RESUMEN

Phosphoramide mustard and acrolein are toxic and reactive metabolites of the widely used anticancer drug and known teratogen cyclophosphamide. To study the mechanism(s) involved and to determine which of the active metabolites of cyclophosphamide is responsible for the production of limb malformations, the effects of exposure of cultured limb buds to phosphoramide mustard and acrolein were investigated. Fore- and hindlimbs were excised from ICR mice on day 12 of gestation and cultured in roller bottles for 6 days. Limbs were exposed to either phosphoramide mustard or acrolein (10 or 50 micrograms/ml) for the first 20 hours of the culture period. Exposure to phosphoramide mustard produced limb reduction malformations in both the fore- and hindlimbs; total limb bone area was greatly reduced, while the relative contribution of the paw to this area in forelimbs was increased. There was a fourfold reduction in both DNA and RNA; protein content was reduced only by one-half. Alkaline phosphatase activity was significantly decreased in fore- and hindlimbs exposed to phosphoramide mustard, whereas creatine phosphokinase activity was only reduced in hindlimbs in the limbs exposed to the higher concentration of phosphoramide mustard. Exposure to acrolein also produced malformed limbs with a mangled appearance; however, total limb bone area and the relative contribution of the long bones versus paw structures were not altered. Acrolein exposure had little effect on growth parameters such as DNA (decreased only in hindlimbs exposed to 50 micrograms/ml), RNA (increased in hindlimbs exposed to 50 micrograms/ml), or protein content. Alkaline phosphatase and creatine phosphokinase activities were not altered in acrolein-exposed fore- or hindlimbs. Thus, phosphoramide mustard and acrolein have dramatically different effects on developing limbs in vitro; this observation may indicate that they have different targets and/or mechanisms of action as teratogens in the limb. The effects of phosphoramide mustard are very similar to those of "activated" cyclophosphamide (4-hydroperoxycyclophosphamide).

Asunto(s)

RESUMEN

Opioid kappa-agonists bremazocine and dynorphin (1-13), sigma-agonist SKF 10.047 and delta-agonist D-Ala2, D-Leu5-enkephalin (DADL) induce postural asymmetry of rats hind limbs under subarachnoidal administration below the level of spinal cord section (T3-T4). The side of the flexed leg depends on the opioid agonist type: bremazocine and dynorphin (1-13) induce predominantly right flexion. SKF 10.047--the left flexion, but not in all doses, DADL--in small doses (1 and 100 pg per animal)--of the right one, in larger doses (up to 10 ng per animal)--of the left one. Saline and opiate mu-agonist morphine do not induce postural asymmetry. Opiate antagonist naloxone prevents asymmetry development when injected prior opioid agonists, and also decreases the number of asymmetries induced by these agonists. Naloxone alone does not influence the per cent of animals with pose asymmetry. The opioid receptors are involved in asymmetry development. The revealed ability of opioid kappa-, delta- and sigma-agonists may be based on lateralization of opioid receptors in the rat spinal cord.

Asunto(s)

RESUMEN

Recently, beta-adrenergic agents, which repartition muscle and fat, have been used to develop more muscular carcasses in broilers, steers, lambs, and pigs. Cimaterol, one such repartitioning agent, effectively improves carcass quality in pigs. Since the mode of action of repartitioning agents is uncertain, and because they may indirectly affect skeletal development or the integrity of feet, the purpose of this study was to assess the effect of cimaterol on selected growth cartilages and feet. Pigs were randomly placed in four groups and fed a ration that included Cimaterol at 0.00, 0.25, 0.50, or 1.00 mg/kg. At 100 kg live-weight, pigs were slaughtered and selected growth cartilages, bones, and feet were examined macroscopically, radiologically, and microscopically. Although the majority of pigs had lesions in feet, or had dyschondroplastic changes typical of osteochondrosis in many growth cartilages, particularly physes, there were no significant differences in frequency of pigs with lesions between groups. Cimaterol enhanced carcass quality with no detrimental effect on bones or feet.

Asunto(s)

RESUMEN

Administration of 2-methoxyethanol to pregnant rats on day 12 of gestation induced ventral duplication of the autopod, presumably via its oxidative metabolite, methoxyacetic acid. Morphological observations indicate that the limb bud periderm is severely damaged by methoxyacetic acid so that large patches of this structure are actually missing during an extended period of limb bud development. A high concentration of methoxyacetic acid (10 mM) was found in the extraembryonic fluid and we postulate that the damage to the periderm was initiated from this extraembryonic exposure. The ventral duplication of the autopod is thought to arise through an attempt by the embryo to repair the periderm lesion.

Asunto(s)

RESUMEN

We have investigated whether insulin or growth hormone (GH) can affect growth of transplanted fetal rat paws by direct and/or indirect actions. Paws from 15-day rat fetuses were transplanted under the kidney capsule of adult female hosts, and grown for 7 days. In hypophysectomized (HX) or diabetic hosts their growth was reduced by 65% and 35%, respectively. The direct effects of insulin and GH were studied by inserting a catheter connected to an osmotic minipump into the left renal artery. Thus transplants on the left (infused) kidney were exposed directly to much higher concentrations of hormone than were those on the right (uninfused) side. In HX hosts, infusion of GH (0.1 microgram X g body wt-1 X day-1) had no effect on growth of paws on either kidney. At 0.3 or 1.0 microgram X g body wt-1 X day-1 GH caused a dose-related restoration of transplant growth that was equivalent on both sides. In diabetic hosts infusion of insulin (2 U X kg body wt-1 X day-1) partially restored growth of paws on the infused kidney without affecting those on the right. Insulin at 6 U X kg body wt-1 X day-1 caused full restoration of growth of the paws on the left and a partial increase in those on the right. At 9 U X kg body wt-1 X day-1 insulin caused full restoration of transplant growth on both kidneys. These results indicate that insulin promotes normal growth of transplanted fetal paws by direct and possibly indirect mechanisms, but the effects of GH are apparently only indirect.

Asunto(s)

RESUMEN

The in vivo administration of syngeneic lymph significantly modified lymphocyte migration in the mouse. When administered intravenously, lymph inhibited cell localization into lymph nodes, an effect that could be mimicked by lymphocyte pre-incubation with lymph in vitro. The unilateral intrafootpad injection of FR2 of lymph did enhance cell migration, both to the draining popliteal node and to the site of injection when compared to the contralateral foot or draining node. Furthermore, the subcutaneous transplant of polyurethane sponges soaked in lymph or serum into both flanks of a mouse led to increased migration and accumulation of cells in the sponges coated with lymph when compared to sponges treated with mouse serum alone.

Asunto(s)

RESUMEN

Indomethacin was not observed to produce any significant effect upon hamster buccal pouch carcinogenesis. No statistically significant difference in delayed hypersensitivity response to dinitrochlorobenzene was found between indomethacin-treated, tumor-bearing and control groups.

Asunto(s)

RESUMEN

Benzamide, an inhibitor of (ADP-ribose) transferase, augmented chondrocytic differentiation of chick limb bud mesenchymal cells in micromass cultures; the incorporation of 35SO4(2-) into the trichloroacetic-acid-insoluble constituents of cell masses as well as the formation of cartilage nodules (Nishio, Nakanishi, Doull & Uyeki, 1983) occurred about 24 h earlier than in untreated cultures and continued to be enhanced in benzamide-treated cultures of stage 23- to 24-chick limb bud cells. Benzamide also significantly increased cell proliferation. However, benzamide did not affect DNA and RNA syntheses except for one period: 24 to 30 h after the start of culture, RNA synthesis was stimulated. From 48 h of culture, (ADP-ribose) transferase activity decreased daily in untreated cultures, whereas benzamide treatment diminished (ADP-ribose) transferase activity 24 h earlier. On the other hand, intracellular NAD levels increased daily in untreated cultures, and benzamide significantly increased the NAD levels above untreated cultures. ATP levels did not differ significantly during the culture period, and benzamide did not affect ATP levels.

Asunto(s)

RESUMEN

A double-blind study was performed to evaluate the postoperative analgesic effects of dexamethasone sodium phosphate. This steroid or normal saline was randomly injected immediately after surgery into both feet of 51 patients who had identical procedures performed on each foot for the correction of bunion deformities. Pain as assessed by the patients at 24 hr. and from 4 to 7 days postoperatively was significantly less in the feet treated with the steroid. No complications were attributed to the steroid treatment. This study supports the use of dexamethasone sodium phosphate for postoperative analgesia.

Asunto(s)

RESUMEN

The New Zealand green-lipped mussel (Perna canaliculus) is the source of a para-pharmaceutical called Seatone. Claims have been made that the preparation may be helpful in the management of inflammatory joint disease but results of clinical studies to date have been contradictory. An earlier experimental study demonstrated anti-inflammatory activity in the crude preparation and further experiments to isolate and characterise the active fraction were indicated. A two-step fractionation procedure resulted in an extract, which although only 16 percent by weight of the parent material, retained anti-inflammatory activity. Experiments involving alternative routes of administration, with heat or enzyme treatment of the active extract and a comparative analysis of fractions from related bivalves, all demonstrated that the anti-inflammatory effect was genuine and did not result from counter-irritancy. The initial results suggest that the active agent is a proteinaceous macromolecule.

Asunto(s)

RESUMEN

The aim of this experiment was to determine the inflammatory effect of aluminium phosphate on the rat paw and to compare it with those of carrageenan, calcium hydrogen phosphate dihydrate and natural diamond powder. At the probability threshold of the various tests used there was a significant increase in volume of the treated paw relative to the control paw for all the substances at all times, except for the two concentrations of diamond (effect no longer significant from 30 min on), of calcium phosphate (not significant from 2 h), and of aluminium phosphate (not significant from 24 h). The effects were not significantly different between diamond and calcium phosphate (both concentrations). The effects of aluminium phosphate were significantly different from those of the two until at least 2 h after the injection ; there was no significant difference between the two doses of this substance. The kinetics of the effects produced by carrageenan differed from the kinetics of the other materials, its effects were not significantly different from those produced by aluminium phosphate until 2 h and later. The inflammatory effect that we have demonstrated in this study is added information suggesting that in addition to apatite, calcium pyrophosphate dihydrate, and sodium monourate, aluminium compounds can play a role in the unexpected appearance of inflammatory manifestations in haemodialysed patients with chronic renal insufficiency treated with aluminium gels.

Asunto(s)

RESUMEN

In the chick embryo, large scales (scuta) form on days 9-11 on the anterior face of the shank and the upper surface of the toes; smaller scales (scutella) appear on day 11 on the posterior face of the shank; most of the smallest scales (reticula) form on days 12 and 13 on the plantar surface of the foot. A single injection of 125 micrograms of retinoic acid (RA) into the amniotic cavity caused the formation of feathers on the foot scales in locations and percentages differing according to the age of embryos at the time of treatment. Injection at 10 days caused feathers to form on the feet in 57% of the embryos, almost all of which bore feathers on their scuta and scutella; a few reticula were occasionally affected. When treated at 11 days, 48% of embryos had feathered feet, the tarsometatarsal scutella and digital reticula being most frequently affected. Treatment at 12 days resulted in feathers on the feet of 15% of the embryos, all of which bore feathers on the reticula only, while the scuta and scutella were not affected. It was concluded that the foot skin regions which were affected by RA treatment were those in which scale morphogenesis was starting or about to start at the time of injection. These regions contained pre-placodal or placodal stages of scuta and scutella, and the pre-elevation or elevation stages of reticula.

Asunto(s)

Asunto(s)

Asunto(s)

Asunto(s)

RESUMEN

The work deals with the study of the skin oxygen rate in obliterating diseases of the lower extremities. In 40 patients the skin oxygen tension was studied in the first web space of the foot. 19 of these patients were the control group. In the main group (21 patients) nitrous oxide was injected in the subcutaneous fat of the lower extremities within the complex of the conservative treatment. In obliterating arterial diseases of the lower extremities the disorders of the tissue oxygen rate, particularly pronounced in the late stages of the pathological process, were found. The subcutaneous injections of nitrous oxide improved the regional blood flow in the low extremities.

Asunto(s)

Asunto(s)

Asunto(s)

RESUMEN

Vinblastine was injected into the amniotic cavity of 6-5-day-old chick embryos. Acropods were fixed 0, 2, 3-5, 6, 12, 18, 24, 36 and 48 h after treatment and 1 mum thick sections were prepared from the region of digit IV and interdigit III-IV. Cell counts were mainly performed in a distal zone (see Fig. 2) comprising the ectodermal apical ridge, the distal non-ridge ectoderm and the distal underlying mesoderm. In control non-treated embryos, the mitotic index does not vary significantly in either of the three tissues between 6-5 and 8 days except for a temporary increase at 7 days in the mesoderm. In treated embryos, the mitotic index increases rapidly in the non-ridge ectoderm and in the mesoderm to a maximum of 44 and 35% respectively, 18 h after injection, after which it decreases almost as rapidly to a level of about 15% 36 h after injection. In the apical ridge ectoderm, the increase of the mitotic index is much slower and reaches its maximum value of about 30% only 36 h after injection. This suggests that most of the cells participating in the AER do not arise within the ridge but are generated in more proximal zones of the ectoderm. Due to mitotic arrest, the number of mesodermal cells is thus decreased to approximately half the normal value within 36 h and the AER disappears earlier than normal. These alterations are the direct cause of the hypophalangy observed at the morphological level. A particular distribution pattern of arrested mitoses is revealed: in the digital as well as in the interdigital mesoderm, the majority of blocked metaphases is located in a dorsal and a ventral wing-shaped subectodermal 500 mum long area whose thickness is maximal at the level of the marginal sinus and gradually decreases in proximal direction. In the central-part of the mesoderm blocked mitoses are relatively rare. The present results are discussed in view of the recent literature on the morphogenetic processes of limb development.

Asunto(s)

Asunto(s)