Phase I trial and pharmacokinetic analysis of ifosfamide in cats with sarcomas

OBJECTIVE: To determine the maximally tolerated dose (MTD) and dose-limiting toxicosis (DLT) of ifosfamide in tumor-bearing cats. ANIMALS: 38 cats with resected, recurrent, or metastatic sarcomas. PROCEDURE: The starting dosage of ifosfamide was 400 mg/m(2) of body surface area, IV, and dosages were increased by 50 to 100 mg/m(2) in cohorts of 3 cats. To protect against urotoxicosis, mesna was administered at a dosage equal to 20% of the calculated ifosfamide dosage. Diuresis with saline (0.9% NaCl) solution before and after administration of ifosfamide was used to minimize nephrotoxicosis. Samples for pharmacokinetic analysis were obtained after the MTD was reached. RESULTS: 38 cats were entered into this phase I study and were administered a single dose of ifosfamide at various dosages. The MTD was 1,000 mg/m(2), and neutropenia was the DLT. Seven of 8 episodes of neutropenia were on day 7 after treatment, and 1 cat developed severe neutropenia on day 5. Adverse effects on the gastrointestinal tract were generally mild and self-limiting, the most common of which was nausea during ifosfamide infusion. One cat had signs consistent with a drug-induced hypersensitivity reaction. There were no episodes of hemorrhagic cystitis or nephrotoxicosis. Correlations between pharmacokinetic variables and ifosfamide-associated toxicoses were not found. Preliminary evidence of antitumor activity was observed in 6 of 27 cats with measurable tumors. CONCLUSIONS AND CLINICAL RELEVANCE: The dosage of ifosfamide recommended to treat tumor-bearing cats is 900 mg/m(2) every 3 weeks. This dosage should be used in phase II clinical trials.     

Modeling the effect of initial planting density on within tree variation of stiffness in loblolly pine

Context

Modulus of elasticity (MOE) is an important mechanical property determining the end-use and value of loblolly pine (Pinus taeda L.) lumber.

Aim

In this study, a model was developed to predict the within tree variation of MOE, from pith-to-bark and stump-to-tip, using data collected from a 21-year-old unthinned stand where trees were planted under seven initial stand density levels (746?C2,243 trees/hectare).

Methods

The study was laid out in a randomized complete block design, with seven levels of initial planting density, replicated three times. Seven trees were destructively sampled from each plot, and bolts were cut from each tree at heights of 2.4, 7.3, and 12.2?m. Static bending samples (of dimension 2.5?×?2.5?×?40.6?cm) representing pith-to-bark variation were cut from each bolt and MOE measured. A three-parameter logistic function was used to model the pith-to-bark variation in stiffness with distance from pith as an explanatory variable.

Results

Based on the final fitted model, it was found that the asymptotic parameter (maximum outerwood MOE?=?13.48?GPa) was not influenced by sampling height, initial planting density, and stem slenderness. However, the inflection and scale parameters were significantly influenced by these variables.

Conclusions

In summary, we found that initial planting density had a significant influence on the amount of corewood produced with higher initial planting densities producing a lower proportion of corewood as indicated by a linear decrease in inflection point with an increase in planting density.     

Effects of salinity on growth characteristics and osmoregulation of juvenile cobia,Rachycentron canadum (Linnaeus 1766), reared in potassium‐amended inland saline groundwater

The suitability of inland saline groundwater as a medium to culture juvenile cobia, Rachycentron canadum, was assessed. In the first experiment, juvenile cobia stocked in raw (unamended) saline groundwater at salinities of 5, 10, and 15 g/L exhibited complete mortality after 108, 176, and 195 hr, respectively. The second experiment evaluated the rearing of juvenile cobia (mean weight ~9.23 ± 0.12 g) in potassium (K⁺)‐amended saline groundwater (100% K⁺ fortified) and reconstituted seawater at salinities of 5, 10, and 15 g/L to assess growth and osmoregulation in distinct culture media. Following 60 days of culture, all fish survived the experimental period. Final mean bodyweight of cobia reared in K⁺‐amended saline groundwater (103.2–115.8 g) and seawater (111.2–113.8 g) of different salinities did not vary significantly (p > .05). No differences (p > .05) were observed in specific growth rate, weight gain (%), and feed conversion ratio between treatment groups. Serum osmolality increased with salinity and was significantly higher (p < .05) for fish in K⁺‐amended saline groundwater (353–361 mOsmol/Kg) than in reconstituted seawater (319–332 mOsmol/Kg), although differences were not observed between salinities by water type. Cobia stocked in saline groundwater of different salinities were osmoregulating normally, and the higher values observed may be because of variations in ionic composition and other interfering ions in saline groundwater. Trial results suggest that juvenile cobia can achieve optimal growth in K⁺‐amended saline groundwater of low and intermediate salinities.     

Pollination-induced oxidative stress in floral organs of Cymbidium pendulum (Roxb.) Sw. and Cymbidium aloifolium (L.) Sw. (Orchidaceae): A biochemical investigation

A perusal of literature showed that a little is known about the metabolic changes related to senescence in orchid flowers. It was observed that unpollinated flowers of Cymbidium pendulum (Roxb.) Sw. remained fresh for 20 days and senesced within 8 days after pollination (DAP), while that of Cymbidium aloifolium (L.) Sw. took 18 days when unpollinated but showed senescence in 7 DAP. A higher level of electrolyte leakage was recorded in all the floral organs of pollinated flowers in both the species. There was a concomitant increase in levels of malondialdehyde (MDA) and hydrogen peroxide (H₂O₂); indicators of oxidative damage, in all the organs for both the species. Ascorbic acid, on the other hand, decreased significantly. Higher amount of electrolyte leakage, MDA and H₂O₂ content were recorded in C. pendulum as compared of the other species while the ascorbic acid, on the other hand, was observed to be decreased and this decrease was more in C. pendulum than C. aloifolium suggesting a higher oxidative damage to the floral organs in the former species than the latter. TIBA, i.e. tri-iodobenzoic acid (an auxin inhibitor; 0.25 μM) and silver nitrate (ethylene inhibitor; 0.25 μM) application to pollinated flowers partially prevented the elevation of oxidative damage and consequently senescence suggesting the involvement of these hormones in governing these changes in orchid flowers. Comparatively, AgNO₃ was more effective than TIBA in delaying senescence.     

Isolation,Characterization and Quantification of Tricin and Flavonolignans in the Medicinal Rice Njavara (<Emphasis Type="Italic">Oryza sativa</Emphasis> L.), as Compared to Staple Varieties

Njavara is an important medicinal rice variety of Kerala, India, widely used in Ayurveda as a ‘health food’ and in the treatment of rheumatoid arthritis, paralysis, neurodegenerative diseases and in rejuvenation therapy. Phytochemical investigations and spectroscopic studies of the diethyl ether fraction of methanolic extract of Njavara Black (NB) rice bran gave three important compounds namely, tricin and two rare flavonolignans- tricin 4′-O-(erythro-β-guaiacylglyceryl) ether and tricin 4′-O-(threo-β-guaiacylglyceryl) ether. The EC₅₀ values of these compounds in DPPH system were 90.39, 352.04 and 208.1 μg/ml, respectively. Quantification of the compounds by HPLC in NB and staple, non-medicinal rice varieties Sujatha (SJ) and Palakkadan Matta (PM) showed that tricin is present 39.64 and 16.12 fold higher in NB, compared to SJ and PM, respectively. This is the first report on the occurrence of tricin at significantly higher levels in Njavara and occurrence of the two flavonolignans in Oryza sativa species. Of the three compounds, tricin and the threo- form of flavonolignan showed anti-inflammatory effect of >65% after 5 h, at 2 mg/kg, in carrageenan-induced, paw edema experiments in rats. The results of the study corroborate with the preferential use of Njavara in indigenous medicine, over staple varieties.     

1,2,4-Triazolyl functionalized allyl sulfide with antifungal potential for the control of Fusarium fujikuroi causing foot rot of rice

European Journal of Plant Pathology - The present study focuses on antifungal potential of 1,2,4-triazole derivatives of allyl sulfides. The antifungal potential of synthesized...     

Evidence of increased Hepatitis E virus exposure in Lao villagers with contact to ruminants

Although pigs are the main reservoir, ruminants have also been shown to be susceptible to hepatitis E virus (HEV). We investigated zoonotic transmission of HEV in rural settings of Lao People's Democratic Republic (Lao PDR) where humans are in close contacts with ruminants and where pigs are rare. Villagers with (n = 171, risk group) and without (n = 155, control group) cattle were recruited in seven villages in Vientiane Capital. Owners of pigs were excluded. Blood, as well as information on socio‐demographics, animal contact, dietary habits and awareness of zoonoses were collected to assess risk factors. Blood and rectal swabs were collected from cattle (n = 173) and other ruminants (27 goat, 5 buffaloes) to measure anti‐HEV antibody and virus prevalence. A similar anti‐HEV antibody seroprevalence was found in cattle (6.8%) and other ruminants (8%). HEV RNA was detected in none of the animal rectal swabs and human sera. Anti‐HEV IgG seroprevalence was higher in cattle farmers than in the control group (59.1% vs. 43.9%, p = 0.008) and increased significantly with age. Other risk factors included male gender, close contact with cattle and consumption of undercooked meat. We find that HEV is highly endemic in rural Laos and provide first evidence that HEV circulates in free‐roaming ruminants with open access to village water sources. Despite some awareness about hygiene, villagers are likely constantly exposed to zoonotic diseases by dietary and lifestyle habits. Cattle farmers had a higher risk of HEV infection than other villagers. Our study highlights the need to raise the awareness of the rural population about water‐ and food‐borne pathogens, and about the role of cattle as a possible source of infection. The knowledge gained on local risk factors and husbandry conditions should guide future awareness raising campaigns and promote appropriate hygienic measures including handwashing and the consumption of safe food and water.     

On the occurrence,distribution and taxonomy of <Emphasis Type="Italic">Momordica subangulata</Emphasis> Blume subsp. <Emphasis Type="Italic">renigera</Emphasis> (G. Don) de Wilde in India

Different authors in India and South East Asia treat dioecious species in the genus Momordica differently. The cultivated ‘bhat karela’ of East and North East India is referred to as Momordica dioica Roxb. by botanists and herbarium curators whereas agricultural scientists, in general, designate it as Momordica cochinchinensis Spreng. A critical study of 266 herbarium sheets housed at CAL and BSISH and in situ field studies at specific pockets in the North East India followed by preliminary characterization revealed its correct identity as Momordica subangulata Blume subsp. renigera (G. Don) de Wilde. First hand information on its occurrence, taxonomy and distribution in India is given. The species was found in wild as well as in homestead cultivation in North Eastern India and exemplify direct utilization of biodiversity by indigenous people.

Cellulose synthase-like CslF genes mediate the synthesis of cell wall (1,3;1,4)-beta-D-glucans

A characteristic feature of grasses and commercially important cereals is the presence of (1,3;1,4)-beta-d-glucans in their cell walls. We have used comparative genomics to link a major quantitative trait locus for (1,3;1,4)-beta-d-glucan content in barley grain to a cluster of cellulose synthase-like CslF genes in rice. After insertion of rice CslF genes into Arabidopsis, we detected (1,3;1,4)-beta-d-glucan in walls of transgenic plants using specific monoclonal antibodies and enzymatic analysis. Because wild-type Arabidopsis does not contain CslF genes or have (1,3;1,4)-beta-d-glucans in its walls, these experiments provide direct, gain-of-function evidence for the participation of rice CslF genes in (1,3;1,4)-beta-d-glucan biosynthesis.