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PubMed1989

[Hemostatic effect of local intramural injection of dehydrated ethanol in the canine gastrointestinal tract].

The relative value of a subserosal injection of 98% ethanol (0.2 ml x 4) in controlling acute and chronic bleeding from serosal vessels was assessed in dogs. Blood flow was measured from gastric serosal vessels (average diameter 1.6 mm) severed immediately after, 24 hours after, and 48 hours after ethanol injection. Blood flow from severed colonic serosal vessels (averaging diameter 1.0 mm) was measured prior to and immediately after ethanol injection. The safety of ethanol injection was tested by endoscopically guided submucosal injection which were sequentially observed endoscopy at one hour, 24 hours, and weekly for weeks after injection. Ethanol injection had no effect on bleeding from larger gastric vessels unless the injection was made 24 or 48 hours prior to vessel severence. Ethanol injection was effective in reducing bleeding from the smaller colonic vessels when done immediately prior to vessel severence. Gastric submucosal injections led to ulcers which extended into the muscle layer at on week and healed completely by three weeks; none perforated or bleed. These data support the potential efficacy of therapeutic ethanol injection for the control of small vessel (1.0 mm diameter) bleeding and the potential prophylactic value against rebleeding from larger vessels. Further studies are needed to determine if these findings are organ related as opposed to being diameter specific.

Animals↗
PubMed1995

[A study on the effective way and dosage of intravas deferens injection of HFMC for male contraception].

To investigate the effective way and dosage of intravas deferens injection of HFMC for male contraception, Teflon tubes of 1 mm caliber were used to imitate intravas injection of HFMC. We injected HFMC first, then the precipitant; thus HFMC could adhere to the walls and blend with the precipitant to precipitate. Eight adult male rabbits, exposed reproductive ducts were injected with dyed HFMC in opposite directions (upward and downward), HFMC flowed out of the distal end of the vas easily when its volume was more than that of the vas. 14 adult rabbits were used for the comparison of sperm density and fertility index between upward and downward injections of HFMC, and between the dosage of HFMC (50 microliters and 100 microliters) injected upward. The results show that it is difficult to attain contraception by intravas injection of HFMC downward, but contraception is quite possible by intravas injection of HFMC upward providing the volume is enough. The result also suggest that HFMC should be injected into vas deferens upward first; its volume should be 3 time as much as the natural volume of the vas from the injecting point to the epididymal end. Then a little precipitant is injected into the vas.

Animals↗
PubMed1995

[Efficacy and tolerance of intracavernous injection of moxisylyte in patients with erectile dysfunction: double-blind placebo-controlled study].

OBJECTIVE: To evaluate the efficacy of intracavernous moxisylyle versus placebo in patients with erectile dysfunction of various origins. To assess the local tolerance and systemic safety of moxisylyte by self-administered injection. METHODS: Multicentre study, comprising two treatment phases: The first, double-blind phase, was conducted in two parallel groups of randomized patients, over a 1-month period (1 injection per week) in the investigator's office; the second phase was conducted under open conditions in the patient's home, over a period of 3 to 11 months. Self-administered injections (1 to 2 per week) were performed using a prefilled syringe containing 10 mg of moxisylyte. RESULTS: Out of 307 patients evaluated during the first phase, the qualitative and quantitative superiority of erectile response induced by moxisylyte compared to placebo was confirmed (p < 0.0001). The stability of the response to moxisylyte was also confirmed on 4 injections, and the frequency of responses compatible with sexual intercourse ranged from 48% to 52% from one injection to another. This efficacy was also maintained during the open phase, as 92% of the 4,487 self-administered injections generated positive erectile responses. The quality of these responses was considered sufficient to allow sexual intercourse after 62% of injections. The local tolerance was considered to be excellent for more than 95% of injections, without any major adverse effects, and a very low risk of prolonged erection and fibrotic reaction. The systemic safety was also considered to be excellent for more than 98% of erections. CONCLUSION: This study confirms the possibility of obtaining an erectile response by intracavernous injection of 10 mg of moxisylyte with a very low incidence of local and systemic adverse effects. It also tends to confirm the superior efficacy of moxisylyte by self-administered injections at home than by injection in the doctor's office.

Adult↗
PubMed1996

[Increase of blood levels of creatine kinase following intramuscular injection].

BACKGROUND: To analyze the effect of intramuscular injections of drugs on serum creatine kinase (CK) and to evaluate the possible existence of factors that lead to predict the probability of appearance of serum CK increase after injection. PATIENTS, MATERIAL AND METHODS: One hundred and seventy six consecutive patients admitted to a short-term medical ward for non-cardiac reasons who had normal serum CK levels, were selected for the study. 120 of them, selected for random allocation, received a single 0 multiple injections of drugs (with broad use in emergency medicine) in the gluteal muscle (group IM). The remaining 56 patients were the group control, in all the cases serum CK was measured at 0, 6, 12, 24 and 48 h since the admission. RESULTS: A significant elevation of serum CK levels occurred in 58.3% cases of group IM. The higher ratio of cases with increment of CK levels was observed after the injection of chlorpromazine (100%), followed of diclofenac (74.2%), metamizol (60%) and multiple drugs (60%). In most cases the highest increment was observed at 12 h after injection. A tenfold increase in serum CK level was found after intramuscular injection of diclofenac. There were significant differences between the elevation or not of serum CK and the type of drug administered (p < 0.05), sex (p < 0.05), and the solvent of the drug injected (p < 0.05). A higher probability of serum CK elevation was observed in men (p = 0.009) and when the solvent of the drug injected was ethanol (p = 0.0499). CONCLUSIONS: There is a high probability of serum CK increment after intramuscular injection of drugs. The sex and the solvent of the drug injected have influence on this probability. The magnitude of this enzymatic increment depends on the kind of the drug injected, being non steroidal anti-inflammatory drugs those higher serum CK increment have been produced in the present study.

Adolescent↗
PubMed1998

Doxorubicin chemomyectomy is enhanced when performed two days following bupivacaine injections: the effect coincides with the peak of muscle satellite cell division.

PURPOSE: Doxorubicin is effective in permanently removing muscle after direct injection into the eyelid for treatment of blepharospasm and hemifacial spasm. However, patients often require two or more injection series before full abatement of their spasms is achieved. Local anesthetics cause muscle necrosis, followed by regeneration, a process that requires activation and division of muscle satellite cells. This study examined whether the muscle toxicity of doxorubicin could be amplified by injection of doxorubicin into the eyelid of rabbits 2 days after a local anesthetic injury, perhaps exploiting the toxic effects of doxoribicin on satellite cells at the peak time of their division after injury. METHODS: Rabbit eyelids received two series of injections of bupivacaine and hyaluronidase spaced 18 hours apart. Two days later, the eyelids were injected with either 0.5 or 1 mg doxorubicin. Animals were monitored daily for onset and duration of skin injury. After 1 month, the eyelids were assessed for muscle loss using histologic and morphometric techniques. RESULTS: Injection of doxorubicin during the peak of satellite cell activation and division 2 days after injury significantly increased muscle loss over doxorubicin alone. This treatment did not result in increased skin injury compared with doxorubicin alone. CONCLUSIONS: Permanent muscle loss was increased when doxorubicin was injected at the peak of satellite cell division 2 days after injury of the muscle with bupivacaine in rabbit eyelid, taking advantage of the antimitotic effects of doxorubicin on satellite cell division during the period of active regeneration. When local anesthetic injection immediately preceded the doxorubicin injection, increased myotoxicity was not seen. The injection of doxorubicin into muscle 2 days after a previous injury maximizes muscle loss. The increased muscle loss provided by this double treatment may decrease the number of injection visits required by blepharospasm and hemifacial spasm patients during their course of treatment, thus reducing the number of patients with side effects, which increases with repeated exposures of the eyelid to doxorubicin.

Anesthetics, Local↗
PubMedDate not supplied

A pharmacokinetic study of injectable testosterone undecanoate in hypogonadal men.

Testosterone undecanoate (TU) provides testosterone (T) replacement for hypogonadal men when administered orally but requires multiple doses per day and produces widely variable serum T levels. We investigated the pharmacokinetics of a newly available TU preparation administered by intramuscular injection to hypogonadal men. Eight patients with Klinefelter's syndrome received either 500 mg or 1,000 mg of TU by intramuscular injection; 3 months later, the other dose was given to each man (except to one, who did not receive the 1,000-mg dose). Serum levels of reproductive hormones were measured at regular intervals before and after the injections. Mean serum T levels increased significantly at the end of the first week, from less than 10 nmol/L to 47.8+/-10.1 and 54.2+/-4.8 nmol/ L for the lower and higher doses, respectively. Thereafter, serum T levels decreased progressively and reached the lower-normal limit for adult men by day 50 to 60. Pharmacokinetic analysis showed a terminal elimination half-life of 18.3+/-2.3 and 23.7+/-2.7 days and showed a mean residence time of 21.7+/-1.1 and 23.0+/-0.8 days for the lower and higher doses, respectively. The area under the serum T concentration-time curve and the T-distribution value related to serum T concentration were significantly higher following the 1,000-mg dose than following the 500-mg dose. The 500-mg dose, when given as the second injection, yielded optimal pharmacokinetics (defined as mean peak T values not exceeding the normal range and persistence of normal levels for at least 7 weeks), suggesting that repeated injections of 500 mg at 6-8-week intervals may provide optimal T replacement. The mean serum levels of estradiol were normalized following the injections, and prolactin levels were normal throughout the study. Significant decrease of serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels was observed, with the decrease in LH levels being more pronounced. There were no significant differences in serum LH and FSH levels between the two doses. Sex hormone-binding globulin (SHBG) levels before any T therapy were near the upper limit of normal for adult men and were reduced by approximately 50% just prior to the second dose of TU. The decreased SHBG levels produced by the first TU injection could have led to lower peak total T levels and to a more rapid clearance of T following the second TU injection. We conclude that single-dose injections of TU to hypogonadal men can maintain serum T concentration within the normal range for at least 7 weeks without immediately apparent side effects. It is likely that this form of T would require injections only at 6-8-week or longer intervals, not at the 2-week intervals necessary with currently used T esters (enanthate and cypionate). This injectable TU preparation may provide improved substitution therapy for male hypogonadism and, in addition, may be developed as an androgen component of male contraceptives.

Adolescent↗
PubMed1999

Parent and general practitioner preferences for infant immunisation. Reactogenicity or multiple injections?

AIM: To explore the relative importance parents and general practitioners place on less reactogenic vaccines and multiple injections at each childhood immunisation encounter. METHOD: A random sample of western Sydney parents (n = 162) and GPs (n = 154) completed telephone questionnaires about their preference for either a single injection of pentavalent vaccine (whole-cell pertussis/diphtheria/tetanus/Hib/hepatitis B), or regimen containing the less reactogenic acellular pertussis vaccine requiring two separate injections (acellular pertussis/diphtheria/tetanus and Hib or three separate injections (acellular pertussis/diphtheria/tetanus and Hib and hepatitis B). Potential confounders were examined by univariate and multivariate analysis. RESULTS: Regimens containing acellular pertussis vaccine (2 injections or 3 injections) were preferred by 72% and 58% of parents respectively. Those whose children were already vaccinated were less concerned about side effects and were twice (or = 2.0, 95% CI 1.0-4.0) as likely to select the pentavalent (single injection) option. 69% and 77% of GPs preferred the pentavalent rather than the two or three injection acellular option, although previous experience with a systemic adverse reaction to immunisation increased their preference for the acellular pertussis vaccine (or = 2.9, 95% CI 1.1-7.6). Only 54% of parents and 28% of GPs favoured three injections at one visit. CONCLUSION: Parent and GP concerns regarding reactogenicity and multiple injections differ. Parents are more concerned about vaccine reactogenicity than multiple injections. However, if the GP recommends a particular regimen, it is likely to be accepted by parents.

Analysis of Variance↗
PubMedDate not supplied

The influence of intravenous Albunex injections on pulmonary arterial pressure, gas exchange, and left ventricular peak intensity.

Contrast ultrasonography may be used to assess regional tissue perfusion. The purpose of this study was to evaluate the safety and efficacy of a new, commercially prepared ultrasound contrast agent (Albunex) in dogs. The injections were administered from peripheral intravenous (IV), right atrial (RA), and pulmonary artery (PA) sites. Acute pulmonary hemodynamic and gas exchange effects of low-dose (0.5, 1.0, 2.0 ml) Phase I injections, and high-dose (2.0, 5.0, 10, 20 ml) Phase II injections of Albunex were evaluated in nine dogs. Immediately before and after each injection, pulmonary artery pressure (PAP) and oxygen tension (PO2) were determined. In addition, left ventricular cavity opacification was assessed visually and by videodensitometric off-line analysis. Visual assessment was performed by four blinded observers who graded on a scale of 0 to 3 (0 = no contrast enhancement of the left ventricular (LV) cavity; 1 = weak or suboptimal contrast enhancement; 2 = optimal or excellent contrast enhancement; and 3 = attenuation of the ultrasound signal following a contrast injection). Peak pixel intensity was also determined with videodensitometric analysis. Results showed that significant changes in PAP or PO2 were not noted after Albunex injections, regardless of injection site or dose range. The average change in PAP after Albunex injection was 1.0 mm Hg +/- 1.2 mm Hg (NS), and the average change in PO2 after Albunex injections was 6.2 mm Hg +/- 6.7 mm Hg (NS). The left ventricular cavity peak pixel intensity was dependent on both injection site (PA = RA > IV) and dose range (2.0 = 1.0 > 0.5).(ABSTRACT TRUNCATED AT 250 WORDS)

Albumins↗
PubMed2005

Effects of intra-peritoneal injection with NH4Cl, urea, or NH4Cl+urea on nitrogen excretion and metabolism in the African lungfish Protopterus dolloi.

This study aimed to (1) determine if ammonia (as NH(4)Cl) injected intra-peritoneally into the ureogenic slender African lungfish, Protopterus dolloi, was excreted directly rather than being converted to urea; (2) examine if injected urea was retained in this lungfish, leading to decreases in liver arginine and brain tryptophan levels, as observed during aestivation on land; and (3) elucidate if increase in internal ammonia level would affect urea excretion, when ammonia and urea are injected simultaneously into the fish. Despite being ureogenic, P. dolloi rapidly excreted the excess ammonia as ammonia within the subsequent 12 h after NH(4)Cl was injected into its peritoneal cavity. Injected ammonia was not detoxified into urea through the ornithine-urea cycle, probably because it is energetically intensive to synthesize urea and because food was withheld before and during the experiment. In addition, injected ammonia was likely to stay in extracellular compartments available for direct excretion. At hour 24, only a small amount of ammonia accumulated in the muscle of these fish. In contrast, when urea was injected intra-peritoneally into P. dolloi, only a small percentage (34%) of it was excreted during the subsequent 24-h period. A significant increase in the rate of urea excretion was observed only after 16 h. At hour 24, significant quantities of urea were retained in various tissues of P. dolloi. Injection with urea led to an apparent reduction in endogenous ammonia production, a significant decrease in the hepatic arginine content, and a significantly lower level of brain tryptophan in this lungfish. All three phenomena had been observed previously in aestivating P. dolloi. Hence, it is logical to deduce that urea synthesis and accumulation could be one of the essential factors in initiating and perpetuating aestivation in this lungfish. Through the injection of NH(4)Cl + urea, it was demonstrated that an increase in urea excretion occurred in P. dolloi within the first 12 h post-injection, which was much earlier than that of fish injected with urea alone. These results suggest that urea excretion in P. dolloi is likely to be regulated by the level of internal ammonia in its body.

Amino Acids↗
PubMed1990

Cleavage development of bovine oocytes fertilized by sperm injection.

Whole in vitro capacitated bovine spermatozoa were microinjected directly into the ooplasm of in vitro matured bovine oocytes in order to determine whether oocytes fertilized by sperm injection could undergo normal pronuclear formation and cleavage development. Immature oocytes recovered from follicles (2-5 mm) of unstimulated ovaries were cultured for 24-25 h in modified TCM 199 medium supplemented with heat-treated day 20 cow serum, luteinizing hormone (LH), and estradiol 17-B. In vitro capacitated, frozen-thawed spermatozoa were injected into the ooplasm, and the injected oocytes were cultured for an additional 24-28 h. Twenty-one percent (21/101) of the sperm-injected oocytes contained a sperm within the ooplasm; however, only 2% (2/101) cleaved. The remaining oocytes either did not contain a sperm or had degenerated. After oocyte activation induced by a 5 min incubation in 1 microM A23187, sperm nuclear decondensation occurred in the A23187-activated, injected oocytes but not in the unactivated, injected controls (37% vs. 0% after 3 h). Those injected, activated oocytes that contained a male pronucleus also exhibited a female pronucleus and second polar body. Furthermore, a significantly higher number (28%, 6/21) of the injected, activated oocytes cleaved to a two- to four-cell stage after 48 h than did the injected, unactivated oocytes (4%). These results indicate that, unlike hamster and rabbit oocytes, bovine oocytes are not sufficiently stimulated by the injection procedure to complete meiosis, but, upon activation by calcium ionophore, they will undergo normal-appearing cleavage development following fertilization by sperm injection.

Animals↗
PubMed1995

Use of injectable fat to obstruct the urethra in rabbits.

Bulking agents have been injected to correct urinary incontinence for at least 15 years. The injection seeks to increase bladder outlet resistance by partially obstructing the urethra and thereby reduce urinary leakage in patients with stress urinary incontinence. Although the implant is effective and requires a shorter in-hospital stay than more traditional procedures, no ideal implant substance has been discovered. To assess the effectiveness of injected fat as a bulking agent, we injected small volumes of perivesical fat into the bladder neck in New Zealand White (NZW) rabbits and tested the effect on the bladder. In eight rabbits, we harvested perivesical fat and partially closed the urethral lumen with an initial injection. A second injection 1 month later completely closed the urethral lumen. We injected six other rabbits with similar volumes of saline as controls. Two weeks after the second injection, we measured micturition frequency, bladder weight, response to electrical field stimulation, and response to bethanecol in each group. Fat implants were present at the injection site in each case 4 weeks after the first injection. Rabbits receiving fat implants had increased micturition frequency, increased bladder weight, and increased response to bethanecol and field stimulation. Previous studies have demonstrated that these changes are characteristic of mild outlet obstruction in rabbits. Injected fat can be made to close the urethra and create bladder outlet obstruction in rabbits. The short-term success of fat as a bulking agent in this experiment is encouraging and suggests the need for longer term studies.

Adipose Tissue↗
PubMed1999

Inflammatory arthritic process, iridocyclitis and immune response to articular and ocular antigens in Wistar rats injected with T. gondii trophozoites.

The present study deals with the potential role of T. gondii in inducing an arthritic inflammatory process. Wistar rats were injected subcutaneously (sc) into the right footpad with viable T. gondii trophozoites emulsified in incomplete Freund's adjuvant (IFA). The control group was injected with IFA. All parasite-injected animals developed a local inflammatory process characterized by hind limb swelling and marked restriction of ankle motility approximately 25 days after injection. Histopathogical studies of the joints, carried out 90 days after injection, revealed intense mononuclear infiltration, proliferation of granulation tissue, giant cells and necrosis in the synovia of 90% of T. gondii-injected rats. Strikingly, 40% (4/10) of the parasite-injected animals developed iridocyclitis, which was characterized by intense mononuclear infiltration around the iris-ciliary microvasculature in two animals and a slightly pronounced infiltrate of polymorphonuclear and mononuclear cells in two other animals. Antibodies to soluble T. gondii antigens (STAg) were detected in all parasite-injected rats. Antibodies against articular and ocular antigens such as proteoglycans, type II collagen, retinal S antigen and iris antigens were detected by ELISA in 40, 80, 70 and 70% of T. gondii -injected animals, respectively. Control animals injected with IFA failed to develop any articular or ocular process or humoral immune response. The present study demonstrated that footpad sc injection of Wistar rats with viable T. gondii trophozoites was able to induce a localized inflammatory arthritic process which, in some of the animals, was accompanied by iridocyclitis and immune response against articular and ocular components.

Animals↗
PubMed1983

Kinetics of 57Co-bleomycin in sheep after intra-arterial injection in the head and neck region.

Intra-arterial (i.a.) chemotherapy for the treatment of head and neck tumors is performed on the basis of clinical reports. The hypothetical aim of i.a. chemotherapy is to achieve higher drug concentrations in the tumor than are achieved by systemic intravenous (i.v.) administration. Therefore, it is postulated that i.a. chemotherapy leads to an increased therapeutic effect at the tumor site and to a decrease in systemic drug toxicity. The lack of adequate animal experiments and the absence of prospective randomized clinical trials comparing i.a. with i.v. chemotherapy led to the present kinetic study, concerned with various modes of administration of bleomycin with the aim of achieving high cytotoxic concentrations at the required site. Radioactive bleomycin (57Co-bleomycin) was injected locally (buccal plane, group I), intra-arterially (transverse facial artery, group II; superficial temporal artery, group III; external carotid artery, group IV), and intravenously (saphenous vein, group V) in five sheep per group. Between 1 and 360 min after injection of radioactive bleomycin the urine and the systemic blood activities were determined, and the activities in the hypothetical tumor area (buccal plane) were measured continuously. The animals were killed 360 min after injection and the activities in the hypothetical tumor area, in the lymph nodes draining this area (submandibular, parotic, lateral pharyngeal) and in different tissues and organs were determined. For all groups, 70%-80% of the injected bleomycin was eliminated by the kidneys, without any significant differences among the five groups tested. The systemic blood activities measured at 5-min intervals exhibited no differences for the groups injected i.a. (II-IV) and i.v. (V). Only animals which received local injections (group I) showed lower activities for 60 min after injection as compared with the other four groups. The activities of radioactively labeled bleomycin in the hypothetical tumor area during the entire experiment (360 min) were again similar for the groups injected i.a. (II-IV) and those injected i.v. (V). However, only animals injected locally (group I) showed significantly increased activities. After the death of the animals there was again no significant difference between i.a. and i.v. administration. Only local injection led to significantly increased tissue activities. Similar results also obtained for the lymph nodes draining the hypothetical tumor area.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1990

Single injection into the cerebrospinal fluid of antibodies against the secretory material of the subcommissural organ reversibly blocks formation of Reissner's fiber: immunocytochemical investigations in the rat.

An antibody (cf. Rodríguez et al. 1984b) raised in rabbits against the glycoproteins of the bovine Reissner's fiber (RF) was injected into the lateral brain ventricle of 38 rats with the aim to interfere with RF formation. The rats were killed 20 min; 1, 4, 8, 12 h; and 1, 2, 3, 5, and 8 days after the injection. Based on the fact that the material secreted by the subcommissural organ (SCO) into the cerebrospinal fluid (CSF) first condenses on the organ surface as a distinct layer (pre-RF material) and then becomes assembled to form RF and that both structures are distinguishable in tissue sections, three immunostaining procedures were applied. They served to visualize: (i) secretory material that had not bound the injected antibody; (ii) secretory material-antibody complexes formed in vivo; and (iii) antibody not bound to its antigen and present in the ventricles and the subarachnoid space. After a single injection of the above-mentioned antibody the following events were observed: (1) The antibody was present in the brain cavities for at least 8 h. (2) The injected antibody bound selectively to the pre-RF and RF. (3) Pre-RF displayed antibody binding during the 24 h following the injection. During the 2nd and 3rd post-injection days, the pre-RF was free of antibody, indicating that it was formed by newly released secretory material. (4) Approximately 4 h after the injection, the RF detached from the SCO and underwent fragmentation. Clusters of these fragments were found in the Sylvian aqueduct and fourth ventricle. (5) In the fragmented original RF the injected antibody against Reissner's fiber remained bound throughout the entire period of observation, i.e. for 8 days. (6) In rats of the 1-, 3-, 5- and 8-day-groups, RF was missing from the central canal of the spinal cord. (7) One day after the injection, a new RF structure started to grow from the rostral end of the SCO. This newly formed fiber could be distinguished from the original RF because of (i) its normal appearance; (ii) it did not display binding of the injected antibody. (8) At day 3, the growing RF had not yet extended to the Sylvian aqueduct. (9) At day 8, the new RF reached the fourth ventricle. Control experiments involved the intraventricular administration of (i) an antibody against the secretory material extracted from the entire bovine SCO; (ii) antivasopressin; and (iii) rabbit IgG. From these only antibody (i) bound to pre-RF and RF.

Animals↗
PubMed1990

Effects of subconjunctival 5-fluorouracil injections on the corneal endothelium and ciliary epithelium.

The effects of 14 successive daily subconjunctival 5-fluorouracil (5-FU) injections on corneal endothelial and ciliary epithelial cells were studied in pigmented rabbits. A total of 100 microliters 5% or 1.25% 5-FU was injected subconjunctivally in one eye and vehicle solution was injected in the other eye. At 12 h or 14 days after the 14th and last injection, both eyes were processed for observation with scanning or transmission electron microscopy. In other groups of rabbits injected with 5% 5-FU, effects on the corneal thickness, corneal endothelial permeability, blood-aqueous barrier permeability, intraocular pressure and aqueous flow rate were also studied. In the fellow eyes and treated eyes examined 14 days after the last injection, no significant morphological changes were seen. In eyes examined 12 h after the last injection, the following findings were obtained. The corneal endothelial cells showed moderate cytoplasmic swelling and mitochondrial swelling and vacuolation. The changes were dose-dependent and most marked in the area near the injection site, whereas they were minimal in the area apposing it. In the ciliary body adjacent to the injection site, disarrangement of the basal infoldings of non-pigmented epithelial cells was seen in eyes injected with 5% 5-FU, whereas no significant change was observed in those injected with 1.25% 5-FU. However, the physiological parameters examined remained unaltered.

Animals↗
PubMed2001

Effects on the fusimotor-muscle spindle system induced by intramuscular injections of hypertonic saline.

Intramuscular injection of hypertonic saline (HS) is a procedure widely adopted to experimentally induce deep muscle pain in humans. This study was undertaken to test whether intramuscular injections of HS (5%) influence the activity of primary and secondary muscle spindle afferents (MSAs) from homonymous as well as heteronymous muscles. The experiments were performed on six cats anaesthetised with alpha-chloralose. Usually responses of two to nine MSAs from gastrocnemius medialis (GM) and/or gastrocnemius lateralis (GL) muscles were recorded simultaneously, while HS was injected either into the receptor-bearing muscle (homonymous responses) or into a close (GM/GL) or remote synergistic muscle (posterior biceps, PB, heteronymous responses). The mean rate of discharge and the depth of modulation of the MSA responses to sinusoidal stretching of the receptor-bearing muscle were calculated. Out of the 42 afferents tested (7 from GM and 35 from GL), 38 (90%) exhibited statistically significant responses to injections of HS into homonymous and/or heteronymous muscles. With injections into the homonymous muscle, the average maximal increase in mean rate of discharge was 74% and the average decrease in depth of modulation was --18%. The mean duration of the effects was 2.1 min. The corresponding values for heteronymous injections into a close synergist were 87%, -17% and 2.1 min (GM or GL), and for injections into PB 52%, -11%, and 1.8 min. The majority of the responses (72%) were compatible with reflex action on static fusimotor neurones, whereas 20% of the responses could be attributed to mixed static and dynamic fusimotor action. The remaining 8% of the responses were attributed to inhibition of fusimotor activity. There were no statistically significant differences between the responses following injections into homonymous or heteronymous muscles. Injections of Tyrode's solution did not induce any significant alterations in MSA responses, implying that they were not induced by direct and/or injury effects of the injections. HS-related changes in MSA activity were completely abolished after the nerves to corresponding muscles were cut, confirming the reflex nature of the effects. Thus, intramuscular injections of HS induce reflex changes in MSA activity from both homonymous and heteronymous muscles, most likely via fusimotor reflexes. Predominantly static fusimotor neurones were activated. The possible role of the fusimotor-muscle spindle system in altered motor control during experimentally induced muscle pain is discussed.

Action Potentials↗
PubMed2000

Effects of macrophage-colony-stimulating factor on cyclophosphamide-injected mouse NK1.1+ cell activity.

We injected cyclophosphamide into mice and examined their natural killer (NK) activity both in vitro and in vivo. Cyclophosphamide injection temporarily abrogated the lung clearance activity of Yac-1 lymphoma cells, which is considered to be an index of NK activity in vivo. However, administration of recombinant human macrophage-colony-stimulating-factor (rhM-CSF) to cyclophosphamide-injected mice restored the lung clearance activity. To clarify whether the administration of rhM-CSF activated NK cells, we purified NK1.1+ cells from mice treated with cyclophosphamide and/or rhM-CSF and examined their functions (cytotoxicity, proliferation, and interferon gamma production) in vitro. Cyclophosphamide injection decreased the number, but did not suppress the functions of NK1.1+ cells. The numbers of NK1.1+ cells in cyclophosphamide-injected mice restored by rhM-CSF administration. And the functions of NK1.1+ cells from both saline-injected and cyclophosphamide-injected mice were accelerated by rhM-CSF administration. These results suggested that the temporary abrogation of NK activity in vivo caused by cyclophosphamide injection was due to a decrease in the number and not to suppression of the functions of NK1.1+ cells. The injection of cyclophosphamide into mice increased the number of tumor (B16 melanoma) nodules formed in the lungs and liver. However, treatment with rhM-CSF recovered the anti-metastatic activity in the lungs of cyclophosphamide-injected mice. These results show that administration of rhM-CSF restores NK activity suppressed by cyclophosphamide injection in vivo.

Animals↗
PubMed1980

Regional brain glucose utilization following intrastriatal injections of kainic acid.

Regional brain glucose utilization following intrastriatal injections of kainic acid (KA) was studied by [14C]deoxyglucose autoradiography. In halothane anesthetized rats intrastriatal injections of 0.5-1.9 nmol KA produced histological lesions characterized by neuronal necrosis and glial reaction which varied in volume from approximately 3 to 25 cu. mm. These lesions were restricted to the striatal injection site. Intrastriatal injections of 3.8 nmol led to large lesions in striatum but also in ipsilateral hippocampus, pyriform cortex, entorhinal cortex, and amygdaloid nuclei. Injection doses of 0.5-3.8 nmol KA produced a large increase in striatal glucose utilization within 1 h; 7 days after injections however, glucose utilization was reduced below control levels in a dose-dependent manner. In addition to striatum there were large transient increases in glucose utilization in deep layers of frontal cortex, substantia nigra pars reticulata, ventral tier nuclei of thalamus, and lateral septum. Each of these structures bear close physical or synaptic proximity to the striatal injection site. Also, structures far distant from the striatal injection site exhibited large, transient, dose-dependent increases in glucose utilization; these regions included hippocampus, pyriform cortex, entorhinal cortex, and amygdaloid nuclei. There was a close correlation between the development of areas of neuronal necrosis and a reduction in glucose utilization. These results suggest that intrastriatal injections of KA may cause metabolic and perhaps electrical activation not only of structures near or synaptically connected to the injection site, but also of far distant, but particularly 'sensitive' brain structures probably by diffusion of small amounts of drug. The occurrence of neuronal death in limbic structures after injections of relatively high doses of KA into striatum may result from prolonged firing in those circuits which continues without the prolonged presence of KA.

Animals↗