Low blood lead concentration in association with infertility in women

This study investigated the relationship between low-level lead exposure and risk of infertility in women. Study participants consisted of 64 cases recruited at a private infertility clinic and 83 control women from the postpartum clinic unit at a medical center in Kaohsiung, Taiwan. With informed consent, venous blood samples were obtained from subjects, during their early follicular phases (the 1st to 5th days of the menstrual cycle), for measuring concentrations of lead and hormones. Information on other potential risk factors associated with infertility, including reproductive history, Chinese herbal Medicine use, dairy product consumption, residential environment, and sociodemographic status, was obtained during an in-person interview. The mean blood lead level (BLL) in infertile women was significantly higher than that in controls (3.55 vs 2.78 microg/dL, P=0.007). Compared to women with BLL < or = 2.5 microg/dL, women with BLL>2.5 microg/dL were associated with a threefold increased risk for infertility (adjusted odds ratio=2.94, 95% confidence interval 1.18-7.34), after controlling for age, body mass index, smoking, Chinese herbal Medicine use, and irregular menstruation. Women's BLL was a significant predictor of the serum estradiol concentration also. These findings suggest an important role of very low BLL in the risk of infertility in women.     

Surgical treatment for severe visual compromised patients after pituitary apoplexy

Background Pituitary apoplexy is a rare neurovascular insult. Early surgical decompression is the most effective treatment, especially for rapid deterioration of visual acuity or for altered consciousness. The timing of rapidly expanded mass was strongly related to the treatment outcome.Methods Thirteen patients who presented with severe visual defect after pituitary apoplexy were enrolled retrospectively. Six patients without severe underlying diseases were considered non-complicated and were treated early. Another seven patients who received delayed treatment after medical problems were stabilized and/or conservative management failed were considered to be complicated. The visual acuity of each individual eye was evaluated and organized into six grades based on visual acuity. Twelve patients received transsphenoidal surgery and one craniotomy was performed for tumor removal.Results The delay of surgical treatment was 3.5 days and 8.7 days in the two groups, respectively. Overall, 19 out of 26 eyes (73%) improved after surgery; 100% in non-complicated group and 50% in complicated group. The average grade of visual improvement was 2.66 vs. 0.71 by each individual eye, and the difference was statistically significant (P<0.000). The ratio of regained useful vision was significant in non-complicated patients (P<0.000). The incidence of requirement long-term hormone replacement was high in the complicated group (2/6 vs. 6/7). The resection rate was total in 8 patients, subtotal in 3, partial in 1, with one loss of image follow-up. Conclusions Early decompression significantly improved visual outcomes and the need for hormone replacement was minimal. We postulated old age, underlying malignant diseases, and coagulation disorders played the predisposing factors of poor outcome in these cases.     

Ultrasound stimulates cyclooxygenase-2 expression and increases bone formation through integrin, focal adhesion kinase, phosphatidylinositol 3-kinase, and Akt pathway in osteoblasts

It has been shown that ultrasound (US) stimulation accelerates fracture healing in animal models and in clinical studies. Here we found that US stimulation transiently increased the surface expression of alpha2, alpha5, beta1, and beta3 integrins in cultured osteoblasts, as shown by flow cytometric analysis and immunofluorescence staining. US stimulation increased prostaglandin E(2) formation and the protein and mRNA levels of cyclooxygenase-2 (COX-2). At the mechanistic level, anti-integrin alpha5beta1 and alphavbeta3 antibodies or rhodostomin, a snake venom disintegrin, attenuated the US-induced COX-2 expression. Phosphatidylinositol 3-kinase (PI3K) inhibitors 2-(4-morpholinyl)-8-phenyl-1(4H)-benzopyran-4-one hydrochloride (LY294002) and wortmannin also inhibited the potentiating action of US. US stimulation increased the phosphorylation of focal adhesion kinase (FAK), extracellular signal-regulated kinases (ERK), p85 subunit of PI3K, and serine 473 of Akt. COX-2 promoter activity was enhanced by US stimulation in cells transfected with pCOX2-Luc. Cotransfection with dominant-negative mutant of FAK(Y397F), p85(Deltap85), Akt(K179A), or ERK2(K52R) inhibited the potentiating action of US on COX-2 promoter activity. Expression of mineralized nodule was lower in dominant-negative mutants of FAK, p85, and Akt-transfected clones than in vector-transfected control cells. Taken together, our results provide evidence that US stimulation increases COX-2 expression and promotes bone formation in osteoblasts via the integrin/FAK/PI3K/Akt and ERK signaling pathway.     

A community-based epidemiologic study of gender differences in the relationship between insulin resistance/beta-cell dysfunction and diabetic retinopathy among type 2 diabetic patients in Kinmen, Taiwan

PURPOSE: The purpose of this study was to explore whether there were gender differences in the relation of insulin resistance and beta-cell dysfunction to diabetic retinopathy among type 2 diabetic patients. METHODS: From 1999 to 2002, a screening regimen for diabetic retinopathy was performed by a panel of ophthalmologists using ophthalmoscopy and 45-degree color fundus photography to examine the fundus in a total of 971 type 2 diabetic patients examined between 1991 and 1993 in Kinmen, Taiwan. Seven hundred and twenty-five type 2 diabetic patients (301 males and 424 females) attended ophthalmological fundus checkup. RESULTS: The response rate in males and females was 71.3 and 77.2%. The proportion of diabetic retinopathy at the first eye screening was 16.3% in males and 20.1% in females. From the multiple logistic regression, the type of diabetes (known cases vs. new cases) was a significant factor of diabetic retinopathy in both males (OR = 3.65, 95% CI: 1.59-8.37) and females (OR = 3.66, 95% CI: 2.01-6.70). Diabetic retinopathy was also strongly affected by the homeostasis model assessment of insulin resistance (HOMA IR) and homeostasis model assessment of beta-cell dysfunction (HOMA beta-cell) (p < 0.0001 for trend test). In males, those who were in the 2nd quartile, 3rd quartile, and 4th quartile of HOMA IR had 4.87 times (95% CI: 1.18-20.11), 6.83 times (95% CI: 1.91-24.46), and 10.15 times (95% CI: 2.42-42.56) the risk for diabetic retinopathy as compared to those in the 1st quartile. There was a reduced risk for diabetic retinopathy in relation to HOMA beta-cell for the 2nd quartile, 3rd quartile, and 4th quartile of 86% (95% CI: 37-97%), 95% (95% CI: 77-99%), and 96% (95% CI: 78-99%) as compared to that in the 1st quartile. Only the 4th quartile had a significant risk (OR = 2.62, 95% CI: 1.17-5.86) for diabetic retinopathy as compared to that in the 1st quartile in females. The reduced risk for diabetic retinopathy found in relation to HOMA beta-cell for the 3rd and 4th quartiles were 66% (95% CI: 6-88%) and 66% (95% CI: 10-87%) as compared to that in the 1st quartile. CONCLUSIONS: Gender differences in the relationship between insulin resistance/beta-cell dysfunction and diabetic retinopathy were demonstrated in type 2 diabetic patients.     

Immuno-suppressive effect of blocking the CD28 signaling pathway in T-cells by an active component of Echinacea found by a novel pharmaceutical screening method

AFTIR (after flowing through immobilized receptor) is a novel method for screening herbal extracts for pharmaceutical properties. Using AFTIR, we identified Cynarin in Echinacea purpurea by its selective binding to chip immobilized CD28, a receptor of T-cells, which is instrumental to immune functioning. The results of surface plasma resonance show that binding between immobilized CD28 and Cynarin is stronger than the binding between CD28 and CD80, a co-stimulated receptor of antigen presenting cells. Cynarin's function was verified by its ability to downregulate CD28-dependent interleukin-2 (IL-2) expression in a T-cell culture line. AFTIR offers promise as an efficient screening method for herbal medicines.     

Visual association memory test in differentiating early stage of Alzheimer's disease from vascular dementia

We studied the results of the Visual Association Memory Test (VAMT) in differentiating Alzheimer's disease (AD) and vascular dementia (VaD). In addition, other basic neuropsychological tests, including the Mini-Mental State Examination (MMSE) and the Clinical Dementia Rating (CDR) were also used. Generally, with the VAMT, AD patients had a worse performance than VaD patients. Particularly among patients with a CDR = 0.5, the AD patients had statistically significantly lower VAMT scores (score less than 3) (p = 0.026) compared to those of VaD patients. However, the VAMT could not predict clinical severity or disease progression. The VAMT, as revealed in this study, is a brief, simply administered, and less biased test, and may offer a diagnostic adjunct to differentiate AD from VaD especially in an early dementia state.     

Exercise test in the inter-attack period of thyrotoxic periodic paralysis: a useful diagnostic tool

Exercise test was reported to be useful for some patients with periodic paralysis. We report here the results of exercise test in three cases of thyrotoxic periodic paralysis, for whom the exercise test was all positive. Exercise test could be one of the diagnostic tools in the "inter-attack" state of the probable cases with thyrotoxic periodic paralysis. However, the case number of this study is small and larger-scale studies may be warranted in the future.     

Mothers tended to overreport categorical infant birth weight of their children

OBJECTIVES: We validated infant birth weight by interview with mothers. STUDY DESIGN AND SETTING: Infant birth weights obtained from maternal interview were compared with the data documented in birth certificates. Study subjects were mothers of 1,432 schoolchildren who participated in a diabetes mass screening program in 1992-1997, Taiwan. Data of infant birth weight obtained from telephone interview with mothers were compared with those from birth certificates to evaluate the accuracy of maternal report in eight categorized groups: <2,000, 2,000-2,499, 2,500-2,999, 3,000-3,499, 3,500-3,999, 4,000-4,499, 4,500-4,999, and >or=5,000 g. RESULTS: The exact agreement was as low as 15.9% but increased substantially to 67.7% if maternal reports of weight one category higher than birth registry weight were considered to be indicative of agreement. Lower orders of birth weight were significantly associated with reports of higher category. But teen mothers and/or low-income mothers were associated with lower risks of overreport. CONCLUSION: Our data suggested that birth weight-associated studies in Taiwan should "round number" to an upper category rather than a lower category to avoid serious misclassification in birth weight.     

Lead exposure is associated with decreased serum paraoxonase 1 (PON1) activity and genotypes

Lead exposure causes cardiac and vascular damage in experimental animals. However, there is considerable debate regarding the causal relationship between lead exposure and cardiovascular dysfunction in humans. Paraoxonase 1 (PON1), a high-density lipoprotein-associated antioxidant enzyme, is capable of hydrolyzing oxidized lipids and thus protects against atherosclerosis. Previous studies have shown that lead and several other metal ions are able to inhibit PON1 activity in vitro. To investigate whether lead exposure has influence on serum PON1 activity, we conducted a cross-sectional study of workers from a lead battery manufactory and lead recycling plant. Blood samples were analyzed for whole-blood lead levels, serum PON1 activity, and three common PON1 polymorphisms (Q192R, L55M, -108C/T). The mean blood lead level (+/-SD) of this cohort was 27.1+/-15 microg/dL. Multiple linear regression analysis showed that blood lead levels were significantly associated with decreased serum PON1 activity (p<0.001) in lead workers. This negative correlation was more evident for workers who carry the R192 allele, which has been suggested to be a risk factor for coronary heart disease. Taken together, our results suggest that the decrease in serum PON1 activity due to lead exposure may render individuals more susceptible to atherosclerosis, particularly subjects who are homozygous for the R192 allele.