Ventricular obstruction: effect on drinking induced by intracranial injection of angiotensin.

Lesions of the subfornical organ (SFO) severely attenuated drinking induced by injections of angiotensin II into the lateral ventricles, but a few days (4 to 14) later a recovery of the drinking response is observed. A possible explanation for this is that other dipsogenic sites are involved which are beyond the interventricular foramen and that SFO lesions produce an obstruction by edema or debris at the foramen which blocks access of cerebrospinal fluid-borne angiotensin to those sites. This hypothesis is supported by tracer studies and by direct injection into the third ventricle of SFO-lesioned animals. Other studies reported implicate the anteroventral third ventricle as a likely site for angiotensin receptors.

The Inability to Screen Exhibition Swine for Influenza A Virus Using Body Temperature.

Agricultural fairs create an unconventional animal-human interface that has been associated with swine-to-human transmission of influenza A virus (IAV) in recent years. Early detection of IAV-infected pigs at agricultural fairs would allow veterinarians to better protect swine and human health during these swine exhibitions. This study assessed the use of swine body temperature measurement, recorded by infrared and rectal thermometers, as a practical method to detect IAV-infected swine at agricultural fairs. In our first objective, infrared thermometers were used to record the body surface temperature of 1,092 pigs at the time of IAV nasal swab collection at the end of the exhibition period of 55 agricultural fairs. IAV was recovered from 212 (19.4%) pigs, and the difference in mean infrared body temperature measurement of IAV-positive and IAV-negative pigs was 0.83°C. In a second objective, snout wipes were collected from 1,948 pigs immediately prior to the unloading of the animals at a single large swine exhibition. Concurrent to the snout wipe collection, owners took the rectal temperatures of his/her pigs. In this case, 47 (2.4%) pigs tested positive for IAV before they entered the swine barn. The mean rectal temperatures differed by only 0.19°C between IAV-positive and IAV-negative pigs. The low prevalence of IAV among the pigs upon entry to the fair in the second objective provides evidence that limiting intraspecies spread of IAV during the fairs will likely have significant impacts on the zoonotic transmission. However, in both objectives, the high degree of similarity in the body temperature measurements between the IAV-positive and IAV-negative pigs made it impossible to set a diagnostically meaningful cut point to differentiate IAV status of the individual animals. Unfortunately, body temperature measurement cannot be used to accurately screen exhibition swine for IAV.

Metal ion chelating peptides with superoxide dismutase activity.

The superoxide dismutase activities of two novel synthetic chelating peptides are reported. The peptides comprise a polyaminocarboxylic acid chelator (EDTA) conjugated to tyrosine (ET(1)) and phenylalanine (EP(1)). Superoxide dismutase (SOD) activity was exhibited for Cu(II) but not the Fe(III) complexes. The mimetic activities were compared to bovine erythrocyte SOD (3730 U/mg) and exhibited activities of 1119 U/mg for ET(1)-Cu(II) and 551 U/mg for EP(1)-Cu(II). Thus, small alterations in structure can have significant effects on the enzymatic activity of metallopeptides. These synthetic chelators have dual potential anti-inflammatory activity by chelating deleterious non-protein bound metal ions and concomitantly affording anti-oxidant mimetic activity.

Pharmacologic evaluation of megestrol acetate oral suspension in cachectic AIDS patients.

The objective of our study was to define the pharmacokinetics and pharmacodynamics of megestrol acetate in patients with human immunodeficiency virus (HIV) infection. A new suspension formulation of megestrol acetate (40 mg/ml) was administered as a single oral dose of 800 mg per day in an open label pharmacokinetic study for 21 days. On day 21 of therapy, patients were evaluated for changes in body weight and plasma samples were obtained for steady-state pharmacokinetic analysis. Ten HIV-infected men with an involuntary weight loss of > 10% baseline were evaluated. A high degree of interpatient variability in megestrol acetate pharmacokinetics was observed, with an 8- and 5-fold range in the rate and extent of absorption, respectively. All patients reported an increase in appetite, and 8 of 10 patients gained weight by 3 weeks; the median change in weight in all patients at 3 weeks was 1.8-kg gain (range: 2.3-kg loss to 6.4-kg gain). The two patients who did not gain weight had the lowest area under the curve (AUC), Cmax, and Cmin values. A statistically significant correlation between the ratio of body weight at 3 weeks/initial weight (weight index) and the percentage of the 24-h dosing interval that megestrol acetate concentrations exceeded a 300-ng/ml threshold was observed. These data indicate variable levels of systemic exposure to drug following a fixed dose of a suspension formulation of megestrol acetate. Increase in weight during the early stages of megestrol acetate therapy is related to the extent of in vivo drug exposure above a threshold concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

Tail pinch-induced eating, gnawing and licking behavior in rats: dependence on the nigrostriatal dopamine system.

Mild-tail-pinch induces a syndrome of eating, gnawing and licking behavior in rats in the presence of food. Detailed behavioral, pharmacological and biochemical analyses of this phenomenon resulted in the following conclusions. (1) This is an unusually reliable phenomenon, demonstrable in each of more than 200 animals tested. (2) Eating is by far the predominant response to tail-pinch. (3) Tail-pinch behavior is critically dependent on the nigrostriatal dopamine system. (4) There are striking pharmacological parallels between tail-pinch behavior and schizophrenia.

Anteroventral third ventricle site of action for angiotensin induced thirst.

The central site of action for angiotensin induced thirst was investigated in rats. Subfornical organ lesions resulted in a temporary abolition of drinking induced by lateral preoptic or lateral ventricle microinjections of angiotensin but drinking to anteroventral third ventricle microinjections of angiotensin (or carbachol) was unaffected. Drinking to elevated systemic levels of angiotensin was attenuated but not abolished by subfornical organ lesions. When spread of injected angiotensin via cerebrospinal fluid circulation was controlled by placing plugs at selected locations in the ventricles, drinking was elicited only when intracranial microinjections of angiotensin gained access to anteroventral third ventricle. It was concluded that subfornical organ is not the exclusive dipsogenic receptor for angiotensin, rather angiotensin exerts at least part of its dipsogenic effect by spread through the ventricular system to receptors in the vicinity of the anteroventral third ventricle.

Cholinergic and dopaminergic blocking agents modulate water intake elicited by deprivation, hypovolemia, hypertomicity and isoproterenol.

In order to identify and differentiate separate components of an overall drinking system on neurochemical grounds, a few neuropharmacological blocking agents, already shown to affect the mediation of some thirst-related behaviors, were tested against a wide range of manipulations that elicit drinking behavior. Peripheral injections of scopolamine, an anticholinergic agent, or haloperidol, a catecholamine blocking agent with pronounced antidopaminergic actions, substantially reduced the water intake of rats induced to drink by periods of deprivations or by subcutaneous injections of either hypertonic saline, polyethylene glycol, or isoproterenol. When a combined injection of both scopolamine and haloperidol was given, hypovolemic and isoproterenol-induced drinking were about entirely eliminated but salt-aroused or deprivation-induced drinking were not totally abolished. In control studies, eating behavior elicited by either food deprivation or peripheral injection of 2-deoxy-d-glucose was not affected by these blocking agents. These experiments suggest that activation of cholinergic and dopaminergic neurons within central thirst-related systems are important physiological events underlying drinking behavior.

Vitamin C contributes to inflammation via radical generating mechanisms: a cautionary note.

Reactive oxygen and nitrogen species (RONS) have been ascribed an important role in oxidative stress contributing to the progression of inflammatory diseases such as Crohn's disease and rheumatoid arthritis. Redox-active metal ions such as Fe(II) and Cu(I) further activate RONS and thus perpetuate their damaging effects. High intake of ascorbic acid exerts a pro-oxidant effect by its interaction with metal ions via a number of established RONS generating systems. Caution should be exerted regarding surplus ascorbic acid intake for patients with chronic inflammatory diseases.

Herpetic whitlow of the digits.

Herpes simplex viral infection of the digits, also known as herpetic whitlow, is a rather common hand problem encountered in dental and medical personnel. Treatment is controversial. This report summarises the author's successful experience in a series of ten patients using a non-operative local care technique, supplemented when indicated by a systemic antiviral agent.