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Results for “Injections, Subcutaneous”

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PubMed1999

Stimulation of neonatal and adult brain neurogenesis by subcutaneous injection of basic fibroblast growth factor.

Mounting evidence indicates that extracellular factors exert proliferative effects on neurogenetic precursors in vivo. Recently we found that systemic levels of basic fibroblast growth factor (bFGF) regulate neurogenesis in the brain of newborn rats, with factors apparently crossing the blood-brain barrier (BBB) to stimulate mitosis. To determine whether peripheral bFGF affects proliferation during adulthood, we focused on regions in which neurogenesis persists into maturity, the hippocampus and the forebrain subventricular zone (SVZ). In postnatal day 1 (P1) rats, 8 hr after subcutaneous injection (5 ng/gm body weight), bFGF increased [(3)H]thymidine incorporation 70% in hippocampal and SVZ homogenates and elicited twofold increases in mitotic nuclei in the dentate gyrus and the dorsolateral SVZ, detected by bromodeoxyuridine immunohistochemistry. Because approximately 25% of proliferating hippocampal cells stimulated in vivo expressed neuronal traits in culture, bFGF-induced mitosis may reflect increased neurogenesis. bFGF effects were not restricted to the perinatal period; hippocampal DNA synthesis was stimulated by peripheral factor in older animals (P7-P21), indicating the persistence of bFGF-responsive cells and activity of peripheral bFGF into late development. To begin defining underlying mechanisms, pharmacokinetic studies were performed in P28 rats; bFGF transferred from plasma to CSF rapidly, levels rising in both compartments in parallel, indicating that peripheral factor crosses the BBB during maturity. Consequently, we tested bFGF in adults; peripheral bFGF increased the number of mitotic nuclei threefold in the SVZ and olfactory tract, regions exhibiting persistent neurogenesis. Our observations suggest that bFGF regulates ongoing neurogenesis via a unique, endocrine-like pathway, potentially coordinating neuron number and body growth, and potentially providing new approaches for treating damaged brain during development and adulthood.

Aging↗

PubMed1997

Central c-Fos expression in neonatal and adult rats after subcutaneous injection of hypertonic saline.

Centrally-mediated responses to plasma hyperosmolality include compensatory drinking and pituitary secretion of vasopressin and oxytocin in both adult and neonatal rats. However, the anorexia that is produced by plasma hyperosmolality in adult rats is not evident in neonates, perhaps due to functional immaturity of osmoresponsive hindbrain circuits. To examine this possibility, the present study compared treatment-induced brain expression of the immediate-early gene product c-Fos as a marker of neural activation in adult and two-day-old rats after subcutaneous injection of 2 M NaCl (0.1 ml/10 g body weight). This treatment produced marked hypernatremia in adult and two-day-old rats without altering plasma volume. Several brain regions (including components of the lamina terminalis, the paraventricular and supraoptic nuclei of the hypothalamus, and the area postrema) were activated to express c-Fos similarly in adult and two-day-old rats after 2 M NaCl injection, consistent with previous reports implicating a subset of these regions in osmotically-stimulated drinking and neurohypophyseal secretion. In contrast, other areas of the brain that were activated to express c-Fos in adult rats after 2 M NaCl injection were not activated in neonates: these areas included the central nucleus of the amygdala, the parabrachial nucleus and catecholamine cell groups within the caudal medulla. This study demonstrates that certain brain regions that are osmoresponsive in adult rats (as defined by induced c-Fos expression) are not osmoresponsive in two-day-old rats. When considered in the context of known differences between the osmoregulatory capacities of adult and neonatal rats, our results are consistent with the idea that osmoresponsive forebrain centres are primarily involved in osmotically-stimulated compensatory drinking and neurohypophyseal secretion, whereas osmoresponsive regions of the hindbrain are important for concomitant inhibition of feeding and gastric emptying.

Animals↗

PubMed1988

Effect of subcutaneous injection of a long-acting analogue of somatostatin (SMS 201-995) on plasma thyroid-stimulating hormone in normal human subjects.

SMS 201-995 (SMS), a synthetic analogue of somatostatin (SRIF) has been shown to be effective in the treatment of the hypersecretion of hormones such as in acromegaly. However, little is known about the effects of SMS on the secretion of thyroid-stimulating hormone (TSH) in normal subjects. In this study, plasma TSH was determined with a highly sensitive immunoradiometric assay, in addition to the concentration of SMS in plasma and urine with a radioimmunoassay, following subcutaneous injection of 25, 50, 100 micrograms of SMS (4 subjects/dose) or a placebo (6 subjects) to normal male subjects, at 0900 h after an overnight fast. The plasma concentrations of SMS were dose-responsive and the peak levels were 1.61 +/- 0.09, 4.91 +/- 0.30 and 8.52 +/- 1.18 ng/ml, which were observed at 30, 15 and 45 min after the injection of 25, 50 and 100 micrograms of SMS, respectively. Mean plasma disappearance half-time of SMS was estimated to be 110 +/- 3 min. Plasma TSH was suppressed in a dose dependent manner and the suppression lasted for at least 8 hours. At 8 hours after the injection of 25, 50 and 100 micrograms of SMS, the plasma TSH levels were 43.8 +/- 19.4, 33.9 +/- 9.4 and 24.9 +/- 3.2%, respectively, of the basal values. The results suggest that SMS suppresses secretion of TSH from the normal thyrotrophs in man and thus also that attention should be paid to possible hypothyroidism during the long-term treatment of patients such as those with acromegaly with this potent analogue of SRIF.

Adult↗

PubMed1995

Inhibition of cytokine gene expression in mouse skin by subcutaneous injection of cyclosporine.

Cyclosporine A (CsA) has been shown to be an effective therapeutic agent for a wide variety of cutaneous diseases yet its exact mechanism of action is still unclear, although one well-defined effect of CsA is the inhibition of T-cell-derived cytokine expression. We recently demonstrated in vitro that CsA inhibits cell proliferation and suppresses cytokine gene expression in keratinocytes. In this study, we report the in vivo effects of CsA on skin cytokine gene expression as determined by reverse-transcriptase polymerase chain reaction. C57BL6 mice (female, 8-10 weeks old) were subcutaneously injected with CsA in olive oil (0, 5 and 10 mg/kg) every other day for 3 weeks. Treatment with 5 mg/kg CsA inhibited both interleukin (IL)-1 alpha and tumor necrosis factor alpha gene expression by about 70 and 90%, respectively, relative to vehicle control levels. However, IL-6 gene expression did not significantly change. Injection of 10 mg/kg CsA inhibited expression of all three genes by 80-90% relative to control levels. These data show that CsA can inhibit constitutive cytokine gene expression in mouse skin.

Animals↗

PubMed1992

Chronical administration of anti-DNA antibodies by subcutaneous injection of hybridoma clones in BALB/c and NZBxNZW/F1 mice. Experimental model of the pathogenic role of DNA in acute lupus disease.

Several sets of data suggest that specific classes of anti-DNA antibodies could be implicated in the genesis of glomerular lesions in SLE. The goal of this work is to investigate if this pathogenic role could be related to the antibodies' genetic origin--from BALB/c or NZBxNZW/F1 mice--or to their physiological origin--induced either by DNA or by polyclonal B cell activation in normal mice. For this purpose, anti-DNA antibody hybridoma clones produced from different origins were subcutaneously injected in BALB/c or NZBxNZW/F1 female mice, followed by studies of immunological parameters and kidney lesions. Results concur that the induced anti-DNA antibodies can play a role in fatal disease development, related to clonal specificity but not to the way of stimulation which was either polyclonal B cell activation or DNA immunization. Also, they emphasize the possible very lethal role of serum circulating DNA.

Acute Disease↗

PubMed2000

Long-lasting cholecystokinin(2) receptor blockade after a single subcutaneous injection of YF476 or YM022.

Histamine-forming ECL cells in the rat stomach operate under the control of gastrin. They represent a convenient target for studying cholecystokinin-B/gastrin (CCK(2)) receptor antagonists in vivo. We examined the effectiveness and duration of action of two CCK(2) antagonists, YM022 and YF476, with respect to their effect on ECL-cell histidine decarboxylase (HDC) activity in the rat. Oral administration of subcutaneous deposition of YF476 or YM022 reduced the HDC activity. The maximum/near-maximum dose for both drugs and for both modes of administration was 300 micromol kg(-1) (effects measured 24 h after dose). At this dose and time the serum concentration of YF476 was 20 - 40 nmol l(-1). The dose 300 micromol kg(-1) was used in all subsequent studies. A single subcutaneous injection of YF476 inhibited the HDC activity for 8 weeks. The circulating concentration of YF476 remained high for the same period of time (>/=15 nmol l(-1)). Subcutaneous YM022 suppressed the HDC activity for 4 weeks. A single oral dose of YF476 or YM022 inhibited the HDC activity for 2 - 3 days. Chronic gastric fistula rats were used to study the effect of subcutaneous YF476 on gastrin-stimulated acid secretion. A single injection of YF476 prevented gastrin from causing an acid response for at least 4 weeks (the longest time studied). We conclude that a single subcutaneous injection of 300 micromol kg(-1) YF476 causes blockade of CCK(2) receptors in the stomach of the rat for 8 weeks thus providing a convenient method for studies of the consequences of long-term CCK(2) receptor inhibition.

Administration, Oral↗

PubMed1995

Subcutaneous injection of an analog of neuropeptide FF prevents naloxone-precipitated morphine abstinence syndrome.

There is evidence that neuropeptide FF (NPFF) has antiopiate activity and may play a role in opiate dependence and subsequent abstinence syndrome. A fragment of NPFF was modified at the C-terminal in an effort to convert it to an NPFF antagonist. It was also dansylated at the N-terminal in an effort to render it more lipophilic and increase its penetration of the blood-brain barrier. Third ventricle administration of the resulting compound, dansyl-PQRamide (0.75 microgram and 1 microgram), dose-dependently antagonized the quasi-morphine abstinence activity of NPFF (10 micrograms) in opiate-naive rats. Subcutaneous injection of dansyl-PQRamide (13 mg/kg) in chronically morphine-infused rats attenuated opiate dependence as indicated by prevention of naloxone-precipitated abstinence syndrome. Dansyl-PQRamide displaced radiolabelled ligand from NPFF receptors in a concentration-dependent manner with a Ki of 13 microM, and had a half-life over 300 times longer than NPFF under aminopeptidase digestion.

Animals↗

PubMed2004

Elevated nociceptive thresholds in rats with multifocal brain damage induced with single subcutaneous injections of lithium and pilocarpine.

To quantify the variability in thermal pain perception of rats with chemically induced brain injury following subcutaneous lithium and pilocarpine administration, 9 female Wistar rats were subjected to a nociceptive (hotplate) paradigm. At approximately 200 days of age, subjects were injected subcutaneously with 3 mEq/kg of lithium chloride followed 4 hr. later by 30 mg/kg of the cholinergic agonist pilocarpine to generate lesions that mimic human temporal lobe (limbic) epilepsy. Over 2 trials 4 of 9 subjects exhibited thermal latencies that exceeded 60 sec. while the remaining subjects obtained mean latencies of 13.40 sec. before demonstrating the criterion nociceptive response. These findings suggest that the multifocal neuronal necrosis subsequent to single peripheral injections of lithium and pilocarpine, followed by the neuroleptic, acepromazine, may significantly augment pain thresholds in certain rats within experimentally epileptic populations.

Acepromazine↗

PubMed1991

Determination of the levels of unfractionated and low-molecular-weight heparins in plasma: their effect on thrombin-mediated feedback reactions in vivo. Preliminary results after subcutaneous injection.

We define a standard independent unit (SIU) of heparin as that amount that, in plasma containing 1 mumol of ATIII, raises the (pseudo-)first-order breakdown constant of factor Xa by 1 min-1. These units measure all material with a high affinity for ATIII (HAM); only material above the critical chain length of 17 monosaccharide units (above critical chain length material; ACLM) catalyzes the inactivation of thrombin. An SIU of ACLM is therefore analogously defined as the amount that, in plasma containing 1 mumol of ATIII, will raise the (pseudo-)first-order breakdown constant of thrombin by 1 min-1. Of any given heparin preparation one can determine the specific HAM and ACLM activities in terms of SIU/mg. On the basis of the factor Xa and thrombin breakdown constants found in a plasma sample one can then determine the levels of HAM and ACLM. Preliminary experiments were carried out in plasma samples obtained after subcutaneous injection of unfractionated heparin (UFH) and of two types of low-molecular-weight heparin (LMWH). About three times more of UFH activity than of LMWH activity has to be injected to obtain the same levels of ACLM in the plasma. Only with the LMWHs significant amounts of BCLM are found, which rises higher and persists longer than the ACLM. We determined the course of thrombin generation in platelet-rich plasma (PRP) and in platelet-poor plasma (PPP), as well as in the PPP factor Xa generation curve and the course of prothrombin conversion. The observed inhibitions correlated much better with the levels of ACLM than with those of below critical chain length material. The difference between UFH and LMWHs can therefore not be explained in terms of antithrombin and anti-factor-Xa activity. The essential difference between UFH and LMWH appears in the feedback effect of thrombin in PRP, where thrombin generation is both inhibited and retarded by LMWH, while it is only retarded but hardly inhibited by UFH.

Adult↗

PubMed1996

An experimental model of fasciitis-panniculitis. Induction of chronic fibrosing panniculitis in the rat by subcutaneous injections of lipase.

We describe an experimental model of the fasciitis-panniculitis syndrome, which includes eosinophilic fasciitis and its related disorders. Rats were given a single or repeated subcutaneous injections of saline or a 10% lipase solution. The injection sites were studied histologically and histomorphometrically. With few exceptions, the subcutaneous-fascial unit of the saline-injected rats was normal. An acute necrotizing panniculitis with inflammatory involvement of the adjacent fascia was found 2 days after a single injection of lipase. Three to 6 weeks after a single injection of lipase, the subcutaneous fat tissue and fascia were fibrotically thickened and chronically inflamed. Similar but more advanced alterations had developed in animals killed 3 weeks after three weekly injections of lipase. Progressive fibrotic thickening of the subcutaneous-fascial unit was observed following an increasing number of weekly lipase injections. The acute-phase reaction expresses a pattern of steatonecrotic tissue damage. In the ohronic phase, the fibrotically thickened subcutaneous layers typify a reaction pattern analogous to that of the human fasciitis-panniculitis syndrome. This experimental model permits better appreciation of the disorder's nonspecific pathogenesis and may help in the search for alternative therapeutic modalities.

Acute-Phase Reaction↗

PubMed2005

Acute cyanide poisoning by subcutaneous injection.

A 30 year old woman with a history of depression and previous suicide attempts was brought to the emergency department in coma. She had injected herself with cyanide subcutaneously and had severe metabolic acidosis. She underwent sustained haemodialysis in the intensive care unit (ICU) before laboratory confirmation of cyanide poisoning. The serum cyanide concentration was 4.6 microg/ml. After 48 hours the patient, now asymptomatic, was discharged from the ICU.

Acute Disease↗

PubMed1996

Does warming local anesthetic reduce the pain of subcutaneous injection?

The most frequent complaint noted with the use of lidocaine (or other amide local anesthetic) is stinging or burning pain associated with subcutaneous infiltration. The purpose of this study was to evaluate the efficacy of warming buffered lidocaine for reducing the pain of infiltration. Forty adult volunteers were entered into a randomized, crossover study conducted at a community teaching hospital. Blinded subjects underwent 1-mL subcutaneous injections of the study agent through 27-gauge needles over 30 seconds. Following a crossover protocol, "room temperature" buffered lidocaine (20 degrees C) was injected into one midvolar forearm and "body temperature" buffered lidocaine (37 degrees C) into the opposite arm. The order and the handedness of the two injections were randomized; an independent observer prepared the anesthetic solutions. Pain was assessed using a 100-mm visual analog pain scale and subjects' comparison of pain on injection. Twenty subjects (50%) reported that 20 degrees C buffered lidocaine was more painful and 17 (42.5%) reported that the 37 degrees C solution was more painful (sign test, P = .74). Similarly, a median pain score difference of 5.0 mm favoring 37 degrees C lidocaine was not statistically significant (sign rank test, P = .42). The order or the initial side of the injection did not influence the pain scores. The study had a power of 80% to detect a 10-mm difference between the two solutions at alpha = .05. These results suggest that warming buffered lidocaine to body temperature (37 degrees C) does not reduce the pain of subcutaneous infiltration.

Adult↗

PubMed1985

Relation between components of the immune response in rats sensitized by aerosol and subcutaneous injections.

Relations between the appearance of various components of the immune response were analyzed in two groups of rats sensitized by aerosol and subcutaneous injections in the neck region, respectively. The relations were expressed by Spearman rank correlation coefficient and studied by cluster analysis. In the aerosol-sensitized animals, there was a close association between IgA and IgG antibody levels in bronchial fluid and these in turn were related to IgG levels in serum and more loosely to IgE levels in bronchial fluid. There was an apparent association between IgE antibody formation and mast cell maturation in cultures of regional lymph node cells and the appearance of mucous cells in the lungs. These variables seemed associated with spontaneous cell proliferation in vitro and the numbers of mast cells in the lungs. This indicates that local stimulation with antigen induces local immune responses and immune-mediated migration of cells. In subcutaneously sensitized animals, formation of IgG antibodies in vitro seemed related to the stimulated proliferation of regional lymph node cells. The levels of IgG and IgE antibodies in bronchial fluid and in serum also appeared to be related. Unlike the findings in aerosol-sensitized animals there was no apparent relation between the differentiation of mast cells and mucous cells. This was possibly due to lack of immune-mediated antigen-induced cell migration. The different immune response patterns in aerosol and subcutaneously sensitized rats should be considered when studies are designed aiming to explore the pathogenesis of allergic inflammatory diseases. The findings also indicate that the various parameters of immunity are more closely related in aerosol than in subcutaneously immunized animals.

Aerosols↗

PubMed1991

Metabolic changes in the mouse kidney after subcutaneous injection of butyl 2-chloroethyl sulfide.

Subcutaneous exposure to vesicants such as butyl 2-chloroethyl sulfide (butyl mustard, BCS) produces local tissue injury (vesication) primarily by alkylation and cross-linking of the purine nucleotides and rapidly binding to proteins. We recently reported that administering BCS can cause other biochemical and morphological alterations, not only in tissues at the injection site but in other areas as well. In this study, we have examined the metabolic effects of BCS administration on the mouse kidney. At 1, 24, and 48 h after injection (5 microliters neat, sc), treated mice were terminated along with an untreated control group, and the kidneys were analyzed for metabolic changes. Glutathione (GSH) peroxidase (GPx) activity markedly increased, (+78 and +85%), but NADP-dependent isocitrate dehydrogenase activity decreased (-43 and -37%) at 1 and 24 h, respectively. Glucose-6-phosphate dehydrogenase (G6PD) remained unchanged at 1 and 24 h, but increased 20% (p less than .05) at 48 h after injection. Kidney glutathione S-transferase (GST) was increased at 24 h after injection. Both total and oxidized GSH levels were significantly lower than control values (approximately 30%) at all time points. Lipid peroxidation, as estimated by the thiobarbituric (TBA) acid-reactive products, was 45% lower (p less than .05) after 1 h. Kidney GPx, G6PD, and GT activities and kidney GSH levels were consistent with changes associated with oxidative stress or detoxication mechanism for BCS. The decrease in TBA-reactive products suggests that mouse kidney metabolic response to BCS injection was different from responses observed for other organs (eyes, brain, and lung).

Animals↗

PubMed2004

Detection of the sentinel node in breast carcinoma using method of a single subcutaneous injection of radiopharmaceutical.

The objective of this work is retrospective evaluation of results of the intraoperative detection of sentinel node in breast carcinoma after a single subcutaneous injection of radiopharmaceutical (RF) within a two-day protocol. From May/2001 to June/2002, lymphoscintigraphy of the sentinel node (SN) and its subsequent radioguided intraoperative detection (RGS) was performed in 43 women having stage T1-T2, N0 breast carcinoma. The static scans in the anterior and relevant lateral projections were performed using a gamma camera at approximately 30-minute intervals after the subcutaneous administration of 15 MBq 99mTc Senti-Scint, until the SN was displayed. The localization of the SN was marked on the overlying skin with a water-resistant permanent marker in 1-2 projections. RGS was accessed within 18-24 hours after the injection of the RF and all patients underwent an axillary dissection. The SN was detected in all patients, and in all cases was localized in the ipsilateral axilla. In 26 patients (60%), no metastatic process was found either in the SN or in any other axillary node. However, in one node, deposits of the carcinoma were detected in surrounding fatty tissue with propagation along the vessels and nerve. In 16 patients (37%), metastases in the SN were proved, in 7 cases (16%), a metastatic process was proved at the same time even in further lymph nodes. A number of false negative findings (5.8%) is consistent with the literature data. The method fails in the detection of intramammary localized SNs.

Adult↗

PubMed1998

Skin necrosis and venous thrombosis from subcutaneous injection of charcoal lighter fluid (naptha).

A 33-year-old white man injected approximately 4 cc of charcoal lighter fluid (99.4% naptha/0.6% inert ingredients) subcutaneously into his left antecubital fossa. The injection resulted in the toxic necrosis of his volar forearm skin extending proximally to mid-humerus and distally to the metacarpophalangeal joints of the left hand dorsally over a 6-day period. The patient ultimately required extensive surgical debridement, secondary operative closure, and approximately 150 cm2 of split-thickness skin grafting. This case demonstrates the potential for widespread, delayed toxic necrosis of the skin resulting from subcutaneous injection of naptha. This patient's case appears to represent the most severe and widespread case of toxic necrosis of the skin resulting from the subcutaneous injection of hydrocarbons reported in the literature. This case also demonstrates extensive toxic thrombophlebitis not reported in prior cases involving subcutaneous injection of hydrocarbons.

Adult↗

PubMed1977

Infection of Clethrionomys G. glareolus Schreb. (red mice) with Mycobacterium tuberculosis and Mycobacterium bovis injected subcutaneously.

Groups of red mice were injected with doses from 10 mg to 10(-8) mg semidried culture of a strain of M. tuberculosis and with doses from 10(-1) to 10(-8) mg of a strain of M. bovis. Some animals were killed about 1 1/2 and 3 months after injection and the remainder lived until death occurred spontaneously. The number of tubercle bacilli in the organs was evaluated by microscopy of smears, in some cases by quantitative culture. Among the mice injected with M. tuberculosis in doses of up to about 2 million viable units, not one case of death occurred which could be attributed to tuberculosis. The autopsy findings consisted exclusively of lesions at the site of injection and in the regional lymph glands. Quantitative culture showed growth of a few viable units in the lymph glands, spleen or lungs, but no sign of progressive infection. Out of 10 mice injected with a giant dose of 3 X 10(7) viable units, only two died of tuberculosis. M. bovis provoked fatal tuberculosis in all animals injected with doses from 6.9 million to 7 viable units. Severe caseous lesions developed at the site of injection, in the lymph glands, in the lung, and often also in liver and spleen. The number of bacteria in the organs was enormous, particulary in the spontaneously dead animals. The survival times, which were dependent on dosage, varied from 51 to 159 days.

Animals↗

PubMed1982

Biotelemetric detection of the disappearance of subcutaneously injected 125I-NPH insulin.

A biotelemetric method with Geiger-Müller (GM) detectors fixed to the skin surface was used for continuous registration of the disappearance rate of subcutaneously injected 125I-NPH insulin. Methodological problems concerning counting geometry were investigated by comparing the disappearance of radioactivity, measured the GM- and NaI-detectors, respectively, and by scanning of the radioactive source. The size and position of the subcutaneous depot was unchanged throughout the study. Movement artifacts could be avoided. The coefficient of variation for distribution of ratios between count rates for GM- and NaI-detectors was 3.0% +/- 1.1 (SD) (range 0.9-4.0%) over periods of 24 h. It is concluded that the biotelemetry technique proved to be a clinically useful procedure for insulin absorption studies.

Adult↗