scholarly journals Phosphocholine Steroid Conjugates: Are these Compounds the Mammalian Cardiotonic Steroids?

Author(s):  
Fred Chasalow

Cardiotonic glycoside toxins, originally isolated from plants or amphibians, have been proposed as mammalian cardiotonic hormones. This paper is a review and update of the discovery of [i] a new class of steroid hormones, [ii] the path for their biosynthesis and [iii] some preliminary data on their function. The compounds are phosphoester conjugates and share a characteristic structural feature, a lactone ring, with [a] one class of synthetic potassium sparing diuretics and with [b] plant and amphibian cardiotonic steroids. Purification was initially monitored by cross reaction with steroid sulfate assays and later with digoxin-specific assays. Six compounds were purified by HPLC to near homogeneity and characterized by Tandem mass spectroscopy (MS-MS) and 31P-NMR. Three were digoxin-like materials (DLM) with 23 carbon atoms. The two extra carbon atoms form a spiral lactone E-ring. Several additional spiral lactones have been identified by MS-MS. In a pilot study, based on MS analysis, we evaluated phosphocholine steroid levels in individual serum samples in patients with pre-eclampsia (n=20). The control group of normotensive pregnant women (n=20) was used to estimate the mean and standard deviation. Twelve of the women with pre-eclampsia had a z-score over 2 for at least one of the four phosphocholine steroids. In contrast, only 1 sample from the normotensive women had a z-score over 2. The observation that there are two patterns, one with elevated phosphocholine steroid levels and one without the elevation, suggests that there may be two different underlying causes of pre-eclampsia. We now need to extend the study to determine which pattern predicts progression to life-threatening hypertension in pregnant women. This pilot study illustrates that it is possible to evaluate individual endogenous cardiotonic hormones without relying on antibodies developed to plant or amphibian toxins.

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Agnes M. Schitter ◽  
Marko Nedeljkovic ◽  
Heiner Baur ◽  
Johannes Fleckenstein ◽  
Luigi Raio

Background. WATSU (WaterShiatsu) is a complementary therapeutic treatment method comprising passive stretches and massage techniques administered in 35°C warm water. Pregnant women claim safe methods to reduce pain, stress, and fatigue. Therefore, we conducted a pilot study evaluating the effects of WATSU on pregnancy-related complaints in third trimester pregnant women.Methods. Nine healthy pregnant women at gestational week ≥34 were included in an intervention group (receiving WATSU) and compared to eight women in a passive control group (receiving no treatment). WATSU was performed on days 1 and 4 of the study, accompanied by ultrasound examinations. Outcomes include physiological and psychometric as well as qualitative data. Participants in the control group completed questionnaires only.Results. WATSU was found to significantly lower participants’ levels of stress and pain and to improve their mental health-related quality of life and mood. In comparison to the passive control group, participants in the intervention group reported reduction in perceived stress from day 1 to day 8 (P=0.036, Cohen’sf=0.57). Qualitative data indicate that WATSU was appreciated as enjoyable and deeply relaxing. No negative side effects were reported.Conclusion. Our findings support the notion that WATSU yields therapeutic benefits for pregnant women and warrant further research. This study has been registered at ClinicalTrials.gov:NCT01708018.


2013 ◽  
Vol 5 (3) ◽  
pp. 510-513 ◽  
Author(s):  
Arsenia M. Asuncion ◽  
Consuelo Cagande ◽  
Sherry Schlagle ◽  
Barbara McCarty ◽  
Krystal Hunter ◽  
...  

Abstract Background Research suggests pediatrics practitioners lack confidence and skills in the end-of-life (EOL) care. Objective This pilot study explored the impact of a curriculum designed to prepare future pediatricians to manage pain and provide comfort for children and infants with life-threatening conditions and to be more confident and competent in their EOL discussions with families. Methods Participants included 8 postgraduate year (PGY)-2 residents in the study group and 9 PGY-3 residents in a control group. The EOL curriculum included 4, 1-hour sessions consisting of didactic lectures, videos, and small-group, interactive discussions. Topics included discussing EOL with families, withdrawal of care, and pain assessment and management. Curriculum evaluation used an objective structured clinical examination (OSCE), self-assessment confidence and competency questionnaire, and a follow-up survey 18 months after the intervention. Results The OSCE showed no statistically significant differences between PGY-2 versus PGY-3 residents in discussing EOL issues with family (mean  =  48.3 [PGY-2] versus 41.0 [PGY-3]), managing withdrawal of care (mean  =  20.9 [PGY-2] versus 18.91 [PGY-3]), and managing adolescent pain (mean  =  30.97 [PGY-2] versus 29.27 [PGY-3]). The self-assessment confidence and competency scores improved significantly after the intervention for both PGY-2 residents (0.62 versus 0.86, P < .01) and PGY-3 residents (0.61 versus 0.85, P < .01). Conclusions An EOL curriculum for PGY-2 pediatrics residents delivered during the intensive care unit rotation is feasible and may be effective. Residents reported the curriculum was useful in their practice.


Antioxidants ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1318
Author(s):  
Arpita Basu ◽  
Jeannette Crew ◽  
Jeffrey L. Ebersole ◽  
Jefferson W. Kinney ◽  
Arnold M. Salazar ◽  
...  

Pregnancies affected by obesity are at high risk for developing metabolic complications with oxidative stress and adipocyte dysfunction contributing to the underlying pathologies. Few studies have examined the role of dietary interventions, especially those involving antioxidants including polyphenolic flavonoids found in fruits and vegetables on these pathologies in high-risk pregnant women. We conducted an 18 gestation-week randomized controlled trial to examine the effects of a dietary intervention comprising of whole blueberries and soluble fiber vs. control (standard prenatal care) on biomarkers of oxidative stress/antioxidant status and adipocyte and hormonal functions in pregnant women with obesity (n = 34). Serum samples were collected at baseline (<20 gestation weeks) and at the end of the study period (32–26 gestation weeks). Study findings showed maternal serum glutathione and antioxidant capacity to be significantly increased, and malondialdehyde to be decreased in the dietary intervention vs. control group (all p < 0.05). Among the adipokine biomarkers, serum plasminogen activator inhibitor-1 and visfatin, as biomarkers of adipocyte dysfunction and insulin resistance, were also decreased following dietary intervention (all p < 0.05). These findings support the need for supplementing maternal diets with berries and fiber to improve oxidative stress and risks of metabolic complications during pregnancy.


2018 ◽  
Vol 69 (6) ◽  
pp. 1509-1514
Author(s):  
Elena Mihalceanu ◽  
Daniela Cristina Dimitriu ◽  
Ioan Tudor Lazar ◽  
Brindusa Alina Petre ◽  
Gabriel Constantinescu ◽  
...  

The objectives of the research herein are to detect if the modifications of sFlt-1 and PlGF can be correlated with the clinical and biochemical status of the hypertensive pregnant woman and if the sFlt-1/PlGF ratio is a good predictor for preeclampsia in case of the investigated patients. In the study herein, 100 pregnant women were evaluated; they were distributed in the following groups: The group of pregnant women diagnosed with HTN at the time of hospital admission � including 50 pregnant women, of which 16 pregnant women presented medium and severe forms of preeclampsia and 34 pregnant women with pregnancy-induced hypertension and 50 pregnant women with normal pregnancy evolution as control group. We have performed hematological and biochemical tests, using serum samples from all analyzed patients and measured the serum concentrations of sFlt-1 and PlGF angiogenic factors. We found a significant correlation between the value of the arterial blood pressure, the proteinuria, the serum creatinine and the AST, on one hand, and the sFlt-1/PlGF ratio, on the other hand. The ROC curve has emphasized the fact that the proteinuria (AUC = 0.849), the AST (AUC = 0.664), the value of the arterial blood pressure SBP/DBP (AUC = 0.683/0.631), the serum creatinine (AUC = 0.674) and the sFlt-1/PlGF ratio, at a cut off value = 200, are effective preeclampsia predictors. Similarly, statistically significant increase (p = 0.001) of the sFlt-1 serum concentration in case of the pregnant women from the PE group (14365�6464 pg/mL) and from the PIH group (9892�8443 pg/mL), compared to the control group (3278�1444 pg/mL) and, respectively, a significant decrease (p = 0.003) of the PlGF pro-angiogenic marker for the group of pregnant women suffering from preeclampsia (119.30�56.63 pg/mL) and from PIH (129.12�21.41 pg/mL), compared to the control group (327.57�59.62 pg/mL). The results obtained within this research show that sFlt-1/PlGF ratio represents an effective preeclampsia predictor, confirming the fact that the study of the angiogenic factors may help to analyze the stratification of the risk degree in HTN pregnant women.


2021 ◽  
Author(s):  
Sayed hojjat Hosseini ◽  
Ata Ghadiria ◽  
Abdolah Mousavi Salehi ◽  
Saber Rokhafrooz ◽  
Mahin Najafian ◽  
...  

Abstract Preeclampsia (PE) is a syndrome related with pregnancy and characterized by hypertension and proteinuria, occurring in approximately 6-8% of pregnancies and accounting for approximately 40% of premature births. This study aimed to investigate the polymorphisms of -634C/G and +936C/T in VEGF gene and their relationship with serum VEGF levels in pregnant women with PE. In this case-control study, peripheral blood samples were collected from 135 women with PE and 135 normal pregnant women as the control group. DNA was extracted using the phenol-chloroform method. Then, the polymorphisms of VEGF gene were detected by PCR-RFLP method using specific primers. Besides, VEGF concentrations were measured by ELISA method on serum samples and control subjects using ELISA kits. In this research, maternal age, gestational week, maternal hemoglobin and BMI were significantly correlated with the likelihood of PE, while the occurrence season variable was not effective in PE among the pregnant women. There was no significant difference in the two polymorphisms of -634C/G and +936C/T in VEGF gene between the two groups. Also, the serum VEGF level in PE patients was significantly higher than the normal group (P<0.001). Despite a significant increase in serum VEGF concentrations in women with PE, it seems that -634C/G and +936C/T polymorphisms of VEGF gene are not related with the onset of PE. Further studies are required to fully understand the risk factors related to preeclampsia syndrome.


Author(s):  
Taylan Onat ◽  
Nihal Inandiklioglu

Abstract Objective The objective of this study was to assess the levels of serum myonectin and irisin in pregnant women with and without gestational diabetes mellitus (GDM). Method A total of 80 pregnant women participated in our study (which consisted of 40 patients with GDM, 40 participants as the control group). Myonectin and irisin levels were analyzed through the ELISA technique, in addition to metabolic parameters in the serum samples of the participants. Results It was found that the levels of irisin and myonectin were lower in the GDM group compared to the control group. Moreover, it was determined that the values of age (p<0.001), body mass index (p=0.001), gravida (p=0.001), parity (p = 0.016), fasting serum glucose (p=0.001), fasting serum insulin (p=0.007), postprandial serum glucose (p=0.006), HbA1c (p<0.001), HOMA-IR (p<0.001) were higher; HDL cholesterol (p<0.001) was lower. Insulin resistance was significantly higher in the GDM group. Conclusions Levels of myonectin and irisin were determined to be low in the GDM group. Our results have demonstrated that myonectin and irisin could play a role in the development of GDM and that irisin as well as myonectin could be a novel biomarker for GDM.


Author(s):  
Agnieszka Marek ◽  
Rafał Stojko ◽  
Agnieszka Drosdzol-Cop

Pregnancy-induced hypertension (PIH) occurs in 6–8% of pregnancies, and increases the risk of many severe obstetric complications. The etiology of PIH has not been fully explained, and hence, treatment is only palliative in nature, and prevention is not fully effective. It has been proposed that PIH development is influenced by the arginine vasopressin pathway, whose surrogate biomarker is copeptin. The aim of this study is a prospective assessment of the relationship between the level of copeptin in pregnant women and the occurrence of PIH, and to identify its usefulness in predicting complications. The study involved a group of 21 pregnant women who developed PIH and 37 women with uncomplicated pregnancies as a control group. Blood samples were collected at the three trimesters of gestation (<13 HBD, between 13 and 26 and> 26 HBD) and then frozen. Copeptin levels [pg/mL] were measured in serum samples obtained in the first, second and third trimesters of gestation from women in the PIH and control groups. The concentration of copeptin in the second and third trimesters of pregnancy was statistically significantly higher in the PIH group (p < 0.05). For copeptin determined in the first trimester, which could be used to screen for PIH, the area under the ROC curve was 0.650. The highest risk of PIH occurred in patients with high concentrations of copeptin in the first trimester of pregnancy and obesity OR = 5.5 (95% CI 1.0–31.3). The risk of PIH was augmented in patients with high levels of copeptin and an abnormal Doppler result of the uterine arteries OR = 28.4 (95% CI 5.3–152). In conclusion, copeptin levels were found to be elevated in pregnant women before the diagnosis of PIH; however, copeptin should not be used as a stand-alone marker. The combination of copeptin concentration with the other risk factors (diabetes, maternal age and preeclampsia in previous pregnancy) did not improve the diagnostic values of the use of copeptin in the PIH risk assessment, but the combination of copeptin concentration with BMI may be useful in clinical practice. Measurement of copeptin together with a Doppler examination of uterine arteries in the first trimester of pregnancy may be a useful marker in predicting the development of PIH.


2020 ◽  
Vol 40 (6) ◽  
Author(s):  
Fanghua Shen ◽  
Hongdao Lv ◽  
Yun Shi ◽  
Sandy Lau ◽  
Fang Guo ◽  
...  

Abstract To date there is no effective treatment for pregnancies complicated by fetal growth restriction (FGR). Salvia miltiorrhiza, a traditional Chinese herb has been shown to promote blood flow and improve microcirculatory disturbance. In this pilot study, we evaluated whether S. miltiorrhiza can potentially become a possible therapy for FGR. Nineteen pregnant women with FGR were treated with S. miltiorrhiza and ATP supplementation for an average of 7 days, and 17 cases received ATP supplementation as controls. The estimated fetal weights (EFWs) were measured by ultrasound after treatment, and the birthweights were recorded after birth. After treatment with S. miltiorrhiza, 7 (37%) FGR cases showed an increase in EFW to above the 10th percentile, compared with 4 (23%) FGR cases in controls (odds ratio: 1.896, 95% confidence limits (CLs): 0.44–8.144). At delivery, 10 (53%) FGR cases in the treatment group delivered babies with a birthweight above the 10th percentile, compared with 6 (35%) FGR cases in the control group (odds ratio: 2.037, 95% CL: 0.532–7.793); 80 or 64% FGR cases in the treatment group showed an increase in fetal abdominal circumference (AC) or biparietal diameter (BPD) above the 10th percentile before delivery. While 44 or 30% FGR cases in the control group showed an increase in AC or BPD. No improvement of head circumference (HC) or femur length (FL) was seen. These pilot data suggest the need for multicenter randomized clinical trials on the potential of S. miltiorrhiza to improve perinatal outcome in pregnant women complicated by FGR.


Antibiotics ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 359
Author(s):  
Dilip Roy ◽  
Amol Kulkarni ◽  
Manu Chaudhary ◽  
Saransh Chaudhary ◽  
Anurag Payasi ◽  
...  

Despite the crucial role of Polymyxin-B in treating life-threatening gram-negative infections, its clinical utility is limited due to the risk of acute kidney injury. In response, a novel formulation of polymyxin-B is being developed to mitigate drug-induced kidney injury. In this study, we have assessed the toxicity of four variants of that novel formulation (VRP034_F21-F24) in comparison with standard polymyxin-B using kidney injury biomarkers in rats. Sprague-Dawley rats were subcutaneously administered either polymyxin-B (control) or one of the four polymyxin-B formulations at a dose of 25 mg/kg/day (HED: 4 mg/kg/day) in four divided doses for two days. Serum samples were collected at baseline and at the end of day 2 for the determination of serum biomarkers. Necropsy was done on day 2 and kidney was collected for histopathological evaluation. In the control group, statistically significant increase (p < 0.0001) in all biomarkers was observed on day 2 as compared to baseline values [urea: 311%; creatinine: 700%; KIM-1: 180%; cystatin-C: 66%] and 50% of the animals died (one after the 7th dose and two after the 8th dose) before scheduled necropsy. In contrast, animals treated with novel formulations did not show a significant increase across any of the biomarkers and no mortality was observed. Histopathology of the control group kidney confirmed necrotic changes in tissues with congestion and vacuolization, whereas only minor tubular damage was noted in two formulation groups (VRP034_F21, F24) and no appreciable damage was detected in the other two groups (VRP034_F22-23). The novel formulation of polymyxin-B tested in this study significantly reduced the risk of polymyxin-induced kidney injury in rats.


Author(s):  
Obioma Raluchukwu Emeka-Obi ◽  
Nancy C. Ibeh ◽  
Emmanuel Ifeanyi Obeagu ◽  
Hope M. Okorie

Preeclampsia is a serious and life-threatening pregnancy complication. In this study, the levels of haemostatic parameters were measured in preeclamptic women in Owerri, Imo State. A total of 120 pregnant women aged 18-45 years at 20-40 weeks of pregnancy were recruited; 60 were preeclamptic women (test group) while 60 were normotensive pregnant women (control group). Preeclampsia was determined by the presence of ≥2+ protein in the urine using combi 2 dipstick for urinalysis and sphygmomanometer blood pressure reading of ≥ 140/90 mmHg. From the demographic data obtained in the studied subject through questionnaire, it showed that nulliparity and family history of high blood pressure were the most dominant risk factor of preeclampsia. The mean haemostatic parameters (PT, APTT, Fibrinogen, D-dimer and t-PA) of the test group were 12.3±0.94sec, 32.17±3.38sec, 627.31±106.93mg/ld, 2.23±0.50mg/l, 2.65±0.57ng/ml respectively, while the control group were 11.76±0.97sec, 28.69±2.64sec, 554±124.81 mg/dl, 1.89±0.44mg/l and 2.37±0.66 ng/ml respectively. There was a significant difference between the haemostatic parameter of the test group when compared with the control group. The results indicated that although anaemia and activation of coagulation and fibrinolysis occur within the peripheral circulation of both preeclamptic and normotensive pregnancy, an abnormal pattern of haemostasis occurs more in preeclamptic women.


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