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Results for “Injections, Subcutaneous”

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PubMed1991

Selective inhibition of duodenal and jejunal villous cell alkaline phosphatase by the duodenal ulcerogen cysteamine.

We have found that cysteamine-HCl, a potent duodenal ulcerogen, after a single subcutaneous injection (30 mg/100 g body weight), inhibited villous cell duodenal and jejunal alkaline phosphatase (APase) under in vivo and under in vitro conditions. The duodenal and jejunal crypt-cell APase was not susceptible to cysteamine inhibition. Ileal APase from both the villous and the crypt cells was unaffected by cysteamine. Tissue-nonspecific APase from the kidney and liver was not affected by cysteamine either. The differences in tissue and cellular accumulation of cysteamine, the submolecular differences in APase molecules, and its anatomical localization in mucosal cells along the small intestine could explain the different degrees of susceptibility to cysteamine inhibition. The extent of duodenal APase inhibition by cysteamine was highly pH-dependent and varied from 5% to 85% within a pH range of 7.5-10.5. A shift in pH optimum from 9.6 to 9.3 was found in the presence of cysteamine. The inhibition of duodenal villous cell APase was greatly dependent on cysteamine concentration (Ki = 2.65 mM). At a fixed concentration of cysteamine it was not influenced by substrate concentration. Cysteamine did not change the Km value for duodenal APase but did decrease its Vmax to 46% and 15% of the controls when added in the assay or injected subcutaneously, respectively, indicating that the inhibition was of the linear, 'noncompetitive' type. Somehow cysteamine increased the requirement in the activation energy for substrate hydrolysis as well. The data indicate that macromolecular transformations could take place in the mucosal cells of duodenum after cysteamine administration.

Alkaline Phosphatase↗

PubMed2006

Massive systemic silicone embolism: a case report and review of literature.

Subcutaneous injections of inert or quasi-inert plastic material designed to smooth out wrinkled skin or to create a more esthetically sought appearance have become very popular with the American public in general, and, in particular, with certain groups highly focused on their physical image. The case of the injection procedure has attracted into the field of plastic medicine a substantial number of illegal, incompetent, and unscrupulous operators. Their ignorance of involved medical risks and procedures not uncommonly results in severe complications, disfigurement, and death of patients. We report the typical pathological and chemical findings of a systemic fatal silicone embolism in a 53-year-old heterosexual woman following illegal chronic injections of silicone in her hips and buttocks. The injected subcutaneous silicone apparently migrated rapidly from the interstitial subcutaneous tissue into the general blood stream resulting in a fatal systemic silicone embolism. An analysis of the presented case in conjunction with a review of the pertinent medical literature, including a recent article, revealed a marked similarity in the clinicopathologic findings between silicone embolism and fat embolism.

Blood Chemical Analysis↗

PubMed1994

Insulin acts centrally to enhance reflex tachycardia in conscious rats.

Systemic and central insulin treatment for 10 days were compared in conscious rats given insulin either by daily subcutaneous injection or by continuous intracerebroventricular infusion. To measure changes in baroreflex sensitivity, heart rate responses elicited reflexly by elevating blood pressure with phenylephrine or lowering it with sodium nitroprusside were recorded before and after insulin treatment. Although reflex bradycardia and basal mean pressures and heart rates were unaffected, reflex tachycardia was consistently more pronounced in rats treated with insulin (whether given systemically or centrally) than in vehicle-treated controls. Plasma glucose was reduced and plasma insulin was elevated but only in insulin-treated rats injected subcutaneously and not in those infused intracerebroventricularly. Inasmuch as reflex tachycardia was still enhanced when insulin was infused intracerebroventricularly despite the absence of hypoglycemia and hyperinsulinemia, our results are compatible with the interpretation that insulin acts directly on the brain to enhance reflex tachycardia. This interpretation furthermore implies that insulin, even after chronic systemic treatment, could reach the brain and alter baroreflex regulation.

Animals↗

PubMed1976

Histocompatibility of polyvinyl acetate, an ingredient of chewing gum.

The histocompatibility of polyvinyl acetate (PVA), an ingredient of chewing gum, was evaluated from both a direct irritant (toxic reaction) and an allergic (antigen-antibody) standpoint. Subcutaneous injections in rats and topical application of hamster pouches were utilized. Polyvinyl acetate was shown to cause a moderate to severe inflammatory reaction when injected subcutaneously, which peaked at day 7 and was minimal at day 42. The histologic appearance of the hamster cheek pouch was not significantly altered by the PVA. Although PVA has been used as a plasticizer in chewing gum, it was not possible to induce any histologic changes in tissues which resembled the specific changes present in atypical gingivostomatitis (plasma-cell gingivostomatitis).

Acetates↗

PubMed2006

Tool from ancient pharmacopoeia prevents vision loss.

PURPOSE: Bear bile has been used in Asia for over 3,000 years to treat visual disorders, yet its therapeutic potential remains unexplored in Western vision research. The purpose of this study was to test whether treatment of mice undergoing retinal degeneration with tauroursodeoxycholic acid (TUDCA), a primary constituent of bear bile, alters the course of degeneration. METHODS: Two retinal degeneration models were tested: the rd10 mouse, which has a point mutation in the gene encoding the beta subunit of rod phosphodiesterase, and light induced retinal damage (LIRD). For LIRD studies, albino Balb/C adult mice were subcutaneously injected with TUDCA (500 mg/kg body weight) or vehicle (0.15 M NaHCO(3)). Sixteen h later, each mouse received repeat injections. Half of each treatment group was then placed in bright light (10,000 lux) or dim light (200 lux) for seven h. At the end of exposure, animals were transferred to their regular housing. Electroretinograms (ERGs) were assessed 24 h later, mice sacrificed, eyes embedded in paraffin and sectioned, and retina sections assayed for morphology and apoptosis by TUNEL and anti-active caspase-3 immunoreactivity via fluorescent confocal microscopy. A subset of mice were sacrificed 8 and 15 days after exposure and retina sections analyzed for morphology and apoptosis. For rd10 studies, mice were injected subcutaneously with TUDCA or vehicle at postnatal (P) days 6, 9, 12, and 15. At p18, ERGs were recorded, mice were euthanized and eyes were harvested, fixed, and processed. Retinal sections were stained (toluidine blue), and retinal cell layers morphometrically analyzed by light microscopy. Consecutive sections were analyzed for apopotosis as above. RESULTS: By every measure, TUDCA greatly slowed retinal degeneration in LIRD and rd10 mice. ERG a-wave and b-wave amplitudes were greater in mice treated with TUDCA compared to those treated with vehicle. Retinas of TUDCA-treated mice had thicker outer nuclear layers, more photoreceptor cells, and more fully-developed photoreceptor outer segments. Finally, TUDCA treatments dramatically suppressed signs of apoptosis in both models. CONCLUSIONS: Systemic injection of TUDCA, a primary constituent of bear bile, profoundly suppressed apoptosis and preserved function and morphology of photoreceptor cells in two disparate mouse models of retinal degeneration. It may be that bear bile has endured so long in Asian pharmacopeias due to efficacy resulting from this anti-apoptotic and neuroprotective activity of TUDCA. These results also indicate that a systematic, clinical assessment of TUDCA may be warranted.

Animals↗

PubMed1984

Effect of ivermectin in heifers on mortality and egg production of Psoroptes ovis.

Ten stanchioned heifers, heavily infested with Psoroptes ovis (Hering), were each given a single subcutaneous injection of 200 micrograms of ivermectin/kg. Another 10 heavily infested heifers (stanchioned) were injected subcutaneously with the solvent system (vehicle) used to formulate the ivermectin. Treatment with the vehicle did not reduce mite populations or total egg counts. The 10 heifers treated with ivermectin had an immediate reduction in live mite and egg counts (an increase in the percentage of mortality of mites) and were completely free of psoroptic mites by 20 days after treatment. Ivermectin was equally effective against adult and immature psoroptic mites.

Animals↗

PubMed2002

Treatment of aerosolized cowpox virus infection in mice with aerosolized cidofovir.

The Brighton strain of cowpox virus causes lethal bronchopneumonia when delivered as a small-particle (1 microm) aerosol to weanling BALB/c mice. We showed previously that this disease can be prevented or cured with one subcutaneous injection of cidofovir (HPMPC, Vistide). To determine whether even better results could be obtained by delivering the drug directly to the respiratory tract, we administered cidofovir by small-particle aqueous aerosol before or after aerosolized cowpox infection. In a series of five experiments, aerosol doses of 0.5-5 mg/kg were always more effective than 25 mg/kg and sometimes more effective than 100 mg/kg injected subcutaneously, as measured by changes in body and lung weight, lung viral titers, pulmonary pathology and survival. A cyclic analog ((1-[(S)-2-hydroxy-2-oxo-1,4,2-dioxaphosphorinan-5-yl)methyl] cytosine) (cHPMPC) was less protective. The results suggest that aerosolized cidofovir would be effective for prophylaxis or early post-exposure therapy of human smallpox or monkeypox virus infection.

Administration, Inhalation↗

PubMed1993

Investigations on allergogenic properties of Tołpa Peat Preparation.

The ability of Tołpa Peat Preparation (TPP) to induce or enhance an allergic sensitization was tested on mice and guinea pigs. The levels of IgE antibody in the mouse sera and IgG1 as well as IgE antibody levels in guinea pig sera were evaluated by PCA (Passive Cutaneous Anaphylaxis) tests. TPP adsorbed on aluminium hydroxide gel (alum) and introduced into BALB/c mice by several subcutaneous injections was unable to stimulate the noticeable anti-TPP IgE antibody response. TPP introduced together with ovalbumin (OA) into the mice in the course of immunization with OA did not enhance anti-OA IgE antibody response. TPP adsorbed on alum and injected subcutaneously into guinea pigs was unable to induce noticeable IgG1a, IgG1b and IgE antibody response, and mast cells obtained from lung and mesentery of these animals did not release histamine when challenged with TPP in vitro at 37 degrees C. In conclusion, our results show that under the experimental conditions used in the present experiments TPP was unable to induce or enhance an allergic sensitization of mice and guinea pigs.

Amino Acids↗

PubMed2002

Heroin-associated environmental stimuli modulate the expression of inducible nitric oxide synthase in the rat.

RATIONALE: Heroin (diacetylmorphine) administration has been shown to alter the induction of nitric oxide, a molecule known to play a critical role in the regulation of immune responses and resistance to infectious challenges. There is evidence that the physiological and behavioral effects of opioids can be conditioned to environmental stimuli associated with drug administration. OBJECTIVES: The present study tests whether environmental stimuli paired with the administration of heroin alter the expression of inducible nitric oxide synthase (iNOS), one of the isoforms of the enzyme responsible for nitric oxide production. METHODS: The experimental group of rats received three conditioning sessions each involving a subcutaneous injection of heroin (1.0 mg/kg) immediately upon being placed in a chamber that served as the conditioned stimulus. Following the conditioning sessions, the rats remained in their home cages for 6 days to recover from the effects of heroin per se. The rats then were re-exposed to the conditioning chamber in the absence of heroin and immediately following the session were injected subcutaneously with lipopolysaccharide (LPS) to induce iNOS expression. Six hours later, the expression of iNOS messenger ribonucleic acid (mRNA) and protein was determined in spleen, lung, and liver using real-time reverse transcriptase polymerase chain reaction (RT-PCR) and western blotting, respectively. Control procedures were used to determine whether the alterations in iNOS expression were due to conditioning processes. RESULTS: The results showed that exposure to the conditioned stimulus produced a pronounced reduction in the expression of iNOS mRNA and protein in spleen, lung, and liver tissue. Control procedures showed that this effect was due to conditioning processes. CONCLUSIONS: This study provides the first evidence that heroin-induced alteration of iNOS expression can be conditioned to environmental stimuli, and suggest that environmental stimuli associated with drug use may contribute to the alteration in susceptibility to infection.

Animals↗

PubMed1998

Preparation and characterization of a cocrystalline suspension of [LysB28,ProB29]-human insulin analogue.

Soluble preparations of [LysB28,ProB29]-human insulin analogue (LysPro) exhibit more rapid absorption than human insulin upon subcutaneous injection. Biphasic mixtures of LysPro and intermediate-acting insulin suspensions could provide advantages over current preparations for the treatment of diabetes. To prepare biphasic mixtures of LysPro, a suspension formulation of the analogue is required. We have devised a method for crystallizing LysPro with the basic peptide protamine yielding neutral protamine LysPro (NPL) suspension. The crystallization conditions are strongly dependent on the precipitation procedure and temperature. Using various techniques, the crystalline and suspension characteristics of NPL are found to be similar to human insulin (neutral protamine Hagedorn, NPH) (8:1 molar ratio insulin:protamine, rod-shaped crystals, particle size of 4.0-6.0 microns, and Point of Zero Charge at 6.0-7.0). Using a dog model with NPL or NPH injected subcutaneously and glucose levels clamped at basal, NPL was found to have kinetic and dynamic responses analogous to human insulin NPH [Cmax (maximal insulin or LysPro concentration, ng/mL) of 2.61 +/- 0.22, NPL; 2.58 +/- 0.36, NPH, attained at Tmax (min) of 93 +/- 22, NPL; 145 +/- 33 NPH, and Rmax (maximal rate of glucose infusion, mg/kg min) of 10.8 +/- 1.2, NPL; 13.2 +/- 1.9, NPH, attained at TRmax (min) of 277 +/- 58, NPL; 265 +/- 38, NPH]. There are no statistically significant differences between the insulin curves or the glucose responses. These results provide insight into the mechanism of action of NPH suspensions and the relationship to duration of action. Furthermore, the formulation of a suspension of LysPro having an intermediate time-action makes possible the preparation of stable biphasic mixtures containing LysPro and NPL.

Analysis of Variance↗

PubMed1997

Inhibition of nonselective cation channels reduces focal ischemic injury of rat brain.

The effect of the novel inhibitor of receptor-activated and calcium store-operated nonselective cation channels, (RS)-(3,4-dihydro-6,7-dimethoxyisoquinoline-1-gamma 1)-2-phenyl-N, N-di-[2(2,3,4-trimethoxyphenyl) ethyl]acetamide (LOE 908 MS), on focal cerebral ischemia was studied in halothane-anesthetized rats submitted to permanent suture occlusion of the right middle cerebral artery (MCA). The treated group (n = 7) received subcutaneous injections of 30 mg/kg LOE 908 MS (in 1 ml saline) 10 min after vascular occlusion and again after 3 h. The untreated group (n = 11) was injected subcutaneously with 1 ml saline at the same times. Evolution of infarct was monitored by electrophysiological recording of EEG and cortical steady potential and by diffusion-weighted magnetic resonance imaging during the initial 6 h of vascular occlusion. The hemodynamic, biochemical, and morphological changes were studied after 6 h by combining autoradiographic measurement of blood flow with histological stainings and pictorial measurements of ATP, glucose, and tissue pH. In the untreated animals, the ischemic lesion volume [defined as the region in which the apparent diffusion coefficient (ADC) of water declined to below 80% of control] steadily increased by approximately 50% during the initial 6 h of vascular occlusion relative to the first set of data 10 min postocclusion. In the treated animals, in contrast, the ADC lesion volume declined by approximately 20% during the same interval. Treatment also led to a significant reduction in the number of periinfarct depolarizations. After 6 h of vascular occlusion, blood flow was significantly higher in the treated animals, and the volume of ATP-depleted and morphologically injured tissue representing the infarct core was 60-70% smaller. The volume of severely acidic tissue, in contrast, did not differ, indicating that LOE 908 MS does not reduce the size of ischemic penumbra. These findings demonstrate that postocclusion treatment of permanent focal ischemia with LOE 908 MS delays the expansion of the infarct core into the penumbra for a duration of at least 6 h and therefore substantially prolongs the window of opportunity for the reversal of the ischemic impact in the peripheral parts of the evolving infarct.

Acetamides↗

PubMed2001

Progesterone metabolism in ovariectomised non-lactating Holstein-Friesian cows treated with progesterone with two levels of feed intake.

The goal of this study was to measure the effects of level of feeding and the form of progesterone (P4) administration on the concentrations and yields of faecal P4 metabolites relative to differences in plasma P4 concentrations in non-lactating cows. Six non-lactating Holstein-Friesian cows were ovariectomised (OVX) and allocated to two groups: (i) P4 by subcutaneous injection (P4-s.c., n=3); and (ii) P4 administration per vaginum (P4-p.v., n=3). Each cow in the P4-s.c. group was injected subcutaneously once daily with 200mg P4. Each cow in the P4-p.v. group had a CIDR device inserted for 11 days when it was removed and replaced with a second device for further 11 days. Cows were fed a ration containing lucerne (33%) and oaten (66%) chaff at a maintenance level (M) in two portions in the first period of the study, and at a half-maintenance (1/2M) level during the second period. Chromic oxide capsules (Cr(2)O(3)) were administered twice daily to allow faecal output (FO) to be estimated. Plasma P4 and faecal P4 metabolites (FP4M; 20-oxo-pregnanes, 20alpha- and 20beta-OH-pregnanes) were measured during the treatment period. Daily FO declined after reducing the M diet to 1/2M (4.77 versus 2.61kg; P<0.01), whereas plasma P4 concentrations increased in the P4-s.c. group (4.2 versus 6.2ng/ml; P<0.05), but not in the P4-p.v. group (0.9 versus 1.0ng/ml; P>0.2). The mass of P4 released from a CIDR device during each 11-day period (M or 1/2M) was similar (0.66 versus 0.63g). Faecal 20-oxo-pregnanes (20-oxo-) concentrations were not affected by day or level of feeding, whereas faecal 20alpha-OH (20alpha-) and 20beta-OH (20beta-) concentrations were increased with the 1/2M diet in the P4-s.c. group (4.3 versus 5.6 microg/gDM; 2.2 versus 5.6 microg/gDM, respectively; P<0.05), but not in the P4-p.v. group (2.3 versus 2.7 microg/gDM; 1.7 versus 3.04 microg/gDM P>0.05). These changes in concentration only partly compensated for the reduced FO with the 1/2M diets as daily yields of FP4M (20-oxo- and 20alpha-) were greater during the M diet period (20-oxo-: 6.9 versus 4.1 microg/gDM; 2.7 versus 1.5 microg/gDM, for P4-s.c. and P4-p.v. groups, respectively; P<0.05, 20alpha-: 19.9 versus 13.6 microg/gDM; 10.9 versus 6.6 microg/gDM for P4-s.c. and P4-p.v. groups, respectively; P<0.05). The level of feeding and the route of P4 administration had key roles in controlling P4 concentrations in blood and daily FP4M yield.

Administration, Intravaginal↗

PubMed1985

Radioimmunoassay of an analog of luteinizing hormone-releasing hormone, [D-Ser(tBu)]6des-Gly-NH2(10) ethylamide (Buserelin).

A sensitive and specific radioimmunoassay is described for plasma and urinary levels of [D-Ser(tBu)]6des-Gly-NH2(10) ethylamide (buserelin). No appreciable cross-reaction (less than 0.05%) was observed with LH-RH and its analogs other than buserelin fragments (1.6-45%). The sensitivity was 3 pg per tube. At buserelin concentrations of 125, 250 and 500 pg/ml, the intra- and inter-assay coefficients of variation were 7.9, 10.0 and 10.0%, and 19.0, 7.8 and 6.8% respectively. Recovery of buserelin added to plasma was quantitative (62.5 pg/ml, 101.6%; 125 pg/ml, 76.8% and 250 pg/ml, 63.4%). A dose of 5 micrograms buserelin injected subcutaneously into 5 normal male adults, reached a peak plasma level in 45 min (mean value 119.3 +/- 47.3 pg/ml) and remained detectable for at least 4 h. The half disappearance time was 118.8 +/- 26.0 min. Between 9 and 16% of the administered dose was excreted in the urine within 24 h. Buserelin could also be detected in the plasma after intranasal administration of doses of 150, 300 and 450 micrograms. There was a significant difference in the area under the curve (AUC) for plasma levels after subcutaneous injection of 5 micrograms and intranasal administration of 150 micrograms, but not between the AUC values after the three intranasal doses. These results indicate that this method for radioimmunoassay of buserelin is suitable for analyzing the pharmacokinetics and bioavailability of buserelin in man.

Administration, Intranasal↗

PubMed1986

Effect of insulin antibodies and their kinetic characteristics on plasma free insulin dynamics in patients with diabetes mellitus.

To determine the influence of insulin antibodies (and their equilibrium kinetic properties) on the pharmacokinetics of insulin, we examined the relationship between insulin antibody binding and the initial rate of increase, time to peak, and return to baseline of therapeutic doses of insulin injected subcutaneously (0.15 U/kg) and the half-life, distribution space, and metabolic clearance rate of intravenously infused insulin (2 mU/kg/min) in insulin-treated patients with diabetes mellitus. Compared to age-weight-matched nondiabetic subjects, the diabetic subjects had reduced initial rates of increase (0.33 +/- 0.2 v 0.44 +/- 0.03 microU/mL/min, P less than 0.05), delayed time to peak (130 +/- 12 v 86 +/- 8 min, p less than 0.02), and prolonged return to baseline (485 +/- 37 v 313 +/- 13 min, P less than 0.01) of plasma free insulin levels after subcutaneous injection of insulin, and a prolonged half-life (19.8 +/- 5.8 v 4.3 +/- 0.3 min, P less than 0.02), increased distribution space (904 +/- 284 v 109 +/- 10 mL/kg, P less than 0.001), and augmented metabolic clearance rate (28.5 +/- 1.8 v 17.3 +/- 0.7 mL/kg/min, P less than 0.001) after intravenously infused insulin. All of these abnormal parameters were significantly correlated with binding of insulin to insulin antibodies at tracer insulin concentrations (Bo) and with the high affinity of insulin antibody binding sites as determined by Scatchard analysis. However, patients with 125I insulin antibody binding (Bo) less than 10 percent had normal or near normal plasma free insulin pharmacokinetics.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1996

The peripheral antinociceptive effect of morphine in a rat model of facial pain.

The present study compared the peripheral and systemic antinociceptive effect of morphine on formalin-induced facial pain behavior in the rat. Formalin (5%, 50 microliters) was injected subcutaneously into the vibrissal pad of adult rats (250-300 g). Morphine sulfate at doses of 100-1000 micrograms was subcutaneously injected locally (same area) or systemically (in the neck), 30 min before, or simultaneously with, formalin. The typical biphasic face grooming response, consisting of an early phasic phase (0-6 min) and a delayed tonic phase (12-42 min), displayed by control animals, was suppressed by both local and systemic administration of morphine; this effect was dose dependent. However, the suppression of the early phase with local morphine administration 30 min before formalin could be significantly greater (49-52%) than with systemic administration, depending on the dose used. Administration of local morphine simultaneously with formalin produced up to 34% reduction in the early and an additional 32% reduction of the late phases of face grooming, compared to systemic injections. Local injection of naloxone (10 micrograms) almost completely reversed the antinociceptive effect of 1000 micrograms of morphine (early phase 85 +/- 7%, late phase 100 +/- 26% reduction), whereas the same dose of naloxone applied systemically (i.p.) produced only partial reversal (early phase 29 +/- 16%, late phase 36 +/- 1% reduction). This study further indicates that locally administered morphine can exert an analgesic effect superior to systemic administration in the case of inflammatory and non-inflammatory pain through a peripheral site of action. These results support the clinical use of peripheral opioid administration in the treatment of human painful conditions.

Analgesics, Opioid↗

PubMed1991

In vivo and in vitro studies on the effects of vitamin A on the chemiluminescent response of murine peritoneal exudate cells.

Retinoids are known to enhance macrophage function and enhance bacterial clearance during experimental infection. The purpose of these experiments was to determine if one indicator of macrophage activation, chemiluminescence (CL), was enhanced by retinoids. Peritoneal exudate cells (PEC) harvested from mice injected intraperitoneally for 5 days with retinol palmitate (25, 125, or 250 U/g body wt./d) showed significantly enhanced chemiluminescence (CL) when exposed to opsonized zymosan. A direct dose-response effect was observed, in that the more retinol palmitate was injected, the more CL was observed. The same dose of retinol palmitate injected subcutaneously did not result in enhanced CL. In vitro incubation of murine PEC with physiological concentrations of retinol palmitate or retinoic acid for 1, 6 or 24 h did not result in enhanced CL. The reasons for the effect of the route of administration of retinol palmitate are unknown, but may include poor absorption from the site of subcutaneous injection or an adjuvant effect when injected intraperitoneally due to the particulate nature of the water-dispersible retinol palmitate preparation.

Animals↗

PubMed1998

Corticotropin-releasing factor administered centrally, but not peripherally, stimulates hippocampal acetylcholine release.

In addition to corticotropin-releasing factor's well-known role in mediating hormonal and behavioral responses to stress, this peptide also reportedly affects arousal and cognition, processes that classically have been associated with forebrain cholinergic systems. Corticotropin-releasing factor stimulation of cholinergic neurons might thus provide a mechanism for this peptide's cognitive effects. To examine this possibility, the present experiments characterize the effect of corticotropin-releasing factor on cholinergic neurotransmission, using in vivo microdialysis to measure hippocampal acetylcholine release. Corticotropin-releasing factor (0.5-5.0 microg/rat intracerebroventricularly) was found to increase dialysate concentrations of acetylcholine in a dose-dependent manner in comparison with a control injection, the ovine peptide having a greater effect than the same dose of the human/rat peptide. This effect was found to be centrally mediated, independent of the peripheral effects of an exogenous corticotropin-releasing factor injection; subcutaneous injections of the peptide increased plasma concentrations of corticosterone, the adrenal hormone ultimately secreted in the rat's stress response, to the same level as did the central injections, without affecting hippocampal acetylcholine release. These results demonstrate that corticotropin-releasing factor, acting centrally, regulates hippocampal cholinergic activity, and suggest that corticotropin-releasing factor/acetylcholine interactions may underlie some of the previously identified roles of these neurotransmitters in arousal, cognition, and stress.

Acetylcholine↗

PubMed1988

Semisynthetic human insulin: pharmacokinetics and biological potency in healthy subjects in comparison with highly purified porcine insulin.

Pharmacokinetics and the biological activity of a new semisynthetic human insulin (VEB Berlin-Chemie) were investigated in 5 healthy men. Following an overnight fast, 0.2 IU per kg body weight of human and pork insulins (SNC insulin; VEB Berlin-Chemie) were injected subcutaneously into thigh of each individual at a time interval of 8 days. To assess biological potency of both insulins all subjects were twice connected to the BIOSTATOR. A very similar pattern of serum insulin levels (IRI) was observed following subcutaneous injection of human and pork insulin, marked by a sharp initial increase and maximum values reached after 2.5 hours. 8 hours after the insulin administration the original fasting concentrations were nearly attained. According to C-peptide levels, both insulins inhibited endogenous insulin secretion. Evaluation of insulin action was determined by euglycemic clamp technique, provided by the BIOSTATOR, whose function was transformed into a glucose-controlled dextrose infusion system. The amount of glucose delivered by the system in order to keep the blood glucose steady state concentrations at the fasting level was utilized as the measure of biological activity of the injected insulin on glucose metabolism. Maximum values of glucose infusion were achieved between 3 and 4 hr after injection of human and pork insulins. At the end of the study (8 hr) the glucose administration did not return to its initial rate. After administration of both the human and porcine insulins, a marked but similar decrease of FFA concentrations was observed. This indicated a clear-cut inhibition of lipolysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption↗