Verrucosamide,a Cytotoxic 1,4-Thiazepane-Containing Thiodepsipeptide from a Marine-Derived Actinomycete

A new cytotoxic thiodepsipeptide, verrucosamide (1), was isolated along with the known, related cyclic peptide thiocoraline, from the extract of a marine-derived actinomycete, a Verrucosispora sp., our strain CNX-026. The new peptide, which is composed of two rare seven-membered 1,4-thiazepane rings, was elucidated by a combination of spectral methods and the absolute configuration was determined by a single X-ray diffraction study. Verrucosamide (1) showed moderate cytotoxicity and selectivity in the NCI 60 cell line bioassay. The most susceptible cell lines were MDA-MB-468 breast carcinoma with an LD₅₀ of 1.26 µM, and COLO 205 colon adenocarcinoma with an LD₅₀ of 1.4 µM. Also isolated along with verrucosamide were three small 3-hydroxy(alkoxy)-quinaldic acid derivatives that appear to be products of the same biosynthetic pathway.     

Physiological responses of young thoroughbred horses to intermittent high-intensity treadmill training

Background

Training of young Thoroughbred horses must balance development of cardiopulmonary function and aerobic capacity with loading of the musculoskeletal system that can potentially cause structural damage and/or lameness. High-speed equine treadmills are sometimes used to supplement exercise on a track in the training of young Thoroughbreds because the horse can run at high speeds but without the added weight of a rider. We tested the hypothesis that intermittent high-intensity exercise on a treadmill of young Thoroughbred horses entering training can enhance development of aerobic capacity (Vo₂max) and running performance more than conventional training under saddle, and do so without causing lameness.

Results

Twelve yearling Thoroughbreds trained for 8 months with conventional riding (C) only, conventional riding plus a short (2 month, S) interval of once-per-week high-intensity treadmill exercise, or a long (8 month, L) interval of once-per-week high-intensity treadmill exercise. Three treadmill exercise tests evaluated Vo₂max, oxygen transport and running performance variables in June of the yearling year (only for L), October of the yearling year and April of the 2-year-old year. No horses experienced lameness during the study. Aerobic capacity increased in all groups after training. In both October and April, Vo₂max in L was higher than in C, but did not differ between L and S or S and C. Running speeds eliciting Vo₂max also increased in all groups after training, with S (809 ± 3 m/s) and L (804 ± 9 m/s) higher than C (764 ± 27 m/s). Maximum heart rate decreased for all groups after training. Hematocrit and hemoglobin concentration increased for L throughout training.

Conclusions

Young Thoroughbred horses can increase aerobic capacity and running performance more than by strictly using track training under saddle with the addition of intermittent high-intensity treadmill exercise, and they can do so without experiencing lameness. This finding suggests that young racehorses might be able to achieve higher aerobic fitness during training without subjecting their musculoskeletal systems to increased loading and risk of developing lameness. The findings of this preliminary study do not indicate a specific protocol to best achieve this goal.     

Characterisation of agricultural drainage ditch sediments along the phosphorus transfer continuum in two contrasting headwater catchments

Purpose

This study investigated the phosphorus (P) source, mobilisation and transport potential of ditch bed sediments as well as surrounding field and bank soils in two agricultural headwater catchments with contrasting soil drainage capacities. This information is important for discerning the potential for ditches to attenuate or augment transfers of P from upstream sources and thus for developing appropriate management strategies for these features.

Materials and methods

Phosphorus sources were characterised using the Mehlich3-P, water-soluble P and total P tests. Phosphorus mobilisation potential was characterised using the Mehlich3-AL/P, Mehlich3-Ca/P and DESPRAL P tests. Phosphorus transport potential was characterised using data collected on the presence/absence of surface water in ditches during field surveys and downstream turbidity data.

Results and discussion

Ditch sediments had similar P source contents (Mehlich3-P, water-soluble P and total P) to the surrounding field soils and higher P contents than bank soils. However, calcium contents of sediments in the poorly drained catchment reflected the deep sub-soils rather than the surrounding field and bank soils. Mehlich3-Al/P and Mehlich3-Ca/P contents of ditch sediments in the well (non-calcareous) and poorly (calcareous) drained catchments respectively indicated potential for P retention (above thresholds of 11.7 and 74, respectively). However, sediments were less aggregated than field soils and may mobilise more particulate P (PP) during rain events. Nevertheless, the majority of surveyed ditches dried out from March to September 2011; thus, their potential to mobilise PP may be less important than their capacity to attenuate soluble and PP during this time.

Conclusions

In these and similar catchments, soluble P attenuation and particulate P mobilisation should be maximised and minimised, respectively, for example, by cleaning out the sediments before they become saturated with P and encouraging vegetation growth on ditch beds. This study also highlighted the influence of deep sub-soils on soluble P retention in ditches and thus the utility of characterising soils below depths normally included in soil classifications.

     

Surgical procedure and postoperative management of a perineal urethrostomy in a chimpanzee (Pan troglodytes).

A chimpanzee (Pan troglodytes) with traumatic loss of the distal penis developed a gradually enlarging ventral urethral swelling and progressive dysuria. Endoscopy identified a urethral diverticulum, and endoscopic resection of the diverticulum wall was performed. Postoperative infection caused extensive necrosis of the penis, which necessitated a perineal urethrostomy. Complications of the urethrostomy included urethral obstruction from recurrent urethral stricture. The stricture was managed by regular dilatation using urethral bougies. Because of considerable postoperative swelling, catheterization was required to allow micturition following both the diverticular resection and polyp debulking. A shortened catheter sutured to the skin was tolerated for up to 10 days. Four yr after the urethrostomy, the animal is healthy and asymptomatic with endoscopic examinations performed at 12 mo intervals. This case demonstrates that with appropriate aftercare, perineal urethrostomy is an effective technique in the treatment of chronic distal urethral obstruction in the chimpanzee and probably other primate species.     

Strategies for reducing subsurface drainage in irrigated agriculture through improved irrigation

The traditional approach ofinstalling subsurface drainage systems tosolve shallow ground water problems is notfeasible along the west side of the SanJoaquin Valley of California because of thelack of drain water disposal methods thatare economical, technically feasible, andenvironmentally friendly. Thus, optionssuch as drainage reduction through improvedirrigation and drain water reuse are beingexamined as methods for coping with thesubsurface drainage problem. This paperdiscusses options for reducing subsurfacedrainage through improved irrigationpractices. Options are discussed forimproving irrigation system design such asupgrading existing irrigation methods andconverting to systems with higher potentialirrigation efficiencies. Methods forimproving water management are alsopresented. Case studies on upgradingexisting systems or converting to otherirrigation methods are presented along with study results of the effect of variouspolicies on reducing subsurface drainage.     

Subsurface drip irrigation for corn production: a review of 10 years of research in Kansas

Kansas State University initiated studies in 1989 to develop the methodology for successful application of subsurface drip irrigation (SDI) for corn production on the deep silt loam soils of the Central Great Plains, USA. Irrigation water use for corn can be reduced by 35–55% when using SDI compared with more traditional forms of irrigation in the region. Irrigation frequency has not been a critical issue when SDI is used for corn production on the deep silt loam soils of the region. A dripline spacing of 1.5 m has been found to be most economical for corn grown in 0.76 m spaced rows. Nitrogen fertigation was a very effective management tool with SDI, helping to maximize corn grain yield, while obtaining high efficiencies of nitrogen and water use. The research SDI systems have been utilized since 1989 without replacement or major degradation. SDI systems lasting 10–20 years are cost competitive for corn production with the more traditional forms of irrigation in the Great Plains for certain field sizes.Communicated by P. Thorburn     

Eel acetylcholinesterase inhibition studies with heteroarylphosphinates

The inhibition of eel acetylcholinesterase by the 4-nitrophenyl esters of 2-furyl(methyl)-, methyl(2-thienyl)-, di-2-furyl-, and di-2-thienylphosphinic acid (I, II, III, and IV, respectively) was investigated at pH 6.90 in 0.067 M phosphate buffer (25.0°C) using stopped-flow instrumentation and automated data processing. Our evaluation of the dissociation constant, K_d, the unimolecular bonding rate constant, k₂, and the bimolecular reaction constant, k_i, are the first reported values for these constants for alkyl/heteroaryl and diheteroaryl esters of phosphinic acids. The largest k_i value (19,330 M^?1 sec^?1) was observed for the reaction of I with the enzyme. The order for the remaining three is II > IV > III. There is no direct relationship between the hydrolysis rates of the esters and their anticholinesterase activities on eel acetylcholinesterase. Likewise, there is no direct relationship between their anticholinesterase activities and the LD₅₀ values in rats.     

Effect of continuous intravenous administration of a 50% dextrose solution on phosphorus homeostasis in dairy cows

OBJECTIVE: To determine the effect of continuous IV administration of 50% dextrose solution on phosphorus homeostasis in lactating dairy cows. DESIGN: Clinical trial. ANIMALS: 4 multiparous Jersey cows. PROCEDURES: Cows were administered 50% dextrose solution IV (0.3 g/kg/h [0.14 g/lb/h]) for 5 days. Plasma concentrations of glucose, immune-reactive insulin (IRI), and phosphorus were determined before, during, and for 72 hours after dextrose infusion. Phosphorus intake and losses of phosphorus in urine, feces, and milk were determined. Each cow received a sham treatment that included instrumentation and sampling but not administration of dextrose. RESULTS: Plasma glucose, IRI, and phosphorus concentrations were stable during sham treatment. Plasma phosphorus concentration decreased rapidly after onset of dextrose infusion, reaching a nadir in 24 hours and remaining less than baseline value for 36 hours. Plasma phosphorus concentration increased after dextrose infusion was stopped, peaking in 6 hours. Urinary phosphorus excretion did not change during dextrose infusion, but phosphorus intake decreased because of reduced feed intake, followed by decreased fecal phosphorus loss and milk yield. Rapid changes in plasma phosphorus concentration at the start and end of dextrose infusion were temporally associated with changes in plasma glucose and IRI concentrations and most likely caused by compartmental shifts of phosphorus. CONCLUSIONS AND CLINICAL RELEVANCE: Hypophosphatemia developed in response to hyperglycemia or hyperinsulinemia in dairy cows administered dextrose via continuous IV infusion. Veterinarians should monitor plasma phosphorus concentration when administering dextrose in this manner, particularly in cows with decreased appetite or preexisting hypophosphatemia.     

Disseminated protothecosis diagnosed by evaluation of CSF in a dog

A 5-year-old female spayed Shetland Sheepdog Mix dog was evaluated for a history of recent seizure activity, progressive hind limb ataxia, polyuria, and polydipsia and no history of gastrointestinal signs. Physical examination findings included conscious proprioceptive deficits, ataxia, and anterior uveitis along with a hypermature cataract in the right eye. Results of a CBC, serum biochemical profile, urinalysis, and computed tomography scan of the brain were unremarkable. Cerebrospinal fluid (CSF) analysis revealed marked eosinophilic pleocytosis and rare organisms consistent with Prototheca spp within neutrophils and macrophages. On postmortem histologic examination, mononuclear inflammation and numerous intralesional algal organisms, similar to those seen on the cytologic preparation of CSF, were found in the brain, eyes, kidneys, and heart. Abnormalities were not detected on gross and histologic examination of the gastrointestinal tract. Cultures of CSF and subdural/olfactory bulb, but not intestinal tract, yielded growth of Prototheca spp, and PCR analysis and DNA sequencing confirmed the organism as Prototheca zopfii genotype 2. We have reported a rare case of disseminated protothecosis that was diagnosed by evaluation of CSF in a dog presented with neurologic signs and no overt enteric disease. Protothecosis should be considered as a rare cause of seizures, even in the absence of obvious enteric signs, and should be included in the differential diagnosis of eosinophilic pleocytosis.