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Intertransverse process fusion with the aid of chemosterilized autolyzed antigen-extracted allogeneic (AAA) bone.

Forty intertransverse process spinal fusions were performed across two to three vertebrae in four cases of fracture-dislocations of the dorsolumbar region and 36 cases of degenerative joint and disk disease, including spinal stenosis and spondylolisthesis of lumbosacral segments. In all cases, arthrodesis was performed with a composite of AAA cortical bone strips and local autologous spongiosa, including lamellar bone chips. The iliac crest was not used as a donor site in any case. The apophyseal joints were erased, packed with autologous bone slivers, and transfixed with AAA bone pegs. In selected cases, AAA cortical bone "H-blocks" were also placed between the spinous process as in a routine posterior lateral arthrodesis. In cases of bilateral total laminectomy for fractures or spinal stenosis, the excised cancellous bone chips were cleaned of soft parts and transplanted across the transverse processes beneath and around the AAA cortical bone implants. In the above-described operations, graded by the Anatomic-Functional Economic (AEF) system, the long-term excellent and good results were: 4/4 in fracture dislocations; 23/28 in degenerative arthritis and spinal stenosis; 5/8 in spondylolisthesis. Overall, there were over 80% excellent and good results; the pseudarthrosis rate was 12%. In a comparable surgical procedure with autologous iliac bone in 58 control cases, reported in the foregoing article in this volume, the minimum pseudarthrosis rate was 8%. Raw band bone, either frozen or freeze-dried, is now either so infrequently considered or unavailable for lumbar spinal operations or unavailable for lumbar spinal operations that further investigations of AAA bone grafts are warranted in a statistically significant number of patients. Although autologous bone is the ideal bone for a graft, the most important incentive for further investigations of AAA bone is the avoidance of complications of excision of massive bone grafts from iliac crests.

Adolescent↗

Chemosterilized autolyzed antigen-extracted allogeneic (AAA) bone matrix gelatin for repair of defects from excision of benign bone tumors: a preliminary report.

In a series of 33 bone graft operations, antigen-extracted, autolyzed, allogeneic (AAA) bone matrix gelatin was substituted for autologous bone. The period of follow-up was 2.0 to 3.5 years. AAA bone gelatin was resorbed more rapidly than whole bone. AAA bone gelatin was replaced by new bone in the same intervals of time as observed with autologous bone. In treatment of bone tumors with AA bone gelatin, the results of the operation depend upon the nature of the pathologic processes in the host bed. In normal host bed, tight contact between implant and recipient bone is essential for success. The overall results of a preliminary study of 33 cases of 91% successful.

Antigens↗

[Queens' technic in Pharaoh's ant control. 2. Synergistic effects].

The alkylating (Tepa, Metepa, Thiotepa, Apholate) and non-alkylating (Hempa, Hemel) chemosterilants have been tested in a screening programme together with 6 synergists of insecticides (Pieronylbutoxide, Bucarpolate, Sulfoxide, Safroxan, Demethylsulfoxide, S-421) for cumulative and synergistic effects. Since all of the insecticide synergists were repellent in contrast to the chemosterilants, the substances have been screened only by the dipping test. The synergists increased in solutions of acetone in contrary to the chemosterilants not the mortality of the queens. A combination of Tepa acetone in contrary to the chemosterilants not the mortality of the queens. A combination of Tepa and Piperonylbutoxide resulted in real synergistic effects. The sterility of the queens of the pharaoh's ant was increased at a relation of 1 part of Tepa to 5 parts of Piperonylbutoxide up to twentyfold. It is probably the first evidence of synergism between conventional chemosterilants and insecticide synergists. Unfortunately this excellent effect can not be used for practical control measures because only the baiting method leads to an eradication. - All the other screened combinations showed neither cumulative nor synergistic effects.

Animals↗

Efficacy of alpha-chlorhydrin in sewer rat control.

A single application of the male chemosterilant, alpha-chlorhydrin, to a problem sewer rat infestation resulted in reductions of rat numbers and distribution which was comparable to effects of warfarin baiting methods. Rat numbers were reduced by more than 85% by both methods. More rapid mortality and recruitment were evident for warfarin effects; the alpha-chlorhydrin treated population had a longer lag phase of growth so that reinfestation of sewer habitat to pre-treatment numbers, and distribution over a 40 square block area, required approximately 1.5-2 times longer after alpha-chlorhydrin treatment when compared with warfarin treatment. Comparisons of changes in rat densities in infested sewers following the two treatments indicate that recovery of warfarin treated populations is achieved by reproductive recruitment followed by dispersal while alpha-chlorhydrin treated populations recover by slower immigration and later reproductive recruitment. Alpha-chlorohydrin should be a useful addition to a limited arsenal of rat control agents because of its specificity for the Norway rat, its single dose effectiveness as a toxicant-chemosterilant, and its short environmental half-life.

Animals↗

Synthesis of aziridinylallylaminophosphine oxides and sulfides as potential adjuvant cancer chemotherapeutic agents.

Bis (1-aziridinyl)(hexahydro-1H-azepin-1-yl)phosphine sulfide, an active anticancer agent with low hematopoietic toxicity in animals and man, was recommended several years ago for breast cancer adjuvant chemotherapy as an alternate drug to thiotepa. This hope had led to the syntheses of aziridinylallylaminophosphine oxides or sulfides (compounds I-XVII) in our laboratories. The resurgent interest in this area of cancer chemotherapy encouraged us to report our synthetic work as well as their evaluation as both anticancer agents and insect chemosterilants. Based on observed antitumor activity in animals, low chemosterilant activity in female species (insects and rats), and histochemical observation of tissue toxicity in rat testes but not in ovaries, these new agents are of potential interest to the breast cancer adjuvant chemotherapy program.

Animals↗

Biological and behavioural studies of rodents as a basis for control.

Domestic rodents, particularly those living in urban populations, represent a serious public health problem, and effective control measures are required to deal with this threat to human health. Because of the characteristic interactions between individual animals, certain behaviour patterns occur in rodent populations that are of particular concern to control biologists. The genus Rattus is an extremely diverse group whose ecological requirements are variable and flexible, while the genus Mus, on account of its small size, limited range, and modest requirements in terms of food and water, is also very difficult to control. For any control operation a knowledge of the growth dynamics of domestic rodent populations is needed; after a period of logarithmic growth, population increases cease when the habitat is fully exploited. Consequently, control operations that merely remove some animals lead only to renewed population growth. Trapping, poisoning, and predation are traditional control measures of this kind. Environmental modification is a more certain, but more difficult, approach. The use of chemosterilants offers some hope of radical control in the future, but at present, although some field trials have been made, these substances are not available for general use, one reason being their lack of specificity. Another problem connected with the use of chemosterilants is that, on account of the sexual behaviour and physiology of domestic rodents, it would be necessary to reach nearly 100% of the population to obtain effective control.

Animals↗

Sterilization of Culex pipiens fatigans Wiedemann by apholate.

The use of alkylating agents has been found to be a promising way of chemosterilizing mosquitos for control purposes. The investigation discussed in the present paper has shown that apholate (2,2,4,4,6,6-hexahydro-2,2,4,4,6,6-hexakis (1-aziridinyl)-1,3,5,2,4,6-triazatriphosphorine) can induce sterility rates of from 43% to 95% in Culex pipiens fatigans Wiedemann treated in the larval stage, and from 80% to 100% in C. fatigans treated in the adult stage; treatment in the pupal stage produced no significant sterility.Of the methods of application of the apholate tested (immersion of larvae and pupae in water containing apholate, exposure of anaesthetized adults to residual deposits of apholate and dusting of anaesthetized adults with apholate powder), the dusting method was found to be effective.Apholate induces sterility in both sexes. Females were affected much more when they were treated in the adult stage. The average number of eggs laid by a treated female was found to be reduced no matter whether the treatment was during the larval or the adult phase.Male mosquitos chemosterilized by dusting were more competitive than normal males.

Alkylating Agents↗

Studies on the population dynamics of the housefly, Musca domestica L.

The population level and potential rate of increase of a population of houseflies, Musca domestica L., on Grand Turk Island was studied for about 2 years to determine what changes occurred when no control was applied (the first year) and when the population was totally suppressed by the application of chemosterilant baits (the second year). During the first year the population was relatively stable (the highest density occurred in June and the lowest in January) and the difference between the high and low levels was only 3-fold. When chemosterilant baits were applied over a 40-week period and total suppression was achieved, calculations based on the sterility achieved and the resulting control revealed that the population showed potential rates of increase ranging up to 4-fold during the period from June through October and from 4-fold to 11-fold from December through April. Thus, in the field, the potential rates of increase of the housefly are low despite its high biotic potential.

Animals↗

[The queen technic for ant control. I. The effect of tepa on laboratory colonies of the pharaoh ant].

The present paper discussed at the example of Tepa [Tris (1-aziridinyl) phosphine oxide] in which manner the control of pharaoh's ant in the sense of the "queen technique" with chemosterilants is possible; which points of view must be considered and which condition an acceptable substance should be fulfilled. The application of Tepa is ralized according to various techniques (e.g. dipping, baiting, tarsal contact), in the course of which the baiting technique is preferred. The influence of different concentrations in various baits on the brood, workers and queens are described. In baits with 1% of the substance a permanent sterilization could be achieved. In combination with other population depressing factors (larval and worker mortality) resulted in eradication of the colonies. The action extended also to the larvae of the sexuals, so that the queenless colonies failed in the production of new queens and males. Histological investigations showed in the females at higher concentrations distinct pathological alterations (pycnosis, vacuolizations, proliferation in the follicles epithelium); whereas the spermatogenesis in the males is decreased but not entirely suppressed. At lower concentrations only the fertility but not the fecundity was influenced. A handing-over of recessive lethal mutations to the progeny does not take place. The practical points of view for the use of chemosterilants in the control of pharaoh's ant are discussed. Whereas the low biological stability of Tepa does not exclude an introduction in the practice, the high mutagenic activity prevents an application in the field.

Animals↗

The induction of bone in osteogenic composites of bone matrix and porous hydroxyapatite replicas: an experimental study on the baboon (Papio ursinus).

This study evaluated the morphogenetic properties of osteogenic composites of bone matrix and porous coralline hydroxyapatite (HA) replicas after intramuscular implantation in adult baboons (Papio ursinus). Composite implants were prepared by inserting rods of nonresorbable HA replicas, 20 mm in length, and 5 or 7 mm in diameter, into the medullary canals of 90 diaphyseal baboon bone cylinders, 20 mm in height, sequentially extracted and chemosterilized to obtain autolysed antigen-extracted allogeneic (AAA) bone matrix, preserving the bone morphogenetic protein (BMP) activity. Composites were implanted in the rectus abdominis and in the dorsal musculature of 24 adult male baboons. Before implantation, 45 composites were coated with an allogeneic fibrin-fibronectin protein concentrate (AFFP) prepared from fresh-frozen baboon plasma. Histologic analysis of undecalcified and decalcified specimens procured at 3, 6, and 9 months showed bone differentiation by induction along the endosteal surfaces of the chemosterilized matrix and within the porous spaces of the HA substratum. Bone formation was often extensive, culminating in complete penetration of the porous spaces. Histomorphometry showed that bone in the HA substratum increased at each time period. The biochemical treatment of the composite implants with AFFP did increase significantly the amount of induced bone, although only in the HA substratum. Bone differentiation was confirmed by fluorescence microscopy of the mineralization fronts after intravital double tetracycline labeling. The differentiation of bone in composites of bone matrix and porous HA replicas in extraskeletal sites of adult baboons may help to design appropriate delivery systems for the controlled therapeutic initiation of bone formation for craniofacial and orthopedic applications in man.

Animals↗

Evaluation of single intratesticular injection of calcium chloride for nonsurgical sterilization of male Black Bengal goats (Capra hircus): a dose-dependent study.

This study describes the induction of chemosterilization in three groups each of six adult male Black Bengal goats at 30 days after a single bilateral intratesticular injection of a calcium chloride (CaCl(2), 2H(2)O) solution at the doses of 10, 20 or 40 mg/kg body weight/testis, always in a 2 ml volume of normal saline. Another one group of animals received only 2 ml of normal saline per testis as a control. The induction of chemosterilization was measured using relative testicular weight as well as histomorphological parameters including seminiferous tubular architecture and germ cell association in seminiferous tubules along with morphology of the interstitial space. Biochemical markers included activities of testicular Delta(5), 3beta-hydroxysteroid dehydrogenase (Delta(5), 3beta-HSD), 17beta-hydroxysteroid dehydrogenase (17beta-HSD), catalase, glutathione peroxidase (GPx), glutathione S-transferase (GST) and superoxide dismutase (SOD) as well as monitoring the level of testicular thiobarbituric acid reactive substances (TBARS), conjugated dienes and reduced glutathione (GSH) content along with plasma concentrations of testosterone, LH and FSH. Histomorphological measures of testes showed total necrosis of testicular tissue at 30 days after an injection of either 20 or 40 mg CaCl(2) along with fibrosis in seminiferous tubules and interstitial spaces. Infiltration of leucocytes was observed with the 40 mg dose. Disintegration of germ cell arrangement in seminiferous tubules and washing out of germ cells from the tubules were noted with the 10mg dose. Relative organ weights, plasma concentrations of testosterone, testicular activities of Delta(5), 3beta-HSD, 17beta-HSD, catalase, GPx, GST, and SOD and testicular contents of GSH all were declined. Increases occurred in testicular TBARS, conjugated dienes and plasma concentrations of LH and FSH with each of the treatments by comparison with the control group. Plasma concentrations of cortisol and fasting blood sugar level as well as packed cell volume (PCV) and total plasma protein were recorded to monitor the changes of chronic stress in the experimental animals. Changes in these parameters were not significant. An intratesticular injection of calcium chloride at specified doses could be a suitable method of sterilization in preference to surgical castration of goats.

Animals↗

The origins, fate, and ecological significance of free amino compounds released by freshwater pulmonate snails.

The mass-specific accumulation rates (MSAR) of both total (TFAC) and individual free amino compounds (FAC) in conditioned media were measured by HPLC, using the orthophthaldialdehyde (OPA) methods, in the following cases: (a) laboratory-reared freshwater snails (B. glabrata) with chemosterilized shells; (b) Biomphalaria glabrata with non-chemosterilized shells; (c) B. glabrata faeces; (d) isolated shells of B. glabrata; and (e) 10 other species of freshwater gastropods from the Lewes Brooks, East Sussex, U.K. The MSAR values for B. glabrata show that 95% of the TFAC's (predominantly ethanolamine, phosphoserine, and the amino acids leucine, isoleucine, valine, aspartic acid, and glycine/threonine) originated from the snails themselves as the faeces and shells contributed only 5.0 and 0%, respectively. In contrast, epizootic organisms on the shells of all 10 snail species from the Lewes Brooks released significant amounts of FAC with the two smallest species (Planorbis vortex and Planorbis contortus) having the highest MSAR values. The MSAR for isolated B. glabrata mucus was 42.45 micromol x g(-1)h(-1). As 500 mg snails can release 16.67 mg of mucus daily, this could potentially result in the daily loss of 707.5 micromol of FAC. The cost/benefits of mucus secretion and the various anatomical, physiological, biochemical, and ecological mechanisms which allow freshwater snails to recover FAC's lost as a result of a high rate of urine production in their hypotonic environment, are discussed.

Amines↗

Bone induction in nonhuman primates. An experimental study on the baboon.

Development leading to local bone differentiation in response to intramuscular and subcutaneous implantation of demineralized bone matrix has been predominantly investigated in rodents. To investigate bone differentiation by induction in primates, diaphyseal bone was harvested from ten male baboons and chemosterilized to obtain autolyzed, antigen-extracted allogeneic (AAA) bone containing the bone morphogenetic protein essential for osteoinduction. A total of 96 AAA bone diaphyseal cylinders were implanted intramuscularly in 24 adult male baboons and harvested at three, six, and nine months. Histologic analysis showed that the matrix had undergone considerable resorption, particularly at six and nine months. Seventy-three implants showed variable amounts of newly formed bone at the internal and external surfaces of the chemosterilized matrix. Numerous specimens showed florid bone formation, and newly formed woven bone persisted in association with the matrix for as long as nine months. Coating the AAA bone matrix with an allogeneic fibrin-fibronectin protein concentrate prepared from fresh-frozen baboon plasma did not significantly increase the amount of induced bone. Bone formation was confirmed by intravital double tetracycline labeling of the mineralization fronts. The unequivocal demonstration of bone formation by induction in a large series of adult nonhuman primates provides evidence that long-lived higher vertebrates retain the bone-inductive proteins in the extracellular matrix of bone and the crucial set of responding mesenchymal cells capable of transformation and differentiation into osteoblastic cell lines.

Animals↗

A method for detecting therapeutic activity against Schistosoma mansoni in mice.

A simple and rapid assay, suitable for routine screening against Schistosoma mansoni in mice, can be achieved by using a reduction in the severity of hepatic lesions as the chief criterion of efficacy. Previous attempts to use this criterion were largely hampered by the use of inappropriate time schedules. Provided the timing of treatment and necropsy is restricted to a certain schedule, a mere glance at the opened abdomen of an infected mouse is sufficient to determine whether schistosome reproduction has been suppressed (by chemosterilization or by broader anthelmintic effects). The essence of the necessary schedule is treatment beginning at 4 weeks after infection and prolonged (continuously or intermittently) for 2 weeks, followed by necropsy at 8 weeks after infection. Using the methods described, two persons can easily examine mice for therapeutic response at the rate of 300 per hour. The assay has been shown to detect both schistosomaticidal and chemosterilizing compounds.

Animals↗

Genetic control of insects of public health importance.

During recent years many advances have been made in the development of insect control by genetic manipulation. These methods include the sterile-male technique, now well known, which depends on ionizing radiation or chemosterilization. The recent field experiment carried out by WHO in Rangoon, Burma, on Culex fatigans has demonstrated that naturally occurring cytogenetic mechanisms such as cytoplasmic incompatibility can be used successfully without the use of radiations or chemosterilants. The paper not only describes the experiment on Culex fatigans but also discusses basic concepts and theoretical considerations involved in genetic control of insects of public health importance. The possibility of using genetic mechanisms for the control of other vector species is also discussed. There are a number of problems which require study before genetic control can be used on an operational scale. These problems and suggestions for future research in this field are also outlined.

Animals↗

The chemotherapy of onchocerciasis XVII. A clinical evaluation of albendazole in patients with onchocerciasis; effects of food and pretreatment with ivermectin on drug response and pharmacokinetics.

Three pharmacokinetic studies were conducted in Ghanaian patients in support of investigations of albendazole and its combination with ivermectin in the treatment of onchocerciasis. These included dose-finding studies, investigations into the influence of a fatty meal on the relative bioavailability of albendazole as assessed by the measurement of concentrations of albendazole sulphoxide and the effect of prior treatment with ivermectin on antiparasitic efficacy and plasma concentrations of albendazole suphoxide. Increasing the dose of albendazole from 800 mg x 3 daily to 1200 mg x 3 daily produced no additional antiparasitic effects although plasma concentrations of albendazole sulphoxide were increased in proportion to dose size. Moreover, the plasma concentration vs time profiles suggest that most of the effects observed may have been due to the first 800 mg dose. Administration of ivermectin had no effect on the pharmacokinetics of albendazole sulphoxide and there was no additive effect on the parasite. Albendazole was well tolerated and its administration 5-7 days after ivermectin produced little additional reaction. Although it is not macrofilaricidal, it does possess important chemosterilant properties which are enhanced by its administration with a fatty breakfast. Under these conditions, the relative bioavailability of albendazole is increased four-fold. These studies support further work with albendazole administered with food either as a single dose, as multiple single doses repeated at intervals of several months and its coadministration with ivermectin. They also encourage the belief that a more potent and bioavailable benzimidazole may be macrofilaricidal or a permanent chemosterilant for Onchocerca volvulus on single dosage.

Adolescent↗