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Effects of timed melatonin injections on reproduction in pinealectomized Peromyscus leucopus.

Fifty reproductively mature female pinealectomized or sham-operated white-footed mice (Peromyscus leucopus) were injected daily for 7 weeks with 50 micrograms melatonin at 12 hr after lights on. The injections started either on the day following surgery or 2 weeks after surgery. All mice were maintained at room temperature under long-day photoperiod (LD 16:8). Pinealectomized and sham-operated mice injected immediately following surgery and sham-operated mice injected beginning 2 weeks after surgery had reduced reproductive tract weights (30 +/- 6, 33 +/- 6, and 33 +/- 3 mg, respectively) compared to the pinealectomized mice injected beginning 2 weeks after surgery (78 +/- 8 mg). In a second study 74 pinealectomized or sham-operated mice were injected at either 2, 7.5, 12, or 15 hr after lights on with 50 micrograms melatonin. Irrespective of surgical treatment, mice injected at 15 hr had a mean (+/- SE) reproductive tract weight (33 +/- 10 mg) which was substantially less than the 2-hr group (78 +/- 17 mg) while the 7.5- and 12-hr groups were intermediate (P less than 0.001). Pinealectomized and sham-operated animals responded similarly to melatonin injections at these four time points (P less than 0.35). The clearance rate of plasma melatonin after a single 50-micrograms melatonin injection or after 2 weeks of daily injections at either 2 or 12 hr after lights on was determined. Melatonin concentrations were determined using high-performance liquid chromatography and radioimmunoassay.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Analeptic effects of centrally injected TRH and analogues of TRH in the pentobarbitone-anaesthetized rat.

The effect of intracerebral injection of TRH and several biologically stable TRH analogues in the pentobarbitone anaesthetized rat was examined. Bilateral injection of TRH (5.0 micrograms total dose) and the analogues RX 77368 (0.01-1.0 microgram), CG 3509 (0.1-1.0 microgram), DN-1417 (1.0 microgram) and MK-771 (1.0 microgram) into the nucleus accumbens reduced the pentobarbitone-induced sleeping time. The TRH metabolite DKP (5 micrograms) had no effect on the sleeping time following intra-accumbens injection. Intra-septal injection of TRH (1.0-5.0 micrograms), RX 77368 (0.1-1.0 microgram) and CG 3509 (0.1-1.0 microgram) also reversed the pentobarbitone-induced sleeping time. In contrast, TRH (5 micrograms) injected into the striatum had no effect on the pentobarbitone-induced sleeping time, and CG 3509 (0.1 microgram) and RX 77368 (0.1 microgram) had weaker effects following intrastriatal injection compared to injection of these analogues into the nucleus accumbens and septum. Measurements of core temperature and respiration rate in rats following intra-accumbens or septal injection of TRH, CG 3509 and RX 77368 showed these peptides to reverse pentobarbitone-induced hypothermia and stimulate respiration rate. However, while intrastriatal injections of CG 3509 and RX 77368 caused an increase in respiration rate they had no effect on core temperature. These results suggest a close association between peptide-induced respiratory stimulation and reversal of pentobarbitone-induced anaesthesia. Since intra-accumbens and septal injection of dopamine (20-100 micrograms) failed to reverse anaesthesia, it is unlikely that the peptide-induced responses are mediated via dopamine release.

Anesthesia↗

Peptidergic control of male rat sexual behavior: the effects of intracerebral injections of substance P and cholecystokinin.

Behavioral experiments examined the roles of substance P (SP) and cholecystokinin (CCK) in male rat copulatory behavior. Male copulatory behavior was recorded subsequent to injections of different doses of CCK and SP into the medial preoptic-anterior-hypothalamic area (MPOA-AH), caudate/putamen (CP), or the lateral ventricles (LV) in sexually experienced male rats. In the first experiment, three different doses of SP (10, 100, and 200 ng/cannula) injected bilaterally into the MPOA-AH produced marked changes in several components of male copulatory behavior. Latencies were most affected. All three doses significantly shortened the interval to initiate copulation, and the 10 and 100 ng, but not 200 ng dose also significantly reduced ejaculation latencies. Injections of 10 ng of SP into the CP did not affect sexual behavior, while injections into the LV produced changes different from those of MPOA-AH injections. These data argue for some degree of site specificity of the effects of the MPOA-AH injections. Bilateral injections of 10 ng of SP into the MPOA-AH, were incapable of inducing copulatory behavior in castrated rats deprived of testosterone. Injections of an undiluted SP antiserum (2 microliters/cannula) into the MPOA-AH produced a dramatic impairment of male copulatory behavior. These injections significantly lengthened amount, intromission, and ejaculation latencies, while having no effect on the number of mounts or intromissions prior to ejaculation. In contrast, bilateral injections of CCK-8 (10, 100, and 200 ng/cannula) into the MPOA-AH failed to affect any parameter of male copulatory behavior.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Site-specific effects of intracerebral injections of three neurokinins (neurokinin A, neurokinin K, and neurokinin gamma) on the expression of male rat sexual behavior.

Accumulating evidence indicates that neurokinins play a role in the neural regulation of male rat copulatory behavior. We have previously reported that injections of the neurokinin substance P into the medial preoptic nucleus facilitated male rat copulatory behavior. Recently, a number of other neurokinins, neurokinin K (neuropeptide K), neurokinin A (substance K), and neurokinin gamma (derived from the same gene as substance P), have been identified in the mammalian CNS. Therefore, in a series of experiments we examined the effects on male copulatory behavior following bilateral injections of different doses of neurokinin K (NkK), neurokinin A (NkA), or neurokinin gamma (Nk gamma) into the medial preoptic area (MPOA), bed nucleus of the stria terminalis (BnST), or the caudate/putamen. Bilateral injections of NkK into the MPOA or BnST inhibited the expression of male copulatory behavior. The most marked effect was seen following bilateral injections of 0.25 and 0.52 nmol of NkK into the MPOA and the BnST. These injections produced a dramatic suppression of copulatory behavior in previously sexually vigorous male rats when compared to control injections. In contrast, bilateral injections of three different doses of NkA into the MPOA failed to affect any parameter of male copulatory behavior. Bilateral injections of 0.431 nmol of Nk gamma into the MPOA failed to affect the expression of copulatory behavior, but significantly delayed its initiation when compared to controls. Bilateral injections of 0.251 nmol of NkK into the caudate/putamen had no significant effect on copulatory behavior in sexually vigorous male rats when compared to control injections. The results of the present study provide further support for a role of neurokinins in the regulation of copulatory behavior in male rat. Taken together, these results suggest that the effects of neurokinins upon the expression of male copulatory behavior are site specific for brain regions in the sexually dimorphic vomeronasal pathway which includes the MeA, BnST, and MPOA.

Amygdala↗

Fever response in lean (Fa/-) and obese (fa/fa) Zucker rats and its lack to repeated injections of LPS.

The thermal responses of Fa/- and fa/fa Zucker rats to injections of sterile saline and to four injections of 20 micrograms/kg LPS at 3-day intervals were measured by means of radiotelemetry. In response to injections of saline, only the Fa/- rats developed a short stress-induced increase in abdominal temperature. Such a stress-induced rise of core temperature was also monitored in Fa/- rats after a change of the animals' cages. In response to the first injection of LPS, the Fa/- rats developed the same stress-induced rise in abdominal temperature as observed after injection of solvent followed by a biphasic fever, the first phase within 100 and 225 min, and the second phase within 240 and 480 min after LPS injection. In the fa/fa rats the stress-induced rise in body temperature and the first phase of LPS-induced fever were significantly suppressed, whereas the second phase of LPS-fever was identical in FA/- and fa/fa rats. In response to further injections of LPS no febrile response was measurable at all; just the short stress-induced rise in abdominal temperature remained manifest in the Fa/- rats. When the first injection of 20 micrograms/kg LPS was followed by injections of 100 and 1000 micrograms/kg LPS, a febrile response remained manifest, but the second phase of fever was attenuated in response to the repeated challenge with higher doses of LPS. The complete endotoxin tolerance observed in response to the second and further injections of 20 micrograms/kg seems thus to be due to a strongly reduced sensitivity to LPS after its first administration. Because data from the literature indicate a reduced sympathetic outflow to brown adipose tissue of fa/fa rats in general and during fever in particular, we tried to determine the activity of the sympathetic nervous system by measurement of excreted amounts of noradrenaline. Attempts failed to determine noradrenaline excretion during fever in lean and in obese animals. The daily excretion of noradrenaline at an ambient temperature of 22 degrees C (basal values) was 53.8 +/- 4.7 nmol/kg in Fa/- and 25.9 +/- 3.4 nmol/kg in fa/fa rats. These values were increased by a cold exposure (5 degrees C) for 24 h to 123.1 +/- 12.4 nmol/kg in Fa/- rats (229% of the basal value) vs. just 48.7 +/- 2.5 nmol/kg in fa/fa rats (188% of the basal value). This small, but significantly larger rise of cold-stimulated noradrenaline excretion in Fa/- rats is indicative of a reduced sympathetic function in the fa/fa rats, but does not explain the lack of stress-induced rise in body temperature and of the first phase of LPS-induced fever in the obese animals.

Animals↗

Depression of follicle stimulating hormone in bulls injected with follicular fluid.

Eight bulls were divided into two groups and injected with either charcoal-extracted steer blood serum or charcoal-extracted bovine follicular fluid (bFF). Ten-milliliter injections were given subcutaneous every 12 h for 4 wk. Jugular blood collected before, during and after the injection period was analyzed for follicle-stimulating hormone (FSH) and luteinizing hormone (LH) by radioimmunoassay. All bulls were exposed to restrained, estrual heifers for 15 min every 2 wk for 16 wk starting 4 wk before the first injection. The number of mounts and services by each bull was recorded. Semen was collected with an artificial vagina and evaluated on alternate weeks during the same period. The concentration of FSH in serum decreased (P < 0.05) by 12 h after the first injection and remained 61% lower than that of serum-injected bulls during the injection period. The concentration of FSH increased (P < 0.05) by 3 d after the last injection. Injections of bFF did not affect the concentration of LH in serum. Bovine follicular fluid injections significantly depressed FSH; however, libido, serving capacity, and semen characteristics were unchanged.

Journal Article↗

Neurochemical lesioning in the rat brain with iontophoretic injection of the 1-methyl-4-phenylpyridinium ion (MPP+).

Iontophoretic injections of the 1-methyl-4-phenylpyridinium ion (MPP+) were made in the dopaminergic part of the substantia nigra to see whether this injection technique could be used for inducing localized neurochemical lesions in dopaminergic cell groups and to assess the effects of MPP+ on non-dopaminergic neurons. Three days after the iontophoretic injection of MPP+, a gliosis or necrotic hole was found in the dopaminergic and non-dopaminergic target areas. This effect depended on the injection parameters that were used; iontophoretic injections of short duration (less than or equal to 3 minutes) and low current strength (1.5 microA) caused the gliosis, higher injection parameters gave lesions. The estimated injected amount of MPP+ was between 0.5 and 10.8 nmol. Control injections, with sodium iodide, sodium chloride or N-methylpyridinium iodide showed that the neurodegeneration is not a side-effect of the iontophoretic injection procedure. It is concluded that iontophoretically injected MPP+ is toxic for all neurons, irrespective of the neurotransmitter used, and also for glia cells and fibers of passage. Excessive formation of free radicals, causing induction of lipid peroxidation, may be involved in the neurodegenerative process observed.

1-Methyl-4-phenylpyridinium↗

High resolution autoradiographic determination of the topographic distribution of radioactivity in the hippocampal formation after injection of [1-14C]glucose or 2-deoxy[14C]glucose.

Using high resolution autoradiography, the accumulation of radioactivity after intravenous injection of [1-14C]glucose was measured in the corpus callosum, hippocampus, dorsal hippocampal commissure, somatosensory cortex, inferior colliculus and pontine periaqueductal grey. Autoradiograms were prepared by thaw-mounting 4 micron frozen sections on nuclear emulsion-coated slides, and were evaluated quantitatively with a computer-assisted video system for automated counting of silver grains. In all brain regions examined, silver grain densities were greater in rats killed 30 min after injection of [1-14C]glucose compared to rats killed 10 min after injection. After intravenous injection of [1-14C]glucose or 2-deoxy[14C]glucose, the relative uptake and retention of radioactivity in different hippocampal subregions was compared. Striking differences were found in the hippocampus between 2-deoxy[14C]glucose and [1-14C]glucose autoradiograms. After injection of 2-deoxy[14C]glucose, there were large variations in the uptake and retention of radioactivity among different pyramidal cell fields. The CA 3 pyramidal cell field retained considerably more radioactivity than other pyramidal cell fields after injection of 2-deoxy[14C]glucose, while after injection of [1-14C]glucose, the retention of radioactivity was similar in all pyramidal cell fields. After [1-14C]glucose injection, the dentate gyrus contained relatively high levels of radioactivity and more 14C accumulated in the granular layer, compared to the molecular layer. In contrast, after 2-deoxy[14C]glucose injection, there was uniformly less radioactivity throughout the dentate gyrus when compared to rats injected with [1-14C]glucose and there was no preferential accumulation of 2-deoxy[14C]glucose in the granular layer compared to the molecular layer.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Evaluation of different injection techniques in the gas chromatographic determination of thermolabile trace impurities in a drug substance.

Thermodegradation of labile compounds in the hot injection port of a gas chromatograph causes many problems and can lead to ambiguous, poorly reproducible results. Splitless injection used in trace analysis in order to achieve a lower detection limit may even enhance the difficulties due to the longer residence time of the volatized sample in the injection port. Different techniques were tested to avoid thermodegradation of an epoxide and its corresponding chlorohydrin in a drug substance: variation of the injector temperature, high inlet flow rate during injection by electronic pressure programming, and cool on-column injection. The results showed that on-column injection was superior to splitless injection. The chlorohydrin formed epoxide by release of HCl upon splitless injection. A more detailed investigation of the factors that affect epoxide formation indicates that active sites within the injector are responsible for the degradation and that the reaction is temperature dependent. However, results equivalent to those obtained by on-column injection were obtained for splitless injection when inert materials were used in the injector.

Chlorohydrins↗

Role of micro-chimerism in inducing immunological tolerance by intraportal injection of donor spleen cells in rats.

Recently, we reported that intraportal (IP) injection of donor spleen cells (SPCs) prevented liver allograft rejection. Moreover, we developed a new method using polymerase chain reaction (PCR)-mediated restriction fragment length polymorphism (RFLP) analysis, and demonstrated micro-chimerism (MC) at the DNA level in the spleen 14 days after IP injection. In the present study, the long-term presence of injected allogeneic SPCs was investigated at the cellular level by immunofluorescence staining as well as the DNA level using RFLP analysis. Male ACI (RT1a) rats were used as the donors and Lewis (RT1(1)) rats as the recipients. After DNA preparation from the lymphoid organs, RT1B beta domain 1 region was amplified by PCR, and RFLP analysis was performed with PvuII restriction enzyme. In the immunofluorescence staining, the monoclonal antibody, MN4-91-6, was used to detect the injected donor ACI SPCs in a frozen specimen. We did not detect MC in Lewis rats intravenously injected with 5 x 10(7) ACI SPCs on day 14. On the other hand, stable chimerism in the spleen was observed in intraportally injected rats up to 28 days after injection at not only the DNA level but also the cellular level. No chimerism was detected in other organs (including the thymus, lymph nodes, and liver). In conclusion, the long-term presence of injected allogeneic SPCs in the spleen was demonstrated after IP injection but not after IV injection, and this phenomenon may be one of the mechanisms involved in portal venous immunosuppression.

Animals↗

Increasing use and associated harms of crystal methamphetamine injection in a Canadian setting.

BACKGROUND: There is a growing concern surrounding crystal methamphetamine use in Canada despite surprisingly little empirical data to support such claims. We evaluated the trends in crystal methamphetamine injection and factors associated with injection of the drug among a cohort of injection drug users (IDU) in Vancouver. METHODS: We conducted a prospective analysis of factors associated with crystal methamphetamine injection among participants enrolled in the Vancouver Injection Drug Users Study (VIDUS). Since serial measures for each individual were available, variables potentially associated with crystal methamphetamine injection were evaluated using generalized estimating equations (GEE) with logit link for binary outcomes. RESULTS: Overall, 1587 IDU were enrolled into the VIDUS cohort between May 1996 and December 2004. The proportion of IDU who reported injecting crystal methamphetamine during the last 6 months increased during the study period (Cochran-Armitage trend test, p<0.001). In multivariate GEE analyses, crystal methamphetamine injection was independently associated with younger age (adjusted odds ratio [AOR]: 4.77, 95% confidence interval [CI]=3.40-6.70), Caucasian ethnicity (AOR=2.21, 95% CI=1.57-3.12), syringe borrowing (AOR=1.62, 95% CI=1.22-2.13), and syringe lending (AOR=1.40, 95% CI=1.02-1.86). INTERPRETATION: There was a significant trend towards increasing crystal methamphetamine injection in this setting and elevated HIV risk behavior and younger age were independently associated with crystal methamphetamine injection. Given that banning precursor chemicals has had a limited effect on reducing methamphetamine supply in other jurisdictions, pragmatic and effective interventions are needed to address the growing use of this drug.

Adult↗

Chemical fingerprint and metabolic fingerprint analysis of Danshen injection by HPLC-UV and HPLC-MS methods.

HPLC-UV and HPLC-MS techniques were used in fingerprint analysis of Danshen injection and its raw materials (roots and rhizoma of Salvia miltiorrhiza). HPLC profiles of Danshen injections from a Chinese pharmaceutical factory and their raw materials were established as their characteristic fingerprint and employed to assess their consistency and difference. To develop the representative fingerprint of Danshen injection, 10 batches of samples were analyzed under the same HPLC conditions. The results showed that 10 batches of Danshen injections had very similar HPLC fingerprints. To characterize the major constituents of Danshen injection for quality control, 11 major chromatographic peaks were characterized by their MS spectra and comparison with the reference standards. Through comparison of the HPLC profiles of Danshen injection with its raw material, it was found that they are greatly different, which indicated the changes of major constituents in the course of preparation procedure. In addition, the rat's plasma was analyzed by HPLC-MS technique after intravenous administration of Danshen injection at different time intervals to explore the in vivo metabolism of the major active constituents. Except for protocatechuic aldehyde, the major phenolic acids in Danshen injection appeared in rat's plasma after intravenous administration, but quantity of each phenolic acids was very different from that in Danshen injection. With the administration time prolonged danshensu and salvianolic acid B disappeared quickly, salvianolic D, lithospermic acid and salvianolic A slowly decreased and maintained relatively high concentration after 30 min of intravenous administration. This indicated that polyphenolic acids were significant for biological activity of Danshen injection. It might be concluded that chemical fingerprint combined with metabolic fingerprint is a useful means to control the quality and to clarify the possible mechanism of action of herbal products.

Animals↗

Electrophysiologic effect of injectates on peripheral nerve stimulation.

BACKGROUND AND OBJECTIVES: A small volume of local anesthetic or normal saline abolishes the muscle twitch induced by a 1ow current (0.5 mA) during electrolocation. This study examines the hypothesis that the mechanism of this phenomenon is primarily the electrophysiologic effect of the injectate on the electrical current density at the needle tip. METHODS: Five pigs were studied. An insulated Tuohy needle was inserted in each pig toward the left and right brachial plexuses and the left and right femoral nerves. The needle was advanced until corresponding motor responses were observed at each site, using a current of 0.5 mA. The effect of injecting 1 mL each of normal saline and 5% dextrose in water (NS and D5W) on muscle twitch was investigated at all 20 needle insertion sites. Changes in the conductive area induced by the injectates were also demonstrated using gel electrophoresis. RESULTS: In all cases, the muscle twitches were abolished immediately after the injection of NS and recovered instantaneously after a subsequent injection of D5W. The electrical resistance between the needle and the ground electrodes decreased instantly after the NS injection. The resistance not only recovered but also increased after the injection of D5W. In the gel electrophoresis experiment, the results demonstrated that the expanded conductive area induced by the saline column surrounding the insulated needle was similar to that observed with the uninsulated needle. CONCLUSION: The injection of a conducting solution (i.e., NS) rendered the current that was previously sufficient to elicit a motor response (0.5 mA) ineffective. The most likely reason for this change is that the conductive area surrounding the stimulating needle expanded after the injection and dispersion of the conducting solution (i.e., NS), thereby reducing the current density at the target nerve. This effect can be reversed by injecting a nonconducting solution (i.e., D5W) via the stimulating needle.

Animals↗

Quantitative pressure injection of picoliter volumes into Limulus ventral photoreceptors.

Many pharmacological probes must be applied to the interior of cells to produce their effects. Ideally, a method for injecting such materials should be simple, rapid, and independent of the chemical properties of the material to be injected. In addition, one might desire to confirm immediately that an injection occurred and to estimate the volume injected shortly thereafter. We report that these conditions are fulfilled when the injection of materials from micropipettes by pressure pulses is confirmed by visualization of injection-induced disturbances in cells viewed on a video monitor. Volumes of aqueous droplets subsequently injected into a nearby oil pool may be used to estimate the volumes injected into cells. We have obtained a calibration curve for these quantitative estimates of injected volumes by injecting radioactively labeled sulfate into Limulus photoreceptor cells. We find that the estimates are accurate within a range covering one order of magnitude. We assess the sources of systematic and random errors in making these estimates.

Animals↗

Drug-related deaths by region, sex, and age group per 100 injecting drug users in Scotland, 2000-01.

BACKGROUND: In 2000 and 2001, there were 292 and 332 drug-related deaths in Scotland, respectively. Of the 332 people who died in 2001, 65 were of female sex, 80 were younger than 25 years, and 112 were older than 34 years. We assessed the effect of region, sex, and age group on drug-related deaths in Scotland per 100 injecting drug users. METHODS: We used published regional estimates of current injecting drug users (n=22805), their sex (30% female) and age distribution (8% older than 34 years in mid-1990s), or corresponding data for problem drug users (21% older than 34 years in 2000) to compare observed with expected drug-related deaths by region, sex, and age group per 1000 population or per 100 injecting drug users. FINDINGS: Regional population-based expectations fitted poorly to observed drug-related deaths, but those based on injecting drug users fitted tolerably. Drug-related deaths in 2001 per 100 injecting drug users were significantly lower in female (0.9 [95% CI 0.6-1.1]) than in male drug users (1.5; 1.3-1.7). They were between two and six times more frequent per 100 injecting drug users older than 34 years than younger than 25 years, depending on whether current injecting drug users' age distribution was assumed to be the same as problem drug users' or as injecting drug users' in the mid-1990s (2.1 [1.7-2.5] or 5.3 [4.3-6.3], respectively). INTERPRETATION: Older and male injecting drug users were at highest risk of drug-related death. Injecting drug users' age distribution should be assessed and compared across countries.

Adolescent↗

In vivo distribution of radioactivity in mice after injection of biodegradable polymer microspheres containing 14C-labeled tetanus toxoid.

Radiolabeled tetanus toxoid (TT) was prepared by detoxifying chromatographically purified tetanus toxin with 14C-labeled formaldehyde. 14C-TT was encapsulated inside poly (D,L-lactide-co-glycolide, 50/50) microspheres (MS) of varying average size (approximately 10 microns and approximately 50 microns). Balb/c mice were injected subcutaneously with 5 Lf (approximately 15 micrograms) of 14C-TT, encapsulated in MS, mixed with blank MS without encapsulated antigen, as soluble antigen or adsorbed onto aluminum phosphate (AlPO4) and radioactivity was monitored at the site of injection, draining lymph nodes, blood, liver, spleen, and kidneys at various intervals. At one day, approximately 95% and 90% radioactivity disappeared from site of injection for soluble TT or blank MS mixed TT and AlPO4 adsorbed TT, respectively, whereas approximately 55% and 70% radioactivity disappeared from site of injection for MS of average size approximately 50 microns and approximately 10 microns, respectively. By 7 days, 99% of radioactivity disappeared from site of injection for soluble TT or blank MS mixed TT, whereas 2-3% radioactivity persisted at the site of injection for AlPO4 adsorbed TT for 4 weeks. In contrast, approximately 20% radioactivity stayed at the site of injection for MS injected mice up to 4 weeks. At all time points, large MS (approximately 50 microns) showed more radioactivity at the site of injection than small MS (approximately 10 microns). Other organs showing radioactivity were draining lymph nodes and kidneys. Small MS with encapsulated TT showed highest level of radioactivity in lymph nodes at 4 h. In kidneys, soluble and AlPO4 adsorbed TT showed a peak of radioactivity at 4 h whereas TT encapsulated in MS showed a peak of radioactivity at 7 days. These results indicate that AlPO4 did not act as a depot for TT at the site of injection, but TT encapsulated in MS did form a depot for approximately 1 month.

Animals↗

Metallothionein does not protect mouse endocrine cells from damage induced by alloxan injection.

Effects of metallothionein (MT) on pancreatic endocrine cells of mice, injected with alloxan and at different zinc status were studied. Mice were given drinking water containing four different concentrations of zinc (0, 0.05, 0.1 or 0.5%) for 18 days, and alloxan was injected once on the 14th day. When zinc was added to the drinking water, pancreatic zinc and MT contents increased after injection of alloxan, but did not change with injection of vehicle alone, except in the group of mice drinking 0.5% zinc in water. However, plasma glucose level was increased in all the alloxan injected groups, and was independent of their zinc status. In mice given water with 0.5% of zinc, both pancreatic zinc and MT contents were higher than control mice given water alone. There was no difference in zinc and MT contents of the pancreas in mice drinking 0.5% zinc in groups injected with either alloxan or vehicle. The increase in plasma alpha-amylase activity, an indicator of pancreatic exocrine toxicity, was observed only in mice drinking water with 0.5% zinc after injection of both alloxan and vehicle. Histochemically, degranulation of zymogen and duct-like structures of exocrine cells and atrophy and disappearance of islet cells were observed in alloxan-injected mice drinking 0.5% zinc in water. The zymogen degranulation was observed on the vehicle-injected mice drinking 0.5% zinc in water. MT was immunohistochemically detected in the exocrine cells of both alloxan- and vehicle-injected mice given 0.5% zinc in water. No MT was detected in islet cells of mice in any group. The results show that an increase of zinc content may be followed by induction of MT synthesis in the pancreas of mice given increasing amounts of zinc in drinking water. However, MT dose not provide any protection against damage caused by alloxan to endocrine cells of the pancreas.

Alloxan↗

Corticosteroid injections for lateral epicondylitis: a systematic review.

Patients with lateral epicondylitis (tennis elbow) are frequently treated with corticosteroid injections, in order to relieve pain and diminish disability. The objective of this review was to evaluate the effectiveness of corticosteroid injections for lateral epicondylitis. Randomised controlled trials (RCTs) were identified by a highly sensitive search strategy in six databases in combination with reference tracking. Two independent reviewers selected and assessed the methodological quality of RCTs that included patients with lateral epicondylitis treated with corticosteroid injection(s), and reported at least one clinically relevant outcome measure. Standardised mean differences were computed for continuous data and relative risks (RR) for dichotomous data. A best-evidence synthesis was conducted, weighting the studies with respect to their internal validity, statistical significance, clinical relevance, and statistical power. Thirteen studies consisting of 15 comparisons were included in the review, evaluating the effects of corticosteroid injections compared to placebo injection (n=2), injection with local anaesthetic (n=5), another conservative treatment (n=5), or another corticosteroid injection (n=3). Almost all studies had poor internal validity scores. For short-term outcomes ( or=6 months), no statistically significant or clinically relevant results in favour of corticosteroid injections were found. Although the available evidence shows superior short-term effects of corticosteroid injections for lateral epicondylitis, it is not possible to draw firm conclusions on the effectiveness of injections, due to the lack of high quality studies. No beneficial effects were found for intermediate or long-term follow-up. More, better designed, conducted and reported RCTs with intermediate and long-term follow-up are needed.

Adrenal Cortex Hormones↗