Oral diacetylmorphine (heroin) yields greater morphine bioavailability than oral morphine: bioavailability related to dosage and prior opioid exposure

AIMS: In the Swiss heroin substitution trials, patients are treated with self-administered diacetylmorphine (heroin). Intravenous administration is not possible in patients that have venosclerosis. Earlier studies have demonstrated that oral diacetylmorphine may be used, although it is completely converted to morphine presystemically. Morphine bioavailability after high-dose oral diacetylmorphine is considerably higher than would be predicted from low-dose trials. The aim was to investigate whether the unexpectedly high bioavailability is due to a difference in the drug examined, and whether it depends on previous exposure or on dose. METHODS: Opioid-naive healthy volunteers and dependent patients from the Swiss heroin trials (n = 8 per group) received low doses of intravenous and oral deuterium-labelled morphine and diacetylmorphine, respectively. Patients also received a high oral diacetylmorphine dose. RESULTS: The maximum plasma concentration (C(max)) of morphine was twofold higher after oral diacetylmorphine than after morphine administration in both groups. However, morphine bioavailability was considerably higher in chronic users [diacetylmorphine 45.6% (95% confidence interval 40.0, 51.3), morphine 37.2% (30.1, 44.3)] than in naive subjects [diacetylmorphine 22.9% (16.4, 29.4), morphine 23.9% (16.5, 31.2)] after low oral doses (48.5 micromol) of either diacetylmorphine or morphine. Morphine clearance was similar in both groups. Moreover, oral absorption of morphine from diacetylmorphine was found to be dose dependent, with bioavailability reaching 64.2% (55.3, 73.1) for high diacetylmorphine doses (1601 micromol). CONCLUSIONS: Oral absorption of opioids is substance-, dose- and patient collective-dependent, suggesting that there may be a saturation of first-pass processes, the exact mechanism of which is not yet understood.

VOLUME YIELDS OF SMALLHOLDER Eucalyptus grandis W. HILL EX MAIDEN STANDS IN EASTERN PARAGUAY

Smallholders in eastern Paraguay plant small stands of Eucalyptus grandis W. Hill ex Maiden intended for sale on the local market. Smallholders have been encouraged to plant E. grandis by local forestry extension agents who offer both forestry education and incentive programs. Smallholders who practice recommended forestry techniques geared towards growing large diameter trees of good form are financially rewarded by the local markets which desire saw log quality trees. The question was posed, are smallholders engaging in recommended silvicultural practices and producing reasonable volume yields? It was hypothesized that smallholders, having received forestry education and having financial incentives from the local market, would engage in silvicultural practices resulting in trees of good form and volume yields that were reasonable for the local climate and soil characteristics. Yield volume results from this study support this hypothesis. Mean volume yield was estimated at 70 cubic meters per hectare at age four and 225 cubic meters per hectare at age eight. These volume yields compare favorably to volume yields from other studies of E. grandis grown in similar climates, with similar stocking levels and site qualities.

Self-Absorption and Luminescence Quantum Yields of Dye-Zeolite L Composites

Electronic absorption and fluorescence spectra based on transmission measurements of thin layers obtained from new perylene−zeolite L composites and new dye1,dye2−zeolite L sandwich composites, the latter acting as antenna systems, have been investigated and analyzed. The influence of extra- and intraparticle self-absorption on the spectral shape and fluorescence quantum yield is discussed in detail. Due to its intraparticle origin, self-absorption and re-emission can often not be avoided in organized systems such as dye−zeolite L composites where a high density of chromophores is a prerequisite for obtaining the desired photophysical properties. We show, however, that it can be avoided or at least minimized by preparing dye1,dye2−zeolite L sandwich composites where donors are present in a much larger amount than the acceptors because they act as antenna systems.

Integration of Year-round Forage Management Systems for Spring-calving and Fall-calving Beef Cows (A Progress Report)

Animal production, hay production and feeding, winter forage composition changes, and summer pasture yields and nutrient composition of a year-round grazing system for spring-calving and fall-calving cows were compared to those of a conventional, minimal land system. Cows in the year-round and minimal land systems grazed forage from smooth bromegrassorchardgrass-birdsfoot trefoil (SB-O-T) pastures at 1.67 and 3.33 acres, respectively, per cow in the summer. During the summer, SB-O-T pastures in the year-round grazing system also were grazed by stockers at 1.67 stockers per acre, and spring-calving and fall-calving cows grazed smooth bromegrass–red clover (SB-RC) and endophyte-free tall fescue–red clover (TF-RC) at 2.5 acres per cow for approximately 45 days in midsummer. In the year-round grazing system, spring-calving cows grazed corn crop residues at 2.5 acres per cow and stockpiled SB-RC pastures at 2.5 acres per cow; fallcalving cows grazed stockpiled TF-RC pastures at 2.5 acres per cow during winter. In the minimal land system, in winter, cows were maintained in a drylot on first-cutting hay harvested from 62.5–75% of the pasture acres during summer. Hay was fed to maintain a body condition score of 5 on a 9-point scale for springcalving cows in both systems and a body condition score of 3 for fall-calving cows in the year-round system. Over 3 years, mean body weights of fall-calving cows in the year-round system did not differ from the body weights of spring-calving cows in either system, but fall-calving cows had higher (P < .05) body condition scores compared to spring-calving cows in either system. There were no differences among all groups of cows in body condition score changes over the winter grazing season (P > .05). During the summer grazing season, fall-calving cows in the year- round system and springcalving cows in the minimal land system gained more body condition and more weight (P < .05) than springcalving cows in the year-round grazing system. Fall calves in the year-round system had higher birth weights, lower weaning weights, and lower average preweaning daily gains compared to either group of spring calves (P < .05). However, there were no significant differences for birth weights, weaning weights, or average pre-weaning daily gains between spring calves in either system over the 3-year experiment (P > .05). The amount of total growing animal production (calves and stockers) per acre for each system did not differ in any year (P > .05). Over the 3-year experiment, 1.9 ton more hay was fed per cow and 1 ton more hay was fed per cow–calf pair in the minimal land system compared to the year-round grazing system (P < .05).

An Economic Comparison of Rotational Grazing Systems to Eight Crop Alternatives and the CRP Option for Highly Erodible Land in Southwest Iowa

Economic comparisons of income on highly erodible land (HEL) in Adams County were made utilizing five years of grazing data collected from a 13- paddock intensive-rotational grazing system and a four-paddock rotational-grazing system and four years of data collected from an 18-paddock intensive-rotational grazing system, all at the Adams County CRP Research and Demonstration Farm near Corning. Net income from the average grazing weight-gain of Angus-sired calves nursing crossbred cows was compared to the net income from grazing yearling steers, to the net income of eight NRCS-recommended crop rotations, and to the Conservation Reserve Program (CRP) option. Results of these comparisons show the 13-paddock intensive rotational grazing system with cow-calf pairs to be the most profitable alternative, with a net return of $19.86 per acre per year. The second most profitable alternative is the CRP option, with a net return of $13.09 per acre, and the third most profitable option is the fourpaddock rotation with cows and calves with a net return of $12.53 per acre. An 18-paddock system returned a net income of $2.47 per acre per year with cows and calves in 1993, but lost an average of $107.69 per acre each year in 1994 and 1995 with yearling steers. Each year, the steers were purchased high and sold low, contributing to the large loss per acre. The following recommended crop rotations all show net losses on these 9-14 % slope, Adair-Shelby Complex soils (ApD3): continuous corn; corn-soybean rotation; corn-soybean rotation with a farm program deficiency payment; corn-corn-corn-oats-meadow-meadow rotation with grass headlands; continuous corn to “T” with grass headlands and buffer strips; continuous corn to “T” with grass headlands, buffer strips, and a deficiency payment; corn-corn-oats-meadow rotation to “T”; and corn-soybeans-oats-meadow-meadow-meadow-meadow rotation to “T”. Per-acre yield assumptions of 90 bushels for corn, 30 bushels for soybeans, 45 bushels for oats, and four tons for alfalfa were used, with per-bushel prices of $2.40 on corn, $5.50 on soybeans, and $1.50 on oats. Alfalfa hay was priced at $40.00 per ton and grass hay at $33.33 per ton. The calf weight-gain in the cow/ calf systems was valued at $.90 per pound. All crop expenses except land costs were calculated from ISU publication Fm 1712, “Estimated Costs of Crop Production in Iowa - 1995.” Land costs were determined by using an opportunity cost and actual property tax figures for the land at the grazing site. In preparation for the end of the CRP beginning in 1996, further economic comparisons will be made after additional grazing seasons and data collection. This project is an interagency cooperative effort sponsored by the Southern Iowa Forage and Livestock Committee which has special permission from the USDA Farm Service Agency (FSA) to use CRP land for research and demonstration.

Integrating the Use of Spring- and Fall-Calving Beef Cows in a Year-round Grazing System (A Progress Report)

Animal production, hay production and feeding, and the yields and composition of forage from summer and winter grass-legume pastures and winter corn crop residue fields from a year-round grazing system were compared with those of a conventional system. The year-round grazing system utilized 1.67 acres of smooth bromegrass-orchardgrass-birdsfoot trefoil pasture per cow in the summer, and 1.25 acres of stockpiled tall fescue-red clover pasture per cow, 1.25 acres of stockpiled smooth bromegrass-red clover pasture per cow, and 1.25 acres of corn crop residues per cow during winter for spring- and fall-calving cows and stockers. First-cutting hay was harvested from the tall fescue-red clover and smooth bromegrass-red clover pastures to meet supplemental needs of cows and calves during winter. In the conventional system (called the minimal land system), spring-calving cows grazed smooth bromegrass-orchardgrass-birdsfoot trefoil pastures at 3.33 acres/cow during summer with first cutting hay removed from one-half of these acres. This hay was fed to these cows in a drylot during winter. All summer grazing was done by rotational stocking for both systems, and winter grazing of the corn crop residues and stockpiled forages for pregnant spring-calving cows and lactating fall-calving cows in the year-round system was managed by strip-stocking. Hay was fed to springcalving cows in both systems to maintain a mean body condition score of 5 on a 9-point scale, but was fed to fall-calving cows to maintain a mean body condition score of greater than 3. Over winter, fall-calving cows lost more body weight and condition than spring calving cows, but there were no differences in body weight or condition score change between spring-calving cows in either system. Fall- and spring-calving cows in the yearround grazing system required 934 and 1,395 lb. hay dry matter/cow for maintenance during the winter whereas spring-calving cows in drylot required 4,776 lb. hay dry matter/cow. Rebreeding rates were not affected by management system. Average daily gains of spring-born calves did not differ between systems, but were greater than fall calves. Because of differences in land areas for the two systems, weight production of calves per acre of cows in the minimal land system was greater than those of the year-round grazing system, but when the additional weight gains of the stocker cattle were considered, production of total growing animals did not differ between the two systems.

Efficacy of Grazing Stockpiled Perennial Forages for Winter Maintenance of Beef Cows

In a three year study, wintering systems utilizing the grazing of stockpiled perennial hay crop forages or corn crop residues were compared to maintaining cows in a drylot. In the summer of 1992, two cuttings of hay were harvested (June 22 and August 2) from three 10-acre fields containing “Johnstone” endophyte-free tall fescue and “Spreador II” alfalfa, and one cutting of hay was harvested from three 10- acre fields of smooth brome grass. “Arlington” red clover was frost-seeded into the smooth bromegrass fields in 1993 and into tall fescue-alfalfa and smooth bromegrass fields into 1994. Two cuttings of hay were harvested from all fields in subsequent years, and three-year average hay yields for tall fescue-alfalfa and smooth bromegrass-red clover were 4,336 and 3,481 pounds per acre, respectively. Regrowth of the forage following the August hay harvest of each year was accumulated for winter grazing. Following a killing frost in each year, two fields of each stockpiled forage were stocked with cows in midgestation at two acres per cow. Two 10-acre fields of corn crop residues were also stocked at two acres per cow, following the grain harvest. Mean dry matter forage yields at the initiation of grazing were 1,853, 2,173 and 5,797 pounds per acre for fields containing tall fescue-alfalfa, smooth bromegrass-red clover, and cornstalks, respectively. A drylot was stocked with 18 cows in 1992 and 1993 and 10 cows in 1994. All cows were fed hay as necessary to maintain a body condition score of five. During grazing, mean losses of organic matter were -6.4, -7.6, and -10.7 pounds per acre per cow from tall fescue-alfalfa, smooth bromegrass-red clover, and cornstalk fields. Average organic matter loss rates from stockpiled forages due to weathering alone were equal to only 30% of the weathering losses of the corn crop residues. In vitro digestibility of both stockpiled forages and cornstalks decreased at equal rates during grazing each year, with respective annual loss rates of .14, .08, and .06% per day. Cows grazing corn crop residues required an average of 1,321 pounds per cow less hay than cows maintained in the drylot to maintain equivalent body condition during the grazing season. Cows grazing tall fescue-alfalfa or smooth bromegrass-red clover had body weight gains and condition score changes equal to cows maintained in a drylot but required 64% and 62% less harvested hay than cows in the drylot during the grazing season. Over the entire stored forage cows grazing tall fescue-alfalfa and smooth bromegrass-red clover required an average of 2,390 and 2,337 pounds per cow less than those maintained in the drylot. Because less hay was needed to maintain cows grazing stockpiled forages, average annual excesses of 5,629 and 3,868 pounds of hay dry matter per cow remained in the stockpiled tall fescue-alfalfa and smooth bromegrass-red clover systems.

Evaluation of a Year-Round Grazing System: Winter Progress Report

The winter component of a year-round grazing system involving grazing of corn crop residues followed by grazing stockpiled grass-legume forages was compared at the McNay Research Farm with that of the winter component of a minimal land system that maintained cows in drylot. In the summers of 1995 and 1996, two and one cuttings of hay per year were harvested from two 15-acre fields containing “Johnston” low endophtye tall fescue and red clover. Two cuttings of hay in 1995 and one cutting in 1996 were harvested from two 15-acre fields of smooth bromegrass and red clover. Hay yields were 4,236 and 4,600 pounds of dry matter per acre for the tall fescue-red clover in 1995 and 1996, and 2,239 and 2,300 pounds of dry matter per acre for the smooth bromegrass-red clover in 1995 and 1996. Following grain harvest, four 7.5-acre fields containing corn crop residues were stocked with cows at midgestation at an allowance of 1.5 acres per cow. Forage yields at the initiation of corn crop grazing in 1995 and 1996 were 3,757 and 3,551 pounds of dry matter per acre for corn crop residues. Stockpiled forage yields were 1,748 and 2,912 pounds of dry matter for tall fescue-red clover and 1,880 and 2,187 pounds for smooth bromegrass-red clover. Corn crop residues and stockpiled forages were grazed in a strip stocking system. For comparison, 20 cows in 1995 and 16 cows in 1996 were placed in two drylots simultaneously with initiation of corn crop grazing, where they remained throughout the winter and spring grazing periods. Cows maintained in drylots or grazing corn crop residue and stockpiled forages were supplemented with hay as large round bales to maintain a body condition score of five. In both years, no seasonal differences in body weight and body condition score were observed between grazing cows or cows maintained in drylots, but grazing cows required 85% and 98% less harvested hay in years 1 and 2 than cows in drylot during the winter and spring. Because less hay was needed to maintain grazing cows, excesses of 12,354 and 5,244 pounds of hay dry matter per cow in 1995 and 1996 remained in the year-round grazing system. During corn crop grazing, organic matter yield decreased at 23.5 and 28.8 pounds of organic matter per day from grazed areas of corn crop residues in 1995 and 1996. Organic matter losses due to weathering were 6.8, 10.3, and 12.7 pounds per day in corn crop residue, tall fescue-red clover and smooth bromegrass-red clover in 1995 and 12.1, 10.7, and 12.1 in 1996. Organic matter losses from grazed and ungrazed areas of tall fescue-red clover and smooth bromegrass-red clover during stockpiled grazing were 6.9, 6.9, and 2.1, 2.9 in 1995 and 13.4, 4.3, and +6.9, 4.4 pounds per day in 1996.

Evaluation of a Year-Round Grazing System: Winter Progress Report

The winter component of a year-round grazing system involving grazing of corn crop residues followed by grazing stockpiled grass legume forages was compared at the McNay Research Farm with that of the winter component of a minimal land system that maintained cows in drylot,. In the summer of 1995, two cuttings of hay were harvested from two 15-acre fields containing “Johnston” endophyte-free tall fescue and red clover, and two cuttings of hay were taken from two 15-acre fields of smooth bromegrass and red clover. Hay yields were 4,236 and 4,600 pounds of dry matter per acre for the tall fescue--red clover and smooth bromegrass--red clover. Following grain harvest four 7.5-acre fields containing corn crop residue were stocked with cows at midgestation at an allowance of 1.5 acres per cow. Forage yields at the initiation of corn crop grazing were 3,766pounds of dry matter per acre for corn crop residue, 1,748 pounds for tall fescue--red clover, and 1,.880 pounds for smooth bromegrass--red clover. Corn crop residues and stockpiled forages were grazed in a strip stocking system. For comparison, 20 cows were placed in two drylots simultaneously to the initiation of corn crop grazing where they remained throughout the winter and spring grazing seasons. Cows maintained in drylot or grazing corn crop residue and stockpiled forages were supplemented with hay as large round bales to maintain a body condition score of five. No seasonal differences in body weight and body condition were observed between grazing cows or cows maintained in drylot, but grazing cows required 87% and 84% less harvested hay than cows in drylot during the winter and spring respectively. Because less hay was needed to maintain grazing cows, an excess of 11,905 and 12,803 pounds of hay dry matter per cow remained in the year-round grazing system. During corn crop grazing, organic matter yield decreased at 27.3 pounds of organic matter per day from grazed areas of corn crop residue. Organic matter losses due to weathering were 9.4, 12.9, and 15.8 pounds per day in corn crop residue, tall fescue-red clover and smooth bromegrass-red clover. Organic matter losses from grazed and ungrazed areas during stockpiled grazing were 7.3 and 6.9 for tall fescue--red clover and 2.1, 2.9 for smooth bromegrass--red clover.

Use of Stockpiled Berseem Clover as a Supplement for Grazed Corn Crop Residues

In the fall of 1994, mature Charolais cross cows in midgestation were allotted to duplicate 15 acre fields containing corn crop residues or a 2-to-1 mixture of corn crop residues and berseem clover planted in 3 strips at an allowance of 2.5 acres/cow for a 140 day wintering season. Similar cows were allotted duplicate drylots. All cows were fed hay as necessary to maintain a body condition score of 5. Cows grazing corn crop residues with or without berseem clover required 2596 pounds less hay per cow than cows maintained in a drylot. There was no difference in the amounts of hay required by cows grazing corn crop residues alone or with berseem clover. Initial organic matter yield of berseem clover was nearly that of corn crop residues and did not decrease as rapidly as corn crop residues. Berseem clover had a higher organic matter digestibility than corn crop residues at the initiation of grazing. Organic matter digestibility of berseem clover, however, decreased more rapidly than corn crop residues because of weathering during the winter.

A non-coding genomic duplication at the HMX1 locus is associated with crop ears in highland cattle.

Highland cattle with congenital crop ears have notches of variable size on the tips of both ears. In some cases, cartilage deformation can be seen and occasionally the external ears are shortened. We collected 40 cases and 80 controls across Switzerland. Pedigree data analysis confirmed a monogenic autosomal dominant mode of inheritance with variable expressivity. All affected animals could be traced back to a single common ancestor. A genome-wide association study was performed and the causative mutation was mapped to a 4 Mb interval on bovine chromosome 6. The H6 family homeobox 1 (HMX1) gene was selected as a positional and functional candidate gene. By whole genome re-sequencing of an affected Highland cattle, we detected 6 non-synonymous coding sequence variants and two variants in an ultra-conserved element at the HMX1 locus with respect to the reference genome. Of these 8 variants, only a non-coding 76 bp genomic duplication (g.106720058_106720133dup) located in the conserved region was perfectly associated with crop ears. The identified copy number variation probably results in HMX1 misregulation and possible gain-of-function. Our findings confirm the role of HMX1 during the development of the external ear. As it is sometimes difficult to phenotypically diagnose Highland cattle with slight ear notches, genetic testing can now be used to improve selection against this undesired trait.

Agroecosystem resilience and farmers’ perceptions of climate change impacts on cocoa farms in Alto Beni, Bolivia

Cocoa-based small-scale agriculture is the most important source of income for most farming families in the region of Alto Beni in the sub-humid foothills of the Andes. Cocoa is grown in cultivation systems of varying ecological complexity. The plantations are highly susceptible to climate change impacts. Local cocoa producers mention heat waves, droughts, floods and plant diseases as the main impacts affecting plants and working conditions, and they associate these impacts with global climate change. From a sustainable regional development point of view, cocoa farms need to become more resilient in order to cope with the climate change related effects that are putting cocoa-based livelihoods at risk. This study assesses agroecosystem resilience under three different cocoa cultivation systems (successional agroforestry, simple agroforestry and common practice monocultures). In a first step, farmers’ perceptions of climate change impacts were assessed and eight indicators of agroecological resilience were derived in a transdisciplinary process (focus groups and workshop) based on farmers’ and scientists’ knowledge. These indicators (soil organic matter, depth of Ah horizon, soil bulk density, tree species diversity, crop varieties diversity, ant species diversity, cocoa yields and infestation of cocoa trees with Moniliophthora perniciosa) were then surveyed on 15 cocoa farms and compared for the three different cultivation systems. Parts of the socio-economic aspects of resilience were covered by evaluating the role of cocoa cooperatives and organic certification in transitioning to more resilient cocoa farms (interviews with 15 cocoa farmers combined with five expert interviews). Agroecosystem resilience was higher under the two agroforestry systems than under common practice monoculture, especially under successional agroforestry. Both agroforestry systems achieved higher cocoa yields than common practice monoculture due to agroforestry farmers’ enhanced knowledge regarding cocoa cultivation. Knowledge sharing was promoted by local organizations facilitating organic certification. These organizations were thus found to enhance the social process of farmers’ integration into cooperatives and their reorientation toward organic principles and diversified agroforestry.

Challenging conservation agriculture on marginal slopes in Sehoul, Morocco

In Sehoul, Morocco, the use of marginal land for agriculture became a necessity for the local population due to increased poverty and the occupation of the best land by new owners. Desertification poses an additional threat to agricultural production on marginal slopes, which are often stony and degraded. In a participatory process embedded in the EU DESIRE research project, potential sustainable land management measures were selected to address land degradation and desertification. Promising experiences with no-tillage practices elsewhere in Morocco had motivated the Moroccan government to promote conservation agriculture throughout the country. This combination of crop rotation, minimal soil disturbance and soil cover maintenance, however, had not yet been tested on sloping degraded land. Field trials of grazing enclosure combined with no or minimum tillage were conducted on the plots of two farmers, and trial results were analyzed based on stakeholders’ criteria. Results suggest that increased soil cover with barley residues improved rainwater use efficiency and yields only slightly, although soil water was generally enhanced. Soil moisture measurements revealed that no-tillage was favorable mainly at soil depths of 5 cm and in connection with low-rainfall events (<20 mm); under these circumstances, moisture content was generally higher under no-tillage than under conventional tillage. Moreover, stakeholder discussion confirmed that farmers in Sehoul remain primarily interested in animal husbandry and are reluctant to change the current grazing system. Implementation of conservation agriculture is thus challenged both by the degraded, sloping and stony nature of the land, and by the socio-economic circumstances in Sehoul.