Ml Of Propylene Glycol Research Articles

Effects of propylene glycol drenching on energy balance, plasma glucose, plasma insulin, ovarian function and conception in dairy cows

We postulated that daily drenching of propylene glycol to cows in early lactation would increase plasma glucose and insulin concentrations and improve fertility in postpartum cows. Thirty-six Holstein cows were assigned to treatment or control groups. Each treatment cow was given 500 ml of propylene glycol by drenching daily from 7 to 42 days of lactation. Blood samples for glucose, insulin, nonesterified fatty acids (NEFA), and plasma urea N were collected at 0, 30, and 90 min postdrenching once weekly during 1–6 weeks. Blood samples were collected for progesterone analysis and cows were palpated three times per week until 11 weeks to assess ovarian status. Propylene glycol did not affect dry matter intake (DMI), milk yield or energy balance in treatment cows. After drenching, propylene glycol increased ( P<0.01) plasma glucose and insulin and decreased ( P<0.01) NEFA; plasma urea N of the treatment group tended ( P=0.07) to be higher than that of the control group through 90 min. Days to first service, days open, and services per conception were not different between groups. Conception rates to first insemination were 33% in the control group and 57% in treated cows, but these were not significantly different. First ovulation of treatment cows occurred earlier than that of control cows (32.3 versus 44.5 days, P=0.06) and the length of the first luteal phase was longer in treated cows (13.1 versus 7.3 days, P<0.05). These data are consistent with the hypothesis that insulin is important for normal ovarian function. During negative energy balance, treatment with propylene glycol, which induced small increases in plasma concentrations of insulin, prevented the short luteal phase characteristic of the first estrous cycle in control cows.

Etiology of Fatty Liver in Dairy Cattle: Effects of Nutritional and Hormonal Status on Hepatic Microsomal Triglyceride Transfer Protein

We conducted three experiments to determine the effects of nutritional and hormonal status on microsomal triglyceride transfer protein (MTP) activity and mass. In experiment 1, 18 nonlactating Holstein cows, 75 d before expected calving date, in their second gestation or greater were monitored from d 75 to 55 prepartum. Cows were fed a control diet from d 75 to 62 prepartum for covariable measurements. From d 61 to 55 prepartum, six cows continued to receive the control diet, six cows were restricted to 2.3kg of grass hay/d, and six cows were fed the control diet plus 1.8kg of concentrate/ d and 500ml of propylene glycol given 2 times/d as an oral drench. Plasma glucose and serum insulin concentrations were highest in cows that received propylene glycol and lowest in feed restricted cows. Plasma nonesterified fatty acids (NEFA) and liver triglyceride (TG) concentrations were highest in feed restricted cows and not different between cows that received the control diet and cows that received propylene glycol. Hepatic MTP activity and mass were not affected by treatment in experiment 1. In experiment 2, bovine hepatocytes isolated from the caudate process of five preruminating Holstein bull calves were incubated with either 0, 0.5, 1.0, or 2.0mM NEFA for 48h. Intracellular TG increased linearly as NEFA concentration in the media increased. Concentration of NEFA in the incubation media had no effect on MTP activity or mass. There was a quadratic effect of concentration of NEFA in the incubation media on MTP mRNA. In experiment 3, bovine hepatocytes isolated from the caudate process of five preruminating Holstein bull calves were incubated with 2mM [1–14C]oleate for 24h to accumulate TG, followed by a 36-h period of TG depletion, during which hepatocytes were incubated with no hormone, 10 nM insulin, or 10 nM glucagon. There was no effect of insulin or glucagon on intracellular TG, MTP activity or mass. Cells incubated with no hormone had higher levels of MTP mRNA compared to cells incubated with insulin or glucagon during the depletion period. Results suggest that hepatic MTP mRNA may be affected by TG accumulation, insulin, and glucagon in vitro. However, hepatic MTP activity and mass are not affected by nutritional status of nonlactating dairy cows, TG accumulation in vitro, or insulin and glucagon in vitro.

The synovial response to exogenous phospholipid (synovial surfactant) injected into the equine radiocarpal joint compared with that to prilocaine, hyaluronan and propylene glycol

Aims. To determine the effects of the intra-articular injection of surface-active phospholipid in a propylene glycol carrier on synovial fluid composition and joint function of horses, and to compare these effects with those observed after the intra-articular administration of prilocaine, hyaluronan and propylene glycol alone. Methods. Twenty-four horses were randomly allocated to four treatment groups: Group 1 — 100 mg of surface- active phospholipid in 1 ml of propylene glycol; Group 2 — 1 ml of propylene glycol; Group 3 — 10 ml of prilocaine; Group 4 — 2 ml of hyaluronan. Left radiocarpal joints were injected with the treatments and the right radiocarpal joints were injected with volume-matched saline as controls. Examinations for lameness, arthrocenteses and synovial fluid analyses were performed before and at 1, 3 and 7 days after injection. Results. No horses became lame but treated joints temporarily developed mild to moderate effusions. Synovial fluid analyses indicated significantly greater inflammation in treated compared to control joints and this differenc:e was greatest 24 hours after injection. There were no differences between the four treatments based on synoviall fluid analysis except for neutrophil counts and alkaline phosphatase activities, which were significantly higher in prilocainetreated joints. Conclusion. In horses, the intra-articular injection of surface-active phospholipid in a propylene glycol carrier induces clinically insignificant, temporary abnormalities in synovial fluid. Surface-active phospholipid was no more injurious to the synovium than prilocaine or hyaluronan. None of the agents used in this experiment caused lameness when injected into the joints of horses. Relevance. This dose and formulation appear suitable for use in future experiments investigating the efficacy of surface-active phospholipid in the treatment or prevention of osteoarthritis in horses.

Effect of Propylene Glycol Dosage During Feed Restriction on Metabolites in Blood of Prepartum Holstein Heifers

Different doses of propylene glycol were compared for lowering plasma NEFA concentration during restricted feed intake. Eight Holstein heifers, averaging 90 d prior to calving at initiation of the trial, were in a 4 × 4 Latin square design with 12-d periods. Heifers consumed alfalfa silage on an ad libitum basis during d 1 to 7 of each period. During d 8 to 12, heifers were gradually restricted to 50% of ad libitum intake. Heifers received an oral drench of 0, 296. 592, or 887ml of propylene glycol once daily at 6h prior to feeding on d 8 to 12. Propylene glycol linearly increased glucose and insulin and decreased BHBA and NEFA in blood. Quadratic effects of propylene glycol on plasma glucose, BHBA, and NEFA also occurred; response per milliliter of propylene glycol was greatest at the lowest dose. The highest dose of propylene glycol returned blood glucose, insulin, and NEFA concentrations to those prior to feed restriction. Ruminal acetate to propionate ratio decreased as propylene glycol dose was increased, indicating ruminal conversion of propylene glycol to propionate. A dose of 296ml of propylene glycol was almost as effective as a dose of 887ml in reducing lipid mobilization during restricted feed intake.

Analysis of [3H]estradiol-17beta metabolites in calf perirenal fat.

Residues of estradiol-17 beta (E2 beta) in the kidney fat of one milk-fed calf were studies using radiometric methodologies. A three-month old Friesian male veal calf was injected intramuscularly daily for 3 d with 333 mg of [6,7(n)-3H]-E2 beta (specific activity: 7.55 MBq mmol-1) dissolved in 2 ml of propylene glycol and slaughtered 3 h after the last administration. Total estrogens were about 280 ng g-1 in perirenal fat. After a de-lipidation step, the relatively polar metabolites that were extractable with dichloromethane represented the main fraction of the metabolites, which accounts for almost 50% of the total radioactivity of the tissue, of which E2 beta was the major metabolite (19.7%) and E1 and E2 alpha represented only 7.7 and 3.2%, respectively. Conjugated estrogens accounted for only 15.2% of the total estrogen content. Non-polar estrogens (about 25% of total estrogens) were removed specifically with isooctane during the de-lipidation step and were further purified on silica and alumina columns before being chromatographed by normal-phase HPLC. The radioactive metabolites were eluted as estrogen-17 esters. The HPLC analysis of the estrogens released following hydrolysis of the esters indicated that E2 beta was the main estrogen acylated by long-chain fatty acids in the fraction of lipoidal estrogens. The presence of such a class of estrogens in fat could be of interest for the detection of estrogens a considerable time after estradiol administration.

Topical Cyclosporine in Alopecia Areata

<h3>To the Editor.—</h3> The recent article by Biren and Barr¹advocates the use of cyclosporine therapy in alopecia areata. We report here our experience with the topical application of the drug. <h3>Report of a Case.—</h3> A 23-year-old man had had alopecia universalis for three years. He had been successfully treated with oral corticosteroids, but his hair had fallen again after discontinuation of the treatment. After consent, in May 1985, he initiated applying a lotion containing 250 mg of cyclosporine in 80 mL of isopropyl alcohol, 10 mL of propylene glycol, and 15 mL of distilled water once a day to his bald scalp (Fig 1). Since a congenital nevus was present on the vertex, he was advised not to apply the lotion to it. In September 1985, no hair growth was registered, but the patient continued applying the lotion. In March 1986, regrowth was apparent, sparing the nevus of the vertex

Chronic Hypercalcemia Effect on Total Antral Gastrin Cell Counts

Earlier reports have indicated increases in gastrin cell (G cell) mass in many disease states including hyperparathyroidism. This correlation has not been confirmed experimentally, nor has the influence of hypercalcemia separate from that of elevated parathormone been discerned. Sprague-Dawley rats (n = 16) were divided into experimental and control groups. The controls received biweekly intraperitoneal injections of 0.2 ml of propylene glycol and ethanol. Experimental rats received biweekly injections of cholecalciferol (125 µg/ml) in the above carrier and were then divided into 2 groups, group A with 5 weeks and group B with 8 weeks of treatment. Weekly blood was drawn for serum calcium (AA) and serum gastrin (RIA). At sacrifice, serum for parathormone assay (RIA) was drawn and the antral mucosa was stripped and digested. Total mucosa cells were counted and pelleted. Pellets were fixed and sectioned. Straining for G cells was performed using a double-antibody immunofiuorescence technique. Significant hypercalcemia was achieved by vitamin D treatment: mean serum calcium was 13.2 ± 1.2 and 13.5 ± 5.0 versus 10.7 ± 0.6 ml/dl in the controls (p < 0.05). Serum gastrin decreased from a mean value in controls of 98 ± 24 to 34 ± 10 pg/ml (both in group A and group B) (p < 0.05). The total number of antral G cells also decreased: controls 18.24 X 10⁴ ± 10.97 × 10⁴ to 5.22 × 10⁴ ± 2.25 ± 10⁴ in group A and 3.15 × 10⁴ ± 1.38 × 10⁴ in group B (p < 0.05). In this model, hypercalcemia resulted in a significant decrease in G cells as well as in a decrease in serum gastrin, despite a noticeable increase in gastric mucosal thickness. Hypercalcemia may not be a mechanism for G cell hyperplasia, but may be a direct or indirect inhibitor.

Use of a Combination of Propylene Glycol and Niacin for Subclinical Ketosis

Twenty-six cows that developed positive milk tests for ketosis in early lactation were randomly assigned to one of three groups: 1) control, 2) propylene glycol (125 ml/d), or 3) 125ml of propylene glycol plus 12g of niacin daily. Treatments were administered for 7 d. Changes in milk production, milk composition, and feed intake were similar for all three groups. None of the cows in any of the groups developed clinical ketosis. During the 14-d monitoring period from the start of treatment there were similar increases in blood glucose in all groups. Declines in plasma beta-hydroxybutyrate and free fatty acids over the period were also similar for all treatments. Results reinforce the concept that optimum feeding and management reduces the need for additives for ketosis control.

Synchronization of estrus in cyclic beef heifers with the prostaglandin analog alfaprostol

Seventy-eight Hereford-Angus crossbred heifers were injected intramuscularly twice with 6 mg of alfaprostol b b Alfaprostol, 18,19,20-trinor-19-cyclohexyl-13,14 didehydro-PGF 2α-methylester, was supplied by Hoffman-LaRoche Inc., Nutley, NJ 07110. in 6 ml of propylene glycol. On each representative day of a 20-day estrous cycle (estrus = Day 0), either three or four heifers received their first injection. The second injection was given 12 days after the first, regardless of the response to the first injection. Thirty-nine heifers were not treated. The first alfaprostol injection reduced serum progesterone to less than 1 ng/ml in all heifers injected after Day 4. A total of 79.5% ( 62 78 ) of the heifers exhibited estrus by five days after the first injection. Average interval from injection to estrus was 63 hours. The second injection occurred on Days 6 through 16 for all but one heifer, with 75.6% ( 59 78 ) falling on Days 8 through 11 of the estrous cycle. Estrus was detected in 93.6% ( 73 78 ) of the heifers within five days after the second injection, with an average interval to estrus of 66 hours. Day of cycle at second injection did not affect the interval to estrus. Conception occurred in 79.4% ( 58 73 ) of the heifers inseminated in the five days after the second injection. Occurrence of estrus and conception was no different in treated heifers after five days of the insemination period than in nontreated heifers after 21 days of the insemination period, where 94.9% ( 37 39 ) were observed in estrus and 83.8% ( 31 37 ) conceived. Overall percent conception for a 55-day insemination period was 89.7 ( 70 78 ) for treated and 87.2 ( 34 39 ) for nontreated heifers. Day of cycle at first or second injection did not affect conception after the second injection. Some signs of estrus were observed in 11 of the 16 heifers injected before Day 5. A second trial to determine if alfaprostol induced luteolysis early in the cycle was conducted. Twenty purebred Angus, Hereford, or Simmental heifers received either one or two injections of alfaprostol on either Day 1, 2, 3, or 4. Only five heifers showed any signs of estrus, and the three that were inseminated did not conceive. Subsequent cycle length indicated that luteolysis occurred in only one heifer. Data suggest that alfaprostol is an effective luteolytic agent in cyclic beef heifers after Day 4 and that two injections 12 days apart will effectively synchronize estrus in heifers when distributed throughout the cycle at the first injection without affecting conception rate.

MANAGEMENT OF THE NEUROGENIC BOWEL USING DUROLAX SOLUTION

A simple and effective bowel care regime is described which has been in use in the Spinal Injuries Unit at Prince Henry Hospital, Sydney, for more than 10 years. Three times a week, Durolax solution (bisacodyl 10 mg in 5 ml of propylene glycol), usually 5 mL undiluted or diluted with 5 mL of tap water, is introduced into the rectum using a catheter and syringe. A faecal softener is given 24 hours before the Durolax solution. Evacuation usually results within 30 minutes, tending to occur sooner with continued use of the regime. The procedure is well tolerated and there have been no serious problems.

Effect of Melengestrol Acetate on Growth and Reproduction in Rats

Effects of melengestrol acetate on reproductive performance of 48 female rats and 20 of their female progeny were evaluated in two experiments. Treatments of 0, .01, and .1mg in .1ml of propylene glycol were given three groups of 16 rats for 7 days. From day 7 following sperm detection (10-day breeding period), half from each group received .1mg per day for 14 days. Experiment 2 tested performance of 10 progeny exposed or unexposed to in utero treatment.Cyclic changes in Experiment 1 were inhibited only in animals receiving daily initial treatment of .1mg. Estrus was detected in 61.5% of animals within 48h of treatment withdrawal. Synchronization caused no significant changes in conception rates or postbreeding results of treatment. Treatment during gestation lowered weight gain for dams, increased gestation length, and decreased number of pups per litter. Treatment lowered mean weight per litter and weight per pup. It also caused high mortality among pups.In Experiment 2, there were no differences between progeny groups in gestation length, litter size, weight per litter, weight per pup, or mortality rate.

Seizures: A significant side effect of chlorambucil therapy in children

Because the seizures in this patient occurred only during the period when propylene glycol was being ingested, the frequency of seizures increased in spite of anti-convulsant therapy, and a change in the medication was accompanied by complete relief from seizures which has lasted for over three years, the clinical course of this patient suggests a causal relationship between the seizures and the ingestion of propylene glycol. Propylene glycol is relatively safe because it enters the normal metabolic pathways of the body! It is partly excreted in the urine and partly metabolized to lactic and pyruvic acids and then to carbon dioxide and water. However, some patients seem to develop a reversible central nervous system effect associated with the ingestion of the compound. Martin and Finberg' described uncon­ sciousness, tachycardia, tachypnea, and diaphoresis in a 15-month-old child eight days after beginning the daily ingestion of 7.5 ml of propylene glycol. They refer to two instances of stupor associated with ingestion of 60 ml of propylene glycol. Seizure activity has not previously been ascribed to the ingestion of propylene glycol. The associa­ tion seen in this patientcould be related either to the long­ term ingestion of propylene glycol or to an idiosyncratic reaction peculiar to this patient. Another possibility is that the precipitation of seizures by propylene glycol was related to a lower than normal threshold for seizures. This mechanism is similar to the precipitation of seizures by ethyl alcohol, a substance chemically related to propyl­ ene glycol. Hypoglycemia has been suggested as a factor in the CNS symptoms related to propylene glycol ingestion, I an idea not supported by the findings in this case. The reversal of the symptoms suggests that the toxic manifes­ tations are related to the concentration of propylene glycol or one of its metabolites in the blood or tissues. The mechanism which caused the seizures in this patient can be only speculative in the absence of more specific metabolic data. The purpose of this report is to alert physicians to the possible relationship between ingestion of propylene glycol and CNS symptoms in some patients. It is a further reminder that toxic symptoms from medications can be caused not only by the primary medication but also by the vehicle used in preparation of it.

Reactions to peroral propylene glycol.

A peroral challenge test with 2--15 ml of propylene glycol (PG) was made in 38 patients with allergic-type epicutaneous test reactions to PG. Eight of 10 patients with a positive epicutaneous reaction to 2 % PG and seven of the other 28 patients with a positive epicutaneous reaction to 100-100 % PG developed an exanthem 3--16 h after ingestion of the drug. In all but one case the rash disappeared within 24--48 h without any medication. In one case the exanthem was treated with prednisone for 4 days, and the symptoms disappeared gradually in 6 days. None of the 20 control patients had skin symptoms. Nausea, vertigo and a curious sensation were recorded in four PG-sensitive patients and in three control patients. These symptoms were apparently due to the general pharmacodynamic effects of PG and they were regarded as non-allergic in nature. It was concluded that PG is a potential allergen and it must be added to the list of causes of drug exanthems.