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Biomedical subjects

C R White

Publications and source records attributed to C R White.

At least 19 recordsLinked to original sources
PubMed2006

Pouch young removal and return to oestrus in wild southern hairy-nosed wombats (Lasiorhinus latifrons).

The southern hairy-nosed wombat (Lasiorhinus latifrons) is a seasonal breeding, burrowing marsupial adapted to a semi-arid environment and the closest relative of the endangered northern hairy-nosed wombat (Lasiorhinus krefftii). Females typically give birth to one to two young every 3 years with young weaned at 360-400 days. This study examined the occurrence of polyoestry in a wild population of southern hairy-nosed wombats, and in particular the ability of this species to produce additional offspring in the same breeding season if a young was prematurely lost or removed. Pouch young were removed during the breeding seasons of 1996/1997 and 2003. No females from the 1996 (n=3)/1997 (n=3) group gave birth to a second pouch young in the same breeding season. However, two females in this group gave birth to young the following season. In contrast, all the 2003 group of females (n=6) produced a second offspring in the same breeding season after removal of pouch young (RPY). The reason for the different response to RPY between the two groups is unknown. These studies confirm that southern hairy-nosed wombats are polyoestrus in the wild and are capable of producing more than one offspring in a single breeding season. Females that failed to return to oestrus in the breeding season that pouch young were removed bred again in the following season. Rapid replacement of southern hairy-nosed wombat pouch young in the same breeding season as RPY suggests that this procedure, linked to either hand-rearing or interspecific cross-fostering, should be seriously considered as a priority conservation action to increase the population size of the critically endangered sister species, the northern hairy-nosed wombat.

Animals↗
PubMed2005

Allometric estimation of metabolic rate from heart rate in penguins.

Studies of the relationship between heart rate (f(H)) and rate of oxygen consumption (V(.) (O(2))), which are then used to predict field metabolic rate, frequently fail to incorporate body mass as a predictive variable. This is a potentially important omission in the study of animals whose body mass fluctuates substantially during their annual cycle. In an attempt further to improve estimates of field metabolic rate from f(H), we re-evaluated data on M(b), f(H) and V(.) (O(2)) from previous studies of macaroni penguins (Eudyptes chrysolophus) and king penguins (Aptenodytes patagonicus) and derived a new relationship to integrate these three quantities. This relationship is at least as accurate and precise as previously determined relationships. We applied this same principle to published data on 11 of the 20 recognised penguin taxa to derive a relationship to predict V(.) (O(2)) from f(H) and M(b) in penguins of any species. This result has interesting implications in terms of reducing the logistical burden in studies of field metabolic rate.

Animals↗
PubMed2005

Assessing NO-dependent vasodilatation using vessel bioassays at defined oxygen tensions.

Results from vessel bioassays have provided the foundation for much of our understanding of the mechanisms that control vascular homeostasis and blood flow. The seminal observations that led to the discovery that nitric oxide (NO) is a critical mediator of vascular relaxation were made with the use of such methodology, and many studies have used NO-dependent vessel relaxation as an experimental readout for understanding mechanisms that regulate vascular NO function. Studies have coupled controlling oxygen tensions within vessel bioassay chambers to begin to understand how oxygen-specifically hypoxia-regulate NO function, and this context has identified red cells-specifically hemoglobin within-as critical modulators. Alone, vessel bioassays or measuring oxygen partial pressures (pO2) is relatively straightforward, but the combination necessitates consideration of several factors. We use the example of deoxygenated red cells/hemoglobin-dependent potentiation of nitrite-dependent dilation to illustrate the salient factors that are critical to consider in designing and interpreting experiments aimed at understanding the interplay between oxygen and NO function in the vasculature.

Erythrocytes↗
PubMed2003

The neointimal response to endovascular injury is increased in obese Zucker rats.

BACKGROUND: Restenosis after revascularization procedures is accelerated in persons with type 2 diabetes. AIM: The current study tested the hypothesis that the neointimal response to endovascular injury is enhanced in female obese Zucker (OZ) rats, a model of type 2 diabetes. METHODS: Animals were randomized to receive either a standard diet (SD) or a diabetogenic diet (DD) for 6 weeks. Four weeks later, balloon injury of the right common carotid artery was induced. All rats were euthanized 2 weeks after injury. Lean Zucker (LZ) rats served as controls. RESULTS: At the time of death, plasma glucose was elevated in OZ rats fed a SD (208 +/- 13 mg/dl) and a DD (288 +/- 21 mg/dl) compared to corresponding LZ rats (SD: 153 +/- 8; DD: 132 +/- 7 mg/dl). The ratio of high-density lipoprotein cholesterol (HDLc) to total cholesterol (Totc), an index of atherogenicity, was reduced in OZ rats on both diets (SD: 0.77 +/- 0.06; DD: 0.80 +/- 0.09) compared to LZ controls (SD: 1.11 +/- 0.02; DD: 1.20 +/- 0.05). Histomorphometric analysis of injured arteries showed that the intima to media (I : M) ratio was significantly increased in OZ (1.37 +/- 0.07) compared to LZ (0.79 +/- 0.08) rats. Elevations in plasma glucose and triglycerides (Tg) correlated positively and decreases in HDLc negatively with an increased I : M ratio. Administration of the DD did not further enhance the I : M ratio in LZ (0.87 +/- 0.06) or OZ (1.29 +/- 0.09) rats. CONCLUSIONS: These results suggest that neointima formation following endoluminal injury of the carotid artery is enhanced at an early stage in the development of diabetes mellitus.

Animals↗
PubMed2002

Preventing transmission of sarcoptic mange from sows to their offspring by injection of ivermectin. Effects on swine production.

A blind and controlled field study was conducted on a pig farm in Australia to evaluate the activity of 1% ivermectin solution when injected into pregnant sows that were naturally infested with mites. The study was designed to appreciate the tolerance of the product on sows (litter size, litter birth weights, litter weaning weights, pre-weaning mortality) and to show the effects of sarcoptic mange on the growth performances of their offspring. Twenty sows were selected and ranked on Day-10, prior to the start of the study, on the basis of positive mite counts and parity. Sows were randomly allocated into two groups, A and B. On Day-7, they were injected once with product A (1 ml/33 kg; yielding 300 microg ivermectin/kg BW) or product B (placebo), respectively and then moved to the farrowing unit. Mite counts, ear and body lesions were scored and recorded. The average daily weight gain (ADG) was calculated on piglets from birth to Day-45 (ADG(45)) and birth to Day-70 (ADG(70)). Ivermectin was 100% efficient in preventing the transmission of scabies mites and did not have negative effect on the pregnant sows. Growth performances (ADG(45) and ADG(70)) of piglets from treated sows were significantly higher (452 and 541.5 g per day) than that from untreated sows (433.5 and 518.4 g per day) respectively, confirming that sarcoptic mange is detrimental to the production performances of growing pigs.

Animals↗
PubMed2002

Mohs' micrographic surgery using frozen sections alone may be unsuitable for detecting single atypical melanocytes at the margins of melanoma in situ.

BACKGROUND: It remains questionable whether micrographic surgery with frozen sections is an appropriate technique for excision of melanoma in situ (MIS) of the lentigo maligna type. Advocates of the technique have interpreted MIS as being histologically defined by nests and contiguous atypical melanocytes on the basal layer. Others, however, have viewed the periphery of MIS as consisting of scattered single atypical melanocytes, a finding that may be difficult or impossible to establish on frozen sections. OBJECTIVES: To examine the reliability of micrographic surgery using frozen sections interpreted by an experienced Mohs' surgeon, in the excision of MIS. METHODS: From a total of 154 specimens, frozen sections from the 50 specimens with margins that were considered difficult to interpret were thawed, sent for routine processing and then examined 'blind' by a dermatopathologist. RESULTS: Using the dermatopathologist's report on paraffin-embedded sections as a reference point, the sensitivity and specificity of frozen sections were calculated to be 59% and 81%, respectively. CONCLUSIONS: Using these histological criteria, micrographic surgery with frozen sections alone is unreliable in the excision of MIS.

Adult↗
PubMed2001

Oxygen radical inhibition of nitric oxide-dependent vascular function in sickle cell disease.

Plasma xanthine oxidase (XO) activity was defined as a source of enhanced vascular superoxide (O(2)( *-)) and hydrogen peroxide (H(2)O(2)) production in both sickle cell disease (SCD) patients and knockout-transgenic SCD mice. There was a significant increase in the plasma XO activity of SCD patients that was similarly reflected in the SCD mouse model. Western blot and enzymatic analysis of liver tissue from SCD mice revealed decreased XO content. Hematoxylin and eosin staining of liver tissue of knockout-transgenic SCD mice indicated extensive hepatocellular injury that was accompanied by increased plasma content of the liver enzyme alanine aminotransferase. Immunocytochemical and enzymatic analysis of XO in thoracic aorta and liver tissue of SCD mice showed increased vessel wall and decreased liver XO, with XO concentrated on and in vascular luminal cells. Steady-state rates of vascular O(2)( *-) production, as indicated by coelenterazine chemiluminescence, were significantly increased, and nitric oxide (( *)NO)-dependent vasorelaxation of aortic ring segments was severely impaired in SCD mice, implying oxidative inactivation of ( *)NO. Pretreatment of aortic vessels with the superoxide dismutase mimetic manganese 5,10,15,20-tetrakis(N-ethylpyridinium-2-yl)porphyrin markedly decreased O(2)( small middle dot-) levels and significantly restored acetylcholine-dependent relaxation, whereas catalase had no effect. These data reveal that episodes of intrahepatic hypoxia-reoxygenation associated with SCD can induce the release of XO into the circulation from the liver. This circulating XO can then bind avidly to vessel luminal cells and impair vascular function by creating an oxidative milieu and catalytically consuming (*)NO via O(2)( small middle dot-)-dependent mechanisms.

Alanine Transaminase↗
PubMed2001

Effects of treatments with endectocide on the weight gain of grazing cattle in a warm temperate climate.

Five groups of 20 weaned beef calves were injected subcutaneously with either an ivermectin, a doramectin, an abamectin long-acting formulation, an ivermectin long-acting formulation or a saline control, at turnout and 60 and 120 days later. The animals grazed the same pasture and were sampled and weighed at turnout and 30, 60, 90, 120, 150 and 180 days later. At turnout the mean bodyweights of all the groups were similar and faecal culture showed that they had a mixed strongyle infection of Cooperia, Haemonchus, Ostertagia, Oesophagostomum and Trichostrongylus species. After 180 days, the mean bodyweight gains of each group were respectively 62.1 kg, 102.2 kg, 106.4 kg, 107.3 kg and 110.1 kg for the control, ivermectin, doramectin, ivermectin long-acting and abamectin long-acting groups. All the products significantly improved the weight gains of the cattle, and significantly reduced their faecal egg counts.

Animals↗
PubMed2001

Comparative efficacy, persistent effect, and treatment intervals of anthelmintic pastes in naturally infected horses.

Eighty horses were involved in a comparative, controlled, and randomised field study conducted in Australia and Brazil. This study was undertaken to address the duration of efficacy (by faecal egg count reduction) of four anthelmintic pastes and to measure the time required between treatments on horses naturally infected by gastrointestinal nematodes. The treatment interval was based on the egg reappearance period (ERP), defined as "the period after treatment when horses have reached a positive egg count equal or superior to 200 eggs per gram (epg) of faeces". Horses were ranked according to pre-treatment faecal egg counts and randomly allocated on Day 0 to one of the four treatment groups (n=16). Group A received a combination of ivermectin at 200 microg/kg and praziquantel at 1.5mg/kg, Group B received an ivermectin paste at 200 microg/kg, Group C received a reference product containing ivermectin at 200 microg/kg, Group D received a moxidectin paste at 400 microg/kg, and Group E received a placebo. Horses were individually faecal sampled at weekly interval from Days 0 to 70 after treatment and coprocultures were made on pooled samples at the pre-treatment time on D-7 in Brazil and D-6 in Australia. The nematode population was mainly composed of small strongyles (Cyathostominae, Gyalocephalus spp., Triodontophorus spp.). All products were efficient (>90% efficacy) until Day 42 with no statistical difference between groups. From Day 49 onwards, Group C reached the threshold, while Group B exceeded this threshold on Day 56. Groups A and D remained below 200 epg for the entire study period (70 days). The interval between two anthelmintic treatments can vary according to the threshold. The ERP was defined as the period after treatment while the output of eggs is negligible or considered as acceptable. The mean number of days calculated to recurrence of 200 epg and more was, respectively, 60 days for product A, 56 days for products B and C, and 64 days for product D. If treatments are combined with other methods of limiting exposure to infective larvae on pasture, the number of treatments required will be reduced even further.

Animals↗
PubMed2001

L-arginine chlorination products inhibit endothelial nitric oxide production.

The myeloperoxidase-derived oxidant hypochlorous acid (HOCl) is thought to contribute to endothelial dysfunction, but the mechanisms underlying this inhibitory effect are unknown. The present study tested the hypothesis that HOCl and L-arginine (L-Arg) react to form novel compounds that adversely affect endothelial function by inhibiting nitric oxide (NO) formation. Using spectrophotometric techniques, we found that HOCl and L-Arg react rapidly (k = 7.1 x 10(5) m(-1) s(-1)) to form two major products that were identified by mass spectrometry as monochlorinated and dichlorinated adducts of L-Arg. Pretreatment of bovine aortic endothelial cells with the chlorinated L-Arg metabolites (Cl-l-Arg) inhibited the -induced formation of the NO metabolites nitrate (NO(3)(-)) and nitrite (NO(2)(-)) in a concentration-dependent manner. Preincubation of rat aortic ring segments with Cl-L-Arg resulted in concentration-dependent inhibition of acetylcholine-induced relaxation. In contrast, blood vessels relaxed normally to the endothelium-independent vasodilator sodium nitroprusside. In vivo administration of Cl-L-Arg to anesthetized rats increased carotid artery vascular resistance. A greater than 10-fold excess of L-Arg was required to reverse the inhibitory effects of Cl-L-Arg in vivo and in vitro. Reaction of HOCl with D-arginine (D-Arg) did not result in the formation of inhibitory products. These results suggest that HOCl reacts with L-Arg to form chlorinated products that act as nitric-oxide synthase inhibitors.

Animals↗
PubMed2001

Temporal gradients in shear, but not spatial gradients, stimulate endothelial cell proliferation.

BACKGROUND: The effect of temporal and spatial gradients in shear on primary human endothelial cell (HUVEC) proliferation was investigated. The sudden-expansion flow chamber (SEFC) model was used to differentiate the effect of temporal gradients in shear from that of spatial gradients. With a sudden onset of flow, cells are exposed to both temporal and spatial gradients of shear. The temporal gradients can be eliminated by slowly ramping up the flow. METHODS AND RESULTS: HUVEC proliferation in the SEFC remained unstimulated when the onset of flow was slowly ramped. Sudden onset of flow stimulated a 105% increase of HUVEC proliferation (relative to ramped onset) within the region of flow reattachment. To further separate temporal and spatial gradients, a conventional parallel-plate flow chamber was used. A single 0.5-second impulse of 10 dyne/cm(2) increased HUVEC proliferation 54+/-3% relative to control. When flow was slowly ramped over 30 seconds, HUVEC proliferation was not significantly different from controls. Steady laminar shear over 20 minutes inhibited HUVEC proliferation relative to controls regardless of step (36+/-8%) or ramp (21+/-5%) onsets of flow. CONCLUSIONS: The results indicate that temporal gradients in shear stress stimulate endothelial cell proliferation, whereas spatial gradients affect endothelial proliferation no differently than steady uniform shear stress.

Cell Division↗
PubMed2001

Formation of novel bioactive metabolites from the reactions of pro-inflammatory oxidants with polyphenolics.

Dietary polyphenolics such as those in soy or red wine can have beneficial effects on the development of chronic human diseases. The mechanisms of action of isoflavones have been diverse and include their roles as weak estrogens, inhibitors of tyrosine kinase-dependent signal transduction processes and as antioxidants. Recent insights into the oxidative stress model of atherosclerosis suggest an interesting synthesis of these concepts. Sites of inflammation are associated with the formation of complex mixtures of reactive oxygen, nitrogen and halogenating species capable of modifying both endogenous biomolecules and polyphenolics. Of particular significance are the halogenation reactions mediated by myeloperoxidase that can modify key amino acids such as arginine and polyphenolics such as genistein. Hypochlorite, the reaction product of myeloperoxidase can halogenate polyphenolics to form stable derivatives with modified biological activity. Thus the in situ metabolism at sites of inflammation is unique and generates novel pharmacophores with potentially distinct modes of action from the parent compounds.

Flavonoids↗
PubMed2001

Analysis of temporal shear stress gradients during the onset phase of flow over a backward-facing step.

Endothelial cells in blood vessels are exposed to bloodflow and thus fluid shear stress. In arterial bifurcations and stenoses, disturbed flow causes zones of recirculation and stagnation, which are associated with both spatial and temporal gradients of shear stress. Such gradients have been linked to the generation of atherosclerotic plaques. For in-vitro studies of endothelial cell responses, the sudden-expansion flow chamber has been widely used and described. A two-dimensional numerical simulation of the onset phase of flow through the chamber was performed. The wall shear stress action on the bottom plate was computed as a function of time and distance from the sudden expansion. The results showed that depending on the time for the flow to be established, significant temporal gradients occurred close to the second stagnation point of flow. Slowly ramping the flow over 15 s instead of 200 ms reduces the temporal gradients by a factor of 300, while spatial gradients are reduced by 23 percent. Thus, the effects of spatial and temporal gradients can be observed separately. In experiments on endothelial cells, disturbed flow stimulated cell proliferation only when flow onset was sudden. The spatial patterns of proliferation rate match the exposure to temporal gradients. This study provides information on the dynamics of spatial and temporal gradients to which the cells are exposed in a sudden-expansion flow chamber and relates them to changes in the onset phase of flow.

Algorithms↗
PubMed2001

Endothelial dysfunction is induced by proinflammatory oxidant hypochlorous acid.

The myeloperoxidase (MPO)-derived oxidant hypochlorous acid (HOCl) plays a role in tissue injury under inflammatory conditions. The present study tests the hypothesis that HOCl decreases nitric oxide (NO) bioavailability in the vasculature of Sprague-Dawley rats. Aortic ring segments were pretreated with HOCl (1-50 microM) followed by extensive washing. Endothelium-dependent relaxation was then assessed by cumulative addition of acetylcholine (ACh) or the calcium ionophore A23187. HOCl treatment significantly impaired both ACh- and A23187-mediated relaxation. In contrast, endothelium-independent relaxation induced by sodium nitroprusside was unaffected. The inhibitory effect of HOCl on ACh-induced relaxation was reversed by exposure of ring segments to L-arginine but not D-arginine. In cellular studies, HOCl did not alter endothelial NO synthase (NOS III) protein or activity, but inhibited formation of the NO metabolites nitrate (NO3(-) and nitrite (NO2(-). The reduction in total NO metabolite production in bovine aortic endothelial cells was also reversed by addition of L-arginine. These data suggest that HOCl induces endothelial dysfunction via modification of L-arginine.

Acetylcholine↗
PubMed2001

Endothelial transcytosis of myeloperoxidase confers specificity to vascular ECM proteins as targets of tyrosine nitration.

Nitrotyrosine formation is a hallmark of vascular inflammation, with polymorphonuclear neutrophil-derived (PMN-derived) and monocyte-derived myeloperoxidase (MPO) being shown to catalyze this posttranslational protein modification via oxidation of nitrite (NO(2)(-)) to nitrogen dioxide (NO(2)(*)). Herein, we show that MPO concentrates in the subendothelial matrix of vascular tissues by a transcytotic mechanism and serves as a catalyst of ECM protein tyrosine nitration. Purified MPO and MPO released by intraluminal degranulation of activated human PMNs avidly bound to aortic endothelial cell glycosaminoglycans in both cell monolayer and isolated vessel models. Cell-bound MPO rapidly transcytosed intact endothelium and colocalized abluminally with the ECM protein fibronectin. In the presence of the substrates hydrogen peroxide (H(2)O(2)) and NO(2)(-), cell and vessel wall-associated MPO catalyzed nitration of ECM protein tyrosine residues, with fibronectin identified as a major target protein. Both heparin and the low-molecular weight heparin enoxaparin significantly inhibited MPO binding and protein nitrotyrosine (NO(2)Tyr) formation in both cultured endothelial cells and rat aortic tissues. MPO(-/-) mice treated with intraperitoneal zymosan had lower hepatic NO(2)Tyr/tyrosine ratios than did zymosan-treated wild-type mice. These data indicate that MPO significantly contributes to NO(2)Tyr formation in vivo. Moreover, transcytosis of MPO, occurring independently of leukocyte emigration, confers specificity to nitration of vascular matrix proteins.

Animals↗
PubMed2001

Human angiotensin II type 1 receptor isoforms encoded by messenger RNA splice variants are functionally distinct.

Human tissues that express the angiotensin II (Ang II) type 1 receptor (hAT(1)R) can synthesize four distinct alternatively spliced hAT(1)R mRNA transcripts. In this study, we show that the relative abundance of these mRNA transcripts varies widely in human tissues, suggesting that each splice variant is functionally distinct. Here we demonstrate, for the first time, that the hAT(1)R-B mRNA splice variant encodes a novel long hAT(1)R isoform in vivo that has significantly diminished affinity for Ang II (i.e. >3-fold) when compared with the short hAT(1)R isoform (encoded by hAT(1)R-A mRNA splice variant). This reduced agonist affinity caused a significant shift to the right in the dose-response curve for Ang II-induced inositol trisphosphate production and Ca(2+) mobilization of the long hAT(1)R when compared with that of the short hAT(1)R. The functional differences between these isoforms allows Ang II responsiveness to be fine-tuned by regulating the relative abundance of the long and short hAT(1)R isoform expressed in a given human tissue.

Adrenal Cortex Neoplasms↗
PubMed2001

Enhanced antioxidant activity after chlorination of quercetin by hypochlorous acid.

BACKGROUND: Several epidemiological studies indicate that moderate consumption of red wine decreases both the incidence and mortality associated with cardiovascular disease. Quercetin and rutin (quercetin-3-rutinoside) are polyphenols present in relatively large concentrations in red wine and may play a role in this cardioprotective phenomenon. The precise mechanisms of cardioprotection remain unclear but may involve the action of these polyphenols as antioxidants, which attenuate the tissue injury that results from the production of proinflammatory oxidants such as hypochlorous acid (HOCl). METHODS: To study the interaction of these polyphenols with proinflammatory oxidants, we mixed quercetin or rutin with HOCl (0-150 microM) and analyzed the reaction products by high-performance liquid chromatography, mass spectrometry, and nuclear magnetic resonance. RESULTS: Stable mono- and dichlorinated derivates were detected for both quercetin and the glycoside derivative, rutin, which suggests that both the conjugated and unconjugated forms of quercetin reacted with HOCl similarly. Chlorination of quercetin occurred only at two sites, and the derivates (6-chloroquercetin, 6,8-dichloroquercetin) were more potent antioxidants toward oxidative modification of low-density lipoproteins and ABTS radical formation than the unmodified form. CONCLUSIONS: These data suggest that under certain pathological conditions in vivo (e.g., inflammation), flavonols may be converted to chlorinated derivates, which exhibit an enhanced antioxidant potential and thereby play a role in cardioprotection.

Analysis of Variance↗