Hyperplastic Effect Research Articles

Investigation of the protective effect of vitamin K1 on the heart in streptozotocin induced type 1 diabetes model

Maternal and fetal diabetes are directly associated with increased morbidity and mortality risk. Along with this increased risk, the incidence of congenital malformations in newborns also increases depending on the mother’s diabetes. Vitamin K1 is used as a therapeutic and protective agent in diabetes and various clinical conditions. For this reason, it was aimed to investigate the effect of vitamin K1 on chick embryo hearts immunohistochemically and morphologically by creating type 1 diabetes mellitus with streptozotocin in a chick embryo model. In our study, 5 different experimental groups will be created and a total of 50 SPF fertilized eggs, 10 in each group, will be used. The first group will be the control group, the second group will be the diabetes group, and the other three groups will be the treatment groups given different doses of vitamin K1. All solutions will be given on the 12th day ofincubation, and the hearts of all embryos will be analyzed immunohistochemically and morphologically on the 18th day of incubation. It was determined that the weight, length and ventricular thickness of the chick embryo hearts were statistically significantly decreased in the streptozotocin group compared to the control group embryo hearts. It was determined that the heart weights, lengths, and ventricular thicknesses increased depending on the dose of vitamin K1 compared to the streptozotocin group in the groups therapeutically administered vitamin K1 (p<0.05). In addition, caspase-3 expression was also evaluated in our study, and a statistically significant increase was found in the streptozotocin group compared to the control group. Again, as a result of vitamin K1 administration, caspase-3 expressions decreased depending on the applied dose (p<0.05). In conclusion, it was concluded thatthe therapeutically applied vitamin K1 to diabetes mellitus reduces the degenerative and hyperplastic effects of diabetes mellitus.

Anti-hyperplastic effects of the Dacryodes edulis (Burseraceae) leaves aqueous extract on tamoxifen-induced endometrium hyperplasia on Wistar rat.

Combining tamoxifen, the most common breast cancer hormonal therapy, with natural antitumor substances may prevent its hyperplastic effects on the uterine endometrium. Dacryodes edulis (DE) is traditionally recommended for the treatment of cancerous diseases. To investigate its antiproliferative properties, the present study was designed to assess the ability of the combined administration of tamoxifen with the aqueous extract of DE leaves to inhibit the trophic effect of this hormone therapy on rat uterine endometrium without compromising its non-proliferative effect on breast tissue. Ovariectomized (OVX) female Wistar rats were simultaneously treated with tamoxifen (10mg/kg) intraperitoneally and DE leaves (at doses of 25, 50 and 100mg/kgBW) by gavage. Control groups received either distilled water or tamoxifen alone. Treatments lasted 37days. The 38th day, animals were sacrificed under anesthesia (diazepam: 10mg/kgBW and ketamine: 50mg/kgBW). The relative uterine weight was determined and the histological analysis of the uterus and mammary gland was performed. The oxidative status of the uterus was assessed and the levels of cholesterol and estradiol were evaluated in serum and uterus. Tamoxifen increased uterine weight and induced endometrial hyperplasia. This effect was associated with increased uterine levels of cholesterol (164.22%; p<0.001), estradiol (927.5%; p<0.001) and malondiadehyde (86%; p<0.05), but unchanged antioxidant enzymes activities. The administration of DE leaves unchanged tamoxifen-increased uterine weight but reduced uterine epithelium hypertrophy (56.4%; p<0.01). DE also increased uterine levels of malondiadehyde and antioxidant enzymes. The levels of estradiol and cholesterol in the uterus decreased while no changes were observed in the mammary gland of animals treated with tamoxifen alone or in co-administration with DE. D.edulis has antiproliferative properties and could complement endocrine therapy of estrogen-dependent breast cancer.

Simvastatin mitigates depressive-like behavior in ovariectomized rats: Possible role of NLRP3 inflammasome and estrogen receptors’ modulation

It is well known that females are more vulnerable than males to stress-related psychiatric disorders, particularly during perimenopausal and postmenopausal periods. Hormone replacement therapy (HRT) has been widely used for the management of postmenopausal depression. However, HRT could be associated with severe adverse effects, including increased risk for coronary heart disease, breast cancer and endometrial cancer. Thus, there is a pressing demand for novel therapeutic options for postmenopausal depression without sacrificing uterine health. Simvastatin (SIM) was proven to have neuroprotective activities besides its hypocholesterolemic effect, the former can be attributed to its, antioxidant, anti-apoptotic and anti-inflammatory activities. Moreover, many reports highlighted that SIM has estrogenic activity and was able to induce the expression of estrogen receptors in rats. The present study showed that SIM (20 mg/kg, p.o.) markedly attenuated depressive-like behavior in ovariectomized (OVX) rats. Moreover, SIM prohibited hippocampal microglial activation, abrogated P2X7 receptor, TLR2 and TLR4 expression, inhibited NLRP3 inflammasome activation, with subsequent reduction in the levels of pro-inflammatory mediators; IL-1β and IL-18. Furthermore, a marked elevation in hippocampal expression of ERα and ERβ was noted in SIM-treated animals, without any significant effect on uterine relative weight or ERα expression. Taken together, SIM could provide a safer alternative for HRT for the management of postmenopausal depression, without any hyperplastic effect on the uterus.

Safety Assessment of AAV2-hGDNF Administered Via Intracerebral Injection in Rats for Treatment of Parkinson's Disease.

Glial cell line-derived neurotrophic factor (GDNF) is a potent neuroprotective biologic in Parkinson's disease models. Adeno-associated viral vector serotype 2 (AAV2)-human GDNF safety was assessed in rats treated with a single intracerebral dose of vehicle, 6.8 × 108, 6.8 × 109, or 5.2 × 1010 vector genomes (vg)/dose followed by interim sacrifices on day 7, 31, 90, and 376. There were no treatment-related effects observed on food consumption, body weight, hematology, clinical chemistry, coagulation parameters, neurobehavioral parameters, organ weights, or serum GDNF and anti-GDNF antibody levels. Increased serum anti-AAV2 neutralizing antibody titers were observed in the 5.2 × 1010 vg/dose group. Histopathological lesions were observed at the injection site in the 6.8 × 109 vg/dose (day 7) and 5.2 × 1010 vg/dose groups (days 7 and 31) and consisted of gliosis, mononuclear perivascular cuffing, intranuclear inclusion bodies, and/or apoptosis on day 7 and mononuclear perivascular cuffing on day 31. GDNF immunostaining was observed in the injection site in all dose groups through day 376 indicating no detectable impacts of anti-AAV2 neutralizing antibody. There was no evidence of increased expression of calcitonin gene-related peptide or Swann cell hyperplasia in the cervical and lumbar spinal cord or medulla oblongata at the 5.2 × 1010 vg/dose level indicating lack of hyperplastic effects. In conclusion, no systemic toxicity was observed, and the local toxicity observed at the injection site appeared to be reversible demonstrating a promising safety profile of intracerebral AAV2-GDNF delivery. Furthermore, an intracerebral dose of 6.8 × 108 AAV2-GDNF vg/dose was considered to be a no observed adverse effect level in rats.

The ethanol extract of avocado [Persea americana Mill. (Lauraceae)] seeds reduced the hyperplastic effect of tamoxifen on uterine endometrium without changing its effect on the mammary gland

Tamoxifen is the most common hormonal treatment for estrogen receptor positive (ER+) breast cancer. However, the long-term use of tamoxifen was associated with increased risks of endometrial cancer. The literature suggests that combining tamoxifen with substances endowed with antiproliferative properties could increase tamoxifen’s chemopreventive benefit. The ethanol extract of Persea americana Mill. (Lauraceae) seeds was found exhibiting antiproliferative properties in vitro. The present study therefore aimed at evaluating the ability of such an extract to prevent tamoxifen-induced endometrial hyperplasia without changing its activity on the mammary gland. This study was performed in ovariectomized rats receiving simultaneously tamoxifen (by the intraperitoneal route) and the ethanol extract of P. americana seeds (by gavage) at doses of 25, 50, 100 and 200 mg/kg. Co-administrations were performed for 37 consecutive days and animals were sacrificed thereafter. Uterine and serum levels of estradiol and cholesterol were assessed. The oxidative status of the uterus was also evaluated. Histology of the uterus and the mammary gland was performed. Results showed that the ethanol extract of P. americana seeds did not alter tamoxifen-induced uterine steroidogenesis but reduced its proliferative effect by decreasing uterine epithelial height (p < 0.001). T his antiproliferative effect was associated with increased uterine levels of malondialdehyde and antioxidant enzymes. On the mammary gland, the non-proliferative effect of tamoxifen was not altered by P. americana extract. In conclusion, the ethanol extract of P. americana seeds could be a complementary treatment to prevent tamoxifen-induced endometrial hyperplasia during the treatment of ER+ breast cancer.

Estrogen receptor activation in response to Azadirachtin A stimulates osteoblast differentiation and bone formation in mice.

The positive effectsof the sex hormone in sustaining bone homeostasis areexercised by maintaining the equilibrium betweencell activity and apoptosis. In this regard, the importance of estrogen receptors in maintaining the bone is that it is anattractive drug target,if devoid of known side effects. In this study, we show that a natural pure compound Azadirachtin A (Aza A) isolated from Azadirachta indica binds selectively to a site in the estrogen receptor, identifying itself to bea selective tissue modifier. Using computational and medicinal chemistry, we show that Aza A binds potentially and selectively to estrogen receptor-α (ERα) as compared with ERβ. This preferential binding of Aza A to ERα with good pharmacokinetic distribution in the body forms metabolites, showing that it is well absorbed. In in vivo estrogen deficiency models for osteoporosis, Aza A at a much lower dose enhances new bone formation at both sites of the trabecular and cortical bone with increased bone strength and presentswith no hyperplastic effect in the uterus.

Anti-osteoporotic effect of Gengnian Jianshen decoction in rats

Purpose: To investigate the therapeutic effect and mechanism of action of Gengnian Jianshen Decoction (GJD) on ovariectomy-induced osteoporosis in rats.Methods: Female Sprague-Dawley rats were randomly assigned to a sham-operated group (control), and five ovariectomy (OVX) sub-groups, that is, OVX with vehicle (OVX), OVX with Xianling Gubao capsule (positive control drug, 120 mg/kg/day), and OVX with GJD doses (70, 140, and 280 mg/kg/day). The treatments were given orally daily for 16 weeks (starting 4 weeks after the rats were subjected to ovariectomy. Bone mineral density (BMD) of the L4 vertebrae and right femur of each rat was estimated. Serum levels of estradiol (E2), follicle-stimulating hormone (FSH) and luteinizing hormone (LH), as well as interleukin-6 (IL-6) and insulin-like growth factor 1(IGF-1) of rats in all the groups were determined using ELISA.Results: The results showed that GJD dose-dependently inhibited BMD reduction in L4 vertebrae and femur, and significantly increased serum E2, FSH and LH levels (p &lt; 0.05) in the osteoporotic rats. Moreover, GJD significantly decreased serum IL-6 levels and increased levels of IGF-1 (p &lt; 0.05).Conclusion: These findings indicate that GJD prevents OVX-induced osteoporosis in rats without hyperplastic effects on the uterus. Thus, GJD has potential for use in the treatment of post-menopausal osteoporosis.Keywords: Gengnian Jianshen decoction, Osteoporosis, Ovariectomy, Bone mineral density

Protective effect of &lt;i&gt;Rhizoma drynariae&lt;/i&gt; extract on osteoporosis in ovariectomized rat model

Purpose: To investigate the therapeutic effect of Rhizoma Drynariae extract (RDE) on ovariectomyinduced osteoporosis in rats.Methods: Female Sprague-Dawley rats were randomly assigned to a sham-operated group (control) and five ovariectomy (OVX) subgroups: OVX with vehicle (OVX), OVX with 17ß-estradiol (E2, 25 μg/kg/day), and OVX with RDE doses (40, 80, and 160 mg/kg/day). Daily oral administration of E2 or RDE started 4 weeks after OVX and lasted for 16 weeks. The bone mineral density (BMD) of the L4 vertebrae and right femurs was estimated. The length of each femur was measured with a micrometer gauge, and the center of the diaphysis determined. Three representatives L4 vertebrae were selected to evaluate the trabecular microarchitecture. Serum alkaline phosphatase (ALP), urinary calcium (U-Ca),urinary phosphorus (U-P), urinary creatinine (Cr) and osteocalcin (OC) levels were measured.Results: The study showed that high-dose of RDE significantly inhibited the bone mineral density (BMD) reduction of L4 vertebrae (0.20 ± 0.02 g/cm3, p &lt; 0.05) and femurs (0.18 ± 0.02 g/cm3, p &lt; 0.05) caused by OVX and prevented the deterioration of trabecular microarchitecture (p &lt; 0.05), which were accompanied by a significant decrease in skeletal remodeling (p &lt; 0.05) as evidenced by the lowerlevels of bone turnover markers. High-dose of RDE improved morphometric parameters, namely, Tb-N (3.8 ± 0.2 mm, p &lt; 0.05), Tb-Th (0.083 ± 0.011 mm, p &lt; 0.05) and Tb-Sp (0.19 ± 0.01 mm, p &lt; 0.05) in L4 vertebrae significantly. The present study indicates that the administration of RDE at higher doses over a 16-week period can prevent OVX-induced osteoporosis in rats without hyperplastic effects on the uterus.Conclusion: Thus, RDE is a potential natural alternative for postmenopausal osteoporosis treatment in elderly women.Keywords: Rhizoma Drynariae, Postmenopausal osteoporosis, Ovariectomy, Bone mineral density, Morphometric

Puerarin prevents bone loss in ovariectomized mice and inhibits osteoclast formation in vitro

The present study aimed at investigating the effects of Puerarin (PR), a major isoflavonoid isolated from the Chinese medicinal herb Puerariae radix, on bone metabolism and the underlying mechanism of action. The in vivo assay, female mice were ovariectomized (OVX), and the OVX mice were fed with a diet containing low, middle, and high doses of PR (2, 4, and 8 mg·d−1, respectively) or 17β-estradiol (E2, 0.03 μg·d−1) for 4 weeks. In OVX mice, the uterine weight declined, and intake of PR at any dose did not affect uterine weight, compared with the control. The total femoral bone mineral density (BMD) was significantly reduced by OVX, which was reversed by intake of the diet with PR at any dose, especially at the low dose. In the in vitro assay, RAW264.7 cells were used for studying the direct effect of PR on the formation of osteoclasts. PR reduced the formation of tartrate resistant acid phosphatase (TRAP)-positive multi-nucleated cells in the RAW 264.7 cells induced by receptor activator for nuclear factor-κB Ligand (RANKL). MC3T3-E1 cells were used for studying the effects of PR on the expression of osteoprotegerin (OPG) and RANKL mRNA expression in osteoblasts. The expression of OPG mRNA and RANKL mRNA was detected by RT-PCR on Days of 5, 7, 10, and 12 after PR exposure. PR time-dependently enhanced the expression of OPG mRNA and reduced the expression of RANKL mRNA in MC3T3-E1 cells. In conclusion, our results suggest that PR can effectively prevent bone loss in OVX mice without any hyperplastic effect on the uterus, and the antiosteoporosis activity of PR may be related to its effects on the formation of osteoclasts and the expression of RANKL OPG in osteoblasts.

Endothelial cell derived endothelin‐1 (ET‐1) regulates skin Na + storage: evidence for sex differences

The skin stores sodium in response to chronic high salt intake providing a buffer for extracellular fluid volume through macrophage recruitment and lymph hyperplasia. ET-1 is increased in response to high salt intake and promotes pro-inflammatory and hyperplastic effects, although its role in skin Na+ storage is unknown. Therefore, the current study was designed to determine if vascular endothelial derived ET-1 is important to the skin buffering capacity and if sex differences exist in this response. After 2 weeks of either low (LS, .02%) or high (HS, 4%) NaCl diet, floxed control mice had a slight, but not statistically significant increase in skin Na+ concentration. Na+ content was similar in both males and females. This response was significantly exacerbated in VEET KO mice. Furthermore, tissue ET-1 peptide levels were significantly higher in response to HS in the ear, a highly vascularized skin tissue, of male floxed mice (85.9±0.9 ng/mg LS vs. 106.4± 6.8 ng/mg HS, p<0.05). Male VEET KO mice had significantly lower ET-1 in the ear compared to floxed controls with no difference between LS and HS (76.4±5.7 ng/mg LS vs. 65.7±7.9 ng/mg). In contrast, female mice have elevated ET-1 in the ear compared to males. Both floxed and VEET KO female mice have a similar increase in ear ET-1 in response to HS (floxed; LS vs. HS respectively, 113±13 vs. 141±23 ng/mg; VEET KO; LS vs. HS respectively, 112.0±16.2 LS vs. 156.3±24.1 ng/mg). These data support the hypothesis that vascular endothelial derived ET-1 plays a critical role in mediating skin storage of Na+ in response to a high salt intake. We also suggest that female mice have another source of ET-1 within the skin interstitium that may contribute to a greater ability to store and clear Na+ in the skin.

Preventive effect of crocin on osteoporosis in an ovariectomized rat model.

The purpose of this study was to investigate the therapeutic effects of crocin on ovariectomy-induced osteoporosis in rats. Female Sprague-Dawley rats were randomly assigned to a sham-operated group (sham) and five ovariectomy (OVX) subgroups, that is, OVX with vehicle (OVX), OVX with 17β-estradiol (E 2, 25 μg/kg/day), and OVX with graded crocin doses (5, 10, or 20 mg/kg/day). Daily oral administration of E 2 or crocin started 4 weeks after OVX and lasted for 16 weeks. Our results showed that crocin dose-dependently inhibited the BMD reduction of L4 vertebrae and femurs caused by OVX and prevented the deterioration of trabecular microarchitecture, which were accompanied by a significant decrease in skeletal remodeling as evidenced by the lower levels of bone turnover markers. Furthermore, crocin reversed the oxidative stress status in both serum and bone tissue. The present study indicates that the administration of crocin at higher doses over a 16-week period can prevent OVX-induced osteoporosis in rats without hyperplastic effects on the uterus, which may, at least partially, be attributed to crocin's antioxidative property. In brief, crocin is a natural alternative for postmenopausal osteoporosis treatment in elderly women.

Long-term resveratrol treatment prevents ovariectomy-induced osteopenia in rats without hyperplastic effects on the uterus

Resveratrol (Res), a polyphenol that is abundant in many medicinal plants and is a selective oestrogen receptor modulator, exhibits multiple biological activities. In the present study, we determined whether Res prevents oestrogen deficiency-induced osteopenia and whether Res administration decreases pathological changes in the endometrium and lumen of the uterus compared with oestradiol replacement therapy (ERT). A total of sixty 3-4-month-old female Wistar rats were randomly divided into a sham-operated group (Sham) and five ovariectomy (OVX) subgroups, i.e. OVX rats as a control group (OVX); OVX rats receiving oestradiol valerate (ERT, 0·8 mg/kg); and OVX rats receiving Res 20, 40 and 80 mg/kg. Daily oral administration was initiated at week 2 after OVX for 12 weeks. A dose-response difference was observed in the effects of Res on bone mineral density (BMD) and trabecular microarchitecture. Only at the highest dose, bone loss was almost equivalent to that observed in the ERT group. The dose-response effects of Res on the biochemical parameters (alkaline phosphatase, IL-6, TNF-α and transforming growth factor-β1 concentrations in the serum as well as urinary Ca and P excretion) and the expressions of receptor activator of nuclear factor κB ligand (RANKL) and the RANKL:osteoprotegerin protein ratio in the femur were also observed. Furthermore, the thickening of the endometrium and the infiltration of lymphocytes were prevented in all the three Res-treated groups compared with the ERT group. In conclusion, Res treatment not only improves BMD and trabecular microarchitecture but also does not affect the uterus and Res might be a potential remedy for the treatment of postmenopausal osteoporosis.

A Humanized Pattern of Aromatase Expression Is Associated with Mammary Hyperplasia in Mice

Aromatase is essential for estrogen production and is the target of aromatase inhibitors, the most effective endocrine treatment for postmenopausal breast cancer. Peripheral tissues in women, including the breast, express aromatase via alternative promoters. Female mice lack the promoters that drive aromatase expression in peripheral tissues; thus, we generated a transgenic humanized aromatase (Arom(hum)) mouse line containing a single copy of the human aromatase gene to study the link between aromatase expression in mammary adipose tissue and breast pathology. Arom(hum) mice expressed human aromatase, driven by the proximal human promoters II and I.3 and the distal promoter I.4, in breast adipose fibroblasts and myoepithelial cells. Estrogen levels in the breast tissue of Arom(hum) mice were higher than in wild-type mice, whereas circulating levels were similar. Arom(hum) mice exhibited accelerated mammary duct elongation at puberty and an increased incidence of lobuloalveolar breast hyperplasia associated with increased signal transducer and activator of transcription-5 phosphorylation at 24 and 64 wk. Hyperplastic epithelial cells showed remarkably increased proliferative activity. Thus, we demonstrated that the human aromatase gene can be expressed via its native promoters in a wide variety of mouse tissues and in a distribution pattern nearly identical to that of humans. Locally increased tissue levels, but not circulating levels, of estrogen appeared to exert hyperplastic effects on the mammary gland. This novel mouse model will be valuable for developing tissue-specific aromatase inhibition strategies.

Effects of Cheonnyuncho (Opuntia humifusa) seeds treatment on the mass, quality, and the turnover of bone in ovariectomized rats

Cheonnyuncho (Opuntia humifusa), rich in polyphenols and flavonoids, is known to have medicinal benefits in the treatment of arteriosclerosis and inflammation. This study was undertaken to evaluate the effects of cheonnyuncho seed powder (OHS) on postmenopausal osteoporosis in ovariectomized rats. OHS treatment prevented an ovariectomy (OVX)-induced decrease in biomechanical quality of femurs. OHS also dose-dependently inhibited bone mineral density (BMD) decreases in femurs, which were accompanied by a significant decrease in skeletal remodeling, as evidenced by decreased levels of the bone turnover markers osteocalcin, alkaline phosphatase (ALP) activity, and serum and urinary Ca excretion. Micro-CT analysis of femoral metaphysics showed that OHS prevented the OVX-induced decrease in bone volume/tissue volume, trabecular thickness, and trabecular number. Concluded, the treatment with OHS improves bone biomechanical quality through modification of BMD and trabecular microarchitecture without hyperplastic effects on the uterus. For these reasons, OHS may be suitable as an alternative treatment of postmenopausal osteoporosis.

Protease-Activated Receptor-2 Modulates Protease-Activated Receptor-1–Driven Neointimal Hyperplasia

Emerging evidence suggests that protease-activated receptors-1 and -2 (PAR1 and PAR2) can signal together in response to proteases found in the rapidly changing microenvironment of damaged blood vessels. However, it is unknown whether PAR1 and PAR2 promote or mitigate the hyperplastic response to arterial injury. Using cell-penetrating PAR1 pepducins and mice deficient in PAR1 or PAR2, we set out to determine the respective contributions of the receptors to hyperplasia and phenotypic modulation of smooth muscle cells (SMCs) in response to arterial injury. SMCs were strongly activated by PAR1 stimulation, as evidenced by increased mitogenesis, mitochondrial activity, and calcium mobilization. The effects of chronic PAR1 stimulation following vascular injury were studied by performing carotid artery ligations in mice treated with the PAR1 agonist pepducin, P1pal-13. Histological analysis revealed that PAR1 stimulation caused striking hyperplasia, which was ablated in PAR1(-/-) and, surprisingly, PAR2(-/-) mice. P1pal-13 treatment yielded an expression pattern consistent with a dedifferentiated phenotype in carotid artery SMCs. Detection of PAR1-PAR2 complexes provided an explanation for the hyperplastic effects of the PAR1 agonist requiring the presence of both receptors. We conclude that PAR2 regulates the PAR1 hyperplastic response to arterial injury leading to stenosis.

Achyranthes bidentata root extract prevent OVX-induced osteoporosis in rats

AimThe objective of the present study was to systematically investigate the effects of Achyranthes bidentata root extract (ABRE) on postmenopausal osteoporosis. Materials and methodsEighty 3-month-old female Sprague–Dawley rats were used and randomly assigned into sham-operated group (SHAM) and five ovariectomy (OVX) subgroups, i.e. OVX with vehicle (OVX); OVX with 17β-ethinylestradiol (E2, 25μg/kg/day); OVX with ABRE of graded doses (100, 300, or 500mg/kg/day). Daily oral administration of ABRE or E2 started on week 4 after OVX for 16 weeks. Bone mass, bone turnover and strength were analyzed by dual-energy X-ray absorptiometry (DEXA), biochemical markers and three-point bending test. The trabecular bone microarchitecture was evaluated by microcomputed tomography (μCT). Results16 weeks treatment of ABRE slowed down the body weight gain and prevented the loss of bone mass induced by the OVX. The prevention effect on bone loss was due to altering the rate of bone remodeling, which could be inferred from the decreased level of bone turnover markers, such as serum alkaline phosphatase (ALP), osteocalcin (OC) and urinary deoxypyridinoline (DPD). The changes of urinary calcium and phosphorus excretion provided the same evidence. The treatment could also enhance the bone strength and prevent the deterioration of trabecular microarchitecture. ConclusionsWe conclude that 16 weeks of ABRE treatment improve bone biomechanical quality through modifications of bone mineral density (BMD), and trabecular microarchitecture without hyperplastic effect on uterus, and it might be a potential alternative medicine for treatment of postmenopausal osteoporosis.

Correlation Between Circulating Leptin Level with Left Ventricle Mass in Normotensive Men

Background . Obesity is one of Cardiovascular risk factor. Obesity caused increase in heart mass due to cellular hypertrophic and metaplastic proses, independently of hemodynamic factors such as blood pressure. There were hyperleptinemia in obesity due to the selective Leptin resistency in central nervous system and peripheral organs. Study with cultured rat cardiomyocyte have shown hypertrophy and hyperplastic effect of Leptin to cardiomyocyte. Some clinical studies have shown correlation between circulating Leptin level with Left Ventricle Mass in hypertensive and insulin resistance men. Objective . This study aimed to elaborate the correlation between circulating Leptin level with Left Ventricle Mass in normotensive men. Methods . A cross sectional study was performed with normotensive men, which included 40 obese normotensive and 40 normoweight men. All patients underwent physical and laboratory assessment and examination of Left Ventricle with echocardiography. The circulating Leptin level were determined by ELISA method. The Leptin level were expressed as median (25th percentile; 75th percentile) Results . The circulating Leptin level were significantly different between the obese normotensive and the lean group. The Left Ventricle Mass in Obese increased, although have not fulfilled the criteria for Left Ventricle Hypertrophy. There were significant correlation between Left Ventricle Mass with BMI (r = 0,711; p<0,001) and waist circumference (r = 0,732; p<0,001). Respectively, there were significant correlation between Left Ventricle Mass Index with BMI (r = 0.541; p<0.001) and waist circumference (r = 0,558; p<0.001. There were significant correlation between circulating Leptin level with Left Ventricle Mass (r = 0,510; <0,001) and Left Ventricle Mass Index (r = 0,414; p<0,001) inobese men. Conclusion . Circulating Leptin level is correlated with Left Ventricle Mass in normotensive men.

Quercetin-6-C-β-d-glucopyranoside isolated from Ulmus wallichiana planchon is more potent than quercetin in inhibiting osteoclastogenesis and mitigating ovariectomy-induced bone loss in rats

The aim of this study was to determine the skeletal effect of quercetin-6-C-β-D-glucopyranoside (QCG) isolated from the extract of Ulmus wallichiana and compare this effect with quercetin (Q) in a rat model of postmenopausal bone loss. Murine bone marrow cells were used to study the effect of QCG or Q on osteoclast differentiation. QCG or Q (1.0 and 5.0 mg kg(-1) d(-1) doses) was administered orally to ovarietomized (OVx) rats for 12 weeks. Sham-operated + vehicle and OVx + vehicle groups served as positive and negative controls, respectively. Bone mineral density, bone microarchitecture, biomechanical strength, bone turnover markers, and uterotrophic effect were studied. One-way analysis of variance was used to test significance of effects. QCG at 1.0 nM significantly inhibited differentiation of multinucleated osteoclasts and expression of osteoclastogenic genes from bone marrow cells, whereas Q at 10.0 μM had comparable results. OVx rats treated with QCG exhibited significantly higher bone mass and better microarchitecture in trabecular and cortical bones compared with OVx + vehicle. QCG treatment of OVx rats had better functional impact than did Q-treated OVx rats, evident from increased bone biomechanical strength. Serum osteocalcin and urinary fragments of type 1 collagen were significantly lower in QCG-treated OVx rats compared with OVx + vehicle group. The protective effect of QCG under ovariectomy-induced bone loss setting was found to be significantly better than Q. Uterine histomorphometry parameters of OVx rats did not change with QCG treatment. QCG improves bone biomechanical quality more effectively than Q through positive modifications of bone mineral density and bone microarchitecture without a hyperplastic effect on the uterus.

Impact of Finasteride on Stroma of Benign Hyperplasia of Prostate

Benign prostatic hyperplasia (13P11) is a hyperplastic process of the strontal and epithelial cells of the prostate due to effect of male sex hormone testosterone. Testosterone is the main male sex hormone, responsible for growth of sexual character and accessory sex organs. Despite its effectiveness as an male sex hormone, it causes benign prostatic hyperplasia (BM resulting in urinary dysfunction. On the other hand, finasteride. a 4-azastroid, inhibits the hyperplastic effect of testosterone and benign prostatic hyperplasia. The objective of the study was to observe the effects of finasteride on the stroma of testosterone induced prostatic hyperplasis in long Evans rats. This experimental study was carried out in the Department of Anatomy, Sir Salimullah Medical College, Dhaka from January to December 2006. Total 45 matured male long Evans rats of age 8-10 weeks and weighing 200-300 gm were used in this study. They were divided into three equal groups. Group A was vehicle (olive oil) control group, Group 13 was testosterone treated group and Group C was testosterone and finasteride treated group. The rats were sacrificed on the eleventh day. It was concluded that finasteride is an effective drug that successfully inhibits the testosterone induced prostatic hvperplasia

A novel flavonoid, 6-C-β-d-glucopyranosyl-(2S,3S)-(+)-3′,4′,5,7-tetrahydroxyflavanone, isolated from Ulmus wallichiana Planchon mitigates ovariectomy-induced osteoporosis in rats

The aim of this study was to determine the skeletal effect of 6-C-beta-d-glucopyranosyl-(2S,3S)-(+)-3',4',5,7-tetrahydroxyflavanone (GTDF)/Ulmoside A, a new compound isolated from the extract of Ulmus wallichiana in a rat model of postmenopausal bone loss. GTDF (1.0 and 5.0 mg kg d) was given orally to ovariectomized (OVx) rats (180-200 g) for 12 weeks. Sham operated + vehicle, ovariectomy + 17beta-estradiol (2.5 microg kg d), and ovariectomy + vehicle groups served as various controls. Bone mineral density (BMD), trabecular microarchitecture, bone biomechanical strength, levels of bone turnover/resorption markers, uterotropic effect, and plasma pharmacokinetics were studied. One-way analysis of variance was used to test significance of effects. OVx rats treated with both doses of GTDF exhibited significantly higher BMD in the trabecular (distal femur, proximal tibia, and vertebrae) and cortical (femur shaft) regions compared with the ovariectomy + vehicle group. Micro-CT demonstrated that OVx rats treated with 5.0 mg kg day of GTDF had better bone microarchitectural parameters compared with the ovariectomy + vehicle group. Serum osteocalcin and urinary C-terminal teleopeptide of Type I collagen levels in OVx rats treated with GTDF (at both doses) were significantly lower than those in the ovariectomy + vehicle group. At neither of the two doses did GTDF exhibit uterine estrogenicity. A pharmacokinetic study revealed that GTDF achieved maximum plasma concentration (40.67 ng mL) at approximately 1 hour, indicating its slow absorption. Its absolute bioavailability was found to be 1.04% with a plasma elimination half-life of approximately 5 hours. GTDF, a novel compound isolated from U wallichiana extract, improves bone biomechanical quality through positive modifications of BMD and trabecular microarchitecture without a hyperplastic effect on the uterus.