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PubMed2005

Anti-tumour effects of triple therapy with octreotide, galanin and serotonin in comparison with those of 5-fluorouracil/leukovorin on human colon cancer.

Human colon cancer cells were injected subcutaneous in nude mice. After 8 days the animals were divided in two groups, the first group received triple therapy with octreotide, galanin and serotonin (40 microg/kg body weight/day) through an ALZET osmotic pump implanted intraperitoneally (i.p.) for 14 days, followed by 5 days of subcutaneous injections (200 microg/kg body weight/ day). The second group was injected i.p. for 5 days with 5-fluorouracil/leukovorin (5-FU/LV) at concentrations of 4 mg and 2 mg/kg body weight, respectively. After 9 days without any treatment, the mice received i.p. injection with 5-FU/LV (20 mg and 10 mg/kg body weight/day, respectively) for another 5 days. The volume and weight of the tumours were measured at the end of the experiment. Apoptosis, proliferation, blood vessels, epidermal growth factor (EGF) and vascular endothelial cell growth factor (VEGF) were detected with immunocytochemistry. Apoptosis was also detected using the TUNEL-method. Quantification was performed using computed image analysis. There was no statistical significance between tumours treated with 5-FU/LV or triple therapy regarding the volume and weights of the tumours, apoptotic, proliferation, VEGF indces and the density of tumour blood vessels. The EGF labelling index was, however significantly lower in the tumours treated with triple therapy than those treated with 5-FU/LV. In conclusion, treatment with triple therapy using octreotide, galanin and serotonin appear to be comparable with 5-FU/LV that is the standard chemotherapeutic agent for colorectal cancer.

Animals↗
PubMed2005

Effect of D-004, a lipid extract from Cuban royal palm fruit, on histological changes of prostate hyperplasia induced with testosterone in rats.

Benign prostatic hyperplasia (BPH) is the nonmalignant, uncontrolled growth of prostate gland cells and stroma leading to difficulty in urinating. Lipid extracts from Saw palmetto (Arecaceae) fruits are used to treat BPH. The Cuban royal palm (Roystonea regia) is a member of this family and D-004, a lipid extract from its fruits, prevents prostate hyperplasia (PH) induced with testosterone, as opposed to dihydrotestosterone, in rodents. This study investigated whether D-004 could prevent the histological features of testosterone-induced PH in rats. Rats were distributed into six groups (10 rats per group): A negative control group receiving subcutaneous injections of soy oil and treated with vehicle, and five groups injected subcutaneously with testosterone and treated with the vehicle (positive control), D-004 (100, 200 and 400 mg/kg) or Saw palmetto (400 mg/kg). Treatments were given orally for 14 days. At sacrifice, prostates were removed and processed for light microscopy. The histopathological findings of PH were assessed according to a score-chart protocol. D-004 200 and 400 mg/kg, but not 100 mg/kg, significantly and moderately in a dose-dependent manner prevented prostate enlargement and the testosterone-induced histological changes. Compared with positive controls, D-004 200 and 400 mg/kg inhibited prostate size increases and the histological score up to 56.1% and 60.7%, respectively, while Saw palmetto 400 mg/kg reduced such variables by 45.8% and 49.0%, respectively. The effects of D-004 400 mg/kg on the histological changes, not on prostate size, were greater (p < 0.05) than those of Saw palmetto. D-004 and Saw palmetto did not affect body weight values. In conclusion, D-004 200 and 400 mg/kg administered orally for 14 days prevented the increase of prostate size and the testosterone-induced histological changes in rats, its effects being comparable or mildly better than those of Saw palmetto. These results extend previous data showing preventive effects of D-004 on testosterone-induced prostate enlargement with in rodents, and further studies are required to explore the mechanisms underlying such effects.

Administration, Oral↗
PubMed1989

Effect of vitamin K deficiency on urinary gamma-carboxyglutamic acid excretion in rats.

Since gamma-carboxyglutamic acid (Gla) in Gla-containing proteins is stoichiometrically excreted into urine as free Gla, urinary Gla excretion is believed to reflect the rate of synthesis and degradation of vitamin K-dependent proteins and the utilization of vitamin K in body. We studied the daily changes in urinary Gla excretion and plasma vitamin K-dependent clotting factor levels in rats fed vitamin K-deficient diets followed by subcutaneous injection of vitamin K1 or after the oral administration of Warfarin. Urinary Gla excretion in normal rats fed a standard diet that contained about 500 ng of vitamin K1 per gram of diet was 2.35 +/- 0.25 mumoles/day, but the level in rats fed a markedly vitamin K-deficient diet (less than 5 ng/g) decreased to 1.40 +/- 0.14 mumoles/day. When rats were fed a moderately vitamin K-deficient diet (20-50 ng/g), plasma vitamin K-dependent clotting factor levels decreased significantly, but urinary Gla excretion did not decrease. Warfarin, a vitamin K antagonist, caused a significant decrease in urinary Gla excretion and plasma clotting factor levels. When vitamin K, (200 micrograms/kg) was injected subcutaneously in rats fed a markedly vitamin K-deficient diet, the plasma vitamin K-dependent clotting factor levels recovered quickly to normal, but urinary Gla excretion showed only a partial recovery to 1.74 +/- 0.15 mumoles/day. These results indicate that urinary Gla excretion decreases in vitamin K deficiency, but changes in urinary Gla excretion do not reflect vitamin K deficiency in rats as sensitively as changes in the prothrombin time and plasma K-dependent clotting factor levels.

1-Carboxyglutamic Acid↗
PubMed1987

[Endocrinological background of pituitary desensitization during pulsatile LH-RH therapy for ovulation induction in amenorrheic women].

In order to elucidate the endocrinological background of patients in whom ovulation induction by pulsatile LH-RH administration resulted in failure, 16 women with hypothalamic amenorrhea were treated with 10 to 20 micrograms of LH-RH injected subcutaneously every 2 hrs. Six women did not ovulate, and 5 of them showed pituitary desensitization since the basal gonadotropin concentration gradually decreased and the response to LH-RH test (100 micrograms i.v.) became blunted by the treatment. No significant differences between the ovulated and desensitized groups were seen in basal LH, FSH, E2, PRL levels, LH/FSH ratio and response to LH-RH test performed prior to the treatment. In addition, the plasma LH-RH profile after subcutaneous injection of 10 micrograms of LH-RH was highly pulsatile in both groups. However, in the desensitized group, all were obese, showed impaired GH response to both insulin tolerance and GH-RH tests, and had episodic LH secretion with higher frequency compared to the ovulated group. These results suggest that the desensitized women had occult pituitary dysfunction and hypersecretion of endogenous LH-RH which stimulated the pituitary close to the level of desensitization. The mechanism of hypersecretion of endogenous LH-RH is discussed.

Adult↗
PubMed1986

Experimental Escherichia coli endotoxin-induced sensitisation and abortion in sows.

Subcutaneous injection of 235 micrograms endotoxin from E coli 08: K87, K88ab into two sows 14 days before the expected farrowing date elicited a toxic shock reaction but the sows recovered and farrowed normally. No reaction was observed in two other sows which had received endotoxin-free 0.9 per cent saline. In a subsequent pregnancy, the same four sows were injected subcutaneously with 23 mg of the same endotoxin preparation. Those which had previously received endotoxin exhibited a severe shock reaction and aborted after 28 and 40 hours, respectively, while the other two sows showed a milder reaction and farrowed normally.

Abortion, Veterinary↗
PubMed1986

[Evaluation of the effect of Royat thermal gas in arteriopathy of the legs using thallium-201 muscular scintigraphy].

12 patients (group II) suffering from an arteriopathy of the lower limbs, stage II, were examined by thallium 201 muscular scanning. The aim of this study was to look for a possible muscular effect of Royat thermal gas injected subcutaneously. A preliminary study was conducted at rest, and consisted of recording the initial decay curve of thallium in the thighs and the study of the muscular fixation by different segments of the limbs, including the determination of the ratios of amounts fixed by the muscular and non-muscular zones. The results were compared with those obtained in 11 healthy subjects (group I) and no significant difference was noted between the two groups at rest. On the other hand, a considerable improvement of the fixation in the legs was observed after subcutaneous injection of thermal gas. The results are discussed in relation to the clinical and paraclinical data.

Adult↗
PubMed1985

The effect of adjuvants and prior immunization on the rate and mode of uptake of antigen into afferent popliteal lymph from sheep.

Experiments were carried out to determine the effect of a range of adjuvants on the antibody response of sheep to a subcutaneous injection of ovalbumin. Incomplete Freund's adjuvant (IFA) was the best of the repository type adjuvants. From a range of soluble immunopotentiating substances tested, the polyion DEAE-dextran, or dextran sulphate, produced the greatest enhancement of the response. These results were confirmed in a factorial experiment, but no interactions were found between various classes of adjuvants. Further experiments were carried out to determine the effect of superior adjuvants, prior immunization or intradermal injection on the rate and mode of uptake of antigen from the injection site to afferent lymph. These experiments showed that, with IFA, most antigen is retained at the injection site, less than 15% entering lymph by 3 days. There was some delay in antigen uptake with adjuvant 65, while for aluminium phosphate precipitated antigen, the rate of uptake was the same as following a saline injection. There was some delay in uptake of antigen following injection with DEAE-dextran or in primed sheep but, following intradermal injection, the rate of uptake into lymph was the same as aqueous antigen injected subcutaneously. Experiments in which the distribution of radioactive antigen between cells and plasma in lymph was examined showed that, in unprimed sheep, virtually all antigen is unassociated with cells. In primed sheep, however, about 0.5% of antigen in lymph was found to be cell-associated. Gel filtration of lymph plasma from primed sheep demonstrated that nearly all the antigen in lymph is carried to the node as high molecular weight material, presumably antigen-antibody complexes.

Adjuvants, Immunologic↗
PubMed1982

Mice do not respond with delayed hypersensitivity to penicillin-derived determinants.

Penicillin structures of varying lipophilicity were used to induce delayed hypersensitivity (DH) in different strains of mice. Epicutaneous application on inflamed skin or intracutaneous or subcutaneous injection with Freund's complete adjuvant did not induce DH, despite the fact that picrylchloride readily produced such responses. Sheep, rabbit and mouse red cells as well as mouse lymph node and epidermal cells conjugated with various amounts of penicillin injected subcutaneously in the base of the tail did not induce a DH reaction to penicillin either, whereas such responses to other cellular components and also to the TNP determinant after using picryl sulphonic acid conjugated spleen cells were recorded. Since the mice in other studies have been shown to respond with antibodies to soluble penicilloyl protein conjugates, but never to penicillin itself, we concluded that this species of animal is incapable of responding to penicillin with DH.

Animals↗
PubMed1983

Effects of superoxide dismutase and catalase on disseminated intravascular coagulation in rats.

The effects of superoxide dismutase (SOD) and catalase on endotoxin-induced experimental disseminated intravascular coagulation (DIC) were studied in rats. Experimental DIC was induced by a 4 hr sustained infusion of endotoxin at a dose of 100 mg/kg. The rats were subcutaneously injected with SOD at 0.5, 5.0 or 50.0 mg/kg, or catalase at 0.01, 0.1 or 1.0 mg/kg, followed by the continuously infusion of 100 mg/kg/4hr of endotoxin. A preventive effect against DIC was noted in all the parameters, such as fibrinogen and fibrin degradation products, fibrinogen level, prothrombin time, partial thromboplastin time, platelet count and the number of renal glomeruli with fibrin thrombi, in the rats treated with 50.0 mg/kg of SOD or 1.0 mg/kg of catalase. When 50.0 mg/kg of SOD or 1.0 mg/kg of catalase was injected subcutaneously at 1, 2 or 3 hr after the initiation of the endotoxin-infusion, the protective effect against DIC was noted in all the parameters.

Animals↗
PubMed1995

Time-action profiles of the intermediate-acting insulin analogue des(64,65)-human proinsulin.

Des(64,65)-proinsulin (DPRO) is one of several endogenous intermediates arising during the conversion of proinsulin to insulin. In pharmaceutic preparations it is a clear solution containing no other proteins. Animal experiments and preliminary human studies indicated that DPRO should have a protracted time-action profile similar to that of NPH-insulin. Accordingly, we compared the time-action profiles of these two preparations, using the euglycaemic glucose clamp-technique in 9 healthy male volunteers. Different doses of DPRO (0.1, 0.15, 0.2 U/kg) or equipotent doses of NPH ( 0.2, 0.3, 0.4 U/kg) were injected subcutaneously into the abdominal wall. The maximal metabolic effect (GIRmax) of DPRO was greater than that of NPH-insulin (p < 0.05). With increasing doses, GIRmax differed significantly for DPRO but not for NPH-insulin. The time to maximal metabolic effect (tmax) was similar for the three doses of either preparation. However, tmax was reached 30 min earlier with DPRO than with NPH-insulin (p < 0.01). the decline to half-maximal after maximal activity was significantly faster with DPRO than with NPH-insulin (p < 0.0001). Subcutaneous injection of DPRO thus produced a time-action profile between that of regular insulin and NPH-insulin.

Adult↗
PubMedDate not supplied

Tumor necrosis factor (TNF)-induced cutaneous necrosis is mediated by TNF receptor 1.

Tumor necrosis factor (TNF) is a central mediator of immune and inflammatory responses. Its activities have been shown to be mediated by two distinct receptors, TNFR1 (p55) and TNFR2 (p75). The cytoplasmic domains of both TNF receptors are unrelated, suggesting that they link to different intracellular signaling pathways. To determine their role in vivo in lipopolysaccharide (LPS)- and TNF-induced skin inflammatory necrosis, TNFR1-, TNFR2-, and TNF lymphotoxin-alpha (LT alpha)-deficient mice were used. Skin abscesses were experimentally induced with local application of TNF or LPS. Large macroscopic ulcerations were observed in TNF-injected wild-type animals and to a slightly lesser extent in TNFR2-deficient mice with tissue destruction in both cases extending deep into the dermis. Tissue destruction was accompanied by an intense immune infiltrate composed mainly of neutrophils, lymphocytes, and macrophages. TNFR1-deficient and TNFR1/TNFR2-double-deficient mice, however, did not exhibit any ulceration and showed only a very mild inflammatory infiltrate. In TNF/LT alpha-double ligand0-deficient animals, a moderate epidermal necrosis was observed with a reduced inflammatory infiltrate compared to wild-type animals. As with TNF injections, subcutaneous injection of LPS induced a comparable pattern of skin necrosis in wild-type and TNF receptor mutant mice, yet a slightly more acute inflammatory level was observed regardless of the type of animal tested. As found for TNF-induced skin necrosis, the extent of LPS-induced skin necrosis was reduced in TNF/LT alpha-deficient mice compared to wild-type animals. The present data strongly suggest that TNFR1, rather than TNFR2, is engaged in LPS- and TNF-induced skin necrosis and highlight the predominant role played by TNF in LPS-induced inflammatory diseases.

Animals↗
PubMed2006

Randomized comparison of the single-injection volar subcutaneous block and the two-injection dorsal block for digital anesthesia.

BACKGROUND: Two commonly used methods of digital nerve block with local anesthetic are the two-injection dorsal technique and the single-injection volar subcutaneous technique. The authors compared these two digital block techniques with respect to local anesthetic injection pain and recipient preference of anesthetic technique. METHODS: Twenty-seven volunteers had the long finger of each hand injected with 2% lidocaine with 1:100,000 epinephrine. The two-injection dorsal method was used on one long finger and the other long finger received the volar single-injection technique. Volunteers completed a pain scale for each block and were then asked which technique they would prefer. The area of anesthetic skin was assessed in each finger by pinprick testing, and photographs were taken. RESULTS: Although there was a lower pain score for the volar single-injection block, the difference in pain scores between the two techniques was not statistically significant. However, 22 of the 27 subjects indicated that they would select the volar over the dorsal block if a future block was required, and this preference for the volar block was statistically significant. CONCLUSIONS: Although the difference in pain scores between the two techniques was not statistically significant, volunteers who received both blocks would prefer the volar single-injection subcutaneous block if given a choice. Therefore, the single-injection volar subcutaneous block is recommended as the technique of choice for anesthesia of the digit, except in patients for whom anesthesia over the dorsum of the proximal phalanx is required. These patients may prefer a supplementary dorsal nerve block or a traditional two-injection block.

Adult↗
PubMed1986

Monoclonal antibody imaging of human melanoma. Radioimmunodetection by subcutaneous or systemic injection.

Fab fragments of monoclonal antibodies (MoAb) to melanoma, radiolabeled with 131I, were evaluated as diagnostic reagents to determine their ability to localize systemic--MoAb injected intravenously (IV)--or nodal metastatic disease--injected subcutaneously (SQ) at a site proximal to draining lymph nodes. Sixty-one scans were performed (40 IV, 21 SQ) in 59 patients who had injections of 0.2-50 mg of 131I coupled (0.2-12 mCi) antibody. These included 48.7, which identifies a high molecular weight antigen (HMW), or 96.5, which identifies a transferrin like molecule, p97. 125I coupled nonspecific Fab 1.4, reacting with murine leukemia virus, or the whole antibody BL3, reactive with a human B cell idiotypic determinant, was generally used in tandem with the patients injected SQ as a nonspecific control. All patients had immunohistochemical studies performed on biopsied lesions and demonstrated binding to the antibodies injected. Of the IV patients, 22/38 (58%) had (+) scans, 13 at SQ or nodal sites, four at visceral sites, and five at visceral and SQ sites. Patients with clinical stage II disease had SQ injection of MoAb, including 11 additional patients injected with the whole antibody 9.2.27 (anti-HMW) labeled with 111In (6 patients) or 131I (5 patients). Nodal dissection was performed 2-4 days later. All 111In coupled antibodies demonstrated excellent nodal delineation without specific identification of tumor deposits. Of the 21 patients injected SQ with MoAb, 17 had confirmed tumor in nodes. Of patients injected with Fab fragments, 4/8 (50%) had specific uptake of MoAb, although only two were successfully imaged. Increased uptake of antimelanoma antibodies was observed in some patients in lymph nodes not containing tumor and was possibly related to antigen shedding. Clearance of labeled antibody from the injection site occurred with a half life of 16-50 hours. Toxicity was limited to local discomfort at the site of SQ injection. Melanoma metastases can be identified with IV or SQ injection or radiolabeled antibodies. These reagents may be useful in the diagnosis or therapy of human melanoma. Further evaluation will be required before they could be considered clinically useful.

Adult↗
PubMed1997

Subcutaneous self-injection and oral self-administration of metallic mercury--case report.

This paper presents a case of 16-year-old schoolboy who injected subcutaneously about 6 ml of metallic mercury to both forearms and administered orally about 5 ml of it. The patient was admitted to hospital two weeks after this incident without any clinical symptoms. Physical examination and all laboratory tests, including chest x-ray were unremarkable except for granulomata at the injection sites. X-ray examination showed numerous, dispersed globules of mercury in subcutaneous tissue of both forearms and in the digestive tract, mainly in the appendix. Granulomatous tissue with a part of mercury from both forearms as well as appendix were surgically removed. During a six-month period no toxic effects of mercury have been observed, in spite of the fact, that blood mercury level was 132 micrograms/L and urinary mercury level was 500 micrograms/L.

Administration, Oral↗
PubMed1999

Epinephrine absorption after different routes of administration in an animal model.

BACKGROUND: The administration of epinephrine is the most important initial treatment in systemic anaphylaxis. PURPOSE: We wanted to determine the relationship between the route of epinephrine administration and the rate and extent of epinephrine absorption. METHODS: In a prospective, randomized, five-way crossover study in rabbits, we measured plasma epinephrine concentrations before, and at intervals up to 180 min after epinephrine administration by intramuscular or subcutaneous injection, or by inhalation, with intravenous epinephrine and intramuscular saline as the positive and negative controls, respectively. RESULTS: Maximum plasma epinephrine concentrations were higher, and occurred more rapidly, after intramuscular injection than after subcutaneous injection or inhalation, and were 7719+/-3943 (S.E.M.) pg/mL at 32.5+/-6.6 min, 2692+/-863 pg/mL at 111.7+/-30.8 min and 1196+/-369 pg/mL at 45. 8+/-19.2 min, respectively. Intravenous injection of epinephrine resulted in a plasma concentration of 3544+/-422 pg/mL at 5 min, and an elimination half-life (t(1/2)) of 11.0+/-2.5 min. In the saline control study, the endogenous epinephrine concentration peaked at 518+/-142 pg/mL. CONCLUSION: In this model, absorption of epinephrine was significantly faster after intramuscular injection than after subcutaneous injection or inhalation. The extent of absorption was satisfactory after both intramuscular and subcutaneous injections. Neither the rate nor the extent of absorption was satisfactory after administration by inhalation.

Absorption↗
PubMed1983

Abnormal development of blood pressure and growth in rats exposed to perinatal injection stress.

Subcutaneous injections of alkaline saline were made perinatally in Sprague-Dawley rats according to two schedules. In a pre-/postnatal group, dams were treated from 19th gestational day to 9th day postpartum and pups from day 0-9. In a postnatal group, pups alone were injected from day 0-6. At 19-23, 50-56 and 82-86 days of age, injected rats and uninjected controls were anesthetized and arterial blood pressure measured. Rats from the pre-/postnatal group had higher blood pressures (58%) and body weights at 19-23 days and lower blood pressure (35%) and body weight at 82-86 days of age. Blood pressure and body weight were comparable to control at all ages in the postnatal injection group. It is concluded that as a result of the maternal stress produced by the injections there was a generalized disturbance of growth processes resulting in hypotension and decreased body weight in adulthood.

Aging↗
PubMed2006

Subcutaneous bolus injection of deferoxamine is an alternative method to subcutaneous continuous infusion.

The objective of this study was to compare the short- and long-term efficacy of deferoxamine (DFO) given by subcutaneous (SC) continuous infusion over 10 hours via a pump (n = 10) versus a twice-daily subcutaneous bolus injection of the same overall dose (n = 10) in 20 thalassemic children. Urinary iron excretion was measured in 24-hour urine samples after DFO treatment in the 20 patients. The patients were randomized to two groups: 10 patients continued SC continuous infusion with a pump and the remaining 10 received the same overall dose of DFO by twice-daily SC bolus injection for a year. Serum ferritin levels and T1-weighted spin-echo and T2-weighted fast spin-echo signal intensities of liver and paraspinal muscle were determined at initiation and 1 year after initiation of the therapy. In 12 patients, six from each group, liver biopsies were performed and hepatic iron concentration was determined at initiation of therapy and 1 year after treatment. A similar and significant decrease in ferritin levels and improvement in signal intensities of the liver were observed in response to chelation therapy with DFO in both groups (P < 0.01, within each group). Hepatic iron concentration decreased in all patients in the SC bolus injection group (P < 0.05) and in four patients in the SC continuous infusion group (P > 0.05). Hepatic iron concentration was noted to be slightly increased in two patients in the SC continuous infusion group, which may be due to poor compliance. Based on these results, twice-daily SC bolus injection of DFO is as effective as administration via SC continuous infusion using a pump. Subcutaneous bolus injection, being more convenient for the patient, may be a more preferable method of DFO administration.

Adolescent↗