Reference Intervals of Mineral Elements in Plasma of Anesthetized Free-Ranging Adult Females of South American Sea Lion, Otaria flavescens.

Levels of zinc (Zn), copper (Cu), potassium (K), calcium (Ca), magnesium (Mg), and phosphorus (P) in plasma of Otaria flavescens females (n = 29) were evaluated. Reference intervals were established for each element, being the first report for this species.

The electrocardiogram of anaesthetized southern sea lion (Otaria flavescens) females.

OBJECTIVES: The goal of this study was to characterize for the first time the electrocardiogram (ECG) of the southern sea lion (SSL) Otaria flavescens. ANIMALS, MATERIALS AND METHODS: Thirteen wild SSL females were captured at Isla de Lobos (Uruguay) and anaesthetized with isoflurane. Electrocardiographic recording was performed on anaesthetized animals at ventral recumbence following standardized procedures. RESULTS: The ECG recordings showed normal sinus rhythm. Amplitude and duration of P and T waves, QRS complex, PR interval, QT interval and ST segment (STS) were determined for all animals in all leads. QT corrected was determined in lead II. P wave polarity was consistent among animals (positive in LI, LII, LIII and AVF leads and negative in AVL and AVR leads for all animals), but T wave polarity did not present any constant pattern among animals, being either positive, negative or biphasic in different leads and different animals. The PR interval (0.15 ± 0.2 s) was similar to the allometric prediction for most of mammalian species including humans. The STS were normal in 10 of the SSL but showed STS depression in three of the animals. Almost all animals had a negative electrical axis (-30° to -120°), with one exception that showed a positive electrical axis (120°). Mean eupnoeic heart rate was 104.61 ± 10.06 (range = 88-120) beats per minute. CONCLUSIONS: This study was the first ECG description for this species, and provides valuable information for cardiac monitoring during anaesthesia.

Metallothioneins pattern during ontogeny of coastal dolphin, Pontoporia blainvillei, from Argentina.

Metallothioneins are signals of metal exposure and widely used in biomonitoring. Franciscana dolphin is an endemic cetacean from the Southwestern Atlantic Ocean, classified as Vulnerable A3d by the IUCN. Metallothionein, copper and zinc in Franciscana were assessed in two geographic groups; one inhabits La Plata River estuary, anthropogenically impacted, and the other inhabits marine coastal ecosystems, with negligible pollution. Despite the environment, hepatic and renal MT concentrations were similar, but there was a declining trend from early to later developmental stages. Metallothionein K/L, Cu and Zn levels corresponded to normal reported ranges. MT was not related with Cd. Fetal concentrations were higher than its mother. These results and the health status of dolphins are suggesting that MT correspond to physiological ranges for the species, and they are closely to homeostasis of Zn and Cu, according to its ontogenetic changes. The information constitutes the first MT information on Franciscana dolphin and can be considered as baseline for the species conservation.

Resting metabolic rate and heat increment of feeding in juvenile South American fur seals (Arctocephalus australis).

Bio-energetic models used to characterize an animal's energy budget require the accurate estimate of different variables such as the resting metabolic rate (RMR) and the heat increment of feeding (HIF). In this study, we estimated the in air RMR of wild juvenile South American fur seals (SAFS; Arctocephalus australis) temporarily held in captivity by measuring oxygen consumption while at rest in a postabsorptive condition. HIF, which is an increase in metabolic rate associated with digestion, assimilation and nutrient interconversion, was estimated as the difference in resting metabolic rate between the postabsorptive condition and the first 3.5h postprandial. As data were hierarchically structured, linear mixed effect models were used to compare RMR measures under both physiological conditions. Results indicated a significant increase (61%) for the postprandial RMR compared to the postabsorptive condition, estimated at 17.93±1.84 and 11.15±1.91mL O2 min(-1)kg(-1), respectively. These values constitute the first estimation of RMR and HIF in this species, and should be considered in the energy budgets for juvenile SAFS foraging at-sea.

Fine scale distribution constrains cadmium accumulation rates in two geographical groups of Franciscana dolphin from Argentina.

Franciscana dolphin is an endemic cetacean in the southwestern Atlantic Ocean and is classified as Vulnerable A3d by the International Union for Conservation of Nature. Cadmium accumulation was assessed in two geographic groups from Argentina; one inhabits the La Plata River estuary, a high anthropogenic impacted environment, and the other is distributed in marine coastal, with negligible pollution. Despite the environment, marine dolphins showed an increase of renal Cd concentrations since trophic independence; while in estuarine dolphins was from 6 years. This is associated with dietary Argentine anchovy which was absent in the diet of estuarine dolphins, being a trophic vector of cadmium in shelf waters of Argentina. Cluster analysis also showed high levels of cd in association with the presence of anchovy in the stomach. The difference in the fine scale distribution of species influences dietary exposure to Cd and, along with other data, indicates two stocks in Argentina.

Phase II study of bryostatin 1 in patients with relapsed multiple myeloma.

Bryostatin 1, a macrocyclic lactone isolated from the marine bryozoan Bugula neritina, is a protein kinase C (PKC) modulator which has shown both preclinical and clinical activity in lymphoid malignancies. We conducted a phase II trial of bryostatin 1 administered at a dose of 120 microg/m2 by 72-h continuous infusion every 2 weeks in patients with relapsed multiple myeloma. Treatment was well tolerated with myalgias constituting the primaray toxicity. There were no responses in nine evaluable patients. The preclinical anti-lymphoid activity is strong enough to support further exploration of bryostatin 1 in different schedules and in combination therapy for multiple myeloma.

Phase II trial of bryostatin 1 in patients with relapsed low-grade non-Hodgkin's lymphoma and chronic lymphocytic leukemia.

Bryostatin 1 is a natural product isolated from the marine bryozoan Bugula neritina in 1982 and is currently undergoing evaluation in a number of malignancies. Twenty-five patients with relapsed, low-grade non-Hodgkin's lymphoma or chronic lyphocytic leukemia (CLL) received bryostatin 1 by 72-h continuous infusion every 2 weeks at a dose of 120 microg/m2 per course. Patients who progressed while receiving bryostatin 1 alone could participate in a feasibility study by receiving vincristine administered by bolus i.v. injection immediately after the completion of the bryostatin 1 infusion. The dose of vincristine was escalated in groups of three patients as follows: level 1, 0.5 mg/m2; level 2, 1.0 mg/m2; and level 3, 1.4 mg/m2 with vincristine doses capped at 2.0 mg for all patients. Bryostatin 1 alone resulted in one complete remission and two partial remissions. Nine patients received sequential treatment with bryostatin 1 and vincristine. The addition of vincristine at a dose of 2 mg was feasible and caused the expected dose-related sensory neuropathy. Phenotypic analysis by flow cytometric analysis on pre- and post-bryostatin 1-treated peripheral blood lymphocytes revealed up-regulation in the coexpression of CD11c/ CD22 on CD20+ B cells in two of four CLL patients studied, which is consistent with in vitro findings of differentiation of CLL cells to a hairy cell phenotype.

Phase I study of bryostatin 1 in patients with relapsed non-Hodgkin's lymphoma and chronic lymphocytic leukemia.

PURPOSE: To define, in a phase I study in relapsed non-Hodgkin's lymphoma (NHL) and chronic lymphocytic leukemia (CLL), the maximum-tolerated dose (MTD), major toxicities, and possible antitumor activity of bryostatin 1, a macrocyclic lactone. PATIENTS AND METHODS: Bryostatin 1 was delivered by 72-hour continuous infusion every 2 weeks to patients with relapsed NHL or CLL, at doses that ranged from 12 microg/m2 to 180 microg/m2 per course. Correlative investigations included evaluations of total protein kinase C (PKC) in peripheral blood and lymphoid differentiation in patient tumor tissue. RESULTS: Twenty-nine patients were treated, including three patients with CLL and 26 with NHL. Generalized myalgia was the dose-limiting toxicity (DLT) and occurred in two of three patients treated with bryostatin 1 at 180 microg/m2 per course. Myalgias were dose-related and cumulative, and often started in the thighs and calves, improved with activity, were somewhat responsive to analgesics, and often took weeks to resolve once taken off study. Six patients were treated at the MTD of 120 microg/m2 per course. Myalgia, headache, and fatigue were common. Hematologic toxicity was uncommon. Total cumulative doses of bryostatin 1 up to 1,134 microg/m2 have been administered without untoward toxicity. Eleven patients achieved stable disease for 2 to 19 months. An in vitro assay for total PKC evaluation in patient peripheral-blood samples demonstrated activation within the first 2 hours with subsequent downregulation by 24 hours, which was maintained throughout the duration of the 72-hour infusion. CONCLUSION: This phase I study defined the MTD and recommended phase II dose of bryostatin 1, when administered over 72 hours every 2 weeks, to be 120 microg/m2 (40 microg/m2/d for 3 days). Generalized myalgia was the DLT. Future studies will define the precise activity of bryostatin 1 in subsets of patients with lymphoproliferative malignancies and its efficacy in combination with other agents.

Environmental contamination and marine mammals in coastal waters from Argentina: an overview.

Environmental contamination become an increasing global problem. Different scientific strategies have been developed in order to assess the impact of pollutants on marine ecosystems. The distribution of toxic contaminants in tissues of different marine mammal species--both cetaceans and pinnipeds--has been studied in many ecosystems, as well as several related ecological processes, like pollutant accumulation or transfer through the food web. A research program directed towards evaluating the occurrence of pollutants in marine mammals from the coastal waters of Argentina (southwestern Atlantic Ocean) has been developed since 1985, and includes the study of heavy metal contents in stranded or incidentally caught animals. The marine mammal species studied during this period were: the seals Otaria flavescens and Arctocephalus australis, and small cetaceans Tursiops gephyreus, Pontoporia blainvillei, Kogia breviceps and Ziphius cavirostris. In most of the cases, high contents of heavy metals (total mercury, cadmium, zinc, and copper) have been recorded. Moreover, liver showed the maximum capability for accumulation of heavy metals in all studied species. The biological and ecological characteristics of each species of the above-mentioned marine mammals (feeding habits, age, migratory pathways, or sex) contributed to the understanding of the metal sources. Considering the results as obtained during the study period it can be assumed that: (1) The global distribution of toxic contaminants also affects the southwestern Atlantic Ocean ecosystems, and (2) Marine mammals could be appropriate bioindicator species in order to assess this kind of environmental problem.

Clincal pharmacology of O2,2'-cyclocytidine.

Two metabolites of 2-14C-cyclocytidine (cyclo-C) were found in the plasma and urine and a hydrolytic product, arabinosylcytosine (ara-C), and its deaminated product, arabinosyluracil (ara-U), were found in patients with cancer; 80% of the dose was found in urine in 24 hr, 70% as cyclo-C and 10% as ara-C and ara-U. The plasma disappearance curve of ara-C curvilinear; the half-life of ara-C estimated from the terminal phase is 8 hr. By 6 hr, the ara-C level is 0.35 mug/ml and falls exponentially to 0.006 mug/ml by 24 hr. Plasma concentration ratios of ara-U to ara-C are 0.1 to 0.3, 0.3 to 0.4, and 1.1 to 1.3 at 10 min, 1 hr, and 4 hr following intravenous injection of cyclo-C at 200 mg/m2. Five min after an equal dose of ara-C, this ratio is approximately 2, and by 4 hr, plasma ara-C levels are immeasurable. After intramuscular and subcutaneous administration, cyclo-C is rapidly absorbed. The plasma disappearance curves of the cyclo-C hydrolytic product, ara-C, are similar to those of the intravenous route. Intramuscularly, subcutaneously, and intravenously cyclo-C should be equally effective. Intrathecal injections of cyclo-C (50 mg/m2) result in an effective ara-C level (0.1 mug/ml) in cerebrospinal fluid (CSF) at 24 hr. When cyclo-C is given orally to fasting patients, less than 15% of the dose is excreted in urine in 24 hr and none can be detected in the plasma.