Sorption behaviour of oxadiazon in tropical rice soils.

The soprtion behaviour of a pre-emergent herbicide, oxadiazon (5-tert-butyl-3-(2,4-dichloro-5-isopropoxyphenyl)-1,3,4-oxadiazol-2 (3H)-one) was investigated in tropical rice soils using a batch equilibrium method. There is no information available on the fate of oxadiazon in Bangladeshi soils; Bangladesh rice soil is a unique environment. The experiment was performed using radiolabelled (14C) oxadiazon. The sorption and desorption isotherm of oxadiazon was described using the Freundlich equation. L-type sorption isotherms were observed. The correlation coefficient (r2) was 0.995 to 0.997 and the linearity of the slope was in the range 0.96-1.07. Sorption of oxadiazon was related to organic carbon. Sorption of oxadiazon by soil was a rapid process; sorption kinetics indicated that most of the sorption occurred within two hours. Changes in sorption of oxadiazon by soils was investigated by repeated application. Sorption after the first cycle was in the range 81-92% whereas sorption capacity decreased in the following cycles.

Improved survival in primary nonmetastatic pediatric osteosarcoma of the extremity.

UNLABELLED: A prospective study using a dose-intensified neoadjuvant intra-arterial chemotherapy regimen was designed to improve survival rates of young patients with primary, nonmetastatic osteosarcoma of the extremity. Arteriography was implemented to individualize duration of therapy by serially assessing change in tumor neovascularity. Intravenous doxorubicin and intra-arterial cisplatin were administered repetitively at 3-week intervals until > or = 90% reduction in tumor neovascularity was achieved. Surgery was delayed until this good arteriographic response was documented. After resection, prediction of tumor neovascularity was compared with tumor necrosis. Since 1987, 62 eligible patients younger than 22 years old were treated with an average of four neoadjuvant courses. Toxicities were manageable. Fifty-four (87%) patients had a good histologic response. The rate of limb preservation surgery was 93.5% (58/62). Accuracy and sensitivity of serial arteriography in predicting histologic response were 92% and 98% respectively, and greatly assisted surgical planning. With an average followup of 91 months, estimated Kaplan-Meier survival at 10 years was 93% and event-free survival was 86%. Osteosarcoma survival rates were significantly improved by the use of this regimen compared with previously reported results. Serial arteriography succeeded in individualizing duration of neoadjuvant therapy and led to a higher rate of good histologic response. LEVEL OF EVIDENCE: Therapeutic study, level II-1 (prospective cohort study). See the Guidelines for Authors for a complete description of levels of evidence.

Comparison of two methods for estimation of soil sorption for imidacloprid and carbofuran.

Predicting the fate and transport of pesticides in soil environment is an important issue especially in understanding and modelling of the environmental behaviour of pesticides. Classical batch sorption method often has been identified as insufficient to derive the actual extent of sorption. In this study, the batch equilibrium method was compared to the centrifugation method, which can permit measurement of sorption under more natural conditions. The results of the comparison of the batch with the centrifugation method for imidacloprid and carbofuran pesticides indicate that the batch method overestimates sorption in comparison to the centrifugation method. These results are in agreement with others, which use high soil:solution ratios with batch and those that used the centrifugation method.

A novel therapeutic strategy for Ehlers-Danlos syndrome based on nutritional supplements.

Ehlers-Danlos syndrome is a rare disorder, comprising a group of related inherited disorders of connective tissue, resulting from underlying abnormalities in the synthesis and metabolism of collagen. This proposal is specifically concerned with Ehlers-Danlos syndrome classic type (formerly Types I-III), which is characterized by joint hypermobility and susceptibility to injury/arthritis, skin and vascular problems (including easy bruising, bleeding, varicose veins and poor tissue healing), cardiac mitral valve prolapse, musculo-skeletal problems (myopathy, myalgia, spinal scoliosis, osteoporosis), and susceptibility to periodontitis. No treatment is currently available for this disorder. The novel aspect of this proposal is based on: (i) increasing scientific evidence that nutrition may be a major factor in the pathogenesis of many disorders once thought to result from defective genes alone; (ii) the recognition that many of the symptoms associated with Ehlers-Danlos syndrome are also characteristic of nutritional deficiencies; (iii) the synergistic action within the body of appropriate combinations of nutritional supplements in promoting normal tissue function. We therefore hypothesize that the symptoms associated with Ehlers-Danlos syndrome may be successfully alleviated using a specific (and potentially synergistic) combination of nutritional supplements, comprising calcium, carnitine, coenzyme Q(10), glucosamine, magnesium, methyl sulphonyl methane, pycnogenol, silica, vitamin C, and vitamin K, at dosages which have previously been demonstrated to be effective against the above symptoms in other disorders.

Synergistic and antagonistic interactions of anticholinesterase terpenoids in Salvia lavandulaefolia essential oil.

In vitro anticholinesterase activities of eight commercially available terpenoid constituents of Salvia lavandulaefolia have been investigated. These included 1,8-cineole, camphor, alpha-pinene, beta-pinene, borneol, caryophyllene oxide, linalool and bornyl acetate. Dose-dependent inhibition of acetylcholinesterase (AChE) by these chemical constituents was determined using the method of Ellman [Biochem. Pharmacol. 7 (1961) 88]. The IC50 value of 1,8-cineole was 0.06+/-0.01 mg/ml similar to that of the essential oil (0.05+/-0.01 mg/ml). Analyses of the expected inhibitions based on the prediction of a zero interactive response of a combination at its naturally occurring ratios were carried out in comparison with observed inhibition. Minor synergy was apparent in 1,8-cineole/alpha-pinene and 1,8-cineole/caryophyllene oxide combinations, with interaction indexes not exceeding 0.5. In contrast, a combination of camphor and 1,8-cineole was antagonistic with an interaction index of 2. A combination of all eight compounds was zero interactive. A combination of six constituents, excluding 1,8-cineole and camphor, was used to compare the method of expected response of a combination with a method of summation. These findings reveal that the inhibitory activity of the oil results from a complex interaction between its constituents, which produce both synergistic and antagonistic responses between the component terpenes. Understanding such interactions is important in comparing species on the basis of chemical composition.

The use of a closed expandable prosthesis for pediatric sarcomas.

PURPOSE: The purpose of this paper is to review our experience with a non-invasive expandable prosthesis for skeletally immature patients following limb-salvage for malignant tumors about the knee. MATERIALS & METHODS: Between 1998 and 2002, Repiphysis prostheses (Wright Medical Technology, Memphis, Tenn.) were implanted in 18 patients. 16 patients had at least 12 months follow-up. There were 10 males and 8 females. The diagnosis was Stage IIB osteosarcoma in all patients. Sites included femur 14, and 4 proximal tibias. The average age was 10.7 years (range 8-16); the average age for males was 12 years and females, 9 years. Fifteen of the prostheses were implanted at the time of surgical resection and the remainder was conversions of previous surgery. RESULTS: Follow-up averaged 24.8 months (range 12-47). Fourteen patients have undergone a total of 58 lengthening procedures. Average expansion 38 mm per patient (range, 10-76 mm). An average of 8.5 mm per lengthening procedure. There was only one failure to lengthen. ISOLS functional scores averaged 83.5%. For those with a current functional prosthesis, the ISOLS score averaged 94%. Three patients have reached maximal expansion and converted to a conventional prosthesis. There were complications in 7 patients: 2 expandable component fractures, 1 femoral component fracture, 2 stem fractures, 1 stem loosening and 1 deep infection. Of the two expandable component fractures, 1 patient reached full expansion and was converted to an endoprosthesis. The femoral component fracture and 2 stem fractures were revised to a new prosthesis 13 months post-op and are functioning well. The 1 loose stem was revised to an APC. CONCLUSIONS: The Repiphysis prosthesis utilizes energy stored in a spring that is held compressed by a locking mechanism. Controlled release of the locking mechanism via an external electromagnetic field allows for lengthening of the device. In our early experience, the functional results were excellent similar to conventional modular devices. Complications should be anticipated but are salvageable. This device allows limb salvage in pediatric patients when amputation would be otherwise chosen.

Effect of gas-plasma sterilization on the osteoinductive capacity of demineralized bone matrix.

The current study evaluated the effect of low-temperature hydrogen peroxide gas plasma sterilization on the osteoinductive capability of human demineralized bone matrix using a rat model. Twelve athymic rats received three separate implants consisting of steam-sterilized demineralized bone matrix (negative control), sterile-harvest demineralized bone matrix (positive control), and gas-plasma-sterilized demineralized bone matrix. A demineralized bone matrix pellet from each sterilization group was placed individually into one of three separate soft tissue pockets created in the epaxial musculature of each rat. All 12 rats were euthanized 9 weeks after implantation. Each implantation site was removed along with 0.5-cm normal tissue around the implant. Histologic examination was done on each implant site to determine the presence or absence of new bone, cartilage, or bone marrow elements. All 12 sterile harvest demineralized bone matrix sites histologically contained new bone elements, whereas none of the negative control or gas plasma sterilized demineralized bone matrix sites contained any of these same elements. The results of this study indicate that demineralized bone matrix sterilized with low-temperature, gas-plasma sterilization loses its osteoinductive capacity in a manner similar to that of steam-sterilized demineralized bone matrix, making low-temperature, gas- plasma sterilization unsuitable as a method of secondary sterilization of demineralized bone matrix.

The use of a surgical grade calcium sulfate as a bone graft substitute: results of a multicenter trial.

In a prospective, nonrandomized, multicenter study, 109 patients with bone defects were treated with a surgical grade calcium sulfate preparation as a bone graft substitute. The calcium sulfate pellets were used in place of morselized cancellous bone graft for the treatment of patients with bone defects who usually would require grafting secondary to trauma, periprosthetic bone loss, tumor, or fusion. The calcium sulfate was used alone or mixed with other materials such as bone marrow aspirate, demineralized bone matrix, or autograft. The defects that were treated were contained and were not necessary for the stability of the bony structure. Radiographic and clinical data were collected at predetermined intervals for 12 months. At 6 months postoperatively, radiographic results for all patients showed that 99% of the calcium sulfate had been resorbed and 88% of the defect was filled with trabeculated bone. There were 13 complications; however, only four (3.6%) were attributable to the product. The results of a subgroup of 46 patients with benign bone lesions treated in the same manner are identical to the results of the overall study population. Surgical grade calcium sulfate pellets are considered a convenient, safe, and readily available bone graft substitute that yield consistent successful results.

The Phenix expandable prosthesis: early American experience.

One of the major dilemmas in limb preservation in skeletally immature children involves the ability to maintain leg length equality. Many attempts have been made to design a prosthesis that could be expanded easily either nonoperatively or through a minor surgical procedure. Most of these designs have had mechanical difficulty or the lengthening procedure becomes a major surgical endeavor. The Phenix technology has been used in France for several years. The basic principle involves storage of energy in a spring which is maintained compressed by an original locking system. Once implanted, prosthetic lengthening is achieved via exposure to an external electromagnetic field that pilots the locking system and allows controlled release of the spring energy. Seven Phenix prostheses have been implanted in six patients. All patients had been treated for Stage II-B osteosarcoma. Six of the seven prostheses were implanted during revision procedures in salvage situations; one prosthesis was implanted during an index procedure. The surgical procedures were completed without complications. One patient sustained a fracture of the prosthesis in a fall and had an infection develop after implantation of the second prosthesis. Twenty-one expansions have been performed in six patients (mean lengthening at each procedure, 8 mm). There were no acute complications attributable to the lengthening procedure. Prosthetic expansions required an average of 20 to 30 seconds and were accompanied by very mild discomfort, if any. Most patients were given an oral analgesic either before or during the lengthening procedure. The Phenix prosthesis shows promise in handling the difficult problem of limb preservation in a growing child. Additional investigation is underway regarding limb lengthening and other dynamic applications.

Unicameral bone cysts.

Unicameral, or solitary, bone cysts are unusual tumors seen in the ends of long bones in skeletally immature persons. The etiology of these lesions is poorly understood. Various hypotheses have included dysplastic processes, synovial cysts, and abnormalities in the local circulation. Most patients present with a nondisplaced pathologic fracture, but occasionally cysts are found incidentally. Plain radiographs typically show a symmetric lesion with cortical thinning and expansion of the cortical boundaries. Once diagnosed, unicameral bone cysts continue to be a treatment dilemma. Traditional methods, such as prednisolone therapy, usually involve multiple anesthetics and injections and are associated with high recurrence rates. Major surgical procedures, such as wide exposure, curettage, and bone grafting, may be somewhat more effective, but still carry with them significant morbidity and recurrence rates. Newer techniques involving percutaneous grafting with allograft or bone substitutes or a combination of the two are promising in light of their low complication rate and lower reoperation rate.

Controlled release of a herbicide from matrix granules based on solvent-fractionated organosolv lignins.

An organosolv (Alcell) lignin was fractionated with both sequential solvent-extraction and solvent-mixture precipitation using various organic solvent systems. The resulting fractionated lignins were used to prepare matrix granules with bromacil as a model compound using a melt process. The release rates of bromacil in vitro from the granular matrix system were influenced by both the lignin used as carrier and the solution fractionation. The variations in release rates were related to the high proportion of low-molecular-weight fraction and its associated water-soluble lignin in the fractionated lignins. Fickian diffusion was a predominant factor in controlling the release of bromacil from the matrix granules based on the low-molecular-weight fraction (L(fr1)). For the matrix granules based on the other fractionated lignins, the release of bromacil was of super-case II transport. The fine structure of the matrix granules before and after release was also studied. An unique release pattern of bromacil was observed for the matrix granules based on the low-molecular-weight fraction (L(fr1)), showing a fast release followed by zero-order release, which was a result of remarkable changes in the structure of the matrix granules during the course of release.

Bioassayed demineralized bone matrix and calcium sulfate: use in bone-grafting procedures.

BACKGROUND AND AIMS: A combination product of bioassayed, demineralized bone matrix (AlloGro, AlloSource, Denver CO) and calcium sulfate pellets (OsteoSet, Wright Medical Technology, Arlington TN) was utilized in a prospective clinical study in 50 patients in need of bone-grafting procedures. It was proposed that the osteoinductive activity of the demineralized bone matrix combined with the osteoconduction and rapid dissolution of the calcium sulfate pellets would complement each other in promoting bone formation. MATERIALS AND METHODS: The patients were evaluated clinically and radiographically at regular intervals post-operatively by an independent clinician. A total 10-point healing score was used to determine healing characteristics and progress. Fifty patients (24 males and 26 females) were treated for benign bone lesions (35), nonunion (11), osteomyelitis (3), and acute fracture (1). The average age was 33 years (range, 3-64 years). Lesions were located in the femur (16), tibia (15), humerus (7), and other sites (12). RESULTS: The average length of follow-up was 14 months (range, 6-32 months). Forty-nine of 50 patients healed their lesions (98%), requiring an average time to heal of 11.8 weeks (range, 3-48 weeks). There were no graft-related complications. CONCLUSIONS: The results of this preliminary clinical study suggest that a combination of bioassayed demineralized bone matrix and calcium sulfate is very effective in treating benign lesions of bone, as well as nonhealing fractures, which is comparable to grafting with autograft. Future studies have been undertaken utilizing this combination in all acute operative settings and fracture management situations.

Controlled release of aldicarb from lignin loaded ionotropic hydrogel microspheres.

Aldicarb loaded microspheres of carboxymethyl cellulose, CMC, of various compositions were prepared with the crosslinking action of Al(III). Into these microspheres, lignin was introduced as a filler to further regulate the rate of release. The encapsulation efficiency was low (4.15-13.00%) due to the high water solubility of aldicarb. Release into aqueous media was quite rapid and almost complete within 24h. Initial stages of the release (60% of AS released) was investigated to determine the release mechanism and it was found that release from the microspheres was governed by Fickian diffusion. Among the various parameters, the ratio of lignin to CMC and aldicarb to CMC were found to be influential on the rate of release from the crosslinked CMC-lignin microspheres. The soil behaviour confirmed the delayed release effect of the controlled release formulation compared to Temik (a commercial preparation of aldicarb), especially when lignin was incorporated.

Comparative effect of fenitrothion treatment on intracellular protease activities in insecticide-resistant and susceptible strains of Musca domestica L.

In order to further elucidate the biochemical mechanisms responsible for insecticide resistance in insects, we have determined changes in the activity levels of a comprehensive range of proteolytic enzymes (cytoplasmic and lysosomal proteinases and peptidases, which play a key role in normal cell functioning) in fenitrothion-resistant (571ab) and susceptible (Cooper) strains of Musca domestica following in vivo exposure to the insecticide fenitrothion. Untreated insects of the resistant strain had significantly higher levels (20-100%) of activity for many protease types compared to the susceptible strain (whole body analysis). Exposure to fenitrothion resulted in further activity increases for most proteases at some point during the subsequent 24 h period in resistant strain insects; susceptible strain insects were also capable of similar increases in protease activities. We therefore suggest that it must be the combination of intrinsically higher protease levels (prior to pesticide exposure), together with the capacity to further increase protease activities following insecticide exposure, which is important in the mechanism by which proteases may confer survival advantages in insecticide resistant insects. We further speculate that this mechanism may involve increased supply of precursor amino acids from proteolytic degradation products to the intracellular pool, prior to de novo synthesis of detoxifying enzymes following insecticide exposure.

Comparison of proteolytic enzyme activities in adults of insecticide resistant and susceptible strains of the housefly M. domestica L.

Intracellular proteolytic activity in a DDT-resistant and a susceptible strain of M. domestica was determined by assaying a comprehensive range of cytoplasmic and lysosomal enzymes. The resistant strain showed significantly higher protease activities in whole body, head, thorax, abdomen and gut homogenates compared to the susceptible strain. The activity of alanyl- and arginyl aminopeptidase from both strains increased substantially after topical treatment with DDT at 1, 2 and 3 h, suggesting an involvement of proteolytic enzymes in the induction of detoxifying enzymes, thus indicating a possible role of the intracellular proteolytic activities in the resistance mechanism.

Effect of Tri-O-cresyl phosphate (TOCP) on proteolytic enzyme activities in mouse liver in vivo.

To develop a clearer understanding of the biochemical mechanisms of toxicity in higher animals, we determined the effect of four sublethal dosages (0.25 to 1.0 g/Kg) of organophosphate (OP), and of tri-ortho-cresyl phosphate (TOCP) on the activities of a representative range of cytoplasmic and lysosomal proteolytic enzymes in mouse liver in vivo. Administration of the lowest sublethal dosage of TOCP (0.25g/1Kg, 24 hours) resulted in significant inhibition (10 to 30% of control activity) of the cytoplasmic proteases tripeptidyl aminopeptidase and proline endopeptidase only. An increasing dosage of TOCP (1g/Kg for 7 days) resulted in significant inhibition (10 to 50% of control activity) of the cytoplasmic proteases alanyl aminopeptidase, leucyl aminopeptidase, tripeptidyl aminopeptidase, and proline endopeptidase, as well as the lysosomal proteases dipeptidyl aminopeptidase I and cathepsins B, D, and L. The activities of the cytoplasmic proteases arginyl aminopeptidase and dipeptidyl aminopeptidase IV, and of lysosomal proteases dipeptidyl aminopeptidase II and cathepsin H were not significantly altered following TOCP administration at this higher dosage. All of the above proteases are involved in the general process of intracellular protein turnover (common to all tissues), and may also have more specialized functions such as the processing of physiologically active hormonal peptides, and the processing of antigenic proteins in the immune response. Data obtained in the present study suggest that inhibition of the above enzymes by OP such as TOCP may represent a previously unrecognized toxicity hazard induced by the latter compound in higher animals.