Fluid balance, electrolyte profiles and plasma parathyroid hormone concentrations in ewes treated with epidermal growth factor

1992 ◽  
Vol 135 (1) ◽  
pp. 91-101 ◽  
Author(s):  
C. B. Gow ◽  
M. Wilkinson ◽  
M. J. Silvapulle ◽  
G. P. M. Moore

ABSTRACT The infusion of low doses of epidermal growth factor (EGF) into lactating ewes stimulates water intake and urine volume. The plasma concentrations and daily output of various electrolytes in milk and urine are also affected. We have investigated this further by recording the effects of EGF infusion on fluid balance, electrolyte profiles and plasma concentrations of glucose and parathyroid hormone (PTH) in non-pregnant, non-lactating ewes. Twenty-four animals (n= 8 per group) received infusions of 100 ml saline/day into the jugular vein for 10 days (days 1–10) followed by EGF at a dose rate of either 1 (low dose), 5 (medium dose) or 10 (high dose) μg/kg liveweight per day in 100 ml saline for 5 days (days 11–15). All ewes then received an infusion of 100 ml saline/day for 10 days (days 16–25). Most plasma and urine samples had undetectable concentrations of EGF-immunoreactive material during the periods of saline infusion. During EGF infusion, the highest amounts of EGF infusate excreted in urine were 1·6, 5·9 and 5·6% for ewes in low, medium and high dose groups respectively. Water intake increased by 17% (0·5 kg), 88% (2·5 kg) and 89% (2·3 kg) and urine volume increased by 29% (0·5 kg), 108% (2·2 kg) and 134% (2·1 kg) for the three groups respectively. Fluid balance and feed intake were not affected by EGF infusion, but the output of faecal dry matter was reduced in ewes receiving the two higher doses of EGF. All levels of EGF resulted in hypocalcaemia, increased plasma PTH concentrations and hypermagnesaemia. There was no effect of EGF on plasma concentrations of K+ and glucose or on daily urinary excretion of K+ and Mg2+. The only response to the low dose was a reduced plasma concentration of Na+ and an increased daily urinary urate excretion. The two higher doses increased the daily urinary excretion of Na+, PO43− and urate, but had no effect on the respective concentrations in plasma. Urinary Ca2+ excretion was reduced only during infusion of the medium dose of EGF. The responses of most variables were similar during infusion of the medium and high doses of EGF. All three doses of EGF induced polydipsic and diuretic responses in ewes, and infusions of 5–10 μg EGF/kg liveweight per day affected renal excretion of Ca2+, Na+ and PO3−4. We interpret the responses of the kidney and plasma PTH concentrations as a means of maintaining the homeostasis of plasma profiles of electrolytes. Journal of Endocrinology (1992) 135, 91–101

1993 ◽  
Vol 265 (1) ◽  
pp. R203-R210 ◽  
Author(s):  
C. B. Gow ◽  
P. A. Phillips ◽  
K. D. Chandler ◽  
G. P. Moore

Epidermal growth factor (EGF) has been shown to increase water intake and urine volume. To further characterize these responses the effects of EGF on fluid balance, electrolyte, and hormone profiles were examined. After an 8-day control period, ewes received intravenous EGF at doses of 0 (n = 6), 2 (low dose, n = 6), 10 (medium dose, n = 6), or 20 micrograms/h (high dose, n = 5) for 4 days. During EGF treatment, water intake and urine volume increased (both P < 0.001) in a dose-related fashion, although fluid balance was unaffected. Feed intake and fecal dry matter output were reduced (both P < 0.001) by the two higher doses of EGF. EGF had no effect on plasma potassium, sodium, or osmolality, but there was a dose-related natriuresis (P < 0.001). Treatment with EGF increased plasma renin activity and aldosterone in the medium and high dose groups (both P < 0.001). Thus chronic intravenous infusion of 10-20 micrograms EGF/h into sheep caused polydipsia, polyuria, and natriuresis with neutral fluid balance. Whether the resultant polydipsia or polyuria was the primary response to EGF remains unclear.


1995 ◽  
Vol 13 (5) ◽  
pp. 1231-1237 ◽  
Author(s):  
G Somlo ◽  
J H Doroshow ◽  
A Lev-Ran ◽  
D C Ahn ◽  
L Hwang ◽  
...  

PURPOSE To evaluate the protective effect of low-dose dopamine given as continuous infusion in patients who undergo chemotherapy with the nephrotoxin cisplatin. PATIENTS AND METHODS Forty-two patients who received high-dose cisplatin-containing chemotherapy entered a prospective, randomized, double-blind, placebo-controlled trial. Twenty-one patients received dopamine, and 21 received placebo. Patients were to receive either infusional dopamine 2 micrograms/kg/min over 48 hours or placebo. Cisplatin 125 mg/m2 was administered 12 hours after initiating dopamine (group D) or placebo (group P). This schedule was repeated twice, 1 week apart. Measurements of serum creatinine, urinary electrolytes and creatinine, urinary excretion of epidermal growth factor (EGF), ototoxicity, parameters of hematopoietic recovery, and duration of hospitalization were analyzed. RESULTS We observed an increase in serum creatinine level to a peak of 1.9 mg/dL (range, 0.8 to 7.8) in the dopamine group, in comparison to 1.4 mg/dL (range, 0.9 to 3.3) in the placebo group (P = .04). Urinary magnesium excretion increased and EGF excretion decreased in both groups. Urinary sodium, chloride, and potassium excretion were increased in both groups, but more so in the placebo group. Dopamine had no measurable effect on hearing loss, duration of hospitalization, or hematopoietic recovery. CONCLUSION The use of prophylactic dopamine increased peak serum creatinine levels relative to placebo and failed to prevent cisplatin-induced renal toxicity or ototoxicity. Determination of whether dopamine could reverse chemotherapy-induced renal damage would require a randomized prospective trial.


1995 ◽  
Vol 82 (3) ◽  
pp. 620-633 ◽  
Author(s):  
P. Talke ◽  
J. Li ◽  
U. Jain ◽  
J. Leung ◽  
K. Drasner ◽  
...  

Background Dexmedetomidine, a highly selective alpha 2-adrenergic agonist, increases perioperative hemodynamic stability in healthy patients but decreases blood pressure and heart rate. The goal of this study was to evaluate, in a preliminary manner, the hemodynamic effects of perioperatively administered dexmedetomidine in surgical patients at high risk for coronary artery disease. Methods Twenty-four vascular surgery patients received a continuous infusion of placebo or one of three doses of dexmedetomidine, targeting plasma concentrations of 0.15 ng/ml (low dose), 0.30 ng/ml (medium dose), or 0.45 ng/ml (high dose) from 1 h before induction of anesthesia until 48 h postoperatively. All patients received standardized anesthesia and hemodynamic management. Blood pressure, heart rate, and Holter ECG were monitored; additional monitoring included continuous 12-lead ECG preoperatively, anesthetic concentrations and myocardial wall motion (echocardiography) intraoperatively, and cardiac enzymes postoperatively. Results Preoperatively, there was a decrease in heart rate (low dose 11%, medium dose 5%, high dose 20%) and systolic blood pressure (low dose 3%, medium dose 12%, high dose 20%) in patients receiving dexmedetomidine. Intraoperatively, dexmedetomidine groups required more vasoactive medications to maintain hemodynamics within predetermined limits. Postoperatively, demedetomidine groups had less tachycardia (minutes/monitored hours) than the placebo group (placebo 23 min/h; low dose 9 min/h, P = 0.006; medium dose 0.5 min/h, P = 0.004; high dose 2.3 min/h, P = 0.004). Bradycardia was rare in all groups. There were no myocardial infarctions or discernible trends in the laboratory results. Conclusions Infusion of dexmedetomidine up to a targeted plasma concentration of 0.45 ng/ml appears to benefit perioperative hemodynamic management of surgical patients undergoing vascular surgery but required greater intraoperative pharmacologic intervention to support blood pressure and heart rate.


Author(s):  
Kristin E Killoran ◽  
Courtney A Walsh ◽  
Jennifer L Asher ◽  
Molly B Tarleton ◽  
Steven R Wilson

Anesthesia in rhesus macaques is required for many procedures. Although ketamine is the backbone of most anestheticprotocols, tolerance to the drug can develop, resulting in the need for higher doses to provide sufficient restraint. Combination with other drugs, such as α-agonists, can be ketamine-sparing, providing for sufficient restraint at lower ketamine doses. In addition, because α-agonists are reversible, recovery from anesthesia has the potential to be much shorter. We hypothesized that use of a low dose of ketamine with a high dose of dexmedetomidine, an α2 receptor selective agonist, in male and female rhesus macaques less than 15 y of age would provide adequate anesthesia for short procedures and that recovery would be faster than in macaques given a higher dose of ketamine (10 mg/kg) alone. We found that the combination, in conjunction with atipamezole for reversal, provided smooth induction of anesthesia and significantly shorter recovery time than did ketamine alone, with no significant effects of sex. The combination of low dose ketamine and high dose dexmedetomidine also provided a 30-min window of anesthesia with analgesia sufficient for mild to moderately painful procedures.


2020 ◽  
Author(s):  
Tao Hong ◽  
Hao Chen ◽  
Li Liu ◽  
Weiqi Liu ◽  
Longxue Li ◽  
...  

Abstract Background Coix seed is a traditional Chinese medicine with pharmacological effects and food efficacy. It is well-know and widely used in China and other Asian countries. Fayiren is a new artillery material processed from Coix Seed. This is the first study of the diuretic activities of Fayiren and coix seed in normal rats. Methods Forty-eight rats were randomly divided into 6 groups (8 rats/group) according to body mass and urine volume stratification, namely model (physiological saline) group, positive control (furosemide 20 mg/kg) group, coix seed (1666 mg/kg) group, low-dose of Fayiren group (166 mg/kg) and high-dose Fayiren group (1666 mg/kg). Rats were fasted for 16 h before the experiment, with normal water supply. Immediately after administration, each group of rat was placed in a metabolic cage, and urine was collected once after every hour for a total of 6 times. The urine volume at each time point for collection was measured, and then totaled. After the 6 h recording procedure, the treatments were administered once a day and the urine was collected at the 24th, 48th, 72th, 96th, 110th, 134th, and 158th hours from the start respectively. The urine pH and Na +, K +, Ca 2+, Cl - concentrations at each time point of each group of rats were measured. The contents of ALD, ANP, ADH, Na+-K+-ATPase, the gene expression and protein levels of AQP1, AQP2 and AQP3 in urine of rats in each group were determined. SPSS22.0 statistical software was used to analyze the experimental data. One way ANOVA and multiple comparisons between LSD groups were performed. The difference is considered significant When p < 0.05 or p < 0.01. Results After the administration of Fayiren and coix seed, compared with normal rats, the total output of urine in the high-dose coix seed & Fayiren group and the positive control group both increased; In addition, the contents of Na+ and Cl-in urine in these groups increased as well. However, the content of K+ did not increase in all groups. Contents of ALD and ADH was decreased and increased contents of ANP observed in urine in both high-dose and low-dose Fayiren groups with significant differences from model group (P < 0.05). Coix seed significantly reduced ADH and increased ANP levels compared with model group (P < 0.05). There was no obvious change in the urine pH content in urine of all rats. All the aquaporin (AQP1, AQP2, and AQP3) contents were decreased comparing to the model group, the coix seed group, as well as the Fayiren group. The effect of coix seed was particularly notable on AQP2, and the difference was significant against the Furosemide group (P < 0.05). By contrast, Fayiren showed greater effects on AQP1 and AQP3, with statistically significant difference comparing to the model group (P༜0.05). Conclusions This study will provide experimental evidence for explaining the different mechanisms of diuretic effects in natural medicine use of coix seed and artillery material processed from Coix Seed. The Fayiren may affect the reabsorption of water in the kidney through mechanisms related to increased ANP secretion,decreased ALD and ADH secretion in urine, and it significantly affect the expression of aquaporin 1 and aquaporin 3. However, coix seed may increase ANP but decreased ADH secretion, further affecting the expression of aquaporin2 and exert diuretic effect.


Animals ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. 313 ◽  
Author(s):  
Rihong Guo ◽  
Fang Chen ◽  
Cheng Mei ◽  
Zicun Dai ◽  
Leyan Yan ◽  
...  

This study was conducted to investigate the feasibility of improving fertility in dairy cows via immunization against inhibin. Thirty-two cows were divided into Control (n = 11), Low-dose (n = 10) and High-dose (n = 11) groups. The High-dose and Low-dose cows were treated with 1 and 0.5 mg of the inhibin immunogen, respectively. All the cows were subjected to the Ovsynch protocol from the day of antigen administration and were artificially inseminated. Blood samples were serially collected over a 24-day period from the start of the Ovsynch protocol to 14 days after insemination. The results showed that immunization against inhibin dose-dependently increased the plasma concentrations of follicle-stimulating hormone (FSH), estradiol (E2), and activin A, but decreased progesterone (P4) concentrations in the luteal phase. Immunization also increased the plasma interferon (IFN)-τ concentrations in pregnant cows on day 14 after initial insemination. The conception rates in High-dose (45.5%) and Low-dose (40%) cows marginally increased compared to that in Control cows (27.3%), but the increases were not significant (p > 0.05). In conclusion, a single immunization against inhibin has the potential to improve conception rates, despite impaired luteal development. To further improve the reproductive performance of dairy cows, additional luteal-stimulating treatments are suggested in combination with immunization against inhibin and Ovsynch techniques.


2020 ◽  
Vol 29 ◽  
pp. 096368972091268
Author(s):  
Yajun Xue ◽  
Boda Zhou ◽  
Jian Wu ◽  
Guobin Miao ◽  
Kun Li ◽  
...  

As the impairment of myocardial microenvironments due to coronary microembolization (CME) compromises the treatment effect of percutaneous coronary intervention and leads to adverse prognosis, we hypothesized that endothelial progenitor cells (EPCs) transplantation could improve cardiac function in the condition of CME. Low- (2 × 105) and high- (2 × 106) dose rat bone marrow-derived EPCs were transplanted in a model of CME. To develop a CME model, rats were injected with autologous micro-blood-clots into the left ventricle. Echocardiograph was examined before and 1, 7, and 28 days after EPC transplantation; serum cardiac troponin I (cTNI), von Willebrand factor (vWF), and cardiac microRNA expression were examined one day after EPCs transplantation. Heart morphology and vascular endothelial growth factor (VEGF), vWF, and basic fibroblast growth factor (bFGF) expression were examined one day after EPC transplantation. After 10 days of culture inductions, BM-EPCs have high purity as confirmed by flow cytometry. Cardiac function reflected by left ventricular ejection fraction significantly decreased after CME treatment and rescued by low-dose EPC. Compared to the sham group, cTNI and vWF serum levels increased significantly after CME treatment and rescued by low-dose EPC and high-dose EPC. Low-dose EPC treatment decreased myocardial necrosis and fibrosis and elevated cardiac expression of VEGF and vWF, while decreasing the cardiac expression of bFGF. Low-dose EPC treatment significantly suppressed cardiac expression of microRNA-19a but significantly enhanced microRNA-21, microRNA-214, and microRNA-486-3p expression. In conclusion, our results indicate that low-dose EPC transplantation may play a proangiogenic, antifibroblast, antifibrosis, and antinecrosis role and enhance cardiac function in a rat model of CME through a microRNA-related pathway.


1993 ◽  
Vol 75 (6) ◽  
pp. 2561-2569 ◽  
Author(s):  
K. Kambara ◽  
M. Arakawa ◽  
T. Segawa ◽  
F. Ando ◽  
M. Ohno ◽  
...  

We studied the effects of acetylsalicylic acid (ASA) on pressor response, microvascular filtration coefficient (Kf), extravascular lung water, and plasma concentrations of cyclooxygenase- and 5-lipoxygenase-derived products in 21 blood-perfused dog lungs with constant flow. The lungs were perfused for 1 h with an intrapulmonary injection of saline as vehicle (n = 5), a low dose of ASA [136 +/- 25 (SD) micrograms/ml perfusate; n = 5], a high dose of ASA (1,006 +/- 278 micrograms/ml perfusate; n = 6), or alloxan (1,000 mg; n = 5). Alloxan significantly increased Kf and extravascular lung water, whereas neither the low nor high dose of ASA increased Kf or extravascular lung water. The ASA-induced increase in vascular resistance did not correlate with the extent of the decrease in perfusate 6-keto-prostaglandin F1 alpha or the ratio of perfusate 6-ketoprostaglandin F1 alpha to thromboxane B2. Moreover, ASA did not enhance the generation of perfusate leukotrienes B4, D4, or E4. We conclude that pulmonary microvascular permeability is unaltered by ASA and that neither the decrease in plasma prostacyclin nor the increase in plasma sulfidopeptide leukotrienes may account for ASA-induced pulmonary vasoconstriction.


2020 ◽  
Vol 46 (Supplement_1) ◽  
pp. S216-S217
Author(s):  
Chao Ma ◽  
Yan Wu ◽  
Pei Chen ◽  
Yuan Jia ◽  
Dongqing Yin ◽  
...  

Abstract Background Our previous study indicated a therapeutic effect of Shi-Zhen-An-Shen-Tang (SZAST), a Chinese herb formula, on schizophrenia, but the related mechanism is unknown(citation). A large body of evidence suggests the important role of white matter of the brain in the pathophysiology of schizophrenia. This study was designed to evaluate the effect of SZAST on schizophrenia with demyelinated mice. Methods Male C57BL/6 mice were given mixed cuprizone (CPZ, a copper chelator, 0.2 %, w/w) rodent chow for six successive weeks to induce demyelination. During the last two weeks, mice were given an oral gavage of saline, or SZAST of three different doses (a low dose of 5.5g·kg-1·d-1, a medium dose of 8.24g·kg-1·d-1, or a high dose of 10.98 g·kg-1·d-1), or quetiapine, respectively. Behavioral tests were conducted after the last treatment. Meanwhile, the expression of myelin basic protein (MBP) and neuregulin-1(NRG1) in the brain was tested by immunohistochemistry staining or Western Blot. Results Mice exposed to CPZ for six weeks showed obvious schizophrenia-like behaviors, including lower nest-building activity, sensory gating activity, and higher locomotor activity. CPZ-fed mice also displayed a lower myelin density in the corpus callosum, hippocampus, and cerebral cortex and a reduction of MBP and NRG1 protein in the hippocampus compared with controls. Both quetiapine and SZAST significantly alleviated the abnormal schizophrenia-like behaviors and the impairment of myelin sheath in CPZ-fed mice, however, SZAST with medium dose showed better neuroprotective effect than the low dose or the high dose of SZAST. Furthermore, the expression of NRG1protein in the hippocampus was slightly, but not significantly increased in all SZAST-treated and quetiapine-treated groups. Discussion These results indicate that the neuroprotective effect of SZAST in demyelinated mice might partially relate to remyelination in the hippocampus in CPZ-fed mice.


2020 ◽  
Vol 75 (Supplement_1) ◽  
pp. i88-i99
Author(s):  
D Torumkuney ◽  
A Tunger ◽  
B Sancak ◽  
A Bıçakçıgil ◽  
B Altun ◽  
...  

Abstract Objectives To determine antibiotic susceptibility of Streptococcus pneumoniae and Haemophilus influenzae isolates from community-acquired respiratory tract infections (CA-RTIs) collected in 2015–17 from Turkey. Methods MICs were determined by CLSI broth microdilution and susceptibility was assessed using CLSI, EUCAST (dose-specific) and pharmacokinetic/pharmacodynamic (PK/PD) breakpoints. Results A total of 179 S. pneumoniae and 239 H. influenzae isolates were collected. Few (27.9%) pneumococci were penicillin susceptible by CLSI oral or EUCAST low-dose breakpoints, but by EUCAST high-dose or CLSI IV breakpoints 84.4% were susceptible. The most active antibiotics (excluding penicillin IV) by CLSI breakpoints were fluoroquinolones (98.9% of isolates susceptible), ceftriaxone (83.2%), amoxicillin (78.8%) and amoxicillin/clavulanic acid (78.8%). Pneumococcal susceptibility to amoxicillin and amoxicillin/clavulanic acid was lower using EUCAST low-dose breakpoints (49.7%), although susceptibility increased when using EUCAST high-dose (57.0%–58.1%) and PK/PD (78.8%–87.7%) breakpoints. Twenty-three H. influenzae isolates were β-lactamase positive, with 11 characterized as β-lactamase negative and ampicillin resistant following EUCAST criteria and 5 by CLSI criteria. Generally antibiotic susceptibility was high using CLSI breakpoints: ≥92.9% for all antibiotics except ampicillin (87% by CLSI and EUCAST breakpoints) and trimethoprim/sulfamethoxazole (67.4% and 72% by CLSI and EUCAST breakpoints, respectively). Susceptibility using EUCAST breakpoints (where these are published) was similar, except for cefuroxime (oral) with 3.8% of isolates susceptible. PK/PD breakpoints indicated low susceptibility to macrolides (5.9%–10%) and cefaclor (13%). The application of different EUCAST breakpoints for low and higher doses for some of the antibiotics (amoxicillin, amoxicillin/clavulanic acid, ampicillin, penicillin, ceftriaxone, clarithromycin, erythromycin, levofloxacin and trimethoprim/sulfamethoxazole) allowed, for the first time in a SOAR study, the effect of raising the dosage on susceptibility to be quantified. Conclusions Antibiotic susceptibility of S. pneumoniae was generally low, which is in keeping with evidence of inappropriate and high antibiotic use in Turkey. H. influenzae susceptibility was high. These data are important for empirical therapy of CA-RTIs.


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