Steroid hormone levels and bone mineral density in women over 65 years of age.

Previous studies using immunoassays for steroid measurements have focused on the association between steroid hormone levels and bone mineral density (BMD) in postmenopausal women, obtaining contradictory results. This study aimed to assess this association using a highly sensitive bioanalytical method. A total of 68 postmenopausal women, aged 65-89 years, were enrolled in a cross-sectional study. Measurements of the BMD of the hip and lumbar spine were performed using dual energy X-ray absorptiometry, and serum hormone levels were quantified by gas chromatography and tandem mass spectrometry. Associations between estradiol (E2), testosterone, dehydroepiandrosterone (DHEA), androstenedione and T score levels of the hip and lumbar spine were evaluated, after adjustment for confounding variables. The analysis revealed a statistically significant association between testosterone and the T score of the hip (p = 0.035), but not that of the lumbar spine. No statistically significant associations were found between E2, DHEA, androstenedione and the T scores of the hip and the lumbar spine. Using a highly sensitive hormone assay method, our study identified a significant association between testosterone and BMD of the hip in women over 65 years of age, suggesting that lower testosterone increases the risk of osteoporosis.

Steroid hormone levels in postmenopausal hysterectomised women with and without ovarian conservation: the continuous endocrine function of the ovaries.

This study aims to clarify the effect of postmenopausal bilateral oophorectomy on plasma steroid hormone levels. Women who were submitted in the postmenopausal period to hysterectomy for uterine benign conditions were divided into two groups: 18 women had isolated hysterectomy and 11 had hysterectomy with bilateral salpingo-oophorectomy. In both groups serum hormone levels were quantified by solid phase extraction and gas chromatography and tandem mass spectrometry. Differences in dehydroepiandrosterone (DHEA), testosterone, androstenedione and oestradiol were determined in both groups. The analysis revealed lower steroid levels in the bilateral salpingo-oophorectomy group when compared to the isolated hysterectomy group with statistically significant differences found for DHEA (5.8 ± 3.2 vs. 9.4 ± 4.4 ng/mL; p = 0.019) and oestradiol (0.69 ± 0.4 vs. 1.48 ± 4.3 ng/mL; p = 0.007). The results are consistent with a significant endocrine activity of the postmenopausal ovary. The clinical consequences of these findings need to be clarified and postmenopausal prophylactic bilateral salpingo-oophorectomy re-evaluated.IMPACT STATEMENTWhat is already known on this subject? Although it is consensual that premenopausal prophylactic bilateral oophorectomy should not be performed because it has harmful effects on women's health, the evidence regarding the effects of postmenopausal prophylactic bilateral oophorectomy is scarce and this procedure continues to be a regular practice. Few studies have demonstrated that postmenopausal ovaries still have endocrine activity that may impact older women's health.What do the results of this study add? This is the first study to compare hormone levels of postmenopausal women based on their hysterectomy and oophorectomy status using GC-MS/MS, a highly sensitive bioanalytical assay for the measurement of steroid hormones. Previous studies relied on immunoassays and did not compare DHEA levels, which according to the intracrinology theory is a precursor for androgens and oestrogens. In this study, statistically significant lower levels of DHEA and oestradiol were found after postmenopausal bilateral salpingo-oophorectomy.What are the implications of these findings for clinical practice and/or further research? This is a pilot study that may lead to further investigation in this area to clarify the impact of the prophylactic removal of postmenopausal ovaries on older women's health and lead to changes in surgical procedures.

Differentiating Swyer syndrome and complete androgen insensitivity syndrome: a diagnostic dilemma.

BACKGROUND: Swyer syndrome and complete androgen insensitivity syndrome are disorders of sex development in which patients present a female phenotype and 46,XY karyotype. CASE: The authors present a case report of an 18-year-old patient with primary amenorrhea and delayed puberty. The karyotype was 46,XY. No mutations of sex-determining region Y gene and androgen receptor genes were identified, and imaging methods failed to show müllerian structures. A diagnosis of complete androgen insensitivity syndrome was presumed, but after hormonal replacement therapy was started a "hidden" uterus developed, leading to the definite diagnosis of Swyer syndrome. SUMMARY AND CONCLUSION: The diagnosis of Swyer syndrome can be challenging, because visualization of müllerian structures is sometimes difficult and analysis of genetic mutations is not helpful in the majority of cases.

Dietary restriction improves systemic and muscular oxidative stress in type 2 diabetic Goto-Kakizaki rats

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Type 2 diabetes is a heterogeneous metabolic disease characterized by insulin resistance and Beta-cell dysfunction leading to hyperglycaemia and dyslipidaemia. Dietary intervention seems to improve some of these cellular complications, namely insulin resistance. Our aim was to evaluate the effects of dietary restriction on systemic and skeletal muscle oxidative stress and insulin resistance in normal Wistar rats and (..) (AU)

Dietary restriction improves systemic and muscular oxidative stress in type 2 diabetic Goto-Kakizaki rats.

Type 2 diabetes is a heterogeneous metabolic disease characterized by insulin resistance and ß-cell dysfunction leading to hyperglycaemia and dyslipidaemia. Dietary intervention seems to improve some of these cellular complications, namely insulin resistance. Our aim was to evaluate the effects of dietary restriction on systemic and skeletal muscle oxidative stress and insulin resistance in normal Wistar rats and Goto-Kakizaki (GK) rats, a non-obese type 2 diabetic animal model. Four-month-old normal and diabetic rats were separated in four groups. One group of each strain was maintained with ad libitum standard diet, and the other group was submitted to a dietary restriction (50% of control animals daily food intake), during 2 months. Metabolic profile, insulin resistance indexes and muscle lipids were determined. Oxidative stress parameters were also measured at systemic and muscle levels: protein carbonyl, 8-hydroxy-2'-deoxyguanosine and free 8-isoprostane. Dietary restriction improved lipid profile in both strains and urinary free 8-isoprostane and plasma carbonyl compounds in diabetic rats. An improvement of muscle triglycerides accumulation and 8-isoprostane concentration and a reduction of insulin resistance were also observed in GK rats. Our data show that dietary restriction ameliorates systemic and skeletal muscle oxidative stress state in type 2 diabetes, which is associated with improved insulin resistance.

Metformin restores endothelial function in aorta of diabetic rats.

BACKGROUND AND PURPOSE: The effects of metformin, an antidiabetic agent that improves insulin sensitivity, on endothelial function have not been fully elucidated. This study was designed to assess the effect of metformin on impaired endothelial function, oxidative stress, inflammation and advanced glycation end products formation in type 2 diabetes mellitus. EXPERIMENTAL APPROACH: Goto-Kakizaki (GK) rats, an animal model of nonobese type 2 diabetes, fed with normal and high-fat diet during 4 months were treated with metformin for 4 weeks before evaluation. Systemic oxidative stress, endothelial function, insulin resistance, nitric oxide (NO) bioavailability, glycation and vascular oxidative stress were determined in the aortic rings of the different groups. A pro-inflammatory biomarker the chemokine CCL2 (monocyte chemoattractant protein-1) was also evaluated. KEY RESULTS: High-fat fed GK rats with hyperlipidaemia showed increased vascular and systemic oxidative stress and impaired endothelial-dependent vasodilatation. Metformin treatment significantly improved glycation, oxidative stress, CCL2 levels, NO bioavailability and insulin resistance and normalized endothelial function in aorta. CONCLUSION AND IMPLICATIONS: Metformin restores endothelial function and significantly improves NO bioavailability, glycation and oxidative stress in normal and high-fat fed GK rats. This supports the concept of the central role of metformin as a first-line therapeutic to treat diabetic patients in order to protect against endothelial dysfunction associated with type 2 diabetes mellitus.

Mitochondria from distinct tissues are differently affected by 17ß-estradiol and tamoxifen.

This study was aimed to analyse and compare the bioenergetics and oxidative status of mitochondria isolated from liver, heart and brain of ovariectomized rat females treated with 17ß-estradiol (E2) and/or tamoxifen (TAM). E2 and/or TAM did not alter significantly the respiratory chain of the three types of mitochondria. However, TAM significantly decreased the phosphorylation efficiency of liver mitochondria while E2 significantly decreased the phosphorylation efficiency of heart mitochondria. E2 also significantly decreased the capacity of heart and liver mitochondria to accumulate Ca(2+) this effect being attenuated in liver mitochondria isolated from E2+TAM-treated rat females. TAM treatment increased the ratio of glutathione to glutathione disulfide (GSH/GSSG) of liver mitochondria. Brain mitochondria from TAM- and E2+TAM-treated females showed a significantly lower GSH/GSSG ratio. However, heart mitochondria from TAM- and E2+TAM-treated females presented a significant decrease in GSSG and an increase in GSH/GSSG ratio. Thiobarbituric acid reactive substances levels were significantly decreased in liver mitochondria isolated from E2+TAM-treated females. Finally, E2 and/or TAM treatment significantly decreased the levels of hydrogen peroxide produced by brain mitochondria energized with glutamate/malate. These results indicate that E2 and/or TAM have tissue-specific effects suggesting that TAM and hormonal replacement therapies may have some side effects that should be carefully considered.

Insulin and metformin may prevent renal injury in young type 2 diabetic Goto-Kakizaki rats.

Type 2 diabetes is increasing at epidemic proportions throughout the world, and diabetic nephropathy is the principal cause of end stage renal failure. Approximately 40% of patients with type 2 diabetes may progress to nephropathy and a good metabolic control can prevent the development of diabetic renal injury. The aim of our study was to evaluate, in young type 2 diabetic Goto-Kakizaki (GK) rats fed with atherogenic diet, the effects of the anti-diabetic compounds insulin, metformin and gliclazide on renal damage. GK rats fed with atherogenic diet showed increased body weight and fasting blood glucose, total cholesterol, triglycerides, C-reactive protein and protein carbonyl levels and lower HDL-cholesterol concentration; renal markers of inflammation and fibrosis were also elevated. All the anti-diabetic agents ameliorated fasting glycaemia and insulin resistance but only insulin and metformin were able to improve glycoxidation, fibrosis and inflammation kidney parameters. Our data suggest that insulin and metformin treatments, improving glicoxidative, inflammatory and fibrotic renal damage markers, play a key role in the prevention of diabetic nephropathy.

"MitoTea": Geranium robertianum L. decoctions decrease blood glucose levels and improve liver mitochondrial oxidative phosphorylation in diabetic Goto-Kakizaki rats.

Several chemical compounds found in plant products have proven to possess beneficial properties, being currently pointed out due to their pharmacological potential in type 2 diabetes mellitus complications. In this context, we studied the effect of Geranium robertianum L. (herb Robert) leaf decoctions in Goto-Kakizaki (GK) rats, a model of type 2 diabetes. Our results showed that oral administration of G. robertianum leaf decoctions over a period of four weeks lowered the plasma glucose levels in diabetic rats. Furthermore, the treatment with G. robertianum extracts improved liver mitochondrial respiratory parameters (state 3, state 4 and FCCP-stimulated respiration) and increased oxidative phosphorylation efficiency.

Beneficial effects of dietary restriction in type 2 diabetic rats: the role of adipokines on inflammation and insulin resistance.

Inflammation plays an important role in diabetes mellitus and its complications. In this context, the negative cross-talk between adipose tissue and skeletal muscle leads to disturbances in muscle cell insulin signalling and induces insulin resistance. Because several studies have shown that energy restriction brings some benefits to diabetes, the aim of the present study was to evaluate the effects of dietary restriction on systemic and skeletal muscle inflammatory biomarkers, such C-reactive protein, adipokines and cytokines, and in insulin resistance in Goto-Kakizaki rats. This is an animal model of spontaneous non-obese type 2 diabetes with strongly insulin resistance and without dyslipidaemia. Animals were maintained during 2 months of dietary restriction (50 %) and were killed at 6 months of age. Some biochemical determinations were done using ELISA and Western blot. Data from the present study demonstrate that in Goto-Kakizaki rats the dietary restriction improved insulin resistance, NEFA levels and adipokine profile and ameliorated inflammatory cytokines in skeletal muscle. These results indicate that dietary restriction in type 2 diabetes enhances adipose tissue metabolism leading to an improved skeletal muscle insulin sensitivity.

Effect of ferrous sulphate on aspartate and alanine aminotransferases of brain of Tilapia mossambica.

Iron in the form of ferrous sulphate coming from sources such as mines, writing inks, blue pigments, dyeing industries, photography, medicine, deodorizers, disinfectants, fungicides and molluscides, etc. contributes in elevating ferrous sulphate of water bodies. The present study investigated the action of ferrous sulphate on the local fish Tilapia mossambica. Tilapia exposed to 0.001 g/L ferrous sulphate for 30 days showed reduction of cytosolic AST and ALT activities of cerebral cortex by 35.4% and 29.1%, respectively, while exposure to 0.01% ferrous sulphate promoted 49.2% and 38.4% reduction of AST and ALT activities. Similarly mitochondrial AST and ALT activities reduced by 50% and 34.8%, respectively, on exposure to 0.001 g/L ferrous sulphate while 0.01 g/L ferrous sulphate promoted 51% and 47.8% reductions of AST and ALT activities at the end of 30 days, suggesting interference in the glutamate and protein metabolism of Tilapia brain.

Supplementation of coenzyme Q10 and alpha-tocopherol lowers glycated hemoglobin level and lipid peroxidation in pancreas of diabetic rats.

The importance of nutritional supplementation in diabetes remains an unresolved issue. The present study was undertaken to examine the effects of alpha-tocopherol and CoQ(10), powerful antioxidants, on metabolic control and on the pancreatic mitochondria of GK rats, a model of type 2 diabetes. We also evaluated the efficacy of these nutrients in preventing the diabetic pancreatic lesions observed in GK rats. Rats were divided into 4 groups, a control group of diabetic GK rats and 3 groups of GK rats administered with alpha-tocopherol and CoQ(10) alone or both in association, during 8 weeks. Fasting blood glucose levels were not significantly different between the groups, nor were blood glucose levels at 2 hours after a glucose load. HbA1c level was significantly reduced in the group supplemented with both antioxidants. Diabetes induced a decrease in coenzyme Q plasma levels that prevailed after treatment with antioxidants. In addition, the plasma alpha-tocopherol levels were higher after treatment with the antioxidants. An increment in some components of the antioxidant defense system was observed in pancreatic mitochondria of treated GK rats. Moreover, the antioxidants tested either alone or in association failed to prevent the pancreatic lesions in this animal model of type 2 diabetes. In conclusion, our results indicate that CoQ(10) and alpha-tocopherol decrease glycated HbA1c and pancreatic lipid peroxidation. These antioxidants increase some components of the antioxidant defense system but do not prevent pancreatic lesions. Thus, we cannot rule out the potential benefit of antioxidant treatments in type 2 diabetes in the prevention of their complications.

Metformin protects the brain against the oxidative imbalance promoted by type 2 diabetes.

We aimed to investigate whether metformin protects the brain against the oxidative imbalance promoted by type 2 diabetes. This study analyzed the effect of metformin on oxidative stress markers (thiobarbituric acid reactive substances (TBARS), malondialdehyde (MDA) and carbonyl groups), hydrogen peroxide (H(2)O(2)) levels, non-enzymatic antioxidant defenses [reduced (GSH) and oxidized (GSSG) glutathione and vitamin E] and enzymatic antioxidant defenses [glutathione peroxidase (GPx), glutathione reductase (GRed) and manganese superoxide dismutase (MnSOD)] in brain homogenates of diabetic GK rats, a model of type 2 diabetes. For this purpose we compared brain homogenates obtained from untreated GK rats versus GK rats treated with metformin during a period of 4 weeks. Brain homogenates obtained from Wistar rats were used as control. The MDA levels, GPx and GRed activities are significantly higher in untreated GK rats, while TBARS levels, carbonyl groups, glutathione content and vitamin E levels remain statistically unchanged when compared with control rats. In contrast, MnSOD activity and the levels of H(2)O(2) are significantly decreased in untreated GK rats when compared with control animals. However, metformin treatment normalized the majority of the parameters altered by diabetes. We observed that metformin, besides its antihyperglycemic action, induces a significant decrease in TBARS and MDA levels, GPx and GRed activities and a significant increase in GSH levels and MnSOD activity. These results indicate that metformin protects against diabetes-associated oxidative stress suggesting that metformin could be an effective neuroprotective agent.

The effect of soybean oil on glycaemic control in Goto-kakizaki rats, an animal model of type 2 diabetes.

UNLABELLED: Several studies in humans and laboratory animals with type 2 diabetes indicate that antioxidant supplements lessen the impact of oxidative damage caused by dysregulation of glucose metabolism. The present study was undertaken to examine the effect of soybean oil on glycaemic control and lipid metabolism in Goto-kakizaki (GK) rats, a model of type 2 diabetes. Rats were divided into three groups, a control group of non-diabetic (Wistar) rats, a group of diabetic GK rats and a group of GK rats treated with soybean oil. Plasma samples from the different groups were analysed for total alpha-tocopherol, coenzyme Q and glucose levels. Glycated haemoglobin was also compared between the different groups. Fasting and non-fasting blood glucose levels were significantly decreased in soybean oil group compared with GK group. There was also a 14 % reduction in the levels of HbA(1c) in SO-treated GK when compared with the diabetic control group. Diabetes induced a decrease in coenzyme Q plasma levels that prevailed after treatment with soybean oil. Moreover, the plasma alpha-tocopherol levels were higher after treatment with soybean oil. CONCLUSIONS: Our observations suggest that soybean oil treatment may be beneficial in type 2 diabetes. Since soybean oil has very high amounts of coenzyme Q and other antioxidants one possible mechanism of action could be as an antioxidant.

Endothelial dysfunction in type 2 diabetes: effect of antioxidants.

Individuals with insulin resistance and diabetes mellitus have increased cardiovascular morbidity and mortality, caused in part by vascular complications. Endothelial dysfunction has been implicated in the pathogenesis of vascular diabetic disease. This abnormal function of the vasculature precedes cardiovascular disease and is associated with impaired endothelium-dependent vasorelaxation. The main etiology of the increased mortality and morbidity of type 2 diabetic patients is atherosclerosis. Increased production of free radicals is associated with the pathophysiology of diabetes, resulting in oxidative damage to lipids and proteins. Reduction of oxidative stress in diabetic patients may delay the onset of atherogenesis and the appearance of micro- and macrovascular complications. Alpha-lipoic acid (LA) is a multifunctional antioxidant that has been shown to have beneficial effects on polyneuropathy and on markers of oxidative stress in various tissues. This study was conducted to investigate the effects of LA on endothelial function in diabetic and hyperlipidemic animal models. Carbohydrate and lipid metabolism, endothelial function, plasma malondialdehyde (MDA) and urinary 8-hydroxydeoxyguanosine (8-OHdG) were assessed in non-diabetic controls (Wistar rats), untreated diabetic Goto-Kakizaki (GK) rats and, atherogenic diet (AD)-fed GK rats (fed with atherogenic diet only, treated with alpha-lipoic acid and treated with vehicle, for 3 months). AD resulted in a 3-fold increase in both total and non-HDL serum cholesterol levels and in a 2-fold increase triglyceride levels while endothelial function was significantly reduce MDA and 8-OHdG levels were higher in the GK and GK hyperlipidemic groups and were completely reversed by the antioxidant. Hyperlipidemic GK diabetic rats showed significantly reduced endothelial function that was partially improved with LA. Furthermore, lipoic acid significantly reduced serum cholesterol levels, without lowering HDL cholesterol. Alpha-lipoic acid supplementation represents an achievable adjunct therapy to improve endothelial function and reduce oxidative stress, factors that are implicated in the pathogenesis of atherosclerosis in diabetes.

Estradiol affects liver mitochondrial function in ovariectomized and tamoxifen-treated ovariectomized female rats.

Given the tremendous importance of mitochondria to basic cellular functions as well as the critical role of mitochondrial impairment in a vast number of disorders, a compelling question is whether 17beta-estradiol (E2) modulates mitochondrial function. To answer this question we exposed isolated liver mitochondria to E2. Three groups of rat females were used: control, ovariectomized and ovariectomized treated with tamoxifen. Tamoxifen has antiestrogenic effects in the breast tissue and is the standard endocrine treatment for women with breast cancer. However, under certain circumstances and in certain tissues, tamoxifen can also exert estrogenic agonist properties. We observed that at basal conditions, ovariectomy and tamoxifen treatment do not induce any statistical alteration in oxidative phosphorylation system and respiratory chain parameters. Furthermore, tamoxifen treatment increases the capacity of mitochondria to accumulate Ca(2+) delaying the opening of the permeability transition pore. The presence of 25 microM E2 impairs respiration and oxidative phosphorylation system these effects being similar in all groups of animals studied. Curiously, E2 protects against lipid peroxidation and increases the production of H(2)O(2) in energized mitochondria of control females. Our results indicate that E2 has in general deleterious effects that lead to mitochondrial impairment. Since mitochondrial dysfunction is a triggering event of cell degeneration and death, the use of exogenous E2 must be carefully considered.

CoQ10 therapy attenuates amyloid beta-peptide toxicity in brain mitochondria isolated from aged diabetic rats.

Using brain mitochondria isolated from 20-month-old diabetic Goto-Kakizaki rats, we evaluated the efficacy of CoQ10 treatment against mitochondrial dysfunction induced by Abeta1-40. For that purpose, several mitochondrial parameters were evaluated: respiratory indexes (RCR and ADP/O ratio), transmembrane potential (DeltaPsim), repolarization lag phase, repolarization and ATP levels and the capacity of mitochondria to produce hydrogen peroxide. We observed that 4 microM Abeta1-40 induced a significant decrease in the RCR and ATP content and a significant increase in hydrogen peroxide production. CoQ10 treatment attenuated the decrease in oxidative phosphorylation efficiency and avoided the increase in hydrogen peroxide production induced by the neurotoxic peptide. These results indicate that CoQ10 treatment counteracts brain mitochondrial alterations induced by Abeta1-40 suggesting that CoQ10 therapy can help to avoid a drastic energy deficiency that characterizes diabetes and Alzheimer's disease pathophysiology.