scholarly journals The impact of rosuvastatin on hypothalamic–pituitary–testicular axis activity in metformin-treated and metformin-naïve men with low testosterone levels: a pilot study

Author(s):  
Robert Krysiak ◽  
Marcin Basiak ◽  
Witold Szkróbka ◽  
Bogusław Okopień

Abstract Background Intense statin therapy was found to impair testosterone production in men. Metformin administered to subjects with hypergonadotropic hypogonadism decreased gonadotropin production. The current study was aimed at investigating whether metformin treatment modulates the impact of high-dose rosuvastatin therapy on hypothalamic–pituitary–testicular axis activity in men. Methods The study included 43 very high cardiovascular risk men with late-onset hypogonadism, 20 of whom had been treated with metformin (1.7–3 g daily) for at least 6 months. In all subjects, unsuccessful initial statin treatment was replaced with rosuvastatin (20–40 mg daily). Plasma lipid levels, glucose homeostasis markers, as well as circulating levels of gonadotropins, testosterone, bioavailable testosterone, dehydroepiandrosterone-sulfate, prolactin, estradiol and creatinine were measured at the beginning of the study and 4 months later in 28 individuals in whom rosuvastatin reduced LDL cholesterol levels to below 70 mg/dL. Results There were no differences between treatment-induced changes in plasma lipids. In both study groups, rosuvastatin reduced total and bioavailable testosterone levels. However, only in metformin-naïve men, rosuvastatin increased LH and FSH levels and slightly impaired insulin sensitivity. The impact on gonadotropin concentrations correlated with treatment-induced decrease in testosterone levels. There were no significant differences between baseline and posttreatment values of dehydroepiandrosterone-sulfate, prolactin, estradiol and the glomerular filtration rate. Conclusion The obtained results suggest that metformin prevents the compensatory increase in gonadotrope function induced by intense statin therapy.

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Nirupa R Matthan ◽  
Anne V Kane ◽  
William Evan Johnson ◽  
Solaiappan Manimaran ◽  
Tyler Faits ◽  
...  

Considerable data is available on the effect of carbohydrate (carb) quantity on CVD risk factors but data for carb quality is limited. Our objective was to determine the relative comparability for an isocaloric exchange of unrefined-carb (endosperm+germ+bran, e.g., whole wheat flour), refined-carb (endosperm only, e.g., white flour) and simple-carb (sucrose, e.g., high fructose corn syrup), on cardiometabolic risk factors and the gut microbiome. All foods/beverages (60%E total carb, 15%E protein, 27%E fat [7%E SFA, 10%E MUFA, 10%E PUFA], 80mg cholesterol/1000 kcal) were provided to study subjects (n=11 men and women, 65 years, BMI 27.5 kg/m 2 , LDL-C ≥100 mg/dL) for 5 weeks (randomized, single-blind, cross-over design). Body weight was maintained constant. At the end of each diet phase plasma lipid profile, inflammatory factors and glucose homeostasis were determined using standard methods. Fecal microbiota taxa was characterized by 16S rRNA sequencing and data analyzed using QIIME and PathoScope. Plasma LDL-C levels differed among diets (125 ± 29 mg/dL b , 129 ± 29 mg/dL a,b and 136 ± 24 mg/dL a , unrefined-, simple- and refined-carb , respectively). Carb quality had no significant effect on HDL-C, TG, FFA, glucose, insulin, CRP or IL-6 levels. There were 21 genera that had a mean relative abundance (RA) of ≥1% and 4 genera (Roseburia, Oscillospira, Ruminococcus and Coprococcus) varied significantly across diets but after multiple testing adjustment, only Roseburia RA variations remained significant ( 2.58% a , 0.99% b , and 0.81% b , unrefined-, simple- and refined-carb , respectively). Interesting trends were observed between the RA of the following genera and plasma lipids: Roseburia was negatively associated with LDL-C (r=0.28, p=0.097) and HDL-C (r=-0.39, p=0.022); Oscillospira was negatively associated with TG (r=-0.53, p=0.097), and Anaerostipes was positively associated with TG (r=0.40, p=0.0585) levels. These data suggest that carb quality alters the RA of butyrate-producing bacteria, presumably leading to higher short chain fatty acid production, with subsequent alterations in plasma lipids. This study provides novel information about the impact of carb quality on the phylogenetic structure and functional capacity of the fecal microbiome.


Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5397-5397 ◽  
Author(s):  
Beth Faiman ◽  
Surbhi Sidana ◽  
Paul Elson ◽  
Kellie Bruening ◽  
Hien K. Duong ◽  
...  

Abstract Background We hypothesized lenalidomide (len) related diarrhea (LRD) may correlate with activation of an immune response against multiple myeloma (MM) based on colon biopsies that showed crypt apoptosis reminiscent of GVHD in 3 MM patients with severe LRD but without prior allogeneic stem cell transplantation or gastrointestinal disorder. To investigate whether survival may be influenced by the presence of LRD we performed a retrospective chart review. Methods Patients who developed symptomatic MM on or after 1/1/2005 as defined by the start of anti-MM therapy and had been on len for at least 6 consecutive months by 12/31/2010 were included in the analysis. Significant LRD was considered present if the treating physician attributed the diarrhea to len and recommended supportive therapy in at least two clinic notes.  The first time treatment for LRD was recommended was used as the date of onset of LRD. As possible confounding factors age at the start of len therapy, number of prior regimens, prior high dose chemotherapy with autologous stem cell transplant (ASCT), and use of antineoplastic agents other than corticosteroids at any time during the continuous len therapy were collected. The primary outcome was overall survival (OS), which was calculated from the start of len. Fisher’s exact test, Mann-Whitney test, and the logrank test were used to compare characteristics and duration of len between patients with and without LRD. Proportional hazards models were used to assess the impact of LRD on OS. The lag between the start of len and development of LRD was accounted for by treating LRD as a time-varying covariate in these models. Results 161 patients were identified, 47 (29%) had LRD, and 59 (37%) died during follow up. LRD and no LRD groups were balanced for gender, age, number of prior regimens, prior transplant, and use of antineoplastic agents other than corticosteroids with len, but len treatment duration differed; LRD patients had received a median of  43.4 consecutive months of len (range 5.8-82.9) compared to 14.6 (range 5.9-89) for patients without LRD (p=0.001). Onset of LRD occurred after a median of 17.7 months (range 0.3-75.4) of len therapy. In multivariable analyses, development of LRD (HR 0.46, 95% C.I. 0.21-1.00, p=0.05) was associated with improved OS as were the number of prior therapies (0-2, vs >2, HR 0.16, 95% C.I. 0.08-0.32, p<0.0001) and no use of antineoplastic therapy other than corticosteroids during len therapy (HR 0.52, 95% C.I. 0.29-0.93, p=0.03), while age and prior ASCT (p=0.52 and 0.49, respectively) were not. Conclusion Late onset of lenalidomide related diarrhea (LRD) is compatible with an immune mediated effect that may signal anti-MM immune activity since LRD requiring supportive measures correlated with survival in MM in analyses that adjusted for lag time. While more study is needed to prove this hypothesis, our findings suggest that diarrhea on len may argue for continued therapy rather than discontinuation. Disclosures: Faiman: Celgene: Consultancy, Speakers Bureau; Millennium: Consultancy, Speakers Bureau; Onyx: Consultancy, Speakers Bureau. Duong:Celgene: Honoraria, Research Funding. Valent:Celgene: Speakers Bureau; Millennium: Speakers Bureau. Reu:Celgene: Research Funding; Onyx: Speakers Bureau.


PLoS ONE ◽  
2020 ◽  
Vol 15 (12) ◽  
pp. e0240449
Author(s):  
Hugues Beaufrère ◽  
Sara M. Gardhouse ◽  
R. Darren Wood ◽  
Ken D. Stark

Dyslipidemias and lipid-accumulation disorders are common in captive parrots, in particular in Quaker parrots. Currently available diagnostic tests only measure a fraction of blood lipids and have overall problematic cross-species applicability. Comprehensively analyzing lipids in the plasma of parrots is the first step to better understand their lipid metabolism in health and disease, as well as to explore new lipid biomarkers. The plasma lipidome of 12 Quaker parrots was investigated using UHPLC-MS/MS with both targeted and untargeted methods. Targeted methods on 6 replicates measured 432 lipids comprised of sterol, cholesterol ester, bile acid, fatty acid, acylcarnitine, glycerolipid, glycerophospholipid, and sphingolipid panels. For untargeted lipidomics, precursor ion mass-to-charge ratios were matched to corresponding lipids using the LIPIDMAPS structure database and LipidBlast at the sum composition or acyl species level of information. Sterol lipids and glycerophospholipids constituted the majority of plasma lipids on a molar basis. The most common lipids detected with the targeted methods included free cholesterol, CE(18:2), CE(20:4) for sterol lipids; PC(36:2), PC(34:2), PC(34:1) for glycerophospholipids; TG(52:3), TG(54:4), TG(54:5), TG(52:2) for glycerolipids; SM(d18:1/16:0) for sphingolipids; and palmitic acid for fatty acyls. Over a thousand different lipid species were detected by untargeted lipidomics. Sex differences in the plasma lipidome were observed using heatmaps, principal component analysis, and discriminant analysis. This report presents the first comprehensive database of plasma lipid species in psittacine birds and paves the way for further research into blood lipid diagnostics and the impact of diet, diseases, and drugs on the parrot plasma lipidome.


2005 ◽  
Vol 93 (4) ◽  
pp. 543-547 ◽  
Author(s):  
Tomonori Unno ◽  
Motomi Tago ◽  
Yuko Suzuki ◽  
Ayumu Nozawa ◽  
Yuko M Sagesaka ◽  
...  

Epidemiological surveys suggest that a higher intake of tea may be associated with a lower risk of CHD. There is accumulating evidence that postprandial lipaemia makes a substantial contribution to the incidence of CHD. Our aim was, therefore, to evaluate the effect of tea catechins (major ingredients in green tea) on postprandial lipid responses in human subjects after the consumption of test meals. In a randomized triple-crossover design, nine male subjects with mild or borderline hypertriacylglycerolaemia consumed 10 (control), 224 (moderate dose) and 674 mg (high dose) of the assigned tea catechins three times each along with a standardized light meal consisting of a piece of bread spread with 20 g butter. Plasma lipids were measured in the fasting state and 1, 2, 3, 4 and 6 h after consuming the light meal. Results showed that, compared with the control, moderate and high doses of tea catechins reduced the incremental area under the plasma triacylglycerol curves by 15·1 and 28·7 %, respectively. Next, the rapid elevation of remnant-like particle cholesterol was significantly inhibited by a high dose of tea catechins 2 h after consuming the light meal (P<0·01). In the range of tea catechin dosages, no significant differences were observed in the postprandial responses for plasma total cholesterol or NEFA at any time point. In conclusion, this trial demonstrated that tea catechins attenuated the postprandial increase in plasma triacylglycerol levels following a fat load. These results may provide evidence for one of the possible mechanisms involved in lowering the incidence of CVD, and may prove useful in further studies on the beneficial health effects of tea drinking.


2020 ◽  
Vol 12 (4) ◽  
pp. 1
Author(s):  
Alvaro San Antonio Gil ◽  
JL Hermoso Martínez ◽  
JM Redondo Enríquez ◽  
MP Martín González-Haba

El desarrollo de insuficiencia renal aguda (IRA) constituye una problemática frecuente en las unidades de cuidados críticos (UCI), concretamente en las subpoblaciones ingresadas con diagnóstico de sepsis o shock séptico. En la literatura, las indicaciones de aplicación de TCRR están claras (tanto de origen renal como extrarrenal). Sin embargo, no parece claro en ningún estudio publicado previamente el momento ideal del inicio de dichas técnicas, ni la repercusión que esto tiene en la morbimortalidad. El objetivo de este ensayo clínico es analizar si existen diferencias en la mortalidad entre 2 grupos de pacientes con lesión renal aguda y shock séptico, según el inicio precoz o tardío de las TCRR. Es abierto (no hay enmascaramiento), pudiendo caer en sesgo de medición durante la medición de los datos. Los grupos de estudio fueron homogéneos, con aleatorización al azar. Sin embargo, no especifican el tipo de modalidad de TCRR utilizada. El tamaño muestral calculado inicialmente según la potencia conferida al estudio no fue alcanzado finalmente. Las mediciones fueron objetivas. Sin embargo, no aclaran por qué designan como precoz al inicio de las TCRR en las primeras 12 horas desde el desarrollo de LRA y tardío a 48 horas después. Resultados: No hay diferencias de mortalidad a los 90 días (P=0.38, no significativo). Sin embargo, en el grupo tardío un 38% no recibieron TCRR, y 17 % lo recibieron precozmente. El grupo tardío presentó de forma significativa menos días con TCRR. No hubo diferencias en días de ventilación mecánica, vasopresores ni estancia en UCI. ABSTRACT Continuous renal-replacement therapies (CRRT). Early or late? What is the ideal time to start? The development of acute kidney injury (AKI) is a frequent problem in critical care units (ICUs), specifically in subpopulations admitted with a diagnosis of sepsis or septic shock. In the literature, the indications for the application of CRRT are clear (both of renal and extrarenal origin). However, it seems unclear in any previously published study the ideal time of the beginning of these techniques, nor the impact this has on morbidity and mortality. The objective of this clinical trial is to analyze whether there are differences in mortality between 2 patients groups with AKI and septic shock, depending on the early or late onset of CRRT. It is open (no masking), and may fall into measurement bias during the measurement of the data. The study groups were homogeneous and randomized. However, they do not specify the type of CRRT mode used. The sample size initially calculated according to the power conferred on the study was not finally reached. The measurements were objective. Nonetheless, they do not clarify why they designate the early CRRT as early in the first 12 hours after the development of AKI and late 48 hours later. Results: There are no mortality differences at 90 days (P = 0.38, not significant). It seems that in the late group 38% did not receive CRRT, and 17% received it early. The late group presented significantly fewer days with CRRT. There were no differences in days of mechanical ventilation, vasopressors or ICU stay.  


2012 ◽  
Vol 82 (2) ◽  
pp. 85-93 ◽  
Author(s):  
Y. Kim ◽  
H. Shin ◽  
S. Lee

In the present study, the nutritional quality of four grains including adlay (AD), buckwheat (BW), glutinous barley (GB), and white rice (WR) were evaluated in terms of plasma lipid parameters, gut transit time, and thickness of the aortic wall in rats. The rats were then raised for 4 weeks on the high-fat diet based on the American Institute of Nutrition-93 (AIN-93 G) diets containing 1 % cholesterol and 20 % dietary lipids. Forty male rats were divided into 4 groups and raised for 4 weeks with a diet containing one of the following grains: WR, AD, BW, or WB. The level of thiobarbituric acid-reactive substances (TBARS) in liver was shown to be higher in rats by the order of those fed WR, AD, GB, and BW. This indicates that other grains decreased oxidative stress in vivo more than WR. The superoxide dismutase, glutathione, glutathione peroxidase, and glutathione reductase levels in the AD, BW, and GB groups were significantly higher than those in the WR group (p < 0.05). Plasma lipid profiles differed significantly according to grain combination, and decreased aortic wall thickness was consistent with the finding of decreased plasma low-density lipoprotein cholesterol (LDL-C) (p < 0.05) and increased high-density lipoprotein (HDL-C) in rats fed AD, BW, and GB (p < 0.001). The antioxidant and hypolipidemic capacities of grains are quite high, especially those of adlay, buckwheat, and glutinous barley. In conclusion, this study has demonstrated that the whole grains had a cardioprotective effect. This effect was related to several mechanisms that corresponded to lowering plasma lipids, decreasing TBARS, and increasing antioxidant activities.


2019 ◽  
Vol 9 (02) ◽  
Author(s):  
Amal Kamil Abdul Sada ◽  
Amany Mohamed Al-Kaysi

This is an experimental trial to prepare a vaccine from gamma-irradiated Giardia lamblia which is evaluated in experimental animals. The study was conducted from December 2015 to April 2016. The field survey of the parasite was conducted from those patients attending the laboratories of the Alawi Children's Hospital in Rusafa and the Al-Yarmouk Teaching Hospital in Karkh, through which 1250 stool samples of different age groups were examined. Five groups of mice were used in the study; the first was injected with normal saline and considered as a negative control group, the second was injected with cystic form of non-irradiated Giardia lamblia and considered as a positive control group, whereas the other three groups were injected with gamma irradiated Giardia lamblia at three different doses 10, 15 and 25 rad respectively. Giardia lamblia was primarily cultivated in liver infusion agar for ten days to obtain the active phase. On the sixth day, the cystic phase was purified and standardized to be used in the infection of mice with or without the exposure of gamma rays. Mice showed high sensitivity to parasitic infestation, in the gamma non-irradiated and the irradiated with gamma 10 rad, and 15 rad irradiated groups which was 100%. The results expressed an excystation process of the depleted phases and the release of the feeder phases. The results of the three irradiated groups consisted of histopathological changes of the small, and the rectum by dissection after two weeks of infection, with intestine amputation lesions, as well as ulceration and inflammation of the inflammatory cells represented in small numbers of neutrophil, lymphocytes, and eosinophils. The presence of ulceration and fall of epithelial cells in the intestinal cavity has been shown, and different forms of the parasite have been observed. Mice which was injected with irradiated G lamblia at high dose (25 rad), not show and sensitivity to the challenge infection and no excystation of thy parasite had been done. After 2 wreaks, a comparison was achieved between all study groups in which no histopathological changes were noticed in the mice irradiated with dose of25 rad. After another two weeks, a challenge dose was given (un-attenuated G lamblia) and mice were dissected after another two weeks, no changes on the level of histopathology of intestinal tissue were noticed the results suggested that mice acquire an immunity against the parasite infection.


2020 ◽  
Vol 133 (1) ◽  
pp. 182-189
Author(s):  
Tae-Jin Song ◽  
Seung-Hun Oh ◽  
Jinkwon Kim

OBJECTIVECerebral aneurysms represent the most common cause of spontaneous subarachnoid hemorrhage. Statins are lipid-lowering agents that may expert multiple pleiotropic vascular protective effects. The authors hypothesized that statin therapy after coil embolization or surgical clipping of cerebral aneurysms might improve clinical outcomes.METHODSThis was a retrospective cohort study using the National Health Insurance Service–National Sample Cohort Database in Korea. Patients who underwent coil embolization or surgical clipping for cerebral aneurysm between 2002 and 2013 were included. Based on prescription claims, the authors calculated the proportion of days covered (PDC) by statins during follow-up as a marker of statin therapy. The primary outcome was a composite of the development of stroke, myocardial infarction, and all-cause death. Multivariate time-dependent Cox regression analyses were performed.RESULTSA total of 1381 patients who underwent coil embolization (n = 542) or surgical clipping (n = 839) of cerebral aneurysms were included in this study. During the mean (± SD) follow-up period of 3.83 ± 3.35 years, 335 (24.3%) patients experienced the primary outcome. Adjustments were performed for sex, age (as a continuous variable), treatment modality, aneurysm rupture status (ruptured or unruptured aneurysm), hypertension, diabetes mellitus, household income level, and prior history of ischemic stroke or intracerebral hemorrhage as time-independent variables and statin therapy during follow-up as a time-dependent variable. Consistent statin therapy (PDC > 80%) was significantly associated with a lower risk of the primary outcome (adjusted hazard ratio 0.34, 95% CI 0.14–0.85).CONCLUSIONSConsistent statin therapy was significantly associated with better prognosis after coil embolization or surgical clipping of cerebral aneurysms.


2019 ◽  
Vol 72 (8) ◽  
pp. 1426-1436
Author(s):  
Justyna Rosińska ◽  
Joanna Maciejewska ◽  
Robert Narożny ◽  
Wojciech Kozubski ◽  
Maria Łukasik

Introduction: Elevated concentrations of platelet-derived microvesicles are found in cerebrovascular diseases. The impact of acetylsalicylic acid on these microvesicles remains inconsistent, despite its well-established effect on platelet aggregation. High residual platelet aggregation is defined as high on-treatment platelet reactivity, while “treatment failure” is the occurrence of vascular events despite antiplatelet treatment. The aim of this study was to determine whether the antiaggregatory effect of acetylsalicylic acid correlates with platelet-derived microvesicles in convalescent ischaemic stroke patients and cardiovascular risk factor controls as well as to evaluate the association between high on-treatment platelet reactivity and recurrent vascular events with the studied platelet-derived microvesicle parameters. Materials and methods: The study groups consisted of 76 convalescent stroke patients and 74 controls. Total platelet-derived microvesicles, annexino-positive microvesicles number, and platelet-derived microvesicles with surface expression of proinflammatory (CD40L, CD62P, CD31) and procoagulant (PS, GPIIb/IIIa) markers were characterized and quantified using flow cytometry. Cyclooxygenase-1-specific platelet responsiveness, with whole blood impedance platelet aggregation under arachidonic acid stimulation and the serum concentration of thromboxane B2, were evaluated. Results: Neither acetylsalicylic acid intake nor modification of its daily dose caused statistically significant differences in the studied microvesicle parameters. Additionally, no statistically significant differences in the studied microvesicle parameters were revealed between high on-treatment platelet reactivity and non-high on-treatment platelet reactivity subjects in either study subgroup. However, elevated concentrations of PAC-1+/CD61+, CD62P+/CD61+ and CD31+/CD61+ microvesicles were found in stroke patients with treatment failure, defined in this study as a recurrent vascular events in a one-year follow-up period. Conclusions: This study revealed no relationship between circulating microvesicle number and platelet aggregation. The procoagulant and proinflammatory phenotype of circulating platelet-derived microvesicles might contribute to acetylsalicylic acid treatment failure.


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