Therapy of cancer metastasis by tumoricidal activation of tissue macrophages using liposome-encapsulated immunomodulators

Published results of hepatic cryotherapy are now available for almost 900 patients. Its safety is well established and its clinical role in treating patients with unresectable hepatoma or liver metastases from colorectal carcinoma is well supported by tumour marker and survival data; the results in the treatment of neuroendocrine liver metastases are promising. Its role as an alternative to liver resection is not yet well supported by long-term data. Although different adjuvant treatment protocols have been used following the cryotherapy of colorectal liver metastases, the effect of adjuvant treatment on recurrence or survival has not been assessed in prospective studies. Laparoscopic hepatic cryotherapy is feasible in selected patients with suitable tumour locations. However, the proportion of patients who might be usefully treated with this technique is not yet well established. The mechanisms of tissue destruction by freezing are reviewed.     

Ultrasound-induced destruction of low levels of estrogen hormones in aqueous solutions

The removal of estrogen hormones from water and wastewater is of importance due to their adverse effects toward ecosystems and potential risks to human health. The ultrasound-induced destruction of estrogen compounds in aqueous solutions is studied in a batch reactor using a 1.1 W/mL sonication unit and in a continuous flow reactor using a 2.1 W/mL sonication unit. The estrogen compounds of interest are 17alpha-estradiol, 17beta-estradiol, ethinyl estradiol, estrone, equilin, gestodene, levonorgestrel, and norgestrel. Effects of process variables such as temperature, pH, and pressure are examined. The degradation of estrogens follows pseudo first-order kinetics. The reaction likely takes place in the interfacial region where supercritical environment is produced upon cavity implosion and in the bulk solution with radical species. Low solution pH is more favorable for destruction of estrogens. A kinetic degradation model is developed to predict the destruction of estrogen compounds. Low solution temperature shows favorable destruction of estrogens. Increasing the fluid pressure is detrimental to reaction efficiency.     

Efficacy of oral potassium chloride administration in treating lactating dairy cows with experimentally induced hypokalemia,hypochloremia, and alkalemia

Hypokalemia occurs commonly in lactating dairy cows. The objectives of this study were to determine (1) whether a 24-h oral KCl dose of 0.4 g/kg of body weight (BW) was effective and safe in hypokalemic cattle; (2) whether potassium was best administered as 2 large doses or multiple smaller doses over a 24-h period; and (3) the effect of oral KCl administration on plasma Mg concentration and urine Mg excretion in fasted lactating dairy cattle. Plasma K and Cl concentrations were decreased, and blood pH increased, in 15 lactating Holstein-Friesian cows by administering 2 intramuscular (i.m.) 10-mg injections of isoflupredone acetate 24 h apart followed by 2 i.m. injections of furosemide (1 mg/kg of BW) 8 h apart and by decreasing feed intake. Cows were randomly assigned to 1 of 3 treatment groups with 5 cows/group: untreated control (group C); oral administration of KCl at 0.05 g/kg of BW 8 times at 3-h intervals (group K3); and oral administration of KCl at 0.2 g/kg of BW twice at 12-h intervals (group K12). A 24-h KCl dose rate of 0.4 g/kg of BW increased plasma and milk K concentration and plasma Cl concentration, and corrected the metabolic alkalosis and alkalemia, with no clinically significant difference between 2 large doses (group K12) or multiple small doses (group K3) of KCl over 24 h. Oral KCl administration decreased peripheral fat mobilization in cattle with experimentally induced hypokalemia, as measured by changes in plasma nonesterified fatty acid concentration, and slightly augmented the fasting-induced decrease in plasma Mg concentration. Our findings support recommendations for a 24-h oral KCl dose of 0.4 g/kg of BW for treating moderately hypokalemic cattle. Additional Mg may need to be administered to inappetant lactating dairy cattle being treated with oral KCl to minimize K-induced decreases in magnesium absorption.     

Evaluation of the analytical performance of a portable ion-selective electrode meter for measuring whole-blood,plasma, milk,abomasal-fluid,and urine sodium concentrations in cattle

A portable ion-selective electrode (ISE) meter (LAQUAtwin B-722; Horiba Instruments Inc., Irvine, CA) is available for measuring the sodium ion concentration ([Na]) in biological fluids. The objective of this study was to characterize the analytical performance of the ISE meter in measuring [Na] in whole-blood, plasma, milk, abomasal fluid, and urine samples from cattle. Method comparison studies were performed using whole-blood and plasma samples from 106 sick calves and 11 sick cows admitted to a veterinary teaching hospital, 80 milk and 206 urine samples from 16 lactating Holstein-Friesian cows with experimentally induced free water, electrolyte, and acid-base imbalances, and 67 abomasal fluid samples from 7 healthy male Holstein-Friesian calves fed fresh milk with or without an oral electrolyte solution. Deming regression and Bland-Altman plots were used to determine the accuracy of the meter against reference methods. The meter used in direct mode on undiluted samples measured whole-blood [Na] 9.7 mmol/L (7.3%) lower than a direct ISE reference method and plasma [Na] 16.7 mmol/L (12.7%) lower than an indirect ISE reference method. The meter run in direct mode measured milk [Na] 3.1 mmol/L lower and abomasal fluid [Na] 9.0% lower than indirect ISE reference methods. The meter run in indirect mode on diluted samples accurately measured urine [Na] compared with an indirect ISE reference method. We conclude that, after adjustment for the bias determined from Bland-Altman plots, the LAQUAtwin ISE meter provides a clinically useful and low-cost cow-side instrument for measuring [Na] in whole blood, plasma, milk, and abomasal fluid.     

Comparative effects of two oral rehydration solutions on milk clotting, abomasal luminal pH, and abomasal emptying rate in suckling calves

The effect of adding an oral rehydration therapy (ORT) solution containing bicarbonate, citrate, and acetate to cow's milk on milk clotting, abomasal luminal pH, and abomasal emptying rate was determined in suckling calves. Six male Holstein-Friesian calves with abomasal cannulae, 5 to 13 d of age, were used in a crossover design. Calves were fed 2 L of cow's milk alone, milk with an ORT solution containing a low bicarbonate concentration (25 mmol/L), acetate (12 mmol/L), citrate (12 mmol/L), and glycine (7 mmol/L; group BACG), or milk with an ORT solution containing formate (58 mmol/L) and acetate (15 mmol/L) in randomized order. Clotting of milk was assessed in vivo and in vitro. Abomasal luminal pH was monitored continuously. Abomasal emptying rates were determined by using the change in abomasal luminal pH, acetaminophen absorption, and glucose absorption. The addition of a BACG-ORT solution to cow's milk increased in vitro clotting time by approximately 6 min. All 3 test solutions clotted in vivo by 15 min after the beginning of suckling. The addition of a BACG-ORT solution to cow's milk increased the pH of cow's milk and abomasal fluid by approximately 0.3 pH units. The addition of a BACG-ORT or a formate and acetate-ORT solution to cow's milk increased solution osmolality and slowed the rate of abomasal emptying. We concluded that the addition of BACG-ORT solution to cow's milk did not affect milk clotting in vivo. Recommendations based on the results of in vitro studies that bicarbonate- or citrate-containing ORT solutions should not be fed concurrently with cow's milk do not appear to be relevant to in vivo conditions when 2 L of a low-bicarbonate (25 mmol/L), low-citrate (12 mmol/L) ORT solution is fed.     

Effects of local anesthesia and flunixin meglumine on the acute cortisol response,behavior, and performance of young dairy calves undergoing surgical castration

This study assessed the effects of flunixin meglumine (FM) and a local anesthetic block (LA) on postcastration performance, plasma cortisol concentration, and behavior in dairy calves. Thirty 2- to 3-mo-old Holstein-Friesian bull calves were allocated to 5 treatments: castration with LA (2% lidocaine injected into the testes and subcutaneously), castration with FM (1.1 mg/kg, i.v.), castration with LA+FM, castration without drugs (CC), and sham castration (SC). Castration was performed using a Newberry knife and Henderson castrating tool. Feed intake and body weight gain were recorded for 10 d postcastration. Plasma cortisol concentration and behavior frequency and duration were monitored for 8 h postcastration. Variables with repeated measures were analyzed using PROC MIXED (SAS Institute Inc., Cary, NC); one-way ANOVA was used for nonrepeated measures. No differences in feed intake or body weight gain were detected among groups. Calves in the CC, LA, and FM groups had transient (<60, <60, and <45 min, respectively) increases in plasma cortisol concentration after castration, with a second increase at 120 min in the LA group, whereas cortisol concentration remained at baseline in the LA+FM and SC groups. Mean cortisol concentrations were lower for calves in the LA+FM and SC groups than in the CC group. The area under the plasma cortisol concentration curve during the first 3 h postcastration was greater in CC- and LA-treated calves than in SC controls. Castration without drugs was associated with higher frequencies of crouching and statue standing and less oral activity compared with SC controls. Administering LA alone before castration was associated with higher frequencies of head turning, statue standing, and postural changes, and less feeding behavior compared with SC controls. More leg lifting to groom was seen in LA+FM-treated calves than in SC controls. Calves administered FM alone before castration exhibited less crouching than CC calves, fewer postural shifts, and more feeding behavior than LA-treated calves. In summary, FM alone tended to shorten the duration of cortisol response and reduce crouching after surgical castration. Combining LA+FM eliminated the cortisol response to castration but was associated with more leg lifting behavior. Treatment with LA alone did not mitigate the cortisol response and was associated with several behavioral differences compared with SC, FM-treated, or FM+LA-treated calves. Results suggest that LA alone did not effectively control discomfort in young dairy calves castrated using the Henderson castration tool.     

Periparturient effects of feeding a low dietary cation-anion difference diet on acid-base, calcium, and phosphorus homeostasis and on intravenous glucose tolerance test in high-producing dairy cows

Feeding rations with low dietary cation-anion difference (DCAD) to dairy cows during late gestation is a common strategy to prevent periparturient hypocalcemia. Although the efficacy of low-DCAD rations in reducing the incidence of clinical hypocalcemia is well documented, potentially deleterious effects have not been explored in detail. The objective of the study presented here was to determine the effect of fully compensated metabolic acidosis on calcium and phosphorus homeostasis, insulin responsiveness, and insulin sensitivity as well as on protein metabolism. Twenty multiparous Holstein-Friesian dairy cows were assigned to 1 of 2 treatment groups and fed a low-DCAD ration (DCAD = −9 mEq/100 g, group L) or a control ration (DCAD = +11 mEq/100 g, group C) for the last 3 wk before the expected calving date. Blood and urine samples were obtained periodically between 14 d before to 14 d after calving. Intravenous glucose tolerance tests and 24-h volumetric urine collection were conducted before calving as well as 7 and 14 d postpartum. Cows fed the low-DCAD ration had lower urine pH and higher net acid excretion, but unchanged blood pH and bicarbonate concentration before calving. Protein-corrected plasma Ca concentration 1 d postpartum was higher in cows on the low-DCAD diet when compared with control animals. Urinary Ca and P excretion was positively associated with urine net acid excretion and negatively associated with urine pH. Whereas metabolic acidosis resulted in a 6-fold increase in urinary Ca excretion, the effect on renal P excretion was negligible. A more pronounced decline of plasma protein and globulin concentration in the periparturient period was observed in cows on the low-DCAD diets resulting in significantly lower total protein and globulin concentrations after calving in cows on low-DCAD diets. Intravenous glucose tolerance tests conducted before and after calving did not reveal group differences in insulin response or insulin sensitivity. Our results indicate that fully compensated metabolic acidosis increased the Ca flux resulting in increased urinary calcium excretion before calving and increased plasma Ca concentration on the day after calving, whereas the effect on P homeostasis was unlikely to be clinically relevant. The clinical relevance of the effect of metabolic acidosis on the plasma protein and globulin concentration is unclear but warrants further investigation.