Split-dose recovery for radiation-induced tumours in rat skin.

Tumour-related recovery in rat skin was estimated from the dependence of tumour yield on time between split doses of electron radiation. Tumour yield versus dose was established at nine dose points, and at three points the dose was split into two equal fractions spaced 0-25, 3-2 or 6-3 hours apart. After irradiation the rats were observed periodically for at least 64 weeks, and at death the tumours were examined histologically. The dependence of yield on dose for single doses was consistent with a quadratic function up to a peak yield at about 1600 rad. The effect of split doses on tumour yield depended on the position on the dose--response curve. At the lowest split dose, the yield declined with a half-time of about 1-8 hours. At the intermediate split dose, an initial increase was followed by a decline with a half-time of about 3-9 hours. At the highest split dose, the tumour yield increased with time between exposures. Fractionation-induced increases in tumour yield were explained as a sparing effect on cell lethality, whereas tumour-related recovery per se was indicated at the lower two doses.     

Hormonal priming, induction of ovulation and in-vitro fertilization of the endangered Wyoming toad (Bufo baxteri)

The endangered Wyoming toad (Bufo baxteri) is the subject of an extensive captive breeding and reintroduction program. Wyoming toads in captivity rarely ovulate spontaneously and hormonal induction is used to ovulate females or to stimulate spermiation in males. With hormonal induction, ovulation is unreliable and egg numbers are low. The sequential administration of anovulatory doses of hormones (priming) has increased egg numbers and quality in both anurans and fish. Consequently, we tested the efficacy of a combination of human Chorionic Gonadotrophin (hCG) and Luteinizing Hormone Releasing Hormone analogue (LHRHa) administered as one dose, or two or three sequential doses to Bufo baxteri on egg numbers, fertilization and early embryo development. Spawning toads deposited eggs into Simplified Amphibian Ringers (SAR) solution to enable controlled in-vitro fertilization (IVF) with sperm from hormonally induced male toads. Unprimed females receiving a single mixed normally ovulatory dose of 500 IU hCG plus 4 micrograms of LHRHa produced no eggs. Whereas females primed with this dose and an anovulatory dose (100 IU hCG and 0.8 micrograms of LHRHa) of the same hormones, or primed only with an anovulatory dose, spawned after then receiving an ovulatory dose. Higher total egg numbers were produced with two primings than with one priming. Moreover, two primings produced significantly more eggs from each individual female than one priming. The cleavage rate of eggs was not found to differ between one or two primings. Nevertheless, embryo development with eggs from two primings gave a significantly greater percentage neurulation and swim-up than those from one priming. Of the male toads receiving a single dose of 300 IU hCG, 80% produced spermic urine with the greatest sperm concentration 7 hours post-administration (PA). However, peak sperm motility (95%) was achieved at 5 hours PA and remained relatively constant until declining 20 hours PA. In conclusion, Bufo baxteri egg numbers and quality benefited from sequential priming with LHRHa and hCG whereas spermic urine for IVF was produced from males with a single dose of hCG. The power of assisted reproduction technology in the conservation of endangered amphibians is shown by the release of nearly 2000 tadpoles produced by IVF during this study.     

Some teratogenic properties of ethanol and acetaldehyde in C57BL/6J mice: implications for the study of the fetal alcohol syndrome

To investigate the teratogenic effect of acute alcohol exposure, pregnant C57BL/6J mice were exposed to 25% ethanol (either two doses of 2.9g/kg or one dose 5.8g/kg) during the organogenic period either by intraperitoneal injections or by intubation. The incidence of malformations varied according to (1) the stage of embryonic development at the time of exposure, (2) the route of administration of the alcohol, and (3) the amount of alcohol given and the time period over which it was administered. Oral doses of alcohol were teratogenic although less so than the same dose given intraperitoneally, and two intraperitoneal doses four hours apart produced significantly more malformation than the same two doses six hours apart. The primary metabolite of alcohol, acetaldehyde, was also investigated for its teratogenicity. It was found that one or two doses of four percent acetaldehyde (0.32g/kg), administered intraperitoneally were teratogenic. A further attempt was made to raise blood acetaldehyde levels by exposing mice to disulfiram, an inhibitor of acetaldehyde dehydrogenase, prior to administration of alcohol. The disulfiram pretreatment did not increase the malformation rate. Treatment with alcohol on day 7 or 8 caused a variety of facial abnormalities, some of which were comparable to those seen in children with fetal alcohol syndrome. Exposure on day 9 or 10 resulted in limb defects. The results suggest that one or more episodes of heavy maternal drinking at critical periods in pregnancy may severely damage the embryo and may produce many features of the fetal alcohol syndrome.     

The effects of verapamil and ethanol on body temperature and motor coordination

Male, adult mice of the Binghamton heterogeneous stock received one of two doses of ethanol (1.0 g/kg or 2.0 g/kg in saline) alone or in combination with the calcium (Ca2+) slow channel blocker, verapamil (5.45 mg/kg in 25% v/v ethanol in saline). Hypothermic responses and motor incoordination were assessed in terms of rectal temperatures and rotorod activity both 20 and 60 min after drug administration. Verapamil alone did not affect body temperature, but it potentiated ethanol-induced hypothermia at both post-administration test times. Both verapamil and ethanol impaired muscular coordination and these effects were additive at the two observation periods. Verapamil did not affect ethanol blood levels from 10 to 80 min after administration of the drugs. Since motor impairment was observed when verapamil was administered with only its ethanol vehicle, this suggests a powerful interactive effect between the two drugs.     

百日草根尖和花药愈伤组织染色体制片技术

以种子萌发根尖和花药愈伤组织为材料,研究了取样时间、预处理方法对百日草染色体制片的影响。结果表明:根尖上午8:00～9:00,花药愈伤继代3～5d上午9:00～10:00为最佳取样预处理时间;采用三种药剂预处理活体根尖,以4℃下饱和对二氯苯溶液或0.002mol/L的8-羟基喹啉液预处理8h效果最佳,花药愈伤则以饱和对二氯苯溶液预处理6h效果最佳。本实验的预处理温度是固定的,可克服预处理随季节和时间温度的变化而带来的不稳定性,且百日草花药愈伤染色体观察为首次报道。     

Interaction of apolipoprotein AIV with cholecystokinin on the control of food intake

Apolipoprotein AIV (apo AIV) and cholecystokinin (CCK) are peptides that act both peripherally and centrally to reduce food intake by decreasing meal size. The present study examined the effects of intraperitoneally administered bolus doses of recombinant apo AIV, CCK-8, and a combination of subthreshold doses of apo AIV and CCK on 4-h food intake in rats that were fasted overnight. Apo AIV at 100 microg/kg reduced food intake significantly relative to the saline control for 1 h, as did doses of CCK-8 at or above 0.125 microg/kg. Doses of apo AIV (50 microg/kg) or CCK (0.06 microg/kg) alone had no effect on food intake. However, when these subthreshold doses of apo AIV and CCK were administered together, the combination produced a significant inhibition of food intake relative to saline controls (P < 0.001), and the duration of the effect was longer than that caused by the administration of either apo AIV or CCK alone. The satiation effect produced by CCK-8 + apo AIV was attenuated by lorglumide, a CCK1 receptor antagonist. We conclude that, whereas the intraperitoneal administration of doses of either recombinant apo AIV or CCK at or above threshold levels reduces food intake, the coadministration of subthreshold doses of the two peptides is highly satiating and works via CCK1 receptor.     

Effects of opioid blockade with nalmefene in older impotent men

We evaluated the effect of the opioid antagonist nalmefene on the HPG axis and on food consumption in 14 older impotent men. These patients had low to low normal mean serum testosterone values and normal gonadotrophin levels on screening evaluation. Normal response to GnRH was demonstrated in all the men. The protocol called for 24 hours of evaluation before and during administration of nalmefene 2.0 mg IV every 8 hours for 3 doses. During each 24 hour period, the following determinations were made: serum testosterone, FSH, and LH by five separate determinations between 8 AM and noon; 8 AM and 11 PM serum cortisols; 24 hour urine collections for free cortisol; and nocturnal penile tumescence (NPT). Food consumption was measured from 4 PM to 10 AM during the two periods. Nalmefene resulted in significant rises in testosterone, LH, and FSH. Nalmefene significantly elevated morning and evening cortisol measurements in all the patients. Nalmefene decreased total calorie consumption, principally by decreasing fat consumption. There was no effect on NPT. We conclude that in older impotent men, nalmefene acutely increases activity of the HPG axis and decreases calorie intake predominantly by decreasing fat consumption.     

Characterization of the effects produced by neurokinins and three agonists selective for neurokinin receptor subtypes in a spinal nociceptive reflex of the rat

In the awake restrained rat the intrathecal (i.th.) administration of 6.5 pmol-40 nmol of substance P (SP), neurokinin A (NKA) or one of two selective NK-1 receptor agonists [Pro9, Met(O2)11]SP, denoted ana1 and [beta-Ala4, Sar9, Met(O2)11]SP , denoted ana2 decreased reaction time (RT) to a noxious radiant heat stimulus in a dose-related manner. The following rank order of potency was observed in relation to this response: ana1 = ana2 greater than SP much greater than NKA. The decrement of tail-flick latency was greatest at 1 min and RT returned to the basal level within 6-11 min post-administration. However, in some rats SP produced a small increase in RT (anti-nociception) at 6-11 min post-administration. The i.th. administration of neurokinin B (NKB) or a selective NK-3 receptor agonist [beta-Asp4, MePhe7]NKB), denoted ana3 induced an antinociceptive effect which was greatest at 1 min and lasted less than 11 min after NKB or more than 30 min after ana3 administration. The magnitude of the increase in RT produced by 65 pmol-40 nmol doses of these peptides is ana3 much greater than NKB much greater than SP. The effect of NKB (8.0 nmol) was significantly blocked (P less than 0.005) by prior i.th. administration of naloxone (opioid antagonist) but not by idazoxan (alpha 2-adrenoceptor antagonist), [Thi5,8, D-Phe7]BK (kinin antagonist), or following bilateral adrenalectomy. From these results, we conclude that NKB-induced antinociception is mediated by the spinal release of an opioid and not through a BK or NA mechanism. The results also suggest that the nociceptive and antinociceptive effects of neuro-kinins are mediated by the activation of NK-1 and NK-3 receptor subtypes respectively, in the rat spinal cord.     

Topical analgesia for the cutting of split-skin grafts: a multicenter comparison of two doses of a lidocaine/prilocaine cream

The topical analgesic effect of two doses of a local anesthetic cream (EMLA, Astra) in the harvesting of split-skin grafts was compared in a double-blind multicenter trial. A standardized area of 200 cm2 at the donor site of 78 patients was randomly treated with 30 or 60 gm of cream 2 to 5 hours before the operation. There was no difference in pain between the groups (p = 0.53). In each group, 92 percent of the patients rated the pain as either none or slight, and 8 percent rated it as either moderate or severe. In conclusion, with the application times of 2 to 5 hours used in this trial, a dose of 15 gm EMLA cream per 100 cm2 is sufficient to provide analgesia for the cutting of split-skin grafts.     

The effects of subcurative doses of chloroquine on Plasmodium vinckei petteri gametocytes and on their infectivity to mosquitoes

The effects of subcurative doses of chloroquine on rodent and human Plasmodium transmission to the mosquito have been studied by several authors who showed a short-term (12 h) enhancement of gametocyte infectivity by the drug, restricted to chloroquine-resistant strains, and a long term (4-6 days) enhancement of gametocytogenesis of chloroquine-sensitive strains of Plasmodium chabaudi. We investigated both short- and long-term effects of chloroquine on Plasmodium vinckei petteri, a chloroquine-sensitive rodent Plasmodium strain. Chloroquine treatment reduced the index of gametocytogenesis to 73% (5 mg/kg) and 55% (2.5 mg/kg) of controls, on day 6 post-infection (p.i.). The reduction was statistically significant with 5 mg/kg chloroquine. However, the reduction of gametocyte numbers did not affect the transmission capabilities of the strain. Our experiments showed that doses of 1 mg/kg chloroquine had no effect on the oocyst counts, 12 h post-administration to mice. A statistically non-significant 61% reduction of oocyst numbers was observed in mosquitoes fed on mice treated with 5 mg/kg chloroquine. The effect of 5 mg/kg chloroquine administration on the infectivity of gametocytes to mosquitoes fed 1 h post-treatment was also investigated. An overall 41% reduction of oocyst numbers was observed. This immediate effect was statistically significant in 73% of the mice. These results are consistent with the hypothesis that the short-term enhancing effect of chloroquine on transmission is restricted to the drug-resistant strains of Plasmodium.     

Effect of actinomycin D on DNA replication and c-myc expression during rat liver regeneration

In an attempt to elucidate the mechanisms that control the hepatic DNA replication, effect of low doses of actinomycin D on DNA synthesis and c-myc expression during the early stage of liver regeneration was investigated. Small amounts of actinomycin D, in amounts that had no effect on the rate of RNA synthesis in normal rats, were multiple injected at 0, 2 and 4 hours after partial hepatectomy. DNA synthesis and c-myc expression in these rats were compared with those in untreated rats. Hepatic DNA synthesis in the treated rats was delayed about 4 to 6 hours in comparison with control rats. In contrast, time course of c-myc expression in inhibitor treated rats was very similar to that in control rats.     

Local subcutaneous heparin as treatment for venous insufficiency in replanted digits.

In the treatment of venous insufficiency unsuitable for surgical correction in replanted digits, a small ungual window was surgically created to infiltrate subcutaneous heparin in the congested digit. The initial heparin dose was 1000 units. This dose made possible a continuous bleeding during 24 to 48 hours, solely through the ungual window. Further doses were applied based on the degree of congestion of the replanted digit, but usually it was necessary to infiltrate up to 500 units of heparin every 24 to 48 hours until vascular stability was achieved. Three patients were treated with this technique. One opted for quitting the treatment. A replanted thumb suffered venous congestion on the seventh postoperative day and was treated with local subcutaneous heparin for 3 days. A replanted fingertip suffered venous thrombosis 24 hours after surgery and was treated likewise for 18 days. In these two patients, success was attained. Blood transfusions were carried out in the latter two, and none had any systemic changes in partial thromboplastin or thrombin time. This treatment is based on the mechanism of action of heparin at high doses but applied only to the congested segment. Besides their anticoagulant effect through antithrombin, high doses of heparin slow platelet aggregation, may induce angiogenesis, and have a longer-than-normal half-life. With the above technique, heparin has been applied to the congested segment at an approximate dose of 33,000 to 40,000 units/kg, and continuous bleeding solely through the ungual window for 24 to 48 hours has been achieved, which has allowed us to save two replanted segments with no complications at all. This method may offer another alternative for the medical treatment of venous insufficiency in replanted segments.     

Effect of a synthetic platelet activating factor on steroidogenesis of cultured porcine granulosa cells

An embryo-derived platelet activating factor has been demonstrated to play an important role in reproduction. This report examined the effect of various doses of a synthetic platelet activating factor on the production of progesterone by porcine granulosa cells in culture. Granulosa cells aspirated from ovarian follicles of prepubertal gilts were grown for 24 hours in Dulbecco's Modified Eagles Media: Ham's F-12 with 5% fetal bovine serum and 1 micrograms/ml insulin. Cells were washed once in serum-free media and then cultured for an additional 48 hours with 0 to 5000 ng/ml of the platelet activating factor in media containing either 0.25% bovine serum albumin or 1% fetal bovine serum. Cells grown with fetal bovine serum produced 50% of the amount of progesterone that was produced in the absence of serum. Low doses of the platelet activating factor caused a slight decrease in progesterone production. Higher doses (greater than 500 ng/ml) in serum-free media caused a marked decrease in progesterone production. Serum had a protective effect at high doses of platelet activating factor which was probably mediated by enzymatic degradation of the platelet activating factor. In summary, platelet activating factor had no stimulatory effect on production of progesterone by porcine granulosa cells in culture.     

Sperm quality and fertility of boar seminal doses after 2 days of storage: Does the type of extender really matter?

The present approach was designed to evaluate the extender effects on sperm quality and fertility of short-term refrigerated seminal doses from Landrace boars lodged in husbandry-controlled conditions. For this purpose, we analyzed the sperm quality of seminal doses diluted in short-term (Beltsville Thawing Solution) and extra-long-term (Duragen) extenders from Days 0 to 2 of storage at 17 °C during an 8-month period. Pregnancy rates and litter size were evaluated from double inseminations within an interval of 12 hours (36 and 48 hours of refrigeration) of multiparous females using seminal doses diluted in each extender type. Sperm quality was assessed from the analyses of sperm motility and kinetics, sperm viability, expressed as plasma and acrosome membrane integrity, membrane lipid disorder, intracellular calcium levels, and acrosin activity. Results indicated significant differences between the extenders in the sperm quality of seminal doses. Therefore, the seminal doses diluted in Duragen had higher percentages of progressive motile spermatozoa and membrane-intact spermatozoa than those diluted in Beltsville Thawing Solution throughout all the experimental months. Nevertheless, despite these differences in preserving the sperm quality, pregnancy rates (>90%) and litter sizes (>10 piglets born per litter) were similar between the extenders. Our results had great relevance from a practical point of view because they reported lack of an extender effect on the reproductive performance of seminal doses during short-tem storage.     

Morphological study of the rat pituitary follicle stimulating hormone cells after alternate day treatment with luteinizing hormone-releasing hormone (LHRH)

The action of the luteinizing hormone-releasing hormone (LHRH) on the hypophyseal gonadotrophins has either an activatory or inhibitory effect depending on the doses administered or on the treatment followed. Both factors can induce a different response in the two hormones. In this work, the effect after the administration of 8 doses (40 micrograms/day) of LHRH at intervals of 48 hours, on the serum levels of follicle stimulating hormone (FSH), as well as the numerical density, distribution, intensity of staining and morphometrical parameters of the cells which react against the anti-FSH serum, are assessed. It has been found that with the treatment an increase of FSH serum levels, without modification in the number of immunoreactive cells, but a clear increase in the lightly stained cells, is produced. The distribution of the reactive cells, uniform in normal animals, shows a large numerical density in the dorsal and posterior hypophyseal areas in the treated animals. No change was observed in the nuclear and cellular areas between the different groups.     

Reduction of 3-methoxytyramine concentrations in the caudate nucleus of rats after exposure to high-energy iron particles: evidence for deficits in dopaminergic neurons

Exposure to low doses of high-energy iron particles can alter motor behavior. The ability of rats to hang from a wire has been reported to be significantly degraded after exposure to doses as low as 0.5 Gy. In addition, deficits in the ability of acetylcholine to regulate dopamine release in the caudate nucleus (an area in the brain important for motor function) have been found. The concentrations of 3-methoxytyramine (3-MT), a metabolite of dopamine whose concentrations reflect dopamine release in vivo, were measured after rats were exposed to different doses of high-energy iron particles to gain further information about the effect of radiation on the dopaminergic system. Concentrations of 3-MT were significantly reduced 3 days after exposure to 5 Gy but returned to control values by 8 days. After 6 months, concentrations were again less than control values. Exposure to 5 Gy of high-energy electrons or gamma photons had no effect 3 days after exposure. Very high doses of electrons were needed to alter 3-MT concentrations. One hundred grays of electrons decreased 3-MT 30 min after irradiation but levels returned to control values by 60 min. Gamma photons had no effect after doses up to 200 Gy. These results provide further evidence that exposure to heavy particles can degrade motor behavior through an action on dopaminergic mechanisms and that this can occur after doses much lower than those needed for low-LET radiation.     

Patients' accounts of calling the doctor out of hours: qualitative study in one general practice.

OBJECTIVE: To investigate patients'' accounts of calling the doctor out of hours. DESIGN: Qualitative analysis of semi-structured interviews with two groups of patients who called their doctors out of hours from one general practice. SUBJECTS: 23 people who had called the doctor on their behalf or on behalf of another adult and 23 people who had called on behalf of a child between 6 pm and 8 am on a week day (omitting the weekend from 6 pm on Friday to 8 am on Monday). RESULTS: although respondents described symptoms as the main reason for the call, they also described a range of other factors that led to the call, including their feelings, concerns about specific illnesses, their responsibility for others, and their previous attempts to manage the problem themselves. They also described past experiences with health services that were important in explaining the current out of hours call or explaining their general approach to using services. CONCLUSIONS: The pursuit of a model of out of hours care based on medical necessity that neglects the psychosocial context of illness may not be appropriate. The importance of previous experiences of health services and contacts with health professionals in explaining current service use requires wider acknowledgement by health professionals across sectors. Separate educational programmes to encourage patients to use out of hours services more appropriately that neglect these issues may be too simplistic.     

Insulin tolerance in rats.

Insulin tolerance was studied in young (8- to 10-week-old) Wistar rats: a) after the administration of mounting doses of long-acting insulin (10, 40, 160 and 320 units/kg bw.) to animals fed ad libitum on two different diets); b) after the administration of long-acting insulin (1 and 5 units/kg b.w.) to animals which had fasted for different lengths of time. In rats fed ad libitum on the two diets, graded doses of insulin induced (except for the smallest dose) hypoglycaemia of roughly the same intensity, but varying in duration in correlation to the dose. The administration of insulin to fasting rats showed differences in insulin tolerance which were correlated to the duration of the fast. A significant decrease in insulin tolerance was already found after 6 hours. During the given testing period (72 hours), the lowest insulin tolerance was found after a 12 hours' fast and the highest after 48 hours. Insulin tolerance after 24 and 72 hours' fasting was approximately the same; it was higher than after 12 hours, but lower than after 48 hours. The initial blood sugar level (before administering insulin) was not in any way correlated to insulin tolerance determined at various intervals during fasting.     

Comparison of cefoxitin and ceftizoxime in a hospital therapeutic interchange program.

OBJECTIVE: To determine whether (a) ceftizoxime can replace cefoxitin in the prevention and treatment of various infections in a major teaching hospital, (b) a previously applied two-stage intervention program is an effective method of instituting a therapeutic interchange of ceftizoxime for cefoxitin and (c) the replacement of cefoxitin with ceftizoxime results in a more cost-effective therapy. DESIGN: Two-phase, open, sequential study. SETTING: Tertiary care teaching hospital. PATIENTS: One hundred patients who received cefoxitin during the 6 months immediately before the start of the interchange program (phase 1) and 100 who received ceftizoxime during the 6 months immediately after the start of the program (phase 2) were randomly selected. RESULTS: The demographic characteristics of the two patient groups were similar except for sex (p < 0.05). The cefoxitin doses were usually given every 6 hours (in 33% of the cases) or every 8 hours (in 61%), whereas the ceftizoxime doses were usually given every 12 hours (in 98%). Prescriber distribution was stable throughout the study period, the Department of General Surgery being responsible for about 70% of the orders. Prophylactic indications accounted for over 60% of the treatment courses. The proportion of prophylactic treatment courses that resulted in a successful clinical outcome did not differ between the two groups (cefoxitin 92% and ceftizoxime 91%). Of the empiric or directed treatment courses clinical success or improvement was observed in 89% of the cefoxitin and 91% of the ceftizoxime recipients. Microbiologic eradication was seen in 65% of the cefoxitin and 90% of the ceftizoxime directed treatment courses. Pathogens isolated during therapy were similar in the two treatment groups. Diarrhea was the most common adverse effect, occurring in 8% of the cefoxitin and 10% of the ceftizoxime recipients; no Clostridium difficile or C.-difficile-producing toxin was identified in these patients. The ceftizoxime therapy was 36% less expensive than the cefoxitin therapy on average, and the annual savings was estimated to be $83,123. An estimated 5615 drug doses were avoided annually, for an additional savings of $24,875 in drug administration. Therefore, the total estimated annual cost savings resulting from this two-stage interchange program was $107,998. Given the cost of $4856 to implement and maintain the program, the estimated net savings for the first year was $103,142. CONCLUSION: Ceftizoxime can replace cefoxitin in the prevention and treatment of various infections. The form of evaluation described herein is valuable when any formulary modification is being considered in a hospital.     

Hexamethonium and hydralazine hydrochloride for treatment of hypertension

Twenty-one patients have been treated for hypertension with oral doses of hexamethonium salts, Apresoline(R) or combinations of both. Three of 18 patients had good or excellent response to hexamethonium alone. Five of 13 treated with hexamethonium salts plus Apresoline had good or excellent results, as did 8 of 14 treated with Apresoline alone. The addition of very small doses of hexamethonium chloride to optimal doses of Apresoline improved the effect of the Apresoline in three patients. Postural hypotension and constipation due to hexamethonium were the most serious undesirable effects.