Developmental changes in rat thyroid responsiveness to thyrotropin administered by the subcutaneous and peroral route

It has been demonstrated that orally administered thyrotropin (bovine, bTSH) evokes an increase in circulating T4 and T3 levels in 15-day-old suckling rat pups, but not in weaned animals. Because the feedback mechanisms of the hypothalamo-pituitary-thyroid axis change dramatically during the neonatal period, we chose to examine the efficacy of exogenous bTSH in eliciting a thyrostimulatory response via the subcutaneous (sc) or peroral (po) route in rat pups at 5, 8, 12, and 15 days postpartum. Suckling pups were divided into four groups and received one of the following: (i) 2 IU bTSH/100 g body wt administered sc; (ii) distilled H2O (dH2O) sc; (iii) 2 IU bTSH/100 g body wt given po; (iv) dH2O po. Animals were sacrificed at Time 0 and 1, 2, and 3 hr post-treatment, and the collected serum was analyzed for T4 and T3 by RIA. Maximum serum T4 levels were attained at 2-3 hr post-treatment, and the T4 response to sc-bTSH was significantly greater than that of the po-bTSH groups at all ages examined. This difference became progressively greater with increasing age, due to a persistent decline in T4 responsiveness in animals receiving po-bTSH. No significant differences in T4 or T3 levels attained were observed in 8-day-old rat pups treated with rat vs bovine TSH, either sc or po. Percentage T4 response (vs basal levels) steadily declined between Days 5 and 15 postpartum, in both sc- and po-bTSH treatment groups. Percentage T3 responsiveness to sc-bTSH also declined between 5 and 12 days postpartum, after which time T3 generation increased. Our results suggest that the neonatal rat is highly responsive to exogenous TSH late in the first week of life, and that the permeability of the gut at this stage of development further facilitates the impact of orally ingested TSH in the suckling.     

Protective effect of various antioxidants on the toxicity of sulphur mustard administered to mice by inhalation or percutaneous routes

Protective effect of various antioxidants, trolox (water soluble analogue of vitamin E), quercetin (bioflavonoid) and glutathione reduced (GSH), was studied following sulphur mustard (SM) intoxication. SM, a blistering agent was administered to Swiss albino female mice through inhalation (1 LC50=42.3 mg/m3 for 1 h duration; 14 days observation for mortality) and percutaneous (1 LD50=154.7 mg/kg; 7 days observation for mortality) routes. The antioxidants were administered three times at the dose of trolox, 500 microg/kg; quercetin, 5 mg/kg and GSH, 400 mg/kg body weight by intraperitoneal injection, one immediately following SM exposure, then once each day for 2 days after SM treatment. The effect of antioxidants on survival, markers of oxidative damage and purine metabolites was investigated. Survival study animals were observed for 14 days. Oxidative markers (in blood, liver and lung) and purine metabolites (in blood and urine) were investigated 72 h after SM treatment. Survival time increased significantly following trolox and quercetin treatments through the inhalation route. Significant decrease in GSH and increase in the level of malondialdehyde (MDA) indicated oxidative damage to liver and lung tissues following SM inhalation and percutaneous exposure. Blood and urinary uric acid, end product of purine metabolism showed an increased following both routes of exposures. The antioxidants, trolox and quercetin protected the liver and lung tissues from oxidative damage caused by SM exposure through inhalation and percutaneous routes. This study showed that antioxidants could enhance survival time, protect liver and lung from oxidative damage and reduce accumulation of purine metabolites in blood following SM intoxication.     

Infection of wild rats with Angiostrongylus costaricensis by intraperitoneal subcutaneous route

Three groups of cotton rats (Sigmodon hispidus) were infected with Angiostrongylus costaricensis; the first was inoculated by stomach tube; the second intraperitoneally and the third subcutaneously. In all the groups each rat received 50 L3. The highest rates of infection (51.5%) were obtained by the intraperitoneal route, followed by oral inoculation (47.1%). Poor results were observed (10.5%) subcutaneously.     

Rapid thin-layer chromatography of various weak analgesics in saliva

A thin-layer chromatographic method was developed to analyze phenacetin, 4-amino-phenazone and N-methyl-4-aminophenazone (5 and 1.25 μg/ml); bucetin (4-ethoxy-β-hydroxybutyranilide), propyphenazone and N-acetyl-4-aminophenazone (2.5 and 1.25 μg/ml); phenazone (15 and 1.25 μg/ml); and N-acetylsalicylamide (0.25 μg/ml). The method was designed to study the bioavailability of different commercial tablets from salivary concentration data.     

Evaluating postoperative analgesics in mice using telemetry

The study examined the efficacy of preemptive or postoperative analgesia on surgical pain in the mouse. Radiotelemetry transmitters were surgically implanted in 28 female ICR mice. A mock ova implantation surgery was then performed. Mice were treated with a single dose of buprenorphine or flunixin meglumine prior to or after surgery, three doses of buprenorphine, or were untreated. Heart rate, blood pressure, home cage activity, food and water consumption, and body weight were measured. The no-analgesia group showed no significant differences between any parameters collected prior to surgery and those collected at similar times during the day of surgery. Significant increases in mouse activity on the day of surgery occurred with all analgesic treatments, compared with pre-surgical activity. There were no consistent significant changes in any other telemetry parameter after treatment with analgesics compared with no analgesia. Food consumption and body weight the day after surgery were reduced significantly in the animals treated with three doses of buprenorphine compared with untreated mice and mice given a single dose of buprenorphine. We conclude that the mock ova implant procedure does not induce sufficient pain to cause alterations in heart rate and blood pressure in the mouse. Activity was significantly reduced in the first 6 h after surgery in mice without analgesia, compared with activity prior to surgery. There were no significant differences between pre-emptive and postoperative analgesia. Body weight and food and water consumption were poor measures of pain because analgesia alone affected these parameters.     

Lack of carcinogenicity of agaritine by subcutaneous administration in mice

Agaritine (A), an ingredient of the cultivated mushroom of commerce Agaricus bisporus, was administered by subcutaneous injection to two groups of randomly bred Swiss mice. In the first group the animals of both sexes were treated at a 100 g/g body weight basis five times at weekly intervals, while in the second group the mice received a single A treatment of 100 g/g body weight for females and 50 g/g body weight for males. The administration of the compound resulted in no detectable carcinogenic effect in the animals. Since some of the breakdown products of A were shown to be carcinogenic in mice and the mushroom itself was found to be mutagenic, the field is discussed in the light of the obtained results.     

Inhibition of inflammatory angiogenesis by distant subcutaneous tumor in mice

We investigated angiogenesis, inflammatory cells accumulation and endogenous production of cytokines in sponge implants of tumor-bearing mice. Seven days after inoculation of Ehrlich tumor cells (2.5 x 10(6)), sponge discs were implanted subcutaneously in the dorsa of mice to induce the formation of fibrovascular tissue. The implants of tumor-bearing and non tumor-bearing animals were assessed for neovascularization and leukocyte accumulation, together with levels of relevant cytokines, vascular endothelial growth factor VEGF), tumor necrosis factor alpha (TNF-alpha), CXCL1-3/KC and CCL2/JE. In the implants of tumor-bearing animals angiogenesis (assessed by hemoglobin content and VEGF levels in the implants) and leukocyte accumulation (assessed by myeloperoxidase -MPO- and N- acetylglucosaminidase-NAG-enzyme activities) were all significantly less than those in the implants of non tumor-bearing animals. Although the chemokine CXCL1-3/KC was lower in the implants of tumor-bearing animals, the chemokine CCL2/JE was increased in this group. The production of TNF-alpha in the implants was not modified by the presence of the subcutaneous tumor. The combination of the methodologies used in this study has provided a novel approach to investigate the interaction between two distinct proliferating tissues that share common features (angiogenesis, cell recruitment, inflammation) and has shown that the predominant inhibitory effect of a tumor mass over repair process is associated with altered cytokine production.     

Comparative evaluation of various analgesics in reducing pain in irreversible pulpitis

It is of interest to evaluate a single dose of three different analgesics compared to placebo in patients with symptomatic irreversible pulpitis. 120 patients were enrolled with severe pain in this prospective clinical trial. Patients were randomly divided into four groups after shaping and cleaning of root canals. This includes placebo, piroxicam 20mg, acetaminophen 325mg with aceclofenac sodium 100mg and acetaminophen 650mg. Participants were given a questionnaire to note the pain scores at various time intervals (6 hrs, 12 hrs, and 24 hrs) along with the respective tablets in a concealed manner. Data thus collected was analyzed for statistical significance. The severity of pain decreased in all the three interventional groups compared to the control group (p <0.01) at 6 hours. Zerodol-P and dolonex showed better pain reduction in comparison to the placebo and dolo 650 group (p <0.05) at 12 and 24 hours. Data shows that both zerodol-P and dolonex groups had similar effects at all time intervals. Thus, a single dose of analgesic such as Zerodol-P and Dolonex following shaping and cleaning of root canals relieved pain at all time intervals of the treatment. However, Dolo 650 performed better during the initial 6hrs after completion of the shaping and cleaning of root canals compared to the placebo.     

Action of opiate peptides and narcotic analgesics on the cerebral cortex

The chronic experiments on freely moving cats have shown that the opiate peptides, FK33--824 (Tyr--D--Ala--Gly--MePhe--Met(o)--ol) and tetrapeptide (Tyr--D--Ala--Gly--Phe--NH2), as well as the narcotic analgesics, morphine, phentanyl and pentazocine in doses close to analgesic ones, suppress the recovery cycles of primary responses (PR) in the second somatosensory and associative zones of the brain cortex, recorded at paired stimulation of the fibres of thalamo-cortical radiation (TCR). In larger doses these agents slightly increase PR recorded at single stimulation of TCR, provoke the convulsive discharges on EEG and motor excitation of the animals. Naloxon eliminates all the mentioned effects of the tested opiate peptides and narcotic analgesics.     

A comparative analysis of distribution of glyprolines administered by various routes

The distribution of the glyprolines Pro-Gly-Pro and Thr-Lys-Pro-Arg-Pro-Gly-Pro (Selanc) was analyzed and compared in tissues of rat organs after different ways of their administration using the peptides uniformly labeled with tritium. Comparative data on changes in concentrations of the peptides in the rat organs after their intraperitoneal, intranasal, intragastric, and intravenous administration are given. The intranasal administration of both peptides was shown to be optimal for the delivery of glyproline molecules in the CNS. A high affinity of the studied glyprolines for gastric tissues was found for all the ways of their administration. We suggest that a high efficiency of action of glyprolines on homeostasis of the gastric mucous tunic was partially provided by accumulation of these peptides (to high concentrations) in gastric tissues.