Adverse Physiological Changes Research Articles

Reversal of cerebral vasospasm using an intrathecally administered nitric oxide donor.

Intrathecal bolus administration of (Z)-1-[N-(2-aminoethyl)-N-(2-ammonioethyl)aminio]diazen++ +-1-ium-1,2-diolate (DETA/NO), a long half-life diazeniumdiolate-class nitric oxide (NO) donor, was evaluated for safety and efficacy in the treatment of delayed cerebral vasospasm in a canine model of subarachnoid hemorrhage (SAH). The baseline basilar artery (BA) diameter of 25 dogs was measured with the aid of angiography on Day 0. Vasospasm was then induced by intracisternal injection of autologous arterial blood on Days 0 and 2. Repeated arteriography on Day 7 revealed an average BA diameter of 58% of baseline. Each dog was then randomized to one of four groups: a pathology control group (SAH only, four animals); a treatment control group (SAH plus 2 micromol of the inactive drug carrier DETA, eight animals); a low-dose treatment group (SAH plus 0.2 micromol DETA/NO, six animals); or a high-dose treatment group (SAH plus 2 micromol DETA/NO, six animals). The drugs were administered in a 2-ml intrathecal bolus via the cisterna magna. Arterial caliber was monitored by angiography over the subsequent 4 hours. A 2-micromol dose of the drug was then given and serial arteriography continued for an additional hour to screen for tachyphylaxis. Intracranial pressure and respiratory and hemodynamic parameters were continuously monitored. Histopathological analyses of the animals' brains were performed after the dogs were killed on Day 8. The drug DETA/NO produced reversal of vasospasm in a dose-dependent fashion that roughly followed a double exponential time course. Doses of 2 micromol DETA/NO resulted in restoration of the angiographically monitored BA diameter to the prevasospasm size at 1.5 hours posttreatment, and this was sustained at 88% of baseline at 4 hours (p < 0.01, independent samples t-test). By contrast, the treatment control group remained on average at 54% of baseline diameter. The low-dose treatment group achieved only partial and more transitory relaxation. Histopathological analyses showed findings consistent with chronic SAH but did not demonstrate any toxicity associated with the NO donor. No adverse physiological changes were seen. This study indicates that long-acting NO donors are potentially useful as agents to restore circulation in patients suffering from cerebral vasospasm.

Acute hemodynamic effects of recently developed monomer and dimer magnetic resonance imaging contrast media: A comparative study

We evaluated and compared the acute cardiovascular effects of equiosmolar doses of recently developed nonionic monomer and macrocyclic dimer magnetic resonance (MR) imaging contrast media with the clinically available ionic and nonionic MR contrast media. Normotensive adult Sprague-Dawley rats were divided into six groups of seven rats per group. Group 1 received the nonionic monomer Gd-CMPA-BMPA (500 mmol/l solution); group 2 received the nonionic dimer Gd(2)2(O)DO3A (500 mmol/l solution); group 3 also received Gd(2)2(O)DO3A but at a higher concentration (1,000 mmol/l solution); group 4 received gadopentetate dimeglumine (500 mmol/l solution); and group 5 received gadodiamide (500 mmol/l solution). Each rat received a rapid (1-2 sec) bolus intravenous injection of 0.1, 0.25, and 0.5 mmol/kg of each contrast agent. Group 6 was used to test the peak effects of quiosmolar glucose solutions (500, 1,000, and 2,000 mOsm/kg water). Data were acquired at baseline, 20 sec (peak effect) after injection, and 1, 3, 5, and 10 min after injection. Peripheral (systolic, diastolic, and mean) pressure, central venous pressure, left ventricular (LV) pressure (peak systolic and end diastolic) pressure, first derivative of left ventricular pressure (+/-dP/dt), rate pressure product, and heart rate were measured. Bolus administration (0.1, 0.25, and 0.5 mmol/kg) of Gd-CMPA-BMPA and gadodiamide (500 mmol/l) had no significant effects on the monitored cardiovascular parameters. Bolus injection of 0.25 and 0.5 mmol/kg Gd(2)2(O)DO3A (500 and 1,000 mmol/l) and gadopentetate dimeglumine (500 mmol/l) caused transient cardiovascular depression, including decreased peripheral blood pressure, LV systolic pressure, peak positive and negative dP/dt, and rate pressure product, but an increased LV end diastolic pressure. These cardiovascular effects were slightly less profound than those produced by gadopentetate dimeglumine. Gd-CMPA-BMPA and gadodiamide have no adverse cardiovascular effects. Gd(2)2(O)DO3A and gadopentetate dimeglumine cause vasodilation and reduced cardiac performance. Therefore, presuming similar effects, if Gd(2)2(O)DO3A and gadopentetate dimeglumine are to be used at high doses for the MR quantification of blood volume or as a bolus for perfusion study, appropriate consideration should be given to possible adverse physiologic changes.

Toxicological evaluation of jimson weed ( Datura stramonium) seed

Diets containing 0.5, 1.58 and 5.0% jimson weed seed were fed to male and female rats (20/group) in a 90-day subchronic feeding study. The alkaloid content was 2.71 mg atropine and 0.66 mg scopolamine/g of seed. Gross clinical observations, body weights and feed and water intakes were recorded weekly. Tear production and pupil dilation measurements were made throughout the study. At 90 days, all of the animals were autopsied and clinical-chemistry analyses, complete haematology and bone-marrow evaluation for evidence of clastogenic effects were performed. Tissues from control (0% seed) and high-dose animals were examined histologically. The principal effects of jimson weed seed were: decreased body-weight gain, serum albumin and serum calcium; increased liver and testes weights (as a percentage of body weight), serum alkaline phosphatase and blood urea nitrogen. Female rats showed more marked responses to jimson weed seed than did males. In addition to the effects seen in both sexes, the females developed decreased serum total protein and cholesterol, and increased serum glutamic-pyruvic transaminase and chloride, red blood cell count, haemoglobin concentration and packed red cell volume. No histological lesions were associated with ingestion of jimson weed seed at 5.0%. It is concluded that jimson weed seed at concentrations of 0.5% or more in the diet produced adverse physiological changes in rats.

Effects of interleukin-2 on renal function in patients receiving immunotherapy for advanced cancer.

Adoptive transfer of autologous lymphokine-activated killer cells in conjunction with recombinant interleukin-2 in patients with advanced cancer has produced significant regression of metastatic disease in selected patients. We analyzed the effects of interleukin-2 regimens on renal function in 99 consecutive patients. Interleukin-2 therapy with or without lymphokine-activated killer cells was associated with varying degrees of hypotension, fluid retention, azotemia, oliguria, and low fractional sodium excretion. After the patients completed the interleukin-2 regimens, their renal function improved promptly. Renal function values returned to baseline levels within 7 days in 62% of patients, within 14 days in 84%, and within 30 days in 95%. Pretherapy serum creatinine values above 1.4 mg/dL predicted the severity of azotemia and prolonged duration of renal functional recovery, interleukin-2 therapeutic regimens induce prerenal azotemia. Careful selection of patients and early detection of adverse physiologic changes may alleviate the side effects of interleukin-2 therapy.

Oral Contraceptives and Physiological Variables

Physiological variables were compared among women who had never used oral contraceptives, past users, and current users. Randomly selected subjects were aged 30 to 59 years. Blood was sampled for determination of blood glucose, serum cholesterol and triglyceride, and plasma insulin concentration. Summed postchallenge glucose and insulin values were used in analyses to represent the magnitude of response. Contours of glucose and insulin curves were represented by single numerical variables termed "G-CON" and "I-CON." Current users of oral contraceptives had significantly higher values of G-CON, I-CON, triglyceride, and systolic blood pressure than women who never used oral comtraceptives. Current users also had significantly higher levels of summed glucose, G-CON, and I-CON than former users. Use of currently prescribed oral contraceptives is associated with adverse physiological changes that are reversible after discontinuing such use.

Physiological Factors in Childhood Epilepsy

The identification and correction of adverse physiological changes that lead to seizures in children can improve the effectiveness of current therapeutic practices in epilepsy. It is proposed that various circadian rhythms (respiration, hormones, water balance, electrolytes, intracranial pressure, blood pressure), meteorological phenomena (barometric presure, ambient environmental temperature, relative humidity), and developmental processes can profoundly influence the precipitation or prevention of seizures through their physiological effects.

Treatment of the Aging Skin by Dermatologic Methods*

Adverse physiologic and biochemical changes in the aging skin are aggravated by unprotected, continuous or repeated exposure to the harmful rays of the sun. Waning hormonal activity contributes to these changes. The associated clinical entities are skin dryness, accentuation of facial lines and wrinkles, hyperpigmentation, and multiple benign or malignant growths. The skin should be protected by sunscreening and sunblocking agents. Overexposure to the sun must be avoided. Repeated applications of moisturizing creams, vegetable oils, and appropriate hormonal cosmetics may be helpful in hydrating the skin and thus improving its external appearance. Chemosurgery (peeling) and dermabrasion may reduce hyperpigmentation and fine facial lines and wrinkles. New growths can be removed by various surgical methods. Biopsy should be performed to determine the presence of a malignant lesion requiring additional x-ray therapy.

The role of alkaloids in the poisoning of mammals by sclerotia of Claviceps spp.

Several alkaloids occurring naturally in the sclerotia of Claviceps spp. have powerful pharmacological properties and ingestion of the sclerotia on infected host plants or in contaminated feedstuffs may result in adverse physiological changes affecting peripheral circulation, fertility, lactation or general behaviour. The relative significance of certain Claviceps spp., parasitic on plant hosts of economic importance, is described. Factors affecting the fungal epidemiology and the availability to the animal of the sclerotial alkaloids are discussed. Recent investigations on the role of C. purpurea sclerotia in animal poisoning are presented. These indicate that many clinical cases in farm animals, previously attributed to ergot poisoning, were probably due to some other agent. Agalactia, caused in pigs by the millet ergot fungus ( C. fusiformis), has in mice been shown to be due to the main alkaloidal component, agroclavine, which is a clavine-type ergot alkaloid previously regarded as having little pharmacological interest. A 2 per cent millet ergot diet fed during the latter part of pregnancy inhibits mammary hypertrophy and prevents lactation. A 5 per cent ergot diet elicits a pronounced central response and is lethal in 5–8 days. Female mice fed on a 2 per cent ergot diet fail to establish a pregnancy. This has also been shown to be due to the alkaloid which, while allowing ovulation and conception, prevents implantation of the blastocysts. Once implantation is complete the same diet has no effect on pregnancy apart from inducing the agalactia syndrome.

Physiological and Color Aspects of Turfgrasses with Fall and Winter Nitrogen1

AbstractFall and winter N fertilization was studied on bentgrass and fescue to investigate the possibility of maintaining green foliage during winter. Research also involved the effects of this N on top growth, reserve carbohydrates, and photosynthesis.Desirable turf color was maintained throughout the winter in Virginia latitudes without adverse physiological changes. Green foliage during winter was not the result of residual color from fall but was induced even during the coldest periods of winter. Although no measurable top growth occurred during winter, turf fertilized with high N was very dense.Reserve carbohydrates generally increased from fall to winter and then decreased slowly until spring when there were sharp declines. Stem carbohydrates varied from 44% dry matter in late fall or winter to 5% in spring. More carbohydrates were found in stems than in leaves and similar trends for sugar occurred in both separates. Higher N rates generally lowered the available carbohydrates, but the opposite was found with certain winter conditions. With determinations made on five dates, net photosynthesis appeared to be higher during winter than spring or summer; however, dark respiration increased with temperatures. Photosynthetic and respiration rates during winter or spring were increased with N fertilization.

Toxicity Testing of Fat Emulsions for Intravenous Administration

Abstract : Clinical and histopathologic toxicity studies were conducted on fourteen fat emulsions including Lipomul, Intralipid, Lipofundin and cottonseed or soybean oil emulsions prepared commercially or experimentally for intravenous use. These emulsions were administered to rabbits and/or rats in a daily dose of 2.0 to 3.0 gm. of fat per kg. of body weight. Clinical studies included observation of the animals' general reaction to the infusion, local reaction at the site of injection, variation in body weight, and weekly hemograms and urinalyses. The animals were sacrificed at least ten days after infusion and a detailed necropsy was performed. No gross lesions could be attributed to the fat emulsion. However, histopathologic examination revealed the deposition of intravenous fat pigment in the liver and spleen of every animal. The most pigment was found in animals given cottonseed oil emulsions and the least in animals given emulsion SR-151. Lipoid granulomas were observed in all test animals except those given emulsion SR-141. Mild hepatic fibrosis was observed in animals receiving Lipofundin. Adverse clinical reactions in rabbits included death in two animals, produced by Lipofundin K399, and hyperpyrexia, anorexia, decreased water intake, weight loss, and decrease in hemoglobin and hematocrit following infusion. The best performance in rabbits was obtained with Intralipid 293011 and in rats with SR-4734-107A. Although Lipofundin was well tolerated by rats, in general, soybean oil-egg yolk phosphatide-glycerol type emulsions produced the least adverse physiologic and histopathologic changes in the test animals. (Author)