SEARCH · PubMed Health

Results for “Subcutaneous”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 289 records · Page 16Linked to original sources

PubMed2000

Chronic intraperitoneal insulin delivery, as compared with subcutaneous delivery, improves hepatic glucose metabolism in streptozotocin diabetic rats.

We have previously shown that chronic insulin treatment by the intraperitoneal route normalizes the elevated glucose production (GP) in streptozotocin (STZ) diabetic rats, while insulin delivered by the subcutaneous route only partially normalizes GP. To investigate the biochemical mechanism of the effect of chronic insulin delivery by either route on hepatic glucose metabolism, we measured the hepatic activity of glucose 6-phosphatase (G6Pase) and glucokinase (GK). Four groups of rats were used: (1) nondiabetic rats (N, n = 7), (2) untreated STZ diabetic rats (D, n = 8), (3) diabetic rats treated intraperitoneally (IP, n = 6), or (4) subcutaneously (SC, n = 8) (both 3 U of insulin/d). Glucose levels, higher in D, were normalized by insulin treatment regardless of route. Peripheral insulin levels were lowest in D and highest in SC as expected (N, 162 +/- 18 pmol/L; D, 66 +/- 12; IP, 360 +/- 96; SC, 798 +/- 198). STZ diabetes resulted in a 10-fold decrease in GK (P < .001), and a 2-fold increase in G6Pase activity (P < .01). Both intraperitoneal and subcutaneous treatments normalized G6Pase activity. In contrast, with subcutaneous but not intraperitoneal treatment, GK activity was still 35% less than normal (SC v N, P < .05). Glucose 6-phosphate (G6P) levels did not differ among the groups. In summary: (1) the increase in GP in D reflected increased activity of G6Pase and reduced activity of GK, (2) the partial suppression of GP with subcutaneous insulin treatment reflected correction of increased G6Pase activity, but only partial correction of low GK activity, and (3) the normalization of GP with intraperitoneal insulin treatment reflected correction of both increased G6Pase activity and low GK activity. Our current studies indicate that chronic intraperitoneal insulin treatment is superior to subcutaneous treatment with regard to hepatic glucose metabolism.

Animals↗

PubMed2003

Differences in plasminogen activator inhibitor 1 in subcutaneous versus omental adipose tissue in non-obese and obese subjects.

Human adipose tissue can produce plasminogen activator inhibitor-1 (PAI-1). It has been suggested that high levels of PAI-1 are of importance in enhanced cardiovascular disease observed among obese subjects, especially abdominally obese individuals. In the present study, we investigated the level of mRNA and production of PAI-1 in adipose tissue from two adipose tissue depots (omental vs. subcutaneous). Adipose tissue from both depots was obtained from obese (mean BMI, 46.9 kg/m 2) and non-obese (mean BMI, 23.9 kg/m 2) women. PAI-1 mRNA was measured both in fresh adipose tissue obtained immediately after surgery and after the adipose tissue (fragments) had been incubated for up to 72 h. In immediately frozen adipose tissue, PAI-1 mRNA expression was similar in omental and subcutaneous adipose tissue. No differences between obese and non-obese women were found. However, when adipose tissue fragments were cultured, PAI-1 mRNA and PAI-1 production were significantly higher in omental than in subcutaneous adipose tissue (p < 0.05). In the culture system, the production of PAI-1 in obese subjects was higher than in non-obese subjects in both subcutaneous (p < 0.05) and in omental adipose tissue (p = 0.19). In order to test whether these regional differences observed after incubation of the adipose tissue were due to differences in local accumulation of cytokines that may stimulate PAI-1 by a paracrine or autocrine manner, we investigated the expression of transforming growth factor beta1 (TGF-beta1) mRNA and tumor necrosis factor alpha (TNF-alpha) mRNA and protein. No differences between the two fat depots were found. In conclusion, no differences in PAI-1 expression between omental and subcutaneous adipose tissue were observed in biopsies frozen immediately after removal, but after incubation of adipose tissue (which somehow stimulates PAI-1 production), higher levels of PAI-1 were found in omental adipose tissue than in subcutaneous adipose tissue. Finally, PAI-1 production in adipose tissue from obese women was higher in non-obese women after incubation for 72 h.

Adipose Tissue↗

PubMed2000

[Prevention of thrombosis with subcutaneous recombinant hirudin in heparin-induced thrombocytopenia type II. A pilot study].

BACKGROUND: Heparin-induced thrombocytopenia (HIT) type II is a severe complication of heparin therapy with a high incidence of thromboembolic events. AIM: The aim of this prospective study was to evaluate efficacy and safety of prophylaxis of thromboembolism with subcutaneous r-hirudin (25 mg twice daily) in patients with HIT type II. PATIENTS AND METHODS: From 01/06/1997 until 01/08/1999, 19 patients were prospectively included into the study. During subcutaneous r-hirudin application (25 mg twice daily) the activated partial thromboplastin time (aPTT) and ecarin clotting time (ECT) were measured twice daily prior to and 2 hours after the morning injection. RESULTS: Ten patients (mean age: 68 years; two men, eight women) with thromboembolic events were intravenously treated with r-hirudin (mean 19.3 days) with a target aPTT of 1.5 to 2.5 times normal values followed by subcutaneous r-hirudin (mean 22.5 days). Five Patients without thromboembolism immediately received subcutaneous r-hirudin (mean 25.9 days; mean age: 61 jahre; two men, three women) after cessation of heparin. Four patients requiring prophylaxis of thromboembolism received subcutaneous r-hirudin (mean 32 days; mean age: 68 years; four women) because of HIT type II in the past. Mean aPTT-values prior to and 1.5-2.5 hours after the morning injection were 1.2 to 1.7 and 2.0 to 2.3 times normal values, respectively. The ECT was prolonged by 1.2 to 1.7 and 2.3 to 2.5 times the upper normal value, respectively. Thromboembolic or bleeding events were not observed during the study. CONCLUSION: The subcutaneous application of r-hirudin provides an alternative for primary and secondary prophylaxis of thromboembolism in HIT type II patients.

Aged↗

PubMed1998

Subcutaneous compared with intravenous epoetin in patients receiving hemodialysis. Department of Veterans Affairs Cooperative Study Group on Erythropoietin in Hemodialysis Patients.

BACKGROUND: Several studies have suggested that if recombinant human erythropoietin (epoetin) is administered subcutaneously rather than intravenously, a lower dose may be sufficient to maintain the hematocrit at a given level. METHODS: In a randomized, unblinded trial conducted at 24 hemodialysis units at Veterans Affairs medical centers, we assigned 208 patients who were receiving long-term hemodialysis and epoetin therapy to treatment with either subcutaneous or intravenous epoetin. The dose was initially reduced until the hematocrit was below 30 percent and then was gradually increased to a level that would maintain the hematocrit in the range of 30 to 33 percent for 26 weeks. We compared the average doses in the 26-week maintenance phase and the discomfort associated with the two routes of administration. RESULTS: For the 107 patients treated by the subcutaneous route, the average weekly dose of epoetin during the maintenance phase was 32 percent less than that for the 101 patients treated by the intravenous route (mean [+/-SD], 95.1+/-75.0 vs. 140.3+/-88.5 U per kilogram of body weight per week; P<0.001). Only one patient in the subcutaneous-therapy group withdrew from the study because of pain at the injection site, and 86 percent rated the pain associated with subcutaneous administration as ranging from absent to mild. CONCLUSIONS: In patients receiving hemodialysis, subcutaneous administration of epoetin can maintain the hematocrit in a desired target range, with an average weekly dose of epoetin that is lower than with intravenous administration.

Algorithms↗

PubMed2000

Delivery of recombinant product from subcutaneous implants of encapsulated recombinant cells in canines.

Delivering recombinant therapeutic proteins from a universal microencapsulated cell line is an alternate method for gene therapy. It has proved effective in the treatment of several murine models of human genetic diseases. However, in scaling up to large animal models, intraperitoneal Implantations of these microcapsules in canines were associated with excessive Inflammatory response and rapid degradation. We now show that subcutaneous implantation of microencapsulated cells in canines is effective in delivering recombinant product systemically for extended periods, provides a surgically benign site, leads to less inflammatory response, and permits longer-term survival of microcapsules. Allogeneic MDCK cells engineered to secrete human growth hormone (hGH) were microencapsulated in alginate-poly-L-lysine-alginate and implanted subcutaneously. Systemic delivery of hGH was evident within 4 hours and peaked by day 1 after implantation in all dogs. The gradual decline of hGH in the circulation in the first 2 weeks coincided with the development of anti-hGH antibodies by day 11. The high titer persisted for more than 1 month, demonstrating indirectly the persistent delivery of hGH. Microcapsules retrieved from the subcutaneous implant maintained their structure throughout the experiment and were free of host cellular adhesions. The mechanical integrity of the subcutaneously implanted microcapsules also appeared superior to that of the intraperitoneal implant. Hence the subcutaneously implanted microcapsules required minimal surgical intervention and led to a low level of inflammatory response, and the implant survived for at least 1 month, thus demonstrating the feasibility of systemic delivery of recombinant products via subcutaneous implantation in large animals.

Animals↗

PubMed2000

Subcutaneous human menopausal gonadotropin administration for controlled ovarian hyperstimulation with intrauterine insemination cycles.

OBJECTIVE: This study was undertaken to determine the feasibility of administering human menopausal gonadotropin subcutaneously for controlled ovarian hyperstimulation with intrauterine insemination. STUDY DESIGN: This was a prospective nonrandomized matched-group comparison. Study patients (n = 25) undergoing controlled ovarian hyperstimulation with intrauterine insemination infertility treatment between June 1998 and March 1999 self-administered human menopausal gonadotropin subcutaneously for ovulation induction. Cycles (n = 39) were analyzed for duration of human menopausal gonadotropin treatment, total number of ampules of human menopausal gonadotropin used, peak serum estradiol level, number of mature follicles (> or =15 mm), cycle fecundity, and acceptability of the subcutaneous route of human menopausal gonadotropin administration. Age-matched historical control subjects who followed the same protocol except for the route of human menopausal gonadotropin administration, which was instead intramuscular, were used for comparison. RESULTS: Study and control cycles did not differ with respect to duration of human menopausal gonadotropin treatment (7.49 vs 8.18 d), total number of ampules of human menopausal gonadotropin used (17.44 vs 19.55), peak serum estradiol level (881 vs 769 pg/mL), number of mature follicles (>/=15 mm; 3.39 vs 2.92), or cycle fecundity rate (15.4% vs 17.9%). Two study patients were switched from subcutaneous to intramuscular administration because of minor local injection site reactions. CONCLUSION: Subcutaneous human menopausal gonadotropin administration for controlled ovarian hyperstimulation with intrauterine insemination treatment cycles was generally well tolerated and yielded stimulation parameters and pregnancy rates similar to those associated with the intramuscular route. Patients subjectively preferred subcutaneous human menopausal gonadotropin administration because of the ability to self-administer the injections, the use of a smaller injection needle, and reduced muscular pain at the injection site.

Adult↗

PubMed2006

A reduced protein diet induces stearoyl-CoA desaturase protein expression in pig muscle but not in subcutaneous adipose tissue: relationship with intramuscular lipid formation.

A reduced protein diet (RPD) is known to increase the level of intramuscular lipid in pig meat with a smaller effect on the amount of subcutaneous adipose tissue. This might be due to tissue-specific activation of the expression of lipogenic enzymes by the RPD. The present study investigated the effect of a RPD, containing palm kernel oil, soyabean oil or palm oil on the activity and expression of one of the major lipogenic enzymes, stearoyl-CoA desaturase (SCD) and on the level of total lipids and the fatty acid composition of muscle and subcutaneous adipose tissue in pigs. The RPD significantly increased SCD protein expression and activity in muscle but not in subcutaneous adipose tissue. The level of MUFA and total fatty acids in muscle was also elevated when the RPD was fed, with only small changes in subcutaneous adipose tissue. A positive significant correlation between SCD protein expression and total fatty acids in muscle was found. The results suggest that an increase in intramuscular but not subcutaneous adipose tissue fatty acids under the influence of a RPD is related to tissue-specific activation of SCD expression. It is suggested that the SCD isoform spectra in pig subcutaneous adipose tissue and muscle might be different.

Acetyl-CoA Carboxylase↗

PubMed2002

Correlation between blood glucose concentration and glucose concentration in subcutaneous adipose tissue evaluated with microdialysis during intensive care.

BACKGROUND: Hyper- as well as hypoglycemia may be detrimental for brain energy metabolism and even a moderate increase in blood glucose concentration can affect outcome adversely. During physiological conditions, glucose concentration obtained from microdialysis of subcutaneous adipose tissue adequately reflects plasma glucose concentration. This study examines whether this correlation is also obtained during intensive care in patients with severe injuries. METHODS: The study included 62 patients with severe traumatic brain injuries. All patients received one 30 mm microdialysis catheter (CMA 60, CMA Microdialysis) inserted into periumbilical subcutaneous adipose tissue. The probe was perfused (0.3 microl/min) with a Ringer solution from a microinfusion pump and analyzed for glucose, lactate, and glycerol. The study included 2.434 simultaneous analyses of glucose concentration in arterial blood and subcutaneous adipose tissue. RESULTS: The correlation coefficient for glucose concentration in blood and interstitial fluid was 0.743 for the whole material. The correlation was relatively poor for 1-6 h after insertion of the probes. During this period, a continuous increase in the subcutaneous level of glucose and decreases in lactate and glycerol were noted. CONCLUSIONS: The correlation between blood glucose concentration and glucose concentration in subcutaneous adipose tissue was not as good during intensive care as in normal humans. The poor correlation during the first 6 h probably reflects a stress reaction (and possibly local vasoconstriction). Microdialysis of subcutaneous adipose tissue permits frequent bedside analyses of the biochemical composition of the extracellular fluid and may be of value during routine intensive care provided the methodological limitations are recognized.

Adipose Tissue↗

PubMed2004

Intrasubject variability of inhaled insulin in type 1 diabetes: a comparison with subcutaneous insulin.

We compared intrasubject variability of insulin and glucose profiles after a standardized meal between insulin inhaled via the AERx insulin Diabetes Management System (AERx iDMS, Aradigm Corp., Hayward, CA) and given as a subcutaneous injection. In this single-center, parallel, randomized, open-labeled trial, 17 male, non-smoking patients with type 1 diabetes (mean age, 27.7 years; body mass index, 23.4 kg/m(2)) received a fixed, individualized dose of human insulin, on four treatment days followed by an individualized breakfast, administered either by inhalation via AERx iDMS (n = 9) or by subcutaneous injection. Serum insulin and serum glucose levels were determined at regular intervals for 6 h postdose. Intrasubject variability was expressed as coefficient of variation. No statistically significant differences in intrasubject variability were observed between the treatments for the areas under the insulin curves for 0-6 h [27% vs. 19% (inhaled insulin vs. subcutaneous)] and areas under the glucose curves 0-6 h (30% vs. 23%). Intrasubject variability values for insulin half-life, terminal elimination rate constant, and mean residence time were significantly less in the inhaled insulin group compared with the subcutaneous insulin group (P = 0.01-0.02). Only one potentially trial product-related adverse event (an audible wheeze) was reported, and no clinically relevant changes in pulmonary function were detected. The intrasubject variability was comparable between patients receiving inhaled insulin and subcutaneous insulin, thereby confirming the reproducibility of administering insulin via AERx iDMS. Inhaled insulin was well tolerated and is a feasible alternative to subcutaneous insulin in patients with type 1 diabetes.

Administration, Inhalation↗

PubMed2005

Reduction of postincisional allodynia by subcutaneous bupivacaine: findings with a new model in the hairy skin of the rat.

BACKGROUND: An incision of hairy skin of the rat's back provides a new model for postincisional pain to determine the importance of cutaneous anesthesia. METHODS: Male Sprague-Dawley rats were anesthetized with sevoflurane and given a 0.6-ml subcutaneous injection of bupivacaine (0.25%) under the incision site or the medial lumbar dorsum or at the nuchal midline, 30 min before a 1.0-cm skin incision. Mechanical stimuli (von Frey hairs, 18-250 mN) were applied to measure nociception, indicated by twitching of local subcutaneous muscles, the cutaneus trunci muscle reflex. A graded response score, averaging the twitches weighted by their vigor, or a population response score, measuring the fraction of rats that showed any response, was assessed for 3 days before and over 7 days after incision. von Frey hairs were applied 0.5 cm from the incision to test primary hyperalgesia and 2.0 cm contralateral to the incision for secondary hyperalgesia. RESULTS: Incision induced responses to stimuli that had no effect on intact skin (allodynia) and also enhanced responses to forces that normally gave less than the full reflex (hyperalgesia). Hyperalgesia was present 30 min after surgery, peaked at 3-6 h, and persisted through the week; allodynia had a similar onset but was briefer. Both changes were transiently reversed by subcutaneous morphine (2.5 mg/kg intraperitoneal). Subcutaneous bupivacaine (0.25%), injected preoperatively at the incision site and anesthetizing skin for 2-3 h, suppressed primary allodynia for 1 week but had no effect on hyperalgesia. Secondary allodynia was obliterated, and secondary hyperalgesia attenuated by this treatment. Bupivacaine injected subcutaneously at the nuchal midline before surgery was also effective in abbreviating primary and secondary allodynia, with no signs of sedation, ataxia, or preconvulsive behavior. CONCLUSIONS: Incision of rat hairy skin changes pain responses, similar to pain in humans. Preincisional subcutaneous bupivacaine selectively suppresses and shortens allodynia for times far outlasting its local anesthesia, an effect largely from systemic actions.

Animals↗

PubMedDate not supplied

Subcutaneous nodules at the injection site of low-molecular-weight heparin: a mimic of metastatic disease at CT.

PURPOSE: To describe the appearance and prevalence of subcutaneous nodules in the anterior abdominal wall seen at CT in cancer patients receiving subcutaneous injections of low-molecular-weight heparin (LMWH). METHODS: CT examinations were reviewed in 426 patients receiving subcutaneous abdominal wall injections of LMWH for the presence of nodules. Nodules were evaluated for contour, maximal diameter, CT attenuation, and presence of hazy changes or air in the surrounding fat. RESULTS: Fourteen (3%) of the 426 patients had nodules attributable to subcutaneous injections of LMWH. Findings included poorly defined borders (100%), adjacent hazy soft tissue changes (100%), adjacent air (57%), and a mean CT attenuation of -4.4 HU (range: -50-40 HU). Three (0.7%) of 426 patients had nodules caused by metastatic disease. One (33%) nodule had poorly defined borders, two (67%) had surrounding hazy changes, one (33%) had air in adjacent tissue, and there was a mean CT attenuation of 44 HU (range: 14-140 HU). One (0.2%) patient had a subcutaneous nodule of uncertain etiology. CONCLUSION: Patients receiving subcutaneous injections of LMWH may develop nodules at the injection sites. Such nodules can resemble metastatic tumor deposits at CT, and careful correlation with clinical history and growth trends of metastatic deposits elsewhere in the patient is needed to avoid misdiagnosis.

Abdominal Muscles↗

PubMed2004

Suture closure of subcutaneous fat and wound disruption after cesarean delivery: a meta-analysis.

OBJECTIVE: To define the role of suture closure of the subcutaneous dead space in preventing wound complications after cesarean delivery. DATA SOURCES: We searched MEDLINE, the Cochrane Database of Systematic Reviews, and the bibliographies of major texts and review articles. METHODS OF STUDY SELECTION: Only studies in which patients undergoing cesarean delivery were randomly assigned to closure of the subcutaneous space or to no closure were included. Each study was required to report on at least 1 of the following outcomes: wound infection, hematoma, seroma, or separation. The studies also reported "wound disruption," a combination of these outcomes which either explicitly stated or strongly implied the need for further wound care. Six studies meeting criteria were identified. TABULATION, INTEGRATION, AND RESULTS: Three studies included 875 patients with any subcutaneous thickness and noted a decrease in wound disruption with closure (relative risk [RR] 0.56; 95% confidence interval [CI] 0.36, 0.86). Two studies reported results from 181 patients with incision depth of 2 cm or less and noted no difference (RR 1.01; 95% CI 0.46, 2.20). Five studies reported results on 887 patients with wound thickness greater than 2 cm. Although only 1 study had a significant effect by itself, when results were combined, there was a significant decrease in wound disruption (RR 0.66; 95% CI 0.48, 0.91). This reduction seems to be largely a result of decreased wound seromas (4 studies, 852 patients, RR 0.42; 95% CI 0.24, 0.75). In women with wound thickness greater than 2 cm, subcutaneous closure resulted in a risk reduction of 6.2%, and 16.2 women would need subcutaneous closure to prevent 1 wound disruption (number needed to treat). CONCLUSION: Suture closure of subcutaneous fat during cesarean delivery results in a 34% decrease in risk of wound disruption in women with fat thickness greater than 2 cm.

Adipose Tissue↗

PubMed2005

Quality of life in a clinical trial of highly active antiretroviral therapy alone or with intravenous or subcutaneous interleukin-2 administration.

OBJECTIVE: To assess the impact of subcutaneous and intravenous interleukin-2 (IL-2) on health-related quality of life (HRQOL) in adults with HIV-1 receiving highly active antiretroviral therapy (HAART). DESIGN: Randomized clinical trial. SETTING: Twenty-two institutions from the Adult AIDS Clinical Trials Group. PATIENTS: One hundred forty-eight HIV-infected adults randomized, with baseline HRQOL data. METHODS: HAART (indinavir plus 2 nucleoside analogues) for 12 weeks, followed by 72 weeks of continued HAART alone, HAART plus subcutaneous IL-2, or HAART plus intravenous IL-2. OUTCOME MEASURES: Scores for 8 dimensions of HRQOL, an unweighted summary score, and a visual analogue health rating score. RESULTS: The IL-2 subcutaneous group had the best mean change in 6 of 8 dimension subscales and in the summary scale at 28 weeks (16 weeks after baseline). At 52 weeks, the IL-2 subcutaneous group had the best mean change in all the subscales and the summary scale. The differences were statistically significant for 3 subscales and the summary scale. Midcycle changes were statistically significantly worse for the subcutaneous IL-2 group for 4 subscales and the summary scale. CONCLUSIONS: We found evidence of a short-term but not long-term adverse impact of IL-2 on HRQOL and some evidence of long-term benefit for the subcutaneous group.

Acquired Immunodeficiency Syndrome↗

PubMed2005

Subcutaneous sarcoidosis--clinicopathological study of 10 cases.

BACKGROUND: Subcutaneous sarcoidosis is a specific cutaneous lesion of sarcoidosis that is rarely reported. OBJECTIVE: Our purpose was to analyse the clinicopathological features of 10 patients with subcutaneous sarcoidosis and its relationship with the systemic features of the disease. PATIENTS AND METHODS: The patients with systemic sarcoidosis, diagnosed from 1974 to 2002 at a university hospital in Barcelona, Spain, who developed subcutaneous involvement, were included in the study. The diagnosis of systemic sarcoidosis was made according to conventional criteria. All the patients were monitored prospectively at the sarcoidosis clinic of the hospital. Skin biopsies were performed when granulomatous cutaneous involvement was suspected clinically. RESULTS: Granulomatous cutaneous involvement was demonstrated in 85 of 480 patients with systemic sarcoidosis. In 10 of these 85 patients subcutaneous sarcoidosis was diagnosed (11.8%). The lesions were most frequently located in the extremities, involving the forearms in nine patients. Indurated linear bands from the elbow to the hand were observed in five patients. In all of our patients the subcutaneous nodules appeared at the beginning of the disease. In six patients, the nodules remitted spontaneously in less than 2 years. In two cases foreign particles were detected under polarized light. CONCLUSIONS: Subcutaneous sarcoidosis is a quite uniform clinicopathological entity usually appearing at the beginning of the disease. It usually heralds forms of sarcoidosis with nonsevere systemic involvement and is not associated with chronic fibrotic disease.

Adult↗

PubMed2006

A comparison of non-contact, subcutaneous, and rectal temperatures in captive owl monkeys (Aotus sp.).

BACKGROUND: Three methods of body temperature measurement were compared in owl monkeys: non-contact infrared thermometry, subcutaneous transponder, and rectal probe. METHODS: Forty owl monkeys (Aotus sp.) were used. Animals were implanted with subcutaneous microchip transponders. Infrared thermometry was used at three different sites. All measurements were taken and repeated randomly. RESULTS: Infrared and subcutaneous measurements did not agree well with rectal thermometry. Subcutaneous and rectal temperatures were highly repeatable, and subcutaneous temperatures were most agreeable to rectal temperatures. CONCLUSIONS: Further investigation is needed into subcutaneous implant sites and use of different infrared thermometers in this species.

Animals↗

PubMed1989

Pharmacokinetics of subcutaneous azidothymidine in rhesus monkeys.

The pharmacokinetics of subcutaneous bolus and continuous infusion azidothymidine (AZT) was studied in rhesus monkeys. Three animals received 100 mg/m2 as a bolus injection both intravenously and subcutaneously, with the order of administration randomly determined. Two animals received a continuous subcutaneous infusion of 25 mg/m2 per h for 12 or 24 h. AZT was measured in plasma by a reverse-phase high-pressure liquid chromatographic assay. Following intravenous bolus administration, AZT elimination was rapid, with a mean half-life of 1.2 h and a mean clearance of 318 ml/min per m2 (range, 200 to 441 ml/min per m2). The bolus subcutaneous dose was rapidly (time to peak concentration, 15 to 30 min) and nearly completely (fraction absorbed, 92%) absorbed without evidence of local tissue toxicity. With continuous subcutaneous infusion of AZT, the steady state was attained within 4 h and steady-state concentrations in plasma in the two animals exceeded 3.0 mumol/liter. No local tissue toxicity was observed at the infusion site. The subcutaneous route may be a practical alternative to intravenous administration of AZT and deserves further clinical study.

Animals↗

PubMed1978

Continuous subcutaneous insulin infusion: an approach to achieving normoglycaemia.

A study was performed to examine the feasibility of achieving long periods of near-normoglycaemia in patients with diabetes mellitus by giving a continuous subcutaneous infusion of insulin solution from a miniature, battery-driven, syringe pump. Twelve insulin-dependent diabetics had their insulin pumped through a subcutaneously implanted, fine nylon cannula; the basal infusion rate was electronically stepped up eightfold before meals. The blood glucose profile of these patients was closely monitored during the 24 hours of the subcutaneous infusion and compared with the profile on a control day, when the patients were managed with their usual subcutaneous insulin. Diet and exercise were standardised on both days. In five out of 14 studies the subcutaneous insulin infusion significantly lowered the mean blood glucose concentration without producing hypoglycaemic symptoms; in another six patients the mean blood glucose concentration was maintained. As assessed by the M value the level of control was statistically improved in six out of 14 studies by the infusion method and maintained in six other patients. To assess the effects of blood glucose control on diabetic microvascular disease it will be necessary to achieve long-term normoglycaemia in selected diabetics. The results of this preliminary study suggest that a continuous subcutaneous insulin infusion may be a means of maining physiological glucose concentrations in diabetics. Though several problems remain--for example, in determining the rate of infusion--longer-term studies with the miniature infusion pumps are now needed.

Adult↗

PubMed2006

Chronic ethanol feeding to rats decreases adiponectin secretion by subcutaneous adipocytes.

Chronic ethanol feeding to mice and rats decreases serum adiponectin concentration and adiponectin treatment attenuates chronic ethanol-induced liver injury. Although it is clear that lowered adiponectin has pathophysiological importance, the mechanisms by which chronic ethanol decreases adiponectin are not known. Here, we have investigated the impact of chronic ethanol feeding on adiponectin expression and secretion by adipose tissue. Rats were fed a 36% Lieber-DeCarli ethanol-containing liquid diet or pair-fed control diet for 4 wk. Chronic ethanol feeding decreased adiponectin mRNA but had no effect on adiponectin protein in subcutaneous adipose tissue. Chronic ethanol feeding also reduced adiponectin secretion by isolated subcutaneous and retroperitoneal adipocytes despite the maintenance of equivalent intracellular concentrations of adiponectin between subcutaneous adipocytes from ethanol- and pair-fed rats. Treatment with brefeldin A suppressed adiponectin secretion by subcutaneous adipocytes from pair-fed rats but had little effect after ethanol feeding. In subcutaneous adipocytes from pair-fed rats, adiponectin was enriched in endoplasmic reticulum (ER)/Golgi relative to plasma membrane; however, after chronic ethanol feeding, adiponectin was equally distributed between plasma membrane and ER/Golgi fractions. In conclusion, chronic ethanol feeding impaired adiponectin secretion by subcutaneous and retroperitoneal adipocytes; impaired secretion likely contributes to decreased adiponectin concentrations after chronic ethanol feeding.

Adipocytes↗