sample of 219 women for this analysis. Magnesium intake was assessed by a food frequency questionnaire in 1990 and categorized into quartiles. Cross-sectional geometric means of fasting insulin concentrations by quartiles of magnesium intake were obtained with Generalized Linear Model and adjusted for several risk factors and lifestyle characteristics. RESULTS: After adjustment for age, body mass index (BMI), total energy, physical activity, hours per week spent sitting outside work, alcohol intake, smoking, and family history of diabetes, magnesium intake was inversely associated with fasting insulin concentration. The multivariate adjusted geometric mean for women in the lowest quartile of magnesium intake was 11.0 microU/mL and 9.3 microU/mL among those in the highest quartile of magnesium intake (p for trend = 0.04). The inverse association remained when we considered magnesium from only food sources. CONCLUSION: Higher magnesium intake is associated with lower fasting insulin concentrations among women without diabetes. Because lower fasting insulin concentrations generally reflect greater insulin sensitivity, these findings provide a mechanism through which higher dietary magnesium intake may reduce the risk of developing type 2 diabetes mellitus.     

Healthy nations: reducing substance abuse in American Indian and Alaska Native communities

Since 1993, 14 American Indian and Alaska Native (AIAN) communities have worked diligently to reduce the harm due to substance abuse in their communities. Funded by the Robert Wood Johnson Foundation's Healthy Nations Initiative I, these communities implemented creative strategies that span the continuum from community-wide prevention, early identification and treatment to aftercare. Drawing upon the unique strengths of their own cultural traditions to find solutions to local substance abuse problems, these efforts have identified important and useful lessons for not only other AIAN communities, but also for sponsors of substance abuse programming in Indian country and elsewhere. Described here are successful strategies for developing and sustaining substance abuse programs in AIAN communities and an assessment of their impacts and accomplishments.     

Relevance of mitogen activated protein kinase (MAPK) and phosphotidylinositol-3-kinase/protein kinase B (PI3K/PKB) pathways to induction of apoptosis by curcumin in breast cells

Following observations that curcumin inhibited proliferation (IC(50)=1-5 microM), invasiveness and progression through S/G2/M phases of the cell cycle in the non-tumourigenic HBL100 and tumourigenic MDA-MB-468 human breast cell lines, it was noted that apoptosis was much more pronounced in the tumour line. Therefore, the ability of curcumin to modulate signalling pathways which might contribute to cell survival was investigated. After pre-treatment of cells for 20 min, curcumin (40 microM) inhibited EGF-stimulated phosphorylation of the EGFR in MDA-MB-468 cells and phosphorylation of extracellular signal regulated kinases (ERKs) 1 and 2, as well as ERK activity and levels of nuclear c-fos in both cell lines. At a lower dose (10 microM), it also inhibited the ability of anisomycin to activate JNK, resulting in decreased c-jun phosphorylation, although it did not inhibit JNK activity directly. In contrast, the activation of p38 mitogen activated protein kinase (MAPK) by anisomycin was not inhibited. Curcumin inhibited basal phosphorylation of Akt/protein kinase B (PKB) in both cell lines, but more consistently and to a greater extent in the MDA-MB-468 cells. The MAPK kinase (MKK) inhibitor U0126 (10 microM), while preventing ERK phosphorylation in MDA-MB-468 cells, did not induce apoptosis. The PI3K inhibitor LY294002 (50 microM) inhibited PKB phosphorylation in both cells lines, but only induced apoptosis in the MDA-MB-468 line. These results suggest that while curcumin has several different molecular targets within the MAPK and PI3K/PKB signalling pathways that could contribute to inhibition of proliferation and induction of apoptosis, inhibition of basal activity of Akt/PKB, but not ERK, may facilitate apoptosis in the tumour cell line.     

Growth-inhibitory effects of the chemopreventive agent indole-3-carbinol are increased in combination with the polyamine putrescine in the SW480 colon tumour cell line

Background

Many tumours undergo disregulation of polyamine homeostasis and upregulation of ornithine decarboxylase (ODC) activity, which can promote carcinogenesis. In animal models of colon carcinogenesis, inhibition of ODC activity by difluoromethylornithine (DFMO) has been shown to reduce the number and size of colon adenomas and carcinomas. Indole-3-carbinol (I3C) has shown promising chemopreventive activity against a range of human tumour cell types, but little is known about the effect of this agent on colon cell lines. Here, we investigated whether inhibition of ODC by I3C could contribute to a chemopreventive effect in colon cell lines.

Methods

Cell cycle progression and induction of apoptosis were assessed by flow cytometry. Ornithine decarboxylase activity was determined by liberation of CO₂ from¹⁴C-labelled substrate, and polyamine levels were measured by HPLC.

Results

I3C inhibited proliferation of the human colon tumour cell lines HT29 and SW480, and of the normal tissue-derived HCEC line, and at higher concentrations induced apoptosis in SW480 cells. The agent also caused a decrease in ODC activity in a dose-dependent manner. While administration of exogenous putrescine reversed the growth-inhibitory effect of DFMO, it did not reverse the growth-inhibition following an I3C treatment, and in the case of the SW480 cell line, the effect was actually enhanced. In this cell line, combination treatment caused a slight increase in the proportion of cells in the G₂/M phase of the cell cycle, and increased the proportion of cells undergoing necrosis, but did not predispose cells to apoptosis. Indole-3-carbinol also caused an increase in intracellular spermine levels, which was not modulated by putrescine co-administration.

Conclusion

While indole-3-carbinol decreased ornithine decarboxylase activity in the colon cell lines, it appears unlikely that this constitutes a major mechanism by which the agent exerts its antiproliferative effect, although accumulation of spermine may cause cytotoxicity and contribute to cell death. The precise mechanism by which putrescine enhances the growth inhibitory effect of the agent remains to be elucidated, but does result in cells undergoing necrosis, possibly following accumulation in the G₂/M phase of the cell cycle.     

Racial differences in sex hormone levels in women approaching the transition to menopause

OBJECTIVE: Evaluate racial differences in reproducibility of hormone levels over time (estradiol, DHEAS, FSH, and testosterone) while adjusting for covariates previously identified as relevant in the study population. DESIGN: Longitudinal cohort study. SETTING: Healthy, late-reproductive-age women in a community-based sample. PATIENT(S): African American and Caucasian women identified by random digit dialing. INTERVENTION(S): Hormone levels measured in the early follicular phase of the menstrual cycle four times over 9 months. A multivariate, linear mixed model estimated effects on hormone levels of race, age at enrollment, age at menarche, number of pregnancies, current smoking, alcohol consumption, body mass index (BMI), waist/hip ratio (WHR), and menstrual cycle length. MAIN OUTCOME MEASURE(S): Follicular plasma levels of estradiol, FSH, DHEAS, and testosterone. RESULT(S): African American but not Caucasian women had significantly lower levels of estradiol and DHEAS with increasing age. African American but not Caucasian women had significantly decreased levels of estradiol and significantly increased levels of DHEAS with increasing BMI. No racial differences in reproducibility of hormone measures were found. CONCLUSION(S): There are racial differences in associations of hormone levels with age and BMI in late reproductive age women. Further study is needed to replicate these findings and to determine the relationships of these hormonal associations with menopausal symptoms.