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Social factors related to syringe sharing among injecting partners: a focus on gender.

The study of social networks has become an increasingly utilized method of examining the relationship between injection drug users' social environment and risk of HIV. This study examined relational aspects of two injection drug users (IDUs) within a single social network as they relate to sharing syringes. Data presented in this study were derived from baseline interviews of 508 IDUs from Baltimore, MD. Analyses were performed separately for male and female participants in an effort to understand gender differences in social aspects of syringe sharing. Among this sample, women shared syringes with a significantly higher percentage of injecting partners compared to men. In separate multilevel logistic regression models, significant variables associated with males' and females' syringe sharing were: sharing drugs daily with female injecting partners, injecting partners' provision of drugs when indexes' were withdrawing, being sexual partners, and injecting partners' injecting speedballs. Factors associated with male injecting dyads sharing of syringes were: being kin, injecting partners' injection of heroin and daily drug use, and drinking alcohol together. Results from this study demonstrate the usefulness of examining relationship characteristics of injecting dyads related to syringe sharing as they differ between men and women.

Acquired Immunodeficiency Syndrome↗

Targeted killing of migrating glioma cells by injection of HTK-modified glioma cells.

The "bystander effect" describes the killing of nearby unmodified cells and herpes simplex thymidine kinase (HTK)-transduced cells by ganciclovir (GCV) treatment. This effect is thought to be produced by contact between these cells. In this study, we showed that injected glioma cells migrated rapidly to a place distant from the injection point whereas injected virus-producing fibroblast cells did not migrate in a murine brain model. Moreover, the initially injected glioma cells and glioma cells injected at a later time mix very well, even at a place distant from the injection point. This suggested that glioma cells migrating after injection could be targeted by HTK-modified glioma cells introduced in a second injection and be killed together by GCV treatment. Therefore, we injected HTK-modified glioma cells 3 days after injection of wild glioma cells to investigate whether wild-type glioma cells that migrated to a place distant from the injection point could also be killed by GCV treatment. Tumor growth was suppressed after the GCV treatment. Suppression of tumor growth of wild glioma cells is not solely mediated by the immune response, which may be triggered by the killing of HTK-modified glioma cells with GCV, because inoculation of HTK-modified glioma to the contralateral side followed by GCV treatment did not cure the initial wild glioma. Moreover, the migration of the second inoculum of glioma cells is necessary for effective killing, because early administration of GCV resulted in insufficient killing.

Animals↗

Stability and activity of alteplase with injectable drugs commonly used in cardiac therapy.

The stability, activity, and compatibility of alteplase with eight drugs frequently used in cardiovascular disease were studied. Alteplase 1 mg/mL was mixed with each of the following: heparin sodium 80 units/mL in 0.9% sodium chloride injection, dobutamine 10 mg/mL (as the hydrochloride salt) in 0.9% sodium chloride injection or 5% dextrose injection, dopamine hydrochloride 1.6 mg/mL in 0.9% sodium chloride injection or 5% dextrose injection, morphine sulfate 2 mg/mL in 0.9% sodium chloride injection or 5% dextrose injection, lidocaine hydrochloride 8 mg/mL in 0.9% sodium chloride injection or 5% dextrose injection, propranolol hydrochloride 1 mg/mL, metoprolol tartrate 1 mg/mL, or nitroglycerin 0.8 mg/mL in 0.9% sodium chloride injection or 5% dextrose injection. Each mixture was assayed immediately and after storage for 24 hours at 25 degrees C; mixtures containing heparin were also assayed at 4 hours. The alteplase concentration and percentage of the single-chain molecule in each mixture were analyzed by using size-exclusion high-performance liquid chromatography (HPLC). Alteplase bioactivity was determined by a clot-lysis assay. Drug concentrations were assayed by HPLC, pH values of the mixtures were determined, and the mixtures were visually inspected. Instability was defined as a > 10% decrease in concentration; inactivity was defined as a > 10% decrease in activity; incompatibility was defined as detection of a precipitate, opalescence, or color change. Alteplase was not stable in the presence of heparin sodium, morphine sulfate, or dobutamine and was not active in the presence of dopamine hydrochloride. Alteplase was compatible with and stable and active (in vitro) in the presence of lidocaine hydrochloride, propranolol hydrochloride, metoprolol tartrate, or nitroglycerin.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiotonic Agents↗

Factors associated with adolescent initiation of injection drug use.

OBJECTIVE: The purpose of this study was to evaluate the extent to which demographic, sexual, and non-injection drug use practices predict adolescent initiation of injection drug use. METHODS: Street recruited injection drug users 15-30 years of age in Baltimore, Maryland, who initiated injection within five years of study enrollment, completed a questionnaire that included a year-by-year history regarding the five years prior to initiation of injection. Factors associated with initiation during adolescence (< or = 21 years of age) versus young adulthood (>21 ) were determined using logistic regression. RESULTS: Of 226 participants, most were female (61%) and African American (64%). Median age of participants was 25; median age at initiation of injection was 23. Factors significantly associated with adolescent initiation in multivariate analysis included race other than African American, and practices prior to initiating injection including condom use, lack of cocaine use, exclusive crack smoking just prior to initiation, and smoking marijuana. Adolescent initiates also had shorter durations of illicit drug use prior to initiating injection. CONCLUSION: Short-term non-injection drug use, particularly exclusive crack smoking, was associated with adolescent initiation of injection drug use. Early prevention efforts targeting this high-risk group of younger drug users are warranted in order to delay or prevent onset of injection drug use.

Adolescent↗

Production of nuclear transfer horse embryos by Piezo-driven injection of somatic cell nuclei and activation with stallion sperm cytosolic extract.

We investigated the use of direct nuclear injection using the Piezo drill and activation by injection of stallion sperm cytosolic extract for production of cloned equine embryos. When metaphase II horse oocytes were injected with either of two dosages of sperm extract and cultured 20 h, similar activation rates (88% vs. 90%) and cleavage rates (49% vs. 46%) were obtained. The successful reconstruction rate of horse oocytes with horse somatic cell donor nuclei after direct injection using the Piezo drill was 82%. Four dosages of sperm extract (containing 59, 176, 293, or 1375 microg/ml protein) and two activation times (1.5-2 vs. 8-10 h after nuclear transfer) were examined. Cleavage and activation (pseudopronucleus formation) rates of oocytes injected with sperm extract containing 59 microg/ml protein were significantly (P < 0.05) lower than any other dosage. The percentage of embryos cleaving with normal nuclei in oocytes injected with the 1375 microg/ml preparation 1.5-2 h after donor injection was significantly (P < 0.05) higher than that of the 293 microg/ml preparation 8-10 h after donor injection (22 vs. 6%). Embryos developed to a maximum of 10 nuclei. Interspecies nuclear transfer was performed by direct injection of horse nuclei into enucleated bovine oocytes, followed by chemical activation. This resulted in 81% reconstruction (successful injection of the donor cell), 88% cleavage, and 73% cleavage with normal nuclei. These results indicate that direct nuclear injection using the Piezo drill is an efficient method for nuclear transfer in horse and cattle oocytes and that sperm extract can efficiently activate horse oocytes both parthenogenetically and after nuclear transfer

Animals↗

The use of an injectable, biodegradable calcium phosphate bone substitute for the prophylactic augmentation of osteoporotic vertebrae and the management of vertebral compression fractures.

STUDY DESIGN: A biomechanical study comparing two materials for augmentation of osteoporotic vertebral bodies and vertebral bodies after compression fracture. OBJECTIVES: To compare an injected, biodegradable calcium phosphate bone substitute with injected polymethylmethacrylate bone cement for strengthening osteoporotic vertebral bodies and improving the integrity of vertebral compression fractures. SUMMARY OF BACKGROUND DATA: Injection of polymethylmethacrylate bone cement into fractured vertebral bodies has been used clinically. However, there is concern about thermal damage to the neural elements during polymerization of the polymethylmethacrylate bone cement as well as its negative effects on bone remodeling. Biodegradable calcium phosphate bone substitutes have been studied for enhancement of fixation in fractured vertebrae. METHODS: Forty fresh osteoporotic thoracolumbar vertebrae were used for two separate parts of this study: 1) injection into osteoporotic vertebrae: intact control (n = 8), calcium phosphate (n = 8), and polymethylmethacrylate bone cement (n = 8) groups. Each specimen then was loaded in anterior compression until failure; 2) injection into postfractured vertebrae: calcium phosphate (n = 8) and polymethylmethacrylate bone cement (n = 8) groups. Before and after injection, the specimens were radiographed in the lateral projection to determine changes in vertebral body height and then loaded to failure in anterior bending. RESULTS: For intact osteoporotic vertebrae, the average fracture strength was 527 +/- 43 N (stiffness, 84 +/- 11 N/mm), 1063 +/- 127 N (stiffness, 157 +/- 21 N/mm) for the group injected with calcium phosphate, and 1036 +/- 100 N (stiffness, 156 +/- 8 N/mm) for the group injected with polymethylmethacrylate bone cement. The fracture strength and stiffness in the calcium phosphate bone substitute group and those in the polymethylmethacrylate bone cement group were similar and significantly stronger than those in intact control group (P < 0.05). For the compression fracture study, anterior vertebral height was increased 58.5 +/- 4.6% in the group injected with calcium phosphate and 58.0 +/- 6.5% in the group injected with polymethylmethacrylate bone cement as compared with preinjection fracture heights. No significant difference between the two groups was found in anterior vertebral height, fracture strength, or stiffness. CONCLUSION: This study demonstrated that the injection of a biodegradable calcium phosphate bone substitute to strengthen osteoporotic vertebral bodies or improve vertebral compression fractures might provide an alternative to the use of polymethylmethacrylate bone cement.

Absorbable Implants↗

Transitions to injecting drug use among noninjecting heroin users: social network influence and individual susceptibility.

OBJECTIVES: To determine the incidence/predictors of transitions to injecting among noninjecting heroin users (NIUs). METHODS: Street-recruited NIUs in New York City, March/1996-March/2003, were interviewed for a prospective cohort study about social network influence (communication promoting injecting; exposure to injectors) and individual susceptibility. A transition to injecting was the first drug injection following baseline. Hazards ratios (HRs) (P < 0.05) were estimated by Cox proportional hazards regression, stratified by baseline injecting history. RESULTS: Of 369 (64% of 579) followed, former-injectors were more likely to transition to injecting (33% or 53/160 vs. 12% or 25/209; 16.0/100 person-years-at-risk [pyar] vs. 4.6/100 pyar; HR = 3.25). Independent predictors among never-injectors included using > or =2 bags of heroin daily (HR = 7.0); social network influence (communication) and homelessness (HR = 6.3); shorter-term heroin use (HR = 5.3); social network influence (exposure) and physically abused (HR = 4.7); friends approve/condone drug injecting (HR = 3.5); lower perceived social distance from injectors (HR = 2.9); and younger age at first heroin use (HR = 1.2). Independent predictors among former-injectors were social network influence (communication) and lower perceived social distance from injectors (HR = 3.4); white race/ethnicity (HR = 2.0); not very afraid of needles (HR = 1.8); and younger age (HR = 1.1). CONCLUSIONS: The risk of initiating injecting was lower than the risk of resuming injecting. Social network influence facilitates transitioning to injecting among those susceptible. Interventions to prevent injecting should address both social network influence and individual susceptibility.

Adult↗

Underuse of intra-articular and periarticular corticosteroid injections by primary care physicians: discomfort with the technique.

Musculoskeletal disorders account for 11% to 13% of office visits in ambulatory care clinics and 9% of all physician visits in the United States. Intra-articular or periarticular aspiration or injections are an integral part of the management of arthritis or periarthritis. Our aim was to determine the use and level of comfort of administering intra-articular and periarticular injections by primary care physicians (PCPs) practicing in a university setting.A self-administered questionnaire with 20 questions querying experience and training in local injection therapy was mailed to 82 physicians (junior residents, senior residents, and faculty) offering primary care at the University of Chicago. Comfort scores were measured with a scale of 1 to 10 (1 = minimum and 10 = maximum). The response rate to the questionnaire was 67% (36 residents and 19 faculty). Seventy-one percent of PCPs routinely suggested the procedure for severe arthritis and bursitis, but only 19% had (self-administered) performed it themselves. Eighty-nine percent of the PCPs referred their patients to specialty clinics. Forty-eight percent referred their patients to rheumatology, 11.5% to orthopedics, and 29% to both. Other PCPs were consulted for the procedure by 9.6%. Discomfort with the performance of the technique was the predominant reason for 83% of the referrals. The mean comfort score for intra-articular or periarticular injections was 3.10 +/- 2.14 in general and 4.45 +/- 2.92 for knee joint. The mean comfort score for other joints and bursae ranged from 1.20 to 2.15. Ninety-five percent of PCPs regarded themselves to be inadequately trained. Regarding the training, 41% had received a lecture during medical school and residency, while 40% had received demonstration of the techniques during residency. Of the faculty, 26% had never received any formal lecture, and 5.2% had never received formal demonstration of the techniques during their training. Joint injections observed ranged from 89% for knee to 59% for shoulder and 22% for wrist joints. Only 11% of faculty had performed more than 5 intra-articular injections during their training. A need for formal training in these techniques was identified by 95% of the subjects, of whom 65% thought the residency period was the best time to do so. Performing 5 to 10 intra-articular injections during residency was considered optimal training by 60%. On subanalysis, the mean comfort scores were higher in the residents in general (3.60 +/- 2.29 versus 2.18 +/- 1.47;P = 0.01) as compared with faculty. The residents' scores were also higher across different joints as compared with those of faculty but assumed statistical significance only for olecranon bursa injection (2.32 +/- 2.76 versus 1.27 +/- 0.67;P = 0.04) and subacromial bursa injection (2.08 +/- 2.27 versus 1.27+/- 0.75;P = 0.06). The mean comfort scores were lower by 1.74 (P = 0.007) for women physicians. There is underuse of self-administered intra-articular and periarticular injection techniques by PCPs in the management of arthritis or periarthritis. The reasons include inadequate training and low comfort in performing these procedures. Eighty-nine percent of PCPs would refer their patients to subspecialty clinics for these "routine" injections. There is a clear need for a training in these procedures during residency.

Journal Article↗

Patients prescribed injectable heroin or methadone -their opinions and experiences of treatment.

AIMS: To describe the opinions and experiences of treatment of a cohort of patients prescribed injectable opiate treatment (IOT). DESIGN, SETTING, PARTICIPANTS: Cross-sectional survey of all patients on injectable diamorphine or methadone at a tertiary referral clinic in the northwest of England in June 2000. FINDINGS: A total of 104 subjects were prescribed IOT, mostly male (87.5%) and with a mean age of 36.3 years (SEM 0.66, range 20-53). The majority (75.0%) were prescribed injectable methadone with the remainder (25.0%) on injectable diamorphine. Most subjects (93.3%) used intravenously, many (58.7%) into the femoral vein. Treatment was sought most frequently in order to procure a drug supply of known dose and purity, to improve family relationships and to avoid trouble with the police. Half were satisfied with their treatment but many wanted to change to injectable diamorphine or to increase their doses. Subjects cited many advantages of injectable diamorphine over injectable methadone, although benefits of injectable methadone were acknowledged. CONCLUSIONS: Subjects articulated a consistent desire for IOT in order to 'stabilize' their lives in a number of ways. This sample was recruited from one of the country's largest specialist IOT clinics. The generalizability of this study's findings to all patients in the United Kingdom currently prescribed IOT, however, was not examined. Nevertheless, these findings suggest that clinicians and policy makers should be aware of many heroin users' perception of IOT as long-term treatment and their clear preference for injectable diamorphine. Further investigation of differential outcomes between oral and injectable OT and between different injectable opiates is warranted.

Adult↗

Public injecting and the need for 'safer environment interventions' in the reduction of drug-related harm.

BACKGROUND: One key structural dimension in the distribution of drug-related harm associated with injecting drug use is the injecting environment. Epidemiological evidence associates elevated blood-borne viral risk with injecting in 'public' and 'semipublic' environments. Yet the quality of evidence on public injecting and related viral risk is variable, and is lacking in many countries such as the United Kingdom. AIM: This commentary considers the micro-injecting environment as a critical dimension of risk, exploring the need for 'safer injecting environment interventions'. METHODS: We draw upon published research evidence and qualitative case examples. RESULTS: We note the limits in epidemiological evidence on public injecting and emphasize the need for ethnographic research to determine the 'social relations' of how drug users and risk practices interact with injecting environments. We identify three main forms of 'safer environment intervention': purpose-built drug consumption rooms; interventions within existing spatial relations; and spatial programming and urban design. While drug consumption rooms find evidence-based support, they are not a panacea. We emphasize the potential of interventions embedded within existing spatial and social relations. These include low-cost pragmatic interventions enhancing facilities and safety at public and semipublic injecting sites and, primarily, peer-based interventions, including peer-supervised injecting sites. We caution against spatial programming and urban design interventions which can cause the displacement of socially marginalized populations and the redistribution of harm. CONCLUSIONS: Public health interventions in the addictions field have in the past focused upon individual behavioural change at the cost of social interventions and environmental change. We wish to focus greater attention on reducing risks related to public injecting and encourage greater debate on 'safer environment interventions' in harm reduction.

Environment↗

Exploring risk perception and behaviour of homeless injecting drug users diagnosed with hepatitis C.

Injecting drug users (IDUs) are at the greatest risk of hepatitis C infection by using any item of injecting equipment that has come into contact with contaminated blood. Alongside this, homeless IDUs have been identified as being at increased risk of harm in their illicit drug taking behaviour. This study interviewed 17 hepatitis C positive homeless IDUs about their injecting practices. In-depth interviews explored the impact of a positive hepatitis C diagnosis on their injecting and identified their risk behaviours and perceptions. The interviews were tape-recorded, transcribed and analysed using the framework approach. Homeless IDUs engaged in both high risk and unhygienic injecting practices, such as using drugs outside and in public places, sharing injecting equipment and re-using cleaned needles. Excessive needle reuse whilst in prison was also identified. However, the findings were not universally bleak as a positive diagnosis of hepatitis C did lead to some behaviour change towards safer injecting and some adopted other lifestyle and behaviour changes. It was, however, common for homeless people to devolve responsibility for preventing hepatitis C transmission to their peers, especially when injecting with others. Knowledge regarding possible transmission through injecting paraphernalia appeared to make users more careful to reduce it through these routes. Placing a continuous emphasis on health promotion is therefore important in educating IDUs about the hepatitis C transmission risks associated with injecting drug use. Information regarding safer and hygienic use, including accurate information regarding the most effective methods to clean used equipment, must be re-enforced by people working with homeless injecting drug users.

Blood-Borne Pathogens↗

The non-specific enhancement of allergy. III. Precipitation of bronchial anaphylactic reactivity in primed rats by injection of alum or B. pertussis vaccine: relation of response capacity to IgE and IgG2a antibody levels.

SD rats were sensitized by an i.p. injection of 1 microgram or 10 micrograms ovalbumin (OA) together with 10 mg Silica gel. At the indicated time after sensitization, allergic response capacity of the animals was estimated by measuring changes in intratracheal pressure induced by an i.v. injection of 0.3 mg OA (low challenge dose) or 5 mg OA (high challenge dose). Animals given 1 microgram OA in Silica gel showed no response capacity at 14, 35 or 47-48 days after sensitization. Animals injected with 10 micrograms OA showed a clear-cut response with a peak at 14 days; at 7 weeks after immunization the response capacity had faded almost completely. Specific OA-IgE antibody and total IgE serum levels were examined by radioimmunoassay. A slight increase in OA-IgE antibody was recorded in animals injected 14 days before test with 10 micrograms ovalbumin and Silica gel; animals given 1 microgram OA and Silica showed no OA-IgE antibody. Five weeks after sensitization, some animals of each group were injected i.p. with 100 mg alum, B. pertussis vaccine (2 ml of Perthydral), or saline, all injections being made without any further antigen addition. 12-13 days after such an injection, alum-treated animals showed high response capacity at bronchial anaphylactic tests and high OA-IgE antibody levels but comparably low levels of total IgE. Animals injected with B. pertussis, on the other hand, showed low response capacity (bronchial anaphylactic tests and OA-IgE antibody levels) but high total IgE-antibody levels. The bronchial anaphylactic response in the B. pertussis-injected animals but not the alum-injected animals was significantly correlated to serum IgG2a antibody levels. These results show that injection of alum or B. pertussis vaccine without antigen can precipitate/enhance anaphylactic response capacity and production of specific and non-specific IgE and IgG2a.

Adjuvants, Immunologic↗

Analysis of in vitro lymphoproliferative responses and antibody formation following subcutaneous injection of Actinobacillus actinomycetemcomitans and Wolinella recta in a murine model.

The potential of Wolinella recta and Actinobacillus actinomycetemcomitans to cause abscesses and induce an immune response was tested in BALB/c mice. Mice were injected subcutaneously with W. recta, A. actinomycetemcomitans or a mixture of these 2 microorganisms. Mice injected with A. actinomycetemcomitans alone, or with both organisms, demonstrated abscesses at the injection site 2 days later, from which pure cultures of A. actinomycetemcomitans were isolated. Mice injected with W. recta had small, flat abscesses at the injection site from which no bacteria could be cultured. W. recta was cultured from injection sites only when associated with A. actinomycetemcomitans. Mice developed positive serum IgG antibody responses to W. recta by 20 days post-injection but not to A. actinomycetemcomitans whether injected in pure culture or mixed infection. In vitro lymphoproliferative responses following injection of W. recta and/or A. actinomycetemcomitans resulted in increased lymphocyte reactivity in unstimulated cultures and decreased in vitro responses to phytohemagglutinin. In vitro lymphoproliferative responses to Escherichia coli LPS or Salmonella typhimurium LPS were depressed in mice injected with A. actinomycetemcomitans, but not in mice injected with W. recta.

Abscess↗

Resistance to excessive bodyweight gain in risperidone-injected rats.

1. The present study was carried out to explain the resistance of rats injected subcutaneously with risperidone, the atypical antipsychotic drug, for 21 consecutive days at 0.1 mg/kg per day (a dose equivalent to the one used for patients) to result in an excessive bodyweight despite the increase in diet-uptake in rats against risperidone-induced decrease in body temperature. 2. Rectal temperature measurements were made in 8-week-old male Sprague-Dawley rats maintained under standard laboratory conditions using a 12 h daylight cycle. A s.c. injection of risperidone (0.05 mg/kg) produced hypothermia in rats, which was observed during the daily injection for 21 consecutive days. 3. Sera, white and brown adipose tissues, skeletal muscle and liver were extracted from 8-week-old male Sprague-Dawley rats injected subcutaneously with risperidone (0.01 or 0.1 mg/kg per day) or a vehicle for 21 consecutive days. Serum levels of lipids, ketones and thyroid hormone were measured. The mRNA expression levels in these tissues and organs of the genes encoding the substances involved in heat production and/or lipid metabolism were investigated by using quantitative real-time polymerase chain reaction amplification. 4. Serum nonesterified fatty acid levels in risperidone 0.1 mg/kg per day s.c. injected rats were significantly lower than those in vehicle-injected ones. Serum beta-hydroxybutyrate levels in risperidone-injected rats tended to decrease compared with those in vehicle-injected ones. The serum level of neither triiodothyronine nor thyroxine was affected by risperidone s.c. injection at the doses examined, although their values were within normal limits. 5. Risperidone injection (0.1 mg/kg per day) for 21 consecutive days upregulated mRNA expressions in white adipose tissue of uncoupling protein 3 which dissipates energy as heat; peroxisome proliferator-activated receptor (PPAR) gamma coactivator 1alpha which activates mitochondrial biogenesis to expand the oxidative machinery; and PPARalpha which is necessary for the fat-depletion of adipocytes for thermogenesis. The mRNA of lipogenic enzymes (acetyl-CoA carboxylase alpha, fatty-acid synthase and glycerol-3-phosphate acyltransferase), hormone sensitive lipase and beta1-adrenoceptor were also enhanced in white adipose tissue by the injection of 0.1 mg/kg per day risperidone. 6. These findings suggest that the materials for heat generation in white adipose tissue would be readily supplied, which in turn would reduce a storage of lipids in white adipose tissue resulting in the lower rate of bodyweight gain of rats.

Adipose Tissue↗

Inulin single injection clearance. Microsample technique useful in children for determination of glomerular filtration rate.

The agreement between single injection inulin (polyfructosan) clearance and two reference methods for glomerular filtration rate (GFR) determination, namely standard inulin constant infusion clearance and 51-Cr-EDTA single injection clearance, was investigated. Studies were also made to see whether different results were obtained when capillary and venous blood samples were used in the single injection clearance method. The investigation was made in children from one year of age, adult patients and volunteers. For the single injection technique with inulin or 51-Cr-EDTA, five to seven blood samples were taken in a period of up to 180 min after injection. A bi-exponential plasma disappearance curve was used for calculations of single injection clearances. Good agreement was obtained between venous inulin single injection clearance on the one hand, and standard inulin clearance (correlation coefficient r = 0.86) and 51-Cr-EDTA single injection clearance on the other (r = 0.85). With use of capillary blood samples in inulin single injection clearance, similar good agreement was obtained both with venous 51-Cr-EDTA and with venous inulin single injection clearance (r = 0.85 and r = 0.89 respectively). From these results we conclude that inulin single injection clearance is a reliable method for GFR determinations. This method is recommended, especially in children, as capillary blood samples can be used.

Adolescent↗

The effect of calcium injection on the intracellular sodium and pH of snail neurones.

1. Ion-sensitive glass micro-electrodes were used to measure the intracellular pH (pHi) and the intracellular sodium ion concentration, [Na+]i, in identified Helix aspersa neurones. 2. The injection of small volumes of 0-1 McaCl2, which increased the membrane potential by 10-15 mV for 1-2 min, had little or no effect on [Na+]i. Increases of up to 1 mM in [Na+]i could be reversibly induced by larger injections. 3. Calcium injection caused an immediate decrease in pHi, which appeared to be directly proportional to the amount of calcium injected. Injections causing hyperpolarizations of 10-20 mV which recovered in 2-5 min caused pHi decreases of 0-04-0-15 units. After each of these injections both pHi and the membrane potential recovered exponentially but with different time constants. 4. The injection of calcium at a low rate could decrease pHi without affecting the membrane potential. 5. Neither membrane potential nor pHi were affected by the injection of small volumes of 0-1 M-MgCl2, Injection of CoCl2 produced a large transient decrease in pHi but no significant change in membrane potential. 6. Exposure of the cell to saline equilibrated with 2-5% CO2 greatly reduced the pHi decrease caused by calcium injection but had only small effects on the membrane potential response. 7. It is concluded that most of the injected calcium is exchanged for protons inside the cell.

Animals↗

Stimulation by injected guanosine triphosphate of the sodium efflux in barnacle muscle fibres.

1. A study has been made of the mechanism by which injected disodium GTP stimulates the ouabain-insensitive Na efflux in single muscle fibres from the barnacle, Balanus nubilus. 2. Injection of GTPNa2 causes a stimulatory response which is usually transitory and almost completely reversed by injecting MgCl2 (but not KCl). 3. Injected 5'-guanylylimidodiphosphate, Gpp(NH)p, mimics this action of GTP but the reversal seen with injected Mg2+ is less pronounced. 4. (i) Pre-treatment of these fibres with verapamil reduces the size of the stimulatory response to GTP and Gpp(NH)p. (ii) Pre-injection of protein kinase inhibitor (PKI) or regulatory subunits reduces the response as well. (iii) Pre-treatment with imipramine or trifluoperazine reduces the response to injected GTP; in combination with verapamil, a greater reduction in response is seen. 5. Injection of EDTA leads to a stimulatory response which is transitory. This response is largely abolished by verapamil. 6. Injection of cholera toxin leads to a sustained stimulatory rather than a transitory response. GTP or Gpp(NH)p when injected following peak stimulation by cholera toxin leads to a moderate sustained stimulation. 7. These results support the view that the stimulatory response to injected GTPNa2 is the result of activation of Ca2+ channels and of increased availability of GTPMg and that these two conditions bring about activation of adenylate cyclase and hence activation of cyclic AMP-protein kinase by newly formed cyclic AMP.

Animals↗

Intravenous injection of Candida-derived mannan results in elevated tumor necrosis factor alpha levels in serum.

Intravenous injection of Candida albicans into mice produced elevated serum tumor necrosis factor alpha (TNF-alpha) levels. We hypothesized that immunostimulants released in vivo from C. albicans during fungal sepsis might contribute to the elevated levels of TNF-alpha in serum. We tested this hypothesis in mice with C. albicans mannan (CAM). Increased serum TNF-alpha levels were observed following intravenous and intraperitoneal injections of CAM. Injection of CAM into mice resulted in increased serum TNF-alpha concentrations that reached 1,200 pg/ml of blood, compared with 2,400 microg/ml of blood following injection of 10 microg of endotoxin. The response to CAM was concentration dependent, requiring a minimum dose of 20 microg of CAM per g of body weight. Sera from mice were tested 30, 60, 90, and 120 min after intravenous injections with CAM. TNF-alpha concentrations were minimal 30 and 120 min after intravenous injection and maximal 60 and 90 min after CAM injection. The relative distribution of CAM in vivo in decreasing order was determined to be as follows: blood > liver > lung > spleen, 90 min following injection of a single 5-mg dose of CAM. CAM was confirmed as the stimulating substance by utilizing anti-CAM antibodies in vivo to block the response. Rabbit anti-mannan antibodies administered by intraperitoneal injection 24 h before CAM injection significantly suppressed (P < 0.05) the accumulation of TNF-alpha in the sera. Dexamethasone administered to mice before intravenous injection of mannan significantly reduced (40 to 90% reduction; P < 0.05) the concentrations of TNF-alpha in the sera of treated mice. Thus, when in vivo CAM clearance mechanisms are exceeded, sufficient CAM may become available to stimulate TNF-alpha production, making CAM an important part of pathogenesis in Candida sepsis.

Animals↗